Thread by @imtryam

For the year 2022, I aim to read one research (/review) article per day, every day. This thread will summarise the essence of the paper. While oncology is my field of interest, I will also explore papers from other domains and classics, of course. Bon voyage.📋 #APaperADay

https://twitter.com/imtryam/status/1344968670661885953

Day 1 of #APaperADay challenge. I read this classic piece of Dr Barbara McClintock where she described the transposons. It was a seminal discovery breaking the age-old concept of the linear arrangement of genes like beads on a string.
pnas.org/content/36/6/3…

She described such mobile elements, Ac (Activator) and Ds (Dissociation) loci, in maize. These loci change their position which would reversibly alter the gene expression once inserted in the chromosomes. The removal would restore the gene function. #APaperADay

The discovery communicated by her in 1950 was widely reported and recognized only by the 1970s. Now it is known that the transposons constitute at least 45% of the human genome. After 33 years of this, she was awarded the 1983 @NobelPrize in Physiology or Medicine. #APaperADay

Day 2 of #APaperADay challenge. This article in @eLife discusses the role of Hydrogen sulfide in HIV latency reversal. The pertinent challenge in HIV management is the relapse of latent cellular reservoirs once there is an interruption in the therapy.

elifesciences.org/articles/68487

Hydrogen sulfide (H2S) modulates the antimicrobial activity and inflammatory response during bacterial and viral infections. Authors report that reduced levels of endogenous H2S and a metabolite in its synthesis, CTH lead to the reactivation of HIV. #APaperADay

Notably, the slow-releasing H2S donor GYY4137 inhibits residual levels of HIV transcription during antiretroviral therapy (ART) & blocks viral reactivation. This in combination with ART not only prevents the viral rebound but will also overcome the resistant mutants. #APaperADay

Day 3 of #APaperADay challenge. I read this @MBoCjournal article on cellular dynamics and interaction between cadherins & actin filaments. Authors use reversible cross-link immunoprecipitation (ReCLIP) approach to study linkage via coimmunoprecipitation.
molbiolcell.org/doi/10.1091/mb…

Authors identify a novel catenins dependent interaction between Rho-associated protein kinase 1 (ROCK1) and the cadherin complex. They support the complex role for p120 controlling of RhoA signaling in the cadherin complex. #APaperADay

I am particularly intrigued by the use of DSP [dithiobis (succinimidyl propionate)] linkage. It forms stable amide bonds at pH 7-9 and allows crosslinking of intracellular proteins. This identifies the weak or transient protein interactions using immunoprecipitation. #APaperADay

This calls for the follow-up paper in @PLOSONE of the same group where they describe in detail about the ReCLIP (Reversible CrossLink Immuno-Precipitation) technique. I explore this in today's #APaperADay.

journals.plos.org/plosone/articl…

The application of chemical crosslinkers like DSP has been successful in the coimmunoprecipitation of weakly interacting binding partners. This can be used to characterize weak and transient complexes by mass spectrometry. #APaperADay

DSP has a spacer-arm of 12 A˚ and forms crosslinks between lysine residues of interacting proteins. It is commonly used in a variety of protein-interaction studies owing to a high abundance of lysine residues in proteins. #APaperADay

In conclusion, the authors developed ReCLIP technique that can be used to retain weak interactions without compromising on specificity and/or sensitivity.

I aim to replicate this technique for my research. Let's see how that goes. #APaperADay

In today's #APaperADay challenge, I read this article from Prof @i_UCSY's lab authored by @HAgraval. It describes the role of Fisetin, a plant flavonol in suppressing the EMT induced by cigarette smoke in A549 cells.

https://twitter.com/i_UCSY/status/1468109822465695745?s=20

Besides causing COPD, cigarette smoke (CS) leads to upregulation of cyclooxygenase-2 (COX-2) which sustains and promotes tumor. It is also a known inducer of MMPs which leads to EMT. Authors check the role of fisetin in CS-induced COX-2 generation and EMT in cells. #APaperADay

The CS decreased the cell viability and increased cell death. Fisetin significantly increased cell viability at different concentrations of CS. Fisetin also normalises COX2 and MMP2 proteomic expression by WB and zymography. #APaperADay

CS and COX2 increase the expression of mesenchymal markers and downregulate epithelial markers. CS significantly increases the migration of cells which is impeded by fisetin and COX2 inhibitor. Stimulation of prostaglandin E2 yielded EMT features nullified by fisetin. #APaperADay

The sphere formation was significant in CS treated cells. The treatment of fisetin and COX2 inhibitor significantly decreased the spheroid perimeter. Overall this study supports fisetin in containing the CS-induced EMT. It will be interesting to see in vivo studies. #APaperADay

On day 6 of the #APaperADay, I read this paper from one of my favourite journals @JoVEJournal on the generation of monoclonal antibodies using hybridoma technology. This is a great technology that I am also going to use to generate antibody for my research
jove.com/t/54832/genera…

Briefly, a host (rabbit, goat, donkey, or sheep) is repeatedly injected with the antigen against which Ab is to be generated. The serum is harvested to check Ab production. The Ab producing B lymphocytes are fused with immortal cell lines to form hybridomas. #APaperADay

The Ab can be isolated from hybridomas using protein A/G beads or specific Ag affinity chromatography. Thus hybridomas are an infinite source of Ab with added immortality. The mAb generation, however, requires detailed epitope analysis with regard to conformation.
#APaperADay

This is the brainchild of Köhler and Milstein who worked at @MRC_LMB independently.
Köhler: Could produce specific Ab with limited life.
Milstein: Cancerous cells producing Ab of unknown specificity. #APaperADay
Their collaboration resulted in this marvel.

https://twitter.com/imtryam/status/1285626220382756875?s=20

Day 7 of #APaperADay challenge, I read this article in @ScienceMagazine on COVID mortality in India. The findings indicate the underrepresentation of COVID cases and mortality. Interesting to see @YRDeshmukh's statistical skills in life sciences.
science.org/doi/full/10.11…

Authors attribute incomplete certification to COVID deaths and deaths without medical attention to the inadequate representation of COVID mortality in India. Till September 2021, the death toll remains significantly higher than reported. Excellent findings.
#APaperADay

For #APaperADay, I read this paper on the selection of reference genes for the normalization in qRT-PCR. It is pivotal in transcriptomics due to its sensitivity & reproducibility in the measurement of gene expression differences or transcript abundance.
journals.plos.org/plosone/articl…

The housekeeping gene selection is the most crucial part in qRT-PCR. An endogenous reference gene is used to normalize the expression. It should be sufficiently abundant and have stable expression across the cells and should not vary with experimental conditions. #APaperADay

Absolute Cq values for each gene under different conditions was measured in specific qPCR reaction. Using different algorithms, authors analyse the optimal reference genes. 18S rRNA, ACTB and PUM1 were identified to be the 3 most stably expressed reference genes. #APaperADay

The stability of the reference gene varies as per the cell lines and transfections.
Basal cells: ACTB and GAPDH
ER+ve: HSPCB and ACTB
Transfection: 18S rRNA, ACTB and PUM1
Overall Analysis: 18S rRNA-ACTB combination
Discourage the use of: HPRT1 and GAPDH

#APaperADay

Day 9 of #APaperADay. This article in @SciReports describes the role of Androgens in the invasiveness of TNBC cells. Authors use AR knockdown and Co-immunoprecipitation experiments to elucidate the signalling cascade in androgens induced invasiveness.
nature.com/articles/s4159…

Authors report varied expression of Androgen Receptor (AR) in the two cells used, MDAMB231 & MDAMB453 which undergoes nuclear translocation. AR mediates invasion & migration in TNBC which is impeded by anti-androgen bicalutamide or S1 peptide that mimics AR motif. #APaperADay

To address the notion that GR may substitute the AR induced invasiveness, authors Knockdown AR by siRNA induced silencing. The results validate that AR, but not GR, mediates the hormone-induced migration and invasiveness of TNBC cells.
#APaperADay

https://twitter.com/imtryam/status/1340277610127888384?s=20

Androgens induce migration and invasiveness of both cells through the assembly of the AR/Src/PI3-K/FAK complex. The KD of AR reveals its role in the androgen-induced complex assembly and activation of its dependent pathway. The S1 peptide disrupts this complex. #APaperADay

The authors in the concluding statement offer new insights for the identification of biomarkers predictive of TNBC malignancy. The S1 peptide inhibitor of the AR/Src complex may provide new hints for the exploration of novel drugs in clinical application. #APaperADay

In today's #APaperADay challenge, I read this article in @JBI_Journal on epitope prediction using bioinformatics tools. This paper explores the scope of in silico tools to design vaccine candidates against computationally predicted targets in lesser time.
sciencedirect.com/science/articl…

The authors highlight that epitope-based vaccines can be screened using bioinformatics approaches and may elicit an immune response. It is also reiterated that prediction is an indicator of the potential function and should be validated with experimental data. #APaperADay

Next authors discuss strategies employed to develop vaccines using bioinformatic tools against hypervariable viruses such as human immunodeficiency (HIV) and influenza viruses. They enlist potential vaccines against HIV & influenza designed in silico. #APaperADay

Day 11 of #APaperADay. This article is from the same group on the role of Androgen Receptor (AR) in Breast Cancer. Published in @FrontEndocrinol, this review analyses the role of AR and its antagonists in BrCa in particular TNBC.
frontiersin.org/articles/10.33…

https://twitter.com/imtryam/status/1480155349181100034?s=20

Authors explore literature dealing with the levels of androgens and BrCa risk. It posts opposing actions on ER+ve BrCa and in ER-ve BrCa. "AR can inhibit or promote the ER+ cell growth, while it predominantly stimulates the cellular proliferation of ER-BC." #APaperADay

"AR acts in a genomic and in non-genomic way, both in ER-positive and negative BC." From preclinical and clinical findings, it has an irrefutable role in BrCa pathogenesis. Thus, AR can be exploited as an excellent therapeutic target, particularly for AR+ve TNBC. #APaperADay

ATP as energy currency is known to every Biology student. On his birth anniversary, I read this paper attributing this notion. I bow before the genius of Dr Yellapragada Subbarow not only for this but a multitude of inventions. #APaperADay
link.springer.com/article/10.100…

The controversy over the discovery of ATP arises since two groups; Otto Meyerhof's school in Germany lead by Karl Lohmann and in USA by
Cyrus Fiske and Y Subbarow. Both in 1929, published their papers in @Nature and @ScienceMagazine respectively. #APaperADay

The timeline of events.
Dec 1926: Fiske's notebook had mentioned ATP. Did not publish.
1927-28: OM group discovers AMP.
One theory: Meyerhof had visited Fiske at Harvard in 1928 or early
1929, at which time Fiske told Meyerhof about his results with
ATP. #APaperADay

In 1929
Jan: Fiske paper on the Ca salt of ATP
Jan-Feb: Lohman isolates PPi
Aug 2: L paper on ATP published
Aug 21: L gives talk on ATP in Physiological conf. Fiske objects
Aug 23: Subbarow gives unofficial talk on ATP
Oct 18: Fiske-SubbaRow paper published in Science
#APaperADay

"However, as regards the discovery of ATP, it is quite
fair to state simply that ATP was discovered independently by
Fiske and Subbarow, and by Lohmann, in 1929, as Joseph
Fruton and Fritz Lipmann have written." #APaperADay

https://twitter.com/imtryam/status/1262963333919117314?t=oEW8NkPXLxdnkmlFQ1cSVw&s=19

Birthday tributes to one of greatest Indian scientists, Dr Yellapragada Subbarow. His contributions are relevant almost a century later and need wider recognition.
@PrinSciAdvGoI @shekhar_mande @ARanganathan72 @arshukla

In today's #APaperADay, I read this article on the immunomodulatory effect of glucocorticoid steroid dexamethasone (Dex) in cancer patients undergoing chemotherapy. This is a great article dealing with immune challenges induced by Dex co-medication.
tandfonline.com/doi/full/10.10…

Dex is administered as co-medication with chemotherapy to control skin rashes, emesis, and inflammatory side effects in patients with advanced cancer. Dex being GC induces immunosuppressive and anti-inflammatory effects. #APaperADay

https://twitter.com/imtryam/status/1273575724197146625?s=20

The authors attempt to comprehend the nature and scope of immunological changes induced in response to Dex used in chemo medication in malignant pleural mesothelioma (MPM). This is crucial to understand in the context of combining immunotherapy with chemotherapy. #APaperADay

Retrospective analysis of data from chemoimmunotherapy clinical trials in patients with MPM, authors report large-scale lymphodepletion of CD4+ and CD8+ cells. This effect was significantly more pronounced in CD4+ cells, as shown by the CD4:CD8 ratio. #APaperADay

The authors highlight on negating the impacts of Dex on immunotherapy modalities by optimising dose and/or timing of administration. This clinical data may decide the planning of combined chemoimmunotherapy modalities. #APaperADay

Time for a classic in today's #APaperADay challenge. I am reading this 1977 @PNASNews paper explaining DNA sequencing using the chain termination method. This article earned him the @NobelPrize in chemistry in 1980.
pnas.org/content/74/12/…

Taking a cue from Atkinson et al. who employed the inhibitory activity of 2',3'-dideoxythymidine triphosphate (ddTTP) on DNA polymerase I into the growing oligonucleotide chain. The lack of 3'OH in ddTTP group halts the chain synthesis at T residues. #APaperADay

Sanger et. al. extended this idea to prepare a dideoxy mix of ddATP while ddGTP and ddCTP were prepared previously. They incubated the ddNTPs along with 1 µl of DNA polymerase. The lack of 3'OH terminates the phosphodiester bond formation. #APaperADay

The terminated fragments (Φ174 DNA) were analysed on 12% acrylamide gel at 40 mA for 14 hr. These are read from bottom to top across the lanes that would yield a 5' to 3' sequence of the DNA. Currently, ddNTPs are fluorescent labelled and used in a single reaction. #APaperADay

Authors ask for the validation of this technique to obtain an accurate determination of sequence. This actually is true for any other technique. With the advent of PCR, it is now impossible to think beyond PCR for any molecular biology experiments. #APaperADay

In today's #APaperADay, I am reading this paper from @embojournal. Authors in this paper have assessed multi-protein complexes that bind to the β-globin locus in erythroleukemic K562 cells. These have implications in molecular processes and epigenetics.
embopress.org/doi/full/10.10…

They hypothesized the functional link between proteins recruited to the locus control region and the initiation of replication for the initiation of transcription & replication. To achieve this, they performed EMSA & mass spectrometry to uncover multiprotein complex. #APaperADay

Tailing EMSA showed various DNA-protein complexes at DNase-1 hypersensitive (HS) sites, in particular, HS4-9 in K562 cells. Biochemical purification and MS/MS analysis revealed this to be DARRT components. Further IP and coIP suggested the DARRT exists in a complex. #APaperADay

Overall authors report the identification of DARRT complex that has roles in DNA replication, histone modification, and transcriptional regulation of β-globin locus. #APaperADay

Day 16 of #APaperADay. I am reading this excellent article in @CellCellPress which floats an assay for the analysis of individual HIV infected cells, to simultaneously capture the transcriptional activity, sequence, and the chromosomal IS of proviruses.
cell.com/cell/fulltext/…

The viremic rebound with an interruption in treatment necessitates continuous antiretroviral therapy (ART). The strategies of “shock-and-kill” to induce the proviruses into producing new viruses and then being targetted by immune cells have made little progress. #APaperADay

The authors have examined 1270 proviruses in the PBMCs of six people at different points of ART. Out of these 1270, 147 encoded for the genome-intact HIV-1. The integration sites were frequently in the intronic regions of highly expressed genes. #APaperADay

Further, intact proviruses were more frequently located in nongenic regions relative to defective proviruses. These exhibited lower transcriptional activity likely due to nonpermissive genomic and epigenetic chromatin features at chromosomal IS. #APaperADay

They suggest a progressive selection of proviruses with lower transcriptional activity and integration into nongenic/satellite DNA locations during prolonged ART. Not all proviruses responded to the latency reversal agents, indicating the role of chromosomal locations #APaperADay

Authors conclude that HIV can integrate almost anywhere in the human genome. The viral reservoir cells are frequently transcriptionally active and dynamically evolving in response to host-dependent selection forces. #APaperADay

The authors also suggest that with deeper latency and lower transcriptional activity, the proviral reservoir landscape can easily be controlled by the host immunity. This may allow for peaceful coexistence between HIV and the host; enabling drug-free control of HIV. #APaperADay

In today's #APaperADay challenge, I am reading this article from @NatureComms on the evasion of anti-HER2 therapy in HER2 + breast cancers (BrCa). Authors through extensive genomic profiling of HER2-amplified BrCa identify the set of somatic alterations.
nature.com/articles/s4146…

Emerging de novo and acquired resistance reduce the efficacy of anti-HER2 therapy. Authors report enrichment of MAPK pathway mutations in advanced cancers. This promotes a switch in pathway dependence from PI3K/AKT to MEK/ERK, leading to resistance to α-HER2 therapies.#APaperADay

Authors further comment that "MAPK activation in HER2 + breast cancers promotes a switch in cell cycle control from AKT to MAPK that drives resistance to HER2-targeted agents but also enforces a strong and targetable dependence on MEK/ERK signaling." #APaperADay

Mutations acquired against targeted therapy are capable of disabling feedback suppressive mechanisms, and rewiring signaling input to effector pathways. Authors support extensive clinical sequencing studies to fully comprehend the scope of these signaling phenomena. #APaperADay

Today's #APaperADay article on the Epithelial to Mesenchymal (EMT) Transition in Breast Cancer. Authors discuss EMT through a process of dedifferentiation that confers stem-like features, chemoresistance, as well as the capacity to migrate and invade.
mdpi.com/2072-6694/9/10…

Invasion and metastasis contribute towards the majority of death (90%) in breast cancer patients. EMT is characterized by the loss of cellular adhesion, polarization changes, migration, intravasation, survival in the vascular system, extravasation, and metastasis. #APaperADay

An intriguing capacity of the EMT process is its potential reversibility into mesenchymal-to-epithelial transition (MET). The authors further discuss the roles of different signalling pathways in breast cancer EMT. #APaperADay

TGF-β Pathway: Dual role in breast tumorigenesis. In early lesion, it suppresses tumor while in later stages it leads to metastasis mainly through the induction of EMT.
Wnt Pathway: It promotes cell migration, metastatic behaviour, and EMT.
#APaperADay

Notch Pathway: It may act as either an oncogene or a tumor suppressor gene. Its activation correlates with poor prognosis and poor patient survival.
Receptor Tyrosine Kinases Pathway: Growth factors stimulate RTKs to initiate intracellular signaling that promotes EMT. #APaperADay

The authors also discuss the prospects of extracellular matrix and paracrine mechanisms in the EMT. The induction of MET appears as one therapeutic opportunity besides others to aid current traditional cytotoxic chemotherapy more effective. #APaperADay

#APaperADay challenge. I am going through this @Oncotarget article on the expression of AR transcript variants in Breast Cancer. Authors target the expression pattern and clinical implications of constitutively expressed AR variant 7 (AR-V7).
oncotarget.com/article/6296/t…

AR has shown dichotomous roles depending upon ERα status & molecular subtype. In ERα+ it has a favourable prognostic role while in ERα- tumor its sustains growth and proliferation. This notion is supported by the treatment of bicalutamide (AR antagonist) in AR+ TNBC. #APaperADay

Anti-androgen therapy is the mainstay of treatment for Prostate cancer. This, however, leads to resistance against the disease, termed castration-resistant prostate cancer (CRPC). C terminally truncated AR variants that lack LBD are resistant to α-androgen/αAR drugs. #APaperADay

Using the TCGA database and prospective cohort studies, authors report that AR-V7 is expressed in about 50% of primary breast tumors and is positively correlated with AR-FL expression. #APaperADay

Authors further confirm the constitutive expression of AR-V7 in cell lines and it is resistant to AR-FL antagonists, bicalutamide & enzalutamide. Knockdown of AR-V7 resulted in an equivalent growth reduction suggesting that it predominantly promotes growth. #APaperADay

I am going through a follow-up paper by the same group in today's #APaperADay. In this @NatureMedicine article using clinically relevant panel of cell-line and patient-derived models, the authors demonstrate that AR has a tumor suppressor role in ER+ BrCa.
nature.com/articles/s4159…

Androgens were historically used to treat BrCa even with a rudimentary knowledge of hormone receptors in the breast. It was discontinued with the advent of endocrine therapy targeting ER directly. Resistance to this therapy opens the scope for alternative strategies. #APaperADay

Since almost all ER+ BrCa express AR and there is a wide availability of clinical AR modulators, research is underway to investigate AR agonists and AR antagonists role in BrCa. #APaperADay

Authors report AR to be a favourable prognostic marker of ER+ breast cancer survival. Androgen inhibits estrogen-stimulated proliferation in clinical breast tissues as observed. #APaperADay

Ultimately, the authors provide extensive evidence that AR is a tumor suppressor in multiple contexts of ER+ breast cancer, including endocrine resistance. AR treatment strategy has the potential to become an alternative endocrine therapy for breast cancer. #APaperADay

I am reading this article on the role of Oxygen in mammalian cell culture. There is a wide discrepancy in oxygen tension in organs and a substantial gradient is observed with an organ. This tension decreases with intense exercise or in Cancer. #APaperADay nature.com/articles/s4225…

In mammalian cell culture, humidified CO2 cell culture incubator contains 140 mm Hg O2 which is way above the maximum partial pressure of O2 experienced by the lung alveoli (~110 mm Hg). Authors question our supra-physiological oxygen concentrations in cell cultures. #APaperADay

Authors further review six broad categories of cellular processes known to be affected by oxygen. The seeding density, surface area-to-volume ratio of the culture vessels and time influence the oxygen tension of an experiment and the rate at which oxygen is depleted. #APaperADay

Cell culture is one of the mainstays of modern biomedical research. Authors suggest considering the influence oxygen can have on findings. It has the potential to discover new facets, robust experiments & the likelihood of the findings having in vivo relevance. #APaperADay

In today's #APaperADay, I read this @PNASNews perspective highlighting the significance of The Earth BioGenome Project that aims to sequence the genomes of all eukaryotes (~ 2 million species). This will create a digital library of life on Earth.
pnas.org/content/119/4/…

"To date, much of comparative genomics has centered on deep analysis of a short roster of species, focused around Humans." The digital library will transform our understanding of how life evolved, help us build a sustainable future, & support an innovative bioeconomy. #APaperADay

This project will help establish correct phylogenetic trees and resolve the root of the tree and the placement of many eukaryotes. This will further complement our understanding of the origin of the eukaryotic cell from prokaryotic precursors. #APaperADay

Authors further support the project in comprehending the symbiosis in eukaryotes, chromosomal evolution, and gene regulation. It will foster the growth of the future, sustainable agriculture, new bioeconomies, and expanded medical pharmacopoeia. #APaperADay

In today's #APaperADay challenge, I read this article in @EMBOPress on AR regulated transcription in molecular apocrine (ER- AR+) tumors. AR binds and regulates ER cis-regulatory elements as exhibited by ER-mediated transcription in ER+ BrCa.
embopress.org/doi/full/10.10…

