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 carbohydrate moieties present on laminin play a crucial role in the multiple biological activities of this basement membrane glycoprotein. We report the identification of a human laminin binding protein with an apparent molecular mass of 14 kDa on sodium dodecyl sulfate-polyacrylamide gels that was found, after purification and amino acid microsequencing, to be identical to the previously described 14-kDa galactoside binding soluble L-14 lectin. We have designated this human laminin binding protein as HLBP14. HLBP14 was purified from human melanoma cells in culture by laminin affinity chromatography and gel electroelution. We demonstrate that HLBP14 binds specifically to the poly-N-acetyllactosamine residues of murine laminin and does not bind to other glycoproteins that do not contain such structures, such as fibronectin. HLBP14 was eluted from a murine laminin column by lactose, N-acetyllactosamine, and galactose but not by other control saccharides, including glucose, fucose, mannose, and melibiose. It did not bind to laminin treated with endo-beta-galactosidase. Lactose also eluted HLBP14 off a human laminin affinity column, implying that human laminin also contains poly-N-acetyllactosamine residues. On immunoblots, polyclonal antibodies raised against HLBP14 recognized HLBP14 as well as 31- and 67-kDa molecules that are also laminin binding proteins, indicating that these proteins share common epitopes. L-14, a dimeric lactose binding lectin, is expressed in a wide variety of tissues. Although the expression of this molecule has been linked to a variety of biological events, the elucidation of its specific functions has been elusive. The observation that HLBP14, a human cancer cell laminin binding protein, is identical to L-14 strongly suggests that the functions attributed to this lectin could be mediated, at least in part, through its ability to interact with the poly-N-acetyllactosamine residues of laminin. HLBP14 could potentially play a role during tumor invasion and metastasis by modulating the interactions between cancer cells and laminin.
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PMID:Identification of a 14-kDa laminin binding protein (HLBP14) in human melanoma cells that is identical to the 14-kDa galactoside binding lectin. 138 13

Life-style has a major influence on the incidence of breast cancer. To evaluate the effects of life-style related metabolic-endocrine factors on breast cancer risk we conducted a case-control study comparing 223 women aged 38 to 75 years presenting with operable (stage I or II) breast cancer and 441 women of the same age having no breast cancer, who participated in a population-based breast cancer screening program. Women reporting diabetes mellitus were excluded. Sera from 110 women of the same age group presenting with early stage melanoma, lymphoma or cervical cancer were used as a second 'other-cancer control group'. Serum levels of C-peptide were significantly higher in early breast cancer cases compared to controls. The same was found for the ratios C-peptide to glucose or C-peptide to fructosamine, indicating insulin resistance. Sex hormone binding globulin was inversely, triglycerides and available estradiol were positively related to C-peptide. Serum C-peptide levels were related to body mass index (BMI), and to waist/hip ratio (WHR), in particular in controls. However, the relative increase of C-peptide, C-peptide to glucose or C-peptide to fructosamine in cases was independent of BMI or WHR. The log relative risk was linearly related to the log C-peptide levels. Relative risk according to quintiles, and adjusted for age, family history, BMI and WHR, for women at the 80% level was 2.9 as compared with those at the 20% level for C-peptide. Elevated C-peptide or C-peptide to fructosamine values were not observed in the sera from women belonging to the 'other-cancer control group'. This study suggests that hyperinsulinemia with insulin resistance is a significant risk factor for breast cancer independent of general adiposity or body fat distribution.
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PMID:Insulin resistance and breast-cancer risk. 139 28

