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)

4-S-cysteinylphenol (4-S-CP), the S-homologue of tyrosine, has been recently synthesized as a selective chemotherapeutic agent against malignant melanoma and has been shown to be a specific substrate for tyrosinase in vitro. In vivo incorporation of 4-S-CP into the B16 and Harding Passey (HP) melanomas and the systemic organs have been evaluated by the autoradiographic method. The distribution of the silver grains indicated that 4-S-CP was selectively incorporated into both the B16 and HP melanomas. 4-S-CP was excreted mainly from the kidneys and there was an accumulation of 4-S-CP in the reticulo-endothelial system. These results seemed to contribute to the utilization of 4-S-CP and other related compounds as chemotherapeutic agents against malignant melanoma.
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PMID:Histological localization of 4-S-cysteinylphenol in melanoma-bearing mice. 332 27

In this paper, 26 cases of malignant melanoma (MM) were analysed as to 10 items of clinicopathology, and 13 cases were followed. MM frequently occurs in the lower limbs. The peak age was 41 approximately 60 years. There was a history of having a black nevus (30.8%) and evident trauma (37.5%). Black nevus, located in the sole or palm, was able to undergo malignant change through long-term friction, irritation and so on. Therefore, preventive resection is necessary. Basing on the follow up study of 13 cases, three problems related to survival time are discussed: (1) Location of the tumor: MM in the mucosa has a worse prognosis than in the cutis. It might be considered as the rich blood supply to the mucosal tissue, easily resulting in hematogenous metastasis. (2) Clinical stage of the disease: The more advanced clinical stage, the shorter survival time. Early diagnosis and timely treatment play a key role in the prognosis. (3) TREATMENT: It is believed that extensive resection of the primary focus with dissection of the regional lymph nodes followed by adjuvant chemotherapy or Chinese traditional medicine is required. Correct diagnosis relies on the compositive analysis of 3 kinds of stain (iron reaction, fader and silver stain). The reticulum stain might be of benefit in differentiating the benign from malignant tumors. Diagnosis for the colorless MM depends on the finding of premelanin corpuscles by electronmicroscopy. In addition to Zhu Yuede's 9 criteria of diagnosis for MM, the authors propose that 4 features of MM in histostructure and cytomorphology be adhered to.
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PMID:[Pathomorphologic observation and prognostic analysis of 26 cases of malignant melanoma]. 344 70

A chromosomal examination of cells from the earliest available passage of the human melanoma cell line MeWo revealed the presence of seven hypodiploid cell types that shared common complex marker chromosomes. Two of the cell types had long homogeneously staining regions (HSR) by Q-banding on three different chromosomes. Distamycin A/DAPI staining and silver staining for active nucleolar organizing regions (NOR) confirmed that the HSR were derived from chromosome #15. All HSR-containing cells had 4-9 pairs of large NOR distributed along the length of each HSR, with all acrocentric chromosomes being negative. The HSR-lacking cells differed primarily with respect to the morphology of the short arm of one #13 chromosome and NOR activity. One cell type had four chromosomes with active NOR, whereas all other cell types had a single active NOR on one #13. One of these cell types had a satellited #8 with NOR. Cells from three other MeWo cultures at higher passages were examined. Two of these contained both hypodiploid and hypotetraploid cells, some of which had satellited X chromosomes or satellited #3 chromosomes with active NOR. The majority of the new chromosomal rearrangements in cells from the later cultures involved the NOR-containing regions, many of which were associated with the distamycin A/DAPI-positive centromeric heterochromatin from chromosome #15. These results indicate that the chromosomal instability in the MeWo cultures is mainly limited to sequences containing active NOR and centromeric heterochromatin from chromosomes #13 and #15. This may be due to a selective pressure to increase the number of active NOR in the MeWo cells. If this is so, it would appear that amplification of active NOR occurs more readily than the activation of the many silent NOR present in these cells.
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PMID:Rearrangements of chromosomal regions containing ribosomal RNA genes and centromeric heterochromatin in the human melanoma cell line MeWo. 345 62

