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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four melanin pigment-containing intracranial tumors were found in three Long-Evans rats in the course of experimental oncogenesis by transplacental ethylnitrosourea (ENU). One of them was a leptomeningeal melanoma. Aside from the presence of scattered melanin-pigmented cells, the other three had the typical histological features of ENU-induced malignant nerve sheath tumors. Two of the three tumors were studied by electron microscopy and in tissue and organ culture systems. One of them demonstrated progressive melanogenesis in vitro; the other failed to produce more melanin and showed increasing differentiation, with a Schwannoma-like pattern by light microscopy. Melanosomes and premelanosomes were identified in both tumors by electron microscopy; the other fine structural features were those of malignant Schwannomas. These observations are relevant to the controversy on the histogenesis of pigmented nerve sheath tumors occasionally encountered in man and on the relationship of these tumors to pigmented nevi. The findings in the present study support the view of Masson that neoplastic nerve sheath cells are capable of melanogenesis.
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PMID:Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. III. Melanin pigment and melanogenesis in experimental neurogenic tumors: a reappraisal of the histogenesis of pigmented nerve sheath tumors. 127 30

Sunlight, particularly its UVB component, is thought to be the most important environmental factor for oncogenesis of melanoma. Its intensity, at the ground level, is a positive function of altitude and a negative function of latitude. Sun exposure and susceptibility in childhood seem to be major risk factors at least in Anglo-saxon countries. UV radiations are able to act as complete carcinogen. Eumelanin/pheomelanin ratio also appears as an important risk factor. Ionizing radiations, heat and traumas have been seldom related to melanoma carcinogenesis. Several chemicals, among them drugs and toxic drugs, add to the list of possible causative agents. Loss of alleles encoding for suppressor factors, caused by UV radiation, might play a significant role in carcinogenesis. A model is proposed, for "mediterranean" vs "caledonian" melanoma, in which the phenotypic sequence melanocytic nevus----melanoma would exhibit peculiar characteristics.
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PMID:[Etiopathogenesis of malignant melanoma of the skin. III. Disease factors inherent in the environment. Pathogenetic hypothesis]. 219 29

Recently it has been suggested that proto-oncogene plays a role not only in cellular proliferation, development and differentiation, but also in neoplastic transformation. We now show the expression and its localization of c-myc, c-fms and c-sis proto-oncogenes in human developing chorionic tissue and fresh surgical specimens of mole and choriocarcinoma with the method of Northern blotting and In-situ hybridization. The 2.4kb c-myc transcript has been localized to the cytotrophoblast in early placenta and also localized to the C and S typed trophoblastic cells in mole and choriocarcinoma. The 4.0kb c-fms transcript has been localized to the syncytiotrophoblast, especially the highly differentiated syncytiotrophoblast in the second and third trimesters and S typed trophoblastic cells in mole and choriocarcinoma. Moreover, the 4.0kb c-sis transcript has been localized to the cytotrophoblast in early placenta, but not detected in mole or choriocarcinoma. First, these results suggest that the stage and site specific expression of c-myc, c-fms and c-sis proto-oncogenes are clearly related to the proliferation, development and differentiation of normal trophoblastic cells. Second, the expression of c-myc, c-fms proto-oncogenes may be of particular importance in the tumorigenesis and progression of trophoblastic disease.
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PMID:[The expression of c-myc, c-fms, c-sis oncogenes in the trophoblast of normal pregnancy and trophoblastic disease]. 285 Mar 28

Epidermal growth factor (EGF) receptor is expressed selectively by human melanoma cells which show the presence of an extra copy of chromosome 7. None of the cells of benign pigmented lesions (nevi) or radial growth phase (nonmetastatic) primary melanoma expressed EGF receptor and none of these cells showed an extra copy of chromosome 7. The results indicate that a single extra dose of a gene (for EGF receptor) may provide a selective advantage to cells in the late stages of tumorigenesis.
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PMID:Expression of the receptor for epidermal growth factor correlates with increased dosage of chromosome 7 in malignant melanoma. 298 38

