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 identification of circulating tumor cells in the peripheral blood of patients with malignant melanoma by detection of melanoma associated protein transcripts using the reverse transcriptase polymerase chain reaction (RT-PCR) technique has been introduced as a noninvasive and sensitive technique for early detection of tumor progression and metastatic disease. An alternative approach is the analysis of S-100 protein in the serum of melanoma patients by a luminoimmunometric assay (LIA). In this study, the sensitivities of RT-PCR and LIA were compared. Seventy-seven blood samples of 59 melanoma patients were analyzed for tyrosinase, Melan-A/MART-1, MAGE-3, gp100, and p97 expression by multimarker RT-PCR; 540 serum samples of 352 melanoma patients were analyzed for S-100 protein concentration by LIA. In stage III 23.8% and in stage IV 37.5% of the samples were positive for at least one marker in multimarker RT-PCR, versus 8.1% and 48.1% of elevated S-100 levels analyzed by LIA, respectively. In a direct comparison, 31 identical samples were analyzed by multimarker RT-PCR and by S-100 LIA. In stage III 18.2% and in stage IV 45% of the samples were positive by multimarker RT-PCR versus 45.5% and 80% by S-100 LIA, respectively. S-100 LIA was more sensitive in detection of metastatic disease in melanoma patients than multimarker RT-PCR and should be evaluated in further studies. RT-PCR might be more useful in the analysis of micrometastases in anatomic compartments other than peripheral blood.
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PMID:Tumor markers in peripheral blood of patients with malignant melanoma: multimarker RT-PCR versus a luminoimmunometric assay for S-100. 1054 77

Rex3, the first reverse transcriptase (RT)-encoding retrotransposon isolated from the melanoma fish model Xiphophorus, is a non-long-terminal-repeat element related to the RTE family. The essential features of Rex3 are (1) an endonuclease and a reverse transcriptase, (2) 5' truncations of most of the copies, (3) a 3' tail consisting of tandem repeats of the sequence GATG, and (4) short target site sequence duplications of variable length. Compilation of Rex3 sequences from the pufferfish genome project suggested that, as observed for other members of the RTE family, no additional large open reading frame was present upstream of the endonuclease/reverse transcriptase open reading frame. There are about a thousand copies of Rex3 in the haploid genome of Xiphophorus, some of them probably resulting from recent retrotransposition events. Rex3 RNA was detected by RT-PCR in melanoma and in nontumorous tissues, as well as in melanoma-derived and embryonic cell lines. Rex3 is present in a broad panel of teleost species and was found in the promoter region and in introns of various genes. To our knowledge, Rex3 is the first autonomous retrotransposon described to date which is widespread in teleosts. This wide distribution and occasional association with coding sequences may confer on Rex3 a predisposition to play a role in genome evolution in teleosts.
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PMID:The non-LTR retrotransposon Rex3 from the fish Xiphophorus is widespread among teleosts. 1055 74

The functions of Thy-1, a 35-kDa cell-surface glycoprotein, and its natural ligand are still unknown. Anchoring to the membrane via linkage to phosphatidyl-inositol (PI) raises the possibility of cleavage off the membrane by PI-specific phospholipases. Soluble Thy-1 (sThy-1) could interfere with the binding of the unknown natural ligand followed by regulation of different cell functions. In this study we established an enzyme-linked immunosorbent assay (ELISA) to measure and quantify sThy-1 in serum and wound fluid. Recombinant human Thy-1 (rhThy-1) was expressed in Drosophila S2 cells, purified from culture supernatant and used as standard for quantitation of sThy- by the ELISA technique. There were no differences in sThy-1 levels in serum of healthy donors and patients with systemic sclerosis, leg ulcers, or rheumatoid arthritis, respectively, detected by ELISA. In contrast, at the local site of inflammation, in wound fluid of venous leg ulcers and in synovial fluid from joint puncture, we found strongly elevated levels of sThy-1 compared with sThy-1 in the serum of the same patient. Thy-1 is expressed in humans on brain cells, fibroblasts, a subpopulation of CD34+ blood stem cells, and possibly activated human dermal microvascular endothelial cells. In this study, we never found Thy-1 mRNA or protein expression in resting endothelial cells as shown by reverse transcriptase polymerase chain reaction (RT-PCR) and flow-cytometry. Thy- expression could be induced on endothelial cells by phorbol myristate acetate and to a lesser extent by tumor necrosis factor-alpha (TNF-alpha). In situ, monoclonal antibodies to Thy-1 did not stain endothelial cells in normal skin, whereas endothelial cells in the synovial membrane of rheumatoid arthritis patients and endothelial cells surrounding melanoma express Thy-1. In summary, our data indicate that Thy-1 is present in soluble form in serum. Furthermore, Thy-1 seems to be a marker for endothelial cell activation. Therefore, activated endothelial cells as well as fibroblasts might be a possible source of sThy-1.
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PMID:Detection of human soluble Thy-1 in serum by ELISA. Fibroblasts and activated endothelial cells are a possible source of soluble Thy-1 in serum. 1057 Nov 19

