Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Development of multidrug-resistance (MDR) remains a major cause of failure in the treatment of cancer with chemotherapeutic agents. In our efforts to explore alternative treatment regimens for multidrug-resistant tumors we have examined the sensitivity of MDR tumor cell lines to lymphokine activated killer (LAK) cells. Adriamycin (ADM) resistant B16-BL6 melanoma, L1210 and P388 leukemic cell lines were tested for sensitivity to lysis by LAK cells in vitro. While ADM-resistant B16-BL6 and L1210 sublines were found to exhibit at least 2-fold greater susceptibility to lysis by LAK cells, sensitivity of ADM-resistant P388 cell was similar to that of parental cells. Since ADM-resistant B16-BL6 cells were efficiently lysed by LAK cells in vitro, the efficacy of therapy with LAK cells against the ADM-resistant B16-BL6 subline in vivo was evaluated. Compared to mice bearing parental B16-BL6 tumor cells, the adoptive transfer of LAK cells and rIL2 significantly reduced formation of experimental metastases (P less than 0.009) and extended median survival time (P less than 0.001) of mice bearing ADM-resistant B16-BL6 tumor cells. Results suggest that immunotherapy with LAK cells and rIL2 may be a useful modality in the treatment of cancers with the MDR phenotype.
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PMID:Therapeutic efficacy of interleukin-2 activated killer cells against adriamycin resistant mouse B16-BL6 melanoma. 162 50

A novel antitumor compound, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea (HO-221) was evaluated for its antitumor activity in experimental tumor models. HO-221 preparation was given orally to tumor-bearing animals. The compound exhibited significant effects against various tumors such as P388 and L1210 leukemias; M5076 reticulum-cell sarcoma; colon 38 carcinoma; human xenografts MX-1, LX-1, GA-1, and Co-1; Lewis lung carcinoma; sarcoma 180; and Walker 256 carcinosarcoma and was especially effective against solid tumors. However, its effect on murine B16 melanoma was moderate. Intermittent administration of HO-221 produced better results. The effects of HO-221 on human tumor xenografts were compared with those of other antitumor agents. HO-221 showed activity against LX-1 lung and Co-1 gastrointestinal tumor and was also effective against advanced-stage L1210 leukemia and Lewis lung carcinoma. Furthermore, the effect of HO-221 on drug-resistant tumors was examined using murine leukemias L1210 and P388. It showed no cross-resistance with the known antitumor agents Adriamycin (ADM), daunomycin (DM), vincristine (VCR), mitomycin C (MMC), cisplatin (CDDP), 5-fluorouracil (5-FU), cytosine arabinoside (Ara-C), methotrexate (MTX), cyclophosphamide (CPA), or carboquone (CQ), and collateral sensitivity to HO-221 was found in MMC-, CDDP-, and CPA-resistant sublines. HO-221 exhibits significant reproducible, broad-spectrum antitumor activity against experimental tumors as well as human neoplasms.
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PMID:Antitumor activity on murine tumors of a novel antitumor benzoylphenylurea derivative, HO-221. 191 78

Intratumoral heterogeneity was observed in two tumor lines (SbC11 and SbC12) derived from a single biopsy of a melanoma patient. Differences in drug sensitivity were observed in three cell lines of small cell lung carcinoma derived from the same patient, before (AE1), and after (AE2 and AE3) therapy with Adriamycin (ADM) and Cisplatinum (DDP). Moreover, heterogeneity in biological features and in drug sensitivity was observed in three continuous human glioma derived cell lines (LI, DF, and DP). The results show the importance of continuous cell lines for studying tumor heterogeneity and evaluating the effectiveness of antineoplastic agents.
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PMID:[The use of continuous cell cultures for the study of tumor heterogeneity and drug sensitivity]. 196 94

The effect of N-methylformamide (NMF) in combination with Adriamycin (ADM) and cis-diamminedichloroplatinum (DDP) on the cell survival and cell cycle kinetics of two human tumour lines was assessed: HT29 colon carcinoma and M14 melanoma cells were exposed to ADM and DDP alone or in combination with a non-cytotoxic dose of NMF, according to different schedules. The results demonstrate that NMF exposure sensitized both tumour cell lines to the lethal activity of ADM and DDP; however, reverse sequences had to be applied to reach an increase in the lethal activity of the two different drugs. The ADM-NMF combination determined a powerful decrease in the surviving fraction of the two cell lines when ADM was given as the first agent (ADM----NMF), while the reverse sequence did not increase the ADM cytotoxic effect. With respect to the DDP-NMF association, the sequence which accounted for a greater sensitizing effect was NMF administration followed by DDP treatment (NMF----DDP). This work demonstrates the importance of timing in combined treatments which involve NMF. A delay in cell proliferation elicited by NMF exposure could be responsible for the effectiveness of the combined treatment.
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PMID:Importance of cell cycle perturbations on the effectiveness of N-methylformamide and anti-neoplastic drugs in combination. 203 5

Exposure of cultured human melanoma cells from three different cell lines to Adriamycin and carmustine at non-cytotoxic (micromolar) concentrations results in a rapid, reversible depletion of cellular glutathione; maximal depletion is achieved within 1 h, and glutathione levels recover within 2-3 h. Glutathione depletion is accompanied by an enhancement of the cytotoxic effects of the alkylating agent melphalan, which ranges from 15- to 55-fold. These results suggest that the combination of Adriamycin and carmustine may provide a rational drug combination for the rapid depletion of glutathione from malignant melanoma, thereby sensitizing these tumor cells to alkylating agent cytotoxicity.
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PMID:Sensitization of human melanoma cells to melphalan cytotoxicity by adriamycin and carmustine. 206 51

A novel antitumor antibiotic, 2a,3,4,5,6,6a,7,11b-octahydro-11-methoxy-12-methyl-3,6-imino-1H-2-oxa-11 c- azanaphth(1,2,3-cd)azulene-5-carboxylic acid monocitrate (quinocarmycin citrate; KW2152) was selected for investigation in a number of experimental tumor systems because of its efficacy against P388 leukemia. In the initial studies with P388 leukemia (i.p.-i.p.), KW2152 gave an increase in life span of greater than 80%. The activity was schedule dependent and daily administration was the most effective. KW2152 caused marginal activity against L1210 leukemia, B16 melanoma, and M5076 sarcoma. The effect on cultured cells suggested that KW2152 was not cross-resistant to Adriamycin (ADM) but was cross-resistant to mitomycin C (MMC); however, KW2152 caused prolongation of life span against mice bearing P388/ADM or P388/MMC. In tests against human tumors xenografted s.c. in nude mice, KW2152 significantly inhibited the growth of MX-1 mammary carcinoma with all tumors cured at i.v. doses of 4.4 mg/kg/day and p.o. doses of 26.2 mg/kg/day given daily for 7 days. KW2152 also inhibited distinct human gastric carcinomas, St-4 and St-15 tumors, and colon carcinoma Co-3 by daily administration for 7 days. Against St-4, KW2152 gave a treated versus control percentage of 27, compared to 52 for cis-diamminedichloroplatinum. Against Co-3, KW2152 was at least as effective as MMC, ADM, cis-diamminedichloroplatinum, and bleomycin, giving a treated versus control percentage of 18 at a dose of 8.6 mg/kg/day given daily for 7 days. KW2152 showed growth inhibitory activity against cultured murine tumors and human cells. The order of in vitro efficacy of KW2152 against murine tumors, P388 leukemia greater than L1210 leukemia, B16 melanoma, correlated with the order of the sensitivity on the i.p.-i.p. systems of these tumors. The 50% inhibitory concentrations against P388 leukemia cells were 5.3 X 10(-6) and 1.1 X 10(-7) M after 1 and 72 h exposure, respectively. KW2152 caused significant inhibition of RNA synthesis after a short time exposure. In P388 leukemia cells exposed for 1 h with KW2152, the 50% inhibitory concentration for RNA synthesis was 10(-5) M, 30-fold less than that for DNA synthesis. White blood cell depression or platelet depression was not significant after administration of the i.v. 10% lethal dose given daily for 7 days. Because of its good activity against human mammary tumor MX-1 and some effectiveness against other gastric and colon carcinomas and its water solubility, a novel antitumor antibiotic, KW2152, is being developed as a Phase I anticancer agent.
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PMID:Antitumor activity of a novel antitumor antibiotic, quinocarmycin citrate (KW2152). 243 18

Aclacinomycin is a member of naturally occurring anthracyclines having three sugar moieties in the molecule. It showed antitumour activity on various mouse and rat tumours. Combination therapy with AraC etc. gave remarkable clinical results on acute myeloid leukaemia. Aclacinomycin strongly inhibits RNA synthesis of the tumour cells. It has lower cardiac toxicity than adriamycin and no mutagenicity. THP-Adriamycin is a derivative of adriamycin designed from the structure of baumycins. It showed stronger effects than adriamycin in inhibiting many mouse tumours such as L1210 and P388 leukaemia, B16 melanoma and colon 38 adenocarcinoma. THP-Adriamycin is rapidly taken up by both adriamycin-sensitive and resistant leukaemic cells. Its level of cardiac toxicity is as low as that of aclacinomycin. Ditrisarubicins are new naturally occurring anthracyclines isolated from Streptomyces having six sugar moieties in the molecule. Ditrisarubicin has a potent cytostatic and antitumour activities on adriamycin resistant mouse leukaemia. Its binding constant to DNA is extremely high compared with other anthracyclines.
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PMID:Experimental studies of new anthracyclines: aclacinomycin, THP-adriamycin and ditrisarubicins. 244 79

A kinetic study of plasma concentration of Doxorubicin (Adriamycin) was performed in 25 cases of malignant melanoma of the extremity with malignant adenopathy, treated with the same dose (20 mg per m2). Drug concentration was measured using a radioimmunoassay, with good intra-assay and inter-assay reproducibility. The kinetic analysis used the multiple compartmental method and a simulation of the plasma curves. Adriamycin injected intravenously quickly leaves the plasma into an exchangeable compartment with a slow plasma return and subsequent prolonged mean duration of the plasma half life at a low concentration. Thus, the intravenous perfusion results in a high plasma concentration only during the time of infusion. After intra arterial injection proximal to the tumor, a fraction variable (average 35%) is not released back into the circulation, or released very slowly. This local sequestration (important in terms of local concentration) explains the efficiency and the potential local toxicity of this method of administration. The rapid release of about 70% of the drug into the plasma, with kinetics similar to that observed after intravenous infusion, allows for no significant reduction of systemic toxicity.
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PMID:Kinetics of adriamycin injected proximal to a tumor: a comparative study between venous and arterial injections. 258 5

Four of seven human melanoma cell lines were sensitive to killing by L-dopa (D37 1.0-4.7 microM) compared with fibroblasts, Hela, and three ovarian tumor cell lines (D37 12-59 microM). All seven melanoma lines, however, were sensitive to DL-buthionine(S,R)sulfoximine (BSO) (D37 0.73-8.5 microM) compared with the nonmelanoma cells (D37 25-68 microM). The melanoma line most sensitive to BSO (MM418) was highly melanized, proliferated slowly and was resistant to other agents [dopa, 5-(3-methyl-1-triazeno)5-imidazole-4-carboxamide, melphalan, methotrexate, hydroxyurea, etoposide, Adriamycin]. In most cell lines, L-dopa and BSO blocked cell proliferation in all phases of the cell cycle. Cellular sensitivity to dopa or BSO did not correlate with levels of total soluble SH, glutathione (GSH), GSH reductase, GSH peroxidase or GSH transferase, or with the extent of GSH depletion induced by the drug. No GSH transferase activity could be detected in the dopa-resistant HeLa line, indicating that detoxification of quinones is not an important mechanism of resistance. Within the group of melanoma cell lines, sensitivity to dopa correlated with decreased level of gamma-glutamyl transpeptidase (r = 0.81). However, the gamma-glutamyl transpeptidase inhibitor azaserine was less effective than BSO in enhancing the toxicity of dopa. It can be inferred that (a) there is no simple relationship between GSH metabolism and sensitivity to dopa or BSO in human melanoma cells, and (b) BSO may be an effective agent for melanoma.
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PMID:Sensitivity of human melanoma cells to L-dopa and DL-buthionine (S,R)-sulfoximine. 270 20

A series of 2-aminoalkyl-5-nitropyrazolo [3,4,5-kl]acridines (pyrazoloacridines) were tested in vitro against a panel of multidrug-resistant cell lines comprising Adriamycin-resistant P388 leukemia, B16 melanoma, and mammary adenocarcinoma 16c. This new class of anticancer agents, particularly the 9-substituted methoxy derivatives, exhibited significant activity against all of the lines tested. The degree of cross-resistance to these compounds ranged from zero to 8-fold in the 138-fold Adriamycin-resistant P388/ADR line and was greatly diminished in the B16/ADR and 16c/ADR lines. Selected pyrazoloacridines were subsequently tested in vivo against B16 and B16/ADR cells established as solid tumors from the tissue culture line and shown to retain a significant degree of Adriamycin resistance. Whereas the B16/ADR line exhibited 2 logs less net tumor-cell kill than the B16 parent in response to Adriamycin treatment, the resistant tumor was completely sensitive to the pyrazoloacridines tested and proved in some experiments to be collaterally sensitive. The favorable activity of the pyrazoloacridines against these Adriamycin-resistant tumor lines points to the potential efficacy of these compounds against multidrug-resistant tumors encountered clinically.
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PMID:Activity of the pyrazoloacridines against multidrug-resistant tumor cells. 275 1


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