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PurposeCirculating tumor DNA (ctDNA) analyses allow for postoperative risk stratification in patients with curatively treated colon and breast cancers. Use of ctDNA in esophagogastric cancers (EGC) is less characterized and could identify high-risk patients who have been treated with curative intent.MethodsIn this retrospective analysis of real-world data, ctDNA levels were analyzed in the preoperative, postoperative, and surveillance settings in patients with EGC using a personalized multiplex polymerase chain reaction-based next-generation sequencing assay. Plasma samples (n = 943) from 295 patients at > 70 institutions were collected before surgery, postoperatively, and/or serially during routine clinical follow-up from September 19, 2019, to February 21, 2022. ctDNA detection was annotated to clinicopathologic features and recurrence-free survival.ResultsA total of 295 patients with EGC were analyzed, and 212 patients with stages I-III disease were further explored. Pretreatment ctDNA was detected in 96% (23/24) of patients with preoperative time points. Postoperative ctDNA was detected in 23.5% (16/68) of patients with stage I-III EGC within 16 weeks (molecular residual disease window) after surgery without receiving systemic therapy. ctDNA detection at any time point after surgery (hazard ratio [HR], 23.6; 95% CI, 10.2 to 66.0; P < .0001), within the molecular residual disease window (HR, 10.7; 95% CI, 4.3 to 29.3; P < .0001), and during the surveillance period (HR, 17.7; 95% CI, 7.3 to 50.7; P < .0001) was associated with shorter recurrence-free survival. In multivariable analysis, ctDNA status and clinical stage of disease were independently associated with outcomes.ConclusionUsing real-world data, we demonstrate that postoperative tumor-informed ctDNA detection in EGC is feasible and allows for enhanced patient risk stratification and prognostication during curative-intent therapy.

Although hormonal therapy (HT) inhibits the growth of hormone receptor-positive (HR+) breast and prostate cancers, HT resistance frequently develops within the complex metastatic microenvironment of the host organ (often the bone), a setting poorly recapitulated in 2D culture systems. To address this limitation, we cultured HR+ breast cancer and prostate cancer spheroids and patient-derived organoids in 3D extracellular matrices (ECM) alone or together with bone marrow stromal cells (BMSC). In 3D monocultures, antiestrogens and antiandrogens induced anoikis by abrogating anchorage-independent growth of HR+ cancer cells but exhibited only modest effects against tumor cells residing in the ECM niche. In contrast, BMSC induced hormone-independent growth of breast cancer and prostate cancer spheroids and restored lumen filling in the presence of HR-targeting agents. Molecular and functional characterization of BMSC-induced hormone independence and HT resistance in anchorage-independent cells revealed distinct context-dependent mechanisms. Cocultures of ZR75-1 and LNCaP with BMSCs exhibited paracrine IL6-induced HT resistance via attenuation of HR protein expression, which was reversed by inhibition of IL6 or JAK signaling. Paracrine IL6/JAK/STAT3-mediated HT resistance was confirmed in patient-derived organoids cocultured with BMSCs. Distinctly, MCF7 and T47D spheroids retained ER protein expression in cocultures but acquired redundant compensatory signals enabling anchorage independence via ERK and PI3K bypass cascades activated in a non-IL6-dependent manner. Collectively, these data characterize the pleiotropic hormone-independent mechanisms underlying acquisition and restoration of anchorage-independent growth in HR+ tumors. Combined analysis of tumor and microenvironmental biomarkers in metastatic biopsies of HT-resistant patients can help refine treatment approaches. SIGNIFICANCE: This study uncovers a previously underappreciated dependency of tumor cells on HR signaling for anchorage-independent growth and highlights how the metastatic microenvironment restores this malignant property of cancer cells during hormone therapy.

Sustainable banking practices have increased prominently in the recent times as financial institutions realises the importance of integrating ESGs into their businesses. This paper aims to examine various sustainable banking practices that includes sustainable lending, green finance, responsible banking and also examines their contribution towards sustainable development and financial stability. The paper aims to insights the effectiveness of sustainable banking practices in promoting environmental sustainability, social inclusion and long term financial resilience.

The research study was pursued with an attempt to Study the Role of Psychological Contract in the Employees Engagement with specific objectives of Learning the Role of Psychological Contract in the Employees Engagement, identifying the numerousmagnitudes of Employee Engagement, studying the impact of Psychological Contract on every aspect of Employee Engagement and studying the impact of age, tenure and gender on Employee Engagement. Stratified random sampling technique was adopted as means of data collection from 600 full-time employees working in private HEI in Uttarakhand using structured and self-administered questionnaires: PC Questionnaire and ER Questionnaire checking their validity and reliability. The need of the study was to establish relationship between employee engagement or retention with the psychological contracts and the outcomesestablish the same.Many Organisations willantagonize difficulties in the coming years. Major amongst the most imperiousproblems will be procuring, preparing, overseeing and holding millennial employees. A theoretical commitment of this examination is that it joins two territories of research not already explored together with regards to establishments; psychological contracts and worker retention. The outcomes show that there is a solid connection between psychological contract satisfaction and employee engagement, however the relationship does not seem, by all accounts, to be directed by some other factor, for example, age, gender or tenure. Following specific results were from a practical perspective, there is a growing interest in understanding employee engagement, as it is perceived that the growth and prosperity of organizations will rely heavily on the committed and competent workforce. The suggestion that the relationship between PCfulfilment and ER are positively related irrespective of age and gender is indicative of the fact that management need to pay more focus on the fulfilment of motivating psychological contract rather than adherence to merely hygiene factors.