Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is often stated that persons of Celtic origin have an increased risk of skin cancer, but the evidence for this is almost exclusively anecdotal. We believe that the possibility of the Celts being at greater risk of skin cancer has important implications with regard to management in particular and in assisting our understanding of carcinogenesis in general. For these reasons we have reviewed all those studies implicating Celtic ancestry in the development of both malignant melanoma and nonmelanoma skin cancer.
 ...
PMID:Increased risk of skin cancer: another Celtic myth? A review of Celtic ancestry and other risk factors for malignant melanoma and nonmelanoma skin cancer. 767

Mutations of the p53 tumor-suppressor gene are the most common genetic alterations in human cancer, found in approximately 50% of all tumors. The importance of p53 in human cancer attracts attention in molecular studies dealing with the pathogenesis, diagnosis and prognosis in tumor pathology. This review summarizes the current understanding of p53 both on the genetic and protein level. Frequency and spectrum of somatic p53 mutations in the carcinogenesis of breast cancer, colorectal cancer, gastric cancer, hepatocellular carcinoma, squamous-cell carcinoma of the skin and malignant melanoma are discussed including our own investigations and studies published in the literature.
 ...
PMID:[Tumor suppressor gene p53. Theoretical principles and their significance for pathology]. 871 Jul 88

Nonmelanoma skin cancer, including both squamous cell carcinoma and basal cell carcinoma, is a significant and increasing health problem in the United States. The precursor lesion of cutaneous squamous cell carcinoma, actinic keratosis (AK), is a major risk factor for nonmelanoma skin cancer, and it is also a marker of long-term sun exposure. AKs themselves can serve as biomarkers in chemopreventive studies, but in addition, they may contain phenotypic and genetic alterations that are related to the process of UV-induced skin carcinogenesis. One of these alterations, the tumor suppressor gene p53, is altered early in UV-induced skin carcinogenesis in humans. p53 protein expression was measured by immunohistochemistry in biopsies from AKs, tissue immediately adjacent to AKs (AK-adjacent), normal-appearing upper medial arm skin, and non-sun-exposed skin from 19 subjects. There was a significant difference and a progressively increasing mean p53 labeling index in total epidermis (basal and suprabasal layers) between upper medial arm skin (0.9 +/- 1.8%) and AK-adjacent (12.1 +/- 14.4%; P = 0.0004) and between AK (27.7 +/- 21.3%) and AK-adjacent skin (P = 0.04), whereas upper medial arm skin was marginally different from non-sun-exposed skin (0.1 +/- 0.2; P = 0.05). This pattern of p53 expression was also seen when epidermis was separated into basal and suprabasal layers. We conclude that epidermal p53 protein expression is associated with histological evidence of chronic sun damage.
 ...
PMID:Expression of p53 protein in actinic keratosis, adjacent, normal-appearing, and non-sun-exposed human skin. 926 70

Ultraviolet B (UVB, 290-320 nm) exposure results in a variety of cellular insults including induction of cyclobutane pyrimidine dimers in DNA. Accumulation of these lesions can lead to mutations in critical genes and contribute to the development of nonmelanoma skin cancer. Topically applied alpha-tocopherol (vitamin E) has previously been shown to prevent the induction of skin tumors in UVB irradiated female C3H/HeNTac mice. We hypothesized that alpha-tocopherol, which absorbs strongly in the UVB, may act as a sunscreen to prevent photodamage. To explore possible mechanisms of photoprotection, we topically applied alpha-tocopherol dispersed in a neutral cream vehicle to the dorsal epidermis of female C3H/HeNTac mice and exposed them to 2.5 J/m2/s of UVB for 60 min. Immediately after exposure, we analyzed thymine dimer levels in DNA by capillary gas chromatography with electron capture detection. Epidermal DNA from mice receiving this UVB dose contained 247 +/- 42 pmol thymine dimers/micromol thymine. Topical application of alpha-tocopherol inhibited dimer formation in a dose-dependent manner. A 1% alpha-tocopherol dispersion inhibited the formation of thymine dimers to 43% of levels in vehicle controls. Several vitamin E compounds, including alpha-tocopherol acetate, alpha-tocopherol methyl ether, gamma-tocopherol, and delta-tocopherol also inhibited thymine dimer formation, but were five- to ten-fold less potent than alpha-tocopherol. A variety of commercially available sunscreens were also less potent than alpha-tocopherol in their ability to reduce dimer formation. These results suggest that DNA photoprotection is an important mechanism by which topically applied alpha-tocopherol can inhibit UVB induced skin cancer. Alpha-Tocopherol acetate, the most common form of vitamin E in commercial skin care products, conferred less protection, perhaps due to its lower absorptivity in the UVB. Our results further underscore the importance of determining which forms of vitamin E can inhibit specific lesions involved in photocarcinogenesis.
Carcinogenesis 1997 Aug
PMID:Inhibition of UVB induced DNA photodamage in mouse epidermis by topically applied alpha-tocopherol. 927 38

