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  1. Melanoma Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing melanoma cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  2. Melanoma risk prediction models

    Directory of Open Access Journals (Sweden)

    Nikolić Jelena

    2014-01-01

    Full Text Available Background/Aim. The lack of effective therapy for advanced stages of melanoma emphasizes the importance of preventive measures and screenings of population at risk. Identifying individuals at high risk should allow targeted screenings and follow-up involving those who would benefit most. The aim of this study was to identify most significant factors for melanoma prediction in our population and to create prognostic models for identification and differentiation of individuals at risk. Methods. This case-control study included 697 participants (341 patients and 356 controls that underwent extensive interview and skin examination in order to check risk factors for melanoma. Pairwise univariate statistical comparison was used for the coarse selection of the most significant risk factors. These factors were fed into logistic regression (LR and alternating decision trees (ADT prognostic models that were assessed for their usefulness in identification of patients at risk to develop melanoma. Validation of the LR model was done by Hosmer and Lemeshow test, whereas the ADT was validated by 10-fold cross-validation. The achieved sensitivity, specificity, accuracy and AUC for both models were calculated. The melanoma risk score (MRS based on the outcome of the LR model was presented. Results. The LR model showed that the following risk factors were associated with melanoma: sunbeds (OR = 4.018; 95% CI 1.724- 9.366 for those that sometimes used sunbeds, solar damage of the skin (OR = 8.274; 95% CI 2.661-25.730 for those with severe solar damage, hair color (OR = 3.222; 95% CI 1.984-5.231 for light brown/blond hair, the number of common naevi (over 100 naevi had OR = 3.57; 95% CI 1.427-8.931, the number of dysplastic naevi (from 1 to 10 dysplastic naevi OR was 2.672; 95% CI 1.572-4.540; for more than 10 naevi OR was 6.487; 95%; CI 1.993-21.119, Fitzpatricks phototype and the presence of congenital naevi. Red hair, phototype I and large congenital naevi were

  3. Development and External Validation of a Melanoma Risk Prediction Model Based on Self-assessed Risk Factors.

    Science.gov (United States)

    Vuong, Kylie; Armstrong, Bruce K; Weiderpass, Elisabete; Lund, Eiliv; Adami, Hans-Olov; Veierod, Marit B; Barrett, Jennifer H; Davies, John R; Bishop, D Timothy; Whiteman, David C; Olsen, Catherine M; Hopper, John L; Mann, Graham J; Cust, Anne E; McGeechan, Kevin

    2016-08-01

    Identifying individuals at high risk of melanoma can optimize primary and secondary prevention strategies. To develop and externally validate a risk prediction model for incident first-primary cutaneous melanoma using self-assessed risk factors. We used unconditional logistic regression to develop a multivariable risk prediction model. Relative risk estimates from the model were combined with Australian melanoma incidence and competing mortality rates to obtain absolute risk estimates. A risk prediction model was developed using the Australian Melanoma Family Study (629 cases and 535 controls) and externally validated using 4 independent population-based studies: the Western Australia Melanoma Study (511 case-control pairs), Leeds Melanoma Case-Control Study (960 cases and 513 controls), Epigene-QSkin Study (44 544, of which 766 with melanoma), and Swedish Women's Lifestyle and Health Cohort Study (49 259 women, of which 273 had melanoma). We validated model performance internally and externally by assessing discrimination using the area under the receiver operating curve (AUC). Additionally, using the Swedish Women's Lifestyle and Health Cohort Study, we assessed model calibration and clinical usefulness. The risk prediction model included hair color, nevus density, first-degree family history of melanoma, previous nonmelanoma skin cancer, and lifetime sunbed use. On internal validation, the AUC was 0.70 (95% CI, 0.67-0.73). On external validation, the AUC was 0.66 (95% CI, 0.63-0.69) in the Western Australia Melanoma Study, 0.67 (95% CI, 0.65-0.70) in the Leeds Melanoma Case-Control Study, 0.64 (95% CI, 0.62-0.66) in the Epigene-QSkin Study, and 0.63 (95% CI, 0.60-0.67) in the Swedish Women's Lifestyle and Health Cohort Study. Model calibration showed close agreement between predicted and observed numbers of incident melanomas across all deciles of predicted risk. In the external validation setting, there was higher net benefit when using the risk prediction

  4. Communication about melanoma and risk reduction after melanoma diagnosis.

    Science.gov (United States)

    Rodríguez, Vivian M; Berwick, Marianne; Hay, Jennifer L

    2017-12-01

    Melanoma patients are advised to perform regular risk-reduction practices, including sun protection as well as skin self-examinations (SSEs) and physician-led examinations. Melanoma-specific communication regarding family risk and screening may promote such behaviors. To this end, associations between patients' melanoma-specific communication and risk reduction were examined. Melanoma patients (N = 169) drawn from a population-based cancer registry reported their current risk-reduction practices, perceived risk of future melanoma, and communication with physicians and relatives about melanoma risk and screening. Patients were, on average, 56 years old and 6.7 years' post diagnosis; 51% were male, 93% reported "fair/very fair" skin color, 75% completed at least some college, and 22% reported a family history of melanoma. Patients reported varying levels of regular (always/nearly always) sun protection: sunscreen use (79%), shade seeking (60%), hat use (54%), and long-sleeve shirt use (30%). Only 28% performed thorough SSE regularly, whereas 92% reported undergoing physician-led skin examinations within the past year. Participants who were female, younger, and had a higher perceived risk of future melanoma were more likely to report past communication. In adjusted analyses, communication remained uniquely associated with increased sunscreen use and SSE. Encouraging melanoma patients to have a more active role in discussions concerning melanoma risk and screening with relatives and physicians alike may be a useful strategy to promote 2 key risk-reduction practices post melanoma diagnosis and treatment. Future research is needed to identify additional strategies to improve comprehensive risk reduction in long-term melanoma patients. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Familial skin cancer syndromes: Increased melanoma risk.

    Science.gov (United States)

    Ransohoff, Katherine J; Jaju, Prajakta D; Jaju, Prajaka D; Tang, Jean Y; Carbone, Michele; Leachman, Sancy; Sarin, Kavita Y

    2016-03-01

    Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  6. Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations.

    Science.gov (United States)

    Goldstein, Alisa M; Landi, Maria Teresa; Tsang, Shirley; Fraser, Mary C; Munroe, David J; Tucker, Margaret A

    2005-09-01

    Major risk factors for melanoma include many nevi, especially dysplastic nevi, fair pigmentation, freckling, poor tanning ability, and germ line mutations in the CDKN2A, CDK4, or MC1R genes. We evaluated the relationship between MC1R and melanoma risk in CDKN2A melanoma-prone families with extensive clinical and epidemiologic data. We studied 395 subjects from 16 American CDKN2A families. Major melanoma risk factors were assessed by clinical examination or questionnaire; MC1R was sequenced. Odds ratios were estimated by unconditional and conditional logistic regression models. We examined the distribution of MC1R variants and median ages at melanoma diagnosis in multiple primary melanoma (MPM) and single primary melanoma (SPM) patients. Presence of multiple MC1R variants was significantly associated with melanoma, even after adjustment for major melanoma risk factors. All 40 MPM patients had at least one MC1R variant; 65% of MPM patients versus only 17% of SPM patients had at least two MC1R variants (P MC1R variants increased (P = 0.010 and P = 0.008, respectively). In contrast, no significant reduction in age at melanoma diagnosis was observed for SPM patients (P = 0.91). The current study suggests that the presence of multiple MC1R variants is associated with the development of multiple melanoma tumors in patients with CDKN2A mutations. Additional studies are needed to confirm these findings and to explore the mechanisms that may contribute to this relationship.

  7. Coffee, tea, and melanoma risk among postmenopausal women.

    Science.gov (United States)

    Wu, Haotian; Reeves, Katherine W; Qian, Jing; Sturgeon, Susan R

    2015-07-01

    Laboratory research suggests that components in coffee and tea may have anticarcinogenic effects. Some epidemiologic studies have reported that women who consume coffee and tea have a lower risk for melanoma. We assessed coffee, tea, and melanoma risk prospectively in the Women's Health Initiative - Observational Study cohort of 66,484 postmenopausal women, followed for an average of 7.7 years. Coffee and tea intakes were measured through self-administered questionnaires at baseline and at year 3 of follow-up. Self-reported incident melanomas were adjudicated using medical records. Cox proportional hazard models were used to estimate risk, adjusting for covariates, with person-time accumulation until melanoma diagnosis (n=398), death, loss to follow-up, or through 2005. Daily coffee [hazard ratio (HR)=0.87, 95% confidence interval (CI) 0.68-1.12] and tea (HR=1.03, 95% CI 0.81-1.31) intakes were not significantly associated with melanoma risk compared with nondaily intake of each beverage. No significant trends were observed between melanoma risk and increasing intakes of coffee (P for trend=0.38) or tea (P for trend=0.22). Women who reported daily coffee intake at both baseline and year 3 had a significantly decreased risk compared with women who reported nondaily intake at both time points (HR=0.68, 95% CI 0.48-0.97). Consistent daily tea intake was not associated with decreased melanoma risk. Overall, there is no strong evidence that increasing coffee or tea consumption can lead to a lower melanoma risk. We observed a decrease in melanoma risk among long-term coffee drinkers, but the lack of consistency in the results by dose and type cautioned against overinterpretation of the results.

  8. Risk factors for second primary melanoma among Dutch patients with melanoma

    NARCIS (Netherlands)

    Schuurman, M.S.; Waal, A.C. de; Thijs, E.J.M.; Rossum, M.M. van; Kiemeney, L.A.L.M.; Aben, K.K.H.

    2017-01-01

    BACKGROUND: Patients with melanoma are at increased risk of developing subsequent primary melanomas. Knowledge about risk factors for these subsequent primaries is scarce. More evidence may help clinicians in tailoring surveillance schedules by selecting patients who could benefit from intensified

  9. Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas.

    Science.gov (United States)

    Gillard, Marc; Cadieu, Edouard; De Brito, Clotilde; Abadie, Jérôme; Vergier, Béatrice; Devauchelle, Patrick; Degorce, Frédérique; Dréano, Stephane; Primot, Aline; Dorso, Laetitia; Lagadic, Marie; Galibert, Francis; Hédan, Benoit; Galibert, Marie-Dominique; André, Catherine

    2014-01-01

    Spontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a 4-yr follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types - 'nevocytoid type' and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Barriers and Facilitators to Melanoma Prevention and Control Behaviors Among At-Risk Children.

    Science.gov (United States)

    Wu, Yelena P; Parsons, Bridget G; Mooney, Ryan; Aspinwall, Lisa G; Cloyes, Kristin; Hay, Jennifer L; Kohlmann, Wendy; Grossman, Douglas; Leachman, Sancy A

    2018-04-06

    Melanoma prevention is essential for children who are at elevated risk for the disease due to family history. However, children who carry a familial risk for the disease do not optimally adhere to recommended melanoma preventive behaviors. The current study sought to identify perceived barriers to and facilitators of children's engagement in melanoma preventive behaviors among children at elevated risk for melanoma due to family history of the disease (i.e., having a parent with a history of melanoma) from both parents' and childrens' perspectives. Qualitative methods were employed and consisted of separate focus group discussions with children (ages 8-17 years, n = 37) and their parents (n = 39). Focus group transcripts were coded using content analysis. Parents and children reported a number of barriers and facilitators, including on the individual (e.g., knowledge and awareness, preferences), social (e.g., peer influences, family modeling and communication), and contextual (e.g., healthcare provider communication) levels. The identified categories of barriers and facilitators both confirm and extend the literature documenting the reasons children who are at elevated risk for melanoma do not engage in melanoma prevention and control behaviors. Programs aiming to decrease melanoma risk among children of melanoma survivors could help families address their barriers to preventive behavior implementation and build on facilitators. Melanoma survivors and their children could benefit from support on their interactions with healthcare providers, schools, peers, and other caregivers about melanoma prevention.

  11. Risk of malignant melanoma in men with prostate cancer. Nationwide, population-based cohort study

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Folkvaljon, Yasin; Garmo, Hans

    2016-01-01

    obtained from nationwide registers. Melanoma was diagnosed in 830/108,145 (0.78%) men with prostate cancer and in 3,699/556,792 (0.66%) prostate cancer-free men. In multivariable Cox regression models, men with prostate cancer had a significantly increased risk of melanoma (HR 1.18, 95% CI 1......An increased risk of malignant melanoma has been observed in men with prostate cancer. To assess potential shared risk factors and confounding factors, we analysed risk of melanoma in men with prostate cancer including information on tumor characteristics and demographics including socioeconomic...... status. In The Prostate Cancer data Base Sweden, risk of melanoma was assessed in a cohort of men with prostate cancer and in a comparison cohort of prostate-cancer free men. Data on prostate cancer risk category, melanoma stage, basal cell carcinoma, location of residency, and socioeconomic status were...

  12. Melanoma

    Science.gov (United States)

    ... Lentigo maligna melanoma; Melanoma in situ; Superficial spreading melanoma; Nodular melanoma; Acral lentiginous melanoma ... and brown. It is most common in Caucasians. Nodular melanoma usually starts as a raised area that is ...

  13. Individual risk of cutaneous melanoma in New Zealand: developing a clinical prediction aid.

    Science.gov (United States)

    Sneyd, Mary Jane; Cameron, Claire; Cox, Brian

    2014-05-22

    New Zealand and Australia have the highest melanoma incidence rates worldwide. In New Zealand, both the incidence and thickness have been increasing. Clinical decisions require accurate risk prediction but a simple list of genetic, phenotypic and behavioural risk factors is inadequate to estimate individual risk as the risk factors for melanoma have complex interactions. In order to offer tailored clinical management strategies, we developed a New Zealand prediction model to estimate individual 5-year absolute risk of melanoma. A population-based case-control study (368 cases and 270 controls) of melanoma risk factors provided estimates of relative risks for fair-skinned New Zealanders aged 20-79 years. Model selection techniques and multivariate logistic regression were used to determine the important predictors. The relative risks for predictors were combined with baseline melanoma incidence rates and non-melanoma mortality rates to calculate individual probabilities of developing melanoma within 5 years. For women, the best model included skin colour, number of moles > =5 mm on the right arm, having a 1st degree relative with large moles, and a personal history of non-melanoma skin cancer (NMSC). The model correctly classified 68% of participants; the C-statistic was 0.74. For men, the best model included age, place of occupation up to age 18 years, number of moles > =5 mm on the right arm, birthplace, and a history of NMSC. The model correctly classified 67% of cases; the C-statistic was 0.71. We have developed the first New Zealand risk prediction model that calculates individual absolute 5-year risk of melanoma. This model will aid physicians to identify individuals at high risk, allowing them to individually target surveillance and other management strategies, and thereby reduce the high melanoma burden in New Zealand.

  14. Melanoma

    Science.gov (United States)

    Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...

  15. Melanoma

    Science.gov (United States)

    ... if they're dark skinned, young, and have no family history. Even for them, behaviors like too much sun exposure and not enough skin protection are important risk factors. How Do People Know They Have It? Many melanomas start out as a mole or a bump ...

  16. Melanoma risk after ovarian stimulation for in vitro fertilization

    NARCIS (Netherlands)

    Spaan, M.; van den Belt-Dusebout, A. W.; Schaapveld, M.; Mooij, T. M.; Burger, C. W.; van Leeuwen, F. E.; Schats, R.; Lambalk, C. B.; Kortman, M.; Laven, J. S. E.; Jansen, C. A. M.; Helmerhorst, F. M.; Cohlen, B. J.; Braat, D. D. M.; Smeenk, J. M. J.; Simons, A. H. M.; van der Veen, F.; Evers, J. L. H.; van Dop, P. A.

    2015-01-01

    STUDY QUESTION: Do women treated with ovarian stimulation for IVF have an increased risk of melanoma? SUMMARY ANSWER: Ovarian stimulation for IVF does not increase risk of melanoma, even after a prolonged follow-up. WHAT IS KNOWN ALREADY: Although exposure to ultraviolet radiation is the major risk

  17. Non melanoma skin cancer and subsequent cancer risk.

    Directory of Open Access Journals (Sweden)

    Judy R Rees

    Full Text Available Several studies have shown an increased risk of cancer after non melanoma skin cancers (NMSC but the individual risk factors underlying this risk have not been elucidated, especially in relation to sun exposure and skin sensitivity to sunlight.The aim of this study was to examine the individual risk factors associated with the development of subsequent cancers after non melanoma skin cancer.Participants in the population-based New Hampshire Skin Cancer Study provided detailed risk factor data, and subsequent cancers were identified via linkage with the state cancer registry. Deaths were identified via state and national death records. A Cox proportional hazard model was used to estimate risk of subsequent malignancies in NMSC patients versus controls and to assess the potential confounding effects of multiple risk factors on this risk.Among 3584 participants, risk of a subsequent cancer (other than NMSC was higher after basal cell carcinoma (BCC (adjusted HR 1.40 [95% CI 1.15, 1.71] than squamous cell carcinoma (SCC (adjusted HR 1.18 [95% CI 0.95, 1.46] compared to controls (adjusted for age, sex and current cigarette smoking. After SCC, risk was higher among those diagnosed before age 60 (HR 1.96 [95% CI 1.24, 3.12]. An over 3-fold risk of melanoma after SCC (HR 3.62; 95% CI 1.85, 7.11 and BCC (HR 3.28; 95% CI 1.66, 6.51 was observed, even after further adjustment for sun exposure-related factors and family history of skin cancer. In men, prostate cancer incidence was higher after BCC compared to controls (HR 1.64; 95% CI 1.10, 2.46.Our population-based study indicates an increased cancer risk after NMSC that cannot be fully explained by known cancer risk factors.

  18. Non melanoma skin cancer and subsequent cancer risk.

    Science.gov (United States)

    Rees, Judy R; Zens, M Scot; Gui, Jiang; Celaya, Maria O; Riddle, Bruce L; Karagas, Margaret R

    2014-01-01

    Several studies have shown an increased risk of cancer after non melanoma skin cancers (NMSC) but the individual risk factors underlying this risk have not been elucidated, especially in relation to sun exposure and skin sensitivity to sunlight. The aim of this study was to examine the individual risk factors associated with the development of subsequent cancers after non melanoma skin cancer. Participants in the population-based New Hampshire Skin Cancer Study provided detailed risk factor data, and subsequent cancers were identified via linkage with the state cancer registry. Deaths were identified via state and national death records. A Cox proportional hazard model was used to estimate risk of subsequent malignancies in NMSC patients versus controls and to assess the potential confounding effects of multiple risk factors on this risk. Among 3584 participants, risk of a subsequent cancer (other than NMSC) was higher after basal cell carcinoma (BCC) (adjusted HR 1.40 [95% CI 1.15, 1.71]) than squamous cell carcinoma (SCC) (adjusted HR 1.18 [95% CI 0.95, 1.46]) compared to controls (adjusted for age, sex and current cigarette smoking). After SCC, risk was higher among those diagnosed before age 60 (HR 1.96 [95% CI 1.24, 3.12]). An over 3-fold risk of melanoma after SCC (HR 3.62; 95% CI 1.85, 7.11) and BCC (HR 3.28; 95% CI 1.66, 6.51) was observed, even after further adjustment for sun exposure-related factors and family history of skin cancer. In men, prostate cancer incidence was higher after BCC compared to controls (HR 1.64; 95% CI 1.10, 2.46). Our population-based study indicates an increased cancer risk after NMSC that cannot be fully explained by known cancer risk factors.

  19. Non Melanoma Skin Cancer and Subsequent Cancer Risk

    Science.gov (United States)

    Rees, Judy R.; Zens, M. Scot; Gui, Jiang; Celaya, Maria O.; Riddle, Bruce L.; Karagas, Margaret R.

    2014-01-01

    Introduction Several studies have shown an increased risk of cancer after non melanoma skin cancers (NMSC) but the individual risk factors underlying this risk have not been elucidated, especially in relation to sun exposure and skin sensitivity to sunlight. Purpose The aim of this study was to examine the individual risk factors associated with the development of subsequent cancers after non melanoma skin cancer. Methods Participants in the population-based New Hampshire Skin Cancer Study provided detailed risk factor data, and subsequent cancers were identified via linkage with the state cancer registry. Deaths were identified via state and national death records. A Cox proportional hazard model was used to estimate risk of subsequent malignancies in NMSC patients versus controls and to assess the potential confounding effects of multiple risk factors on this risk. Results Among 3584 participants, risk of a subsequent cancer (other than NMSC) was higher after basal cell carcinoma (BCC) (adjusted HR 1.40 [95% CI 1.15, 1.71]) than squamous cell carcinoma (SCC) (adjusted HR 1.18 [95% CI 0.95, 1.46]) compared to controls (adjusted for age, sex and current cigarette smoking). After SCC, risk was higher among those diagnosed before age 60 (HR 1.96 [95% CI 1.24, 3.12]). An over 3-fold risk of melanoma after SCC (HR 3.62; 95% CI 1.85, 7.11) and BCC (HR 3.28; 95% CI 1.66, 6.51) was observed, even after further adjustment for sun exposure-related factors and family history of skin cancer. In men, prostate cancer incidence was higher after BCC compared to controls (HR 1.64; 95% CI 1.10, 2.46). Conclusions Our population-based study indicates an increased cancer risk after NMSC that cannot be fully explained by known cancer risk factors. PMID:24937304

  20. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

    Science.gov (United States)

    Kircher, David A.; Silvis, Mark R.; Cho, Joseph H.; Holmen, Sheri L.

    2016-01-01

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

  1. Melanoma risk perception and prevention behavior among African-Americans: the minority melanoma paradox

    Directory of Open Access Journals (Sweden)

    Goldenberg A

    2015-08-01

    Full Text Available Alina Goldenberg,1 Igor Vujic,2,3 Martina Sanlorenzo,2,4 Susana Ortiz-Urda2 1Department of Internal Medicine/Dermatology, University of California, San Diego, 2Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA; 3Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria; 4Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy Introduction: Melanoma is the most deadly type of skin cancer with 75% of all skin cancer deaths within the US attributed to it. Risk factors for melanoma include ultraviolet exposure, genetic predisposition, and phenotypic characteristics (eg, fair skin and blond hair. Whites have a 27-fold higher incidence of melanoma than African-Americans (AA, but the 5-year survival is 17.8% lower for AA than Whites. It is reported continuously that AA have more advanced melanomas at diagnosis, and overall lower survival rates. This minority melanoma paradox is not well understood or studied. Objective: To explore further, the possible explanations for the difference in melanoma severity and survival in AA within the US. Methods: Qualitative review of the literature. Results: Lack of minority-targeted public education campaigns, low self-risk perception, low self-skin examinations, intrinsic virulence, vitamin D differences, and physician mistrust may play a role in the melanoma survival disparity among AA. Conclusion: Increases in public awareness of melanoma risk among AA through physician and media-guided education, higher index of suspicion among individuals and physicians, and policy changes can help to improve early detection and close the melanoma disparity gap in the future. Keywords: acral, advanced, African-American, disparity, melanoma, survival

  2. Interpretation of Melanoma Risk Feedback in First-Degree Relatives of Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Jennifer L. Hay

    2012-01-01

    Full Text Available Little is known about how individuals might interpret brief genetic risk feedback. We examined interpretation and behavioral intentions (sun protection, skin screening in melanoma first-degree relatives (FDRs after exposure to brief prototypic melanoma risk feedback. Using a 3 by 2 experimental pre-post design where feedback type (high-risk mutation, gene environment, and nongenetic and risk level (positive versus negative findings were systematically varied, 139 melanoma FDRs were randomized to receive one of the six scenarios. All scenarios included an explicit reminder that melanoma family history increased their risk regardless of their feedback. The findings indicate main effects by risk level but not feedback type; positive findings led to heightened anticipated melanoma risk perceptions and anticipated behavioral intentions. Yet those who received negative findings often discounted their family melanoma history. As such, 25%, 30%, and 32% of those who received negative mutation, gene-environment, and nongenetic feedback, respectively, reported that their risk was similar to the general population. Given the frequency with which those who pursue genetic testing may receive negative feedback, attention is needed to identify ideal strategies to present negative genetic findings in contexts such as direct to consumer channels where extensive genetic counseling is not required.

  3. MC1R germline variants confer risk for BRAF-mutant melanoma.

    Science.gov (United States)

    Landi, Maria Teresa; Bauer, Jürgen; Pfeiffer, Ruth M; Elder, David E; Hulley, Benjamin; Minghetti, Paola; Calista, Donato; Kanetsky, Peter A; Pinkel, Daniel; Bastian, Boris C

    2006-07-28

    Germline variants in MC1R, the gene encoding the melanocortin-1 receptor, and sun exposure increase risk for melanoma in Caucasians. The majority of melanomas that occur on skin with little evidence of chronic sun-induced damage (non-CSD melanoma) have mutations in the BRAF oncogene, whereas in melanomas on skin with marked CSD (CSD melanoma) these mutations are less frequent. In two independent Caucasian populations, we show that MC1R variants are strongly associated with BRAF mutations in non-CSD melanomas. In this tumor subtype, the risk for melanoma associated with MC1R is due to an increase in risk of developing melanomas with BRAF mutations.

  4. SOLAR RADIATION AS A RISK FACTOR FOR CUTANEOUS MELANOMA: REVIEW

    Directory of Open Access Journals (Sweden)

    Marianna Pesce

    2013-04-01

    Full Text Available Melanoma is a particularly aggressive type of skin cancer, and its incidence has been increasing steadily since the 1970s. In this article we have reviewed the main risk factors for this disease in particular: sun exposure, the use of tanning beds or sunlamps and skin phototype. We also mention the importance of primary prevention in subjects at risk to reduce the onset of cutaneous melanoma.

  5. Nonsteroidal Anti-Inflammatory Drugs and Risk of Melanoma

    Directory of Open Access Journals (Sweden)

    Joanne M. Jeter

    2011-01-01

    Full Text Available Because nonsteroidal anti-inflammatory drugs (NSAIDs inhibit tumor growth in vitro, we investigated the association between NSAIDs and melanoma to determine if there was epidemiologic evidence of a chemopreventive effect from these medications. Three hundred twenty-seven subjects with incident melanoma and 119 melanoma-free controls completed a structured interview assessing melanoma risk factors. The unadjusted odds ratio (OR for use of nonaspirin NSAIDs was 0.58 (95% CI 0.31–1.11, in a comparison of subjects with melanoma to controls. After adjustment for melanoma risk factors, the OR was 0.71 (95% CI 0.23–2.02. Aspirin users had an unadjusted OR of 0.85 (95% CI 0.45–1.69 and an adjusted OR of 1.45 (95% CI 0.44–4.74. In this pilot study, we found no evidence of a significant association between analgesic use and melanoma risk when potential confounders are assessed. Based on conflicting reports in the literature, meta-analysis may be appropriate.

  6. Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition.

    Science.gov (United States)

    Caini, Saverio; Masala, Giovanna; Saieva, Calogero; Kvaskoff, Marina; Savoye, Isabelle; Sacerdote, Carlotta; Hemmingsson, Oskar; Hammer Bech, Bodil; Overvad, Kim; Tjønneland, Anne; Petersen, Kristina E N; Mancini, Francesca Romana; Boutron-Ruault, Marie-Christine; Cervenka, Iris; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; Floegel, Anna; Trichopoulou, Antonia; Valanou, Elisavet; Kritikou, Maria; Tagliabue, Giovanna; Panico, Salvatore; Tumino, Rosario; Bueno-de-Mesquita, H B As; Peeters, Petra H; Veierød, Marit B; Ghiasvand, Reza; Lukic, Marko; Quirós, José Ramón; Chirlaque, Maria-Dolores; Ardanaz, Eva; Salamanca Fernández, Elena; Larrañaga, Nerea; Zamora-Ros, Raul; Maria Nilsson, Lena; Ljuslinder, Ingrid; Jirström, Karin; Sonestedt, Emily; Key, Timothy J; Wareham, Nick; Khaw, Kay-Tee; Gunter, Marc; Huybrechts, Inge; Murphy, Neil; Tsilidis, Konstantinos K; Weiderpass, Elisabete; Palli, Domenico

    2017-05-15

    In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma. © 2017 UICC.

  7. Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.

    Science.gov (United States)

    Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

    2014-01-01

    Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. © 2013 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

  8. Using a family systems approach to investigate cancer risk communication within melanoma families

    Science.gov (United States)

    Harris, Julie N.; Hay, Jennifer; Kuniyuki, Alan; Asgari, Maryam M; Press, Nancy; Bowen, Deborah J.

    2009-01-01

    OBJECTIVE The family provides an important communication nexus for information and support exchange about family cancer history, and adoption of family-wide cancer risk reduction strategies. The goals of this study were to: 1) use the family systems theory to identify characteristics of this sample of families at increased risk of developing melanoma and 2) to relate familial characteristics to the frequency and style of familial risk communication. METHODS Participants were first-degree relatives (n=313) of melanoma patients, recruited into a family web-based intervention study. We used multivariable logistic regression models to analyze the association between family functioning and family communication. RESULTS Most participants were female (60%), with an average age of 51 years. Fifty percent of participants reported that they spoke to their relatives about melanoma risk and people were more likely to speak to their female family members. Familial adaptation, cohesion, coping, and health beliefs were strongly associated with an open style of risk communication within families. None were associated with a blocked style of risk communication. Only cohesion and adaptation were associated with the amount of risk communication that occurred within families. CONCLUSIONS Overall, individuals who came from families that were more highly cohesive, adaptable, and shared strong beliefs about melanoma risk were more likely to communicate openly about melanoma. The fact that this association was not consistent across blocked communication and communication frequency highlights the multifaceted nature of this process. Future research should focus on the interplay between different facets of communication. PMID:20119933

  9. Telomere length and the risk of cutaneous melanoma and non-melanoma skin cancer: a review of the literature and meta-analysis.

    Science.gov (United States)

    Caini, Saverio; Raimondi, Sara; Johansson, Harriet; De Giorgi, Vincenzo; Zanna, Ines; Palli, Domenico; Gandini, Sara

    2015-12-01

    There is much evidence supporting the role of telomeres in cancer pathogenesis, however the studies that investigated the association between telomere length and skin cancer risk provided inconsistent results. To help clarify this issue, we performed a systematic review and meta-analysis of published papers on the association between peripheral leukocytes telomere length (PLTL) and the risk of cutaneous melanoma and non-melanoma skin cancer (NMSC). We calculated summary relative risks (SRR) and 95% confidence intervals (95% CI) using random effect models with maximum likelihood estimates, and explored causes of between-studies heterogeneity of risk estimates. We included 1629 cutaneous melanoma and 1439 NMSC from eight independent studies published until March 2015. The SRR of cutaneous melanoma for those in the lowest (vs. highest) category of PLTL distribution was 0.25 (95% CI 0.09-0.67). The results were less clear for NMSC, with two studies reporting no association and one study showing an increase in risk for those in the lowest (vs. highest) category of PLTL distribution. For both cutaneous melanoma and NMSC, the between-studies heterogeneity was large, mainly due to inclusion of hospital-based case-control studies. Our meta-analysis shows evidence of an association between short PLTL and reduced risk for cutaneous melanoma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Common Genetic Risk for Melanoma Encourages Preventive Behavior Change

    Directory of Open Access Journals (Sweden)

    Lori Diseati

    2015-02-01

    Full Text Available There is currently great interest in using genetic risk estimates for common disease in personalized healthcare. Here we assess melanoma risk-related preventive behavioral change in the context of the Coriell Personalized Medicine Collaborative (CPMC. As part of on-going reporting activities within the project, participants received a personalized risk assessment including information related to their own self-reported family history of melanoma and a genetic risk variant showing a moderate effect size (1.7, 3.0 respectively for heterozygous and homozygous individuals. Participants who opted to view their report were sent an optional outcome survey assessing risk perception and behavioral change in the months that followed. Participants that report family history risk, genetic risk, or both risk factors for melanoma were significantly more likely to increase skin cancer preventive behaviors when compared to participants with neither risk factor (ORs = 2.04, 2.79, 4.06 and p-values = 0.02, 2.86 × 10−5, 4.67 × 10−5, respectively, and we found the relationship between risk information and behavior to be partially mediated by anxiety. Genomic risk assessments appear to encourage positive behavioral change in a manner that is complementary to family history risk information and therefore may represent a useful addition to standard of care for melanoma prevention.

  11. Using risk factors for detection and prognostication of uveal melanoma

    Science.gov (United States)

    Rishi, Pukhraj; Koundanya, Vikram V; Shields, Carol L

    2015-01-01

    The early detection of malignancy, particularly uveal melanoma, is crucial in protecting visual acuity, salvaging the eye, and preventing metastasis. Risk factors for early detection of uveal melanoma have been clearly delineated in the literature and allow identification of melanoma when it is tiny and simulates a nevus. These factors include thickness >2 mm, presence of subretinal fluid (SRF), symptoms, the orange pigment, margin near optic disc, acoustic hollowness, surrounding halo, and absence of drusen. The importance of early detection is realized when one considers melanoma thickness, as each millimeter increase in melanoma thickness imparts 5% increased risk for metastatic disease. Newer imaging modalities like enhanced depth imaging optical coherence tomography and fundus autoflouroscence facilitate in detection of SRF and orange pigment. Additional molecular biomarkers and cytological features have been identified which can predict the clinical behavior of a small melanocytic lesion. Features that suggest a poor prognosis include higher blood levels of tyrosinase m-RNA, vascular endothelial growth factor, insulin-like growth factor; monosomy 3 and gains in chromosome 8. Management of uveal melanoma includes enucleation (for large), local eye wall resection, brachytherapy, charged particle irradiation, and thermotherapy (for small to medium tumors). Although the role of a good clinical evaluation cannot be underestimated, it is advisable to evaluate the various radiological, molecular, and cytological features, to enhance the accuracy of early diagnosis and improved prognosis. PMID:25827540

  12. Using risk factors for detection and prognostication of uveal melanoma

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2015-01-01

    Full Text Available The early detection of malignancy, particularly uveal melanoma, is crucial in protecting visual acuity, salvaging the eye, and preventing metastasis. Risk factors for early detection of uveal melanoma have been clearly delineated in the literature and allow identification of melanoma when it is tiny and simulates a nevus. These factors include thickness >2 mm, presence of subretinal fluid (SRF, symptoms, the orange pigment, margin near optic disc, acoustic hollowness, surrounding halo, and absence of drusen. The importance of early detection is realized when one considers melanoma thickness, as each millimeter increase in melanoma thickness imparts 5% increased risk for metastatic disease. Newer imaging modalities like enhanced depth imaging optical coherence tomography and fundus autoflouroscence facilitate in detection of SRF and orange pigment. Additional molecular biomarkers and cytological features have been identified which can predict the clinical behavior of a small melanocytic lesion. Features that suggest a poor prognosis include higher blood levels of tyrosinase m-RNA, vascular endothelial growth factor, insulin-like growth factor; monosomy 3 and gains in chromosome 8. Management of uveal melanoma includes enucleation (for large, local eye wall resection, brachytherapy, charged particle irradiation, and thermotherapy (for small to medium tumors. Although the role of a good clinical evaluation cannot be underestimated, it is advisable to evaluate the various radiological, molecular, and cytological features, to enhance the accuracy of early diagnosis and improved prognosis.

  13. Thin melanoma.

    Science.gov (United States)

    Elder, David E

    2011-03-01

    The incidence of malignant melanoma is increasing and a preponderance of the melanomas diagnosed today are "thin in terms of Breslow criteria. Although thin melanomas, as a group, are associated with a very good prognosis, a subset of these tumors may metastasize and cause death. These cases can be identified by using prognostic models, including the "standard" American Joint Committee on Cancer criteria, and other attributes identified in follow-up studies. To review the history of concepts of prognostic modeling in melanoma, focusing on thin melanomas. Selected literature. About 40 years ago, it was realized that malignant melanoma, once almost uniformly fatal, could be divided into categories with better or worse prognosis through the use of prognostic models. The first simple models, Clark levels of invasion and Breslow thickness, are still in use. Thickness remains the single most useful variable. Breslow recognized that melanomas less than 0.76 mm in thickness were associated with a very good prognosis, with no metastases in his limited initial study. The American Joint Committee on Cancer selected a cutoff of 1.0 mm, which achieves a similar result, with stage modifiers, although some metastases and deaths do occur with stage I lesions. Clark demonstrated an almost equally good prognosis for his level II invasive melanomas and recognized that most of these lesions, although invasive, lacked the ability to form tumors or to undergo mitosis in the dermis and were therefore "nontumorigenic" and "nonmitogenic" and lacked competence for metastasis. Studies of these low-risk melanomas have led to the development of criteria for earlier diagnosis and a steady, but still inadequate, improvement in prognosis for melanoma overall. Multivariable models currently can identify groups of patients within the "thin melanoma" category whose prognosis varies, from a disease-free survival of close to 100% to about 70%. Prognosis declines more or less linearly with increasing

  14. Treatment with levodopa and risk for malignant melanoma

    DEFF Research Database (Denmark)

    Olsen, Jørgen H; Tangerud, Karina; Wermuth, Lene

    2007-01-01

    with nonmelanoma skin cancer, and 172 control subjects, we investigated the hypothesis that treatment with levodopa increases the risk for skin cancer. Information on diagnoses and treatment was retrieved from medical records. We observed a significant fourfold to fivefold increase in the risk for malignant...... melanoma in a subgroup of patients with a probable diagnosis of idiopathic Parkinson's disease as compared with other patients. There was apparently no effect of levodopa on the risk for malignant melanoma as indicated by an odds ratio of 1.0 (95% confidence interval, 0.8-1.3) per 1,000 g cumulative intake...... of the drug. We conclude that the increased rate of malignant melanoma observed in patients treated at hospital for Parkinson's disease is restricted to those with idiopathic Parkinson's disease, however, unrelated to the treatment with levodopa. (c) 2007 Movement Disorder Society....

  15. Plasma 25-hydroxyvitamin D and risk of non-melanoma and melanoma skin cancer: a prospective cohort study.

    Science.gov (United States)

    Afzal, Shoaib; Nordestgaard, Børge G; Bojesen, Stig E

    2013-03-01

    Sun exposure is a major risk factor for skin cancer and is also an important source of vitamin D. We tested the hypothesis that elevated plasma 25-hydroxyvitamin D (25-OH-vitD) associates with increased risk of non-melanoma and melanoma skin cancer in the general population. We measured plasma 25-OH-vitD in 10,060 white individuals from the Danish general population. During 28 years of follow-up, 590 individuals developed non-melanoma skin cancer and 78 developed melanoma skin cancer. Increasing 25-OH-vitD levels, by clinical categories or by seasonally adjusted tertiles, were associated with increasing cumulative incidence of non-melanoma skin cancer (trend P=2 × 10(-15) and P=3 × 10(-17)) and melanoma skin cancer (P=0.003 and P=0.001). Multivariable adjusted hazard ratios of non-melanoma skin cancer were 5.04 (95% confidence interval (CI): 2.78-9.16) for 25-OH-vitD ≥50 vs. melanoma skin cancer were 4.7 (0.96-23.3) for 25-OH-vitD ≥50 vs. melanoma skin cancer and 1.5% for melanoma skin cancer, in participants with age >60 years, 25-OH-vitD winter levels ≥50 nmol  l(-1), and performing outdoor exercise. In conclusion, we show that increasing levels of 25-OH-vitD are associated with increased risk of non-melanoma and melanoma skin cancer.

  16. MC1R variants increase melanoma risk in families with CDKN2A mutations: a meta-analysis.

    Science.gov (United States)

    Fargnoli, Maria Concetta; Gandini, Sara; Peris, Ketty; Maisonneuve, Patrick; Raimondi, Sara

    2010-05-01

    We performed a meta-analysis to assess whether MC1R variants increase the risk of melanoma in CDKN2A mutation carriers of melanoma-prone families. Data from 96 CDKN2A-positive melanoma-prone families from seven independent populations of Europe, United States and Australia were included in the analysis. Summary risk estimates were calculated by random-effect models. We explored between-study heterogeneity and publication bias. Association between MC1R variants and age at diagnosis was assessed by the non-parametric Wilcoxon test. CDKN2A mutation carriers with 1 MC1R variant showed a double melanoma risk as compared to CDKN2A mutation carriers without MC1R variants (Summary OR; 95%CI: 2.2; 1.1-4.5). MC1R heterozygous subjects had no significantly higher melanoma risk than wild-type subjects (1.6; 0.5-5.4) while carriers of multiple MC1R variants had a more than four-times higher melanoma risk (4.6; 1.3-16.4). Carriers of red hair colour (RHC) variants showed an increased melanoma risk with a Summary OR of 3.5 (95%CI: 1.3-9.9). CDKN2A mutation carriers with MC1R variants had a statistically significant lower median age at melanoma diagnosis than CDKN2A mutation carriers with no MC1R variants (37years versus 47years, p-valueMC1R variants significantly increase penetrance of CDKN2A mutations in melanoma-prone families, especially with respect to multiple MC1R variants and to RHC variants. A significant anticipation of melanoma diagnosis is observed in CDKN2A mutation carriers with MC1R variants. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  17. The Melanoma care study: protocol of a randomised controlled trial of a psycho-educational intervention for melanoma survivors at high risk of developing new primary disease.

    Science.gov (United States)

    Dieng, Mbathio; Kasparian, Nadine A; Morton, Rachael L; Mann, Graham J; Butow, Phyllis; Menzies, Scott; Costa, Daniel S J; Cust, Anne E

    2015-01-01

    Despite a good prognosis for most melanoma survivors, many experience substantial fear of new or recurrent melanoma, worry and anxiety about the future, and unmet healthcare needs. In this protocol, we outline the design and methods of the Melanoma Care Study for melanoma survivors at high risk of developing new primary disease. The objective of this study is to evaluate the efficacy and cost-effectiveness of a psycho-educational intervention for improving psychological and behavioural adjustment to melanoma risk. The study design is a two-arm randomised controlled trial comparing a psycho-educational intervention to usual care. The intervention is comprised of a newly-developed psycho-educational booklet and three telephone sessions delivered by a trained psychologist. A total of 154 melanoma survivors at high risk of developing new primary disease who are attending one of three melanoma high risk clinics in New South Wales, Australia, will be recruited. Participants will be assessed at baseline (6 weeks before their high risk clinic dermatological appointment), and then 4 weeks and 6 months after their appointment. If effectiveness of the intervention is demonstrated at 6 months, an additional assessment at 12 months is planned. The primary outcome is fear of new or recurrent melanoma, as assessed by the Fear of Cancer Recurrence Inventory (FCRI). Secondary outcomes include anxiety, depression, unmet supportive care needs, satisfaction with clinical care, knowledge, behavioural adjustment to melanoma risk, quality of life, and cost-effectiveness of the intervention from a health system perspective. Following the intention-to-treat principle, linear mixed models will be used to analyse the data to account for repeated measures. A process evaluation will also be carried out to inform and facilitate potential translation and implementation into clinical practice. This study will provide high quality evidence on the efficacy and cost-effectiveness of a psycho

  18. Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy—From Animal Models to Clinical Trials

    Directory of Open Access Journals (Sweden)

    Martyna Śniegocka

    2018-04-01

    Full Text Available The focus of the present review is to investigate the role of melanin in the radioprotection of melanoma and attempts to sensitize tumors to radiation by inhibiting melanogenesis. Early studies showed radical scavenging, oxygen consumption and adsorption as mechanisms of melanin radioprotection. Experimental models of melanoma in hamsters and in gerbils are described as well as their use in biochemical and radiobiological studies, including a spontaneously metastasizing ocular model. Some results from in vitro studies on the inhibition of melanogenesis are presented as well as radio-chelation therapy in experimental and clinical settings. In contrast to cutaneous melanoma, uveal melanoma is very successfully treated with radiation, both using photon and proton beams. We point out that the presence or lack of melanin pigmentation should be considered, when choosing therapeutic options, and that both the experimental and clinical data suggest that melanin could be a target for radiosensitizing melanoma cells to increase efficacy of radiotherapy against melanoma.

  19. Risk factors for keratinocyte skin cancer in patients diagnosed with melanoma, a large retrospective study.

    Science.gov (United States)

    Espinosa, Pablo; Pfeiffer, Ruth M; García-Casado, Zaida; Requena, Celia; Landi, Maria Teresa; Kumar, Rajiv; Nagore, Eduardo

    2016-01-01

    Melanoma survivors are at an increased risk of developing other malignancies, including keratinocyte skin cancer (KSC). While it is known that many risk factors for melanoma also impact risk of KSC in the general population, no previous study has investigated risk factors for KSC development in melanoma patients. We assessed associations of personal and clinical characteristics, including skin phenotype and variations in the melanocortin 1 receptor (MC1R) gene, with KSC risk in melanoma patients. We used prospective follow-up information on 1200 patients treated for melanoma at the Instituto Valenciano de Oncología, Spain, between 2000 and 2011. We computed hazard ratios and 95% confidence intervals (CIs) for the association of clinical, personal and genetic characteristics with risk of KSC, squamous cell carcinoma (SCC), or basal cell carcinoma (BCC) from Cox proportional hazard models. Five-year cumulative incidence based on competing risk models of SCC, BCC or KSC overall was computed using multivariate subdistribution hazard models. To assess predictive performance of the models, we computed areas under the receiver-operating characteristic curves (AUCs, discriminatory power) using cross-validation. Median follow-up was 57.2 months; a KSC was detected in 163 patients (13.6%). In multivariable Cox models, age, sex, sunburns, chronic sun exposure, past personal history of non-melanoma skin cancer or other non-cutaneous neoplasia, and the MC1R variants p.D294H and p.R163Q were significantly associated with KSC risk. A cumulative incidence model including age, sex, personal history of KSC, and of other non-cutaneous neoplasia had an AUC of 0.76 (95% CI: 0.71-0.80). When p.D294H and p.R163Q variants were added to the model, the AUC increased to 0.81 (95% CI: 0.77-0.84) (p-value for difference skin characteristics, and sun exposure, p.R163Q and p.D294H MC1R variants significantly increased KSC risk among melanoma patients. Our findings may help identify patients

  20. Coffee Drinking and Cutaneous Melanoma Risk in the NIH-AARP Diet and Health Study

    Science.gov (United States)

    Freedman, Neal D.; Graubard, Barry I.; Hollenbeck, Albert R.; Shebl, Fatma M.; Mayne, Susan T.; Sinha, Rashmi

    2015-01-01

    Background: Cutaneous melanoma is the fifth most common cancer in the United States. Modifiable risk factors, with the exception of exposure to ultraviolet radiation (UVR), are poorly understood. Coffee contains numerous bioactive compounds and may be associated inversely with melanoma. However, previous epidemiological evidence is limited. Methods: Coffee intake was assessed at baseline with a food frequency questionnaire in the National Institutes of Health–AARP prospective cohort study. Among 447 357 non-Hispanic whites who were cancer-free at baseline, 2904 incident cases of malignant melanoma were identified during 4 329 044 person-years of follow-up, with a median of 10.5 years of follow-up. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coffee intake and subsequent melanoma risk with non–coffee drinkers as the reference group. Statistical tests were two-sided, and P values less than .05 were interpreted as statistically significant. Results: The highest category of coffee intake was inversely associated with malignant melanoma (≥4 cups/day: HR = 0.80, 95% CI = 0.68 to 0.93, P trend = .01). This association was statistically significant for caffeinated (≥4 cups/day: HR = 0.75, 95% CI = 0.64 to 0.89, P trend = .01) but not for decaffeinated coffee (P trend = .55). Conclusions: Higher coffee intake was associated with a modest decrease in risk of melanoma in this large US cohort study. Additional investigations of coffee intake and its constituents, particularly caffeine, with melanoma are warranted. PMID:25604135

  1. DNA Repair Variants, Indoor Tanning and Risk of Melanoma

    Science.gov (United States)

    Torres, Salina M.; Luo, Li; Lilyquist, Jenna; Stidley, Christine A; Flores, Kristina; White, Kirsten A. M.; Erdei, Esther; Gonzales, Melissa; Paine, Susan; Vogel, Rachel Isaksson; Lazovich, DeAnn; Berwick, Marianne

    2013-01-01

    Summary Although ultraviolet radiation (UV) exposure from indoor tanning has been linked to an increased risk of melanoma, the role of DNA repair genes in this process is unknown. We evaluated the association of 92 single nucleotide polymorphisms (SNPs) in 20 DNA repair genes with the risk of melanoma and indoor tanning among 929 melanoma patients and 817 controls from the Minnesota Skin Health Study. Significant associations with melanoma risk were identified for SNPs in ERCC4, ERCC6, RFC1, XPC, MGMT, and FBRSL1 genes; with a cut-off of p<0.05. ERCC6 and FBRSL1 gene variants and haplotypes interacted with indoor tanning. However, none of the 92 SNPs tested met the correction criteria for multiple comparisons. This study, based on an a priori interest in investigating the role of DNA repair capacity using variants in base excision and nucleotide excision repair, identified several genes that may play a role in resolving UV-induced DNA damage. PMID:23659246

  2. Heterogeneity in host risk factors for incident melanoma and non-melanoma skin cancer in a cohort of US women.

    Science.gov (United States)

    Qureshi, Abrar A; Zhang, Mingfeng; Han, Jiali

    2011-01-01

    Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) are 3 types of skin cancer that have distinct biologic characteristics and prognoses. We evaluated phenotypic differences in the risk of these cancers in US women. We conducted a prospective study of 113 139 female nurses from 1984 to 2002. Over the 18 years of follow-up, there were 375 cases of melanoma, 495 cases of SCC, and 9423 cases of BCC. Women with melanoma were more likely to have a family history of melanoma (melanoma: RR 1.94, 95% confidence interval [CI] 1.36-2.76; SCC: RR 0.82, 95% CI 0.58-1.37; BCC: RR 1.49, 95% CI 1.38-1.62) and 6 or more moles on the left arm (melanoma: RR 3.66, 95% CI 2.15-6.24; SCC: RR 1.53, 95% CI 0.83-2.79; BCC: RR 1.48, 95% CI 1.28-1.72). Polytomous logistic regression analysis showed that age at diagnosis (P melanoma (P = 0.016), and number of moles on the left arm (P = 0.007) were significantly different across the 3 cancers. This prospective observational study demonstrated that known phenotypic factors for skin cancer have a differential impact on the risk of melanoma, SCC, and BCC.

  3. Risk of multiple primary cancers following melanoma and non-melanoma skin cancer.

    Science.gov (United States)

    Stracci, F; Fabrizi, V; D'Alò, D; La Rosa, F; Papini, M

    2012-11-01

    The relationship between cutaneous malignancies and successive primary cancers has been studied since several years, but it still remains controversial. The aim of this study was to evaluate the excess risk of multiple primary cancer among the population of Umbria, Italy, that survived a skin cancer. The data registered in the Umbrian Population Cancer Registry from 1994 to 2006 were collected, recorded, and analysed in accordance to the standard methods recommended for cancer registries. Among skin cancer patients, those with multiple cutaneous and non-cutaneous cancers were selected. Only sites with a frequency of more than five cases were considered. The expected number of cases was obtained from indirect standardization with regional incidence rates in several sites that incurred in the overall period. The significance of the observed/expected ratios and the corresponding 95% CI were based on the Poisson distribution. In men, a significant standardized incidence ratio (SIR) was found for melanoma (2.21), non-melanoma skin cancers (1.86), Hodgkin's (4.95) and non-Hodgkin lymphoma (1.82), and tongue/mouth cancer (2.47). In women, melanoma, non-melanoma skin and breast cancer showed a significant high SIRs (4.13, 1.55 and 1.28 respectively). All other cancers showed a non-significant SIR. Considering all sites combined and all sites except skin cancers, the analysis showed a significant excess in men, whereas a significant risk was observed in women only when also skin cancers were considered. Data from the whole of Umbrian population revealed that skin cancer patients experience marked excess risk of further primary cancers. The main risk in both genders is skin melanoma and other skin cancers. The excess of lymphomas and tongue/mouth cancers is also significant in men, and breast cancer in women. These observations prompt us to include a screening for these cancers in the follow-up of our patients surviving a skin malignancy. © 2011 The Authors. Journal of the

  4. Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: a comprehensive review and meta-analysis.

    Science.gov (United States)

    Caini, Saverio; Boniol, Mathieu; Tosti, Giulio; Magi, Serena; Medri, Matelda; Stanganelli, Ignazio; Palli, Domenico; Assedi, Melania; Marmol, Veronique Del; Gandini, Sara

    2014-10-01

    Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60-3.53) and 1.64 (95% CI 1.02-2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63-1.13) for CM and 1.03 (95% CI 0.95-1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Current State of Animal (Mouse Modeling in Melanoma Research

    Directory of Open Access Journals (Sweden)

    Omer F. Kuzu

    2015-01-01

    Full Text Available Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Advancement of next-generation sequencing technology allowed better identification of alterations that trigger melanoma development. As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated. In this article, besides traditional mouse models of melanoma, we will discuss recent ones, such as patient-derived tumor xenografts, topically inducible BRAF mouse model and RCAS/TVA-based model, and their advantages as well as limitations. Although mouse models of melanoma are often criticized as poor predictors of whether an experimental drug would be an effective treatment, development of new and more relevant models could circumvent this problem in the near future.

  6. Multicenter case-control study of risk factors for cutaneous melanoma in Valencia, Spain.

    Science.gov (United States)

    Ballester, I; Oliver, V; Bañuls, J; Moragón, M; Valcuende, F; Botella-Estrada, R; Nagore, E

    2012-11-01

    It is important to identify subgroups within the general population that have an elevated risk of developing cutaneous melanoma because preventive and early-detection measures are useful in this setting. The findings of most studies that have evaluated risk factors for cutaneous melanoma are of limited application in Spain because the populations studied have different pigmentary traits and are subject to different environmental factors. To identify the phenotypic characteristics and amount of exposure to sunlight that constitute risk factors for cutaneous melanoma in the population of the Autonomous Community of Valencia, Spain. We performed a multicenter observational case-control study. In total, the study included 242 patients with melanoma undergoing treatment in 5 hospitals and 173 controls enrolled from among the companions of the patients between January 2007 and June 2008. The information was collected by means of a standardized, validated questionnaire. The odds ratio (OR) was calculated for each variable and adjusted using a multiple logistic regression model. The risk factors found to be statistically significant were skin phototypes I and II, blond or red hair, light eye color, abundant melanocytic nevi, and a personal history of actinic keratosis or nonmelanoma skin cancer. After the multivariate analysis, only blond or red hair (OR=1.9), multiple melanocytic nevi (OR=3.1), skin phototypes i and ii (OR=2.1), and a personal history of actinic keratosis (OR=3.5) or nonmelanoma skin cancer (OR=8.1) maintained significance in the model as independent predictive variables for melanoma. Our study supports the importance of certain factors that indicate genetic predisposition (hair color and skin phototype) and environmental factors associated with exposure to sunlight. Patients with multiple acquired melanocytic nevi and patients with markers of chronic skin sun damage (actinic keratosis and nonmelanoma cancer) presented a significant increase in risk

  7. Chronology of metastasis in cutaneous melanoma: growth rate model.

    Science.gov (United States)

    Tejera-Vaquerizo, Antonio; Nagore, Eduardo; Meléndez, Juan J; López-Navarro, Norberto; Martorell-Calatayud, Antonio; Herrera-Acosta, Enrique; Traves, Victor; Guillén, Carlos; Herrera-Ceballos, Enrique

    2012-04-01

    In humans, it is not possible to obtain experimental evidence of when a cancer begins to metastasize. The purpose of this study was to estimate the time of onset of metastatic dissemination in cutaneous melanoma using a model based on its growth rate (GR). The critical time of onset of metastatic dissemination below which no cases of fatal melanomas were seen may be described with a potential function in which this time is inversely proportional to the GR. The critical time of development beyond which a melanoma may metastasize presents great variation. This time was just 1 month for those melanomas with a fast GR, whereas it was over 5 years for those with a very slow GR. Quantitatively, the fastest-growing melanomas began metastasizing with a greater thickness than the slowest-growing melanomas. A correlation exists between the critical time of onset of metastatic potential and the GR of the melanoma. These results may well have relevance to the understanding of mechanisms of tumor dissemination and for the design of future studies on melanomas, irrespective of whether they are basic studies on biomolecular mechamisms or clinical studies.

  8. Targeting subjects at high-risk of melanoma.

    Science.gov (United States)

    Chiarugi, Alessandra

    2017-06-01

    The current strategies for early diagnosis result at the moment insufficient to make further progresses in the fight against the melanoma. Reaching people not reached by screening activity yet is necessary for reducing mortality from this tumor. The well-known risk factors are still effective, but they have to be implemented by other variables at risk, like sex and age. People aged over 50 years old should be considered at risk, independently from other features. Renewed messages should be addressed to population and general practitioners. In this paper the old and new evidences on main risk factors will be analyzed and supported by the evidences of the literature.

  9. Diagnosis and clinical management of melanoma patients at higher risk of a new primary melanoma: A population-based study in New South Wales, Australia.

    Science.gov (United States)

    Watts, Caroline G; Madronio, Christine M; Morton, Rachael L; Goumas, Chris; Armstrong, Bruce K; Curtin, Austin; Menzies, Scott W; Mann, Graham J; Thompson, John F; Cust, Anne E

    2017-11-01

    To describe the method of diagnosis, clinical management and adherence to clinical practice guidelines for melanoma patients at high risk of a subsequent primary melanoma, and compare this with melanoma patients at lower risk. The Melanoma Patterns of Care study was a population-based, observational study based on doctors' reported clinical management of melanoma patients in New South Wales, Australia, diagnosed with in situ or invasive melanoma over a 12-month period from October 2006. Of 2605 patients with localised melanoma, 1019 (39%) were defined as at higher risk due to the presence of one or more of the following factors: a family history of melanoma (11%), multiple primary melanomas (17%), or many naevi (24%). Compared to patients at lower risk, high risk patients were more likely to receive their initial care from a primary care physician (56% vs 50%, P = 0.002), have their melanoma detected during a routine skin check (40% vs 33%, P < 0.001), have their lesion assessed with dermoscopy (63% vs 56%, P = 0.002), and be encouraged to have skin surveillance (84% vs 77%, P < 0.001) and skin self-examination (87% vs 83%, P = 0.03). Higher socioeconomic status and urban residence were associated with patients at higher risk receiving initial treatment from a specialist doctor. Clinical management of higher risk patients was more likely to conform to clinical practice guidelines for diagnosis and skin surveillance than to melanoma patients at lower risk. © 2016 The Australasian College of Dermatologists.

