In vitro chemosensitivity testing of hematological cancer patients: detection of ornithine decarboxylase.
The development of reliable methods for the in vitro testing of sensitivity of cancer cells to various drugs has been a longstanding objective in cancer research and treatment Early attempts to develop individualized chemotherapy were based on clonogenic assays. These attempts failed because of low plating efficiencies. Nonclonogenic assays, such as the MMT test or ATP determinations, are based on metabolic activities and do not reflect the ability of cells to proliferate. To detect proliferation, we selected a universal marker--ornithine decarboxylase (ODC), which is expressed early in the cell cycle and has a short half-life. This marker was detected in hematological cancer cells by quantitative immunohistochemical analyses using an ODC antibody and a FITC-linked second antibody. Drug resistance was detected in five patients, who subsequently died. Lymphocytes from normal individuals were sensitive to all drugs tested, whereas 33 leukemia and lymphoma patients showed different sensitivities to certain drugs. The method also permitted testing of the effect of new drugs on the proliferation of lymphocytes from hematological cancer patients. This test is sensitive, and 100-1,000 cells are required per assay, which can be completed within 2 days. It is very likely that the assay could also be used to test solid tumor patients.
Bachrach
Uriel
U
Department of Molecular Biology Hebrew University-Hadassah, Medical School, P.O. Box 12272, Jerusalem, Israel. bachur@md2.huji.ac.il
Wang
Yongchun
Y
D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000032:analysis*
D000970:Antineoplastic Agents; D015415:Biomarkers; D009955:Ornithine Decarboxylase