Until now, measurement of human antitumor immunity to organ-specific cancer neoantigen (OSN) by the leukocyte adherence inhibition (LAI) assay depended on using crude extracts of cancer. In this study, a new method is presented to generate and to isolate a highly enriched OSN from spent medium of a lung cancer cell line, NCI-H69, grown in chemically defined medium. Production of large quantities of OSN with minimal contamination by extraneous proteins was possible. Four physicochemical steps were used to give a 1000-fold enrichment of OSN activity: anion-exchange and molecular-sieve chromatography; Blue Sepharose affinity chromatography; and finally anion-exchange high-pressure liquid chromatography. The enriched OSN isolates showed dose-response antigenicity when tested in LAI assay with leukocytes from lung cancer patients but had no antigenicity with leukocytes from control subjects or patients having malignant melanoma, colon cancer, or pancreatic cancer. Cross-reactive antigenicity was observed with leukocytes from patients with breast cancer and slight reactivity with leukocytes from bladder cancer patients. The final isolate from the four-step separation procedure as well as the isolates produced using additional separation techniques consistently had antigenicity at less than 10 ng in blocking LAI and 500 ng in the direct assay and showed components with molecular weights of about 62,000 +/- 3,000 (SD) (p62), 40,000 +/- 3,000 (p40), and 25,000 +/- 1,000 (p25) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The OSN isolates on two-dimensional gels showed p40 to have microheterogeneity (seven spots), with a pl from 6.2 to 7.6, and p62 and p25 as even more basic streaks. The polypeptide bearing the antigenic determinant was not purified, although we tried to separate p62, p40, and p25 to determine whether they carried the OSN determinant. The results of this study are important in showing that an isolate of an organ-specific tumor antigen containing 5 to 13 components, as determined by highly sensitive silver stains and radiolabeled patterns on single and two-dimensional gels, can be used successfully in LAI to measure tumor immune responses.
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PMID:An isolated enriched organ-specific cancer neoantigen of human lung cancer for leukocyte adherence inhibition assays. 388 36

Cutaneous melanomas of Tyr-SV40E transgenic mice (mice whose transgene consists of the tyrosinase promoter fused to the coding regions of simian virus 40 early genes) strikingly resemble human melanomas in their development and progression. Unlike human melanomas, the mouse tumors all arise in genetically identical individuals, thereby better enabling expression of specific genes to be characterized in relation to advancing malignancy. The products of pigment genes are of particular interest because peptides derived from these proteins have been reported to function as autoantigens with immunotherapeutic potential in some melanoma patients. However, the diminished pigmentation characteristic of many advanced melanomas raises the possibility that some of the relevant products may no longer be expressed in the most malignant cells. We have therefore investigated the contributions of several pigment genes in melanotic vs. relatively amelanotic components of primary and metastatic mouse melanomas. The analyses reveal marked differences within and among tumors in levels of mRNAs and proteins encoded by the wild-type alleles at the albino, brown, slaty, and silver loci. Tyrosinase (the protein encoded by the albino locus) was most often either absent or undetectable as melanization declined. The protein encoded by the slaty locus (tyrosinase-related protein 2) was the only one of those tested that was clearly present in all the tumor samples. These results suggest that sole reliance on targeting tyrosinase-based antigens might selectively favor survival of more malignant cells, whereas targeting the ensemble of the antigens tested might contribute toward a more inclusive and effective antimelanoma strategy.
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PMID:Changes in expression of putative antigens encoded by pigment genes in mouse melanomas at different stages of malignant progression. 747 44

The expression of various melanogenic proteins, including tyrosinase, the tyrosinase-related proteins 1 (TRP1) and 2 (TRP2/DOPAchrome tautomerase), and the silver protein in human melanocytes was studied in six different human melanoma cell lines and compared to a mouse derived melanoma cell line. Analysis of the expression of tyrosinase, TRP1, TRP2, and the silver protein using flow cytometry revealed that in general there was a positive correlation between melanin formation and the expression of those melanogenic enzymes. Although several of the melanoma cell lines possessed significant activities of TRP2, the levels of DOPAchrome tautomerase in extracts of human cells were relatively low compared to those in murine melanocytes. Melanins derived from melanotic murine JB/MS cells, from melanotic human Ihara cells and HM-IY cells, from sepia melanin, and from C57BL/6 mouse hair were chemically analyzed. JB/MS cells, as well as Ihara cells and HM-TY cells, possessed significant amounts of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) derived melanins, this being dependent on the activity of TRP2. Kinetic HPLC assays showed that 5,6-dihydroxyindole (DHI) produced during melanogenesis was metabolized quickly to melanin in pigmented KHm-1/4 cells, whereas DHI was stable in amelanotic human SK-MEL-24 cells. A melanogenic inhibitor that has been purified from SK-MEL-24 cells that suppressed oxidation of DHI in the presence or absence of tyrosinase, but had no effect on DHICA oxidation. The sum of these results suggests that the expression of melanogenic enzymes as well as the activity of a melanogenic inhibitor are critical to the production of melanin synthesis in humans.
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PMID:The expression of tyrosinase, tyrosinase-related proteins 1 and 2 (TRP1 and TRP2), the silver protein, and a melanogenic inhibitor in human melanoma cells of differing melanogenic activities. 765 83

