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.     

Performance of the Rapidec®Carba NP assay for the detection of different carbapenemases in Klebsiella pneumoniae and Escherichia coli strains

PurposeThe spread of infections caused by Enterobacterales strains resistant to carbapenems is a global public health problem, and early detection of carbapenemases is very important to prevent their spread. The rapid detection of carbapenemase production with the new commercial assay Rapidec® Carba NP test is based on the biochemical detection of imipenem hydrolysis. Our study aims to evaluate the performance of the Rapidec® Carba NP test in OXA-48 positive isolates highly prevalent in our country and also in isolates with more than one carbapenemase gene that have an increased prevalence and to examine whether it can be used for confirmation of carbapenemase positivity in the routine laboratory.MethodsA total of 97 strains of 94 carbapenem-resistant Klebsiella pneumoniae and three carbapenem-resistant Escherichia coli isolated from various clinical specimens were included in the study. The results of the Rapidec® Carba NP assay were compared with those obtained by the multiplex PCR test.ResultsThe sensitivity of the Rapidec® Carba NP test was 97.8% for all carbapenemase-positive isolates. Of 90 PCR positive isolates, one OXA-48 and one OXA-48 ?+ ?NDM positive isolates were negative with Rapidec® Carba NP test.ConclusionsThe positive results detected by the Rapidec® Carba NP test make an important contribution to the early detection of carbapenemase production and infection control practices. Since two carbapenemase positive isolates were found to be negative with the Rapidec® Carba NP test in our study, it was concluded that negative results of carbapenem-resistant isolates obtained with this assay should be confirmed with an additional carbapenemase detection method to exclude false-negative results.     

Analysis of AcrB in Klebsiella pneumoniae reveals natural variants promoting enhanced multidrug resistance

Infections caused by Klebsiella pneumoniae are often difficult to manage due to the high frequency of multidrug resistance, often conferred by efflux pumps. In this study, we analyzed sequence variations of the major RND family multidrug efflux pump AcrB from 387 assembled K. pneumoniae genomes. We confirm that AcrB is a highly-conserved efflux pump in K. pneumoniae, and identified several variants that were prevalent in clinical isolates. Molecular dynamics analyses on two of these variants (L118M and S966A) suggested conformational changes that may correlate with increased drug efflux capabilities. The L118M change resulted in enhanced protein rigidity while the flexibility of drug binding pockets was stable or increased, and the interactions between the proximal pockets and water molecules were stronger. For S966A, the significantly enlarged proximal pocket suggested higher drug accommodation ability. Consistent with these predictions, the L118M and S966A variants conferred a slightly increased ability to grow in the presence of tetracycline and to survive cefoxitin exposure when overexpressed. In summary, our results suggest that the emergence of enhanced-function AcrB variants may be a potential risk for increased antibiotic resistance in clinical K. pneumoniae isolates.