Studies on DNA topoisomerase-targeted anti-cancer chemotherapy in gynecologic malignancy.

DNA拓扑异构酶靶向抗癌化疗在妇科恶性肿瘤中的研究。

• 批准号: 04670995
• 负责人: NIWA Kenji
• 金额: $ 1.34万
• 依托单位: GIFU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670995/
• 关键词: DNA topoisomerase I; mRNA; RT-PCR; Cancer cell lines; Camptothecin; Cytokines; anti-proliferative activity; Chemotherapy; DNA topoisomerase; camptotecin; CPT-11; cell lines; ギャップ・ジャンクション; paclitaxel; コネキシン43; 化学療法; 婦人科癌

1. The anti-proliferative effects of INF-gamma and CPT-11, a new derivative of camptothecin, on two human endometrial cancer cell lines were examined in vitro. In both cell lines, INF-gamma enhanced the anti-proliferative activity of CPT-11.2. Expression of DNA topoisomerase (Topo) -I mRNA in various cancer cell lines was detected using reverse transcription-polymerase chain reaction (RT-PCR) method. The cytoplasmic polyadenylated RNA isolated from cancer cell lines was reverse-transcribed and the complementary DNA was amplified by PCR primed with Topo-I specific primers. The level of Topo-I mRNA was correlated positively with the cytotoxicity of a Topo-I inhibitor.3.The combination therapy of CPT-11 and INF-gamma will be examined in tumor-bearing mice or rats.

1. 体外研究了INF-γ和喜树碱新衍生物CPT-11对两种人子宫内膜癌细胞系的抗增殖作用。在这两种细胞系中，INF-γ 增强了 CPT-11.2 的抗增殖活性。采用逆转录聚合酶链式反应（RT-PCR）方法检测多种癌细胞系中DNA拓扑异构酶（Topo）-I mRNA的表达。对从癌细胞系中分离的细胞质聚腺苷酸化 RNA 进行逆转录，并通过以 Topo-I 特异性引物引发的 PCR 扩增互补 DNA。 Topo-I mRNA水平与Topo-I抑制剂的细胞毒性呈正相关。3.CPT-11和INF-γ的联合治疗将在荷瘤小鼠或大鼠中进行检查。

项目成果

K.Niwa,H.Mori & T.Tamaya et al.: "Enhancing effects of estrogens on endometrial carcinogensis initiated by N-methyl-N-nitrosurea in ICR mice." Jpn.J.Cancer Res.84. 951-955 (1993)

丹羽康、森宏

NIWA K, et al.: "Semi-quantitative analysis of DNA topoisomerase-I mRNA level using reverse transcription-polymerase chain reaction in cancer cell lines : its relation to cytotoxicity against camptothecin derivative." Jpn.J.Cancer Res.85. 869-874 (1994)

NIWA K 等人：“在癌细胞系中使用逆转录聚合酶链式反应对 DNA 拓扑异构酶 I mRNA 水平进行半定量分析：其与喜树碱衍生物的细胞毒性的关系。”

K.Niwa,H.Mori & T.Tamaya et al.: "Changes of the numbers of silver-stained nucleolar organizer regions in the normal,pre-neoplastic and neoplastic endometrium" Cancer Detect Prev.(in press). (1994)

丹羽康、森宏

H.Mori & T.Tamaya et al.: "Expression of interleukin-1(IL-1)beta messenger ribonucleic acid(mRNA)and IL-1 receptor antagonist mRNA in peritoneal macophages from patients with endometriosis." Fertil.Steril.57. 535-542 (1992)

森宏

MORI H, et al.: "Augmentation of anti-proliferative activity of CPT-11, a new derivative of camptothecin, by tumor necrosis factor against proliferation of gynecologic tumor cell lines." Anti-Cancer Drugs. 2. 469-474 (1991)

MORI H 等人：“通过肿瘤坏死因子增强喜树碱新衍生物 CPT-11 的抗增殖活性，对抗妇科肿瘤细胞系的增殖。”