Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.10.3.1 (tyrosinase)
9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detection of circulating tumor cells (CTCs) might improve current staging procedures by identifying a subgroup of patients with minimal residual disease and thus a higher risk of disease recurrence. Forty patients with > or =2-mm-thick cutaneous melanoma with or without lymph node metastasis were enrolled. After standard radical surgery and adjuvant therapy in case of lymph node metastasis, patients were followed up with routine physical and radiologic assessments as well as serial PCR-based analysis of CTCs using 2 melanoma markers (tyrosinase and Melan-A/Mart-1). After a median follow-up of 30 months, 18 patients had disease recurrence and 28 were PCR-positive before the disease became clinically evident. The sensitivity of the molecular test was 83%. Median time to PCR positivity and median PCR-to-relapse time were 12 and 8 months, respectively. At multivariate analysis, PCR positivity was an independent predictor of disease recurrence (hazard ratio=2.06, 95% CI 1.07-3.35; p=0.03). Among high-risk melanoma patients, serial PCR-based analysis of CTCs can identify a subgroup at higher risk of disease recurrence, with clinically significant advance. Therefore, CTC detection might be employed for the selection of patients for adjuvant treatment and during follow-up for early indication of therapeutic failure.
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PMID:Molecular detection of circulating tumor cells is an independent prognostic factor in patients with high-risk cutaneous melanoma. 1525 44

BACKGROUND: In the management of cutaneous melanoma, it is desirable to complete the regional lymphadenectomy during the initial surgical procedure for wide excision of biopsy site and sentinel lymph node (SLN) biopsy. In this study, we optimized and evaluated a rapid 17 minutes immunostaining protocol. The discriminatory immunostaining pattern associated with the 'MCW Melanoma Cocktail' (mixture of Melan- A, MART- 1, and tyrosinase) facilitated the feasibility of intraoperative evaluation of imprint smears of SLNs for melanoma metastases. METHODS: Imprint smears of 51 lymph nodes from 25 cases (48 SLNs and 3 non-SLNs, 1 to 4 SLNs/case) of cutaneous melanoma were evaluated. RESULTS: Sixteen percent, 8/51 lymph nodes (28%, 7/25 cases) were positive for melanoma metastases in immunostained permanent sections with the 'MCW melanoma cocktail'. All of these melanoma metastases, except 1 SLN from 1 case, were also detected in rapidly immunostained wet-fixed and air-dried smears (rehydrated in saline and postfixed in alcoholic formalin). The cytomorphology was superior in air-dried smears, which were rehydrated in saline and postfixed in alcoholic formalin. Wet-fixed smears frequently showed air-drying artifacts, which lead to the focal loss of immunostaining. None of the 5 SLNs from 5 cases exhibiting capsular nevi showed a false positive result with immunostained imprint smears. CONCLUSIONS: Melanoma metastases can be detected intraoperatively in both air-dried smears and wet-fixed smears immunostained with the MCW Melanoma cocktail. Air-dried smears rehydrated in saline and postfixed in alcoholic formalin provide superior results and many practical benefits.
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PMID:Optimization of an immunostaining protocol for the rapid intraoperative evaluation of melanoma sentinel lymph node imprint smears with the 'MCW melanoma cocktail' 1550 Jul 2

This pilot study was carried out to gain a first insight into the effects of peptide vaccination in melanoma patients in the high-risk adjuvant disease setting. From the adjuvant peptide vaccination studies carried out in our institution since 1998, we identified all melanoma patients with a history of at least 3 completely resected metastases during the year preceding enrollment into the trial and describe the clinical and immunologic observations. Out of a total of 44 patients with resected cutaneous melanoma entered into adjuvant peptide vaccination trials, 9 patients were identified with more than 3 metastases in the year before vaccination. After initiation of vaccination, 2 patients remained relapse-free for 27 and 42+ months, 2 patients experienced single or several initial relapses and subsequent relapse-free intervals of 18 and 65+ months, whereas 5 patients progressed. In both patients with relapse after prolonged relapse-free intervals, the relapses were initially confined to the small intestine and could be resected. Induction or boosting of functional tyrosinase peptide-specific T cells was noted in 6 of 8 patients, including all 4 patients with prolonged relapse-free intervals. In conclusion, adjuvant peptide vaccination was associated with cessation of recurrences in 4 of 9 patients, of whom all 4 had an immunologic response to the vaccine.
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PMID:Peptide vaccination after repeated resection of metastases can induce a prolonged relapse-free interval in melanoma patients. 1564 83