The authors took the molecular apocrine model, MDAMB453 cells to clarify the role of AR in ER- BrCa using chromatin immunoprecipitation (ChIP) sequencing. They determined the mechanisms underlying AR-mediated chromatin interactions and transcriptional potential. #APaperADay

AR mediates its effects by binding to chromatin in a ligand-dependent manner, which can be perturbed by anti-androgen, bicalutamide. AR binding profile in MDAMB453 cells was more similar to ER binding in MCF7 and substantially distinct from AR binding in LNCaP. #APaperADay

The data suggest that in MDAMB453 cells more than half of AR binding to the genome occurs in a similar pattern to ER binding in MCF7. Hence in the absence of ER, it appears that AR is capable of mimicking ER in its ability to bind to DNA and catalyse transcription. #APaperADay

Almost all AR binding events occur at FoxA1 binding regions and FoxA1 is required for AR to bind chromatin. The overlap in FoxA1 binding across the three cell lines was similar to what has been reported across three ER+ BrCa cell lines, MCF7, ZR75-1 and T-47D. #APaperADay

Today's #APaperADay article on the role of AR in Estrogen induced cyclin D1 expression in ER+ breast cancer cells. These findings support the AR targeting in ER+ BrCa to complement the anti-estrogen adjuvant therapies. bmccancer.biomedcentral.com/articles/10.11…

AR expression is associated with improved prognosis in ER+ tumors and worse prognosis in ER- ones. Estrogens exert their proliferative effects by induction of the G1 progression & G1/S transition through the transcriptional control of cell cycle regulatory gene; CCND. #APaperADay

In this paper, authors examined the possibility of the existence of an additional mechanism by which androgens, through their own receptor, may inhibit E2-induced cyclin D1 expression thus modulating estrogen-dependent breast cancer cell proliferation.. #APaperADay

Prolonged DHT administration resulted in a significant reduction of basal as well as E2-dependent MCF-7 cell proliferation. Estrogen induction of cyclin D1 expression and promoter activity is reduced by over-expression of the androgen receptor. #APaperADay

Considering the fact that both AR and ERα use a common pool of co-factors, authors investigated the role of the steroid receptor coactivator AIB1. siRNA knockdown of AIB1 expression completely negated the increase in cyclin D1 protein expression induced by estradiol. #APaperADay

In today's #APaperADay challenge, I am reviewing this @OACellBiology article on proteome-wide analysis using co-Immunoprecipitation and mass spectrometry to identify partners of TET1 in the myelinating cells.
cellandbioscience.biomedcentral.com/articles/10.11…

The authors have previously reported the high expression of TET1 in oligodendrocytes and siRNA mediated TET1 silencing impairs OL differentiation. In this work, they used mass spectrometry-based proteomics approach to gain insights into the TET1 interacting patterners.#APaperADay

"Analysis of the protein-protein interaction (PPI) networks for TET1 showed that in OPCs, proteins associated with TET1 were involved in cell homeostasis or protein synthesis." The data explores the distinctive functional role of TET1 in oligodendrocyte biology. #APaperADay

Authors speculate that in oligodendrocytes, TET1 may play a role in recruitment with HDAC1 to affect histone acetylation, which may further influence chromosome structure and gene transcription activation. #APaperADay

Today's #APaperADay article is from @Curr_Protocols on the identification of protein-protein interactions using co-immunoprecipitation coupled with Mass Spectroscopy. Authors present this article as one way of identifying signalplex partners. …rentprotocols.onlinelibrary.wiley.com/doi/10.1002/04…

In MS-based proteomics, the protein itself is used as an affinity reagent to isolate its binding partners. The protein is in its processed form, the interactions are in the native environment, and multi-component complexes can be isolated in a single step. #APaperADay

The authors list three essential components for successfully identifying neuronal proteins (or any protein complex) using MS-based proteomics:
- immunoprecipitation of the protein bait
-purification of the complex
-the identification of the interacting partners

#APaperADay

The article discusses two methods for performing MS-based proteomics.
1. Affinity tags to endogenous proteins followed by IP with antibodies against the affinity tag.
2. Protein identification from native systems with endogenous proteins with commercial Ab available.
#APaperADay

In today's #APaperADay, I am going through this review in @IJMS_MDPI on approaches to improve immunostaining. This is an excellent piece for protocol optimization, sample processing, and antibody signal
enhancement.
mdpi.com/1422-0067/23/3…

Immunostaining is widely used in clinicopathological research to understand protein localization, distributions, and abundance. It is divided into two parts.
1. Direct: Primary Ab attached to the label
2. Indirect: labelled secondary antibody binds to primary Ab.
#APaperADay

In an excellent way, the authors discuss the common immunostaining methods and walk through some of the common disadvantages. With a metaphor of a highway, they also describe the parameters taken to counter these drawbacks. #APaperADay

They suggest alternatives to counter drawbacks in protein alterations, metabolic/biochemical changes, sample damages, low permeabilization, low Ab signal, high background, unmasking epitopes as well as the over-emission of fluorescence given by nuclear counterstain. #APaperADay

Revisiting @PNASNews classic in today's #APaperADay on the primary kingdoms of Carl Woese. The paper authored by Carl Woese and Gorge Fox described the 16S rRNA gene as a molecular and evolutionary marker to define the three domains of life on Earth.
pnas.org/content/74/11/…

Woese and Fox isolated rRNA from several primitive organisms and digested with T1 RNase. The resulting digests were subjected to 2D electrophoretic separation to produce an oligonucleotide fingerprint. Multiple comparisons of the data led to the formation of groups. #APaperADay

Based on proportionate numbers of mutations they say "it cannot be proven that the three lines of descent branched from the common ancestral line at about the same time." These tripartite phylogenetic structure of the living world are Bacteria, Eukaryota, and Archaea. #APaperADay

In today's #APaperADay, I am reviewing this article on the spectrum of EGFR mutations in non-small-cell lung carcinomas (NSCLC). In this excellent study, the authors correlate the mutation profile with treatment response and disease progression. @djaiims
lungcancerjournal.info/article/S0169-…

Mutations in exons 18–21 of EGFR encoding for Tyrosine Kinase domain (TKD) lead to constitutive expression of EGFR that leads to tumorigenesis. TK inhibitors competitively inhibit ATP binding to the kinase domain and thus block its activation. #APaperADay

The mutations can be common {exon19del, exon 21 (L858R)}, uncommon, and rarely compound. These mutations dictate the response against the EGFR TKI. Authors in this paper assess the range of mutations in subjects with NSCLC and compare the treatment response & outcome. #APaperADay

The sample studied was selected both, retrospectively and prospectively from treatment-naive patients (n=1252). EGFR mutation testing was done using a qPCR-based kit. Clinical data were analysed for response to the treatment and Progression-free survival (PFS). #APaperADay

Male predominance was observed with an M to F ratio of 2.19:1. 31.8 % of the samples tested had EGFR mutations out of which exon19del and L858R occurred as single or in compound mutations in 91.8 % of cases. Patients with compound and single mutations presented early. #APaperADay

Patients with single common mutations responded significantly well to EGFR TKIs versus chemotherapy compared to those harbouring uncommon & compound mutations. Authors caution about the heterogeneous nature of uncommon and compound mutations and warrant further study. #APaperADay

Day 30 of #APaperADay challenge. Today's article is from @NatureComms and deals with mammary tissue remodelling during pregnancy and lactation. The authors using single-cell transcriptomic analysis provide cellular dynamics into play during the phases.
nature.com/articles/s4146…

The mammary gland undergoes cycles of tissue remodelling throughout a woman’s reproductive lifespan that are particularly pronounced during pregnancy, lactation and the return of the mammary gland to its resting state post involution. #APaperADay

These molecular dynamics occurring in mammary glands is necessitated not only to understand normal mammary gland function but also may point towards a mechanism explaining the reduced long-term breast cancer risk associated. #APaperADay

The authors in this paper performed a single-cell transcriptomic analysis of viable breast cells isolated from human milk or non-lactating breast tissue. They report distinct molecular profiles in cells isolated from milk or breast tissue. #APaperADay

They provide evidence to support the viability of milk-derived epithelial cells and can be maintained in vitro, similar to cells isolated from human breast tissue. Further, mammary cells isolated from the milk do not directly contribute to breast cancer formation. #APaperADay

Another @NatureComms paper on the month-end of #APaperADay challenge. Using the CRISPR-Cas9 strategy, authors produce male- or female-only litters with absolute efficiency. This approach can be extended to other vertebrate species also. @TheCrick
nature.com/articles/s4146…

With ongoing ethical discussions, animals are used for various purposes. Some require specific sex and hence the remainder needs to be culled. Hence, it is urgently needed to generate single-sex litters in research and agriculture. #APaperADay

Authors "show that targeting the essential gene Top1 in a synthetic lethal system produces single-sex mouse litters." This will be of great help in biomedical research and can also be amenable to the development and implementation of sex selection in other mammals. #APaperADay

In today's #APaperADay challenge, I am reading this @CR_AACR article that uncovers AR transcript variants in Prostate Cancer. The variant-specific expression in PCa suggests a potential biomarker and probable therapeutic target.
cancerres.aacrjournals.org/content/69/1/1…

Androgenic signalling contributes towards Prostate cancer progression and survival. Hormonal therapies for advanced PCa target AR-mediated functions. Even though resulting in clinical regression, it is not curative due to progression to hormone-refractory PCa (HRPC). #APaperADay

Some AR variants are functionally active even in the absence of androgens owing to the cleavage of the Ligand Binding Domain (LBD). Authors unveil multiple novel AR variants without LBD which are overexpressed in HRPC. They also generated variant-specific Ab. #APaperADay

HRPC specimens expressed consistently higher levels of AR-V1 & AR-V7. AR-V7 is constitutively active. The detection of such variants may predict hormone therapy efficacy & could guide the decision-making process about the type and timing of therapies for pt with PCa. #APaperADay

Today's #APaperADay article from @CR_AACR "on the transfer of some of the hard won information about the p53 protein, its mutations, structures, and activities learned in the basic science laboratory and translated to the clinic."
cancerres.aacrjournals.org/content/82/3/3…

The p53 transcription factor responds by increasing its concentration and activity, to intrinsic and extrinsic stresses that may lead to increased rates of mutation, due to replicating damaged DNA or other processes during cellular replication. #APaperADay

Cancer being a heterogeneous disease can not be described by a common feature, mutated gene, causative agent, or treatment for this disease. 50 % of spontaneous cancers in humans have Tp53 mutations and most with wild-type (WT) compromised Tp53 gene. #APaperADay

The authors enlist and describe a large number of compounds and agents that have been or are being tested in the clinic and have yielded a number of interesting results. #APaperADay

Today's #APaperADay article is from @Nature. The authors precisely show that response to treatment is modulated by the pre-treated tumour ecosystem, and its multi-omics landscape can be integrated in predictive models using machine learning.
nature.com/articles/s4158…

Authors have identified individual pre-therapy clinical, molecular and digital pathology features associated with pCR and integrated them within machine learning models to predict responses, which were then validated in an independent dataset.#APaperADay

They identified clinical, digital pathology, genomic and transcriptomic features present in the naive tumour ecosystem that are associated with response to therapy. With that, they integrated machine learning framework into a predictive model of pCR. #APaperADay

They report that machine learning models for prediction of therapy response that combine clinical, molecular and digital pathology data significantly outperform those based on clinical variables. Similar prediction models can be extended to other cancers. #APaperADay

In today's #APaperADay, I am reading this Science Translational Medicine paper on exploratory single-cell RNA sequencing in Lung Cancer. The lung plasma lipidomic profiling reveals nine commonly dysregulated lipids in patients with early-stage lung tumors.
science.org/doi/abs/10.112…

Lung cancer currently has the highest incidence of mortality and the second highest incidence of morbidity among all tumors in both sexes worldwide. Screening tests have limitations with high false positivity, radiation exposure, and high cost. #APaperADay

Authors highlight the urgency of early-stage detection and screening of lung cancer, particularly in high-risk populations. Metabolites are the end products of biological metabolism & may reliably reflect the status of biological systems than the genome/transcriptome. #APaperADay

The scRNA-seq reveals aberrant lipid metabolism in early-stage lung cancer. The average proportion of the different cell types in healthy lung samples varied greatly with early-stage lung cancer tissues. #APaperADay

They carried out plasma lipidomics to characterize the plasma lipid-omics of early-stage lung cancer using high-performance liquid chromatography–MS. They developed plasma lipidomics & machine learning-based method Lung Cancer Artificial Intelligence Detector (LCAID). #APaperADay

Since there is a paucity of effective liquid-based tests for detecting early-stage Lung Cancer. LCAID may be helpful in clinical detection and screening that too in 90 minutes. This will hence reduce unnecessary exposure to radiation & invasive diagnostic procedures. #APaperADay

In today's #APaperADay I am reading this @ASCO article on the correlation of circulating T-cell repertoires with tumor response in breast cancer patients receiving Neoadjuvant Chemotherapy (NACT).
ascopubs.org/doi/full/10.12…

NACT is widely used for locally advanced BrCa leading to tumor shrinkage, stage reduction, and even pathologic complete remission (pCR). Except for patients achieving pCR, NACT is of not enough therapeutic value which is a pertinent clinical issue. #APaperADay

T cells play a key role in antitumor immune responses. Through T-cell receptor (TCR) high-throughput sequencing, TCR repertoire sequence T-cell clonal composition and frequency can be assessed. Authors analyze circulating TCR repertoire in BrCa pt receiving NACT. #APaperADay

The authors isolated RNA from PBMCs of 94 patients. RNA was reverse transcribed to cDNA and PCR was run. The PCR products were purified and sequenced which was analysed for TCRβ repertoire using in silico tools. Appropriate statistical analysis was performed. #APaperADay

Authors report TCR diversity was associated with age. Younger and early-stage patients had higher TCR diversity than those with older age and advanced stage respectively. TCR repertoire was also influenced by the HER2 expression status. #APaperADay

The results show variability in TCR repertoire during NACT and with characteristics of the tumor. TCR diversity decreased more in patients with a good clinical response indicating a stronger immune response. These data may be helpful in tailoring therapeutic regimens. #APaperADay

@jbiolchem editors' pick article in today's #APaperADay challenge. It highlights an example of how the microbiome is integrally involved in producing metabolites that support our health and in preventing the formation of compounds that promote disease.
jbc.org/article/S0021-…

The composition of the microbiome can determine our own well-being. A lot of research is going on identifying the constituent organisms and defining their metabolic pathways, metabolites, and the association of individual genes with health or disease. #APaperADay

Author comments on the Ellenbogen et al. article where they have identified a microbiome associated demethylase that short-circuits the production of trimethylamine-N-oxide which is correlated with cardiovascular & kidney diseases as well as colorectal & liver cancer. #APaperADay

Effects of Testosterone on the Breast in today's #APaperADay article. Published in @EndoSocJournals this article sheds light on Androgens endocrinology, effects in preclinical and clinical studies, and implications in Breast Cancer.
academic.oup.com/edrv/article/2…

Steroids & their nuclear receptors play crucial roles in the development & maintenance of normal functions of the human mammary gland. Preclinical studies report that AR expression is a necessary requirement for androgenic effects on breast cancer cell proliferation. #APaperADay

in vivo data indicate that in estrogen-replete normal breast tissue, androgens diminish estrogen-induced breast epithelial proliferation and abolish estrogen-induced ER gene expression. In the absence of estrogen, androgen action mimics that of progestins. #APaperADay

In vitro and in vivo studies indicate that both testosterone and DHT have a predominantly inhibitory influence on the mitogenic and cancer-promoting effects of estrogen in breast cells and promote apoptosis via the AR. #APaperADay

In today's #APaperADay, I read this intuitive article on mRNA vaccine against HIV. Published in @NatureMedicine, this article using the same platform used for COVID-19 mRNA vaccines reduces the risk of infection in rhesus macaques.
nature.com/articles/s4159…

The authors designed vaccine co-expressing membrane-anchored HIV-1 envelope (Env) and simian immunodeficiency virus (SIV) Gag proteins to generate virus-like particles (VLPs). #APaperADay

The results ensure the safety of the novel vaccine and elicit anticipated antibody and cellular immune responses against the simian-human immunodeficiency virus (SHIV). The macaques receiving the vaccine had a 79% lower risk of infection compared to unvaccinated ones. #APaperADay

@JournalGIM article in today's #APaperADay. A randomized controlled trial was used to compare Acute care at home to traditional hospital care. The majority of patients declined enrollment in a home hospital and had similar sociodemographic characteristics.
link.springer.com/article/10.100…

A “home hospital” has shown lower cost, utilization, and readmission and improved patient experience and physical activity. Despite these benefits, many patients decline to participate in a home hospital model over traditional hospitalization. #APaperADay

Authors demonstrated that patients who declined to enroll had generally similar sociodemographic characteristics to those who enrolled and declined most often for perceptions surrounding safety at home and the ease of remaining in the hospital.
Safety and comfort. #APaperADay

Having done multiple western blots, the paper in today's #APaperADay is like a quick note to glance through while doing multiple incubations. This article walks through the theory of the technique to troubleshooting. Always a delightful read.
najms.org/article.asp?is…

Management of primary tumor in stage IV of Breast cancer is today's #APaperADay article I am going to read. The oncology grand rounds article in @JCO_ASCO is case presentation followed by a literature review and management approaches.
ascopubs.org/doi/full/10.12…

Nearly 6% of newly diagnosed breast cancer patients have concurrent distant metastases. Routine systemic imaging for early-stage (I or II) BrCa without symptoms is not recommended due to less likelihood (~2%) of metastatic disease with stages I & II. #APaperADay

The likelihood of distant metastasis elevates to 15%-20% with stage III. This calls for a focused CT of the chest, abdomen, & pelvis with a bone scan. This is followed by the biopsy of the lesion to confirm the diagnosis & immunophenotype of the metastatic carcinoma. #APaperADay

Locoregional management in stage IV was pursued for palliation and local control to improve quality of life. However, in 2006 it was suggested that resection of primary tumor confers benefits in terms of reduction of additional distant disease and improved survival. #APaperADay

Authors cite one randomized trial from @ACTREC_TMC that evaluated Local Therapy in the setting of de novo stage IV BrCa. There was no survival benefit in patients with LT who responded to frontline Systemic Treatment and that resection should not be routine practice. #APaperADay

There have been other trials comparing survival between LT and ST alone in de novo stage IV Breast Cancer. The results support the data from the Mumbai trial albeit with better overall survival in the two arms due to improved systemic therapy and treatment resources. #APaperADay

The authors present their approach is to always defer surgery in the setting of stage IV disease, and refer to medical oncology for initiation of systemic therapy. Longevity will be determined by response to treatment and the extent of metastasis. #APaperADay

The effectiveness of systemic therapy for breast cancer has largely relegated local therapy in the setting of stage IV disease to a minimal role. This therapy provides substantive rates and lengths of survival, even in the setting of stage IV disease. #APaperADay

On his birthday, I am reading this 1800 article by #CharlesDarwin in the #APaperADay. He describes a series of experiments involving basic chemistry. I aim to read his "The Origin of Species" which popularised the evolutionary aspects of human beings.
pubmed.ncbi.nlm.nih.gov/30490902/

In today's #APaperADay challenge, I am reading this @clinadvances article that reviews the standard of care targeted therapies and agents currently under investigation for advanced hormone receptor-positive breast cancer.
hematologyandoncology.net/archives/augus…

Estrogen is the main driver of cancer cell proliferation in HR+ breast cancer that accounts for 70% of early and de novo metastatic breast cancer. Key treatment plans involve estrogen deprivation. However, this leads to resistance against endocrine therapy. #APaperADay

Standard-of-Care Strategies to Address Endocrine Resistance:
-CDK4/6 or PI3K Inhibitors

Novel Targeted Therapies for Patients With Endocrine-Resistant HR+ BrCa:
-Novel agents targeting ER
-AKT, mTORC, RTK, Protein Kinase Inhibitors
-Targetting apoptotic, AR pathways
#APaperADay

Article on the role of Ectodysplasin A Receptor (EDAR) in today's #APaperADay. Ectodysplasin A is a member of the TNF family. Mutations in EDA/EDAR/EDAR associated death domain (EDARADD) contribute to hypohidrotic ectodermal dysplasia in newborns.
frontiersin.org/articles/10.33…

Several studies have reported that EDA and its receptors are involved in cancer pathogenesis by regulating the apoptosis, proliferation, differentiation, and migration of cancer cells. Authors review EDA/EDAR in various signaling pathways and their pathophysiology. #APaperADay

One study reports that EDAR promoted tumor cell proliferation by inducing Wnt/β-catenin signaling. Silencing EDAR in colorectal cancer (CRC) cells leads to a decrease in β-catenin abundance. #APaperADay

EDA is essential for the formation of skin appendages such as hair, teeth, sweat glands, and eyelids. EDA can induce the apoptosis of hair follicle cells and regulate the hair follicle growth cycle. #APaperADay

EDA secreted from liver tissues is associated with insulin resistance, diabetes, and NAFLD and stimulating EDA or blocking EDA signaling may modulate hepatic steatosis and insulin resistance. #APaperADay

Wang et al., 2020 showed that EDAR expression was upregulated in CRC tissues and cell lines relative to their respective controls. Together, these findings suggest EDA be closely linked with cancer cell proliferation, migration, differentiation, and local recurrence. #APaperADay

@Nature article on the mutational signatures of a DNA topoisomerase in today's #APaperADay challenge. Authors show ID4-a cancer insertion-deletion (indel) mutation signature of unknown aetiology is due to a transcription-associated mutagenesis process.
nature.com/articles/s4158…

Driver mutations fuel cancers' uncontrolled multiplications. Common mutational profiles are catalogues as reference sets of mutational ‘signatures’. Much work is done on point mutations except for the causes of mutational footprints characterized by small indels. #APaperADay

The authors examine the overlap between the genome deletions characteristic of ID4 and those induced by the erroneous activity of a cellular enzyme, DNA topoisomerase 1 (TOP1), at specific genomic sites. #APaperADay

TOP1 is an evolutionarily conserved enzyme that untwists and relaxes the supercoiled DNA. It is a major source of transcription-associated mutagenesis and results in a distinctive transcription-dependent signature of 2–5 bp deletions at tandem repeat sequences. #APaperADay

They show that the deletion patterns seen in yeast are similar to the ‘indel signature 4’ (ID4) signature in cancer reported in the COSMIC database. The mutagenic activity of TOP1 is conserved in different cellular contexts, different disease states and organisms. #APaperADay

The authors establish a biological basis for the ID4 cancer signature, experimentally demonstrating that it occurs in RNase-H2-deficient cells both in vitro and in vivo. #APaperADay

They conclude that alongside its essential role in relieving DNA torsional stress, TOP1 also drives mutagenesis in somatic and germline contexts, relevant to neoplasia, inherited disease and human variation. #APaperADay

On his birth anniversary, I read this biographical essay on Ernst Haeckel in @CurrentBiology. Authors portray him as arguably the most influential champion of Darwin’s theory of evolution on the European continent and one of the most significant worldwide.cell.com/current-biolog…

