Abstract

The overall objective of this program is to improve the chemotherapy of human cancer. To acomplish that objective a coordinated series of multidisciplinary studies are conducted as follows: 1. Selected agents, synthesized within our Institute and from outside sources, are tested in established experimental tumor systems, in tumor cells in culture, and in special models for antitumor activity as well as in antiviral assays both in vitro and in mice. 2. Additional systems, new or new in our laboratory, are developed and utilized for antitumor tests, such as a rat colon carcinoma or models for metastatic brain tumors. We also investigate the action and effects of antitumor agents on immune systems. 3. To improve the usefulness of known chemotherapeutic agents we attempt the development of new combination therapy regimens including immunopotentiators. 4. Studies of the mechanism of therapeutic action of antitumor agents are aimed at elucidating primary biochemical lesions, the nature of resistance, and the factors responsible for therapeutic selectivity. In regard to selectivity, emphasis is placed on transport mechanisms, in particular, those concerned with the uptake and retention of antifols.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA018856-13
Application #
3092792
Study Section
Cancer Therapeutics Program Project Review Committee (CTR)
Project Start
1985-01-01
Project End
1989-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
13
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

He, Ling; Chang, He-Xi; Chou, Ting-Chao et al. (2003) Design of antineoplastic agents based on the '2-phenylnaphthalene-type' structural pattern--synthesis and biological activity studies of 11H-indolo[3.2-c]quinoline derivatives. Eur J Med Chem 38:101-7
Lin, Y; Ince, T A; Scotto, K W (2001) Optimization of a versatile in vitro transcription assay for the expression of multiple start site TATA-less promoters. Biochemistry 40:12959-66
Johnson, R A; Ince, T A; Scotto, K W (2001) Transcriptional repression by p53 through direct binding to a novel DNA element. J Biol Chem 276:27716-20
Chang, H X; Chou, T C; Savaraj, N et al. (1999) Design of antineoplastic agents based on the ""2-phenylnaphthalene-type"" structural pattern. 4. Synthesis and biological activity of 2-chloro-3-(substituted phenoxy)-1, 4-naphthoquinones and related 5,8-dihydroxy-1,4-naphthoquinones. J Med Chem 42:405-8
Chou, T C; Otter, G M; Sirotnak, F M (1996) Schedule-dependent synergism of taxol or taxotere with edatrexate against human breast cancer cells in vitro. Cancer Chemother Pharmacol 37:222-8
Kim, J Y; Su, T L; Chou, T C et al. (1996) Cyclopent[a]anthraquinones as DNA intercalating agents with covalent bond formation potential: synthesis and biological activity. J Med Chem 39:2812-8
Piper, J R; Ramamurthy, B; Johnson, C A et al. (1996) Analogues of 10-deazaaminopterin and 5-alkyl-5,10-dideazaaminopterin with the 4-substituted 1-naphthoyl group in the place of 4-substituted benzoyl. J Med Chem 39:614-8
Su, T L; Chou, T C; Kim, J Y et al. (1995) 9-substituted acridine derivatives with long half-life and potent antitumor activity: synthesis and structure-activity relationships. J Med Chem 38:3226-35
Sacks, P G; Harris, D; Chou, T C (1995) Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: a rationale for combination therapy with chemotherapeutic agents. Int J Cancer 61:409-15
Schlemmer, S R; Yang, C H; Sirotnak, F M (1995) Functional modulation of multidrug resistance-related P-glycoprotein by Ca(2+)-calmodulin. J Biol Chem 270:11040-2

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