CRF促进大鼠垂体释放MSH

最近对绵羊促肾上腺皮质激素释放因子(CRF)结构的阐明,为研究控制垂体—肾上腺皮质对应激性刺激的反应机理开辟了新途径。无论在体大鼠还是离体的腺垂体细胞,CRF都是促进促肾上腺皮质激素(ACTH)分泌的强烈刺激物。     

GABA直接作用MSH细胞:影响激素释放

最近,从大鼠的免疫组织化学观察中指出,对     

结直肠癌P27表达与Ki-67、P170、MLH1、MSH2、MSH6的关系及意义

目的:探讨P27表达与结直肠癌侵袭转移、多药耐药及预后的关系,并初步分析其机制.方法:随机选取北京大学肿瘤医院结直肠外科2008-03/2012-03收治的散发性结直肠癌患者263例,所有病例均经组织学证实,全部肿瘤病例术前均未行放化疗.应用免疫组织化学SP法检测大肠癌组织中P27、Ki-67、P170、MLH1、MSH2和MSH6的表达;并结合其临床病理特征进行回顾性分析.结果:P27、Ki-67、P170、MLH1、MSH2和MSH6在结直肠癌组织中的阳性表达率依次为71.1%、81.4%、82.5%、86.7%、87.8%和71.1%.P27蛋白表达与患者性别、年龄、肿瘤的大体形态无关;而其表达缺失与肿瘤的大小、部位、分化类型、侵袭深度、脉管癌栓和淋巴结转移密切相关.P27表达与Ki-67(r=-0.315,P=0.00)、P170(r=-0.163,P=0.01)呈明显的负相关.而P27与MLH1(r=0.129,P=0.03)、MSH2(r=0.136,P=0.03)、MSH6(r=0.159,P=0.01)的表达均呈明显的正相关.结论:P27蛋白与结直肠癌发生发展、侵袭转移密切相关,其状态与结直肠癌MSI状态密切相关.P27蛋白的检测可以作为一个反映结直肠癌疾病进展的重要指标,并对临床化疗用药和预防多药耐药具有一定的指导意义.     

Tolerance of human MSH2+/? lymphoblastoid cells to the methylating agent temozolomide

Members of hereditary nonpolyposis colon cancer (HNPCC) families harboring heterozygous germline mutations in the DNA mismatch repair genes hMSH2 or hMLH1 present with tumors generally two to three decades earlier than individuals with nonfamilial sporadic colon cancer. We searched for phenotypic features that might predispose heterozygous cells from HNPCC kindreds to malignant transformation. hMSH2(+/-) lymphoblastoid cell lines were found to be on average about 4-fold more tolerant than wild-type cells to killing by the methylating agent temozolomide, a phenotype that is invariably linked with impairment of the mismatch repair system. This finding was associated with an average 2-fold decrease of the steady-state level of hMSH2 protein in hMSH2(+/-) cell lines. In contrast, hMLH1(+/-) heterozygous cells were indistinguishable from normal controls in these assays. Thus, despite the fact that HNPCC families harboring mutations in hMSH2 or hMLH1 cannot be distinguished clinically, the early stages of the carcinogenic process in hMSH2 and hMLH1 mutation carriers may be different. Should hMSH2(+/-) colonocytes and lymphoblasts harbor a similar phenotype, the increased tolerance of the former to DNA-damaging agents present in the human colon may play a key role in the initiation of the carcinogenic process.     

组织芯片检测胃癌及癌前病变中错配修复基因MSH2的表达及意义

目的探讨MSH2在胃癌及癌前病变组织中的表达及意义。方法构建包含正常胃黏膜组织、肠化生、异型增生、胃癌组织的组织芯片,免疫组化技术研究MSH2从正常胃黏膜到胃癌组织的表达变化趋势。结果在正常胃黏膜、肠化、异型增生、胃癌中MSH2表达呈递增趋势。结论组织芯片具有高效、快速、低耗、自身内对照和可比性强的特点。MSH2在胃癌及癌前病变组织的表达与正常胃黏膜比较均有较大差异,与胃癌的演变密切相关,     