Sharing some excerpts:
"Contemporary biology is not conceivable without terms coined by Haeckel, such as Metazoa, ‘phylogeny’, ‘ontogeny’, ‘monophyletic’, ‘polyphyletic’ or ‘ecology’. Moreover, his theories were admired by Darwin himself.". #APaperADay

Born today in 1834, he was a medical doctor by the age of 23. Three years later, impressed by Darwin’s 'On the Origin of Species' he received a second doctorate (in 1865). Haekel became one of the most influential advocates and popularizers of evolutionism. #APaperADay

Even though it was Darwin who formulated the first phylogenetic tree, it was in its abstract form. Haeckel for the first time conceived a detailed Darwinian phylogenetic tree as a diagram visualizing the hypothetic course of evolution as it could really have proceeded.#APaperADay

Haeckel contributed significantly to the deepening, widening and establishment of Darwinian theory. By the end of the 19th century, he was one of the most popular, if not the most popular of Darwin’s supporters worldwide. #APaperADay

#APaperADay article on the interactions between the DNA-binding domain (DBD) and ligand-binding domain (LBD) of the androgen receptor. Using a combination of in silico modeling and docking, authors point out a putative interface between AR-DBD and AR-LBD.
journals.asm.org/doi/10.1128/MC…

AR being Nuclear receptors is a transcription factors that contains a DBD composed of 2 zinc fingers and a LBD formed by 12 α helices. Authors investigate the residues at the surface of the AR-DBD and AR-LBD that might be involved in such DBD-LBD communications. #APaperADay

"Two mutations (R617P and L768A) affected the primary function of the receptor domain that they are situated in (DBD and LBD, respectively), thus explaining their inactivating effect on the receptor's function in the transactivation assay." #APaperADay

Three mutations that affect AR ligand binding are located at the surface of the DBD, again strongly suggesting DBD-LBD communications. In summary, they identified seven residues that are implicated in interdomain communications between the DBD and LBD of the AR. #APaperADay

The domains in the AR do not act independently but that optimal activation of transcription by the AR requires allosteric communications between different domains. #APaperADay

They discovered seven residues in the AR which we propose to be involved in a DBD-LBD interaction. These residues are most likely involved in direct intra- or intermolecular communications between the DBD and LBD of the AR. #APaperADay

@JCO_ASCO article on Immunotherapy in Metastatic breast cancer (mBrCa) in today's #APaperADay challenge. The authors in this study investigate the immunogenicity of somatic mutations in 42
patients with mBrCa.
ascopubs.org/doi/full/10.12…

In the clinical trial of 42 women with metastatic breast cancer, 28 (or 67%) generated an immune reaction against their cancer. The approach was used to treat six women, half of whom experienced measurable tumor shrinkage. #APaperADay

Researchers used whole-genome sequencing to identify mutations in tumor samples that progressed despite all other treatments. The data suggests that this form of immunotherapy can be used to treat some people with mBrCa who have exhausted all other treatment options. #APaperADay

Day 50 of the #APaperADay challenge and the birthday of @doudna_lab calls for an article from her team. In this review, they discuss the CRISPR–Cas regulatory biomolecules & strategies to enhance or inhibit CRISPR–Cas immunity.
Happy Birthday, Dr Doudna.🎂
nature.com/articles/s4158…

CRISPR–Cas systems aid adaptive immunity to bacterial & archaeal species against invading mobile genetic elements. This has been harnessed for research and clinical applications. Authors herein describe the regulatory and control mechanisms underlying CRISPR systems. #APaperADay

Accelerated article preview in today's #APaperADay challenge. Published in @Nature this article deals with the brain autoimmunity in multiple sclerosis (MS).
nature.com/articles/s4158…

"The authors analysed antibody-producing immune cells called B cells in blood samples from people with multiple sclerosis (MS) and identified antibodies that recognize small regions of protein (antigens) corresponding to proteins of the Epstein–Barr virus". #APaperADay

"Such antibodies also recognize the protein GlialCAM, which is a component of glial cells in the brain. This result indicates that GlialCAM can act as a target of these antibodies, providing an ‘autoantigen’ for self-directed autoimmunity." #APaperADay

Another @JCO_ASCO article in today's #APaperADay challenge. This review presents the details on circulating tumor DNA (ctDNA) minimal residual disease (MRD) detection in patients with non–small-cell lung cancer (NSCLC).
ascopubs.org/doi/full/10.12…

Liquid biopsy analyses bodily fluid for cancer detection. ctDNA is composed of tumor-derived mutations in plasma cell-free DNA (cfDNA) assists in the identification of alterations from plasma that guide treatment decisions in patients with metastatic NSCLC. #APaperADay

The authors comprehensively reviewed studies conducted in patients with NSCLC who underwent curative-intent treatment in which different ctDNA technologies were applied to detect MRD. #APaperADay

The ctDNA assays' sensitivity to predict disease relapse ranged from 36%-100% when restricting ctDNA MRD measurement to the initial post-treatment timepoint, but improved to 82%-100% when considering all available post-treatment follow-up timepoints. #APaperADay

ctDNA MRD (+) patients had significantly higher rates of disease relapse and worse survival outcomes compared with their ctDNA MRD (–) counterparts. It suggests that ctDNA MRD detection predicts disease relapse and is associated with worse outcomes. #APaperADay

Excellent read in @CR_AACR on Hypoxia-Inducible Factor-1 Activation Pathway Induction in HER2 Overexpressing Cells. It results in constitutively active Akt and turns on HIF-1α independently of hypoxia, which is weaker than hypoxic conditions. #APaperADay
aacrjournals.org/cancerres/arti…

They present that HER2-mediated VEGF expression under normoxic conditions could be almost totally blocked by dominant-negative Akt. Dominant-negative Akt also could partially block VEGF mRNA expression under hypoxic conditions by 20% to 50%. #APaperADay

HER2 up-regulates HIF-1α activity in the absence of hypoxic stimulation and that the activated HIF-1α protein and its activity can be repressed by the genetic and chemical inhibition of the PI-3K/Akt pathway. This however is less significant under hypoxic conditions. #APaperADay

Overall the data suggest that HER2-mediated phosphorylation of Akt contributes to HIF-mediated VEGF secretion and that by inhibiting HER2 or Akt phosphorylation, VEGF secretion and angiogenesis is inhibited. #APaperADay

The PI3K/Akt controls HIV-1 pathogenesis by regulating several molecular axes both at the cellular & viral levels. The activation of the PI3K/Akt pathway by viral proteins induces an increase in cell survival and an inhibition of the immune response to the infection. #APaperADay

The viral latency is characterised by the induction of transcriptional silencing of the viral genome. This is a major roadblock in HIV management. Akt is involved in cell survival, particularly of infected cells thus allowing the establishment of viral reservoirs. #APaperADay

The protein kinase B (Akt) is a key regulator of survival, metabolism, growth and proliferation and is targeted by HIV1. Phosphoinositide 3-kinase (PI3K) is the effector upstream of Akt and PI3K/Akt pathway is involved in the progression of HIV-1 pathogenesis. #APaperADay

The PI3K/Akt controls HIV-1 pathogenesis by regulating several molecular axes both at the cellular & viral levels. The activation of the PI3K/Akt pathway by viral proteins induces an increase in cell survival and an inhibition of the immune response to the infection. #APaperADay

Due to its critical role in HIV pathogenesis, targeting PI3K/Akt pathway could control HIV entry, viral latency/replication, cell survival of infected cells, cell-to-cell spread, & the immune microenvironment which could ultimately allow curtailing the HIV reservoir. #APaperADay

PI3K/Akt inhibitors have been developed as anticancer drugs. These drugs could be repurposed to counter HIV infection. These can help modulate the latency/reactivation of the virus and to complement the conventional “shock and kill” & “block and lock” strategies. #APaperADay

I read this @Nature article in today's #APaperADay. Authors in this paper using a trispecific antibody against HER2, CD3 and CD28 stimulate regression of breast cancers in a humanized mouse model.
nature.com/articles/s4158…

Despite the successes and a long history of HER2-targeted therapies for breast cancer, these are often associated with low response rates and drug resistance. These limitations warrant alternative therapeutic strategies. #APaperADay

The HER2/CD3×CD28 trispecific antibody stimulated T cell activation and proliferation through dual signalling of CD3 and CD28. The HER2 trispecific antibody stimulated T cell activation and provided a survival signal that induced T cell proliferation. #APaperADay

These activated T cells effectively lysed breast cancer cell lines that are clinically classified as HER2− in that they express low-to-medium levels of HER2. This is a potential benefit to the majority of patients who do not respond to current HER2-based therapies. #APaperADay

I am reading this #APaperADay article from Nature Chemical Biology. Published yesterday, this paper discusses deubiquitinase-targeting chimeras (DUBTACs) that stabilizes the levels of specific proteins degraded in a ubiquitin-dependent manner.
nature.com/articles/s4158…

Targeted protein stabilization (TPS) is necessitated for proteins undergone aberrant ubiquitination and degradation. Targeted protein degradation (TPD) tackles the undruggable proteome by targeting specific proteins for ubiquitination and proteasomal degradation. #APaperADay

There have been molecules to enable targeted ubiquitination, phosphorylation and dephosphorylation, but none for targeted deubiquitination and subsequent stabilization of proteins. Active ubiquitination have been root cause of various diseases including cancer.#APaperADay

They hypothesized that TPS could be enabled by a recruiter of a deubiquitinase linked to a protein-targeting ligand which would induce the deubiquitination & stabilization of proteins. Authors in this study introduce this heterobifunctional stabilizer a DUBTAC. #APaperADay

Enjoyed this NPJ Breast Cancer article in today's #APaperADay challenge. The authors analyse STimulator of INterferon Genes (STING) signaling pathway using an immunohistochemistry-based assay in ER+ and ER- Breast Cancer.
nature.com/articles/s4152…

ctDNA MRD (+) patients had significantly higher rates of disease relapse and worse survival outcomes compared with their ctDNA MRD (–) counterparts. It suggests that ctDNA MRD detection predicts disease relapse and is associated with worse outcomes. #APaperADay

Using a novel digital pathology approach assessing STING on IHC sections, and subsequently identifying a gene signature, authors validated their finding of poor prognosis in pnSTINGlow ER + breast cancer in both chemotherapy and hormone therapy treated tumors. #APaperADay

Interestingly, while there was an observed connection between pnSTING and immune infiltration in ER + BrCa, this was not the case in ER- disease. Measuring pnSTING may be able to add granularity to the activation state of the immune infiltrate in ER + disease. #APaperADay

Using a novel digital pathology IHC-based approach, they have identified tumors with high intrinsic STING activation. With the identification of immune infiltration, this may identify tumors which respond favorably to immune checkpoint blockade and/or STING agonists. #APaperADay

Today's #APaperADay article quantifies uptake of a fluorescent glucose analog 2-NBDG in a large panel of breast cancer cells and demonstrates potential to monitor changes in glycolysis caused by anticancer and endocrine therapies.
link.springer.com/article/10.100…

Functional imaging of glucose uptake has been valuable in breast cancer therapeutics. Glycolysis is commonly measured with fluoro-deoxyglucose (FDG) in PET. These techniques are, however, expensive, manually intensive, and/or technologically complex. #APaperADay

The authors use confocal microscopy to image the fluorescence signal from 2-NBDG, western blot analysis to quantify GLUT 1 and HK I proteins, various treatments to analyse the study. #APaperADay

The results showed that 2-NBDG accumulation in breast cell lines occurs in cells that express GLUT 1 regardless of receptor status. All breast cancer cells demonstrated the ability to uptake 2-NBDG albeit with variations in overall uptake. #APaperADay

2-NBDG uptake is a simple method to monitor changes in glycolysis and effectiveness of therapy. 2-NBDG can be further implemented in animal models to monitor the effects of drugs that affect glycolysis over time in vivo. #APaperADay

@PLOSPathogens article in today's #APaperADay challenge. Authors in this In this review discuss the emerging SARS-CoV-2 variants; the structural basis for antibody-mediated neutralization & nAb classification; & identification of the RBD escape mutations.
journals.plos.org/plospathogens/…

The structural analyses of SARS-CoV-2 spike protein, variants, in complex with numerous mAbs provide a comprehensive map of nAb epitopes on the spike protein. However, these analyses do not directly measure how/which mutations will escape from antibody binding. #APaperADay

Comprehensive knowledge of immunodominant epitopes on the spike protein and escape mutations would aid efforts to understand viral evolution and rational design of antibody therapeutics, vaccines, and other countermeasures. #APaperADay

Antibodies isolated from the early COVID-19 phase had a relatively low somatic mutations. Later studies reveal that these antibodies show affinity maturation by somatic hypermutation, which empower them for increased binding affinity and neutralization of SARS-CoV-2. #APaperADay

vaccine-induced immunity will continue to protect against currently circulating SARS-CoV-2 variants. With continued evolution of SARS-CoV-2, worldwide genomic surveillance, better vaccination drive, development of bnAbs, and new drugs are vital to combat COVID-19. #APaperADay

@NatureComms article in today's #APaperADay. Authors
show a strategy for improving lead compounds for Mdm2 and MdmX inhibition. Overexpressed Mdm2 and its homolog MdmX impair p53 activity cancers. Small molecules mimicking a p53 peptide can effectively inhibit Mdm2 but not MdmX.

Protein–protein interactions are fundamental mechanisms of cellular signaling pathways but present a challenge to drug design. The inhibitors of Mdm2 targeting N-Mdm2 are the successful cases of the transformation of peptide modulators into small molecules. #APaperADay

They determined crystal structures of MdmX in complex with nutlin-3a. Nutlin-3a docks into the N-MdmX-binding pocket in the appropriate orientation to p53p, as it does in N-Mdm2, suggesting that Mdm2 inhibitors are excellent “drug leads” for affinity optimization. #APaperADay

Their work demonstrated a general strategy to aid the transformation of peptide modulators into small molecules for drug design targeting aberrant protein–protein interactions. #APaperADay

I am reading this @TheLancetInfDis paper in today's #APaperADay challenge. Older adults are prioritised for COVID-19 vaccination owing to advanced age being a key risk factor for morbidity and mortality associated with SARS-CoV-2 infection.
thelancet.com/journals/lanin…

The omicron variant shows substantial resistance to vaccine-induced serum neutralising activity and hence is of particular concern. Authors determined SARS-CoV-2-neutralising serum activity in a prospective cohort of 37 individuals with a median age of 82 years. #APaperADay

In the absence of omicron variant-specific vaccines, booster immunisations are crucial to restore vaccine effectiveness against severe outcomes. They found that booster immunisations can elicit omicron variant-neutralising activity in the majority of aged individuals. #APaperADay

@NatureBiotech news feature in today's #APaperADay. This article discusses Protective encapsulating devices and gene-editing technologies that could obviate the need for antirejection drugs in stem-cell-derived therapies for diabetes.
nature.com/articles/s4158…

In late 1990s, researchers showed that pancreatic islet cells recovered from deceased donors could help patients with T1D live an insulin-free existence. A limited number of donor pancreases are available, however, and those organs are often of variable quality. #APaperADay

So clinicians have long sought an alternative source of tissue for transplantation — hence the focus on stem cell differentiation protocols geared toward producing near-limitless quantities of insulin-producing beta cells. #APaperADay

Meanwhile, as efforts around gene editing grow, many companies continue to tinker with encapsulation technologies, including several startups pitching new platforms intended to solve some of the design problems that have dogged commercial efforts in the past. #APaperADay

An interesting visual guide of the p53 protein in today’s #APaperADay challenge. This article gives a concise summary of most studied gene with over more than 10000 citations.

nature.com/articles/d4158…

@GenesDev article in today’s #APaperADay challenge. The authors in this paper using expression profiling of an immortalized human prostate epithelial cell line, HPr-1AR, identified 205 novel androgen-responsive genes (ARGs). @CSHLPress genesdev.cshlp.org/content/21/16/…

Today is an important day for scientific publishing. The first truly scientific journal, Philosophical Transactions of the @royalsociety was published today on March 6, 1665. I am reading a relevant article today. #APaperADay.
royalsocietypublishing.org/doi/10.1098/rs…
📷@Wikimedia/@royalsociety

On 6 March 1665, the first issue of Philosophical Transactions was published under the visionary editorship of Henry Oldenburg who was also the first Secretary of the Society. Since its inception, it attracted a diverse range of correspondence. #APaperADay

The journal has witnessed considerable changed in past 357 years. At the outset, the journal focused on the latest scientific discoveries and development, now it invites commentary to outline the significance of the latest developments in line with its glorious past. #APaperADay

I am reviewing this classic article by Prof David Baltimore on his Birthday. In this @Nature June 1970 issue, he reports the discovery of RNA dependent DNA polymerase (Reverse Transcriptase) from RNA tumor viruses (R-MLV & RSV). #APaperADay
Happy Birthday!
nature.com/articles/22612…

The experiments indicate the DNA polymerase nature in the viruses. However, the inhibition of its activity by ribonucleases suggests that the enzyme is an RNA dependent DNA polymerase. It also implies that all RNA tumor viruses should have this activity. #APaperADay

This along with Howard Temin's independent discovery of reverse transcriptase shook the foundation of the central dogma of molecular biology. Interestingly both articles were published in the same @Nature issue back to back.
Here is a thread. #APaperADay

https://twitter.com/imtryam/status/1217105137899950082?s=20&t=mbRHqGUvnZjeeFDJgMnJmg

@CCR_AACR article by @WagleLab in today's #APaperADay challenge. In this excellent work, the authors using WES report somatic alterations in three genes (PIK3CA, GATA3, and ARID1A) at different frequencies in young versus older women with luminal A BrCa.
aacrjournals.org/clincancerres/…

~4% BrCa is diagnosed in women < 40 yo with unfavorable clinicopathological features. Authors performed whole-exome seq of tumor & germline samples from a cohort of ≤35 yo. Compared this genomic landscape with the older women from TCGA in a subtype-specific manner. #APaperADay

The SNV and indels comparison between young and aged women among the same histological subtypes was made. PIK3CA alterations were significantly enriched in older women whereas GATA3 and ARID1A alterations were significantly more common in younger women. #APaperADay

The literature demonstrates that younger women with luminal A tumors experience worse breast cancer outcomes. The presence of PIK3CA mutation correlates with improved long-term outcomes in early-stage breast cancer. This is in accordance with the data presented. #APaperADay

Lower GATA3 expression and alterations in ARID1A correlate with a worse prognosis. The increased GATA3 in younger patients could possibly explain some of the less favorable outcomes. ARID1A alterations in young women with luminal A is consistent with the literature. #APaperADay

In today's #APaperADay article, I go through the @Annals_Oncology review by Prof De Bono et al. Authors summarize a decade of PARP inhibitor clinical development that has resulted in the registration of several PARP inhibitors in breast and ovarian cancer.
annalsofoncology.org/article/S0923-…

Originally developed as radio and chemo-sensitizing drug, PARPi targets PARPs which are DNA damage and DNA breaks repair enzyme. Several PARPi in clinical development have different potencies as PARP1 catalytic inhibitors and as PARP-‘trappers’. #APaperADay

In addition, PARP1 also binds directly to DNA to act as transcription factor and regulate chromatin structure remodelling. It has also raised interest in breast and ovarian cancers with expansion to other biomarker-driven indications expected in the near future. #APaperADay

@NatureRevCancer article in today's #APaperADay challenge. In this review, the authors discuss the distinctive features of senescent cancer cells and how these changes in cellular physiology might be exploited for the selective eradication of these cells.
nature.com/articles/s4156…

Combination therapies have been used clinically that can forestall resistance development. However, the efficacy of drug combinations is limited by toxicity. Sequential drug treatment regimens are hailed in order to combat drug-associated toxicity. #APaperADay

Senescence-inducing therapies can be combined with senolytic treatments. Pro-senescence therapy is well suited for use in a sequential treatment regimen. Such drugs should show selectivity for cancer cells over normal cells as inducing senescence in normal tissues. #APaperADay

The authors conclude with "key advantages of senescence-based therapies, such as sequential treatment opportunities and attraction of immune cells by senescent cells, warrant further investigation of this approach." #APaperADay

An illustrious article on the discovery of reverse transcriptase in today's #APaperADay. Published in @MBoCjournal this article recollects the simultaneous discovery in 1970 of RT in virions of retroviruses by Howard Temin & David Baltimore.
molbiolcell.org/doi/10.1091/mb…

Historically molecular biologists believed in two things.
1. What’s true for E coli is true for the elephant.
2. “the Central Dogma,” can not be reversed.
#APaperADay

Temin joined the Dulbecco lab as a graduate student in 1956. Through his work, he could sense transient genetic information in the RNA genome of the virus being converted into DNA as a permanent part of the infected cell genome. Thus was born the idea of the provirus. #APaperADay

Baltimore, an Associate Professor at MIT, was already a very well-known and highly regarded virologist, who had devoted most of his career to that point to the study of poliovirus replication and had made numerous fundamental contributions to the subject. #APaperADay

Temin presented his work at the 10th International Cancer Congress (May 22–29, 1970). Upon his return, he would receive a call from Baltimore, who informed Temin that he had obtained exactly the same result and, worse, had already submitted his paper to Nature.#APaperADay

The good news was that Nature was willing to hold the Baltimore paper for a short time to wait for Temin’s. He and Mizutani rushed to get theirs finished and air mailed to England, where it arrived June 15, and the two papers appeared back to back June 27. #APaperADay

The scientific impact of this work was immediate, even before publication. RT turned out to be one of the key tools that enabled modern molecular biology. In addition to basic virology, there was also an immediate effect on the U.S. cancer research program. #APaperADay

Article on Fine-Needle Aspiration Cytology (FNAC) in Breast Cancer in today's #APaperADay. Authored by my co-supervisors in @WorldJSurg this paper hails FNAC as a reliable diagnosing tool in suspicious breast lesions with good sensitivity. @mathuraiims
link.springer.com/article/10.100…

FNAC and core needle biopsy (CNB) assist in the pathological assessment of BrCa. FNAC is preferred since it is relatively less painful for a quick diagnosis. CNB is favored as it preserves tissue architecture, guides in pathological subtype, grade, & receptor status. #APaperADay

In developing countries like India, performing an expensive and painful test like CNB for routine diagnosis is unwarranted. Through this study, the authors analyzed the usefulness of FNAC as a primary tool in diagnosing malignancy and guiding lumpectomy. #APaperADay

698 patients were included in this study who underwent FNAC at @aiims_newdelhi between 1993-2014. FNAC diagnosed malignancy in 627 patients, inconclusive in 69 & false -ve in 2 pt.
Absolute sensitivity: 89.8%
Complete sensitivity: 99.7%
Positive predictive value: 100%
#APaperADay

They conclude FNAC as a reliable tool for diagnosing cancer in suspicious breast lesions with a good sensitivity and PPV in hands of an experienced cytopathologist. A non-diagnostic FNAC invites further diagnostic tests like CNB/excisional biopsy. #APaperADay

Today's #APaperADay article on recently FDA approved adjuvant olaparib for the treatment of BRCA-mutated, HER2-negative breast cancer. Published in @NEJM, it presents the findings of phase 3, double-blind, RCT with a primary end point of invasive DFS.
nejm.org/doi/full/10.10…

