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: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with malignant melanoma and distant metastases generally have an unfavorable prognosis, with a median survival of about 6 months. The mechanisms of hematogenous spread and implantation of melanoma cells are, however, poorly understood, because the standard diagnostic methods are not sensitive enough to detect oligocellular micrometastases. Recently a method using reverse transcription and polymerase chain reaction to determine tyrosinase mRNA in peripheral blood, which indicates the presence of circulating melanoma cells, has been developed. We utilized this assay to examine blood samples of 56 patients with malignant melanoma in different stages of disease. In one of 10 patients in stage I (localized disease) and in six of 17 patients with regional lymph nodes metastases (stage II) tyrosinase mRNA was detected. Tyrosinase transcripts were found in all 29 patients with distant metastases (stage III). Interestingly, tyrosinase mRNA was also detected in six patients with metastatic amelanotic malignant melanoma. In contrast, tyrosinase mRNA was not detectable in any of 39 healthy subjects or 17 patients with other malignancies. These findings may be helpful to define a patient group at high risk for systemic spread of disease.
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PMID:Hematogenous spread of malignant melanoma cells in different stages of disease. 824 18

The beta chain of human chorionic gonadotropin (hCG) hormone is produced by fetal cells, gonadal cell tumors and several types of non-gonadal carcinoma. hCG is composed of an alpha and a beta chain, the latter of which can be used to distinguish the molecule from other related gonadotropin hormones. Detection of beta-hCG mRNA transcripts can be potentially useful as a marker to identify tumor cells. We devised a highly specific and sensitive assay to detect the atavistic expression of beta-hCG in cutaneous melanoma by RT-PCR. Twenty-four melanoma cell lines and 43 melanoma biopsies were evaluated for beta-hCG mRNA expression. An RT-PCR assay was developed to specifically distinguish beta-hCG poly-A mRNA from other related gonadotropin beta chains. This was performed by endonuclease digestion of a unique Sty 1 site in the beta chain, followed by Southern blot analysis with a beta-hCG cDNA probe. Of the 24 melanoma cell lines analyzed, 18 expressed beta-hCG mRNA. Analysis of melanoma biopsy specimens revealed beta-hCG mRNA expression in 17/25 melanoma-positive TDLN, and in only 5/15 non-lymphoid melanoma metastases. Beta-hCG mRNA expression had a 53% correlation to tyrosinase mRNA, a predominant melanoma marker. Beta-hCG mRNA was not detected in normal donor PBL and normal lymph nodes. Detection of beta-hCG mRNA expression may be a useful molecular marker to define a subset of malignant melanoma.
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PMID:Detection of beta-human chorionic gonadotropin mRNA as a marker for cutaneous malignant melanoma. 862 Dec 27

Antigenic peptides derived from differentiation antigens of the melanocyte lineage were recently identified in human melanomas as targets for MHC-restricted cytotoxic T lymphocytes (CTL). CTL directed against peptides derived from the Melan A/MART-1, tyrosinase and gp100/Pmel17 antigens can be detected in melanoma patients and in healthy controls. The presence of defined antigenic peptides and corresponding precursor CTL in patients with metastatic melanoma opens perspectives for the development of antigen-specific tumor vaccines. In this study, we examined the expression of Melan A/MART-1, tyrosinase and gp100lPmel17 in fresh melanoma tissues of HLA-A2+ patients and the spontaneous CTL reactivity against antigenic peptides derived from these antigens. Our results demonstrate an inverse correlation of antigen expression and CTL response to Melan A/MART-1 and tyrosinase in patients with metastatic melanoma. In 2 patients with advanced disease, CTL responses against Melan A/MART-1 and tyrosinase were induced by intradermal immunization with synthetic nona- or deca-peptides derived from these antigens. Metastases increasing in size over time showed a loss of Melan A/MART-1 expression in the presence of CTL in one patient. The regression of a metastasis with persistent tyrosinase expression was observed in the other patient after the induction of CTL, reactive against tyrosinase. We conclude that CTL responses against melanocyte differentiation antigens may mediate regression of antigen-positive tumors and select for antigen-loss variants in vivo.
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PMID:Inverse relationship of melanocyte differentiation antigen expression in melanoma tissues and CD8+ cytotoxic-T-cell responses: evidence for immunoselection of antigen-loss variants in vivo. 863 62

Tyrosinase mRNA produced by melanoma cells can be detected by reverse transcriptase-polymerase chain reaction (rt-pcr) with fine-needle tissue punctures. Fine-needle punctures from six suspected skin and lymph node metastases in three patients with malignant melanoma were analysed via rt-pcr for tyrosinase mRNA. All the suspected metastases were surgically removed and histologically examined separately. In each case the rt-pcr results and the histological diagnosis corresponded. This less invasive and highly sensitive method could prove to be a useful alternative in the diagnosis of melanoma metastasis.
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PMID:[Detection of tyrosinase mRNA using reverse transcription/polymerase chain reaction with fine needle punctures of melanoma metastases]. 864 2

