Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer

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外泌体在肿瘤细胞与TAMs之间相互作用中“桥梁”和调控作用的研究进展北大核心

外泌体是一类直径为30~100 nm的圆盘囊泡,其内包含许多组分,诸如复杂RNA和蛋白质等,主要参与细胞间的信号转导。肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)是肿瘤微环境中普遍存在的巨噬细胞,通过对肿瘤生长、免疫逃逸、侵袭和转移、耐药性等多方面的作用影响肿瘤进程。外泌体在肿瘤相关巨噬细胞的招募、极化及抗肿瘤免疫调控等方面发挥着重要的调节功能。同时,TAMs以外泌体为媒介作用于肿瘤细胞,从而构成了外泌体、TAMs与肿瘤细胞之间相互作用的调控通路。综上所述,本文旨在阐明肿瘤细胞与TAMs之间,以外泌体为“桥梁”相互影响的潜在机制,以及靶向肿瘤细胞和TAMs来源的外泌体在恶性肿瘤治疗中的展望。     

Robotic-assisted central pancreatectomy: A minimally invasive approach for benign and low-grade lesions

BackgroundCentrally located pancreatic lesions are often treated with extended pancreaticoduodenectomy or distal pancreatectomy resulting in loss of healthy parenchyma and a high risk of diabetes and exocrine insufficiency. Robotic central pancreatectomy (RCP) is a parenchyma sparring alternative that has been shown safe and feasible [[1], [2]].MethodsIn this article, we describe our operative technique and the perioperative outcomes of a series of RCP for low-grade or benign pancreatic tumors.ResultsSix patients (5 female and 1 man) with a median age of 51.5 (44–68) years underwent a RCP for 2 serous cystadenomas, 2 mucinous cystic tumors, 1 neuroendocrine tumor, and 1 autoimmune pancreatitis. There were no conversions, intraoperative complications, or perioperative transfusions. Median operative time and was 240 (230–291) minutes and median blood loss was 100 (100–400) ml. The median hospital stay was 8 (5–27) days. There were no mortalities, reoperations, or readmissions. One patient developed a grade B pancreatic fistula which was successfully managed conservatively. All resections had free margins and the median tumor size was 2.5 (1.5–3.5) cm. After a mean follow-up of 46 months, no patients presented new-onset diabetes or exocrine insufficiency.ConclusionsRCP represents the least invasive option for both the patient and the pancreatic parenchyma. With a standardized technique, RCP results in low postoperative morbidity and excellent long-term pancreatic function. Although our results are excellent, POPF still represents the main complication of central pancreatectomy with an incidence ranging from 0 to 80% depending on multiple factors such as the surgeon, technique, and pancreatic texture.     

Special issue “The advance of solid tumor research in China”: Multi-omics analysis based on 1311 clear cell renal cell carcinoma samples identifies a glycolysis signature associated with prognosis and treatment response

In clear cell renal cell carcinoma (ccRCC), glycolysis is enhanced mainly because of the increased expression of key enzymes in glycolysis. Hence, the discovery of new molecular biomarkers for glycolysis may help guide and establish a precise system of diagnosis and treatment for ccRCC. Expression profiles of 1079 tumor samples of ccRCC patients (including 311 patients treated with everolimus or nivolumab) were downloaded from public databases. Proteomic profiles of 232 ccRCC samples were obtained from Fudan University Shanghai Cancer Center (FUSCC). Biological changes, tumor microenvironment and prognostic differences were explored between samples with various glycolysis characteristics. There were significant differences in CD8⁺ effector T cells, epithelial-to-mesenchymal transition and pan-fibroblast TGFb between the Low and High glyScore groups. The tumor mutation burden of the Low glyScore group was lower than that of the High glyScore group. And higher glyScore was significantly associated with worse overall survival (OS) in 768 ccRCC patients (P < .0001). External validation in FUSCC cohort also indicated that glyScore was of strong ability for predicting OS (P < .05). GlyScore may serve as a biomarker for predicting everolimus response in ccRCC patients due to its significant associations with progression-free survival (PFS). And glyScore may also predict overall survival in patients treated with nivolumab. We calculated the glyScore in ccRCC and the defined glyScore was of strong ability for predicting OS. In addition, glyScore may also serve as a biomarker for predicting PFS in patients treated with everolimus and could predict OS in patients treated with nivolumab.     

