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)

Validity of the tritiated water assay technique for tyrosine hydroxylase activity as a qualitative method was demonstrated with mushroom tyrosinase. Using this method, isolated murine melanoma "tyrosinase" (L-dopa oxidase) showed no tyrosine hydroxylase activity. This finding supports previous studies in our laboratory which used a variety of histochemical and biochemical methods. The nonenzymatic production of tritiated water caused by tritium exchange with hydrogen peroxide complicates the use of the tritiated water assay technique with crude systems, since hydrogen peroxide is generated by a variety of oxidase reactions. For this reason, previous studies using the tritiated water assay technique with crude systems are ambiguous.
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PMID:Inability to demonstrate hydroxylation of tyrosine by murine melanoma "tyrosinase" (L-DOPA oxidase), using the tritiated water assay technique. 10 47

A phase I investigation of chlorozotocin, a new-water soluble chloroethylnitrosourea, was undertaken to define its pharmacologic effects in man. Forty-three patients received single intravenous doses ranging from 5 to 175 mg/m2 every 6 wk. No signs of toxicity were observed at doses of under 120 mg/m2, but thrombocytopenia occurred at higher doses. The thrombocytopenic nadir appeared to be dose-dependent and occurred 4 wk after treatment. Platelet transfusions were required in 2 patients who had previously received intensive chemotherapy. No significant leukopenia occurred. A mild reversible and delayed elevation of hepatic transaminases was found in 25% of courses of 120 mg/m2 or more. No renal toxicity was observed and gastrointestinal toxicity was mild. Investigation of clinical pharmacology revealed a rapid triphasic plasma clearance with initial t1/2S of 3, 15, and 30 min. The concentration of N-nitroso intact drug at 1 hr was 10% of the initial peak level. Renal excretion accounted for half of the dose. No significant concentration of N-nitroso intact or radiolabeled drug was detected in the cerebrospinal fluid of 2 patients in whom it was examined. There were objective signs of therapeutic activity in 5 patients, 3 of whom had melanoma. Based on these studies, the recommended dose for phase II investigation of chlorozotocin is 120 mg/m2 every 6 wk.
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PMID:Phase I studies on chlorozotocin. 14 44

The rates of adhesion of melanoma cells (carcinogenic) onto nonionic polymer surfaces were studied by using radioactively labeled cells and measuring the fraction of cells which adhered to the surface in a given time. Glow discharge (plasma) polymerization of 1,1,3,3-tetramethyldisiloxane and of nitrogen-acetylene-water (mole ratio 0.4:1.0:0.2) was used to modify the surface energy of the substrate. The cell adhesion rate was found to be given by Y = 1 - exp [-k0(gammas - gamma0)t], where Y is the fraction of cells adhered, -k0 is a characteristic rate constant, gammas is the total surface energy of the substrate, gamma0 is the threshold surface energy of cell adhesion, and t is time.
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PMID:The rate of adhesion of melanoma cells onto nonionic polymer surfaces. 35 60

Cultured human diploid skin fibroblasts incubated with [G-3H]benzo(a)pyrene yielded about 10 times more H2O-=soluble benzo(a)pyrene metabolites and DNA adducts of stationary growth phase than did proliferating cultures. This increased formation could be blocked by alpha-naphthoflavone. Trichloropropenoxide and cyclohexenoxide, inhibitors of the epoxide hydratase, inhibited predominantly the formation of DNA adducts. Cultures from older individuals formed significantly more benzo(a)pyrene metabolites and DNA adducts, but control cultures from patients with either lung cancer or melanoma did not. The age influence was not apparent when the ratio of DNA adducts to H2O-soluble metabolites was determined for each individual cell line. However, the proportion of DNA-bound material in the cells from patients with lung cancer was significantly increased compared to cells from melanoma patients or healthy individuals.
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PMID:Metabolism and formation of DNA adducts of benzo(a)pyrene in human diploid fibroblasts. 42 49

Tumor-associated antigens were demonstrated in phenol water extracts of human malignant melanoma by migration tests with leukocytes from melanoma patients and controls: in 25 out of 60 melanoma patients weak reactivity was observed, usually stimulation of leukocyte migration, while leukocytes from 37 controls were negative in 100 tests. The frequency of positive reactions did not differ significantly in patients with and without metastases. Humoral antibodies against antigens of phenol water extracts were not detectable in melanoma patients. Rabbits did not produce antibodies against tumor typical substances after immunization with phenol water extracts. Tumor associated antigens of phenol water extracts are presumably not targets of antitumor immune reactions that can influence the clinical course.
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PMID:Human malignant melanoma antigenic properties of phenol water extracts. 44 60

A novel nitrosourea derivative, methyl-6-[[[(2-chloroethyl)nitrosoamino]carbonyl]-amino]-6-deoxy-alpha-D-glucopyranoside (MCNU), is a water-soluble compound in which a methoxyl group is attached to the C-1 position and an N-(2-chloroethyl)-N-nitrosoureido group is attached to the C-6 position of the glucose moiety. MCNU exhibited a marked life-prolongation or growth-inhibitory effect against mouse L1210 leukemia, adenocarcinoma 755, Nakahara-Fukuoka sarcoma, Lewis lung carcinoma, and B16 melanoma. Ip, oral, or iv administration of MCNU was markedly effective against L1210 leukemia, and the therapeutic ratio by ip administration was larger than that of chlorozotocin or CCNU. The life-prolongation effect of MCNU against established Lewis lung carcinoma was similar to that of methyl-CCNU. The bone marrow toxicity of MCNU was less than that of CCNU but considerably more than that of chlorozotocin.
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PMID:Biologic activity of MCNU: a new antitumor agent. 46 55

