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)

During the period 1965-1976, 158 patients with stage I malignant melanoma of the extremities were treated by regional isolated perfusion with L-phenylalanine mustard (Melphalan) and local excision. In order to study local recurrence and survival, only patients with a primary melanoma Clark level IV or V and a tumor thickness of more than 1.5 mm were accepted in this study. The determinate survival in patients followed for 5-16 years is 74%; 20% developed positive regional lymph nodes. The local skin recurrence rate was 9% (14 patients); nine of these 14 patients simultaneously had distant metastases; the other five patients are alive with NED after retreatment. So far, this series of patients has shown no statistically significant difference in local recurrence after normothermic and hyperthermic perfusion: 2/19 (11%) and 12/132 (9%), respectively. However, mean tumor thickness in the patients treated by hyperthermic perfusion proved to exceed that in the normothermically perfused patients.
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PMID:[Regional perfusion treatment in primary malignant melanomas of the extremities. (Microstage IV/V according to Clark and tumor thickness over 1.5 mm)]. 717 25

During the period 1965-1974, 110 patients with stage I malignant melanoma of the extremities were treated by regional isolated perfusion with L-phenylalanine mustard and local excision. In order to study local recurrence and survival, only patients with a primary melanoma Clark Level IV or V and a tumor thickness of more than 1.5 mm were accepted in this study. The determinate survival in patients followed for 5-14 years in 78%; 17% developed positive regional lymph nodes. The local skin recurrence rate was 9% (9 patients); four of these 9 patients simultaneously had distant metastases; the other five patients are alive with NED after retreatment. This series of patients, too, shows that tumor thickness determines the prognosis, both as to local recurrence and as to survival. The mean tumor thickness in the hyperthermically perfused patients was found to clearly exceed that in the normothermically perfused, the mean values being 4.85 mm and 3.87 mm, respectively. Yet local recurrence and regional lymph node metastases proved to be less frequent after hyperthermic than after normothermic perfusion, although the difference was not statistically significant.
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PMID:Local recurrence and survival in patients with (Clark Level IV/V and over 1.5-mm thickness) stage I malignant melanoma of the extremities after regional perfusion. 729 6

A rare case of primary melanoma of the cervix is reported. The patient presented with vaginal bleeding and was thought to have a degenerated cervical fibroid. A radical hysterectomy with pelvic node dissection was performed and followed postoperatively with chemotherapy (phenylalanine mustard). The patient died within one year with widespread metastases.A brief review of the literature showed only seven cases of primary cervical melanoma. Prognosis is generally unfavorable regardless of treatment modality.
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PMID:Primary melanoma of the cervix: report of a case. 732 90

The antitumor effect of some N alpha-benzyloxycarbonyl-N,N-bis-(2-halogenethyl)hydrazide derivatives of lysine, glycine, cystine, phenylalanine and p-chlorophenylalanine, was studied. Six of eight newly synthesized compounds show considerable antitumor effect on solid Walker carcinosarcoma 256 (about 95% tumor growth inhibition). Three of these compounds under study increased the lifespan of mice with leukemia L1210. The investigation of the effect of N alpha-benzyloxycarbonyl,D,L-phenylalanine-N,N-bis(2-chloroethyl)hydrazine on various mouse tumors showed remarkable growth inhibition of the Ehrlich ascites carcinoma, sarcoma 37, colon adenocarcinoma akatol and lesser antitumor effect also on solid adenocarcinoma 755, Lewis lung carcinoma and melanoma B16. All investigated compounds exhibited depression of leukocyte count--their toxicity being, however, lower than that of sarcolysine in parallel experiments.
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PMID:Antitumor effect of N alpha-benzyloxycarbonyl-N,N-bis-(2-halogenethyl)-hydrazide derivatives of amino acids. 739 53

Seventy patients with invasive malignant melanoma confined to one limb were treated by isolated perfusion with 1-phenylalanine-dihydrochloride (melphalan) and regional lymphadenectomy between 1959 and 1979. Five patients were perfused twice. This treatment did not modify the results of appropriate local excision in early melanoma. Twenty-one patients with stage I disease have had 76 per cent 5-year survival. Forty-eight per cent of 29 patients with extensive local recurrent tumour showed marked tumour regression. Nine of these had subsequent local recurrence with a mean remission of 7 months. Survival in those who responded was 2 years longer than in those who did not. In 6 patients with slight local recurrence, and 19 patients with regional node metastases, response could not be assessed directly. Their 5-year survival was 52 per cent. There have been no deaths as a result of the procedure and no amputations. Mean postoperative hospital stay was 25 days. We conclude that this technique has a useful place in the palliation of extensive local recurrent melanoma.
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PMID:Isolated limb perfusion with melphalan in the treatment of malignant melanoma. 742 69

The influence of the radiosensitizer misonidazole on the effectiveness of several alkylating agents and cis-platinum against advanced solid murine tumors was investigated. Tumor regrowth delay, frequency of tumor regressions, and animal life span were used to evaluate misonidazole in combination with cyclophosphamide, L-phenylalanine mustard, 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea, aziridinyl-benzoquinone, and cis-platinum. In the advanced M5076 ovarian carcinoma, misonidazole enhanced the activity of cyclophosphamide, L-phenylalanine mustard, 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea, and aziridinyl benzoquinone, but not cis-platinum. In early B16 melanoma, misonidazole plus cyclophosphamide was no more effective than cyclophosphamide alone. In advanced Lewis lung carcinoma, misonidazole enhanced the antitumor activity of cyclophosphamide but not 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea. Misonidazole, at 1000 mg/kg, increased the antitumor effectiveness of L-phenylalanine mustard and cyclophosphamide in M5076 tumors by factors of 2.2 and 1.8, but caused only a 1.2- and 1.3-fold increase in the myelotoxicity of these agents as determined by spleen colony assay of normal bone marrow. Misonidazole also increased the toxicity of cyclophosphamide and L-phenylalanine mustard in non-tumor-bearing mice but to a lesser degree than it enhanced antitumor activity. These results indicate that misonidazole is capable of enhancing the effects not only of ionizing radiation but of alkylating agents as well.
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PMID:Enhancement of antitumor activity of alkylating agents by the radiation sensitizer misonidazole. 747 Oct 58

