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)

Two major classes of protein, i.e., structural matrix and enzymic, exist in the melanosome. In normal melanocytes, synthesis of these two components is under a strict genetic control with regulatory steps associated with transcription and translation coded with appropriate pigment genes. In abnormal neoplastic melanocytes, they become markedly aberrant. The aberrant melanogenesis can be typically manifested by an abnormality in fine structure of the melanosome. The fine structural heterogeneity of the melanosome can often be diagnostic to certain forms of malignant melanoma and dysplastic melanocytic nevus. This study brings about the importance of the structural matrix protein for the expression of fine structural heterogeneity in the melanosome by developing the 2 monoclonal antibodies, MoAb HMSA-1 and HMSA-2. The 2 MoAbs recognized the cytoplasmic antigen on paraffin embedded sections, which under immunoelectron microscopy and cell fractionation studies, were found to be localization the melanosome and smooth ER, but not Golgi complex and coated vesicles as seen in the tyrosinase studies. It is indicated (a) that the sites of the synthesis for the melanosomal protein and tyrosinase are different, (b) that the melanosomal structural protein is accumulated in the dilated vacuole of smooth ER from which the stage I melanosome is synthesized, (c) that the synthesis of melanosomal protein becomes markedly aberrant and directly reflects the abnormal fine structure of the melanosome and (d) the heterogeneity in synthesis of melanosomal protein as expressed by MoAb HMSA-1 and HMSA-2 is a useful adjunct for immunohistopathological differentiation of malignant melanoma cells from benign nevoid cells and normal melanocytes.
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PMID:Nature and biosynthesis of structural matrix protein in melanosomes: melanosomal structural protein as differentiation antigen for neoplastic melanocytes. 336 88

A mouse-mouse monoclonal antibody, MoAb HMSA-2, was raised against the melanosomal protein of human malignant melanoma. To characterize the nature of dysplastic melanocytic nevi (DMN), we examined the reactivity of DMN with MoAb HMSA-2 in comparison to that of superficial spreading melanoma (SSM) and common melanocytic nevi (CMN) including junctional melanocytic nevi (JMN) on routine paraffin sections. MoAb HMSA-2 showed several unique immunohistochemical findings: a) MoAb HMSA-2 reacted with melanocytes of DMN in both the epidermis and the dermis, including the pigment granules in the keratinocytes; b) the pigment granules in the keratinocytes of DMN were found to be immature melanosomes transferred from dysplastic melanocytes to keratinocytes; c) the reactivity of epidermal melanocytes in DMN and SSM was stronger than that of junctional component in CMN, though SSM revealed a much stronger reaction than DMN; and d) keratinocytes, especially in a "shoulder" lesion of DMN which was associated with dermal lymphocytic infiltrates, often showed a strong reactivity with MoAb HMSA-2. Thus our study suggested a unique immunohistochemical feature of DMN with deranged melanogenesis as indicated by the reactivity with MoAb HMSA-2.
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PMID:Positive reactivity of dysplastic melanocytes with a monoclonal antibody against melanoma melanosomes, MoAb HMSA-2. 341 Nov 43

Some coat-color loci in mice are considered to control melanosome formation. In order to investigate genetic control of melanosome-associated proteins, we prepared monoclonal antibodies against mouse melanosomes. Melanosomes were isolated from B16 mouse melanoma through differential fractionation. BALB/c mice were immunized with an SDS-solubilized melanosome fraction. The spleen cells were subsequently fused with mouse myeloma cells, the resulting hybridomas cloned. Their secreted IgG was screened for reactivity to the SDS-solubilized melanosome fraction. One monoclonal antibody, M10, was shown to react to melanosomes by immunoelectronmicroscopy. It recognized a single protein band of 61,000 dalton on immunoblots of gel-fractionated melanosomes. The reactivities of M10 to skin homogenates from various coat-color mutants were examined by the ELISA method. Five congenic genotypes, non-agouti (a/a), brown (b/b), albino (c/c), dilute (d/d), and pink-eyed dilution (p/p) were examined. Among these, b/b and p/p showed significantly lower reactivities than a/a. Our results seem to suggest that the pigment abnormalities in these mutants result from abnormalities of the melanosomal proteins. In the case of albino mice, the reactivity of M10 to skin homogenate was almost the same as the wild-type mouse. It seems that the albino mice are capable of producing the melanosomal protein.
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PMID:Deficient melanosome formation in some coat-color mutant mice revealed by a monoclonal antibody against melanosome. 350 65