Adjuvant olaparib post local treatment and or with (neo)adjuvent chemotherapy in patients with high-risk, HER2-negative early breast cancer and germline BRCA1/BRCA2 variants induced significantly longer survival free of invasive or distant disease than in placebo. #APaperADay

Today's paper is a biographical review of Paul Ehrlich, born today in 1854, and his contributions to the Foundation and Birth of Translational Medicine. He worked in the diverse fields of hematology, immunology & chemotherapy. #APaperADay
Happy Birthday!
karger.com/Article/Fullte…

His work laid the foundation and birth of not only modern hematology and immunology, but also the development of chemotherapy and specific targeted treatment concepts. Such a myriad of scientific works. #APaperADay

📷: @KargerPublisher

@Oncotarget article on by @FredSanter et al in today's #APaperADay. The authors in this paper analyze MCL1, a known mediator of chemotherapy resistance. They report higher mRNA and protein expression of MCL1 in cancerous tissue compared to benign ones.
oncotarget.com/article/3368/t…

Despite the initial relief from Androgen deprivation therapy (ADT), patients succumb to a more aggressive phenotype termed castration-resistant PCa (CRPCa). To improve the efficacy of ADT, combination therapies are warranted. #APaperADay

The authors through this paper demonstrate that high expression of MCL1; a pro-survival member of the BCL2 family, promotes the survival of steroid-deprived and cell cycle-arrested PCa cells. #APaperADay

MCL1 has a pro-survival role to protect cells. Authors report that MCL1 is also protecting against the cell death-inducing effects of endocrine therapy. Targeting MCL1 along with apoptosis induction in PCa could prevent/delay the development of castration resistance. #APaperADay

Research briefing from @NatureBiotech in today's #APaperADay challenge. This paper describes the application of synthetic introns that express therapeutic proteins selectively in cells bearing cancer-initiating mutations, barring healthy cells.
nature.com/articles/s4158…

Spliceosomal mutations that affect RNA splicing factors are common in malignancies with poor prognosis & have limited treatment. Currently, there are no therapeutics specifically targeting the protumorigenic, altered splicing activity caused by spliceosomal mutations. #APaperADay

Authors engineered synthetic introns that would be selectively recognized by mutant splicing factors. These synthetic introns inserted into an open reading frame of mutant, but not wild-type, would selectively express therapeutic proteins in cancer cells. #APaperADay

Using this approach of splicing engineered synthetic introns in SF3B1-mutant, authors report killing of SF3B1-mutant leukemia, breast cancer, and uveal melanoma cells while leaving wild-type, healthy cells unharmed. #APaperADay

This study provides a roadmap for harnessing disease-associated mis-splicing for therapeutic benefit and can be extended to other common cancer-associated mutations affecting RNA splicing factors. #APaperADay

An excellent review on the use of ctDNA as a biomarker for detection of molecular residual disease (MRD) in today's #APaperADay challenge. It also highlights the potential impact that ctDNA testing could have on the conduct of clinical trials.
ascopubs.org/doi/full/10.12…

The literature search data indicate that ctDNA-based MRD detection predicts recurrence with high sensitivity and specificity, and with lead times that precede standard imaging by up to 12 months. #APaperADay

@Nature Research round-up on Ageing in today's #APaperADay. This article sums up nicely on the frailty measures, microbial ‘fountains of youth’, screening for social isolation, and other highlights from studies into ageing.

nature.com/articles/d4158…

Day 78 of #APaperADay. I read this @NatureComms article on RNA diversification. Authors performed long-term evolution experiments of RNA that replicates using a self-encoded RNA replicase. The results further support the Darwinian evolution.
nature.com/articles/s4146…

The results demonstrate an evolutionary transition of molecular replicators from a single common ancestor to a multi-membered network. During long-term replication, a clonal host RNA population gradually diversified into multiple host and parasitic RNA lineages. #APaperADay

In today's #APaperADay, I am reading this @EndoCancer article on AR splice variants in prostate cancer. AR-Vs produced by alternative splicing play a role in castration-resistance in PCa. The authors in this thematic review discuss the current findings.
erc.bioscientifica.com/view/journals/…

Over 20 AR-Vs have been identified in PCa cells & tissues. Some are constitutively active. Except for AR-45, all contain an intact NTD, an intact DBD and truncated (all or some) LBD. The hinge region coded by parts of exon 3-4 contains the nuclear localization signal. #APaperADay

AR-Vs arise from genomic rearrangement or by the involvement of specific splicing factors. mechanisms governing AR-V production could be cell-context specific and may involve more layers of regulation beyond splicing factors. #APaperADay

Clinical studies showed an association between AR-V expression and PCa progression, therapy resistance, and poor clinical outcome. Higher AR-V7 in hormone-naïve PCa correlates with increased risk of recurrence after radical prostatectomy and rapid progression to CRPC. #APaperADay

Further investigations of the mechanisms of how AR-Vs are activated to regulate downstream genes and crosstalk with other signaling pathways will continue to benefit the search for more effective therapeutic approaches and targets. #APaperADay

@NatureComms article in today's #APaperADay. Authors in this paper report identification of a peptidoglycan hydrolase in the vibrioid-shaped predatory bacterium Bdellovibrio bacteriovorus which invades replicates within the periplasm of Gram-ve bacteria.
nature.com/articles/s4146…

Today's #APaperADay article from @AdvSciNews. Authors in this excellent piece demonstrate that SPHK1 colocalizes and associates with Extracellular Vesicles (EV) proteins, facilitating the extracellular production of S1P.
onlinelibrary.wiley.com/doi/10.1002/ad…

Checkpoint immunotherapy trials such as programmed cell death protein-1/programmed death ligand-1 (PD-1/PD-L1) inhibitor therapy seemed promising for ovarian cancer patients at the beginning of their treatments. However, these show fairly low response rates. #APaperADay

S1P is synthesized when sphingosine kinase-1 (SPHK1) phosphorylates sphingosine. SPHK1/S1P signaling is linked to cancer progression and metastasis, as it modulates many oncogenic events, such as proliferation, migration, invasion, adhesion, angiogenesis, & apoptosis. #APaperADay

They demonstrated that
1. EVs-SPHK1 (SPHK1-packaged EVs) induce immune suppression in ovarian cancer
2. Targeting SPHK1 with a specific inhibitor, in combination with anti-PD-1 therapy enhanced immune activation in ovarian cancer patients, thereby improving survival. #APaperADay

@JournalofExper1 article in today's #APaperADay challenge. Authors in this study conclude that HSP27 assists the AR in regulating the malignant behavior of molecular apocrine breast cancer (MABC), & these findings might be helpful in the treatment of MABC.
jeccr.biomedcentral.com/articles/10.11…

AR is chaperoned with heat shock proteins (HSP) in the absence of ligands. HSP27 is one such oligomer that regulates multiple cellular survival & signaling pathways. They analyze the location of the AR & HSP27, and its effects on the tumorigenic capacity of MABC cells #APaperADay

The results showed that HSP27 phosphorylation induced by androgen played a vital role in the process of AR translocation from the cytoplasm to the nucleus, which could affect the proliferation of tumor cells and tumorigenic capacity. #APaperADay

Inflammatory signaling in BRCA1/2-mutant cancers is today's #APaperADay article. An excellent paper by @eileen_parkes in @trendscancer dealing on the genomic instability triggered inflammatory signaling and therapeutic activation of the immune system. sciencedirect.com/science/articl…

Genomic instability a hallmark of cancer varies significantly between tumors. This is more in cases of somatic mutations in DNA repair genes, in particular, defective repair of double-stranded DNA breaks (DSBs) and in Breast cancer 1 (BRCA1) & Breast cancer 2 (BRCA2). #APaperADay

Loss-of-function mutations in BRCA1/2, and in other HR genes, leads to a defect in genome maintenance. The authors review Inflammatory signaling as a consequence of genomic instability in BRCA1/2-mutant cancers. #APaperADay

The BRCA1/2 mutational spectrum is further complexed by site-specific TME. The new insights into the immune-evading mechanisms assisted with evolving techniques of immune phenotyping of tumors may enable combinatorial approaches for improvements in patient outcomes. #APaperADay

I read this article in @Cells_MDPI in today's #APaperADay challenge. The androgen receptor splice variant 7 (ARV7) is known to induce resistance against AR targetted therapies. Authors describe highly sensitive and specific qPCR-based assay to detect ARV7.
mdpi.com/2073-4409/8/9/…

Prostate cancer (PCa) burdens men tremendously. Screening tissue biopsies are invasive and can be associated with adverse effects. Liquid biopsies [circulating tumor cells (CTCs)] and circulating nucleic acids from blood samples have gained remarkable attention. #APaperADay

Multiple studies indicate that ARV7 mRNA & protein expression in CTCs is associated with resistance towards novel hormone therapies. ARV7 expressing patients benefit more from taxane-based therapy. The authors develop a protocol for ARV7 detection from CTC from PBMC. #APaperADay

After a few commercial antibodies against ARV7 could not get the Immunocytochemical staining, authors subsequently aimed at establishing a qPCR-based approach to detect ARV7 on an mRNA level. This would act as an alternative to protein-based detection of ARV7. #APaperADay

Their novel approach ensures the specific detection of ARV7 transcripts in CTCs. The specificity of the assay ensured no signals for ARV7 or K19 from 9 blood samples from healthy, males. Their protocol works in 7.5 mL of blood even after 24 h of storage. #APaperADay

An interesting article on blood sucking behaviour of vampire bats in today's #APaperADay. Published in @ScienceAdvances this paper attempts to elucidate genomic changes associated with this dietary adaptation.
science.org/doi/10.1126/sc…

Vampire bats are the only mammals feeding exclusively on blood. They performed a genome-wide screen for genes that are specifically lost in the vampire bat lineage. #APaperADay

This screen revealed 10 previously unknown gene losses that are likely associated with derived phenotypic features of vampire bats, such as reduced insulin secretion (FFAR1 and SLC30A8) and glycogen synthesis (PPP1R3E) and a distinct gastric physiology (CTSE). #APaperADay

In summary, this study provides novel insights into the genomic changes related to adaptations to sanguivory and the evolutionary importance of gene loss in general. It also highlights the need to characterize the phenotypic side of adaptations to their unique diet. #APaperADay

Today's #APaperADay aricle on Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) promoted tumor cell survival in response to therapeutic intervention. Authors report NRF2 disruption leads to collateral damage in the form of CRISPR-mediated exon skipping.
nature.com/articles/s4143…

I am revisiting a @PNASNews classic from the legendary Prof Linus Pauling. In this article Pauling, Corey, & Branson resolve the mystery behind the structure of proteins. A delightful read in today's #APaperADay on the alpha-helical structure of proteins.
pnas.org/doi/full/10.10…

Using interatomic distances, bond angles, and other configurational parameters they constructed two reasonable hydrogen-bonded helical configurations for the polypeptide chain. Dr Pauling got a @NobelPrize in Chemistry in 1954. (later in 1962 Nobel Peace Prize). #APaperADay

Authors in this paper presents SHOOT. SHOOT is a software tool for rapidly searching a phylogenetically partitioned and structured database of biological sequences. This is comparable to BLAST. Good read in today's #APaperADay.
genomebiology.biomedcentral.com/articles/10.11…

A very interesting report in today's #APaperADay. This article assesses the patient-specific changes in the expression of estrogen- and progesterone-regulated genes (ERGs and PRGs) and proliferation-associated genes (PAGs) during the menstrual cycle.
nature.com/articles/s4152…

Authors hypothesised that with consistent differences in ERGs and PAGs expression in ER+ breast tumours in premenopausal women due to the variations in plasma conc of E2 and Pg during the menstrual cycle, the absence of such change could signify hormone insensitivity. #APaperADay

In this study, patients were drawn from two prospective studies. Three pre-defined menstrual cycle windows: W1 (days 27–35 and 1–6; low E2 and low Pg), W2 (days 7–16; high E2 and low Pg) and W3 (days 17–26; intermediate E2 and high Pg) were assigned for the study. #APaperADay

Unsupervised clustering of the gene expression data from all samples showed that most pairs clustered together indicating that the changes in gene expression during the menstrual cycle were not as great as the variation between patients in the majority of cases. #APaperADay

Nonetheless, the clustering revealed contrasting clusters enriched for tumours taken in W2 and W3 indicating the timing of the menstrual cycle had some effect on the clustering. #APaperADay

Thus, in the absence of a functional oestrogen-activated ER complex, PgR activation can stimulate proliferation but when oestrogen and a progestogen are combined, reductions in the oestrogen-induced growth response have been reported both in vitro and ex vivo. #APaperADay

In conclusion, the data indicate that there are significant changes in ERG, PRG and PAG expression in line with the hormone changes that occur during the menstrual cycle. This needs to be noted in hormone-related studies of breast cancer in premenopausal patients. #APaperADay

I read today's #APaperADay article from @MobDNAjournal. This manuscript attempts to fill this gap by providing a set of detailed computer protocols, software recommendations & video tutorials for those aiming to manually curate transposable elements (TEs).
mobilednajournal.biomedcentral.com/articles/10.11…

@Cancers_MDPI paper in today's #APaperADay. Authors report from AR & AR-V7 immunohistochemical staining on a tissue microarray on 410 PCa patients that AR-V7 is an independent prognostic factor for relapse-free survival (RFS) in PCa patients.
mdpi.com/2072-6694/12/9…

PCa is dependent on AR signaling and hence androgen deprivation therapies (ADT) are the standard care for locally advanced or metastatic disease. This, however, leads to castration-resistant PCa (CRPC) or its metastatic form (mCRPC). #APaperADay

From Immunohistochemistry AR was detected in the nucleus and cytoplasm, whereas AR-V7 expression was observed in the cytoplasm (cytoplasmic) or in distinct granular structures in the cytoplasm (granular), but only occasionally in the nucleus. #APaperADay

AR staining in the nucleus or in the cytoplasm and AR-V7 staining in both the cytoplasm and the cytoplasmic granules were not associated with OS, DSS, or RFS. However, positive AR-V7 staining in the cytoplasm was a negative prognostic marker for RFS. #APaperADay

They suggest that, in addition to nuclear AR-V7 protein staining, cytoplasmic AR-V7 protein staining should be included in further analyses to characterize its prognostic ability for PCa patients. Interesting to note Golgi localization of AR-V7 that had increased RFS. #APaperADay

Today's article in #APaperADay is from @JoVEJournal on proteomics workflow for identifying protein interaction partners. This includes subcellular fractionation, IP, filter aided sample preparation, offline cleanup, MS, and a bioinformatics pipeline.
jove.com/t/60432/label-…

Today's #APaperADay article is from @SciReports on the generation of suspension culture technique for cancer organoids. Authors report that these cancer organoids are genetically & phenotypically similar to their counterparts grown in standard conditions.
nature.com/articles/s4159…

Organoids are a three-dimensional long-term cell culture model grown in an extracellular matrix. In the cancer setting, patient-derived tumour organoid cultures are valuable preclinical tools that complement existing models such as 2D cell lines and mouse models. #APaperADay

The authors have developed a culture methodology that increases the efficiency of growing organoid cultures while retaining genomic and phenotypic stability. This provides a robust alternative technique for cost-effective and easier expansion of organoids #APaperADay

@JEndocrinology article in today's #APaperADay. This paper reports that membrane-initiated ERα (mERα) signalling can modulate Selective estrogen receptor modulators (SERMs) responses in a tissue-specific manner. joe.bioscientifica.com/view/journals/…

SERMs act as estrogen receptor (ER) agonists in some tissues, and as antagonists in others. SERMs are mainly used to prevent and treat osteoporosis & BrCa and alleviate postmenopausal symptoms, but also to maintain a beneficial lipid profile in postmenopausal women. #APaperADay

In this study, E2 treatment resulted in an increase in uterus weight in C451A mice. However, this E2 effect in mice was significantly attenuated compared to the control mice, indicating that a normal E2 response on uterus weight is dependent on mERα signalling. #APaperADay

Google reminds me that today is the birthday of Prof Venki Ramakrishnan; a hero of mine. On this occasion, I read this biographical note on him. His is the story of grit, determination, and hard work. Happy Birthday Prof Venki.
#APaperADay
nobelprize.org/prizes/chemist…

@TheEndoSociety minireview on the role of Androgen Receptor in breast tissues in today's #APaperADay. This article discusses AR induced distinct gene expression programs and opposing proliferative response in luminal type vs molecular apocrine BrCa.
academic.oup.com/mend/article/2…

The authors propose that there exists an optimal range of relative AR and ERα expression that allows ERα signaling to stimulate, and AR signaling to suppress normal and malignant breast epithelial cell proliferation. #APaperADay

In the event that estrogen action is reduced or nullified, either via loss of ERα or under conditions of long-term estrogen deprivation, AR levels increase, coregulatory interactions change, and AR becomes a surrogate ERα to sustain tumor growth. #APaperADay

At a certain level of AR expression, breast cancer cells may adopt a phenotype similar to prostate cancer cells in which AR exerts oncogenic rather than tumor suppressor activity. These insights may assist in a more personalized way to approach hormone therapy. #APaperADay

Today's article in #APaperADay challenge is from classic @jbiolchem. Published in January 2022, this paper shows that ALKBH1 promotes adipogenic differentiation of hMSCs and 3T3-L1 cells, leading to excessive accumulation of adipose in mice.
jbc.org/article/S0021-…

Mesenchymal stem cells (MSCs) differentiate into different types of somatic cells. Altered pathology shifts osteogenesis to adipogenesis, resulting in various metabolic disorders. The connection between DNA methylations and pluripotency MSCs remains unclear. #APaperADay

ALKBH1, a 2-oxoglutarate and Fe2+-dependent hydroxylase mediates the demethylation of mRNA, tRNA, and methylated lysine of histone H2A. The authors report that ALKBH1 demethylates DNA N6-adenine methylation (6mA) of HIF-1α and GYS1 to augment HIF-1 pathway activation. #APaperADay

Results:
1. ALKBH1 is more expressed in mature adipocytes and is upregulated during adipogenic differentiation
2. siRNA knockdown of ALKBH1 inhibits adipogenic differentiation in vitro
3. ALKBH1 overexpression promotes adipogenesis
4. ALKBH1 regulates the HIF1 pathway
#APaperADay

Depletion of Alkbh1 increased the 6mA level in whole genomic DNA, while overexpression of ALKBH1 reduced 6mA modifications in 3T3-L1 cells. Simultaneous overexpression of HIF-1α and GYS1 restores the adipogenic differentiation of Alkbh1-deficient cells. #APaperADay

An interesting article in today's #APaperADay on cardiovascular disease (CVD) and mortality risk in women with breast cancer. Published in @JCO_ASCO, this paper reports increased incidence and mortality associated with CVD in women with BrCa.
ascopubs.org/doi/full/10.12…

Today's #APaperADay article discusses whole genome sequencing (WGS) practice recommendations for the interpretation and reporting. This includes discussion of challenges and emerging approaches to harness the full potential of this comprehensive test.
nature.com/articles/s4152…

Day 100 of #APaperADay challenge. Today I am reading @NatureComms paper on functional mapping of HIV-host interactions. This study identified 86 candidate HIV host factors in primary CD4+ T cells, 47 of which were validated in follow-up assays.
nature.com/articles/s4146…

This functional map of HIV host factors in primary cells provides several leads for future functional interrogation and will hopefully open the door to additional therapeutics that physically antagonize virus–host protein–protein interactions. #APaperADay

@eLife article in today's #APaperADay on ‘cryptic’ exons. Certain exons can be included or excluded when splicing together the mature mRNA. Known as alternative splicing, this mechanism allows a single gene to code for two or more proteins.
elifesciences.org/articles/00476

@SciReports articles from departmental colleagues in today's #APaperADay challenge. They demonstrate the involvement of transcription factor NFκB (RelA) in transcriptional up-regulation of human Heterogeneous Ribonucleoprotein D (hnRNPD) in oral cancer.
nature.com/articles/s4159…

hnRNPD is an ARE (AU-Rich Element) binding protein that regulates the stability of mRNA encoded by genes involved in tumorigenesis, cell cycle, senescence, proliferation and apoptosis. Its overexpression is reported in several cancers including OSCC. #APaperADay

The authors aim to elucidate the molecular mechanism of hnRNPD over-expression in OSCC. They cloned full length human hnRNPD promoter and mapped its transcription start site followed by promoter deletion analysis, site-directed mutagenesis and ChIP assays. #APaperADay

They cloned a 1663 bp 5ʹ upstream region of hnRNPD gene. By nucleotide sequence analysis, they identified a TATA box, CAAT box and multiple GC boxes in hnRNPD promoter. #APaperADay

Deletion of hnRNPD promoter and SDM of NFκB (RelA) binding motif present in this region resulted in a decrease in promoter activity. Treatment of oral cancer cells by PDTC, a known NFκB inhibitor resulted in a reduction in transcript and protein level of hnRNPD. #APaperADay

Results of the present study suggest that anti-inflammatory agents could be used to downregulate hnRNPD over-expression and hence improve the disease out come in OSCC. #APaperADay

@NatureGenet paper in today's #APaperADay challenge. Using single-cell whole-genome sequencing of proximal bronchial basal cells from 33 participants they report an increase in the frequency of single-nucleotide variants and small insertions and deletions.
nature.com/articles/s4158…

Today's #APaperADay article is from @JCO_ASCO. This paper reports the findings of a phase III trial combining the 21-gene expression assay and response to 3-week preoperative endocrine therapy (ET) to guide systemic therapy in early breast cancer.
ascopubs.org/doi/full/10.12…

In luminal early breast cancer, which patients need chemotherapy in addition to endocrine therapy is still questionable in clinical practice. This trial combines a gene expression assay and response to 3-week preoperative ET to guide systemic therapy in early BrCa. #APaperADay

In patients with regional lymph node status 0-1, HER+ HER– early breast cancer, 5-year invasive disease-free survival was 92.6% with recurrence score (RS) 12-25 and endocrine response (experimental arm) versus 93.9% with RS 0-11 (control arm) without CT. #APaperADay

5-Year distant disease-free survival was 95.6% versus 96.3%, and 5-year overall survival 97.3% versus 98.0%, respectively; differences were similar in age and nodal subgroups. #APaperADay

@FrontCellDevBio article in PARP inhibitors in today's #APaperADay challenge. The authors in this review discuss the recent advances in the mechanisms of action of PARPi, biomarkers of the tumor response to PARPi, and clinical advances in PARPi therapy.
frontiersin.org/articles/10.33…

Chemotherapeutic regimens remain the gold standard in the treatment of several cancer types. It, however, is associated with several side effects. Targeted therapies are often favoured due to improved patient outcomes and fewer off-target side effects. #APaperADay

PARP Poly (ADP-ribose) polymerases are involved in several cellular processes. PARP inhibitors (PARPi) are a novel class of anti-cancer therapies that have shown to be effective in the treatment of homologous recombination repair (HR) deficient tumors. #APaperADay

There are several proposed mechanisms of action by which PARP inhibitors induce their anti-cancer activities. These include
Inhibiting SSB Repair,
Replication Fork Stalling,
Activation of the NHEJ Repair Pathway,
Disrupted Processing of Okazaki Fragments.
#APaperADay