The melanoma cell adhesion molecule was identified as a human melanoma-associated antigen that increases in expression as tumors increase in thickness and begin to acquire metastatic potential. Clinical and experimental evidences suggest that the development of metastatic capacity might be the consequence of increased melanoma cell adhesion molecule expression. The mechanisms for upregulation of the melanoma cell adhesion molecule during melanoma progression are, however, still poorly understood. In this study, we show that melanoma cell adhesion molecule expression is tightly regulated at the transcriptional level. Using a combination of CAT reporter assays and semiquantitative reverse transcriptase-polymerase chain reaction, we observed that cyclic adenosine monophosphate significantly increases transcription of the melanoma cell adhesion molecule in nonmetastatic melanoma cells. In metastatic cells, transcription of the gene was constitutive and could not be further increased by cyclic adenosine monophosphate. On the other hand, melanoma cell adhesion molecule promoter activity was impeded upon treatment with phorbol esters or in the presence of stem cell factor, a phenomenon which was protein kinase C-dependent. Promoter-deletion studies demonstrated that the first 196 nt of the melanoma cell adhesion molecule promoter region are sufficient to get full expression in metastatic melanoma cells. This fragment contains five binding sites for the transcription factor Sp1 and DNA mobility shift experiments showed direct binding of Sp1 to the promoter. In conclusion, our results indicate that Sp1 is sufficient to drive constitutive melanoma cell adhesion molecule expression in metastatic melanoma cells. In nonmetastatic cells, however, melanoma cell adhesion molecule expression is repressed and we speculate that stem cell factor/c-Kit signaling might be responsible for the control of melanoma cell adhesion molecule synthesis, and thus, perhaps, of melanoma progression and metastasis.
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PMID:Regulation of the melanoma cell adhesion molecule gene in melanoma: modulation of mRNA synthesis by cyclic adenosine monophosphate, phorbol ester, and stem cell fFactor/c-kKit signaling. 1057 24

Dissemination of uveal melanomas is almost exclusively haematogenous, making angiogenesis of the tumour a prerequisite for the formation of metastases. Uveal melanomas must employ strategies to evade the immune system in order to escape immune surveillance. We therefore determined the expression of the following angiogenic and immunosuppressive factors in seven human uveal melanoma cell lines using reverse transcriptase-polymerase chain reaction (RT-PCR): secreted interleukin-1 receptor antagonist (sIL-1ra), interleukin (IL)-6, IL-8, IL-10, transforming growth factor (TGF)-alpha, TGFbeta, vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), basic fibroblast growth factor (bFGF), angiopoietin-1 and angiopoietin-2. In addition, the secretion of sIL-1ra, IL-6, IL-8, IL-10, TGFbeta and VEGF was assayed by enzyme linked immunosorbent assay (ELISA). The potential of uveal melanoma cell lines to convert plasminogen to angiostatin was tested in an in vitro assay. All the factors except angiopoietin-1 were determined in one or more cell lines using RT-PCR, although these results were not necessarily confirmed by ELISA. Expression of VEGF and angiopoietin-2 was found in all seven cell lines. Production of angiostatin was observed in one cell line. All seven cell lines examined expressed angiogenic factors and most cell lines expressed immunosuppressive factors. The expression of VEGF and angiopoietin-2 in combination with a lack of angiopoietin-1 expression suggest high vascular remodelling capacity and could be of great relevance for the metastatic potential of uveal melanoma.
Melanoma Res 1999 Oct
PMID:Expression of angiogenic and immunosuppressive factors by uveal melanoma cell lines. 1059 10

