Relationship of chemotherapy on human cancer xenografts in nude mice to clinical response in donor patient

Abstract

Responsiveness of experimental chemotherapy on human cancer xenografts in nude mice was directly compared with clinical response to the same chemotherapy in their donor patients. These xenografts were 1 line of rectal cancer (H-26), two lines of gastric cancer (H-08 and H-22), and 1 line of breast cancer (H-62). Experimental chemotherapies studied were single-drug FT-207 to four lines of xenografts and a combination of mitomycin C, 5-FU, and cytosine arabinoside (MFC) to a line of gastric cancer H-08. Single-drug treatment with FT-207 to H-26 resulted in remarkable retardation of the tumor growth. The comparative treatment with FT-207 suppository to the donor patient of H-26 showed appreciable response. All the other chemotherapies to three other lines (H-08, H-22, and H-62) induced no significant response, which was parallel to the corresponding clinical response in each donor patient. The sensitivity to chemotherapeutic drugs was thought to be still preserved in human cancer xenografts in nude mice.

MEN4901/T-0128, a New Camptothecin Derivative–Carboxymethyldextran Conjugate, Has Potent Antitumor Activities in a Panel of Human Tumor Xenografts in Nude Mice

“…Improved pharmacokinetic properties of MEN4901/T-0128 in terms of plasma half-life, tissue distribution, and tumor T-2513 accumulation may account for the effectiveness. Because the efficacies of some drugs in this human cancernude mouse panel correlated well with their clinical outcomes in patients with the same type of cancers (14,16,23,24), the findings provide direct support that MEN4901/T-0128 is more efficacious than CPT-11 and is an excellent candidate for clinical trials for the treatment of solid tumors. Although MEN4901/T-0128 embodies many of the essential properties indicated for clinical success, it is not peerless as other polymer-and polysaccharide-based CPT conjugates have shown comparable pharmacokinetic properties (3, 4, 6 -8, 10, 11).…”

FK317, a Novel Substituted Dihydrobenzoxazine, Exhibits Potent Antitumor Activity against Human Tumor Xenografts in Nude Mice

“…Since human tumor xenografts are among the best models for predicting drug efficacy in clinical settings, [14][15][16] the activity of FK317 against many human tumors xenografted in athymic mice was examined and compared with those of clinically used antitumor agents, MMC, ADR, CDDP, taxol and CPT-11. FK317 could produce regression and/or ≥80% tumor growth inhibition of almost all tumor xenografts examined, except PC-9 and effects.…”

Dependence of chemotherapy response on p53 mutation status in a panel of human cancer lines maintained in nude mice

“…1,10) In previous experiments, we compared the results of experimental chemotherapy of 17 tumor lines with those of chemotherapy in the original patients and found a good correlation between the responses to chemotherapeutic agents of the original tumors and the cell lines. 11,12) We also analyzed determinant factors for chemosensitivity in the same panel and found that the combination of tumor volume doubling time (VDT) and the vascularity of the tumor correlates well with chemosensitivity. 1,13) Oncogenes and tumor-suppressor genes are believed to be chemosensitivity determinant factors.…”