MGMT蛋白的表达与乳腺癌预后关系初探

目的:探讨MGMT蛋白在乳腺癌中的表达及其与乳腺癌预后的关系。方法:应用免疫组化法检测135例乳腺癌患者MGMT蛋白的表达,并探讨其与乳腺癌临床特征及预后的关系。结果:135例乳腺癌中MGMT蛋白总阳性率为84.4 %(114/135),但存在异质性。MGMT蛋白的阳性表达与患者年龄、月经状态、原发肿瘤大小、淋巴结转移情况及肿瘤的临床分期无明显相关性(P>0.05),与生存期无明显相关性(P>0.05),但与ER状况相关(P<0.025)。结论:MGMT蛋白的表达不能作为乳腺癌的一个预后指标。     

甲醛对小鼠脏器MGMT的影响

目的　研究甲醛对小鼠脏器O6 -甲基鸟嘌呤 -DNA甲基转移酶 (MGMT )表达的影响。方法　选择健康昆明小鼠 40只 ,随机分为 4组 :甲醛低剂量组 (2 5mg/m3)、中剂量组 (5mg/m3)、高剂量组 (10mg/m3)、对照组 (无甲醛暴露 ) ,每组 10只。除阴性对照组外 ,其余 3组每日吸入甲醛 1次 ,每次 4h ,连续 9周。应用链霉亲和素生物素-过氧化物酶 (SABC)免疫组化法对小鼠脑、肺、肝及肾组织中MGMT进行检测。结果　 3个染毒组小鼠肝和肺组织中MGMT表达降低 ,与对照组比较具有显著性差异 (P <0 0 5或P <0 0 1) ;脑和肾组织MGMT表达各组之间无显著性差异 (P >0 0 5)。结论　甲醛对小鼠肝和肺组织MGMT表达可能具有抑制作用     

卵巢癌组织中MGMT表达意义

目的探讨6-氧-甲基鸟嘌呤-DNA甲基转移酶（MGMT）在卵巢癌中的表达及临床意义.方法应用免疫组化（SP）法对60例卵巢癌及癌旁正常组织中MGMT的表达进行检测.结果60例卵巢癌组织中MGMT的表达率为46.7%,癌旁正常组织MGMT的表达率为100%（P＜0.05）.MGMT的表达与卵巢癌的组织学类型和临床分期无关（P＞0.05）,但与卵巢癌的病理分级有关（P＜0.05）.结论卵巢癌组织中存在MGMT的表达缺失,MGMT的功能失活可能是卵巢癌发生的重要机制之一.     

O6-Methylguanine-DNA Methyltransferase (MGMT) as a Determinant of Resistance to Camptothecin Derivatives

The precise mechanisms of resistance to camptothecin (CPT)-derived DNA topoisomerase (topo I) inhibitors and the determinants remain unclear. We found that a DNA repair protein, O⁶-methylguanine-DNA methyltransferase(MGMT), participated in resistance to irinotecan hydrochloride (CPT-11), its active metabolite SN-38, and a novel CPT derivative, DX-8951f. In 17 human cancer cell lines, MGMT gene expression level closely correlated with sensitivity to the CPT derivatives, and inhibition of MGMT activity by nontoxic 5 μM O⁶-benzylguanine augmented the drug activity in relation to the MGMT expression levels in 8 cell lines examined. Transfection of pCR/MGMT-sense into U-251MG and pCR/MGMT-antisense into T98G and HEC-46 cells revealed that increased MGMT expression decreased the sensitivity to CPT-11, SN-38, and DX-8951f, whereas repressed MGMT expression sensitized cells to the drugs. Western analysis revealed that treatment of MGMT -expressing T98G cells with the drugs caused a decrease of both MGMT and topo I in a dose-dependent manner. Although, in the transfectants, MGMT expression did not so closely correlate with the sensitivity to drugs as to nimustine hydrochloride (ACNU), MGMT is probably an important resistance determinant to CPT derivatives, and may play some role in the topo I-mediated DNA damage and/or the repair process.     