  10. Phosphodiesterase Type 5 Inhibitors and the Risk of Melanoma Skin Cancer.

    Science.gov (United States)

    Lian, Yi; Yin, Hui; Pollak, Michael N; Carrier, Serge; Platt, Robert W; Suissa, Samy; Azoulay, Laurent

    2016-11-01

    The association between phosphodiesterase type 5 inhibitors (PDE5-Is), drugs used in the treatment of erectile dysfunction (ED), and melanoma skin cancer is controversial. To assess whether the use of PDE5-Is is associated with an increased risk of melanoma skin cancer. Using the UK Clinical Practice Research Datalink, we assembled a cohort of men newly diagnosed with ED between 1998 and 2014 and followed until 2015. PDE5-I exposure was considered as a time-varying variable lagged by 1 yr for latency purposes. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of incident melanoma associated with PDE5-I use overall and by number of prescriptions and pills received. Identical analyses were conducted for basal and squamous cell carcinoma, two cancers for which PDE5-related pathways are not thought to be involved. The cohort included 142 983 patients, of whom 440 were newly diagnosed with melanoma during follow-up (rate: 63.0 per 100 000 person-years). Compared with nonuse, PDE5-I use was not associated with an overall increased risk of melanoma (rates: 66.7 vs 54.1 per 100 000 person-years; HR: 1.18; 95% CI, 0.95-1.47). The risk was significantly increased among those who had received seven or more prescriptions and ≥25 pills (HR: 1.30 [95% CI, 1.01-1.69] and 1.34 [95% CI, 1.04-1.72], respectively). In contrast, there was no overall association with basal and squamous cell carcinoma, with an unclear association with numbers of prescriptions and pills received. The use of PDE5-Is was not associated with an overall increased risk of melanoma skin cancer. The increased risks observed in the highest prescription and pill categories require further validation. In this study, the use of phosphodiesterase type 5 inhibitors was not associated with an increased risk of melanoma skin cancer. Copyright © 2016. Published by Elsevier B.V.

  11. Interval cancers after skin cancer screening: incidence, tumour characteristics and risk factors for cutaneous melanoma.

    Science.gov (United States)

    Hübner, J; Waldmann, A; Geller, A C; Weinstock, M A; Eisemann, N; Noftz, M; Bertram, S; Nolte, S; Volkmer, B; Greinert, R; Breitbart, E; Katalinic, A

    2017-01-17

    The rate of interval cancers is an established indicator for the performance of a cancer-screening programme. We examined the incidence, tumour characteristics and risk factors of melanoma interval cancers that occurred in participants of the SCREEN project, which was carried out 2003/2004 in Schleswig-Holstein, Germany. Data from 350 306 SCREEN participants, who had been screened negative for melanoma, were linked to data of the state cancer registry. Melanoma interval cancers were defined as melanomas diagnosed within 4-24 months after SCREEN examination. Results were compared with melanomas of the pre-SCREEN era (1999-2002), extracted from the cancer registry. The overall relative incidence of melanoma interval cancers in terms of observed/expected ratio was 0.93 (95% CI: 0.82-1.05; in situ: 1.61 (1.32-1.95), invasive: 0.71 (0.60-0.84)). Compared with melanomas of the pre-SCREEN era, the interval melanomas were thinner and had a slightly greater proportion of lentigo maligna melanomas whereas nodular melanomas were less frequent. The results indicate a moderate performance of the SCREEN intervention with an excess of in situ melanomas. In part, the findings might be due to specifics of the SCREEN project, in particular a short-term follow-up of patients at high risk for melanoma.

  12. A melanoma risk score in a Brazilian population Um escore de risco para melanoma em uma população brasileira

    Directory of Open Access Journals (Sweden)

    Lucio Bakos

    2013-04-01

    Full Text Available BACKGROUND: Important risk factors for cutaneous melanoma (CM are recognized, but standardized scores for individual assessment must still be developed. OBJECTIVES: The objective of this study was to develop a risk score of CM for a Brazilian sample. METHODS: To verify the estimates of the main risk factors for melanoma, derived from a meta-analysis (Italian-based study, and externally validate them in a population in southern Brazil by means of a case-control study. A total of 117 individuals were evaluated. Different models were constructed combining the summary coefficients of different risk factors, derived from the meta-analysis, multiplied by the corresponding category of each variable for each participant according to a mathematical expression. RESULTS: the variable that best predicted the risk of CM in the studied population was hair color (AUC: 0.71; 95% CI: 0.62-0.79. Other important factors were freckles, sunburn episodes, and skin and eye color. Consideration of other variables such as common nevi, elastosis, family history, and premalignant lesions did not improve the predictive ability of the models. CONCLUSION: The discriminating capacity of the proposed model proved to be superior or comparable to that of previous risk models proposed for CM. FUNDAMENTOS: importantes fatores de risco para melanoma cutâneo são reconhecidos, mas escores padronizados para avaliação individual ainda precisam ser elaborados. OBJETIVOS: o objetivo deste estudo foi desenvolver um escore de risco de melanoma cutâneo para uma amostra brasileira. MÉTODOS: verificar as estimativas dos principais fatores de risco para melanoma, derivado de uma meta-análise (estudo de base italiano e, externamente, validar em uma população do sul do Brasil por um estudo caso-controle. Um total de 117 indivíduos foram avaliados. RESULTADOS: a variável com maior poder preditivo para o risco de melanoma cutâneo na população estudada foi a cor do cabelo (AUC: 0

  13. Risco crescente de melanoma de pele no Brasil Increasing risk of cutaneous melanoma in Brazil

    Directory of Open Access Journals (Sweden)

    Guinar Azevedo e Silva Mendonça

    1992-08-01

    Full Text Available A ocorrência de melonoma maligno de pele no Brasil é analisada a partir dos dados de mortalidade disponíveis no Ministério da Saúde e dos dados de incidência dos seis Registros de Câncer de Base Populacional, localizados em seis capitais brasileiras. Os coeficientes de incidência nessas capitais situam-se em padrões intermediários se comparadas às cifras mundiais. Para o Município de Porto Alegre, uma das capitais estudas, que apresentou os maiores coeficientes de incidência, é feita comparação entre os dados relativos ao período 1979-1982 e 1987, constatando-se que houve aumento relativo de 38% entre homens e de 11% entre mulheres. Concluiu-se pela necessidade de se conduzir estudos no Brasil entre comunidades de indivíduos de pele clara, os quais apresentam risco potencializado para o desenvolvimento de melanoma, para que sejam definidas medidas específicas e eficazes de controle.The occurrence of cutaneous malignant melanoma in Brazil is analysed on the basis of available mortality data from the National Ministery of Health and from the incidence data of six Population-based Cancer Registries (Recife, Fortaleza, S.Paulo, Porto Alegre, Goiânia e Belém. The incidence in these State capitals has an intermediate pattern if compared to the world pictures. For Porto Alegre, the capital that had the highest rates, a comparison between the periods 1979-1982 and 1987 showed a proportional increases of 38% among males and 11% among females. The conclusion is reached that it is necessary to undertake studies in Brazil among fairskinned people from particular communities which may show a potentialized risk for the development of cutaneous melanoma in order to be able to define what kind of specific control actions should be developed.

  14. Adjuvant treatment for high risk melanoma. Where are we now?

    Directory of Open Access Journals (Sweden)

    Anand Sharma

    2011-12-01

    Full Text Available The survival rate for stage 3 and 4 melanoma is very poor. In the absence of effective treatments for metastatic disease focus has shifted to the adjuvant setting. While we are now able to identify those who are at high risk of recurrence the role of adjuvant systemic treatment in these individuals is still undefined. This is partly due to the lack of effective treatments, despite the advances in the understanding of the biology of melanoma and the natural history of the disease process. Of the various treatments studied in the adjuvant setting only interferons and vaccines have been shown to affect the clinical outcome but no agent has been accepted as a standard, with differences in practice between the US and Europe. In this review article we will report what is known at this time about the different agents studied in the adjuvant setting and refer to some new areas of research that may play a bigger role in the future management of melanoma.

  15. A genetic model of melanoma tumorigenesis based on allelic losses

    Energy Technology Data Exchange (ETDEWEB)

    Hayward, N.K.; Palmer, J.M.; Walters, M.K. [Queensland Institute of Medical Research, Herston (Australia)] [and others

    1994-09-01

    Previous karyotypic studies have indicated a possible series of non-random chromosomal events involved in the progression of melanoma. We sought to define a model of melanocyte tumorigenesis by studying allelic deletions of polymorphic simple tandem repeat markers mapping to chromosome 1, 6q, 7, 9p, 10, 11, 17, and 21 in thirty matched pairs of melanoma and constitutional DNAs. The most frequent and earliest deletions were found on 9p (57%) and 10q (32%) and with the exception of one case, no sample has loss of markers on another chromosome without concomitant loss of markers on 9p and/or 10q. Losses on 6q were also a frequent (32%) event that sometimes occurred in primary melanomas, whereas losses of loci on distal 1p (26%) or 11q (26%) occurred only in metastic melanomas. A background rate (0-17%) of allele loss was seen on chromosomes 7, 17, and 21. Homozygous deletions in a panel of 31 melanoma cell lines were only detected for markers on 9p (4 cases). These data strongly support the previous model of melanoma tumorigenesis based primarily on karyotypic findings in melanocytic lesions. However, we have been able to further augment the model by delimiting the regions of loss on 10q to a region distal to D10S254, and on 1p, to between D1S243 and D1S160.

  16. Antiestrogen therapy for breast cancer modifies the risk of subsequent cutaneous melanoma.

    Science.gov (United States)

    Huber, Caroline; Bouchardy, Christine; Schaffar, Robin; Neyroud-Caspar, Isabelle; Vlastos, Georges; Le Gal, Frédérique-Anne; Rapiti, Elisabetta; Benhamou, Simone

    2012-01-01

    Increased risk of secondary melanoma after breast cancer has been reported. Several lines of evidence suggest that elevated estrogen levels may be implicated in melanoma etiology. Accordingly, use of antiestrogens should be associated with decreased risk of melanoma. We compared melanoma incidence among a cohort of breast cancer patients with and without antiestrogen therapy, with data from the Geneva Cancer Registry. The cohort consisted of 7,360 women diagnosed with breast cancer between 1980 and 2005. About 54% of these patients received antiestrogens. All women were followed until December 2008. We compared cutaneous melanoma incidence rates among patients with and without antiestrogens with those expected in the general population by age and period standardized incidence ratios (SIR). A total of 34 women developed a melanoma during the follow-up period. Compared with the general population, the risk of melanoma was higher for patients who did not receive antiestrogens (SIR: 1.60, 95% CI: 1.08-2.12, P = 0.02). On the contrary, the risk was close to 1 (SIR: 0.98, 95% CI: 0.40-1.56, P = 0.57) for patients who received antiestrogen therapy. This study suggests that antiestrogen therapy modifies the risk of melanoma after breast cancer. Although our results are in agreement with the hypothesis that estrogens could play a role in melanoma occurrence, they need to be replicated in a larger study with data on potential confounders. . ©2011 AACR

  17. MC1R Genotype Modifies Risk of Melanoma in Families Segregating CDKN2A Mutations

    OpenAIRE

    Box, Neil F.; Duffy, David L.; Chen, Wei; Stark, Mitchell; Martin, Nicholas G.; Sturm, Richard A.; Hayward, Nicholas K.

    2001-01-01

    Mutations in the exons of the cyclin-dependent kinase inhibitor gene CDKN2A are melanoma-predisposition alleles which have high penetrance, although they have low population frequencies. In contrast, variants of the melanocortin-1 receptor gene, MC1R, confer much lower melanoma risk but are common in European populations. Fifteen Australian CDKN2A mutation–carrying melanoma pedigrees were assessed for MC1R genotype, to test for possible modifier effects on melanoma risk. A CDKN2A mutation in ...

  18. Occupational exposure to electromagnetic fields and sex-differential risk of uveal melanoma

    DEFF Research Database (Denmark)

    Behrens, Thomas Flensted; Lynge, Elsebeth; Cree, Ian

    2010-01-01

    The association between occupational exposure to electromagnetic fields (EMF) and the risk of uveal melanoma was investigated in a case-control study in nine European countries.......The association between occupational exposure to electromagnetic fields (EMF) and the risk of uveal melanoma was investigated in a case-control study in nine European countries....

  19. Plasma 25-Hydroxyvitamin D and Risk of Non-Melanoma and Melanoma Skin Cancer

    DEFF Research Database (Denmark)

    Afzal, Shoaib; Nordestgaard, Børge G; Bojesen, Stig E

    2013-01-01

    with increasing cumulative incidence of non-melanoma skin cancer (trend P=2 × 10(-15) and P=3 × 10(-17)) and melanoma skin cancer (P=0.003 and P=0.001). Multivariable adjusted hazard ratios of non-melanoma skin cancer were 5.04 (95% confidence interval (CI): 2.78-9.16) for 25-OH-vitD 50 vs. 60 years, 25-OH...

  20. Obesity as a risk factor for malignant melanoma and non-melanoma skin cancer.

    Science.gov (United States)

    Karimi, K; Lindgren, T H; Koch, C A; Brodell, Robert T

    2016-09-01

    The dramatic increases in incidence of both obesity and many cancers including skin cancer emphasize the need to better understand the pathophysiology of both conditions and their connections. Melanoma is considered the fastest growing cancer and rates of non-melanoma skin cancer have also increased over the last decade. The molecular mechanisms underlying the association between obesity and skin cancer are not clearly understood but emerging evidence points to changes in the tumor microenvironment including aberrant cell signaling and genomic instability in the chronic inflammatory state many obese individuals experience. This article reviews the literature linking obesity to melanoma and non-melanoma skin cancer.

  1. Common Moles, Atypical Moles (Dysplastic Nevi), and Risk of Melanoma

    Science.gov (United States)

    ... Melanoma—Patient Version Moles, Dysplastic Nevi, and Melanoma Recognition Tool Skin Cancer (Including Melanoma)—Patient Version What ... government may be owned by the writer, and graphics may be owned by their creator. In such ...

  2. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  3. Doctors' recognition and management of melanoma patients' risk: An Australian population-based study.

    Science.gov (United States)

    Madronio, C M; Armstrong, B K; Watts, C G; Goumas, C; Morton, R L; Curtin, A; Menzies, S W; Mann, G J; Thompson, J F; Cust, A E

    2016-12-01

    Guidelines recommend that health professionals identify and manage individuals at high risk of developing melanoma, but there is limited population-based evidence demonstrating real-world practices. A population-based, observational study was conducted in the state of New South Wales, Australia to determine doctors' knowledge of melanoma patients' risk and to identify factors associated with better identification and clinical management. Data were analysed for 1889 patients with invasive, localised melanoma in the Melanoma Patterns of Care study. This study collected data on all melanoma diagnoses notified to the state's cancer registry during a 12-month period from 2006 to 2007, as well as questionnaire data from the doctors involved in their care. Three-quarters (74%) of patients had doctors who were aware of their risk factor status with respect to personal and family history of melanoma and the presence of many moles. Doctors working in general practice, skin cancer clinics and dermatology settings had better knowledge of patients' risk factors than plastic surgeons. Doctors were 15% more likely to know the family history of younger melanoma patients (risk status, by doctors practising in plastic surgery, dermatology and skin cancer clinic settings, and by female doctors. Both patient-related and doctor-related factors were associated with doctors' recognition and management of melanoma patients' risk and could be the focus of strategies for improving care. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Melanoma screening: Informing public health policy with quantitative modelling.

    Directory of Open Access Journals (Sweden)

    Stephen Gilmore

    Full Text Available Australia and New Zealand share the highest incidence rates of melanoma worldwide. Despite the substantial increase in public and physician awareness of melanoma in Australia over the last 30 years-as a result of the introduction of publicly funded mass media campaigns that began in the early 1980s -mortality has steadily increased during this period. This increased mortality has led investigators to question the relative merits of primary versus secondary prevention; that is, sensible sun exposure practices versus early detection. Increased melanoma vigilance on the part of the public and among physicians has resulted in large increases in public health expenditure, primarily from screening costs and increased rates of office surgery. Has this attempt at secondary prevention been effective? Unfortunately epidemiologic studies addressing the causal relationship between the level of secondary prevention and mortality are prohibitively difficult to implement-it is currently unknown whether increased melanoma surveillance reduces mortality, and if so, whether such an approach is cost-effective. Here I address the issue of secondary prevention of melanoma with respect to incidence and mortality (and cost per life saved by developing a Markov model of melanoma epidemiology based on Australian incidence and mortality data. The advantages of developing a methodology that can determine constraint-based surveillance outcomes are twofold: first, it can address the issue of effectiveness; and second, it can quantify the trade-off between cost and utilisation of medical resources on one hand, and reduced morbidity and lives saved on the other. With respect to melanoma, implementing the model facilitates the quantitative determination of the relative effectiveness and trade-offs associated with different levels of secondary and tertiary prevention, both retrospectively and prospectively. For example, I show that the surveillance enhancement that began in

  5. Structural insight with mutational impact on tyrosinase and PKC-β interaction from Homo sapiens: Molecular modeling and docking studies for melanogenesis, albinism and increased risk for melanoma.

    Science.gov (United States)

    Banerjee, Arundhati; Ray, Sujay

    2016-10-30

    Human tyrosinase, is an important protein for biosynthetic pathway of melanin. It was studied to be phosphorylated and activated by protein kinase-C, β-subunit (PKC-β) through earlier experimentations with in vivo evidences. Documentation documents that mutation in two essentially vital serine residues in C-terminal end of tyrosinase leads to albinism. Due to the deficiency of protective shield like enzyme; melanin, albinos are at an increased peril for melanoma and other skin cancers. So, computational and residue-level insight including a mutational exploration with evolutionary importance into this mechanism lies obligatory for future pathological and therapeutic developments. Therefore, functional tertiary models of the relevant proteins were analyzed after satisfying their stereo-chemical features. Evolutionarily paramount residues for the activation of tyrosinase were perceived via multiple sequence alignment phenomena. Mutant-type tyrosinase protein (S98A and S102A) was thereby modeled, maintaining the wild-type proteins' functionality. Furthermore, this present comparative study discloses the variation in the stable residual participation (for mutant-type and wild-type tyrosinase-PKCβ complex). Mainly, an increased number of polar negatively charged residues from the wild-type tyrosinase participated with PKC-β, predominantly. Fascinatingly supported by evaluation of statistical significances, mutation even led to a destabilizing impact in tyrosinase accompanied by conformational switches with a helix-to-coil transition in the mutated protein. Even the allosteric sites in the protein got poorly hampered upon mutation leading to weaker tendency for binding partners to interact. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Use of phosphodiesterase type 5 inhibitors and risk of melanoma: a meta-analysis of observational studies

    Directory of Open Access Journals (Sweden)

    Han X

    2018-02-01

    Full Text Available Xinming Han,1 Yan Han,2 Yongsheng Zheng,1 Qiang Sun,1 Tao Ma,1 Li Dai,1 Junyi Zhang,1 Lianji Xu1 1Plastic Surgery Department, Beijing Tongren Hospital, Capital Medical University, Beijing, 2Plastic and Reconstructive Surgery Department, Chinese PLA General Hospital, Beijing, China Background: Phosphodiesterase type 5 inhibitor (PE5i administration may stimulate the proliferation and survival of melanocytes. However, discrepancies remain regarding the association between PDE5i use and melanoma risk in observational studies in humans.Aim: To evaluate the association between PDE5i use and melanoma in a meta-analysis.Materials and methods: Studies were identified by searching the PubMed and Embase databases. A random-effects model was applied to synthesize the data. A stratified study was performed to evaluate the influence of study characteristics on outcomes.Results: Four prospective cohort studies and three case–control studies with 1,534,615 male participants and 16,053 melanoma cases were incorporated. Patients who received a PDE5i had a significantly increased risk for melanoma (adjusted risk ratio [RR] =1.12, 95% CI =1.03–1.33, P=0.008 with moderate heterogeneity (I2=54%. Cohort studies (adjusted RR =1.22, 95% CI =1.02–1.46, P=0.03 largely contributed to this result rather than case–control studies. Subsequent stratified analyses revealed that sildenafil was associated with an increased risk of melanoma (adjusted RR =1.26, 95% CI =1.07–1.50, P=0.007, but tadalafil and vardenafil were not. Also, PDE5i use was associated with a significantly increased risk of in situ melanoma (adjusted RR =1.31, 95% CI =1.01–1.69, P=0.04, but not of localized or nonlocalized melanoma.Conclusion: PDE5i use may be associated with a significantly increased risk for melanoma in men. However, further research is needed to determine whether the association is causative. Keywords: phosphodiesterase type 5 inhibitors, melanoma, meta-analysis, sildenafil 

  7. Personal History of Prostate Cancer and Increased Risk of Incident Melanoma in the United States

    Science.gov (United States)

    Li, Wen-Qing; Qureshi, Abrar A.; Ma, Jing; Goldstein, Alisa M.; Giovannucci, Edward L.; Stampfer, Meir J.; Han, Jiali

    2013-01-01

    Purpose Steroid hormones, particularly androgens, play a major role in prostatic carcinogenesis. Personal history of severe acne, a surrogate for higher androgen activity, has been associated with an increased risk of prostate cancer (PCa), and one recent study indicated that severe teenage acne was a novel risk factor for melanoma. These findings suggest a possible relationship between PCa and risk of melanoma. We prospectively evaluated this association among US men. Methods A total of 42,372 participants in the Health Professionals' Follow-Up Study (HPFS; 1986 to 2010) were included. Biennially self-reported PCa diagnosis was confirmed using pathology reports. Diagnosis of melanoma and nonmelanoma skin cancer (NMSC) was self-reported biennially, and diagnosis of melanoma was pathologically confirmed. We sought to confirm the association in 18,603 participants from the Physicians' Health Study (PHS; 1982 to 1998). Results We identified 539 melanomas in the HPFS. Personal history of PCa was associated with an increased risk of melanoma (multivariate-adjusted hazard ratio [HR], 1.83; 95% CI, 1.32 to 2.54). Although we also detected a marginally increased risk of NMSC associated with PCa (HR, 1.08; 95% CI, 0.995 to 1.16), the difference in the magnitude of the association between melanoma and NMSC was significant (P for heterogeneity = .002). We did not find an altered risk of melanoma associated with personal history of other cancers. The association between PCa and risk of incident melanoma was confirmed in the PHS (HR, 2.17; 95% CI, 1.12 to 4.21). Conclusion Personal history of PCa is associated with an increased risk of melanoma, which may not be entirely a result of greater medical scrutiny. PMID:24190118

  8. Coat color genotypes and risk and severity of melanoma in gray quarter horses.

    Science.gov (United States)

    Teixeira, R B C; Rendahl, A K; Anderson, S M; Mickelson, J R; Sigler, D; Buchanan, B R; Coleman, R J; McCue, M E

    2013-01-01

    Both graying and melanoma formation in horses have recently been linked to a duplication in the STX17 gene. This duplication, as well as a mutation in the ASIP gene that increases MC1R pathway signaling, affects melanoma risk and severity in gray horses. To determine if melanoma susceptibility in gray Quarter Horses (QH) is lower than gray horses from other breeds because of decreased MC1R signaling resulting from a high incidence of the MC1R chestnut coat color allele in the QH population. A total of 335 gray QH with and without dermal melanomas. Blood or hair root samples were collected from all horses for DNA extraction and genotyping for STX17, ASIP, and MC1R genotypes. Age, sex, and external melanoma presence and grade were recorded. The effect of age and genotype on melanoma presence and severity was evaluated by candidate gene association. Melanoma prevalence (16%) and grade (0.35) in this QH cohort was lower than that reported in other breeds. Age was significantly associated with melanoma prevalence (P = 5.28 × 10(-11)) and severity (P = 2.2 × 10(-13)). No significant effect of MC1R genotype on melanoma prevalence or severity was identified. An effect of ASIP genotype on melanoma risk was not detected. Low STX17 homozygosity precluded evaluation of the gray allele effect. Melanoma prevalence and severity is lower in this population of gray QH than what is reported in other breeds. This could be because of the infrequent STX17 homozygosity, a mitigating effect of the MC1R mutation on ASIP potentiation of melanoma, other genes in the MC1R signaling pathway, or differences in breed genetic background. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  9. Ultraviolet Radiation and Melanoma: AN Interdisciplinary Risk Assessment

    Science.gov (United States)

    Charache, Darryl H.

    1995-01-01

    A multidisciplinary study involving atmospheric, demographic, and epidemiologic disciplines has been conducted to investigate the relation between ultraviolet (UV) dose and melanoma incidence rate on a global scale. A multiple scattering radiative transfer model has been developed to estimate spectral irradiance and integrated biologically effective dose amounts in the UV-B and UV-A wavelength regime. Global maps of seasonally averaged and peak biologically effective dose on a 1^circ x 1^circ resolution have been created for significant land areas using satellite- and surface-derived atmospheric and topographic data sets. These maps have been coupled with worldwide melanoma incidence rates obtained from the International Agency for Research on Cancer (IARC) database and an ethnically-derived skin type classification system to estimate a "global" biological amplification factor (BAF) for males and females. With these BAFs, future estimates of incidence rates and number of additional melanoma cases that may be expected based on simulated increases in UV dose between the years 1980 -2000 can be estimated under simplifying atmospheric and demographic assumptions. Using worldwide melanoma rates and corresponding UV doses, BAFs of 1.67 and 1.26 were derived for white males and females, respectively. No significant relation was found for non-white skin types. Despite relatively low current incidence rates, projections indicate greater percentage changes in incidence rates at higher latitudes where downward trends in ozone are highest. Greater increases in total number of cases appear in countries having high white skin populations; the increase in total cases in these countries is due primarily to population size rather than estimated increases in UV dose. The integration of atmospheric, epidemiological, and demographic models in this study has established a framework that can be used to improve assessments when more data become available, and can be adapted to analyze

  10. Competing risk bias to explain the inverse relationship between smoking and malignant melanoma

    NARCIS (Netherlands)

    Thompson, Caroline A.; Zhang, Zuo-Feng; Arah, Onyebuchi A.

    2013-01-01

    The relationship between smoking and melanoma remains unclear. Among the different results is the paradoxical finding that smoking was shown to be inversely associated with the risk of malignant melanoma in some large cohort and case-control studies, even after control for suspected confounding

  11. The risk of melanoma and hematologic cancers in patients with psoriasis.

    Science.gov (United States)

    Reddy, Shivani P; Martires, Kathryn; Wu, Jashin J

    2017-04-01

    The risk of melanoma and hematologic cancers in patients with psoriasis is controversial. We sought to assess the risk of melanoma and hematologic cancers in patients with psoriasis, and the association with different treatments. We used case-control and retrospective cohort designs to determine melanoma or hematologic cancer risk in patients with psoriasis. Risk with treatment type was assessed using Fisher exact test. Patients with psoriasis had 1.53 times greater risk of developing a malignancy compared with patients without psoriasis (P psoriasis and malignancy did not have significantly worse survival than patients without psoriasis. It is possible that patients developed malignancy subsequent to the follow-up time included in the study. Patients with psoriasis may experience an elevated risk of melanoma and hematologic cancers, compared with the general population. The risk is not increased by systemic or biologic psoriasis therapies. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. Decreased risk of melanoma and nonmelanoma skin cancer in patients with vitiligo: a survey among 1307 patients and their partners.

    Science.gov (United States)

    Teulings, H E; Overkamp, M; Ceylan, E; Nieuweboer-Krobotova, L; Bos, J D; Nijsten, T; Wolkerstorfer, A W; Luiten, R M; van der Veen, J P W

    2013-01-01

    Vitiligo is a common skin disease characterized by autoimmune melanocyte destruction. Recent genetic studies suggest a lower susceptibility to melanoma in patients with vitiligo; however, lifetime melanoma prevalence in patients with vitiligo has not previously been studied. Nonmelanoma skin cancer (NMSC) prevalence has been studied, but only in small studies and with contradictory results. This retrospective, comparative cohort survey was designed to assess lifetime prevalences of melanoma and NMSC in patients with vitiligo compared with nonvitiligo controls. Patients with nonsegmental vitiligo, who visited our clinic between January 1995 and September 2010, and were aged 50 years or older at the time of the study, were invited to participate in a postal survey. The questions regarded demographics, vitiligo characteristics, phototherapy history, skin cancer risk factors and the number of skin cancers experienced during the patient's lifetime. Patients were asked to have their partner fill in a control questionnaire. All skin cancers were validated by a pathology report. In total 2635 invitations were sent and 1307 eligible questionnaires were returned (50%). Multivariate logistic regression models were used to quantify adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between vitiligo and lifetime prevalences of melanoma and NMSC.  Adjusted for confounders, patients with vitiligo had a threefold lower probability of developing melanoma (adjusted OR 0·32; 95% CI 0·12-0·88) and NMSC (adjusted OR 0·28; 95% CI 0·16-0·50). Subgroup analyses of patients treated with narrowband ultraviolet (UV) B, and psoralen and UVA did not show dose-related trends of increased age-adjusted lifetime prevalence of melanoma or NMSC. Our findings suggest that patients with vitiligo have a decreased risk of both melanoma and NMSC. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  13. Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma.

    Science.gov (United States)

    Puig, Susana; Potrony, Miriam; Cuellar, Francisco; Puig-Butille, Joan Anton; Carrera, Cristina; Aguilera, Paula; Nagore, Eduardo; Garcia-Casado, Zaida; Requena, Celia; Kumar, Rajiv; Landman, Gilles; Costa Soares de Sá, Bianca; Gargantini Rezze, Gisele; Facure, Luciana; de Avila, Alexandre Leon Ribeiro; Achatz, Maria Isabel; Carraro, Dirce Maria; Duprat Neto, João Pedreira; Grazziotin, Thais C; Bonamigo, Renan R; Rey, Maria Carolina W; Balestrini, Claudia; Morales, Enrique; Molgo, Montserrat; Bakos, Renato Marchiori; Ashton-Prolla, Patricia; Giugliani, Roberto; Larre Borges, Alejandra; Barquet, Virginia; Pérez, Javiera; Martínez, Miguel; Cabo, Horacio; Cohen Sabban, Emilia; Latorre, Clara; Carlos-Ortega, Blanca; Salas-Alanis, Julio C; Gonzalez, Roger; Olazaran, Zulema; Malvehy, Josep; Badenas, Celia

    2016-07-01

    CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736.

  14. Microwave applicator for hyperthermia treatment on in vivo melanoma model

    Czech Academy of Sciences Publication Activity Database

    Togni, P.; Vrba, J.; Vannucci, Luca

    2010-01-01

    Roč. 48, č. 3 (2010), s. 285-292 ISSN 0140-0118 R&D Projects: GA AV ČR(CZ) IAA500200510 Institutional research plan: CEZ:AV0Z50200510 Keywords : Melanoma in vivo model * Superficial hyperthermia * Microwave applicator Subject RIV: EC - Immunology Impact factor: 1.791, year: 2010

  15. Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas

    Directory of Open Access Journals (Sweden)

    Belen Hernandez

    2018-01-01

    Full Text Available Melanoma remains mostly an untreatable fatal disease despite advances in decoding cancer genomics and developing new therapeutic modalities. Progress in patient care would benefit from additional predictive models germane for human disease mechanisms, tumor heterogeneity, and therapeutic responses. Toward this aim, this review documents comparative aspects of human and naturally occurring canine melanomas. Clinical presentation, pathology, therapies, and genetic alterations are highlighted in the context of current basic and translational research in comparative oncology. Somewhat distinct from sun exposure-related human cutaneous melanomas, there is growing evidence that a variety of gene copy number alterations and protein structure/function mutations play roles in canine melanomas, in circumstances more analogous to human mucosal melanomas and to some extent other melanomas with murine sarcoma viral oncogene homolog B (BRAF, Neuroblastoma RAS Viral (V-Ras Oncogene Homolog (NRAS, and neurofibromin 1 tumor suppressor NF1 triple wild-type genotype. Gaps in canine genome annotation, as well as an insufficient number and depth of sequences covered, remain considerable barriers to progress and should be collectively addressed. Preclinical approaches can be designed to include canine clinical trials addressing immune modulation as well as combined-targeted inhibition of Rat Sarcoma Superfamily/Mitogen-activated protein kinase (RAS/MAPK and/or Phosphatidylinositol-3-Kinase/Protein Kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR signal transduction, pathways frequently activated in both human and canine melanomas. Future investment should be aimed towards improving understanding of canine melanoma as a predictive preclinical surrogate for human melanoma and for mutually benefiting these uniquely co-dependent species.

  16. Malign Melanoma: Risk Factors and Major Clinical Findings

    Directory of Open Access Journals (Sweden)

    Can Baykal

    2015-03-01

    Full Text Available Malignant melanoma (MM shows rapid increase in the incidence and it is the most common cause of death due to skin cancer. On the other hand, MM can completely be removed in patients noticing the lesions early and applying to physicians on time. Thus the life expectancy of these patients is not altered. Although MM can occur in every individual, it is more common in patients with some of the established risk factors such as fair skin, increased sun exposure, genetic basis (CDKN2A mutation, and existence of increased number of melanocytic nevi and/or dysplastic nevi. A specialized care of patients with risk factors and their regular follow-up is critical to lower the mortality and morbidity in MM. Early diagnosis of MM prevents metastasis and decreases mortality rate. Nowadays, there are many newly developed imaging methods to help the clinicians before biopsy. However, the suspicion of MM should initially be based upon major clinical findings of the lesion subject to changes during the evolution of the tumor. In this review, risk factors of MM will be summarized and clues for early diagnosis of this dangerous tumor will be discussed.

  17. Risk Factors for Melanoma Among Survivors of Non-Hodgkin Lymphoma

    Science.gov (United States)

    Lam, Clara J.K.; Curtis, Rochelle E.; Dores, Graça M.; Engels, Eric A.; Caporaso, Neil E.; Polliack, Aaron; Warren, Joan L.; Young, Heather A.; Levine, Paul H.; Elmi, Angelo F.; Fraumeni, Joseph F.; Tucker, Margaret A.; Morton, Lindsay M.

    2015-01-01

    Purpose Previous studies have reported that survivors of non-Hodgkin lymphoma (NHL) have an increased risk of developing cutaneous melanoma; however, risks associated with specific treatments and immune-related risk factors have not been quantified. Patients and Methods We evaluated second melanoma risk among 44,870 1-year survivors of first primary NHL diagnosed at age 66 to 83 years from 1992 to 2009 and included in the Surveillance, Epidemiology, and End Results-Medicare database. Information on NHL treatments, autoimmune diseases, and infections was derived from Medicare claims. Results A total of 202 second melanoma cases occurred among survivors of NHL, including 91 after chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 111 after other NHL subtypes (cumulative incidence by age 85 years: CLL/SLL, 1.37%; other NHL subtypes, 0.78%). Melanoma risk after CLL/SLL was significantly increased among patients who received infused fludarabine-containing chemotherapy with or without rituximab (n = 18: hazard ratio [HR], 1.92; 95% CI, 1.09 to 3.40; n = 10: HR, 2.92; 95% CI, 1.42 to 6.01, respectively). Significantly elevated risks also were associated with T-cell activating autoimmune diseases diagnosed before CLL/SLL (n = 36: HR, 2.27; 95% CI, 1.34 to 3.84) or after CLL/SLL (n = 49: HR, 2.92; 95% CI, 1.66 to 5.12). In contrast, among patients with other NHL subtypes, melanoma risk was not associated with specific treatments or with T-cell/B-cell immune conditions. Generally, infections were not associated with melanoma risk, except for urinary tract infections (CLL/SLL), localized scleroderma, pneumonia, and gastrohepatic infections (other NHLs). Conclusion Our findings suggest immune perturbation may contribute to the development of melanoma after CLL/SLL. Increased vigilance is warranted among survivors of NHL to maximize opportunities for early detection of melanoma. PMID:26240221

  18. MC1R variants increase risk of melanomas harboring BRAF mutations.

    Science.gov (United States)

    Fargnoli, Maria Concetta; Fargnoli, Maria Concetia; Pike, Kris; Pfeiffer, Ruth M; Tsang, Shirley; Rozenblum, Ester; Munroe, David J; Golubeva, Yelena; Calista, Donato; Seidenari, Stefania; Massi, Daniela; Carli, Paolo; Bauer, Juergen; Elder, David E; Bastian, Boris C; Peris, Ketty; Landi, Maria T

    2008-10-01

    Melanocortin-1 receptor (MC1R) variants have been associated with BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations in non-CSD (chronic solar-damaged) melanomas in an Italian and an American population. We studied an independent Italian population of 330 subjects (165 melanoma patients and 165 controls) to verify and estimate the magnitude of this association and to explore possible effect modifiers. We sequenced MC1R in all subjects and exon 15 of BRAF in 92/165 melanoma patients. Patients with MC1R variants had a high risk of carrying BRAF mutations in melanomas (odds ratio (OR)=7.0, 95% confidence interval (CI)=2.1-23.8) that increased with the number of MC1R variants and variants associated with red hair color. Combining these subjects with the originally reported Italian population (513 subjects overall), MC1R variant carriers had a 5- to 15-fold increased risk of BRAF-mutant melanomas based on carrying one or two variants (PMC1R-melanoma risk association is confined to subjects whose melanomas harbor BRAF mutations.

  19. Variants of the xeroderma pigmentosum variant gene (POLH) are associated with melanoma risk.

    Science.gov (United States)

    Di Lucca, Julie; Guedj, Mickael; Lacapère, Jean-Jacques; Fargnoli, Maria Concetta; Bourillon, Agnes; Dieudé, Philippe; Dupin, Nicolas; Wolkenstein, Pierre; Aegerter, Philippe; Saiag, Philippe; Descamps, Vincent; Lebbe, Celeste; Basset-Seguin, Nicole; Peris, Ketty; Grandchamp, Bernard; Soufir, Nadem

    2009-12-01

    Xeroderma pigmentosum variant (XPV) is a rare recessive autosomal genodermatosis predisposing to multiple early onset skin cancers, including melanoma. XPV results from mutations of the POLH gene that encodes a DNA translesion polymerase. In this work, we tested the hypothesis that POLH variants could be associated with melanoma risk. A common non-synonymous POLH variant, c.1783A>G p.M595V, was genotyped in 1075 melanoma patients and in 1091 ethnic-matched controls from France. In addition, we searched for rare POLH variants by sequencing the entire coding sequence in 201 patients having a familial history of melanoma (n=123), sporadic multiple melanomas (n=65) and a melanoma associated with a skin carcinoma (n=13). Overall, the c.1783G, p.595V allele was statistically associated with melanoma (respective allelic frequencies, 0.040 versus 0.022, P-value=1.17 x 10(-3), odds ratio (OR)=1.86 [1.27-2.71]), which was further confirmed by a meta-analysis including 274 patients and 174 matched controls from Italy (P-value=7.7 x 10(-4), OR=1.84 [1.29-2.63]). Interestingly, three non-synonymous POLH variants were identified in three patients (c.295G>A p.V99M, c.815T>C p.I272T and c.1745C>T p.S582L) which were absent in 352 chromosome controls from healthy subjects. Besides severe deficiencies in translesion synthesis which are major risks factors for skin carcinomas and melanomas, less deleterious POLH variants could act as low penetrance melanoma predisposing alleles. The ongoing identification of genetic markers implied in skin cancer predisposition could help to identify high-risk subjects as targets for clinical follow-up. Replication studies in other populations are awaited to assess these data.

  20. Non-melanoma skin cancer in Portuguese kidney transplant recipients - incidence and risk factors.

    Science.gov (United States)

    Pinho, André; Gouveia, Miguel; Cardoso, José Carlos; Xavier, Maria Manuel; Vieira, Ricardo; Alves, Rui

    2016-01-01

    Cancer is currently among the three leading causes of death after solid organ transplantation and its incidence is increasing. Non-melanoma skin cancer - squamous cell carcinoma and basal cell carcinoma - is the most common malignancy found in kidney transplant recipients (KTRs). The incidence of non-melanoma skin cancer in KTRs has not been extensively studied in Portugal. To determine the incidence of non-melanoma skin cancer in KTRs from the largest Portuguese kidney transplant unit; and to study risk factors for non-melanoma skin cancer. Retrospective analysis of clinical records of KTRs referred for the first time for a dermatology consultation between 2004 and 2013. A case-control study was performed on KTRs with and without non-melanoma skin cancer. We included 288 KTRs with a median age at transplantation of 47 years, a male gender predominance (66%) and a median transplant duration of 3.67 years. One fourth (n=71) of KTRs developed 131 non-melanoma skin cancers, including 69 (53%) squamous cell carcinomas and 62 (47%) basal cell carcinomas (ratio squamous cell carcinoma: basal cell carcinoma 1.11), with a mean of 1.85 neoplasms per patient. Forty percent of invasive squamous cell carcinomas involved at least two clinical or histological high-risk features. The following factors were associated with a higher risk of non-melanoma skin cancer: an older age at transplantation and at the first consultation, a longer transplant duration and the presence of actinic keratosis. KTRs treated with azathioprine were 2.85 times more likely to develop non-melanoma skin cancer (p=0.01). Non-melanoma skin cancer was a common reason for dermatology consultation in Portuguese KTRs. It is imperative for KTRs to have access to specialized dermatology consultation for early referral and treatment of skin malignancies.

  1. Atypical mole syndrome and dysplastic nevi: identification of populations at risk for developing melanoma - review article

    Directory of Open Access Journals (Sweden)

    Juliana Hypólito Silva

    2011-01-01

    Full Text Available Atypical Mole Syndrome is the most important phenotypic risk factor for developing cutaneous melanoma, a malignancy that accounts for about 80% of deaths from skin cancer. Because the diagnosis of melanoma at an early stage is of great prognostic relevance, the identification of Atypical Mole Syndrome carriers is essential, as well as the creation of recommended preventative measures that must be taken by these patients.

  2. Risk factors and outcomes of cutaneous melanoma in women less than 50 years of age.

    Science.gov (United States)

    Tellez, Alejandra; Rueda, Steven; Conic, Ruzica Z; Powers, Kristin; Galdyn, Izabela; Mesinkovska, Natasha Atanaskova; Gastman, Brian

    2016-04-01

    Melanoma is the fifth most common cancer in the United States, with recent reports indicating increasing incidence among young women. This study sought to investigate histopathology, staging, risk factors, and outcomes of cutaneous melanoma in women younger than 50 years. All female patients aged up to 49 years with biopsy-proven diagnosis of melanoma between 1988 and 2012 were included. Patients with a follow-up of less than 2 years were excluded. A total of 462 patients were identified, with mean age of 34.7 years. Invasive melanoma was less common in women 19 years of age or younger (P melanoma had a significantly worse prognosis in comparison with a control group of nonpregnant patients, with a 9-fold increase in recurrence (P melanoma for women younger than 50 years suggests that regular skin checks and self-examinations are warranted. In addition, in women given the diagnosis of melanoma during or within 1 year after childbirth, regular follow-up and monitoring for recurrence are recommended. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  3. Nestin expression in primary and metastatic uveal melanoma - possible biomarker for high-risk uveal melanoma.

    Science.gov (United States)

    Djirackor, Luna; Shakir, Dilem; Kalirai, Helen; Petrovski, Goran; Coupland, Sarah E

    2018-01-16

    Nestin, a member of the intermediate filament protein family, has been described as a putative cancer stem cell marker (CSC) in uveal melanoma and poor prognostic factor in a variety of tumours, including cutaneous melanoma. In this study, we examined the expression of nestin in primary (PUM) and metastatic uveal melanoma (MUM) samples, and correlated the findings with histological, clinical and survival data. Nestin expression was assessed by immunohistochemistry in 141 PUM and 26 MUM samples; 11 PUM cases were matched with their corresponding metastases. The percentage of tumour cells expressing nestin was scored by three independent observers. Statistical analysis of all data was performed with SPSS. Nestin expression was identified in both the cytoplasm and membrane of UM cells. Increased expression of nestin in PUM samples was associated with known poor prognostic parameters, including epithelioid cell morphology (p < 0.001), closed loops (p = 0.001), higher mitotic count (p < 0.001), monosomy 3 (p = 0.007) and chromosome 8q gain (p < 0.001). Primary uveal melanoma (PUM) with nestin expression levels above a cut-off value of 10% [as determined by receiver operating characteristic (ROC) analysis] was associated with a significantly reduced survival time (Log-rank, p = 0.002). In MUM, a higher percentage of nestin-positive tumour cells combined with poor prognostic markers in the PUM led to a shorter survival time following the development of metastases. In conclusion, increased nestin expression in PUM is a predictor of a tumour phenotype associated with metastatic progression and reduced survival time at onset of metastasis. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  4. DNA Methylation Levels of Melanoma Risk Genes Are Associated with Clinical Characteristics of Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Érica S. S. de Araújo

    2015-01-01

    Full Text Available In melanoma development, oncogenic process is mediated by genetic and epigenetic mutations, and few studies have so far explored the role of DNA methylation either as predisposition factor or biomarker. We tested patient samples for germline CDKN2A methylation status and found no evidence of inactivation by promoter hypermethylation. We have also investigated the association of clinical characteristics of samples with the DNA methylation pattern of twelve genes relevant for melanomagenesis. Five genes (BAP1, MGMT, MITF, PALB2, and POT1 presented statistical association between blood DNA methylation levels and either CDKN2A-mutation status, number of lesions, or Breslow thickness. In tumors, five genes (KIT, MGMT, MITF, TERT, and TNF exhibited methylation levels significantly different between tumor groups including acral compared to nonacral melanomas and matched primary lesions and metastases. Our data pinpoint that the methylation level of eight melanoma-associated genes could potentially represent markers for this disease both in peripheral blood and in tumor samples.

  5. Satellite in transit metastases in rapidly fatal conjunctival melanoma: implications for angiotropism and extravascular migratory metastasis (description of a murine model for conjunctival melanoma).

    Science.gov (United States)

    Barnhill, Raymond L; Lemaitre, Stéphanie; Lévy-Gabrielle, Christine; Rodrigues, Manuel; Desjardins, Laurence; Dendale, Rémi; Vincent-Salomon, Anne; Roman-Roman, Sergio; Lugassy, Claire; Cassoux, Nathalie

    2016-02-01

    Little information is currently available concerning loco-regional metastases such as satellite and in transit metastases and their natural history in conjunctival melanoma as compared to cutaneous melanoma. Angiotropism, a marker of extravascular migration of melanoma cells along vascular channels, often appears responsible for microscopic satellite, satellite and in transit metastases development in cutaneous melanoma. In addition, diffuse tissue microscopic satellites are correlated with widespread melanoma dissemination and death. Herein we report rapid conjunctival melanoma progression and a fatal outcome in four of five patients following recurrence as satellite in transit metastases. Five patients aged 31, 60, 63, 56, and 67 years developed primary conjunctival melanoma, histologically characterised by tumour thicknesses of 4, 4, 1.1, 3, and 2 mm. Two or more conjunctival melanomas manifested ulceration, significant mitotic rates, necrosis, angiotropism, and intralesional transformation. The conjunctival melanoma recurred in a matter of months as one or more discrete satellite in transit lesions in the vicinity of the primary melanoma. Histological examination revealed well-defined micronodules containing atypical melanocytes in the subepithelial connective tissue stroma. All lesions were extravascular and most appeared angiotropic. Four of five patients subsequently developed parotid or other loco-regional nodal disease and rapidly ensuing widespread metastases and death. The time course from diagnosis to the demise of the patients averaged about 13 (range 7-20) months. Our findings suggest that satellite in transit metastases constitute an important new risk marker for possible rapid metastatic disease progression and death in patients with conjunctival melanoma. This finding appears to take on even greater significance if such lesions develop rapidly, i.e., in a matter of weeks or months following diagnosis of primary conjunctival melanoma, and if the

  6. Cutaneous melanoma: hints from occupational risks by anatomic site in Swedish men

    Science.gov (United States)

    Perez-Gomez, B; Pollan, M; Gustavsson, P; Plato, N; Aragones, N; Lopez-Abente, G

    2004-01-01

    Aims: To improve knowledge of the epidemiology of melanoma by comparing occupational risks of cutaneous melanoma (CM) by anatomic site in Swedish workers. Methods: Male workers employed in 1970 and living in the country in 1960 were followed up from 1971 to 1989 using the Swedish Registers of Death and Cancer. A more specifically exposed subcohort included men reporting the same occupation in 1960 and 1970. For each location, occupational risk ratios (RRs) were extracted from Poisson regression models adjusted by age, period, town size, and geographical area. To diminish the influence of socioeconomic factors, intrasector analyses, comparing only jobs belonging to the same occupational sector, were performed. Risk patterns for different locations were compared. Results: High RRs for different sites were found among workers exposed to UV sources (dentists, physiotherapists, and lithographers), and sun exposed workers (harbour masters, and lighthouse/related work). Risk excesses were seen in fur tailors, tanners/fur dressers, patternmakers/cutters, electrical fitters/wiremen, telephone/telegraph installers/repairmen, and some glass/pottery/tile workers. Results for lower and upper limbs were significantly correlated but somewhat independent of those found in thorax, the most frequent location. Correlation between head/neck and thorax was moderate. Specific risk excesses were found for rolling mill workers in head/neck, for chimney sweeps in upper limbs, and for aircraft pilots/navigators/flight engineers in lower limbs. Conclusions: High RRs in the trunk among occupations with UV exposure from artificial sources suggest an effect not restricted to exposed sites. An unusual distribution of cases and RRs in chimney sweeps, rolling-mill, or glass/pottery/tile workers suggests local effects of exposures. The not previously reported risk excess in this job and in fur related processes, and the RR in electrical fitters and telephone/telegraph installers deserve further

  7. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-03

    Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin\\'s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

  8. Risk factors for presumptive melanoma in skin cancer screening: American Academy of Dermatology National Melanoma/Skin Cancer Screening Program experience 2001-2005.

    Science.gov (United States)

    Goldberg, Matthew S; Doucette, John T; Lim, Henry W; Spencer, James; Carucci, John A; Rigel, Darrell S

    2007-07-01

    Since its inception in 1985, the American Academy of Dermatology (AAD) National Melanoma/Skin Cancer Screening Program has strived to enhance early detection of cutaneous malignant melanoma (MM) by providing nationwide skin cancer education campaigns in combination with free skin cancer screenings. To analyze the AAD screening data from 2001 to 2005 in order to identify factors associated with MM detection, and thereby derive a model of increased likelihood for MM detection through visual skin examinations at screenings. Patients completed a standardized AAD pre-screening form with historical and phenotypic information. Clinicians then recorded suspected clinical findings noted at visual skin examination. Statistical analyses were conducted using SPSS 14 (SPSS Inc., Chicago, Ill). Five factors, which can be remembered with the acronym HARMM, independently increased the likelihood of suspected MM being found in the 362,804 persons screened: History of previous melanoma (odds ratio [OR] = 3.3; 95% confidence interval [CI], 2.9-3.8); Age over 50 (OR = 1.2; 95% CI, 1.1-1.3); Regular dermatologist absent (OR = 1.4; 95% CI, 1.3-1.5); Mole changing (OR = 2.0; 95% CI, 1.9-2.2); and Male gender (OR = 1.4; 95% CI, 1.3-1.5). Individuals at highest risk (4 or 5 factors) comprised only 5.8% of the total population, yet accounted for 13.6% of presumptive MM findings, and were 4.4 times (95% CI, 3.8-5.1) more likely to be diagnosed with suspected MM than individuals at lowest risk (0 or 1 factor). Receipt of a total skin examination at screening independently increased the likelihood for identifying suspected MM (OR = 1.4; 95% CI, 1.3-1.6). However, significantly fewer screenees in the highest risk group versus those in the lowest risk group underwent total skin examinations (53.7% vs 62.5%). Risk factors studied limited to variables collected in screenee enrollment form. A higher-risk subgroup of the skin cancer screening population can be identified through assessment of MM

  9. Surgical wound complications after groin dissection in melanoma patients - a historical cohort study and risk factor analysis

    NARCIS (Netherlands)

    Stuiver, M. M.; Westerduin, E.; ter Meulen, S.; Vincent, A. D.; Nieweg, O. E.; Wouters, M. W. J. M.

    2014-01-01

    Wound complications occur frequently after inguinal lymph node dissection (ILND) in melanoma patients. Evidence on risk factors for complications is scarce and inconsistent. This study assessed wound complication rates after ILND and investigated associated risk factors, in the melanoma unit of a

  10. A case-control study: occupational cooking and the risk of uveal melanoma

    Directory of Open Access Journals (Sweden)

    Marr Anja

    2010-10-01

    Full Text Available Abstract Background A European-wide population based case-control study (European rare cancer study undertaken in nine European countries examined risk factors for uveal melanoma. They found a positive association between cooks and the risk of uveal melanoma. In our study we examine whether cooks or people who worked in cook related jobs have an increased uveal melanoma risk. Methods We conducted a case-control study during 2002 and 2005. Overall, 1653 eligible subjects (age range: 20-74 years, living in Germany participated. Interviews were conducted with 459 incident uveal melanoma cases, 827 population controls, 180 ophthalmologist controls and 187 sibling controls. Data on occupational exposure were obtained from a self-administered postal questionnaire and a computer-assisted telephone interview. We used conditional logistic regression to estimate odds ratios adjusting for the matching factors. Results Overall, we did not observe an increased risk of uveal melanoma among people who worked as cooks or who worked in cook related jobs. When we restricted the source population of our study to the population of the Federal State of Northrhine-Westphalia, we observed an increased risk among subjects who were categorized as cooks in the cases-control analysis. Conclusion Our results are in conflict with former results of the European rare cancer study. Considering the rarity of the disease laboratory in vitro studies of human uveal melanoma cell lines should be done to analyze potential exposure risk factors like radiation from microwaves, strong light from incandescent ovens, or infrared radiation.

  11. MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations.

    Science.gov (United States)

    Box, N F; Duffy, D L; Chen, W; Stark, M; Martin, N G; Sturm, R A; Hayward, N K

    2001-10-01

    Mutations in the exons of the cyclin-dependent kinase inhibitor gene CDKN2A are melanoma-predisposition alleles which have high penetrance, although they have low population frequencies. In contrast, variants of the melanocortin-1 receptor gene, MC1R, confer much lower melanoma risk but are common in European populations. Fifteen Australian CDKN2A mutation-carrying melanoma pedigrees were assessed for MC1R genotype, to test for possible modifier effects on melanoma risk. A CDKN2A mutation in the presence of a homozygous consensus MC1R genotype had a raw penetrance of 50%, with a mean age at onset of 58.1 years. When an MC1R variant allele was also present, the raw penetrance of the CDKN2A mutation increased to 84%, with a mean age at onset of 37.8 years (P=.01). The presence of a CDKN2A mutation gave a hazard ratio of 13.35, and the hazard ratio of 3.72 for MC1R variant alleles was also significant. The impact of MC1R variants on risk of melanoma was mediated largely through the action of three common alleles, Arg151Cys, Arg160Trp, and Asp294His, that have previously been associated with red hair, fair skin, and skin sensitivity to ultraviolet light.

  12. Superficial spreading and nodular melanoma are distinct biological entities: a challenge to the linear progression model.

    Science.gov (United States)

    Greenwald, Holly S; Friedman, Erica B; Osman, Iman

    2012-02-01

    The classification of melanoma subtypes into prognostically relevant and therapeutically insightful categories has been a challenge since the first description of melanoma in the 1800s. One limitation has been the assumption that the two most common histological subtypes of melanoma, superficial spreading and nodular, evolve according to a linear model of progression, as malignant melanocytes spread radially and then invade vertically. However, recent clinical, pathological, and molecular data indicate that these two histological subtypes might evolve as distinct entities. Here, we review the published data that support distinct molecular characterization of superficial spreading and nodular melanoma, the clinical significance of this distinction including prognostic relevance and the therapeutic implications.

