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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reverse transcriptase polymerase chain reaction (RT-PCR)-based assays to detect occult neoplastic cells offer the highest sensitivity for the study of tumour dissemination and minimal residual disease. The detection of small numbers of tumour cells in a clinical sample may result in a redefinition of what constitutes residual disease and relapse, affecting future patient management. However, there remains disparity in the published data on the clinical value of RT-PCR for the detection of circulating tumour cells. This most likely reflects differences in the methods for sample preparation, RNA extraction, and cDNA synthesis among laboratories. Consequently the need for implementation of standard quality control measures is pressing in order to facilitate meaningful assessment of the methodology and it's clinical value. A 2-day workshop organized by the immunotherapy subgroup of the EORTC Melanoma Cooperative Group was held on this topic at the Ludwig Institute in Epalinges-sur-Lausanne, Switzerland in January 1996, with Stefan Carrel as the local host. Many pertinent issues were discussed in great detail, covering every step from sample handling to quality control. This workshop resulted in a concerted action leading to the preparation of laboratory guidelines, which are summarized in this review.
Melanoma Res 1997 Aug
PMID:Polymerase chain reaction detection of circulating tumour cells. EORTC Melanoma Cooperative Group, Immunotherapy Subgroup. 957 29

Conjunctival melanomas, which have a relatively good prognosis as compared to other mucosal melanomas, have been investigated morphologically and pathologically. We examined the gene expression of several cytokines in a patient with conjunctival melanoma and compared them to those of other pigment cells of the eye, because no reports have discussed cytokine expression in melanoma of the eye. Samples were collected from a 64-year-old woman with conjunctival melanoma and mRNAs were extracted and reverse-transcriptase polymerase chain reaction was performed. We found that potent inhibitors of tumor cell growth such as interleukin 2, 4, 6 and gamma-interferon were expressed in the tumor. These inhibitors were not expressed in other pigment cells of the eye, in blood, in conjunctival melanosis or in choroidal melanomas. The basic fibroblast growth factor gene, which has also been known to stimulate melanoma cell growth, was not expressed in the conjunctival melanoma, and it showed +/- or weak expression in choroidal melanomas, but it was expressed in the pigment cells in the eye and in conjunctival melanosis. Although only limited cytokine expression was examined here, these results may suggest an influence of these cytokines to the growth of conjunctival melanoma.
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PMID:Expression of cytokine genes in a patient with conjunctival melanoma compared with other pigment cells. 966 56

Circulating tumour cells in the peripheral blood may be important for haematogenous spread of malignant disease. Monitoring these cells may therefore be of prognostic value. Reverse transcriptase-polymerase chain reaction (RT-PCR)-based assays to detect occult neoplastic cells offer the highest sensitivity for the study of tumour dissemination and minimal residual disease. This review summarises technical considerations and clinical investigations in melanoma patients of various disease stages. The clinical data are promising, but to clearly define the clinical usefulness of messenger RNA (mRNA) tumour markers, methodological issues must be resolved and the clinical value must be assessed prospectively in sufficiently large patient cohorts.
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PMID:New prognostic factors in melanoma: mRNA tumour markers. 984 8

Telomerase is a ribonucleoprotein complex with reverse-transcriptase activity responsible for telomere reconstitution. High telomerase activity was found in cancer cells, but not in differentiated homologous nonmalignant tissues. We demonstrated previously that the disappearance of telomerase activity is a reliable marker of tumor cell killing in human cancer cell lines. We have investigated the possibility of evaluating chemosensitivity of neoplastic cells of different origin [ovary, lung, breast, gastrointestinal, skin (melanoma)] obtained from cancer patients, by measuring residual telomerase activity after drug treatment in vitro. Using the classical telomeric repeat amplification protocol ("TRAP") assay based on polymerase chain reaction, we examined telomerase activity of untreated or drug-treated tumor cell suspensions, derived from the processing of surgical specimens. Feasibility and reproducibility of the assay were evaluated according to various parameters, including drug concentration, time of in vitro culture, and type of tumor. The results indicated that the assay is highly sensitive and reproducible, and can be performed using surgical specimens in a reasonable percentage of cases, ranging from 40% (breast cancer) to 100% (ovarian cancer). Moreover, the assay provides comparable results using a wide range of tumor cells, and the presence of normal cells does not interfere with the results. Prolonged tumor cell culture is not required because the assay can be completed within 24 to 72 hours after sample collection. In conclusion, the present investigation provides the technical bases for future studies to evaluate whether this assay would be able to predict patient's response to antitumor agents.
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PMID:Suppression of telomerase activity as an indicator of drug-induced cytotoxicity against cancer cells: in vitro studies with fresh human tumor samples. 1046 37

