Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to address the prognostic significance of circulating melanoma cells by reverse transcriptase-polymerase chain reaction in the peripheral blood of stage IIB and III melanoma patients on high-dose adjuvant interferon at multiple sequential time points from initiation of treatment. Tyrosinase mRNA in peripheral blood from these patients was assayed by reverse transcriptase polymerase chain reaction prior to initiation of adjuvant interferon, at completion of 1 month of intravenous interferon and at 3 monthly intervals until progression. Four hundred and eighteen blood samples from 60 melanoma patients were analysed. The median follow-up time calculated from the time of inclusion in the study was 23 months (range 2-38 months). Tyrosinase mRNA in blood was detected in 42 (70%) of 60 patients: 16 (76%) of 21 stage IIB patients and 26 (66% ) of 39 stage III patients. The presence of tyrosinase mRNA in blood was correlated with a shorter disease-free survival (P : 0.03) and in multivariante analysis was an independent prognostic factor for relapse. Patients who seroconverted to a negative reverse-transcriptase-polymerase chain reaction after induction treatment had a significantly lower probability of recurrence. The presence of circulating melanoma cells is a marker of a high relapse risk and shorter disease-free survival whether detected postoperatively or during follow-up. Tyrosinase mRNA amplification by reverse-transcriptase-polymerase chain reaction may be a useful tool for monitoring the efficacy of adjuvant treatment in stage IIB and III melanoma patients.
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PMID:Prognostic significance of the sequential detection of circulating melanoma cells by RT-PCR in high-risk melanoma patients receiving adjuvant interferon. 1264 40

Malignant melanoma is one of the most rapidly increasing cancer types, and patients with metastatic disease have a very poor prognosis. Detection of metastatic melanoma cells in circulation may aid the clinician in assessing tumor progression, metastatic potential, and response to therapy. Tyrosinase is a key enzyme in melanin biosynthesis. The gene is actively expressed in melanocytes and melanoma cells. Melan A is a differentiation antigen that is expressed in melanocytes. The presence of these molecules in blood is considered a marker for circulating melanoma cells. In this study, we analyzed the usefulness of this marker combination in evaluating the response to therapy in the blood of 30 patients with malignant melanoma. Circulating cells were detected by a reverse-transcriptase-polymerase-chain reaction. The tyrosinase expression was observed in 9 (30%) patients and Melan A in 19 (63.3%) patients before therapy. Following treatment, the tyrosinase mRNA was detected in only one patient, while Melan A transcripts were still present in 14 patients. We suggest that this molecular assay can identify circulating melanoma cells that express melanoma-associated antigens and may provide an early indication of therapy effectiveness.
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PMID:Detection of circulating melanoma cells by a two-marker polymerase chain reaction assay in relation to therapy. 1268 15

The activity of melanosome-associated tyrosinase in human melanocytes differs based on racial skin type. In melanocytes from Black skin, tyrosinase activity is high while in White melanocytes the activity of the enzyme is low. Recent studies suggest that low tyrosinase activity in White melanocytes may be due to an acidic pH environment within the melanosome. Because sodium/hydrogen (Na(+)/H(+)) exchangers (NHEs) are known to regulate intracellular pH, melanocytes were treated with NHE inhibitors to determine what effect this inhibition might have on tyrosinase activity. Treatment of Black melanocytes with ethyl-isopropyl amiloride (EIPA) caused a rapid dose-dependent inhibition of tyrosinase activity. This inhibition was not due to either direct enzyme inhibition or to a decrease in tyrosinase abundance. In contrast, treatment of White melanocytes with EIPA, cimetidine, or clonidine resulted in little inhibition of tyrosinase activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis showed that both Black and White melanocytes expressed mRNA and protein for NHE-1, NHE-3, NHE-5, NHE-6, and NHE-7. Immunohistochemical analysis showed that NHE-7 and NHE-3 co-localized with the melanosomal protein, Tyrosinase Related Protein-1 (TRP-1). In addition, the vesicular proton pump, vesicular ATPase (V-ATPase), was found to be present in both White and Black melanosomes, indicating that organelles from both racial skin types are capable of being acidified. The results suggest that one or more NHEs may help regulate melanosome pH and tyrosinase activity in human melanocytes.
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PMID:The relationship between Na(+)/H(+) exchanger expression and tyrosinase activity in human melanocytes. 1526 99

Reverse transcriptase-polymerase chain reaction (RT-PCR)-mediated detection of melanoma cells may be a prognostic factor for disease outcome. We investigated the presence of melanoma cells in lymphatic drainage and blood in melanoma patients after lymph node dissection (LND) via the highly sensitive multimarker (MM) RT-PCR assay. We collected 24-h lymph fluid (LY) and peripheral blood (BL) from 107 stage III melanoma patients after radical LND (59 axillary and 48 ilioinguinal LND). Tyrosinase, MART1 and uMAGE mRNA levels were determined by RT-PCR to detect melanoma cells, and the presence of at least one marker signified a positive result. All patients underwent follow-up (median for survivors, 21 months, range: 4-37 months). Forty patients (37.4%) were positive for LY MM RT-PCR and 28 (26.2%) were positive based on BL MM RT-PCR. No differences for disease-free survival (DFS) curves according to BL MM RT-PCR were observed, but we found significant differences in the estimated 24-month DFS rate for patients with at least one marker and those without any marker in lymph fluid [18.9% (95% confidence interval: 1.4-37.5%) and 42.1% (95% confidence interval: 29.7-54.5%), median: 9.9 and 15.3 months, respectively] (P=0.04). Detection of multiple markers in lymph fluid correlated with shorter DFS. Approximately 37% of lymph fluid after radical LND were positive by MM RT-PCR, which correlated significantly with early melanoma recurrences and shorter survival. The LY MM RT-PCR seems to be an effective prognostic tool for stage III melanoma patients. The MM RT-PCR analysis of single peripheral blood sample in these patients did not have additional prognostic value.
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PMID:Molecular staging by multimarker reverse transcriptase-polymerase chain reaction assay of lymphatic drainage and blood from melanoma patients after lymph node dissection. 1862 8