Implementing Real-World RECIST-based Tumor Response Assessment in Patients With Metastatic Non-small Cell Lung Cancer

BackgroundTo accelerate drug approvals while maintaining scientific rigor in the evaluation of a therapeutic's efficacy and safety, the United States Food and Drug Administration now considers real-world data (RWD) to support New Drug Applications and expanded indications. Response Evaluation Criteria in Solid Tumors (RECIST) are the gold standard in clinical trials, but the derivation of RECIST-based treatment response from RWD is unproven. This study investigated the feasibility of implementing RECIST criteria in RWD by comparing lung cancer response assessments from RECIST-based measurement of lesions on archived radiologic films with results from medical oncologist and radiologist narratives recorded in electronic health records (EHR).Materials and MethodsResponse to index treatment via different assessment approaches was compared among 30 metastatic non-small cell lung cancer (mNSCLC) patients receiving systemic treatment (index) after progression on a platinum or anti-PD(L)-1-containing regimen. Specifically, responses based on assessments documented in the medical oncologists’ narratives were compared to a radiologist's assessments of archived images using RECIST v1.1 criteria. Each patient's best overall response was characterized as complete or partial (CR/PR), stable disease (SD), progressive disease (PD), or not evaluable (NE).ResultsSimilar distributions of best overall response and substantial concordance (77%) between medical oncologist-reported and radiologist re-assessed responses were observed. There were no instances of CR/PR to PD or PD to CR/PR discordance.ConclusionsResults suggest that accurate treatment responses, similar to RECIST, may be derived using RWD. Further validation and improvement of real-world response assessment are needed to develop a scalable real-world approach for response assessment.     

Preoperative risk stratification of lymph node metastasis for non-functional pancreatic neuroendocrine neoplasm: An international dual-institutional study

Background/Objectives: Although the presence of lymph node metastasis (LNM) defines malignant potential, preoperative prediction of LNM has not been established for non-functional pancreatic neuroendocrine neoplasm (NF-PNEN). We sought to develop a prediction system using only preoperatively available factors that would stratify the risk of LNM for NF-PNEN.MethodsWe retrospectively reviewed patients who underwent R0/1 resection of NF-PNEN at Kyoto University (2007–2019) and the University of California, San Francisco (2010–2019). Risk stratification of LNM was developed using preoperative factors by the logistic regression analysis. Long-term outcomes were compared across the risk groups.ResultsA total of 131 patients were included in this study. Lymph nodes were pathologically examined in 116 patients, 23 (20%) of whom had LNM. Radiological tumor size [1.5–3.5 cm (odds ratio: 13.5, 95% confidence interval: 1.77–398) and >3.5 cm (72.4, 9.06–2257) against ≤1.5 cm], <50% cystic component (8.46 × 10^6, 1.68 × 10^106-), and dilatation of main pancreatic duct ≥5 mm (31.2, 3.94–702) were independently associated with LNM. When patients were classified as the low-risk (43 patients), intermediate-risk (44 patients), and high-risk groups (29 patients), proportions of LNM differed significantly across the groups (0%, 14%, and 59%, respectively). Recurrence-free survival (RFS) of the low- and intermediate-risk groups were significantly better than that of the high-risk group (5-year RFS rates of 92.2%, 85.4%, and 47.1%, respectively).ConclusionsThe prediction system using preoperative radiological factors stratifies the risk of LNM for NF-PNEN. This stratification helps to predict malignant potential and determine the surgical procedure and necessity of regional lymphadenectomy.