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)

Ocular melanoma is the most common malignant tumor of the eye and accounts for 70 to 80 percent of all extracutaneous melanomas. Its biologic behavior differs from that of its cutaneous counterpart. To elucidate this, 62 patients with histologically proven melanoma of eye (58 uveal tract and 4 conjuntiva) at Roswell Park Memorial Institute from 1945 to 1977 were studied. The prominent contradistinctions from other head and neck melanomas were (1) a very high percentage of patients had either locally advanced or systemic disease at diagnosis, although the eye is the most sensitive organ; (2) regional lymph node involvement was absent even in the late stages of disease; (3) hematogenous spread involved single organs, most commonly the liver and the lung; (4) local recurrence was rare; (5) most recurrences occurred evenly in first 10 years after treatment; (6) regional resection, chemotherapy or both are advocated for distant metastases since they are confined to a single organ and are amenable to it; and (7) despite hematogenous spread and advanced disease at diagnosis, the overall prognosis of ocular melanoma is comparable to that of cutaneous melanoma.
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PMID:Biologic behavior of ocular malignant melanoma and comparison with melanoma of the head and neck. 742 36

A series of 206 patients with cutaneous melanoma of the head and neck has been studied. Ninety patients had a regional lymph node dissections performed. Seventeen lymph node dissections were done therapeutically and 73 were done electively. Thirty-one patients had histologically positive lymph nodes and, of these, 30 patients have been followed to the present time or death. Twenty-nine of these patients (97%) have developed systemic melanoma. Twenty-six patients have died and three are alive with disease. No patient had local recurrence alone while four had local recurrence synchronously with systemic metastases. This contrasts with 29 patients followed for greater than five years with histologically negative nodes, 27 (93.1%) of whom are alive with no evidence of recurrent disease. Regional node metastases with melanoma of the head and neck is an almost certain indication of systemic disease. A selective surgical approach to invasive melanoma in this region is proposed based on the observation in the 31 patients who had radical neck dissections with histologically positive nodes. The metastases always involved the nodal group adjacent to the primary site. This selective approach should allow optimal local control and accurate pathologic staging while limiting the extent of the surgery.
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PMID:Selective surgical management of cutaneous melanoma of the head and neck. 743 92

Difficulties in obtaining clinical samples from primary melanomas have meant that most genetic analyses of melanoma have concentrated on cell lines and metastases. Because the Breslow thickness of the primary tumour is the single best prognostic indicator, it is important to identify genetic abnormalities in primary melanomas and relate these changes to the thickness of the lesion. We have investigated 47 sporadic melanomas, of which 41 were primary lesions, for loss of heterozygosity (LOH) on several chromosomal arms, including areas where genes involved in familial melanoma and other relevant hereditary syndromes map, and where LOH has previously been reported in cell lines, or metastatic lesions. LOH was identified at 66 (18%) of 358 informative loci in primary melanomas, and there was a significant relationship between the overall frequency of LOH and Breslow thickness (P < 0.0005). Loss of chromosome arm 9p was most frequent, occurring in 15 (47%) of 32 informative primary tumours, and was observed in 3 of 11 informative lesions < or = 1.5 mm in depth. LOH on chromosome arms 3p, 6q, 10q, 11q, and 17p was also relatively frequent, with loss of 3p and 10q heterozygosity in lesions < or = 1.5 mm in depth, while LOH on 6q, 11q, and 17p was only detected in more invasive tumours. The results suggest that loss of these chromosome regions are important in sporadic cutaneous melanoma, and are consistent with chromosome arm 9p loss occurring before loss of other chromosome arms.
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PMID:Loss of heterozygosity in sporadic primary cutaneous melanoma. 753 89

Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastasis formation in a number of different animal and human cancers. Because human cutaneous melanoma is among the most aggressive human cancers, we explored expression of CD44 isoforms (CD44v) in lesions of melanocytic tumor progression. In addition, by RT-PCR and FACS analysis we assessed CD44v RNA species and cell surface expression of CD44v in cultured melanocytes isolated from human foreskin and in a panel of 2 non-, 2 sporadically and 2 highly metastatic human melanoma cell lines. We observed that all melanocytic lesions examined showed strong uniform expression of standard CD44 (CD44s) epitopes. We did not detect CD44v6 expression in the melanocytic lesions. However, CD44 isoforms containing v5 or v10 were differentially expressed. V5 was expressed in 16%, 0%, 20%, 67% and 58% of common nevi, atypical nevi, early primary melanomas (< or = 1.5 mm), advanced primary melanomas (> 1.5 mm) and metastases, respectively, and hence was related to tumor progression. In contrast, CD44v10 was expressed in all common nevi, whereas part of the atypical nevi and most primary melanomas and metastases lacked v10. CD44v RNA patterns were closely similar in cultured melanocytes and all melanoma cell lines. Melanocytes expressed high levels of CD44s but no CD44v, whereas all melanoma cell lines expressed CD44v at the surface. Interestingly, expression of v5 was strongly increased in the highly metastatic cell lines. Our results suggest a role for CD44 variant domains, particularly v5 and v10, in human melanocytic tumor progression.
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PMID:Expression of CD44 splice variants in human cutaneous melanoma and melanoma cell lines is related to tumor progression and metastatic potential. 754 41

