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)

The anti-tumour properties of Cy 233, a new nitrosoureido sugar, were investigated in two murine solid tumours: B16 melanoma and subcutaneously implanted colon adenocarcinoma. Injected i.v., Cy 233 exerted a strong anti-tumour effect against the established B16 melanoma: long-term survivors were recorded with all schedules of treatment. The drug was even more effective against advanced colon 38 adenocarcinoma: it produced a high percentage of total tumour regression, regardless of the route of administration (i.p., i.v., p.o.). The marked in vivo activity of Cy 233 against advanced colon 38 adenocarcinoma, which is known to be resistant to such major anti-cancer drugs as BCNU and chlorozotocin, its water solubility and its stability in aqueous media are further elements warranting toxicological and clinical studies of this agent.
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PMID:Characterization of the anti-tumour activity against solid tumours of a new nitrosoureido sugar: Cy 233. 259 12

Eight patients with advanced malignant melanoma were treated with high-dose melphalan (80-90 mg/m2) and BCNU (600-800 mg/m2). In all patients autologous bone marrow preservation was performed prior to therapy. Bone marrow was stored for 48 h in a refrigerator at 10 degrees C and reinfused 48 h post-therapy. Three patients had a complete response (CR), 1 a partial response and 4 patients no response. Two patients with CR died 4 and 5 months after therapy. One had an interstitial pneumonitis and 1 patient died from unknown cause. The third patient had a relapse 12 months after therapy. Major side effects were severe nausea/vomiting and a mild mucositis. Two patients suffered from BCNU-related encephalopathy. All patients had a full hematologic reconstitution after 6 weeks. High-dose chemotherapy with autologous bone marrow support achieves a high response rate. Long-term disease-free survival, however, was not seen with this approach.
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PMID:High-dose chemotherapy with autologous bone marrow support in advanced malignant melanoma. 269 12

CGP 6809 is a water-soluble nitrosourea derivative with quite distinct chemical and biological properties as compared with the well-known representatives of this class of compounds. It is related to the antibiotic streptozotocin, from which it is distinguished in the structure of the sugar moiety and the position of the methylnitrosourea residue. CGP 6809 possesses practically the same alkylating potential as streptozotocin; however, its carbamoylating activity is comparable with that of CCNU. In contrast to other nitrosourea derivatives, CGP 6809 showed relatively little activity in murine leukemias but was markedly active in solid transplantable melanomas (Harding-Passay, B16), in the 11095 prostate carcinoma, and in a substrain of Yoshida hepatoma (AH 7974) resistant to BCNU and CCNU. In the Ehrlich and Yoshida ascitic tumors complete responses were seen with no toxic death. Dose-dependent activity was found in the human lung carcinoma MBA 9812 and almost complete growth inhibition was achieved in the human melanoma WM 47 by both the oral and parenteral routes of administration. However, mammary tumor lines (Ca 755, 2661/61, R-3230AC), the Guerin-T8 uterus epithelioma, and the Rous sarcoma/S-R proved to be relatively refractory to this drug. This was also the case for the Lewis lung carcinoma implanted i.m. or s.c. However, development of lung metastases was markedly inhibited. Combination therapy using CGP 6809 with cyclophosphamide, 5-fluorouracil, or chlorambucil in the same model led to partial responses of the primary tumor as well as almost total eradication of lung metastases.
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PMID:CGP 6809, a sugar-containing nitrosourea derivative: pharmacological and physicochemical properties. 271 56

