On predictivity of malignant change og familial adenomatous polyposis.

家族性腺瘤性息肉病恶变的预测性。

• 批准号: 01570745
• 负责人: IWAMA Takeo
• 金额: $ 1.34万
• 依托单位: Tokyo Medical And Dental University, Medical School (TMDU)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570745/
• 关键词: Ornithine decarboxylase (2); Loss of heterozygosity; Colonic adenoma; Colonic carcinoma; p53; 大腸腺腫症; ポリ-プ; オルニチン脱炭素酵素活性値; ヒト大腸癌

1)Time and location specific ornithine decarboxylase(ODC)activity was measured during and after injection of DMH in rats. ODC activity of the colonic mucosa increased before development of colonic carcinoma(12 weeks from the beginning of DMH injection). The ODC activity was lowest at the rectum and highest at the cecum. Number of carcinoma was higher in the proximal colon than in the distal colon except cecum.2)ODC activity was measured on the colorectal normal mucosa, carcinoma, and polyps -of patients of colorectal carcinoma and familial adenomatous polyposts(FAP). ODC activity of adenoma was as high as carcinoma. ODC activity in colonic carcinoma was correlated with age, and ODC activity of carcinoma was higher in the younger patients than in the older patients. This was same at the normal mucosa. We concluded that ODC activity is one of indicator for showing growth activity of colonic mucosa and may be used as risk factor for development of neoplasms in the mucosa in which ODC activity is enhanced, but it will not be used to predict development of carcinoma in FAP patients.3)Loss of heterozygosity(LOH)was observed in adenomas of FAP patients on chromosome 5q(12%), 17p(8%), and 22q(2%). The frequency of LOH in the colonic carcinoma was 5q(38%), 17p(57%), 22q(35%). The frequency of LOH was correlated with the stage of carcinoma.4)p53 was not constantly stained in colonic carcinoma by immunohistochemical staining.As a result, detection of LOH or mutation on the chromosome 5q and 17p may be effective for a prediction of the malignant change of adenomas, but more practical method is to be developed.

1)在大鼠注射DMH期间和之后，测定时间和位置特异性鸟氨酸脱羧酶（ODC）活性。结肠粘膜的ODC活性在结肠癌发生前（注射DMH开始后12周）增加。ODC活性在直肠最低，在盲肠最高。近端结肠癌的发生率高于远端结肠（盲肠除外）。2）在大肠癌和家族性腺瘤性息肉（FAP）患者的大肠正常粘膜、癌和息肉中检测ODC活性。ODC活性在腺瘤和癌中均较高。结肠癌组织中ODC活性与年龄有关，青年组ODC活性高于老年组。正常粘膜也是如此。我们得出的结论是，ODC活性是显示结肠粘膜生长活性的指标之一，可以作为ODC活性增强的粘膜中肿瘤发生的危险因素，但不能用于预测FAP患者的癌症发生。3）在FAP患者的腺瘤中观察到杂合性缺失（洛），位于染色体5 q（12%）、17 p（8%）、17 p（12%）、17 p（17）、1 22q（2%）。在大肠癌中洛缺失频率为5 q（38%）、17 p（57%）、22 q（35%）。洛缺失的发生率与肿瘤分期有关; 4）p53在结肠癌组织中的表达不稳定，因此，检测染色体5 q和17 p上的洛缺失或突变对预测腺瘤恶变可能是有效的，但更实用的方法尚待开发。

项目成果

Ono C,Iwama T,Mishima Y.: "A case of familial adenomatous polyposis complicated by thyroid carcinoma,carcinoma of the ampulla of Vater and adrenocortical adenoma." Jpn.J.Surg. 21. 234-240 (1991)

Ono C，Iwama T，Mishima Y.：“家族性腺瘤性息肉病并发甲状腺癌、Vater壶腹癌和肾上腺皮质腺瘤一例。”

Okamoto M,Iwama T,Miyaki M,et al: "Molecular nature of chromozome 5q loss in colorectal tumors and desmoids from patients with familial adenomatous polyposis." Human Genetics. 85. 595-599 (1990)

Okamoto M、Iwama T、Miyaki M 等人：“家族性腺瘤性息肉病患者结直肠肿瘤和硬纤维瘤中染色体 5q 丢失的分子性质。”

家城和男,岩間毅夫,三島好雄 ほか: "腺腫成分を認めなかった早期大腸癌症例における臨床病理戦的検討" 消化器癌の発生と進展. 1. 67-71 (1989)

Kazuo Iashiro、Takeo Iwama、Yoshio Mishima 等：“无腺瘤成分的早期结直肠癌病例的临床病理学检查”胃肠癌的发生和进展1. 67-71 (1989)。

T.Iwama et al: "Ehlers-Danlos syndrom complicated by eventration of the diaphlagm,colonic perforation and jejunal perforation.A case report" Jpn.J.Surg. 19(3). 376-380 (1989)

T.Iwama 等：“Ehlers-Danlos 综合征并发膈肌膨出、结肠穿孔和空肠穿孔。病例报告”Jpn.J.Surg。

Shirasawa S,Urabe K,Iwama T,Sasazuki T,et al: "p53 gene mutation in colorectal tumors from patients with familial polyposis coli." Cancer Research. 51. 2874-2878 (1991)

Shirasawa S、Urabe K、Iwama T、Sasazuki T 等人：“家族性息肉病患者结直肠肿瘤中的 p53 基因突变。”