Silencing KLF16 inhibits oral squamous cell carcinoma cell proliferation by arresting the cell cycle and inducing apoptosis

Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.     

免疫检查点抑制剂应用于晚期胃癌治疗的研究进展

我国属胃癌高发国家,且以进展期胃癌为主。以手术和化疗为主的多学科治疗无法有效改善晚期胃癌患者的预后。近年来,免疫检查点抑制剂类药物的疗效在诸多癌症中得到了证实,因此,该类药物在胃癌中的治疗效果也受到了广泛的关注。本文对近年来的相关研究成果进行综述,全面介绍了免疫检查点抑制剂类药物在胃癌治疗中的临床应用情况、联合用药情况以及不良反应。对于其他治疗均失败的晚期胃癌患者,PD-1抑制剂是一个可行的治疗选项,其代表药物派姆单抗是目前唯一被美国食品药品监督管理局批准应用于胃癌治疗的免疫抑制剂类药物,而我国国家食品药品监督管理总局尚未批准任何此类药物应用于胃癌的临床治疗。如何进一步提高治疗的客观缓解率,将会是后续临床和基础研究的一大焦点。     

Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

晚期肺癌化疗患者医院感染的病原学与危险因素分析

目的研究晚期肺癌化疗患者发生医院感染的病原学特点,分析其危险因素,降低晚期肺癌化疗患者医院感染率。方法选择2012年1月-2015年12月收治的532例晚期肺癌化疗患者为研究对象,采集患者痰液或呼吸道分泌物标本进行细菌培养,应用SAS 9.3软件进行统计分析,并分析晚期肺癌化疗患者发生医院感染的危险因素。结果 125例晚期肺癌化疗患者发生医院感染,感染率为23.50%,其主要感染部位为呼吸道、胃肠道、口腔黏膜,分别占52.00%、15.20%、14.40%;共分离病原菌104株,其中革兰阴性菌51株占49.04%、革兰阳性菌30株占28.85%、真菌23株占22.11%;logistics回归显示,住院时间长、接受侵入性操作、使用抗菌药物是晚期肺癌化疗患者发生医院感染的危险因素。结论晚期肺癌化疗患者医院感染率较高,主要病原菌以革兰阴性菌为主,通过缩短患者住院时间、减少侵入性操作、合理使用抗菌药物等措施,降低晚期肺癌化疗患者医院感染的发生。     

Clinical analysis of peritoneal dialysis in the treatment of rapidly progressive glomerulonephritis

Objective To observe the clinical characteristics and prognosis of patients with rapidly progressive glomerulonephritis (RPGN) caused by lupus nephritis, antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, or primary glomerulonephritis who were treated with peritoneal dialysis (PD) and then withdrew PD because of renal recovery. Methods Data of the above patients were retrospectively analyzed. The patients were diagnosed as RPGN and received PD therapy in Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University from February 2009 to August 2018. The patients were divided into early withdrawal group (PD time≤183 days, n=24) and late withdrawal group (PD time＞183 day, n=24). The differences of clinical characteristics between the two groups were compared. The cumulative incidence of adverse events in both groups was analyzed using Kaplan-Meier curves. Cox proportional hazards model was used to analyze the risk factors influencing the prognosis of patients. Results Forty-eight RPGN patients were included. The median time of maintaining PD was 178(76, 378) days. Compared with the late withdrawal group, the patients in early withdrawal group had lower levels of urine volume, serum albumin and parathyroid hormone, and lower rates of gross hematuria and hypertension at the beginning of PD, and received higher rates of methylprednisolone impulse, combined immunosuppressive agents, and hemodialysis or continuous renal replacement therapy (all P＜0.05). At the time of PD withdrawal, the levels of serum creatinine, serum calcium, serum albumin and parathyroid hormone in the early withdrawal group were significantly lower than those in the late withdrawal group (all P＜0.05). The Kaplan-Meier curves showed that there was no significant difference in the cumulative survival of patients in both groups (log-rank test χ2=3.485, P=0.062). Cox regression analysis revealed serum creatinine≥209 μmol/L at the time of PD withdrawal was an independent risk factor for poor prognosis (HR=5.253，95%CI 1.757-15.702, P=0.003). Conclusions PD can be used for RPGN patients caused by lupus nephritis, ANCA-associated vasculitis and primary nephritis. Serum creatinine≥209 μmol/L at the time of PD withdrawal is an independent risk factor for poor prognosis.