The Tyr-SV40E transgenic mouse model of malignant skin melanoma has been used here to generate melanomas in genetically identical (C57BL/6) mice for analysis of the plasminogen activator (PA) system during tumor development and progression. Twenty-two melanocytic lesions were examined by in situ zymography for PA activity and by immunohistochemistry for concomitant visualization of PA proteins; these lesions encompassed 3 nevi and 19 primary melanomas ranging from melanotic through mixed tumors to amelanotic tumors. Although urokinase-type plasminogen activator (u-Pa) activity was not detected at premalignant stages, it began to appear early in tumorigenesis and became more prominent in later stages of a majority of the tumors. The activity was largely attributable to the endothelium of sprouting capillaries and to a lesser degree to granulocytes, fibroblastic cells, and occasional melanoma cells within tumors. Tissue-type plasminogen activator (t-PA) was undetectable or low in all cases. Of the inhibitors (PAI), PAI-1 was seen in endothelial and fibroblastic cells and in the extracellular matrix, whereas PAI-2 occurred in only one case and was melanoma cell associated. Eleven additional melanomas were analyzed by reverse transcription-PCR for PA expression in RNA extracts from relatively large tumor samples. These were obtained from eight primary melanomas and three metastases, again spanning melanotic, mixed, and amelanotic cases. From four of the mixed primary tumors with distinct melanotic and amelanotic zones, the respective components were propagated separately in transgenic hosts as s.c. transplants to obtain data for clearly identifiable melanotic versus amelanotic parts. u-PA and PAI-1 mRNAs were expressed in all. t-PA expression varied greatly and was notably high in several amelanotic tumors or tumor components, possibly as a result of large blood vessels, as such vessels were seen to be t-PA positive in normal tissue. The u-PA activity in sprouting capillaries may indicate a role in neoangiogenesis. Therefore, according to these mouse models, u-PA may indirectly be a potential therapeutic target against melanoma progression.
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PMID:Expression of plasminogen activators and plasminogen activator inhibitors in cutaneous melanomas of transgenic melanoma-susceptible mice. 755 49

The BCL-2 gene is the prototype of a newly described family of oncogenes involved in tumorigenesis by blocking apoptosis, or programmed cell death. Overexpression of BCL-2 protein was originally described in follicular B-cell lymphomas bearing the 14;18 translocation. BCL-2 overexpression has also been described in other lymphomas and more rarely in neoplasms outside the lymphoid tissue. The aim of this paper is to determine the immunohistochemical expression of BCL-2 in intradermal nevi and primary invasive and metastatic melanoma. Formalin-fixed and paraffin-embedded tissues from 4 cutaneous melanoma metastases, 10 primary invasive melanomas, and 10 intradermal melanocytic nevi were immunolabeled with monoclonal antibodies directed against BCL-2 protein (Dako, clone 124) and Ki-67 antigen (Amac, clone MIB-1), after antigen retrieval techniques. Morphologically normal epidermal melanocytes expressed BCL-2, as did nevi and melanomas in virtually all cells. However, whereas the labeling in normal melanocytes and nevus cells showed a uniformly strong reactivity, melanoma cells showed a variable but mainly weak reactivity. Ki-67 antigen expression was restricted to melanomas. The widespread expression of BCL-2 suggests that this oncoprotein cannot be involved in the malignant transformation of melanocytic cells. It seems likely that the decreased BCL-2 expression detected in melanomas may reflect one further step of tumor progression in melanocytic neoplasms.
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PMID:Immunohistochemical expression of BCL-2 in melanomas and intradermal nevi. 786 49

Studies on melanoma cell lines indicate the expression of actin-binding protein (ABP), a peripheral cytoplasmic protein that crosslinks actin, is important for melanoma cell motility. We used an ABP-specific monoclonal antibody to characterize ABP expression in 18 benign nevi and 28 primary and metastatic malignant melanomas. Heterogeneous expression of ABP staining was observed in metastatic melanoma. No clear differences in ABP staining were identified among compound nevi, dysplastic nevi, and superficial spreading melanoma; however, the lentiginous intraepidermal component of the benign and malignant lesions and the pagetoid cells of superficial spreading malignant melanoma were negative for ABP. In contrast, the nested intraepidermal and dermal components of both benign nevi and primary malignant melanoma were positive. The differential expression of ABP of the lentiginous component as opposed to the intraepidermal nests and pagetoid cells of benign nevi or melanoma may represent a capacity of the nested melanocytes to migrate from the epidermis to the dermis during maturation or invasion. Taken together, the findings support that ABP may be important for cell-cell adhesion during tumorigenesis and may play a role in tumor cell ameboid motility during tissue invasion.
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PMID:Actin-binding protein expression in benign and malignant melanocytic proliferations. 786 58

