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Background: Survival rates among non-small cell lung cancer (NSCLC) stage IIIA (N2) patients are generally low and depend on the treatment. Patients and methods: We aimed to identify predictive markers for long term survival in responders and non-responders to chemotherapy, analyzing tumour and non-tumour samples by microarray (n=35) and whole exome sequencing (WES, n=25). Results: WES data showed correlation of overall survival of all patients with rs9905892 in the SLFN12L gene. High frequency of mutations (4/6, 66.7%) was identified in members of SWI/SNF complex in responder patients and in patients that were alive after seven years. Microarray data for immune components showed that VISTA (VSIR) was down-regulated in tumoral tissue. Conclusion: Our research suggests that mutations in SWI/SNF complex associate with long term survival after multimodal treatment, while down-regulation of VISTA might indicate its immunomodulatory role in NSCLC stage III (N2) patients. [ABSTRACT FROM AUTHOR]

Background & Aims. A point mutation (gp130Y757F/ Y759F) was identified as being responsible for aberrant activation of gp130 in mice and associated with gastric adenocarcinoma induction. As a result, we investigated the possible role of key point mutations in Tyr from IL6ST exon 17 that encode for the catalytic domain of gp130, and of its respective activators (IL-6 family member cytokines) in human gastric cancer initiation and development. Method. DNA, protein and plasma from 51 patients with gastric adenocarcinoma have been used in exploring gp130 status. We used sequencing analysis of IL6ST exon 17 in order to identify possible mutations that would lead to constitutive active forms of the receptor. The levels of gp130 activators (IL-6, IL-11, LIF) were analyzed by ELISA in plasma and mucosa of patients with gastric adenocarcinoma. Results. Sequencing analysis did not identify mutations in gp130 key positions (Y759, Y767, Y814, Y905 and Y915). An increased IL-6 and IL-11 level in gastric mucosa was observed, correlated with staging, indicating these cytokines as gp130 activators in tumor epithelial cell. Those variations were consistent with increased IL-6 level in plasma. Furthermore, IL-6, but not IL-11 showed a significant correlation with patient's survival time, suggesting that tissue and plasma concentration of IL-6 might be a marker of tumor aggressiveness with prognostic value. Conclusions. According to our results, no mutations were detected in gp130 key positions in human gastric adenocarcinoma samples. However, gp130 activation may occur due to the increased level of IL-6 and IL-11 cytokines detected that can become valuable biomarkers. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct with a poor prognosis owing to limited therapeutic options. The incidence of intrahepatic CCA (iCCA) is increasing worldwide, and its molecular basis is emerging. Environmental factors may contribute to regional differences in the mutation spectrum of European patients with iCCA, which are underrepresented in systematic genomic and transcriptomic studies of the disease., Methods: We describe an integrated whole-exome sequencing and transcriptomic study of 37 iCCAs patients in Germany., Results: We observed as most frequently mutated genes ARID1A (14%), IDH1, BAP1, TP53, KRAS, and ATM in 8% of patients. We identified FGFR2::BICC1 fusions in two tumours, and FGFR2::KCTD1 and TMEM106B::ROS1 as novel fusions with potential therapeutic implications in iCCA and confirmed oncogenic properties of TMEM106B::ROS1 in vitro. Using a data integration framework, we identified PBX1 as a novel central regulatory gene in iCCA. We performed extended screening by targeted sequencing of an additional 40 CCAs. In the joint analysis, IDH1 (13%), BAP1 (10%), TP53 (9%), KRAS (7%), ARID1A (7%), NF1 (5%), and ATM (5%) were the most frequently mutated genes, and we found PBX1 to show copy gain in 20% of the tumours. According to other studies, amplifications of PBX1 tend to occur in European iCCAs in contrast to liver fluke-associated Asian iCCAs., Conclusions: By analyzing an additional European cohort of iCCA patients, we found that PBX1 protein expression was a marker of poor prognosis. Overall, our findings provide insight into key molecular alterations in iCCA, reveal new targetable fusion genes, and suggest that PBX1 is a novel modulator of this disease., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Severe sepsis and septic shock are associated with an inflammatory cascade that is primarily responsible for multiple organ dysfunction. To date, there are no specific treatments designed to modulate and rebalance inflammatory cytokines levels. We present a case of a 50 years old man with postoperative septic shock after undergoing cephalic pancreatectomy for a pancreatic cystic tumor. The use of a haemoadsorbtion device (CytoSorb ® ) in combination with continuous veno-venous haemofiltration was associated with a decrease in TNFα, IL-1β and IFNγ and an increase in IL-10 levels measured before and after two consecutive procedures. The effect of CytoSorb ® on inflammatory cytokines translated into a more stable haemodynamic profile with a stable cardiac output and normalization of systemic vascular resistance index and decreased vasopressor requirements. Further prospective large clinical trials are required in order to determine the indications for CytoSorb ® and to evaluate the overall outcome., Competing Interests: Conflict of interest Nothing to declare

Background/aims: This study aimed to understand gradual biological variations during gastric tumorigenesis, and to identify the candidate genes that are involved in tumor progression and metastasis., Methodology: cDNA microarray data were obtained from 10 pair of cancerous and normal adjacent tissue from gastric adenocarcinoma patients. The samples were divided in primary and advanced gastric adenocarcinoma with lymph node metastasis. Validation of the microarray data was accomplished by quantitative RT-PCR on additional 41 samples. The significantly modified genes were grouped in clusters according to their functional annotation, and comparison was done regarding molecular mechanisms involved tumor progression., Results: A total of 136 genes were up-regulated and 96 genes were down-regulated by at least fourfold in tumor tissue. The analysis of gene clusters revealed a complex remodelling of normal gastric epithelium morphology and function associated with the tumorigenesis and metastasis. A large number of proteases are being overexpressed, together with keratins, genes associated with morphogenesis and anti-apoptosis. Between the most significant down-regulated genes, there were genes involved in gastric motility and synthesis and genes related to metabolic and pro-apoptotic processes. We also report, the identification of seven genes, significant up-regulated, that seem to be associated with tumor progression: KRT17, COL10A2, KIAA1199, SPP1, IL11, S100A2, and MMP3., Conclusions: Our cDNA microarray study identified several genes that appeared to meet the criteria of a good biomarker, and may therefore be especially useful for the development of diagnostic tools, for the early detection, or for the prediction of tumor progression.