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

It is suggested that melanocytes may be characterized by a differentiation pathway with four distinct stages during normal tissue maintenance: the nerve-sheath precursor stage, the dermal migratory stage, the junctional migratory stage, and the dendritic stage. Carcinogenic action on cells in these four stages may produce four classes of lesions: neurotropic melanoma, invasive malignant melanoma, epidermal melanocytic precursors of invasive malignant melanoma, and isolated atypical epidermal melanocytes. Morphologic variations within a class are interpretable as reflecting varying degrees of aberration from the behavior of normal cells in the corresponding stage. This theory accounts for morphologic variations and salient clinicopathologic correlations during the neoplastic development of malignant melanoma. It is consistent with fundamental principles of carcinogenesis, modern ideas about stem cells and differentiation, and current understanding of the pathogenesis of metastasis. It may be of some value in resolving present controversies and may contribute to the development of improved methods of diagnosis and management of malignant melanoma. Further study is necessary before these concepts may be prudently applied in clinical practice.
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PMID:The neoplastic development of malignant melanoma. A biological rationale. 652 33

Chromosome studies were done on direct preparations, early passage cultures, and/or cell lines derived from melanocytic lesions of 17 patients. There were 5 nevi (3 dysplastic); 1 early primary melanoma (radial growth phase); 1 advanced primary melanoma (vertical growth phase) with multiple metastases; and 10 metastatic lesions. The 5 nevi had normal karyotypes, while each of the tumors had a predominantly abnormal karyotype. The early melanoma was pseudodiploid, including a 6p;22 translocation. Ten of the 11 advanced melanomas had one or more aberrations involving chromosome #1, with 9 having deletions or translocations of lp that involved the proximal segment 1p12----1p22 9 times in 8 lesions. Six advanced tumors had additional material involving 7q, including extra #7s (4 cases) and 7q+ (2 cases). Nine melanomas, including the early tumor, had alterations in chromosome #6. Three had additional copies of 6p (as iso6p or t6p); the others showed no consistent pattern. In one advanced tumor, the primary lesion and 5 metastases (removed seriatim over an 18-month period) had nearly identical karyotypes, indicating the clonal nature of the neoplasm. The nonrandom cytogenetic changes suggest that genes important in melanoma carcinogenesis are located on the proximal portion of 1p, on 7q, and on chromosome #6. More data on early lesions are needed to identify the relation of these various cytogenetic changes to the different stages of malignant melanoma development.
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PMID:Cytogenetics of human malignant melanoma and premalignant lesions. 658 3

Endogenous hormones probably do not initiate cancer directly but may influence carcinogenesis by facilitation or inhibition of endogenous production of carcinogens; effects on the metabolic activation or inactivation of carcinogens; alteration of the susceptibility of tissues to the initiation of cancer; promotion of the development of clinical cancer from initiated cells; and (theoretically) alteration of the body's capacity to eliminate initiated cells. Evidence exists for a role of endogenous hormones in cancers of the salivary gland, colon and rectum, liver, gall-bladder, pancreas, breast, cervix uteri, corpus uteri, ovary, prostate, testis, kidney, thyroid and pituitary glands and malignant melanoma. Oestrogens are the most commonly implicated hormone, and there is sufficient evidence for their causal association with cancers of the breast and endometrium. The most commonly postulated mechanisms of action are alteration of the susceptibility of tissues to initiation, and promotion of the once-initiated cancer. In human beings and, to some extent, in animals it is difficult to distinguish between these two mechanisms, both of which are based on hormone-induced cell proliferation, because the time of initiation cannot be pinpointed. Environmental factors may influence carcinogenesis by effects on the production, transport, peripheral action, inactivation and excretion of endogenous hormones. Examples that illustrate some of these possibilities may be derived from the effects of diet on risk of breast, endometrial and thyroid cancers.
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PMID:Endocrine factors in human carcinogenesis. 675 85

