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 chemotherapeutic activity of analogs of the anthracycline antibiotic, nogalamycin, was investigated in the P388 and L1210 leukemias and the B16 melanoma in mice. Among the compounds tested, 7-con-O-methylnogarol was found to have superior activity. Depending on the route and schedule of administration, increases in lifespan (ILS) in excess of 100% were observed in all three tumor systems. Additional testing of 7-con-O-methylnogarol demonstrated significant activity in the murine colon 26 and colon 38 tumors and the CD8F1 mammary tumor. 7-Con-O-methylnogarol was not significantly effective against murine Lewis lung carcinoma, although ILSs of 38% and 29% were achieved in two experiments. Activity was observed against ip inoculated P388 leukemia after ip, sc, oral, and iv drug administration. 7-Con-O-methylnogarol was also highly active (ILS greater than or equal to 120%) after ip drug administration to mice with iv inoculated P388 leukemia. Significant ILS values resulted from a variety of schedules of administration against ip inoculated P388 leukemia and B16 melanoma. Experiments in which the time of single-dose administration was varied prior to the time of ip P388 leukemia inoculation showed that residual drug or bioactive drug-related materials remained in mice for 8 hours after 50 mg/kg administered ip and for 48 hours after 200 mg/kg administered sc.
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PMID:Treatment of mouse tumors with 7-con-O-methylnogarol and other analogs of the anthracycline antibiotic, nogalamycin. 52 31

Clinical interest in the pharmacology of medicinals from marine organisms has heightened due to anticancer effects indicated for Mercenaria marine clam components. This report further characterizes the anticancer principle. Hydrophilic products were extracted by aqueous and/or salting-out methods followed by dialysis. Organic solvent extraction produced a new family of active agents related to the hydrophilic component. Thin layer and liquid column chromatography as well as enzymatic degradation were used to secure a more pure product for analysis. Assay included P388 leukemia and B16 melanoma. Oligonucleotide fractions and smaller components were observed to increase survival rate; treated mice remained at 67% survival when control animals had reached zero. A many-fold purified product was effectively reduced from 300 mg/kg body weight to 5 mg/kg to achieve anticancer activity. Chemical analysis suggested a product composed of carbohydrate, phosphate, peptide, and an unidentified material. Acid hydrolysis revealed the presence of hexoses, pentoses, and a full spectrum of amino acids. Several distinct components found to comprise the active samples may act as the effective product or as a carrier.
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PMID:Chemical characterization and biological activity of an anticancer agent of marine origin. 54 3

The chemotherapeutic effects of 6-diazo-5-oxo-L-norleucine (DON) and N-[N-gamma-glutamyl-6-diazo-5-oxo-norleucinyl]6-diazo-5-oxo-norleucine (azotomycin) were evaluated in a spectrum of transplantable experimental tumor systems including xenografts of human tumors in athymic mice. Both drugs displayed remarkable activity against the murine leukemia L1210 and P388, the Colon Tumors C26 and C38 and the CD8F1 mammary tumor. No significant activity was observed against Lewis lung carcinoma, B16 carcinoma, B16 melanoma, and intracranial ependymoblastoma. DON and azotomycin also exhibited striking inhibitory effects on the growth of s.c. human tumor (MX-1 mammary, LX-1 lung and CX-1 and CX-2 colon) xenografts in athymic mice. With the exception of one colon xenograft (CX-1), all tumor lines were markedly responsive to both drugs. Tumor regressions below the initial tumor sizes of 100 to 300 mg, albeit temporary, were brought about by one course of treatment every 4 days for 3 doses (at optimal dose) with either drug. Although these drugs have been tested previously in the clinic and have shown only limited therapeutic effectiveness, they seem to worthy of a second and closer look in light of the recent laboratory results.
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PMID:Efficacy of 6-diazo-5-oxo-L-norleucine and N-[N-gamma-glutamyl-6-diazo-5-oxo-norleucinyl]-6-diazo-5-oxo-norleucine against experimental tumors in conventional and nude mice. 57 61

A total alkaloid and two purified alkaloid extracts of Alangium vitiense were found to be oncostatic for L1210 leukemia; the total alkaloid exerted a noticeable activity, and the purified extracts exerted a borderline activity. These two purified extracts are noticeably oncostatic for two other lymphoid neoplasias in mice, P388 leukemia and Gardner lymphosarcoma. These compounds are not active on Warner myelomonocytic leukemia WEH13 or on B16 melanoma.
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PMID:Oncostatic effects of Alangium vitiense extracts (ICIG-EORTC 1131, 1186 and 1207) on lymphoid murine tumors. 58 Apr 15