A panel of four cell sublines, each selected for resistance to a different antineoplastic agent, has been developed from a human malignant melanoma cell line G3361. Following repeated exposure to escalating doses of the drug of interest, cloned sublines were developed that are 9-fold resistant to cisplatin (G3361/CP), 11-fold resistant to 4-hydroxyperoxy-cyclophosphamide (4-HC) (G3361/HC), 4-fold resistant to carmustine (BCNU) (G3361/BCNU), and 4-fold resistant to melphalan (G3361/PAM). The cross-resistance of each resistant cell line was determined for cisplatin, BCNU, 4-HC, melphalan, carboplatin, nitrogen mustard, and Adriamycin. In general, the alkylating agent-resistant cell lines were specifically resistant to the drug used for selection with the exception of the G3361/CP line, which was greater than 10-fold resistant to the cisplatin analogue carboplatin, 4-fold resistant to 4-HC, and slightly (1.5-fold) resistant to melphalan, and the G3361/BCNU line, which was slightly (1.8-fold) resistant to melphalan. Collateral sensitivity of the G3361/CP, G3361/PAM, and G3361/4HC lines to killing by BCNU was also observed. Glutathione-S-transferase activity was elevated in each of the alkylating agent-resistant cell lines by 3- to 5-fold with chlorodinitrobenzene substrate. On Western blotting, the glutathione-S-transferase-pi (GST-pi) isoenzyme protein was elevated in the resistant cells by 3- to 5-fold. A complementary DNA (pTS4-10) coding for GST-pi has been cloned from a lambda gt11 library, sequenced, and used as a probe to determine the relative levels of GST-pi mRNA in the alkylating agent-resistant cell lines. GST-pi mRNA levels were elevated (8- to 15-fold) in the resistant cell lines, indicating that the GST-pi increases were mediated through an increase in mRNA levels. GST-pi elevations are a frequent event in cells selected for alkylating agent resistance, and in some cases, of multiple drug resistance. However, the lack of cross-resistance among cell lines selected for resistance to different alkylating agents, all of which have elevated GST-pi levels, indicates that increased levels of GST-pi cannot be the predominate mechanism for resistance to the tested drugs in these cell lines.
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PMID:Cross-resistance and glutathione-S-transferase-pi levels among four human melanoma cell lines selected for alkylating agent resistance. 280 68

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

Twenty-six adults, ages 27 to 60, with refractory metastatic solid tumors were treated with high-dose cyclophosphamide (Cy) + carmustine (BCNU) at one of three escalating dose schedules followed by autologous bone marrow transplantation (ABMT). Toxicity was severe and dose-related, with the maximum tolerated dose for the combination determined to be Cy 160 mg/kg and BCNU 900 mg/m2. Median time to WBC recovery (greater than or equal to 1,000/microL) was 13 days post-ABMT (range, nine to 22 days) and to a platelet count of greater than or equal to 50,000/microL, 22 days (range, 13 to 83 days). Sixteen of 20 evaluable patients (80%) responded to therapy with at least 50% reduction in measurable tumor, and three patients achieved complete remission (CR). Responders included eight of nine evaluable patients with breast carcinoma, two of five with melanoma, two of two with sarcoma, and four of four with colon carcinoma. Response durations were short (median, 4 months), even for complete responders, and relapses generally occurred at sites of previous metastases. In order for this approach to have a more significant impact on overall survival, it may need to be applied earlier in the natural history of the malignancy.
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PMID:High-dose combination alkylating agent therapy with autologous bone marrow rescue for refractory solid tumors. 304 66

One hundred forty-five patients with disseminated malignant melanoma have participated in five Phase II clinical trials utilizing leukocyte A recombinant interferon (IFN-alpha 2A) (96 patients), recombinant interferon gamma (rIFN-gamma) (29), or IFN-alpha 2A concomitant with rIFN-gamma (20 patients). The overall response rate was 17%, with most regressions occurring with the IFN-alpha 2A regimens. The median times to progression (1 month) and survival (6 months) were generally similar to those from chemotherapeutic agents. However, a limited cohort of patients had complete regressions or durable partial responses even after treatment was discontinued or maintained at less than or equal to 25% of the starting dosage. Most objective regressions were partial, occurred in nonvisceral sites, and were detected within 2 months of the beginning of therapy. The most noteworthy sequelae from these regimens were predominantly constitutional, but without any obvious long-term complications. These interferon programs can be conveniently self-administered on an outpatient basis. Although single-agent interferon regimens for advanced malignant melanoma will probably not offer a substantive therapeutic advance, combinations of these molecules with other biological agents (tumor necrosis factor), biochemical modulators (difluoromethylornithine), and cytotoxic agents (bischloroethylnitrosourea, BCNU) offer innovative therapeutic dimensions in the design of future clinical investigations.
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PMID:Recombinant interferons in the management of advanced malignant melanoma. Updated review of five prospective clinical trials and long-term responders. 314 48