  13. Malignant melanoma

    NARCIS (Netherlands)

    de Braud, Filippo; Khayat, David; Kroon, Bin B. R.; Valdagni, Riccardo; Bruzzi, Paolo; Cascinelli, Natale

    2003-01-01

    In the European Community cutaneous melanoma accounts for 1 and 1.8% of cancers occurring in men and women, respectively. The incidence rate is increasing faster than that of any other tumour. Sun exposure, patient's phenotype, family history, and history of a previous melanoma are the major risk

  14. Embryonic chicken transplantation is a promising model for studying the invasive behaviour of melanoma cells.

    Directory of Open Access Journals (Sweden)

    Aparna eJayachandran

    2015-02-01

    Full Text Available Epithelial-to-mesenchymal transition is a hallmark event in the metastatic cascade conferring invasive ability to tumor cells. There are ongoing efforts to replicate the physiological events occurring during mobilization of tumor cells in model systems. However, few systems are able to capture these complex in vivo events. The embryonic chicken transplantation model has emerged as a useful system to assess melanoma cells including functions that are relevant to the metastatic process, namely invasion and plasticity. The chicken embryo represents an accessible and economical 3-dimensional in vivo model for investigating melanoma cell invasion as it exploits the ancestral relationship between melanoma and its precursor neural crest cells. We describe a methodology which enables the interrogation of melanoma cell motility within the developing avian embryo. This model involves the injection of melanoma cells into the neural tube of chicken embryos. Melanoma cells are labelled using fluorescent tracker dye, Vybrant DiO, then cultured as hanging drops for 24 hours to aggregate the cells. Groups of approximately 700 cells are placed into the neural tube of chicken embryos prior to the onset of neural crest migration at the hindbrain level (embryonic day 1.5 or trunk level (embryonic day 2.5. Chick embryos are reincubated and analysed after 48 hours for the location of melanoma cells using fluorescent microscopy on whole mounts and cross-sections of the embryos. Using this system, we compared the in vivo invasive behavior of epithelial-like and mesenchymal-like melanoma cells. We report that the developing embryonic microenvironment confers motile abilities to both types of melanoma cells. Hence the embryonic chicken transplantation model has potential to become a valuable tool for in vivo melanoma invasion studies. Importantly, it may provide novel insights into and reveal previously unknown mediators of the metastatic steps of invasion and

  15. Use of the Chick Embryo Model in Uveal Melanoma

    Science.gov (United States)

    Kalirai, Helen; Shahidipour, Haleh; Coupland, Sarah E.; Luyten, Gregorius

    2015-01-01

    Animal models play a crucial role in basic and translational oncology research. Conventional rodent experiments, however, face ethical, practical and technical issues that limit their use. The chick embryo represents an accessible and economical in vivo model, which has long been used in developmental biology and for the study of angiogenesis. It is also a recognised xenograft model, and because of its lack of immune system in early development, the chick embryo has established itself as a key model system for cancer research, with which to study various steps in the metastatic process. In this chapter, we review the chick embryo model and the technical approaches adopted by cancer biologists, including advances in real-time imaging, and discuss how this has been or can be applied to improve our understanding of the biological events during uveal melanoma development and metastasis. PMID:27171889

  16. A Large French Case-Control Study Emphasizes the Role of Rare Mc1R Variants in Melanoma Risk

    Directory of Open Access Journals (Sweden)

    Hui-Han Hu

    2014-01-01

    Full Text Available Background. The MC1R gene implicated in melanogenesis and skin pigmentation is highly polymorphic. Several alleles are associated with red hair and fair skin phenotypes and contribute to melanoma risk. Objective. This work aims to assess the effect of different classes of MC1R variants, notably rare variants, on melanoma risk. Methods. MC1R coding region was sequenced in 1131 melanoma patients and 869 healthy controls. MC1R variants were classified as RHC (R and non-RHC (r. Rare variants (frequency < 1% were subdivided into two subgroups, predicted to be damaging (D or not (nD. Results. Both R and r alleles were associated with melanoma (OR = 2.66 [2.20–3.23] and 1.51 [1.32–1.73] and had similar population attributable risks (15.8% and 16.6%. We also identified 69 rare variants, of which 25 were novel. D variants were strongly associated with melanoma (OR = 2.38 [1.38–4.15] and clustered in the same MC1R domains as R alleles (intracellular 2, transmembrane 2 and 7. Conclusion. This work confirms the role of R and r alleles in melanoma risk in the French population and proposes a novel class of rare D variants as important melanoma risk factors. These findings may improve the definition of high-risk subjects that could be targeted for melanoma prevention and screening.

  17. Risk of melanoma and non-melanoma skin cancer in ulcerative colitis patients treated with thiopurines: a nationwide retrospective cohort.

    Science.gov (United States)

    Abbas, Ali M; Almukhtar, Rawaa M; Loftus, Edward V; Lichtenstein, Gary R; Khan, Nabeel

    2014-11-01

    There are limited data on the risk of non-melanoma skin cancer (NMSC) and melanoma skin cancer (MSC) among thiopurine-treated patients with ulcerative colitis (UC). Our aim was to investigate the risk while on, by cumulative years, and after stopping thiopurine therapy. Nationwide data were obtained from the Veterans Affairs (VA) health-care system during 2001-2011. We performed a retrospective cohort study evaluating patients with UC. Cox regression was used to investigate the association between thiopurines use and time to NMSC while adjusting for demographics, ultraviolet radiation exposure, and VA visiting frequency. A matched nested case-control study was conducted to investigate the association between thiopurine use and MSC. We included 14,527 patients with UC in the analysis, with a median follow-up of 8.1 years. A total of 3,346 (23%) patients used thiopurines for a median duration of 1.6 years. We identified 421 NMSC and 45 MSC cases. The adjusted hazard ratios of developing NMSC while on and after stopping thiopurines were 2.1 (P<0.0001) and 0.7 (P=0.07), respectively, as compared with unexposed patients. The incidence rate of NMSC among those who never used thiopurines was 3.7 compared with 5.8, 7.9, 8.3, 7.8, and 13.6 per 1,000 person-years for the 1st, 2nd, 3th, 4th, and 5th year of thiopurine use, respectively. No statistically significant association was observed between thiopurine use and MSC, odds ratio 0.8 (P=0.6). In this predominantly white male nationwide cohort, there was a twofold increase in the risk of NMSC while on thiopurines. The incidence rate of NMSC significantly increased with subsequent years of cumulative exposure to thiopurines. Stopping thiopurines reduced the risk of NMSC to pre-exposure levels irrespective of the prior exposure duration.

  18. A questionnaire to measure melanoma risk, knowledge and protective behaviour: Assessing content validity in a convenience sample of Scots and Australians

    Directory of Open Access Journals (Sweden)

    Lee Amanda J

    2011-08-01

    Full Text Available Abstract Background The aim of this study was to assess the content validity of a questionnaire to measure melanoma risk, knowledge and protective behaviour in a convenience sample of Scots and Australians. Australia has the highest melanoma incidence worldwide but has developed a culture of skin cancer avoidance with a long history of skin cancer primary prevention campaigns of proven effectiveness. Scotland has lower incidence, but has shown a greater rate of increase between 1985 and 2007. There is an urgent need in Scotland, therefore, to identify those groups at greatest risk and provide them with effective preventative advice. Method A self-administered postal survey was completed by four groups formed from convenience samples in two geographical locations (Northeast Scotland and Western Australia. In univariate analysis scores on personal risk, level of concern, protective behaviour, and knowledge were compared by nationality, previous skin cancer diagnosis and personally knowing someone with melanoma. Multivariate linear regression analysis modelled the influence of potential predictor variables upon each of the scores. Results 540 people completed the questionnaire, 273 Scots (50.6%. 133 (24.6% Scots and 83 (15.4% Australians previously had melanoma or non-melanoma skin cancer, whilst 120 (22.2% Scots and 190 (35.2% Australians personally knew someone with melanoma. Australians had higher knowledge (p , level of concern (p and protective behaviour (p scores than the Scottish. Australian nationality was the strongest independent predictor of a higher knowledge score (p , followed by a previous skin cancer diagnosis (p = 0.003, personal knowledge of someone with melanoma (p = 0.011, female gender (p = 0.005 and higher education status (p (R2 = 0.163. Conclusion The questionnaire detected higher levels of knowledge and skin cancer protective behaviours in Australians than in Scottish people. This was expected and supports the content

  19. Risk-adjusted melanoma skin cancer incidence rates in Whites (United States).

    Science.gov (United States)

    Merrill, Ray Martell

    2011-12-01

    The objective of this study was to obtain a better population-based measure of risk for melanoma skin cancer. A method has been previously proposed for estimating cancer incidence rates for data collected from the Surveillance, Epidemiology, and End Results (SEER) program. Unlike conventionally reported incidence rates in the USA, this method uses the first primary cancer and adjusts for population-based cancer prevalence to obtain a better measure of cancer risk. The study involves SEER data for white men and women. Conventional melanoma incidence rates overestimate risk for men, increasingly so from 3.3% in the age group of 30-39 years to 11.3% in the age group of 80 years and older. Overestimation in risk for women ranged from 3.3% in the age group of 30-39 years to 8.9% in the age group of 80 years and older. Overestimation of risk was more pronounced when both in-situ and malignant melanomas were considered. Increasing trends in conventional rates were slightly greater than trends in risk-adjusted incidence rates (RAIRs). In 2007, the estimated number of cases with malignant melanoma among the white population based on conventional cancer incidence rates is 37 636 (64 125 including in-situ cases) for men and 28 935 (49 361 including in-situ cases) for women. The estimated number of cases in the USA based on RAIRS is 34 652 [(7.9%); 55 413 (13.6%) including in-situ cases] for male and 27 178 [(6.1%); 44 467 (9.9%) including in-situ cases] for women. We concluded that RAIRs are a better measure of melanoma skin cancer risk and should be used for estimating the number of cancer patients in the USA.

  20. HLA class II polymorphisms in Spanish melanoma patients: homozygosity for HLA-DQA1 locus can be a potential melanoma risk factor.

    Science.gov (United States)

    Planelles, D; Nagore, E; Moret, A; Botella-Estrada, R; Vila, E; Guillén, C; Montoro, J A

    2006-02-01

    The association of melanoma with HLA class II loci is under extensive debate. Different investigators have found discrepant results due to, at least in part, sample size, patient series heterogeneity, choice of control population and differences in the techniques employed for the detection of HLA antigens and alleles. This study was designed to analyse the possible association of melanoma with HLA class II loci with regard to different clinic pathological factors and to investigate other risk factors for melanoma susceptibility, such as HLA homozygosity. HLA-DRB1, -DQA1 and -DQB1 genotyping was performed for 117 eastern Spanish patients presenting with primary melanoma. Although there were no significant alterations in the phenotypic frequencies of HLA-DQA1, -DQB1 or -DRB1 alleles in any subgroup of patients when compared with controls, patients exhibited a statistically significant increase in HLA-DQA1 homozygosity rate. This DQA1 homozygosity-specific association was particularly dependent on some features in melanoma patients such as light hair colour, skin type I or II, early age at diagnosis, absence of atypical naevi, or abscence of atypical naevus syndrome phenotype (aetiological fractions about 10-20%). Analysis of homozygosity for single DQA1 alleles showed an increased homozygosity rate for DQA1*0505 and DQA1*0301 in comparison with controls. These DQA1 alleles are in strong linkage disequilibrium with DQB1*0301 in white populations, and DQB1*0301 homozygous individuals were significantly increased in red in or fair-haired patients (relative risk 5.65). Our results indicate that the contribution of HLA class II alleles to primary melanoma incidence is not significant in the Spanish population. However, homozygosity for the HLA-DQA1 locus (and, perhaps, for the HLA-DQB1*0301 allele) might be considered a potential risk factor for developing melanoma depending on the person's genetic background and, perhaps, on certain environmental conditions.

  1. Cancer risks and survival in patients with multiple primary melanomas: Association with family history of melanoma and germline CDKN2A mutation status.

    Science.gov (United States)

    Helgadottir, Hildur; Tuominen, Rainer; Olsson, Håkan; Hansson, Johan; Höiom, Veronica

    2017-11-01

    Worse outcomes have been noted in patients with multiple primary melanomas (MPMs) than in patients with single primary melanomas. We investigated how family history of melanoma and germline CDKN2A mutation status of MPM patients affects risks of developing subsequent melanomas and other cancers and survival outcomes. Comprehensive data on cancer diagnoses and deaths of MPM patients, their first-degree relatives, and matched controls were obtained through Swedish national health care and population registries. Familial MPM cases with germline CDKN2A mutations were youngest at the diagnosis of their second melanoma (median age 42 years) and had among the MPM cohorts the highest relative risks (RR) compared to controls of developing >2 melanomas (RR 238.4, 95% CI 74.8-759.9). CDKN2A mutated MPM cases and their first-degree relatives were the only cohorts with increased risks of nonskin cancers compared to controls (RR 3.6, 95% CI 1.9-147.1 and RR 3.2, 95% CI 1.9-5.6, respectively). In addition, CDKN2A mutated MPM cases had worse survival compared with both cases with familial (HR 3.0, 95% CI 1.3-8.1) and sporadic wild-type MPM (HR 2.63, 95% CI 1.3-5.4). Our study examined outcomes in subgroups of MPM patients, which affected the sample size of the study groups. This study demonstrates that CDKN2A mutation status and family history of melanoma significantly affects outcomes of MPM patients. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. F-18 FDG PET in the initial evaluation of high risk melanoma

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    Wagner, T.; Zerdoud, S.; Faurie, C.; Chevreau, C.; Courbon, F. [Institut Claudius Regaud, 31 - Toulouse (France)

    2008-02-15

    Introduction. - Localized melanoma is a potentially aggressive tumor. Its prognosis depends mainly on pathologic factors, namely: thickness (Breslow index), presence of ulceration and microscopic nodal metastasis. FDG PET is the modality of choice for evaluation of advanced melanoma and has proven its superiority in terms of sensitivity, specificity and accuracy compared to conventional imaging. Early stages of melanoma do not seem to benefit from PET FDG. However the value of PET FDG in staging localized high risk melanoma is yet to be determined. Patients and methods. - We have evaluated 87 patients with high risk melanoma with PET FDG. 32 patients presented with a Breslow index superior or equal to 4 mm, 21 with a Breslow index inferior to 4 mm and ulceration and 34 with a positive sentinel lymphadenectomy. PET FDG was realized after at least 6 h of fasting on a hybrid PET-CT G.E. Discovery S.T. scan for 65 of them. The rest of the patients were evaluated on a Siemens Ecat H.R. + scan. Scans were interpreted by an experimented nuclear medicine physician and were classified as positive or negative. All equivocal scans or cases for which there was discordance between the scan result and follow up were reviewed by 2 experimented nuclear medicine physicians and a consensus was reached. Results. - FDG PET was positive in seven patients, four scans were true positive and identified regional metastatic disease. No distant metastatic visceral disease was found. The three false positive scans consisted of a cyst adeno-lymphoma in one case, mediastinal and axillary uptake in the other two cases and no sign of evolution more than six months after the scan. Four patients with a negative scan showed metastatic disease in the six months following the PET scan. FDG PET had an impact on therapeutic management on two patients (2%). When evaluating FDG PET for regional disease with sentinel node biopsy as a reference, we found values of sensitivity, specificity, predictive

  3. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics

    DEFF Research Database (Denmark)

    Mercer, Louise K; Askling, Johan; Raaschou, Pauline

    2017-01-01

    with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy. METHODS: Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country......: This large European collaborative project did not confirm an overall increased risk of melanoma following exposure to TNFi....

  4. Inverse association between dietary vitamin D and risk of cutaneous melanoma in a northern Italy population

    Science.gov (United States)

    Vinceti, Marco; Malagoli, Carlotta; Fiorentini, Chiara; Longo, Caterina; Crespi, Catherine M.; Albertini, Giuseppe; Ricci, Cinzia; Lanzoni, Anna; Reggiani, Maurizio; Virgili, Annarosa; Osti, Federica; Lombardi, Mara; Santini, Marcello; Fanti, Pier Alessandro; Dika, Emi; Sieri, Sabina; Krogh, Vittorio; Seidenari, Stefania; Pellacani, Giovanni

    2010-01-01

    The possibility of an inverse association between vitamin D and risk of cancer and, in particular, of cutaneous malignant melanoma has been suggested, but results of epidemiologic studies are still conflicting. We examined the relation between dietary vitamin D intake and melanoma risk through a population-based case-control study (380 cases, 719 controls) in a northern region of Italy, a country with average vitamin D intake lower than in northern Europe or the US. We assessed average daily intake of vitamin D from foodstuffs using the European Prospective Investigation into Cancer and Nutrition (EPIC) semiquantitative food frequency questionnaire. In this population, levels of vitamin D intake were considerably lower than those observed in recent US studies. We found an inverse relation between dietary vitamin D and melanoma risk in the sample as a whole, in both crude and adjusted analyses. In sex and age-specific analyses, this association appeared to be stronger among males and among older subjects. These findings suggest that, at the relatively low levels of intake observed in this sample, an inverse relation between dietary vitamin D and risk of cutaneous malignant melanoma may exist. PMID:21541899

  5. A prospective study of measured body size and height and risk of keratinocyte cancers and melanoma.

    Science.gov (United States)

    Lahmann, Petra H; Hughes, Maria Celia B; Williams, Gail M; Green, Adèle C

    2016-02-01

    The potential influence of measured body weight and height on keratinocyte skin cancer risk has scarcely been studied. Some evidence indicates melanoma risk increases as self-reported height increases, but an association with body mass index (BMI) is less certain. We measured body weight and height of 1171 Australian men and women in a community-based skin cancer study in Queensland and prospectively examined the association of BMI, body surface area (BSA) and height and incidence of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma while accounting for skin phenotype, sun exposure, clinical/cutaneous signs of chronic photodamage and other risk factors. During 16 years of follow-up, 334 and 188 participants newly developed BCC and SCC, respectively; 28 participants were diagnosed with primary melanoma. BMI and BSA were unrelated to skin cancer incidence. After full adjustment, height was significantly associated with SCC development in men (relative risk (RR)=1.66; 95% confidence interval (CI)=1.11-2.48, for ≥175cm vs ≤171cm, Ptrend=0.017), and BCC in women (Ptrend=0.043). Melanoma in men, was similarly positively associated with height (RR per 5cm increment=1.55; 95%CI 0.97-2.47, P=0.067) though not significantly. This study shows that after adjusting for sun exposure tall stature may be a risk factor for the most common types of skin cancer BCC, SCC, and melanoma, while body mass and surface area appear unrelated to risk. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Association between risk factors and detection of cutaneous melanoma in the setting of a population-based skin cancer screening.

    Science.gov (United States)

    Hübner, Joachim; Waldmann, Annika; Eisemann, Nora; Noftz, Maria; Geller, Alan C; Weinstock, Martin A; Volkmer, Beate; Greinert, Rüdiger; Breitbart, Eckhard W; Katalinic, Alexander

    2017-07-07

    Early detection is considered to improve the prognosis of cutaneous melanoma. The value of population-based screening for melanoma, however, is still controversial. The aim of this study was to evaluate the predictive power of established risk factors in the setting of a population-based screening and to provide empirical evidence for potential risk stratifications. We reanalyzed data (including age, sex, risk factors, and screening results) of 354 635 participants in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany project conducted in the German state of Schleswig-Holstein (2003-2004). In multivariable analysis, atypical nevi [odds ratio (OR): 17.4; 95% confidence interval (CI): 14.4-20.1], personal history of melanoma (OR: 5.3; 95% CI: 3.6-7.6), and multiple (≥40) common nevi (OR: 1.3; 95% CI: 1.1-1.6) were associated with an increased risk of melanoma detection. Family history and congenital nevi were not significantly associated with melanoma detection in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany population. The effects of several risk-adapted screening strategies were evaluated. Hypothesizing a screening of individuals aged more than or equal to 35 years, irrespective of risk factors (age approach), the number needed to screen is 559 (95% CI: 514-612), whereas a screening of adults (aged ≥20) with at least one risk factor (risk approach) leads to an number needed to screen of 178 (95% CI: 163-196). Converted into one screen-detected melanoma, the number of missed melanomas is 0.15 (95% CI: 0.12-0.18) with the age approach and 0.22 (95% CI: 0.19-0.26) with the risk approach. The results indicate that focusing on individuals at high risk for melanoma may improve the cost-effectiveness and the benefit-to-harm balance of melanoma screening programs.

  7. CDKN2a mutation-negative melanoma families have increased risk exclusively for skin cancers but not for other malignancies.

    Science.gov (United States)

    Helgadottir, Hildur; Höiom, Veronica; Tuominen, Rainer; Jönsson, Göran; Månsson-Brahme, Eva; Olsson, Håkan; Hansson, Johan

    2015-11-01

    Germline CDKN2A mutations are found in 5-20% of melanoma families. Numerous studies have shown that carriers of CDKN2A mutations have increased risks of non-melanoma cancers, but so far there have been no studies investigating cancer risks in CDKN2A wild type (wt) melanoma families. In this prospective cohort study, index melanoma cases (n = 224) and their first-degree relatives (n = 944) were identified from 154 confirmed CDKN2A wt melanoma families. Cancer diagnoses in family members and matched controls were obtained from the Swedish Cancer Registry. Relative risks (RR), odds ratios (OR) and two-sided 95% confidence intervals (95% CI) were calculated. In index cases and first-degree relatives, the prospective RR for melanoma was 56.9 (95% CI 31.4-102.1) and 7.0 (95% CI 4.2-11.4), respectively, and for squamous cell skin cancers 9.1 (95% CI 6.0-13.7) and 3.4 (95% CI 2.2-5.2), respectively. In neither group, elevated risks were seen for non-skin cancers. In a subgroup analysis, CDKN2A wt melanoma families with young (melanoma cases were found to have increased risk of non-skin cancers (RR 1.5, 95% CI 1.0-1.5). Further, MC1R gene variants were increased in familial melanoma cases compared to controls (OR 2.4, 95% CI 1.6-3.4). Our findings suggest that in the majority of CDKN2A wt melanoma families, a segregation of variants in low-risk melanoma genes such as MC1R causes increased skin cancer susceptibility, rather than mutations in high-risk cancer predisposing genes, such mutations are more probable to be found in melanoma families with young melanoma cases. This study further supports an implication of CDKN2A mutation screening as a clinical test that determines counseling and follows up routines of melanoma families. © 2015 UICC.

  8. Pediatric Predispositional Genetic Risk Communication: Potential Utility for Prevention and Control of Melanoma Risk as an Exemplar.

    Science.gov (United States)

    Wu, Yelena P; Mays, Darren; Kohlmann, Wendy; Tercyak, Kenneth P

    2017-10-01

    Predispositional genetic testing among minor children is intensely debated due to the potential benefits and harms of providing this type of genetic information to children and their families. Existing guidelines on pediatric genetic testing state that predispositional testing could be appropriate for minors if preventive services exist that mitigate children's risk for or severity of the health condition in question. We use the example of hereditary melanoma to illustrate the rationale for and potential application of genetic risk communication for an adult-onset cancer to a pediatric population where childhood behaviors may reduce risk of disease later in life. We draw from the adult melanoma genetic risk communication and pediatric health behavior change literatures to suggest ways in which genetic test reporting and complementary education could be delivered to children who carry a hereditary risk for melanoma and their families in order to foster children's engagement in melanoma preventive behaviors. Genetic discoveries will continue to yield new opportunities to provide predispositional genetic risk information to unaffected individuals, including children, and could be delivered within programs that provide personalized and translational approaches to cancer prevention.

  9. NM23 deficiency promotes metastasis in a UV radiation-induced mouse model of human melanoma.

    Science.gov (United States)

    Jarrett, Stuart G; Novak, Marian; Harris, Nathan; Merlino, Glenn; Slominski, Andrezj; Kaetzel, David M

    2013-01-01

    Cutaneous malignant melanoma is the most lethal form of skin cancer, with 5-year survival rates of melanoma are not well understood, in part due to a paucity of animal models that accurately recapitulate the disease in its advanced forms. We have employed a transgenic mouse strain harboring a tandem deletion of the nm23-m1 and nm23-m2 genes to assess the combined contribution of these genes to suppression of melanoma metastasis. Crossing of the nm23-h1/nm23-h2 knockout in hemizygous-null form ([m1m2](+/-)) to a transgenic mouse strain (hepatocyte growth factor/scatter factor-overexpressing, or HGF(+) strain) vulnerable to poorly-metastatic, UVR-induced melanomas resulted in UVR-induced melanomas with high metastatic potential. Metastasis to draining lymph nodes was seen in almost all cases of back skin melanomas, while aggressive metastasis to lung, thoracic cavity, liver and bone also occurred. Interestingly, no differences were observed in the invasive characteristics of primary melanomas of HGF(+) and HGF(+) × [m1m2](+/-) strains, with both exhibiting invasion into the dermis and subcutis, indicating factors other than simple invasive activity were responsible for metastasis of HGF(+) × [m1m2](+/-) melanomas. Stable cell lines were established from the primary and metastatic melanoma lesions from these mice, with HGF(+) × [m1m2](+/-) lines exhibiting increased single cell migration and genomic instability. These studies demonstrate for the first time in vivo a potent metastasis suppressor activity of NM23 in UVR-induced melanoma, and have provided new tools for identifying molecular mechanisms that underlie melanoma metastasis.

  10. Telomere length and the risk of cutaneous malignant melanoma in melanoma-prone families with and without CDKN2A mutations.

    Directory of Open Access Journals (Sweden)

    Laura S Burke

    Full Text Available INTRODUCTION: Recent evidence suggests a link between constitutional telomere length (TL and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations. MATERIALS AND METHODS: We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT. RESULTS: We found that longer telomeres were associated with an increased risk of CMM (adjusted OR = 2.81, 95% CI = 1.02-7.72, P = 0.04. The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P = 0.002. One SNP in TERT, rs2735940, was significantly associated with TL (P = 0.002 after Bonferroni correction. DISCUSSION: Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk.

  11. Phosphodiesterase type 5 inhibitors and risk of melanoma: A meta-analysis.

    Science.gov (United States)

    Tang, Huilin; Wu, Wenting; Fu, Shuangshuang; Zhai, Suodi; Song, Yiqing; Han, Jiali

    2017-09-01

    The association between phosphodiesterase type 5 (PDE5) inhibitors and melanoma risk is controversial. We quantify the association between use of PDE5 inhibitors and melanoma. We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for studies that were conducted up to July 13, 2016, and evaluated the association between PDE5 inhibitors and skin cancer. Random effects meta-analyses were used to calculate the adjusted odds ratio (OR) with the 95% confidence interval (CI). Five observational studies were included. Compared with PDE5 inhibitor nonuse, PDE5 inhibitor use was slightly but significantly associated with an increased risk for development of melanoma (OR, 1.12; 95% CI, 1.03-1.21) and basal cell carcinoma (OR, 1.14; 95% CI, 1.09-1.19) but not squamous cell carcinoma. For melanoma risk, none of the prespecified factors (dose of PDE5 inhibitor, study design, and study region) significantly affected the results (P > .05). Our sensitivity analysis confirmed the stability of the results. We included only observational studies, which had some heterogeneities and inconsistent controlling for potential confounders. Use of PDE5 inhibitors may be associated with a slightly increased risk for development of melanoma and basal cell carcinoma but not squamous cell carcinoma. However, further large well-conducted prospective studies with adequate adjustment for potential confounders are required for confirmation. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. Risk of non-melanoma skin cancer in myasthenia patients treated with azathioprine

    DEFF Research Database (Denmark)

    Pedersen, E G; Pottegård, A; Hallas, J

    2014-01-01

    The association between use of azathioprine and risk of non-melanoma skin cancer (NMSC) in patients with myasthenia was evaluated in a nationwide setting. Treatment of autoimmune myasthenia frequently involves long-term exposure to immunosuppressants, including azathioprine. Use of azathioprine i...... increases the risk of NMSC in organ recipients and probably also in patients with other autoimmune disorders. No previous study has specifically investigated the risk of NMSC in myasthenia patients treated with azathioprine.......The association between use of azathioprine and risk of non-melanoma skin cancer (NMSC) in patients with myasthenia was evaluated in a nationwide setting. Treatment of autoimmune myasthenia frequently involves long-term exposure to immunosuppressants, including azathioprine. Use of azathioprine...

  13. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    International Nuclear Information System (INIS)

    Abschuetz, Oliver; Osen, Wolfram; Frank, Kathrin; Kato, Masashi; Schadendorf, Dirk; Umansky, Viktor

    2012-01-01

    Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy

  14. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Dirk Schadendorf

    2012-04-01

    Full Text Available Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA tyrosinase, tyrosinase related protein (TRP-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy.

  15. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Abschuetz, Oliver [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Osen, Wolfram [Division of Translational Immunology, German Cancer Center, Heidelberg 69120 (Germany); Frank, Kathrin [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Kato, Masashi [Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi 487-8501 (Japan); Schadendorf, Dirk [Department of Dermatology, University Hospital Essen, Essen 45122 (Germany); Umansky, Viktor, E-mail: v.umansky@dkfz.de [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany)

    2012-04-26

    Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy.

  16. Protective effect of copy number polymorphism of glutathione S-transferase T1 gene on melanoma risk in presence of CDKN2A mutations, MC1R variants and host-related phenotypes.

    Science.gov (United States)

    Chaudru, Valérie; Lo, M T; Lesueur, F; Marian, C; Mohamdi, H; Laud, K; Barrois, M; Chompret, A; Avril, M F; Demenais, F; Bressac-de Paillerets, B

    2009-01-01

    The effect of CDKN2A, the major high-risk melanoma susceptibility gene, has been shown to be modified by host-related phenotypes and variants of MC1R gene. The glutathione S-transferase (GSTs) genes, implicated in detoxification of metabolites after UV exposure, are candidates for modulating CDKN2A penetrance. Few case-control studies have investigated the effect of GSTs on melanoma risk, and have led to controversial results while these genes have not yet been studied in CDKN2A melanoma-prone families. We examined the effect of GSTP1, GSTM1 and GSTT1 genotypes on melanoma risk in 25 multi-generational melanoma-prone families with CDKN2A mutations, in presence of MC1R gene variants, sun exposure, and host-related phenotypes. These data included 195 genotyped subjects for all studied genes. We applied the GEE (Generalized Estimating Equations) approach to test for the effect of GSTs while adjusting for age, sex and CDKN2A mutation status and including successively MC1R, sun exposure and host factors in the model. No significant effect of null GSTM1 allele and GSTP1 variants (p.I105V, p.A114V) on melanoma risk was found. However, a significant protective effect of carrying >or=1 null GSTT1 allele was shown: OR(adjusted for age,sex,CDKN2A ) = 0.41 (0.18-0.94) and OR(adjusted for age,sex,CDKN2A,MC1R ) = 0.24 (0.15-0.58). Altogether, the factors modifying significantly the melanoma risk associated with CDKN2A mutations (stepwise procedure) were: MC1R and dysplastic nevi (increasing the risk) and GSTT1 (decreasing the risk). This study shows that even when a high-risk gene (CDKN2A) has been identified, multiple genetic modifiers influence melanoma risk.

  17. Characterization of melanoma susceptibility genes in high-risk patients from Central Italy.

    Science.gov (United States)

    Pellegrini, Cristina; Maturo, Maria Giovanna; Martorelli, Claudia; Suppa, Mariano; Antonini, Ambra; Kostaki, Dimitra; Verna, Lucilla; Landi, Maria Teresa; Peris, Ketty; Fargnoli, Maria Concetta

    2017-06-01

    Genetic susceptibility to cutaneous melanoma has been investigated in Italian high-risk melanoma patients from different geographical regions. CDKN2A, CDK4, and MC1R genes have been screened in most studies, MITF and POT1 were screened in only one study, and none analyzed the TERT promoter. We carried out a mutational analysis of CDKN2A, CDK4 exon 2, POT1 p.S270N, MITF exon 10, MC1R, and the TERT promoter in 106 high-risk patients with familial melanoma (FM) and sporadic multiple primary melanoma (spMPM) from Central Italy and evaluated mutations according to the clinicopathological characteristics of patients and lesions. In FM, CDKN2A mutations were detected in 8.3% of the families, including one undescribed exon 1β mutation (p.T31M), and their prevalence increased with the number of affected relatives within the family. MC1R variants were identified in 65% of the patients and the TERT rs2853669 promoter polymorphism was identified in 58% of the patients. A novel synonymous mutation detected in MITF exon 10 (c.861A>G, p.E287E), although predicted as a splice site mutation by computational tools, could not functionally be confirmed to alter splicing. For spMPM, 3% carried CDKN2A mutations, 79% carried MC1R variants, and 47% carried the TERT rs2853669 promoter polymorphism. MC1R variants were associated with fair skin type and light hair color both in FM and in spMPM, and with a reduction of age at diagnosis in FM patients. Mutations in CDK4 exon 2 and the POT1 p.S270N mutation were not detected. A low frequency of CDKN2A mutations and a high prevalence of MC1R variants characterize high-risk melanoma patients from Central Italy.

  18. Intention to Obtain Genetic Testing for Melanoma among Individuals at Low to Moderate Risk for Hereditary Melanoma

    Science.gov (United States)

    Vadaparampil, Susan T.; Azzarello, Lora; Pickard, Jennifer; Jacobsen, Paul B.

    2007-01-01

    Background: Melanoma is a serious skin cancer that has been on the rise in the United States. Some genetic component is apparent. Purpose: The purpose of this study was to identify demographic, clinical, attitudinal, and health belief factors associated with intention to obtain genetic testing for hereditary melanoma among unaffected first-degree…

  19. Melanoma risk associated with MC1R gene variants in Latvia and the functional analysis of rare variants.

    Science.gov (United States)

    Ozola, Aija; Azarjana, Kristīne; Doniņa, Simona; Proboka, Guna; Mandrika, Ilona; Petrovska, Ramona; Cēma, Ingrīda; Heisele, Olita; Eņģele, Ludmila; Streinerte, Baiba; Pjanova, Dace

    2013-03-01

    To evaluate the association of melanocortin 1 receptor gene (MC1R) variants with melanoma risk in a Latvian population, the MC1R gene was sequenced in 200 melanoma patients and 200 control persons. A functional study of previously uncharacterized, rare MC1R variants was also performed. In total, 26 different MC1R variants, including two novel variants Val165Ile and Val188Ile, were detected. The highest risk of melanoma was associated with the Arg151Cys variant (odds ratio (OR) 4.47, 95% confidence interval (CI) 2.19-9.14, PLatvia. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Modeling tandem AAG8-MEK inhibition in melanoma cells

    International Nuclear Information System (INIS)

    Sun, Bing; Kawahara, Masahiro; Nagamune, Teruyuki

    2014-01-01

    Drug resistance presents a challenge to the treatment of cancer patients, especially for melanomas, most of which are caused by the hyperactivation of MAPK signaling pathway. Innate or acquired drug-resistant relapse calls for the investigation of the resistant mechanisms and new anti-cancer drugs to provide implications for the ultimate goal of curative therapy. Aging-associated gene 8 (AAG8, encoded by the SIGMAR1 gene) is a chaperone protein profoundly elaborated in neurology. However, roles of AAG8 in carcinogenesis remain unclear. Herein, we discover AAG8 antagonists as new MEK inhibitors in melanoma cells and propose a novel drug combination strategy for melanoma therapy by presenting the experimental evidences. We report that specific antagonism of AAG8, efficiently suppresses melanoma cell growth and migration through, at least in part, the inactivation of the RAS-CRAF-MEK signaling pathway. We further demonstrate that melanoma cells that are resistant to AAG8 antagonist harbor refractory CRAF-MEK activity. MEK acts as a central mediator for anti-cancer effects and also for the resistance mechanism, leading to our proposal of tandem AAG8-MEK inhibition in melanoma cells. Combination of AAG8 antagonist and very low concentration of a MEK inhibitor synergistically restricts the growth of drug-resistant cells. These data collectively pinpoint AAG8 as a potential target and delineate a promising drug combination strategy for melanoma therapy

  1. The risk of melanoma in airline pilots and cabin crew: a meta-analysis.

    Science.gov (United States)

    Sanlorenzo, Martina; Wehner, Mackenzie R; Linos, Eleni; Kornak, John; Kainz, Wolfgang; Posch, Christian; Vujic, Igor; Johnston, Katia; Gho, Deborah; Monico, Gabriela; McGrath, James T; Osella-Abate, Simona; Quaglino, Pietro; Cleaver, James E; Ortiz-Urda, Susana

    2015-01-01

    Airline pilots and cabin crew are occupationally exposed to higher levels of cosmic and UV radiation than the general population, but their risk of developing melanoma is not yet established. To assess the risk of melanoma in pilots and airline crew. PubMed (1966 to October 30, 2013), Web of Science (1898 to January 27, 2014), and Scopus (1823 to January 27, 2014). All studies were included that reported a standardized incidence ratio (SIR), standardized mortality ratio (SMR), or data on expected and observed cases of melanoma or death caused by melanoma that could be used to calculate an SIR or SMR in any flight-based occupation. Primary random-effect meta-analyses were used to summarize SIR and SMR for melanoma in any flight-based occupation. Heterogeneity was assessed using the χ2 test and I2 statistic. To assess the potential bias of small studies, we used funnel plots, the Begg rank correlation test, and the Egger weighted linear regression test. Summary SIR and SMR of melanoma in pilots and cabin crew. Of the 3527 citations retrieved, 19 studies were included, with more than 266 431 participants. The overall summary SIR of participants in any flight-based occupation was 2.21 (95% CI, 1.76-2.77; P < .001; 14 records). The summary SIR for pilots was 2.22 (95% CI, 1.67-2.93; P = .001; 12 records). The summary SIR for cabin crew was 2.09 (95% CI, 1.67-2.62; P = .45; 2 records). The overall summary SMR of participants in any flight-based occupation was 1.42 (95% CI, 0.89-2.26; P = .002; 6 records). The summary SMR for pilots was 1.83 (95% CI, 1.27-2.63, P = .33; 4 records). The summary SMR for cabin crew was 0.90 (95% CI, 0.80-1.01; P = .97; 2 records). Pilots and cabin crew have approximately twice the incidence of melanoma compared with the general population. Further research on mechanisms and optimal occupational protection is needed.

  2. Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study.

    Directory of Open Access Journals (Sweden)

    Jibin Liu

    Full Text Available Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM risk.Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015. Study-specific risk estimates were pooled under the random-effects model.Two case-control studies (846 MM patients and 843 controls and five cohort studies (including 844,246 participants and 5,737 MM cases were identified. For caffeinated coffee, the pooled relative risk (RR of MM was 0.81 [95% confidential interval (95% CI = 0.68-0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912-0.999 for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326. Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81-1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake.This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings.

  3. Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study

    Science.gov (United States)

    Liu, Jibin; Shen, Biao; Shi, Minxin; Cai, Jing

    2016-01-01

    Background Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM) risk. Methods Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015). Study-specific risk estimates were pooled under the random-effects model. Results Two case-control studies (846 MM patients and 843 controls) and five cohort studies (including 844,246 participants and 5,737 MM cases) were identified. For caffeinated coffee, the pooled relative risk (RR) of MM was 0.81 [95% confidential interval (95% CI) = 0.68–0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912–0.999) for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326). Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81–1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake). Conclusions This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings. PMID:26816289

  4. Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma

    OpenAIRE

    Duffy, David L.; Zhao, Z. Z.; Sturm, Richard A.; Hayward, Nicholas K.; Martin, Nicholas G.; Montgomery, Grant W.

    2009-01-01

    We have previously described the role of red hair (Melanocortin 1 Receptor, MC1R) and blue eye (Oculocutaneous Albinism Type 2, OCA2) gene polymorphisms in modulating risk of cutaneous malignant melanoma (CMM) in a highly sun-exposed population of European descent. A number of recent studies, including genome-wide association studies (GWAS), have identified numerous polymorphisms controlling human hair, eye and skin colour. In this paper, we test a selected set of polymorphisms in pigmentatio...

  5. The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish models.

    Science.gov (United States)

    Yen, Jennifer; White, Richard M; Wedge, David C; Van Loo, Peter; de Ridder, Jeroen; Capper, Amy; Richardson, Jennifer; Jones, David; Raine, Keiran; Watson, Ian R; Wu, Chang-Jiun; Cheng, Jiqiu; Martincorena, Iñigo; Nik-Zainal, Serena; Mudie, Laura; Moreau, Yves; Marshall, John; Ramakrishna, Manasa; Tarpey, Patrick; Shlien, Adam; Whitmore, Ian; Gamble, Steve; Latimer, Calli; Langdon, Erin; Kaufman, Charles; Dovey, Mike; Taylor, Alison; Menzies, Andy; McLaren, Stuart; O'Meara, Sarah; Butler, Adam; Teague, Jon; Lister, James; Chin, Lynda; Campbell, Peter; Adams, David J; Zon, Leonard I; Patton, E Elizabeth; Stemple, Derek L; Futreal, P Andy

    2013-01-01

    Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process. To decipher the genetics of these melanomas, we sequence the protein coding exons of 53 primary melanomas generated from several BRAF(V600E) or NRAS(Q61K) driven transgenic zebrafish lines. We find that engineered zebrafish melanomas show an overall low mutation burden, which has a strong, inverse association with the number of initiating germline drivers. Although tumors reveal distinct mutation spectrums, they show mostly C > T transitions without UV light exposure, and enrichment of mutations in melanogenesis, p53 and MAPK signaling. Importantly, a recurrent amplification occurring with pre-configured drivers BRAF(V600E) and p53-/- suggests a novel path of BRAF cooperativity through the protein kinase A pathway. This is the first analysis of a melanoma mutational landscape in the absence of UV light, where tumors manifest with remarkably low mutation burden and high heterogeneity. Genotype specific amplification of protein kinase A in cooperation with BRAF and p53 mutation suggests the involvement of melanogenesis in these tumors. This work is important for defining the spectrum of events in BRAF or NRAS driven melanoma in the absence of UV light, and for informed exploitation of models such as transgenic zebrafish to better understand mechanisms leading to human melanoma formation.

  6. Plaque Brachytherapy for Uveal Melanoma: A Vision Prognostication Model

    International Nuclear Information System (INIS)

    Khan, Niloufer; Khan, Mohammad K.; Bena, James; Macklis, Roger; Singh, Arun D.

    2012-01-01

    Purpose: To generate a vision prognostication model after plaque brachytherapy for uveal melanoma. Methods and Materials: All patients with primary single ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106 plaque brachytherapy between January 1, 2005, and June 30, 2010, were included. The primary endpoint was loss of visual acuity. Only patients with initial visual acuity better than or equal to 20/50 were used to evaluate visual acuity worse than 20/50 at the end of the study, and only patients with initial visual acuity better than or equal to 20/200 were used to evaluate visual acuity worse than 20/200 at the end of the study. Factors analyzed were sex, age, cataracts, diabetes, tumor size (basal dimension and apical height), tumor location, and radiation dose to the tumor apex, fovea, and optic disc. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log rank analysis) were used to estimate freedom from vision loss. Results: Of 189 patients, 92% (174) were alive as of February 1, 2011. At presentation, visual acuity was better than or equal to 20/50 and better than or equal to 20/200 in 108 and 173 patients, respectively. Of these patients, 44.4% (48) had post-treatment visual acuity of worse than 20/50 and 25.4% (44) had post-treatment visual acuity worse than 20/200. By multivariable analysis, increased age (hazard ratio [HR] of 1.01 [1.00-1.03], P=.05), increase in tumor height (HR of 1.35 [1.22-1.48], P<.001), and a greater total dose to the fovea (HR of 1.01 [1.00-1.01], P<.001) were predictive of vision loss. This information was used to develop a nomogram predictive of vision loss. Conclusions: By providing a means to predict vision loss at 3 years after treatment, our vision prognostication model can be an important tool for patient selection and treatment counseling.

  7. Plaque Brachytherapy for Uveal Melanoma: A Vision Prognostication Model

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Niloufer [Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio (United States); Khan, Mohammad K. [Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia (United States); Bena, James [Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio (United States); Macklis, Roger [Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio (United States); Singh, Arun D., E-mail: singha@ccf.org [Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio (United States)

    2012-11-01

    Purpose: To generate a vision prognostication model after plaque brachytherapy for uveal melanoma. Methods and Materials: All patients with primary single ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106 plaque brachytherapy between January 1, 2005, and June 30, 2010, were included. The primary endpoint was loss of visual acuity. Only patients with initial visual acuity better than or equal to 20/50 were used to evaluate visual acuity worse than 20/50 at the end of the study, and only patients with initial visual acuity better than or equal to 20/200 were used to evaluate visual acuity worse than 20/200 at the end of the study. Factors analyzed were sex, age, cataracts, diabetes, tumor size (basal dimension and apical height), tumor location, and radiation dose to the tumor apex, fovea, and optic disc. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log rank analysis) were used to estimate freedom from vision loss. Results: Of 189 patients, 92% (174) were alive as of February 1, 2011. At presentation, visual acuity was better than or equal to 20/50 and better than or equal to 20/200 in 108 and 173 patients, respectively. Of these patients, 44.4% (48) had post-treatment visual acuity of worse than 20/50 and 25.4% (44) had post-treatment visual acuity worse than 20/200. By multivariable analysis, increased age (hazard ratio [HR] of 1.01 [1.00-1.03], P=.05), increase in tumor height (HR of 1.35 [1.22-1.48], P<.001), and a greater total dose to the fovea (HR of 1.01 [1.00-1.01], P<.001) were predictive of vision loss. This information was used to develop a nomogram predictive of vision loss. Conclusions: By providing a means to predict vision loss at 3 years after treatment, our vision prognostication model can be an important tool for patient selection and treatment counseling.

  8. Pesticide exposure in farming and forestry and the risk of uveal melanoma.

    Science.gov (United States)

    Behrens, Thomas; Lynge, Elsebeth; Cree, Ian; Lutz, Jean-Michel; Eriksson, Mikael; Guénel, Pascal; Merletti, Franco; Morales-Suarez-Varela, Maria; Afonso, Noemia; Stengrevics, Aivars; Févotte, Joëlle; Sabroe, Svend; Llopis-González, Agustin; Gorini, Giuseppe; Hardell, Lennart; Stang, Andreas; Ahrens, Wolfgang

    2012-01-01

    Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries. Incident cases of uveal melanoma and population as well as hospital controls were included and frequency-matched by country, 5-year age groups and sex. Self-reported exposure was quantified with respect to duration of exposure and pesticide application method. We calculated the exposure intensity level based on application method and use of personal protective equipment. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression analyses and adjusted for several potential confounders. 293 case and 3,198 control subjects were interviewed. We did not identify positive associations with activities in farming or forestry, pesticide application or pesticide mixing. No consistent positive associations were seen with exposure intensity level scores either. The only statistically significantly raised association in this study was for exposure to chemical fertilizers in forestry (OR = 8.93; 95% CI 1.73-42.13), but this observation was based on only six exposed subjects. Results did not change when we restricted analyses to morphologically verified cases and excluded proxy interviews as well as cancer controls. We did not observe effect modification by sex or eye color. Risk estimates for pesticide exposures and occupational activities in agriculture and forestry were not increased and did not indicate a hormonal mechanism due to these exposures.

  9. Integrative genetic analysis suggests that skin color modifies the genetic architecture of melanoma.

    Science.gov (United States)

    Hulur, Imge; Skol, Andrew D; Gamazon, Eric R; Cox, Nancy J; Onel, Kenan

    2017-01-01

    Melanoma is the deadliest form of skin cancer and presents a significant health care burden in many countries. In addition to ultraviolet radiation in sunlight, the main causal factor for melanoma, genetic factors also play an important role in melanoma susceptibility. Although genome-wide association studies have identified many single nucleotide polymorphisms associated with melanoma, little is known about the proportion of disease risk attributable to these loci and their distribution throughout the genome. Here, we investigated the genetic architecture of melanoma in 1,888 cases and 990 controls of European non-Hispanic ancestry. We estimated the overall narrow-sense heritability of melanoma to be 0.18 (P < 0.03), indicating that genetics contributes significantly to the risk of sporadically-occurring melanoma. We then demonstrated that only a small proportion of this risk is attributable to known risk variants, suggesting that much remains unknown of the role of genetics in melanoma. To investigate further the genetic architecture of melanoma, we partitioned the heritability by chromosome, minor allele frequency, and functional annotations. We showed that common genetic variation contributes significantly to melanoma risk, with a risk model defined by a handful of genomic regions rather than many risk loci distributed throughout the genome. We also demonstrated that variants affecting gene expression in skin account for a significant proportion of the heritability, and are enriched among melanoma risk loci. Finally, by incorporating skin color into our analyses, we observed both a shift in significance for melanoma-associated loci and an enrichment of expression quantitative trait loci among melanoma susceptibility variants. These findings suggest that skin color may be an important modifier of melanoma risk. We speculate that incorporating skin color and other non-genetic factors into genetic studies may allow for an improved understanding of melanoma

  10. Whole body positron emission tomography in follow-up of high risk melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Koskivuo, Ilkka O.; Suominen, Erkki A. [Dept. of Surgery, Turku Univ. Hospital (Finland); Seppaenen, Marko P.; Minn, Heikki R.I. [Turku PET Centre, Turku Univ. Hospital (Finland)

    2007-07-15

    The aim of this study was to determine the clinical impact of whole body positron emission tomography (FDG PET) to detect clinically silent metastases in the follow-up of patients with high risk melanoma. FDG PET was performed to 30 asymptomatic melanoma patients (AJCC stage IIB-IIIC) 7-24 months after the primary surgery and sentinel node biopsy. FDG PET was able to detect six of seven recurrences, constituting 20% of all study patients. One patient presented with a negative FDG PET finding at the very first scanning, but was positive later in a repeated scan after manifestation of palpable mass in the axilla. The positive PET finding had an impact on treatment decisions in every case: three patients underwent surgical resection and four patients received chemotherapy or interferon. The mean follow-up time was 27 months (range, 12-48 months) and during that time the other 23 patients with true negative FDG PET were disease-free. One of the seven recurrences was in remission after surgical metastasectomy. In conclusion, whole body FDG PET is a valuable follow-up tool in high risk melanoma to diagnose recurrences and to select the patients, who are suitable for surgical metastasectomy.

  11. Sunbed use during adolescence and early adulthood is associated with increased risk of early-onset melanoma

    Science.gov (United States)

    Cust, Anne E; Armstrong, Bruce K; Goumas, Chris; Jenkins, Mark A; Schmid, Helen; Hopper, John L; Kefford, Richard F; Giles, Graham G; Aitken, Joanne F; Mann, Graham J

    2010-01-01

    Sunbed use is associated with increased risk of melanoma. Younger people might be more susceptible to the carcinogenic effects of ultraviolet radiation. We investigated the association between sunbed use and risk of early-onset cutaneous malignant melanoma. From the Australian Melanoma Family Study, a multi-centre, population-based, case-control-family study, we analysed data for 604 cases diagnosed between ages 18 and 39 years and 479 controls. Data were collected by interview. Associations were estimated as odds ratios (ORs) using unconditional logistic regression, adjusting for age, sex, city, education, family history, skin colour, usual skin response to sunlight, and sun exposure. Compared with having never used a sunbed, the OR for melanoma associated with ever-use was 1.41 (95% confidence interval (CI) 1.01-1.96), and 2.01 (95% CI 1.22-3.31) for more than 10 lifetime sessions (Ptrend 0.01 with cumulative use). The association was stronger for earlier age at first use (Ptrend 0.02). The association was also stronger for melanoma diagnosed when aged 18-29 years (OR for more than 10 lifetime sessions = 6.57, 95% CI 1.41-30.49) than for melanoma diagnosed when 30-39 years (OR 1.60, 95% CI 0.92-2.77; Pinteraction 0.01). Among those who had ever used a sunbed and were diagnosed between 18-29 years of age, three quarters (76%) of melanomas were attributable to sunbed use. Sunbed use is associated with increased risk of early-onset melanoma, with risk increasing with greater use, an earlier age at first use and for earlier onset disease. PMID:20669232

  12. High frequency of brain metastases after adjuvant therapy for high-risk melanoma.

    Science.gov (United States)

    Samlowski, Wolfram E; Moon, James; Witter, Merle; Atkins, Michael B; Kirkwood, John M; Othus, Megan; Ribas, Antoni; Sondak, Vernon K; Flaherty, Lawrence E

    2017-11-01

    The incidence of CNS progression in patients with high-risk regional melanoma (stages IIIAN2a-IIIC) is not well characterized. Data from the S0008 trial provided an opportunity to examine the role of CNS progression in treatment failure and survival. All patients were surgically staged. Following wide excision and full regional lymphadenectomy, patients were randomized to receive adjuvant biochemotherapy (BCT) or high-dose interferon alfa-2B (HDI). CNS progression was retrospectively identified from data forms. Survival was measured from date of CNS progression. A total of 402 eligible patients were included in the analysis (BCT: 199, HDI: 203). Median follow-up (if alive) was over 7 years (range: 1 month to 11 years). The site of initial progression was identifiable in 80% of relapsing patients. CNS progression was a component of systemic melanoma relapse in 59/402 patients (15% overall). In 34/402 patients (9%) CNS progression represented the initial site of treatment failure. CNS progression was a component of initial progression in 27% of all patients whose melanoma relapsed (59/221). The risk of CNS progression was highest within 3 years of randomization. The difference in CNS progression rates between treatment arms was not significant (BCT = 25, HDI = 34, P = 0.24). Lymph node macrometastases strongly associated with CNS progression (P = 0.001), while ulceration and head and neck primaries were not significant predictors. This retrospective analysis of the S0008 trial identified a high brain metastasis rate (15%) in regionally advanced melanoma patients. Further studies are needed to establish whether screening plus earlier treatment would improve survival following CNS progression. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  13. Melanoma epidemiology, prognosis and trends in Latvia.

    Science.gov (United States)

    Azarjana, K; Ozola, A; Ruklisa, D; Cema, I; Rivosh, A; Azaryan, A; Pjanova, D

    2013-11-01

    Melanoma incidence and mortality rates are increasing worldwide within the white population. Clinical and histological factors have been usually used for the prognosis and assessment of the risk for melanoma. The aim of the study was to describe the clinical and histopathological features of the cutaneous melanoma (CM) in the Latvian population, to test the association between melanoma features and patient survival, and to assess the time trends for melanoma incidence. We undertook a descriptive, retrospective analysis of archive data of 984 melanoma patients treated at the largest oncological hospital of Latvia, Riga East University Hospital Latvian Oncology Centre (LOC), between 1998 and 2008. Cox proportional hazards model was used to analyse patient survival and autoregressive models were applied to detect trends in melanoma incidence over time for various categories of melanoma. The study showed a significant ascending trend in melanoma incidence in Latvia during the time period from 1998 to 2008 (ß = 1.83, 95% CI = 1.15-2.91, P = 0.011). Nodular melanoma was the most common tumour subtype with a frequency of 39.2%. Ulceration was present in 45.2% of melanomas. The mean Breslow thickness was 6.0 mm (6.8 mm) and no significant decline in median Breslow thickness was observed during the study period (P = 0.609). A better overall prognosis was detected for females in comparison with males (HR = 1.49; 95% CI = 1.22-1.81; P Latvia with the majority of melanomas diagnosed at late stages with poor prognosis for survival. © 2012 The Authors Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  14. Enhanced expression of melanoma progression markers in mouse model of sleep apnea

    Directory of Open Access Journals (Sweden)

    S. Perini

    2016-07-01

    Full Text Available Introduction: Obstructive sleep apnea has been associated with higher cancer incidence and mortality. Increased melanoma aggressivity was reported in obstructive sleep apnea patients. Mice exposed to intermittent hypoxia (IH mimicking sleep apnea show enhanced melanoma growth. Markers of melanoma progression have not been investigated in this model. Objective: The present study examined whether IH affects markers of melanoma tumor progression. Methods: Mice were exposed to isocapnic IH to a nadir of 8% oxygen fraction for 14 days. One million B16F10 melanoma cells were injected subcutaneously. Immunohistochemistry staining for Ki-67, PCNA, S100-beta, HMB-45, Melan-A, TGF-beta, Caspase-1, and HIF-1alpha were quantified using Photoshop. Results: Percentage of positive area stained was higher in IH than sham IH group for Caspase-1, Ki-67, PCNA, and Melan-A. The greater expression of several markers of tumor aggressiveness, including markers of ribosomal RNA transcription (Ki-67 and of DNA synthesis (PCNA, in mice exposed to isocapnic IH than in controls provide molecular evidence for a apnea–cancer relationship. Conclusions: These findings have potential repercussions in the understanding of differences in clinical course of tumors in obstructive sleep apnea patients. Further investigation is necessary to confirm mechanisms of these descriptive results. Keywords: Apnea, Melanoma, Biological markers

  15. The 2017 complete overhaul of adjuvant therapies for high-risk melanoma and its consequences for staging and management of melanoma patients.

    Science.gov (United States)

    Eggermont, Alexander M M; Dummer, Reinhard

    2017-11-01

    The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab in fully resected stage IIIB/C-IV and of the combination of dabrafenib (D) plus trametinib (T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo will complete the picture in the early 2018. Toxicity profiles are in line with the experience in advanced melanoma, i.e. favourable for the anti-PD1 agents and for D + T and problematic for ipilimumab. The 2017 outcomes are practice changing and put an end to the use of interferon (IFN) and ipilimumab. In countries with only access to IFN, its use can be restricted to patients with ulcerated melanoma, based on the individual patient data meta-analysis recently published. Because of the results of the Melanoma Sentinel Lymph node Trial-2 (MSLT-2) trial, completion lymph node dissection (CLND) will decrease sharply, leading to a lack of optimal prognostic information. Prognosis in sentinel node-positive stage IIIA/B patients is extremely heterogeneous with 5-year survival rates varying from 90% to 40% and depends mostly on the number of positive nodes identified by CLND. This information is crucial for clinical decision-making. How to guarantee optimal staging information needs to be discussed urgently. Further improvements of adjuvant therapies will have to address all these questions as well as the exploration of neoadjuvant use of active drugs and combination approaches. Important paradigm shifts in the management of high-risk melanoma patients are upon us. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Risk of interactions between complementary and alternative medicine and medication for comorbidities in patients with melanoma.

    Science.gov (United States)

    Loquai, Carmen; Dechent, Dagmar; Garzarolli, Marlene; Kaatz, Martin; Kaehler, Katharina C; Kurschat, Peter; Meiss, Frank; Stein, Annette; Nashan, Dorothee; Micke, Oliver; Muecke, Ralph; Muenstedt, Karsten; Stoll, Christoph; Schmidtmann, Irene; Huebner, Jutta

    2016-05-01

    Complementary and alternative medicine (CAM) is used widely among cancer patients. Beside the risk of interaction with cancer therapies, interactions with treatment for comorbidities are an underestimated problem. The aim of this study was to assess prevalence of interactions between CAM and drugs for comorbidities from a large CAM usage survey on melanoma patients and to classify herb-drug interactions with regard to their potential to harm. Consecutive melanoma outpatients of seven skin cancer centers were asked to complete a standardized CAM questionnaire including questions to their CAM use and their taken medication for comorbidities and cancer. Each combination of conventional drugs and complementary substances was evaluated for their potential of interaction. 1089 questionnaires were eligible for evaluation. From these, 61.6% of patients reported taking drugs regularly from which 34.4% used biological-based CAM methods. Risk evaluation for interaction was possible for 180 CAM users who listed the names or substances they took for comorbidities. From those patients, we found 37.2% at risk of interaction of their co-consumption of conventional and complementary drugs. Almost all patients using Chinese herbs were at risk (88.6%). With a high rate of CAM usage at risk of interactions between CAM drugs and drugs taken for comorbidities, implementation of a regular assessment of CAM usage and drugs for comorbidities is mandatory in cancer care.

