Program Description
Synthetic deltanoids (vitamin analogs) exhibit in vivo and in vitro evidence of antiproliferative, proapoptotic, prodifferentiating, and antiangiogenic activities indicative of chemopreventive efficacy. One such analog, QW-1624F2-2 possesses a substantially improved chemopreventive index in terms of its chemopreventive efficacy vs. calcemic toxicity. Preliminary results have shown that it is a potent, effective inhibitor of carcinogenesis in vivo. RAPID support will include synthesis of bulk material for preclinical studies, mutagenicity and short term preclinical toxicity testing, and in vivo screening and efficacy studies.

Contact Information
Gary H. Posner, Ph.D.
Johns Hopkins University School of Arts and Sciences
Department of Chemistry
Baltimore, MD
Tel: 410-516-4670
Fax: 410-516-8420

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Program Description
Investigators will conduct preclinical development of a next generation human papillomavirus vaccine. Human papillomaviruses play a critical role in the development of several cancers, the most common being cervical cancer. A second generation papillomavirus vaccine that is both economical and stable is being developed. Preliminary data showed it offers protection against experimental viral challenge in the canine model. RAPID support will include:

• In vivo and in vitro preclinical efficacy testing,
• Preclinical toxicology,
• GMP production, formulation, and an IND support.

Contact Information
Robert L. Garcea, M.D.
University of Colorado School of Medicine
Boulder, CO
Tel: 303-3154-3247
Fax: 303-315-3244

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Program Description
Investigators will conduct preclinical development of four flavonoids from Broussonetia papyrifera. Bioassay-guided fractionation of an extract from Broussonetia papyrifera, an endemic edible plant, using an in vitro aromatase inhibition assay led to isolation of four active flavonoid compounds. Preliminary results suggest that these compounds may be effective chemopreventive agents in preventing formation of estrogen-dependent tumors in the breast and the prostate. RAPID support will include:

• Synthesis of bulk materials for preclinical studies,
• Mutagenicity and short term preclinical toxicity testing, and
• In vivo screening and efficacy studies.

Contact Information
John M. Pezzuto, Ph.D.
Dean, College of Pharmacy
University of Hawaii
Tel: 808-933-2909
Fax: 808-933-2974

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Program Description
Investigators will conduct preclinical development of sulforaphane, a major constituent in broccoli. The consumption of cruciferous vegetables is associated with a reduced risk of cancer at various organ sites. Isothiocyanates are abundantly present in these vegetables and are thought to be major contributors to their chemopreventive activities. Sulforaphane is a major isothiocyanate in broccoli and has shown chemopreventive activity in various animal models. RAPID support will include:

• Synthesis of bulk and 14C-labeled material for preclinical studies,
• Mutagenicity and short term preclinical toxicity testing,
• Preclinical absorption, distribution, metabolism, elimination and pharmacokinetic studies,
• In vivo screening and efficacy studies, and
• Formulation.

Contact Information
Fung-Lung Chung, Ph.D.
Presently Professor, Department of Oncology
Lombardi Comprehensive Cancer Center
Georgetown University Medical Center
3800 Reservoir Rd. NW LL(S) level
Rm 128, Box 571465
Washington, DC 20057-1465
Tel: 202-687-3021

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Program Description
Investigators will conduct preclinical development of certain marine derived products.

Contact Information
Peter Collin
Coastside Research
Stonington, ME
Tel: 207-367-2297
Fax: 207-367-5929

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Program Description
Investigators will evaluate Se-Methylselenocysteine, a selenium containing amino acid. The substance is a good precursor of methylselenol and this monomethylated selenium is an important factor in chemoprevention. Se-Methylselenocysteine is found in many plant species, e.g. garlic, broccoli, and onions. It has been shown to inhibit the growth of chemically induced tumors in animal models at dietary concentrations as low as 2 ppm selenium. RAPID support will include:

• Mutagenicity and short-term preclinical toxicity testing,
• GMP synthesis, formulation, and packaging, and IND support.

Contact Information
Clement Ip, Ph.D.
Roswell Park Cancer Institute
New York, NY
Tel: 716-845-8875
Fax: 716-845-8100

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Program Description
Investigators will conduct preclinical development of DHEA-analog, Fluasterone, for efficacy trials in cancer prevention. The already developed synthetic steroid, fluasterone (16a-fluoro-5-androsten-17-one), which like its naturally occurring counterpart, adrenocortical steroid DHEA (dehydroepiandrosterone) exhibits chemopreventive activity in laboratory rodent models. However, fluasterone unlike DHEA lacks sex hormonal and liver perixosome proliferating effects. RAPID support will include studies:

• Chronic preclinical toxicology studies in dog and rat,
• Synthesis of C-14 fluasterone,
• Preclinical absorption, distribution, metabolism, elimination and pharmacokinetic.

Contact Information
Arthur G. Schwartz, Ph.D.
Temple University School of Medicine,
Fels Institute for Cancer Research and Molecular Biology
Pennsylvania
Tel: 215-707-4349
Fax: 215-707-7473

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Program Description
Investigators will conduct preclinical development of 5,6-dihydro-4H-cyclopenta-1,2-dithiole-3-thione, a Selective Phase II Enzyme inducer for cancer prevention. Induction of phase II enzymes, which neutralize reactive electrophiles and act as indirect antioxidants, is an effective means for achieving protection against a variety of carcinogens in animals an humans. A new generation of selective phase II inducers, dithiolethiones with greater efficacy and potency than oltipraz, was developed. One of these, 5,6-dihydro-4H-cyclopenta-1,2-dithiole-3-thione appears to have desirable safety and efficacy profile and an easy and inexpensive synthesis. RAPID support will include:

• Synthesis of bulk material for preclinical studies,
• Mutagenicity and short term preclinical toxicity testing,
• And in vivo screening and efficacy studies.

Contact Information
Thomas W. Kensler, Ph.D.
Johns Hopkins University
Bloomberg School of Hygiene and Public Health
Baltimore, MD
Tel: 410-955-4712
Fax: 410-955-0116

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Program Description
Investigators will evaluate 4'-Bromoflavone for cancer prevention. Induction of phase II detoxifying enzymes is an important mechanism of chemoprevention. 4'-Bromoflavone was shown to induce glutathione S-transferase and quinone reductase. It has been also shown to inhibit carcinogen covalent binding to cellular DNA and to inhibit incidence and multiplicity and increase tumor latency in carcinogen animal models. RAPID support will include:

• Synthesis of bulk material for preclinical studies,
• Mutagenicity and short term preclinical toxicity testing,
• And in vivo screening and efficacy studies.

Contact Information
John M. Pezzuto, Ph.D.
Dean, College of Pharmacy
University of Hawaii
Tel: 808-933-2909
Fax: 808-933-2974

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Program Description
Investigators will conduct clinical testing of farnesol and geraniol in human pancreative cancer. Pancreatic cancer is rapidly growing and highly lethal. An average survival is less than 12 months and present chemotherapy extends survival by only few months. Farnesol and geraniol are found at low levels in several foods and essential oils and have been found to be potent inhibitors of human pancreatic tumor cell growth in vitro and pancreatic tumor growth in hamsters in vivo. RAPID support will include:

• Mutagenicity and short term preclinical toxicity testing,
• In vivo screening and efficacy testing,
• GMP synthesis, formulation, packaging, IND support, and
• Phase I studies.

Contact Information
Harold Newmark, D.Sci.
Rutgers, The State University of New Jersey
New Jersey
Tel: 732-445-3400, ext. 242
Fax: 732-445-0687

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