Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psoralen and UVA (PUVA) photochemotherapy is associated with a dose-dependent increased risk of nonmelanoma skin cancer in patients treated for psoriasis. Like ultraviolet B radiation, PUVA is both mutagenic and immunosuppressive and may thus act as a complete carcinogen; however, the reversed squamous to basal cell carcinoma ratio (SCC:BCC) in PUVA-treated patients, also seen in immunosuppressed renal transplant recipients, suggests a possible cofactor role for human papillomavirus (HPV) infection. In this study we examine a large series of benign and malignant cutaneous lesions for the presence of HPV DNA from patients treated with high dose (> or =500 J per cm2) ultraviolet A. A panel of degenerate primers based on the L1 (major capsid protein) open reading frame was employed, designed to detect mucosal, cutaneous, and epidermodysplasia verruciformis HPV types with high sensitivity and specificity. HPV DNA was detected in 15 of 20 (75%) non-melanoma skin cancer, seven of 17 (41.2%) dysplastic PUVA keratoses, four of five (80%) skin warts, and four of 12 (33%) PUVA-exposed normal skin samples. The majority of HPV positive lesions contained epidermodysplasia verruciformis-related HPV including HPV-5, -20, -21, -23, -24, and -38. Possible novel epidermodysplasia verruciformis types were identified in further lesions. Mixed infection with epidermodysplasia verruciformis, cutaneous, and/or mucosal types was present in six of 30 (20%) of all HPV positive lesions, including in normal skin, warts, dysplastic PUVA keratoses, and squamous cell carcinomas. The prevalence and type of HPV infection in cutaneous lesions from PUVA-treated patients is similar to that previously reported in renal transplant-associated skin lesions, and suggests that the role of HPV in PUVA-associated carcinogenesis merits further study.
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PMID:Detection of human papillomavirus DNA in PUVA-associated non-melanoma skin cancers. 966 98

A number of commonly used medications including quinolone antibiotics, psoralens and various tetracycline derivatives are photosensitizers. These chemicals enhance the erythema response to sunlight. The effect of such exposures on cancer risk has only been quantified in humans for oral psoralen photochemotherapy (PUVA). The experience of a cohort of 1380 patients followed for more than 20 years who received PUVA therapy for the treatment of psoriasis documents that long-term high dose exposure to PUVA greatly increases the risk of squamous cell carcinoma. After 15 years, the risk of melanoma is also increased among high dose patients. With PUVA therapy, an agent which is immunosuppressive in the skin, induces psoralen DNA adducts, is genotoxic and mutagenic. Substantially increased risk is only observed after many purposeful exposures to ultraviolet and this drug. These data suggest that at least some photosensitizing chemicals can substantially increase the risk of skin cancer in humans, but long-term multiple exposures appear to be necessary for a clinical meaningful increase of risk.
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PMID:Photocarcinogenicity of drugs. 1002 84

We have studied DNA repair in patients with psoriasis aiming at investigating the importance of repair in chemically induced cancer. An increased risk of non-melanoma skin cancer has been observed in psoriasis patients extensively treated with tar, methotrexate and photochemotherapy (psoralen + UVA). We measured the DNA repair capacity (DRC) by a host cell reactivation (HCR) assay in lymphocytes from psoriasis patients with and without basal cell cancer and non-psoriatic persons with and without basal cell cancer (4 x 20 study persons). Among psoriasis patients we observed a significant lower DRC in patients with skin cancer compared to patients without skin cancer (P = 0.015; Mann-Whitney, one-sided). Using the median of the healthy control group (group 4) as a cutoff value to divide the psoriasis patients into groups of high and low repair, we found that individuals who had a low repair capacity had a 6.4-fold increased skin cancer risk compared to individuals with high repair (95% confidence interval (CI), 1.44-28.5). The level of DNA repair was correlated with the age at which the psoriasis patients got their first skin cancer. The lower the level of DNA repair, the earlier the psoriasis patients had their first skin tumor (P = 0.070 Spearman; one-sided). Psoriasis patients without BCC had marginally higher repair than healthy controls (P = 0.11, Mann-Whitney, two-sided). We found no difference between BCC patients without psoriasis and healthy controls. In conclusion, these findings suggest a protective role of DNA repair in a predominantly chemically induced cancer.
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PMID:Low DNA repair is a risk factor in skin carcinogenesis: a study of basal cell carcinoma in psoriasis patients. 1004 75