1alpha,25-dihydroxyvitamin D(3) (VD) is a pleiotropic nuclear hormone that also has effects on cell cycle regulation. VD and its synthetic analogues are known inhibitors of cellular growth and inducers of apoptosis, however, the primary mediator genes of these effects largely remain unknown. In order to identify novel targets for VD, that may be involved in the regulation of the cell cycle, a differential display PCR (ddPCR) approach was applied to the MCF-7 human breast cancer cell line, which provided the gene for cyclin C as an interesting candidate. Quantitative assessment of cyclin C expression showed that the gene was significantly upregulated by VD and its analogues, EB1089 and CB1093 both on the level of mRNA expression and more so on the level of protein expression in MCF-7 cells. Upregulation of cyclin C protein expression could also be confirmed in MeWo human melanoma and in U937 human promyelocytic leukemia cells. This observation adds a new gene candidate to the list of primary VD responding genes. Cyclin C is not a typical cyclin, as it apparently modulates the activity of the RNA polymerase II complex, which provides fresh insight into the mechanisms of cell cycle and general transcriptional regulation by VD and its analogues.
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PMID:Cyclin C is a primary 1alpha,25-dihydroxyvitamin D(3) responding gene. 1067 18

Histamine has been implicated as one of the mediators involved in regulation of proliferation in both normal and neoplastic tissues. Histidine decarboxylase, the only enzyme that catalyzes the formation of histamine from L-histidine, is an essential regulator of histamine levels. In this study, we investigated the gene and protein expression of histidine decarboxylase in melanoma. Reverse transcriptase polymerase chain reaction and in situ hybridization studies of WM-35, WM-983/B, HT-168, and M1 human melanoma cell lines both resulted in positive signals for histidine decarboxylase messenger RNA. A polyclonal chicken antibody was developed against human histidine decarboxylase and protein expression was confirmed by western blot analysis of the cell lysates, revealing a predominant immunoreactive band at approximately 54 kDa corresponding to monomeric histidine decarboxylase. Protein expression of histidine decarboxylase was also shown by flow cytometric analysis and strong punctate cytoplasmic staining of melanoma cell lines. Moreover, both primary and metastatic human melanoma tissues were brightly stained for histidine decarboxylase. When compared with the very weak or no reactions on cultivated human melanocytes both western blot and immunohistochemical studies showed much stronger histidine decarboxylase expression in melanoma cells. These findings suggest that expression of histidine decarboxylase is elevated in human melanoma.
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PMID:Histidine decarboxylase expression in human melanoma. 1095 Dec 67

The circadian clock is a cellular machine composed of proteins with regulated expression that gives rise to circadian rhythms. Two main new concepts have arisen from recent research in the field in the last few years: (i) at least three to five key genes are involved in maintaining the basic circadian cellular rhythms, and (ii) their expression is fairly ubiquitous, extending beyond the traditionally considered pacemaker in mammals, the suprachiasmatic nucleus. We have demonstrated the expression of two circadian clock genes, clock and period1, in human skin cells. Reverse transcriptase polymerase chain reaction revealed the presence of clock and period1 mRNA in cultured human keratinocytes, melanocytes, and dermal fibroblasts, as well as in the human keratinocyte cell line HaCaT and the human melanoma line A375. In addition, antibodies to these two proteins produced immuno-positive staining in these cell types. Our investigations demonstrate for the first time that skin cells express circadian clock proteins constitutively although regulation of their expression and activity has not been elucidated. These proteins may have a role in cutaneous and/or systemic circadian biology and the skin and skin cells may provide an attractive model for the study of circadian rhythms.
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PMID:Expression of the circadian clock genes clock and period1 in human skin. 1099 56