Detection of micrometastases in the regional tumor-draining lymph nodes is critical for staging and prognosis in melanoma patients. We applied a quantitative multiple-marker RT-PCR assay to improve the detection of occult melanoma cells in the sentinel lymph node (SLN). From 139 patients with primary cutaneous melanoma who underwent sentinel lymphadenectomy, a total of 235 SLN were assessed for Melan-A and tyrosinase expression by real-time quantitative RT-PCR. Twenty-three patients (17%) were positive by histopathology and expressed messenger RNA of one or two markers. Of the patients with histopathologically negative SLN 39 (28%) were reclassified by positive RT-PCR. Patients were examined for tumor recurrences during a median follow-up period of 29 mo. Tumor recurrences were demonstrated in eight patients (35%) with histopathologically positive SLN, in four patients (10%) with submicroscopic tumor cells detected exclusively by real-time RT-PCR, and in none of the patients negative by both methods. The differences in recurrence rates were statistically significant (p=0.01). These data indicate that real-time quantitative RT-PCR for the detection of minimal residual melanoma in SLN improves the prediction of disease-free survival.
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PMID:Quantification of melanoma micrometastases in sentinel lymph nodes using real-time RT-PCR. 1573 83

Prevailing reports support the status of sentinel lymph node biopsy as the standard of care in the management of cutaneous melanoma. However, the evaluation of sentinel lymph nodes for melanoma metastases with traditionally used immunomarkers such as S100 protein and HMB45 has proved challenging. The MCW melanoma cocktail (a mixture of MART-1 [1:500], Melan-A [1:100] and tyrosinase [1:50] monoclonal antibodies) has demonstrated a highly discriminatory immunostaining pattern. Contrary to conventionally used immunomarkers such as S100 protein, the MCW melanoma cocktail facilitates detection of even singly scattered melanoma cells in sentinel lymph nodes, not only in permanent sections but also in imprint smears.
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PMID:MCW melanoma cocktail for the evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma. 1593 8

The search is on for biomarkers for use in the diagnosis, staging, prognosis, and management of patients with melanoma. As with many types of cancer, the hematogenous spread of melanoma is a bad prognostic sign, and many groups have attempted to detect circulating melanoma cells in patients with different stages of melanoma. Some studies have used direct extraction of intact tumor cells from the peripheral blood and others the detection of surrogate markers of circulating melanoma cells, such as tyrosinase or MART-1. However, a correlation between the detection of intact melanoma cells in the circulation and prognosis is controversial. Many other biomarkers have also been studied, including lactate dehydrogenase, S100, TA90, and C-reactive protein. Much progress has been made, and preliminary studies have shown promise with many of these markers. Finally, the detection of tumor-specific circulating DNA has shown promise as a prognostic and diagnostic marker of disease in melanoma as well. In this review we examine the most promising biomarkers for use in patients with cutaneous melanoma.
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PMID:Tumor cell and circulating markers in melanoma: diagnosis, prognosis, and management. 1609 Dec

Immune responses contribute to the pathogenesis of vitiligo and target melanoma sometimes associated with vitiligo-like depigmentation in some melanoma patients. We analyzed the sera from patients with vitiligo and cutaneous melanoma for reactivity toward tyrosinase peptide sequences 1) endowed with low level of similarity to human proteome, and 2) potentially able to bind HLA-DR1 Ags. We report that the tyrosinase autoantigen was immunorecognized with the same molecular pattern by sera from vitiligo and melanoma patients. Five autoantigen peptides composed the immunodominant anti-tyrosinase response: aa95-104FMGFNCGNCK; aa175-182 LFVWMHYY; aa176-190FVWMHYYVSMDALLG; aa222-236IQKLTGDENFTIPYW, and aa233-247 IPYWDWRDAEKCDIC. All of the five antigenic peptides were characterized by being (or containing) a sequence with low similarity level to the self proteome. Sera from healthy subjects were responsive to aa95-104FMGFNCGNCK, aa222-236IQKLTGDENFTIPYW, and aa233-247 IPYWDWRDAEKCDIC, but did not react with the aa175-182LFVWMHYY and aa176-190FVWMHYYVSMDALLG peptide sequences containing the copper-binding His180 and the oculocutaneous albinism I-A variant position F176. Our results indicate a clear-cut link between peptide immunogenicity and low similarity level of the corresponding amino acid sequence, and are an example of a comparative analysis that might allow to comprehensively distinguish the epitopic peptide sequences within a disease from those associated to natural autoantibodies. In particular, these data, for the first time, delineate the linear B epitope pattern on tyrosinase autoantigen and provide definitive evidence of humoral immune responses against tyrosinase.
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PMID:Proteomic scan for tyrosinase peptide antigenic pattern in vitiligo and melanoma: role of sequence similarity and HLA-DR1 affinity. 1627 62

