突变型p53与胃癌细胞多药耐药性关系的研究

目的：研究胃癌细胞中突变型p53和MDR-1基因的表达及其与不同化疗药物敏感性的关系。方法：将突变型p53、sv40Tag（封闭p53）导入胃癌细胞株SGC-7901中，研究胃癌细胞中MDR-1基因表达的变化；用MTT法比较各组细胞对化疗药的敏感性。结果：导入突变型p53细胞株的MDR-1基因mRNA表达比导入突变型p53＋sv40Tag细胞株、对照组MDR-1基因mRNA表达强；导入突变型P53细胞株对5-氟脲嘧啶（5-Fu）耐药性与导入突变型P53＋sv40Tag细胞株和对照组比较均有显著性差异（P〈0．05），而后两者之间耐药性差异无显著性（P〉0．05）；导入突变型p53细胞株和导入突变型p53＋sv40Tag细胞株对阿霉素（ADM）耐药性与对照组比较均有显著性差异（P〈0．05），而前两者之间对ADM的耐药性差异无显著性（P〉0．05）。导入突变型p53细胞株、导入突变型p53＋sv40Tag细胞株及对照组细胞株对顺铂（CDDP）耐药性均无显著性差异（P〉0．05）。结论：突变型p53能促进MDR-1 mRNA表达，与肿瘤细胞发生多药耐药密切相关。     

贲门腺癌术中综合治疗对预后的影响

目的探讨贲门腺癌术中综合治疗对贲门腺癌患者预后的影响。方法将中晚期患者随机分为A、B两组,A组单纯行根治术;B组在根治手术同时行术中全身化疗,癌床局部化疗及胸腹腔温热化疗(IPHC),观察其并发症的发生率、复发转移率、生存率的差别;结果两组术后并发症发生率无显著差异(P>0.05),B组3年生存率远高于A组(P<0.01),而复发转移率明显低于A组(P<0.01);结论贲门腺癌术中综合治疗对预后有重要意义,明显降低术后复发转移率、可提高患者生存率。     

A mechanistic basis for the role of cycle arrest in the genetic toxicology of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), formed during the cooking of meat, induces tumors of the prostate, colon, and mammary gland when fed to rats. PhIP is readily absorbed and efficiently metabolized to a genotoxic derivative by CYP1 enzymes. Although metabolism and mutational potential of PhIP have previously been well characterized, the intervening cellular and genomic responses to the chemical are not fully understood. We have examined the cellular response to PhIP exposure in human mammary epithelial MCF10A cells, which retain characteristics of normal breast epithelial cells. Because these cells fail to activate PhIP, they were cocultured with a human lymphoblastoid cell line MCL-5, which constitutively expresses CYP1A1, and have been transfected to express human CYPs1A2, 2A6, 3A4, and 2E1. The MCL-5 cells were irradiated (2,000 rads) prior to coculture, rendering them unable to replicate yet still retaining metabolic competency. MCF10A cells were treated (in the presence of MCL-5 cells) with PhIP (1-100 microM) and harvested at various time-points. Compared to DMSO control, treatment (24 or 48 h) with PhIP resulted in a significant dose-dependent fall in cell number. Cells treated for 48 h then cultured in the absence of PhIP (and MCL-5 cells) for a further 6 days showed a much greater dose-dependent reduction in cell number. Flow cytometric analysis indicated that PhIP treatment (48 h) resulted in a dose-dependent accumulation of cells in the G1 population. Western blotting revealed elevated expression of p53 and the cyclin dependent kinase inhibitor p21WAF1/CIP1 after PhIP treatment. Levels of MDM2, a negative regulator of p53, and the hypophosphorylated form of RB were also elevated, consistent with the triggering of G1 cell cycle checkpoint. These cell cycle effects are critical, as they enable cells to effect genome repair, accept mutation, or eliminate excessively damaged cells.     