From the time of its inception in 1955, the Drug Development Program of the National Cancer Institute has relied primarily on transplanted rodent tumor systems in vivo for the evaluation and selection of potential antitumor agents. Although greater emphasis has been placed in recent years on rationally designed drugs, the major effort throughout the history of the program has involved the empirical screening of a wide variety of chemical structures and natural products of varying sources. The initial screening spectrum consisted of three mouse tumors, Sarcoma 180, Carcinoma 755 and Leukemia 1210, based on the retrospective analysis presented in the GELLHORN-HIRSCHBERG Report. As a result of further expermental studies and analyses, the screens changed successively to (1) L1210 plus a spectrum of mouse, rat and hamster tumors, (2) L1210 plus the rat tumor, WALKER 256, (3) L1210, plus P388 for natural products and B16 melanoma and LEWIS lung carcinoma for special studies, and finally (4) P388 as a pre-screen followed by a panel of transplanted tumors and xenografts representing the major tumor sites. The rationale underlying each of the successive changes, and results obtained with each approach, will be discussed.
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PMID:Antitumor screening procedures of the National Cancer Institute. 61 10

Fluphenazine was found to possess moderate reproducible activity against the intraperitoneal L-1210 and P-388 leukemia murine tumor models. Seven ether derivatives of fluphenazine and eight compounds in which the terminal side-chain hydroxyl group was replaced by an amine function were prepared and evaluated in the intraperitoneal L-1210, P-388, and B16 melanoma systems as well as the intracerebral L-1210 and ependymoblastoma brain tumor models. While no substantial intracerebral activity was observed, seven derivatives possessed reproducible activity in the intraperitoneal L-1210 or P-388 system. Several gave T/C values of 150%. No B16 melanoma activity was observed. These compounds were also tested for their cytotoxic properties in culture against L-1210, P-388, and KB cells. The amine isosteres, while possessing little in vivo activity, were the most cytotoxic of the compounds prepared, with several having ED50 values less than 1 microgram/ml.
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PMID:Potential CNS antitumor agents-phenothiazines II: fluphenazine analogs. 62 29

A structure-activity relationship study was conducted on a number of bis(substituted aminoalkylamino)anthraquinones. These compounds were prepared by the condensation of substituted or unsubstituted leucoquinizarin with appropriate amines, followed by air oxidation. Both the position and the nature of the center nitrogen atom of the side chain are vital to the antineoplastic activity. The possible mode of action of these aminoquinones was discussed. 1,4-Dihydroxy-5,8-bis[[2-(hydroxyethyl)amino]ethyl]amino-9,10-anthracenedione (DHAQ) was found to possess potent inhibitory activity against both the P-388 leukemia system (T/C of 299 at 0.5 mg/kg with 4/6 cures) and the B-16 melanoma system (T/C of 503 at 1 mg/kg with 7/10 cures).
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PMID:Antineoplastic agents. Structure-activity relationship study of bis(substituted aminoalkylamino)anthraquinones. 62 5

A murine model of immune responsiveness had been adapted to study anergic conditions associated with neoplasia. Marked anergy observed in mice bearing L1210 leukemia and P-388 lymphoma is contrasted to the minimal immune depression associated with B-16 melanotic melanoma and Sarcoma 180J. The ability of N,N-bis(2-chloroethyl)-N-nitrosourea chemotherapy to reduce tumor burden without prolonged suppression of delayed cutaneous hypersensitivity is compared to the profound suppression of the cutaneous response observed with Adriamycin cytoreductive therapy. The applications of our model are discussed in relation to tumor-associated anergy, new approaches to the evaluation of pharmaceuticals, and studies of combined chemoimmunotherapy regimens.
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PMID:Delayed cutaneous hypersensitivity to oxazolone in mice with tumors. 63 44

Computed tomography proved insensitive to leptomeningeal spread of hematologic malignancies including leukemia, lymphoma, and malignant histiocytosis. In only 3% of patients did it directly demonstrate leptomeningeal tumor. In comparison, the detection rate of leptomeningeal tumor secondary to carcinoma was 44% and for melanoma, 100%. Intracranial subarachnoid seeding from primary brain gliomas was detected in each instance. The simultaneous presence of parenchymal metastases with leptomeningeal carcinomatosis occurred in 18% of patients with nonhematologic malignancies. Computed tomography evidence of communicating hydrocephalus, previously thought to be a major factor in clinical symptomatology, occurred in only 11% of patients.
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PMID:Computed tomography in leptomeningeal spread of tumor. 70 24

The therapeutic usefulness of chlorpromazine (CPZ) and caffeine (CAF) in combination with selected nitrosoureas was investigated in mice bearing L1210 leukemia, Lewis lung carcinoma, and B16 melanoma. We found that using BCNU with either CAF or CPZ was therapeutically superior to using either agent alone to treat mice bearing L1210 leukemia. Administering all three drugs in combination did not improve upon the therapeutic responses obtained with the two-drug combinations. In mice implanted with Lewis lung carcinoma or B16 melanoma, responses to treatment with the triple combination of methyl-CCNU, CAF, and CPZ suggested, but did not clearly establish, superiority over each two-drug combination or methyl-CCNU alone.
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PMID:Therapeutic potentiation of nitrosoureas using chlorpromazine and caffeine in the treatment of murine tumors. 75 16


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