  17. Combination therapy targeting the tumor microenvironment is effective in a model of human ocular melanoma

    Directory of Open Access Journals (Sweden)

    Schafer Peter H

    2007-07-01

    Full Text Available Abstract Background Ocular melanoma is the leading intraocular malignancy. There is no effective treatment for metastatic ocular melanoma. We sought a treatment targeting the tumor microenvironment as well as the tumor cells. Methods Migration of HUVEC cells, the ability of HUVEC cells to form tubes, and proliferative capacity of a human ocular melanoma cell line were tested in the presence of lenalidomide and sorafenib alone and in combination. The compounds were also tested in a rat aortic ring assay and were tested in a highly aggressive human ocular melanoma xenograft model. Results Lenalidomide and Sorafenib inhibit HUVEC ability to migrate and form tubes and when used in combination the inhibition is increased. The agents alone and in combination inhibit outgrowth in the rat aortic ring model. The combination of the agents improved the inhibition over either single agent. In a xenograft model, combination therapy inhibited tumor growth over inhibition by single agent alone in a significant fashion (p Conclusion Lenalidomide and sorafenib are effective at targeting endothelial cells, inhibiting growth of ocular melanoma cells and can inhibit growth of tumors in a xenograft model as well as inhibit development of metastases. Combining these agents works in an additive to synergistic way to inhibit the growth of tumors and development of metastases.

  18. Keratinocytes drive melanoma invasion in a reconstructed skin model.

    NARCIS (Netherlands)

    Kilsdonk, J.W.J. van; Bergers, M.; Kempen, L.C.L.T. van; Schalkwijk, J.; Swart, G.W.

    2010-01-01

    Melanoma progression is a multistep progression from a common melanocytic nevus through the radial growth phase, the invasive vertical growth phase finally leading to metastatic spread into distant organs. Migration and invasion of tumor cells requires secretion of proteases to facilitate remodeling

  19. Immunological response in the mouse melanoma model after local hyperthemia

    Czech Academy of Sciences Publication Activity Database

    Kubeš, J.; Svoboda, Jan; Rosina, J.; Starec, M.; Fišerová, Anna

    2008-01-01

    Roč. 57, č. 3 (2008), s. 459-465 ISSN 0862-8408 R&D Projects: GA AV ČR IAA5020403; GA AV ČR IAA500200620 Institutional research plan: CEZ:AV0Z50200510 Keywords : local hyperthermia * melanoma * monocytes Subject RIV: EC - Immunology Impact factor: 1.653, year: 2008

  20. Predictive risk factors for radiation retinopathy and optic neuropathy after proton beam therapy for uveal melanoma.

    Science.gov (United States)

    Seibel, Ira; Cordini, Dino; Hager, Annette; Tillner, Johanna; Riechardt, Aline I; Heufelder, Jens; Davids, Anja M; Rehak, Matus; Joussen, Antonia M

    2016-09-01

    This study was performed in order to evaluate the incidence of radiation retinopathy and optic neuropathy occurring after proton beam therapy for uveal melanoma. Included in this study were all patients who had been treated with primary proton beam therapy for uveal melanoma at the oncology service between May 1998 and June 2014 with a minimum follow-up of 12 months. Excluded were all patients who underwent re-irradiation, or vitrectomy due to exudative retinal detachment or for tumor-resection. During this period, 1127 patients matched the inclusion criteria, of whom 768 (68.1 %) and 463 (41.0 %) developed radiation retinopathy and optic neuropathy after a median time of 18.9 months (2.0-99.84 months) and 19.8 months (0.2-170.4 months), respectively. Mean follow-up was 53.4 months (12-170.4 months). Included were 558 men (49.5 %) and 569 women (50.5 %). Mean age was 61 years (16-89 years). Visual acuity slightly decreased from initial levels of 0.3 logMAR-0.4 logMAR in patients without developing any radiation-induced complication but severely decreased to 1.0 logMAR or 1.5 logMAR in the case of developing radiation retinopathy only or optic neuropathy, respectively. Independent risk factors for radiation retinopathy were a centrally (<2.5 mm from sensitive structures) located tumor or a thick tumor located more than 2.5 mm from sensitive structures, while those for radiation optic neuropathy comprised a short distance and applied dose to the optic disk. The risk for radiation retinopathy is higher in central uveal melanoma. Mid-/peripheral tumors are at high risk for radiation retinopathy and maculopathy if presenting with increased thickness.

  1. Skin Cancer Risk (Nonmelanoma Skin Cancers/Melanoma) in Vitiligo Patients.

    Science.gov (United States)

    Rodrigues, Michelle

    2017-04-01

    The relative genetic and immune protection against melanoma and nonmelanoma skin cancers in those with vitiligo is reassuring. The results of recent studies allow us to be cautiously optimistic when discussing the risk of skin cancer caused by therapeutic exposure to narrow-band ultraviolet B light. However, we should continue to recommend sun protection at all other times to avoid burning in vitiliginous skin and to decrease incidental ultraviolet exposure. It is also important to perform full skin checks regularly in light of the prolonged courses of phototherapy required to repigment vitiliginous skin and maintain repigmentation thereafter. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Hydrochlorothiazide use and risk of non-melanoma skin cancer

    DEFF Research Database (Denmark)

    Arnspang, Sidsel; Gaist, David; Johannesdottir Schmidt, Sigrun Alba

    2018-01-01

    cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHODS: From the Danish Cancer Registry, we identified patients (cases) with NMSC during 2004-2012. Controls were matched 1:20 by age and sex. Cumulative hydrochlorothiazide use (1995-2012) was assessed from the Danish Prescription Registry......BACKGROUND: Hydrochlorothiazide, one of the most frequently used diuretic and antihypertensive drugs in the United States and Western Europe, is photosensitizing and has previously been linked to lip cancer. OBJECTIVE: To examine the association between hydrochlorothiazide use and the risk of basal...

  3. Spontaneous canine oral melanoma: A large animal model for BNCT

    International Nuclear Information System (INIS)

    Gavin, P.R.; Kraft, S.L.; DeHaan, C.E.; Sande, R.D.; Papageorges, M.; Bauer, W.F.

    1992-01-01

    Oral melanomas in dogs are the most common malignant neoplasm of the oral cavity. Prevalence has been recorded at 127 per 100,000 dogs/year. There is a predilection for the gingiva of male dogs with heavy pigmentation. The tumors are resistant to treatment with conventional radiation and chemotherapy. The tumors are very aggressive and have generally metastasized to the regional lymph nodes at the time of initial diagnosis. Distant metastases occur in approximately 85% of patients. Metastatic sites include lungs, kidneys, liver, brain, skeleton, and gastrointestinal (GI) tract. Fifteen (15) dogs with oral lesions biopsied and diagnosed as malignant melanoma were entered in the study. A thorough diagnostic regimen was performed in an attempt to detect the regional spread and distant metastases of the tumor

  4. Relevance of in vivo models in melanoma skin cancer

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.B.

    1995-12-31

    A discussion of possible wavelength dependence of induction of cutaneous malignant melanoma (CMM) is provided. Strengths and weaknesses of various experimental approaches to better understanding of the prevalence of CMM in different human populations including latitude effects are compared. Further the advantages and limitations of the use of the laboratory opossum (Monodelphis domestic), transgenic mice containing SV40 ongogene sequences under tyrosinase promoter control, and a backcross hybrid fish of the genus Xenophorus are contrasted.

  5. MC1R genotype as a predictor of early-onset melanoma, compared with self-reported and physician-measured traditional risk factors: an Australian case-control-family study.

    Science.gov (United States)

    Cust, Anne E; Goumas, Chris; Vuong, Kylie; Davies, John R; Barrett, Jennifer H; Holland, Elizabeth A; Schmid, Helen; Agha-Hamilton, Chantelle; Armstrong, Bruce K; Kefford, Richard F; Aitken, Joanne F; Giles, Graham G; Bishop, D; Newton-Bishop, Julia A; Hopper, John L; Mann, Graham J; Jenkins, Mark A

    2013-09-04

    Melanocortin-1 receptor (MC1R) gene variants are very common and are associated with melanoma risk, but their contribution to melanoma risk prediction compared with traditional risk factors is unknown. We aimed to 1) evaluate the separate and incremental contribution of MC1R genotype to prediction of early-onset melanoma, and compare this with the contributions of physician-measured and self-reported traditional risk factors, and 2) develop risk prediction models that include MC1R, and externally validate these models using an independent dataset from a genetically similar melanoma population. Using data from an Australian population-based, case-control-family study, we included 413 case and 263 control participants with sequenced MC1R genotype, clinical skin examination and detailed questionnaire. We used unconditional logistic regression to estimate predicted probabilities of melanoma. Results were externally validated using data from a similar study in England. When added to a base multivariate model containing only demographic factors, MC1R genotype improved the area under the receiver operating characteristic curve (AUC) by 6% (from 0.67 to 0.73; P factors that contributed significantly to the AUC were MC1R genotype, number of nevi and previous non-melanoma skin cancer; the AUC was 0.78 (95% CI 0.75-0.82) for the model with self-reported nevi and 0.83 (95% CI 0.80-0.86) for the model with physician-counted nevi. Factors that did not further contribute were sun and sunbed exposure and pigmentation characteristics. Adding MC1R to a model containing pigmentation characteristics and other self-reported risk factors increased the AUC by 2.1% (P = 0.01) and improved the quartile classification by a net 10% (95% CI 1-18%, P = 0.03). Although MC1R genotype is strongly associated with skin and hair phenotype, it was a better predictor of early-onset melanoma than was pigmentation characteristics. Physician-measured nevi and previous non-melanoma skin cancer were

  6. Risk of a second primary cancer after non-melanoma skin cancer in white men and women: a prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Fengju Song

    Full Text Available Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC and risk of subsequent cancer at other sites. The purpose of this study is to prospectively examine the risk of primary cancer according to personal history of NMSC.In two large US cohorts, the Health Professionals Follow-up Study (HPFS and the Nurses' Health Study (NHS, we prospectively investigated this association in self-identified white men and women. In the HPFS, we followed 46,237 men from June 1986 to June 2008 (833,496 person-years. In the NHS, we followed 107,339 women from June 1984 to June 2008 (2,116,178 person-years. We documented 29,447 incident cancer cases other than NMSC. Cox proportional hazard models were used to calculate relative risks (RRs and 95% confidence intervals (CIs. A personal history of NMSC was significantly associated with a higher risk of other primary cancers excluding melanoma in men (RR=1.11; 95% CI 1.05-1.18, and in women (RR=1.20; 95% CI 1.15-1.25. Age-standardized absolute risk (AR was 176 in men and 182 in women per 100,000 person-years. For individual cancer sites, after the Bonferroni correction for multiple comparisons (n=28, in men, a personal history of NMSC was significantly associated with an increased risk of melanoma (RR=1.99, AR=116 per 100,000 person-years. In women, a personal history of NMSC was significantly associated with an increased risk of breast (RR=1.19, AR=87 per 100,000 person-years, lung (RR=1.32, AR=22 per 100,000 person-years, and melanoma (RR=2.58, AR=79 per 100,000 person-years.This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women.

  7. Comparative analysis of melanoma deregulated miRNAs in the medaka and Xiphophorus pigment cell cancer models.

    Science.gov (United States)

    Mishra, Rasmi R; Kneitz, Susanne; Schartl, Manfred

    2014-06-01

    Malignant melanoma is the most aggressive and deadly form of skin cancer, with an almost 100% development of resistance to current therapeutic approaches at progression stages. The incidence of melanoma is steadily increasing worldwide. Although many details leading to the development of malignant melanoma are known, the complex process of melanomagenesis is poorly understood. MicroRNAs (miRNAs) are a class of small noncoding-RNAs of ~22nt length that regulate gene expression at the post-transcriptional level. It is now well established that deregulated miRNA expression is seen in many cancers including melanoma. To further study the miRNA functions in melanoma formation and progression we use a transgenic melanoma model in Japanese ricefish (medaka; Oryzias latipes) and the natural Xiphophorus melanoma model. In these fishes, dependent on the genetic background various histo- and patho-types of tumors appear, comparable to human melanoma types. We have studied expression profiles of ten known human melanoma-associated miRNAs and their respective target gene expression in the fish melanoma models. We show that miRNAs of the miR-17-92 cluster (miR-20a2, miR-92a1, miR-17 and miR-18a), miR-126, miR-182, miR-210 and miR-214 are upregulated and their respective target genes (RUNX1, HIF1A, TGFBR2, THBS1 and JAK2) are down-regulated in melanoma. MicroRNA-125b is down-regulated and the target genes (ERBB3a and ERBB3b) are upregulated in fish melanomas. Results provide clear evidence that the fish melanoma-associated miRNAs and respective target genes are deregulated generally like in human melanoma. Our results confirm the value of fish; such as medaka and Xiphophorus as good model systems to identify and decipher molecular mechanisms associated with malignant melanoma. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Skills training to learn discrimination of ABCDE criteria by those at risk of developing melanoma.

    Science.gov (United States)

    Robinson, June K; Turrisi, Rob

    2006-04-01

    To develop skin self-examination skills by improving the use of the ABCDE criteria by those at risk of developing melanoma. Ten single-sex groups of 10 unrelated adults received a knowledge-based intervention followed by skills training. Classroom in the ambulatory care area of a hospital. Patients One hundred unrelated adults with either a personal or family history of melanoma and no previous skin self-examination counseling. Interventions A dermatologist presented information, and each subject read a brochure and reviewed a bookmark. The facilitator led the group discussions about scoring each feature and the decision to seek medical care. Measurement of moles with a ruler and a pencil eraser and the use of an illuminated magnifying lens were demonstrated. Preintervention and postintervention assessments were performed for each intervention. Recognition of A, B, C, D, and E traits. The subjects preferred the bookmark (87% of subjects), opaque ruler (94% of subjects), and lighted magnifying lens (81% of subjects) to reading the brochure, which was felt to take too long. Recognition of border irregularity, color variation, and diameter improved significantly after the intervention. Women recognized color variation more often than men (94% vs 62%; odds ratio [OR], 23.7; 95% confidence interval [CI], 16.1-50.5). Men identified irregular borders more often than women (91% vs 75%; OR, 16.8; 95% CI, 4.5-22.6). Women appropriately decided to see a physician more often than men (81% vs 57%; OR, 13.5; 95% CI, 7.1-28.4). Determining the presence of the A, B, C, and E criteria is challenging for the novice. Skills training aided performance of skin self-examination. Differences in proclivities according to sex suggest that if men and women form partnerships for skin checks, they may learn from each other, and their combined strengths will promote detection of early melanomas.

  9. Dual Role of Host Par2 in a Murine Model of Spontaneous Metastatic B16 Melanoma

    Czech Academy of Sciences Publication Activity Database

    Olejár, Tomáš; Větvička, D.; Zadinová, M.; Poučková, P.; Kukal, J.; Ježek, Petr; Matěj, R.

    2014-01-01

    Roč. 34, č. 7 (2014), s. 3511-3515 ISSN 0250-7005 R&D Projects: GA ČR(CZ) GAP302/10/0346 Institutional support: RVO:67985823 Keywords : PAR2 * melanoma * metastasis * murine model Subject RIV: EA - Cell Biology Impact factor: 1.826, year: 2014

  10. Antitumor activity of histamine and clozapine in a mouse experimental model of human melanoma.

    Science.gov (United States)

    Massari, Noelia A; Medina, Vanina A; Cricco, Graciela P; Martinel Lamas, Diego J; Sambuco, Lorena; Pagotto, Romina; Ventura, Clara; Ciraolo, Pablo J; Pignataro, Omar; Bergoc, Rosa M; Rivera, Elena S

    2013-12-01

    Functional presence of histamine H4 receptor (H4R) was demonstrated in human melanoma cell lines and biopsies. The purposes of this work were to investigate signal transduction pathways and biological responses triggered by the activation of H4R in human primary (WM35) and metastatic (M1/15) melanoma cell lines and to evaluate the in vivo antitumor activity of histamine (HA) and clozapine (CLZ) on human M1/15 melanoma xenografts. Clonogenic assay, incorporation of BrdU, cell cycle distribution, phosphorylation levels of ERK1/2 and cAMP production were evaluated in vitro. An experimental human melanoma model was developed into athymic nude mice. Tumor growth, survival and histochemical studies were performed in order to investigate the expression levels of H4R, HA, PCNA, mitotic index (MI), and angiogenesis. The results indicate that H4R agonists inhibited forskolin-induced cAMP levels only in M1/15 cells while increased phosphorylation levels of ERK1/2 and decreased proliferation in both cell types. In vivo studies show that HA and CLZ (1mgkg(-1), sc) significantly increased median survival and decreased tumor volume. These effects were associated to a reduction in MI, in the expression of proliferation marker and in intratumoral neovascularization. We conclude that HA and CLZ exhibit an antitumoral effect in vitro and in vivo on human melanoma, suggesting the therapeutic potential of these compounds for the treatment of malignant melanoma. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  11. Inflammatory Cytokine Pattern Is Sex-Dependent in Mouse Cutaneous Melanoma Experimental Model

    Directory of Open Access Journals (Sweden)

    Mihaela Surcel

    2017-01-01

    Full Text Available We present the evaluation of inflammatory cytokines in mouse cutaneous melanoma experimental model, as markers of disease evolution. Moreover, to test our experimental model, we have used low doses of dacarbazine (DTIC. C57 BL/6J mouse of both sexes were subjected to experimental cutaneous melanoma and treated with low doses of DTIC. Clinical parameters and serum cytokines were followed during tumor evolution and during DTIC therapy. Cytokine/chemokine pattern was assessed using xMAP technology and the following molecules were quantified: interleukins (IL-1-beta, IL-6, IL-10, IL-12 (p70, interferon (IFN-gamma, granulocyte macrophage colony-stimulating factor (GM-CSF, tumor necrosis factor (TNF-alpha, macrophage inflammatory protein (MIP-1alpha, monocyte chemoattractant protein (MCP-1, and keratinocyte-derived chemokine (KC. Significant differences were found between normal females and males mice, female mice having a statistically higher serum concentration of IL-1-beta compared to male mice, while males have a significantly higher concentration of MIP-1-alpha. During melanoma evolution in the female group, IL-1-beta, MIP-1-alpha, and KC circulatory levels were found 10-fold increased, while other cytokines doubled their values. In the male mice group, only circulatory KC increased 4 times, while IL-1-beta and TNF-alpha doubled their circulatory values. Various serum cytokines correlated with the disease evolution in cutaneous melanoma mouse model.

  12. Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs

    NARCIS (Netherlands)

    Garritsen, F.M.; Schaft, J. van der; Reek, J.M.P.A. van den; Politiek, K.; Os-Medendorp, H. van; Dijk, M.; Hijnen, D.J.; Graaf, M de; Bruijnzeel-Koomen, C.A.; Jong, E.M.G.J. de; Schuttelaar, M.A.; Bruin-Weller, M.S. de

    2017-01-01

    There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma (SCC), in patients with atopic dermatitis (AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the

  13. Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs

    NARCIS (Netherlands)

    Garritsen, Floor M.; Van der Schaft, Jorien; Van den Reek, Juul M.; Politiek, Klaziena; Van Osmedendorp, Harmieke; Van Dijk, Marijke; Hijnen, Dirk J.; De Graaf, Marlies; Bruijnzeel-Koomen, Carla A.; De Jong, Elke M.; Schuttelaar, Marie-Louise A.; De Bruin-Weller, Marjolein S.

    There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma (SCC), in patients with atopic dermatitis (AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the

  14. Risk factors for non-melanoma skin cancer in patients with essential thrombocythemia and polycythemia vera.

    Science.gov (United States)

    Gómez, Montse; Guillem, Vicent; Pereira, Arturo; Ferrer-Marín, Francisca; Álvarez-Larrán, Alberto; Kerguelen, Ana; Estrada, Natàlia; Martínez-López, Joaquín; Angona, Anna; Amat, Paula; Navarro, Blanca; Besses, Carles; Hernández-Boluda, Juan-Carlos

    2016-03-01

    Population-based studies have reported an increased incidence of skin cancer in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We have examined the risk factors for non-melanoma skin cancer (NMSC) in patients diagnosed with ET or PV during 1973-2012. A case-control study was performed to compare the clinical and treatment-related data of 51 ET/PV patients who had NMSC with that of 401 patients who did not. We also evaluated whether polymorphisms in 12 genes involved in DNA integrity predisposed to NMSC. By multivariate logistic regression analysis, risk factors for NMSC were older age (OR: 1.7, 95% CI: 1.3-2.1, P factors independently associated with increased cumulative incidence of NMSC were age (5% increased risk per year; P risk; P = 0.022), and hydroxycarbamide exposure (22% increased risk; P = 0.065). No susceptibility gene variant was identified. These findings suggest that the risk to develop NMSC in ET/PV patients results from the combined effect of common risk factors (age, male sex) together with cytoreductive treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Current Data on Risk Factor Estimates Does Not Explain the Difference in Rates of Melanoma between Hispanics and Non-Hispanic Whites

    Directory of Open Access Journals (Sweden)

    Sonia Kamath

    2016-01-01

    Full Text Available United States Hispanics have seven times lower melanoma incidence rates than non-Hispanic whites (NHW. It is unclear whether this difference can be explained solely by phenotypic risk factors, like darker skin, or whether modifiable risk factors, like sun exposure, also play a role. The purpose of this paper is to summarize what is currently known about melanoma risk factors among Hispanics and NHWs, and whether or not those differences could explain the difference in melanoma incidence. Through literature review, relative risks and prevalence of melanoma risk factors in Hispanics and NHWs were identified and used to calculate the expected rate in Hispanics and rate ratio compared to NHWs. We found that melanoma risk factors either have similar frequency in Hispanics and NHWs (e.g., many large nevi or are less frequent in Hispanics but do not explain a high proportion of disease variation (e.g., red hair. Considering current knowledge of risk factor prevalence, we found that melanoma incidence rates in the two groups should actually be similar. Sun exposure behavior among Hispanics may contribute to the explanation for the 7-fold difference in melanoma rates. Currently, limited data exist on sun exposure behavior among Hispanics, but possibilities for improving primary prevention by further studying these practices are substantial.

  16. Non-genetic risk factors for cutaneous melanoma and keratinocyte skin cancers: An umbrella review of meta-analyses.

    Science.gov (United States)

    Belbasis, Lazaros; Stefanaki, Irene; Stratigos, Alexander J; Evangelou, Evangelos

    2016-12-01

    Skin cancers have a complex disease mechanism, involving both genetic and non-genetic risk factors. Numerous meta-analyses have been published claiming statistically significant associations between non-genetic risk factors and skin cancers without applying a thorough methodological assessment. The present study maps the literature on the non-genetic risk factors of skin cancers, assesses the presence of statistical biases and identifies the associations with robust evidence. We searched PubMed up to January 20, 2016 to identify systematic reviews and meta-analyses of observational studies that examined associations between non-genetic factors and skin cancers. For each meta-analysis, we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We also assessed the between-study heterogeneity (I 2 metric), evidence for small-study effects and excess significance bias. Forty-four eligible papers were identified and included a total of 85 associations. Twenty-one associations were significant at Pmelanoma, skin type, sunburns, premalignant skin lesions, common and atypical nevi for melanoma) presented high level of credibility. The majority of meta-analyses on non-genetic risk factors for skin cancers suffered from large between-study heterogeneity and small-study effects or excess significance bias. The associations with convincing and highly suggestive evidence were mainly focused on skin photosensitivity and phenotypic characteristics. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Local Recurrence After Primary Proton Beam Therapy in Uveal Melanoma: Risk Factors, Retreatment Approaches, and Outcome.

    Science.gov (United States)

    Seibel, Ira; Cordini, Dino; Rehak, Matus; Hager, Annette; Riechardt, Aline I; Böker, Alexander; Heufelder, Jens; Weber, Andreas; Gollrad, Johannes; Besserer, Angela; Joussen, Antonia M

    2015-10-01

    To evaluate the risk factors, recurrence rates, retreatments, and long-term patient outcomes following proton beam therapy for uveal melanoma. Retrospective interventional case series. All patients treated with primary proton beam therapy for uveal melanoma at the oncology service at Charité-Berlin and Helmholtz-Zentrum-Berlin between May 1998 and December 2008 were reviewed for local recurrence. Of 982 patients, 982 eyes matched the inclusion criteria. The data were obtained from electronic health records, operative reports, discharge letters, and radiation planning. Comparisons of fundus photographs and ultrasound measurements were performed to assess the growth pattern of the tumor and to determine the success of retreatment, in the case that a globe-retaining therapy was undertaken. Of 982 patients, 35 patients (3.6%) developed local recurrence. The median follow-up was 60.7 months (6.0-170.4 months). Local control rate was 96.4% and the overall eye retention rate was 95.0% in this cohort. Local recurrence was correlated with a higher risk for metastasis and reduced survival. Largest tumor diameter was identified as the sole statistically significant risk factor for local recurrence (P = .00001). All globe-retaining retreatment approaches for local recurrence, including proton beam therapy, brachytherapy, and transpupillary thermotherapy used for recurrences at the tumor margins, showed good local tumor control and similar metastasis-free survivals. This study showed that each globe-retaining retreatment approach can result in satisfying local tumor control. In case of early detection of local recurrence, preservation of the globe can be warranted. Therefore, regularly performed follow-ups should be ensured. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Risks of different skin tumour combinations after a first melanoma, squamous cell carcinoma and basal cell carcinoma in Dutch population-based cohorts: 1989-2009.

    Science.gov (United States)

    van der Leest, R J T; Hollestein, L M; Liu, L; Nijsten, T; de Vries, E

    2018-03-01

    Skin cancer patients are primarily at increased risk of developing subsequent skin cancers of the same type. Shared risk factors might also increase the occurrence of a different type of subsequent skin cancer. To investigate risks of different skin tumour combinations after a first melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). All melanoma and SCC patients included in the national Netherlands Cancer Registry (NCR) and all BCC patients included in the regional Eindhoven Cancer Registry (ECR) between 1989 and 2009 were followed until diagnosis of a subsequent different skin cancer (melanoma, SCC or BCC), date of death or end of study. Cumulative risks, standardized incidence ratios (SIR) and absolute excess risks (AER) of subsequent skin cancers were calculated. A total of 50 510 melanoma patients and 64 054 patients with a SCC of the skin were included (national data NCR). The regional data of the ECR consisted of 5776 melanoma patients, 5749 SCC patients and 41 485 BCC patients. The 21-year cumulative risk for a subsequent melanoma after a first SCC or BCC was respectively 1.7% and 1.3% for males and 1.3% and 1.2% for females; SCC after melanoma or BCC was 4.6% and 9.3% (males) and 2.6% and 4.1% (females); BCC after melanoma or SCC was respectively 13.2% and 27.8% (males) and 14.9% and 21.1% (females). SIRs and AERs remained elevated up to 21 years after the first melanoma, SCC or BCC. This large population-based study investigating risks of developing a different subsequent cutaneous malignancy showed high-cumulative risks of mainly KC and markedly increased relative and absolute risks of all tumour combinations. These estimates confirm a common carcinogenesis and can serve as a base for follow-up guidelines and patient education aiming for an early detection of the subsequent cancers. © 2017 European Academy of Dermatology and Venereology.

  19. Childhood Body Size and the Risk of Malignant Melanoma in Adulthood

    DEFF Research Database (Denmark)

    Meyle, Kathrine D; Gamborg, Michael; Sørensen, Thorkild I A

    2017-01-01

    ), and body surface area (BSA) at ages 7-13 years and birth weight are associated with adult MM. Data from the Copenhagen School Health Records Register, containing annual height and weight measurements of 372,636 Danish children born in 1930-1989, were linked with the Danish Cancer Registry. Cox regression...... years and age 13 years had a significantly increased MM risk compared with children who grew taller between those ages. Birth weight was positively associated with MM. We conclude that associations between body size and MM originate early in life and are driven largely by height and birth weight......Malignant melanoma (MM) is the most aggressive form of skin cancer. Adult anthropometry influences MM development; however, associations between childhood body size and future melanomagenesis are largely unknown. We investigated whether height, body mass index (BMI; weight (kg)/height (m)2...

  20. Risk factors for the development of locoregional cutaneous metastases as the sole form of recurrence in patients with melanoma.

    Science.gov (United States)

    Messeguer, F; Agustí-Mejías, A; Traves, V; Alegre, V; Oliver, V; Nagore, E

    2013-01-01

    While locoregional cutaneous metastases (in transit and satellite) in melanoma have received little attention from researchers to date, they have pathogenic and prognostic features that distinguish them from other forms of locoregional recurrence. Identifying predictors of these metastases would be of great value for their prevention, early diagnosis, and treatment. The aim of this study was to identify the risk factors associated with locoregional cutaneous metastases as the first form of recurrence in the metastatic progression of melanoma. Between 2000 and 2010, we prospectively collected the data of 1327 patients diagnosed with stage I and II melanoma. During follow up, 112 patients (8.4%) developed metastases. Of these, 36 had exclusively locoregional cutaneous metastases. The clinical and histological characteristics of this subgroup were evaluated. In the univariate analysis, significant predictors were patient age, primary tumor thickness, site, ulceration, mitotic index, and histological type. After multivariate analysis, the independent risk factors were tumor thickness (risk ratio [RR] 5.6; 95% CI: 2.7-11.5) and the location of the primary tumor on the lower limbs (RR 3.4; 95% CI: 1.0-11.5), on the head or neck (RR 4.8; 95% IC: 1.7-13.5), or in acral sites (RR 6.7; 95% IC: 2.2-20.8). Patients who have melanomas with a Breslow thickness of more than 2mm located on the lower limbs, head, neck, or acral sites have a higher risk of developing locoregional cutaneous metastases. These findings could be useful in the design of future guidelines for the monitoring and management of melanoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  1. MC1R variation and melanoma risk in relation to host/clinical and environmental factors in CDKN2A positive and negative melanoma patients.

    Science.gov (United States)

    Ghiorzo, Paola; Bonelli, Luigina; Pastorino, Lorenza; Bruno, William; Barile, Monica; Andreotti, Virginia; Nasti, Sabina; Battistuzzi, Linda; Grosso, Marco; Bianchi-Scarrà, Giovanna; Queirolo, Paola

    2012-09-01

    Host, environmental and genetic factors differently modulate cutaneous melanoma (CM) risk across populations. Currently, the main genetic risk determinants are germline mutations in the major known high-risk susceptibility genes, CDKN2A and CDK4, and variants of the low-risk gene MC1R, which is key in the pigmentation process. This case-control study aimed at investigating the influence of the main host and environmental risk factors and of MC1R variation on CM risk in 390 CDKN2A-negative and 49 CDKN2A-positive Italian individuals. Multivariate analysis showed that MC1R variation, number of nevi and childhood sunburns doubled CM risk in CDKN2A-negative individuals. In CDKN2A-positive individuals, family history of CM and presence of atypical nevi, rather than MC1R status, modified risk (20.75- and 2.83-fold, respectively). Occupational sun exposure increased CM risk (three to sixfold) in both CDKN2A-negative and CDKN2A-positive individuals, reflecting the occupational habits of the Ligurian population and the geographical position of Liguria. © 2012 John Wiley & Sons A/S.

  2. Data-derived modeling characterizes plasticity of MAPK signaling in melanoma.

    Directory of Open Access Journals (Sweden)

    Marti Bernardo-Faura

    2014-09-01

    Full Text Available The majority of melanomas have been shown to harbor somatic mutations in the RAS-RAF-MEK-MAPK and PI3K-AKT pathways, which play a major role in regulation of proliferation and survival. The prevalence of these mutations makes these kinase signal transduction pathways an attractive target for cancer therapy. However, tumors have generally shown adaptive resistance to treatment. This adaptation is achieved in melanoma through its ability to undergo neovascularization, migration and rearrangement of signaling pathways. To understand the dynamic, nonlinear behavior of signaling pathways in cancer, several computational modeling approaches have been suggested. Most of those models require that the pathway topology remains constant over the entire observation period. However, changes in topology might underlie adaptive behavior to drug treatment. To study signaling rearrangements, here we present a new approach based on Fuzzy Logic (FL that predicts changes in network architecture over time. This adaptive modeling approach was used to investigate pathway dynamics in a newly acquired experimental dataset describing total and phosphorylated protein signaling over four days in A375 melanoma cell line exposed to different kinase inhibitors. First, a generalized strategy was established to implement a parameter-reduced FL model encoding non-linear activity of a signaling network in response to perturbation. Next, a literature-based topology was generated and parameters of the FL model were derived from the full experimental dataset. Subsequently, the temporal evolution of model performance was evaluated by leaving time-defined data points out of training. Emerging discrepancies between model predictions and experimental data at specific time points allowed the characterization of potential network rearrangement. We demonstrate that this adaptive FL modeling approach helps to enhance our mechanistic understanding of the molecular plasticity of melanoma.

  3. European ancestry and polymorphisms in DNA repair genes modify the risk of melanoma: a case-control study in a high UV index region in Brazil.

    Science.gov (United States)

    Gonçalves, Fernanda T; Francisco, Guilherme; de Souza, Sonia P; Luiz, Olinda C; Festa-Neto, Cyro; Sanches, José A; Chammas, Roger; Gattas, Gilka J F; Eluf-Neto, José

    2011-10-01

    UV radiation is the major environmental factor related to development of cutaneous melanoma. Besides sun exposure and the influence of latitude, some host characteristics such as skin phototype and hair and eye color are also risk factors for melanoma. Polymorphisms in DNA repair genes could be good candidates for susceptibility genes, mainly in geographical regions exposed to high solar radiation. Evaluate the role of host characteristics and DNA repair polymorphism in melanoma risk in Brazil. We carried out a hospital-based case-control study in Brazil to evaluate the contribution of host factors and polymorphisms in DNA repair to melanoma risk. A total of 412 patients (202 with melanoma and 210 controls) were analyzed regarding host characteristics for melanoma risk as well as for 11 polymorphisms in DNA repair genes. We found an association of host characteristics with melanoma development, such as eye and hair color, fair skin, history of pigmented lesions removed, sunburns in childhood and adolescence, and also European ancestry. Regarding DNA repair gene polymorphisms, we found protection for the XPG 1104 His/His genotype (OR 0.32; 95% CI 0.13-0.75), and increased risk for three polymorphisms in the XPC gene (PAT+; IV-6A and 939Gln), which represent a haplotype for XPC. Melanoma risk was higher in individuals carrying the complete XPC haplotype than each individual polymorphism (OR 3.64; 95% CI 1.77-7.48). Our data indicate that the host factors European ancestry and XPC polymorphisms contributed to melanoma risk in a region exposed to high sun radiation. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  4. The nature and structure of psychological distress in people at high risk for melanoma: a factor analytic study.

    Science.gov (United States)

    Kasparian, Nadine A; Sansom-Daly, Ursula; McDonald, Roderick P; Meiser, Bettina; Butow, Phyllis N; Mann, Graham J

    2012-08-01

    This study examined the psychometric properties of two commonly used measures of psychological distress, the Hospital Anxiety and Depression Scale (HADS) and the Impact of Events Scale (IES) in a sample of individuals at high risk of developing melanoma due to strong family history. One hundred thirty-two individuals with a known family-specific CDKN2A mutation (74% response rate) completed a mailed, self-administered questionnaire including the HADS and the IES. Initial correlational analyses were followed by both exploratory and confirmatory factor analyses, according to a predetermined procedure for order of analyses. Exploratory factor analyses found that neither a two-, three- or four-factor solution satisfactorily accounted for all IES items in the present sample. By contrast, a unidimensional account of the data emerged to best account for all IES items, leaving no items unaccounted for. In contrast, the traditional two-factor (anxiety and depression) structure of the HADS appeared to fit the data well. The traditional, two-factor (intrusion and avoidance) structure of the IES was not borne out within this familial melanoma cohort. Assessment of a single dimension of emotional distress in response to melanoma risk may facilitate more meaningful explorations of psychological adjustment in this context. These findings also raise questions about whether a post-traumatic stress framework is indeed the most appropriate framework to capture the unique nature of melanoma- or cancer-related distress. Copyright © 2011 John Wiley & Sons, Ltd.

  5. Which melanoma patient carries a BRAF-mutation? A comparison of predictive models.

    Science.gov (United States)

    Eigentler, Thomas; Assi, Zeinab; Hassel, Jessica C; Heinzerling, Lucie; Starz, Hans; Berneburg, Mark; Bauer, Jürgen; Garbe, Claus

    2016-06-14

    In patients with advanced melanoma the detection of BRAF mutations is considered mandatory before the initiation of an expensive treatment with BRAF/MEK inhibitors. Sometimes it is difficult to perform such an analysis if archival tumor tissue is not available and fresh tissue has to be collected. 514 of 1170 patients (44%) carried a BRAF mutation. All models revealed age and histological subtype of melanoma as the two major predictive variables. Accuracy ranged from 0.65-0.71, being best in the random forest model. Sensitivity ranged 0.76-0.84, again best in the random forest model. Specificity was low in all models ranging 0.51-0.55. We collected the clinical data and mutational status of 1170 patients with advanced melanoma and established three different predictive models (binary logistic regression, classification and regression trees, and random forest) to forecast the BRAF status. Up to date statistical models are not able to predict BRAF mutations in an acceptable accuracy. The analysis of the mutational status by sequencing or immunohistochemistry must still be considered as standard of care.

  6. Early experiences of planning stereotactic radiosurgery using 3D printed models of eyes with uveal melanomas

    Directory of Open Access Journals (Sweden)

    Furdová A

    2017-01-01

    Full Text Available Alena Furdová,1 Miron Sramka,2 Andrej Thurzo,3 Adriana Furdová3 1Department of Ophthalmology, Faculty of Medicine, Comenius University, 2Department of Stereotactic Radiosurgery, St Elisabeth Cancer Inst and St Elisabeth University College of Health and Social Work, 3Department of Simulation and Virtual Medical Education, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic Objective: The objective of this study was to determine the use of 3D printed model of an eye with intraocular tumor for linear accelerator-based stereotactic radiosurgery.Methods: The software for segmentation (3D Slicer created virtual 3D model of eye globe with tumorous mass based on tissue density from computed tomography and magnetic resonance imaging data. A virtual model was then processed in the slicing software (Simplify3D® and printed on 3D printer using fused deposition modeling technology. The material that was used for printing was polylactic acid.Results: In 2015, stereotactic planning scheme was optimized with the help of 3D printed model of the patient’s eye with intraocular tumor. In the period 2001–2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma and 11 ciliary body melanoma were treated. The median tumor volume was 0.5 cm3 (0.2–1.6 cm3. The radiation dose was 35.0 Gy by 99% of dose volume histogram.Conclusion: The 3D printed model of eye with tumor was helpful in planning the process to achieve the optimal scheme for irradiation which requires high accuracy of defining the targeted tumor mass and critical structures. Keywords: 3D printing, uveal melanoma, stereotactic radiosurgery, linear accelerator, intraocular tumor, stereotactic planning scheme

  7. An Australian cohort of 210 patients with multiple invasive squamous cell carcinomas: risk factors and associated increased risk of melanoma and internal malignancies.

    Science.gov (United States)

    Banan, Parastoo; Marvi, Salman K; McMeniman, Erin; De'Ambrosis, Brian

    2016-02-01

    Patients with a history of non-melanoma skin cancer (NMSC) have a 50% risk of developing subsequent NMSC.(13) Currently there are limited data on the association between multiple squamous cell carcinomas (SCC) and the risk of other cancers, including melanomas. To assess the risk factors in a cohort of 210 Australians with a history of multiple invasive SCC, focusing on the association between multiple SCC and other cancers. Data were collected from patients of a private practice in south-east Queensland. A fair complexion and childhood sun exposure were found to be common in this cohort. Approximately half the patients who had their first SCC at or before the age of 30 years subsequently developed a melanoma. There was also an increased risk of internal cancer, prostate cancer being the commonest, followed by bowel and breast cancer. Patients with a history of multiple invasive SCC should be aware of their increased risk of future NMSC and of melanomas. The results of thisstudy suggest such patients and their care providers should also consider an appropriate screening for internal malignancies. © 2015 The Australasian College of Dermatologists.

  8. CASE REPORT: NODULAR MELANOMA

    Directory of Open Access Journals (Sweden)

    Tina Zupančič

    2015-05-01

    Full Text Available Nodular melanoma is a rare type of cutaneous melanoma with an increased risk of death. It often mimics benign cutaneous tumors and inflammatory lesions. It has pronounced vertical growth phase and greater thickness at the time of diagnosis which caries ominous prognostic value. Nodular melanoma quickly develops metastases which are often present before the disease is clinically recognised. Here, we report a case of nodular melanoma clinically mimicking seborrheic keratosis. Therapy and 36 months follow-up after primal excision are also presented.

  9. On the geometric modulation of skin lesion growth: a mathematical model for melanoma

    Directory of Open Access Journals (Sweden)

    Ana Isabel Mendes

    Full Text Available Abstract Introduction Early detection of suspicious skin lesions is critical to prevent skin malignancies, particularly the melanoma, which is the most dangerous form of human skin cancer. In the last decade, image processing techniques have been an increasingly important tool for early detection and mathematical models play a relevant role in mapping the progression of lesions. Methods This work presents an algorithm to describe the evolution of the border of the skin lesion based on two main measurable markers: the symmetry and the geometric growth path of the lesion. The proposed methodology involves two dermoscopic images of the same melanocytic lesion obtained at different moments in time. By applying a mathematical model based on planar linear transformations, measurable parameters related to symmetry and growth are extracted. Results With this information one may compare the actual evolution in the lesion with the outcomes from the geometric model. First, this method was tested on predefined images whose growth was controlled and the symmetry known which were used for validation. Then the methodology was tested in real dermoscopic melanoma images in which the parameters of the mathematical model revealed symmetry and growth rates consistent with a typical melanoma behavior. Conclusions The method developed proved to show very accurate information about the target growth markers (variation on the growth along the border, the deformation and the symmetry of the lesion trough the time. All the results, validated by the expected phantom outputs, were similar to the ones on the real images.

  10. Uveal Melanoma Risk Factors: A Systematic Review of Meta-Analyses.

    Science.gov (United States)

    Nayman, Taylor; Bostan, Cristina; Logan, Patrick; Burnier, Miguel N

    2017-08-01

    There is currently no clinical risk-assessment tool allowing identification of patients at risk for developing uveal melanoma (UM) who might benefit from regular screening. As a first step toward the elaboration of such a tool, we systematically reviewed UM risk factors already established by meta-analysis. Two reviewers independently screened Pubmed, Medline, Embase, and Web of Science from their respective inception dates until July 2016 using a combination of keywords and MeSH terms. Eligible studies were meta-analyses or systematic reviews providing pooled odds ratios (ORs) of risk factors for UM development or sufficient information to calculate them. Methodological quality was evaluated using the Assessment of Multiple Systematic Reviews tool. Four meta-analyses with a mean methodological quality score of 65.9% (min: 54.5%; max: 72.7%) were included. The following significant risk factors were identified: atypical cutaneous nevi (OR 2.82, 95% CI 1.10-7.26), welding (OR 2.05, 95% CI 1.20-3.51), occupational cooking (OR 1.81, 95% CI 1.33-2.46), fair skin color (OR 1.80, 95% CI 1.31-2.47), light eye color (OR 1.75, 95% CI 1.31-2.34), common cutaneous nevi (OR 1.74, 95% CI 1.27-2.39), propensity to sunburn (OR 1.64, 95% CI 1.29-2.09), iris nevi (OR 1.53, 95% CI 1.03-2.27), and cutaneous freckles (OR 1.27, 95% CI 1.09-1.49). Non-significant factors included outdoor leisure activity, occupational sunlight exposure, latitude of birth, and hair color. Moderate quality of evidence determined nine significant risk factors for developing UM. Knowledge of these variables will assist researchers in the elaboration of a formal risk-assessment tool allowing clinicians to estimate susceptibility to the disease and necessity of regular screening.

  11. The risk of developing a second primary cancer in melanoma patients: a comprehensive review of the literature and meta-analysis.

    Science.gov (United States)

    Caini, Saverio; Boniol, Mathieu; Botteri, Edoardo; Tosti, Giulio; Bazolli, Barbara; Russell-Edu, William; Giusti, Francesco; Testori, Alessandro; Gandini, Sara

    2014-07-01

    The number of cutaneous melanoma survivors has been increasing for years due to improvements in early diagnosis and subsequent prolonged survival. These patients are at increased risk of developing a second melanoma and a second primary malignancy (SPM) at other sites as well. We performed a review of scientific literature and meta-analysis to evaluate the risk of developing a SPM (other than melanoma) among melanoma patients. Twenty-three independent papers and over 350,000 melanoma patients were included. Risk of cancer among melanoma survivors was increased overall (1.57, 95% CI 1.29-1.90) and at several sites: bone (2.09, 95% CI 1.08-4.05), non-melanoma skin cancer (4.01, 95% CI 1.81-8.87), soft tissue (6.80, 95% CI 1.29-35.98), colon-rectum (1.12, 95% CI 1.00-1.25), female breast (1.14, 95% CI 1.07-1.22), kidney (1.34, 95% CI 1.23-1.45), prostate (1.25, 95% CI 1.13-1.37) and non-Hodgkin lymphoma (1.37, 95% CI 1.22-1.54). The overall risk of SPM showed a tendency to decrease as the time from melanoma diagnosis lengthened. Most of our findings may be explained by the tendency of some exposures, which are risk factors for different tumors, to occur simultaneously in the same individuals. These results suggest primary and secondary cancer prevention counselling for melanoma survivors. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  12. The risk of enucleation after proton beam irradiation of uveal melanoma

    International Nuclear Information System (INIS)

    Egan, K.M.; Gragoudas, E.S.; Seddon, J.M.; Glynn, R.J.; Munzenreider, J.E.; Goitein, M.; Verhey, L.; Urie, M.; Koehler, A.

    1989-01-01

    Enucleation after proton beam irradiation of uveal melanomas occurred in 64 (6.4%) of 994 eyes with a median follow-up time of 2.7 years. The median time between irradiation and enucleation in the 64 enucleated eyes was 13 months. The probability of retaining the eye was 95 and 90%, 2 and 5 years postirradiation, respectively. Three percent of eyes were enucleated during posttreatment year 1, and the yearly rate was 1% by the fourth year. No patient had enucleation later than 5 1/2 years posttreatment. The complication most likely to result in enucleation was neovascular glaucoma although this was frequently managed without enucleation. Other common reasons for enucleation were documented or suspected tumor growth and complete retinal detachment with associated loss of vision. The leading risk factors for enucleation were anterior tumor margin involving the ciliary body, tumor height greater than 8 mm, and proximity of the tumor to the fovea. Based on the presence or absence of these factors, 5-year eye retention rates were 99, 92, and 76% for low-, moderate-, and high-risk groups, respectively. Thus, the probability of eye retention after proton beam irradiation is high even among those at greatest risk of enucleation

  13. Lymph node dissection in patients with malignant melanoma is associated with high risk of morbidity

    DEFF Research Database (Denmark)

    Ul-Mulk, Jamshaid; Hölmich, Lisbet Rosenkrantz

    2012-01-01

    Malignant melanoma is one of the most rapidly increasing cancer types globally, and it is by far the most serious skin cancer. Patients with a melanoma ≥ 1 mm in Breslow thickness are offered sentinel node (SN) biopsy and subsequent radical lymph node dissection if the biopsy is positive...

  14. Malignant melanoma risk after exposure to fertility drugs: results from a large Danish cohort study

    DEFF Research Database (Denmark)

    Hannibal, C.G.; Jensen, A.; Sharif, H.

    2008-01-01

    . A detailed data collection including information about type and amount of treatment was conducted. Using case-cohort techniques, we calculated rate ratios (RRs) of malignant melanoma associated with different fertility drugs after adjustment for parity status. RESULTS: 112 malignant melanomas were identified...

  15. Non-melanoma skin cancer and risk of Alzheimer's disease and all-cause dementia.

    Directory of Open Access Journals (Sweden)

    Sigrun A J Schmidt

    Full Text Available Cancer patients may be at decreased risk of Alzheimer's disease. This hypothesis is best developed for non-melanoma skin cancer (NMSC, but supportive epidemiological data are sparse. We therefore conducted a nationwide cohort study of the association between NMSC and Alzheimer's disease (main outcome and all-cause dementia. Using Danish medical databases, we identified adults diagnosed with NMSC between 1 January 1980 and 30 November 2013 (n = 216,221 and a comparison cohort of five individuals matched to each NMSC patient by sex and birth year (n = 1,081,097. We followed individuals from the time of diagnosis, or corresponding date for matched comparators, until a dementia diagnosis, death, emigration, or 30 November 2013, whichever came first. We used stratified Cox regression adjusted for comorbidities to compute hazard ratios (HRs associating NMSC with dementia. We computed cumulative risks of dementia, treating death as a competing risk. NMSC was associated with a HR of 0.95 (95% confidence interval [CI]: 0.92-0.98 for Alzheimer's disease and 0.92 (95% CI: 0.90-0.94 for all-cause dementia. HRs were similar for basal cell and squamous cell carcinoma, the two most common forms of NMSC. Estimates of risk reduction were more pronounced in the beginning of follow-up, reaching null after 5-10 years. At the end of follow-up (34 years, cumulative risk of Alzheimer's disease was 4.6% (95% CI: 4.4%-4.8% among patients with NMSC vs. 4.7% (95% CI: 4.6%-4.9% in the comparison cohort. In conclusion, NMSC was associated with 2%-10% reductions in relative risks of Alzheimer's disease and all-cause dementia. However, these small inverse associations may have been caused by ascertainment bias due to decreased awareness of NMSC tumors in persons with undiagnosed early cognitive impairment or by confounding from a more neuroprotective lifestyle among persons with NMSC.

  16. Clinical characteristics and management of melanoma families

    NARCIS (Netherlands)

    Rhee, Jasper Immanuel van der

    2013-01-01

    Being a member of a melanoma family is a major risk factor for cutaneous malignant melanoma. In this thesis clinical characteristics and management of melanoma families are discussed. In the first part of the thesis clinical and histological characteristics of melanoma (patients) from families with

  17. Tumor-immune interaction, surgical treatment, and cancer recurrence in a mathematical model of melanoma.

    Directory of Open Access Journals (Sweden)

    Steffen Eikenberry

    2009-04-01

    Full Text Available Malignant melanoma is a cancer of the skin arising in the melanocytes. We present a mathematical model of melanoma invasion into healthy tissue with an immune response. We use this model as a framework with which to investigate primary tumor invasion and treatment by surgical excision. We observe that the presence of immune cells can destroy tumors, hold them to minimal expansion, or, through the production of angiogenic factors, induce tumorigenic expansion. We also find that the tumor-immune system dynamic is critically important in determining the likelihood and extent of tumor regrowth following resection. We find that small metastatic lesions distal to the primary tumor mass can be held to a minimal size via the immune interaction with the larger primary tumor. Numerical experiments further suggest that metastatic disease is optimally suppressed by immune activation when the primary tumor is moderately, rather than minimally, metastatic. Furthermore, satellite lesions can become aggressively tumorigenic upon removal of the primary tumor and its associated immune tissue. This can lead to recurrence where total cancer mass increases more quickly than in primary tumor invasion, representing a clinically more dangerous disease state. These results are in line with clinical case studies involving resection of a primary melanoma followed by recurrence in local metastases.

  18. Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma.

    Science.gov (United States)

    Duffy, David L; Zhao, Zhen Z; Sturm, Richard A; Hayward, Nicholas K; Martin, Nicholas G; Montgomery, Grant W

    2010-02-01

    We have previously described the role of red hair (melanocortin-1 receptor, MC1R) and blue eye (oculocutaneous albinism type II, OCA2) gene polymorphisms in modulating the risk of cutaneous malignant melanoma (CMM) in a highly sun-exposed population of European descent. A number of recent studies, including genome-wide association studies, have identified numerous polymorphisms controlling human hair, eye, and skin color. In this paper, we test a selected set of polymorphisms in pigmentation loci (ASIP (Agouti signalling protein, nonagouti homolog (mouse) gene), TYR (tyrosinase), TYRP1 (tyrosinase-related protein 1), MC1R, OCA2, IRF4 (interferon regulatory factor 4), SLC24A4 (solute carrier family 24, member 4), and SLC45A2 (solute carrier family 45, member 2)) for association with CMM risk in a large Australian population-based case-control study. Variants in IRF4 and SLC24A4, despite being strongly associated with pigmentation in our sample, did not modify CMM risk, but the other six did. Three single nucleotide polymorphisms (rs28777, rs35391, and rs16891982) in the MATP gene (SLC45A2) exhibited the strongest crude association with risk, but this was attenuated to approximately the same effect size as that of a MC1R red hair color allele by controlling for ancestry of cases and controls. We also detected significant epistatic interactions between SLC45A2 and OCA2 alleles, and MC1R and ASIP alleles. Overall, these measured variants account for 12% of the familial risk of CMM in our population.

  19. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Damsky, William E. Jr. [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States); Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont (United States); Rosenbaum, Lara E.; Bosenberg, Marcus, E-mail: Marcus.Bosenberg@yale.edu [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States)

    2010-12-30

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  20. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    International Nuclear Information System (INIS)

    Ungerer, Christopher; Doberstein, Kai; Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning; Boehm, Beate; Pfeilschifter, Josef; Dummer, Reinhard; Mihic-Probst, Daniela; Gutwein, Paul

    2010-01-01

    Research highlights: → Strong ADAM15 expression is found in normal melanocytes. → ADAM15 expression is significantly downregulated in patients with melanoma metastasis. → TGF-β can downregulate ADAM15 expression in melanoma cells. → Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. → Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-γ and TGF-β downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  1. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ungerer, Christopher; Doberstein, Kai [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning [Department of Dermatology, Clinic of the Goethe-University, Theodor-Stern-Kai, Frankfurt (Germany); Boehm, Beate [Division of Rheumatology, Goethe University, Frankfurt am Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Dummer, Reinhard [Department of Pathology, Institute of Surgical Pathology, University Hospital, Zurich (Switzerland); Mihic-Probst, Daniela [Department of Dermatology, University Hospital Zurich (Switzerland); Gutwein, Paul, E-mail: p.gutwein@med.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany)

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  2. [Skin cancer risk factors in childhood: findings of a survey conducted within Italian areas with a different incidence of melanoma].

    Science.gov (United States)

    Ramazzotti, Valerio; Cercato, Maria Cecilia; Terrenato, Irene; Santi, Pieluigi; Falcini, Fabio; Assennato, Giorgio; Gattei, Elena; Catricalà, Caterina; Natali, Pier Giorgio

    2011-01-01

    to evaluate the association between phenotype and sun sensitivity factors, sun protection behavior, ethnicity and the area of residence in school-aged children. a cross-sectional study in the framework of a survey of children using a self-administered questionnaire to be filled in by parents. 56390 children attending primary schools located in the Italian provinces of Brindisi, Rome, Forlì and Genova, in the period between 1998-2002. Odds Ratios (ORs) and their relative 95% Confidence Intervals (95% CI) are to be computed through univariate and multivariate logistic regression models. "FOTO positive" phenotype, a proxy variable of the fair phenotype, was directly and significantly associated with the tendency to sunburn (OR 4.75; 95% CI 4.54-4.96), the use of sunscreens (OR 1.79; 95% CI 1.63-1.97), the number of grandparents born in the northern areas (OR 1.63; 95% CI 1.45-1.83, for four northern grandparents versus none), the presence of freckles on the face (OR 1.62; 95% CI 1.53-1.72) and of naevi on the left forearm (OR 1.20; 95% CI 1.15-1.26). A positive association was also found for the residence in the northern areas using the area of Brindisi as the reference category, (Rome: OR 1.02; 95% CI 0.95-1.10; Forlì: OR 1.05; 95% CI 0.96-1.15; Genova: OR 1.16; 95% CI 1.08-1.26); the ORs increase with latitude, as does the incidence rate of melanoma in Italy. An inverse association was observed with the male sex (OR 0.92; 95% CI 0.88-0.96), the increase of school-class level (OR 0.65; 95% CI 0.60-0.69, for the highest versus the lowest school-class level) and the ability to tan (OR 0.40; 95% CI 0.36-0.43). these findings confirmed that the fairness phenotype is associated with other skin cancer risk factors in children and pointed out that the high-risk phenotype has a geographical distribution consistent with the pattern of melanoma incidence in the Italian areas covered by the study.

  3. Non-melanoma skin cancer: occupational risk from UV light and arsenic exposure.

    Science.gov (United States)

    Surdu, Simona

    2014-01-01

    Non-melanoma skin cancer (NMSC) has a significant impact on public health and health care costs as a result of high morbidity and disfigurement due to the destruction of surrounding tissues. Although the mortality rates of these tumors are low, the high incidence rates determine a considerable number of deaths. NMSC is the most common type of skin cancer, representing about 1/3 of all malignancies diagnosed worldwide each year. The most common NMSC are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Studies on humans and experimental animals indicate that ultraviolet (UV) light and arsenic play important roles in the development of these skin malignancies. Several epidemiological studies have investigated the risk of developing NMSC and the potential link between exposure to sunlight and arsenic in the agricultural and industrial occupational settings. To date, the published literature suggests that there is no apparent skin cancer risk as regards workplace exposure to artificial UV light or arsenic. Concerning UV light from sun exposure at the workplace, most published studies indicated an elevated risk for SCC, but are less conclusive for BCC. Many of these studies are limited by the methodology used in the evaluation of occupational exposure and the lack of adjustment for major confounders. Therefore, further epidemiological studies are required to focus on exposure assessment at the individual level as well as potential interactions with other occupational and non-occupational exposures and individual susceptibility. In doing so, we can better quantify the true risk of skin cancer in exposed workers and inform effective public health prevention programs.

