XAF1基因与p53基因在结直肠肿瘤中的表达研究

目的观察两个相邻位置的抑癌基因XIAP相关因子1(XAF1)与p53基因在结直肠肿瘤中的表达。方法选取结肠癌细胞株Colo205、Colo320、LoVo、SW1116为体外研究对象,另取41例结直肠癌、28例结直肠腺瘤/息肉以及31例正常人结肠黏膜为体内研究对象。应用逆转录聚合酶链反应检测XAF1mRNA与p53mRNA在体内外的表达,应用免疫组化法检测P53蛋白在结直肠组织中的表达。结果4种细胞株中XAF1表达均较为低下,p53mRNA表达均较高。结直肠肿瘤组织中的XAF1mRNA表达显著低于正常组织(P<0.01),结直肠癌中的表达又显著低于良性肿瘤(P<0.05)。结直肠肿瘤组织中的p53mRNA表达显著高于正常组织(P<0.01),但在良、恶性肿瘤中的表达差异无统计学意义(P<0.05)。P53蛋白在正常组织中未见表达,良、恶性肿瘤组的组织P53蛋白表达之间差异无统计学意义(P>0.05)。结论XAF1基因在结直肠肿瘤中表达降低,且结直肠癌XAF1mRNA表达显著低于良性肿瘤,可作为判断良、恶性肿瘤的鉴别指标。     

Immunohistochemical analysis of expression of a 65 kDa oncofetal protein (p65), epidermal growth factor receptor (EGFR), oncogene c-erb B2 and tumor suppressor gene p53 protein products in breast cancer patients

Paraffin-embedded tissue slides from 88 infiltrating ductal breast carcinoma were examined by immunohistochemistry technique with the use of monoclonal antibody against human p65 antigen and polyclonal antibody against p65-like protein present in fetal bovine serum. Immunohistochemical analysis of expression of growth factor receptors (EGFR), protein product of oncogene c-erb B2 as well as protein product of mutated anti-oncogene p53 was also done. It was established that there is no correlation between p65 and c-erbB2, EGFR or p53 expression. In low differentiated tumors (grade III) high p53 index and high EGFR and c-erbB2 expression was connected with low p65 expression. The lack of c-erbB2 and EGFR and low p53 expression was combined usually with high p65 oncoprotein levels.     

Acute Lymphoblastic Leukemia Expressing b3a2 (p210), e1a2 (p190), and Variant e1a2 BCR-ABL Transcripts: A Case Report and Review of the Literature

No abstract available.     

Relationship between genetic polymorphisms of drug-metabolizing enzymes (CYP1A1, CYP2E1, GSTM1, and NAT2), drinking habits, histological subtypes, and p53 gene point mutations in Japanese patients with gastric cancer

Background Genetic polymorphisms of drug-metabolizing enzymes have recently been shown to affect susceptibility to chemical carcinogenesis. However, the molecular mechanisms of individual susceptibility to gastric cancer have not been fully understood. Therefore, we studied the relationship between the genetic polymorphisms of drug-metabolizing enzymes, drinking habits, histological subtypes, and p53 gene point mutations in Japanese patients with gastric cancer.Methods The genotypes of cytochromes P450 (CYP) 1A1 and 2E1, glutathione S-transferase (GST) M1, and N-acetyltransferase (NAT) were investigated by polymerase chain reaction (PCR), allele-specific PCR, or restriction fragment length polymorphism (RFLP) following PCR in 146 Japanese patients with gastric cancer (67 intestinal-type and 79 diffuse-type carcinomas) and 177 autopsied controls. In addition, p53 gene point mutations of exons 5 through 9 in gastric cancer tissues were determined.Results The frequency of either being a habitual drinker or having a CYP2E1^*1A/^*1A genotype was significantly higher in patients with intestinal-type gastric cancer than in control subjects. The difference between the frequencies of habitual drinkers with the CYP2E1^*1A/^*1A genotype and non-drinkers with the CYP2E1^*5B allele was much more significant in the intestinal-type cancer versus the control group. Among intestinal-type cancer patients with the CYP2E1^*1A/^*1A genotype, p53 point mutations were significantly more frequent in the group of habitual drinkers than in that of non-drinkers. On the other hand, the combination of GSTM1 null and CYP2E1^*1A/^*1A genotypes increased the risk for diffuse-type gastric cancer, but had no influence on the frequency of p53 gene mutations.Conclusions The present study suggests that individuals with both the CYP2E1^*1A/^*1A genotype and a history of habitual drinking have an increased risk of intestinal-type gastric cancer with a high frequency of p53 gene point mutations in the gastric mucosa.     

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。     

L3MBTL1 polycomb protein, a candidate tumor suppressor in del(20q12) myeloid disorders, is essential for genome stability

The l3mbtl1 gene is located on the long arm of chromosome 20 (q12), within a region commonly deleted in several myeloid malignancies. L3MBTL1 is a human homolog of the Drosophila polycomb L(3)MBT tumor suppressor protein and thus a candidate tumor suppressor in del(20q12) myeloid disorders. We used the loss-of-function approach to explore the possible tumor suppressive mechanism of L3MBTL1 and found that depletion of L3MBTL1 from human cells causes replicative stress, DNA breaks, activation of the DNA damage response, and genomic instability. L3MBTL1 interacts with Cdc45, MCM2-7 and PCNA, components of the DNA replication machinery, and is required for normal replication fork progression, suggesting that L3MBTL1 causes DNA damage, at least in part, by perturbing DNA replication. An activated DNA damage response and genomic instability are common features in tumorigenesis and a consequence of overexpression of many oncogenes. We propose that the loss of L3MBTL1 contributes to the development of 20q(-) hematopoietic malignancies by inducing replicative stress, DNA damage, and genomic instability.     

Loss of heterozygosity on chromosomes 2p, 3p, 18q21.3 and 11p15.5 as a poor prognostic factor in stage II and III (FIGO) cervical cancer treated by radiotherapy

Loss of heterozygosity (LOH) has been shown to be an important prognostic factor in a variety of malignant neoplasm's. Cervical cancer develops as result of multiple genetic alterations. The aim of this study was to analyze presence of LOH in cervical cancer and to identify the correlation between LOH and survival and relapse-free survival time in patients treated with radiotherapy. Studies were performed on tumor specimens and venous blood from 20 patients with cervical cancer (squamous cell carcinoma G2 and G3) in stage II and III (FIGO) treated with radiotherapy. DNA was isolated using organic extraction. Additional microcolumn purification was performed. The fluorescent multiplex polymerase chain reaction (PCR) was used to amplify 10 microsatellite loci included in commercially available human identification kits. Microsatellite marker BAT 26 was amplified in separate PCR reactions. 75% cervical cancers manifested LOH. LOH in BAT 26 analysis (chromosome 2) was present in all these specimens. 60% of the cases showed LOH at one or more of other examined loci (mostly on 3p, 18q21.3, and 11p15.5). Eight of nine cervical cancers in clinical stage III showed LOH. All cases of G3 squamous cell carcinoma of the cervix manifested LOH on 2p. Patients with LOH have worse prognosis for survival and relapse-free survival compared to patients without LOH.