We applied an enzyme-linked immunospot (ELISPOT) assay for the detection and quantification of blood-derived CD8+ T cells recognizing peptide antigens presented by HLA-A2.1. CD8+ T lymphocytes were isolated from peripheral blood and were stimulated for 40 h with peptide-loaded A2.1-positive 0.174 x CEM.T2 cells. Tumor necrosis factor alpha (TNF-alpha) secreted by single T cells in response to antigen contact was trapped on nitrocellulose membranes precoated with anti-TNF-alpha antibodies and was then immunochemically visualized as spots. With this assay, up to 25% of cloned cytolytic T lymphocytes (CTL) were detected during the test period that recognized defined melanoma antigens in association with HLA-A2.1. CD8+ lymphocytes responsive to a known immunogenic HLA-A2.1-binding peptide from reverse transcriptase of the human immunodeficiency virus (HIV) were only detectable in HIV-infected patients, but not in anti-HIV-negative donors. T cells reacting with a peptide derived from a mutated cyclin-dependent kinase 4 (CDK4-R24C) were exclusively detected among CD8+ lymphocytes isolated from blood of the patient, whose melanoma had previously been found to carry the CDK4-R24C allele. T cells responding to HLA-A2.1-associated peptides of normal melanocyte differentiation antigens tyrosinase and Melan-A/MART-1 were found at low frequencies in almost all donors tested, which might reflect a natural autoimmunity to these antigens. However, in a melanoma patient we found a few days after surgery of melanoma metastases high frequencies of T cells against Melan-A/MART-1 and tyrosinase peptides (up to 38 per 10(5) CD8+ T cells), which gradually decreased during the following months. In an HIV-infected patient with progressive disease we observed a loss of T cells reactive with the HIV reverse transcriptase peptide. These observations provide evidence that peptide-dependent TNF-alpha spot formation in vitro resulted from previous antigen exposure in vivo. Therefore, the TNF-alpha ELISPOT assay might be useful in monitoring antigen-specific T lymphocyte responses during the natural course of diseases as well as during therapeutic interventions aiming at the induction of protective T cell immunity. In addition, it might help to identify immunodominant T cell epitopes.
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PMID:Detection and quantification of blood-derived CD8+ T lymphocytes secreting tumor necrosis factor alpha in response to HLA-A2.1-binding melanoma and viral peptide antigens. 866 32

Incidence and mortality of human malignant melanoma has risen rapidly over recent decades. Although the notorious resistance to treatment is characteristic for metastatic malignant melanoma, only a few experimental models have been established to study the metastatic cascade or to test new alternative treatment modalities. Thus, new human models are wanted. Here, we describe the metastatic behaviour of seven human melanoma cell lines derived from two primary cutaneous melanomas (WM 98-1, WM 1341) and five metastases established from liver (UKRV-Mel-4), skin (M7, M13), pleural effusion (UKRV-Mel-2) and lymph node (MV3). All cell lines were analysed for their capacity to grow in nude mice after s.c. and i.v. administration. M13 cells developed liver metastases spontaneously after s.c. injection, and subsequent passages of M13 and M7 melanoma cells caused liver metastases after i.v. injection, whereas MV3 and WM98-1 gave rise to lung metastases, using the same inoculation route. In contrast, WM 1341, UKRV-Mel-2 and UKRV-Mel-4 grew only very slowly in nude mice after s.c. injection and did not cause any metastases after i.v. or s.c. administration. The pattern of metastases or growth kinetics did not correlate with the interleukin 8 or tumour necrosis factor secretion of cell lines. Adhesion molecules and growth factor receptor expression on the cell lines differed widely, as determined by flow cytometry, with the low metastatic cell lines (UKRV-Mel-2, UKRV-Mel-4 and WM 1341) demonstrating a marked reduction in VLA-1 and VLA-5 expression compared with the metastatic lines (M7, M13, MV3 and WM 98-1). Expression of pigment-related proteins such as tyrosinase, TRP-1, TRP-2, Melan-A/MART-1, gp100, MAGE1 or MAGE-3 was not associated with growth and metastatic characteristics of the melanoma cell lines analysed. In conclusion, the established human melanoma cell lines exhibited diverse growth behaviour in nude mice in congruence with some early established prognostic markers such as VLA-1 and VLA-5. The xenografts provide good models for further study of metastatic processes as well as for evaluation of alternative treatment modalities including new pharmaceutical drugs and gene therapeutic targeting using tissue-specific gene regulatory elements for gene targeting.
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PMID:Metastatic potential of human melanoma cells in nude mice--characterisation of phenotype, cytokine secretion and tumour-associated antigens. 868 21