In order to investigate the metastatic potential of tumors in vivo by measuring hyaluronic acid metabolism, C57BL/6 mice with B16 melanoma variants and C3H/He mice with FM3A tumor variants were evaluated using N-[18F]fluoroacetyl-D-glucosamine (18F-GlcNFAc). The uptake of 18F-GlcNFAc was slightly higher (P less than 0.05) in B16-F10 tumors (high metastatic potential) than in B16-F1 (low metastatic potential). Analysis of metabolites showed that acid-insoluble fraction was the largest one in the liver by 60 min, whereas in the tumors, phosphates fraction was the major metabolite. Slower metabolism in tumors was suggested, and it may be one of the reasons for the difficulty of detecting the characteristics of their hyaluronic acid synthesis. 18F-GlcNFAc uptake by FM3A variants showed no significant correlation with their metastatic potential. In addition, N-acetyl-D-[1-14C]glucosamine, 2-deoxy-D-[1-14C]glucose and [6-3H]thymidine failed to demonstrate any difference between tumors' metastatic variants in vivo.
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PMID:Investigation of tumor metastatic potential with N-[18F]fluoroacetyl-D-glucosamine. 139 95

The dependence of constitutively expressed tyrosinase (dopa oxidase) activity on glycosylation in lightly pigmented human melanoma cells (MM96E) was determined using tunicamycin (TM), which prevents transfer of oligosaccharide chains to nascent protein (core glycosylation), the glucosidase inhibitors castanospermine (CS) and deoxynojirimycin (dNM), and the mannosidase inhibitors deoxymannojirimycin (dMM) and swainsonine (SW). TM caused irreversible inhibition of tyrosinase activity and carbohydrate synthesis as judged by incorporation of 3H-fucose. Tyrosinase in CS- and dNM-treated cells showed 50% loss of activity within 5 h but recovered rapidly when the drugs were removed; dMN and SW had little effect. Expression of the tyrosinase 2B7 epitope and of an 80-kDa melanosomal antigen (B8G3) was inhibited by TM but not by CS, dNM, dMM, or SW. CS and dNM appeared to decrease the half-life of active tyrosinase. Overall, these results indicate that 1) in addition to the requirement for core glycosylation the removal of glucose residues plays a critical role in the formation of active human tyrosinase; 2) glucosidase inhibitors appear to cause an accumulation of inactive tyrosinase and increase the degradation rate of active enzyme; and 3) later stages in oligosaccharide processing are not required for maintaining tyrosinase activity.
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PMID:Rapid and reversible inhibition of tyrosinase activity by glucosidase inhibitors in human melanoma cells. 153 83

The short proton relaxation times in the MR images of malignant melanomas make them different from most other tumors. We have previously shown that the T1 and T2 signals may be significantly influenced when the water distribution of the tumor is changed in vivo and in vitro. In the present work T1 and T2 were estimated and compared with the electron microscopy picture in subcutaneously implanted B16 melanomas in mice. Two hours after the mice were given an i.p. injection of 0.9% NaCl containing 10% glucose and 10% fructose (9 mice) both the T2 components were markedly and the T1 slightly prolonged. At the same time the electron microscopy picture displayed swelling of the melanocytes together with a marked decrease in number and size of their mitochondriae. There were no changes in the MR image or the melanocyte structure in control mice injected with 0.9% NaCl (9 mice) or 0.9% NaCl containing 10% fructose. It is concluded that the changed MR image may be coupled to the metabolism in melanoma.
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PMID:Concomitant changes in MR image and morphology induced by glucose and fructose in B16 mouse melanomas. 159 Nov 32

The potential of 4-borono-2-[18F]fluoro-D,L-phenylalanine ([18F]FBPA), a flurodinated derivative of a target compound for boron neutron capture therapy, for melanoma imaging by positron emission tomography (PET) was studied using animal models. A high uptake of [18F]FBPA was found in murine B16 melanoma or in Greene's melanoma No. 179, a melanotic cell line in hamsters, for the first 6 h after injection. Whole body autoradiography using [18F]FBPA gave a clear image of the B16 tumor. The acid-insoluble 18F in the B16 increased to 27% by 6 h, and most of the free 18F was detected as [18F]FBPA in both B16 and plasma. In the hamster models, No. 179 showed a 1.7 times higher uptake than amelanotic Greene's melanoma No. 178 at 6 h post-injection, although both melanomas indicated similar metabolic activities when examined by a tracer uptake study using L-[14C]methionine, 2-deoxy-D-[14C]glucose and [3H]thymidine. [18F]FBPA may be a very promising PET tracer for melanoma imaging.
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PMID:4-Borono-2-[18F]fluoro-D,L-phenylalanine: a possible tracer for melanoma diagnosis with PET. 162 21