Microphthalmia (MITF) gene product, a transcription factor of the basic-helix-loop-helix type, is thought to play a role in the regulation of genes encoding the enzymes necessary for melanogenesis. These include tyrosinase, TRP-1 and TRP-2. Melanocyte-specific isoform of microphthalmia, MITF-M, is expressed in normal and malignant melanocytes. The presence of two other isoforms of microphthalmia, MITF-A and MITF-H, which differ from MITF-M in the amino-terminus, was demonstrated also in some non-melanocytic lineages. Here we have analyzed the presence of all three known isoforms of MITF mRNA in a panel of 17 human melanoma cell lines by a reverse transcriptase-polymerase chain reaction using isoform-specific primers. While, as expected, the predominant form in melanoma cell lines was MITF-M, low amounts of MITF-A mRNA was found in almost all melanomas, as well as in most of 20 tumor cell lines of the non-melanocyte origin (lung and colon carcinomas, osteosarcomas and neuroblastomas). The expression of MITF-H was not detected, with a few exceptions, in the tested cell lines. Pax3 transcription factor was reported earlier to regulate positively the melanocyte-specific promoter of the MITF gene. We found here that the Pax 3 mRNA was expressed in all melanoma cell lines, even in those that had repressed the MITF-M and were amelanotic. This suggests that additional factors, besides Pax3, are required for the MITF expression. The MSG1 (melanocyte-specific gene 1), a gene originally isolated from melanocytes and containing a strong transcription activation domain, was also found expressed in all melanomas and most non-melanocyte tumor cell lines. Together, these data indicate that the MITF-M isoform is the major type of MITF mRNA present in human melanoma cell lines and show that the expression of the isoform MITF-A and the MSG1 is not restricted to malignant melanocytes and occurs in a wide range of tumor cell lines.
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PMID:Expression of genes for microphthalmia isoforms, Pax3 and MSG1, in human melanomas. 1064 12

Reactivation of telomerase, an RNA-dependent DNA polymerase that synthesizes new telomeric repeats at the end of chromosomes, is a very common feature in human cancers. Telomerase is thought to be essential in maintaining the proliferative capacity of tumor cells and, as a consequence, it could represent an attractive target for new anti-cancer therapies. In this study, we generated a hammerhead ribozyme composed of a catalytic domain with flanking sequences complementary to the RNA component of human telomerase and designed to cleave specifically a site located at the end of the telomerase template sequence. In vitro the ribozyme induced cleavage of a synthetic RNA substrate obtained by cloning a portion of the RNA component of human telomerase. The extent of cleavage was dependent on the ribozyme/substrate ratio as well as the Mg2+ concentration. Moreover, when added to cell extracts from two human melanoma cell lines (JR8 and M14), or three melanoma surgical specimens, the ribozyme inhibited telomerase activity in a concentration- and time-dependent manner. When the ribozyme was delivered to growing JR8 melanoma cells by (N-(1-(2,3 dioleoxyloxy)propil)-N,N,N trimethylammonium methylsulfate-mediated transfer, a marked inhibition of telomerase activity was observed. Next, the ribozyme sequence was cloned in an expression vector and JR8 cells were transfected with it. The cell clones obtained showed a reduced telomerase activity and telomerase RNA levels and expressed the ribozyme. Moreover, ribozyme transfectants had significantly longer doubling times than control cells and showed a dendritic appearance in monolayer culture. No telomere shortening, however, was observed in these clones. Overall, our results indicate that the hammerhead ribozyme is a potentially useful tool for the inactivation of telomerase in human tumors.
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PMID:Inhibition of telomerase activity by a hammerhead ribozyme targeting the RNA component of telomerase in human melanoma cells. 1065 84

