Abstract

We will develop optimal techniques to study the growth and treatment of clonogenic cells from malignant brain tumors. We will utilize further methods to characterize tumor cells and normal cells, and the clonogenic tumor cell hierarchy. We will evaluate the representative nature of the cells dissociated from biopsies and the influence of tumor specimen selection. Optimal means for growing and treating brain tumor cells will be developed with an emphasis on those conditions that simulate mostly the in vivo environment and physiologic drug exposure. Methods of statistical analysis will be developed to analyze cell survival, evaluate error, and provide directions to improve assay methodology. A panel of tumores will be treated with chemotherapeutic agents with known or potential utility to treat patients; an agent's tumor specificity will be evaluated by a comparison with activity against normal glioma cell and non-tumor cells from the same patient. We will compare the results of in vitro clonogenic cell assays to in vivo antitumor responses to define the limitations of and to improve the culture assay system. Finally, we will develop further and validate a bone marrow CFU-GM assay to study selected drugs and drug combinations which have demonstrated efficacy in tumor culture systems.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031882-07
Application #
3169985
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1982-04-01
Project End
1991-05-31
Budget Start
1989-06-01
Budget End
1991-05-31
Support Year
7
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Kaplan, L D; Shiramizu, B; Herndier, B et al. (1995) Influence of molecular characteristics on clinical outcome in human immunodeficiency virus-associated non-Hodgkin's lymphoma: identification of a subgroup with favorable clinical outcome. Blood 85:1727-35
Berens, M E; Bar-Shira, E; Rosenblum, M L et al. (1993) Effects of structural modifications of ether lipids on antiproliferative activity against human glioma cell lines. Anticancer Res 13:401-5
Doz, F; Berens, M E; Deschepper, C F et al. (1992) Experimental basis for increasing the therapeutic index of cis-diamminedicarboxylatocyclobutaneplatinum(II) in brain tumor therapy by a high-zinc diet. Cancer Chemother Pharmacol 29:219-26
Shiramizu, B; Herndier, B; Meeker, T et al. (1992) Molecular and immunophenotypic characterization of AIDS-associated, Epstein-Barr virus-negative, polyclonal lymphoma. J Clin Oncol 10:383-9
Doz, F; Berens, M E; Dougherty, D V et al. (1991) Comparison of the cytotoxic activities of cisplatin and carboplatin against glioma cell lines at pharmacologically relevant drug exposures. J Neurooncol 11:27-35
Doz, F; Berens, M E; Spencer, D R et al. (1991) Experimental basis for increasing the therapeutic index of carboplatin in brain tumor therapy by pretreatment with WR compounds. Cancer Chemother Pharmacol 28:308-10
Jung, H W; Berens, M E; Krouwer, H G et al. (1991) A three-dimensional micro-organ culture system optimized for in vitro growth of human malignant brain tumors. Neurosurgery 29:390-8
Meeker, T C; Shiramizu, B; Kaplan, L et al. (1991) Evidence for molecular subtypes of HIV-associated lymphoma: division into peripheral monoclonal, polyclonal and central nervous system lymphoma. AIDS 5:669-74
Rosenblum, M L (1990) General surgical principles, alternatives, and limitations. Neurosurg Clin N Am 1:19-36
Baumgartner, J E; Rachlin, J R; Beckstead, J H et al. (1990) Primary central nervous system lymphomas: natural history and response to radiation therapy in 55 patients with acquired immunodeficiency syndrome. J Neurosurg 73:206-11

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