Human genes MAGE-1 and MAGE-3 code for antigens that are recognized on melanoma cells by autologous cytolytic T lymphocytes. These antigens may constitute useful targets for specific anti-tumor immunization of cancer patients, since genes MAGE-1 and MAGE-3 are expressed in a number of tumors of different histological types, but are not expressed in normal adult tissues other than testis. This also applies to genes MAGE-2 and MAGE-4, which are closely related to MAGE-1 and MAGE-3. We have analyzed the expression of these 4 MAGE genes in cutaneous melanoma. Sixteen of 100 primary tumors vs. 69 (48%) of 145 metastases from individual patients expressed MAGE-1. Similar differences in the frequency of gene expression between primary and metastatic tumor samples were observed for MAGE-2, MAGE-3, and MAGE-4. MAGE expression in primary tumors was correlated with tumor thickness: there was a significantly increased frequency in the expression of MAGE-1, -2 and -3 in tumors of greater thickness. Benign and dysplastic nevi, as well as in situ melanomas, did not express any of the 4 MAGE genes.
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PMID:Expression of MAGE genes in primary and metastatic cutaneous melanoma. 759 Dec 35

Cytokines have been tested in the treatment of different skin cancers during the last decade, and treatment schedules have been established or proposed for several malignant skin tumors. Preferentially, the interferons and interleukin-2 were found to be effective in treating skin cancers. Interferons alpha and beta have been approved for the treatment of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma, cutaneous T cell lymphoma, and malignant melanoma in several countries. Interferon alpha was found to be most effective in cutaneous T cell lymphoma with 40%-60% overall responses. When combining interferon alpha with psoralens and ultraviolet A (PUVA) or with retinoids, even higher response rates up to 60%-90% were reported, and long-term remissions have been described. A considerable activity of interferon alpha was found in HIV-associated Kaposi's sarcoma with response rates of 30%-50%. The effectiveness of Kaposi's sarcoma's treatment was further improved by combining interferon alpha and zidovudine. Responses to interferon alpha in metastatic malignant melanoma are rather seldom (10%-15%), but a stabilization of the disease with prolonged survival was reported after interferon alpha treatment. Additionally, interleukin-2 was found to be active in metastatic melanoma, with overall response rates of about 20%, and both biological agents were found to have an additive efficacy in combination. Several combined regimens of interferon alpha, interleukin-2, and polychemotherapy have been described in metastatic melanoma, and overall response rates higher than 50% were found with these combined treatment modalities. Interferon alpha and beta were also intralesionally injected into basal cell carcinomas and other epithelial skin cancers, and complete responses were found in more than 80% of tumors treated. Local applications of interferons and interleukin-2 were likewise found to be effective in the treatment of cutaneous melanoma metastases and cutaneous manifestations of Kaposi's sarcoma. Cytokines and their combination with other treatment modalities has greatly enriched the treatment facilities in malignant skin tumors during recent years, and additional new cytokines will be introduced in skin cancer treatment in near future.
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PMID:Perspectives of cytokine treatment in malignant skin tumors. 759 3

Between January 1956 and December 1990, 17 patients younger than 17 years with available pathological screens of de novo cutaneous melanoma, and with no other risk factors (xeroderma pigmentosum, giant congenital naevi, congenital melanoma or a proven family history of dysplastic naevus syndrome) were seen at the Gustave-Roussy Institute. The median age was 9 years and 9 months (range 2 years and 3 months-16 years and 9 months). The primary disease was located in the lower extremities in 10 cases, the trunk in five cases, and the upper extremities or head and neck in one case. The disease was localized for 10 patients at presentation (stage I), six had proven nodal metastasis (stage II) and one patient had nodal and breast metastases. The median thickness of the primary lesion was 2.89 mm (range 0.64-10). Five tumours were at level III on Clark's index, eight at level IV and four at level V. Six cases were classified as superficial spreading, two as unclassified radial growth, three nodular, three with Spitzoid cells, and three were unclassified. Two patients presented local recurrence with an initial unclassified melanoma, with a thickness greater than 2.5 mm. At a median follow-up time of 7 years, two patients had died from recurrent disease, and one patient had died from a second malignancy.
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PMID:Melanoma arising de novo in childhood: experience of the Gustave-Roussy Institute. 762 Mar 39