In the human epidermis, melanocytes are distributed at a distance from each other. In contrast, melanocytes in nevi, which are considered benign neoplasms of melanocytes, are grouped in nests. Although still not well defined, environmental factors are thought to play an important role in the development of nevi. We found that chronic growth stimulation by leukotriene C4, a compound found in increased amounts in inflamed skin, induced pleiotropic modifications in the normal melanocyte phenotype. These changes include loss of contact inhibition and formation of structures resembling tumor spheroids. In parallel with these changes, there was a constitutive expression of Fos protein. Switching these cultures to medium supplemented with phorbol ester sustained growth with reversion of the altered phenotype. In contrast, a cAMP stimulator, cholera toxin, induced features of terminal differentiation. Our findings suggest a role for inflammatory mediators in human epidermal melanocytes. This observation provides insight into melanocyte growth alterations which may have relevance in early stages of melanocyte oncogenesis.
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PMID:Chronic growth stimulation of human adult melanocytes by inflammatory mediators in vitro: implications for nevus formation and initial steps in melanocyte oncogenesis. 838 27

A multistep genetic model of tumorigenesis, based on genetic alterations in benign and primary malignant lesions, has been proposed for neoplasms such as colonic carcinoma. However, evidence for a similar genetic progression in melanoma has relied heavily on findings in cultured lesions or metastases. We have investigated every autosomal arm for loss of heterozygosity in 41 primary cutaneous melanomas and 32 benign melanocytic nevi, and have investigated several chromosome arms that show loss in melanoma in 27 Spitz nevi (a nevus with histological similarities to melanoma). Loss of heterozygosity in primary melanoma was identified most frequently on chromosomes 9p (46%) at loci near the p16INK4 gene, 10q (31%), 6q (31%), and 18q (22%); loss of these chromosome arms were related to the progression of the melanoma. Only two benign melanocytic nevi (both of which showed atypical features on histology) demonstrated genetic alterations, including p9 loss in one case. In addition, two Spitz nevi contained interstitial deletions on chromosome 9p. Our findings show that loss of heterozygosity of 9p is not confined to melanoma, but that other uncultured melanocytic lesions can also display loss of this chromosome arm, and that other genetic changes (e.g., loss of 10q, 6q, and 18q) may be important in conveying the malignant phenotype to melanoma.
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PMID:Allelotypes of primary cutaneous melanoma and benign melanocytic nevi. 856 76

Evidence suggests that the plasminogen activators (PAs), in particular urokinase-type PA (uPA), play a pivotal role in tumor invasion and metastasis. We studied the contribution of the PAs to the malignant phenotype through the chemical induction of melanocytic neoplasms in uPA-deficient mice. Primary tumors were induced and promoted concurrently in 35 uPA-/- deficient and 35 uPA+/+ wild-type mice using a single application of 7,12-dimethylbenz(a)anthracene followed by repetitive applications of croton oil. Animals were sacrificed at 60-day intervals for 1 year. At necropsy, the four largest pigmented lesions in each animal were excised, characterized histologically, and evaluated microscopically for evidence of invasion. The regional lymph nodes, lungs, and solid abdominal visceral organs were sectioned and examined microscopically for evidence of metastatic disease. Cellular blue nevi were induced in 100% of uPA-/- and uPA+/+ promoted animals. Although a reduction in the radial and vertical progression of these lesions was noted in the uPA-deficient mice compared with the wild-type group, more than 95% of cellular blue nevi induced in both groups of animals invaded the underlying tissues. These lesions did not metastasize to the regional lymph nodes. Malignant melanoma arose in 5 of 35 (14.3%) of promoted wild-type mice. These tumors were locally aggressive, produced tissue-type PA, but were not metastatic to the regional nodes, lungs, or abdominal viscera. These results indicate that the invasive capability of melanocytic lesions may depend more on tissue-type PA than uPA activity. No melanomas were induced in the uPA-/- mice. The resistance of the uPA -/- strain to melanoma induction suggests that uPA contributes to malignant progression. We propose that the absence of uPA negatively affects tumorigenesis by decreasing the liberation and availability of growth factors such as basic fibroblast growth factor.
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PMID:Induction of primary cutaneous melanocytic neoplasms in urokinase-type plasminogen activator (uPA)-deficient and wild-type mice: cellular blue nevi invade but do not progress to malignant melanoma in uPA-deficient animals. 875 32


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