Nucleolar organizer regions (NORs) are loops of ribosomal DNA (rDNA) in the nucleolus and are associated with acidic proteins. They are seen in routinely processed paraffin sections by using a one-step colloidal silver (Ag) staining method; they appear as black dots termed "AgNORs". The quantitative assay of AgNORs has been used to differentiate benign from malignant neoplasms. Melanocytic lesions differ significantly in AgNOR counts between malignant melanoma and nevi. However, conflicting results have been reported as to AgNORs' prognostic value in melanoma. A recent study showed AgNOR counts to be a more accurate prognostic indicator than Breslow's thickness. In this study, we counted the AgNORs in 26 patients with primary cutaneous melanomas (CMM) between 2.0 mm and 2.5 mm thick. Of these, 14 are alive without disease (AN) at 5 years after diagnosis (group 1) and 12 are dead of disease (DD) in less than 5 years (group 2). The AgNORs were scored in 30 nuclei per tumor, and the means were calculated. For group 1, the mean number of AgNORs per nucleus was 6.88, ranging from 3.73 to 12.70. For group 2, the mean number was 6.97, ranging from 3.63 to 11.67. Statistical analysis using analysis of variance (ANOVA) showed no significant difference between the groups (p = 0.33). In our study, AgNOR counts did not prove to be of prognostic value in malignant melanoma.
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PMID:Prognostic significance of nucleolar organizer regions (NORS) in malignant melanoma. 769 15

We report a case of amelanotic melanoma arising in the nasal cavity and paranasal sinuses, that could not be positively diagnosed as malignant melanoma before the patient's death in spite of repeated biopsies both from primary and metastatic lesions, including ultrastructural examination and immunohistochemical staining for S-100 protein with usual polyclonal antibody. The patient died of rapid wide-spread dissemination of the tumor. In autopsy specimens, melanin pigment was detected, for the first time, by the Fontana's silver stain. The posthumous diagnosis of malignant melanoma was immunohistochemically confirmed for the specific antibodies, anti alpha-subunit of S-100 protein antibody and SK-46 (original antibody for melanoma made at the Department of Pathology, University of Gunma School of Medicine) from specimens obtained while alive. The application of a specific antibody for S-100 protein is recommended as useful for the diagnosis of malignant melanoma even when routine immunohistochemical procedures fail to demonstrate S-100 protein.
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PMID:Malignant melanoma of the nasal cavity. 777 28

The morphological features of 62 anorectal malignancies diagnosed on sigmoidoscopic biopsy were studied. On haemotoxylin and eosin staining the tumours were diagnosed as adenocarcinomas (43), squamous cell carcinoma (12), malignant melanoma (3), carcinoid (2), clear cell carcinoma (1) and poorly differentiated carcinoma (1). PAS Alcian blue, Grimelius silver stain, AgNOR and immunohistochemical stain for carcinoembryonic antigen (CEA) and human papilloma virus (HPV) were done to further categorise these tumours. The ages of the patients varied from 18 to 77 yr (mean 43.7 yr) and the male: female ratio was 2:1. PAS Alcian blue staining was helpful in differentiating mucinous from non-mucinous adenocarcinomas and reclassifying one poorly differentiated carcinoma as mucin secreting adenocarcinoma. Also, it clearly identified pagetoid spread in two cases of adenocarcinomas. Grimelius silver stain was strongly positive in melanomas and neuroendocrine tumours. Basal silver staining was visualised in metaplastic foci but was absent in dysplastic epithelium. AgNOR counts may be considered useful in differentiating melanomas (high counts) from spindle cell variant of squamous carcinomas (low counts). High AgNOR counts and strong Grimelius positivity in clear cell carcinoma suggested its melanotic origin. Immunostaining for CEA and HPV were of limited value. CEA was positive in the majority of the adenocarcinomas while HPV could only be demonstrated in two squamous cell carcinomas.
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PMID:Morphological & immunohistochemical spectrum in anorectal malignancies. 792 71

The silver mutation in mice causes progressive graying of hair due to the loss of functional follicular melanocytes. Recently the silver locus gene (called Pmel 17) has been cloned; its encoded product shares homology with a chick melanosomal matrix protein and a bovine retinal pigment epithelial protein. Although the sequence of the silver gene and the correlation of its expression with pigment production have been reported, its function in melanogenesis is still unknown. In an effort to characterize that function, we have synthesized the predicted carboxyl-terminal peptide of the mouse Pmel 17 protein and generated a rabbit polyclonal antibody (alpha PEP13) to it; that antibody recognized the silver protein specifically. The immunoaffinity-purified silver protein lacked all of the known melanogenic catalytic activities which other tyrosinase-related proteins (TRP) have, nor did it appear to modulate any of those TRP activities. Metabolic labeling experiments demonstrated that the silver protein disappears in vivo within a few hours, indicating that it is rapidly degraded, or quickly processed to lose its carboxyl terminus. Cross-reactivity experiments showed that a recently reported anti-melanosomal matrix protein antibody (alpha MX) also recognizes the silver protein, although at a different epitope from that of alpha PEP13. Using Western immunoblotting, we analyzed subcellular fractions isolated from B16 F10 melanoma cells and found that the silver protein was rich in the melanosome fraction but was absent from coated vesicles which deliver TRPs to melanosomes. These results suggest that the silver locus product is a melanosomal matrix protein which may contribute to melanogenesis as a structural protein, although the possibility remains that it also has a novel catalytic function in melanogenesis.
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PMID:The Pmel 17/silver locus protein. Characterization and investigation of its melanogenic function. 796 86


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