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

Xeroderma pigmentosum is an autosomal recessive, precancerous dermatosis caused by defective repair of ultraviolet-damaged DNA. Characterized clinically by progressive cutaneous pigmentary alterations and tumorigenesis, it serves as a model for ultraviolet carcinogenesis. We describe the clinical and histopathologic findings in a 31-year-old woman with xeroderma pigmentosum and a massive iris melanoma of the left eye. Histologic examination following enucleation revealed diffuse iris replacement by spindle and epithelioid cells with extension into the trabecular meshwork. Evidence of direct extraocular extension was absent, and a metastatic evaluation showed no abnormalities. To our knowledge, this is the first reported case of xeroderma pigmentosum complicated by melanoma of the iris. It provides further evidence suggesting a role for sunlight exposure in the pathogenesis of uveal melanoma.
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PMID:Malignant melanoma of the iris in xeroderma pigmentosum. 292 65

Epidemiological and etiological research on the pathogenesis of melanoma remins a controversial issue. The main reason for this appears to rest on the relation between the genetically determined susceptibility of the host and ultraviolet radiation (UVR). Basic to understanding this, however, is the knowledge of the clinical and histopathological, the genotypical and phenotypical heterogeneity of this tumor entity. In terms of the multistage concept of carcinogenesis, melanocytes, atypical or normal, are exposed to a mutagenic event, predominantly UVR, initiating malignant growth in a genetically altered and susceptible genome. The initiation could also occur spontaneously or as the result of other insults such as chemical carcinogens, viral infections, ionizing radiation, etc. Promotion through the stage of melanocytic dysplasia or de novo from unaltered skin follows additional exposure to UVR or cocarcinogens and is likely to be modulated by ethnic, dietary, endocrine, but also protective factors and concomitant disease. In terms of descriptive epidemiology, melanoma may be caused by exposure to intermittent and intense sunlight on unacclimatized skin. The mechanism of this association, such as the wavelength responsible, effects of total dose, intensity of dose rate, latency period between exposure and the clinical incidence of disease, and finally, the stage of carcinogenesis affected by UVR and other initiating factors, as well as the impact of any specific modulation for the pathogenesis and clinical course of the disease remain to be elucidated.
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PMID:Etiology of melanoma. 307 59

The occurrence of glutathione transferase in human malignant melanoma cell lines and solid tumor material has been analyzed and compared with the enzyme composition in fibroblasts and naevus samples. All cells and tissues investigated contained essentially only the acidic class Pi glutathione transferase as demonstrated by SDS-PAGE and immunoblotting. The enzyme was purified from tumor material and characterized. Its intracellular concentration was significantly higher in all the melanoma cell preparations analyzed than in the non-malignant cells, supporting the view that the class Pi glutathione transferase may contribute to the drug resistance that is characteristic of malignant melanoma.
Carcinogenesis 1987 Dec
PMID:Expression of class Pi glutathione transferase in human malignant melanoma cells. 311 48

The occurrence of the epidermal growth factor homologue, transforming growth factor alpha (TGF alpha), in embryonic and neoplastic tissues suggests that it may be an oncofetal version of epidermal growth factor. A strong case is developing for TGF alpha to have an autocrine mode of action in sustaining the autonomous growth of several types of tumour. We propose that TGF alpha normally has an autocrine role not only in stimulating the growth of some fetal tissues but also with postnatal epidermal cells in response to local stimuli--in particular ultraviolet radiation (UVR). As a first step to test this hypothesis we have checked whether UVR will induce the production of TGF alpha, measured by radioimmunoassay, using a highly specific monoclonal antibody which recognizes native, biologically active human TGF alpha. We found that cultures of normal foreskin melanocytes do not produce detectable amounts of TGF alpha when grown under routine conditions, but, within 12 h of exposure to low doses of short-wavelength UVR, significant quantities of TGF alpha are produced. The UVR-induced TGF alpha is both cell associated and released into the medium of these cultures. Also, UVR has a promoting action on epidermal cells which have been initiated by carcinogenic activity. A significant part of the promoting activity may be due to autocrine stimulation of multiplication of partially transformed epidermal cells. In this regard we found that UVR induced TGF alpha in HeLa cells and all human melanoma lines so far tested. Induction was complete within 24 h of a single exposure. Dose-response curves of TGF alpha induction in a malignant melanoma cell line showed a distinctive peak of factor induced by low (2 J/m2) doses of UVR. Higher doses which inhibit [3H]thymidine incorporation resulted in lower levels of induced TGF alpha. These findings are consistent with the participation of TGF alpha as an autocrine mediator of UVR-induced tumour promotion, as well as cell multiplication, in sun-exposed skin.
Carcinogenesis 1988 May
PMID:UVR induction of TGF alpha: a possible autocrine mechanism for the epidermal melanocytic response and for promotion of epidermal carcinogenesis. 316 73

