MSH2 is required for cell proliferation, cell cycle control and cell invasiveness in colorectal cancer cells

We have investigated the role of MSH2,a mismatch repair gene in cell proliferation,cell cycle control and cell invasiveness in the SW480 human colorectal cancer cell line.RNAi-mediated inhibition of MSH2 expression was achieved using MSH2 shRNA lentiviral expression vectors.Effective knockdown of endogenous MSH2 expression was determined by real-time PCR analysis.The most efficient MSH2 knockdown vector was selected for subsequent studies using SW480 cells.Endogenous MSH2 mRNA levels decreased after lentiviral delivery of the MSH2-RNAi,indicating efficient silencing of MSH2 expression in SW480 cells.Cell proliferation,cell cycle progression and cell invasiveness were quantified by MTT assays,flow cytometry and transwell assays,respectively.RNAi-mediated inhibition of MSH2 expression in SW480 cells resulted in decreased cell proliferation,cell cycle arrest at the G0/G1 phase and decreased cell invasiveness.Taken together,these results provide evidence that MSH2 stimulates cell proliferation,promotes cell cycle progression and positively regulates cell invasiveness.     

结直肠癌类器官的应用进展与挑战

 结直肠癌（CRC）是全球发病率最高的消化道肿瘤之一,严重威胁人类的健康。近年来,类器官技术取得了令人欣喜的进展,已成为结直肠癌发生机制和临床转化研究的重要新工具。回顾了结直肠癌生态位信号通路的变化,总结了类器官技术在结直肠癌建模、肿瘤微环境研究、药物筛选、个体化治疗等方面的应用进展,讨论了当前类器官面临的挑战,并从类器官培养技术标准化和工程技术应用等角度展望了类器官的未来发展方向。     

大肠癌中MTA1和nm23 - H1蛋白的表达及其意义

目的：探讨大肠癌中MTA1、nm23-H1蛋白的表达及其意义。方法：用免疫组化留法检测84例大肠癌MTA1、nm23-H1蛋白的表达。结果：84例大肠癌中MTA1、nm23-H1阳性表达率分别为61．9％和51．2％;MTA1高表达与大肠癌组织分化程度、Duke’s分期和淋巴结转移关系密切（P〈0．05）;nm23-H1低表达与大肠癌组织分化程度、Duke’s分期和淋巴结转移关系密切（P〈0．05）;大肠癌中MTA1和nm23-H1蛋白表达呈负相关（P〈0．05）。结论：MTA1和nm23-H1蛋白表达与大肠癌分化程度、淋巴结转移和预后密切相关,可作为判断大肠癌患者转移复发的参考指标。     

血管内皮生长因子-C及其受体Flt-4在大肠癌组织中表达的意义

目的：探讨血管内皮生长因子C(VEGF-C)及其Flt-4受体在大肠癌的表达与淋巴管新生及转移的关系。方法：对58例大肠癌组织及12例正常肠黏膜进行VEGF-C、FLt-4及CD34免疫组织化学染色,并计数微淋巴管密度(LMVD)和血管密度(MVD)。结果：VEGF-C在大肠癌中的表达明显高于正常黏膜(P＜O．01)。大肠癌VEGF-C表达与淋巴结转移及Dukes分期呈显正相关(P＜O．01)。大肠癌微淋巴管密度(LMVD)与淋巴结转移呈正相关(P＜O．01)。结论：VEGF-C在大肠癌中表达升高,可能通过旁分泌方式作用于Flt-4信号通路引发淋巴管新生,有助于发生淋巴结转移;VEGF-C对判断大肠癌预后有辅助作用。     

H13对HT-29细胞周期和caspase-3蛋白表达的影响

探讨新型Topo I抑制剂H13对体外培养的人结肠癌细胞HT-29细胞周期和caspase-3表达的影响.以人结肠癌细胞HT-29为研究对象,PI染色,流式细胞仪检测H13处理48 h后细胞周期的分布;Western Blot法检测H13处理48 h后caspase-3表达的变化.2.5和5 g/mL H13处理的HT-29处理48 h后,G1期细胞百分率下降,S期细胞百分率上升,并且有剂量依赖性;2.5,5,10 g/mL H13处理的HT-29处理48 h后,caspase-3蛋白表达升高.H13对诱导HT-29细胞周期阻滞于S期,其机制可能与其上调caspase-3表达有关.     

