Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The growth inhibitory effect of tumour promoters on human leukaemia and lung cancer cell lines was examined using the [3-(4,5 dimethylthiazol)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. The four cell lines used were the K562 human leukaemia cell line, its adriamycin (ADM)-resistant subline (K562/ADM), which shows the mdr phenotype, PC-9 (a human lung adenocarcinoma cell line) and its cisplatin (CDDP)-resistant subline (PC-9/CDDP), which does not show the mdr phenotype. Phorbol 12-tetradecanoate-13-acetate (TPA) and the TPA-type tumour promoters, aplysiatoxin and debromoaplysiatoxin, inhibited the growth of the two parental cell lines, K562 and PC-9. The non-TPA-type tumour promoter, okadaic acid, also inhibited the growth of the two parental cell lines in a dose-dependent manner. TPA-type and okadaic acid inhibited the growth of K562/ADM more weakly than that of K562, and showed no growth inhibition in PC-9/CDDP. Anhydrodebromoaplysiatoxin, an inactive derivative of the TPA-type tumour promoter, could suppress the growth of K562 and K562/ADM only at high concentration (more than 50 pM) and it showed similar growth inhibitory effects on the two cell lines. Okadaic acid tetramethyl ether, the inactive form of the non-TPA-type tumour promoter did not inhibit the growth of any of the cell lines. The growth inhibitory effect of these compounds was well correlated with their tumour-promoting activity. A study of the accumulation of okadaic acid revealed that the amount of 3H-okadaic acid in K562/ADM and PC-9/CDDP was similar to that in their parental cells indicating that cross-resistance to this tumour promoter in the drug-resistant cell lines is not due to a difference in the amount of drug accumulated in sensitive and resistant cells. These results suggest the presence of another common mechanism for resistance to ADM and CDDP as well as to TPA- or non-TPA-type tumour promoters.
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PMID:Cross-resistance to tumour promoters in human cancer cell lines resistant to adriamycin or cisplatin. 220 49

The knowledge about drug resistance in childhood leukemias and acute lymphoblastic leukemia (ALL) in general is limited. This is because of the lack of a suitable in vitro drug sensitivity assay, which is in part due to low in vitro ALL cell survival. We recently adapted the highly efficient 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay to test cells from ALL patients and showed that its results were comparable with those of the DiSC assay, up to now the most valid but laborious assay. In this study, in vitro drug sensitivity was assessed in cells from 82 children with leukemia, 79 of whom had ALL, with the MTT assay. Dose response curves were obtained for 6-mercaptopurine, 6-thioguanine (6-TG), prednisolone (Pred), daunorubicin (DNR), vincristine (VCR), cytosine arabinoside (Ara-C), L-asparaginase (L-Asp), mafosfamide, and mustine. A cytotoxic effect of methotrexate could be detected in only a few cases. Large interindividual differences in drug sensitivity were detected. Compared with leukemia cells from newly diagnosed patients, leukemia cells from relapsed patients were significantly more in vitro resistant to 6-TG, Pred, Ara-C, mafosfamide and mustine but not to DNR, VCR, and L-Asp. Improvements of culture medium and methods to increase MTT reduction were studied. From 10 components tested, addition of insulin and bovine serum albumin to serum-containing medium improved ALL cell survival. Addition of succinate did not increase the amount of MTT reduction. We conclude that the in vitro MTT assay highly facilitates large-scale studies on drug resistance of ALL patients that can lead to rational improvements in existing treatment protocols.
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PMID:In vitro drug sensitivity of cells from children with leukemia using the MTT assay with improved culture conditions. 225 5

We applied the MTT dye reduction assay to the anti-cancer drug sensitivity test using short-term microplate cultures. Blast cells were cultured with approximately 25 anti-cancer drugs for 4 days. After cultivation, MTT dye was placed in each well, and the formazans generated by living cells were dissolved in acidified isopropyl alcohol. The absorbance of each well was measured at a scanning microplate photometer. When we made the table of the cytotoxicity index (CI) that was classified into anti-cancer drugs and concentrations for each leukemic sample, it was possible to compare efficacy with different drugs and to select the effective ones. Retrospectively, the in vitro results were compared with the clinical responses of the 34 patients (26 of acute lymphocytic leukemia [ALL] and eight of acute nonlymphoblastic leukemia [ANLL]) who were treated by combination chemotherapy. The following results were obtained: true-positive rate, 78.1%; true-negative rate, 57.1%; and predictive accuracy, 74.4%. Therefore, the MTT assay-CI table might serve as a reliable tool for the selection of effective chemotherapy in patients with acute leukemia.
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PMID:An in vitro chemosensitivity test for the screening of anti-cancer drugs in childhood leukemia. 230 78