The production and local release of various proteolytic enzymes, either by tumor cells or tumor-associated stromal cells, is thought to facilitate the malignant behavior of solid tumors. Human cutaneous melanoma offers an excellent clinical model to study the possible contribution of such proteases to solid tumor progression because melanoma goes through a series of well defined stages in its pathogenesis; moreover, permanent cell lines have been established from these various stages. As a first step to analyzing the gelatinolytic enzymes in melanoma pathology, we examined cell lines derived from early stage primary melanomas in which patients were cured of their disease and compared the results to those obtained with cell lines established from advanced stage primary lesions or metastases (i.e., from patients who eventually succumbed to the disease). We found that 80% of cell lines examined from early stage lesions constitutively produced only the 72-kDa gelatinase A but never the 92-kDa gelatinase B. In contrast, the majority of advanced stage cell lines examined produced both the 72-kDa gelatinase A and the 92-kDa gelatinase B. Advanced stage cell lines that did not constitutively produce the 92-kDa gelatinase B could be induced to do so with transforming growth factor beta, interleukin 1 beta or 12-O-tetradecanoyl-phorbol-13-acetate. In total, 0 of 5 early stage cell lines constitutively expressed the 92-kDa gelatinase B, and only 2 of 5 could be induced to produce this activity. In contrast, all advanced stage cell lines that were evaluated either constitutively or inducibly produced the 92-kDa gelatinase B. To analyze the mechanism by which 92-kDa gelatinase B production is switched on in the advanced stage melanoma cell lines, somatic cell hybrids were constructed using an advanced stage melanoma cell line as one partner and either one of two early stage cell lines as the other. Constitutive production of the 92-kDa gelatinase B in such hybrids was lost and could not be induced in such hybrids. Coculture of the early and advanced stage cell lines failed to recapitulate what was seen after somatic hybridization, and zymographic analysis of lysates from hybrid cell lines demonstrated no 92-kDa gelatinase B activity. Reverse transcription-PCR analysis demonstrated that the loss of 92-kDa gelatinase B production occurred at the level of steady-state mRNA for the enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The 92-kDa gelatinase B is expressed by advanced stage melanoma cells: suppression by somatic cell hybridization with early stage melanoma cells. 766 94

CD63 has been identified in human melanoma cells by a number of different monoclonal antibodies (MAbs). Studies with MAbs have shown that expression is most marked in naevi and early forms of cutaneous melanoma and reduced in vertical growth phase and metastatic lesions. To investigate further the role of CD63 in progression of melanoma, genomic CD63 was transfected into a CD63-negative human melanoma cell line using an episomal vector. The stable transfected melanoma cells had similar growth rates to control transfected melanoma cells in vitro but much lower growth rates when injected intradermally into athymic nude mice. The CD63-transfected cells also had a reduced number of metastases in the peritoneal cavity and subcutaneous sites when injected intravenously. MAb against CD63 did not influence the growth of CD63-transfected melanoma cells in vitro. Our results confirm previous studies using H-ras-transformed NIH3T3 fibroblasts and suggest that CD63 may have a role as a tumor suppressor gene in human melanoma that acts to limit invasion and progression of melanoma.
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PMID:Suppression of human melanoma cell growth and metastasis by the melanoma-associated antigen CD63 (ME491). 766 37

A hypothesis is presented to explain the apparent difference in the radioresponsiveness of melanoma lesions whether they are located on the skin or in other parts of the body. The hypothesis states that the radiosensitivity of a cell may change when the cell adapts to live and grow in a different environment. The most important environmental factor that affects the radiosensitivity of cutaneous melanoma cells appears to be the partial pressure of oxygen in their immediate environment. By virtue of adapting to grow in an environment having a high partial pressure of oxygen, the melanoma cells located on the skin may have developed a better antioxidant defense mechanism than cells that metastasize to, and grow in, other parts of the body having lower partial pressures of oxygen such as lymph nodes, brain and viscera. Because some of the cell-damaging effects of both oxygen and ionizing radiation are mediated through a similar mechanism, the melanoma cells on the skin become cross-resistant to ionizing radiation because of their higher tolerance to oxygen toxicity.
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PMID:Adaptation and cross-resistance: an explanation for the existence of different radiosensitivities among malignant melanoma cells. 777 7


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