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Biomedical subjects

G L Neil

Publications and source records attributed to G L Neil.

48 records · Page 3Linked to original sources
PubMedDate not supplied

Comparative studies of cyclocytidine (NSC-145668) and cytosine arabinoside (NSC-63878) in mice.

The distribution of cyclocytidine and cytosine arabinoside has been studied in normal BDF mice and in mice bearing 6-day solid L1210 lymphocytic leukemia by whole-body radioautography, bioassay, and radiochemical techniques. Radioactivity was widely distributed throughout the tissues between 15 minutes and 12 hours after a single intravenous dose of either cyclocytidine-2-14C or cytosine arabinoside-2-14C. Whole-body radioautograms demonstrated that for most tissues, cytosine arabinoside-derived 14C was uniformly excreted by 48 hours; cyclocytidine-derived 14C, however, was localized in certain tissues as early as 15 minutes after drug administration and was retained in these sites for 48 hours. Depot loci of 14C included salivary and adrenal glands, fat, cardiac muscle, gastrointestinal tract, and L1210 tumor. The distribution and persistence of cyclocytidine-derived radioactivity is consistent with other reports of toxicity induced by the drug in these tissues. Radiochromatography and bioassay data from BDF mice dosed intraperitoneally with cyclocytidine demonstrated that 65%-95% of the 14C-radioactivity in a number of tissues was the parent compound itself. Thus, cyclocytidine contributed in large measur to the generation of the radioautograms. This study demonstrates that the retention of cyclocytidine in body tissues may serve to effect the sustained release of the deaminase-resistant chemotherapeutic drug from these depot sites and thus prolong cytotoxic levels of drug in tumor tissue.

Adipose Tissue↗
PubMedDate not supplied

Treatment of mouse tumors with 7-con-O-methylnogarol and other analogs of the anthracycline antibiotic, nogalamycin.

The chemotherapeutic activity of analogs of the anthracycline antibiotic, nogalamycin, was investigated in the P388 and L1210 leukemias and the B16 melanoma in mice. Among the compounds tested, 7-con-O-methylnogarol was found to have superior activity. Depending on the route and schedule of administration, increases in lifespan (ILS) in excess of 100% were observed in all three tumor systems. Additional testing of 7-con-O-methylnogarol demonstrated significant activity in the murine colon 26 and colon 38 tumors and the CD8F1 mammary tumor. 7-Con-O-methylnogarol was not significantly effective against murine Lewis lung carcinoma, although ILSs of 38% and 29% were achieved in two experiments. Activity was observed against ip inoculated P388 leukemia after ip, sc, oral, and iv drug administration. 7-Con-O-methylnogarol was also highly active (ILS greater than or equal to 120%) after ip drug administration to mice with iv inoculated P388 leukemia. Significant ILS values resulted from a variety of schedules of administration against ip inoculated P388 leukemia and B16 melanoma. Experiments in which the time of single-dose administration was varied prior to the time of ip P388 leukemia inoculation showed that residual drug or bioactive drug-related materials remained in mice for 8 hours after 50 mg/kg administered ip and for 48 hours after 200 mg/kg administered sc.

Animals↗
PubMedDate not supplied

Enhancement by tetrahydrouridine (NSC-112907) of the oral activity of 5-azacytidine (NSC-102816) in L1210 leukemic mice.

5-Azacytidine is more active when administered parenterally than orally in the treatment of L1210 leukemic mice. Oral coadministration of tetrahydrouridine, a pyrimidine nucleoside deaminase inhibitor with no intrinsic antitumor activity, greatly increases the oral activity of 5-azacytidine. 5-azacytidine (or cytotoxic equivalent) blood levels in BDF mice are much higher after oral administration of the 5-azacytidine-tetrahydrouridine combination than when 5-azacytidine is administered alone by the same route. The therapeutic results (L1210 leukemia) achieved with the oral combination are similar to those observed with parenteral 5-azacytidine alone.

Administration, Oral↗
PubMedDate not supplied

Phase I study of 5-azacytidine (NSC-102816) using 24-hour continuous infusion for 5 days.

The biologic and antitumor activity of 5-azacytidine has been well demonstrated in the past. The drug at present is thought to be primarily cell cycle phase specific. This study was designed to eliminate undesirable side effects (mainly nausea and vomiting) occurring with a bolus dose and to confirm the recent findings of the relative stability of 5-azacytidine's solution with preserved biologic and antitumor activity. In the study we determined that a dose of 150 mg/m2/day given as a 120-hour continuous iv infusion and repeated at 28-day intervals produced safe, manageable, and reproducible toxicity. The drug was freshly prepared at 4-hour intervals. Eleven courses were administered to seven patients at this dose level and no patient experienced nausea or vomiting. Leukopenia was the major toxic effect. Antitumor activity was shown in one patient with colon cancer and another with American Burkitt's lymphoma.

Adult↗