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)

Cell-fibronectin interactions, mediated through several different receptors, have been implicated in a wide variety of cellular properties. Among the cell surface receptors for fibronectin, integrins are the best characterized, particularly the prototype alpha5beta1 integrin. Using [125I]iodine cell surface labeling or metabolic radiolabeling with sodium [35S]sulfate, we identified alpha5beta1 integrin as the only sulfated integrin among beta1 integrin heterodimers expressed by the human melanoma cell line Mel-85. This facultative sulfation was confirmed not only by immunoprecipitation reactions using specific monoclonal antibodies but also by fibronectin affinity chromatography, two-dimensional electrophoresis, and chemical reduction. The covalent nature of alpha5beta1 integrin sulfation was evidenced by its resistance to treatments with high ionic, chaotrophic, and denaturing agents such as 4 M NaCl, 4 M MgCl2, 8 M urea, and 6 M guanidine HCl. Based on deglycosylation procedures as chemical beta-elimination, proteinase K digestion, and susceptibility to glycosaminoglycan lyases (chondroitinase ABC and heparitinases I and II), it was demonstrated that the alpha5beta1 heterodimer and alpha5 and beta1 integrin subunits were proteoglycans. The importance of alpha5beta1 sulfation was strengthened by the finding that this molecule is also sulfated in MG-63 (human osteosarcoma) and HCT-8 (human colon adenocarcinoma) cells.
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PMID:Post-translational modifications of alpha5beta1 integrin by glycosaminoglycan chains. The alpha5beta1 integrin is a facultative proteoglycan. 913 4

Patients with primary ocular tumors are seen infrequently in the medical profession, and most of these patients are referred to specialty centers which has resulted in a good study population. In the past, ocular tumors were treated with enucleation, but the current emphasis is now on organ preservation with sparing of all or partial visual acuity. In the management of these tumors, plaque brachytherapy and particle beam therapy have been used more frequently as an alternative to enucleation. A multi-institutional study, the Collaborative Ocular Melanoma Study (COMS), is currently underway, organized by the National Eye Institute. The COMS isotope of choice is Iodine-125 (I-125). Recurrence after plaque therapy is approximately 15%, although it may be as high as 37% at 15 years for metastatic disease. In one study, nondiffuse iris melanoma has been controlled in 93% of patients by custom plaques utilizing I-125. Plaque brachytherapy also utilizes I-125 for the treatment of retinoblastoma tumors either as primary therapy or following external beam radiation. Currently, through the utilization of plaque radiation therapy, enucleation may be avoided in the majority of patients, and many patients may retrieve some visual acuity. We will review plaque brachytherapy techniques, diagnosis, staging, and some of the pertinent literature of the two most frequently encountered primary ocular tumors: choroidal melanoma, sometimes referred to as uveal melanoma, with an incidence of approximately 1,500 new cases per year in the adult population; and retinoblastoma, the most common intraocular primary malignancy found in childhood, with a frequency of approximately 250 [corrected] new cases per year.
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PMID:Brachytherapy in primary ocular tumors. 914 54

We report intravitreal invasion by melanoma cells from a choroidal melanoma after brachytherapy. A malignant melanoma of the choroid with collar-button configuration was treated with iodine 125 brachytherapy. Years later, the collar button developed a dark-chocolate color and began shedding pigmented debris into the vitreous. Coalescence of this debris into spheroidal aggregates suggested the presence of malignant cells; the eye was enucleated. Histologic sections demonstrated a choroidal melanoma with intraretinal and intravitreal invasion by melanoma. Clinical evidence of intraretinal invasion by melanoma cells along with pigmented debris within the vitreous cavity, especially when clustered in spheroidal aggregates, suggests the presence of intravitreal invasion by malignant cells. In this case, intravitreal invasion was verified histologically.
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PMID:Intravitreal invasion of malignant cells from choroidal melanoma after brachytherapy. 919 33

