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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue plasminogen activator was purified in high yield from pig heart by immunoaffinity chromatography and characterized by analysis of the glycosylation pattern and the N-terminal amino acid sequence. Comparisons with the human enzyme reveals residue exchanges in the A-chain at positions 3 (porcine Arg/human Gln) and 5 (Thr/Ile), and in the B-chain at positions 6 (Tyr/Phe), 10 (Thr/Ala) and 20 (Val/Ala). The glycosylation pattern for the porcine activator was determined by endoglycosidase treatment followed by gel electrophoresis. The A-chain contains a single high-mannose type of N-linked glycan structure and the B-chain contains a complex type of oligosaccharide. A similar but not identical pattern has been observed for the human activator, purified from melanoma cells.
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PMID:Porcine tissue plasminogen activator. Immunoaffinity purification, structural properties and glycosylation pattern. 309

We describe results demonstrating the positive regulation of melanogenesis by two substrates of the melanogenic pathway. We have found that L-tyrosine and L-dihydroxyphenylalanine (L-dopa), whose metabolic fates are affected by the activity of that pathway, can also act as its regulators. In living pigment cells, tyrosinase (EC 1.14.18.1), a crucial and rate-limiting enzyme of melanogenesis, acts in subcellular organelles known as melanosomes. Melanin is laid down only in these organelles. We demonstrate that supplementing Ham's F-10 medium with additional L-tyrosine or L-dopa during the culture of amelanotic Bomirski hamster melanoma cells results in a rapid increase in melanin formation, which is not simply due to greater availability of substrate. There is a rapid increase in tyrosinase activity and a large scale synthesis of melanosomes. The effects of L-tyrosine and L-dopa are prevented by the addition of cycloheximide. The actions of L-tyrosine and L-dopa are specific in that under similar conditions D-tyrosine, D-dopa, N-acetyl-L-tyrosine, L-phenylalanine, L-tryptophan and L-valine have little or no effect. The two substrates, L-tyrosine and L-dopa, appear to act through related but distinct mechanisms. Our findings provide an example of a little-known phenomenon: regulation of a differentiated eukaryotic phenotype through positive control by substrates in the pathway.
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PMID:Positive regulation of melanin pigmentation by two key substrates of the melanogenic pathway, L-tyrosine and L-dopa. 314 38

Dopa phosphates, a new class of compounds, contain phosphate-ester linkages at the 3- and/or 4- positions of the phenylalanine ring of L-dopa. Dopa phosphates have been shown to increase pigment production in the epidermis of hairless mice. Groups of Skh-2 pigmented hairless mice were treated topically with various concentrations of dopa phosphates daily for five weeks. Half of each group received suberythemal UVB radiation three times weekly for four weeks from a bank of filtered FS20 lamps. UVB and dopa phosphates alone each caused a modest increase in epidermal pigmentation. However, treatment of mice with dopa phosphates plus UVB radiation resulted in a marked increase in pigmentation, greater than with either treatment alone. The optimal concentration of dopa phosphates was 0.01% (100 micrograms/ml Tris-glycerol buffer) whether or not they were applied in conjunction with UVB radiation. Histological analyses revealed that dopa phosphates and UVB radiation each caused an increase in the number of pigmented melanocytes in the epidermis. Control groups treated with Tris-glycerol buffer alone, or buffer containing L-phenylalanine or L-dopa showed no significant changes in pigmentation. Our results indicate that dopa phosphates stimulate the production of melanin and affect the development and distribution of melanocytes in the skin of Skh-2 mice. By these criteria, dopa phosphates and UVB act in a similar manner to increase melanin content in the skin. The processes may be related to those recently observed in cultured mouse melanoma cells where dopa phosphates are incorporated into melanin, presumably following enzymatic hydrolysis by cellular phosphatases with the resultant production of L-dopa and inorganic phosphate.
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PMID:Phosphorylated mixed isomers of L-dopa increase melanin content in skins of Skh-2 pigmented hairless mice. 314 38

