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Check out this study on the gender disproportion in the incidence of CRC among younger patients in India.

PURPOSEAccurate understanding of the genomic and transcriptomic data provided by next-generation sequencing (NGS) is essential for the effective utilization of precision oncology. Molecular tumor boards (MTBs) aim to translate the complex data in NGS reports into effective clinical interventions. Often, MTB treatment recommendations differ from those in the NGS reports. In this study, we analyze the discordance between these recommendations and the rationales behind the discordances, in a non–high-income setting, with international input to evaluate the necessity of MTB in clinical practice.METHODSWe collated data from MTB that were virtually hosted in Chennai, India. We included patients with malignancies who had NGS reports on solid tissue or liquid biopsies, and excluded those with incomplete data. MTB forms and NGS reports of each clinical case were analyzed and evaluated for recommendation concordance. Concordance was defined as an agreement between the first recommendation in the MTB forms and the therapeutic recommendations suggested in the NGS report. Discordance was the absence of the said agreement. The rationales for discordance were identified and documented.RESULTSSeventy MTB reports were analyzed with 49 cases meeting the inclusion criteria. The recommendation discordance was 49% (24 of 49). Discordant recommendations were mainly due to low level of evidence for the drug (75% of cases).CONCLUSIONThe discordance between MTB and NGS vendor recommendations highlights the clinical utility of MTB. The educational experiences provided by this initiative are an example of how virtual academic collaborations can enhance patient care and provider education across geographic borders.

Abstract Background The advent of immunotherapies has ushered in a new era in the treatment of non-small cell lung carcinoma. Although immunotherapies are associated with improved clinical outcomes, studies report a median overall survival of 11 months with progression-free survival of 2.5 months with the use of nivolumab for pretreated metastatic non-small cell lung cancer. Herein, we describe a case of advanced non-small cell lung carcinoma that has shown exceptional response to immunotherapy, with the patient being in complete response for the past 6 years since commencement of nivolumab. Case presentation We report the case of a 58-year-old female Caucasian, an ex-smoker with 40-pack-year history of smoking, who presented with cough and chest pain and was subsequently diagnosed with metastatic pulmonary adenocarcinoma. The tumor was positive for Kirsten rat sarcoma virus oncogene KRAS-G12C mutation and had high programmed death-1 ligand expression. She was commenced on first-line chemotherapy with carboplatin and gemcitabine with disease response, then continued on maintenance pemetrexed. She was then commenced on immunotherapy with nivolumab, with complete response for a total of 6 years. She does not report any adverse events. Currently, she shows no evidence of recurrence of non-small cell lung carcinoma. Conclusion The exceptional response to immunotherapy seen in this case may be explained by the presence of Kirsten rat sarcoma virus oncogene mutation, which is associated with enhanced clinical response to programmed death-1 ligand inhibitors. This report emphasizes the urgent need for further studies evaluating the role of Kirsten rat sarcoma virus oncogene mutation in determining the clinical efficacy of immunotherapies. This would enable us to make effective evidence-based clinical interventions in the treatment of non-small cell lung carcinoma.

The rising cost of cancer care has shed light on an important aspect of healthcare delivery. Financial toxicity of therapy must be considered in clinical practice and policy-making. One way to mitigate the impact of financial toxicity of cancer care is by focusing on an approach of healthcare delivery that aims to deliver value to the patient. Should value of therapy be one of the most important determinants of cancer care? If so, how do we measure it? How can we implement it in routine clinical practice? In this viewpoint, we discuss value-based care in systemic therapy in oncology. Strategies to improve the quality of care by incorporating value-based approaches are discussed: use of composite tools to assess the value of drugs, alternative dosing strategies, and the use of Health Technology Assessment in regulatory procedures. We propose that there must be a greater emphasis on value of therapy in determining its use and its cost.

