The anticancer agent's FT-207, N1-(2'-tetrahydrofuryl)-5-fluorouracil, a derivative of 5FU (5-fluorouracil), induced chromosome damage to the human leukocyte was investigated. FT-207 inhibit mitosis and cause chromatid and chromosome breakage and chromatid exchange with 20 ug/ml for 48 to 72 hours of treatment. However, with 15 ug/ml for 72 hours only delayed spiralization was produced in some of the chromosomes in the same cells. The random distribution of chromosome breakage were observed and the effect of FT-207 on the chromosomes of human leukocytes were time dependent rather than concentration dependent. The comparision of the effect of mitomycin C on human leukocytes and the action of FT-207 at specific times during the cell cycle were discussed.
Cells, Cultured ; Chromosome Aberrations* ; Female ; Fluorouracil/analogs & derivatives* ; Human ; Leukocytes/drug effects ; Leukocytes/ultrastructure* ; Male ; Mitotic Index/drug effects ; Tegafur/pharmacology* ; Time Factors

AIMTo synthesize the selenophosphocholine analogues containing tegafur and test their antitumor activities.

METHODSThe cyclic glyceroselenophospholopid conjugate of tegafur was synthesized by the reaction of hexaethylphosphorous triamide with N1-(2-furanidyl)-N3-(hydroxyalkyl)-5-fluyorouracil and 1-O-hexadecyl glycerol as well as selenium in one-pot. Cyclic glyceroselenophospholopid conjugate of tegafur reacted with triethylamine to give title compounds.

RESULTSSix new compounds have been synthesized. Their structures were confirmed by 1H NMR, 13P NMR and elemental analysis. Antitumor activity of the title compounds against PGA1 was tested.

CONCLUSIONThe reaction of triethylamine with cyclic glyceroselenophospholopid conjugate of tegafur very readily occurred, which was finished within 2 h at room temperature. The opening-ring products of trans isomers showed antimutor activity against human uriaryl bladder cancer cell more effective than that of the tegafur.

Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Humans ; Magnetic Resonance Spectroscopy ; Organoselenium Compounds ; chemical synthesis ; pharmacology ; Phosphorylcholine ; analogs & derivatives ; Tegafur ; chemical synthesis ; pharmacology ; Urinary Bladder Neoplasms ; drug therapy ; pathology

BACKGROUND: There is no standard treatment for advanced non-small cell lung cancer (NSCLC) after the failure of two lines of chemotherapy, S-1 as the third generation of fluorouracil derivate with well safety and low toxicity, presented some efficacy in lung cancer treatment. The aim of this study is to explore the efficacy of S-1 for advanced NSCLC patients treated with two or more prior chemotherapy regimens. METHODS: We performed a retrospective analysis of 105 NSCLC patients treated with S-1 monotherapy or S-1 contained chemotherapy as the third or more line of treatment in our hospital from January 2014 to April 2017. S-1 was administrated orally twice daily for 2 weeks, followed by one week of rest, the dose of drug was determined by body surface area (<1.25 m2, 80 mg/d; 1.25 m2-1.5 m2, 100 mg/d; ≥1.5 m2, 120 mg/d), platinum or the third-generation chemotherapy drugs could be combinedly used. Clinical response was assigned every cycle according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Kaplan-Meier analysis was used to estimate progression-free survival (PFS). RESULTS: 42 patients received S-1 monotherapy, the other 63 patients received combined regimens, the median treatment line was 4 (3-11) and the median treatment cycle was 2 (1-14). No complete response (CR) were observed, there were 4 patients with partial response (PR), 34 patients with stable disease (SD) and 67 patients with progressive disease (PD), the objective response rate (ORR) was 3.81%, disease control rate (DCR) was 36.19%. The median PFS was 1.90 months (0.67 months-10.83 months), no difference between monotherapy and combined group (DCR: 28.56% vs 41.27%, P=0.185), the liver metastasis showed poorer PFS (1.40 months vs 1.93 months , P=0.042). CONCLUSIONS S-1 presented some activity in advanced NSCLC treated with more than two lines of treatment. The addition of other drugs cannot improve efficacy. S-1 monotherapy can be used as a choice for heavily-treated patients.
Adult ; Aged ; Antineoplastic Agents ; adverse effects ; pharmacology ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Drug Combinations ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Oxonic Acid ; adverse effects ; pharmacology ; therapeutic use ; Retrospective Studies ; Safety ; Survival Analysis ; Tegafur ; adverse effects ; pharmacology ; therapeutic use ; Treatment Outcome