An analogue of human melanin-concentrating hormone (MCH) suitable for radioiodination was designed in which Tyr13 and Val19 of the natural peptide were replaced by phenylalanyl and tyrosyl residues: [Phe13, Tyr19]-MCH. The peptide was synthesized by the continuous-flow solid-phase methodology using Fmoc-strategy and polyhipe PA 500 and PEG-PS resins. The linear MCH peptides with either acetamidomethyl-protected or free cysteinyl residues were purified to homogeneity and cyclized by iodine oxidation, yielding the final product with the correct molecular weight of 2434.61. Radioiodination of the C-terminal tyrosine was carried out enzymatically using solid-phase bound glucose oxidase/lactoperoxidase, followed by purification on a reversed-phase mini-column and by high-pressure liquid chromatography. The resulting [125I]-[Phe13, Tyr19]-MCH tracer was the first radiolabelled MCH peptide suitable for radioreceptor assay: saturation binding analysis using mouse G4F-7 melanoma cells demonstrated the presence of 1090 MCH receptors per cell. The dissociation constant (KD) was 1.18 x 10(-10) M, indicating high-affinity MCH receptors on these cells. MCH receptors were also found in other cell lines such as mouse B16-F1 and G4F and human RE melanoma cells as well as in PC12 and COS-7 cells. Competition binding analyses with a number of other peptides such as alpha-MSH, neuropeptide Y, substance P and pituitary adenylate cyclase activating peptide, demonstrated that the binding to the MCH receptor is specific. Atrial natriuretic factor was found to be a weak competitor of MCH, indicating topological similarities between MCH and ANF when interacting with MCH receptors.
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PMID:Synthesis and iodination of human (phenylalanine 13, tyrosine 19) melanin-concentrating hormone for radioreceptor assay. 922 84

Radioiodinated methylene blue contains a mixture of components showing selective uptake in human pigmented melanoma, and it has potential for imaging and therapy. Nuclear magnetic resonance and mass spectroscopic studies show that the majority of the radioactivity (85%) is in the form of monoiodinated methylene blue, 4-iodo-3-methylamino-7-dimethylaminophenaza thionium chloride. The amino group ortho-to iodine has become demethylated to a mono-methylamino group. The remainder (15%) of the mixture is the doubly labelled 4,5-diiodo-3,7-bis(methylamino) phenazathionium chloride. The separated components show similar tumour selectivity in athymic mice bearing human pigmented melanomas.
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PMID:Radioiodinated methylene blue for melanoma targeting: chemical characterisation and tumour selectivity of labelled components. 925 28

It is proposed that the prerequisites for a low-risk to major cancers-breast, colon, lung, prostate, melanoma (as, for example in Africans, Chinese and Japanese) - include upregulated hypothalamic dopaminergic activity compared to depressed noradrenergic/thyrogenic function and raised vagal tone, and a neuroendocrine constellation that promotes improved immune efficiency and its inimical to the onset of aversive cell responses. Since the integrity of these tissues is regulated by hypothalamic-hypophyseal hormones, under tonic dopaminergic inhibition, cancers are potentially preventable as long as dopaminergic integrity is maintained, or the decline in ageing in slowed. Evidence for the impact of upregulated dopamine on tumour prevention includes: (1) a reduced (40%) rate of colonic cancer in exercised-trained ageing subjects; (2) reduced expected rates of lung/colon cancers, and skin tumours in prolonged post-menopausal oestrogen replacement; (3) the virtual suppression of all cancers during pregnancy (when dopamine synthesis increases); (4) the low rate of bronchogenic carcinoma correlates with reduced enzymatic conversion of dopamine to noradrenaline; and (5) neuroblastoma (specifically dopamine dysregulated tumour) regresses spontaneously on dopamine normalization. Similar tumour reduction is anticipated by controlling the intake of calories. The subtlety of the switch to upregulated dopamine, the speed of translation at the cellular level and the sustainability of responses as long as the initiating stimulus persists (as exposed by pregnancy), underline the plasticity of the neuroendocrine mechanism and ease of manipulation. Long exposure to environmental iodine deficiency, as seen for example in Africans and Chinese, reveals a crucial dopamine-thyroid action that slows cell timing mechanisms. The common neurohormonal basis identified for the prevention of human cancers has practical application, with reasonably assured positive results.
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PMID:Major human cancers are preventable: physiological stimuli induce a dopamine-thyroid-immune efficient mechanism. 930 74

