弥漫性大B细胞淋巴瘤组织CMYC、叉头框转录蛋白1、ki-67蛋白表达及临床意义

摘要 目的：探讨弥漫性大B细胞淋巴瘤（DLBCL）组织CMYC、叉头框转录蛋白1（FOXP1）、ki-67蛋白表达及临床意义。方法：选择2013年2月～2018年1月我院收治的DLBCL患者100例,以免疫组织化学法分别检测DLBCL组织及癌旁组织中CMYC、FOXP1、ki-67蛋白表达情况,并分析DLBCL组织中上述蛋白表达和患者临床病理特征的关系。此外,对所有患者均进行为期2年的随访观察,将其按照生存情况分成存活组69例和死亡组31例,比较两组CMYC、FOXP1、ki-67蛋白表达情况。结果：DLBCL组织CMYC、FOXP1、ki-67蛋白阳性表达率均高于癌旁组织（P＜0.05）。国际预后指数（IPI）评分为3～4分的患者DLBCL组织CMYC蛋白阳性表达率低于IPI评分为0～2分的患者（P＜0.05）。病理分型为生发中心B细胞来源（GCB）、IPI评分为3～4分的患者DLBCL组织FOXP1蛋白阳性表达率分别低于病理分型为非生发中心B细胞来源（non-GCB）、IPI评分为0～2分的患者（P＜0.05）。年龄＜60岁、Ann Arbor分期为Ⅰ～Ⅱ期、IPI评分为3～4分的患者DLBCL组织ki-67蛋白阳性表达率分别低于年龄≥60岁、Ann Arbor分期为Ⅲ期、IPI评分为0～2分的患者（P＜0.05）。死亡组CMYC、FOXP1、ki-67蛋白阳性表达率均高于存活组（P＜0.05）。结论：DLBCL组织CMYC、FOXP1、ki-67蛋白表达均与IPI评分关系密切,FOXP1蛋白表达与病理分型有关,而ki-67蛋白表达与年龄以及Ann Arbor分期有关,DLBCL患者不良预后可能与上述三项蛋白阳性表达率的异常升高有关。     

HER-2/neu Cancer Vaccines: Present Status and Future Prospects

Immunotherapeutic approaches to cancer should focus on novel undertakings that modulate immune responses by synergistic enhancement of anti-tumor immunological parameters. Cancer vaccines should preferably be composed of multiple defined tumor antigen specific B- and T-cell epitopes. The main focus of this article is to briefly review the present status of Her-2/neu vaccine strategies and to describe the innovative strategies developed in my laboratory for a vaccine against HER-2/neu (ErbB-2) with emphasis on the humoral arm of the immune response. Elucidating the underlining mechanisms of anti-tumor effects elicited by peptide vaccines against a self-protein is a requirement for developing an immunotherapeutic strategy that might be effective in human cancer vaccines. Our approach entails the identification of biologically relevant epitopes, establishing relevant in vitro assays for monitoring vaccine efficacy, devising strategies to engineer conformationally dependent sequences, developing highly immunogenic vaccines for an outbred population and delivering the immunogen/vaccine in a safe and efficacious vehicle, utilizing transgenic animal models for assessing tumor development, and developing challenge models using transplantable tumors to study efficacy of vaccine constructs. We have developed a multi-HER-2/neu B-cell epitope approach and shown in preclinical studies that immunization with a combination of two B-cell epitope was more effective in preventing mammary tumors than a single epitope. We have translated that work to the clinic (OSU 0105) in an FDA approved, NCI sponsored “Phase 1 Active Immunotherapy trial with Chimeric and Multi-epitope based peptide vaccine targeting HER-2 oncoprotein and nor-MDP adjuvant in patients with metastatic and/or recurrent solid tumors” at the James Cancer Hospital at the Ohio State University. The correlation between overexpression of HER-2/neu and up-regulation of VEGF has been demonstrated in breast cancer patients. Thus, blocking angiogenesis is an attractive strategy to inhibit tumor growth, invasion, and metastasis. The hypothesis that combination of anti-angiogenic therapy and tumor immunotherapy of cancer may be synergistic is an important future goal. In this review, I will discuss insights into our preclinical studies that might aid in the design of the next generation of cancer vaccines and become an integrated component of prophylactic/preventive and therapeutic approach.     

Micro-scale flow cytometry-based and biochemical analysis of lipid signaling in primary B cell subpopulations

B cell subpopulations in the spleen have been extensively characterized phenotypically; however, biochemical properties of these cell populations following B cell antigen receptor engagement have not been fully determined due to technical difficulties and limiting cell numbers. We therefore employed mini-scale protocols to assess lipid signaling, particularly that of diacylglycerol and inositol trisphosphate, with as few as 0.5×10⁶ purified early (T1) and late (T2) transitional B cells. Additionally, utilizing flow cytometric techniques, we determined levels of phosphatidylinositol bisphosphate and calcium mobilization in T1 and T2 cells, as well as mature follicular and marginal zone B cells using less than 1×10⁶ primary B cells. Thus, these biochemical and flow cytometric methodologies can be used to analyse signal-induced changes in phosphatidylinositol bisphosphate levels, diacylglycerol and inositol triphosphate production and calcium in each B cell population. These authors contributed equally.     

β细胞与2型糖尿病

非胰岛素依赖型糖尿病(non-insulin-dependent diabetes mellitus,NIDDM)的发病机理尚未完全明了,通常认为胰岛素抵抗(insulin resistance,IR)和β细胞功能不全是两个主要因素。肥胖是NIDDM的早期诱因,它同时引起IR和β细胞功能不全。在同样的诱因下。易感人群将很快发展成NIDDM。NIDDM与环境和遗传都密切相关。