  4. Malignant melanoma-Risk factors and the CDKN2A mutation in relation to phenotypes and other cancers.

    OpenAIRE

    Nielsen, Kari

    2009-01-01

    Background: Cutaneous malignant melanoma (CMM) is an increasingly common cancer in fair-skinned people. The purpose of this thesis was to study high-risk patients with multiple tumours including a CMM, high-risk families with the unique Swedish germline mutation in CDKN2A(113insArg), as well as study risk factors for CMM in women. Methods: Tumours associated with CMM, in individuals/probands with four or more primary tumours including at least one CMM were genotyped. The probands were fur...

  5. Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression

    Science.gov (United States)

    Rose, Amy E.; Poliseno, Laura; Wang, Jinhua; Clark, Michael; Pearlman, Alexander; Wang, Guimin; Vega y Saenz de Miera, Eleazar C.; Medicherla, Ratna; Christos, Paul J.; Shapiro, Richard; Pavlick, Anna; Darvishian, Farbod; Zavadil, Jiri; Polsky, David; Hernando, Eva; Ostrer, Harry; Osman, Iman

    2011-01-01

    Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathological and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (SNP 6.0, Affymetrix) with gene expression array (U133A 2.0, Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N=114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (Pmelanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM. PMID:21343389

  6. Association of MC1R variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study.

    Science.gov (United States)

    Demenais, F; Mohamdi, H; Chaudru, V; Goldstein, A M; Newton Bishop, J A; Bishop, D T; Kanetsky, P A; Hayward, N K; Gillanders, E; Elder, D E; Avril, M F; Azizi, E; van Belle, P; Bergman, W; Bianchi-Scarrà, G; Bressac-de Paillerets, B; Calista, D; Carrera, C; Hansson, J; Harland, M; Hogg, D; Höiom, V; Holland, E A; Ingvar, C; Landi, M T; Lang, J M; Mackie, R M; Mann, G J; Ming, M E; Njauw, C J; Olsson, H; Palmer, J; Pastorino, L; Puig, S; Randerson-Moor, J; Stark, M; Tsao, H; Tucker, M A; van der Velden, P; Yang, X R; Gruis, N

    2010-10-20

    Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited. We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided. Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10(-6) ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; P(trend) = 1.86 × 10(-8)). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10(-6) ≤ P

  7. High accuracy of family history of melanoma in Danish melanoma cases

    DEFF Research Database (Denmark)

    Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

    2015-01-01

    The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor...... but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma...... probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree...

  8. TERT promoter mutations in melanoma survival.

    Science.gov (United States)

    Nagore, Eduardo; Heidenreich, Barbara; Rachakonda, Sívaramakrishna; Garcia-Casado, Zaida; Requena, Celia; Soriano, Virtudes; Frank, Christoph; Traves, Victor; Quecedo, Esther; Sanjuan-Gimenez, Josefa; Hemminki, Kari; Landi, Maria Teresa; Kumar, Rajiv

    2016-07-01

    Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at-risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression-free and melanoma-specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease-free and melanoma-specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease-free survival was 2.3 (95% CI 1.2-4.4) and for melanoma-specific survival 5.8 (95% CI 1.9-18.3). The effect of the mutations on melanoma-specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4-15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1-0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter. © 2016 UICC.

  9. Coffee, tea and melanoma risk : findings from the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Caini, Saverio; Masala, Giovanna; Saieva, Calogero; Kvaskoff, Marina; Savoye, Isabelle; Sacerdote, Carlotta; Hemmingsson, Oskar; Hammer Bech, Bodil; Overvad, Kim; Tjønneland, Anne; Petersen, Kristina E N; Mancini, Francesca Romana; Boutron-Ruault, Marie Christine; Cervenka, Iris; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; Floegel, Anna; Trichopoulou, Antonia; Valanou, Elisavet; Kritikou, Maria; Tagliabue, Giovanna; Panico, Salvatore; Tumino, Rosario; Bueno-de-Mesquita, H. Bas; Peeters, Petra H.; Veierød, Marit B.; Ghiasvand, Reza; Lukic, Marko; Quirós, José Ramón; Chirlaque, Maria Dolores; Ardanaz, Eva; Salamanca Fernández, Elena; Larrañaga, Nerea; Zamora-Ros, Raul; Maria Nilsson, Lena; Ljuslinder, Ingrid; Jirström, Karin; Sonestedt, Emily; Key, Timothy J.; Wareham, Nick; Khaw, Kay Tee; Gunter, Marc; Huybrechts, Inge; Murphy, Neil; Tsilidis, Konstantinos K.; Weiderpass, Elisabete; Palli, Domenico

    2017-01-01

    In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption

  10. Factores de riesgo para melanoma cutáneo: Estudio de casos y controles en Córdoba, Argentina Risk factors for cutaneous melanoma: case-control study in Cordoba, Argentina

    Directory of Open Access Journals (Sweden)

    Alejandro Ruiz Lascano

    2004-12-01

    Full Text Available En los últimos años se han realizado considerables esfuerzos para identificar factores de riesgo asociados al incremento en la incidencia de melanoma maligno en la población blanca mundial. En Argentina los datos concernientes a factores de riesgo para melanoma maligno son limitados. Realizamos en el Hospital Privado de Córdoba un estudio de casos-controles con el objetivo de determinar factores de riesgo para melanoma maligno. El grupo de estudio fue de 65 pacientes con melanoma maligno y 195 controles pareados por sexo y edad. Los siguientes factores de riesgo fueron significativos en el análisis estadístico univariado: abuelos nacidos en Italia o España y en otros países europeos, color de pelo castaño y claro, color de piel claro, color de ojos marrón y claros, efélides, presencia de nevos melanocíticos, quemaduras solares graves antes de los 18 años de edad, exposición solar tanto laboral como recreativa y antecedente familiar de melanoma maligno, de éstos se mantienen como factores de riesgo independientes en el análisis multivariado abuelos nacidos en países europeos (OR 2.27, IC95% 1.08 a 3.46, piel clara (OR 4.99, IC95% 2.72 a 7.28 quemadura solar grave en más de 3 episodios antes de los 18 años (OR 6.47, IC95% 5.29 a 7.65 y antecedentes familiares de melanoma (OR 1525, IC95% 1467 a 1584. La mayoría de los datos que obtuvimos guardan semejanza con los descriptos en otras poblaciones.Over the past years, considerable effort has been directed toward the identification of risk factors associated with the increasing incidence of cutaneous melanoma in white populations worldwide. Limited data are available from Argentine populations concerning risk factors for malignant melanoma. A case-control study was performed in Cordoba to estimate the risk factors for cutaneous malignant melanoma. The study group comprised 65 patients and 195 controls, matched by age and sex. The following risk factors were significant in the

  11. Melanoma cells undergo aggressive coalescence in a 3D Matrigel model that is repressed by anti-CD44.

    Directory of Open Access Journals (Sweden)

    Deborah Wessels

    Full Text Available Using unique computer-assisted 3D reconstruction software, it was previously demonstrated that tumorigenic cell lines derived from breast tumors, when seeded in a 3D Matrigel model, grew as clonal aggregates which, after approximately 100 hours, underwent coalescence mediated by specialized cells, eventually forming a highly structured large spheroid. Non-tumorigenic cells did not undergo coalescence. Because histological sections of melanomas forming in patients suggest that melanoma cells migrate and coalesce to form tumors, we tested whether they also underwent coalescence in a 3D Matrigel model. Melanoma cells exiting fragments of three independent melanomas or from secondary cultures derived from them, and cells from the melanoma line HTB-66, all underwent coalescence mediated by specialized cells in the 3D model. Normal melanocytes did not. However, coalescence of melanoma cells differed from that of breast-derived tumorigenic cell lines in that they 1 coalesced immediately, 2 underwent coalescence as individual cells as well as aggregates, 3 underwent coalescence far faster and 4 ultimately formed long, flat, fenestrated aggregates that were extremely dynamic. A screen of 51 purified monoclonal antibodies (mAbs targeting cell surface-associated molecules revealed that two mAbs, anti-beta 1 integrin/(CD29 and anti-CD44, blocked melanoma cell coalescence. They also blocked coalescence of tumorigenic cells derived from a breast tumor. These results add weight to the commonality of coalescence as a characteristic of tumorigenic cells, as well as the usefulness of the 3D Matrigel model and software for both investigating the mechanisms regulating tumorigenesis and screening for potential anti-tumorigenesis mAbs.

  12. Melanoma during pregnancy

    DEFF Research Database (Denmark)

    de Haan, Jorine; Lok, Christianne A; de Groot, Christianne J M

    2017-01-01

    The management of melanoma during pregnancy is challenging as maternal benefits and fetal risks need to be balanced. Here, we present an overview of the incidence, the demographic and clinical characteristics and the treatment modalities used. After analysis of obstetric, fetal and maternal outcome......, recommendations for clinical practice are provided. From the 'International Network on Cancer, Infertility and Pregnancy' database, pregnant patients with melanoma were identified and analysed. Sixty pregnancies were eligible for analysis. Fifty percent of the patients presented with advanced melanoma during...... pregnancy (14 stage III and 16 stage IV), and 27% were diagnosed with recurrent melanoma. Surgery was the main therapeutic strategy during pregnancy. Only four patients with advanced melanoma were treated during pregnancy with systemic therapy (n=1) or radiotherapy (n=3). Premature delivery was observed...

  13. High plasma 25-hydroxyvitamin D and high risk of non-melanoma skin cancer: a Mendelian randomisation study of 97849 individuals.

    Science.gov (United States)

    Winsløw, U C; Nordestgaard, B G; Afzal, S

    2017-11-16

    High plasma 25-hydroxyvitamin D (25 (OH)D) concentration has been associated observationally with high risk of non-melanoma skin cancer, while many studies suggest that vitamin D could have a protective effect on cancer. The true association between vitamin D and risk of skin cancer remains unclear. In this Mendelian randomisation study we tested the hypothesis that genetically high plasma 25(OH)D protects against non-melanoma skin cancer. We included 103084 individuals from the Danish general population, of whom 35 298 had plasma 25(OH)D measured and 97849 were genotyped for four genetic variants near the DHCR7 and CYP2R1 genes associated with 25(OH)D concentrations. We tested the association between plasma 25(OH)D levels and non-melanoma skin cancer observationally, and between genetically determined 25(OH)D levels and non-melanoma skin cancer through an instrumental variable approach. Multivariable adjusted hazard ratios of non-melanoma skin cancer were 3.27 (95%CI: 2.22;4.84) for plasma 25(OH)D≥50 nmol/L versus melanoma skin cancer, with a corresponding observational multivariable adjusted odds ratio of 1.13 (1.10-1.17). Genetically determined high 25(OH)D did not appear to protect against non-melanoma skin cancer, while high plasma 25(OH)D concentrations were associated with high risk of non-melanoma skin cancer in observational analysis. Thus, the observational association likely reflects confounding by sun exposure rather than causality. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  14. Cellular heterogeneity in vertical growth phase melanoma.

    Science.gov (United States)

    Laga, Alvaro C; Murphy, George F

    2010-12-01

    Melanoma growing as a tumorigenic nodule is one of the most virulent neoplasms to which the flesh is heir. At a considerably small tumor size, it incurs significant risk for widespread metastatic dissemination. There are no effective means of surgical intervention, chemical therapy, or immunologic therapy for advanced and metastatic melanoma. To review the literature and highlight recent cardinal advances in the understanding of melanoma vertical growth, with specific emphasis on how its recognition and characterization may be applied to diagnostic practice and development of novel investigative approaches. Literature review, archival material, personal experience, and research collaborators. The study of tumorigenic melanoma, both in primary lesions and in metastases, is the key to the eventual eradication of this highly virulent neoplasm that may disseminate widely when only occupying the volume of a grain of rice. Morphology often provides the first insight into structure and function. A growing database using meticulous and inclusive criteria to define tumor stem cells in the context of clinically relevant models now indicates that the key to melanoma heterogeneity may reside in a small subpopulation with the ability to self-renew and form tumors despite most cells present being significantly less virulent. Hopefully, from these insights into melanoma tumor progression from radial growth phase to heterogeneous and tumorigenic vertical growth phase will come additional answers to how smart therapies may be developed that specifically target those vertical growth phase cells that most pertain to patient survival.

  15. Clinical Predictors of Regression of Choroidal Melanomas after Brachytherapy: A Growth Curve Model.

    Science.gov (United States)

    Rashid, Mamunur; Heikkonen, Jorma; Singh, Arun D; Kivelä, Tero T

    2018-02-27

    To build multivariate models to assess correctly and efficiently the contribution of tumor characteristics on the rate of regression of choroidal melanomas after brachytherapy in a way that adjusts for confounding and takes into account variation in tumor regression patterns. Modeling of longitudinal observational data. Ultrasound images from 330 of 388 consecutive choroidal melanomas (87%) irradiated from 2000 through 2008 at the Helsinki University Hospital, Helsinki, Finland, a national referral center. Images were obtained with a 10-MHz B-scan during 3 years of follow-up. Change in tumor thickness and cross-sectional area were modeled using a polynomial growth-curve function in a nested mixed linear regression model considering regression pattern and tumor levels. Initial tumor dimensions, tumor-node-metastasis (TNM) stage, shape, ciliary body involvement, pigmentation, isotope, plaque size, detached muscles, and radiation parameters were considered as covariates. Covariates that independently predict tumor regression. Initial tumor thickness, largest basal diameter, ciliary body involvement, TNM stage, tumor shape group, break in Bruch's membrane, having muscles detached, and radiation dose to tumor base predicted faster regression, whether considering all tumors or those that regressed in a pattern compatible with exponential decay. Dark brown pigmentation was associated with slower regression. In multivariate modeling, initial tumor thickness remained the predominant and robust predictor of tumor regression (P future analyses efficiently without matching. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  16. The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish model

    OpenAIRE

    Yen, J.; White, R.M.; Wedge, D.C.; Van Loo, P.; De Ridder, J.; Capper, A.; Richardson, J.; Jones, D.; Raine, K.; Watson, I.R.

    2013-01-01

    Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process.

  17. The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish model

    NARCIS (Netherlands)

    Yen, J.; White, R.M.; Wedge, D.C.; Van Loo, P.; De Ridder, J.; Capper, A.; Richardson, J.; Jones, D.; Raine, K.; Watson, I.R.

    2013-01-01

    Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and

  18. Canine oral melanoma.

    Science.gov (United States)

    Bergman, Philip J

    2007-05-01

    Melanoma is the most common oral malignancy in the dog. Oral and/or mucosal melanoma has been routinely considered an extremely malignant tumor with a high degree of local invasiveness and high metastatic propensity. Primary tumor size has been found to be extremely prognostic. The World Health Organization staging scheme for dogs with oral melanoma is based on size, with stage I = or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis. Median survival times for dogs with oral melanoma treated with surgery are approximately 17 to 18, 5 to 6, and 3 months with stage I, II, and III disease, respectively. Significant negative prognostic factors include stage, size, evidence of metastasis, and a variety of histologic criteria. Standardized treatments such as surgery, coarse-fractionation radiation therapy, and chemotherapy have afforded minimal to modest stage-dependent clinical benefits and death is usually due to systemic metastasis. Numerous immunotherapeutic strategies have been employed to date with limited clinical efficacy; however, the use of xenogeneic DNA vaccines may represent a leap forward in clinical efficacy. Oral melanoma is a spontaneous syngeneic cancer occurring in outbred, immunocompetent dogs and appears to be a more clinically faithful therapeutic model for human melanoma; further use of canine melanoma as a therapeutic model for human melanoma is strongly encouraged. In addition, the development of an expanded but clinically relevant staging system incorporating the aforementioned prognostic factors is also strongly encouraged.

  19. A Model of Dendritic Cell Therapy for Melanoma

    Directory of Open Access Journals (Sweden)

    Ami eRadunskaya

    2013-03-01

    Full Text Available Dendritic cells are a promising immunotherapy tool for boosting an individual's antigen specific immune response to cancer. We develop a mathematical model using differential and delay-differential equations to describe the interactions between dendritic cells, effector-immune cells and tumor cells. We account for the trafficking of immune cells between lymph, blood, and tumor compartments. Our model reflects experimental results both for dendritic-cell trafficking and for immune suppression of tumor growth in mice. In addition, in silico experiments suggest more effective immunotherapy treatment protocols can be achieved by modifying dose location and schedule. A sensitivity analysis of the model reveals which patient-specific parameters have the greatest impact on treatment efficacy.

  20. Inhibition of proliferation and invasion in 2D and 3D models by 2-methoxyestradiol in human melanoma cells.

    Science.gov (United States)

    Massaro, R R; Faião-Flores, F; Rebecca, V W; Sandri, S; Alves-Fernandes, D K; Pennacchi, P C; Smalley, K S M; Maria-Engler, S S

    2017-05-01

    Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and Cyclin B1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assay, including cell lines with acquired resistance to BRAF and BRAF+MEK inhibitors. We further show that 2ME is effective against melanoma with different BRAF and NRAS mutational status. Moreover, 2ME induced the retraction of cytoplasmic projections in a 3D spheroid model and significantly decreased cell proliferation in a 3D skin reconstruct model. Together our studies bring new insights into the mechanism of action of 2ME allowing melanoma targeted therapy to be further refined. Continued progress in this area is expected to lead to improved anti-cancer treatments and the development of new and more effective clinical analogues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Protocol for the melatools skin self-monitoring trial: a phase II randomised controlled trial of an intervention for primary care patients at higher risk of melanoma.

    Science.gov (United States)

    Mills, Katie; Emery, Jon; Lantaff, Rebecca; Radford, Michael; Pannebakker, Merel; Hall, Per; Burrows, Nigel; Williams, Kate; Saunders, Catherine L; Murchie, Peter; Walter, Fiona M

    2017-11-28

    Melanoma is the fifth most common cancer in the UK. Incidence rates have quadrupled over the last 30 years and continue to rise, especially among younger people. As routine screening of the general population is not currently recommended in the UK, a focus on secondary prevention through early detection and prompt treatment in individuals at increased risk of melanoma could make an important contribution to improve melanoma outcomes. This paper describes the protocol for a phase II, multisite, randomised controlled trial, in the primary care setting, for patients at increased risk of melanoma. A skin self-monitoring (SSM) smartphone 'App' was used to improve symptom appraisal and encourage help seeking in primary care, thereby promoting early presentation with skin changes suspicious of melanoma. We aim to recruit 200 participants from general practice waiting rooms in the East of England. Eligible patients are those identified at higher melanoma risk (using a real-time risk assessment tool), without a personal history of melanoma, aged 18 to 75 years. Participants will be invited to a primary care nurse consultation, and randomised to the intervention group (standard written advice on skin cancer detection and sun protection, loading of an SSM 'App' onto the participant's smartphone and instructions on use including self-monitoring reminders) or control group (standard written advice alone). The primary outcomes are consultation rates for changes to a pigmented skin lesion, and the patient interval (time from first noticing a skin change to consultation). Secondary outcomes include patient sun protection behaviours, psychosocial outcomes, and measures of trial feasibility and acceptability. NHS ethical approval has been obtained from Cambridgeshire and Hertfordshire research ethics committee (REC reference 16/EE/0248). The findings from the MelaTools SSM Trial will be disseminated widely through peer-reviewed publications and scientific conferences. ISCTRN16061621

  2. New Trends in Dermoscopy to Minimize the Risk of Missing Melanoma

    Directory of Open Access Journals (Sweden)

    Aimilios Lallas

    2012-01-01

    Full Text Available During the last decades, induction of dermoscopy in the clinical setting resulted in significant modifications in the management of melanocytic lesions. Indeed, the dermatoscope reveals a fascinating world of morphologic structures invisible to the naked eye, adding valuable information to a clinician evaluating a mole. However, since the technique counts only a couple of decades, new research data are continuously gathering and modify the “optimal” management of melanocytic lesions. In the present paper, we summarize the latest trends in dermoscopy concerning early melanoma diagnosis, management of nodular lesions, diagnosis of mucosal melanoma, and digital followup.

  3. New Trends in Dermoscopy to Minimize the Risk of Missing Melanoma

    International Nuclear Information System (INIS)

    Lallas, A.; Apalla, Z.; Chaidemenos, G.

    2012-01-01

    During the last decades, induction of dermoscopy in the clinical setting resulted in significant modifications in the management of melanocytic lesions. Indeed, the dermatoscope reveals a fascinating world of morphologic structures invisible to the naked eye, adding valuable information to a clinician evaluating a mole. However, since the technique counts only a couple of decades, new research data are continuously gathering and modify the o ptimal m anagement of melanocytic lesions. In the present paper, we summarize the latest trends in dermoscopy concerning early melanoma diagnosis, management of nodular lesions, diagnosis of mucosal melanoma, and digital followup

  4. Biodistribution of modular nanotransporter carrying Auger electron emitter and targeted at melanoma cells in murine tumor model

    Science.gov (United States)

    Vorontsova, M. S.; Morozova, N. B.; Karmakova, T. A.; Rosenkranz, A. A.; Slastnikova, T. A.; Petriev, V. M.; Smoryzanova, O. A.; Tischenko, V. K.; Yakubovskaya, R. I.; Kaprin, A. D.; Sobolev, A. S.

    2017-09-01

    Recombinant modular nanotransporter containing α-melanocyte-stimulating hormone peptide sequence (MNT-MSH) as a ligand module was designed for nucleus-targeted delivery of cytotoxic agents into melanoma cells. MNT-MSH radiolabeled with Auger electron emitter (111In-NOTA-MNT-MSH) showed a high antitumor efficacy in mice bearing syngeneic melanoma after intratumoral (i.t.) injection. This study is aimed at evaluating the biodistribution of the radioconjugate in melanoma tumor model in vivo. 111In-NOTA-MNT-MSH was administered i.t. in C57Bl/6j mice bearing subcutaneously implanted B16-F1 murine melanoma cells, expressing high levels of MCR1. The tissue uptake of radioactivity was determined ex vivo by γ-counter measurements. The intravenous route of administration did not provide a desirable level of radioactivity accumulation in the tumor, possibly, due to a high uptake of the transporter in liver tissue. After i.t. administration 111In-NOTA-MNT-MSH provided a high local retention of radionuclide, ranged from 400 to 350 %ID/g within at least 48 hours post-injection. MNT containing Auger electron emitter and α-MSH peptide as vector ligand could be a promising basis for radiopharmaceutical preparations intended for melanoma treatment.

  5. Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

    Science.gov (United States)

    Castelli, Germana; Pelosi, Elvira

    2017-01-01

    Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells. PMID:29156643

  6. Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

    Directory of Open Access Journals (Sweden)

    Ugo Testa

    2017-11-01

    Full Text Available Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells.

  7. Chronic diseases requiring hospitalization and risk of non-melanoma skin cancers-A population based study from Denmark

    DEFF Research Database (Denmark)

    Jensen, Annette Ø; Olesen, Anne B; Dethlefsen, Claus

    2008-01-01

    We examined the associations between chronic diseases requiring hospitalization and the risk of non-melanoma skin cancers (NMSCs) in a population-based case-control study of 4,187 patients diagnosed with a first primary NMSC in 1995 in Denmark. From the National Patient Registry covering all Danish...... incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Although no overall association was found between basal cell carcinoma (BCC) and hospitalization for chronic diseases, an elevated IRR for BCC was found among patients with connective tissue disease (IRR 1.34 (95% CI: 0.99-1.82)), transplants...

  8. Lifestyle factors of smoking, BMI and alcohol on the risk of Non-Melanoma Skin Cancer in adults: a systematic review.

    Science.gov (United States)

    Leonardi-Bee, J; Ellison, T; Bath-Hextall, F

    2012-01-01

    Non-melanoma skin cancer is the most common cancer in humans and the most important risk factors are thought to be age, skin type, and exposure to ultraviolet radiation. Lifestyle factors may also play a part. To date no systematic review has been performed to collate evidence of the effects of smoking, alcohol or body mass index. We performed a systematic review and meta-analysis to assess the effects of smoking, alcohol and body mass index on the risk of non-melanoma skin cancer and its subtypes. Adults (18+ years old) of either sex from any ethnicitySmoking, alcohol, or body mass index (including other anthropometric measurements, such as weight, waist to hip ratio, and the percentage body fat)Non-melanoma skin cancer, cutaneous squamous cell carcinoma, or basal cell carcinomaComparative observational epidemiological studies SEARCH STRATEGY: We performed a comprehensive search of MEDLINE, EMBASE, CINAHL, Cochrane Library and CAB Abstracts from inception to October 2010. We also scanned reference lists to identify further eligible studies. Data from eligible studies were extracted and quality assessed using the Newcastle Ottawa Scale independently by two reviewers. The titles, abstracts and full text identified from the search were assessed independently by two reviewers against pre-specified inclusion/exclusion criteria. Disagreements were resolved through discussion with a third reviewer. For studies with similar exposures, a meta-analysis was performed using a random effects model and results were expressed as pooled odds ratio with 95% confidence intervals. Heterogeneity was assessed using I. Publication bias was assessed using funnel plots. Data were analysed using Review Manager. Thirty studies were included of which 22 used a case control design and the remaining used a cohort design. The overall quality of the studies was variable with a Newcastle Ottawa Scale median score of 6 out of 9 stars. No evidence of asymmetry was detected in the funnel plots

  9. Proteomics in uveal melanoma.

    LENUS (Irish Health Repository)

    Ramasamy, Pathma

    2014-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

  10. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    carcinoma and 174 matched controls, and 168 cases with cutaneous malignant melanoma and 176 matched controls. Controls were matched on age, gender and place of residence. Subjects indicated their hair colour before 7 years of age, and at 25 years of age and their skin phototype. Interviewers assessed...... colour and skin type were found to be independent risk factors for cutaneous malignant melanoma; red hair vs. black/brown: OR >9.7, blond hair vs. brown/black: OR = 2.4, and skin type 11 vs. type IV: OR=2.0. There were no gender-related differences in risk factors for basal cell carcinoma and cutaneous......To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...

  11. Radiotherapy of uveal melanomas experiences with proton beam irradiation of high risk parapapillary, paramaculary tumors

    International Nuclear Information System (INIS)

    Hideghety, K.; Sauerwein, W.; Fluehs, D.; Sack, H.; Quast

    1999-01-01

    The role of the radiotherapy in the treatment of malignant chorioidal melanomas has been established by means of 106 Ru or 125 I applicators and proton therapy. The rationale of the indication to utilize brachytherapy or proton therapy is presented on the basis of the clinical situation and physical characteristic of the different radiation modalities. (author)

  12. Therapeutic groin dissection for melanoma : Risk factors for short term morbidity

    NARCIS (Netherlands)

    Poos, H. P. A. M.; Kruijff, S.; Bastiaannet, E.; van Ginkel, R. J.; Hoekstra, H. J.

    Aims: Ilio-inguinal lymph node dissection for stage III melanoma is often complicated by wound healing disturbances. A retrospective study was performed to investigate the wound healing disturbances after therapeutic ili-inguinal lymphj node dissection. Patients and methods: Between 1989 and 2007,

  13. Selenium for the Prevention of Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Douglas Grossman

    2013-03-01

    Full Text Available The role of selenium (Se supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence.

  14. Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Dasgupta, Amrita [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Katdare, Meena, E-mail: mkatdare@gmail.com [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA 23507 (United States)

    2015-08-14

    Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics.

  15. Occupational exposure to ultraviolet radiation and risk of non-melanoma skin cancer in a multinational European study.

    Directory of Open Access Journals (Sweden)

    Simona Surdu

    Full Text Available BACKGROUND: Studies suggest that ambient sunlight plays an important role in the pathogenesis of non-melanoma skin cancers (NMSC. However, there is ongoing controversy regarding the relevance of occupational exposure to natural and artificial ultraviolet radiation (UV radiation. OBJECTIVES: We investigated potential associations between natural and artificial UV radiation exposure at work with NMSC in a case-control study conducted in Hungary, Romania, and Slovakia. METHODS: Occupational exposures were classified by expert assessment for 527 controls and 618 NMSC cases (515 basal cell carcinoma, BCC. Covariate information was collected via interview and multiple logistic regression models were used to assess associations between UV exposure and NMSC. RESULTS: Lifetime prevalence of occupational exposure in the participants was 13% for natural UV radiation and 7% for artificial UV radiation. Significant negative associations between occupational exposure to natural UV radiation and NMSC were detected for all who had ever been exposed (odds ratio (OR 0.47, 95% confidence interval (CI 0.27-0.80; similar results were detected using a semi-quantitative metric of cumulative exposure. The effects were modified by skin complexion, with significantly decreased risks of BCC among participants with light skin complexion. No associations were observed in relation to occupational artificial UV radiation exposure. CONCLUSIONS: The protective effect of occupational exposure to natural UV radiation was unexpected, but limited to light-skinned people, suggesting adequate sun-protection behaviors. Further investigations focusing on variations in the individual genetic susceptibility and potential interactions with environmental and other relevant factors are planned.

  16. Risk of developing multiple primary cutaneous melanomas in patients with the classic atypical-mole syndrome: a case-control study.

    Science.gov (United States)

    Marghoob, A A; Slade, J; Kopf, A W; Salopek, T G; Rigel, D S; Bart, R S

    1996-11-01

    The classic atypical-mole syndrome (CAMS) and/or a history of malignant melanoma (MM) increases the risk for multiple melanomas. Case notes of 118 CAMS and 173 control patients, each with a history of MM, were reviewed for the occurrence of second primary MMs. The mean (+/-SD) age at diagnosis of the first MM was 38.8 +/- 12.8 and 48.9 +/- 14.7 years (P table risk of 35.5% and 17.0%, respectively (P Periodic total cutaneous examinations are indicated for life in an attempt to identify new MMs when they are thin.

  17. Do polychlorinated biphenyls cause cancer? A systematic review and meta-analysis of epidemiological studies on risk of cutaneous melanoma and non-Hodgkin lymphoma.

    Science.gov (United States)

    Zani, Claudia; Ceretti, Elisabetta; Covolo, Loredana; Donato, Francesco

    2017-09-01

    In 2015 a IARC Working Group upgraded the classification of PCBs to Group 1 "Carcinogenic to humans", also on the basis of evidence from epidemiological studies showing an excess risk for melanoma. Increased risks for non-Hodgkin lymphoma (NHL) and breast cancer were also reported though the evidence was limited. However, some recent reviews of studies on PCB exposure and risk of cancer provided discrepant findings. Therefore, we re-evaluated the association between exposure to PCBs and risk of melanoma and NHL by a systematic review and meta-analysis. We retrieved 11 independent cohort studies on occupationally exposed workers. About half of them showed increased standardized mortality or incidence ratios (SMRs or SIRs) for melanoma and none for NHL. The pooled SMRs were 1.32 (95% CI: 1.05-1.64) for melanoma and 0.94 (0.73-1.23) for NHL. Among population-based cohort and case-control studies with individual measures of PCB exposure, one only study was carried out on PCB exposure and melanoma, showing an odds ratio (OR) of 6.0 (2.0-18.2) for the highest compared to lowest quartile of PCB distribution. 13 cohort and case-control studies evaluated the association between NHL and PCB concentration in blood or subcutaneous fat, with summary OR = 1.5 (1.1-1.7) for the highest vs lowest quantile of PCB distribution. However, two cohort studies on people intoxicated by rice oil containing PCBs found no excess of deaths for skin cancer and inconsistent results for NHL. In conclusion, these findings do not provide a strong evidence that PCB exposure can increase the risk of melanoma and NHL in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Differential effects of vascular endothelial growth factor A isoforms in a mouse brain metastasis model of human melanoma.

    NARCIS (Netherlands)

    Kusters, B.; Waal, R.M.W. de; Wesseling, P.; Verrijp, K.; Maass, C.N.; Heerschap, A.; Barentsz, J.O.; Sweep, C.G.J.; Ruiter, D.J.; Leenders, W.P.J.

    2003-01-01

    We reported previously that vascular endothelial growth factor isoform A (VEGF-A) expression by Mel57 human melanoma cells led to tumor progression in a murine brain metastasis model in an angiogenesis-independent fashion by dilation of co-opted, pre-existing vessels and concomitant enhanced blood

  19. Decreased risk of melanoma and nonmelanoma skin cancer in patients with vitiligo: a survey among 1307 patients and their partners

    NARCIS (Netherlands)

    Teulings, H. E.; Overkamp, M.; Ceylan, E.; Nieuweboer-Krobotova, L.; Bos, J. D.; Nijsten, T.; Wolkerstorfer, A. W.; Luiten, R. M.; van der Veen, J. P. W.

    2013-01-01

    Vitiligo is a common skin disease characterized by autoimmune melanocyte destruction. Recent genetic studies suggest a lower susceptibility to melanoma in patients with vitiligo; however, lifetime melanoma prevalence in patients with vitiligo has not previously been studied. Nonmelanoma skin cancer

  20. Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study

    Directory of Open Access Journals (Sweden)

    Kim Jung Han

    2010-04-01

    Full Text Available Abstract Background We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection. Methods Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5% satisfied the selection criteria. Results Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2% which was followed by nasal cavity (n = 30, 23.3%, genitourinary (n = 21, 16.3%, oral cavity (n = 14, 10.9%, upper gastrointestinal tract (n = 6, 4.7% and maxillary sinus (n = 5, 3.9% in the order of frequency. With the median 64.5 (range 4.3-213.0 months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5 for all patients, and 34.6 (95% CI 24.5-44.7 months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin, and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04. Conclusion Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome.

  1. Indoor tanning in businesses and homes and risk of melanoma and nonmelanoma skin cancer in 2 US case-control studies.

    Science.gov (United States)

    Ferrucci, Leah M; Vogel, Rachel Isaksson; Cartmel, Brenda; Lazovich, DeAnn; Mayne, Susan T

    2014-11-01

    Indoor tanning increases skin cancer risk. Beyond early research describing melanoma and sun lamps, few recent reports describe where individuals indoor tan and whether skin cancer risk varies by location (business, home-based). We sought to assess where individuals tanned indoors and skin cancer risk by tanning device location. Multivariate logistic regression was conducted in 2 US case-control studies of melanoma (1161 cases, 1083 controls, ages 25-59 years) and early-onset basal cell carcinoma (375 cases, 382 controls, agebasal cell carcinoma (odds ratio 1.69, 95% confidence interval 1.15-2.48) compared with non-users. Melanoma risk was also increased in the small number who reported tanning indoors only at home relative to non-users (odds ratio 4.14, 95% confidence interval 1.75-9.78); 67.6% used sun lamps. Self-reported tanning and potential recall bias are limitations. Business-only tanning, despite claims of "safe" tanning, was positively associated with a significant risk of melanoma and basal cell carcinoma. Home tanning was uncommon and mostly from sun lamps, which were rarely used by younger participants. Regardless of location, indoor tanning was associated with increased risk of skin cancer. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Associations of non-melanoma skin cancer and melanoma, extra-cutaneous cancers and smoking in adults: a US population-based study.

    Science.gov (United States)

    Silverberg, J I; Ratner, D

    2015-07-01

    Non-melanoma skin cancer (NMSC) and melanoma are common malignancies in the US and may be associated with other types of cancer. We sought to determine whether NMSC and melanoma are associated with extra-cutaneous cancers and identify modifiable risk factors for such an association. We analysed data from 447,801 adult participants in the 1997-2011 National Health Interview Surveys. Survey logistic regression models were constructed that accounted for the complex sample weights. History of NMSC, melanoma and 27 primary extra-cutaneous cancers was assessed. NMSC was associated with increased odds of one (multinomial survey logistic regression, unadjusted odds ratio [95% CI]: 2.43 [2.20-2.68]) or multiple (2.94 [2.21-3.92]) extra-cutaneous malignancies. Melanoma was also associated with increased odds of one (3.25 [2.70-3.90]) or multiple (6.11 [4.34-8.61]) extra-cutaneous malignancies. Extra-cutaneous cancers were more common in younger patients (ages 18-39 and 40-49 years) and Caucasians with NMSC or melanoma (P melanoma had even higher odds of extra-cutaneous malignancy at ages 18-39 and 40-49 years compared to smokers without NMSC or melanoma (P melanoma, prostate, soft tissue, throat/pharynx, thyroid and uterus. Melanoma was associated with malignancies of the bladder, breast, colon, kidney, lung, pancreas, prostate, soft tissue, throat/pharynx, thyroid and uterus. The prevalence of extra-cutaneous cancers increased between 1997 and 2011 in all subjects (4.51% and 5.73%, P melanoma. Patients with history of NMSC and melanoma have increased odds of developing extra-cutaneous cancers, especially those with younger age and smoking history. © 2014 European Academy of Dermatology and Venereology.

  3. Combination therapy for melanoma with BRAF/MEK inhibitor and immune checkpoint inhibitor: a mathematical model.

    Science.gov (United States)

    Lai, Xiulan; Friedman, Avner

    2017-07-19

    The B-raf gene is mutated in up to 66% of human malignant melanomas, and its protein product, BRAF kinase, is a key part of RAS-RAF-MEK-ERK (MAPK) pathway of cancer cell proliferation. BRAF-targeted therapy induces significant responses in the majority of patients, and the combination BRAF/MEK inhibitor enhances clinical efficacy, but the response to BRAF inhibitor and to BRAF/MEK inhibitor is short lived. On the other hand, treatment of melanoma with an immune checkpoint inhibitor, such as anti-PD-1, has lower response rate but the response is much more durable, lasting for years. For this reason, it was suggested that combination of BRAF/MEK and PD-1 inhibitors will significantly improve overall survival time. This paper develops a mathematical model to address the question of the correlation between BRAF/MEK inhibitor and PD-1 inhibitor in melanoma therapy. The model includes dendritic and cancer cells, CD 4 + and CD 8 + T cells, MDSC cells, interleukins IL-12, IL-2, IL-6, IL-10 and TGF- β, PD-1 and PD-L1, and the two drugs: BRAF/MEK inhibitor (with concentration γ B ) and PD-1 inhibitor (with concentration γ A ). The model is represented by a system of partial differential equations, and is used to develop an efficacy map for the combined concentrations (γ B ,γ A ). It is shown that the two drugs are positively correlated if γ B and γ A are at low doses, that is, the growth of the tumor volume decreases if either γ B or γ A is increased. On the other hand, the two drugs are antagonistic at some high doses, that is, there are zones of (γ B ,γ A ) where an increase in one of the two drugs will increase the tumor volume growth, rather than decrease it. It will be important to identify, by animal experiments or by early clinical trials, the zones of (γ B ,γ A ) where antagonism occurs, in order to avoid these zones in more advanced clinical trials.

  4. Childhood Body Size and the Risk of Malignant Melanoma in Adulthood

    DEFF Research Database (Denmark)

    Meyle, Kathrine D; Gamborg, Michael; Sørensen, Thorkild I A

    2017-01-01

    Malignant melanoma (MM) is the most aggressive form of skin cancer. Adult anthropometry influences MM development; however, associations between childhood body size and future melanomagenesis are largely unknown. We investigated whether height, body mass index (BMI; weight (kg)/height (m)2......), and body surface area (BSA) at ages 7-13 years and birth weight are associated with adult MM. Data from the Copenhagen School Health Records Register, containing annual height and weight measurements of 372,636 Danish children born in 1930-1989, were linked with the Danish Cancer Registry. Cox regression......, without any comparable influence of BMI or BSA. Melanoma transformation is unlikely to be due to height per se; however, height-regulating processes in childhood present new areas for mechanistic explorations of this disease....

  5. High accuracy of family history of melanoma in Danish melanoma cases.

    Science.gov (United States)

    Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

    2015-12-01

    The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree relatives and found only 1 case of melanoma which was not reported in a 3 case melanoma family. Melanoma patients in Denmark report family history of melanoma in first and second degree relatives with a high level of accuracy with a true positive predictive value between 77 and 87%. In 99% of probands reporting a negative family history of melanoma in first degree relatives this information is correct. In clinical practice we recommend that melanoma diagnosis in relatives should be verified if possible, but even unverified reported melanoma cases in relatives should be included in the indication of genetic testing and assessment of melanoma risk in the family.

  6. Do perinatal and early life exposures influence the risk of malignant melanoma? A Northern Ireland birth cohort analysis.

    Science.gov (United States)

    O'Rorke, M A; Black, C; Murray, L J; Cardwell, C R; Gavin, A T; Cantwell, M M

    2013-03-01

    Intrauterine, early life and maternal exposures may have important consequences for cancer development in later life. The aim of this study was to examine perinatal and birth characteristics with respect to Cutaneous malignant melanoma (CMM) risk. The Northern Ireland Child Health System database was used to examine gestational age adjusted birth weight, infant feeding practices, parental age and socioeconomic factors at birth in relation to CMM risk amongst 447,663 infants delivered between January 1971 and December 1986. Follow-up of histologically verified CMM cases was undertaken from the beginning of 1993 to 31st December 2007. Multivariable adjusted unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) of CMM risk. A total of 276 CMM cases and 440,336 controls contributed to the final analysis. In reference to normal (gestational age-adjusted) weight babies, those heaviest at birth were twice as likely to develop CMM OR 2.4 (95% CI 1.1-5.1). Inverse associations with CMM risk were observed with younger (birth and both a higher birth order and greater household density OR 0.61 (95% CI 0.37-0.99) and OR 0.56 (95% CI 0.30-1.0) respectively. This large study of early onset melanoma supports a positive association with higher birth weight (imperatively gestational age adjusted) and CMM risk which may be related to factors which drive intrauterine foetal growth. Strong inverse associations observed with higher birth order and household density suggest that early-life immune modulation may confer protection; findings which warrant further investigation in prospective analyses. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma.

    Science.gov (United States)

    Pontes, Kelly Cristine de Sousa; Groenewoud, Arwin; Cao, Jinfeng; Ataide, Livia Maria Silva; Snaar-Jagalska, Ewa; Jager, Martine J

    2017-12-01

    Conjunctival melanoma (CM) is a rare malignant disease that can lead to recurrences and metastases. There is a lack of effective treatments for the metastases, and we set out to develop a new animal model to test potential therapies. Zebrafish are being used as a model for many diseases, and our goal was to test whether this animal could be used to study CM. Three human CM cell lines (CRMM-1 and CM2005.1, which both harbor a B-RAF mutation, and CRMM-2, which has an N-RAS mutation) were injected into the yolk sac, around the eye, and into the duct of Cuvier of transgenic (fli:GFP) Casper zebrafish embryos. Fluorescent and confocal images were taken to assess the phenotype and the behavior of engrafted cells and to test the effect of Vemurafenib as a treatment against CM. While the cells that had been injected inside the yolk sac died and those injected around the eye sporadically went into the circulation, the cells that had been injected into the duct of Cuvier colonized the zebrafish: cells from all three cell lines proliferated and disseminated to the eyes, where they formed clusters, and to the tail, where we noticed extravasation and micrometastases. Vemurafenib, a potent agent for treatment of B-RAF V600E-positive melanoma, inhibited outgrowth of CRMM-1 and CM2005.1 cells in a mutation-dependent way. The (fli:GFP) Casper zebrafish embryo can be used as an efficient animal model to study metastatic behavior of human CM cells and warrants further testing of drug efficacy to aid care of CM patients.

  8. Bayesian operational risk models

    OpenAIRE

    Silvia Figini; Lijun Gao; Paolo Giudici

    2013-01-01

    Operational risk is hard to quantify, for the presence of heavy tailed loss distributions. Extreme value distributions, used in this context, are very sensitive to the data, and this is a problem in the presence of rare loss data. Self risk assessment questionnaires, if properly modelled, may provide the missing piece of information that is necessary to adequately estimate op- erational risks. In this paper we propose to embody self risk assessment data into suitable prior distributions, and ...

  9. Genetic prognostic factors in uveal melanoma

    NARCIS (Netherlands)

    Maat, Willem

    2012-01-01

    Uveal melanoma (UM) is the most common malignancy of the eye in adults and it is the second most common form of melanoma after cutaneous melanoma (CM). The identification of patients who have a high risk of developing metastases would allow the possibility of providing adjuvant therapies to prevent

  10. Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

    DEFF Research Database (Denmark)

    Schrama, D.; Voigt, H.; Eggert, A.O.

    2008-01-01

    BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune...... of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells...... as demonstrated by in situ TRP-2/K(b) tetramer staining. Mechanistically, targeted LTalpha therapy seems to induce changes at the tumor site which allows a coordinated interaction of immune competent cells triggering the induction of tertiary lymphoid tissue. CONCLUSION: Thus, our data demonstrate that targeted...

  11. Malignant melanoma and other cancers of the skin in Czech Republic (epidemiology, risk factors and prevention possibilities).

    OpenAIRE

    Pojezná, Eliška

    2009-01-01

    two basic types: non-melanoma skin cancer and melanoma. Skin tumors mean up to 5%. The increase in incidence is due to both a strong knowledge ofdevelopment issues and melanoma tumor detection and efforts to reduce its incidence. Also in the diagnosis of melanoma was diagnosis. Although in recent years to s tumor. I see a reduction in its incidence. Also in the diagnostic result in death, but are far from melanoma malignancy. This does not mean that they should vykousanou crayfish or crab. "i...

  12. Antioxidants can increase melanoma metastasis in mice.

    Science.gov (United States)

    Le Gal, Kristell; Ibrahim, Mohamed X; Wiel, Clotilde; Sayin, Volkan I; Akula, Murali K; Karlsson, Christin; Dalin, Martin G; Akyürek, Levent M; Lindahl, Per; Nilsson, Jonas; Bergo, Martin O

    2015-10-07

    Antioxidants in the diet and supplements are widely used to protect against cancer, but clinical trials with antioxidants do not support this concept. Some trials show that antioxidants actually increase cancer risk and a study in mice showed that antioxidants accelerate the progression of primary lung tumors. However, little is known about the impact of antioxidant supplementation on the progression of other types of cancer, including malignant melanoma. We show that administration of N-acetylcysteine (NAC) increases lymph node metastases in an endogenous mouse model of malignant melanoma but has no impact on the number and size of primary tumors. Similarly, NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation. Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis. Furthermore, both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration. These results demonstrate that antioxidants and the glutathione system play a previously unappreciated role in malignant melanoma progression. Copyright © 2015, American Association for the Advancement of Science.

  13. An epigenetic vaccine model active in the prevention and treatment of melanoma

    Directory of Open Access Journals (Sweden)

    Magner William J

    2007-12-01

    Full Text Available Abstract Background Numerous immune genes are epigenetically silenced in tumor cells and agents such as histone deacetylase inhibitors (HDACi, which reverse these effects, could potentially be used to develop therapeutic vaccines. The conversion of cancer cells to antigen presenting cells (APCs by HDACi treatment could potentially provide an additional pathway, together with cross-presentation of tumor antigens by host APCs, to establish tumor immunity. Methods HDACi-treated B16 melanoma cells were used in a murine vaccine model, lymphocyte subset depletion, ELISpot and Cytotoxicity assays were employed to evaluate immunity. Antigen presentation assays, vaccination with isolated apoptotic preparations and tumorigenesis in MHC-deficient mice and radiation chimeras were performed to elucidate the mechanisms of vaccine-induced immunity. Results HDACi treatment enhanced the expression of MHC class II, CD40 and B7-1/2 on B16 cells and vaccination with HDACi-treated melanoma cells elicited tumor specific immunity in both prevention and treatment models. Cytotoxic and IFN-γ-producing cells were identified in splenocytes and CD4+, CD8+ T cells and NK cells were all involved in the induction of immunity. Apoptotic cells derived from HDACi treatments, but not H2O2, significantly enhanced the effectiveness of the vaccine. HDACi-treated B16 cells become APCs in vitro and studies in chimeras defective in cross presentation demonstrate direct presentation in vivo and short-term but not memory responses and long-term immunity. Conclusion The efficacy of this vaccine derives mainly from cross-presentation which is enhanced by HDACi-induced apoptosis. Additionally, epigenetic activation of immune genes may contribute to direct antigen presentation by tumor cells. Epigenetically altered cancer cells should be further explored as a vaccine strategy.

  14. An epigenetic vaccine model active in the prevention and treatment of melanoma.

    Science.gov (United States)

    Khan, A Nazmul H; Magner, William J; Tomasi, Thomas B

    2007-12-10

    Numerous immune genes are epigenetically silenced in tumor cells and agents such as histone deacetylase inhibitors (HDACi), which reverse these effects, could potentially be used to develop therapeutic vaccines. The conversion of cancer cells to antigen presenting cells (APCs) by HDACi treatment could potentially provide an additional pathway, together with cross-presentation of tumor antigens by host APCs, to establish tumor immunity. HDACi-treated B16 melanoma cells were used in a murine vaccine model, lymphocyte subset depletion, ELISpot and Cytotoxicity assays were employed to evaluate immunity. Antigen presentation assays, vaccination with isolated apoptotic preparations and tumorigenesis in MHC-deficient mice and radiation chimeras were performed to elucidate the mechanisms of vaccine-induced immunity. HDACi treatment enhanced the expression of MHC class II, CD40 and B7-1/2 on B16 cells and vaccination with HDACi-treated melanoma cells elicited tumor specific immunity in both prevention and treatment models. Cytotoxic and IFN-gamma-producing cells were identified in splenocytes and CD4+, CD8+ T cells and NK cells were all involved in the induction of immunity. Apoptotic cells derived from HDACi treatments, but not H2O2, significantly enhanced the effectiveness of the vaccine. HDACi-treated B16 cells become APCs in vitro and studies in chimeras defective in cross presentation demonstrate direct presentation in vivo and short-term but not memory responses and long-term immunity. The efficacy of this vaccine derives mainly from cross-presentation which is enhanced by HDACi-induced apoptosis. Additionally, epigenetic activation of immune genes may contribute to direct antigen presentation by tumor cells. Epigenetically altered cancer cells should be further explored as a vaccine strategy.

  15. Tumor load in lymph node positive melanoma: Classification systems, prognostication models and management recommendations

    NARCIS (Netherlands)

    A.P.T. van der Ploeg (Augustinus)

    2014-01-01

    markdownabstract__Abstract__ The incidence and mortality of melanoma, the most malignant type of skin cancer, is increasing worldwide. The sentinel node procedure is accepted as a diagnostic procedure for patients with primary melanoma > 1mm. The prognosis of the group of sentinel node-positive

  16. Adjuvant radiotherapy versus observation alone for patients at risk of lymph-node field relapse after therapeutic lymphadenectomy for melanoma : a randomised trial

    NARCIS (Netherlands)

    Burmeister, Bryan H.; Henderson, Michael A.; Ainslie, Jill; Fisher, Richard; Di Iulio, Juliana; Smithers, B. Mark; Hong, Angela; Shannon, Kerwin; Scolyer, Richard A.; Carruthers, Scott; Coventry, Brendon J.; Babington, Scott; Duprat, Joao; Hoekstra, Harald J.; Thompson, John F.

    Background The use of radiotherapy after therapeutic lymphadenectomy for patients with melanoma at high risk of further lymph-node field and distant recurrence is controversial. Decisions for radiotherapy in this setting are made on the basis of retrospective, non-randomised studies. We did this

  17. Nodular Histologic Subtype and Ulceration are Tumor Factors Associated with High Risk of Recurrence in Sentinel Node-Negative Melanoma Patients

    NARCIS (Netherlands)

    Faut, Marloes; Wevers, Kevin P.; van Ginkel, Robert J.; Diercks, Gilles F. H.; Hoekstra, Harald J.; Kruijff, Schelto; Been, Lukas B.; van Leeuwen, Barbara L.

    Since its introduction, the sentinel lymph node biopsy (SLNB) has become the standard staging procedure in clinical node-negative melanoma patients. A negative SLNB, however, does not guarantee a recurrence-free survival. Insight into metastatic patterns and risk factors for recurrence in SLNB

  18. Evaluation of six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon therapy in the He13A/98 multicenter trial

    Directory of Open Access Journals (Sweden)

    Fountzilas George

    2010-11-01

    Full Text Available ABSTRACT Purpose Interferon is approved for adjuvant treatment of patients with stage IIb/III melanoma. The toxicity and uncertainty regarding survival benefits of interferon have qualified its acceptance, despite significant durable relapse prevention in a fraction of patients. Predictive biomarkers that would enable selection of patients for therapy would have a large impact upon clinical practice. Specific CTLA-4 polymorphisms have previously shown an association with response to CTLA-4 blockade in patients with metastatic melanoma and the development of autoimmunity. Experimental design 286 melanoma patients and 288 healthy controls were genotyped for six CTLA-4 polymorphisms previously suggested to be important (AG 49, CT 318, CT 60, JO 27, JO30 and JO 31. Specific allele frequencies were compared between the healthy and patient populations, as well as presence or absence of these in relation to recurrence. Alleles related to autoimmune disease were also investigated. Results No significant differences were found between the distributions of CTLA-4 polymorphisms in the melanoma population compared with healthy controls. Relapse free survival (RFS and overall survival (OS did not differ significantly between patients with the alleles represented by these polymorphisms. No correlation between autoimmunity and specific alleles was shown. The six polymorphisms evaluated where strongly associated (Fisher's exact p-values Conclusion No polymorphisms of CTLA-4 defined by the SNPs studied were correlated with improved RFS, OS, or autoimmunity in this high-risk group of melanoma patients.

  19. Hmgb1-IL-23-IL-17-IL-6-Stat3 Axis Promotes Tumor Growth in Murine Models of Melanoma

    Directory of Open Access Journals (Sweden)

    Qiu Tang

    2013-01-01

    Full Text Available In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, IL-17 deficiency results in reduced melanoma tumor size, diminished numbers of proliferating cells and blood vessels, and decreased percentage of CD11b+Gr-1+ MDSCs in tumor tissues. IL-17 promotes IL-6 induction and Stat3 activation. Treatment of Stat3 inhibitor WP1066 in B16-F10 tumor cells inoculated wild-type mice inhibits tumor growth. Additional administration of recombinant IL-6 into B16-F10 tumor-bearing IL-17−/− mice results in markedly increased tumor size and p-Stat3 expression, whereas additional recombinant IL-17 administration into B16-F10 tumor-bearing wild-type mice treated with anti-IL-6 mAb does not significantly alter the tumor growth and p-Stat3 expression. In our further study, blockade of Hmgb1-RAGE pathway inhibits melanoma tumor growth and reduces production of IL-23 and IL-17. All these data suggest that Hmgb1-IL-23-IL-17-IL-6-Stat3 axis plays a pivotal role in tumor development in murine models of melanoma, and blocking any portion of this axis will attenuate melanoma tumor growth.

  20. Dermoscopy, Digital Dermoscopy and Other Diagnostic Tools in the Early Detection of Melanoma and Follow-up of High-risk Skin Cancer Patients.

    Science.gov (United States)

    Thomas, Luc; Puig, Susana

    2017-07-05

    Early detection is a key strategy for reducing the mortality and economic burden associated with melanoma. Dermoscopy is a non-invasive and cost-effective tool for melanoma diagnosis, which has been shown to be a reliable and sensitive method for detecting early-stage skin cancer and reducing the number of unnecessary excisions. Patients at high risk of developing melanoma require long-term surveillance. Use of digital dermoscopy follow-up of these patients has led to improved outcomes. Combined follow-up programmes using total-body photography and digital dermoscopy have led to further improvements in early diagnosis and diagnostic accuracy. Dermoscopy is now widely used by dermatologists, but the public health impact of this tool is yet to be evaluated. Despite the clear advantages of dermoscopy and digital follow-up meth-ods, dermoscopy training and access to digital dermoscopy among dermatologists and general practitioners needs to be improved.

  1. Genetics of Melanoma

    Directory of Open Access Journals (Sweden)

    Janet eWangari-Talbot

    2013-01-01

    Full Text Available Genomic variation is a trend observed in various human diseases including cancer. Genetic studies have set out to understand how and why these variations result in cancer, why some populations are predisposed to the disease, and also how genetics affect drug responses. The melanoma incidence has been increasing at an alarming rate worldwide. The burden posed by melanoma has made it a necessity to understand the fundamental signaling pathways involved in this deadly disease. Signaling cascades such as MAPK and PI3K/AKT have been shown to be crucial in the regulation of processes that are commonly dysregulated during cancer development such as aberrant proliferation, loss of cell cycle control, impaired apoptosis and altered drug metabolism. Understanding how these and other oncogenic pathways are regulated has been integral in our challenge to develop potent anti-melanoma drugs. With advances in technology and especially in next generation sequencing, we have been able to explore melanoma genomes and exomes leading to the identification of previously unknown genes with functions in melanomagenesis such as GRIN2A and PREX2. The therapeutic potential of these novel candidate genes is actively being pursued with some presenting as druggable targets while others serve as indicators of therapeutic responses. In addition, the analysis of the mutational signatures of melanoma tumors continues to cement the causative role of UV exposure in melanoma pathogenesis. It has become distinctly clear that melanomas from sun exposed skin areas have distinct mutational signatures including C to T transitions indicative of UV-induced damage. It is thus necessary to continue spreading awareness on how to decrease the risk factors of developing the disease while at the same time working for a cure. Given the large amount of information gained from these sequencing studies, it is likely that in the future, treatment of melanoma will follow a highly personalized route

  2. Serial or Parallel Metastasis of Cutaneous Melanoma? A Study of the German Central Malignant Melanoma Registry.

    Science.gov (United States)

    Gassenmaier, Maximilian; Eigentler, Thomas Kurt; Keim, Ulrike; Goebeler, Matthias; Fiedler, Eckhard; Schuler, Gerold; Leiter, Ulrike; Weide, Benjamin; Grischke, Eva-Maria; Martus, Peter; Garbe, Claus

    2017-12-01

    For more than a century the Halstedian hypothesis of contiguous metastasis from the primary tumor through the lymphatics to distant sites shaped lymph node surgery for melanoma. We challenge this dogma of serial metastatic dissemination. A single-center series of 2,299 patients with cutaneous metastatic melanoma was investigated to analyze overall survival and distant metastasis-free survival of stage IV patients with or without primary lymphatic metastasis. Results were then compared with those of 2,134 patients from three independent centers of the German Central Malignant Melanoma Registry. A multivariate binary logistic regression model was used to identify risk factors for the initial metastatic pathway. Distant metastasis-free survival (hazard ratio = 1.02; 95% confidence interval = 0.91-1.14; P = 0.76) and overall survival (HR = 1.09; 95% CI = 0.96-1.23; P = 0.177) did not differ between stage IV patients with primary hematogenous or primary lymphatic metastasis. Melanoma localization was the only significant risk factor for the initial metastatic pathway. These findings indicate that regional and distant metastases originate from the primary tumor itself in a rather parallel than serial fashion and could explain the lack of survival benefit associated with immediate complete lymph node dissection in sentinel lymph node-positive melanoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. The barrier function of organotypic non-melanoma skin cancer models.