PARPi therapy leads to resistance. Combination therapies minimize dosage requirements and increase drug efficiency. These include Alkylating Agents, Topoisomerase I, PI3k and WEE1 Kinase Inhibitors. It is also complemented with radiation and immunotherapies. #APaperADay

PARP inhibitors have shown promising results in both clinical trials and practice for the treatment of ovarian, breast, prostate and pancreatic cancers. There are currently 286 clinical trials registered on clinicaltrials.gov investigating PARPi therapies. #APaperADay

Today’s #APaperADay article is a biographical note of Dr Greider in @PNASNews. This piece summarises her work on telomeres, independent investigator profile and continued passion for science.

pnas.org/doi/full/10.10…

https://twitter.com/NobelPrize/status/1515028443880169472

Good study on internal mammary node irradiation (IMNI) in patients with node-positive early BrCa. This paper reports decreased the risk of distant recurrence and death by IMNI in a 15-year follow-up, thereby improving long-term overall survival.#APaperADay
ascopubs.org/doi/abs/10.120…

This is a paper I was looking forward to reading in #APaperADay series. The authors in this article have analysed the transcriptomic approaches of 3 commercially available RNA-Seq library preparation kits. For short reads, they report TruSeq having edge.
bmcgenomics.biomedcentral.com/articles/10.11…

This paper with an interesting title illustrates comparative metatranscriptomics of microorganisms encountering increasing microbial complexity for understanding community signal integration, antibiotic responses, & interspecies communication. #APaperADay
journals.asm.org/doi/10.1128/mb…

This is an illustrious article on face mask usage and relevant considerations. Published in @PNASNews, it presents an interdisciplinary narrative review of the literature on the role of masks in reducing COVID-19 transmission in the community. #APaperADay
pnas.org/doi/full/10.10…

In the absence of strong direct evidence from RCT, systematic review or metaanalysis, the authors assess:
Direct epidemiological evidence,
Reviews and RCTs of mask use for other respiratory illnesses,
Population wise and ecological studies.
#APaperADay

This analysis offers evidence in favor of widespread mask use as source control to reduce community transmission. The near-universal adoption of nonmedical masks in public along with complementary public health measures, could successfully reduce community spread. #APaperADay

Today's #APaperADay article is a protocol of co-immunoprecipitation for the analysis of protein interactome. The authors segregate the protocol as:
1. Extraction of protein
2. Generation of beads and antibody coupling
3. Co-IP
4. LC-MS/MS
Troubleshooting.
star-protocols.cell.com/protocols/1489

In today's #APaperADay, I read a classic from Köhler and Milstein where they describe the production of monoclonal antibodies. They could create clones of continuously dividing cells to make antibodies of known specificity.
nature.com/articles/25649…

By the fusion of an antibody-producing cell from an immunized mouse with an immortal cancer cell specialized for antibody secretion, they created a continuously growing cell line. This could yield mAb of the desired specificity. #APaperADay

This study in @ScienceMagazine performed whole-genome sequences of more than 12,000 cancer patients. The researchers could identify 58 new mutational signatures, suggesting some additional causes of cancer that we don't yet fully understand. #APaperADay
science.org/doi/10.1126/sc…

#APaperADay article on the feasibility of a postoperative monitoring program consisting of patient-reported outcomes and a wearable device for women undergoing gynecologic cancer surgery. It is found to be feasible with a good wear time and response rates.
ascopubs.org/doi/abs/10.120…

@natu article in today's #APaperADay. Authors using single-cell genome sequencing, show that people with Alzheimer's have a lot of newly acquired mutations in their neurons (that can disable genes vital to brain function) compared to people w/o Alzheimers.
nature.com/articles/s4158…

Today's #APaperADay article is a mini-review on the role of folate receptor α in cancer. Published in @IntJCanc this review summarizes the folate's role in cancer, compares folate transport systems and tissue distributions of the FR isoforms.
onlinelibrary.wiley.com/doi/10.1002/ij…

Out of three isoforms, FRα, FRβ, and FRγ; FRα is the most widely studied FR isoform. It is highly expressed in tumors of epithelial origin and is associated with decreased survival. The authors also comment on the complex nature of FOLR1 gene regulation & expression. #APaperADay

Today's article in #APaperADay on Curcumin. p53Y220C, one of the most frequently observed mutations in p53 is rescued by naturally occurring curcumin. It also restores the function and structure of mutant p53 to wild-type and activate apoptotic pathways.
sciencedirect.com/science/articl…

An interesting @FrontGenetics article in today's #APaperADay. Authors propose optimal pairs of traditionally used reference genes (RGs) for 12 cancer types and identified novel promising RGs with high expression stability, reliability and convenience.
frontiersin.org/articles/10.33…

They analyzed TCGA transcriptome sequencing data to evaluate the expression stability of widely used RGs and identify novel RG candidates in 12 most common cancer types. RNA-Seq data of TCGA project offer a great opportunity for evaluating gene expression stability. #APaperADay

The alterations of mRNA level were shown for a number of these genes, including the most frequently used GAPDH, in examined cancer types. The analysis across 12 cancer types revealed that PUM1 and IPO8 genes demonstrate the most stable expression among the 32 genes. #APaperADay

@jbiolchem article on prostate cancer. The authors explain that targeting metastasis suppressor NDRG1 using the clinically trialed anticancer agent DpC inhibited Wnt/TnC-mediated interactions between PC cells and the surrounding pancreatic stellate cells.
jbc.org/article/S0021-…

Day 120 of #APaperADay. I am reading @FrontEndocrinol paper on Androgens associated mobility and invasion through the control of actin remodeling in T47D breast cancer cells.
frontiersin.org/articles/10.33…

Steroid hormones are the major modulators of BrCa development and progression. Androgen Receptor is expressed in 70 to 90% of invasive BrCa. Androgens are shown to be involved in signaling cascades linked to actin cytoskeleton remodeling, cell motility, and invasion. #APaperADay

The authors studied whether androgens with different characteristics, such as testosterone (T), dihydrotestosterone (DHT), and DHEA may regulate breast cancer cell motility and invasion through the control of actin remodeling. #APaperADay

They report that in T47D cells androgens:
1. Induce rapid cytoskeletal rearrangements
2. Activate the Actin-Regulatory Protein, Moesin
3. Enhance cell migration and invasion through Moesin activation through ERα and AR
#APaperADay

The main finding of this study is through the modulation of the actin-binding protein, Moesin, androgens alter the architecture of the cytoskeleton in T47D breast cancer cells and promote cell migration and invasion. #APaperADay

Science immunology paper in today's #APaperADay challenge. The authors report a receptor-blocking human monoclonal antibody, 87G7, that retains potent in vitro neutralizing activity against conserved ACE2 of SARS-CoV-2 variants of concerns the Omicron.
science.org/doi/full/10.11…

The human monoclonal antibody 87G7 potently neutralizes Omicron and other SARS-CoV-2 variants. 87G7 protects mice and hamsters from challenges with D614G SARS-CoV-2 and Alpha, Beta, Gamma or Delta variants. #APaperADay

The antigenic evolution of SARS-CoV-2 causes a substantial reduction of neutralizing activity from vaccines. The 87G7 antibody is ACE2-blocking mAb that retains potent neutralization against SARS-CoV-2 VOCs since it targets highly conserved sites on the spike protein. #APaperADay

Authors in this @SciReports article proposed a bioinformatic approach for accurate massive characterisation of gene datasets. They sequence cytochrome c oxidase subunit 1 and the 12S rRNA of vector-borne helminths (VBHs) infesting canids. #APaperADay
nature.com/articles/s4159…

This @jitcancer article explores the role of T cells as a marker of risk for cancer among HIV-infected virally suppressed patients. The peripheral T cell alterations may serve as a biomarker of increased cancer risk among people living with HIV.#APaperADay
jitc.bmj.com/content/10/4/e…

Today in #APaperADay challenge, I am reading this @FrontEndocrinol review on emerging therapeutic approaches in Prostate Cancer. The authors in this paper discuss the recent findings on the diagnostic and clinical management of prostate cancer.
frontiersin.org/articles/10.33…

I read a fascinating article on artificially motorized sperm cells in today's #APaperADay challenge. Published in @NanoLetters this paper reports a hybrid micromotor that transports sperm cells towards the egg mimicking physiological conditions.
pubs.acs.org/doi/pdf/10.102…

The authors in this paper aim to determine treatment-related changes in the circulating metabolome in patients with metastatic colorectal cancer to avoid cumulative toxicities. This can be harnessed in the early assessment of treatment efficacy.#APaperADay
oncotarget.com/article/28165/…

Unfortunate to miss the deadline. But better late than never. Midnight I read this article in #APaperADay on Adiponectin receptor requirement in haematopoietic cells to promote haematopoietic stem cells (HSCs) quiescence and self-renewal.
nature.com/articles/s4155…

@NatureComms article in today's #APaperADay article. Authors show that RNA residents rarely dissociate on their own. They propose that sRNA diversity creates many pairwise interactions with Hfq that allow for distinct biological outcomes.
nature.com/articles/s4146…

@biorxivpreprint in today's #APaperADay on the structural basis of HIV maturation inhibitors (MI). MI disrupt ordered proteolytic processing of the viral Gag polyprotein into its individual domains. Bevirimat (BVM) is a MI that stabilizes the CA-SP1 region
biorxiv.org/content/10.110…

The authors presented MAS-NMR structures of the CA-SP1 lattice in complex with IP6, in the presence/absence of BVM. This adds up the information on BVM-resistance mechanisms and suggests new strategies for the design of more-potent next-generation MIs. #APaperADay

@PNASNews article in today's #APaperADay. The authors describe a mechanism of opposing antagonist and agonist AR regulation determined uniquely by enantiomeric forms of the same drug structure. This would be crucial in overcoming AR drug resistance.
pnas.org/doi/10.1073/pn…

@NatureComms article on GPCRs in today's #APaperADay. Authors investigate 557 GPCR structures to characterize allosteric pockets in GPCRs that have come into the focus as potential binding sites for synthetic modulators.
nature.com/articles/s4146…

An excellent review of Preeclampsia in @NEJM in today's #APaperADay. The authors review the current understanding of preeclampsia with a focus on prediction, prevention, diagnosis, and management of preeclampsia during pregnancy and in the long term.
nejm.org/doi/full/10.10…

@ASCO educational book on ageing and cancer in #APaperADay. The authors discuss the application of innovative digital technologies to improve the care of older patients with cancer beyond academic centres.
ascopubs.org/doi/full/10.12…

RNA-based gene therapy. The authors describe the growing number of RNA therapeutic classes, their molecular mechanisms of action, and the design considerations for their respective delivery platforms. @NatureRevGenet paper in today's #APaperADay.
nature.com/articles/s4157…

Researchers identified genetically engineered mice that are accurately recreated clinical outcomes from human trials. Similarly expanding our understanding of the RNA drug, drug delivery system, and body could benefit patients from effective next-gen gene therapies. #APaperADay

Authors in this @NatureComms paper report the cryo-EM structures of human GLUT4 bound to inhibitor cytochalasin B. This methods for cryo-EM analysis of GLUT4 will also facilitate structural determination of other small size solute carriers. #APaperADay
nature.com/articles/s4146…

@CellCellPress review on Atherosclerosis in today's #APaperADay challenge. The authors present the current understanding of the molecular, cellular, genetic, & environmental contributions to atherosclerosis; the most common form of cardiovascular disease.
cell.com/cell/fulltext/…

On his birth anniversary, I am reading a tribute article on the history of smallpox and vaccination. Dr Edward Jenner born OTD in 1749 is known as the Father of Immunology and rescued the world from deadly smallpox. Great article for today's #APaperADay.
tandfonline.com/doi/abs/10.108…

@jitcancer article in today's #APaperADay challenge. To curb the catastrophe of ovarian cancer, the authors target Mesothelin (MSLN) as a candidate immunotherapy target. This is a great article to utilize classical immunology to fight against cancer.

jitc.bmj.com/content/10/3/e…

Today's #APaperADay article is on TRPM8 modulators as potential anticancer agents in castration-resistant prostate cancer. Authors have designed TRPM8 antagonists that significantly inhibit the growth induced by androgen in various PC cells & CRPC models.
sciencedirect.com/science/articl…

An interesting review in today's #APaperADay on the role of microfluidics to investigate cancer cell migration. 3D matrix-based microfluidic models will allow cell interactions, migration, and dynamic aspects of tumor progression.
cell.com/trends/cancer/…

@SciReports article on single-cell analysis using minimal invasion in today's #APaperADay challenge. The authors report a combinatorial method of mechanical and biochemical treatment for the retrieval of individual adherent cells from cell cultures.
nature.com/articles/srep0…

Using this method, gene transcription levels were analyzed in both harvested and on-chip directly-lysed single cells. The results conclude that the harvesting method they developed and optimized can preserve the RNA profiles in the cells retrieved from microwells. #APaperADay

@NatRevMCB article in today's #APaperADay. The authors present the current understanding of how phosphoinositides shape and direct membrane dynamics to impact on cell physiology, and provide an overview of emerging concepts in phosphoinositide regulation.
nature.com/articles/s4158…

@emboreports article on the legacy of Carl Linnaeus in today's #APaperADay. This is a tributary piece to the man who named, almost everything. Born in 1707 OTD, Dr Carl Linnaeus was tasked with the taxonomic classification and naming of the natural world.
embopress.org/doi/full/10.10…

This article mentions scientists/philosophers prior to Linnaeus who attempted to classify various life forms. Aristotle (384–322 BC), Theophrastus (373–288 BC), Pliny the Elder (23–79 BC) worked in BC to bring order to the living systems. #APaperADay

Systema Naturae (1735, on animals kingdom) and Species Plantarum (1753, for plants) were revolutionary publications by Linnaeus where he systematically standardised the nomenclature. God's organiser’s contributions to free life from chaos remain relevant for eternity. #APaperADay

@CD_AACR review on Metastasis-Initiating cells (MIC) in today's #APaperADay. The authors present the recent advances and the nature of MICs. This will be critical for developing strategies to improve the prevention and treatment of advanced cancer.
aacrjournals.org/cancerdiscover…

This excellent review discusses metastasis, dissemination, CTC, & metastatic dormancy & outbreak. It also sheds light on the mechanisms by which metastatic tumors emerge & develop as phenotypically distinct, therapy-resistant entities in comparison with primary tumors.#APaperADay

On today's #APaperADay challenge, I read this review on mouse models to study breast cancer metastasis. Besides this, the authors report how mice model experimentation can open new avenues to the development of innovative cancer therapy.
…ast-cancer-research.biomedcentral.com/articles/10.11…

@JCOGO_ASCO article in today's #APaperADay. HIV+ve BrCa patients have worse overall survival. This study assesses the pCR and RDI in such cohorts. Administration of optimal chemotherapeutic drugs with ART should be carefully integrated to improve OS.
ascopubs.org/doi/full/10.12…

NPJ Breast Cancer article in today's #APaperADay. Authors report that replication stress is predominantly observed in TNBC. Cyclin E overexpression may be used as a biomarker for clinical evaluation of drugs that target the DNA replication stress response.
nature.com/articles/s4152…

This study examined the relation between oncogene expression and replication stress marker expression in breast cancer subgroups. The varying replication stress and oncogene expression levels have the highest expression in the TNBC and HER2+ BrCa subgroups. #APaperADay

The findings indicate that among breast cancer subgroups, TNBCs and ER/PR−HER2+ tumors are characterized by overexpression of the c-Myc and Cyclin E oncogenes, and by higher expression levels of replication stress markers. #APaperADay

@TheBreastOnline article in today's #APaperADay. The authors validated the prognostic role of urokinase-type plasminogen-activator (uPA) and plasminogen activator inhibitor type-1 in endocrine-responsive early-stage breast cancers from postmenopausal women
thebreastonline.com/article/S0960-…

uPA is an extracellular matrix-degrading protease having a key role in tumor invasion and metastasis in several cancers. Along with its inhibitor, PAI-1, it interacts with ECM proteins and TM receptors to modulate migration, cell-matrix interactions, and signaling. #APaperADay

uPA and PAI-1 are established biomarkers for long-term outcomes in BrCa. uPA+ tumors demonstrated significantly shorter DRFS and worse OS. This study provides level 1b evidence for the prognostic role of stromal uPA in women with endocrine-responsive early BrCa. #APaperADay

Review on Gene therapy in today's #APaperADay. Published in @FrontOncology this article discusses the popular viral vectors used in gene therapy and its kinds, drugs under clinical trials, advances, challenges, perspectives and the way forward.
frontiersin.org/articles/10.33…

Day 150 of #APaperADay. I read @JournalCompBio article on DNA alignment. This paper introduces a greedy alignment algorithm that computes the exact alignment 10 times faster on appropriate data. This algorithm is currently used in an MSA at the @NCBI.
liebertpub.com/doi/10.1089/10…

@NatureComms article authored by a senior in today's #APaperADay. They report that SERINC5, a cellular multipass transmembrane protein inhibits SARSCoV2 entry by blocking virus-cell fusion. This antiviral effect is countered by the ORF7a accessory protein.
nature.com/articles/s4146…

Results:
1. SERINC genes are expressed in pneumocytes and their expression pattern remains unaffected by SARS-CoV-2 infection and type I IFN.
2. SERINC proteins (particularly SERINC5) are incorporated into the SARS-CoV-2 virus and restrict SARS-CoV-2 S-mediated entry.
#APaperADay

3. SERINC5 restricts SARS-CoV-2 entry of different Spike variants
4. SERINC5 blocks SARS-CoV-2 entry by targeting virus-cell membrane fusion
5. ORF7a transmembrane domain is responsible for counteracting SERINC5 restriction of SARS-CoV-2 entry.
#APaperADay

They conclude that "the antiviral effect of SERINC5 on a diverse number of viruses and the presence of SERINC5 viral antagonists demonstrate that its interplay with viral proteins is an attractive target for the development of antiviral therapies." #APaperADay

A landmark @ScienceMagazine article on the first complete sequence of a human genome, telomere-to-telomere, T2T-CHM13 assembly. This consortium presents a complete 3.055 billion base pair sequence of the human genome. A giant leap in genomics. #APaperADay
science.org/doi/10.1126/sc…

Some key moments:
1990: The launch of the Human Genome Project
2001: Publication of the first draft
2004: First reference genome
2013: Release of the current human reference genome by the Genome Reference Consortium (GRC)
2019: patched update; GRCh38.p13.

@JCVenter #APaperADay

The T2T consortium applied the shotgun sequencing approach to facilitate gap-free chromosome assemblies, even in the difficult repetitive regions of the genome. The T2T-CHM13 includes gapless assemblies for all chromosomes except Y, owing to its haploid nature. #APaperADay

#APaperADay article from @CellPressNews on cancer immunotherapy. It reports synthetic receptor proteins called SNIPRs that are humanized & customizable for the programming of therapeutic cells suitable for clinical translation. This will aid CAR T therapy.
cell.com/cell/fulltext/…

@NatImmunol paper dealing with SARS-CoV-2 variants of concern (VOCs) in today's #APaperADay. Authors present a large panel of human broadly neutralizing antibodies to neutralize a diversity of sarbecoviruses and including the Omicron variant.
nature.com/articles/s4159…

Today's #APaperADay article is from @BCRJournal. The authors in this paper attempt to elucidate the role of AR in preclinical models of ER-positive and negative breast cancer. The anti-AR therapy can be initiated in AR+ve tumors regardless of ER status.
…ast-cancer-research.biomedcentral.com/articles/10.11…

@Cancer_Cell review in today's #APaperADay. The authors describe the pathogenic mechanisms shared throughout microbial niches that contribute to the initiation and progression of cancer. They focus on the microbiome & its molecular interaction with cancer.
cell.com/cancer-cell/fu…

@NEJM article on targeting HER2 low expressing breast carcinoma in today's #APaperADay. Authors report from this phase III RCT that trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the standard therapy.
nejm.org/doi/pdf/10.105…

Cancer Medicine review in today's #APaperADay. The authors discuss the key factors that contribute to the persistence of HPV and cervical carcinogenesis, emerging new concepts and technologies for cancer interventions and clinical precision medicine.
onlinelibrary.wiley.com/doi/10.1002/ca…

This article underscores integrating emerging concepts and technologies with the molecular approaches based on HPV profiling that may be translated into precision medicine. #APaperADay

Today is the birthday of one of the tallest pillars of molecular biology, Dr Francis Crick. In this @PNASNews article in 1954, Dr Crick reviews the then advances in the structure of DNA by his contemporaries. Here is a funny anecdote he shares
#APaperADay
pnas.org/doi/epdf/10.10…

Today's #APaperADay article is on a new method of staining proteins in polyacrylamide gel. Interestingly, this method, as described utilizes deionized water and chloroform to stain and visualise gels in less than 6 minutes.
ojs.ptbioch.edu.pl/index.php/abp/…

The authors stained PAG after the run with 0.5% chloroform containing deionized water for 1, 3, and 5 minutes. Gel images were taken in a UV transilluminator after the UV exposure of 1 to 5 minutes followed by image processing and analysis. #APaperADay

They show staining results somewhat better that the classic coomassie blue staining. The chloroform staining depends on the reaction with tryptophan residues. This highly sensitive method requires >6 mins of procedure with without making much changes to PAGE. #APaperADay

Very proud of @iSakshiShukla to have published in @LancetRH_SEAsia. The consortium assessed the infection and reinfection density in health care workers along with vaccine effectiveness against symptomatic infection within omicron transmission. #APaperADay
sciencedirect.com/science/articl…

The paper reports that almost 1/5 of HCWs were infected with SARS CoV-2 during the omicron transmission period, with a predominant mild spectrum of COVID-19. The vaccine effectiveness during the omicron transmission period was found to be 52⋅5% within 14-60 days. #APaperADay

Today's #APaperADay article is from colleagues at AIIMS. They determine the frequency of common copy number alterations and their association with survival in T-ALL patients. The observed molecular heterogeneity may help in risk stratification in such pt.
onlinelibrary.wiley.com/doi/full/10.10…

@IntJCanc article on the expression of AR in circulating tumor cells in today's #APaperADay. Concluding from the AR expression profiles from CTC, FFPE, and tumors, the authors report that AR can be determined in RNA from CTC for AR inhibiting agents.
onlinelibrary.wiley.com/doi/10.1002/ij…

This study determines the AR status of CTCs at the mRNA level in patients with mBC. It assessed whether the AR status differed across the different breast cancer subtypes and determined the discrepancy in AR status between matched primary tumors and CTC samples. #APaperADay

This study showed that AR expression can be detected in 31% of the CTC samples of mBC patients, providing the opportunity to measure the AR status in patients in a minimal invasive way right before the start of a new line of therapy. #APaperADay

In conclusion, AR expression can be detected in CTCs, albeit less prevalent than in the corresponding primary tumors. Establishing the AR status of CTCs will be a valuable, minimally invasive tool, to select mBC patients who may benefit from AR-targeting agents. #APaperADay

A relevant article on synonymous mutations and their effect in today's #APaperADay challenge. In yeast cells, both (syn/non-syn) mutation types reduce the amount of mRNA produced from a gene compared with the amount produced from the original DNA sequence.
nature.com/articles/s4158…