Intratumor macrophage numbers are enhanced by the administration of chemotactic f-MET-LEU-PHE - antitumor antibody - conjugates. The four f-MET-peptides f-MET-LEU-PHE, f-MET-LEU-PHE-o-methylester, formyl-norleucyl-phenylalanine and formyl-methionyl-phenylalanine, all chemotactic for human monocytes, where evaluated alone and conjugated to the melanoma directed monoclonal antibody ZME 018. f-MET-LEU-PHE-o-methyl-ester is the most active peptide, whereas f-MET-LEU-PHE - ZME 018 is the most active conjugate, not only inducing a response at the lowest concentration, but also the highest migrating cell numbers.
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PMID:Chemotactic monoclonal antibody conjugates: a comparison of four different f-Met-peptide-conjugates. 326 21

Fifty-nine patients with melanoma or soft tissue sarcoma of the extremities underwent hyperthermic isolated limb perfusion utilizing cisplatin and wide local excision. Doses of cisplatin ranged from 0.75 to 2 mg/kg. The mortality and morbidity rates were 0 and 6.8 percent, respectively. Pharmacokinetic studies indicate that cisplatin is rapidly bound to perfused tissues and remains bound for 1 month. Maximum tumor response in sarcomas occurs 1 to 2 weeks after perfusion, compared with 1 month after perfusions with l-phenylalanine mustard and actinomycin D. Local and regional recurrence rates were 0 and 3.4 percent, respectively, at 1 year. Further studies of hyperthermic limb perfusions with cisplatin are warranted.
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PMID:Pharmacokinetics, toxicity, and short-term results of cisplatin hyperthermic isolated limb perfusion for soft-tissue sarcoma and melanoma of the extremities. 336 21

The effects of a combined dietary restriction of tyrosine and phenylalanine on metastasis were investigated with the use of 3 rodent tumor cell lines: B16-bladder 6 (BL6) melanoma inoculated into (C57BL/6 X DBA/2)F1 mice, Lewis lung (3LL) carcinoma inoculated into C57BL/6 mice, and RT7-4bs hepatocarcinoma inoculated into BD-IV rats. When examined for effects on spontaneous metastasis, dietary restriction of tyrosine and phenylalanine had no effect on metastasis to draining lymph nodes in either BL6 or 3LL tumors. However, the restriction did reduce metastasis of RT7-4bs cells to draining lymph nodes by 60%. In all tumor systems, the dietary restriction effectively inhibited the subsequent growth of lymph node tumors. The most marked effect of the dietary restriction was on spontaneous hematogenous metastasis, which was almost totally blocked for BL6 cells and was reduced by 85% for RT7-4bs cells. Tumor-associated splenomegaly also was completely inhibited in 3LL tumor-bearing mice. The selective dietary amino acid restriction failed to reduce initial lung colonization in the experimental metastasis assay but clearly inhibited subsequent tumor outgrowth in the lungs. These findings demonstrate that modification of host nutritional status by restriction of the dietary intake of tyrosine and phenylalanine exerts a dramatic antimetastatic effect directed particularly on spontaneous hematogenous metastasis. Although the preliminary data suggest a primary modulating effect on tumor cell populations growing in diet-restricted animals to reduce inherent metastatic ability, the actual mechanisms remain to be defined.
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PMID:Dietary restriction of tyrosine and phenylalanine: inhibition of metastasis of three rodent tumors. 347 May 51

Between 1964 and 1983, 65 patients with Stage II extremity melanoma were treated in a nonrandomized fashion with wide local excision, lymph node dissection, and hyperthermic perfusion with 1-phenylalanine mustard at 1.0-1.5 mg/kg. Southwest Oncology Group Stage II criteria were used, including IIA (node positive), IIB/C (recurrent local/regional), or both. During the study interval, literature reports of 5-year survival for Stage II melanoma ranged from 6% to 50% and averaged approximately 26% to 30%. In this study group, 40% of patients had recurrent disease confined to regional lymph nodes, 33% had recurrent cutaneous disease, and 26% had recurrent disease in both locations. Survival for all Stage II patients at 5 years was 56.6%, and 40% at 10 years. When recurrent disease was confined to regional nodes only (IIA), survival at 5 years was 70.5%, and 40% at 10 years. Survival for patients with Stage IIB/C disease at 5 and 10 years was 58% and 43.7%. When recurrent melanoma was present in both skin and nodes, 5-year survival was 29%. The present study indicates that aggressive treatment of Stage II extremity melanoma, which includes hyperthermic isolation perfusion, can prolong survival in these high-risk patients.
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PMID:Improved survival of patients with stage II melanoma of the extremity using hyperthermic isolation perfusion with 1-phenylalanine mustard. 368 36