Melatonin (N-acetyl-5-methoxytryptamine) is a hormone with multiple functions in humans, produced by the pineal gland and stimulated by beta-adrenergic receptors. Serum melatonin levels exhibit a circadian rhythm with low levels during the day, rise in the evening and maximum levels at night between 2 and 4 a.m. Melatonin participates in the regulation of several physiological processes such as seasonal biological rhythm, daily sleep induction, aging and modulation of immunobiological defence reactions. Furthermore, melatonin has a highly lipophilic molecular structure facilitating penetration of cell membranes and serving as an extra- and intracellular free radical scavenger. Melatonin seems to quench mainly hydroxyl radicals, the most damaging of all free radicals. Melatonin may play a role in the etiology and treatment of several dermatoses e.g. atopic eczema, psoriasis and malignant melanoma. The influence of melatonin on hair growth is another aspect. Topical application of melatonin inhibits the development of UV-erythema. Penetration through skin after topical application and oral bioavailability auxit further investigations on the pharmacokinetic and pharmacodynamic actions of melatonin.
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PMID:[Melatonin in dermatology. Experimental and clinical aspects]. 1006 25

Since the introduction in the 1970s of treatment with oral psoralens with longwave ultraviolet radiation in the A range (PUVA), there has been an increasing concern about the long term carcinogenic effect of the therapy. The main indication for PUVA is psoriasis, a common, chronic and intractable skin disease that affects 1 to 3% of the world's population. The effectiveness of PUVA in inducing and maintaining the remission of severe psoriasis has been amply documented. Although psoriasis is not a life-threatening disorder, it may be associated with restriction of activities and days lost to hospitalisation. Therefore, a number of systemic treatments such as methotrexate and cyclosporin have been used. None of these treatments has been as carefully studied for long term adverse effects as PUVA. The short-term adverse effects of PUVA are generally well known and tolerated. The major mid-term adverse effect, squamous cell carcinoma of the skin, has been well documented in a number of large-scale epidemiological studies that have led to recommendations such as to restrict the lifetime number of treatments. Although squamous cell carcinoma is potentially life-threatening, it is usually slow growing and can be adequately managed by proper surveillance, treatment and follow-up. The situation is quite different for malignant melanoma, which is often fast growing and fatal. Except for anecdotal reports, malignant melanoma has not been observed in PUVA patients until recently. However, a report of a cohort of 1380 patients with psoriasis has concluded that about 15 years after the first treatment the risk of melanoma is increased approximately 5-fold in patients treated with high doses. Although this report needs to be confirmed by other multicentre trials, it is alarming since the association between exposure to ultraviolet light and development of melanoma is well established both in humans and in experimental animals. Until this study is validated, it is recommended that the guidelines for PUVA therapy should be rigorously followed and that the contra-indications should be extended to include history or family history of melanoma and patients who have already received > 200 treatments.
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PMID:Risk of melanoma with psoralen/ultraviolet A therapy for psoriasis. Do the known risks now outweigh the benefits? 1023 May 79

This nationwide follow-up study concerns the pattern of malignant tumours in a cohort of patients with psoriasis, at an average of 9.3 years after discharge from hospital. The study confirms that the significantly increased risk of cancer in these patients, amounting to 1.4 times that in the general population, is mainly due to cancer of the skin and lung in both sexes and cancer of the pharynx and larynx in men. Non-melanoma skin cancer is the most common malignancy, occurring in 196 of 795 patients with cancer: standardized incidence ratio (SIR, the ratio of observed to expected cancers) 2.4 for men and 2.6 for women. This means an overall lifetime risk (up to the age of 75 years) of 14.1%. In particular, squamous cell carcinoma (SCC) by itself (n = 45, SIR 3.9 for men and 4.7 for women), cancer in multiple sites (SIR 5.9 for basal cell carcinoma (BCC) and 11.7 for (SCC) and SCC on the lower extremities (SIR 18.0) are frequent. Women run the highest risk of BCC in the age range 20-40 years, while men in the age range 30-60 years run a particularly high risk of SCC. When monitoring patients extensively treated for psoriasis, this aberrant pattern of cancer should be taken into account.
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PMID:Malignant tumours and psoriasis: a follow-up study. 1023 15

Matrix metalloproteinases (MMP) are involved in remodelling of the extracellular matrix (ECM) proteins suggesting that they play an important role in inflammatory process, in tumour invasion and metastasis. We examined immunohistochemically 330 cases of different skin disorders with the monoclonal antibody against MMP 11, stromelysin-3 (ST-3) protein. We found a positive immunoreactivity in fibroblasts surrounding malignant epithelial tumour cells in 63 of 125 cases (50.4%) of basal cell carcinomas, in four of 25 (16%) squamous cell carcinomas, whereas the tumour cells themselves were negative. Furthermore, the ST-3 protein could be detected in 23 of 40 cases (57.5%) of dermatofibroma, in two of five cases (40%) of atypical fibroxanthoma, in one of eight cases (12.5%) of dermatofibrosarcoma protuberans and, locally, in one of 10 cases (10%) of malignant fibrous histiocytoma. It was not present in the following skin lesions: keratoakanthomas (n = 12), Bowen's disease (n = 10), malignant melanoma (n = 12), melanocytic nevi (n = 28) and Kaposi's sarcomas (n = 25). In eczema (n = 10), psoriasis (n = 10) and virus-induced tissues (i.e. condylomata acuminata, n = 10) we did not observe an expression of ST-3 protein. We conclude first that ST-3 protein is a fibroblastic factor expressed in stromal cells adjacent to carcinoma cells; second, that ST-3 protein seems to be associated with benign fibroblastic tumours; and third, that it does not play a role in eczema, psoriasis or virus-induced skin lesions.
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PMID:Stromelysin-3 (ST-3): immunohistochemical characterization of the matrix metalloproteinase (MMP)-11 in benign and malignant skin tumours and other skin disorders. 1023 68