Today's #APaperADay article is on the clinical relevance of DARC/ACKR1 tumor expression in breast cancer. They report that DARC regulates immune responses in tumors, and its expression is associated with sub-Saharan African-specific alleles. @CEBP_AACR
aacrjournals.org/cebp/article/2…

@Cancer_Cell paper in today's #APaperADay. Authors create alternative breast cancer subtypes incorporating tumor biology beyond clinical hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status to better predict drug responses. cell.com/cancer-cell/fu…

Today's #APaperADay article is from @EUplatinum on the development of AR-V7 detection assay in tumour tissue. The authors report significantly higher nuclear AR-V7 expression in CRPC than in HSPC. Lower AR-V7 is associated with longer OS.
@mathuraiims
sciencedirect.com/science/articl…

The primary objective of this study was analytical validation and clinical qualification of a new antibody to the cryptic exon of AR-V7. This AR-V7 IHC assay is best utilised in conjunction with an AR-NTD antibody to rule out false positives. #APaperADay

They observed a significant increase in nuclear AR-V7 protein levels from HSPC to CRPC. This study highlights that AR-V7 protein expression is a biomarker of poorer prognosis and increases with emerging drug resistance. #APaperADay

The present study demonstrates a significant trend towards poorer outcome among patients with increased AR-V7 protein expression and points to an association between AR-V7 expression and poor prognosis. #APaperADay

Authors in this @Nature paper present a framework to examine the patterns of copy number alterations in human cancer that is widely applicable to a wide range of data. This leads to the global landscape of copy number alterations in cancer. #APaperADay nature.com/articles/s4158…

Authors in this @NatureBiotech paper report the development of qPCR assays for SARS-CoV-2 specific T cell activation. Based on the quantification of CXCL10 mRNA, these are rapid, internally normalized & probe-based to quantify cellular immunity.#APaperADay
nature.com/articles/s4158…

@iScience_CP article in today's #APaperADay challenge. Authors have mapped dynamics across HIV-Env trimers from diverse isolates. This shows that the epitope order of HIV-Env as an antigenic target by broadly neutralizing antibodies varies significantly.
sciencedirect.com/science/articl…

Article on the effect of GC-content on the efficiency of RNA interference in @BMCBioinfo. The authors investigate the mechanistic interpretation of the effect of GC-content on RNAi efficiency. #APaperADay
bmcbioinformatics.biomedcentral.com/articles/10.11…

This article concludes that target site accessibility is more critical than GC content with the highest and significant correlation. There is also an appreciable negative correlation between GC-content and RNAi activity, albeit non-significant. #APaperADay

@NatureComms commentary in today's #APaperADay that proposes a Global Forum on Synthetic Biology. This can establish the preeminent mechanism for global policy-practitioner engagement in the age of engineering biology.
nature.com/articles/s4146…

This Global Forum can guide the co-creation of the scientific and technical language for global policy discussions and collaborate with the existing communities in order to earn trust and trustworthiness. #APaperADay

@CD_AACR perspective in today's #APaperADay challenge. This article discusses the ways to overcome drug resistance associated with experimental cancer drugs and how innovative treatment regimens can help mitigate this challenge.
aacrjournals.org/cancerdiscover…

@CR_AACR article on the constitutively active Androgen Receptor variant in Prostate Cancer. This study aims to understand the mechanism by which AR isoforms regulate the androgen refractory phenotype of 22Rv1 (Androgen refractory PCa) cells. #APaperADay
aacrjournals.org/cancerres/arti…

Androgen ablation initially results in a favourable clinical response but ultimately manifests into a resistant form. Previous studies have shown that the AR NTD may play a major role in mediating PCa therapy resistance. #APaperADay

The data in this study shows for the first time that naturally occurring AR isoforms, consisting of the NTD and DBD, can support the expression of many endogenous AR target genes, as well as the growth of androgen-refractory PCa cells in the absence of androgens. #APaperADay

To conclude, the data indicate that AR truncation, resulting from aberrant splicing of a novel AR exon 2b, uncouples androgen signaling from AR activity. #APaperADay

Day 175 of the #APaperADay. I read @NatureChemistry paper on building synthetic cytoskeletons. Authors demonstrate functional DNA-based cytoskeletons that can be rationally designed and controlled to imitate features of natural cytoskeletons.
nature.com/articles/s4155…

In today's #APaperADay challenge I am reading the @oncogenejournal article on AR splicing in Prostate Cancer cells. The authors in this paper discuss the molecular mechanism by which the AR splice variant, AR-V7 is generated.
nature.com/articles/onc20…

AR-V7 is the most commonly expressed ARV in human tissues. Its levels are correlated with an increased risk of biochemical relapse and shorter survival time for CRPC patients. The authors studied the molecular mechanisms by which AR-V7 is alternatively spliced. #APaperADay

They report that:
1. AR and AR-V7 mRNA levels are increased in response to androgen deprivation
2. AR-V7 expression is important for VCaP cell proliferation under ADT conditions
3. AR-V7 RNA splicing is coupled with AR gene transcription
#APaperADay

This study demonstrates that AR gene transcription rates and splicing factor recruitment to AR pre-mRNA near the AR-V7 3′ss contribute to AR-V7 splicing. This article provides new insights into the complexity of AR gene splicing during the CRPC progression of PCa. #APaperADay

@JCO_ASCO special article on @ASCO guidelines for endocrine therapy for hormone receptor +ve metastatic BrCa in today's #APaperADay. Barring immediately life-threatening disease, hormone therapy, alone/in combination, should be used as initial treatment.
ascopubs.org/doi/10.1200/JC…

@ModernPathology article on the prevalence of AR-V7 in clinical breast cancer. This study involving a large cohort of 196 patients shows comparatively high prevalence of AR-V7 in TNBC subtypes and in metastatic/recurrent patients. #APaperADay
nature.com/articles/s4137…

A delightful read in today's #APaperADay on the treatment of Breast Cancer by Dr George Beatson. Published in 1896, this article discovers that bilateral oophorectomy improved Breast Cancer outcomes. This pioneered hormone therapy targeting ER/PR in BrCa.
ncbi.nlm.nih.gov/pmc/articles/P…

An interesting @Nature article in today's #APaperADay challenge. The authors observe that in both patients with breast cancer and mouse models the most spontaneous circulating tumour cells (CTC) intravasation events occur during sleep.
nature.com/articles/s4158…

The notion is that CTCs are constantly generated from invasive cancerous tissues, or following mechanical cues such as surgery or physical activity. However, the factors that regulate spontaneous CTC intravasation in physiological settings are poorly understood. #APaperADay

Authors report that in both patients with breast cancer and mouse models, the generation of CTCs is highly restricted to the rest phase. The rest-phase CTCs are endowed with a much greater metastatic proclivity compared to active-phase CTCs. #APaperADay

This augmented metastatic ability is conferred by high proliferation rates that occur in a time-dependent manner, and it is influenced by the action of circadian-rhythm-regulated hormones. #APaperADay

Clinical review of endocrine treatment in Prostate Cancer in today's #APaperADay. Authors discuss the androgenic effects on tumor growth and ADT. PCa becomes resistant to ADT and relapses with aggressive features of CRPC, a primary cause of PCa mortality.
academic.oup.com/jcem/article-a…

@PNASNews article in today's #APaperADay challenge. This paper shows that Ten-eleven translocation (TET) proteins are pivotal epigenetic suppressors of β-adrenergic receptor (β-AR) in adipocytes.

pnas.org/doi/10.1073/pn…

The methylated product 5 methylcytosine gets oxidized by three Ten-eleven translocations (TET1, TET2 and TET3) enzymes to 5 hydroxymethylcytosine. TET proteins in fact catalyze a series of oxidation steps which ultimately demethylate the 5mC back to Cytosine. #APaperADay

β-adrenergic receptor (β-AR) signaling plays predominant role in modulating energy expenditure and confers obesity resistance. Obesity is associated with diminished β3-adrenergic receptor (β3-AR) expression and decreased β-adrenergic responses. #APaperADay

Chapter article in Semaphorins in today's #APaperADay challenge. Semaphorins are diverse family of secreted, cell surface-attached and membrane-bound proteins with essential roles in the development and function of many different physiological systems.
ncbi.nlm.nih.gov/pmc/articles/P…

Semas act as signaling ligands that regulate the shape and motility of cells during the development and operation of the nervous, cardiovascular, immune, renal systems among many. It has also been linked to diseases affecting these systems and to cancer progression. #APaperADay

@ScienceMagazine article on mutational shifting in the SARS-CoV-2 receptor-binding domain. The paper sheds light on the extensive evolutionary remodeling in the RBD & provides large-scale sequence-function maps that may play out for SARS-CoV-2. #APaperADay
science.org/doi/10.1126/sc…

NPJ Breast Cancer review on today's #APaperADay challenge. This article discusses the role of AR in various cellular processes that promote tumorigenesis and metastasis as well as the ongoing efforts to target AR targetted therapies, in particular BrCa.
nature.com/articles/s4152…

Today's #APaperADay article is on the role of TRPM8 in BrCa aggressiveness. The overexpression of TRPM8 in cancer cells & tissue might influence metastasis by regulating the EMT phenotype. This can be inducted as a diagnostic marker in the clinical setup.
link.springer.com/article/10.100…

@Cells_MDPI article on the association of AR with Filamin A (FlnA) in today's #APaperADay. FlnA interacts with AR to modulate its nuclear translocation and transcriptional activity. It is imperative to look for druggable targets in PCa. mdpi.com/2073-4409/11/1…

Authors have derived stapled peptide, Rh-2025u from AR. This Rh-2025 peptide could overcome the resistance to the 2nd generation inhibitors, by interfering with the downstream signaling of AR/FlnA complex. #APaperADay

@Nature article in today's #APaperADay challenge. Diffuse large B cell lymphoma (DLBCL) is major non-Hodgkin lymphoma with unexplored non coding region. The authors show hypermutated super-enhancers in individuals with DLBCL linked to proto-oncogenes.
nature.com/articles/s4158…

@Cells_MDPI feature review in today's #APaperADay. This article summarises the recent findings on the epigenetic changes that arise during aging and potential intervention strategies that target epigenetic mechanisms to extend a healthy life span.
mdpi.com/2073-4409/11/3…

Authors in this @NatureComms paper show that induction of lipolysis is required for the regulation by β-adrenergic signals. It generates l metabolic signals that exert profound pleiotropic effects on the function of cultured brown adipocytes. #APaperADay
nature.com/articles/s4146…

Day 191 of #APaperADay challenge and I read this @PLOSONE paper on the upregulation of Mesenchymal markers in PCa cells due to AR splice variants. It shows that N-cadherin is upregulated in LNCaP cells expressing AR-Vs, not in cells overexpressing AR-fl.
journals.plos.org/plosone/articl…

The data suggest that constitutively active AR variants signaling could be a mechanism leading to N-cadherin expression in CRPC. It also shows that AR variants were associated with an increased expression of mesenchymal markers such as VIMENTIN, SNAIL, and ZEB1. #APaperADay

These findings support the hypothesis that the AR variants could contribute to the overexpression of N-cadherin and other mesenchymal markers in PCa, and the systemic dissemination of PCa cells, reinforcing the importance of targeting these AR variants in PCa. #APaperADay

@BMCBioinfo article in today's #APaperADay. The authors have developed an intuitive software: getSequenceInfo to obtain genomic sequences and associated data from public repositories in a relatively simple way with a compatibility for different OS.
bmcbioinformatics.biomedcentral.com/articles/10.11…

In today's #APaperADay, I am reading this article on the interaction between EDAR/EDARADD in ectodermal development. The mutant EDAR suppressed the downstream activity induced by wild-type EDAR and reduced interaction between the WT EDAR and EDARADD.
onlinelibrary.wiley.com/doi/abs/10.111…

@PNASNews article in #APaperADay on a novel mechanism where transposable elements generate adaptive phenotypes. Authors identify a polymorphic TE insertion that reduces viral titers in Drosophila and enables it to escape the harmful effects of infection.
pnas.org/doi/10.1073/pn…

An excellent review on targetting AR in TNBC in today's #APaperADay. This review discusses the role of AR in AR +ve TNBC (LAR) with a better prognosis, less chemotherapy responsiveness, and lower pathologic complete response after neoadjuvant treatment.
sciencedirect.com/science/articl…

@jbiolchem article on the molecular virology of coronavirus infection in today's #APaperADay. Aided with great illustrations, authors highlight aspects of viral life cycle that may be amenable to antiviral targeting as well as key features of its biology.
sciencedirect.com/science/articl…

Today's #APaperADay article is from my dear friend @abhinay62328935 in @FrontOncology. They have studied serum proteins involved in the progression of Metastatic Breast Cancer (MBC) to establish a panel of blood-based diagnostic and prognostic biomarkers.
frontiersin.org/articles/10.33…

This further encourages the panel of proteins (LOX5, Rac1, Rac1b, p38α, phospho-p38α, LIMK1, phospho-LIMK1 (T508), cofilin1, & phospho-cofilin1 (S3)) that can serve as novel blood based non-invasive and cost-effective markers for early detection and prognosis of MBC. #APaperADay

Today's #APaperADay article is a review on the Circulating Tumor Cells (CTCs) in the early detection of cancer. The authors discuss liquid biopsy and how CTCs can be employed as potential biomarkers along with their clinical values in several cancers.
ijbs.com/v18p3251.htm

@NAR_Open article in today's #APaperADay introduces cancer3d.org; an open and user-friendly way to analyze cancer missense mutations in the context of structures of proteins they are found in and in relation to patients’ clinical data.
academic.oup.com/nar/article/47…

The Cancer3D database allows users to analyze patterns of distribution of cancer mutations in the context of their three-dimensional structures integrated with information on clinical correlates of such patterns. #APaperADay

I am reading a preprint in today's #APaperADay. Shared in @biorxivpreprint, this article sheds light on the expression of inhibitory receptors across the CD8+ T-cell landscape. It also proposes TIGIT as a target for precision immunotherapies in PLWH.
biorxiv.org/content/10.110…

@NEJM phase 3 trial report in today's #APaperADay challenge. Involving patients with HER2-low metastatic BrCa, this trial reports that trastuzumab deruxtecan (T-Dxd) results in significantly longer PFS and OS than the physician’s choice of chemotherapy.
nejm.org/doi/10.1056/NE…

T-DXd is infused into a vein as an antibody–drug conjugate consisting of a monoclonal Ab (T, trastuzumab) linked to a chemotherapy drug, deruxtecan. T transports chemotherapy payload (Dxd) directly to tumor cells having HER2 where Dxd ultimately kills the cells. #APaperADay

@JCO_ASCO article in today's #APaperADay. The authors discuss the potential of liquid biopsies to have an impact on treatment decisions and outcomes for patients with CRPC. They highlight the PROPHECY trial evidencing towards AR-V7 has clinical utility.
ascopubs.org/doi/full/10.12…

@NatureMicrobiol article in today's #APaperADay challenge. Authors discuss the microbiome-targeted interventions, such as probiotics and microbiome transplants to reverse deterioration of biodiversity and increase the resilience of wildlife and ecosystems.
nature.com/articles/s4156…

@NatRevImmunol article in today's #APaperADay summarises the role of Vitamin D as potential prophylactic agent. The RCTs have not evidenced towards therapeutic use of vitamin D on mortality, intensive care requirement or hospital stay due to COVID-19.
nature.com/articles/s4157…

Day 205 of #APaperADay challenge. This @NatureComms article provides evidence that cellular senescence inhibits cell competition-mediated elimination of oncogenic cells through HGF signaling, suggesting that it may lead to cancer incidence during aging.
nature.com/articles/s4146…

@Nature article on the #RosalindFranklin in today's #APaperADay. Born OTD in 1920, she contributed majorly towards resolving the mystery behind the structure of DNA double helix. Tributes to this remarkable researcher.💐
nature.com/articles/natur…

https://twitter.com/imtryam/status/1286939006106652672?s=20&t=QLYv_dsasFSGw9kUzos3LQ

@SciReports article in today's #APaperADay. The authors investigate the clinical value and risk assessment of circulating tumor cells (CTCs) and androgen receptor splice variant 7 (AR-V7) as biomarker in mCRPC patients.
nature.com/articles/s4159…

The results of the study indicate that both, CTC + versus CTC − and AR-V7 + versus AR-V7- stratification, can effectively prognosticate clinical outcomes. They demonstrate potential flaws by focusing on AR-V7 as a sole biomarker. #APaperADay

@NatureComms article in #APaperADay. Authors observe an association between bacterial translocation & activation of fibro-inflammatory pathways. They demonstrate that gut microbiota directly influence the hepatic inflammatory microenvironment in mice/men.
nature.com/articles/s4146…

@TheBreastOnline paper on the role of anthracyclines in the treatment of early breast cancer. The authors review available data regarding anthracycline efficacy and toxicity in the EBC setting and the potential directions for future research. #APaperADay
sciencedirect.com/science/articl…

Anthracyclines are one of the most efficacious drugs for breast cancer. They are however associated with possible cardiotoxicity and leukemia, important adverse events that cause significant additional morbidity and mortality. #APaperADay

Supporting data have not demonstrated the superiority of a non-anthracycline regimen in any breast cancer subtype. However, regimens with anthracyclines and taxanes are superior to regimens with taxanes alone, in terms of recurrence and mortality. #APaperADay

@NatureComms article in today's #APaperADay. Exploring different fusion protein designs, the authors in this paper have determined the structure of G protein-coupled receptors without signaling proteins. This strategy can be applicable to other GPCRs.
nature.com/articles/s4146…

In today's #APaperADay I read @JCO_ASCO editorial. It mentions circulating tumor DNA as a surrogate prognostic biomarker of late recurrence. In such cases, secondary prevention trials should focus to determine if this risk can be modified.
ascopubs.org/doi/full/10.12…

@NatureRevMicro article in today's #APaperADay. Authors summarize our understanding of giant virus diversity and biology based on viral isolates as laboratory cultivation has enabled extensive insights into viral morphology and infection strategies.
nature.com/articles/s4157…

@SciReports article in today's #APaperADay challenge. The authors report superSTR; the first method demonstrated to rapidly identify repeat expansions of Short Tandem Repeats in population-scale cohorts without alignment in NGS experiments.
nature.com/articles/s4159…

Editorial on extrahepatic malignancies in chronic hepatitis B (CHB) untreated with nucleos(t)ide analogs in today's #APaperADay. This information stems from nationwide data of 90,944 persons newly diagnosed with CHB.

https://twitter.com/JCO_ASCO/status/1553380038111805440?s=20&t=kbzC-AaJm7BDlrOIyNaOHQ

Patients with CHB not on treatment had a 28% higher risk of malignancy than CHB patients on treatment and a 22% higher risk of malignancy than controls without CHB. This should be extended to other geographic populations to validate these observations. #APaperADay

An interesting dermatology article from Prof Somesh Gupta at @aiims_newdelhi. It suggests that apremilast could be a potential treatment for refractory alopecia areata which is characterized by nonscarring loss of scalp and/or body hair. #APaperADay
tandfonline.com/doi/full/10.10…

@JournalSpectrum article on HIV1 recombinant forms' nanopore sequencing in today's #APaperADay challenge. The authors describe a new nanopore sequencing-based platform that can identify the HIV-1 genome structure, RFs, & dual-infection heterologous HIV-1.
journals.asm.org/doi/full/10.11…

@Nature news and views in today's #APaperADay. It discusses Schneider et al. paper that provides evidence that a key aspect of accurate chromosome transmission during cell division is condensation into a more solid-like state through phase transition.
nature.com/articles/d4158…

Today is birthday of Dr Stephen Fleming, whose remarkable discovery of penicillin could save millions of lives. On his birthday, I am reading his seminal paper. Contamination is cool, sometimes. #APaperADay

ncbi.nlm.nih.gov/pmc/articles/P…

https://twitter.com/imtryam/status/1291258572970397696?t=vcXyVOaqhm6HizfLDT9MjQ&s=19

@NatureGenet article in today's #APaperADay shows a fraction of colorectal cancer cells slowly replicate. The cells use to get around the action of therapies, often leading to treatment failure and disease recurrence.
nature.com/articles/s4158…

Day 220 of #APaperADay challenge. This @NatureComms paper determined the risk of breakthrough infection in fully vaccinated cohort. It reports that quantitative level of anti-spike IgG have limited impact on the risk of breakthrough infection with omicron.
nature.com/articles/s4146…

@CellReports paper on cellular communication in wound healing. This study exposes numerous cellular/molecular targets for functional interrogation and provides a hypothesis-generating resource for future wound healing studies. #APaperADay
cell.com/cell-reports/f…

An interesting @CCR_AACR article that defines an optimal AR cut-point to predict breast cancer survival. This article demonstrated that 78% nuclear positivity of AR in ERα-positive BrCa cohorts revealed robust prognostic capacity. #APaperADay

aacrjournals.org/clincancerres/…

The current study demonstrates that clinical assessment of AR in addition to ERα may permit a more precise prediction of breast cancer outcome in women, particularly those with hormone-sensitive disease, providing an optimal cut-point for AR is utilised. #APaperADay

AR was prognostic in this study for all breast cancer cases in both cohorts, which likely reflects its negative correlation with tumor size and proliferative capacity, regardless of ERα status. #APaperADay

Authors in this review summarize the main mitochondrial features, metabolic pathways, and their alterations in different cancers. They present an overview of current inhibitors, enzymes, and discuss translation of these approaches into clinics.#APaperADay
nature.com/articles/s4141…

@Nature article in today's #APaperADay challenge demonstrates that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate.
nature.com/articles/s4158…

@PNASNews classic in today's #APaperADay describes Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. GSEA focuses on gene sets, groups of genes that share common biological function, chromosomal location, or regulation.
pnas.org/doi/full/10.10…

@Nature article in today's #APaperADay challenge. The authors present a strategy to identify the main interactions between nanoparticle-adsorbed proteins after administration in blood. LDL receptor is reported to be responsible for nanoparticle uptake.
nature.com/articles/s4158…

This @jbiolchem article using whole-exome sequencing, reports that 7.3% of patients harbor mutations of RAD54B having more DNA double-strand breaks. This offers insight into the RAD54B mutations with olaparib treatment in ovarian cancers. #APaperADay
jbc.org/article/S0021-…

Wonderful @TheLancet DB PC-RCT focussing on the Asthma-associated gene networks. They report that a monoclonal antibody, mepolizumab, decreased asthma attacks by 27% in Black & Hispanic children and adolescents who have a form of severe asthma. #APaperADay
thelancet.com/journals/lance…

@BCRJournal article in today's #APaperADay. The authors report PSA, ZAG & PIP as candidate biomarkers reflecting AR activity in BrCa. Their expression levels are closely correlated with a gene signature representing tumor AR activity in all BrCa subtypes.
…ast-cancer-research.biomedcentral.com/articles/10.11…

Day 230 of #APaperADay challenge. This @CellReports article demonstrates that, during head and neck cancer (HNC) progression, tumor-associated neutrophils transmigrate to LNs and shape anti-tumor responses in a stage-dependent manner.
cell.com/cell-reports/f…