Alterations of DNA damage response pathway: Biomarker and therapeutic strategy for cancer immunotherapy

Genomic instability remains an enabling feature of cancer and promotes malignant transformation. Alterations of DNA damage response (DDR) pathways allow genomic instability, generate neoantigens, upregulate the expression of programmed death ligand 1 (PD-L1) and interact with signaling such as cyclic GMP–AMP synthase-stimulator of interferon genes (cGAS–STING) signaling. Here, we review the basic knowledge of DDR pathways, mechanisms of genomic instability induced by DDR alterations, impacts of DDR alterations on immune system, and the potential applications of DDR alterations as biomarkers and therapeutic targets in cancer immunotherapy.     

MGMT启动子与垂体腺瘤侵略性行为及ADC值的相关性研究

目的 探讨垂体腺瘤O-6-甲基鸟嘌呤DNA甲基转移酶(MGMT)启动子甲基化状态与肿瘤侵略性行为及ADC值的相关性.方法 采用前瞻性研究,选取我院2019年01月至2020年08月收治的垂体腺瘤的患者,所有患者术前接受MRI检查(平扫+增强+解剖弥散),术后对肿瘤组织标本进行苏木精-伊红(HE)染色、免疫组化检查,通过...     

Analysis of K-<Emphasis Type="Italic">ras</Emphasis> Codon 12 Mutation in Flat and Nodular Variants of Serrated Adenoma in the Colon

PURPOSE: The developmental process of serrated adenomas is obscure, and the importance of genetic alterations has not been elucidated clearly. The possibility that the developmental process and genetic alterations of serrated adenomas could differ from those of ordinary tubular adenomas was explored in this work. METHODS: Serrated adenomas were obtained by endoscopic resection (n = 57) and divided into two groups: flat (n = 10) and nodular (n = 47). Mutation of the K-ras gene was analyzed by enriched polymerase chain reaction–enzyme-linked mini-sequence assay, which can detect not only the presence of a mutation but also the mutation type of K-ras codon 12 with high sensitivity. Methylation-specific polymerase chain reaction was performed with specific primers for the DNA repair gene O6-methylguanine-DNA methyltransferase. RESULTS: Serrated adenomas located in the rectum were more likely to have a K-ras mutation (9/12, 75 percent), whereas serrated adenomas of the flat type were less likely to have one (1/10, 10 percent). Furthermore, nodular serrated adenomas that occurred in the rectum possessed a high frequency of K-ras gene codon 12 point mutation (8/10, 80 percent) despite an overall frequency of 46.8 percent (22/47). A mutation of the K-ras codon 12 gene was detected in 23 (40.4 percent) of 57 serrated adenomas. Three types of point mutations of codon 12 were detected, with the mutation of GAT being observed most frequently. CONCLUSIONS: This study shows that development of nodular serrated adenomas may depend on the mutation of the K-ras codon 12 gene, whereas development of flat serrated adenomas may not. Additionally, serrated adenomas that occur in the rectum are closely related to the mutation of the K-ras codon 12 gene. K-ras mutations in serrated adenomas may be unaffected by the epigenetic silencing of O6-methylguanine-DNA methyltransferase by promoter hypermethylation.     

Effect of Alcohol Drinking on Gene Expression of Hepatic O6-Methylguanine DNA Methyltransferase in Chronic Liver Diseases

O⁶-methylguanine DNA methyltransferase (MGMT) is a repair protein that transfers methyl groups from O⁶-methylguanine to a cysteine acceptor in its own molecule, and restores DNA to its undamaged state. If left unrepaired, O⁶-methylguanine can pair with either a thymine or a cytosine, causing a C-G to T-A transition, which is considered to be one of the molecular mechanisms of both mutagenesis and carcinogenesis. The expression of MGMT mRNA in liver tissue was quantitatively assessed by the competitive reverse transcrip-tion-polymerase chain reaction method in patients with chronic liver diseases with or without alcohol drinking. MGMT mRNA expression was 1.4 ± 0.9 pg/μg RNA in control livers. Its expression in chronic hepatitis was 3.8 ± 0.7 in alcoholics and 2.7 ± 0.8 in nonalcoholics, which were not statistically different. MGMT mRNA expression in liver cirrhosis was significantly low, compared with that in chronic hepatitis, and 0.8 ± 0.3 in alcoholics and 0.5 ± 0.1 in nonalcoholics, which also were not significantly different. The present study shows that MGMT mRNA was not decreased in patients with chronic liver diseases with alcohol drinking, compared with those without alcohol drinking.