Study of apoptosis induction and telomerase activity of carcinomas in digestive tract

消化道癌凋亡诱导及端粒酶活性研究

• 批准号: 08457324
• 负责人: IKEGUCHI Masahide
• 金额: $ 4.99万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457324/
• 关键词: Apoptosis; Telomerase activity; Familial adenomatous polyposis; Esophageal cancer; 大腸癌; p53; 正常食道粘膜; 胃癌; 化学療法; 遺伝子不安定性; 多発癌

We obtained following results between 1996 and 1998.(1) Human gastric carcinoma cell lines (MKN-28, MKN-45, MKN-74, KATO-III, and HSC-39) were treated with 1 mug/ml cisplatin. Percentages of apoptotic cells were increased more intensively among MKN-45 and MKN-74 cells with a wild-type p53 protein and without bcl-2 protein expression than among HSC-39, MKN-28, and KATO-III cells with a mutation or complete deletion of the gene for p53 and with bcl-2 protein overexpression. The levels of p53 protein increased in MKN-74 cells and the levels of bcl-2 protein were reduced in KATO-III after treatment with cisplatin. Thus, p53 status and the expression of bcl-2 in tumor cells might be good indicators of sensitivity to chemotherapy for patients with gastric cancer.(2) In 8 patients with familial adenomatous polyposis (FAP), all carcinomas and polyps from 5 patients with carcinomas in their colon and rectum showed high telomerase activity, however, all polyps from 3 patients with no carcinomas … More showed no telomerase activity. Telomerase activity was detected in 75% of control 68 colorectal carcinomas from 68 patients with non-FAP and in 32% of 19 adenomas from 19 patients. The incidence of detectable telomerase activity of adenomas from 11 patients with synchronous colorectal carcinoma (45%) was higher than that of detectable telomerase activity of adenomas from 8 patients without colorectal carcinoma (13%). In FAP, the p53 gene mutations were detected in only 2 carcinomas from 2 patients. These findings suggest that telomerase should be activated before occurrence of p53 gene mutation. In FAP, geneticchanges associated with development of colonic adenoma to carcinoma should occur in hole poiyps of colon and rectum and genetic changes in polyps might activate telomerase activity. The detection of telomerase is a useful marker to decide the time of operation for patients with FAP.(3) The telomeric repeat amplification protocol (TRAP) assay was used for detection of telomeraseactivity in esophageal carcinomas and normal esophageal tissues adjacent to carcinomas from 52surgically treated patients and normal esophageal epitheliums from 11 noncancerous patientsobtained by biopsy. Telomerase activity was detected in 77% of 52 esophageal carcinomas, in 87% of normal tissue samples adjacent to carcinomas and in 73% of 11 normal esophageal epitheliums from noncancerous patients. hi esophageal cancer, no significant difference was detected in the clinicopathological findings between the telomerase-positive and -negative cases. These results indicate that normal esophageal epitheliums show strong telomerase activity, so, telomerase activity may not be a good marker for the detection of carcinoma in the esophagus. Less

我们在1996年至1998年期间获得了以下结果。(1)用1 μ g/ml顺铂处理人胃癌细胞系（MKN-28、MKN-45、MKN-74、KATO-III和HSC-39）。与HSC-39、MKN-28和KATO-III细胞中p53基因突变或完全缺失和bcl-2蛋白过表达相比，野生型p53蛋白和无bcl-2蛋白表达的MKN-45和MKN-74细胞中凋亡细胞的数量增加更明显。顺铂处理后，MKN-74细胞p53蛋白表达增加，KATO-Ⅲ细胞bcl-2蛋白表达降低。因此，胃癌细胞p53和bcl-2的表达可作为判断胃癌患者化疗敏感性的指标。(2)在8例家族性腺瘤性息肉病（FAP）中，5例结直肠癌患者的癌和息肉均呈高端粒酶活性，3例非癌患者的息肉均呈高端粒酶活性 ...更多信息 没有端粒酶活性。在68例非FAP患者的68例对照结直肠癌中检测到75%的端粒酶活性，在19例患者的19例腺瘤中检测到32%的端粒酶活性。11例同时性结直肠癌患者腺瘤中端粒酶活性的检出率（45%）高于8例非结直肠癌患者腺瘤中端粒酶活性的检出率（13%）。在FAP中，仅在2例患者的2个癌中检测到p53基因突变。提示端粒酶在p53基因突变发生前即已被激活。在FAP中，与结肠腺瘤向癌发展相关的基因改变应发生在结肠和直肠的孔状息肉中，息肉中的基因改变可能激活端粒酶活性。端粒酶的检测对FAP患者手术时机的选择有一定的参考价值。(3)采用端粒重复序列扩增法（TRAP）检测52例手术治疗患者的食管癌和癌旁正常食管组织以及11例活检获得的非癌患者的正常食管上皮中的端粒酶活性。52例食管癌、癌旁正常组织和11例正常食管上皮组织中端粒酶活性阳性率分别为77%、87%和73%。在食管癌中，端粒酶阳性和阴性病例的临床病理结果无显著差异。提示正常食管上皮细胞端粒酶活性较强，端粒酶活性可能不是食管癌的良好检测指标。少

项目成果

Unate H, Ikeguchi M, et al.: "Telomerase activity and micro satellite instability in colorectal cancer and adenoma" International Journal of Oncology. 13. 1223-1228 (1998)

Unate H、Ikeguchi M 等人：“结直肠癌和腺瘤中的端粒酶活性和微卫星不稳定性”国际肿瘤学杂志。

Ikeguchi M,et al.: "Changes in levels of expression of p53 and the product of the bcl-2 in lines of gastric cancer cells during cisplatin-induced apoptosis" Eur Surg Res. 29. 396-402 (1997)

Ikeguchi M 等：“顺铂诱导的细胞凋亡过程中胃癌细胞系中 p53 和 bcl-2 产物表达水平的变化”Eur Surg Res。

Ikeguchi M,et al.: "Detection of loss of heterozygosity at microsatellite loci in esophageal squamous-cell carcinoma" Oncology. 56. 164-168 (1999)

Ikeguchi M 等人：“食管鳞状细胞癌中微卫星位点杂合性丢失的检测”肿瘤学。

Unate H,et al.: "Telomerase activity and genomic instability in colorectal cancers" Nippon Rinsho. 56. 1218-1222 (1998)

Unate H 等人：“结直肠癌中的端粒酶活性和基因组不稳定性”Nippon Rinsho。

池口正英: "食道癌における癌巣,非癌部粘膜のテロメラーゼ活性" 日本臨床. 56巻,5号. 1176-1180 (1998)

Masahide Ikeguchi：“食道癌癌巢和非癌性粘膜中的端粒酶活性”，日本临床研究，第 56 卷，第 5 期，1176-1180（1998 年）。