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)

Twenty-four patients with far advanced malignant tumors, resistent to established chemotherapy,, were treated with the combination of MNU and Cyclophosphamide. The drugs were administered in six-day cycles sequentially. MNU in doses of 4 mg/kg body weight and Cyclophosphamide in doses of 8 mg/kg body weight were given. Results of treatment showed response (greater than 50% tumor regression) in 10 (42%) of the 24 treated patients. Seven remissions were complete and three partial. Patients with Hodgkin's disease, malignant melanoma and breast cancer responded to this combination chemotherapy. Objective remissions were obtained also in five of thirteen patients with primary or metastatic brain tumors and in five of nine patients with pulmonary metastases. Nausea and vomiting were the main toxic effects, especially after injections of MNU. Myelosuppression was noted in about 50% of treated patients. Since this combination of cytostatics showed significant antitumor activity, further investigations are necessary on a larger number of patients and in other types of malignant tumors.
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PMID:Combination chemotherapy with 1-methyl-1-nitrosourea (MNU) and cyclophosphamide in solid tumors. 14 13

The authors treated the apigmented melanoma IC-Sofia in hamster with various doses of the following cytostatics: Cyclophosphamide, 6-Mercaptopurine, Vinblastine and Actinomycin D for 7 consecutive days. Determination of the tumor growth inhibition on the 8th day (early test) on the basis of tumor weight in the animals treated and untreated with cytostatics indicates that the tumor used is more sensitive to the effect of Cyclophosphamide and 6-MP and less to Vinblastine and Actinomycin D. Nevertheless sensitivity to cytostatic action is high enough for each of the cytostatic agents, depending upon the applied dose. This gives grounds to the authors to assume that hamster apigmented melanoma IC-Sofia is an adequate model for testing and evaluation of antitumor drugs.
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PMID:Hamster apigmented melanoma as a model for screening of potential antineoplastic drugs. 86 46

The extent of tumour, cell kill, produced by treating B16 melanomas with vincristine, cyclophosphamide, 5-fluorouracil and gamma-rays, alone and in combination, was determined using an in vitro colony assay. Cell kill by vincristine was revealed as a reduction in the yield of cells obtained by trypsinization, and as a decrease in the colony-forming ability of the extracted cells. The reduction in cell yield was interpreted as evidence of rapid cell lysis. Cyclophosphamide and gamma-rays also reduced both cell yield and surviving fraction, but in this case the small decrease in cell yield was due to an increase in cell volume. FU had no effect on cell yield, but surviving fraction was reduced. Tumour weight was also measured, and used in conjunction with cell yield and surviving fraction data to calculate the fraction of surviving cells per tumour following treatment with the agents. In combination studies, single doses of two different cytotoxic agents were given either simultaneously, or up to 24 h apart in either sequence, and assays were performed 24 h after the second drug was given. Combinations of vincristine + cyclophosphamide and 5-fluorouracil + gamma-rays were chosen because they had been shown by other workers to exhibit marked schedule dependency, including considerabl potentiation, against leukaemic cell lines. However, in the B16 melanoma there was no evidence of schedule-dependent cell killing with either of these combinations. For all sequences studied, the fraction of surviving cells per tumour was slightly greater than the predicted additive response calculated from single-drug controls.
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PMID:Cell survival in B16 melanoma after treatment with combinations of cytotoxic agents: lack of potentiation. 88 85

A recurrent tumor in a young male demonstrates the progression of an ameloblastic fibroma to an ameloblastic sarcoma. Chemotherapy with Actinomycin D, Vincristine, and Cytoxan produced a complete response without evidence of recurrence 4 years after initiation of chemotherapy. The patient developed an aggressive malignant melanoma 1 year after all chemotherapy was discontinued.
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PMID:Ameloblastic sarcoma: pathogenesis and treatment with chemotherapy. 126 Jun 84