Chemosensitivity testing using a DEA was performed on 91 leukemia samples from 70 patients with leukemia. In 55 patients, comparison of in-vitro results with actual response of the patient was made. There was good correlation in 82% of the cases, the results being highly significant p less than 0.001. The MTT assay was also adapted for the chemosensitivity testing and the usefulness of this assay was evaluated by comparing the results to the DEA for 24 of the samples. Survival results produced by the two assays were very similar. The MTT procedure was also found to be equally effective as the DEA as a predictive assay of chemosensitivity.
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PMID:Chemosensitivity testing of fresh human leukemia cells using both a dye exclusion assay and a tetrazolium dye (MTT) assay. 234 69

Utilizing the P388 murine leukemia cells sensitive (P388/S) and resistant (P388/ADR) to Adriamycin (ADR), we evaluated the effect of quinidine, an anti-arrhythmic agent, on the cytotoxic activity of ADR and Mitoxantrone (MITO), both in vitro as well as in vivo. Quinidine enhanced the cytotoxicity of both ADR and MITO in P388/S and P388/ADR cells, as assessed by the decrease in color intensity of formazan crystal in the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. A dose dependent inhibition of 3H-thymidine and 3H-uridine incorporation was observed when the P388/S and P388/ADR cells were exposed to quinidine alone. A non-toxic concentration of quinidine (5 microM) enhanced the DNA biosynthesis inhibition induced by ADR (55 to 65%) and MITO (37 to 44%) in P388/ADR cells, indicating reversal of resistance, while in P388/S cells only a minimal increase in DNA biosynthesis inhibition was observed. The combination of quinidine at doses of 50 to 100 mg/kg significantly potentiated the antitumor activity of ADR and MITO in P388/ADR bearing mice, whereas the potentiation of ADR and MITO antitumor response was lower in P388/S bearing mice. Quinidine increased the cellular levels of ADR by 53 to 126% in P388/ADR cells in vitro, but failed to indicate such elevated levels of cellular ADR in P388/S cells. This enhanced intracellular accumulation of ADR in P388/ADR cells, explains the therapeutic efficacy of ADR and MITO in P388/ADR, both in vitro as well as in vivo. Results suggest the efficacy of quinidine to ameliorate the antitumor effects of ADR and MITO in drug resistant tumor cells.
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PMID:Evaluation of quinidine effect on the antitumor activity of adriamycin and mitoxantrone in adriamycin-sensitive and -resistant P388 leukemia cells. 236 55

Aliphatic triazenes, such as 1,3-dimethyltriazene, are potent biological alkylating agents because they form alkyldiazonium ions. They are also subject to very rapid proteolytic decomposition, even at physiological pH. The acylated analogues 1,3-dialkyl-3-acyltrizenes are much more stable in aqueous solution, but they also give rise to alkyldiazonium ions. Four acylated 1,3-dimethyltriazenes, where the acyl groups were diethylphosphoryl (DMP), carbethoxy (DMC), acetyl (DMA), and N-methylcarbamoyl (DMM), were studied kinetically. Rate-pH profiles indicated that the acyl group had a profound effect on the mechanism of decomposition. The cytotoxic potential of all four compounds was studied in vitro by using the MTT-tetrazolium assay. The compounds had fair-to-good activity against some cell lines, particularly those deficient in methylation repair. In vivo assays of DMC and DMM against several tumor xenografts in nude mice showed promising activity for some cancers, particularly in the case of DMM. In vitro assays were also carried out on three 1-(2-chloroethyl)-3-methyl-3-acyltriazenes. The acyl groups were carbethoxy (CMC), acetyl (CMA), and N-methylcarbamoyl (CMM). The activity of these compounds largely paralleled that of bis(2-chloroethyl)-N-nitrosourea (BCNU), except for those cell lines which exhibited the Rem phenotype; triazenes were more active in those lines than BCNU. The in vivo activity of CMC, CMA, and CMM was tested in the P388 leukemia assay. All three were active but CMC and CMA proved to be rather toxic. CMM was well tolerated and was examined in several tumor xenografts in nude mice. Significant activity was found against MX-1 mammary carcinoma, against LX-1 small cell lung carcinoma, and particularly against LOX amelanotic melanoma, where complete cures were effected. The antineoplastic activity of the acyltriazenes is well-correlated with their chemical behavior.
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PMID:1,3-Dialkyl-3-acyltriazenes, a novel class of antineoplastic alkylating agents. 239 96

