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  • Biochemistry and Biotechnology  (1)
  • Life and Medical Sciences  (1)
  • 1
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: At the National Cancer Institute, Division of Cancer Prevention and Control, the Chemoprevention Branch and Agent Development Committee develop strategies for efficiently identifying, procuring, and advancing the most promising drugs into clinical trials. Scientific expertise is applied at each phase of development to critically review the testing methods and results, and to establish and apply criteria for evaluating the agents for further development. The Clinical Development Plan, prepared by the Chemoprevention Branch and the Agent Development Committee, is a summary of the status of the agent regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. It also contains the strategy for further development of the drug that addresses pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen Clinical Development Plans are presented here: N-acetyl-l-cysteine (NAC), aspirin, calcium, β-carotene, 2-difluoromethylornithine (DFMO), DHEA analog 8354, 18β-glycyrrhetinic acid, N-(4-hydroxyphenyl)retinamide (4-HPR), ibuprofen, oltipraz, piroxicam, Proscar®, sulindac, tamoxifen, vitamin D3 and analogs and vitamin E. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing chemopreventive drugs. 1994 Wiley-Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0173-0835
    Keywords: Two-dimensional polyacrylamide gel electrophoresis ; Protein database ; Cancer ; Pharmacology ; Chemosensitivity ; Cell culture ; Cell line ; Drug ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: In the last six years, the Developmental Therapeutics Program (DTP) of the US National Cancer Institute (NCI) has screened over 60 000 chemical compounds and a larger number of natural product extracts for their ability to inhibit growth of 60 different cancer cell lines representing different organs of origin. Whereas inhibition of the growth of one cancer cell type gives no information on drug specificity, the relative growth inhibitory activities against 60 different cells constitute patterns that encode detailed information on mechanisms of action and resistance (as reviewed in Boyd and Paull, Drug Devel. Res. 1995, 34, 19-109 and Weinstein et al., Science 1997, 275, 343-349). In order to correlate the patterns of activity with properties of the cells, we and other laboratories are characterizing the cells with respect to a large number of factors at the DNA, mRNA, and protein levels. As part of that effort, we have developed a two-dimensional gel electrophoresis (2-DE) protein expression database covering all 60 cell types (Buolamwini et al., submitted). Here we present analyses of the correlations among protein spots (i) in terms of their patterns of expression and (ii) in terms of their apparent relationships to the pharmacology of a set of 3989 screened compounds. The correlations tend to be stronger for the latter than for the former, suggesting that the spots have more robust signatures in terms of the pharmacology than in terms of expression levels. Links to pertinent databases and tools of analysis will be updated progressively at http://www.nci.nih.gov/intra/lmp/jnwbio.htm and http://epnwsl.ncifcrf.gov:2345/dis3d/dtp.html.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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