Experiments were started with an animal model: Tumor antigens could be solubilized from fibrosarcomas of inbred guinea pigs by extraction with physiological saline. Extracts were fractionated by ammoniumsulfate precipitation, gel filtration, ion exchange chromatography, and polyacrylamide electrophoresis. Skin tests and leucocyte migration assays could detect antigenic activity in a number of fractions different with respect to size and charge. A less heterogeneous antigen could be extracted with phenol-water from guinea pig fibrosarcomas. Tumor associated antigens could be demonstrated in phenol-water extracts of human melanoma by leucocyte migration tests. Weak migration reactions were found with leucocytes from melanoma patients, not with leucocytes from controls. The frequency of positive results was similar in patients with and without metastases. No antibodies against antigens of phenol-water extracts could be detected in sera from melanoma patients. No antibodies against tumor associated substances could be demonstrated after immunization of rabbits with phenol-water extracts. Antigens extracted by phenol-water seem to be weak immunogens. Radioactive antigens were extracted from membranes of labelled cell cultures of human melanoma. Antigenic activity was assayed by double immune precipitation followed by sodium-dodecylsulfate-polyacrylamide-electrophoresis. Yields from available cell quantities were too small for further purification and clinical studies.
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PMID:[Isolation of soluble tumor-associated antigens of human malignant melanoma]. 68 Jun 24

A number of biochemical aspects of melanogenesis were studied in 15 variously melanized human melanomas. The tryosinase activity was correlated with the degree of melanoma varied from 3,667 to 46,183 tryosinase units, in partially melanotic melanoma it varied from 14 to 75 tryrosinase units. The subcellular distribution of tryrosinase activity was limited to the particulate fraction )144,000 x g) of the partially melanotic and amelanotic melanomas. However, the melanotic melanomas contained the enzyme in both particulate and soluble fractions, with the greater tyrosinase activity in the particulate fraction. Electrophoretic resolution of tyrosinase isozymes in the soluble fraction or lipase-solubilized tyrosinase derived from the particulate fraction revealed three isozymes in melanotic melanomas. The isozyme of intermediate mobility always was the dominant form. In partially melaotic melanomas, the solubilized tyrosinase showed six isozymes. Three were similar to those of melanotic melanomas. The remaining three isozymes showed slower mobilities, possibly with greater molecular weights than the isozymes derived from melanotic melanomas. Inhibitors of tyrosinase were present in melanomas. Increased tyrosinase activity occurred after storing the homogenate at 0-4degree, removing of supernatant from the homogenate sediment, and washing the 144,000 x g particulate fraction, which suggested the presence of water-soluble, loosely bound inhibitor (s) in the soluble fraction of partially melanotic melanoma. Another inhibitor was released from the 144,000 x g particulate fraction of melanotic melanoma after lipase digestion. These substances inhibit both the isolated dominant tyrosinase isozyme(human) and mushroom tyrosinase. As inhibition of tyrosinase activity may produce regression of abnormal cell growth, the inhibitors may provide an approach to melanoma chemotherapy.
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PMID:Melanogenesis in human melanomas. 80 70

There is increasing evidence that the use of hyperthermia alone or in conjunction with other modalities may improve the therapeutic effectiveness of treatment of cancer. The present clinical studies were carried out to evaluate the response of normal and tumor tissues in patients with various cutaneous malignant lesions to repeated courses of hyperthermia alone or in conjunction with radiation therapy. Thirty-six patients with malignant cutaneous lesions (mycosis fungoides, Kaposi sarcoma, malignant melanoma, lymphoma cutis, and other metastatic skin lesions) have been studied. The heating methods used were: 1) temperature regulated water bath immersion; and 2) radiofrequency inductive heating. The normal tissue effects of the combined treatments of radiation and hyperthermia do not appear to be greater than those treated with radiation alone. The initial tumor regression rates were faster in patients treated with radiation plus hyperthermia than in radiation alone, particularly in patients with Kaposi sarcoma and lymphoma cutis. Among ten locally recurrent patients, seven showed significant prolonged benefits achieved by the combined treatments as compared with the radiation therapy alone. Fractionated hyperthermia alone caused significant tumor regression in four out of five patients. Possible mechanisms leading to the improved results from the combined treatments are discussed.
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PMID:Local tumor hyperthermia in combination with radiation therapy. 1. Malignant cutaneous lesions. 88 May 48

The procedure for isolating soluble melanoprotein from human malignant melanoma was described. Electron microscopy confirmed the absence of any contaminating organized particles. The melanoprotein was brown hygroscopic substance with 8.8% of melanin, easily soluble in water. The solution revealed general absorption with a shoulder at 280 nm. Chemical composition was typical for a melanoprotein complex with characteristic high sulphur content (2.1%) and abundance in zinc (210 mug Zn/g dry sample). Sedimentation and electrophoretic properties indicated relative homogeneity. Similar substance could also be isolated from Harding-Passey mouse melanoma. Such soluble melanoproteins have been needed for their broad exploitation in tumor immunology.
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PMID:Soluble melanoprotein of tumor origin. 119 35


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