同种异体移植瘤在不同组织微环境中生物学行为的差异及机制

 目的 分析不同的组织微环境对同种异体移植瘤生物学行为的影响因素,并探讨基质金属蛋白酶和转化生长因子β₁与移植瘤生物学行为的关系. 方法 应用常规HE染色观察不同移植瘤的生物学行为表现,并应用免疫组化的方法分别检测两种瘤组织中MMP-2,MMP-9及TGF-β₁的表达情况. 结果 ①不同的组织微环境同种异体移植瘤生物学行为有明显差别,皮下转移瘤表现为明显的膨胀性生长;腹腔转移瘤表现为显著的浸润性生长;②MMP-2及MMP-9的表达:皮下转移瘤两者均为阴性;腹腔转移瘤可见MMP-2及MMP-9阳性表达;③TGF-β₁的表达:皮下转移瘤可见TGF-β₁的间质型表达;腹腔转移瘤可见TGF-β₁的胞浆型表达. 结论 不同组织环境对同种移植瘤的浸润及转移有影响,MMP-2、MMP-9及TGF-β₁表达可能是其中的因素之一.     

多原发癌组织中p53 表达状况研究

 目的 研究多原发癌组织中的p53蛋白表达状况，探讨抑癌基因p53在多原发癌的发生、发展中的意义。方法 应用免疫组织化学方法检测21例双原发癌组织中的p53蛋白表达。结果 21例患者中，第一癌和第二癌p53均阳性者9例(42．85％，9／21)，仅一次p53阳性者9例(42．85％，9／21)，两次均阴性者3例(14．12％，3／21)。结论 抑癌基因p53在多原发癌的发生、发展中可能起重要作用，对这些发现的意义值得进一步研究。     

bcl-2、p53在皮肤肿瘤中的表达及意义

目的探讨bcl-2、p53在几种皮肤肿瘤中的表达及意义。方法采用流式细胞术(FCM)和免疫荧光技术对皮肤鳞状细胞癌(SCC)、恶性黑色素瘤(MM)、基底细胞癌(BCC)、色素痣(PN)bcl-2、p53蛋白的表达进行定量分析,以荧光指数(FI)作为定量表达指标。结果鳞状细胞癌、基底细胞癌的bcl-2、p53基因蛋白的FI值均显著性高于正常对照(P<0.05),基底细胞癌的bcl-2基因的FI值显著性高于鳞状细胞癌(P<0.05),而二者的p53基因蛋白的FI值无显著性差异(P>0.05);恶性黑色素瘤、色素痣的bcl-2、p53基因蛋白的FI值均显著性高于正常对照(P<0.05),恶性黑色素瘤的p53基因的FI值显著性高于色素痣(P<0.05),而二者的bcl-2基因蛋白的FI值无显著性差异(P>0.05)。结论鳞状细胞癌、恶性黑色素瘤、基底细胞癌、色素痣中均有bcl-2的表达,基底细胞癌bcl-2表达显著高于鳞状细胞癌,说明基底细胞癌的发生发展可能与细胞凋亡受抑密切相关;p53在恶性黑色素瘤的表达高于色素痣,说明p53为黑色素瘤的恶性标志,检测p53表达可以作为鉴别皮肤黑色素瘤恶性病变的辅助手段。     

c-kit与p27蛋白在胃肠道间质瘤诊治中的临床意义

目的研究c-kit和p27蛋白在胃肠道间质瘤中的表达及其与间质瘤临床病理特征的关系,为GIST诊断、预后评估提供客观指标。方法收集54例手术切除的胃肠道间质瘤标本,同时取距瘤灶>5cm的正常组织,应用免疫组织化学S-P检测肿瘤组织及正常组织中c-kit和p27蛋白的表达。结果54例胃肠道间质瘤中,c-kit和p27蛋白阳性表达率分别为94.44%和59.26%。c-kit蛋白表达水平在GIST不同分化程度、有无复发及远处转移的差异无显著性意义(P>0.05),p27蛋白表达水平在GIST不同分化程度、有无局部复发间差异有显著性(P<0.01)。结论c-kit作为特异敏感的标志物,对GIST的诊断及鉴别诊断有重要意义,而检测p27蛋白可作为评估GIST恶性程度和判断预后的重要指标。     

