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[人肿瘤克隆形成试验对抗癌药物化学敏感性检测的实验与临床研究]

[Experimental and clinical studies on chemosensitivity tests of anticancer agents by human tumor clonogenic assay].

作者信息

Hirabayashi N

出版信息

Nihon Geka Gakkai Zasshi. 1986 Aug;87(8):834-45.

PMID:3092023
Abstract

In vitro chemosensitivity tests of anticancer agents for 119 fresh human tumors were performed by the human tumor clonogenic assay (HTCA) technique and the following results were obtained. Colony growth (greater than or equal to 5 colonies/dish) was observed in 35 of 50 gastric cancers (70.0%), 10 of 17 colon cancers (58.8%), 13 of 14 breast cancers (92.9%), two of six esophageal cancers (33.3%), three of six sarcomas (50.0%), three of 16 hematological malignancies (18.8%) and seven of 10 other tumors (70.0%). Colony growth rate differed according to the type of tumor. Fifty four tumors formed adequate colony growth (greater than or equal to 30 colonies/dish) for the chemosensitivity test. Mitomycin C (MMC), 5-Fluorouracil (5-FU), 4-hydroperoxy cyclophosphamide (CPM), Adriamycin (ADM), Cis-dichlorodiammineplatinum (CDDP), and alpha-interferon (IFN-alpha) were tested. The average positive rates of MMC, 5-FU, CPM, CDDP, and IFN-alpha were 26.9, 21.6, 10.5, 26.9, 36.8, and 23.3% respectively for all the tumors tested. In gastric cancer, the positive rates of MMC and 5-FU were 24.0 and 21.6% respectively, whereas the rates were 33.3 and 33.3% in colon cancer and 18.2 and 16.7% in breast cancer respectively. Each tumor exhibited its own chemosensitivity rates against various anticancer agents. Eighteen of the results obtained were comparable to clinical responses. The true positive rate was 50.0% (2/4) and the true negative rate 92.9% (13/14). A statistically significant correlation was observed between the results of HTCA and clinical responses (chi 2 test, p less than 0.05). The combined effects of IFN-alpha and MMC were surveyed against 20 gastroenterological tumors. Nine tumors exhibited synergistic effect, though antagonistic effect was observed in three tumors. The effects of oxygen tension (2%, 5%, 20%) on colony growth were investigated. The greatest development of colonies occurred at an oxygen of five percent, which is considered to be physiological oxygen tension, and statistically significant increases of plating efficiencies at 5% O2 as compared to those at 20% O2 were observed (t-test, p less than 0.025).

摘要

采用人肿瘤克隆形成试验(HTCA)技术对119例新鲜人肿瘤进行了抗癌药物的体外化学敏感性试验,结果如下。在50例胃癌中的35例(70.0%)、17例结肠癌中的10例(58.8%)、14例乳腺癌中的13例(92.9%)、六例食管癌中的两例(33.3%)、六例肉瘤中的三例(50.0%)、16例血液系统恶性肿瘤中的三例(18.8%)以及10例其他肿瘤中的七例(70.0%)观察到集落生长(大于或等于5个集落/培养皿)。集落生长率因肿瘤类型而异。54个肿瘤形成了足够的集落生长(大于或等于30个集落/培养皿)用于化学敏感性试验。对丝裂霉素C(MMC)、5-氟尿嘧啶(5-FU)、4-氢过氧环磷酰胺(CPM)、阿霉素(ADM)、顺二氯二氨铂(CDDP)和α-干扰素(IFN-α)进行了测试。所有受试肿瘤中,MMC、5-FU、CPM、CDDP和IFN-α的平均阳性率分别为26.9%、21.6%、10.5%、26.9%、36.8%和23.3%。在胃癌中,MMC和5-FU的阳性率分别为24.0%和21.6%,而在结肠癌中分别为33.3%和33.3%,在乳腺癌中分别为18.2%和16.7%。每种肿瘤对各种抗癌药物都有其自身的化学敏感性率。所获得的18项结果与临床反应具有可比性。真阳性率为50.0%(2/4),真阴性率为92.9%(13/14)。在HTCA结果与临床反应之间观察到统计学上的显著相关性(卡方检验,p<0.05)。针对20例胃肠肿瘤研究了IFN-α和MMC的联合作用。9个肿瘤表现出协同作用,不过在3个肿瘤中观察到拮抗作用。研究了氧张力(2%、5%、20%)对集落生长的影响。集落在5%的氧浓度下生长最为旺盛,5%的氧浓度被认为是生理氧张力,与20%氧浓度相比,在5% O2时接种效率有统计学上的显著提高(t检验,p<0.025)。

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