Epidermal growth factor receptor [EGFR (HER1,erbB1These results suggested that these modification of EGFR by CPT-11, in Lovo cells, is a possible mechanism for the synergistic effect of CPT-11 and gefitinib. These findings imply that the EGFR-TKI gefitinib and CPT-11 will be effective against colorectal tumor cells that express high levels of EGFR, and support clinical evaluation of gefitinib in combination with CPT-11, in the treatment of colorectal cancers.

The two ferrocene compounds, ferrocenylacetic acid (3) and ferrocylthiomalic acid (4), as well as the ferricenium salts, ferricenium tetrachloroferrate (111) (1) and ferricenium trichloroacetatetrichloroacetic acid solvate (2), were investigated by the in vitro human tumor clonogenic assay for their inhibiting effects, in continuous exposure in a double-layer medium, on the colony formation of single-cell suspensions prepared from 30 selected fresh specimens of human adenocarcinoma, squamous cell carcinoma and large-cell carcinoma of the lung. At the high drug concentration level of 100 pg cm-', good response ratios were observed for 3 (79%) and 4 (72%), followed by 1 (67%) and 2 (52%). At the low concentration level of 10 Fg cm-3 response ratios were below 25% for all compounds, best performance (24%) being shown by 1. In vitro experiments probing the schedule dependencies of the compounds' inhibiting effects against the lung carcinoma cell line PC-9 were also performed, as were experiments involving the combination of the ferricenium salt 1 and cisplatin, which showed the combination effect to be additive in both one-hour and continuous-exposure tests.

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These results suggest the usefulness of combinations of KRN5500 with cisplatin, carboplatin or etoposide for chemotherapy for non-small-cell lung cancer.

BACKGROUND Oncoprotein 18 (op18) was first isolated as a molecule overexpressed in several malignant cells, suggesting a function of op18 in malignant processes, such as differentiation in hematologic malignancies, op18 also was found to enhance microtubule deassembly in the cells. Antimitotic agents that bind to tubulin have been used for chemotherapy to treat solid tumors, such as lung carcinoma. Vinca alkaloids, such as vindesine and vincristine, have commonly been used for chemotherapy of nonsmall cell lung carcinoma. The authors examined the role of op18 in the sensitivity of human lung carcinoma cells to antimitotic agents. METHODS Expression of op18 mRNA was detected in all 17 lung carcinoma cell lines tested by Northern blotting. Oncoprotein 18 cDNA was transfected to SBC‐3 human lung carcinoma cells, and the stable transfectants, SBC‐3/op1‐3, were isolated. The sensitivity of these transfectants against antimitotic agents were examined by the MTT assay in vitro. Cell cycle distribution of the transfectants on DNA histogram was analyzed by flow cytometry. RESULTS Oncoprotein 18–transfected cells showed higher sensitivity to vindesine and vincristine, but not to taxanes. Vindesine‐exposure increased the G2/M population of the cell cycle in the Mock transfectants, but not in SBC‐3/op1, suggesting that the cell cycle dynamics were altered by op18 expression in SBC‐3/op1. CONCLUSION Oncoprotein 18 expression is associated with lung carcinoma cell sensitivity to vindesine and may be able to serve as a surrogate marker for the chemosensitivity to Vinca alkaloids in human lung carcinomas. Cancer 2001;91:1494–9. © 2001 American Cancer Society.