ANALYSIS OF GENETIC ALTERATIONS IN RENAL CELL CARCINOMA.

肾细胞癌的基因改变分析。

• 批准号: 10671472
• 负责人: NONOMURA Norio
• 金额: $ 1.73万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671472/
• 关键词: renal cell carcinoma; genetic alteration; CPT-11; interleukin 2; interleukin 7; apoptosis; Fas; soluble Fas; 遺伝子; LOH解析; VHL遺伝子; FHIT遺伝子; インターフェロン; LAK療法; IL2

We have already demonstrated that alteration of genomic imprinting was observed in renal cancer. However, we could not detect the relationship between abnormal epigenetic changes and biological characteristics of renal cancer. CPT-11 showed strong antitumor effect against human renal cancer heterotransplanted in nude mice. CPT-11 can be a new candidate as a therapeutic drug for renal cell carcinoma in the future. Enhancement of interleukin 2-induced lymphokine-activated killer activity by interleukin 7 has been shown against autologous human renal cell carcinoma. Clinical usefulness of this combination therapy against renal cancer has been demonstrated. Susceptibility of brain metastasis by interleukin 2 was neglected by our retrospective study. In terms of apoptosis-related genes, renal cancer cells expressed Fas and showed apoptosis by anti-Fas agonistic antibody. Moreover, this apoptosis was enhanced by interferon-_. In vivo experiments, Fas ligand-transfected mouse renal cancer cells showed more rapid growth than the control cancer cells, probably due to the evasion from T-cell attack. Soluble Fas was detected in high level in the serum from patients with renal cell carcinoma. This may be clinically useful for detecting metastasis or recurrence.

我们已经证实在肾癌中观察到基因组印记的改变。然而，我们不能检测异常表观遗传学改变与肾癌生物学特性之间的关系。CPT-11对人肾癌裸鼠移植瘤有较强的抗肿瘤作用。CPT-11有望成为治疗肾癌的新药物。白细胞介素7增强白细胞介素2诱导的淋巴因子激活的杀伤细胞活性已被证明对自体人肾细胞癌。这种联合治疗对肾癌的临床有效性已得到证实。我们的回顾性研究忽略了白细胞介素2对脑转移瘤的易感性。在凋亡相关基因方面，肾癌细胞表达Fas，抗Fas激动性抗体诱导肾癌细胞凋亡。而且，这种凋亡被干扰素-_增强。在体内实验中，Fas配体转染的小鼠肾癌细胞显示出比对照癌细胞更快的生长，可能是由于逃避T细胞攻击。肾癌患者血清中可溶性Fas水平较高。这可能是临床上有用的检测转移或复发。

项目成果

Igarashi T. 他: "Interferon-alpha and 5-tluorouracil therapy in patients with metastatic renal cell cancer : an open multicenter trial"Urology. 53・1. 52-59 (1999)

Igarashi T.等人：“转移性肾细胞癌患者的干扰素-α和5-氟尿嘧啶治疗：一项开放的多中心试验”泌尿学53・1（1999）。

Igarashi T, Marumo K, Onishi T, Kobayashi M, Aiba K, Tsushima T, Ozono S, Tomita Y, Terachi T, Satomi Y, Kawamura J, and The Japanese Study Group against Renal Cancer: "Interferon-alpha and 5-fluorouracil therapy in patients with metastatic renal cell can

Igarashi T、Marumo K、Onishi T、Kobayashi M、Aiba K、Tsushima T、Ozono S、Tomita Y、Terachi T、Satomi Y、Kawamura J 和日本肾癌研究小组：“干扰素 α 和 5-氟尿嘧啶

Harada Y, Nonmura N, Ono Y, Nishimura K, Tamaki H, Takahara S, Miki T, Sugiyama H, and Okuyama A: "WT1 gene expression in human testicular germ-cell tumors."Molecular Urology. Vol.3, No.4. 357-363 (1999)

Harada Y、Nonmura N、Ono Y、Nishimura K、Tamaki H、Takahara S、Miki T、Sugiyama H 和 Okuyama A：“人类睾丸生殖细胞肿瘤中的 WT1 基因表达。”分子泌尿学。

野々村祝夫: "泌尿器科腫瘍学入門"日本医学館、富田善彦編集. 14 (2000)

野野纪夫：《泌尿肿瘤学概论》，日本医学博物馆，富田义彦编辑 14 (2000)。

Miki T, Nonomura N, Takaha N, Nishimura K, Kojima Y, Sawada M, and Okuyama A: "Antitumor effect of irinotecan hydrochloride (CPT-11) on human renal tumors heterotransplanted in nude mice."International Journal of Urology. Vol. 5, No. 3. 370-373 (1998)

Miki T、Nonomura N、Takaha N、Nishimura K、Kojima Y、Sawada M 和 Okuyama A：“盐酸伊立替康 (CPT-11) 对裸鼠异种移植人肾肿瘤的抗肿瘤作用。”国际泌尿学杂志。