(+)-Ptilocaulin, a novel cyclic guanidine extracted from the Caribbean sponge Ptilocaulis aff. P. Spiculifer, is reported to have broad spectrum antimicrobial activity in vitro as well as in vitro activity against L1210 murine leukemia. To more fully evaluate this compound as an anticancer agent, the in vitro cell growth inhibitory potencies of synthetic racemic ptilocaulin and ten clinical anticancer drugs were determined and compared in 16 different normal and transformed human and murine cell populations. Potency, expressed as the 50% inhibitory concentration (IC50), was determined by a tetrazolium reduction (MTT) assay. Ptilocaulin showed a fairly broad spectrum of in vitro activity against colon and mammary adenocarcinomas, melanomas, leukemias, transformed fibroblasts and normal lymphoid cells (IC50s 0.05- greater than 10 micrograms/ml). This activity was comparable to that of many of the clinical drugs, including vinca alkyloids, antibiotics, alkylators and antimetabolites. Cell viability was affected only after a 72 hr exposure to the compound. In a clonogenic assay, cytocidal effects were observed after 24-72 hr exposures to 10 x IC50 concentrations of ptilocaulin, as evidenced by failure of cells to resume growth after removal of the compound. Cytostatic effects were observed at less than or equal to IC50 concentrations, as evidenced by resumption of growth to near-control levels after removal of the compound. Ptilocaulin was toxic at 50 and 25 mg/kg in an in vivo L1210 tumor model and was ineffective at lower concentrations (T/Cs 100-112%). In vivo studies in a more sensitive tumor system are recommended but are limited by the lack of availability of sufficient quantities of the compound.
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PMID:Cytotoxicity of synthetic racemic ptilocaulin: a novel cyclic guanidine. 279 67

We have determined the feasibility of using the MTT colorimetric assay for measuring the sensitivity of fresh leukaemia cells to cytotoxic agents. A linear relationship was seen between the number of leukaemic cells plated and the resulting absorbance in the MTT assay at day 4. For 2 X 10(5) cells/well from CLL peripheral lymphocytes, the mean absorbance (measured at 540 nm) was 0.41. Similar curves were obtained with the assay carried out between days 3 and 7. ID50 values for CLL lymphocytes exposed to adriamycin (ADM) were in the range of 0.02-0.29 micrograms/ml, a similar range to that given by the DiSC dye exclusion assay. Sensitization of leukaemia cells to ADM by verapamil or cyclosporin A could be demonstrated in some patients but not in others. The lymphocytes from one patient with prolymphocytic leukaemia were abnormally resistant to ionizing radiation. These cells also showed resistance to melphalan and adriamycin but not to vincristine. The MTT assay appears to offer an attractive option for in vitro chemosensitivity testing in leukaemia, determination of cross-resistance profiles and studies of resistance modifiers.
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PMID:Chemosensitivity testing of fresh leukaemia cells using the MTT colorimetric assay. 291 26

The reduction of the tetrazolium salt MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) to a blue-black formazan product by living but not by dead cells can be used to measure chemosensitivity of tumor cells. The main advantages of the MTT assay are its simplicity, rapidity, and the fact that the results are read automatically with a microplate spectrophotometer. Several reports on the use of the MTT assay in chemosensitivity testing have been published, but all these studies dealt with established cell lines and not with specimens obtained directly from patients. Here we present a study in which the MTT assay has been adapted to assess the effect of antineoplastic drugs on lymphoblasts of children with leukemia.
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PMID:Adaptation of the rapid automated tetrazolium dye based (MTT) assay for chemosensitivity testing in childhood leukemia. 316 5

A microcytotoxicity assay employing a tetrazolium salt has been adapted for testing the response of human leukemic blast cells to a variety of chemotherapeutic agents. After exposure to various concentrations of drugs, the viability of fresh leukemic blast cells was measured using a tetrazolium salt, MTT, which is converted to blue formazan crystals by living cells. The amount of formazan produced was quantitated using a microtitre plate spectrophotometer. In the present study, optimal conditions for chemosensitivity testing of human leukemia samples were determined, and the relative chemosensitivity of five patient samples was tested.
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PMID:Use of the MTT assay for rapid determination of chemosensitivity of human leukemic blast cells. 319 42


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