Roles of the tumor microenvironment in the resistance to programmed cell death protein 1 inhibitors in patients with gastric cancer

Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advanced GC.In recent years,with the progress in tumor immunology research,attention has shifted toward immunotherapy as a therapeutic approach for GC.Programmed cell death protein 1(PD-1)inhibitors,as novel immunosuppressive medications,have been widely utilized in the treatment of GC.However,many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy.To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy,to maximize the clinical activity of immunosuppressive drugs,and to elicit a lasting immune response,it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients.This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment,aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.

Experimental study on operative methods of pancreaticojejunostomy with reference to anastomotic patency and postoperative pancreatic exocrine function

AIM:To assess the patency of pancreaticoenterostomy and pancreatic exocrine function after three surgical methods. METHODS: A pig model of pancreatic ductal dilation was made by ligating the main pancreatic duct. After 4 wk ligation, a total of 36 piglets were divided randomly into four groups. The piglets in the control group underwent laparotomy only; the others were treated by three anastomoses: (1) end-to-end pancreaticojejunostomy invagination (EEPJ); (2) end-to-side duct-to- mucosa sutured anastomosis (ESPJ); or (3) binding pancreaticojejunostomy (BPJ). Anastomotic patency was assessed after 8 wk by body weight gain, intrapancreatic ductal pressure, pancreatic exocrine function secretin test, pancreatography, and macroscopic and histologic features of the anastomotic site. RESULTS: The EEPJ group had significantly slower weight gain than the ESPJ and BPJ groups on postoperative weeks 6 and 8 (P < 0.05). The animals in both the ESPJ and BPJ groups had a similar body weight gain.Intrapancreatic ductal pressure was similar in ESPJ and BPJ. However, pressure in EEPJ was significantly higher than that in ESPJ and BPJ (P < 0.05). All three functional parameters, the secretory volume, the flow rate of pancreatic juice, and bicarbonate concentration, were significantly higher in ESPJ and BPJ as compared to EEPJ (P < 0.05). However, the three parameters were similar in ESPJ and BPJ. Pancreatography performed after EEPJ revealed dilation and meandering of the main pancreatic duct, and the anastomotic site exhibited a variable degree of occlusion, and even blockage. Pancreatography of ESPJ and BPJ, however, showed normal ductal patency. Histopathology showed that the intestinal mucosa had fused with that of the pancreatic duct, with a gradual and continuous change from one to the other. For EEPJ, the portion of the pancreatic stump protruding into the jejunal lumen was largely replaced by cicatricial fibrous tissue. CONCLUSION: A mucosa-to-mucosa pancreatico- jejunostomy is the best choice for anastomotic patency when compared with EEPJ. BPJ can effectively maintain anastomotic patency and preserve pancreatic exocrine function as well as ESPJ.

Radiofrequency ablation for hepatic hemangiomas: A consensus from a Chinese panel of experts

Recent studies have shown that radiofrequency(RF) ablation therapy is a safe, feasible, and effective procedure for hepatic hemangiomas, even huge hepatic hemangiomas. RF ablation has the following advantages in the treatment of hepatic hemangiomas: minimal invasiveness, definite efficacy, high safety, fast recovery, relatively simple operation, and wide applicability. It is necessary to formulate a widely accepted consensus among the experts in China who have extensive expertise and experience in the treatment of hepatic hemangiomas using RF ablation, which is important to standardize the application of RF ablation for the management of hepatic hemangiomas, regarding the selection of patients with suitable indications to receive RF ablation treatment, the technical details of the techniques, therapeutic effect evaluations, management of complications, etc. A final consensus by a Chinese panel of experts who have the expertise of using RF ablation to treat hepatic hemangiomas was reached by means of literature review, comprehensive discussion, and draft approval.

MicroRNAs of bone marrow mesenchymal stem cell-derived exosomes regulate acute myeloid leukemia cell proliferation and apoptosis

Background:Acute myeloid leukemia(AML)is a malignant hematological disease,originating from hematopoiesis stem cell differentiation obstruction and clonal proliferation.New reagents or biologicals for the treatment of AML are urgently needed,and exosomes have been identified as candidate biomarkers for disease diagnosis and prognosis.This study aimed to investigate the effects of exosomes from bone marrow mesenchymal stem cells(BMSCs)on AML cells as well as the underlying microRNA(miRNA)-mediated mechanisms.Methods:Exosomes were isolated using a precipitation method,followed by validation using marker protein expression and nanoparticle tracking analysis.Differentially expressed miRNAs were identified by deep RNA sequencing and confirmed by quantitative real-time polymerase chain reaction(qPCR).Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt method,and cell cycle progression and apoptosis were detected by flow cytometry.Functional gene expression was analyzed by qPCR and Western blotting(WB).Significant differences were determined using Student’s t test or analysis of variance.Results:BMSCs-derived exosomes effectively suppressed cell proliferation(both P<0.0001 at 10 and 20μg/mL)and cell cycle progression(P<0.01 at G0-G1 stage),and also significantly enhanced cell apoptosis(P<0.001)in KG-1a cells.There were 1167 differentially expressed miRNAs obtained from BMSCs-derived exosomes compared with KG-1a cell-derived exosomes(P<0.05).Knockdown of hsa-miR-124-5p in BMSCs abrogated the effects of BMSCs-derived exosomes in regulating KG-1a such as the change in cell proliferation(both P<0.0001 vs.normal KG-1a cell[NC]at 48 and 72 h).KG-1a cells treated with BMSCs-derived exosomes suppressed expression of structural maintenance of chromosomes 4(P<0.001 vs.NC by qPCR and P<0.0001 vs.NC by WB),which is associated with the progression of various cancers.This BMSCs-derived exosomes effect was significantly reversed with knockdown of hsa-miR-124-5p(P<0.0001 vs.NC by WB).Conclusions:BMSCs-derived exosomes suppress cell proliferation and cycle progression and promote cell apoptosis in KG-1a cells,likely acting through hsa-miR-124-5p.Our study establishes a basis for a BMSCs-derived exosomes-based AML treatment.