Overexpression of N-cadherin is correlated with metastasis and worse survival in colorectal cancer patients

N-cadherin is related to the progression and metastases of several solid carcinomas. However, it was still unclear whether N-cadherin is overexpressed in colorectal malignant tumors that have stronger malignant tendency. In this study, we used immunohistochemistry to detect the expression patterns of N-cadherin in both the primary tumors and their normal mucosa tissues of 120 patients with colorectal cancer. We revealed that N-cadherin was expressed in 78.3% (94/120) of colorectal tumor tissues and in only 9.2% (11/120) of paired distant normal mucosa tissues with a significant difference (P=0.000). The low, moderate, and high expression of N-cadherin protein was 42.5%, 30.8%, and 26.7%, respectively. N-cadherin overexpression was associated with advanced TNM stage, lymph nodes metastasis and distant metastasis (P<0.05). Patients with N-cadherin overexpressed showed the obvious lower overall survival rate than those with moderate and low expression, and patients with low expression had a better survival rate than those with moderate and high expression (P<0.05). In conclusion, high N-cadherin expression may lead to tumor aggressiveness and metastatic potential in colorectal cancer, and may prove to be a possible prognostic factor.     

新基因SNC 66和SNC 73在大肠粘膜和大肠癌中表达的比较

目的 :研究新基因SNC 6 6和SNC 73的表达状况 ,并探讨其与大肠癌发生的相关性。方法 :采用体外转录的方法合成地高辛标记的探针 ,并用它进行cRNA/mRNA原位分子杂交 ,检测37例大肠癌标本及其相应正常大肠粘膜中SNC 6 6和SNC 73两基因表达mRNA的状况 ,并加以比较。结果 :SNC 6 6和SNC 73基因只在上皮细胞和淋巴细胞中表达 ,在大肠癌组织中都存在明显的表达缺陷 ,尤其以SNC 73的表达缺陷更明显。SNC 6 6在粘膜绒毛上多呈梯度性表达 ,以隐窝处最深 ,到绒毛顶端逐渐变淡 ;SNC 73则多呈均一性表达。结论 :SNC 6 6和SNC 73是表达行为、代谢途径均有所不同的两个免疫球蛋白样大肠癌负相关基因 ,可以作为候选大肠癌抑癌基因加以进一步研究     

老年与青年肺癌的临床特征及预后比较

目的:为了解老年与青年肺癌的临床特征及预后的差异。方法:回顾性收集近7年来在我院肿瘤科经病理学证实的住院肺癌患者,其中符合条件的老年(≥70岁)组188例,青年(≤40岁)组68例,对患者的年龄、性别、组织分类、临床症状、治疗经过及预后等指标进行比较。结果:(1)老年组中女性患者的比例较青年组低,鳞癌类型较高;(2)老年组中胸痛症状的比例较青年组低,而阻塞性肺炎或肺不张等合并症多见;(3)老年组中远处转移较多见,临床分期较晚;(4)老年组接受综合治疗方案比例与青年组相仿。结论:老年人肺癌相比于青年人肺癌,以男性、鳞癌比例较高,合并症、远处转移更多见,易误诊和漏诊,分期较晚,预后较差。早期诊断、积极治疗能提高老年人肺癌的生存期。     

Correlation of chromosomal polysomy with overexpression of c-myc and c-erbB-2 in primary nasopharyngeal carcinoma: Tissue microarray study

