Search PubMed⌕ Search

Biomedical subjects

M R Grever

Publications and source records attributed to M R Grever.

92 records · Page 6Linked to original sources

Phase II evaluation of teniposide and ifosfamide in refractory adult acute lymphocytic leukemia: a Southwest Oncology Group Study.

The Southwest Oncology Group undertook a phase II study of teniposide (VM-26) and ifosfamide in refractory adult acute lymphocytic leukemia. The 49 evaluable patients were heavily pretreated; 15 of these had received only one prior induction attempt. Two treatment regimens were used. Eighteen patients received VM-26 (30 mg/m2) on Days 1-5 and ifosfamide (1000 mg/m2) by continuous iv infusion on Days 1-5. When acceptable toxicity was observed, the dose of VM-26 was increased and 30 patients received VM-26 (50 mg/m2) on Days 1-5 in addition to ifosfamide. Complete remission (CR) was observed in two patients who received the lower-dose VM-26 regimen and in six patients who received the higher-dose regimen. Of the eight patients who achieved CR, six were found among the 15 patients who had received only one prior induction therapy. Hematologic toxicity was the major toxic effect observed, with 41 patients (84%) having wbc counts less than 1000/microliter during induction therapy. Nonhematologic toxicity was dose-limiting in seven patients for the following reasons: hematuria (four patients), neurological disturbance (one), and mucositis (two). The combination of VM-26 and ifosfamide is capable of producing CR in refractory acute lymphocytic leukemia in adults with manageable toxicity. Inclusion of the combination in a multidrug consolidation regimen for newly diagnosed patients is an appropriate avenue for further study.

Adolescent↗

Antiproliferative effect in vitro and antitumor activity in vivo of brefeldin A.

PURPOSE: An empiric in vitro screen of human tumor cell lines found brefeldin A inhibited the growth of immortalized human cell lines, with particular sensitivity to brefeldin in a series of immortalized melanoma cell lines and nonimmortalized prostate carcinoma explants. Brefeldin A alters the morphology and function of the Golgi apparatus, endosomal, and trans-Golgi compartments in different cell types. The studies presented here sought to obtain evidence of in vivo antitumor activity by brefeldin A. METHODS: Antiproliferative activity was studied in prostate carcinoma cells in vitro using cell counts, protein, and viable stains. Activity was also studied in vivo against subcutaneous and subrenal capsule melanoma models. RESULTS: Protracted exposures in vitro (between 24 and 72 hours) are necessary to cause persistent growth inhibition of immortalized PC3 prostate carcinoma cells. In human melanoma athymic mouse xenografts, brefeldin A showed antitumor activity in vivo when given 16 to 64 mg/kg/injection intraperitoneally q 7 h x 2, daily for 5 days. Activity was also observed in the intraperitoneal LOX IMVI (65%-100% increase in life span, with 17%-50% day 60 survivors); early-stage subcutaneous LOX IMVI and SK-MEL-5 (86%-100% growth inhibition), and subrenal capsule SK-MEL-5 and M19-MEL models. CONCLUSIONS: Brefeldin A possesses noteworthy antitumor activity in vivo and antiproliferative effects in vitro in certain cell types. Strategies to allow protracted exposure of tumor cells to brefeldin A while preserving a therapeutic index are needed to assess the clinical potential of brefeldin A.

Animals↗