Anticancer chemosensitivity and growth rate of freshly separated human colorectal cancer cells assessed by in vitro DNA synthesis inhibition assay.
The present study was designed to assess the chemosensitivity profile of freshly separated colorectal cancer cells and to screen effective agents for the design of new combination regimens. The DNA synthesis and chemosensitivity (% inhibition of DNA synthesis by the anticancer agent) were successfully assessed in 184 samples (107 primary and 77 metastatic or recurrent lesions) from 152 patients with colorectal cancer using an 3H-thymidine incorporation assay, and the correlations between these two measures and various clinicopathological factors were analysed. DNA synthesis was highest in nodal metastasis followed by malignant effusion, primary lesion, liver metastasis, and local recurrence. DNA synthesis liver metastasis and local recurrence were significantly lower than in other lesions. The results of the chemosensitivity assay are as follows: 5-FU seems to be the most beneficial for primary colorectal cancer; carboquone (CQ), etoposide (VP-16), 5-FU, and mitomycin-C (MMC) for nodal metastasis; CQ, cisplatin (CDDP), 5-FU, adriamycin (ADR) and VP-16 for malignant effusion; and VP-16, CDDP and CQ for liver metastasis. However, the present results showing the chemosensitivity profiles in different lesions suggest that regimens including 5-FU with VP-16 and CQ in addition to MMC or ADR may be applicable for all kinds of colorectal cancer lesions. These results demonstrated the heterogeneity in the chemosensitivity of colorectal cancer, which suggests not only the necessity of patient-specific chemotherapy dependent on the sensitivity assay, but also the usefulness of the present results in the choice of agents for widely applicable combination regimens for colorectal cancer.
First Department of Surgery, Kyoto University, Japan.
K
K
Kawabata
Y
Y
Nio
M
M
Imamura
M
M
Fukumoto
D000970:Antineoplastic Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015179:Colorectal Neoplasms / Q000473:pathology*; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary*; D008207:Lymphatic Metastasis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm