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)

In order to establish the usefulness of the human tumor-nude mouse system as a predictive screen for anticancer agents, 17 tumors (3 breast, 3 colon, 3 lung, 3 melanoma, 2 ovary, 1 prostate, 1 sarcoma, and 1 larynx), serially transplantable in athymic mice, were used to study antitumor activity of doxorubicin (Adriamycin). BALB/c nude mice were treated i.v. on a weekly basis for 3 to 4 weeks, starting when the tumor volume became relatively large (advanced stage of tumor treatment). All the tumors except lung tumor T 293 showed a 90 to 100% take rate and stable growth. Doxorubicin, at dose levels of 6 and 10 mg/kg/injection i.v. every week for 3 weeks, showed significant activity against all of the three breast tumors studied. As was expected on the basis of clinical data, doxorubicin showed no antitumor activity against the three different colon tumors. In the case of lung tumors, statistically significant activities against oat cell carcinoma T 293 and epidermoid carcinoma T 222 were observed. In contradiction to clinical data, doxorubicin was found to have significant activity against various melanomas studied and slight but not statistically significant activity against ovarian tumor T 17. Experimental results obtained using doxorubicin against prostate, sarcoma, and larynx tumors also parallel the reported clinical data.
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PMID:Therapeutic response of human tumor xenografts in athymic mice to doxorubicin. 744 72

Human malignant melanoma was transplanted to the cheek pouch of immunosuppressed (corticosteroid-treated) hamsters. Significant differences were observed in tumor growth constants for animals treated with methotrexate, DTIC, BCNU, and vincristine (P < 0.05) compared to controls. However, no appreciable effect was demonstrated for Adriamycin, 5-FU, and cytoxan. In addition, single doses as high as 400 mg/kg body weight of methotrexate were no more effective than other agents now used against this neoplasm.
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PMID:Chemotherapy against human melanoma in the hamster cheek pouch. 745 85

Cells from 3 human tumours have been grown in soft agar contained in Millipore diffusion chambers and implanted i.p. in mice. Clonal growth was obtained from fresh biopsy samples, from cryopreserved tissue, and from xenografts of the tissues in immune-suppressed mice. The radiosensitivities of a melanoma and an ovarian carcinoma were evaluated by in vitro irradiation before assay for colony formation. Xenografting did not modify the radiosensitivity of the melanoma. Cells from another tumour were exposed to Adriamycin or cyclophosphamide whilst contained within i.p. diffusion chambers; the sensitivity was similar for cryopreserved and xenografted cells. The results encourage further attempts to quantify the sensitivity of human tumour cells by these methods.
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PMID:Clonogenic cell survival in cryopreserved human tumour cells. 747 Mar 78

The antitumor effect of the novel angiogenesis inhibitor O-(Chloroacetyl-carbamoyl) fumagillol, TNP-470 (TNP, s.c.), a synthetic analogue of fumagillin, was studied in combination with cytotoxic agents--mitomycin C (MMC, i.p.), Adriamycin (i.p.), cisplatin (i.p.), and 5-fluorouracil (i.p.), using B16BL6 melanoma (B16 M) and Lewis lung carcinoma in C57BL/6 mice. When the mice were treated on days 3 and 5, addition of MMC (total dose, 5 mg/kg) or 5-fluorouracil (140 mg/kg) to TNP (150 mg/kg) maximally reduced s.c. B16 M volume from 60 to 15% or from 68 to 40% of control, respectively, and addition of MMC (5 mg/kg) to TNP (150 mg/kg) reduced s.c. Lewis lung carcinoma volume from 75 to 62% of control (P < 0.02, compared to the corresponding single drug treatments). During treatment on days 3, 5, 7, 9, and 11, addition of MMC (5 mg/kg) to TNP (150 mg/kg) reduced s.c. B16 M volume from 43 to 6% of control and reduced the number of pulmonary metastasis of i.v. B16 M from 26 to 5% of control (P < 0.001). For established tumors (> 5 mm in maximal diameter), addition of MMC (12-14 mg/kg), Adriamycin (15-17.5 mg/kg), or cisplatin (4 mg/kg, by one shot) to TNP (120-140 mg/kg) with a 6-7 fractionated dosing schedule reduced s.c. B16 M volume from 50 to 20, 24, or 31% of control and reduced s.c. Lewis lung carcinoma volume from 52 to 34, 27, or 34% of control, respectively (P < 0.02). The effect of combination therapy was additive and dose-dependent, and the earlier fractionated dosing schedule exerted more enhanced antitumor effects. TNP reduced the body weight by approximately 10% of control at maximum, but this toxicity was reversible and was not affected by addition of the cytotoxic agents. The results suggest that the combination of angiogenesis inhibitor TNP and standard cytotoxic agents can be a beneficial addition to the treatment of solid tumors.
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PMID:Enhanced suppression of tumor growth by combination of angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470) and cytotoxic agents in mice. 752 56

The effect of the potent angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), a semisynthetic analogue of fumagillin, on tumor growth and metastasis was studied using rodent tumors. Injection of TNP-470 s.c. inhibited tumor growth in a dose-dependent manner, and the tumor sizes of B16BL6 melanoma, M5076 reticulum cell sarcoma, Lewis lung carcinoma, and Walker 256 carcinoma were maximally reduced to 16, 10, 17, and 4% of that in the respective control. The activity of TNP-470 upon i.v. injection was slightly weaker than that following s.c. injection. This tendency was observed for all the tumors tested. Injection i.v. (infusion) of TNP-470 increased the life span of Walker 256 carcinoma-bearing rats by 183% over the control, while bolus i.v. injection increased the life span by only 47%. TNP-470 reduced the number of pulmonary metastatic foci of i.v. inoculated B16BL6 melanoma in a dose-dependent manner, and the number of metastatic foci was reduced to 10% of that in the control by treatment with TNP-470 at 60 mg/kg, 3 times/week. The mean survival time of B16BL6 tumor-bearing mice treated with TNP-470 using this regimen was extended by 56% over that of control mice. TNP-470 at 10 mg/kg every day also reduced the number of metastatic foci of M5076 sarcoma in the liver after resection of the tumor from the primary site. Adriamycin at the same dose only slightly reduced the number of metastatic foci, even though TNP-470 and Adriamycin showed roughly equal inhibitory activity against M5076 sarcoma growth. TNP-470 extended the mean survival time of M5076 tumor-bearing mice by more than 100% over that of control mice at 30 mg/kg every 3 days, while Adriamycin extended mean survival times by maximally 20% at 10 mg/kg. These results show that the angiogenesis inhibitor TNP-470 has strong inhibitory activities against in vivo growth and metastasis of a wide variety of tumors.
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PMID:Inhibition of tumor growth and metastasis of rodent tumors by the angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470; AGM-1470). 768 30

Adriamycin (ADR), a common antineoplastic drug, was used to study DNA repair synthesis, cell cytotoxicity and DNA single strand breaks in normal human fibroblasts--CLV98 and human melanoma cells--ME18. No repair synthesis was observed in ME18 and CLV98 cells exposed to adriamycin in concentrations up to 10(-5) M. ME18 cells were less sensitive to ADR treatment than CLV98 cells. Adriamycin-induced DNA single strand breaks (at ADR concentration: 1 microgram/ml) were incompletely repaired in ME18 cells and unrepaired in CLV98 cells within 24 h after drug removal. Within 48 h strand breaks were completely repaired in both kinds of cells. No repair of single strand breaks was observed in ME18 and CLV98 cells after drug treatment in the concentration of 5 micrograms/ml.
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PMID:DNA damage and repair in normal and neoplastic cells treated with adriamycin. 773 54

Doxorubicin (DOX) was conjugated to a monoclonal antibody (mAb 425) directed against the human epidermal growth factor receptor. The immunoreactivity of these conjugates, with an average of six to eight molecules of DOX per antibody, was largely conserved, and their in vitro cytotoxicity against metastatic human melanoma cells (M24 met) was improved over that of free DOX. An evaluation of the therapeutic efficacy of mAb 425-DOX indicated that this immunoconjugate suppressed the growth of primary and secondary M24 met tumors in mice with severe combined immunodeficiency and prolonged the life span of these animals, whereas an equivalent dose of free DOX was ineffective. Conjugation of DOX to an irrelevant mAb also increased its antitumor effect over that of equivalent amounts of free drug but to a lesser extent than that achieved by the mAb 425-DOX conjugate. These results demonstrate targeted delivery and striking antitumor activity of DOX immunoconjugates in a preclinical model of spontaneous, metastatic human melanoma that was insensitive to free DOX.
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PMID:Therapeutic efficacy of a doxorubicin immunoconjugate in a preclinical model of spontaneous metastatic human melanoma. 775 86

Quinocarmycin monicitrate (KW2152) and its analogue, DX-52-1, demonstrated specificity for melanomas in the National Cancer Institute in vitro human tumor cell line drug screen. In contrast to most cell lines, a 50% reduction in tumor cell burden (as measured protein) at the end of a 48-h drug incubation was produced in five of eight melanoma lines by KW2152 concentrations (LC50s) ranging from 0.49 to 10.93 microM and by DX-52-1 concentrations ranging from 0.71 to 7.33 microM. Using the COMPARE algorithm, the patterns of differential cytotoxicity for both agents at the LC50 level of effect most closely resembled those for actinomycin D, mithramycin, and Adriamycin. In in vivo studies, both KW2152 (40 mg/kg/day) and DX-52-1 (90 mg/kg/day) caused partial and complete regressions of staged s.c.-implanted LOX IMVI melanoma xenografts following i.p. administration on days 5, 9, and 13 and produced tumor growth delays of 231 and 181%, respectively (P < 0.001). Activity was augmented by more prolonged therapy. Statistically significant growth inhibition of SK-MEL-2, UACC-62, UACC-257, and M14, but not SK-MEL-5 and MALME-3M, melanoma xenografts also was observed following every fourth or seventh day i.p. treatments. Based on these findings, DX-52-1 has been selected by the National Cancer Institute for development to clinical trial especially against melanomas. This agent represents one of the first to be selected for preclinical development based on disease-panel specificity discovered in the National Cancer Institute cancer drug screen.
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PMID:Efficacy of the quinocarmycins KW2152 and DX-52-1 against human melanoma lines growing in culture kand in mice. 785 Aug

The effect of the antibiotic agent novobiocin on the sensitivity of melanoma cells to colchicine and vinblastine was examined in drug-sensitive and drug-resistant B16 melanoma cells. A cell line COL/R was selected for colchicine resistance. The COL/R cell line (resistant to 80 ng/ml colchicine) was found to possess the multidrug-resistant (MDR) phenotype. The cells were shown to be cross-resistant to vinblastine and Adriamycin and to overexpress P glycoprotein. P glycoprotein activity was assessed by using the rhodamine 123 accumulation test. Rhodamine accumulation was markedly decreased in COL/R cells as compared to the parental B16 cells. Verapamil reversed drug resistance and increased rhodamine accumulation in COL/R cells. Novobiocin in combination with colchicine or vinblastine synergistically inhibited the proliferation of parental B16 cells. In COL/R cells, novobiocin markedly decreased colchicine resistance and increased rhodamine accumulation. These data show that novobiocin increases the sensitivity of both parental and MDR melanoma cells to microtubule-disrupting cytotoxic drugs.
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PMID:Novobiocin modulates colchicine sensitivity in parental and multidrug-resistant B16 melanoma cells. 792 31

Rodent cell lines can develop resistance to doxorubicin and methotrexate during hypoxic stress. This has so far not been observed in human tumor cell lines. The purpose of our communication is to show that doxorubicin and methotrexate resistance can also develop in human melanoma cells during exposure to hypoxia. Four cell lines (BEX-c, COX-c, SAX-c, WIX-c) have been studied. Cells were exposed to hypoxia (O2 concentration < 10 ppm) for 24 hr prior to reoxygenation. Doxorubicin and methotrexate cell survival curves were determined immediately after as well as 18 and 42 hr after reoxygenation. The 4 cell lines were relatively sensitive to doxorubicin without hypoxia pre-treatment, and all developed resistance during exposure to hypoxia. Hypoxic stress also induced methotrexate resistance in BEX-c and SAX-c but not in COX-c and WIX-c. BEX-c and SAX-c were sensitive to methotrexate without hypoxia pre-treatment, whereas COX-c and WIX-c were resistant initially. Hypoxia-induced drug resistance was present immediately after reoxygenation and tended to decrease with time but remained statistically significant even 42 hr after reoxygenation.
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PMID:Hypoxia-induced resistance to doxorubicin and methotrexate in human melanoma cell lines in vitro. 802 88


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