Anti-tyrosinase antibodies were measured by enzyme-linked immunosorbent assay in sera of patients with malignant melanoma with either metastatic disease or no evidence of disease, in patients with melanoma and associated hypopigmentation (MAH), in patients with vitiligo and in healthy volunteers. The mean relative absorbance (Arel) was calculated by dividing the absorbance of each sample by the mean value for the control group. Using this method, the Arel of the control group was 1.000(SE 0.083). Arel of patients with metastatic disease (1.516; SE 0.225) was significantly higher (P = 0.03) than the value for the controls, but insignificantly higher than that for patients with no evidence of disease (1.216; SE 0.148). Patients with no evidence of disease, in whom the primary lesion originated in the lower limb, had a significantly higher (P = 0.01) Arel than the healthy volunteers. Patients with metastatic disease showed higher Arel if their primary lesions were confined to the area of the head and neck or to the lower limb. Patients with vitiligo had higher Arel values for their anti-tyrosinase antibody than any of the other groups. However, those with melanoma and MAH (vitiligo-like) had the same Arel of anti-tyrosinase antibodies as the controls or the patients with metastatic melanoma. This observation reflected the possible absorption of anti-tyrosinase antibodies to melanoma antigens, and pointed to the participation of anti-tyrosinase antibodies in the destruction of normal melanocytes in patients with melanoma, as part of the immune reaction towards this disease.
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PMID:Anti-tyrosinase antibodies in malignant melanoma. 870 52

The treatment of unresectable hepatic metastases has generally been limited to systemic or intra-arterial chemotherapy. Cryosurgery has the advantage of potentially ablating such unresectable tumours. From November 1987 to August 1994, 140 patients underwent 155 procedures using hepatic cryosurgery with and without resection for documented metastatic disease. Intra-operative ultrasound was used for monitoring the freezing zone. The tumours were frozen using liquid nitrogen cooled to -196 degrees C for 15 min. The median number of lesions treated was three. Median hospital stay was 10 days. The operative mortality was 4%. Complications included coagulopathy, hypothermia, myoglobinuria, pleural effusions, ATN and infection. The median survival for all patients was 22 months. Of those patients followed for more than 2 years, the median survival was 25 months. Of the 65 patients that are still alive, the median follow-up is 27 months.
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PMID:Hepatic cryosurgery in the treatment of unresectable metastases. 885 24

Reverse transcription (RT) of the tyrosinase mRNA and specific cDNA amplification by nested polymerase chain reactin (PCR) have been reported to facilitate the early detection of circulating tumor cells in melanoma patients. The significance and practical value of this procedure for the diagnosis of tumor dissemination in melanoma patients are unclear. In the current study we analyzed peripheral blood samples of 65 melanoma patients of different clinical stages for the presence of tyrosinase mRNA by RT-PCR using nested oligonucleotide primers specific for tyrosinase cDNA. Furthermore, blood samples were evaluated for tumor cell growth by cell culture assays in vitro. No tyrosinase mRNA was detectable in blood samples of 26 patients with primary melanoma and 16 patients with regional lymph node metastases. In five of 13 patients with visceral metastases we found at least one blood sample positive for tyrosinase mRNA during a 2-to 4-mo interval. Analyses of different blood samples of patients with visceral metastases taken in a 2-h interval, furthermore, indicate that tumor cells only transiently persist in the peripheral blood. We obtained in vitro proliferating melanoma cells from two blood samples derived from different patients with visceral melanoma metastases. This demonstrates that viable melanoma cells indeed circulate in the peripheral blood with retained proliferative capacity in vitro. The analysis of blood samples by RT-PCR for tyrosinase mRNA, however, is not suitable for the early detection of tumor progression in melanoma patients.
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PMID:The analysis of tyrosinase-specific mRNA in blood samples of melanoma patients by RT-PCR is not a useful test for metastatic tumor progression. 900 29

While not all circulating tumor cells survive, one could postulate that patients with circulating tumor cells might be candidates for adjuvant chemotherapy because of the risk of relapse. Recently, reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of circulating tumor cells has been suggested as a potential technique for staging of cancer. In malignant melanoma, the detection of circulating melanoma cells by tyrosinase RT-PCR correlated with the clinical stage of patients and was an independent prognostic factor for recurrence. A strong association was found between the detection of neuroblastoma cells in circulation by tyrosine hydroxylase RT-PCR with bone marrow micrometastasis. This method may be of use to identify early signs of relapse in disease-free patients. In prostatic cancer, the frequency of positivity for detection of circulating tumor cells in peripheral blood by PSA RT-PCR increased with tumor stages but a significant proportion of patients with metastatic disease were negative. The prognostic significance of the detection of tumor cell in blood in other epithelial tumors is not established and will require further long-term follow-up study.
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PMID:[Molecular diagnostic detection of circulating tumor cells and their prognostic implications]. 905 Nov 25


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