The findings suggest the dual role of LN-associated neutrophils during cancer progression: immunostimulatory, anti-tumor properties at the early cancer stage versus immunosuppressive, tumor-supportive activity at late tumor stages. #APaperADay

@ScienceAdvances article in today's #APaperADay challenge. The authors present a mechanistic link between telomeres and a tumor suppressor mechanism. This relates to the long distance gene silencing through telomere position effect over long distances.
science.org/doi/10.1126/sc…

Today's #APaperADay article reviews Prostate cancer, the role of AR signaling during PCa progression, and the relationship between prostate cancer stem cells and AR signaling. It also highlights the stemness score and AR signaling activity across the PCa.
portlandpress.com/essaysbiochem/…

This @CellReports paper investigates the global repertoire of MHC I-associated peptides present on iPSCs. It reports a set of pluripotency- or stemness-associated antigens that are non-mutated & shared between patients across multiple cancers. #APaperADay
sciencedirect.com/science/articl…

@emboreports article in today's #APaperADay challenge. The authors present a method for prospectively isolating hematopoietic stem cells from in vitro cultures having similar molecular profiles as in fetal HSCs.
embopress.org/doi/full/10.15…

@JCOPO_ASCO report in today's #APaperADay. Authors check for the robustness of RNA sequencing in identifying gene fusion events. They conclude it to be a robust technique for gene fusion detection of childhood cancers and can assist in treatment decisions.
ascopubs.org/doi/full/10.12…

This @Nature paper analysed and generated unprecedented data to show that spatial transcriptomic data across multiple cancer types can robustly be used to infer copy number variation, as validated by FISH and WGS. #APaperADay
nature.com/articles/s4158…

A very interesting study assesses the feasibility of adjuvant enzalutamide, an AR antagonist, in early-stage, AR +ve TNBC. This trial demonstrates AE to be a feasible & well-tolerated regimen in patients with an early-stage AR + TNBC. #APaperADay
link.springer.com/article/10.100…

@SciReports article on Malaria transmission in today's #APaperADay. The authors analyze how climate relates to the transmission of malaria in Africa. They show a positive correlation with temperature and rainfall networks except for a short period.
nature.com/articles/s4159…

Today's #APaperADay article from @CommsBio reports that hypothesis-free data, such as Cell Painting & Gene Expression data, in machine learning models can be used to detect toxicity, as well as to help understand modes of toxicity.
nature.com/articles/s4200…

@JMolEndo review article in today's #APaperADay challenge. The authors provide an overview of the recent findings on how the circadian clock and mitochondrial functioning are interrelated with a focus on mitochondrial morphology and respiration.
jme.bioscientifica.com/view/journals/…

@JHEP_Reports article on Acute-on-chronic liver failure (ACLF) in today's #/#APaperADay. It provides evidence of severe net interstitial collagen deposition in ACLF and the novel observation of the association between PRO-C6 and organ failures & mortality.
jhep-reports.eu/article/S2589-…

An interesting study comparing tea consumption and mortality in today's #APaperADay. This concludes that higher tea intake is associated with lower mortality risk among those drinking ≥ 2 cups/day, regardless of genetic variation in caffeine metabolism.
acpjournals.org/doi/10.7326/M2…

Today's #APaperADay reviews complex interplay between microbiota and the immune system and it's role in the onset and progression of Pancreatic Cancer.
wjgnet.com/1007-9327/full…

@VirusesMDPI article in today's #APaperADay challenge. This paper summarises the observations of the mutual impact between SARS-CoV-2 infection and gut microbiota and discuss the consequences and mechanisms of this interaction.
mdpi.com/1999-4915/14/8…

@NatureGenet report in today's #APaperADay. The authors introduce single-cell disease relevance score (scDRS), it links scRNA-seq with polygenic disease risk at single-cell resolution, independent of annotated cell types. This matches the relevant data.
nature.com/articles/s4158…

Today's #APaperADay article is from @ScienceAdvances. The authors show that a part of the TCA cycle is operational in the nucleus. This extended metabolic pathway in the nucleus, warrants a revision of the canonical view on metabolic compartmentalization.
science.org/doi/10.1126/sc…

On the birthday of Prof Shinya Yamanaka, I am reading his review on PSC therapy in today's #APaperADay. Prof Yamanaka discuss two decades of research aimed at inherent properties of tumorigenicity, immunogenicity, and heterogeneity in ESC and iPSC.
cell.com/cell-stem-cell…

@NatureMedicine article in today's #APaperADay discusses Scholler et al. paper that evaluated the TME of patients with DLBCL treated with CAR T cell therapy. The immune content of the TME is associated with clinical response, survival & toxicity outcomes.
nature.com/articles/s4159…

Today's #APaperADay article is from @NatureCancer on AR-targeted therapy resistance. The authors deduce that ectopic activation of JAK–STAT signaling is required for lineage plasticity-driven AR-targeted therapy resistance in mCRPC.
nature.com/articles/s4301…

Today's #APaperADay article is from @TheLancetOncol that estimates the impact of delays in diagnosis on cancer survival outcomes in cancer. The authors anticipate additional deaths due to cancer as a consequence of the national COVID-19 pandemic measures.
sciencedirect.com/science/articl…

@eLife insight sheds light on important distinctions between spliced AR-V7 and full-length AR and their role in CRPC. Further, it would be important to determine the link between the hit-and-run activity and the function of AR-V7. #APaperADay
elifesciences.org/articles/82070

@Oncotarget article in today's #APaperADay. This study highlights the suppressive effect of ASK1 on HCC and its significance. These outcomes broaden the knowledge and provide a novel potential prognostic biomarker and therapeutic target for advanced HCC.
oncotarget.com/article/8478/t…

The authors demonstrate the prognostic value of ASK1 in HCC patients and the inhibitory effect on HCC progression both in vitro and in vivo. These results provide a promising new therapeutic target and a novel prognostic biomarker for HCC. #APaperADay

@Nature research highlight in today's #APaperADay challenge. It discusses qRetro-Cascorder, a tool that employs prokaryotic retrons and CRISPR integrases to write transcriptional events into the genome of Escherichia coli.
nature.com/articles/s4158…

@Nature paper on genomic alterations in today's #APaperADay challenge. The authors show that targeted therapies matched to genomics improves progression-free survival (PFS) when genomic alterations are classified as level I/II according to the ESMO scale.
nature.com/articles/s4158…

This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with metastatic Breast Cancer. #APaperADay

This @NatureGenet paper reports cistrome-wide association study (CWAS), that identifies genotypic and allele-specific effects on chromatin that are also associated with disease. It studies variants that affects transcriptional regulation. #APaperADay
nature.com/articles/s4158…

@NatureMedicine article in today's #APaperADay. The authors present an approach for combining genetic association results for 80 diseases from two biobank studies to provide an overview of the impact of genetic variation on lost healthy life years.
nature.com/articles/s4159…

@CellCellPress article overviewing PanCancer Atlas analyses on oncogenic molecular processes in today's #APaperADay challenge. The authors provide insights into cancer through the synthesis of the findings of the TCGA PanCancer Atlas project.
cell.com/cell/fulltext/…

This work illuminates the complex milieu of oncogenic processes by integrating an enormous corpus of data obtained over the course of TCGA into organized themes. #APaperADay

@Nature article in today's #APaperADay challenge. The authors demonstrate a central role of CDK11 in spliceosome assembly and splicing regulation & characterize OTS964 as a highly selective CDK11 inhibitor that suppresses spliceosome activation & splicing.
nature.com/articles/s4158…

An excellent paper in @NatureCellBio on tumor dormancy in today's #APaperADay. The authors attempt to answer how disseminated tumor cells (DTCs) are kept dormant and what wakes them up. Endothelial-derived thrombospondin-1 induces sustained BCC quiescence.
nature.com/articles/ncb27…

Using mouse models of human breast cancer they demonstrate that
-dormant DTCs reside on the microvasculature of lung, BoMa, and brain in vivo.
-endothelial cells induce and sustain BCC quiescence
- thrombospondin-1 (TSP-1) is an endothelium-derived tumour suppressor.
#APaperADay

-tumour growth is accelerated around neovascular tips, which we show are rich in tumour-promoting factors such as active TGF-β1 and periostin
#APaperADay

This @PNASNews article investigated whether the beneficial contributions of TNF-α could be boosted by activating TNFR2 with the agonist NewStar2. It concludes that TNFR2 activation may be valuable as potential therapy for Alzheimer’s disease. #APaperADay
pnas.org/doi/full/10.10…

@JCM_MDPI article in today's #APaperADay reports the outcomes of a phase I trial assessing the maximum tolerated dose of lapatinib in combination with platinum-containing chemotherapy regimen in patients with Pancreatic ductal adenocarcinoma.
mdpi.com/2077-0383/11/1…

Gastrointestinal toxicity: diarrhea is associated with the drugs. The trial showed that the combination of lapatinib with platinum-containing chemotherapy is safe and feasible in patients with refractory pancreatic cancer and warrants further investigation. #APaperADay

An important article from @aiims_newdelhi in today's #APaperADay challenge. The patients were subjected to multigene panel testing to define the prevalence and describe the mutational profile of hereditary breast cancer in the Indian population.
link.springer.com/article/10.124…

This work reports a high prevalence of pathogenic/likely pathogenic mutations (18.64%) in hereditary cancer susceptibility genes among breast cancer patients. The prevalence of pathogenic mutations is comparatively higher in Indian patients. #APaperADay

@NatureGenet article in today's #APaperADay challenge. The authors in this work show how the nonchromosomal random inheritance pattern of extrachromosomal DNA contributes to poor outcomes for patients with cancer.
nature.com/articles/s4158…

Cell research correspondence in today's #APaperADay challenge. The authors report the immunogenicity and efficacy of the receptor-binding domain (RBD)-dimer mRNA vaccine in mice. They hail it to be potent especially against the Delta and Omicron variants.
nature.com/articles/s4142…

@SciReports article aims to identify the factors responsible for the induction of cancer stem cells. Prostaglandin E2 maybe one of the factors related with inflammation which could initiate cancer converting stem cells or progenitor cells. #APaperADay
nature.com/articles/s4159…

@FrontEndocrinol article in today's #APaperADay challenge. It reports that androgens promote migration and invasion in T47D breast cancer cells via altering the architecture of Moesin cytoskeleton activation.
frontiersin.org/articles/10.33…

It is further reported that testosterone and dehydroepiandrosterone exert their actions via the AR and estrogen receptor (ER), while the non-aromatizable androgen – dihydrotestosterone – only recruits AR. #APaperADay

@LeukemiaJnl review in today's #APaperADay discusses potential applications of circulating tumor DNA in clinical practice and for translational research. It is reviewed how ctDNA can be utilised as a decision-making tool to guide lymphoma treatment.
nature.com/articles/s4137…

Well-explained protocol on Chromatin Immunoprecipitation in today's #APaperADay challenge. Published in @JoVEJournal this article provides detailed methodologies for both bench preparation of materials and for accurate quantitative analysis.
jove.com/v/50064/effici…

@PNASNews article shows that currently reported cancer stem cell markers are coexpressed on cells containing tumor-initiating capacity. It is further reported that CSCs contain multilineage differentiation potential both in vitro and in vivo. #APaperADay
pnas.org/doi/10.1073/pn…

Good article in @SN_Oncology establishing Family with sequence similarity 83 member A (FAM83A) as a key factor in breast cancer initiation. Immunohistochemistry on breast tissue microarray reveals a significant upregulation of FAM83A in cases. #APaperADay
biomarkerres.biomedcentral.com/articles/10.11…

This study elucidates the critical role of FAM83A in breast cancer initiation. When compared with its level in normal breast, FAM83A shows an increased expression in both breast tumors and, to a greater extent, in early phase of BC development. #APaperADay

This work also demonstrates the importance of examining the normal breast tissue to decipher the molecular aberrations occurring in early breast cancer development. #APaperADay

AR assessment in Indian BrCa cohort.
Findings: AR expression is significantly associated with the early stage. AR is also associated with a lower disease burden and hence can be utilized as a predictor of response to neoadjuvant chemotherapy. #APaperADay
karger.com/Article/FullTe…

@NatureProtocols on mass spectrometry for the study of protein complexes. This is a robust protocol that can be used in parallel with ChIP-seq followed by MS identification of the target protein and several dozen interacting proteins. #APaperADay
nature.com/articles/nprot…

@Cancers_MDPI retrospective analysis in today's #APaperADay. AR-V7 expression in PCa patients following ADT might be a reason for reduced or absent therapy effect. This recommends further studies on AR-Vs as predictive biomarkers for therapy response.
mdpi.com/2072-6694/14/1…

This @NatureGenet paper introduces sc-linker, an integrated framework to relate human disease and complex traits to cell types and cellular processes by integrating GWAS and scRNA-seq data from multiple tissues, diseases, and cells. #APaperADay
nature.com/articles/s4158…

Day 275 of #APaperADay challenge. This @NatureRevMicro article reviews the current understanding of RNA-targeting CRISPR–Cas systems. The authors discuss the biological principles underpinning RNA-targeting CRISPR–Cas systems.
nature.com/articles/s4157…

@JCO_ASCO editorial in today's #APaperADay challenge. The authors report the development of PREMMplus, a model which incorporates personal and family history to predict who might benefit from a germline multigene cancer panel test.
ascopubs.org/doi/full/10.12…

It can help in determining who is most likely to benefit from germline genetic testing and reduce the number of unexpected findings. #APaperADay

@Cancers_MDPI article on B-Cell Lymphomas in today's #APaperADay challenge. The authors illustrate the literature data and the major findings related to FDG PET/CT use during Chimeric antigen receptor–engineered (CAR) T cell therapy in B-cell lymphomas.
mdpi.com/2072-6694/14/1…

An interesting @an_chem paper from @iiscbangalore group introduces quantitative endpoint isothermal recombinase polymerase amplification (qeRPA). Comparable to qPCR, qeRPA can yield robust & sensitive nucleic acid estimation at ~RT (37−42 °C). #APaperADay
pubs.acs.org/doi/10.1021/ac…

RPA requires two end-specific primers with a cocktail of recombinase, single-strand binding protein, and a strand displacement DNA polymerase. Recombinase bound to the primers assists in homology search and strand exchange. It can detect single DNA molecule in 30 min. #APaperADay

The authors show that rapid DNA polymerization progressively leads to the formation of DNA amplicon clusters that limit further amplification. Also, RPA amplicons would be dependent on the initial target DNA concentration. #APaperADay

qeRPA bypasses real-time monitoring, lowers background amplification, and enables the use of a DNA intercalating dye for quantification. It can determine the viral load from the clinical samples matching qPCR estimates with a detection limit of 100 DNA molecules. #APaperADay

This @Nature paper reveals a strategy for SARS-CoV-2 to bypass the defence machinery of host cells, mimicking the histone proteins. This mimicry disrupts the host’s ability to regulate gene expression and effective response to infection. #APaperADay
nature.com/articles/s4158…

This article discusses the advances in cell competition & their roles in embryogenesis, tissue homeostasis, & ageing. It further explores the dual role of cell competition as a tumor-suppressive and cancer-promoting mechanism in carcinogenesis. #APaperADay

https://twitter.com/NaturePortfolio/status/1577730594431275028?s=20&t=VmpBl-UsoAEnol60v1Q39Q

@NatureBiotech article on RADAR sensors in today's #APaperADay. The authors demonstrate that RNA sensors using ADAR are modular, programmable, logic capabilities, discriminate disease-relevant variations, and can potentially function in many organisms.
nature.com/articles/s4158…

Today's #APaperADay article is from @NatureComms on the development of Synthetic RNA viruses. These are well tolerated and demonstrate tumor-selective viral production and spread in multiple tumor models, resulting in oncolysis and anti-tumor efficacy.
nature.com/articles/s4146…

@oncogenejournal article on senescence-associated secretory phenotype (SASP) induced tumorigenesis in today's #APaperADay. SASP & chemotherapy upregulated Lipocalin-2 (LCN2) leads to increased migration in BC cells & correlates with worse overall survival.
nature.com/articles/s4138…

Important observations:
1. IL-1-dependent SASP promotes migration, partial EMT program, and cellular plasticity in BC cells
2. LCN2 was the most upregulated transcript in MCF7 cells exposed to senescent CM
3. LCN2 is required for SASP-induced plasticity
#APaperADay

4. SASP-induced LCN2 expression promotes BC progression in vivo
5. Exposure to senescence-inducing stimuli promotes detrimental cellular plasticity in breast tumors through LCN2 expression
6. LCN2 could be a potential prognostic biomarker for breast cancer survival
#APaperADay

An interesting study exploring the impact of poor paternal diet in mice on offspring tissue lipid metabolism. Age-specific changes were observed in offspring tissue lipid abundance, underpinned by specific liver transcriptomic profiles. #APaperADay

https://twitter.com/AdamWatkins78/status/1567855521687814145?s=20&t=JfWJ7kvCIEopUfJj-03uGQ

@MolOncology review in today's #APaperADay. The authors discuss the cell death modalities connected to immunogenic cell death (ICD), the damage-associated molecular patterns exposed during ICD, & the mechanism by which they activate the immune system.
febs.onlinelibrary.wiley.com/doi/10.1002/18…

@Cell_Metabolism paper on brain metastases of Breast Cancer in today's #APaperADay challenge. Patients with HER2 amplification or TNBC are at a higher risk of developing brain metastases than those with ER/PR positive breast cancer.
cell.com/cell-metabolis…

The metastasis maybe-
Synchronous: detected along with the primary tumor
Metachronous: detected after several months to years
Latent: residually hidden for a long duration.

The authors uncovered the impact of metabolic diversity and adaptations on metastatic fitness.
#APaperADay

They identified metabolic vulnerabilities in these cell populations. Genetic or pharmacologic inhibition of these vulnerabilities limits residual and established HER2+ breast cancer brain metastases, identifying a potential therapeutic opportunity. #APaperADay

This @NatureBiotech paper presents a computational pipeline; Protein Modification Integrated Search Engine (PROMISE), that allows combinatorial detection of multiple post-translational modifications from multiple clinical cohorts & cell lines. #APaperADay
nature.com/articles/s4158…

@JCOOP_ASCO review on clinical management of Metastatic Renal Cell Carcinoma (mRCC) in today's #APaperADay challenge. Supplemented with clinically relevant data the authors provide a practical framework for the management of patients with mRCC.
ascopubs.org/doi/full/10.12…

#APaperADay article is from @ScienceAdvances. Using organoids & bioengineered tissue culture, authors report that cellular shape affects intestinal stem cells function by regulating YAP-independent signaling platforms between stem cells & their niche.
science.org/doi/10.1126/sc…

@CommsBio article in today's #APaperADay. This study identified a protective cellular niche of persistent Leishmania parasites in the bone marrow. The long-term hematopoietic stem cells as drug may open therapeutic avenues for leishmaniasis treatment.
nature.com/articles/s4200…

@IJMS_MDPI article in today's #APaperADay challenge emphasizes the importance of enzyme pyruvate kinase M2 in head and neck cancer. Observed Tyrosine 105 phosphorylation in PKM2 emphasizes the need of further investigation of the role of PKM2 in HNSCC.
mdpi.com/1422-0067/23/2…

Today's #APaperADay piece is a review article published in @Cancers_MDPI. It suggests dialysis, as a novel concept to reduce levels of glucose & glutamine, as an adjuvant cancer treatment to increase efficiency and reduce side effects of cancer therapies.
mdpi.com/2072-6694/14/2…

@PNASNews article on Parkinson's in today's #APaperADay. The article provides insight into the mechanism of leucine-rich repeat kinase 2 (LRRK2)-dependent lysosomal damage regulation and supports future study of the role of LRRK2 in lysosomal biology.
pnas.org/doi/10.1073/pn…

@JCO_ASCO article in today's #APaperADay. This is the first study to demonstrate the potential efficacy of combining an antiangiogenic agent with a poly (ADP-ribose) polymerase inhibitor for patients with mCRPC.
ascopubs.org/doi/full/10.12…

This suggests that combination of cediranib & olaparib demonstrated an improved radiographic progression-free survival compared with olaparib alone in patients with mCRPC. Although, this combination is associated with an increased rate of significant adverse effects. #APaperADay

@PLOSONE article on viral infectivity of HIV in today's #APaperADay challenge. The authors analyze the effects of conserved p6* residue mutations on virus processing and viral protease maturation.
journals.plos.org/plosone/articl…

They report that mutations at a putative internal p6* cleavage site markedly impaired virus processing and infectivity, likely due in part to defects in PR maturation and RT package. #APaperADay

Am interesting finding in @scisignal article. It reports Fusobacterium nucleatum an oral commensal promotes tumor progression–associated activity in pancreatic ductal adenocarcinoma cells but not in normal pancreatic epithelial cells. #APaperADay
science.org/doi/abs/10.112…

@NatureComms article in today's #APaperADay. The authors introduce SHARP (SSB-Helicase Assisted Rapid PCR) that has engineered PcrA M6 helicase with enhanced speed & processivity to replace the heating step while retaining desired PCR characteristics.
nature.com/articles/s4146…

@SciReports paper on HBV replication in the placenta in today's #APaperADay challenge. The authors, for the first time, provide experimental evidence suggesting that HBV can enter the placenta and replicate there, which may facilitate viral transmission.
nature.com/articles/s4159…

CT angiography as a predictor of adverse cardiovascular events (ACE). This systematic review & meta-analysis concludes that computational tomography coronary angiography (CTCA) is a safe strategy for investigating patients with stable angina. #APaperADay
heartandlung.org/article/S0147-…

This meta-analysis confirms that there is no significant difference in major ACE compared to an initial non-invasive CT approach in investigating patients with chronic coronary syndrome thus reinforcing the role of CTCA as the investigation of choice in stable angina. #APaperADay

Day 300 of #APaperADay challenge. Today I am reading this @JCOPO_ASCO paper on the molecular characterization of ctDNA in Pediatric Rhabdomyosarcoma. This work evidences ctDNA as a surrogate marker of tumor burden as a minimally invasive biomarker in RMS.
ascopubs.org/doi/full/10.12…

An informative article on CT Angiography in today's #APaperADay challenge. This review summarises the physical principles, fundamentals of CTA physics, and CT hardware and associated software for angiography.
radiologic.theclinics.com/article/S0033-…

@NatureCellBio article in today's #APaperADay challenge. The authors provide evidence that DNAJB6, a molecular chaperone of the heat shock protein network, surveils phenylalanine-glycine-rich nucleoporins (FG-Nups) to aid nuclear pore complex assembly.
nature.com/articles/s4155…

@NatureGenet article in today's #APaperADay challenge. The authors introduce a method for constructing rare variant polygenic scores and applied it to calculate genetically modified hemoglobin A1C thresholds for type 2 diabetes (T2D) diagnosis.
nature.com/articles/s4158…

The authors in this @SciReports articles suggest that EZH2: a histone methyltransferase can be a beneficial treatment marker for patients with esophageal cancer through decrease invasiveness of the disease and efficient response to NACT. #APaperADay
nature.com/articles/s4159…

Today's #APaperADay article is from @Official_SSIM. This review discusses the response to immune checkpoint inhibitors of Innate Lymphoid cells & the current limitations of this immunotherapeutic approach followed by suggesting potential novel strategies.
sciencedirect.com/science/articl…