Reverse-transcriptase polymerase chain reaction (RT-PCR) with multiple markers has been demonstrated to be highly sensitive in detecting metastatic cells in peripheral blood of malignant melanoma (MM) patients, and the circulating MM cells to be significantly correlated with disease stages. We further evaluated the presence of specific PCR-positive mRNA markers in peripheral blood as well as in regional nodes as an expression of tumor progression. Peripheral blood samples from 317 MM patients with either localized (n = 219) or metastatic (n = 98) disease were processed to obtain total cellular RNA. RT-PCR was performed using tyrosinase (TYR), p97, and MelanA/MART1 as mRNA markers. PCR products were analyzed by gel electrophoresis and Southern blot hybridization. In addition, paraffin-embedded samples of histologically proven tumor-negative lymph nodes from the subset of patients with localized disease were analyzed by RT-PCR, using radiolabeled primers for TYR and MelanA/MART1. The presence of mRNA markers was significantly correlated with tumor burden with a good correlation between risk of recurrence (evaluated in stage I-III patients) and increasing number of PCR-positive markers (p = 0.0002). Currently, for each patient, PCR results obtained at different times during follow-up are being analyzed, and any variation in the number of PCR-positive markers is being correlated to the clinical status. Molecular screening of histologically negative nodes for the presence of metastatic MM cells is also under evaluation. Preliminary assessment of a subset of MM patients with higher risk of recurrence will require longer follow-up in order to define the role of RT-PCR in monitoring these patients.
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PMID:Clinical significance of PCR-positive mRNA markers in peripheral blood and regional nodes of malignant melanoma patients. Melanoma Cooperative Group. 1109 47

The vascular endothelial growth factor is produced by a large variety of human tumors, including melanoma, in which it appears to play an important role in the process of tumor-induced angiogenesis. Little information is available on the role of placenta growth factor, a member of the vascular endothelial growth factor family of cytokines, in tumor angiogenesis, even though placenta growth factor/vascular endothelial growth factor heterodimers have been recently isolated from tumor cells. To investigate the role of placenta growth factor and vascular endothelial growth factor homodimers and heterodimers in melanoma angiogenesis and growth, 19 human melanoma cell lines derived from primary or metastatic tumors were characterized for the expression of these cytokines and their receptors. Release of placenta growth factor and vascular endothelial growth factor polypeptides into the supernatant of human melanoma cells was demonstrated. Reverse transcriptase polymerase chain reaction analysis showed the presence of mRNAs encoding at least three different vascular endothelial growth factor isoforms (VEGF(121), VEGF(165), and VEGF(189)) and transcripts for two placenta growth factor isoforms (PlGF-1 and PlGF-2) in human melanoma cells. In addition, placenta growth factor expression in human melanoma in vivo was detected by immunohistochemical staining of tumor specimens. Both primary and metastatic melanoma cells were found to express the mRNAs encoding for vascular endothelial growth factor and placenta growth factor receptors (KDR, Flt-1, neuropilin-1, and neuropilin-2), and exposure of melanoma cells to these cytokines resulted in a specific proliferative response, supporting the hypothesis of a role of these angiogenic factors in melanoma growth. J Invest Dermatol 115:1000-1007 2000
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PMID:Human melanoma cells secrete and respond to placenta growth factor and vascular endothelial growth factor. 1112 Nov 33

Dendritic cell (DC)-mediated cancer immunotherapy is a very promising alternative approach to cancer treatment. In a previous study, we successfully transfected bone marrow-derived dendritic progenitors (BMDDPs) with a T7 vector--a nonviral, cytoplasmic-based autogene expression system--encoding a model tumor antigen, firefly luciferase, and subsequently stimulated the transfected cells to differentiate into DCs. When injected into experimental mice, those DCs generated a strong immune response against tumor cells bearing luciferase, which not only prevented occurrence of metastasis but also eradicated existing tumors. In the present study, we constructed a T7 vector encoding mouse tyrosinase, a well--known melanoma associated tumor antigen, and used it to transfect BMDDPs. Reverse transcriptase polymerase chain reaction and Western analysis confirmed the expression of tyrosinase by DCs differentiated from transfected BMDDPs. Two immunizations of these DCs at a dose of 2 x 10(6) of each successfully prevented tumor growth. More importantly, one injection of 2 x 10(6) of these DCs into mice followed by five doses of recombinant human interleukin-2 administration effectively eradicated existing tumors as indicated by pulmonary metastasis assay.
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PMID:Murine tyrosinase expressed by a T7 vector in bone marrow-derived dendritic progenitors effectively prevents and eradicates melanoma tumors in mice. 1112 87


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