It has been reported that metastatic melanoma cell lines selectively bind in vitro with the synthetic laminin pentapeptide tyrosyl-isoleucyl-glycyl-seryl-arginine (YIGSR). The aim of this study was to investigate whether the same peptide can bind on melanoma cells in vivo as well. Iodine-125-labeled YIGSR was administered to B16 melanoma-bearing animals. Microscopic autoradiography of tumor and organ sections taken 24 h after peptide administration showed that the peptide did accumulate on the surface of certain tumor cells. The peptide binding cells were frequent in metastatic sites and tumors grown for 24 days and rare in tumors grown for 10 days. A similarly radiolabeled control pentapeptide (peptide DRLKY) did not bind to any tumor cell. It is suggested that the YIGSR binding tumor cells may represent a distinct melanoma cell population with a high metastatic potential.
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PMID:In vivo binding of the radioiodinated peptide YIGSR on B16 melanoma cells. 937 Dec 32

We show that efficient permeabilization of murine melanoma can be obtained in vivo by applying electric pulses. More than 80% of the cell population is affected as shown by the penetration of propidium iodide. A protein, beta-galactosidase, can be transferred and expressed into the cells by incorporating either the protein or a plasmid carrying the reporter gene with respective efficiencies of 20% and 4%. This is obtained by a direct injection of either the protein or the plasmid in the tumor, followed by the application of electric pulses with surface electrodes in contact with the skin. This approach is simple and safe to use, reproducible, and specific; moreover, it is potentially applicable to a wide variety of tissues, cell types, and animals.
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PMID:In vivo electrically mediated protein and gene transfer in murine melanoma. 948 24

Analogs of a partial sequence peptide of laminin, i.e., Tyr-Ile-Gly-Ser-Arg (YIGSR) analogs and Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg (CDPGYIGSR) analogs, were prepared by the solid-phase method and their inhibitory effects on experimental metastasis of B16-BL6 melanoma cells were examined. YIGSR analogs in which Ile was replaced by other hydrophobic amino acids (Met, Leu, Phe) were inhibitory. Cys-containing analogs of YIGSR were also prepared, but were less active than the parent peptide, YIGSR. Among them, CYIGSR was easily oxidized to form a disulfide bond. A Cys-containing YIGSR analog cyclized through a disulfide bond, cyclo(CYIGSRC)G, was prepared. The disulfide bond formation was performed on the resin by the silyl chloride-sulfoxide method and by the iodine oxidation method. The yield of the silyl chloride-sulfoxide method was much better than that of the iodine oxidation method.
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PMID:Amino acids and peptides. XXXI. Preparation of analogs of the laminin-related peptide YIGSR and their inhibitory effect on experimental metastasis. 950 69

Extrapolation to humans from experimental radioimmunotherapy in nude mouse xenograft models is confounded by large relative tumour size and small volume of distribution in mice allowing tumour uptake of radiolabelled antibodies unattainable in patients. Our large animal model of human tumours in cyclosporin-immunosuppressed sheep demonstrated tumour uptake of targeted radiolabelled monoclonal antibodies comparable with uptakes reported in clinical trials. Sheep immunosuppression with daily intravenous cyclosporin augmented by oral ketoconazole maintained trough blood levels of cyclosporin within the range 1000-1500 ng ml(-1). Human tumour cells were transplanted orthotopically by inoculation of 10(7) cells: SKMEL melanoma subcutaneously; LS174T and HT29 colon carcinoma into bowel, peritoneum and liver; and JAM ovarian carcinoma into ovary and peritoneum. Tumour xenografts grew at all sites within 3 weeks of inoculation, preserving characteristic morphology without evidence of necrosis or host rejection. Lymphatic metastasis was demonstrated in regional nodes draining xenografts of melanoma and ovarian carcinoma. Colonic LS1 74T xenografts produced mucin and carcinoembryonic antigen (CEA). The anti-CEA IgG1 monoclonal antibody A5B7 was radiolabelled with iodine-131 and administered intravenously to sheep. Peak uptake at 5 days in orthotopic human tumour transplants in gut was 0.027% DI g(-1) (percentage of injected dose per gram) and 0.034% DI g(-1) in hepatic metastases with tumour to blood ratios of 2-2.5. Non-specific tumour uptake in melanoma was 0.003% DI g(-1). Uptake of radiolabelled monoclonal antibody in human tumours in our large animal model is comparable with that observed in patients and may be more realistic than nude mice xenografts for prediction of clinical efficacy of radioimmunotherapy.
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PMID:Orthotopic xenografts of human melanoma and colonic and ovarian carcinoma in sheep to evaluate radioimmunotherapy. 971 32


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