Many genes may be involved in nasopharyngeal carcinoma (NPC) development and progression. Several known oncogenes, including c-myc and c-erb-B2, have been shown to have structural alteration and aberrant expression in NPC. Here, we constructed a tissue microarray to determine the status of c-myc and c-erbB-2 oncogenes at the DNA and protein levels using interphase fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) and to define the diagnostic, prognostic importance of the genetic changes. Results showed that amplification of c-myc and c-erbB-2 was not found in NPC. Polysomy 8 and 17 were observed in 43%-50% and 20%-27% of NPC tumors, respectively. Overexpressions of c-myc and c-erbB-2 oncoproteins were detected in 53.6% and 54.5% cases of NPC with polysomy 8 and 17, respectively. There was no significant correlation between c-myc and c-erbB-2 staining and the clinical stage. But overexpression of c-erbB-2 was associated with polysomy 17 in NPC. These findings suggest that chromosomal polysomy, not gene amplification, may be partially responsible for the upregulated expression of c-erbB-2 oncogene in NPC.     

家族性和三阴性乳腺癌血清中miR-21的表达

目的:检测血清miR-21在乳腺癌中的表达差异,为进一步阐明miR-21在家族性和三阴性乳腺癌发病机制中的作用.方法:收集健康女性体检者、具有患乳腺癌高风险者、不同种类乳腺癌患者的血清.以线虫miR-39为外参,通过实时荧光定量PCR检测77份血清中miR-21的表达水平.结果:家族性乳腺癌组、三阴性乳腺癌组和乳腺癌高风险组血清miR-21水平显著高于正常对照组、其他乳腺癌组(P0.01).血清miR-21的表达水平与淋巴结转移、Ki67高表达有关(P0.01).结果显示血清miR-21表达量在家族性和三阴性乳腺癌中升高,且与淋巴结转移和Ki67表达有关.结论:血清miR-21与三阴性、家族性乳腺癌的发生有紧密联系,其表达增高与乳腺癌的遗传性、恶性程度及预后判断有关.     

胃癌术前介入治疗的临床和病理观察(附250例报告)

目的：研究和评估胃癌患者术前介入治疗的疗效。方法：对２５０例胃癌患者术前进行介入治疗,采用Ｓｅｌｄｉｎｇｅｒ法经一侧股动脉置管达癌肿部位主要动脉,一次性注入化疗药物,５－Ｆｕ５００ｍｇ／ｍ２,Ｅｐｉａｄｒａｍｙｃｉｎ４００ｍｇ／ｍ２,ＭＭＣ１５ｍｇ／ｍ２。在化疗后７～１０天后行根治性切除术,介入组中随机选择８２例并观察大体标本和癌肿组织病理学改变,对照组４０例术前未进行化疗,直接手术切除,进行病理学对比研究,观察大体标本和取癌肿中心部位组织进行病理学观察,详细记录介入化疗的不良反应。结果：①介入组总有效率为７３．２％,癌组织细胞呈典型凋亡特点,间质的炎性反应和纤维组织增生比对照组明显;②介入组６３％出现中～重度坏死,且５６．７％发生在血管周围,对照组只有３０％存在坏死,且与血管无关;③介入组血管内膜增厚和血管内血栓发生率为９５％和７５％,对照组仅为３５％和５％;④随访１、３、５年存活率为９２．９％、５７．１％和４２．８％。单纯行剖腹探查术者半年存活率为７８．２％,１年存活率３４．８％。结论：术前介入治疗能够提高３年和５年存活率,也能作为姑息治疗的一种手段,并能延长存活时间。     

免疫基因和代谢基因 在胃癌患者预后分析中的比较研究

胃癌是1种预后效果较差且预后分析涉及许多因素的恶性肿瘤,其中免疫基因和代谢基因都与胃癌的预后密切相关.首先利用LASSO回归构建预后风险评分模型,经过一系列的图表对比研究后发现利用免疫基因能更好的分析胃癌患者的生存状况,有较高的准确性(AUC=0.799).另外,通过寻找ROC曲线中的最佳截断值(cutoff=-0.0...