Emerging evidence illustrates that RhoC has divergent roles in cervical cancer progression where it controls epithelial to mesenchymal transition (EMT), migration, angiogenesis, invasion, tumor growth, and radiation response. Cancer stem cells (CSCs) are the primary cause of recurrence and metastasis and exhibit all of the above phenotypes. It, therefore, becomes imperative to understand if RhoC regulates CSCs in cervical cancer. In this study, cell lines and clinical specimen-based findings demonstrate that RhoC regulates tumor phenotypes such as clonogenicity and anoikis resistance. Accordingly, inhibition of RhoC abrogated these phenotypes. RNA-seq analysis revealed that RhoC over-expression resulted in up-regulation of 27% of the transcriptome. Further, the Infinium MethylationEPIC array showed that RhoC over-expressing cells had a demethylated genome. Studies divulged that RhoC via TET2 signaling regulated the demethylation of the genome. Further investigations comprising ChIP-seq, reporter assays, and mass spectrometry revealed that RhoC associates with WDR5 in the nucleus and regulates the expression of pluripotency genes such as Nanog. Interestingly, clinical specimen-based investigations revealed the existence of a subset of tumor cells marked by RhoC+/Nanog+ expression. Finally, combinatorial inhibition (in vitro) of RhoC and its partners (WDR5 and TET2) resulted in increased sensitization of clinical specimen-derived cells to radiation. These findings collectively reveal a novel role for nuclear RhoC in the epigenetic regulation of Nanog and identify RhoC as a regulator of CSCs. The study nominates RhoC and associated signaling pathways as therapeutic targets. [ABSTRACT FROM AUTHOR]

Abstract Background The recently constructed river buffalo whole-genome radiation hybrid panel (BBURH5000) has already been used to generate preliminary radiation hybrid (RH) maps for several chromosomes, and buffalo-bovine comparative chromosome maps have been constructed. Here, we present the first-generation whole genome RH map (WG-RH) of the river buffalo generated from cattle-derived markers. The RH maps aligned to bovine genome sequence assembly Btau_4.0, providing valuable comparative mapping information for both species. Results A total of 3990 markers were typed on the BBURH5000 panel, of which 3072 were cattle derived SNPs. The remaining 918 were classified as cattle sequence tagged site (STS), including coding genes, ESTs, and microsatellites. Average retention frequency per chromosome was 27.3% calculated with 3093 scorable markers distributed in 43 linkage groups covering all autosomes (24) and the X chromosomes at a LOD ≥ 8. The estimated total length of the WG-RH map is 36,933 cR5000. Fewer than 15% of the markers (472) could not be placed within any linkage group at a LOD score ≥ 8. Linkage group order for each chromosome was determined by incorporation of markers previously assigned by FISH and by alignment with the bovine genome sequence assembly (Btau_4.0). Conclusion We obtained radiation hybrid chromosome maps for the entire river buffalo genome based on cattle-derived markers. The alignments of our RH maps to the current bovine genome sequence assembly (Btau_4.0) indicate regions of possible rearrangements between the chromosomes of both species. The river buffalo represents an important agricultural species whose genetic improvement has lagged behind other species due to limited prior genomic characterization. We present the first-generation RH map which provides a more extensive resource for positional candidate cloning of genes associated with complex traits and also for large-scale physical mapping of the river buffalo genome.

Background & objectives: The major limiting factor in the prevention of suicide is the limited knowledge on molecular insights in individuals at risk. Identification of peripheral protein markers which can classify individuals at high-risk of suicide might aid in early diagnosis and effective medical intervention. The aim of the present study was, therefore, to analyze the differential regulation of plasma proteins in individuals with deliberate self-harm compared to controls. Methods: Using two-dimensional gel electrophoresis coupled with matrix-assisted laser desorption-ionization mass spectrometry, differentially expressed plasma proteins were identified in study participants with deliberate self-harm compared to age- and gender-matched controls. The finding was validated using mass spectrometry-based isotope-labelled relative quantification and Western blot analysis in a new set of individuals with deliberate self-harm and controls. Results: The plasma proteomic analysis showed that apolipoprotein A-IV (Apo A-IV) was downregulated by 2.63-fold (confidence interval: 1.52-4.54) in individuals with deliberate self-harm (n=10) compared to matched controls, which was consistent in mass spectrometry-based relative quantification and Western blot analysis performed in an independent set of individuals with deliberate self-harm (n=18). In addition, plasma levels of total cholesterol, esterified cholesterol and high-density lipoprotein (HDL) were observed to be significantly lower individuals with deliberate self-harm compared to controls. Interpretation & conclusions: Apo A-IV, which plays a crucial role in the esterification of free cholesterol, was found to be downregulated with concomitantly decreased levels of HDL, esterified cholesterol and total cholesterol in individuals with deliberate self-harm compared to matched controls. The present findings might provide a link between the differential regulation of plasma proteins and the previously reported results on altered cholesterol levels in individuals with deliberate self-harm. [ABSTRACT FROM AUTHOR]