In the design of new approaches to cancer prevention, it is important to realize that most cancers develop stepwise over a long period of time with nonmalignant precursor lesions that only slowly evolve toward cancer. With many chemicals and some radiations, as well as some viruses (DNA and some retroviruses), cancer development can be divided into 3 major stages or periods, initiation, promotion and progression. Initiation is frequently associated with a more or less permanent change in the phenotype of a rare target cell, presumably due to a change in base composition in DNA or to gene rearrangements. During promotion, these rare cells expand by proliferation to generate focal proliferations that resemble benign neoplasms. These in turn exercise at least one of two options, regression to normal appearing tissue or slow evolution to cancer. Progression is self generating but can be modulated by dietary manipulations or by other drugs or xenobiotics. The prolonged nature of the promotion-progression stages in most tissues and its modulatability indicate that these stages are vulnerable sites for the development of dietary and other ways to prevent the progression to cancer. This overall pattern is known to occur in the liver, skin and urinary bladder and is probable in several other tissues or organs including the colon, breast and pancreas. What we know about the human suggests that the patterns may be very similar for cancer development in many sites. The best worked out is melanoma. The phenotypic pattern of the precursor lesions in the experimental animals is remarkably similar in any single organ. For example, the hepatocyte nodules are very similar to each other with many different carcinogens and promoting environments even though the ultimate cancers are quite heterogeneous and diverse. The diversity and heterogeneity appears to be an acquisition that is quite late in the step-by-step development of cancer. Although its exact step has not been delineated as yet, it appears to be acquired as malignancy is. Unlike the cancers, the commonality or homogeneity in the precursor lesions offers many opportunities for interrupting the process and thus in preventing cancer. The experience to date in experimental systems with some hormones, drugs and dietary manipulations indicates that inhibition of the development of cancer may be most readily achieved by affecting the promotion and progression sequences in carcinogenesis.
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PMID:Cancer development and its natural history. A cancer prevention perspective. 316 85

The Melanesians of the North Solomons are exposed to intense equatorial sunlight and yet have a very low incidence of skin cancer. This study reveals no proven cases of basal cell carcinoma in these people, and demonstrates the rarity of squamous cell carcinoma and melanoma arising in normal pigmented skin. Most, if not all squamous cell carcinomas, arise in skin damaged by tropical ulceration, burns or osteomyelitis. Melanoma arises from the unpigmented skin of the sole of the foot. North Solomon Islanders are very deeply pigmented. Presumably, dense cutaneous melanin in normal undamaged skin provides the highly effective protection against solar carcinogenesis which these people enjoy. Chronic or recurrent skin ulceration with subsequent repair, scarring and loss of pigment is the precursor to almost all non-melanoma skin cancer in these people. Most of these cancers could be prevented by split thickness skin grafting of chronic ulcers, and protection of ulcerated, depigmented and scarred skin from solar radiation.
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PMID:Skin cancer in the North Solomons. 317 95

Incidence registration and survival data for non-melanocytic skin neoplasms and cutaneous melanoma have been abstracted from the population-based system of the Cancer Registry of the Swiss Canton of Vaud, which has been operating in a particularly favourable environment, since the large majority of cutaneous lesions resected in the area are examined by a pathologist. Among the 5,712 cases registered, 66.7% were basal-cell carcinomas, 20.6% squamous-cell cancers, 9.3% cutaneous melanomas and 3.4% other miscellaneous histological types. The distribution by histological type did not differ appreciably in the 2 sexes, but there were marked inter-sex differences as regards anatomical site. In both sexes, head and neck was by far the commonest localization for non-melanomatous neoplasms (69 to 81% of all incident cases), followed by trunk for basal-cell cancers (18% in males, 15% in females) and upper limb for squamous-cell (10% in males, 17% in females). The distribution of skin melanomas differed considerably between the 2 sexes, by far the commonest site being the trunk for males (45% of cases) and lower limbs for females (40%), followed by head and neck (22% in both sexes). Incidence rates for both basal- and squamous-cell cancers increased with age, and rates were higher in males for each localization except the lower limb. In contrast, incidence for melanoma was higher in females, and incidence rates did not increase with age above 55 years for all sites except head and neck. This can be interpreted in terms of cohort effect, since mortality from melanoma has substantially increased in Switzerland across subsequent birth cohorts. Although this study is essentially descriptive, accurate inspection of these data provides some support for the major aetiological hypotheses of skin carcinogenesis, i.e., the observation that the large majority of basal- and squamous-cell cancers arise on the head and neck confirms the importance of long-term ultraviolet exposure; the relative excess of squamous-cell as compared to basal-cell neoplasms on the upper limb may suggest the role of exposure to other (chemical) carcinogens; and the proportional excess of melanomas on the trunk in males and lower limb in females further indicates that intermittent exposure to sunlight is probably the relevant aetiologic factor for melanocytic skin neoplasms.
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PMID:Descriptive epidemiology of skin cancer in the Swiss Canton of Vaud. 319 22