    Science.gov (United States)

    Zoschke, Christian; Ulrich, Martina; Sochorová, Michaela; Wolff, Christopher; Vávrová, Kateřina; Ma, Nan; Ulrich, Claas; Brandner, Johanna M; Schäfer-Korting, Monika

    2016-07-10

    Non-melanoma skin cancer (NMSC) is the most frequent human cancer with continuously rising incidences worldwide. Herein, we investigated the molecular basis for the impaired skin barrier function of organotypic NMSC models. We unraveled disturbed epidermal differentiation by reflectance confocal microscopy and histopathological evaluation. While the presence of claudin-4 and occludin were distinctly reduced, zonula occludens protein-1 was more wide-spread, and claudin-1 was heterogeneously distributed within the NMSC models compared with normal reconstructed human skin. Moreover, the cancer altered stratum corneum lipid packing and profile with decreased cholesterol content, increased phospholipid amount, and altered ceramide subclasses. These alterations contributed to increased surface pH and to 1.5 to 2.6-fold enhanced caffeine permeability of the NMSC models. Three topical applications of ingenol mebutate gel (0.015%) caused abundant epidermal cell necrosis, decreased Ki-67 indices, and increased lactate dehydrogenase activity. Taken together, our study provides new biological insights into the microenvironment of organotypic NMSC models, improves the understanding of the disease model by revealing causes for impaired skin barrier function in NMSC models at the molecular level, and fosters human cell-based approaches in preclinical drug evaluation. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Role of COX-2 activity and CRP levels in patients with non-melanoma skin cancer. -765G>C PTGS2 polymorphism and NMSC risk.

    Science.gov (United States)

    Cocoş, Relu; Schipor, Sorina; Nicolae, Ilinca; Thomescu, Cecilia; Raicu, Florina

    2012-07-01

    Non-melanoma skin cancer is one of the most common of all cancers and the incidence has increased in the last years as a result of many factors including increased tanning, life style and possible global climate change. Inflammation plays an important role in cancer development and is frequently evaluated by serum C-reactive protein (CRP) levels. PTGS2 -765C allele coding for COX-2 has been found to be associated with lower plasma levels of CRP. The objectives of this study are: evaluation of the association between PTGS2 -765G>C polymorphism and the occurrence of non-melanoma skin cancer, the relationship between this polymorphism and cyclooxygenase-2 activity in skin tissue, as well as the correlation with serum CRP levels in patients with non-melanoma skin cancer. We used PCR-RFLP technique to explore -765G>C PTGS2 gene polymorphism, colorimetric analysis for cyclooxygenase-2 activity in skin tissue and immunoturbidimetric assay for CRP serum levels in 174 patients with non-melanoma skin cancer [54 patients with basal cell carcinoma (BCC) and 120 patients with squamous cell carcinoma (SCC)] and 80 healthy subjects. PTGS2 -765G>C polymorphism failed to show an association with non-melanoma skin cancer risk. We observed a significant increase in COX-2 activity in SCC and BCC patients compared to control tissue (0.58 ± 0.11 and 0.63 ± 0.09 U/mg protein, respectively vs. 0.16 ± 0.01 U/mg protein). BCC and SCC intra-group analysis showed lower COX-2 activity in C-allele carriers versus non-carriers (p C polymorphism failed to show an association with non-melanoma skin cancer risk. Regarding prognostic indicators, no consistent association emerged between PTGS2 -765G>C polymorphism and COX-2 activity or CRP levels.

  5. The metastatic microenvironment: Claudin-1 suppresses the malignant phenotype of melanoma brain metastasis.

    Science.gov (United States)

    Izraely, Sivan; Sagi-Assif, Orit; Klein, Anat; Meshel, Tsipi; Ben-Menachem, Shlomit; Zaritsky, Assaf; Ehrlich, Marcelo; Prieto, Victor G; Bar-Eli, Menashe; Pirker, Christine; Berger, Walter; Nahmias, Clara; Couraud, Pierre-Olivier; Hoon, Dave S B; Witz, Isaac P

    2015-03-15

    Brain metastases occur frequently in melanoma patients with advanced disease whereby the prognosis is dismal. The underlying mechanisms of melanoma brain metastasis development are not well understood. Identification of molecular determinants regulating melanoma brain metastasis would advance the development of prevention and therapy strategies for this disease. Gene expression profiles of cutaneous and brain-metastasizing melanoma variants from three xenograft tumor models established in our laboratory revealed that expression of tight junction component CLDN1 was lower in the brain-metastasizing variants than in cutaneous variants from the same melanoma. The objective of our study was to determine the significance of CLDN1 downregulation/loss in metastatic melanoma and its role in melanoma brain metastasis. An immunohistochemical analysis of human cells of the melanocyte lineage indicated a significant CLDN1 downregulation in metastatic melanomas. Transduction of melanoma brain metastatic cells expressing low levels of CLDN1 with a CLDN1 retrovirus suppressed their metastatic phenotype. CLDN1-overexpressing melanoma cells expressed a lower ability to migrate and adhere to extracellular matrix, reduced tumor aggressiveness in nude mice and, most importantly, eliminated the formation of micrometastases in the brain. In sharp contrast, the ability of the CLDN1-overexpressing cells to form lung micrometastases was not impaired. CLDN1-mediated interactions between these cells and brain endothelial cells constitute the mechanism underlying these results. Taken together, we demonstrated that downregulation or loss of CLDN1 supports the formation of melanoma brain metastasis, and that CLDN1 expression could be a useful prognostic predictor for melanoma patients with a high risk of brain metastasis. © 2014 UICC.

  6. Ocular Melanoma

    Science.gov (United States)

    ... also occur on the conjunctiva . Because most eye melanomas form in the part of the eye you can’t see when looking in a mirror, they can be difficult to detect. Also, eye melanoma typically doesn’t cause early signs or symptoms . ...

  7. Risk of Non-melanoma Skin Cancer in Patients with Chronic Kidney Disease and its Relationship to Uraemic Pruritus

    Directory of Open Access Journals (Sweden)

    Chia-Chen Wang

    2017-08-01

    Full Text Available This study investigated the risk of non-melanoma skin cancer (NMSC in pre-dialysis patients with chronic kidney disease (CKD and explored associated risk factors. A population-based cohort of 1,515,858 Taiwanese CKD patients was included. The standardized incidence ratio (SIR for incident NMSC was determined. Compared with the general population, a 1.14-fold risk of NMSC was found in the CKD cohort. NMSC risk was significant in patients with pre-dialysis stage 5 CKD and anaemia (1.48-fold, and in those with uraemic pruritus after long-term antihistamine treatment (1.38-fold. A higher SIR for NMSC was found in younger patients with CKD (age < 70 years, 1.34-fold; age 20–39 years, 1.63-fold, stage 5 CKD with anaemia (age < 70 years, 2.09-fold, and uraemic pruritus (age <70 years, 2.22-fold. Pre-dialysis patients with CKD are at higher risk of NMSC, especially those with advanced-stage CKD, and those with uraemic pruritus.

  8. Decision tree analysis to stratify risk of de novo non-melanoma skin cancer following liver transplantation.

    Science.gov (United States)

    Tanaka, Tomohiro; Voigt, Michael D

    2018-03-01

    Non-melanoma skin cancer (NMSC) is the most common de novo malignancy in liver transplant (LT) recipients; it behaves more aggressively and it increases mortality. We used decision tree analysis to develop a tool to stratify and quantify risk of NMSC in LT recipients. We performed Cox regression analysis to identify which predictive variables to enter into the decision tree analysis. Data were from the Organ Procurement Transplant Network (OPTN) STAR files of September 2016 (n = 102984). NMSC developed in 4556 of the 105984 recipients, a mean of 5.6 years after transplant. The 5/10/20-year rates of NMSC were 2.9/6.3/13.5%, respectively. Cox regression identified male gender, Caucasian race, age, body mass index (BMI) at LT, and sirolimus use as key predictive or protective factors for NMSC. These factors were entered into a decision tree analysis. The final tree stratified non-Caucasians as low risk (0.8%), and Caucasian males > 47 years, BMI risk (7.3% cumulative incidence of NMSC). The predictions in the derivation set were almost identical to those in the validation set (r 2  = 0.971, p risk groups at 5/10/20 year was 0.5/1.2/3.3, 2.1/4.8/11.7 and 5.6/11.6/23.1% (p risk of developing NMSC in the long-term after LT.

  9. Acne in late adolescence is not associated with a raised risk of subsequent malignant melanoma among men.

    Science.gov (United States)

    Mota Garcia, Teresa; Hiyoshi, Ayako; Udumyan, Ruzan; Sjöqvist, Hugo; Fall, Katja; Montgomery, Scott

    2017-12-01

    To evaluate the association of acne in late adolescence with the risk for subsequent malignant melanoma (MM) in men. Swedish register-based cohort study of 242,096 males born between 1952 and 1956, who took part in compulsory assessments for Swedish military conscription in late adolescence between 1969 and 1975, with subsequent diagnoses of MM (n=1,058) up to December 31, 2009. Covariates included measures of childhood circumstances and information from adolescence on presence of acne, physical fitness, cognitive function, body mass index (BMI), and a summary of diagnoses. Cox regression was used for the analysis. In total 1,058 men were diagnosed with MM. Acne was not associated with subsequent MM, with an adjusted hazard ratio (and 95% confidence interval) of 0.95 (0.61 to 1.49). Men with parents who were agricultural workers, and men who lived in northern Sweden, had lower physical fitness, or lower cognitive function had a lower risk of MM. Overweight and obesity was associated with a raised risk, with an adjusted hazard ratio of 1.39 (1.14, 1.71). Acne in late adolescence is unlikely to represent a raised risk for subsequent MM in men. Overweight or obesity was identified as a raised risk for MM, possibly due to the associated increased skin surface area. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Credit Risk Modeling

    DEFF Research Database (Denmark)

    Lando, David

    and students in finance, at quantitative analysts in banks and other financial institutions, and at regulators interested in the modeling aspects of credit risk. David Lando considers the two broad approaches to credit risk analysis: that based on classical option pricing models on the one hand......Credit risk is today one of the most intensely studied topics in quantitative finance. This book provides an introduction and overview for readers who seek an up-to-date reference to the central problems of the field and to the tools currently used to analyze them. The book is aimed at researchers...

  11. Credit Risk Modeling

    DEFF Research Database (Denmark)

    Lando, David

    Credit risk is today one of the most intensely studied topics in quantitative finance. This book provides an introduction and overview for readers who seek an up-to-date reference to the central problems of the field and to the tools currently used to analyze them. The book is aimed at researchers...... and students in finance, at quantitative analysts in banks and other financial institutions, and at regulators interested in the modeling aspects of credit risk. David Lando considers the two broad approaches to credit risk analysis: that based on classical option pricing models on the one hand...

  12. Nodular Histologic Subtype and Ulceration are Tumor Factors Associated with High Risk of Recurrence in Sentinel Node-Negative Melanoma Patients.

    Science.gov (United States)

    Faut, Marloes; Wevers, Kevin P; van Ginkel, Robert J; Diercks, Gilles F H; Hoekstra, Harald J; Kruijff, Schelto; Been, Lukas B; van Leeuwen, Barbara L

    2017-01-01

    Since its introduction, the sentinel lymph node biopsy (SLNB) has become the standard staging procedure in clinical node-negative melanoma patients. A negative SLNB, however, does not guarantee a recurrence-free survival. Insight into metastatic patterns and risk factors for recurrence in SLNB negative melanoma patients can provide patient tailored guidelines. Data concerning melanoma patients who underwent SLNB between 1996 and 2015 in a single center were prospectively collected. Cox regression analyses were used to determine variables associated with overall recurrence and distant first site of recurrence in SLNB-negative patients. In 668 patients, SLNBs were performed between 1996 and 2015. Of these patients, 50.4 % were male and 49.6 % female with a median age of 55.2 (range 5.7-88.8) years. Median Breslow thickness was 2.2 (range 0.3-20) mm. The SLNB was positive in 27.8 % of patients. Recurrence rates were 53.2 % in SLNB-positive and 17.9 % in SLNB-negative patients (p Melanoma located in the head and neck region (hazard ratio 4.88, p = 0.003) and increasing Breslow thickness (hazard ratio 1.15, p = 0.013) were predictive for distant first site of recurrence in SLNB-negative patients. SLNB-negative patients with a nodular melanoma and ulceration had a recurrence rate of 43.1 %; the site of recurrence was distant in 64 % of these patients. The recurrence rates of SLNB-negative nodular ulcerative melanoma patients approach those of SLNB-positive patients. Stringent follow-up is recommended in this subset of patients.

  13. Frequency of residual melanoma in wide local excision (WLE) specimens after complete excisional biopsy.

    Science.gov (United States)

    Bolshinsky, Vladimir; Lin, Matthew J; Serpell, Jonathan; Leung, Michael; Wolfe, Rory; McLean, Catriona; Kelly, John W

    2016-01-01

    We sought to better understand the role of wide local excision (WLE) in the treatment of cutaneous melanoma by analyzing residual or locally metastatic disease in WLE specimens of melanomas initially diagnosed with a complete excisional biopsy. This was a retrospective review of 807 consecutive WLEs of melanomas diagnosed after complete excisional biopsy. All specimens were reviewed by a single dermatopathologist. Risk of residual or locally metastatic disease was analyzed using univariate and multivariate logistic regression models. In the 807 WLE specimens, further melanoma was found in 34 cases (4.2%; 95% confidence interval [CI] 2.9-5.8). Residual primary melanoma was found in 33 of these. On univariate analysis, features associated with residual or locally metastatic disease were histologic subtype (odds ratio 3.0; 95% CI 1.3-7.1, P = .01) and tumor location (odds ratio 7.3; 95% CI 2.0-26.6, P melanoma remaining in WLE specimens (odds ratio 2.7; 95% CI 1.0-7.3, P = .04). Residual melanoma in WLE specimens after histologically assessed complete excisional biopsy is not uncommon. Patients with lentigo maligna subtype melanomas are most at risk. Our findings indicate that the procedure of WLE is most important therapeutically for its role in controlling the primary tumor, rather than in preventing local metastatic recurrence. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  14. Multiple melanomas after treatment for Hodgkin lymphoma in a non-Dutch p16-Leiden mutation carrier with 2 MC1R high-risk variants.

    Science.gov (United States)

    Figl, Adina; Thirumaran, Ranjit K; Ugurel, Selma; Gast, Andreas; Hemminki, Kari; Kumar, Rajiv; Schadendorf, Dirk

    2007-04-01

    A 19-base pair germline deletion in exon 2 of the CDKN2A (cyclin-dependent kinase inhibitor 2A) gene (Leiden mutation) has been detected in Dutch families with familial melanomas. The penetrance of CDKN2A mutations varies widely and is influenced by environmental and unrelated genetic factors such as variants in the MC1R gene. We describe a 25-year-old German woman who developed 8 invasive melanomas and 6 in situ melanomas after radiation therapy and polychemotherapy for Hodgkin lymphoma. Genetic testing revealed a constitutional CDKN2A Leiden mutation in the proband and her sister, mother, and mother's sister. The proband also carried high-risk MC1R variant alleles R151C and R160W, which she had inherited from her father and her mother, respectively. The less affected mutation carrier sister did not have high-risk MC1R variant alleles. Analysis of DNA from paraffin-embedded tissues showed loss of heterozygosity at CDKN2A loci in all 3 melanomas studied but not in Hodgkin lymphoma. The pedigree revealed several types of cancers on both sides of the family, but no Dutch ancestors were found. No mutations in the CDK4, B-raf, and N-ras genes were detected either in the germline or in tumors from the patient. This study shows the variability of the penetrance of the CDKN2A Leiden mutation within the same family, which could be due to genetic or exogenous factors.

  15. CREDIT RISK. DETERMINATION MODELS

    Directory of Open Access Journals (Sweden)

    MIHAELA GRUIESCU

    2012-01-01

    Full Text Available The internationalization of financial flows and banking and the rapid development of markets have changed the financial sector, causing him to respond with force and imagination. Under these conditions, the concerns of financial and banking institutions, rating institutions are increasingly turning to find the best solutions to hedge risks and maximize profits. This paper aims to present a number of advantages, but also limits the Merton model, the first structural model for modeling credit risk. Also, some are extensions of the model, some empirical research and performance known, others such as state-dependent models (SDM, which together with the liquidation process models (LPM, are two recent efforts in the structural models, show different phenomena in real life.

  16. Systemic disease-induced salivary biomarker profiles in mouse models of melanoma and non-small cell lung cancer.

    OpenAIRE

    Kai Gao; Hui Zhou; Lei Zhang; Jin Wook Lee; Qing Zhou; Shen Hu; Lawrence E Wolinsky; James Farrell; Guido Eibl; David T Wong

    2009-01-01

    Background Saliva (oral fluids) is an emerging biofluid poised for detection of clinical diseases. Although the rationale for oral diseases applications (e.g. oral cancer) is intuitive, the rationale and relationship between systemic diseases and saliva biomarkers are unclear. Methodology/Principal Findings In this study, we used mouse models of melanoma and non-small cell lung cancer and compared the transcriptome biomarker profiles of tumor-bearing mice to those of control mice. Microarray ...

  17. Multivariate analysis of spatial-temporal scales in melanoma prevalence.

    Science.gov (United States)

    Valachovic, Edward; Zurbenko, Igor

    2017-07-01

    Melanoma is a particularly deadly form of skin cancer arising from diverse biological and physical origins, making the characterization and quantification of relationships with recognized risk factors very complex. Melanoma has known associations with ultraviolet light exposure. Natural variations in solar electromagnetic irradiation, length of exposure, and intensity operate on different and therefore uncorrelated time scale frequencies. It is necessary to separate and investigate the principal components, such as the annual and solar cycle components, free from confounding influences. Kolmogorov-Zurbenko spatial filters applied to melanoma prevalence and environmental factors affecting solar irradiation exposure are able to identify and separate the independent space and time scale components of melanoma. Multidimensional analysis in space and time produces significantly improved model fit of what is in effect a linear regression of maps, or motion picture, in different time scales between melanoma rates and prominent factors. The resulting multivariate model coefficients of influence for each unique spatial-temporal melanoma component help quantify the relationships and are valuable to future research and prevention.

  18. Photosensitizing agents and the risk of non-melanoma skin cancer: a population-based case-control study.

    Science.gov (United States)

    Robinson, Sarah N; Zens, Michael S; Perry, Ann E; Spencer, Steven K; Duell, Eric J; Karagas, Margaret R

    2013-08-01

    It is well-known that UV light exposure and a sun-sensitive phenotype are risk factors for the development of non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In this New Hampshire population-based case-control study, we collected data from 5,072 individuals, including histologically confirmed cases of BCC and SCC, and controls via a personal interview to investigate possible associations between photosensitizing medication use and NMSC. After adjustment for potentially confounding factors (e.g., lifetime number of painful sunburns), we found a modest increase in risk of SCC (odds ratio (OR)=1.2, 95% confidence interval (CI)=1.0-1.4) and BCC (OR=1.2, 95% CI=0.9-1.5), in particular early-onset BCC, (≤ 50 years of age) (OR=1.5, 95% CI=1.1-2.1) associated with photosensitizing medication use. For SCC the association was strongest among those with tendency to sunburn rather than tan. We also specifically found associations with BCC, and especially early-onset BCC, and photosensitizing antimicrobials. In conclusion, certain commonly prescribed photosensitizing medications may enhance the risk of developing SCC, especially in individuals with a sun-sensitive phenotype, and may increase the risk of developing BCC and incidence of BCC at a younger age.

  19. Effects of Zeaxanthin on Growth and Invasion of Human Uveal Melanoma in Nude Mouse Model

    Directory of Open Access Journals (Sweden)

    Xiaoliang L. Xu

    2015-01-01

    Full Text Available Uveal melanoma cells were inoculated into the choroid of nude mice and treated with or without intraocular injection of zeaxanthin. After 21 days, mice were sacrificed and the eyes enucleated. Histopathological analysis was performed in hematoxylin and eosin stained frozen sections. Melanoma developed rapidly in the control group (without treatment of zeaxanthin. Tumor-bearing eye mass and tumor mass in the control group were significantly greater than those in zeaxanthin treated group. Melanoma in the controlled eyes occupied a large part of the eye, was epithelioid in morphology, and was with numerous mitotic figures. Scleral perforation and extraocular extension were observed in half of the eyes. Melanomas in zeaxanthin treated eyes were significantly smaller with many necrosis and apoptosis areas and no extraocular extension could be found. Quantitative image analysis revealed that the tumor size was reduced by 56% in eyes treated with low dosages of zeaxanthin and 92% in eyes treatment with high dosages of zeaxanthin, as compared to the controls. This study demonstrated that zeaxanthin significantly inhibits the growth and invasion of human uveal melanoma in nude mice, suggesting that zeaxanthin may be a promising agent to be explored for the prevention and treatment of uveal melanoma.

  20. Timely Healthcare Checkup Catches Melanoma Early

    Science.gov (United States)

    ... Skin Cancer" Articles Skin Cancer Can Strike Anyone / Skin Cancer: Biology, Risk Factors & Treatment / Timely Healthcare Checkup Catches Melanoma Early / NIH Research to Results / Skin and Sun – ...

  1. The role of nitric oxide in melanoma.

    Science.gov (United States)

    Yarlagadda, Keerthi; Hassani, John; Foote, Isaac P; Markowitz, Joseph

    2017-12-01

    Nitric oxide (NO) is a small gaseous signaling molecule that mediates its effects in melanoma through free radical formation and enzymatic processes. Investigations have demonstrated multiple roles for NO in melanoma pathology via immune surveillance, apoptosis, angiogenesis, melanogenesis, and on the melanoma cell itself. In general, elevated levels of NO prognosticate a poor outcome for melanoma patients. However, there are processes where the relative concentration of NO in different environments may also serve to limit melanoma proliferation. This review serves to outline the roles of NO in melanoma development and proliferation. As demonstrated by multiple in vivo murine models and observations from human tissue, NO may promote melanoma formation and proliferation through its interaction via inhibitory immune cells, inhibition of apoptosis, stimulation of pro-tumorigenic cytokines, activation of tumor associated macrophages, alteration of angiogenic processes, and stimulation of melanoma formation itself. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Treatment patterns of adjuvant interferon-α2b for high-risk melanoma: a retrospective study of the Grupo Español Multidisciplinar de Melanoma - Prima study.

    Science.gov (United States)

    Espinosa, Enrique; Soriano, Virtudes; Malvehy, Josep; Berrocal, Alfonso; Martínez de Prado, Purificación; Quindós, María; Soria, Ainara; Márquez-Rodas, Iván; Palacio, Isabel; Cerezuela, Pablo; López-Vivanco, Guillermo; Alonso, Lorenzo; Samaniego, Elia; Ballesteros, Ana; Puértolas, Teresa; Díaz-Beveridge, Rodrigo; de la Cruz-Merino, Luis; López Castro, Rafael; López López, Rafael; Stevinson, Kendall; Del Barrio, Patricia; Tornamira, Maria V; Guillém, Vicente; Martín-Algarra, Salvador

    2016-06-01

    Adjuvant interferon-α2b (IFN-α2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-α2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-α2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-α2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN-α2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN-α2b treatment provided a benefit consistent with that described previously.

  3. The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma.

    Directory of Open Access Journals (Sweden)

    Travis McMurphy

    Full Text Available Environmental and genetic activation of a brain-adipocyte axis inhibits cancer progression. Leptin is the primary peripheral mediator of this anticancer effect in a mouse model of melanoma. In this study we assessed the effect of a leptin receptor antagonist on melanoma progression. Local administration of a neutralizing nanobody targeting the leptin receptor at low dose adjacent to tumor decreased tumor mass with no effects on body weight or food intake. In contrast, systemic administration of the nanobody failed to suppress tumor growth. Daily intraperitoneal injection of high-dose nanobody led to weight gain, hyperphagia, increased adiposity, hyperleptinemia, and hyperinsulinemia, and central effects mimicking leptin deficiency. The blockade of central actions of leptin by systemic delivery of nanobody may compromise its anticancer effect, underscoring the need to develop peripherally acting leptin antagonists coupled with efficient cancer-targeting delivery.

  4. The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma.

    Science.gov (United States)

    McMurphy, Travis; Xiao, Run; Magee, Daniel; Slater, Andrew; Zabeau, Lennart; Tavernier, Jan; Cao, Lei

    2014-01-01

    Environmental and genetic activation of a brain-adipocyte axis inhibits cancer progression. Leptin is the primary peripheral mediator of this anticancer effect in a mouse model of melanoma. In this study we assessed the effect of a leptin receptor antagonist on melanoma progression. Local administration of a neutralizing nanobody targeting the leptin receptor at low dose adjacent to tumor decreased tumor mass with no effects on body weight or food intake. In contrast, systemic administration of the nanobody failed to suppress tumor growth. Daily intraperitoneal injection of high-dose nanobody led to weight gain, hyperphagia, increased adiposity, hyperleptinemia, and hyperinsulinemia, and central effects mimicking leptin deficiency. The blockade of central actions of leptin by systemic delivery of nanobody may compromise its anticancer effect, underscoring the need to develop peripherally acting leptin antagonists coupled with efficient cancer-targeting delivery.

  5. Sentinel node positive melanoma patients: prediction and prognostic significance of nonsentinel node metastases and development of a survival tree model.

    Science.gov (United States)

    Wiener, Martin; Acland, Katharine M; Shaw, Helen M; Soong, Seng-Jaw; Lin, Hui-Yi; Chen, Dung-Tsa; Scolyer, Richard A; Winstanley, Julie B; Thompson, John F

    2010-08-01

    Completion lymph node dissection (CLND) following positive sentinel node biopsy (SNB) for melanoma detects additional nonsentinel node (NSN) metastases in approximately 20% of cases. This study aimed to establish whether NSN status can be predicted, to determine its effect on survival, and to develop survival tree models for the sentinel node (SN) positive population. Sydney Melanoma Unit (SMU) patients with at least 1 positive SN, meeting inclusion criteria and treated between October 1992 and June 2005, were identified from the Unit database. Survival characteristics, potential predictors of survival, and NSN status were assessed using the Kaplan-Meier method, Cox regression model, and logistic regression analyses, respectively. Classification tree analysis was performed to identify groups with distinctly different survival characteristics. A total of 323 SN-positive melanoma patients met the inclusion criteria. On multivariate analysis, age, gender, primary tumor thickness, mitotic rate, number of positive NSNs, or total number of positive nodes were statistically significant predictors of survival. NSN metastasis, found at CLND in 19% of patients, was only predicted to a statistically significant degree by ulceration. Multivariate analyses demonstrated that survival was more closely related to number of positive NSNs than total number of positive nodes. Classification tree analysis revealed 4 prognostically distinct survival groups. Patients with NSN metastases could not be reliably identified prior to CLND. Prognosis following CLND was more closely related to number of positive NSNs than total number of positive nodes. Classification tree analysis defined distinctly different survival groups more accurately than use of single-factor analysis.

  6. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers.

    Science.gov (United States)

    Mercer, Louise K; Askling, Johan; Raaschou, Pauline; Dixon, William G; Dreyer, Lene; Hetland, Merete Lund; Strangfeld, Anja; Zink, Angela; Mariette, Xavier; Finckh, Axel; Canhao, Helena; Iannone, Florenzo; Zavada, Jakub; Morel, Jacques; Gottenberg, Jacques-Eric; Hyrich, Kimme L; Listing, Joachim

    2017-02-01

    Some studies have reported a possible association between exposure to tumour necrosis factor (TNF) inhibitors and an increased risk of melanoma. The aim of this study was to investigate the incidence of invasive cutaneous melanomas in patients with rheumatoid arthritis (RA) treated with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy. Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country-specific general population of each register as reference, age, sex and calendar year standardised incidence ratios (SIRs) of invasive histology-confirmed cutaneous melanoma were calculated within each register. Pooled SIR and incidence rate ratios (IRRs) comparing biologic cohorts to biologic-naïve were calculated across countries by taking the size of the register into account. Overall 130 315 RA patients with a mean age of 58 years contributing 579 983 person-years were available for the analysis and 287 developed a first melanoma. Pooled SIRs for biologic-naïve, TNFi and rituximab-exposed patients were 1.1 (95% CI 0.9 to 1.4), 1.2 (0.99 to 1.6) and 1.3 (0.6 to 2.6), respectively. Incidence rates in tocilizumab and abatacept-exposed patients were also not significantly increased. IRR versus biologic-naïve patients were: TNFi 1.1 (95% CI 0.8 to 1.6); rituximab 1.2 (0.5 to 2.9). This large European collaborative project did not confirm an overall increased risk of melanoma following exposure to TNFi. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Health-related quality of life in patients with high-risk melanoma randomised in the Nordic phase 3 trial with adjuvant intermediate-dose interferon alfa-2b

    DEFF Research Database (Denmark)

    Brandberg, Y; Aamdal, S; Bastholt, Lars

    2012-01-01

    To compare health-related quality of life (HRQoL) and side-effects in patients with high-risk melanoma participating in a randomised phase III trial of adjuvant interferon alfa-2b (IFN).......To compare health-related quality of life (HRQoL) and side-effects in patients with high-risk melanoma participating in a randomised phase III trial of adjuvant interferon alfa-2b (IFN)....

  8. Whole Body Microwave Irradiation for Improved Dacarbazine Therapeutical Action in Cutaneous Melanoma Mouse Model

    Directory of Open Access Journals (Sweden)

    Monica Neagu

    2013-01-01

    Full Text Available A cutaneous melanoma mouse model was used to test the efficacy of a new therapeutical approach that uses low doses of cytostatics in conjunction with mild whole body microwave exposure of 2.45 GHz in order to enhance cytostatics antitumoral effect. Materials and Methods. A microwave exposure system for C57BL/6 mouse whole body microwave irradiation was designed; groups of 40 mice (males and females bearing experimental tumours were subjected to a combined therapy comprising low doses of dacarbazine in combination with mild whole body irradiation. Clinical parameters and serum cytokine testing using xMAP technology were performed. Results. The group that was subjected to combined therapy, microwave and cytostatic, had the best clinical evolution in terms of overall survival, tumour volume, and metastatic potential. At day 14 the untreated group had 100% mortality, while in the combined therapy group 40% of mice were surviving. Quantifying serum IL-1β, IL-6, IL-10, IL-12 (p70, IFN-γ, GM-CSF, TNF-α, MIP-1α, MCP-1, and KC during tumorigenesis and therapy found that the combined experimental therapy decreases all the inflammatory cytokines, except chemokine MCP-1 that was found increased, suggesting an increase of the anti-tumoral immune response triggered by the combined therapy. The overall metastatic process is decreased in the combined therapy group.

  9. Nanotechnologies: Risk assessment model

    Science.gov (United States)

    Giacobbe, F.; Monica, L.; Geraci, D.

    2009-05-01

    The development and use of nanomaterials has grown widely in the last years. Hence, it is necessary to carry out a careful and aimed risk assessment for the safety of the workers. The objective of this research is a specific assessment model finalized to the workplaces where the personnel work manipulating nanoparticles. This model mainly takes into account the number of exposed workers, the dimensions of particles, the information found in the safety data sheets and the uncertainties about the danger level coming from the exposition to nanomaterials. The evaluation algorithm considers the normal work conditions, the abnormal (e.g. breakdown air filter) and emergency situations (e.g. package cracking). It has been necessary to define several risk conditions in order to quantify the risk by increasing levels ("low", "middle" and "high" level). Each level includes appropriate behavioural procedures. In particular for the high level, it is advisable that the user carries out urgent interventions finalized to reduce the risk level (e.g. the utilization of vacuum box for the manipulation, high efficiency protection PPE, etc). The model has been implemented in a research laboratory where titanium dioxide and carbon nanotubes are used. The outcomes taken out from such specific evaluation gave a risk level equal to middle.

  10. Nanotechnologies: Risk assessment model

    International Nuclear Information System (INIS)

    Giacobbe, F; Monica, L; Geraci, D

    2009-01-01

    The development and use of nanomaterials has grown widely in the last years. Hence, it is necessary to carry out a careful and aimed risk assessment for the safety of the workers. The objective of this research is a specific assessment model finalized to the workplaces where the personnel work manipulating nanoparticles. This model mainly takes into account the number of exposed workers, the dimensions of particles, the information found in the safety data sheets and the uncertainties about the danger level coming from the exposition to nanomaterials. The evaluation algorithm considers the normal work conditions, the abnormal (e.g. breakdown air filter) and emergency situations (e.g. package cracking). It has been necessary to define several risk conditions in order to quantify the risk by increasing levels ('low', 'middle' and 'high' level). Each level includes appropriate behavioural procedures. In particular for the high level, it is advisable that the user carries out urgent interventions finalized to reduce the risk level (e.g. the utilization of vacuum box for the manipulation, high efficiency protection PPE, etc). The model has been implemented in a research laboratory where titanium dioxide and carbon nanotubes are used. The outcomes taken out from such specific evaluation gave a risk level equal to middle.

  11. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair...... colour and skin type were found to be independent risk factors for cutaneous malignant melanoma; red hair vs. black/brown: OR >9.7, blond hair vs. brown/black: OR = 2.4, and skin type 11 vs. type IV: OR=2.0. There were no gender-related differences in risk factors for basal cell carcinoma and cutaneous......To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...

  12. Systemic disease-induced salivary biomarker profiles in mouse models of melanoma and non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Kai Gao

    2009-06-01

    Full Text Available Saliva (oral fluids is an emerging biofluid poised for detection of clinical diseases. Although the rationale for oral diseases applications (e.g. oral cancer is intuitive, the rationale and relationship between systemic diseases and saliva biomarkers are unclear.In this study, we used mouse models of melanoma and non-small cell lung cancer and compared the transcriptome biomarker profiles of tumor-bearing mice to those of control mice. Microarray analysis showed that salivary transcriptomes were significantly altered in tumor-bearing mice vs. controls. Significant overlapping among transcriptomes of mouse tumors, serum, salivary glands and saliva suggests that salivary biomarkers have multiple origins. Furthermore, we identified that the expression of two groups of significantly altered transcription factors (TFs Runx1, Mlxipl, Trim30 and Egr1, Tbx1, Nr1d1 in salivary gland tissue of melanoma-bearing mice can potentially be responsible for 82.6% of the up-regulated gene expression and 62.5% of the down-regulated gene expression, respectively, in the saliva of melanoma-bearing mice. We also showed that the ectopic production of nerve growth factor (NGF in the melanoma tumor tissue as a tumor-released mediator can induce expression of the TF Egr-1 in the salivary gland.Taken together, our data support the conclusion that upon systemic disease development, significant changes can occur in the salivary biomarker profile. Although the origins of the disease-induced salivary biomarkers may be both systemic and local, stimulation of salivary gland by mediators released from remote tumors plays an important role in regulating the salivary surrogate biomarker profiles.

  13. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...... the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases...... were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair...

  14. CDKN2A region polymorphism and genetic susceptibility to melanoma in the melim swine model of familial melanoma

    Czech Academy of Sciences Publication Activity Database

    Chalony, C.; Renard, C.; Naulleas, V. S.; Crechet, F.; Leplatt, J. J.; Tricaud, Y.; Horák, Vratislav; Gruand, J.; Le Roy, P.; Frelat, G.; Geffrotin, C.

    2003-01-01

    Roč. 103, č. 5 (2003), s. 631-635 ISSN 0020-7136 R&D Projects: GA AV ČR KSK5011112; GA ČR GA524/01/0162; GA AV ČR IBS5045113 Institutional research plan: CEZ:AV0Z5045916 Keywords : melim swine model Subject RIV: ED - Physiology Impact factor: 4.375, year: 2003

  15. Genetic alterations and markers of melanoma

    Directory of Open Access Journals (Sweden)

    N. N. Mazurenko

    2014-01-01

    Full Text Available Melanoma remains the most deadly form of malignant skin disease with high risk of metastases. Metastatic melanoma is prognostic highly unfavorable and resistant to traditional chemotherapy and biologic treatment. There is a great progress in understanding of the molecular mechanisms underlying melanoma initiation and progression. The external (ultraviolet irradiation and internal (genetic factors are involved in melanoma genesis. 5–14 % of melanoma cases occur in familial context due to genetic predisposition risk factors. Among them rare germinal mutations in the cell cycle genes regulators CDKN2A and CDK4 and in the master gene of melanocyte homeostasis MITF, as well as single nucleotide polymorphisms of several low-penetrated genes, namely MC1R, have been identified. The main cell signaling pathways and oncogene driver mutations are involved in melanoma pathogenesis. RAS / RAF / MEK / ERK cascade is hyperactivated in 75 % of cutaneous melanoma cases. Activation of PI3K / AKT / mTOR signaling pathway is important for melanoma progression. Recent studies revealed that melanomas are genetically and phenotypically heterogeneous tumors. Spectrum of chromosomal alterations and activating mutations corresponding to tumor molecular portraits varies in melanomas of different location. Most of cutaneous melanomas contain BRAF (50 % or NRAS (20 % mutations, and NRAS mutations occur on chronically sun-exposed skin. Activating KIT mutations have been reported in approximately 20–30 % of certain subtypes of melanoma, including acral and mucosal, and melanoma that develop on photodamaged skin. Cutaneous metastatic melanoma derive from preexisting nevi in 25 % of cases, molecular mechanisms of nevi malignization are discussed. Deepsequencing approaches of melanoma samples of different melanoma types highlighted new melanoma driver genes, that are damaged due to tumorigenic effects of ultraviolet: PPP6C, RAC1, SNX31, TACC1 and STK19. The

  16. Antitumour responses induced by a cell-based Reovirus vaccine in murine lung and melanoma models

    International Nuclear Information System (INIS)

    Campion, Ciorsdan A.; Soden, Declan; Forde, Patrick F.

    2016-01-01

    The ever increasing knowledge in the areas of cell biology, the immune system and the mechanisms of cancer are allowing a new phase of immunotherapy to develop. The aim of cancer vaccination is to activate the host immune system and some success has been observed particularly in the use of the BCG vaccine for bladder cancer as an immunostimulant. Reovirus, an orphan virus, has proven itself as an oncolytic virus in vitro and in vivo. Over 80 % of tumour cell lines have been found to be susceptible to Reovirus infection and it is currently in phase III clinical trials. It has been shown to induce immune responses to tumours with very low toxicities. In this study, Reovirus was examined in two main approaches in vivo, in mice, using the melanoma B16F10 and Lewis Lung Carcinoma (LLC) models. Initially, mice were treated intratumourally (IT) with Reovirus and the immune responses determined by cytokine analysis. Mice were also vaccinated using a cell-based Reovirus vaccine and subsequently exposed to a tumourigenic dose of cells (B16F10 or LLC). Using the same cell-based Reovirus vaccine, established tumours were treated and subsequent immune responses and virus retrieval investigated. Upregulation of several cytokines was observed following treatment and replication-competent virus was also retrieved from treated tumours. Varying levels of cytokine upregulation were observed and no replication-competent virus was retrieved in vaccine-treated mice. Prolongation of survival and delayed tumour growth were observed in all models and an immune response to Reovirus, either using Reovirus alone or a cell-based vaccine was also observed in all mice. This study provides evidence of immune response to tumours using a cell-based Reovirus vaccine in both tumour models investigated, B16F10 and LLC, cytokine induction was observed with prolongation of survival in almost all cases which may suggest a new method for using Reovirus in the clinic

  17. Serum microRNAs as biomarkers for recurrence in melanoma

    Directory of Open Access Journals (Sweden)

    Friedman Erica B

    2012-08-01

    Full Text Available Abstract Background Identification of melanoma patients at high risk for recurrence and monitoring for recurrence are critical for informed management decisions. We hypothesized that serum microRNAs (miRNAs could provide prognostic information at the time of diagnosis unaccounted for by the current staging system and could be useful in detecting recurrence after resection. Methods We screened 355 miRNAs in sera from 80 melanoma patients at primary diagnosis (discovery cohort using a unique quantitative reverse transcription-PCR (qRT-PCR panel. Cox proportional hazard models and Kaplan-Meier recurrence-free survival (RFS curves were used to identify a miRNA signature with prognostic potential adjusting for stage. We then tested the miRNA signature in an independent cohort of 50 primary melanoma patients (validation cohort. Logistic regression analysis was performed to determine if the miRNA signature can determine risk of recurrence in both cohorts. Selected miRNAs were measured longitudinally in subsets of patients pre-/post-operatively and pre-/post-recurrence. Results A signature of 5 miRNAs successfully classified melanoma patients into high and low recurrence risk groups with significant separation of RFS in both discovery and validation cohorts (p = 0.0036, p = 0.0093, respectively. Significant separation of RFS was maintained when a logistic model containing the same signature set was used to predict recurrence risk in both discovery and validation cohorts (p  Conclusion Our data demonstrate that serum miRNAs can improve accuracy in identifying primary melanoma patients with high recurrence risk and in monitoring melanoma tumor burden over time.

  18. A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma

    Science.gov (United States)

    Yokoyama, Satoru; Woods, Susan L.; Boyle, Glen M.; Aoude, Lauren G.; MacGregor, Stuart; Zismann, Victoria; Gartside, Michael; Cust, Anne E.; Haq, Rizwan; Harland, Mark; Taylor, John C.; Duffy, David L.; Holohan, Kelly; Dutton-Regester, Ken; Palmer, Jane M.; Bonazzi, Vanessa; Stark, Mitchell S.; Symmons, Judith; Law, Matthew H.; Schmidt, Christopher; Lanagan, Cathy; O’Connor, Linda; Holland, Elizabeth A.; Schmid, Helen; Maskiell, Judith A.; Jetann, Jodie; Ferguson, Megan; Jenkins, Mark A.; Kefford, Richard F.; Giles, Graham G.; Armstrong, Bruce K.; Aitken, Joanne F.; Hopper, John L.; Whiteman, David C.; Pharoah, Paul D.; Easton, Douglas F.; Dunning, Alison M.; Newton-Bishop, Julia A.; Montgomery, Grant W.; Martin, Nicholas G.; Mann, Graham J.; Bishop, D. Timothy; Tsao, Hensin; Trent, Jeffrey M.; Fisher, David E.; Hayward, Nicholas K.; Brown, Kevin M.

    2012-01-01

    So far, two familial melanoma genes have been identified, accounting for a minority of genetic risk in families. Mutations in CDKN2A account for approximately 40% of familial cases1, and predisposing mutations in CDK4 have been reported in a very small number of melanoma kindreds2. To identify other familial melanoma genes, here we conducted whole-genome sequencing of probands from several melanoma families, identifying one individual carrying a novel germline variant (coding DNA sequence c.G1075A; protein sequence p.E318K; rs149617956) in the melanoma-lineage-specific oncogene microphthalmia-associated transcription factor (MITF). Although the variant co-segregated with melanoma in some but not all cases in the family, linkage analysis of 31 families subsequently identified to carry the variant generated a log odds ratio (lod) score of 2.7 under a dominant model, indicating E318K as a possible intermediate risk variant. Consistent with this, the E318K variant was significantly associated with melanoma in a large Australian case–control sample. Likewise, it was similarly associated in an independent case–control sample from the United Kingdom. In the Australian sample, the variant allele was significantly over-represented in cases with a family history of melanoma, multiple primary melanomas, or both. The variant allele was also associated with increased naevus count and non-blue eye colour. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets. These data indicate that MITF is a melanoma-predisposition gene and highlight the utility of whole-genome sequencing to identify novel rare variants associated with disease susceptibility. PMID:22080950

  19. Inhibition of melanoma development in the Nras((Q61K)) ::Ink4a(-/-) mouse model by the small molecule BI-69A11.

    Science.gov (United States)

    Feng, Yongmei; Lau, Eric; Scortegagna, Marzia; Ruller, Chelsea; De, Surya K; Barile, Elisa; Krajewski, Stan; Aza-Blanc, Pedro; Williams, Roy; Pinkerton, Anthony B; Jackson, Michael; Chin, Lynda; Pellecchia, Maurizio; Bosenberg, Marcus; Ronai, Ze'ev A

    2013-01-01

    To date, there are no effective therapies for tumors bearing NRAS mutations, which are present in 15-20% of human melanomas. Here we extend our earlier studies where we demonstrated that the small molecule BI-69A11 inhibits the growth of melanoma cell lines. Gene expression analysis revealed the induction of interferon- and cell death-related genes that were associated with responsiveness of melanoma cell lines to BI-69A11. Strikingly, the administration of BI-69A11 inhibited melanoma development in genetically modified mice bearing an inducible form of activated Nras and a deletion of the Ink4a gene (Nras((Q61K)) ::Ink4a(-/-) ). Biweekly administration of BI-69A11 starting at 10 weeks or as late as 24 weeks after the induction of mutant Nras expression inhibited melanoma development (100 and 36%, respectively). BI-69A11 treatment did not inhibit the development of histiocytic sarcomas, which constitute about 50% of the tumors in this model. BI-69A11-resistant Nras((Q61K)) ::Ink4a(-/-) tumors exhibited increased CD45 expression, reflective of immune cell infiltration and upregulation of gene networks associated with the cytoskeleton, DNA damage response, and small molecule transport. The ability to attenuate the development of NRAS mutant melanomas supports further development of BI-69A11 for clinical assessment. © 2012 John Wiley & Sons A/S.

  20. Models of Credit Risk Measurement

    OpenAIRE

    Hagiu Alina

    2011-01-01

    Credit risk is defined as that risk of financial loss caused by failure by the counterparty. According to statistics, for financial institutions, credit risk is much important than market risk, reduced diversification of the credit risk is the main cause of bank failures. Just recently, the banking industry began to measure credit risk in the context of a portfolio along with the development of risk management started with models value at risk (VAR). Once measured, credit risk can be diversif...

  1. Comparative Aspects of Canine Melanoma

    Directory of Open Access Journals (Sweden)

    Adriana Tomoko Nishiya

    2016-02-01

    Full Text Available Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are other common locations for these neoplasms. The aim of this review is to report etiological, epidemiological, pathological, and molecular aspects of melanomas in dogs. Furthermore, the particular biological behaviors of these tumors in the different body locations are shown. Insights into the therapeutic approaches are described. Surgery, chemotherapy, radiotherapy, immunotherapy, and the outcomes after these treatments are presented. New therapeutic perspectives are also depicted. All efforts are geared toward better characterization and control of malignant melanomas in dogs, for the benefit of these companion animals, and also in an attempt to benefit the treatment of human melanomas.

  2. Infrared imaging of primary melanomas reveals hints of regional and distant metastases.

    Science.gov (United States)

    Wald, N; Goormaghtigh, E

    2015-04-07

    Melanoma is the deadliest form of skin cancer. Metastatic melanomas are resistant to almost all existing adjuvant therapies such as chemotherapy and radiotherapy, so detection of metastases remains a challenge, and no biomarkers are currently available to detect primary tumors with the highest risk of metastasis. Results presented in this paper show that Fourier Transform Infrared (FTIR) imaging of histological sections followed by supervised partial least squares discriminant analysis (PLS-DA) can accurately (>90%) identify the main cell types commonly found in melanoma tumors. Here we define six cell types: melanoma cells, erythrocytes, connective tissue (includes blood vessel walls, dermis and collagen regions), keratinocytes, lymphocytes and necrotic cells. Interestingly, more than 98% of the melanoma cells are correctly identified. The spectra of the cells identified as melanomas were then further analyzed. First, we compared melanoma cells in primary tumors (from 26 patients) with melanoma cells from metastases (from 25 patients). Neither supervised nor unsupervised analyses revealed any significant difference. Similarly, we found no significant correlation between the infrared spectra of melanoma cells and the number of proliferative cells assessed by Ki67 immunostaining. Finally, we compared the infrared spectra of primary tumors from patients diagnosed at different stages of the disease. Infrared spectroscopy was capable of pointing out differences between primary tumors of patients at stage I or II and patients at stage III or IV, even by unsupervised analysis. We then developed a supervised PLS-DA model capable of predicting whether tumor cells belonged to one of the two aggregated disease stage groups. The model predicted a high rate of true positives (sensitivity of 88.9%) and a good rate of true negatives (specificity of 70.6%) in external validation. These results demonstrate that infrared spectroscopy can be used to help identify melanoma

  3. Modelling survival after treatment of intraocular melanoma using artificial neural networks and Bayes theorem

    International Nuclear Information System (INIS)

    Taktak, Azzam F G; Fisher, Anthony C; Damato, Bertil E

    2004-01-01

    This paper describes the development of an artificial intelligence (AI) system for survival prediction from intraocular melanoma. The system used artificial neural networks (ANNs) with five input parameters: coronal and sagittal tumour location, anterior tumour margin, largest basal tumour diameter and the cell type. After excluding records with missing data, 2331 patients were included in the study. These were split randomly into training and test sets. Date censorship was applied to the records to deal with patients who were lost to follow-up and patients who died from general causes. Bayes theorem was then applied to the ANN output to construct survival probability curves. A validation set with 34 patients unseen to both training and test sets was used to compare the AI system with Cox's regression (CR) and Kaplan-Meier (KM) analyses. Results showed large differences in the mean 5 year survival probability figures when the number of records with matching characteristics was small. However, as the number of matches increased to >100 the system tended to agree with CR and KM. The validation set was also used to compare the system with a clinical expert in predicting time to metastatic death. The rms error was 3.7 years for the system and 4.3 years for the clinical expert for 15 years survival. For <10 years survival, these figures were 2.7 and 4.2, respectively. We concluded that the AI system can match if not better the clinical expert's prediction. There were significant differences with CR and KM analyses when the number of records was small, but it was not known which model is more accurate

  4. A genome-wide scan for familial melanoma in the MeLiM swine model

    Czech Academy of Sciences Publication Activity Database

    Horák, Vratislav; Geffrotin, C.; Crechet, F.; LeChalony, C.; LeRoy, P.; Leplat, J. J.; Renard, C.; Gruand, J.; Milan, D.; Iannuccelli, N.; Tricaud, Y.; Frelat, G.; Vincent-Naulleau, S.

    2002-01-01

    Roč. 15, č. 9 (2002), s. 64 ISSN 0893-5785. [International Pigment Cell Conference /18./. 09.09.2002-13.09.2002, Egmond aan Zee] Institutional research plan: CEZ:AV0Z5045916 Keywords : melanoma Subject RIV: EB - Genetics ; Molecular Biology

  5. Innate immunity based cancer immunotherapy: B16-F10 murine melanoma model

    Czech Academy of Sciences Publication Activity Database

    Caisová, V.; Vieru, A.; Kumžáková, Z.; Glaserová, S.; Husniková, H.; Vácová, N.; Krejčová, G.; Paďouková, L.; Jochmanová, I.; Wolf, K. I.; Chmelař, J.; Kopecký, Jan; Ženka, J.

    2016-01-01

    Roč. 16, č. 1 (2016), č. článku 940. ISSN 1471-2407 Institutional support: RVO:60077344 Keywords : cancer immunotherapy * innate immunity * melanoma * neutrophils * resiquimod * mannan * phagocytosis Subject RIV: EC - Immunology Impact factor: 3.288, year: 2016

  6. Biochemical characterization of a new melanoma model-the minipig MeLim strain

    Czech Academy of Sciences Publication Activity Database

    Borovanský, J.; Horák, Vratislav; Elleder, M.; Fortýn, Karel; Smit, P. M.; Kolb, A. M.

    2003-01-01

    Roč. 13, - (2003), s. 543-548 ISSN 0960-8931 R&D Projects: GA AV ČR KSK5011112; GA ČR GA524/01/0162 Institutional research plan: CEZ:AV0Z5045916 Keywords : melanoma * tyrosinase * devitalization Subject RIV: FD - Oncology ; Hematology Impact factor: 2.190, year: 2003

  7. Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Eshini Perera

    2013-12-01

    Full Text Available Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery, treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar.

  8. Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs

    Directory of Open Access Journals (Sweden)

    Floor M. Garritsen

    2017-03-01

    Full Text Available There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC, including basal cell carcinoma and squamous cell carcinoma (SCC, in patients with atopic dermatitis (AD treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the University Medical Center Utrecht and Groningen, the Netherlands, were analysed. NMSC after oral immunosuppressive treatment was reported in 18 patients (3.2%. The standardized incidence ratio for developing SCC was 13.1 (95% confidence interval (95% CI 6.5–19.7. Patients developing NMSC were older at the start of therapy (p<0.001 and data lock (p<0.001 compared with patients without NMSC. No significant differences were found in sex, cumulative days of oral immunosuppressive drugs and follow-up between these groups (p=0.42, p=0.88, and p=0.34, respectively. In interpreting these results it is important to include other factors, such as lack of association between treatment duration and tumour development and the long interval between treatment discontinuation and tumour development in some patients.

  9. P11-3: Case Report: Early Detection of Melanoma with Sequential Digital Dermoscopy in a High Risk Patient

    OpenAIRE

    Cinotti*, Elisa; Perrot, Jean-Luc; Labeille, Bruno; Thuret, Gilles; Grivet, Damien; Gain, Philippe; Cambazard, Fr?d?ric; Mart?n*, Ignacio G?mez; Fern?ndez, Sara Moreno; Vallverd?, Ramon M Pujol; Tigell, Sonia Segura; Takigami*, Caroline M.; Gamboa, Mauricio; Chavez-Bourgeois, Marion; Aguilera, Paula

    2015-01-01

    Introduction: Blue nevi are ectopic collections of dermal melanocytes present as solitary lesions, but multiple lesions may occur. They are grouped in a circumscribed area or, in rare cases, disseminated. Multiple blue nevi may present a diagnostic challenge and metastatic melanoma must be ruled out. Case 1: A 65-year-old Caucasian man with personal history of in situ melanoma on the trunk 8 years ago, was referred to evaluate multiple, agminated, dark brown macules adjacent to the balano-pre...

  10. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...... carcinoma and 174 matched controls, and 168 cases with cutaneous malignant melanoma and 176 matched controls. Controls were matched on age, gender and place of residence. Subjects indicated their hair colour before 7 years of age, and at 25 years of age and their skin phototype. Interviewers assessed...... the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases...

  11. Therapeutic Efficacy of a {sup 188}Re-Labeled {alpha}-Melanocyte-Stimulating Hormone Peptide Analog in Murine and Human Melanoma-Bearing Mouse Models

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yubin; Owen, Nellie K.; Fisher, Darrell R.; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-01-01

    The purpose of this study was to examine the therapeutic efficacy of {sup 188}Re-(Arg{sup 11})CCMSH in the B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. Method: (Arg11)CCMSH was synthesized and labeled with {sup 188}Re to form {sup 188}Re-(Agr{sup 11})CCMSH. B16/F1 melanoma tumor bearing mice were administrated with 200 Ci, 600 Ci and 2x400 Ci of {sup 188}Re-(Arg{sup 11})CCMSH via the tail vein, respectively. TXM13 melanoma tumor hearing mice were separately injected with 600 Ci, 2x400 Ci and 1000 Ci of 100Re-(Arg{sup 11})CCMSH through the tail vein. Two groups of 10 mice bearing either B16/F1 or TXM13 tumors were injected with saline as untreated controls. Results: In contrast to the untreated control group, {sup 188}Re(Arg11)CCMSH yielded rapid and lasting therapeutic effects in the treatment groups with either B16/F1 or TXM13 tumors. The tumor growth rate was reduced and the survival rate was prolonged in the treatment groups. Treatment with 2x400 Ci of {sup 188}Re-Arg{sup 11}CCMSH significantly extended the mean life of B16/F1 tumor mice (p<0.05), while the mean life of TXm13 tumor mice was significantly prolonged after treatment with 600 Ci and 1000 Ci doses of {sup 188}Re-(Arg{sup 11})CCMSH (p<0.05 High-dose {sup 188}Re-(Arg{sup 11}))CCMSH produced no observed normal-tissue toxicity. Conclusions: The therapy study results revealed that {sup 188}Re-Arg11 CCMSH yielded significant therapeutic effects in both B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. {sup 188}Re-(Arg{sup 11})CCMSH appears to be a promising radiolabeled peptide for targeted radionuclide therapy of melanoma.

  12. Uveal Melanoma

    International Nuclear Information System (INIS)

    Papastefanou, V. P.; Cohen, V. M. L.; Cohen, V. M. L.

