Resistance circumvention strategies tested in clinical leukaemia specimens using the MTT colorimetric assay. 1992

E Lambert, and J K Rees, and P R Twentyman
Department of Clinical Oncology, University of Cambridge, UK.

We have used a 4-day MTT colorimetric assay to study drug sensitivity of leucocytes from leukaemia patients and from normal donors. Response to Adriamycin, vincristine, aclacinomycin A, 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin (MX2), and melphalan has been determined, together with the effects of the resistance modifiers verapamil, cyclosporin A, and ethacrynic acid. Sensitivity of chronic lymphoblastic leukemia (CLL) lymphocytes to vincristine was much greater than that of normal lymphocytes or of leucocytes from myeloid leukaemia patients. These cells were also more sensitive to melphalan. Verapamil and cyclosporin A at clinically achievable doses of 1 microgram/ml produced significant chemosensitisation in normal and leukaemic specimens, but the sensitisation ratio was greater than or equal to 2 only in a minority of specimens, except in the case of sensitisation to vincristine seen in the majority of CLL specimens. Sensitisation was generally greater in the more chemo-resistant specimens. The ratio of sensitivities of cells to Adriamycin compared with aclacinomycin A was greatest in the more Adriamycin-resistant specimens which supports the idea that cross-resistance between these agents may not be great. This was not, however, true for the ratio of Adriamycin/MX2 sensitivity. Use of the MTT assay may allow the identification of patients who would benefit from treatment with resistance modifiers or with 'low-resistance' anthracyclines.