It has been well established that specific alterations in members of the ras gene family, H-ras, K-ras and N-ras, can convert them into active oncogenes. These alterations are either point mutations occurring in either codon 12, 13 or 61 or, alternatively, a 5- to 50-fold amplification of the wild-type gene. Activated ras oncogenes have been found in a significant proportion of all tumors but the incidence varies considerably with the tumor type: it is relatively frequent (20-40%) in colorectal cancer and acute myeloid leukemia, but absent or present only rarely in, for example, breast tumors and stomach cancer. No correlation has been found, yet, between the presence of absence of an activated ras gene and the clinical or biological features of the malignancy. The activation of ras oncogenes is only one step in the multistep process of tumor formation. The presence of mutated ras genes in benign polyps of the colon indicates that activation can be an early event, possibly even the initiating event. However, it can also occur later in the course of carcinogenesis to initiate for instance the transition of a benign polyp of the colon into a malignant carcinoma or to convert a primary melanoma into a metastatic tumor. Apparently, the activation of ras genes is not an obligatory event but when it occurs it can contribute to both early and advanced stages of human carcinogenesis.
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PMID:The ras gene family and human carcinogenesis. 328 42

A monoclonal antibody specific for u.v.-induced thymine-thymine dimers in single-stranded DNA has been used in an enzyme immunoassay to investigate the loss of antigenicity associated with repair of this lesion in the first 2 h following 10 J/m2 254 nm radiation. Variances of +/- 10% for the method and +/- 6.5% for individuals were established using primary cultures of biopsies from healthy individuals. No differences in the rate of loss of antigenicity was observed between 20 normal lymphocyte samples and 10 normal skin biopsies. Of three xeroderma pigmentosum (XP) variant cell lines tested, GM3617 could not be distinguished from normal cells but GM1227 and GM3053 showed lower rates of loss than any of the healthy samples. When the group mean values were compared there was no significant difference between normals and biopsies from sun-shielded skin areas from 16 basal cell carcinomas but similar material from 10 melanoma patients showed a significantly reduced (P = 0.001) rate of loss of antigenicity. Since the rate of loss of antigenicity in normal and XP variant cells reflected their relative abilities to perform unscheduled DNA synthesis, our results suggest that some melanoma patients may also have a minor deficiency in an early stage of excision repair.
Carcinogenesis 1987 Sep
PMID:Immunochemical determination of an initial step in thymine dimer excision repair in xeroderma pigmentosum variant fibroblasts and biopsy material from the normal population and patients with basal cell carcinoma and melanoma. 330 92

The question of whether the steroidal components in oral contraceptives (OCs) may have an initiating or promotional influence on the development of cancer continues to be raised as a public health issue. It is estimated that since the introduction of OCs nearly 25 years ago, more than 150 million women have used 1 or more types of the formulation and nearly 1 billion woman-years of exposure to the steroids have accumulated. Contraceptive practice in Australia would indicate that about 25% of women of reproductive age are using OCs. The debate about the OC's carcinogenic potential has recently been reopened with 2 reports in "The Lancet" of an association between the incidence of breast and cervical cancer and OC usage. Biologically the relationship between the contraceptive steroids and cancer must continue to be regarded as the most important concern with the longterm use of OCs. The demonstration of receptors to these steriods in these organs, in both normal and malignant tissues, further increases the speculation that the steroid hormones have a biological role in carcinogenesis in these target organs. Theoretical reasons exist for the concern about carcinogenesis and contraceptive steroids. This paper reviews the available evicence. Data can be derived only from large-scale epidemiological research, by means of case-control or cohort studies. No clear evidence exists that OCs cause or increase the chance of developing any cancer in the female genital tract and the breast. In fact, OC offers a significant protection against the development of endometrial and ovarian cancer, especially to those women who have taken OCs for a long time. The association between the risk of breast cancer and OC use is less certain, but factors such as the history of benign breast disease, a close relationship with breast cancer, or nulliparity -- previously considered to be important -- do not appear to contribute significantly to the risk. The weight of evidence indicates that no increased risk of breast cancer exists, even in those younger women aged less than 25 years who decide to use OCs before their 1st full-term pregnancy. There is some evidence that suggests that the risk of cervical neoplasia -- dysplasia, carcinoma-in-situ and invasive carcinoma -- may increase slightly in OC users but the actual part played by the patient's sexual history under these circumstances remains to be defined. There is now strong evidence to implicate multiplicity of sexual partners and wart virus infection in carcinogenesis of the uterine cervix. There does not appear to be an overall relationship between OCs and malignant melanoma. Overall, the evidence is reassuring. The low-dose combined OC can be considered safe, not only in terms of cardiovascular and thromboembolic risks, but also in relation to carcinogenesis.
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PMID:Cancer risks and the contraceptive pill. What is the evidence after nearly 25 years of use? 351 57


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