This program project grant is committed to the development of new chemotherapeutic strategies. It tightly integrates laboratory investigators with clinician-scientists resulting in the propagation of ideas directly from the laboratory into clinical trial. The Section of Medical Oncology has been realigned to promote this program through Disease Specific Units. Additional backing comes from the Pharmacology Program Project Grant (Dr. Alan Sartorelli, P.I.) which explores more speculative aspects of tumor biology and metabolism to identify leads for developmental therapeutics. The Comprehensive Cancer Center provides additional support through its core facilities. Dr. Sartorelli, Director, and Dr. Hait, Associate Director for Clinical Affairs, are direct links with this program. Specific projects and their direct applications include: 6- thioguanine and hypoxanthine to induce differentiation of leukemic cells- Leukemia Unia (Sartorelli, Todd); the calcium messenger system in squamous cell differentiation - Head and Neck Unit (Reiss); synergism between BCNU and thymidine-Neuro-oncology and Lymphoma Units (Prusoff, Cooper); new agents to overcome multidrug resistance - Breast Unit and others (Hait, Handschumacher); biochemical aspects to hepatic metastases - GI Unit (Handschumacher); Genetic transfer of drug-resistance-all units (Cadman). The Clinical Trials project provides the clinical outlet for the laboratory programs. The program is supported by four Cores, Administrative, Biostatistics, Clinical Pharmacology, and Clinical Diagnostics.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Yale University
Schools of Medicine
New Haven
United States
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Yang, J M; Sullivan, G F; Hait, W N (1997) Regulation of the function of P-glycoprotein by epidermal growth factor through phospholipase C. Biochem Pharmacol 53:1597-604
Yang, J M; Chin, K V; Hait, W N (1996) Interaction of P-glycoprotein with protein kinase C in human multidrug resistant carcinoma cells. Cancer Res 56:3490-4
Buzaid, A C; Pizzorno, G; Marsh, J C et al. (1995) Biochemical modulation of 5-fluorouracil with brequinar: results of a phase I study. Cancer Chemother Pharmacol 36:373-8
Yang, J M; Chin, K V; Hait, W N (1995) Involvement of phospholipase C in heat-shock-induced phosphorylation of P-glycoprotein in multidrug resistant human breast cancer cells. Biochem Biophys Res Commun 210:21-30
Marsh, J C; Durivage, H J; Davis, C et al. (1992) Phase II study of pulse 5-fluoro-2'-deoxyuridine and leucovorin in advanced colorectal cancer patients previously treated with chemotherapy. Am J Clin Oncol 15:115-8
Aftab, D T; Ballas, L M; Loomis, C R et al. (1991) Structure-activity relationships of phenothiazines and related drugs for inhibition of protein kinase C. Mol Pharmacol 40:798-805
Murren, J R; Ganpule, S; Sarris, A et al. (1991) A phase II trial of cyclosporin A in the treatment of refractory metastatic colorectal cancer. Am J Clin Oncol 14:208-10
Murren, J R; Buzaid, A C; Hait, W N (1991) Critical analysis of neoadjuvant therapy for Stage IIIa non-small cell lung cancer [corrected] Am Rev Respir Dis 143:889-94
Hait, W N; Byrne, T N; Piepmeier, J et al. (1990) The effect of calmodulin inhibitors with bleomycin on the treatment of patients with high grade gliomas. Cancer Res 50:6636-40
Kacinski, B M; Chambers, S K; Stanley, E R et al. (1990) The cytokine CSF-1 (M-CSF) expressed by endometrial carcinomas in vivo and in vitro, may also be a circulating tumor marker of neoplastic disease activity in endometrial carcinoma patients. Int J Radiat Oncol Biol Phys 19:619-26

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