Carmethizole, a novel bis-carbamate alkylating agent, was evaluated in vitro for potential mechanisms of interaction with DNA and in vivo for spectrum and degree of antitumor activity. In vitro, the concentration of carmethizole required to produce a 50% reduction in clonogenic cell survival was identical in O6-alkylguanine DNA alkyltransferase-positive and -negative human cell lines. The CHO cell line UV4, hypersensitive to mono- and bifunctional alkylating agents, was 37-fold more sensitive to carmethizole than normal cells. The UV5 cell line, which is not hypersensitive to cross-linkers, was 13-fold more sensitive to carmethizole than normal cells. Alkaline elution studies in L1210 cells exposed to carmethizole showed the presence of DNA-protein and DNA-DNA cross-links but not DNA strand breaks. These data suggested that the interaction of carmethizole with DNA produces monoadducts, DNA-protein, and DNA-DNA interstrand cross-links at several sites. In vivo, carmethizole was not cross-resistant with 1,3-bis(2-chloroethyl)-1-nitrosourea or Cytoxan as determined by testing against P388 leukemias resistant to the latter 2 agents. Carmethizole activity was similar to that of melphalan across the murine solid tumor panel, which consisted of B16 melanoma; colon adenocarcinomas 11a, 26, and 36; and the KHT sarcoma. Carmethizole, Cytoxan, and melphalan were all active and had comparable activity against the HCT-8 and MX-1 human tumor xenografts. The in vivo spectrum of activity and efficacy of carmethizole was similar to that of melphalan.
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PMID:In vivo and in vitro evaluation of the alkylating agent carmethizole. 187 2

Melanoma antigen vaccines are a conceptually attractive approach to prevent or delay disease recurrence in patients with surgically resected malignant melanoma. However, the immunogenicity of current vaccines is relatively low. Cyclophosphamide, when given in low doses prior to antigen exposure, is an immunomodulator which has been shown to enhance both humoral and cellular antitumor responses in animals and humans. We conducted a prospective, randomized, clinical trial to study whether pretreatment with cyclophosphamide augments the immunogenicity of a polyvalent, allogeneic, melanoma antigen vaccine in patients with melanoma and low tumor burden. Forty-five patients with resected stage II melanoma (regional metastases) were randomly allocated to treatment with melanoma vaccine or melanoma vaccine plus cyclophosphamide. All patients received the same dose and schedule of vaccine immunizations; those randomized to cyclophosphamide received 300 mg/m2 i.v. 3 days prior to each vaccine immunization. Cellular immune responses were evaluated by delayed-type hypersensitivity (DTH) skin reactivity to a test dose of vaccine at baseline (prior to treatment) and following the fourth immunization. Humoral immune responses were measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiographic analysis of indirect immunoprecipitates of patients' sera at the same time points. Twenty-four patients were randomized to cyclophosphamide pretreatment and 21 to vaccine alone; 22 and 18 patients were evaluable in each group, respectively. Differences were statistically nonsignificant with respect to either cellular (DTH) or humoral (antibody) responses between the two groups. DTH responses were induced in 16 of 22 (73%) and 15 of 18 (83%) patients treated with cyclophosphamide plus vaccine and vaccine alone, respectively. The mean posttreatment augmentation in DTH response in the cyclophosphamide group was 9.5 mm, compared with 9.9 mm in the vaccine-only group. Eight of 12 (66%) cyclophosphamide-pretreated patients and 9 of 12 (75%) vaccine-only patients produced increased titers of antimelanoma antibodies following treatment. No differences were observed between the groups in disease-free or overall survival. In summary, low-dose cyclophosphamide pretreatment failed to augment the immunogenicity of a polyvalent, allogeneic, melanoma vaccine in patients with completely resected early-stage melanoma.
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PMID:Lack of effect of cyclophosphamide on the immunogenicity of a melanoma antigen vaccine. 206 22

We have recently initiated clinical trials of active specific immunotherapy evaluating a new polyvalent melanoma cell vaccine in patients with high-risk and/or recurrent melanoma. The vaccine has been administered alone, or in combination with low-dose cyclophosphamide, as an immunomodulator of suppressor cells. Cyclophosphamide is effective in lowering suppressor cell activity in some patients undergoing active specific immunotherapy. This is not associated with an enhanced humoral immune response to melanoma-associated antigens, nor is the clinical course of those patients receiving cyclophosphamide favorably influenced. We are hopeful that other immunomodulators, alone or in combination with lower doses of cyclophosphamide, may be effective in some patients, particularly in those patients whose suppressor cell activity remains high. The optimization of the vaccine and the use of immunomodulators will enhance humoral and cellular immune responses to antigens in the allogenic vaccine that cross react with those present in the autologous melanoma, which should more favorably influence the prognosis of melanoma patients.
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PMID:Active specific immunotherapy in malignant melanoma. 253 8