UI MeSH Term Description Entries
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004317 Doxorubicin Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN. Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D013778 Tetrazolium Salts Quaternary salts derived from tetrazoles. They are used in tests to distinguish between reducing sugars and simple aldehydes, for detection of dehydrogenase in tissues, cells, and bacteria, for determination of corticosteroids, and in color photography. (From Mall's Dictionary of Chemistry, 5th ed, p455) Tetrazolium Salt,Salt, Tetrazolium,Salts, Tetrazolium
D013844 Thiazoles Heterocyclic compounds where the ring system is composed of three CARBON atoms, a SULFUR and NITROGEN atoms. Thiazole
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D014750 Vincristine An antitumor alkaloid isolated from VINCA ROSEA. (Merck, 11th ed.) Leurocristine,Citomid,Farmistin,Oncovin,Oncovine,Onkocristin,Vincasar,Vincasar PFS,Vincristin Bristol,Vincristin medac,Vincristine Sulfate,Vincrisul,Vintec,cellcristin,PFS, Vincasar,Sulfate, Vincristine
D015451 Leukemia, Lymphocytic, Chronic, B-Cell A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease. B-Cell Leukemia, Chronic,B-Lymphocytic Leukemia, Chronic,Chronic Lymphocytic Leukemia,Leukemia, B-Cell, Chronic,Leukemia, Lymphocytic, Chronic,Lymphocytic Leukemia, Chronic, B-Cell,Lymphoma, Small Lymphocytic,B-Cell Chronic Lymphocytic Leukemia,B-Cell Malignancy, Low-Grade,Diffuse Well-Differentiated Lymphocytic Lymphoma,Disrupted In B-Cell Malignancy,Leukemia, B Cell, Chronic,Leukemia, Chronic Lymphatic,Leukemia, Chronic Lymphocytic,Leukemia, Chronic Lymphocytic, B-Cell,Leukemia, Lymphoblastic, Chronic,Leukemia, Lymphocytic, Chronic, B Cell,Lymphoblastic Leukemia, Chronic,Lymphocytic Leukemia, Chronic,Lymphocytic Leukemia, Chronic, B Cell,Lymphocytic Lymphoma,Lymphocytic Lymphoma, Diffuse, Well Differentiated,Lymphocytic Lymphoma, Diffuse, Well-Differentiated,Lymphocytic Lymphoma, Well Differentiated,Lymphocytic Lymphoma, Well-Differentiated,Lymphoma, Lymphocytic,Lymphoma, Lymphocytic, Diffuse, Well Differentiated,Lymphoma, Lymphocytic, Diffuse, Well-Differentiated,Lymphoma, Lymphocytic, Well Differentiated,Lymphoma, Lymphocytic, Well-Differentiated,Lymphoma, Lymphoplasmacytoid, CLL,Lymphoma, Small Lymphocytic, Plasmacytoid,Lymphoma, Small-Cell,Lymphoplasmacytoid Lymphoma, CLL,Small-Cell Lymphoma,B Cell Chronic Lymphocytic Leukemia,B Cell Leukemia, Chronic,B Cell Malignancy, Low Grade,B Lymphocytic Leukemia, Chronic,B-Cell Leukemias, Chronic,B-Cell Malignancies, Low-Grade,B-Lymphocytic Leukemias, Chronic,CLL Lymphoplasmacytoid Lymphoma,CLL Lymphoplasmacytoid Lymphomas,Chronic B-Cell Leukemia,Chronic B-Cell Leukemias,Chronic B-Lymphocytic Leukemia,Chronic B-Lymphocytic Leukemias,Chronic Lymphatic Leukemia,Chronic Lymphatic Leukemias,Chronic Lymphoblastic Leukemia,Chronic Lymphoblastic Leukemias,Chronic Lymphocytic Leukemias,Diffuse Well Differentiated Lymphocytic Lymphoma,Disrupted In B Cell Malignancy,Leukemia, Chronic B-Cell,Leukemia, Chronic B-Lymphocytic,Leukemias, Chronic B-Cell,Leukemias, Chronic B-Lymphocytic,Leukemias, Chronic Lymphatic,Leukemias, Chronic Lymphoblastic,Low-Grade B-Cell Malignancies,Low-Grade B-Cell Malignancy,Lymphatic Leukemia, Chronic,Lymphatic Leukemias, Chronic,Lymphoblastic Leukemias, Chronic,Lymphocytic Leukemias, Chronic,Lymphocytic Lymphoma, Small,Lymphocytic Lymphomas,Lymphocytic Lymphomas, Small,Lymphocytic Lymphomas, Well-Differentiated,Lymphoma, CLL Lymphoplasmacytoid,Lymphoma, Small Cell,Lymphoma, Well-Differentiated Lymphocytic,Lymphomas, CLL Lymphoplasmacytoid,Lymphomas, Lymphocytic,Lymphomas, Small Lymphocytic,Lymphomas, Small-Cell,Lymphomas, Well-Differentiated Lymphocytic,Lymphoplasmacytoid Lymphomas, CLL,Malignancies, Low-Grade B-Cell,Malignancy, Low-Grade B-Cell,Small Cell Lymphoma,Small Lymphocytic Lymphoma,Small Lymphocytic Lymphomas,Small-Cell Lymphomas,Well-Differentiated Lymphocytic Lymphoma,Well-Differentiated Lymphocytic Lymphomas
D015470 Leukemia, Myeloid, Acute Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES. Leukemia, Myelogenous, Acute,Leukemia, Nonlymphocytic, Acute,Myeloid Leukemia, Acute,Nonlymphocytic Leukemia, Acute,ANLL,Acute Myelogenous Leukemia,Acute Myeloid Leukemia,Acute Myeloid Leukemia with Maturation,Acute Myeloid Leukemia without Maturation,Leukemia, Acute Myelogenous,Leukemia, Acute Myeloid,Leukemia, Myeloblastic, Acute,Leukemia, Myelocytic, Acute,Leukemia, Myeloid, Acute, M1,Leukemia, Myeloid, Acute, M2,Leukemia, Nonlymphoblastic, Acute,Myeloblastic Leukemia, Acute,Myelocytic Leukemia, Acute,Myelogenous Leukemia, Acute,Myeloid Leukemia, Acute, M1,Myeloid Leukemia, Acute, M2,Nonlymphoblastic Leukemia, Acute,Acute Myeloblastic Leukemia,Acute Myeloblastic Leukemias,Acute Myelocytic Leukemia,Acute Myelocytic Leukemias,Acute Myelogenous Leukemias,Acute Myeloid Leukemias,Acute Nonlymphoblastic Leukemia,Acute Nonlymphoblastic Leukemias,Acute Nonlymphocytic Leukemia,Acute Nonlymphocytic Leukemias,Leukemia, Acute Myeloblastic,Leukemia, Acute Myelocytic,Leukemia, Acute Nonlymphoblastic,Leukemia, Acute Nonlymphocytic,Leukemias, Acute Myeloblastic,Leukemias, Acute Myelocytic,Leukemias, Acute Myelogenous,Leukemias, Acute Myeloid,Leukemias, Acute Nonlymphoblastic,Leukemias, Acute Nonlymphocytic,Myeloblastic Leukemias, Acute,Myelocytic Leukemias, Acute,Myelogenous Leukemias, Acute,Myeloid Leukemias, Acute,Nonlymphoblastic Leukemias, Acute,Nonlymphocytic Leukemias, Acute

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