@NatImmunol article in today's #APaperADay challenge. This paper defined a time-adjusted signature that predicted antibody responses across vaccines. It provides a transcriptional atlas of immunity to vaccination and define signature of antibody responses.
nature.com/articles/s4159…

An excellent @NIH supported study on cellular-level approach to plaque removal in cases of atherosclerosis in today's #APaperADay challenge. Published in @Biomaterials_, this article introduces a novel Two-pronged approach to facilitate plaque regression.
sciencedirect.com/science/articl…

The scientists apply two strategies to a nanoparticle-based platform.
1. Deliver siRNA to knock down the expression of SR-A to reduce cholesterol influx.
2. Deliver LXR-L to increase expression of cholesterol transporters ABCA1/ABCG1 to enhance cholesterol efflux.
#APaperADay

Very informative review article on mRNA therapeutics in today's #APaperADay. The authors discuss new technologies, challenges, and approaches to optimize mRNA cargos, lipid carriers with inherent tissue tropism and in vivo percutaneous delivery systems.
nature.com/articles/s4158…

@NatureProtocols on 3D atomic models generation of cryo-EM data in today's #APaperADay challenge. The authors developed StarMap interface that offers a general approach for refining structural models of biological macromolecules into cryo-EM density maps.
nature.com/articles/s4159…

@MolTherapy article in today’s #APaperADay challenge. The authors discuss synthetic self-amplifying RNAs (saRNAs) that are safe and strong immune stimulators that can be inexpensively produced in large quantities and work as a promising vaccine platform.
sciencedirect.com/science/articl…

Today's #APaperADay article is from @JCO_ASCO. It sheds light on women harboring germline mutation in BRCA1/2. It is imperative to seek alternatives to risk-reducing mastectomy such as including prophylactic breast irradiation and systemic therapies.
ascopubs.org/doi/full/10.12…

Informative article on aging in today's #APaperADay challenge. Published yesterday, this review sheds light on the recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases.
nature.com/articles/s4139…

@Cancers_MDPI article in day 313 of #APaperADay challenge. In this systemic review (n = 618), the authors consolidate the prognostic significance of miRs expression in Prostate Cancer and on their potential use as alternative non-invasive biomarkers.
mdpi.com/2072-6694/14/2…

Extensive studies over the last 15 years have clearly suggested that miRs are critical regulators in PCa progression and development and indicate the use of miRs as promising non-invasive markers of tumoral diagnosis and prognosis. #APaperADay

Authors conclude that this methodology was used to address the role of miRs in PCa, and their potential as non-invasive biomarkers. This study could pave the way for other studies with larger cohorts, and it could be extended in order to study other cancers/diseases. #APaperADay

@Nature paper on tumour immune microenvironment (TIME). By scRNA-seq of 189 samples, this study illustrates diverse TIME subtypes, immunosuppressive functions of tumour-associated neutrophils and on potential immunotherapies targeting TANs. #APaperADay nature.com/articles/s4158…

Review article on EMT in today's #APaperADay. It discusses the EMT regulators, focusing on the role of Slug in lung cancer carcinogenesis, and how it promotes cancer cells to become motile & invasive by downregulating E markers and upregulating M markers.
academic.oup.com/carcin/article…

@Cancers_MDPI review piece on Drug Resistance in Cancer in today's #APaperADay. This article outlines the current knowledge of mechanisms that promote drug resistance, and the EMT, as well as how inherent tumor cell heterogeneity plays a role in DR.
mdpi.com/2072-6694/6/3/…

Another @Cancers_MDPI article on Agri-Food By-Products in cancer. This paper aims to assess the main targets of these natural derivatives with particular attention on Epidermal growth factor receptor in breast, prostate and colorectal cancers. #APaperADay
mdpi.com/2072-6694/14/2…

@PLOSPathogens pearls in today's #APaperADay challenge. This article summarizes recent observations on the involvement of the capsid structure in postentry replication and resolved some apparent discrepancies raised by earlier reports.
journals.plos.org/plospathogens/…

@SciReports article on cancer cells metabolic profiles. This work using a bladder cancer model of nongenetic plasticity demonstrates that metabolic plasticity plays a crucial role in the rapid phenotypic shifts to & from a drug-resistant state. #APaperADay
nature.com/articles/s4159…

One of the classic @NEJM articles on AR-V7 resistance and tolerance at @JohnsHopkins. The authors evaluated AR-V7 in circulating tumor cells and correlated it with prostate-specific antigen (PSA) response rates PFS, and overall survival. #APaperADay
nejm.org/doi/full/10.10…

They conclude that the Detection of AR-V7 in circulating tumor cells from patients with castration-resistant prostate cancer may be associated with resistance to enzalutamide and abiraterone. #APaperADay

They deduce that "it is possible that AR-V7 could be used as a biomarker to predict resistance to enzalutamide and abiraterone and to facilitate treatment selection." AR-V7 may be a marker of more advanced disease or a higher disease burden. #APaperADay

In conclusion, their data support an association between AR-V7 and resistance to both enzalutamide and abiraterone in patients with castration-resistant prostate cancer. #APaperADay

This review summarises the emerging evidence for metastasis-directed therapy for patients with oligometastases. It provides a summary of the current state, challenges, strategies to overcome these, & roads ahead in the oligometastases research. #APaperADay

https://twitter.com/JCO_ASCO/status/1591457051397398530?s=20&t=5v6gbZ8QiQ1f4w-qQkRH-g

@biorxivpreprint in today's #APaperADay challenge. The authors report atomic-resolution NMR structures of microcrystalline assemblies of CA-SP1 complexed with BVM (HIV-1 maturation inhibitor) and/or the assembly cofactor inositol hexakisphosphate (IP6).
biorxiv.org/content/10.110…

These data confirm that BVM binds inside the pore of the CA-SP1 6-helix bundle, simultaneously with IP6. Additionally, it uncovers previously unknown effects of BVM on IP6 dynamics that likely contribute to preventing protease access to the CA-SP1 cleavage site. #APaperADay

Furthermore, the authors discovered that BVM resistance in SP1-A1V and SP1-V7A variants is associated with loss of maturation inhibitor binding or loss of a stable 6-helix bundle conformation, respectively. #APaperADay

#APaperADay article from @ScienceAdvances on the structural basis of RNA Pol selection. The authors using cryo-electron microscopy determined the structure of the complex between upstream activating factor, native promoter DNA, & TATA-box-binding protein.
science.org/doi/10.1126/sc…

UAF uses its histone fold–based structure to recognize DNA and that it interacts with a conserved regulatory surface of TBP while sequestering it from DNA to enable specific Pol I recruitment. Thus it reveals the molecular principles underlying UAF function. #APaperADay

@MolTherapy paper in today's #APaperADay challenge. The authors demonstrate that a prime-boost, as well as a prime-only application of an saRNA vaccine expressing EBOV GP and NP, conferrs complete protection against EBOV infection in IFNAR−/− mice.
sciencedirect.com/science/articl…

@JCOPO_ASCO original report on day 325 of #APaperADay challenge. In this work, the authors explored the prognostic value of circulating tumor DNA as a marker of minimal residual disease in patients with radically resected liver-limited mCRC.
ascopubs.org/doi/abs/10.120…

The data generated shows the added value of ctDNA on top of current clinicopathologic factors for prognosis prediction in the resected LL-mCRC setting. It supports the potential utility of ctDNA into the design of clinical studies. #APaperADay

In this paper, the authors report cryo-EM structures of soluble envelope trimers from rhesus macaque SIV (SIVmac) in complex with neutralizing antibodies. This would enable a wide array of studies, as demonstrated with HIV-1. #APaperADay
nature.com/articles/s4159…

@Nature_NPJ Vaccines article on vaccine against relapsing malaria in today's #APaperADay challenge. The authors report a sterile protection against homologous sporozoite challenge in P. cynomolgi-rhesus macaque model for relapsing malaria.
nature.com/articles/s4154…

This strategy of following a single-shot high-dose live sporozoite vaccination can be extrapolated to develop efficacious malaria vaccines against relapsing human malaria. #APaperADay

This @J_Immunol paper proposes a model by which the loss of Tlr9 exacerbates Tlr7-dependent disease. The findings suggest new models for how Tlr9 regulates and Tlr7 enhances disease and provides insight into autoimmune disease aspects. #APaperADay
journals.aai.org/jimmunol/artic…

Today's @CIR_AACR article establishes Nitroso-N-methylurea-induced outbred Sprague-Dawley rat model of breast cancer. It recapitulates the mutational profile heterogeneity, ER expression, and immune evasive mechanisms observed in human BrCa. #APaperADay
aacrjournals.org/cancerimmunolr…

The authors further demonstrate that combined PD-L1 and TGFBR inhibition induces effective regression of these tumors and prevents immune escape. This should serve as a carcinogen-induced model of breast cancer in rats that is amenable to preclinical testing. #APaperADay

Today's #APaperADay article on immunogenicity and pathogenesis of malaria. This review summarises the key virulence factors involved in progression to or protection from severe disease and highlight important areas of future research.
tandfonline.com/doi/full/10.10…

Review article on Androgen Receptor in Hepatocellular carcinoma in today's #APaperADay challenge. It examines the role of AR in HCC, non-androgen-mediated mechanisms of induced AR expression, and the existence of AR splice variants (AR-SV) in HCC.
mdpi.com/1422-0067/23/2…

AR signaling plays a key role in HCC progression and the sexual dimorphism of the disease. #APaperADay

@emboreports article in today's #APaperADay. Through a combined approach of data mining, tumor models, proteomics, and sequencing, the authors identify TRIM28 as a new regulator of melanoma plasticity that promotes the expression of pro-invasive genes.
embopress.org/doi/full/10.15…

Day 333 of #APaperADay challenge. This @FEBSJournal paper shows that the tumors treated with neoadjuvant chemotherapy showed significantly lower
expression of metabolic proteins, particularly glycometabolic pathway markers.
febs.onlinelibrary.wiley.com/doi/10.1002/18…

This review in @Nature_NPJ Precision Oncology describes the importance of evaluating immune cell specificity using gene and protein-based analyses of tumor and immune cells and discusses the impact of such evaluations on oncology. #APaperADay
nature.com/articles/s4169…

On #WorldAIDSDay, I read this meticulous assessment of HIV infection from @SEQspain. This review provides a historical journey of the AIDS epidemic, its current status, risk stratification, and concurrent research questions on its eradication. #APaperADay
seq.es/abstract/rev-e…

@Biomed_MDPI article in today's #APaperADay challenge. In this review, the authors provide a comprehensive assessment of cancer metastasis, the relevance of cancer stem cells in tumor growth, and resistance, and current therapeutic interventions.
mdpi.com/2227-9059/10/1…

@oncogenejournal article on EMT in prostate cancer cells. The authors demonstrate that the blockade of either CXCR4 or CXCR7 suppresses obesity-driven EMT and PCa progression in mouse models. #APaperADay
nature.com/articles/s4138…

@Nature paper in today's #APaperADay. This paper demonstrate that the primary genomic signature of Fanconi anaemia (FA) repair deficiency is the presence of high numbers of structural variants. FA pathway deficiency may lead to EMT and aggressive cancer.
nature.com/articles/s4158…

This @Nature paper aims to decider the mechanism behind HER2 and HER3 interaction. Applying cryo-electron microscopy the authors reveal the structure of the active HER2–HER3 complex, which is stabilized by the binding of only one growth factor. #APaperADay
nature.com/articles/s4158…

On day 340 of #APaperADay challenge, I read this @KargerPublisher article on AR in TNBC. The authors characterized the role of GPER involved in AR signalling, expression of AR in TNBC tissues and associated AR expression with clinicopathological data.
karger.com/Article/Fullte…

This article concludes that activation of AR via DHT may promote the proliferation of TNBC through the downregulation of G-protein coupled estrogen receptor. It further provides the rationale and data for the potential target therapy of AR and GPER in TNBC in future. #APaperADay

An excellent commentary on AR activity in metastatic PCa in @jclinicalinvest. It discusses Sena et al. article on phase II clinical trial-enrolled patients with metastatic CRPC.
jci.org/articles/view/…

This study is on bipolar androgen therapy (BAT) in which SPA is pulsed with continuous ADT in order to cycle serum testosterone between high —supraphysiologic — and low — castrate — levels. #APaperADay

High AR activity is a requirement for clinical response to BAT, which is associated with the downregulation of MYC. Although BAT therapy has the potential to improve the outcome of patients with metastatic CRPC, it is not risk free and does not work for all patients. #APaperADay

@FrontVirology article in today's #APaperADay challenge. The authors identified the transmembrane protein MAL as a novel Gag-interacting IFN-stimulated genes product that targets Gag and exhibits anti-HIV activities.
frontiersin.org/articles/10.33…

@ScienceMagazine paper in today's #APaperADay challenge. The authors report FXR1, a member of the fragile X–related (FXR) protein family as a translation activator for stored mRNAs to instruct spermiogenesis in mice.
science.org/doi/10.1126/sc…

@biorxivpreprint in today's #APaperADay challenge. From scRNA-seq of 9683 tumor-infiltrated immune cells isolated from 14 treatment naïve TNBC tumors, the authors identify a new T cell subset, CD8+CXCL8+ naïve T cell, that is associated with poor survival.
biorxiv.org/content/10.110…

Today's #APaperADay article is on the mechanisms behind the aberrant expression of AR-V in PCa. The authors conclude that primary cultured prostate fibroblasts from PCa specimens increase the expression of AR-V7 in PCa cells.
onlinelibrary.wiley.com/doi/abs/10.100…

An excellent @KargerPublisher article in today's #APaperADay. This study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR+ve TNBC. It suggests AR inhibition could be a potential therapeutic approach for AR+ve TNBC.
karger.com/Article/FullTe…

The authors investigate the effect of AR in breast cancer growth and the link between AR and cell cycle-related genes in MSL TNBC in vitro and in vivo models. They also examine the efficacy of AR inhibition bicalutamide as a targeted therapy in AR-positive MSL TNBC. #APaperADay

The data provides a novel insight into AR which functions as an oncogene in TNBC. It supports a therapeutic benefit for the therapy with AR inhibition with bicalutamide in patients with AR-positive TNBC. #APaperADay

This @FrontImmunol paper discusses NK cells induced latency reversal in HIV-1. The data suggest that NK cells might be used in an indirect shock-and-kill strategy instead of directly targeting the latently infected cells which remains a challenge in HIV.
frontiersin.org/articles/10.33…

Today's #APaperADay article reviews the role of androgen and microRNA in TNBC. This article provides comprehensive analysis of BrCa subtypes, AR, and the role of miRNA in TNBC.
content.iospress.com/articles/breas…

This @SpringerPath paper analyses whether the protein levels of uPA and PAI-1, carried out in addition to conventional histopathological parameters, is similarly suitable for the assessment of prognosis as a multigene test such as OncotypeDX®.
diagnosticpathology.biomedcentral.com/articles/10.11…

The study showed that with the help of a combination of the values of Ki67 and uPA/PAI-1 the general trend of the recurrence score (RS) to be expected from the multigene test OncotypeDX® can be estimated. #APaperADay

The protein-based measurement of uPA/PAI from frozen tumour tissue and additional multigene tests enable a more differentiated risk assessment of the biological tumour behaviour than the sole evaluation of conventional criteria. #APaperADay

RNA biology paper in today's #APaperADay challenge discusses the role of circRNAs in EMT of pre-eclampsia. They report that circTNRC18/miR-762/Grhl2 axis serves a key role in trophoblast cell migration and EMT and correlates to PE progression. genomebiology.biomedcentral.com/articles/10.11…

Today's #APaperADay article is from @FrontImmunol. The authors report that HIV-specific CD4+ T cells in the lymph node are rapidly inducible upon experimental injection with HIV immunogens.
frontiersin.org/articles/10.33…

Monitoring evolution of CD4+ T cell memory in LNC with repeated experimental HIV immunization could indicate the strategies most likely to be successful in inducing HIV-specific bNAbs. #APaperADay

@pcan_journal paper in today's #APaperADay addresses prostate-specific antigen (PSA) response and clinical progression-free survival (cPFS) of Black vs. White men with chemotherapy-naïve PC.
nature.com/articles/s4139…

They conclude that Black and White men with presumed chemotherapy-naïve mCRPC had similar PSA responses when treated with enzalutamide, but Black men had better cPFS than White men. #APaperADay

Today's pick in #APaperADay challenge is @Nature_NPJ Breast Cancer. The authors report that upregulated expression of AR in patients with TNBC is associated with an increased risk of locoregional recurrence after radiation therapy.
nature.com/articles/s4152…

The authors performed a novel radiosensitizer screen that identified anti-androgen therapy as a potentially effective strategy for the treatment of AR-positive radioresistant breast cancers. #APaperADay

Overall, this study implicates AR as a mediator of radioresistance in BrCa and provides the preclinical rationale for the initiation of early-phase clinical trials of combination antiandrogens & radiotherapy for women with AR+ve TNBC at high risk of local recurrence. #APaperADay

MDPI Biomedicines article in today's #APaperADay challenge. This review discusses mechanistic insights into cancer metastasis by exploring the role of CSCs and key components of the TME in contributing to tumor growth, metastasis, and treatment resistance.
mdpi.com/2227-9059/10/1…

An excellent classic on qRT-PCR data analysis using multiple housekeeping genes is today's pick for #APaperADay. This @GenomeBiology paper has massive 20k plus citations. It presents a data normalization strategy for accurate RT-PCR expression profiling.
genomebiology.biomedcentral.com/articles/10.11…

The authors extensively evaluated 10 commonly used housekeeping genes in 13 different human tissues and outlined a procedure for calculating a normalization factor based on multiple control genes for more accurate and reliable normalization of gene-expression data. #APaperADay

They recommend the minimal use of the 3 most stable internal control genes for calculation of an RT-PCR normalization factor (NF n , n = 3), and stepwise inclusion of more control genes until the (n + 1)th gene has no significant contribution to the new NF (NFn + 1). #APaperADay

This study provides evidence that a conventional normalization strategy based on a single housekeeping gene leads to erroneous normalization up to 3.0- and 6.4-fold in 25% and 10% of the cases, respectively, with sporadic cases showing error values above 20. #APaperADay

In conclusion, Vandesompele Et al. described and validated a procedure to identify the most stable control genes in a given set of tissue samples, and to determine the optimal number of genes required for reliable normalization of RT-PCR data. #APaperADay

Today's #APaperADay article from @Endocrines_MDPI discusses the role of ERβ in TNBC. It provides a comprehensive overview of the pathways controlled by ERβ through genomic and non-genomic mechanisms and the complexity of ERβ interaction with AR.
mdpi.com/2673-396X/2/3/…

@jbiolchem minireview on Formaldehyde crosslinking in today's #APaperADay. It focuses on the use of Formaldehyde in ChIP and protein-protein interaction studies applied to understand the location and abundance of transcription factor binding along DNA.
jbc.org/article/S0021-…

This article discusses recent randomized phase 3 clinical trials in the second-line therapy setting compared with the standard of care in transplant-eligible patients who have DLBCL R/R within 12 months of completing chemo-immunotherapy. #APaperADay
journals.sagepub.com/doi/full/10.11…

Merry Christmas!!🎅🎄
Today's #APaperADay article is from @NEJM summarising phase 3 trial analysis of patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy.
nejm.org/doi/10.1056/NE…

The results yield that in patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician’s choice of chemotherapy. #APaperADay

One of the top cited articles on TNBC in @CCR_AACR is today's pick for #APaperADay challenge. This article compares the clinical features, history, and outcomes for women with TNBC (n= 1,601) with other types of breast cancer.
aacrjournals.org/clincancerres/…

This study addresses the short-term and long-term outcomes of patients with triple-negative breast cancers within the context of other known prognostic factors. #APaperADay

The data suggest that TNBC had an increased likelihood of distant recurrence and death within 5 years of diagnosis compared to other subtypes. Thus concluding that TNBC have a more aggressive clinical course. #APaperADay

This @oncogenejournal article reports that AR induced suppression of TRIM59, a TRIM family protein is inhibited by AR pathway inhibitors (ARPI) in particular second generation ARPI which leads to treatment-induced neuroendocrine PCa (t-NEPC) #APaperADay
nature.com/articles/s4138…

They demonstrate a prominent elevation of TRIM59 protein levels in human PCa samples after the ARPI treatment. TRIM59 upregulation is strongly correlated with t-NED in PCa. #APaperADay

@jitcancer article in today's #APaperADay. Bufalin, a steroid derivative, has shown antitumor activity in cancers including Hepatocellular carcinoma (HCC). This study evaluated the function of bufalin on the antitumor immune response in the HCC mouse model
jitc.bmj.com/content/10/5/e…

The authors demonstrate that bufalin enhanced the antitumor activity of anti-programmed cell death protein 1 (anti-PD-1) antibody, and the combination synergized to suppress HCC proliferation.#APaperADay

@PLOSONE paper in today's #APaperADay challenge investigates the possibility of combining CDK4/6 inhibitor (ribociclib) with AR inhibitor (enzalutamide) in the AR-positive TNBC cell line.
journals.plos.org/plosone/articl…

The authors report that ribociclib effectively inhibited the CDK4/6 signaling pathways in TNBC cell lines (MDA-MB-231 and MDA-MB-468) and BC cell (MCF-7) growth, and the expression of AR might contribute to ribociclib-mediated G1 arrest in AR-positive cell lines. #APaperADay

Penultimate #APaperADay article is from @CellReports. Fusobacterium nucleatum, a dominant bacteria contributes to tumorigenesis and accelerated cancer cell growth in Colorectal cancer. Authors aimed to identify Fn inhibitors with narrow-spectrum activity.
cell.com/cell-reports/f…

5-fluorouracil, the primary chemotherapeutic agent in CRC, potently inhibits Fn CRC strain growth. This suggests the interplay between the intratumoral microbiota and chemotherapeutics could inform the design of individual treatment regimes for patients with CRC. #APaperADay

I would conclude the #APaperADay challenge on day 365 by reading this classic. Published in @CellPressNews this paper proposes six hallmarks exhibited by cancer cells; "rules that govern the transformation of normal human cells into malignant cancers."
cell.com/cell/fulltext/…

Comparing tumor development analogous to Darwinian evolution, the authors propose that the conversion of normal human cells into cancer cells is the result of the succession of genetic changes, each conferring growth advantage(s). #APaperADay

The six hallmarks of cancer are:
1. Self-sufficiency in growth signals
2. Insensitivity to anti-growth signals
3. Evading apoptosis
4. Sustained angiogenesis
5. Limitless replicative potential
6. Tissue invasion and metastasis

#APaperADay

This list has been updated in their 2011 paper in @CellPressNews which includes the emerging hallmarks.
1. Reprogramming Energy Metabolism
2. Evading Immune Destruction
#APaperADay
cell.com/fulltext/S0092…

In Jan 2022, Hanahan (author of the HoC with Weinberg) revisited the list. Published in @CD_AACR, this article in addition to the classic 8 hallmarks proposes an additional emerging hallmark;
👉🏽Phenotypic plasticity & disrupted differentiation
#APaperADay
aacrjournals.org/cancerdiscover…