Immunotherapeutic agents have often been found to provoke opposite effects on tumor growth--inhibitory or stimulatory--depending on dose, timing or route of administration. The reason for these opposite effects is not yet known. Levan (polyfructose), an immunomodulatory polysaccharide, has been found to exert opposite effects on the growth of the F10 variant of B16 melanoma. Low doses inhibit and high doses enhance the growth of this tumor. Cyclophosphamide (CY) augments the inhibitory effect of the polysaccharide. In order to elucidate the mechanism of these opposite effects, we tried to determine the changes induced by levan at inhibitory and stimulatory doses, alone or in conjunction with CY, on the lymphatic and hematopoietic systems of B16-F10 melanoma-bearing mice. In a previous study we reported the effect of these treatments on the morphology of spleen and lymph nodes (Leibovici, Kopel, Siegal & Gal-Mor (1986). Int. J. Immunopharmac., 8, 391). In the present study, we examined the effect of the treatments on bone marrow and peripheral blood composition. The growth of the tumor itself, as well as the various treatments, induced very marked changes in both bone marrow and blood. Tumor inoculation produced a sharp leukopenia and anemia followed by a restoration of both white and red blood cells. In the bone marrow, the tumor caused a gradual decrease in lymphocyte number. CY accentuated the severe leukopenia caused by the tumor. Lymphocyte depletion was prolonged, while restoration of granulocytes was achieved by day 7. A similar pattern of changes was observed in the bone marrow. With levan, opposite effects were observed in blood and bone marrow with the two doses in relation to the number of the cells of the lymphoid and myeloid lines: while 0.1 mg (tumor inhibitory) doses caused a more active restoration of lymphocytes as compared to 10 mg (tumor stimulatory) doses, an opposite effect was seen on the myeloid series--the high dose induced a more pronounced granulocytosis than the low dose. In the combined treatment, the low levan dose accelerated lymphocyte restoration in bone marrow compared to CY, while the high dose delayed the recovery of these cells. The results of the present study in conjunction with our previous study may explain the basis of the intriguing tumor inhibitory-stimulatory effects of some immunomodulators. Moderate increases in myeloid cell series appear to favor tumor inhibition and high increases favor tumor stimulation. In addition, the results of this study suggest that a regulatory relation might exist between the proliferation of the lymphoid and myeloid cell series.
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PMID:Effect of cyclophosphamide and levan treatment on bone marrow and peripheral blood cells in B16-F10 melanoma-bearing mice. 270 78

The results of 63 patients with advanced malignant tumors treated by combined chemotherapy including high-dose cisplatin (HD-DDP) (single dose 50-100 mg/m2) are reported. The remission rates and duration of the remission for various malignant tumors were: 40% (10 PR out of 25 patients) and 3-8 months for non-small cell lung cancer (NSCLC) treated by PMFV (DDP, MMC, 5FU and VCR) regimen; 87% (4 CR and 9 PR out of 15) and 3-14 months for breast cancer treated by PCMF (DDP, CTX, MTX and 5FU) regimen; 100% (1 CR and 3 PR out of 4) and 3-10 months for testicular cancer treated by PPV (DDP, Pingyangmycin and VCR) regimen; 57% (1CR and 3 PR out of 7) and 5-12 months for malignant melanoma treated by PBDV (DDP, BCNU, DTIC and VCR) regimen; 33% (2 PR out of 6) and 5 months for esophageal cancer treated by PPV regimen. In 6 patients with other malignant tumors, the remission rate was 50% (3 PR). The results show that the combined regimens including HD-DDP in the treatment of breast cancer and NSCLC (remission rate 87% and 40%, respectively) are better than that including low-dose DDP (17% and 7%) (P less than 0.001, P less than 0.01) and that including adriamycin (30% and 13%) (P less than 0.001, P less than 0.05). In the treatment, obvious gastrointestinal reaction, leukopenia, thrombocytopenia and mild functional damage of the liver and kidney were observed.
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PMID:[Evaluation of combined chemotherapy including high-dose cisplatin in the treatment of malignant tumors]. 282 Jun 83

The growth of some human tumor xenografts (3 out of 8, melanoma, non-Hodgkin's lymphoma, squamous cell carcinoma) was successfully--but moderately and temporarily--inhibited, when interferon-alpha (EGIS, Hungary) was given for 10 days. The route of administration (intratumoral or intraperitoneal) was usually not a decisive factor. An attempt to potentiate IFNa action with Zymozan or Cyclophosphamide did not succeed.
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PMID:Effect of interferon-alpha (IFN alpha) on various human tumor xenografts. 338 49


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