Molecular biological analysis of urothelial cancers using short-term cultures of urinary exfoliated cells

使用尿脱落细胞的短期培养物对尿路上皮癌进行分子生物学分析

• 批准号: 08671813
• 负责人: OKUNO Hiroshi
• 金额: $ 1.34万
• 依托单位: KYOTO UNIVERSITY
• 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 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671813/
• 关键词: urothelial; urinary exfoliated cell; short-term culture; intraluminal tumor recurrcncc; p53; immunocytochemistry; 細胞培養; 多中心性発生; 尿路腔内播種; アクリジンオレンジ

Urothelial cancers, in particular of upper urinary tract cancers, is multifocal synchronous and/or metachronous tumor development in the heterotopic urothelium. We investigated the abilities of exfoliated cells in the urine of patients with urothelial cancers to colonize and proliferate in vitro. Short-term cultures of 129 urine samples obtained from patients with urothelial cancers and 53 samples from healthy volunteers were compared as to the growth potential of urinary-exfoliated cells and clinico-pathological features, in particular tumor localization and evidence of intraluminal tumor recurrence. Primary cell outgrowth occurred in 112 (86.8%) of the 129 cell cultures from the patients and in 29 (54.7%) of the 53 from the healthy volunteers (p<0.0001). "Sufficient cell growth" (more than 10^5 cells per flask) was obtained for 77 (59.7%) of the 129 cultures from patients and 7(13.2%) of the 53 from the healthy volunteers (p<0.0001). In terms of tumor localization, the rate of suffic … More ient cell growth was significantly higher for patients with upper urinary tract tumor (21/25,84.0%) than for those with bladder tumor (56/104,53.8%) (p=0.0062). Proportional hazard regression analysis showed that only the growth potential of the urinary-exfoliated cells was significantly predictive of intravesical tumor recurrence in patients with superficial bladder tumors (p=0.011). The potentials for the colonization and proliferation of urinary-exfoliated cells are associated with intraluminal multifocal tumorrecurrence of urothelial cancers.Mutation of the p53 gene together with allelic loss of chromosome 17p correlates well with high grade and invasiveness of urothelial cancer. Using the short-term culture system, immunocytochemical detection of p53 was conducted. Results of immunochemical analyzes of the p53 in the urine cells and those in the tumor samples were identical in 92.1% of the patients. Culture of exfoliated cells in urine is a good method for the molecular diagnosis of urothelial cancer. In particular, it is a non-invasive examination that should prove useful for the early detection and intensive follow-up of tumorswith p53 mutation. Less

尿路上皮癌，特别是上尿路癌，是在异位尿路上皮中发生的多灶性同步和/或异时性肿瘤。我们研究了尿路上皮癌患者尿液中脱落细胞在体外定植和增殖的能力。对129例尿路上皮癌患者和53例健康志愿者的尿液样本进行短期培养，比较尿液脱落细胞的生长潜力和临床病理特征，特别是肿瘤定位和腔内肿瘤复发的证据。在来自患者的129个细胞培养物中的112个（86.8%）和来自健康志愿者的53个细胞培养物中的29个（54.7%）中发生了原代细胞生长（p<0.0001）。在来自患者的129份培养物中，有77份（59.7%）获得了“足够的细胞生长”（每个培养瓶超过10^5个细胞），在来自健康志愿者的53份培养物中，有7份（13.2%）获得了“足够的细胞生长”（p<0.0001）。在肿瘤定位方面， ...更多信息 上尿路肿瘤患者的上皮细胞生长率（21/25，84.0%）显著高于膀胱肿瘤患者（56/104，53.8%）（P=0.0062）。比例风险回归分析表明，只有尿脱落细胞的生长潜力是显着预测膀胱内肿瘤复发的浅表性膀胱肿瘤患者（p=0.011）。尿脱落细胞的定植和增殖能力与尿路上皮癌的腔内多灶性肿瘤复发有关，p53基因突变和17号染色体等位基因缺失与尿路上皮癌的高级别和侵袭性密切相关。采用短期培养系统，进行p53的免疫细胞化学检测。92.1%的患者尿细胞和肿瘤组织中p53的免疫化学分析结果一致。尿脱落细胞培养是尿路上皮癌分子诊断的良好方法。特别是，它是一种非侵入性的检查，应该证明对p53突变肿瘤的早期发现和密切随访是有用的。少

项目成果

Hiroshi Okuno, Yoshiyuki Kakehi, Enver Ozdemir, Toshiro Terachi, Yusaku Okada and Osamu Yoshida.: "Association of in Vitro Growth Potential of Urinary Exfoliated Cells with Tumor Localization and Intraluminal Recurrence rates of Urothelial Cancers." Journ

Hiroshi Okuno、Yoshiyuki Kakehi、Enver Ozdemir、Toshiro Terachi、Yusaku Okada 和 Osamu Yoshida：“尿液脱落细胞的体外生长潜力与肿瘤定位和尿路上皮癌管腔内复发率的关联。”

Hiroshi Okuno, Yoshiyuki Kakehi, Osamu Ogawa, Hitoshi Yamada, Enver Ozdemir, Yusaku Okada and Osamu Yoshida.: "Immunocytochemical Detection of p53 in Cultures of Exfoliated Cells from Urine of Patients with Urothelial Cancers." Japanese Journal of Cancer

Hiroshi Okuno、Yoshiyuki Kakehi、Osamu Okawa、Hitoshi Yamada、Enver Ozdemir、Yusaku Okada 和 Osamu Yoshida.：“尿路上皮癌患者尿液脱落细胞培养物中 p53 的免疫细胞化学检测。”

Okuno,H.et.al.: "Immonocytochemical Detection of p53 in Cultures of Exfoliated Cells from Urine of Patient with Urothelial Cancer" Jpn.J.Cancer Res.87. 718-723 (1996)

Okuno,H.et.al.：“尿路上皮癌患者尿液脱落细胞培养物中 p53 的免疫细胞化学检测”Jpn.J.Cancer Res.87。

Hiroshi Okuno et.al.: "Immunocy to chemical Detection of p53 in Cultures of Exfoliated Cells from Urine of Patients with Urothelial Cancers" Jpn.J.Cancer Res.87. 718-723 (1996)

Hiroshi Okuno 等人：“尿路上皮癌患者尿液脱落细胞培养物中 p53 化学检测的免疫”Jpn.J.Cancer Res.87。

奥野博 他: "尿路上皮癌患者尿中剥離細胞の短期培養系を用いた分子生物学的診断法の開発" 腎泌予防医学誌. 5・1. 2-3 (1997)

Hiroshi Okuno 等人：“使用尿路上皮癌患者尿液中脱落细胞的短期培养系统开发分子生物学诊断方法”，肾病学和预防医学杂志 5・1（1997 年）。