The aromatic fatty acid phenylacetate, a common metabolite of phenylalanine, shows promise as a relatively non-toxic drug for cancer treatment. This slowly metabolized fatty acid alters tumor cell lipid metabolism causing, among other effects, inhibition of protein prenylation critical to malignant growth. In pursuit of more potent analogues, we have examined the activity of related compounds against tumor cell lines established from patients with advanced prostatic carcinoma, glioblastomas, and malignant melanoma. Like phenylacetate, derivatives containing alpha-carbon or ring substitutions induced cytostasis and phenotypic reversion at non-toxic concentrations. Potency was correlated with the degree of calculated lipophilicity of the aromatic fatty acid, and the extent of inhibition of protein prenylation. Remarkably, a parallel cytostatic activity was reported in embryonic plant cells, which respond to phenylacetate and its analogues in the same concentration range and the same rank order of lipophilicity. These data suggest that phenylacetate and its analogues may act through common mechanisms to inhibit the growth of vastly divergent, undifferentiated cell types, and provide a basis for the development of new agents for the treatment of human malignancies.
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PMID:Cytostatic activity of phenylacetate and derivatives against tumor cells. Correlation with lipophilicity and inhibition of protein prenylation. 748 44

We have shown that Tyr and Phe restriction suppresses the malignant phenotype of the highly invasive and metastatic BL6 variant of B16 murine melanoma. Lung-colonizing abilities of Tyr- and Phe-modulated in vivo and in vitro variants of BL6 are inhibited following intravenous inoculation into mice fed normal diet. Although this antimetastatic effect of Tyr and Phe restriction is most likely not due to differences in attachment to endothelium, our data indicate that major impacts of Tyr and Phe restriction are at the level of the tumor, itself. Modulation of host immune responses, which in turn suppresses metastasis, does not appear to contribute significantly to the altered phenotype. Although numbers and function of T cells, mast cells, and NK cells are affected by Tyr and Phe restriction, they are not involved in the Tyr- and Phe-mediated suppression of tumor growth, metastasis, or angiogenesis. Our data do not rule out the importance of other host factors involved in the Tyr and Phe modulation of tumor phenotype. The outcome of this modulation results most likely from complex Tyr/Phe-tumor-host interactions.
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PMID:Evidence for nutrient modulation of tumor phenotype: impact of tyrosine and phenylalanine restriction. 752 Jun 63

A human B lymphoblastoid cell line JWCI-L94 secretes an IgM human monoclonal antibody (HuMAb) that reacts with human melanoma cell lines, M14 and M12. To identify the antigenic epitope of this antibody, we screened lambda gt11 expression libraries constructed from M14 and M12. A total of 12 immunoreactive clones were isolated, and their DNA sequences were determined. The only sequence shared by all these clones was alanine-proline (A-P) at the carboxyl (C) terminal. HuMAb L94 reacted not only with C-terminal A-P-containing fusion proteins, but also with the synthetic dipeptide A-P. None of the peptides containing A-P internally or amino terminally reacted to HuMAb L94. Proline or alanine alone had no ability to bind to HuMAb L94. When alanine was replaced by glycine (G-P) or proline (P-P), the binding activity of these peptides was similar to that of A-P. On the other hand, when alanine was replaced by serine, valine, leucine, glutamine, lysine, methionine, phenylalanine, or hydroxyl proline, the resulting peptide completely lost the antigenic activity of HuMAb L94. These results demonstrate that HuMAb L94 recognizes C-terminal A-P, G-P, or P-P, and that a human antibody can recognize peptides as small as a two-amino acid residue.
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PMID:Peptides with carboxyl-terminal sequence of alanine-proline: detection by a human monoclonal antibody. 753 1

The influence of single amino acid replacements by alanine on the binding affinity and biological activity of alpha-MSH in B16 murine melanoma cells has been studied systematically. alpha-MSH analogues were synthesized by solid-phase peptide synthesis and their binding affinities to the melanocortin receptor expressed by B16 mouse melanoma cells were determined using a radioreceptor assay. Biological activity of the analogues was determined by measuring tyrosinase stimulation. Relative activity and affinity data were generally in agreement with earlier results using terminal deletion fragments of alpha-MSH, but the alanine scan revealed important new insights into the role of individual residues. The three terminal amino acids at either end were not necessary for binding or activity, with amino acids 4-9 forming a core sequence required for receptor binding and triggering of the biological response. It was observed that replacement of the glutamic acid residue in position 5 was possible without loss of affinity or activity, whereas replacement of Met4 resulted in a 100-fold loss of binding affinity and biological activity. Each residue within the conserved melanocortin sequence His-Phe-Arg-Trp was shown to be essential with Phe7, Arg8, and Trp9 being the most sensitive to replacement by alanine. Generally, there was a rank correlation between binding affinity and tyrosinase stimulation within the group of analogues studied. Tyrosinase activity was less affected by alanine substitution than binding affinity, which suggests that full receptor binding is not required for maximum biological response.
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PMID:Synthesis and biological evaluation of alpha-MSH analogues substituted with alanine. 785 84


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