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.
 ...
PMID:Detection of human papillomavirus DNA in PUVA-associated non-melanoma skin cancers. 966 98

Retinoids have been shown to be potent inhibitors of epithelial carcinogenesis. Recent evidence has demonstrated that retinoid actions are mediated through nuclear receptors, which are proteins encoded by the retinoic acid receptor and retinoid X receptor gene families. These receptors are activated by binding to specific retinoids; of the known naturally occurring retinoids, 9-cis retinoic acid is unique in its ability to bind to both receptor families. Because of its unique receptor-binding characteristics, 9-cis retinoic acid may have biological activity not possible with other retinoids. For this reason, we conducted a Phase I trial of 9-cis retinoic acid in adult patients with solid tumors. Twenty-two patients were treated twice daily with p.o. 9-cis retinoic acid at doses ranging from 20 mg/m2/day to 150 mg/m2/day. The patients had non-small cell lung cancer (n = 8), breast cancer (n = 5), colorectal cancer (n = 3), head and neck cancer (n = 2), nonmelanoma skin cancer (n = 2), or ovarian cancer (n = 2). The dose-limiting (WHO grade III) toxic effects, which occurred at the 150-mg/m2/day dose level, were headaches and diarrhea. Less severe (grades I and II) toxic effects included cheilitis, dry skin, conjunctivitis, fatigue, hypertriglyceridemia, alkaline phosphatase elevation, myalgia/arthralgia, and hypercalcemia. Of the 15 patients evaluable for tumor response, no objective responses were observed. Pharmacokinetic analysis revealed a reduction in peak 9-cis retinoic acid plasma levels with chronic administration. Based on this study, the recommended Phase II dose of 9-cis retinoic acid in adult patients with solid tumors is 100 mg/m2/day administered in a divided dose twice daily.
 ...
PMID:Phase I trial of 9-cis retinoic acid in adults with solid tumors. 981 71

As dermatologists, we have all been active in educating patients about sun awareness and sun protection. This is even more important for children, as childhood exposure to ultraviolet light is a significant risk for both melanoma and nonmelanoma skin cancers. The importance of an educational approach in appropriate sun awareness in childhood is further underscored by the recent findings by Rivers et al., in the Vancouver Moles Cohort study, presented at the 1999 American Academy of Dermatology meeting. In a placebo-controlled trial, the findings of Rivers et al. clearly demonstrated that the use of sunscreens can significantly decrease the formation of nevae in children, providing further evidence to support sun awareness education initiatives. The lead article by Gooderham and Guenther in the Basic and Clinical Sciences section evaluates the effectiveness of a particular sun awareness program, and gives valuable insights into how more effective approaches may be used in the future. In addition to ultraviolet light playing a causal role in cutaneous malignancies, it is known to induce a number of other skin problems. One particularly difficult group of disorders is the photosensitive dermatoses, including solar urticaria. Bissonnette et al. describe an innovative approach to the management of refractory solar urticaria with plasma exchange. In the Grand Rounds section, Strauss et al. review the case of an acute SLE and give an insightful discussion related to bullous eruptions in acutely ill children. The mechanism of ultraviolet-light-induced carcinogenesis involves UV-induced DNA damage. Over the past decade, it has become clear that tumour suppressor genes can regulate these processes. In the Review section, Tron et al. discuss the role of the suppressor gene p53, which is mutated or lost in nonmelanoma skin cancer. P53 is crucial in protecting keratinocytes from the harmful effects of ultraviolet radiation, and in their instructive article, these authors use gene-targeted mutant mice lacking p53 to further evaluate the role in UV-induced DNA damage. With the warm weather upon us, we are spending more time in the outdoors and, as a result, are exposed to a vast number of environmental onslaughts. These include such things as Rickettsial disease, summarized in our CME section Summary Notes. Furthermore, in a comprehensive review, Dr. Sasseville examines another outdoor threat as he delineates the wide spectrum of plant contact dermatitis. This represents an important and in-depth reference on phytodermatitis. Our specialty, and indeed all of medicine, is being dramatically altered by recent advances in our understanding of disease at a molecular level. This new understanding of disease has led to the potential of modifying gene expression through the use of gene therapy. This is particularly attractive in skin disease, where gene therapy can be delivered quite readily through the skin. This advancement is insightfully discussed in the article by Somani et al., "Gene Therapy and Dermatology," which is both valuable for the cognoscenti and noncognoscenti alike, and serves as an important reference work in this area.
 ...
PMID:Editorial 1038 44

