Expression of DNA Topoisomerase II alpha and clinical significance in colon cancer.

DNA拓扑异构酶IIα在结肠癌中的表达及其临床意义。

• 批准号: 08671491
• 负责人: YAMADA Kyoji
• 金额: $ 1.47万
• 依托单位: St.Marianna University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-08671491/
• 关键词: DNATopoisomerase; Neoplasm; Colon; 増殖マーカー; Topoisomerase

(Basic study)DNA Topoisomerase II alpha, which catalyzes conformational changes of DNA, is closely involed in processes such as DNA replication, transcription, chromosomal condensation with the formation of transient double strand breaks during DNA TopoisomeraseII reaction. It has recentry been proposed that there is the role of TopoisomeraseII alpha in DNA repair. We analyze TopoII alpha activity during DNA repair phase caused by UV irradiation and antitumor drugs in human colon cancer cell(COLO32ODM) line useing an immunohistochemical approach. In studies on antitumor drugs, we compared TopoII alpha activity in the presence of VP-16 as inhibitors of DNA TopoisomeraseII with CDDP as giving other lesion in DNA.And we observed that it's activity is sighficantly increased in Colo32ODM administered CDDP alone but degrease in the presence of VP-16 and cmbination with CDDP.Serum depieted Colo32ODM colon cancer cell were irradiated with [UV light. Cytospin specimen of these cell were immunoc … More ytochemically stained Topo II alpha, Ki-67, apoptosis( TUNEL method). In order to observed DNA damage and synthesis, thymine dymer and BrdU were mesured simultaneously. After UV irradiation, Topo alpha expression was incresed gradually. These alterration was parallel to thinin dymer but not to Ki-67. These result suggested that Topoisomerase II alpha is involved in DNA repair not in proliferation during repair phase. Immunohistochemical staining of TopoisomeraseII alpha is a maker of cellular activity and site of DNA repair possibility a useful marker of cellular progression to other cell cycle antigen.(Clinical study)DNA topoisomerase II alpha (Topo II alpha) and Ki- 67 antigens in colon cancers from 51 pa-tients were investigated by an immunohi-stochemuical technique using monoclonal anti-Topo II alpha (8D2) and MIB-1 antibodies respectively. Positive cells of TopoII alpha and Ki-67 antigens were observed at progressive sites of all samples.Positive rates of their expressions were calculated as the number of positive cells/lOOOover cancer cells in the section.A posi-tive correlation was detected between Topo II alpha indices and Ki-67 indices (r=O.55).Although there was a relative tendency in Topo II alpha and histological grading, the-re was no significant difference and further examination is necessary for evaluation. It was suggested that Topo II alpha maybe useful as a proliferative marker for detecting colon cancer. Less

(基础研究)DNA拓扑异构酶IIα催化DNA的构象变化，与DNA复制、转录、染色体缩合等过程密切相关，在DNA拓扑异构酶II反应中形成瞬时双链断裂。已有研究表明，拓扑异构酶IIα在DNA修复中具有重要作用。我们用免疫组织化学方法分析了紫外线照射和抗癌药物诱导的人结肠癌细胞株(COLO32ODM)DNA修复过程中Topo IIα的活性。在抗肿瘤药物的研究中，我们比较了Vp-16作为DNA拓扑异构酶II抑制剂时的Topo IIα活性与其他DNA损伤时的CDDP。我们观察到，在Colo32ODM中单独使用CDDP时其活性显著增加，但在VP-16存在下并与CDDP结合时其活性降低。这些细胞的胞浆标本均为免疫…TOPO IIα、Ki-67、细胞凋亡(TUNEL法)染色增强。同时测定胸腺嘧啶二聚体和BrdU，观察DNA损伤和合成。紫外线照射后，Topoα表达逐渐增加。这些变化与Thin-dymer呈平行关系，而与Ki-67无关。这些结果表明，拓扑异构酶IIα参与DNA修复，而不是参与修复阶段的增殖。拓扑异构酶IIα的免疫组织化学染色是细胞活性和DNA修复位置的标志物，是细胞向其他细胞周期抗原进展的有用标志。临床研究分别用抗Topo IIα(8D2)和MIB-1的单抗对51例结肠癌组织中的DNA拓扑异构酶IIα(Topo IIα)和Ki-67抗原进行了检测。所有标本进展点均可见Topo IIα和Ki-67抗原阳性细胞，以阳性细胞数/肿瘤细胞数计算其阳性细胞数。Topo IIα指数与Ki-67指数呈正相关(r=0.55)。Topo IIα指数与组织学分级虽有相对趋势，但差异无统计学意义，有待进一步检验。提示Topo IIα可作为检测结肠癌的增殖标记物。较少

项目成果

R.Makizumi: "Expression of DNATopoisomerase II alpha and Clinical Significant in Advanced Colon Cancer" The St.Marianna Medical Journal. Vol.25, No4. 315-322 (1997)

R.Makizumi：“DNA 拓扑异构酶 II α 的表达及其在晚期结肠癌中的临床意义”《圣玛丽安娜医学杂志》。

野崎久充, 山田恭司, 他: "大腸癌細胞株を用いた紫外線照射によるDNA障害時におけるTopoisomerase IIαの発現" 聖マリアンナ医科大学雑誌. 25. 273-283 (1997)

Hisamitsu Nozaki、Kyoji Yamada 等人：“结直肠癌细胞系中 UV 照射引起的 DNA 损伤期间拓扑异构酶 IIα 的表达”，圣玛丽安娜大学医学院杂志 25. 273-283 (1997)。

野崎久充,山田恭司,他: "大腸癌細胞株を用いた紫外線照射によるDNA障害時におけるTopoisomerase IIの発現" 聖マリアンナ医科大学雑誌. 25. 273-283 (1997)

Hisamitsu Nozaki、Kyoji Yamada 等人：“结直肠癌细胞系中紫外线照射引起的 DNA 损伤期间拓扑异构酶 II 的表达”，圣玛丽安娜大学医学院杂志 25. 273-283 (1997)。

牧角良二: "進行大腸癌におけるDNA Topoisomerase IIαの発現と臨床的意義" 聖マリアンナ医科大学雑誌. 25. 315-322 (1997)

Ryoji Makikado：“DNA 拓扑异构酶 IIα 在晚期结直肠癌中的表达和临床意义”圣玛丽安娜大学医学院杂志 25. 315-322 (1997)。

H.Nozaki, K.Yamada, M.Iwasaki: "Studies on the Role of Human DNA Topoisomerase II alpha During DNA Repair Induced by Ultraviolet Light Irradiation." The St.Marianna Medical Journal. Vol.25, No4. 273-283 (1997)

H.Nozaki、K.Yamada、M.Iwasaki：“人类 DNA 拓扑异构酶 II α 在紫外线照射诱导的 DNA 修复过程中的作用研究”。