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H H Bailey

Publications and source records attributed to H H Bailey.

25 records · Page 2Linked to original sources
PubMed1992

Increase in gamma-glutamylcysteine synthetase activity and steady-state messenger RNA levels in melphalan-resistant DU-145 human prostate carcinoma cells expressing elevated glutathione levels.

The biochemical and molecular basis for the elevation of glutathione (GSH) levels commonly detected in many drug-resistant cells has not been elucidated. In a series of L-phenylalanine mustard-resistant human prostate carcinoma cell lines (DU-145), resistance was associated with elevated GSH levels, increased activity of gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH biosynthesis, and a marked increase in the steady-state levels of GCS-specific transcripts (4.0 and 3.2 kilobases). Loss of the resistant phenotype was accompanied by a reduction in GSH and a return of GCS activity and transcript levels to values comparable to those detected in the drug-sensitive parent cells. These data strongly implicate up-regulation of GCS activity as an important mechanism in the evolution of drug resistance associated with increased levels of intracellular GSH. The results further suggest that the ability to synthesize GSH may be more indicative of resistance than steady-state GSH levels per se.

Drug Resistance↗
PubMedDate not supplied

Paclitaxel, carboplatin, and hexamethyl-melamine (taxchex) as first-line therapy for ovarian cancer.

BACKGROUND: The addition of hexamethylmelamine to therapy with cisplatin, cyclophosphamide, and doxorubicin significantly enhanced outcomes of patients with advanced ovarian cancer. Hexamethylmelamine, also known as altretamine, has potent antineoplastic activity when used as a single agent in patients who have failed to respond to both platinum-based and paclitaxel therapy. We have conducted a pilot study to evaluate the efficacy and safety of adding this drug to the popular ovarian cancer regimen of paclitaxel plus carboplatin. METHODS: Patients with advanced ovarian, fallopian tube, or primary peritoneal cancer (International Federation of Gynecology and Obstetrics stages IIA, IIIC, and IV) were prospectively enrolled to receive six cycles, repeated every 4 weeks, of paclitaxel (150 mg/m2 i.v., day 1), carboplatin (AUC 5.0 i.v., day 1), and hexamethylmelamine (150 mg/m2 p.o., days 2-15). Colony stimulating factors were prohibited. Response and toxicity were monitored by use of Eastern Cooperative Oncology Group criteria. RESULTS: Twenty patients were enrolled, 18 with ovarian cancer, one with fallopian tube cancer, and one with peritoneal cancer; 17 of these patients were evaluable for response and toxicity. At a median follow-up of 6.5 months, 13 of the patients had a complete response (76%), and four had progressive disease. Three of those with a complete response had a recurrence within 1 year of completing treatment. Toxicity was acceptable, with myelosuppression the most severe adverse effect; one patient had grade 3 anemia, one patient had grade 4 thrombocytopenia, and 12 patients had grade 4 neutropenia. Quality of life showed improvement over the course of therapy, particularly in the physical well-being subscale. CONCLUSION: The addition of hexamethylmelamine to paclitaxel and carboplatin is a well-tolerated multidrug combination for women with advanced ovarian cancer that deserves further testing in a phase III study.

Adult↗