The role of human papillomavirus (HPV) in anogenital carcinogenesis is firmly established, but evidence that supports a similar role in skin remains speculative. Immunosuppressed renal transplant recipients have an increased incidence of viral warts and nonmelanoma skin cancer, and the presence of HPV DNA in these lesions, especially types associated with the condition epidermodysplasia verruciformis (EV), has led to suggestions that HPV may play a pathogenic role. However, differences in the specificities and sensitivities of techniques used to detect HPV in skin have led to wide discrepancies in the spectrum of HPV types reported. We describe a degenerate nested PCR technique with the capacity to detect a broad spectrum of cutaneous, mucosal, and EV HPV types. In a series of 51 warts from 23 renal transplant recipients, this method detected HPV DNA in all lesions, representing a significant improvement over many previously published studies. Cutaneous types were found in 84.3% of warts and EV types were found in 80.4% of warts, whereas mucosal types were detected in 27.4% of warts. In addition, the method allowed codetection of two or more distinct HPV types in 94.1% of lesions. In contrast, single HPV types were detected in all but 1 of 20 warts from 15 immunocompetent individuals. In summary, we have established a highly sensitive and comprehensive degenerate PCR methodology for detection and genotyping of HPV from the skin and have demonstrated a diverse spectrum of multiple HPV types in cutaneous warts from transplant recipients. Studies designed to assess the significance of these findings to cutaneous carcinogenesis are under way.
 ...
PMID:Degenerate and nested PCR: a highly sensitive and specific method for detection of human papillomavirus infection in cutaneous warts. 1052 50

The role of ultraviolet (UV) radiation in the induction of nonmelanoma skin cancer is widely accepted, although its precise contribution to the development of primary cutaneous melanoma skin cancer requires further definition. We found that painting aloe emodin, a trihydroxyanthraquinone from Aloe barbadensis, in ethyl alcohol vehicle on the skin of mice in conjunction with exposure to UVB (280-320 nm) radiation results in the development of melanin-containing skin tumors. C3H/HeN mice were treated thrice weekly with aloe emodin in a 25% ethanol in water vehicle and exposed to 15 kJ/m2 UV radiation. Neither ethanol vehicle nor aloe emodin alone induced skin tumors in the absence of UV radiation. In two separate experiments, 20-30% of the mice treated with a combination of UV radiation and ethanol vehicle and 50-67% of the UV-irradiated animals given aloe emodin in ethanol vehicle developed primary cutaneous melanin-containing tumors. The diagnosis of melanoma was established using Fontana silver stain for melanin; these tumors were negative for vimentin and keratin. Melanin-containing melanosomes were observed by transmission electron microscopy in tumors diagnosed as melanomas. Although the mechanism of carcinogenesis in these mice is currently unknown, our findings have led to the development of the first facile murine model for the induction of primary melanoma. This model has the potential to clarify the role of UV radiation in the etiology of malignant melanoma.
 ...
PMID:Induction of primary cutaneous melanomas in C3H mice by combined treatment with ultraviolet radiation, ethanol and aloe emodin. 1098 13

The role of beta-carotene as an anticancer agent has been questioned as a result of clinical trials in which the incidence of nonmelanoma skin cancer was unchanged in patients receiving a beta-carotene supplement and in beta-carotene-supplemented smokers who suffered a significant increase in lung cancer occurrence. In laboratory studies, beta-carotene-supplemented semidefined diets, in contrast to earlier studies employing commercial closed-formula diets, not only failed to provide a protective effect to ultraviolet (UV) carcinogenesis but resulted in significant exacerbation. A rationale for this distinct carcinogenic response to beta-carotene rests with the stability of the carotenoid radical cation, believed to be dependent on the presence of other antioxidants for rapid repair, and suggests that response to beta-carotene depends on the presence and interaction with other dietary factors. Here, we report that diet potentiates beta-carotene-mediated exacerbation of UV carcinogenesis. Although the dietary factor(s) responsible for this effect is unidentified, these studies underscore the potential risk of beta-carotene supplementation in free-living populations where dietary status is widely varied.
 ...
PMID:Diet potentiates the UV-carcinogenic response to beta-carotene. 1114 90


1 2 3 4 5 6 Next >>