肺癌和癌前病变组织中FHIT、MSH2、p21蛋白表达及意义

目的探讨脆性组氨酸三联体（FHIT）、mutS同种组织蛋白2（MSH2）及p21蛋白表达在肺癌发生、发展中的意义。方法应用免疫组化SP法检测89份原发性肺癌组织（原发癌组）、12份淋巴结转移性肺癌组织（转移癌组）、12份肺癌癌前病变组织（癌前变组）及10份正常肺组织（对照组）中FHIT、MSH2及p21蛋白表达情况,分析各指标间相关性及其与肺癌临床病理参数的关系。结果与对照组比较,FHIT、MSH2及p21蛋白在其他三组中表达均下调（P〈0．05）;FHIT、MSH2蛋白表达与肺癌组织学类型、分化程度相关,p21蛋白表达与肺癌分化程度、临床分期及有无淋巴结转移有关（P均〈0．05）;FHIT和MSH2蛋白在原发癌组表达呈显著正相关（P〈0．01）,但均与p21蛋白表达无明显相关。结论FHIT、MSH2及p21蛋白与肺癌发生、发展有关,联合检测三项指标可为临床预测疾病进展提供依据。     

MTHFR、GSTP1、MSH3和ABCG1单核苷酸多态性与结直肠癌辅助化疗疗效和不良反应的相关性研究

目的探讨R0切除结直肠癌(colorectal cancer,CRC)患者MTHFR、GSTP1、MSH3和ABCG1单核苷酸多态性(single nucleotide polymorphisms,SNPs)与术后辅助化疗疗效和不良反应的关系。方法收集2010年8月至2012年3月在河南省肿瘤医院行R0切除的42例CRC患者,术后均接受mFOLFOX6或XELOX方案化疗,并在化疗前收集血样,应用Sanger测序法检测42例CRC患者MTHFR-rs1801131、GSTP1-rs1695、MSH3-rs863221和ABCG1-rs425215的基因型,所有患者术后随访5年,分析各位点基因多态性与患者预后及化疗相关不良反应的关系。结果仅MTHFR-rs1801131多态性与预后相关,MTHFR-rs1801131 AA基因型患者中位(disease-free survival,DFS)和(overall survival,OS)均显著长于AC/CC基因型(25个月vs 6.5个月,P=0.012;44.7个月vs 15.2个月,P=0.010)。GSTP1-rs1695多态性与胃肠道不良反应有关,AA基因型患者Ⅱ级及以上胃肠道不良反应发生率远高于AG/GG基因型(25.0%vs 0,P=0.040)。MSH3和ABCG1多态性与预后和不良反应之间无明显相关性。结论 MTHFR-rs1801131突变是R0切除CRC者辅助化疗效果较差的独立预测因子,GSTP1-rs1695突变患者化疗期间发生胃肠道不良反应更低。     

Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families： Implications for genetic testing

AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplifi cation (MLPA). RESULTS: Eighteen germline mutations (50%) were identifi ed, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the defi nite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam Ⅰ/Ⅱ criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family.CONCLUSION: Our study describes for the f irst time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population.     

Lynch综合征相关子宫内膜癌老年患者的临床特征及家系MSH2基因变异分析

目的研究Lynch综合征相关子宫内膜癌老年患者的临床特征及与家系MSH2基因变异的关系。方法回顾性分析我院收治的473例(2016年1月至2021年1月)老年子宫内膜癌患者临床资料, 采用DNA序列分析、实时定量PCR以及反转录PCR方法检测和验证MSH2基因变异。将患者分为Lynch综合征组、非Lynch综合征组, 比较两组患者临床病理学特征。结果 473例子宫内膜癌患者中共有46例(9.7%)患者存在MMR基因的胚系突变, 确诊为Lynch综合征, 其中MLH1、PMS2、MSH2、MSH6突变例数分别为18例、6例、24例、10例。MSH2基因共计3处突变, 7号外显子1380C>A、12号外显子2011A>G以及13号外显子2756A→AC。Lynch综合征者子宫内膜样腺癌G3级、子宫下段浸润、Lynch综合征相关恶性肿瘤史占比均明显高于非Lynch综合征患者(χ2=8.935, 8.303, 9.770, 均P<0.05)。结论子宫内膜样腺癌低分化、易浸润子宫下段、家族遗传性为Lynch综合征相关子宫内膜癌老年患者临床主要表现, MSH2基因变异为该类患者的...