DNA of a wide spectrum of epidermodysplasia verruciformis-associated human papillomavirus (HPV) types (EV-HPV) has been detected in skin lesions and plucked hairs from both immunosuppressed and a considerable proportion of non-immunosuppressed persons. Recently, the skin of psoriatic patients was claimed to be an important reservoir for a particular EV-HPV type, HPV 5, which is considered as a high-risk HPV type for skin carcinomas. In the present study, we analysed plucked hairs from immunosuppressed renal transplant patients and immunocompetent individuals, utilizing an HPV 5-specific nested polymerase chain reaction. HPV 5 was detected in hairs derived from 14 of 31 (45%) immunosuppressed patients and 21 of 135 (16%) immunocompetent individuals. Both the immunosuppressed and the immunocompetent groups consisted of individuals with and without non-melanoma skin cancer. HPV 5 DNA was detected in similar proportions of hair samples plucked from individuals with and without skin cancer in either group. Our results indicate that HPV 5 is commonly present in the population. The role of HPV 5 in the pathogenesis of skin carcinomas and psoriasis remains to be established.
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PMID:Human papillomavirus type 5 is commonly present in immunosuppressed and immunocompetent individuals. 1046 95

Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) was performed in skin from patients with various malignant and nonmalignant skin diseases using anti-PCNA monoclonal antibodies. The malignant diseases included squamous cell carcinoma (SCC), adult T lymphotrophic leukemia (ATL), mycosis fungoides, malignant melanoma and malignant lymphoma, and the nonmalignant diseases included severe treatment-resistant atopic dermatitis (AD), psoriasis vulgaris, verruca vulgaris, and others. The percentage of PCNA-positive cells (the labeling index, LI) was highest for the malignant diseases (56.5+/-7.1%). The LIs for severe treatment-resistant AD, psoriasis, and verruca vulgaris were also significantly higher than those for the normal control or nonlesional skin of the patients. The PCNA LIs were, however, not significantly elevated in eczema and contact dermatitis. The high PCNA LIs in severe AD and psoriasis vulgaris were considerably lower in the skin improved by treatment. Labeling with Ki67, a nuclear protein expressed in cycling cells, was also performed in skin from subsets of each patient group. The results were very similar to those found with PCNA labeling. PCNA-positive cells were found throughout the dermis as well as the basal layer in the malignant diseases, whereas they were found only in the basal layer in the nonmalignant diseases. The results suggest that in human skin diseases, the extent of staining for PCNA, which is a cofactor of DNA polymerase-delta and is essential for cell proliferation, correlates with the extent to which the disease is treatment-resistant. In addition, our findings suggest that the PCNA LI and distribution of PCNA-positive cells in the skin may be helpful in the early diagnosis of skin malignancies.
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PMID:Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) in malignant and nonmalignant skin diseases. 1048 11

It has been suggested that trioxsalen bath and ultraviolet (UV) A (PUVA) is associated with a very low or no risk of non-melanoma skin cancer, but the numbers of patients in individual studies have been limited. In order to attain statistically relevant information about the cancer risk associated with trioxsalen bath PUVA, two follow-up studies were combined and the joined cancer incidence was analysed among 944 Swedish and Finnish patients with psoriasis. The mean follow-up time for skin cancer was 14.7 years. Standardized incidence ratios (SIR) were calculated as a ratio of observed and expected numbers of cases. The expected numbers of cases were based on the national cancer incidence rates in the respective countries. There was no excess of squamous cell skin carcinoma [SIR 1.1, 95% confidence interval (CI) 0.2-3.2] or malignant melanoma (SIR 0.9, 95% CI 0.1-3.2) in the combined cohort. Basal cell skin carcinoma was not studied. The incidence of all non-cutaneous cancers was not increased (SIR 1.1, 95% CI 0.8-1.4). A threefold excess risk of squamous cell skin carcinoma after trioxsalen bath PUVA could therefore be excluded, which is a markedly lower risk than that associated with oral 8-methoxypsoralen PUVA. The result needs to be confirmed in a future follow-up, however, as the number of patients with high PUVA exposures was low.
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PMID:Trioxsalen bath PUVA did not increase the risk of squamous cell skin carcinoma and cutaneous malignant melanoma in a joint analysis of 944 Swedish and Finnish patients with psoriasis. 1058 54


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