The molecular detection of circulating tumor cells (CTC) and micrometastases may help develop new prognostic markers in patients with solid tumors. In the last 10 years, numerous groups have attempted the detection of occult tumor cells in solid malignancies using the highly sensitive reverse transcriptase polymerase chain reaction (RT PCR) technique. These assays were in the vast majority directed against tissue specific markers. In most studies on prostatic carcinoma, RT PCR was able to specifically detect prostatic tissue specific markers in the peripheral blood (PB), bone marrow (BM) and lymph nodes of patients with localized and metastatic disease. Melanoma related transcripts were detected by RT PCR in the PB, BM and lymph nodes of patients with localized and advanced tumors. In most studies, melanoma related markers were shown to be specific except when assayed in lymph nodes. RT PCR positivity rates were highly variable between studies. Despite tFlese discrepancies, many authors have shown a statistically significant correlation between RT PCR positivity and a poorer outcome in both melanoma and prostatic carcinoma. In breast carcinoma, all markers that have been extensively tested were shown to be non-specific. Because of the many limitations of RT PCR (e.g. false positives), many groups are developing new approaches for the detection occult tumor cells. One of these techniques involves immunobead isolation of CTC and micrometastases prior to down stream analysis. The tumor rich magnetic fraction can be subjected to RT PCR, immunocytochemistry and flow cytometry. In conclusion, the molecular detection of occult tumor cells in solid tumors seems very promising and the techniques used for this purpose are in continuous evolution. Large prospective and interlaboratory variability studies are necessary to determine the accuracy and prognostic value of these assays.
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PMID:Molecular detection of micrometastases and circulating tumor cells in melanoma prostatic and breast carcinomas. 1075 82

Sentinel lymph node dissection (SLND) as originally described by D.L. Morton et al. (Surg Oncol Clin North Am 1992;1:247-59), is currently being used at most tertiary institutions for staging patients with intermediate-level melanomas. Identification and subsequent surgical resection of occult metastasis before the development of clinical disease may improve survival in these patients. This study is a retrospective review of patients with intermediate melanomas treated by the senior author (P.S.D.). Isosulfan blue dye and a radioactive technetium-labeled dye were used to identify the sentinel node. Sentinel nodes were evaluated by routine hematoxylin and eosin staining, immunohistochemical staining for S-100 and HMB-45, and later in the study with multipanel reverse transcriptase-polymerase chain reaction analysis. All patients were followed closely. Fifty-seven patients with primary melanoma were evaluated between December 1995 and June 1998. Thirty-two patients underwent SLND; two patients underwent SLND on two separate drainage basins, for a total of 34 procedures. The median age was 49 years (range, 19-77). There were 11 females and 21 males. The locations of the primary melanoma were: head and neck, seven; extremity, 8; and trunk, 18; 1 patient had a dual primary melanoma at presentation. Clark's levels of invasion among the patients were level III, 5; and level IV, 27; median Breslow thickness was 1.4 mm (range, 0.45-3.8 mm). A sentinel node was not identified in four procedures (11.1%). Twenty-two nodes (73%) were negative by all methods, and eight (27%) were positive by at least one method. All positive patients underwent complete lymphadenectomy, and routine hematoxylin and eosin stains identified no additional positive nodes. Median follow-up was 21 months (6-36 months). Two patients developed recurrent disease. The other 30 patients remain disease free at last follow-up. SLND is a low-morbidity technique that accurately stages patients with intermediate-level melanoma. Early intervention with complete therapeutic lymphadenectomy and possible interferon therapy may improve the survival of patients with stage III melanoma. A complete discussion of the technique for SLND and an update of this data is presented.
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PMID:Sentinel lymphadenectomy for staging patients with intermediate-level melanoma. 1075

Improvement is needed in the ability to evaluate the prognosis of melanoma patients who are clinically disease-free but likely to develop recurrent metastatic disease. The detection of circulating melanoma cells in blood is a potential surrogate marker of subclinical residual disease. We assessed the prognostic clinical utility of a multimarker melanoma reverse transcriptase-PCR (RT-PCR) assay using blood of 46 patients who were clinically disease-free. All patients were followed up for more than 4 years for disease recurrence. There was a significant correlation between number of RT-PCR markers present in blood and American Joint Committee on Cancer stage (P = 0.009). The number of RT-PCR markers detected in blood was an independent prediction factor of disease recurrence in a Cox proportional hazard model (P = 0.02). A risk factor model using American Joint Committee on Cancer stage and number of positive RT-PCR markers significantly predicted disease recurrence in 2, 3, and 4 years of follow-up. These studies demonstrate that molecular detection of circulating melanoma cells may be of significant prognostic value in determining early disease recurrence and may be useful for stratifying patients for adjuvant therapy.
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PMID:Molecular markers in blood as surrogate prognostic indicators of melanoma recurrence. 1078 92


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