The authors report four patients whose initial symptom of tumor recurrence or progression was unilateral numbness of the chin. Two patients had Hodgkin lymphoma, one had malignant melanoma, and one had prostate cancer. Physical examination was notable only for unilateral anesthesia of the chin and lower lip. Diagnostic evaluation, including computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain, plain radiographs of the mandible, and cerebrospinal fluid analysis for protein, glucose, and cytology were normal. Bone scans revealed osseous lesions in the axial skeleton of all patients, whereas only two patients had abnormal uptake in the mandible. The authors conclude that in the setting of a negative evaluation for central nervous system (CNS) or local mandibular disease, mental neuropathy is associated with recurrent or progressive skeletal disease. In addition, to document relapsed or progressive cancer, the skeletal system may have to be examined at sites distant from the mandible.
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PMID:Mental neuropathy (numb chin syndrome). A harbinger of tumor progression or relapse. 843 71

The results of examination of 120 patients with advanced malignant melanoma, soft tissue sarcomas and lung and renal cancer suggest disturbance in mechanisms of energy supply during whole-body guided hyperthermia. Cell glucose uptake was inhibited in hyperglycemic patients. High energy loss in due to utilization of such alternative substrates as lipids and proteins which, in turn, potentiates peroxidation of lipids toxic to cell membranes. These data provide biochemical rationale for developing procedures aimed at managing biochemical dysbalance, increase in carbohydrate utilization included.
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PMID:[The effect of whole-body controlled hyperthermia on the energy resources of cancer patients]. 166 96

To evaluate the usefulness of structural and biochemical imaging techniques for the diagnosis of uveal melanoma, 12 patients with choroidal melanoma were examined. Magnetic resonance imaging was used in 11 of 12 patients, as one had a metal prosthesis. All the subjects underwent single photon planar scintigraphy (SPPS) and single photon emission computed tomography (SPECT) using the 99mTc-labeled F(ab')2 of the anti-melanoma monoclonal antibody 225.28S ([99mTc]MoAb) and positron emission tomography (PET) using [18F]fluorodeoxyglucose ([18F]FDG). Magnetic resonance identified 6 of 11 melanotic lesions (definite melanomas) and 4 of 11 hypomelanotic lesions (probable melanomas), whereas in one case it was inconclusive. [99mTc]MoAb uptake was observed in 5 of 12 lesions using SPPS and 8 of 12 lesions using SPECT. [18F]FDG uptake was observed in 3 of 12 lesions by PET. These results demonstrate that both MR and radioimmunoscintigraphy are sensitive techniques for the diagnosis of choroidal melanomas and suggest that the detection of melanomas by MR, SPPS, and SPECT is largely dependent upon their size. The validity of these conclusions was verified in four subjects in whom the diagnosis was based on MR and/or SPECT findings only and confirmed by histology. The finding that only some of the uveal melanomas of larger size are visualized based on [18F]FDG uptake suggests that melanomas can have either high or low glucose consumption.
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PMID:MRI, antibody-guided scintigraphy, and glucose metabolism in uveal melanoma. 172 12

Athymic BALB/c nude mice, bearing a human melanoma LOX, were given the photosensitizing drug Photofrin II (10 mg/kg body wt.) intraperitoneally. The mice were also given one of the following chemicals intraperitoneally: glucose, galactose and glucose plus nordihydroguaiaretic acid (NDGA) which is an inhibitor of glycolysis. Multiple injections of glucose (3 g/kg body wt. given at -1, 0, +1 and +3 h relative to the injection of 10 mg/kg of Photofrin II at time 0) resulted in a significant increase in the uptake of Photofrin II in the tumor 4 h after a Photofrin II injection, while the uptake of Photofrin II in the other tissues remained unchanged. Administration of galactose had no significant effect on the uptake of Photofrin II in the tissues studied (tumor, muscle, skin and liver). NDGA seemed to abolish the effect of glucose injection.
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PMID:The effect of glucose administration on the uptake of photofrin II in a human tumor xenograft. 182 12


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