The single and combined effects of (a) dietary restriction of phenylalanine and tyrosine, (b) levodopa methylester chemotherapy, and (c) megadose sodium ascorbate supplementation on experimental metastasis was determined in B16-BL6 melanoma. Dietary restriction and levodopa methylester therapy inhibited tumor outgrowth, whereas ascorbate alone was inactive. In combination, however, the effect of dietary restriction and levodopa methylester chemotherapy was augmented by sodium ascorbate. Tumor cells surviving this combination therapy (treated population) were isolated from the lungs of treated mice, and proved to be tumorigenic when inoculated SC into the back of naive mice. The resulting tumors grew more slowly than those produced by inoculation of similarly isolated control cells (control population), irrespective of whether the diet was adequate or deficient in phenylalanine and tyrosine. Failure of the treated tumor cell population to exhibit reduced sensitivity to the combination chemotherapy or, unlike the control population, to exhibit variation in pigmentation levels, suggests that the restriction of phenylalanine and tyrosine during drug therapy alters the tumor response to reduce heterogeneity and perhaps interferes with the emergence of drug resistance.
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PMID:Interaction between specific dietary factors and experimental chemotherapy of metastatic melanoma. 369 64

The pharmacokinetics of melphalan (L-phenylalanine mustard) in isolated perfusion treatment of patients with melanoma in the limbs have been studied at standardized pseudo-physiological perfusion conditions. Perfused tissue volumes ranged from 2.1 to 16 liters as measured by water displacement. A fixed dose of 10 mg of the drug per liter of perfused tissue was applied. The resulting variation in total melphalan dosage gave rise to varying drug concentrations in the perfusate as the extracorporeal system was operated with a fixed volume of priming fluid. Perfusion with melphalan was applied for 60 min. Concentrations of intact drug were assayed by high-performance liquid chromatography. The melphalan concentrations vs. time for each patient were fitted to a biexponential equation using a nonlinear least-squares computer program. Mean half-lives of 4.7 +/- 0.3 and 53.0 +/- 1.6 min were obtained for the alpha and beta phase, respectively. The hybrid constant alpha remained virtually constant with increasing dose (i.e., increasing drug concentration) and beta also appeared independent of dose levels. With increasing tissue volume plasma clearance was found to diminish per unit of tissue volume. This phenomenon, and a levelling off of the steady-state distribution volume with increasing volume of perfused tissue, are discussed in terms of a possibly restricted transfer of drug from intravascular to the extracellular space and of the possibility of saturation of cellular uptake systems in the bulk of the limb tissues.
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PMID:Pharmacokinetics of melphalan in isolated perfusion of the limbs. 370 43

BRO human melanoma cells, which are exceptionally tumorigenic and lethal for nude mice, were inoculated intraperitoneally or intracerebrally in varying numbers. An inverse linear correlation was observed between the logarithm of the number of cells inoculated and host survival. In mice bearing 10(7) cells intraperitoneally, 2.4-2.8 log10 units of cell kill were obtained after a single intraperitoneal injection of vincristine, and some mice inoculated with 10(5) cells were cured by this treatment. Fewer cells were killed by L-phenylalanine mustard. Vincristine did not prolong survival of nude mice with intracerebral BRO tumors. Cell kill after administration of anticancer agents can be quantitated for BRO cells inoculated intraperitoneally or intracerebrally.
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PMID:Quantitative evaluation of anticancer agents against human melanoma cells implanted in nude mice. 374 66


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