生长因子颗粒蛋白前体和肿瘤坏死因子受体基因启动子区改变与阿尔茨 海默病的相关性研究

目的:探讨生长因子颗粒蛋白前体(PGRN)、肿瘤坏死因子受体(TNFR)基因启动子区改变以及全基因组DNA甲基化与阿尔茨海默病的相关性。方法:收集阿尔茨海默病患者血液样本80例以及健康对照血液样本80例,PCR扩增PGRN和TNFR基因启动子区并进行测序,观察两组间的单核苷酸多态性位点是否有差异。同时,用甲基化特异性PCR法检测启动子区DNA甲基化情况以及用ELISA法检测全基因组DNA甲基化水平。结果:在TNFR基因启动子区域发现阿尔茨海默病和对照组之间在多态性位点rs4149570和rs4149569有显著性差异(P0.001和P=0.033)。阿尔茨海默病患者全基因组甲基化水平为(0.79±0.29)%,显著低于对照组的(1.00±0.36)%(P0.001)。结论:TNFR基因多态性位点rs4149570和rs4149569的变异可能与阿尔茨海默病相关,全基因组甲基化水平降低可能与阿尔茨海默病相关。     

成纤维细胞激活蛋白alpha与肿瘤免疫抑制的研究进展

成纤维细胞激活蛋白alpha（Fibroblast activation protein-alpha,FAP-alpha）是一种跨膜丝氨酸蛋白酶,高度表达在90 %的上皮性肿瘤的 间质--肿瘤相关成纤维细胞（Tumor association fibroblast,TAF）上。FAPalpha在促进上皮性肿瘤的恶性进展中起着十分重要的作用, 近年来研究发现,FAP琢在肿瘤微环境中发挥免疫抑制的作用。研究FAPalpha在肿瘤免疫抑制中的作用,已成为肿瘤研究的新的热 点。为基于以FAP-alpha为靶标的抗肿瘤免疫治疗提供参考,本文围绕引起肿瘤免疫抑制的因素、FAPalpha与肿瘤免疫抑制的研究进展 以及FAP-alpha在肿瘤的发展进程的作用作一综述。     

Glypican-5 is a tumor suppressor in non-small cell lung cancer cells

Glypican-5 (GPC5) belongs to the glypican family of proteoglycans that have been implicated in a variety of physiological processes, ranging from cell proliferation to morphogenesis. However, the role of GPC5 in human cancer remains poorly understood. We report that knockdown of GPC5 in bronchial epithelial cells promoted, and forced expression of GPC5 in non-small lung cancer (NSCLC) cells suppressed, the anchorage-independent cell growth. In vivo, expression of GPC5 inhibited xenograft tumor growth of NSCLC cells. Furthermore, we found that GPC5 was expressed predominantly as a membrane protein, and its expression led to diminished phosphorylation of several oncogenic receptor tyrosine kinases, including the ERBB family members ERBB2 and ERBB3, which play critical roles in lung tumorigenesis. Collectively, our results suggest that GPC5 may act as a tumor suppressor, and reagents that activate GPC5 may be useful for treating NSCLC.     

Synthesis and proapoptotic activity of oleanolic acid derived amides

Thirty-one different 3-O-acetyl-OA derived amides have been prepared and screened for their cytotoxic activity. In the SRB assays nearly all the carboxamides displayed good cytotoxicity in the low μM range for several human tumor cell lines. Low EC₅₀ values were obtained especially for the picolinylamides 14–16, for a N-[2-(dimethylamino)-ethyl] derivative 27 and a N-[2-(pyrrolinyl)-ethyl] carboxamide 28. These compounds were submitted to an extensive biological testing and proved compound 15 to act mainly by an arrest of the tumor cells in the S phase of the cell cycle. Cell death occurred by autophagy while compounds 27 and 28 triggered apoptosis.     

Emerging power of proteomics for delineation of intrinsic tumor subtypes and resistance mechanisms to anti-cancer therapies

Introduction: Despite extreme genetic heterogeneity, tumors often show similar alterations in the expression, stability, and activation of proteins important in oncogenic signaling pathways. Thus, classifying tumor samples according to shared proteomic features may help facilitate the identification of cancer subtypes predictive of therapeutic responses and prognostic for patient outcomes. Meanwhile, understanding mechanisms of intrinsic and acquired resistance to anti-cancer therapies at the protein level may prove crucial to devising reversal strategies.

Areas covered: Herein, we review recent advances in quantitative proteomic technology and their applications in studies to identify intrinsic tumor subtypes of various tumors, to illuminate mechanistic aspects of pharmacological and oncogenic adaptations, and to highlight interaction targets for anti-cancer compounds and cancer-addicted proteins.

Expert commentary: Quantitative proteomic technologies are being successfully employed to classify tumor samples into distinct intrinsic subtypes, to improve existing DNA/RNA based classification methods, and to evaluate the activation status of key signaling pathways.     