To characterize the biological property unique to melanocytes and to utilize this property to establish laboratory diagnostic tools for malignant melanoma, monoclonal antibody (MoAb) human melanosome-associated antigen-1 (HMSA-1), a mouse monoclonal antibody, was developed against purified melanosomal fractions of human melanoma. MoAb HMSA-1 belongs to an IgG1 (kappa) subclass. Fractionation of cell organelles combined with enzyme linked immunosorbent assay analysis indicated that the antigen(s) reactive with MoAb HMSA-1 is localized in melanosome and endoplasmic reticulum fractions and that it is related to melanosomal protein and its precursor forms. The localization of the antigen in the melanosome and endoplasmic reticulum was also confirmed by immunoelectron microscopy. Characteristically, MoAb HMSA-1 reacted with formalin-fixed and paraffin-processed tissues of melanocytic nevi and malignant melanoma, including amelanotic lesions. It did not react with normal melanocytes, normal tissues and organs from fetuses and adults, or most non-melanocytic tumors. Thus MoAb HMSA-1 identifies the differentiation antigen for the melanosome-associated property in neoplastic melanocytes and is a useful adjunct for immunohistological diagnosis of melanocytic lesions on routine paraffin sections.
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PMID:Development and characterization of a mouse monoclonal antibody, MoAb HMSA-1, against a melanosomal fraction of human malignant melanoma. 351 87

Pigmentation-associated antigen (PAA) or gp75 is a glycoprotein localized to the melanosomes of human melanomas and melanocytes to which a mouse monoclonal antibody (AbTA99) has been produced (T. M. Thomson et al. (1985) J. Invest. Dermatol. 85, 169). Treatment of 3H-labeled immunoprecipitated melanoma PAA with alkaline-borohydride, hydrazinolysis, or N-glycanase released three families of carbohydrate chains (I, II, and III). Peak I consists of a major component (Ia) of sialylated triantennary N-linked chains which are partially substituted with fucose on terminal positions as well as on the chitobiose core and a minor component (Ib) which is a sialylated biantennary N-linked species. Peak II was not well characterized but may be a monoantennary complex chain species. Peak III consists of typical N-linked high mannose units with six to seven mannose residues. Melanocyte PAA carbohydrate chains have the same general features as melanoma PAA except that the biantennary complex chain predominates; this difference resembles that observed between the cell surface glycopeptides of transformed animal cells and their nontransformed counterparts. The glycosylation characteristics of this melanosomal glycoprotein are compared with those of glycoproteins from endoplasmic reticulum, Golgi, and lysosomes, and with tyrosinase. It is suggested that the glycosylation pattern is a reflection of the biosynthetic origin and cellular destination of a particular organelle and its constituents.
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PMID:Glycosylation characteristics of pigmentation-associated antigen (GP75): an intracellular glycoprotein of human melanocytes and malignant melanomas. 353 23

To elucidate the nature of melanosomal protein in normal and malignant melanocytes, two mouse monoclonal antibodies (MoAbs), designated MoAb HMSA-3 and MoAb HMSA-4, were developed by the solubilized melanosomes of human malignant melanoma. The specificity of the two MoAbs was characterized immunohistochemically by comparison with that of MoAb HMSA-2 in various forms of melanoma tissues. MoAb HMSA-3 and MoAb HMSA-4 were IgM, k subclass while MoAb HMSA-2 was IgG1, k subclass. The three MoAbs possessed many similarities; (a) positive reactivity in formalin-fixed and paraffin-processed specimens, (b) identification of cytoplasmic antigen(s) in melanoma cells, (c) negative reactivity with normal epidermal melanocytes on paraffin-sections, and (d) intense reaction with amelanotic melanoma cells, particularly in superficial spreading and acral lentiginous melanoma and in metastatic lymph nodes. The three MoAbs, however, identified the different cells on the same serial sections, suggesting that the three may recognize the different epitopes. Thus in 32 cases of primary and metastatic melanomas examined, one of the three MoAbs always showed a positive reactivity, though the other two were negatively or weakly reacted. Our study indicated that the melanosomal protein may provide a unique source to develop MoAbs which identify malignant melanocytes on routine paraffin sections.
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PMID:Development of MoAb HMSA-3 and HMSA-4 against human melanoma melanosomes and their reactivities on formalin-fixed melanoma tissues. 368 Sep 82

Pigmented melanoma cells and cultured melanocytes express a differentiation-related glycoprotein designated as pigmentation-associated antigen (PAA) of Mr 70,000-80,000. As described previously, PAA was initially defined by reactivity with antibodies in the serum of a patient with melanoma. Here we describe the production and characterization of a mouse monoclonal antibody to PAA. This antibody (TA99, an IgG2a) was shown by sequential immunoprecipitation experiments to react with the same component as the human antibody. Ab TA99 immunoprecipitated PAA from lysates of cells radiolabeled with [35S]methionine, [3H]glucosamine, [3H]fucose, and [3H]mannose as well as 125I. Using Ab TA99, the distribution of PAA was examined in frozen sections of 19 normal tissues and quantitatively in 68 tissue culture cell lines. In frozen sections, only melanin-containing cells were positive, including epithelial cells in the basal layer of the epidermis, in which pigment originates from melanocytes by transfer of melanosomes, and pigmented cells of the eye. In tissue culture cell lines, only pigmented melanoma cells were positive. PAA is an intracellular antigen, with a distribution very similar to that of melanosomes. This evidence confirms the close association of PAA with melanin production, and suggests that PAA may be a melanosome component. PAA was shown to be different from tyrosinase, the enzyme involved in melanin synthesis, but it was found to be identical to the previously recognized glycoprotein, gp75, characteristic of pigmented melanomas and melanocytes.
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PMID:Pigmentation-associated glycoprotein of human melanomas and melanocytes: definition with a mouse monoclonal antibody. 392 6