Initiation of dermal melanocytes by 7,12-dimethylbenz[a]-anthracene (DMBA) in the dorsal skin of Syrian golden hamsters was investigated for its sensitivity to inhibition by 7,8-benzoflavone (BF). Initiation was carried out by a single intragastric application of DMBA (50 mg/kg body weight) and melanoma development pursued with or without subsequent promotion through repeated topical administration of 12-O-tetradecanoylphorbol-13-acetate (40 nmol/animal, 3 X weekly). A single intragastric application of BF (200 mg/kg body weight) 2 h prior to DMBA resulted in a suppression of melanoma yields by approximately 70%. Further, there were indications that BF generally causes a decrease of melanoma rates and an increase of survival rates. The study provides a first mechanistic concept for melanoma initiation by DMBA. It shows that metabolic activation of DMBA (i) is prerequisite to initiation and (ii) has a similar molecular basis as in other target cells of DMBA, the essential pathway including the cytochrome P-448-dependent monooxygenase system.
Carcinogenesis 1982
PMID:Tumor initiation by 7,12-dimethylbenz[a]anthracene in dermal melanocytes of hamster: inhibition through 7,8-benzoflavone. 681 Nov 49

Model systems to study the effects of chemicals of environmental concern on bacterial and parasitic diseases as well as the immunosurveillance and destruction of transplantable tumor cells were described and evaluated. Studies were conducted in female B6C3F1 mice following adult or pre/postnatal exposure to several prototype chemicals. The prototype chemicals employed included the synthetic estrogen diethylstilbestrol (DES), the polycyclic aromatic hydrocarbon benzo(a)pyrene (B[a]P), and the carcinogenesis promoting agent 12-0-tetradecanoyl-phorbol-13-0-acetate (TPA). The host resistance models employed depend primarily on functional thymus-dependent immunity, although humoral immunity is suggested to have a role in the parasite model as well. These models include: subcutaneous challenge with a dose of PYB6 tumor cell causing a 10-20% incidence (TD(10-20)) of tumor; intravenous challenge with B16 melanoma cells; challenge with a dose of Listeria monocytogenes causing a 10-20% incidence of mortality (LD(10-20)); challenge with a dose of E. coli lipopolysaccharide endotoxin causing a 10-20% incidence of lethality (LD(10-20)); and challenge with larvae of Trichinella spiralis for parasite expulsion kinetic studies. Increased mortality was observed following Listeria monocytogenes challenge in DES-exposed mice. B(a)P and TPA exposure did not alter host resistance to this organism. The increased mortality observed following DES was associated with a significant increase in the number of viable Listeria in the spleens and livers at 4 days, a time when T-cell immunity is thought to be expressed, but bacterial counts were similar to control mice at day 1, a time when MPhi are thought to exert their greatest effect. These data suggest that the increased Listeria susceptibility found following DES exposure may result from a T-cell defect, although the intracellular killing capacity of DES-treated Mvarphi's has not been well examined. Tumor susceptibility studies following challenge with 5 x 10(3) viable syngeneic PYB6 tumor cells revealed that nontreated adult B6C3F1 mice resisted tumor formation, with only a 10-20% incidence of tumor formation. In contrast, mice exposed to DES or TPA as adults had a tumor frequency of from 70-100% following TPA and up to 90% following DES exposure. In all cases the tumors were progressive and resulted in death. B(a)P did not alter the frequency of tumor incidence from controls in this model. Preliminary data, using the B16 melanoma intravenous challenge model and (125)IUdR to quantitate tumor mass revealed this model was sensitive to non-specifically activated macrophage kill. DES treated mice with activated macrophages did not demonstrate increased tumor mass, while mice exposed to TPA or the potent immunosuppressive agent cyclophosphamide had a significantly increased tumor mass in their lungs. Expulsion of Trichinella spiralis adults from the gut also apparently required functional T-cells and possibly some element of humoral immunity. Mice exposed to DES and B(a)P exhibited increased numbers of adult worms in the gut at day 14. Sensitivity to gram-negative endotoxin (LPS) was apparently increased following exposure to DES or B(a)P. These data suggest that the detoxification of LPS is related to an intact Mvarphi population. The data presented here demonstrate the sensitivity of the host resistance assay panel proposed for detecting immune alteration. Alteration of T-cell function appeared to correlate with increased susceptibility to bacterial and tumor cell challenge.
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PMID:Application of tumor, bacterial and parasite susceptibility assays to study immune alterations induced by environmental chemicals. 706 May 48

Mortality rates for all malignant neoplasms (combined) and for 34 site-specific cancer categories for selected high and low altitude populations are compared using two related techniques: confidence interval overlap for strictly descriptive purposes and analysis of standardized mortality ratios using lower and upper 95% statistical significance factors for the ratio of an observed value of a poisson variable to its expectation. Techniques are employed to minimize confounding due to industrialization, urbanization or selected cultural characteristics. Cancer mortality data for U.S. counties averaged over the 20-year period, 1950--1969, were used. For most comparisons a deficit in cancer mortality in high altitude counties was observed. The largest differences between the low and high altitude groups were found for cancers of the tongue and mouth, esophagus, larynx, lung and melanoma. Some limitations of ecologic studies are discussed.
Carcinogenesis 1982
PMID:Relationship of site-specific cancer mortality rates to altitude. 709 9