PLK1 与妇科肿瘤的研究进展

人类肿瘤生成过程由很多复杂环节组成,其主要现象表现为细胞分裂增殖的失调控生长。细胞分裂都必须按照正常细胞程序的每一个步骤进行才能保证机体的正常运转,细胞周期依赖分子PLK1是调节正常细胞有丝分裂、胞质分裂,以及对DNA受损伤后进行一系列反应调节的重要因子。它在细胞周期中的作用已有多位学者共同认识,当细胞失调控时检测到PLK1存在过量的表达,同时大量研究表明,人类PLK1基因不仅在多种已发现的恶性肿瘤中有此现象,而且在一些肿瘤中,它关系到这些肿瘤的发生发展及预后,被认为其可能成为一种新的肿瘤标志物,还可作为肿瘤定向分子靶向治疗中的一个有效目的基因的靶点,并且近年来对PLK1在肿瘤基因蛋白靶向治疗方面的药物研究开发已经成为学者研究的一个热点方向,该文对近年来PLK1在肿瘤生成中的作用,特别是其与妇科肿瘤关系方面的一些研究进展予以以下阐述。     

TL1A increased IL-6 production on fibroblast-like synoviocytes by preferentially activating TNF receptor 2 in rheumatoid arthritis

TNF-like protein 1A (TL1A), a member of tumor necrosis factor family, recognized as a ligand of death receptor 3 (DR3) and decoy receptor 3 (DcR3). The interaction of TL1A and DR3 may participate in the pathogenesis of some autoimmune diseases including rheumatoid arthritis (RA). Our previous results showed that high concentrations of TL1A could be found in synovial and serum in RA patients, and it was correlated with disease severity. In addition, TL1A could promote Th17 differentiation induced by TGF-β and IL-6 and increased the production of IL-17A. In the present study, we found that TL1A could promote the expression of IL-6 on fibroblast-like synoviocytes (FLS) of RA patients via NF-κB and JNK signaling pathway. TL1A-stimulated FLS increased the percentage of Th17 of peripheral blood mononuclear cells (PBMC) in RA via the production of IL-6, a critical cytokine involved in the differentiation of Th17. Moreover, the blocking of tumor necrosis factor receptor 2 (TNFR2) decreased TL1A-stimulated IL-6 production by RA FLS. Our results suggest that TL1A was capable of acting on RA FLS to elevate IL-6 expression, which promoted the production of Th17. More importantly, we showed that TL1A could influence RA FLS through binding to TNFR2 rather than DR3 on FLS, which indicated that the treatment of TNF inhibitors not only blocked the TNF but also suppressed the TL1A in RA patients.     

超声联合钼靶X线对直径小于1 cm的乳腺癌诊断价值分析

目的:探讨超声联合钼靶X线对直径小于1 cm的乳腺癌诊断价值。方法:选择我院2012年1月至2017年12月收治的66例乳腺疾病患者,所有患者术前均经钼靶X线及彩色多普勒超声检查,分析其病理结果,分析钼靶X线、彩色多普勒超声及二者联合对乳腺肿块的检查结果(边缘毛刺征、血管、淋巴结、微小钙化),比较其对乳腺癌的灵敏度、特异度、准确度、阳性预测值及阴性预测值。结果:66例患者中,经病理检查发现恶性肿瘤34例,良性肿瘤32例。与病理检测相比,彩色多普勒超声联合钼靶X线对乳腺肿块的良恶性检出率无差异性(P0.05),而彩色多普勒超声,钼靶X线的良恶性检出率均显著降低(P0.05)。彩色多普勒超声与钼靶X线良恶性检出率对比无差异(P0.05),但均低于彩色多普勒超声联合钼靶X线的检出率(P0.05)。彩色多普勒超声与钼靶X线对乳腺癌的边缘毛刺征的检出率对比无统计学意义(P0.05);彩色多普勒超声对血管和淋巴结的检出率明显高于钼靶X线,而微小钙化的检出率明显低于钼靶X线,对比差异有统计学意义(P0.05)。彩色多普勒超声联合钼靶X线的灵敏度、特异度、准确度、阳性预测值及阴性预测值均明显高于彩色多普勒超声及钼靶X线(P0.05),钼靶X线及彩色多普勒超声间对比无统计学意义(P0.05)。结论:彩色多普勒超声与钼靶X线对直径小于1 cm乳腺癌的诊断各有优势,二者联合应用的诊断价值优于单一诊断方法。     

呼吸窘迫综合征早产儿血清VA、PCT、TNF-α及CRP水平的表达及临床意义

目的:探讨呼吸窘迫综合征(RDS)早产儿血清维生素A(VA)、降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)及C反应蛋白(CRP)水平的表达及临床意义。方法:选取2015年2月～2018年5月期间青岛市妇女儿童医院收治的90例RDS早产儿纳入观察组,根据RDS分级将观察组分为轻度组48例,中重度组42例。另选取同期于本院出生的非RDS早产儿35例作为对照组。根据血清VA水平将125例早产儿分为VA缺乏组(n=72),亚临床VA缺乏组(n=36),正常组(n=17)。比较观察组与对照组、轻度组与中重度组早产儿血清VA、PCT、TNF-α及CRP水平,比较不同血清VA水平早产儿的RDS发病情况,分析观察组早产儿血清VA与PCT、TNF-α及CRP水平的相关性。结果:观察组早产儿血清VA水平明显低于对照组(P0.05),而观察组早产儿血清PCT、TNF-α、CRP明显高于对照组(P0.05)。中重度组早产儿血清VA水平与轻度组比较差异无统计学意义(P0.05),而中重度组早产儿血清PCT、TNF-α、CRP水平明显高于轻度组(P0.05)。随着血清VA水平的升高,RDS发病率逐渐降低,组间比较差异有统计学意义(P0.05)。Pearson相关性分析显示,观察组早产儿血清VA与PCT、TNF-α及CRP水平无显著相关性(P0.05)。结论:RDS早产儿血清VA与PCT、TNF-α及CRP水平均存在明显异常,但四者无明显相关性,血清VA相对较低者更易发生RDS,临床可通过及时干预VA水平以降低RDS的发生风险。