Monoclonal antibodies (mAb) were selected for differential binding to sections of freshly frozen biopsy material of human malignant melanomas and their precursor lesions, the melanocytic nevi. Both melanomas and normal nevi expressed human Ia-like antigens, transferrin receptor and the transferrin-related molecule p97. In contrast, only 1 nevus of 21 tested expressed both glycoprotein gp75, defined by mAb 15.75, and protein p89, defined by mAb P3.58, whereas 12 of 15 melanomas tested expressed both antigens. mAb P3.58 reacted with one additional melanoma and one nevus. The expression of these two molecules therefore appears to be correlated with the appearance of the malignant phenotype of melanocytes.
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PMID:In situ analysis of antigens on malignant and benign cells of the melanocyte lineage. Differential expression of two surface molecules, gp75 and p89. 397 33

There is no available monoclonal antibody which reacts specifically recognizes human tyrosinase. Employing a synthetic peptide, MEKEDYHSLYQSHL, corresponding to the carboxyl terminus of human tyrosinase as an immunogen, we produced a mouse monoclonal antibody MAT-1 of the IgG1 isotype. The epitope for MAT-1 was determined to be EDYH, the sequence of which is not present in human tyrosinase-related protein-1 (TRP-1) or tyrosinase-related protein-2 (TRP-2). By transient expression assays and immunofluorescence technique, we show that MAT-1 reacts specifically with cells expressing human tyrosinase cDNA but not with cells expressing TRP-1 or TRP-2 cDNA. The results of immunohistochemical staining also confirmed that MAT-1 reacts specifically with epidermal melanocytes in human skin sections. MAT-1 should be invaluable for studying the interaction between tyrosinase and TRPs and for detecting the changes in the levels of tyrosinase expression. In addition, MAT-1 should be useful as a sensitive immunohistochemical tool for investigation of various pigmentary disorders and possibly for the diagnosis of melanoma.
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PMID:MAT-1, a monoclonal antibody that specifically recognizes human tyrosinase. 749 Apr 69

To study the relationship between the structure of minor groove ligands and their affinity for specific DNA sequences that regulate gene transcription, three analogues of the A-T-specific DNA minor groove ligands Hoechst 33258 and Hoechst 33342 were synthesized with 5, 8 or 12 carbons in an aliphatic chain attached to the phenolic oxygen of the molecule. There was a striking bimodal relationship between toxicity to HeLa cells and the lipophilicity of the five analogues, toxicity being low for the compounds with a free hydroxyl (Hoechst 33258) or a 12-carbon substituent, yet high for the 5-carbon analogue. Selective killing of human melanoma cells compared with normal fibroblasts was observed for the Hoechst analogue with a 12-carbon chain attached. Hoechst 33258 itself was selectively toxic for the MM96E melanoma cell line compared with other cell lines, induced a highly dendritic morphology, increased tyrosinase activity and tyrosinase mRNA but decreased the level of gp75 (TRP-1) mRNA; message for a third pigment gene, Pmel-17, was unchanged. Tyrosinase activity was decreased in the resistant A2058 melanoma cell line and transcription was affected to a lesser extent than in MM96E. Expression of gp75 protein and two intermediate filament proteins was inhibited by Hoechst 33258 in MM96E cells. There was no major difference in the amount of 125I-Hoechst 33258 taken up by sensitive and resistant cells. Of the five derivatives studied, the parent drug Hoechst 33258 and the 2-carbon analogue (Hoechst 33342) were found to have the most inhibitory effect on affinity of octamer binding proteins for the ATGCAAAT consensus sequence found in the promoter region of certain genes associated with proliferation and differentiation. In contrast to Distamycin A (also an A-T-specific minor groove ligand), Hoechst 33258 displaced proteins already bound to the octamer motif. The G-C ligand chromomycin A3 exhibited a different spectrum of cell toxicity and tyrosinase stimulation compared with Hoechst 33258. Chromomycin A3 but not Hoechst 33258, strongly inhibited the zinc-dependent transcriptional activity of the sheep metallothionein-Ia promoter in reporter gene assays of transfected cells. Since the six metal-responsive elements of the promoter are GC-rich, this provides independent evidence for the sequence-specificity of transcriptional inactivation by one of these drugs in melanoma cells. Overall, the results suggest that Hoechst 33258 acts by inhibiting the transcription of specific genes, cell lines evidently differing in the accessibility to drugs of certain A-T-rich sequences.
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PMID:Transcriptional regulation of differentiation, selective toxicity and ATGCAAAT binding of bisbenzimidazole derivatives in human melanoma cells. 751 Sep 66


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