    2011-01-01

    Uveal melanoma is the most common primary intraocular malignancy and the leading primary intraocular disease which can be fatal in adults. In this paper epidemiologic, pathogenetic, and clinical aspects of uveal melanoma are discussed. Despite the advance in local ocular treatments, there has been no change in patient survival for three decades. Development of metastases affects prognosis significantly. Current survival rates, factors predictive of metastatic potential and metastatic screening algorithms are discussed. Proposed and emerging treatments for uveal melanoma metastases are also overviewed. Current advances in genetics and cytogenetics have provided a significant insight in tumours with high metastatic potential and the molecular mechanisms that underlie their development. Biopsy of those lesions may prove to be important for prognostication and to allow further research into genetic mutations and potential new therapeutic targets in the future

  13. Further assessment of exome-wide UVR footprints in melanoma and their possible relevance.

    Science.gov (United States)

    Mukhopadhyay, Pamela; Roberts, James A; Walker, Graeme J

    2017-06-01

    C>T substitutions at dipyrimidine sites dominate the melanoma genome. We recently analyzed the exomes of spontaneous and neonatal UVR-induced murine melanomas, noting a dramatic change in the genomic footprint at C>T substitutions in the latter. Here we re-analyzed published exome-wide footprints in human melanomas stratified in terms of likely previous sun exposure. Acral and mucosal melanomas were heterogeneous in terms of base substitution types, but most C>Ts occurred in the context of 3'G, probably resulting from spontaneous deamination of the cytosine. C>Ts in sun-exposed melanomas were statistically different from acral/mucosal lesions only in preferring an adjacent 5'T and 3'C. Pyrimidine dimer adducts can form between any pyrimidine (TT, TC, CT, CC). Hence in melanoma C>Ts are overwhelmingly induced at TC or CC photoproducts, or, there are peculiarities in DNA repair that favor the mutation of cytosines with these two pyrimidines adjacent. If melanoma UVR footprints at C>Ts reflect a specific dimer type (eg, 6-4 photoproduct or cyclobutane pyrimidine dimer), these could be removed post UVR, for instance using photolyases, to potentially reduce melanoma risk. If specific modes of DNA repair and/or replication cause these footprints, methodically downregulating selected DNA polymerases in UVR-induced animal models of melanoma, combined with exome sequencing, could begin to assess this. Finally, a preponderance of TpCpC as opposed to NpCpG at C>Ts exome-wide is likely to be a good indicator of whether a melanoma has incurred even a small amount of sun damage. This information will assist epidemiological studies in predicting individual levels of sun exposure. © 2017 Wiley Periodicals, Inc.

  14. Preappointment testing for BRAF/KIT mutation in advanced melanoma: a model in molecular data delivery for individualized medicine.

    Science.gov (United States)

    Mounajjed, Taofic; Brown, Char L; Stern, Therese K; Bjorheim, Annette M; Bridgeman, Andrew J; Rumilla, Kandelaria M; McWilliams, Robert R; Flotte, Thomas J

    2014-11-01

    The emergence of individualized medicine is driven by developments in precision diagnostics, epitomized by molecular testing. Because treatment decisions are being made based on such molecular data, data management is gaining major importance. Among data management challenges, creating workflow solutions for timely delivery of molecular data has become pivotal. This study aims to design and implement a scalable process that permits preappointment BRAF/KIT mutation analysis in melanoma patients, allowing molecular results necessary for treatment plans to be available before the patient's appointment. Process implementation aims to provide a model for efficient molecular data delivery for individualized medicine. We examined the existing process of BRAF/KIT testing in melanoma patients visiting our institution for oncology consultation. We created 5 working groups, each designing a specific segment of an alternative process that would allow preappointment BRAF/KIT testing and delivery of results. Data were captured and analyzed to evaluate the success of the alternative process. For 1 year, 35 (59%) of 55 patients had prior BRAF/KIT testing. The remaining 20 patients went through the new process of preappointment testing; results were available at the time of appointment for 12 patients (overall preappointment results availability, 85.5%). The overall process averaged 13.4 ± 4.7 days. In conclusion, we describe the successful implementation of a scalable workflow solution that permits preappointment BRAF/KIT mutation analysis and result delivery in melanoma patients. This sets the stage for further applications of this model to other conditions, answering an increasing demand for robust delivery of molecular data for individualized medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Empirical Modeling of Physiochemical Immune Response of Multilayer Zinc Oxide Nanomaterials under UV Exposure to Melanoma and Foreskin Fibroblasts

    Science.gov (United States)

    Fakhar-E-Alam, Muhammad; Akram, M. Waseem; Iqbal, Seemab; Alimgeer, K. S.; Atif, M.; Sultana, K.; Willander, M.; Wang, Zhiming M.

    2017-04-01

    Carcinogenesis is a complex molecular process starting with genetic and epigenetic alterations, mutation stimulation, and DNA modification, which leads to proteomic adaptation ending with an uncontrolled proliferation mechanism. The current research focused on the empirical modelling of the physiological response of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip silver capillary and conjugated with protoporphyrin IX (PpIX). Furthermore, PpIX-conjugated ZnO nanomaterials grown on the probe were inserted into human melanoma (FM55P) and foreskin fibroblasts cells (AG01518) under UV-A light exposure. Interestingly, significant cell necrosis was observed because of a loss in mitochondrial membrane potential just after insertion of the femtotip tool. Intense reactive oxygen species (ROS) fluorescence was observed after exposure to the ZnO NWs conjugated with PpIX femtotip model under UV exposure. Results were verified by applying several experimental techniques, e.g., ROS detection, MTT assay, and fluorescence spectroscopy. The present work reports experimental modelling of cell necrosis in normal human skin as well as a cancerous tissue. These obtained results pave the way for a more rational strategy for biomedical and clinical applications.

  16. Empirical Modeling of Physiochemical Immune Response of Multilayer Zinc Oxide Nanomaterials under UV Exposure to Melanoma and Foreskin Fibroblasts.

    Science.gov (United States)

    Fakhar-E-Alam, Muhammad; Akram, M Waseem; Iqbal, Seemab; Alimgeer, K S; Atif, M; Sultana, K; Willander, M; Wang, Zhiming M

    2017-04-24

    Carcinogenesis is a complex molecular process starting with genetic and epigenetic alterations, mutation stimulation, and DNA modification, which leads to proteomic adaptation ending with an uncontrolled proliferation mechanism. The current research focused on the empirical modelling of the physiological response of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip silver capillary and conjugated with protoporphyrin IX (PpIX). Furthermore, PpIX-conjugated ZnO nanomaterials grown on the probe were inserted into human melanoma (FM55P) and foreskin fibroblasts cells (AG01518) under UV-A light exposure. Interestingly, significant cell necrosis was observed because of a loss in mitochondrial membrane potential just after insertion of the femtotip tool. Intense reactive oxygen species (ROS) fluorescence was observed after exposure to the ZnO NWs conjugated with PpIX femtotip model under UV exposure. Results were verified by applying several experimental techniques, e.g., ROS detection, MTT assay, and fluorescence spectroscopy. The present work reports experimental modelling of cell necrosis in normal human skin as well as a cancerous tissue. These obtained results pave the way for a more rational strategy for biomedical and clinical applications.

  17. The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma.

    Science.gov (United States)

    Trinh, Van Anh; Zobniw, Chrystia; Hwu, Wen-Jen

    2017-08-01

    Patients with resected stage II or III melanoma are at high risk of recurrence, with 5-year mortality rate of 40-60%. Adjuvant interferon-alfa has demonstrated a small RFS and OS benefit versus observation in this patient population. However, the adjuvant treatment landscape is evolving rapidly. Areas covered: This review aims to summarize the safety and efficacy profiles of adjuvant IFNα/PEG-IFNα, revisit the controversy surrounding its application, and reappraise its position in the rapidly changing treatment landscape of resected melanoma. A literature search using PubMed database was undertaken using search words melanoma, interferon-alfa, pegylated interferon-alfa, adjuvant therapy. Expert opinion: Currently, there is no international consensus regarding the optimal dosing schedule for adjuvant IFNα, but HD IFNα-2b remains the most widely used regimen. The AEs of HD IFNα-2b are substantial; however, toxicity management experience amassed over the past 2 decades has significantly improved safety. Many exciting studies are ongoing to examine the roles of immune checkpoint inhibitors and BRAF-targeted therapies in the adjuvant setting and will further delineate the role of adjuvant IFNα.

  18. Pro-Inflammatory Cytokines Predict Relapse-Free Survival after One Month of Interferon-α but Not Observation in Intermediate Risk Melanoma Patients.

    Directory of Open Access Journals (Sweden)

    Ahmad A Tarhini

    Full Text Available E1697 was a phase III trial of adjuvant interferon (IFN-α2b for one month (Arm B versus observation (Arm A in patients with resected melanoma at intermediate risk. We evaluated the levels of candidate serum cytokines, the HLA genotype, polymorphisms of CTLA4 and FOXP3 genes and the development of autoantibodies for their association with relapse free survival (RFS in Arm A and Arm B among 268 patients with banked biospecimens.ELISA was used to test 5 autoantibodies. Luminex/One Lambda LABTypeRSSO was used for HLA Genotyping. Selected CTLA4 and FOXP3 Single nucleotide polymorphisms (SNPs and microsatellites were tested for by polymerase chain reaction (PCR. Sixteen serum cytokines were tested at baseline and one month by Luminex xMAP multiplex technology. Cox Proportional Hazards model was applied and the Wald test was used to test the marginal association of each individual marker and RFS. We used the Lasso approach to select the markers to be included in a multi-marker Cox Proportional Hazards model. The ability of the resulting models to predict one year RFS was evaluated by the time-dependent ROC curve. The leave-one-out method of cross validation (LOOCV was used to avoid over-fitting of the data.In the multi-marker modeling analysis conducted in Arm B, one month serum IL2Rα, IL-12p40 and IFNα levels predicted one year RFS with LOOCV AUC = 82%. Among the three markers selected, IL2Rα and IFNα were the most stable (selected in all the cross validation cycles. The risk score (linear combination of the 3 markers separated the RFS curves of low and high risk groups well (p = 0.05. This model did not hold for Arm A, indicating a differential marker profile in Arm B linked to the intervention (adjuvant therapy.Early on-treatment proinflammatory serum markers (IL2Rα, IL-12p40, IFNα significantly predict RFS in our cohort of patients treated with adjuvant IFN-α2b and warrant further study.

  19. Malignant Melanoma of the Foot

    Science.gov (United States)

    ... Javascript in your browser. Malignant Melanoma of the Foot What Is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  20. Systemic Immune-Inflammation Index and Circulating T-Cell Immune Index Predict Outcomes in High-Risk Acral Melanoma Patients Treated with High-Dose Interferon.

    Science.gov (United States)

    Yu, Jiayi; Wu, Xiaowen; Yu, Huan; Li, Siming; Mao, LiLi; Chi, Zhihong; Si, Lu; Sheng, Xinan; Cui, Chuanliang; Dai, Jie; Ma, Meng; Tang, Huan; Xu, Tianxiao; Yan, Junya; Kong, Yan; Guo, Jun

    2017-10-01

    High-dose interferon alfa-2b (IFN-α-2b) improves the survival of patients with high-risk melanoma. We aimed to identify baseline peripheral blood biomarkers to predict the outcome of acral melanoma patients treated with IFN-α-2b. Pretreatment baseline parameters and clinical data were assessed in 226 patients with acral melanoma. Relapse-free survival (RFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox regression analyses were applied after adjusting for stage, lactate dehydrogenase (LDH), and ulceration. Univariate analysis showed that neutrophil-to-lymphocyte ratio ≥2.35, platelet-to-lymphocyte ratio ≥129, systemic immune-inflammation index (SII) ≥615 × 10 9 /l, and elevated LDH were significantly associated with poor RFS and OS. The SII is calculated as follows: platelet count × neutrophil count/lymphocyte count. On multivariate analysis, the SII was associated with RFS [hazard ratio (HR)=1.661, 95% confidence interval (CI): 1.066-2.586, P=.025] and OS (HR=2.071, 95% CI: 1.204-3.564, P=.009). Additionally, we developed a novel circulating T-cell immune index (CTII) calculated as follows: cytotoxic T lymphocytes/(CD4 + regulatory T cells × CD8 + regulatory T cells). On univariate analysis, the CTII was associated with OS (HR=1.73, 95% CI: 1.01-2.94, P=.044). The SII and CTII might serve as prognostic indicators in acral melanoma patients treated with IFN-α-2b. The indexes are easily obtainable via routine tests in clinical practice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Systemic Immune-Inflammation Index and Circulating T-Cell Immune Index Predict Outcomes in High-Risk Acral Melanoma Patients Treated with High-Dose Interferon

    Directory of Open Access Journals (Sweden)

    Jiayi Yu

    2017-10-01

    Full Text Available High-dose interferon alfa-2b (IFN-α-2b improves the survival of patients with high-risk melanoma. We aimed to identify baseline peripheral blood biomarkers to predict the outcome of acral melanoma patients treated with IFN-α-2b. Pretreatment baseline parameters and clinical data were assessed in 226 patients with acral melanoma. Relapse-free survival (RFS and overall survival (OS were assessed using the Kaplan-Meier method, and multivariate Cox regression analyses were applied after adjusting for stage, lactate dehydrogenase (LDH, and ulceration. Univariate analysis showed that neutrophil-to-lymphocyte ratio ≥2.35, platelet-to-lymphocyte ratio ≥129, systemic immune-inflammation index (SII ≥615 × 109/l, and elevated LDH were significantly associated with poor RFS and OS. The SII is calculated as follows: platelet count × neutrophil count/lymphocyte count. On multivariate analysis, the SII was associated with RFS [hazard ratio (HR=1.661, 95% confidence interval (CI: 1.066-2.586, P=.025] and OS (HR=2.071, 95% CI: 1.204-3.564, P=.009. Additionally, we developed a novel circulating T-cell immune index (CTII calculated as follows: cytotoxic T lymphocytes/(CD4+ regulatory T cells × CD8+ regulatory T cells. On univariate analysis, the CTII was associated with OS (HR=1.73, 95% CI: 1.01-2.94, P=.044. The SII and CTII might serve as prognostic indicators in acral melanoma patients treated with IFN-α-2b. The indexes are easily obtainable via routine tests in clinical practice.

  2. Synthesis and Pharmacological Evaluation of Selective Histone Deacetylase 6 Inhibitors in Melanoma Models

    Czech Academy of Sciences Publication Activity Database

    Tavares, M. T.; Shen, S.; Knox, T.; Hadley, M.; Kutil, Zsofia; Bařinka, Cyril; Villagra, A.; Kozikowski, A. P.

    2017-01-01

    Roč. 8, č. 10 (2017), s. 1031-1036 ISSN 1948-5875 R&D Projects: GA ČR GA15-19640S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : HDAC6 inhibitors * nexturastat A * melanoma Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 3.746, year: 2016

  3. An epigenetic vaccine model active in the prevention and treatment of melanoma

    OpenAIRE

    Magner William J; Khan A Nazmul H; Tomasi Thomas B

    2007-01-01

    Abstract Background Numerous immune genes are epigenetically silenced in tumor cells and agents such as histone deacetylase inhibitors (HDACi), which reverse these effects, could potentially be used to develop therapeutic vaccines. The conversion of cancer cells to antigen presenting cells (APCs) by HDACi treatment could potentially provide an additional pathway, together with cross-presentation of tumor antigens by host APCs, to establish tumor immunity. Methods HDACi-treated B16 melanoma ce...

  4. Resiquimod as an Immunologic Adjuvant for NY-ESO-1 Protein Vaccination in Patients with High Risk Melanoma

    Science.gov (United States)

    Gnjatic, Sacha; Cruz, Crystal M.; Vengco, Isabelita; Hasan, Farah; Spadaccia, Meredith; Darvishian, Farbod; Chiriboga, Luis; Holman, Rose Marie; Escalon, Juliet; Muren, Caroline; Escano, Crystal; Yepes, Ethel; Sharpe, Dunbar; Vasilakos, John P.; Rolnitzsky, Linda; Goldberg, Judith; Mandeli, John; Adams, Sylvia; Jungbluth, Achim; Pan, Linda; Venhaus, Ralph; Ott, Patrick A.; Bhardwaj, Nina

    2015-01-01

    The TLR7/8 agonist, Resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide with or without Resiquimod in high-risk melanoma patients. In Part I of the study, patients received 100ug full length NY-ESO-1 protein emulsified in 1.25mL Montanide (day 1) followed by topical application of 1000mg of 0.2% Resiquimod gel on days 1 and 3 (Cohort 1) versus days 1, 3, and 5 (Cohort 2) of a 21 day cycle. In Part II, patients were randomized to receive 100ug NY-ESO-1 protein plus Montanide (day 1) followed by topical application of placebo gel (Arm-A; N=8) or 1000mg of 0.2% Resiquimod gel (Arm-B; N=12) using the dosing regimen established in Part I. The vaccine regimens were generally well-tolerated. NY-ESO-1-specific humoral responses were induced or boosted in all patients, many of whom had high titer antibodies. In Part II, 16 of 20 patients in both arms had NY-ESO-1-specific CD4+ T-cell responses. CD8+ T-cell responses were only seen in 3 of 12 patients in Arm B. Patients with TLR7 SNP rs179008 had a greater likelihood of developing NY-ESO-1-specific CD8+ responses. In conclusion, NY-ESO-1 protein in combination with Montanide with or without topical Resiquimod is safe and induces both antibody and CD4+ T-cell responses in the majority of patients; the small proportion of CD8+ T-cell responses suggests that the addition of topical Resiquimod to Montanide is not sufficient to induce consistent NY-ESO-1-specific CD8+ T-cell responses. PMID:25633712

  5. Transcriptome of melanoma cells from two mouse models, Tyr:NRasQ61Kand Tyr:Rack1-HA, Tyr:NRasQ61K

    Directory of Open Access Journals (Sweden)

    Cécil Campagne

    2017-10-01

    Full Text Available The transcriptome sequencing of melanoma cells from two mouse models differing in the expression level of the scaffold protein Receptor for activated C kinase (RACK1 are presented. Primary melanoma cells were harvested from Tyr:NRasQ61K; Pax3GFP/+ mice, with or without the Tyr:Rack1-HA transgene. Cells were cultured and infected with scramble shRNA or Rack1-targeting shRNA, on technical triplicates of viral infection. Libraries were prepared by selecting polyadenylated mRNAs and RNA Sequencing (RNASeq was performed. Samples are described in the SRA portal (SRP096162 and FASTQ files have been deposited in Sequence Read Archive (accession numbers: SRR5150106 to SRR5150117. The interpretation of these data is presented in the following research article: “RACK1 cooperates with NRASQ61K to promote melanoma in vivo” (Campagne et al., 2017, doi: 10.1016/j.cellsig.2017.03.015 [1].

  6. Preclinical evaluation of radiation and systemic, RGD-targeted, adeno-associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma.

    Science.gov (United States)

    Quinn, T J; Healy, N; Sara, A; Maggi, E; Claros, C S; Kabarriti, R; Scandiuzzi, L; Liu, L; Gorecka, J; Adem, A; Basu, I; Yuan, Z; Guha, C

    2017-01-01

    The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model. Furthermore, this combination appeared to modify the tumor microenvironment, resulting in decreased Tregs in the draining LN and increased tumor-associated macrophages within the primary tumor. Finally, there appeared to be a reduction in metastatic potential and a prolongation of overall survival in the combined treatment group. These results indicate the use of targeted TNF gene therapy vector with radiation treatment could be a valuable treatment option for patients with metastatic melanoma.

  7. Positive interaction between light iris color and ultraviolet radiation in relation to the risk of uveal melanoma: a case-control study.

    Science.gov (United States)

    Schmidt-Pokrzywniak, Andrea; Jöckel, Karl-Heinz; Bornfeld, Norbert; Sauerwein, Wolfgang; Stang, Andreas

    2009-02-01

    To examine the association among phenotypic characteristics, chronic and intermittent ultraviolet (UV) radiation, and the risk of uveal melanoma. Case-control study. Overall, between September of 2002 and March of 2005, 1677 eligible subjects (age range: 20-74 years, living in Germany) participated. Interviews were conducted with 459 incident uveal melanoma cases (response proportion 94%), 827 population controls (55%), 180 ophthalmologist controls (52%), and 187 sibling controls (57%). Data on phenotypic characteristics and chronic and intermittent UV radiation exposure were obtained from a self-administered postal questionnaire and computer-assisted telephone interview. We used conditional logistic regression to estimate odds ratios adjusting for the matching factors. Furthermore, we studied the presence of synergy (super additive of risk or relative excess risk due to interaction) between light iris color and several UV radiation exposures. Hair color at age 20 years, eye color, untanned skin color, ability to tan, propensity to burn on exposure, freckling, occupational sun exposure, artificial UV radiation, burns to the eyes. In all 3 control groups, fair skin color, freckling as a child, nevi on the upper arms, burns to the eyes, use of sunlamps, and ever worked outside for 4 or more hours per day were positively associated with uveal melanoma. The association with eye color was apparent only in population controls (odds ratio = 1.9; 95% confidence interval [CI], 1.4-5.2), resulting in a relative excess risk due to interaction of 0.9 (95% CI, -0.6-2.3) for light iris color and more than 5 eye burns (UV-related keratitis) and 0.6 (95% CI, -0.3 to 1.5) for light iris color and eye protection. Our interaction analyses suggest that there is an etiologic synergism between light iris color and the exposure of UV radiation. People with light iris color may have an especially increased risk for uveal melanoma if they are exposed to UV radiation. The author(s) have no

  8. Study of melanoma invasion by FTIR spectroscopy

    Science.gov (United States)

    Yang, Y.; Sulé-Suso, J.; Sockalingum, G. D.

    2008-02-01

    Compared to other forms of skin cancer, a malignant melanoma has a high risk of spreading to other parts of the body. Melanoma invasion is a complex process involving changes in cell-extracellular matrix (ECM) interaction and cell-cell interactions. To fully understand the factors which control the invasion process, a human skin model system was reconstructed. HBL (a commercially available cell line) melanoma cells were seeded on a skin model with and without the presence of keratinocytes and/or fibroblasts. After 14 days culture, the skin specimens were fixed, parafin embedded and cut into 7 µm sections. The de-parafinised sections were investigated by synchrotron Fourier transformed infrared (FTIR) microspectroscopy to study skin cell invasion behaviour. The advantage of using FTIR is its ability to obtain the fingerprint information of the invading cells in terms of protein secondary structure in comparison to non-invading cells and the concentration of the enzyme (matrix-metalloproteinase) which digests protein matrix, near the invading cells. With aid of the spectral mapping images, it is possible to pinpoint the cells in non-invasion and invasion area and analyse the respective spectra. It has been observed that the protein bands in cells and matrix shifted between non-invasive and invasive cells in the reconstructed skin model. We hypothesise that by careful analysis of the FTIR data and validation by other models, FTIR studies can reveal information on which type of cells and proteins are involved in melanoma invasion. Thus, it is possible to trace the cell invasion path by mapping the spectra along the interface of cell layer and matrix body by FTIR spectroscopy.

  9. Long-term Survival after Metastatic Childhood Melanoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; Bybjerg Jensen, Mette; Krag, Christen

    2014-01-01

    SUMMARY: Malignant melanoma in children is very rare and accounts for only 1-3% of all melanomas. A congenital melanocytic nevus depending on the size of the lesion is one of the risk factors for developing childhood melanoma because of the possible malignant transformation. Childhood malignant m...... survived 26 years without recurrence, thus representing an uplifting case of long-term survival of childhood melanoma....

  10. A new understanding in the epidemiology of melanoma

    OpenAIRE

    Erdei, Esther; Torres, Salina M

    2010-01-01

    The incidence of melanoma is continuing to increase worldwide. UV exposure is a known risk factor for melanoma. Geographic location is known to influence UV exposure and the distribution of the incidence of melanoma. Furthermore, epidemiologic data suggest that gender and genetics may influence the distribution of melanoma on the body surface and histopathologic characteristics of the lesion. This article describes what is known about the impact of gender, ethnicity and geography on the progr...

  11. Fibrin gels loaded with cisplatin and cisplatin-hyaluronate complexes tested in a subcutaneous human melanoma model.

    Science.gov (United States)

    Viale, Maurizio; Rossi, Marta; Russo, Eleonora; Cilli, Michele; Aprile, Anna; Profumo, Aldo; Santi, Pierluigi; Fenoglio, Carla; Cafaggi, Sergio; Rocco, Mattia

    2015-12-01

    Fibrin gels are attractive biomaterials for local delivery of a variety of agents, from drugs to proteins. Similarly, polymer-anticancer-drug conjugates and nanoparticles are emerging as potential candidates for cancer treatment. Combining these different approaches, we have studied the efficacy of fibrin gels loaded with cisplatin (DDP) and a complex of DDP with hyaluronate (DDP-HA) for tumor growth inhibition in a melanoma model. Loaded gels prepared at relatively high fibrinogen concentration (22 mg/ml) showed good in vitro antiproliferative activities, prolonged release of the anticancer drug, and a long persistence (10-15 days) in vivo when implanted subcutaneously (sc) in immunodeficient mice. Gels loaded with DDP or DDP-HA containing 1/3 or even 1/6 of their systemic dose (6 mg/kg) and positioned under the tumor mass in mice bearing a sc human SK-Mel-28 tumor showed an antitumor activity better than that of the original parent compound given intraperitoneally (ip). Moreover, in an additional experiment in vivo, fibrin gels loaded with N-trimethyl chitosan-based nanoparticles containing a DDP-HA complex were assayed, resulting in a further 8 % improvement of anticancer activity, with lesser adverse systemic toxic effects. Taken together, these results suggest that the combination of fibrin gels and drugs complexed with suitable macromolecules holds great promise for loco-regional anticancer therapy of melanoma and other surgically removable cancer types.

  12. Communication Among Melanoma Family Members

    Science.gov (United States)

    Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

    2017-01-01

    Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the case) and an additional first degree relative and a parent of a child 0–17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at one year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range =14–18 percentage points; all pcommunication about cancer risk. PMID:28248624

  13. Transcription analysis in the MeLiM swine model identifies RACK 1 as a potential marker for human melanoma tumoral status

    Czech Academy of Sciences Publication Activity Database

    Egidy, G.; Julé, S.; Bossé, P.; Bernex, F.; Geffrotin, C.; Vincent-Naulleau, S.; Horák, Vratislav; Sastre-Garau, X.; Panthier, J. J.

    2008-01-01

    Roč. 21, č. 4 (2008), s. 300-300 ISSN 1755-1471. [International Pigment Cell Conference /20./ and International Melanoma Research Congress /5./. 07.05.2008-12.05.2008, Sapporo] Institutional research plan: CEZ:AV0Z50450515 Keywords : MeLiM swine model Subject RIV: FD - Oncology ; Hematology

  14. Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model

    DEFF Research Database (Denmark)

    Schmidt, H; Bastholt, L; Geertsen, P

    2005-01-01

    We aimed to create a prognostic model in metastatic melanoma based on independent prognostic factors in 321 patients receiving interleukin-2 (IL-2)-based immunotherapy with a median follow-up time for patients currently alive of 52 months (range 15-189 months). The patients were treated as part...... factors in univariate analyses. Subsequently, a multivariate Cox's regression analysis identified elevated LDH (P

  15. A new animal model for the imaging of melanoma: correlation of FDG PET with clinical outcome, macroscopic aspectand histological classification in Melanoblastoma-bearing Libechov Minipigs

    Czech Academy of Sciences Publication Activity Database

    Boisgard, R.; Naulleau, S. V.; Leplat, J. J.; Bouet, S.; Chalony, C.; Tricaud, Y.; Horák, Vratislav; Geffrotin, C.; Frelat, G.; Tavitian, B.

    2003-01-01

    Roč. 30, č. 6 (2003), s. 826-834 ISSN 1619-7070 R&D Projects: GA ČR GA524/01/0162 Institutional research plan: CEZ:AV0Z5045916 Keywords : melanoma * MeLiM swinw model Subject RIV: ED - Physiology Impact factor: 3.324, year: 2003

  16. Custom v. Standardized Risk Models

    Directory of Open Access Journals (Sweden)

    Zura Kakushadze

    2015-05-01

    Full Text Available We discuss when and why custom multi-factor risk models are warranted and give source code for computing some risk factors. Pension/mutual funds do not require customization but standardization. However, using standardized risk models in quant trading with much shorter holding horizons is suboptimal: (1 longer horizon risk factors (value, growth, etc. increase noise trades and trading costs; (2 arbitrary risk factors can neutralize alpha; (3 “standardized” industries are artificial and insufficiently granular; (4 normalization of style risk factors is lost for the trading universe; (5 diversifying risk models lowers P&L correlations, reduces turnover and market impact, and increases capacity. We discuss various aspects of custom risk model building.

  17. Electrospun PBLG/PLA nanofiber membrane for constructing in vitro 3D model of melanoma.

    Science.gov (United States)

    Wang, Yaping; Qian, Junmin; Liu, Ting; Xu, Weijun; Zhao, Na; Suo, Aili

    2017-07-01

    Though much progress in utilizing tissue engineering technology to investigate tumor development in vitro has been made, the effective management of human melanoma is still a challenge in clinic due to lack of suitable 3D culture systems. In this study, we prepared a poly(γ-benzyl-l-glutamate)/poly(lactic acid) (PBLG/PLA) nanofiber membrane by electrospinning and demonstrated its suitability as a matrix for 3D culture of melanoma cells in vitro. The electrospun PBLG/PLA nanofiber membrane displayed a smooth and uniform fibrous morphology and had a desirable water contact angle of 79.3±0.6°. The average diameter of PBLG/PLA nanofibers was 320.3±95.1nm that was less than that (516.2±163.3nm) of pure PLA nanofibers. The addition of PBLG into PLA decreased the cold crystallization peak of PLA fibers from 93 to 75°C. The in vitro biocompatibility of PBLG/PLA nanofiber membrane was evaluated with B16F10 cells using PLA nanofiber membrane as control. It was found that, compared to PLA nanofiber membrane, PBLG/PLA nanofiber membrane could better support cell viability and proliferation, as indicated by MTT assay and live-dead staining. SEM results revealed that PBLG/PLA rather than PLA nanofiber membrane promoted the generation of tumoroid-like structures. These findings clearly demonstrated that the electrospun PBLG/PLA nanofiber membrane could mimick the extracellular matrix of melanoma microenvironment and be a promising platform for 3D cell culture. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Novel therapeutic mechanisms determine the effectiveness of lipid-core nanocapsules on melanoma models.

    Science.gov (United States)

    Drewes, Carine C; Fiel, Luana A; Bexiga, Celina G; Asbahr, Ana Carolina C; Uchiyama, Mayara K; Cogliati, Bruno; Araki, Koiti; Guterres, Sílvia S; Pohlmann, Adriana R; Farsky, Sandra P

    2016-01-01

    Melanoma is a severe metastatic skin cancer with poor prognosis and no effective treatment. Therefore, novel therapeutic approaches using nanotechnology have been proposed to improve therapeutic effectiveness. Lipid-core nanocapsules (LNCs), prepared with poly(ε-caprolactone), capric/caprylic triglyceride, and sorbitan monostearate and stabilized by polysorbate 80, are efficient as drug delivery systems. Here, we investigated the effects of acetyleugenol-loaded LNC (AcE-LNC) on human SK-Mel-28 melanoma cells and its therapeutic efficacies on melanoma induced by B16F10 in C57B6 mice. LNC and AcE-LNC had z-average diameters and zeta potential close to 210 nm and -10.0 mV, respectively. CytoViva(®) microscopy images showed that LNC and AcE-LNC penetrated into SK-Mel-28 cells, and remained in the cytoplasm. AcE-LNC in vitro treatment (18-90×10(9) particles/mL; 1 hour) induced late apoptosis and necrosis; LNC and AcE-LNC (3-18×10(9) particles/mL; 48 hours) treatments reduced cell proliferation and delayed the cell cycle. Elevated levels of nitric oxide were found in supernatant of LNC and AcE-LNC, which were not dependent on nitric oxide synthase expressions. Daily intraperitoneal or oral treatment (days 3-10 after tumor injection) with LNC or AcE-LNC (1×10(12) particles/day), but not with AcE (50 mg/kg/day, same dose as AcE-LNC), reduced the volume of the tumor; nevertheless, intraperitoneal treatment caused toxicity. Oral LNC treatment was more efficient than AcE-LNC treatment. Moreover, oral treatment with nonencapsulated capric/caprylic triglyceride did not inhibit tumor development, implying that nanocapsule supramolecular structure is important to the therapeutic effects. Together, data herein presented highlight the relevance of the supramolecular structure of LNCs to toxicity on SK-Mel-28 cells and to the therapeutic efficacy on melanoma development in mice, conferring novel therapeutic mechanisms to LNC further than a drug delivery system.

  19. Model Risk in Portfolio Optimization

    Directory of Open Access Journals (Sweden)

    David Stefanovits

    2014-08-01

    Full Text Available We consider a one-period portfolio optimization problem under model uncertainty. For this purpose, we introduce a measure of model risk. We derive analytical results for this measure of model risk in the mean-variance problem assuming we have observations drawn from a normal variance mixture model. This model allows for heavy tails, tail dependence and leptokurtosis of marginals. The results show that mean-variance optimization is seriously compromised by model uncertainty, in particular, for non-Gaussian data and small sample sizes. To mitigate these shortcomings, we propose a method to adjust the sample covariance matrix in order to reduce model risk.

  20. Sinclair swine melanoma

    International Nuclear Information System (INIS)

    Hook, R.R.; Berkelhammer, J.; Hamby, C.V.

    1986-01-01

    Sinclair(S-1) miniature swine spontaneously develop melanomas which have many biologic and histologic features in common with human superficial spreading melanoma. Host control of this neoplasm was indicated by the high incidence of spontaneous regression, a decrease in tumor development with age and a decrease in progressive growth of the tumor as age of tumor development increases. Immunologic mechanisms were implicated in host control by histologic observation of a mononuclear inflammatory infiltration of tumors which lead to depigmentation and fibrosis. In vitro immunologic studies revealed that leukocytes from melanoma swine were sensitized specifically to a tumor associated antigen like substance present in extracts of cutaneous melanomas and cultured swine melanoma cells and that melanoma swine leukocytes were cytotoxic for swine melanoma cells. Furthermore, these studies suggested the existence of a common cross reactive, melanoma associated antigen shared by human and swine melanomas. Antigenic analyses of swine melanomas with mouse monoclonal antibodies developed to a single swine melanoma cell culture and with rabbit antisera developed to pooled extracts of cutaneous melanomas demonstrated the presence of tumor associated antigens in swine melanoma cell culture and cutaneous melanomas. The failure of mouse monoclonal antibodies to detect antigens in cutaneous melanoma extracts and the failure of rabbit antisera to detect antigens in melanoma cell culture extracts suggested a differential in antigen expression between swine melanoma cells grown in vitro and in vivo

  1. Choroidal melanoma

    International Nuclear Information System (INIS)

    Hernandez Quesada, Flora

    2013-01-01

    A useful and practical guide is developed to better track to the uveal melanoma, due to its highly malignant character. Melanoma of the uveal tract (choroid, iris, ciliary body) has been the intraocular tumor most frequent in adults. The biopsy has been inaccessible, due to its location; therefore, the diagnostic should be based on clinical examination and the correct utilization of the diagnostic procedures (ultrasound, fluorescent angiography, computed axial tomography and magnetic resonance). The cases are diagnosed in the histological examination of the operatory piece post-enucleation for other causes. Epidemiological research has been key to determine the associated factors and better to understand the mechanisms of onset of the disease. Anatomopathological studies of choroidal melanoma have permitted to know the natural history of the disease. The decrease of the visual acuity, pain or inflammation are presented as a defect in the visual field. Different techniques to diagnose the disease are explained. Ultrasound in mode A and B, computed axial tomography and magnetic resonance are the diagnostic method of election. Ultrasound has been the primary method of diagnostic, giving the size and vascularisation, useful in tracking, when they are treated in shape conservatively, showing changes in echogenicity and less vascularisation as good response to treatment. The treatments of choroidal melanoma are specified. The correct interpretation of the clinical symptoms and early utilization of diagnostic imaging methods, have permitted to establish the adequate therapeutic and to avoid local and distant metastasis. The uveal melanoma, depending on their size and location, traditionally has been treated by enucleation. Data from the literature and authors, have promoted the conservation of the ocular globe, depending on the size of the tumor. Transpupillary thermotherapy has been an available alternative for small tumors in Costa Rica and level of social security

  2. From Melanocyte to Metastatic Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Bizhan Bandarchi

    2010-01-01

    Full Text Available Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental (exogenous and endogenous, including genetic, risk factors in developing malignant melanoma. 8–12% of familial melanomas occur in a familial setting related to mutation of the CDKN2A gene that encodes p16. The aim of this is to briefly review the microanatomy and physiology of the melanocytes, epidemiology, risk factors, clinical presentation, historical classification and histopathology and, more in details, the most recent discoveries in biology and genetics of malignant melanoma. At the end, the final version of 2009 AJCC malignant melanoma staging and classification is presented.

  3. Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma.

    Science.gov (United States)

    Sabado, Rachel Lubong; Pavlick, Anna; Gnjatic, Sacha; Cruz, Crystal M; Vengco, Isabelita; Hasan, Farah; Spadaccia, Meredith; Darvishian, Farbod; Chiriboga, Luis; Holman, Rose Marie; Escalon, Juliet; Muren, Caroline; Escano, Crystal; Yepes, Ethel; Sharpe, Dunbar; Vasilakos, John P; Rolnitzsky, Linda; Goldberg, Judith; Mandeli, John; Adams, Sylvia; Jungbluth, Achim; Pan, Linda; Venhaus, Ralph; Ott, Patrick A; Bhardwaj, Nina

    2015-03-01

    The Toll-like receptor (TLR) 7/8 agonist resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide (Seppic) with or without resiquimod in patients with high-risk melanoma. In part I of the study, patients received 100 μg of full-length NY-ESO-1 protein emulsified in 1.25 mL of Montanide (day 1) followed by topical application of 1,000 mg of 0.2% resiquimod gel on days 1 and 3 (cohort 1) versus days 1, 3, and 5 (cohort 2) of a 21-day cycle. In part II, patients were randomized to receive 100-μg NY-ESO-1 protein plus Montanide (day 1) followed by topical application of placebo gel [(arm A; n = 8) or 1,000 mg of 0.2% resiquimod gel (arm B; n = 12)] using the dosing regimen established in part I. The vaccine regimens were generally well tolerated. NY-ESO-1-specific humoral responses were induced or boosted in all patients, many of whom had high titer antibodies. In part II, 16 of 20 patients in both arms had NY-ESO-1-specific CD4⁺ T-cell responses. CD8⁺ T-cell responses were only seen in 3 of 12 patients in arm B. Patients with TLR7 SNP rs179008 had a greater likelihood of developing NY-ESO-1-specific CD8⁺ responses. In conclusion, NY-ESO-1 protein in combination with Montanide with or without topical resiquimod is safe and induces both antibody and CD4⁺ T-cell responses in the majority of patients; the small proportion of CD8⁺ T-cell responses suggests that the addition of topical resiquimod to Montanide is not sufficient to induce consistent NY-ESO-1-specific CD8⁺ T-cell responses. ©2015 American Association for Cancer Research.

  4. [Effects of Xiaoyao Powder Extract in co-culture model of melanoma cells and keratinocytes on expression of tyrosinase and its related protein].

    Science.gov (United States)

    Zhang, Ning; Liu, Hui; Zhang, Ming-lei; Liu, Bin; Ren, Yan-dong; Wang, Xue; Li, Jian-min

    2014-06-01

    To observe the effects and mechanism of Xiaoyao Powder extract on the content of melanin in co-culture model of melanoma cells and keratinocytes. Eluting components of Xiaoyao Powder was collected by AB-8 macroporous resin column. Different concentration extracts of Xiaoyao Powder were added into the co-culture model of A375 melanoma cells and HaCat ke- ratinocytes. Hunt method was used to detected the content of melanin. RT-PCR assay was used to detect the effects of the extract of Xi- aoyao Powder on the TYR,TRP-1 and TRP-2 mRNA expression in A375 melanoma cells. Compared with the control group,the extract of Xiaoyao Powder down-regulated content of melanin and mRNA expression of TYR,TRP-1 and TRP-2 in A375 melanoma cells by 82.23% ,93. 01% and 29. 11% ,23.78% ,20. 05% ;25. 13% ,15.02% ,11.64% ,respectively(P Powder can decrease the melanogenesis by down-regulating the mRNA expression of tyrosinase and its related protein.

  5. Modelling allergenic risk

    DEFF Research Database (Denmark)

    Birot, Sophie

    of allergic reaction in the population. In allergen risk assessment, the emphasis was on the threshold data, and no effort was made on consumption data. Moreover, no pan-European consumption data suitable for allergen risk assessment are available. A procedure for grouping food products automatically across...... countries is proposed. Thus, the allergen risk assessment can be performed cross-nationally and for the correct food group. Then the two probabilistic risk assessment methods usually used were reviewed and compared. First order Monte-Carlo simulations are used in one method [14], whereas the other one...... Allergen and Allergy Management) aims at developing strategies for food allergies based on evidences. Especially, food allergen risk assessment helps food producers or authorities to make decisions on withdrawing a food product from the market or adding more information on the label when allergen presence...

  6. Wildfire Risk Main Model

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The model combines three modeled fire behavior parameters (rate of spread, flame length, crown fire potential) and one modeled ecological health measure (fire regime...

  7. Highly focalised thermotherapy using a ferrimagnetic cement in the treatment of a melanoma mouse model by low temperature hyperthermia.

    Science.gov (United States)

    Portela, Ana; Vasconcelos, Mário; Fernandes, Maria Helena; Garcia, Mónica; Silva, António; Gabriel, Joaquim; Gartner, Fátima; Amorim, Irina; Cavalheiro, José

    2013-01-01

    Evaluation of the effectiveness of highly focalised thermotherapy (HFT) in a melanoma mouse model, using a ferrimagnetic cement (FC) and repeated low hyperthermia treatments. A melanoma mouse model was induced with B16F10 cells in C57BL6 mice. The FC, injected into the tumour, was used as the magnetic vehicle for HFT. FC location within the tumour was assessed by radiography and its capability to generate heat, when exposed to an external high frequency magnetic field (HFMF), monitored by thermal camera. The HFT treatment consisted of three HFMF exposures, with 48-h intervals, each one lasting 30 min, with a 5-6°C tumour temperature increase. At the end of the experiment, FC samples were characterised by scanning electron microscopy (SEM) and energy dispersion spectroscopy (EDS). The presence of iron contents was analysed in the tumour, lungs, liver and spleen. Histological evaluation and immunohistochemical staining for caspase-3 were performed. Tumour growth was monitored during the experiment. Surface analysis showed FC stabilisation within the tumour, and iron was absent. The thermal camera confirmed the localised temperature increase in the tumour. HFT treatments inhibited the tumour growth by ∼70% compared to controls. This was due to cell destruction by necrosis and apoptosis. The HFT, using the FC, proved to be a minimally invasive technique that statistically inhibited tumour growth. Results suggested that this methodology seems to be a promising technique for the treatment of solid tumours, allowing repeated low hyperthermia treatments, which can be easier and less traumatic than other hyperthermia techniques.

  8. Operational Risk Modeling

    OpenAIRE

    Gabriela ANGHELACHE; Ana Cornelia OLTEANU

    2011-01-01

    Losses resulting from operational risk events from a complex interaction between organizational factors, personal and market participants that do not fit a simple classification scheme. Taking into account past losses (ex. Barings, Daiwa, etc.) we can say that operational risk is a major financial losses in the banking sector, although until recently have been underestimated, considering that they are generally minor, note setting survival of a bank.

  9. Operational Risk Modeling

    Directory of Open Access Journals (Sweden)

    Gabriela ANGHELACHE

    2011-06-01

    Full Text Available Losses resulting from operational risk events from a complex interaction between organizational factors, personal and market participants that do not fit a simple classification scheme. Taking into account past losses (ex. Barings, Daiwa, etc. we can say that operational risk is a major financial losses in the banking sector, although until recently have been underestimated, considering that they are generally minor, note setting survival of a bank.

  10. Pulse-mediated chemotherapy enhances local control and survival in a spontaneous canine model of primary mucosal melanoma.

    Science.gov (United States)

    Spugnini, Enrico P; Dragonetti, Emanuele; Vincenzi, Bruno; Onori, Nicoletta; Citro, Gennaro; Baldi, Alfonso

    2006-02-01

    Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment options include surgery, chemotherapy, immunotherapy and radiation therapy; however, local recurrence and distant dissemination are still frequent. We treated locally aggressive spontaneous canine oral melanomas that, because of their advanced stage, were not treatable with conventional strategies. A cohort of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs received two sessions of local bleomycin, followed by the application of trains of biphasic pulses. The treatment was well tolerated and resulted in an overall response rate of 80% with 50% long-term control. Of interest, only one of the dogs died of metastatic disease, and four of the long-term survivors showed a vitiligo-like discoloration at the site of treatment, potentially suggesting a recruitment of the immune system by the therapy. Further studies are needed to characterize this approach and to determine its suitability for head and neck mucosal melanoma.

  11. In vitro and in vivo anticancer properties of a Calcarea carbonica derivative complex (M8 treatment in a murine melanoma model

    Directory of Open Access Journals (Sweden)

    Trindade Edvaldo S

    2010-03-01

    Full Text Available Abstract Background Melanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have had only marginal success. Previous studies in mice demonstrated that a high diluted complex derived from Calcarea carbonica (M8 stimulated the tumoricidal response of activated lymphocytes against B16F10 melanoma cells in vitro. Methods Here we describe the in vitro inhibition of invasion and the in vivo anti-metastatic potential after M8 treatment by inhalation in the B16F10 lung metastasis model. Results We found that M8 has at least two functions, acting as both an inhibitor of cancer cell adhesion and invasion and as a perlecan expression antagonist, which are strongly correlated with several metastatic, angiogenic and invasive factors in melanoma tumors. Conclusion The findings suggest that this medication is a promising non-toxic therapy candidate by improving the immune response against tumor cells or even induce direct dormancy in malignancies.

  12. Sox2 is not required for melanomagenesis, melanoma growth and melanoma metastasis in vivo.

    Science.gov (United States)

    Cesarini, V; Guida, E; Todaro, F; Di Agostino, S; Tassinari, V; Nicolis, S; Favaro, R; Caporali, S; Lacal, P M; Botti, E; Costanzo, A; Rossi, P; Jannini, E A; Dolci, S

    2017-08-01

    Melanoma is a dangerous form of skin cancer derived from the malignant transformation of melanocytes. The transcription factor SOX2 is not expressed in melanocytes, however, it has been shown to be differentially expressed between benign nevi and malignant melanomas and to be essential for melanoma stem cell maintenance and expansion in vitro and in xenograft models. By using a mouse model in which BRaf V600E mutation cooperates with Pten loss to induce the development of metastatic melanoma, we investigated if Sox2 is required during the process of melanomagenesis, melanoma growth and metastasis and in the acquisition of resistance to BRAF inhibitors (BRAFi) treatments. We found that deletion of Sox2 specifically in Pten null and BRafV600E-expressing melanocytes did not prevent tumor formation and did not modify the temporal kinetics of melanoma occurrence compared to Sox2 wt mice. In addition, tumor growth was similar between Sox2 wt and Sox2 deleted (del) melanomas. By querying publicly available databases, we did not find statistically significant differences in SOX2 expression levels between benign nevi and melanomas, and analysis on two melanoma patient cohorts confirmed that Sox2 levels did not significantly change between primary and metastatic melanomas. Melanoma cell lines derived from both Sox2 genotypes showed a similar sensitivity to vemurafenib treatment and the same ability to develop vemurafenib resistance in long-term cultures. Development of vemurafenib resistance was not dependent on SOX2 expression also in human melanoma cell lines in vitro. Our findings exclude an oncogenic function for Sox2 during melanoma development and do not support a role for this transcription factor in the acquisition of resistance to BRAFi treatments.

  13. Benchmark risk analysis models

    NARCIS (Netherlands)

    Ale BJM; Golbach GAM; Goos D; Ham K; Janssen LAM; Shield SR; LSO

    2002-01-01

    A so-called benchmark exercise was initiated in which the results of five sets of tools available in the Netherlands would be compared. In the benchmark exercise a quantified risk analysis was performed on a -hypothetical- non-existing hazardous establishment located on a randomly chosen location in

  14. UVEAL MELANOMA EXTENSION TO THE OPTIC CHIASM.

    Science.gov (United States)

    Abdellatief, Amro; Pulido, Jose S; Bartley, George B; Salomao, Diva R; Quinn, Timothy A

    2016-01-01

    Case report describing a patient who developed intracranial extension of a uveal melanoma through the optic nerve. We reviewed the patient's medical history and images. A 41-year-old woman who was blind in one eye had a uveal melanoma that extended through the optic nerve into the optic chiasm and involved the hypophysis. The patient then developed metastasis. The patient developed uveal melanoma extension into the optic chiasm through the optic nerve resulting in a visual field defect in the fellow eye. Uveal melanoma extension through the optic nerve is a devastating complication, which occurs anywhere from 0.6% to 3.7% in patients with uveal melanoma. If enucleation of the affected eye is performed, a representative portion of the optic nerve should be excised to decrease the risk of extension. Patients with phthisical eyes should undergo appropriate imaging techniques to prevent a missed diagnosis of optic nerve involvement.

  15. Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye

    Science.gov (United States)

    2015-06-25

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma

  16. An increased risk of non-melanoma skin cancer during TNF-inhibitor treatment in psoriasis patients compared to rheumatoid arthritis patients probably relates to disease-related factors

    NARCIS (Netherlands)

    van Lümig, P. P. M.; Menting, S. P.; van den Reek, J. M. P. A.; Spuls, P. I.; van Riel, P. L. C. M.; van de Kerkhof, P. C. M.; Fransen, J.; Kievit, W.; de Jong, E. M. G. J.

    2015-01-01

    Concerns exist about a risk of non-melanoma skin cancer (NMSC) in psoriasis patients and rheumatoid arthritis (RA) patients treated with TNF-inhibitors. However, current data also show that in some psoriasis patients, NMSC is diagnosed relatively short after the start of TNF-inhibitors, which

  17. Vitamin D and melanoma incidence and mortality.

    Science.gov (United States)

    Berwick, Marianne; Erdei, Eszter O

    2013-01-01

    The role of vitamin D (25-OH-D, or 25-hydroxyvitamin D) and its potential confounders in relationship to melanoma risk and mortality is discussed. The paradox that ultraviolet radiation (UVR) exposure is the major environmental risk factor for melanoma etiology as well as a major source of vitamin D might be explained by viewing vitamin D levels as the result of a healthy lifestyle rather than a cause of health. © 2012 John Wiley & Sons A/S.

  18. The potential impact of reducing indoor tanning on melanoma prevention and treatment costs in the United States: An economic analysis.

    Science.gov (United States)

    Guy, Gery P; Zhang, Yuanhui; Ekwueme, Donatus U; Rim, Sun Hee; Watson, Meg

    2017-02-01

    Indoor tanning is associated with an increased risk of melanoma. The US Food and Drug Administration proposed prohibiting indoor tanning among minors younger than 18 years. We sought to estimate the health and economic benefits of reducing indoor tanning in the United States. We used a Markov model to estimate the expected number of melanoma cases and deaths averted, life-years saved, and melanoma treatment costs saved by reducing indoor tanning. We examined 5 scenarios: restricting indoor tanning among minors younger than 18 years, and reducing the prevalence by 20%, 50%, 80%, and 100%. Restricting indoor tanning among minors younger than 18 years was estimated to prevent 61,839 melanoma cases, prevent 6735 melanoma deaths, and save $342.9 million in treatment costs over the lifetime of the 61.2 million youth age 14 years or younger in the United States. The estimated health and economic benefits increased as indoor tanning was further reduced. Limitations include the reliance on available data and not examining compliance to indoor tanning laws. Reducing indoor tanning has the potential to reduce melanoma incidence, mortality, and treatment costs. These findings help quantify and underscore the importance of continued efforts to reduce indoor tanning and prevent melanoma. Published by Elsevier Inc.

  19. Experiência de um ano de modelo de programa de prevenção contínua do melanoma na cidade de Jaú-SP, Brasil One year experience of a model for melanoma continuous prevention in the city of Jaú (São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Ana Gabriela Salvio

    2011-08-01

    and early detection. METHODS: A city of around 130,000 inhabitants in the state of São Paulo, Brazil, was chosen for the development of a pilot project covering primary prevention and early diagnosis of melanoma. A nursing team worked for approximately 30 days in each of the 13 health centers in the city of Jaú (SP, providing guidance on self-examination of the skin, photoprotection and recognition of early signs of melanoma. Patients with suspicious lesions were immediately sent to the reference hospital for medical and dermoscopic screening. Excisional biopsies were performed on suspected melanomas. RESULTS: 4 four cases of early stage melanoma and 3 dysplastic nevi were diagnosed. Of the people interviewed, 74% worked either part-time or full-time exposed to sun and over 60% claimed to never use sunscreen. CONCLUSION: This is a new and effective model for melanoma prevention and early diagnosis. In short, the melanoma prevention program is able to quickly identify suspicious lesions, leading to early diagnosis and better chances of survival

  20. Multilevel joint competing risk models

    Science.gov (United States)

    Karunarathna, G. H. S.; Sooriyarachchi, M. R.

    2017-09-01

    Joint modeling approaches are often encountered for different outcomes of competing risk time to event and count in many biomedical and epidemiology studies in the presence of cluster effect. Hospital length of stay (LOS) has been the widely used outcome measure in hospital utilization due to the benchmark measurement for measuring multiple terminations such as discharge, transferred, dead and patients who have not completed the event of interest at the follow up period (censored) during hospitalizations. Competing risk models provide a method of addressing such multiple destinations since classical time to event models yield biased results when there are multiple events. In this study, the concept of joint modeling has been applied to the dengue epidemiology in Sri Lanka, 2006-2008 to assess the relationship between different outcomes of LOS and platelet count of dengue patients with the district cluster effect. Two key approaches have been applied to build up the joint scenario. In the first approach, modeling each competing risk separately using the binary logistic model, treating all other events as censored under the multilevel discrete time to event model, while the platelet counts are assumed to follow a lognormal regression model. The second approach is based on the endogeneity effect in the multilevel competing risks and count model. Model parameters were estimated using maximum likelihood based on the Laplace approximation. Moreover, the study reveals that joint modeling approach yield more precise results compared to fitting two separate univariate models, in terms of AIC (Akaike Information Criterion).

  1. Mistletoe in the treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Esin Sakallı Çetin

    2014-03-01

    Full Text Available Malignant melanoma is a malignant neoplasia drives from melanocytes. Malignant melanoma, the most causing death, is seen in the third place at skin cancer. Malignant melanoma shows intrinsic resistance to chemotherapeutic agents and variability in the course of the disease which are distinct features separating from other solid tumors. These features prevent the development and standardization of non-surgical treatment models of malignant melanoma. Although there is a large number of chemotherapeutic agents used in the treatment of metastatic malignant melanoma, it hasn’t been demonstrated the survival advantage of adjuvant treatment with chemotherapeutic agents. Because of the different clinical course of malignant melanoma, the disease is thought to be closely associated with immune system. Therefore, immunomodulatory therapy models were developed. Mistletoe stimulates the immune system by increasing the number and activity of dendritic cells, thus it has been shown to effect on tumor growth and metastasis of malignant melanoma patient. Outlined in this review are the recent developments in the understanding the role of mistletoe as a complementary therapy for malignant melanoma. J Clin Exp Invest 2014; 5 (1: 145-152

  2. Skin cancer and melanoma

    International Nuclear Information System (INIS)

    Moylan, D.J.

    1991-01-01

    In this chapter, the author discusses various types of non-melanoma malignant skin cancer, as well as malignant melanoma. Non-melanoma skin cancer, such as basal cell and squamous cell carcinomas, occasionally metastasize, but only late in the course of the disease. On the other hand, even relatively small primary melanomas tend to disseminate to regional lymph nodes and to distant sites. The author presents various treatment plans, including radiation therapy. Cutaneous melanomas have been considered relatively radioresistant. This is the rationale for the use of large fraction radiation therapy in the treatment of melanomas with the fraction sizes varying from 4--8 Gy

  3. Testicular Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of testicular cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  4. Pancreatic Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  5. Colorectal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  6. Prostate Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  7. Bladder Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  8. Esophageal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing esophageal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  9. Cervical Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  10. Breast Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  11. Lung Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  12. Liver Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  13. Ovarian Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  14. The Expression Quantitative Trait Loci in Immune Pathways and their Effect on Cutaneous Melanoma Prognosis.

    Science.gov (United States)

    Vogelsang, Matjaz; Martinez, Carlos N; Rendleman, Justin; Bapodra, Anuj; Malecek, Karolina; Romanchuk, Artur; Kazlow, Esther; Shapiro, Richard L; Berman, Russell S; Krogsgaard, Michelle; Osman, Iman; Kirchhoff, Tomas

    2016-07-01

    The identification of personalized germline markers with biologic relevance for the prediction of cutaneous melanoma prognosis is highly demanded but to date, it has been largely unsuccessful. As melanoma progression is controlled by host immunity, here we present a novel approach interrogating immunoregulatory pathways using the genome-wide maps of expression quantitative trait loci (eQTL) to reveal biologically relevant germline variants modulating cutaneous melanoma outcomes. Using whole genome eQTL data from a healthy population, we identified 385 variants significantly impacting the expression of 268 immune-relevant genes. The 40 most significant eQTLs were tested in a prospective cohort of 1,221 patients with cutaneous melanoma for their association with overall (OS) and recurrence-free survival using Cox regression models. We identified highly significant associations with better melanoma OS for rs6673928, impacting IL19 expression (HR, 0.56; 95% CI, 0.41-0.77; P = 0.0002) and rs6695772, controlling the expression of BATF3 (HR, 1.64; 95% CI, 1.19-2.24; P = 0.0019). Both associations map in the previously suspected melanoma prognostic locus at 1q32. Furthermore, we show that their combined effect on melanoma OS is substantially enhanced reaching the level of clinical applicability (HR, 1.92; 95% CI, 1.43-2.60; P = 2.38e-5). Our unique approach of interrogating lymphocyte-specific eQTLs reveals novel and biologically relevant immunomodulatory eQTL predictors of cutaneous melanoma prognosis that are independent of current histopathologic markers. The significantly enhanced combined effect of identified eQTLs suggests the personalized utilization of both SNPs in a clinical setting, strongly indicating the promise of the proposed design for the discovery of prognostic or risk germline markers in other cancers. Clin Cancer Res; 22(13); 3268-80. ©2016 AACR. ©2016 American Association for Cancer Research.