胃癌中p27~(Kip1)、p53表达与其浸润、转移和预后的关系(英文)

目的研究胃癌组织中p27~(Kipl)和 p53的表达与胃癌浸润、转移和预后的关系。方法用免疫组化(二步法)检测100例胃癌组织中的 p27~(Kipl)蛋白和 p53蛋白的表达。结果 100例胃癌组织中 p27~(Kipl)和 p53蛋白阳性表达率分别为44%和49%。在胃癌深部浸润组、淋巴结转移组和5年内死亡组中p27~(kipl)呈显著低表达(P<0.05);在胃癌淋巴结转移组和5年内死亡组中 p53呈显著高表达(P<0.05)。经单变量分析结果显示p27~(Kipl)高表达组5年生存率为70.59%,显著高于低表达组54.55%和阴性组26%;p53高表达组5年生存率为19.23%,显著低于低表达组43.75%和阴性组53.19%。多变量 Cox 回归模型分析显示p27~(Kipl)、p53均是独立的预后指标,但 p27~(Kipt)表达对患者预后的相对危险度(RR=3.06)显著大于 p53表达的相对危险度(RR=2.33,P<0.01)。结论 p27~(Kipl)低表达与 p53高表达的癌细胞常更能浸润与转移,使患者生存率明显降低。p27~(kipl)和 p53是胃癌预后的独立指标,其中 p27~(Kipl)表达评估胃癌预后的作用优于 p53。     

Prognostic Value of PCNA and Mutant p53 Expression in Laryngeal Squamous Cell Carcinoma

The objective of this study was to investigate the prognostic significance of p53, and proliferative cell nuclear antigen (PCNA) in laryngeal squamous cell carcinoma (LSCC). Sixty pathologic specimens from the patients with LSCC were examined for the expression of the p53 and PCNA, with complete follow-up data. Sixty-three percent of the cases displayed nuclear p53 overexpression. There was a correlation between p53 overexpression and histological grades (p = 0.03), and localization site (p = 0.05). Median of PCNA index was 42.2 (range 5.9 to 85.2). There was no difference between the p53 overexpression group and the normal group in proliferative activity determined by PCNA (p = 0.73). In univariate analyses, localization site, grade, stage, invasion pattern, lymph node status, were significant factors in estimating disease free survival (DFS). Grade was the most important factor affecting recurrence (p = 0.002). In multivariate analyses, grade was the only significant predictor for DFS (p = 0.001). Grade (p = 0.001) and invasion pattern (p = 0.03) were found to be significant predictors of overall survival. In conclusion, the histological grade was the most reliable important prognostic factor. Further studies are necessary to facilitate understanding of the mechanisms of laryngeal carcinogenesis.     

Survivin基因在乳腺癌组织中的表达及其与HER2、p53基因表达的关系

Objective： To investigate the relationship between the expression of survivin and mutant p53, C-erbB-2 proteins in breast cancer to explore the possible molecular mechanisms. Methods： The expression of survivin, mutant p53, and C-erbB-2 was detected in 62 specimens of breast carcinoma by using streptavidin-peroxidase （SP） immunocytochemical assay. Results： Among the 62 cases of breast carcinoma, the positive rate of survivin was 67.7%; 35.5% of the tumors were positive for p53; and 37.1% for C-erbB-2 overexpression. Survivin expression was independent on patient＇s menopausal status, tumor histology, clinical stage, tumor size, lymph node metastasis, and estrogen receptor level. Although survivin expression was not correlated with p53 mutations, the positive expression of survivin was associated with C-erbB-2 overexpression （87.0% vs 56.4%, P〈0.05）. Conclusion： The positive expression of survivin was independent on p53 mutation, but dependent on the overexpression of C-erbB-2. C-erbB-2 might up-regulate the expression of survivin.