The use of a cell image processor for the in vitro assessment of drug effects on cell growth, cell kinetics and chromatin organization is described. We have studied the influence of two well documented cytotoxic drugs, i.e. BCNU and vincristine (VIN), on the above mentioned parameters of the P-388 mouse leukemia, MCF-7 human mammary and HBL human melanoma cell lines. The cells were cultured for 1 to 4 days on glass coverslips put in Petri dishes containing or not (control) 10, 1 or 0.1 microgram/ml medium of the drug, after which they were fixed for histology, Feulgen-stained and analyzed through a cell image processor, i.e. the System for Analytical Microscopic Biomedical Applications (SAMBA 200). Our results showed that both BCNU and VIN exerted a well-known antineoplastic effect that was assessed at three different but highly complementary levels on the same sample of cells in a very rapid and simple procedure.
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PMID:A new assay to evaluate cell growth and drug sensitivity in culture using a cell image processor. 317 65

Fifty-nine patients with regional or hematogenous recurrence of malignant melanoma following resection of all the gross tumor were randomized to observation or chemotherapy. The chemotherapy consisted of BCNU 80 mg/M2 I.V. every 4 weeks, actinomycin-D 0.01 mg/kg and vincristine 1.0 mg/M2 I.V. every 2 weeks, for a total of 6 months. The chemotherapy protocol was tolerated well without appreciable objective side effects. At a median follow-up period of 11.5 months, the disease-free survival time for the chemotherapy treated group is significantly longer than for the control group (P = 0.01). The estimated median disease-free survival time is 4 months in the surgical control group and 9 months in the chemotherapy group. At present, the proportion of patients remaining disease-free is 43% for the surgical control and 55% for the chemotherapy treated group. More patients and follow-up are needed, but this preliminary report suggests that nitrosourea-based protocols need to be evaluated further as adjuvant treatment of malignant melanoma.
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PMID:Adjuvant chemotherapy in high-risk malignant melanoma. 330 59

Survival curves and dose escalation studies of four representative human tumor cell lines exposed to the various alkylating agents are presented. With HN2, at a level of one log of cell kill there was a fivefold range in drug concentration required to achieve this degree of cell kill among the cell lines, from 4.5 microM for the SL6 lung adenocarcinoma to 22 microM for the SW2 small-cell lung carcinoma. Four logs of SCC-25 squamous carcinoma cells were killed by 100 microM CDDP; however, there was only about one log of SL6 cells killed by 500 microM CDDP. To kill one log of G3361 melanoma cells required 24 microM 4-HC and to kill one log of SCC-25 cells required 24 microM, approximately a 16-fold difference. The curves for cell kill by L-PAM appeared to be biphasic, with a break at about 100 microM. There was about a threefold range in drug concentration required to achieve one log of cell kill with L-PAM, from 60 microM in the SCC-25 cell line to 18 microM in the SW2 line. To kill one log of SCC-25 cells required 295 microM BCNU and to kill one log of SW2 cell required 120 microM, about a 2.5-fold difference. The range of maximally tolerated HN2 concentrations were from 1200 microM for the SL6 cell line, 48 times the initial concentration, to 300 microM for the SCC-25 line, 16 times the initial concentration. The G3361 line tolerated the highest level of CDDP, 1900 microM, 48 times the initial concentration. The SCC-25 line, on the other hand, tolerated only 600 microM, 30 times the initial concentration. The SL6 cell line maximally tolerated 36 times the initial concentration of 4-HC (1450 microM), whereas the SCC-25 cell line tolerated only 18 times the initial concentration (720 microM). The G3361 melanoma tolerated 1555 microM, 30 times the initial concentration of L-PAM, and the SCC-25 cell line tolerated 700 microM, 14 times the initial concentration. The SL6 cell line tolerated the highest concentration of BCNU, 4200 microM, 24 times the initial concentration. The SCC-25 cell line tolerated 1450 microM, 8 times the initial concentration. In all cases, the SCC-25 cell line was least able to tolerate exposure to increasing concentrations of alkylating agents. The SL6 and G3361 cell lines showed the greatest tolerance for increasing concentrations of alkylating agents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Development of alkylating agent-resistant human tumor cell lines. 337 Jul 36


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