The effects of a single Phenytoin dose, given to patients with malignant melanoma, upon peripheral blood counts, serum immunoglobulins, lymphocyte subpopulations and lymphocytotoxicity (using Chang target cells) were recorded. Sequential blood samples were taken before and 10, 14, 34, 38 and 58 h after the Phenytoin. Early reductions (P less than 0.05) in lymphocyte count, NK, K and PHA induced cytotoxicity, when compared with initial, pre-Phenytoin values were noted. Immunisation with i.v. C. parvum prevented the reductions occurring after a second dose of Phenytoin. Indeed, significant increases above the values of samples taken immediately before the second dose, were observed in T cells, PHA blastogenesis, NK and K cell Cytotoxicity. The second dose did however cause some immunosuppression; the increase in T cells, NK and PHA induced cytotoxicity above initial values expected from previous investigations were not observed. The immunosuppression, particularly of killer cell function, occurring after phenytoin could have implications for the pathogenesis of malignancy and transplacental carcinogenesis, reported as following Phenytoin exposure.
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PMID:Effects of diphenylhydantoin on killer cell activity and other immunological functions. A sequential study including the interaction of Corynebacterium parvum in melanoma patients. 710 99

DNA synthesis was investigated in human melanoma cells irradiated with X-rays. The cells were lysed in dilute alkali which results in the release from the parental DNA of replication intermediates; these are then analyzed by agarose gel electrophoresis. In cells irradiated with 10 Gy we can detect the formation of a new heterogeneous population of DNA replication intermediates with a size greater than 10 kb. We can also demonstrate the presence of other DNA replication intermediates which were earlier described in control cells. The results imply that in melanoma cells changes may occur in th replication in order to comply with alterations in the DNA induced by X-rays.
Carcinogenesis 1982
PMID:Formation of a new population of DNA replication intermediates in X-irradiated human melanoma cells. 711 75

The clinical and laboratory studies on the disorders discussed here have yielded considerable insight into the importance of DNA repair processes in man. That unrepaired or incorrectly repaired damage to DNA can lead to malignancy and compromise the proper development and functioning of the nervous and immune systems is a reasonable conclusion. Our understanding of the relationship between molecular events that mediate DNA metabolism and cytogenetic and cellular phenomena such as chromosomal aberrations, mutagenesis, transformation and carcinogenesis is in its infancy. Continued efforts to clarify this relationship will assist in understanding, predicting and, hopefully, even controlling the carcinogenic process in man. Finally, heterozygous carriers of AT and XP genes would seem to be at increased risk of developing common cancers and non-melanoma skin neoplasms, respectively. The further evaluation of this possibility and its contribution to the overall cancer burden would seem to be of high priority in the study of environmental carcinogenesis.
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PMID:Heritable cancer-prone disorders featuring carcinogen hypersensitivity and DNA repair deficiency. 715 25

Epoxide hydratase activity with benzo[a]pyrene 4,5-oxide and glutathione S-transferase activity with 2,4-dinitrochlorobenzene as substrates were determined in cultured fibroblasts from skin biopsies of different donors and from several biopsies of the same donor. Variation of the results from experiment to experiment was reduced by the use of a reference cell strain and expression of the results as activities relative to those of the reference cells. Epoxide hydratase activity varied 2.3-fold in 39 cultures from the same subject (the variation coefficients were 0.22 and 0.15, respectively). The results indicate that, at least in skin fibroblasts, genetically caused interindividual differences in epoxide hydratase activities do not exist or are negligibly small or very rare. Glutathione S-transferase activity varied more in cultures from different donors (variation coefficient = 0.22) than in different cultures from the same donor (variation coefficient = 0.08), but the highest and the lowest activities only differed by a factor of 2.3. No significant differences in either enzyme activity were observed between males, females, subjects without tumours, lung carcinoma bearers and melanoma patients.
Carcinogenesis 1980 Apr
PMID:Interindividual comparison of epoxide hydratase and glutathione S-transferase activities in cultured human fibroblasts. 727 71


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