Mitf protein is a transcription factor involved all along the life of pigmented cells. This protein is located in the center of multiple signaling pathways which control differentiation, morphology, proliferation and survival of the various cells of the melanocyte lineage: melanoblasts, melanocytes and melanoma. Mitf plays a major role in melanoblasts differentiation, by inducing the key enzyme of melanogenesis, tyrosinase, and its secondary enzymes, Tyrp1 and Dct. Mitf regulates morphology and migration of melanocytes, particularly by regulating cytoskeleton organization and cell-cell adhesion. Mitf plays a double role of inducer/repressor of cellular proliferation. This protein inhibits cell cycle progression and prevents non-proper cell division. In few cases, Mitf can also induce cell cycle. A minimal quantity/activity of Mitf is necessary for melanoblast survival. Essential protein of the melanocyte lineage, Mitf was proposed as diagnostic/pronostic marker for cutaneous melanoma. However, could we then consider MITF as the unique marker of such a cancer?
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PMID:[Malignant melanoma and the role of the paradoxal protein Microphthalmia transcription factor]. 1723 8

Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) for specific melanoma markers is more sensitive than histology for detecting cells of melanocytic origin in sentinel lymph nodes (SLNs) in cutaneous melanoma. The clinical significance of a positive qRT-PCR analysis is unclear. We performed qRT-PCR for the presence of MART-1 and tyrosinase in SLNs from 93 melanoma patients, and then followed these patients clinically (median follow-up time 43.5 months). We found a significant correlation between disease progression and presence of MART-1 mRNA in SLNs (p=0.02), but no correlation with the amount of MART-1 mRNA as measured by qRT-PCR. No correlation between histology and recurrence was detected, recurrence rates being low in both histology-negative (12%) and -positive (15%) patients. We found a significant difference in disease recurrence between patients positive by both histology and RT-PCR and patients negative by both methods (15% vs 0%, p=0.02). However, a significant difference in disease recurrence was also found when comparing patients negative by both methods with patients positive by RT-PCR but negative by histology (0% vs 19%, p=0.009). This suggests that the presence of submicroscopic metastases may influence prognosis, indicating that RT-PCR detection of melanocytic cells in SLNs may be an important diagnostic marker.
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PMID:Quantitative real-time RT-PCR in sentinel lymph nodes from melanoma patients. Detection of melanocytic mRNA predicts disease-free survival. 1837 85

Standard screening of melanoma patients is a useful tool for predicting outcome of patients, however, an instant methodology for exact detection of subclinical disease or monitoring treatment response is under investigation. Detection of circulating melanoma cells is, therefore, a possible novel promising staging method. However, inconsistent data on method sensitivity and on the predicted patient outcome has been shown repeatedly. Recently, a multimarker real-time RT-PCR methodology for quantification of five melanoma markers Melan-A, gp 100, MAGE-3, MIA and tyrosinase was described by our group. In the current prospective trial, blood specimens of 65 patients with AJCC stage IIB-III cutaneous melanoma after surgery were periodically examined. In the above group, 27 % of subjects relapsed during the study. Prior to the disease progression we could observe a statistically significant tumor marker elevation in previous 0 to 9 months in all patients with clinical relapse. MAGE-3 became the most sensitive progression marker. During progression, three concordant positive markers were seen in 39 % of patients, followed by two concordant positive markers in 28 % and 1 marker in 33 %. This study supports the use of a multimarker real-time RT-PCR as a disease progression predictor. The dynamic assessment of serially obtained blood specimens represents a useful method for early metastasis detection and treatment response of melanoma patients.
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PMID:Early detection of melanoma progression by quantitative real-time RT-PCR analysis for multiple melanoma markers. 1838 26


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