  15. Risk modelling in portfolio optimization

    Science.gov (United States)

    Lam, W. H.; Jaaman, Saiful Hafizah Hj.; Isa, Zaidi

    2013-09-01

    Risk management is very important in portfolio optimization. The mean-variance model has been used in portfolio optimization to minimize the investment risk. The objective of the mean-variance model is to minimize the portfolio risk and achieve the target rate of return. Variance is used as risk measure in the mean-variance model. The purpose of this study is to compare the portfolio composition as well as performance between the optimal portfolio of mean-variance model and equally weighted portfolio. Equally weighted portfolio means the proportions that are invested in each asset are equal. The results show that the portfolio composition of the mean-variance optimal portfolio and equally weighted portfolio are different. Besides that, the mean-variance optimal portfolio gives better performance because it gives higher performance ratio than the equally weighted portfolio.

  16. A new understanding in the epidemiology of melanoma.

    Science.gov (United States)

    Erdei, Esther; Torres, Salina M

    2010-11-01

    The incidence of melanoma is continuing to increase worldwide. UV exposure is a known risk factor for melanoma. Geographic location is known to influence UV exposure and the distribution of the incidence of melanoma. Furthermore, epidemiologic data suggest that gender and genetics may influence the distribution of melanoma on the body surface and histopathologic characteristics of the lesion. This article describes what is known about the impact of gender, ethnicity and geography on the progression of melanoma. Advanced-stage cutaneous melanoma has a median survival time of less than 1 year. Surgical removal, radiotherapy, chemotherapy, targeted therapies and a variety of immunotherapies have been utilized in the treatment of melanoma. Current treatment strategies and the results of recent clinical trials are also discussed in this article.

  17. Infantile melanoma--a triple threat: diagnosis and management.

    Science.gov (United States)

    Lambie, Milena; Nadler, Chad; Glat, Paul; Van Duzer, Scott; Halligan, Gregory; Geller, Evan

    2011-07-01

    Cases of infantile melanoma are very rare, and only a few have been presented in the literature. Pediatric melanoma can present to the clinician as a "triple threat" of delayed diagnosis resulting in thick lesions at risk for metastasis, histologic uncertainty of diagnosis, and a lack of data guiding regional node management and adjuvant therapy. Melanoma in childhood is an uncommon condition, and it is even more atypical in infants. There is evidence however that it is increasing in frequency. We present 2 cases of infantile melanoma diagnosed before age 1 and multidisciplinary management performed at our institution. One child was diagnosed with melanoma arising within a congenital melanocytic nevus, and the other presented with melanoma from a de novo acquired scalp lesion. The ambiguity surrounding correct pathologic diagnosis of melanoma in this age group, and the tendency for late diagnosis with thicker lesions presents special staging and treatment challenges to the team of specialists involved in the care of these children.

  18. Discriminating model for diagnosis of basal cell carcinoma and melanoma in vitro based on the Raman spectra of selected biochemicals

    Science.gov (United States)

    Silveira, Landulfo; Silveira, Fabrício Luiz; Bodanese, Benito; Zângaro, Renato Amaro; Pacheco, Marcos Tadeu T.

    2012-07-01

    Raman spectroscopy has been employed to identify differences in the biochemical constitution of malignant [basal cell carcinoma (BCC) and melanoma (MEL)] cells compared to normal skin tissues, with the goal of skin cancer diagnosis. We collected Raman spectra from compounds such as proteins, lipids, and nucleic acids, which are expected to be represented in human skin spectra, and developed a linear least-squares fitting model to estimate the contributions of these compounds to the tissue spectra. We used a set of 145 spectra from biopsy fragments of normal (30 spectra), BCC (96 spectra), and MEL (19 spectra) skin tissues, collected using a near-infrared Raman spectrometer (830 nm, 50 to 200 mW, and 20 s exposure time) coupled to a Raman probe. We applied the best-fitting model to the spectra of biochemicals and tissues, hypothesizing that the relative spectral contribution of each compound to the tissue Raman spectrum changes according to the disease. We verified that actin, collagen, elastin, and triolein were the most important biochemicals representing the spectral features of skin tissues. A classification model applied to the relative contribution of collagen III, elastin, and melanin using Euclidean distance as a discriminator could differentiate normal from BCC and MEL.

  19. Association of Delays in Surgery for Melanoma With Insurance Type.

    Science.gov (United States)

    Adamson, Adewole S; Zhou, Lei; Baggett, Christopher D; Thomas, Nancy E; Meyer, Anne-Marie

    2017-11-01

    Timely receipt of treatment for cancer is an important aspect of health care quality. It is unknown how delays of surgery for melanoma vary by insurance type. To analyze factors associated with delays between diagnosis and surgery for melanoma in patients with Medicare, Medicaid, or private insurance. Retrospective cohort study of patients who received a diagnosis of melanoma between 2004 and 2011 in North Carolina using data from the North Carolina Cancer Registry linked to administrative claims from Medicare, Medicaid, and private insurance. Inclusion criteria were incident patients with a diagnosis of melanoma stage 0 to III and with continuous insurance enrollment from at least 1 month prior to the month of diagnosis to 12 months after diagnosis of melanoma. Surgical delay, defined as definitive surgical excision occurring more than 6 weeks after melanoma diagnosis. Generalized linear models with log link, Poisson distributions, and robust standard errors were used to estimate adjusted risk ratios (RRs) to model risk of delay in definitive surgery. A total of 7629 patients were included (4210 [55%] female; mean [SD] age, 64 [15] years), 48% (n = 3631) Medicare, 48% (n = 3667) privately insured, and 4% (n = 331) Medicaid patients. Privately insured patients were least likely to experience a delay in definitive surgery, followed by Medicare and Medicaid patients (519 [14%], 609 [17%], and 79 [24%], respectively; P insurance (RR, 1.36; 95% CI, 1.09-1.70). Delays were more likely in nonwhite patients (RR, 1.38; 95% CI, 1.02-1.87). Surgical delays were less likely if the physician performing the surgery (RR, 0.82; 95% CI, 0.72-0.93) or the diagnosing clinician (RR, 0.81; 95% CI, 0.71-0.93) was a dermatologist as compared with a nondermatologist. Surgical treatment delays were common but were less prevalent in patients diagnosed or surgically treated by a dermatologist. Medicaid patients experienced the most surgical delays. A reduction in delays in

  20. Identification of five chromosomal regions involved in predisposition to melanoma by genome by genome-wide scan in the MeLiM swine model

    Czech Academy of Sciences Publication Activity Database

    Geffrotin, C.; Crechet, F.; Le Roy, P.; Le Chalony, C.; Leplat, J. J.; Iannuccelli, N.; Barbosa, A.; Renard, C.; Gruand, J.; Milan, D.; Horák, Vratislav; Tricaud, Y.; Bouet, S.; Franck, M.; Frelat, G.; Vincent-Naulleau, S.

    2004-01-01

    Roč. 110, - (2004), s. 39-50 ISSN 0020-7136 R&D Projects: GA ČR GA524/01/0162 Grant - others:Association pour la recherche controle cancer(FR) 9450; Electricité de France(FR) 8703; Integrated actions program(FR) Barande 04710WJ2002-029 Institutional research plan: CEZ:AV0Z5045916 Keywords : familial melanoma * animal model * swine Subject RIV: ED - Physiology Impact factor: 4.416, year: 2004

  1. Non Melanoma Skin Cancer Pathogenesis Overview.

    Science.gov (United States)

    Didona, Dario; Paolino, Giovanni; Bottoni, Ugo; Cantisani, Carmen

    2018-01-02

    (1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer.

  2. Prediction of nonsentinel lymph node metastasis in malignant melanoma.

    Science.gov (United States)

    Cadili, Ali; Smylie, Michael; Danyluk, John; Dabbs, Kelly

    2009-06-15

    Sentinel lymph node biopsy (SLNB) is the standard at many institutions caring for melanoma patients. Patients with positive SLNB results are currently offered completion lymph node dissection (CLND) of the affected lymph node basin. This procedure entails considerable morbidity and is often applied to patients with shortened life expectancies. Because 80% of CLNDs yield no additional positive nodes and there is no proof that CLND leads to survival improvement, criteria are needed to limit this procedure to those most likely to harbor nonsentinel lymph node (SLN) metastases. A retrospective review of 349 cases of melanoma from January 1999 to April 2007 that underwent sentinel lymph node biopsy at a single institution was done. Statistical analysis was used to compare two subgroups of patients: a positive CLND group and a negative CLND group. These two groups were compared with regards to multiple variables related to patient demographics, primary tumor characteristics, and SLN tumor burden. Age and total size of SLN tumor deposit were the factors with the strongest correlation with CLND positivity. By applying a risk score model that uses the cutoff values of age 55 y and SLN tumor deposit of 5 mm, it is possible to predict CLND positivity in SLN-positive melanoma patients. The likelihood of CLND positivity in SLN-positive melanoma patients can be predicted from two criteria readily available: size of SLN tumor deposit and patient age.

  3. Uveal melanoma: From diagnosis to treatment and the science in between.

    Science.gov (United States)

    Chattopadhyay, Chandrani; Kim, Dae Won; Gombos, Dan S; Oba, Junna; Qin, Yong; Williams, Michelle D; Esmaeli, Bita; Grimm, Elizabeth A; Wargo, Jennifer A; Woodman, Scott E; Patel, Sapna P

    2016-08-01

    Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United States, and their age-adjusted risk is 5 per 1 million population. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomic spread, molecular changes, and responses to systemic therapy. Once uveal melanoma becomes metastatic, therapy options are limited and are often extrapolated from cutaneous melanoma therapies despite the routine exclusion of patients with uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress, and data from these well designed investigations will help guide future directions in this orphan disease. Cancer 2016;122:2299-2312. © 2016 American Cancer Society. © 2016 American Cancer Society.

  4. Modeling renewable energy company risk

    International Nuclear Information System (INIS)

    Sadorsky, Perry

    2012-01-01

    The renewable energy sector is one of the fastest growing components of the energy industry and along with this increased demand for renewable energy there has been an increase in investing and financing activities. The tradeoff between risk and return in the renewable energy sector is, however, precarious. Renewable energy companies are often among the riskiest types of companies to invest in and for this reason it is necessary to have a good understanding of the risk factors. This paper uses a variable beta model to investigate the determinants of renewable energy company risk. The empirical results show that company sales growth has a negative impact on company risk while oil price increases have a positive impact on company risk. When oil price returns are positive and moderate, increases in sales growth can offset the impact of oil price returns and this leads to lower systematic risk.

  5. Risk Factors for Neovascular Glaucoma After Proton Beam Therapy of Uveal Melanoma: A Detailed Analysis of Tumor and Dose–Volume Parameters

    International Nuclear Information System (INIS)

    Mishra, Kavita K.; Daftari, Inder K.; Weinberg, Vivian; Cole, Tia; Quivey, Jeanne M.; Castro, Joseph R.; Phillips, Theodore L.; Char, Devron H.

    2013-01-01

    Purpose: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT). Methods and Materials: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log–rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose–volume histogram parameters. Results: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P 30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P 0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02). Conclusions: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height, diameter, and anterior as well as posterior critical structure dose–volume parameters may be used to predict NVG risk

  6. Hereditary Melanoma: Update on Syndromes and Management - Genetics of familial atypical multiple mole melanoma syndrome

    Science.gov (United States)

    Soura, E.; Eliades, P.; Shannon, K.; Stratigos, A.; Tsao, H.

    2015-01-01

    Malignant melanoma is considered the most lethal skin cancer if not detected and treated at its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (i.e. unilateral lineage, multi-generational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. Such patients have a high risk of developing multiple primary melanomas and internal organ malignancies especially pancreatic cancer; thus, a multidisciplinary approach is necessary in many cases. The value of dermoscopy examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. But, this must be performed with care and only by qualified individuals trained in cancer risk analysis. PMID:26892650

  7. Treatment Option Overview (Melanoma)

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  8. General Information about Melanoma

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  9. Stages of Melanoma

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  10. Melanoma - neck (image)

    Science.gov (United States)

    This melanoma on the neck is variously colored with a very darkly pigmented area found centrally. It has irregular ... be larger than 0.5 cm. Prognosis in melanoma is best defined by its depth on resection.

  11. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  12. Molecular Classification of Melanoma

    Science.gov (United States)

    Tissue-based analyses of precursors, melanoma tumors and metastases within existing study populations to further understanding of the heterogeneity of melanoma and determine a predictive pattern of progression for dysplastic nevi.

  13. Melanoma International Foundation

    Science.gov (United States)

    ... the state of Pennsylvania, certificate #29498 © 2013 Melanoma International Foundation. All Rights Reserved. Privacy Policy | Terms of Use Toll-free: 866-463-6663 International: 610-942-3432 Melanoma International Foundation 250 Mapleflower ...

  14. [Ocular melanomas : An update].

    Science.gov (United States)

    Kalirai, H; Müller, P L; Jaehne, D; Coupland, S E

    2017-11-01

    Melanoma is the most common type of primary cancer to affect the adult eye. Approximately 95% of ocular melanomas are intraocular and arise from the uvea (i. e. iris, ciliary body, and choroid), while the remaining 5% are located in the conjunctiva. Although both uveal and conjunctival melanomas are thought to derive from malignantly transformed melanocytes, uveal melanoma is clinically and biologically distinct from conjunctival melanoma, and indeed from its more common cutaneous counterpart. Intense efforts have been recently made to understand the molecular biology involved in the development of ocular melanomas, and in their progression. Molecular advances, particularly for uveal melanoma, have enhanced prognostication and the identification of rational therapeutic targets for disseminated disease. In this review, recent advances in the molecular characterisation of both uveal and conjunctival melanomas are discussed, and how these may be used to develop personalised therapeutic strategies.

  15. Sarcoidosis in Melanoma Patients: Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Beutler, Bryce D., E-mail: brycebeutler@hotmail.com [School of Allied Health Sciences, University of Nevada, Las Vegas, 1060 Wiegand Road, Encinitas, CA 92024 (United States); Cohen, Philip R., E-mail: brycebeutler@hotmail.com [Department of Dermatology, University of California San Diego, 10991 Twinleaf Court, San Diego, CA 92131 (United States)

    2015-06-15

    Sarcoidosis is a systemic inflammatory disease characterized by the development of noncaseating granulomas in multiple organ systems. Many hematologic malignancies and solid tumors, including melanoma, have been associated with sarcoidosis. We describe the clinical and pathologic findings of a 54-year-old man with melanoma-associated sarcoidosis. In addition, we not only review the literature describing characteristics of other melanoma patients with sarcoidosis, but also the features of melanoma patients with antineoplastic therapy-associated sarcoidosis. Sarcoidosis has been described in 80 melanoma patients; sufficient information for analysis was provided in 39 of these individuals. In 43.6% of individuals (17 out of 39), sarcoidosis was directly associated with melanoma; in 56.4% of oncologic patients (22 out of 39), sarcoidosis was induced by antineoplastic therapy that had been administered for the treatment of their metastatic melanoma. The discovery of melanoma preceded the development of sarcoidosis in 12 of the 17 (70.5%) individuals who did not receive systemic treatment. Pulmonary and/or cutaneous manifestations of sarcoidosis were common among both groups of patients. Most patients did not require treatment for sarcoidosis. Melanoma patients—either following antineoplastic therapy or without systemic treatment—may be at an increased risk to develop sarcoidosis. In antineoplastic therapy naive melanoma patients, a common etiologic factor—such as exposure to ultraviolet light—may play a role in their developing melanoma and sarcoidosis.

  16. Dynamics of melanoma tumor therapy with vesicular stomatitis virus: explaining the variability in outcomes using mathematical modeling.

    Science.gov (United States)

    Rommelfanger, D M; Offord, C P; Dev, J; Bajzer, Z; Vile, R G; Dingli, D

    2012-05-01

    Tumor selective, replication competent viruses are being tested for cancer gene therapy. This approach introduces a new therapeutic paradigm due to potential replication of the therapeutic agent and induction of a tumor-specific immune response. However, the experimental outcomes are quite variable, even when studies utilize highly inbred strains of mice and the same cell line and virus. Recognizing that virotherapy is an exercise in population dynamics, we utilize mathematical modeling to understand the variable outcomes observed when B16ova malignant melanoma tumors are treated with vesicular stomatitis virus in syngeneic, fully immunocompetent mice. We show how variability in the initial tumor size and the actual amount of virus delivered to the tumor have critical roles on the outcome of therapy. Virotherapy works best when tumors are small, and a robust innate immune response can lead to superior tumor control. Strategies that reduce tumor burden without suppressing the immune response and methods that maximize the amount of virus delivered to the tumor should optimize tumor control in this model system.

  17. Experimental boron neutron capture therapy for melanoma: Systemic delivery of boron to melanotic and amelanotic melanoma

    International Nuclear Information System (INIS)

    Coderre, J.A.; Glass, J.D.; Micca, P.; Greenberg, D.; Packer, S.

    1990-01-01

    The boron-containing melanin precursor analogue p-boronophenylalanine (BPA) has previously been shown to selectively deliver boron to pigmented murine melanomas when administered in a single intragastric dose. If boron neutron capture therapy is to become a clinically useful method of radiation therapy for human malignant melanoma, the boron carrier must be capable of delivering useful amounts of boron to remote tumor sites (metastases) and to poorly pigmented melanomas. The authors have now determined the ability of BPA to accumulate in several nonpigmented melanoma models including human melanoma xenografts in nude mice. The absolute amount of boron in the nonpigmented melanomas was about 50% of the observed in the pigmented counterparts but was still selectively concentrated in the tumor relative to normal tissues in amounts sufficient for effective neutron capture therapy. Single intragastric doses of BPA resulted in selective localization of boron in the amelanotic Greene melanoma carried in the anterior chamber of the rabbit eye and in a pigmented murine melanoma growing in the lungs. The ratio of the boron concentration in these tumors to the boron concentration in the immediately adjacent normal tissue was in the range of 3:1 to 4:1. These distribution studies support the proposal that boron neutron capture therapy may be useful as a regional therapy for malignant melanoma

  18. Drug effects on melanoma

    NARCIS (Netherlands)

    Koomen, Elsje Rosalie

    2010-01-01

    Cutaneous melanoma is the most aggressive form of skin cancer and its incidence among Caucasian populations has increased whereas mortality rates are stabilizing or decreasing. The total burden of melanoma is expected to be increasing. As effective treatment options for advanced melanoma are

  19. Burden of Melanoma

    NARCIS (Netherlands)

    C. Holterhues (Cynthia)

    2011-01-01

    markdownabstract__Abstract__ Melanoma is a type of skin cancer that arises from melanocytes. More than 95% of all melanomas occur in the skin, but rarely in the pigmented cells of the eye, meninges or mucosa. This thesis will only regard the invasive cutaneous malignant melanomas.

  20. Genetics of familial melanoma

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin A W; Pritchard, Antonia L

    2015-01-01

    Twenty years ago, the first familial melanoma susceptibility gene, CDKN2A, was identified. Two years later, another high-penetrance gene, CDK4, was found to be responsible for melanoma development in some families. Progress in identifying new familial melanoma genes was subsequently slow; however...

  1. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    Mi Ryung Roh, MD

    2017-03-01

    Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.

  2. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    Mi Ryung Roh, MD

    2015-02-01

    Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.

  3. Lymph Node Micrometastases and In-Transit Metastases from Melanoma: In Vivo Detection with Multispectral Optoacoustic Imaging in a Mouse Model

    Science.gov (United States)

    Neuschmelting, Volker; Lockau, Hannah; Ntziachristos, Vasilis; Grimm, Jan

    2016-01-01

    Purpose To study whether multispectral optoacoustic tomography (MSOT) can serve as a label-free imaging modality for the detection of lymph node micrometastases and in-transit metastases from melanoma on the basis of the intrinsic contrast of melanin in comparison to fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). Materials and Methods The study was approved by the institutional animal care and use committee. Sequential MSOT was performed in a mouse B16F10 melanoma limb lymph node metastasis model (n = 13) to survey the development of macro-, micro- and in-transit metastases (metastases that are in transit from the primary tumor site to the local nodal basin) in vivo. The in vitro limit of detection was assessed in a B16F10 cell phantom. Signal specificity was determined on the basis of a simultaneous lymphadenitis (n = 4) and 4T1 breast cancer lymph metastasis (n = 2) model. MSOT was compared with intravenous FDG PET/CT. The diagnosis was assessed with histologic examination. Differences in the signal ratio (metastatic node to contralateral limb) between the two modalities were determined with the two-tailed paired t test. Results The mean signal ratios acquired with MSOT in micrometastases (2.5 ± 0.3, n = 6) and in-transit metastases (8.3 ± 5.8, n = 4) were higher than those obtained with FDG PET/CT (1.1 ± 0.5 [P .1 for both). In vitro, the limit of detection was at an approximate cell density of five cells per microliter (P < .01). Conclusion MSOT enabled detection of melanoma lymph node micrometastases and in-transit metastases undetectable with FDG PET/CT and helped differentiate melanoma metastasis from other lymphadenopathies. © RSNA, 2016 Online supplemental material is available for this article. PMID:27144537

  4. Command Process Modeling & Risk Analysis

    Science.gov (United States)

    Meshkat, Leila

    2011-01-01

    Commanding Errors may be caused by a variety of root causes. It's important to understand the relative significance of each of these causes for making institutional investment decisions. One of these causes is the lack of standardized processes and procedures for command and control. We mitigate this problem by building periodic tables and models corresponding to key functions within it. These models include simulation analysis and probabilistic risk assessment models.

  5. Bimodal mortality dynamics for uveal melanoma: a cue for metastasis development traits?

    International Nuclear Information System (INIS)

    Demicheli, Romano; Fornili, Marco; Biganzoli, Elia

    2014-01-01

    The study estimates mortality dynamics (event-specific hazard rates over a follow-up time interval) for uveal melanoma. Three thousands six hundred seventy two patients undergoing radical or conservative treatment for unilateral uveal melanoma, whose yearly follow-up data were reported in three published datasets, were analysed. Mortality dynamics was studied by estimating with the life-table method the discrete hazard rate for death. Smoothed curves were obtained by a Kernel-like smoothing procedure and a piecewise exponential regression model. The ratio deaths/patients at risk per year was the main outcome measure. The three explored hazard rate curves display a common bimodal pattern, with a sudden increase peaking at about three years, followed by reduction until the sixth-seventh year and a second surge peaking at about nine years after treatment. The bimodal pattern of mortality indicates that uveal melanoma metastatic development cannot be explained by a continuous growth model. Similar metastasis dynamics have been reported for other tumours, including early breast cancer, for which it supported a paradigm shift to an interrupted growth model, the implications of which are episodes of ‘tumour dormancy’. We propose that the concepts of tumour homeostasis, tumour dormancy and enhancement of metastasis growth related to primary tumour removal, convincingly explaining the clinical behaviour of breast cancer, may be used for uveal melanoma as well. To confirm this proposition, a careful analysis of uveal melanoma metastasis dynamics is strongly warranted

  6. Multifractal Value at Risk model

    Science.gov (United States)

    Lee, Hojin; Song, Jae Wook; Chang, Woojin

    2016-06-01

    In this paper new Value at Risk (VaR) model is proposed and investigated. We consider the multifractal property of financial time series and develop a multifractal Value at Risk (MFVaR). MFVaR introduced in this paper is analytically tractable and not based on simulation. Empirical study showed that MFVaR can provide the more stable and accurate forecasting performance in volatile financial markets where large loss can be incurred. This implies that our multifractal VaR works well for the risk measurement of extreme credit events.

  7. Cabin Environment Physics Risk Model

    Science.gov (United States)

    Mattenberger, Christopher J.; Mathias, Donovan Leigh

    2014-01-01

    This paper presents a Cabin Environment Physics Risk (CEPR) model that predicts the time for an initial failure of Environmental Control and Life Support System (ECLSS) functionality to propagate into a hazardous environment and trigger a loss-of-crew (LOC) event. This physics-of failure model allows a probabilistic risk assessment of a crewed spacecraft to account for the cabin environment, which can serve as a buffer to protect the crew during an abort from orbit and ultimately enable a safe return. The results of the CEPR model replace the assumption that failure of the crew critical ECLSS functionality causes LOC instantly, and provide a more accurate representation of the spacecraft's risk posture. The instant-LOC assumption is shown to be excessively conservative and, moreover, can impact the relative risk drivers identified for the spacecraft. This, in turn, could lead the design team to allocate mass for equipment to reduce overly conservative risk estimates in a suboptimal configuration, which inherently increases the overall risk to the crew. For example, available mass could be poorly used to add redundant ECLSS components that have a negligible benefit but appear to make the vehicle safer due to poor assumptions about the propagation time of ECLSS failures.

  8. Information risk and security modeling

    Science.gov (United States)

    Zivic, Predrag

    2005-03-01

    This research paper presentation will feature current frameworks to addressing risk and security modeling and metrics. The paper will analyze technical level risk and security metrics of Common Criteria/ISO15408, Centre for Internet Security guidelines, NSA configuration guidelines and metrics used at this level. Information IT operational standards view on security metrics such as GMITS/ISO13335, ITIL/ITMS and architectural guidelines such as ISO7498-2 will be explained. Business process level standards such as ISO17799, COSO and CobiT will be presented with their control approach to security metrics. Top level, the maturity standards such as SSE-CMM/ISO21827, NSA Infosec Assessment and CobiT will be explored and reviewed. For each defined level of security metrics the research presentation will explore the appropriate usage of these standards. The paper will discuss standards approaches to conducting the risk and security metrics. The research findings will demonstrate the need for common baseline for both risk and security metrics. This paper will show the relation between the attribute based common baseline and corporate assets and controls for risk and security metrics. IT will be shown that such approach spans over all mentioned standards. The proposed approach 3D visual presentation and development of the Information Security Model will be analyzed and postulated. Presentation will clearly demonstrate the benefits of proposed attributes based approach and defined risk and security space for modeling and measuring.

  9. Isolation and Molecular Characterization of Circulating Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Xi Luo

    2014-05-01

    Full Text Available Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice and rapidly declined after B-RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled a comparison of RNA-sequencing profiles with matched primary tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF-targeted therapy. Together, the capture and molecular characterization of CTCs provide insight into the hematogenous spread of melanoma.

  10. Aspirin and other NSAIDs as chemoprevention agents in melanoma

    Science.gov (United States)

    Goodman, James R.; Grossman, Douglas

    2014-01-01

    Melanoma incidence is increasing and, despite recent therapeutic advances, the prognosis for patients with metastatic disease remains poor. Thus early detection and chemoprevention are promising strategies for improving patient outcomes. Aspirin (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) have demonstrated chemoprotective activity in several other cancers, and have been proposed as chemopreventive agents for melanoma. Throughout the last decade, however, a number of case-control, prospective, and interventional studies of NSAIDs and melanoma risk have yielded conflicting results. These inconsistent findings have led to uncertainty about the clinical utility of NSAIDs for melanoma chemoprevention. This mini-review highlights current knowledge of NSAID mechanisms of action and rationale for use in melanoma, provides a comparative review of outcomes and limitations of prior studies, and discusses the future challenges in demonstrating that these drugs are effective agents for mitigating melanoma risk. PMID:24694780

  11. 17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model.

    Science.gov (United States)

    Joshi, Sandeep S; Jiang, Shunlin; Unni, Emmanual; Goding, Stephen R; Fan, Tao; Antony, Paul A; Hornyak, Thomas J

    2018-01-01

    Heat shock protein 90 (HSP90) is a molecular chaperone which stabilizes client proteins with important roles in tumor growth. 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational change which destabilizes client proteins and directs them towards proteosomal degradation. Malignant melanomas have active RAF-MEK-ERK signaling which can occur either through an activating mutation in BRAF (BRAFV600E) or through activation of signal transduction upstream of BRAF. Prior work showed that 17-AAG inhibits cell growth in BRAFV600E and BRAF wildtype (BRAFWT) melanomas, although there were conflicting reports about the dependence of BRAFV600E and BRAFWT upon HSP90 activity for stability. Here, we demonstrate that BRAFWT and CRAF are bound by HSP90 in BRAFWT, NRAS mutant melanoma cells. HSP90 inhibition by 17-AAG inhibits ERK signaling and cell growth by destabilizing CRAF but not BRAFWT in the majority of NRAS mutant melanoma cells. The highly-selective BRAFV600E inhibitor, PLX4032 (vemurafenib), inhibits ERK signaling and cell growth in mutant BRAF melanoma cells, but paradoxically enhances signaling in cells with wild-type BRAF. In our study, we examined whether 17-AAG could inhibit PLX4032-enhanced ERK signaling in BRAFWT melanoma cells. As expected, PLX4032 alone enhanced ERK signaling in the BRAFWT melanoma cell lines Mel-Juso, SK-Mel-2, and SK-Mel-30, and inhibited signaling and cell growth in BRAFV600E A375 cells. However, HSP90 inhibition by 17-AAG inhibited PLX4032-enhanced ERK signaling and inhibited cell growth by destabilizing CRAF. Surprisingly, 17-AAG also stimulated melanin production in SK-Mel-30 cells and enhanced TYRP1 and DCT expression without stimulating TYR production in all three BRAFWT cell lines studied as well as in B16F10 mouse melanoma cells. In vivo, the combination of 17-AAG and cellular immunotherapy directed against Tyrp1 enhanced the inhibition of

  12. Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model.

    Science.gov (United States)

    Choisunirachon, N; Jaroensong, T; Yoshida, K; Saeki, K; Mochizuki, M; Nishimura, R; Sasaki, N; Nakagawa, T

    2015-12-01

    Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma. © 2013 John Wiley & Sons Ltd.

  13. Tumor-targeting properties of {sup 90}Y- and {sup 177}Lu-labeled {alpha}-melanocyte stimulating hormone peptide analogues in a murine melanoma model

    Energy Technology Data Exchange (ETDEWEB)

    Miao Yubin [Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States) and Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States); Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201 (United States)]. E-mail: miaoy@missouri.edu; Hoffman, Timothy J. [Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States); Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201 (United States); Quinn, Thomas P. [Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States); Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201 (United States); Department of Radiology, University of Missouri-Columbia, Columbia, MO 65211 (United States)

    2005-07-01

    The purpose of this study was to compare the tumor-targeting properties of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH in a murine melanoma mouse model. Methods: The in vitro properties of cellular internalization and retention of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were determined in B16/F1 melanoma-bearing C57 mice. Results: {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH exhibited fast cellular internalization and extended cellular retention in B16/F1 cells. High receptor-mediated tumor uptake and retention coupled with fast whole-body clearance of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were 25.70{+-}4.64 and 14.48{+-}0.85 %ID/g at 2 h, and 14.09{+-}2.73 and 17.68{+-}3.32 %ID/g at 4 h postinjection. There was little activity accumulated in normal organs except for kidney. Conclusions: High tumor-targeting properties of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations.

  14. Tumor-targeting properties of 90Y- and 177Lu-labeled α-melanocyte stimulating hormone peptide analogues in a murine melanoma model

    International Nuclear Information System (INIS)

    Miao Yubin; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-01-01

    The purpose of this study was to compare the tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH in a murine melanoma mouse model. Methods: The in vitro properties of cellular internalization and retention of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were determined in B16/F1 melanoma-bearing C57 mice. Results: 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH exhibited fast cellular internalization and extended cellular retention in B16/F1 cells. High receptor-mediated tumor uptake and retention coupled with fast whole-body clearance of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were 25.70±4.64 and 14.48±0.85 %ID/g at 2 h, and 14.09±2.73 and 17.68±3.32 %ID/g at 4 h postinjection. There was little activity accumulated in normal organs except for kidney. Conclusions: High tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations

  15. Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.

    Science.gov (United States)

    von Euler, Henrik; Sadeghi, Arian; Carlsson, Björn; Rivera, Patricio; Loskog, Angelica; Segall, Thomas; Korsgren, Olle; Tötterman, Thomas H

    2008-05-01

    Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.

  16. Fear of new or recurrent melanoma after treatment for localised melanoma.

    Science.gov (United States)

    Bell, Katy J L; Mehta, Yachna; Turner, Robin M; Morton, Rachael L; Dieng, Mbathio; Saw, Robyn; Guitera, Pascale; McCaffery, Kirsten; Low, Donald; Low, Cynthia; Jenkins, Marisa; Irwig, Les; Webster, Angela C

    2017-11-01

    To estimate the amount of fear of new or recurrent melanoma among people treated for localised melanoma in an Australian specialist centre. We randomly selected 400 potential participants from all those treated for localised melanoma at the Melanoma Institute Australia during 2014 (n = 902). They were asked to complete an adapted version of the Fear of Cancer Recurrence Inventory (FCRI). We calculated summary statistics for demographics, clinical variables and total FCRI and subscale scores. Two hundred fifteen people (54%) completed the FCRI questionnaire. The overall mean severity subscale score was 15.0 (95% CI 14.0-16.1). A high proportion of participants had scores above a proposed threshold to screen for clinical fear of cancer recurrence (77% and 63% of participants with and without new or recurrent melanoma had severity subscale scores ≥13). Most participants also had scores above a threshold found to have high specificity for clinical fear of cancer recurrence (65% and 48% of participants with and without new or recurrent melanoma had severity subscale scores ≥16). The severity subscale appeared to discriminate well between groups with differing levels of risk of new or recurrent melanoma. There is a substantial amount of fear of new or recurrent melanoma among this population, despite most having a very good prognosis. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Associations between childhood height and morphologically different variants of melanoma in adulthood

    DEFF Research Database (Denmark)

    Meyle, Kathrine Damm; Gamborg, Michael Orland; Hølmich, Lisbet Rosenkrantz

    2016-01-01

    .5% nodular melanoma (NM), and 2% lentigo maligna melanoma (LMM). The remaining rare melanoma forms were not analysed. Childhood height was positively and significantly associated with SSM, melanoma NOS, and NM, but not LMM, in adulthood. Per height z-score at age 13 years, the hazard ratios were 1.20 (95......AIM OF THE STUDY: Melanoma subtypes have different aetiological characteristics. Child height is positively associated with adult melanoma; however, a clarification of associations with specific melanoma variants is necessary for an improved understanding of risk factors underlying the histologic...... entities. This study investigated associations between childhood height and future development of cutaneous melanoma variants. METHOD: A cohort study of 316,193 individuals from the Copenhagen School Health Records Register, with measured heights at ages 7-13 years who were born from 1930 to 1989. Melanoma...

  18. Risk Factors for Neovascular Glaucoma After Proton Beam Therapy of Uveal Melanoma: A Detailed Analysis of Tumor and Dose–Volume Parameters

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Kavita K., E-mail: kmishra@radonc.ucsf.edu [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Daftari, Inder K.; Weinberg, Vivian [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Cole, Tia [The Tumori Foundation, San Francisco, California (United States); Quivey, Jeanne M.; Castro, Joseph R.; Phillips, Theodore L. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Char, Devron H. [The Tumori Foundation, San Francisco, California (United States)

    2013-10-01

    Purpose: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT). Methods and Materials: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log–rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose–volume histogram parameters. Results: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P<.0001), greater height (P<.0001), higher T stage (P<.0001), and closer proximity to the disc (P=.002). Dose–volume histogram analysis revealed that if >30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P<.0001 for both). Furthermore, if 100% of the disc or macula received ≥28 GyE, the NVG rate was higher (P<.0001 and P=.03, respectively). If both anterior and posterior doses were above specified cut points, NVG risk was highest (P<.0001). Multivariate analysis confirmed significant independent risk factors to include tumor height (P<.0001), age (P<.0001), %disc treated to ≥50% Dose (<100% vs 100%) (P=.0007), larger tumor diameter (P=.01), %lens treated to ≥90% Dose (0 vs >0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02). Conclusions: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height

  19. Lunar Landing Operational Risk Model

    Science.gov (United States)

    Mattenberger, Chris; Putney, Blake; Rust, Randy; Derkowski, Brian

    2010-01-01

    Characterizing the risk of spacecraft goes beyond simply modeling equipment reliability. Some portions of the mission require complex interactions between system elements that can lead to failure without an actual hardware fault. Landing risk is currently the least characterized aspect of the Altair lunar lander and appears to result from complex temporal interactions between pilot, sensors, surface characteristics and vehicle capabilities rather than hardware failures. The Lunar Landing Operational Risk Model (LLORM) seeks to provide rapid and flexible quantitative insight into the risks driving the landing event and to gauge sensitivities of the vehicle to changes in system configuration and mission operations. The LLORM takes a Monte Carlo based approach to estimate the operational risk of the Lunar Landing Event and calculates estimates of the risk of Loss of Mission (LOM) - Abort Required and is Successful, Loss of Crew (LOC) - Vehicle Crashes or Cannot Reach Orbit, and Success. The LLORM is meant to be used during the conceptual design phase to inform decision makers transparently of the reliability impacts of design decisions, to identify areas of the design which may require additional robustness, and to aid in the development and flow-down of requirements.

  20. Whole Body Melanoma Transcriptome Response in Medaka.

    Directory of Open Access Journals (Sweden)

    Manfred Schartl

    Full Text Available The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02 in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma

  1. Fuzzy audit risk modeling algorithm

    Directory of Open Access Journals (Sweden)

    Zohreh Hajihaa

    2011-07-01

    Full Text Available Fuzzy logic has created suitable mathematics for making decisions in uncertain environments including professional judgments. One of the situations is to assess auditee risks. During recent years, risk based audit (RBA has been regarded as one of the main tools to fight against fraud. The main issue in RBA is to determine the overall audit risk an auditor accepts, which impact the efficiency of an audit. The primary objective of this research is to redesign the audit risk model (ARM proposed by auditing standards. The proposed model of this paper uses fuzzy inference systems (FIS based on the judgments of audit experts. The implementation of proposed fuzzy technique uses triangular fuzzy numbers to express the inputs and Mamdani method along with center of gravity are incorporated for defuzzification. The proposed model uses three FISs for audit, inherent and control risks, and there are five levels of linguistic variables for outputs. FISs include 25, 25 and 81 rules of if-then respectively and officials of Iranian audit experts confirm all the rules.

  2. Credit risk & forward price models

    OpenAIRE

    Gaspar, Raquel Medeiros

    2006-01-01

    Doutoramento em Gestão This thesis consists of three distinct parts. Part I introduces the basic concepts and the notion of general quadratic term structures (GQTS) essential in some of the following chapters. Part II focuses on credit risk models and Part III studies forward price term structure models using both the classical and the geometrical approach. Part I is organized as follows. Chapter 1is divided in two main sections. The first section presents some of ...

  3. Tumor progression in uveal melanoma

    NARCIS (Netherlands)

    C.M. Mooij (Cornelia)

    1995-01-01

    textabstractOphthalmic melanomas can be divided in extra-ocular (conjunctiva, caruncle) and intraocular uveal melanomas (iris, ciliary body and choroid). Uveal melanomas account for 95% of ocular melanomas, while only 5% are conjunctival in origin. The extra-ocular and intra-ocular melanomas differ

  4. Model of MSD Risk Assessment at Workplace

    OpenAIRE

    K. Sekulová; M. Šimon

    2015-01-01

    This article focuses on upper-extremity musculoskeletal disorders risk assessment model at workplace. In this model are used risk factors that are responsible for musculoskeletal system damage. Based on statistic calculations the model is able to define what risk of MSD threatens workers who are under risk factors. The model is also able to say how MSD risk would decrease if these risk factors are eliminated.

  5. Pregnancy promotes melanoma metastasis through enhanced lymphangiogenesis.

    Science.gov (United States)

    Khosrotehrani, Kiarash; Nguyen Huu, Sau; Prignon, Aurélie; Avril, Marie-Françoise; Boitier, Françoise; Oster, Michèle; Mortier, Laurent; Richard, Marie-Aleth; Maubec, Eve; Kerob, Delphine; Mansard, Sandrine; Merheb, Charbel; Moguelet, Philippe; Nassar, Dany; Guégan, Sarah; Aractingi, Selim

    2011-04-01

    The relationships of pregnancy and melanoma have been debatable. Our aim was to assess the influence of gestation on the course of melanoma in a classic murine model of tumor progression and in women. B16 mouse melanoma cells were injected in nonpregnant or pregnant mice on day 5 of gestation. Animals were evaluated for tumor progression, metastases, and survival. Tumor sections were analyzed for lymphatic and blood vessel number and relative surface and expression of angiogenic growth factors. Finally, primary melanomas from pregnant and nonpregnant women, matched for age and tumor thickness, were also considered. Tumor growth, metastasis, and mortality were increased in B16-injected pregnant mice. Tumors displayed an increase in intratumoral lymphangiogenesis during gestation. This increased lymphatic angiogenesis was not observed in normal skin during gestation, showing its specificity to the tumor. An analysis of melanoma from pregnant and matched nonpregnant women showed a similar increase in lymphatic vessels. Tumors from pregnant mice had increased expression of vascular endothelial growth factor A at the RNA and protein levels. The increased vascular endothelial growth factor A production by melanoma cells could be reproduced in culture using pregnant mouse serum. In conclusion, pregnancy results in increased lymphangiogenesis and subsequent metastasis. Caution should be applied in the management of patients with advanced-stage melanoma during gestation. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Melanoma m (zero): diagnosis and therapy.

    Science.gov (United States)

    Rastrelli, Marco; Alaibac, Mauro; Stramare, Roberto; Chiarion Sileni, Vanna; Montesco, Maria Cristina; Vecchiato, Antonella; Campana, Luca Giovanni; Rossi, Carlo Riccardo

    2013-01-01

    This paper reviews the epidemiology, diagnosis, and treatment of M zero cutaneous melanoma including the most recent developments. This review also examined the main risk factors for melanoma. Tumor thickness measured according to Breslow, mitotic rate, ulceration, and growth phase has the greatest predictive value for survival and metastasis. Wide excision of the primary tumor is the only potentially curative treatment for primary melanoma. The sentinel node biopsy must be performed on all patients who have a primary melanoma with a Breslow thickness > 1 mm, or if the melanoma is from 0,75 mm to 1 mm thick but it is ulcerated and/or the mitotic index is ≥1. Total lymph node dissection consists in removing the residual lymph nodes in patients with positive sentinel node biopsy, or found positive on needle aspiration biopsy, without radiological evidence of spread. Isolated limb perfusion and isolated limb infusion are employed in patients within transit metastases with a rate of complete remission in around 50% and 38% of cases. Electrochemotherapy is mainly indicated for palliation in cases of metastatic disease, though it may sometimes be useful to complete isolated limb perfusion. The only agent found to affect survival as an adjuvant treatment is interferon alpha-2. Adjuvant radiotherapy improves local control of melanoma in patients at a high risk of recurrence after lymph node dissection.

  7. Epidemiology of uveal melanomas in Moscow

    Directory of Open Access Journals (Sweden)

    E. E. Grishina

    2017-01-01

    Full Text Available Rationale: Melanoma of the uveal tract of the eye is among the most prevalent malignant intraocular tumors.Aim: To identify epidemiological characteristics of uveal melanoma in Moscow.Materials and methods: We performed a retrospective analysis of out-patient files and follow-up charts of patients with uveal melanoma in the Ophthalmological Clinical Hospital of the Department of Healthcare, Moscow, from 1977 to 2012.Results: Within 36 years, 2547 patients with uveal melanoma have been registered, at the age of 16 to 92 years. The male to female ratio was 1:1.5. The rate of patient referrals with subsequent diagnosis of uveal melanoma has not changed from 1977 to 2000 and was on average 1.07 persons per 100,000 of the adult population. From 2001 to 2012, there was some decline in the number of referrals with uveal melanoma to the average of 0.9 persons per 100,000 of the adult population. We analyzed survival among 359 patients with uveal melanoma after enucleation surgery of the eye; 37% of them were men (63.2 ± 1.8 years and 63% women (69.5 ± 2.7 years. Their 5-year metastasis-free survival was 65 ± 3%, whereas the 7-year survival was 60 ± 4%. The mean time to death was 5.5 years. There were no association between the life longevity and patients gender, but their survival was associated with the age of patients. The risk of death from metastatic uveal melanoma among patients above 60 years of age was on average 10% higher. After the enucleation surgery, patients with Т4 melanoma lived significantly less than those with Т1-3 tumor (5 and 6.5 years, respectively; р = 0.05.Conclusion: The rates of diagnosis of uveal melanoma at referrals within 36 years did not increased. Epidemiology of uveal melanoma in Moscow is characterized by a high proportion of elderly women. Shorter overall and metastasis-free survival of patients with uveal melanoma after the enucleation surgery depends from a higher proportion

  8. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

    Science.gov (United States)

    2016-05-06

    Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  9. PIM kinases as therapeutic targets against advanced melanoma

    Science.gov (United States)

    Shannan, Batool; Watters, Andrea; Chen, Quan; Mollin, Stefan; Dörr, Markus; Meggers, Eric; Xu, Xiaowei; Gimotty, Phyllis A.; Perego, Michela; Li, Ling; Benci, Joseph; Krepler, Clemens; Brafford, Patricia; Zhang, Jie; Wei, Zhi; Zhang, Gao; Liu, Qin; Yin, Xiangfan; Nathanson, Katherine L.; Herlyn, Meenhard; Vultur, Adina

    2016-01-01

    Therapeutic strategies for the treatment of metastatic melanoma show encouraging results in the clinic; however, not all patients respond equally and tumor resistance still poses a challenge. To identify novel therapeutic targets for melanoma, we screened a panel of structurally diverse organometallic inhibitors against human-derived normal and melanoma cells. We observed that a compound that targets PIM kinases (a family of Ser/Thr kinases) preferentially inhibited melanoma cell proliferation, invasion, and viability in adherent and three-dimensional (3D) melanoma models. Assessment of tumor tissue from melanoma patients showed that PIM kinases are expressed in pre- and post-treatment tumors, suggesting PIM kinases as promising targets in the clinic. Using knockdown studies, we showed that PIM1 contributes to melanoma cell proliferation and tumor growth in vivo; however, the presence of PIM2 and PIM3 could also influence the outcome. The inhibition of all PIM isoforms using SGI-1776 (a clinically-available PIM inhibitor) reduced melanoma proliferation and survival in preclinical models of melanoma. This was potentiated in the presence of the BRAF inhibitor PLX4720 and in the presence of PI3K inhibitors. Our findings suggest that PIM inhibitors provide promising additions to the targeted therapies available to melanoma patients. PMID:27448973

  10. Comprehensive histopathological comparison of epidermotropic/dermal metastatic melanoma and primary nodular melanoma.

    Science.gov (United States)

    Skala, Stephanie L; Arps, David P; Zhao, Lili; Cha, Kelly B; Wang, Min; Harms, Paul W; Andea, Aleodor A; Fullen, Douglas R; Chan, May P

    2018-02-01

    Metastatic melanoma involving the epidermis and/or upper dermis may show significant histological overlap with primary cutaneous melanoma, especially the nodular subtype. Proper histopathological classification is crucial to appropriate staging and management, but is often challenging. The aim of this study was to identify helpful histopathological features for differentiating epidermotropic/dermal metastatic melanoma (EDMM) and primary nodular melanoma (PNM). A cohort of EDMMs (n = 74) and PNMs (n = 75) was retrospectively reviewed for various histopathological features, and the data were compared between groups by the use of univariate analysis. Features significantly associated with EDMM included a tumour size of 10 mm, ulceration, epidermal collarettes, a higher mitotic rate, necrosis, multiple phenotypes, significant pleomorphism, and lichenoid inflammation. In multivariate analysis, a logistic regression model including large tumour size, ulceration, prominent TIPs, lichenoid inflammation and epidermal collarettes was highly predictive of PNM. Six (8%) EDMMs from three patients showed an 'epidermal-only' or 'epidermal-predominant' pattern closely simulating in-situ or microinvasive melanoma. Two of these cases were tested by fluorescence in-situ hybridisation, which confirmed clonal relationships with their corresponding primary melanomas. This is the first comprehensive histopathological comparison of EDMM and PNM. Recognition of the above histopathological associations should aid in the correct classification and staging of cutaneous melanoma. Epidermotropic metastatic melanomas may occasionally show an epidermal-only/epidermal-predominant pattern; accurate diagnosis requires prudent clinical correlation and, when necessary, ancillary molecular tests. © 2017 John Wiley & Sons Ltd.

  11. Topical calcitriol prior to photodynamic therapy enhances treatment efficacy in non-melanoma skin cancer mouse models

    Science.gov (United States)

    Rollakanti, Kishore; Anand, Sanjay; Maytin, Edward V.

    2015-03-01

    Non-melanoma skin cancers (NMSCs) such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common form of human cancer worldwide, and their incidence is increasing. Photodynamic therapy (PDT), mediated by topically applied aminolevulinic acid (ALA) and subsequent exposure to light (either a laser or a noncoherent source), is being increasingly used for the treatment of dermatological disorders, including BCC and SCC. However, therapeutic responses of NMSCs to ALA-PDT are currently not superior to standard therapies, although the latter have undesirable side effects including scarring. In this study, we report that preconditioning of skin tumors with calcitriol (active form of Vitamin D; Vit D) prior to ALA-PDT, significantly improves the treatment outcome. In BCC and UVB-induced SCC mouse models, we identified an increase in tumor-specific accumulation of ALA induced photosensitizer (protoporphyrin IX, PpIX) due to Vit D preconditioning, of up to 6- fold in vivo. In addition, increased expression of differentiation (145 fold, p < 0.02) and proliferation (42 fold, p <0.005) markers were identified in BCC tumors, all leading to increased tumor destruction (18.3 fold, p < 0.03) with the combination approach, as compared to ALA-PDT alone. Histomorphological changes identified using hematoxylin and eosin staining, and results of TUNEL staining, together documented a beneficial effect of Vit D pretreatment upon tumor cell death. We conclude that this new combination approach with Vit D and ALA-PDT has great potential to achieve complete remission of NMSC tumors, with excellent cosmetic results and an overall beneficial impact upon patient care.

  12. Identification of differentially expressed genes in spontaneously regressing melanoma using the MeLiM Swine Model

    Czech Academy of Sciences Publication Activity Database

    Rambow, F.; Málek, Ondřej; Geffrotin, C.; Leplat, J. J.; Bouet, S.; Piton, G.; Hugot, K.; Bevilacqua, C.; Horák, Vratislav; Vincent-Naulleau, S.

    2008-01-01

    Roč. 21, - (2008), s. 147-161 ISSN 1755-1471 Institutional research plan: CEZ:AV0Z5045916 Keywords : swine melanoma * suppression subtractive hybridization * differential gene expression Subject RIV: FD - Oncology ; Hematology Impact factor: 4.634, year: 2008

  13. Whole-body bioluminescent imaging of human uveal melanoma in a new mouse model of local tumor growth and metastasis.

    NARCIS (Netherlands)

    Notting, I.C.; Buijs, J.; Que, I.; Mintardjo, R.E.; Horst, G. ter; Karperien, M.; Missotten, G.S.; Jager, M.J.; Schalij-Delfos, N.E.; Keunen, J.E.E.; Pluijm, G. van der

    2005-01-01

    PURPOSE: Human uveal melanoma develops in one of the most capillary-rich tissues of the body and has a pure hematogenous dissemination. Radiodiagnostic examinations, such as ultrasonic diagnostic resonance imaging and chest radiographs plus liver enzyme studies in blood, are methods used to detect

  14. Incidence of melanoma in organ transplant recipients in Alberta, Canada.

    Science.gov (United States)

    Tran, Mimi; Sander, Megan; Ravani, Pietro; Mydlarski, P Régine

    2016-10-01

    Many studies have documented the increased risk of non-melanoma skin cancers in organ transplant recipients (OTRs). However, the incidence of melanoma is less well defined. To date, there have been no studies on the incidence of melanoma in Canadian OTRs. Herein, we determine the incidence and clinical features of melanoma in a cohort of OTRs in Southern Alberta, Canada. We used the Southern Alberta Transplant database to identify kidney and liver transplant recipients between the years 2000 and 2012. This population was cross-referenced with the Alberta Cancer Registry for a diagnosis of melanoma. The clinical features of all cases were obtained, and the standardized incidence rate was calculated. We identified 993 OTR patients, representing 5955 person-years. Only one patient developed a melanoma post-transplant, and this was a nodular melanoma. The age-standardized incidence rate was 11 per 100 000 (0.6 per 5955), compared to 13.4 per 100 000 in the general Alberta population (incidence rate ratio of 1.29, with 95% confidence interval of 0.17 to 9.82). This is the first Canadian study to investigate the association between organ transplantation and melanoma. Our study did not identify an increased risk of developing a de novo melanoma post-transplant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Accuracy and prognostic value of sentinel lymph node biopsy in head and neck melanomas.

    Science.gov (United States)

    Patuzzo, Roberto; Maurichi, Andrea; Camerini, Tiziana; Gallino, Gianfranco; Ruggeri, Roberta; Baffa, Giulia; Mattavelli, Ilaria; Tinti, Maria Carla; Crippa, Federica; Moglia, Daniele; Tolomio, Elena; Maccauro, Marco; Santinami, Mario

    2014-04-01

    Debate remains around the accuracy and prognostic implications of sentinel lymph node biopsy (SLNB) for melanoma arising in the head and neck (HN) areas because several analyses have shown discordances between clinically predicted lymphatic drainage pathways and those identified by lymphoscintigraphy. This study assesses the accuracy and prognostic value of SLNB in this critical anatomic region. Retrospective review of a prospectively collected melanoma database identified 331 patients with HN melanomas from January 2000 to December 2012. Primary end points included SLNB result, time to recurrence, site of recurrence, and survival. Multivariate models were constructed for analyses. A sentinel lymph node (SLN) was identified in all 331 patients. There were 59 patients with a positive SLN (17.8%) with a recurrence rate of 88.1% compared with 22.4% in SLN-negative patients (P basin and had undergone a previous SLNB procedure for a false-omission rate of 1.45%. Risks for false-negative SLN occurrences included thick and scalp melanomas. Multivariate analysis on prognostic factors affecting relapse-free survival showed positive SLNB status to be the most prognostic clinicopathologic predictor of recurrence (hazard ratio, 20.56; P < 0.0001). SLNB for patients with HN melanomas is an accurate procedure and has prognostic value. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. AMP kinase-related kinase NUAK2 affects tumor growth, migration, and clinical outcome of human melanoma

    Science.gov (United States)

    Namiki, Takeshi; Tanemura, Atsushi; Valencia, Julio C.; Coelho, Sergio G.; Passeron, Thierry; Kawaguchi, Masakazu; Vieira, Wilfred D.; Ishikawa, Masashi; Nishijima, Wataru; Izumo, Toshiyuki; Kaneko, Yasuhiko; Katayama, Ichiro; Yamaguchi, Yuji; Yin, Lanlan; Polley, Eric C.; Liu, Hongfang; Kawakami, Yutaka; Eishi, Yoshinobu; Takahashi, Eishi; Yokozeki, Hiroo; Hearing, Vincent J.

    2011-01-01

    The identification of genes that participate in melanomagenesis should suggest strategies for developing therapeutic modalities. We used a public array comparative genomic hybridization (CGH) database and real-time quantitative PCR (qPCR) analyses to identify the AMP kinase (AMPK)-related kinase NUAK2 as a candidate gene for melanomagenesis, and we analyzed its functions in melanoma cells. Our analyses had identified a locus at 1q32 where genomic gain is strongly associated with tumor thickness, and we used real-time qPCR analyses and regression analyses to identify NUAK2 as a candidate gene at that locus. Associations of relapse-free survival and overall survival of 92 primary melanoma patients with NUAK2 expression measured using immunohistochemistry were investigated using Kaplan–Meier curves, log rank tests, and Cox regression models. Knockdown of NUAK2 induces senescence and reduces S-phase, decreases migration, and down-regulates expression of mammalian target of rapamycin (mTOR). In vivo analysis demonstrated that knockdown of NUAK2 suppresses melanoma tumor growth in mice. Survival analysis showed that the risk of relapse is greater in acral melanoma patients with high levels of NUAK2 expression than in acral melanoma patients with low levels of NUAK2 expression (hazard ratio = 3.88; 95% confidence interval = 1.44–10.50; P = 0.0075). These data demonstrate that NUAK2 expression is significantly associated with the oncogenic features of melanoma cells and with the survival of acral melanoma patients. NUAK2 may provide a drug target to suppress melanoma progression. This study further supports the importance of NUAK2 in cancer development and tumor progression, while AMPK has antioncogenic properties. PMID:21460252

  17. Primary malignant melanoma

    Directory of Open Access Journals (Sweden)

    A. Ferhat Mısır

    2016-04-01

    Full Text Available Malignant melanomas (MM of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period.

  18. Definitive Management of Oligometastatic Melanoma in a Murine Model Using Combined Ablative Radiation Therapy and Viral Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Blanchard, Miran [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Shim, Kevin G. [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Department of Immunology, Mayo Clinic, Rochester, Minnesota (United States); Grams, Michael P. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Rajani, Karishma; Diaz, Rosa M. [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Furutani, Keith M. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Thompson, Jill [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Olivier, Kenneth R.; Park, Sean S. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Markovic, Svetomir N. [Department of Immunology, Mayo Clinic, Rochester, Minnesota (United States); Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States); Pandha, Hardev [The Postgraduate Medical School, University of Surrey, Guildford (United Kingdom); Melcher, Alan [Leeds Institute of Cancer Studies and Pathology, University of Leeds, Leeds (United Kingdom); Harrington, Kevin [Targeted Therapy Laboratory, The Institute of Cancer Research, London (United Kingdom); Zaidi, Shane [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Targeted Therapy Laboratory, The Institute of Cancer Research, London (United Kingdom); Vile, Richard, E-mail: vile.richard@mayo.edu [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Department of Immunology, Mayo Clinic, Rochester, Minnesota (United States); Leeds Institute of Cancer Studies and Pathology, University of Leeds, Leeds (United Kingdom)

    2015-11-01

    Purpose: The oligometastatic state is an intermediate state between a malignancy that can be completely eradicated with conventional modalities and one in which a palliative approach is undertaken. Clinically, high rates of local tumor control are possible with stereotactic ablative radiation therapy (SABR), using precisely targeted, high-dose, low-fraction radiation therapy. However, in oligometastatic melanoma, virtually all patients develop progression systemically at sites not initially treated with ablative radiation therapy that cannot be managed with conventional chemotherapy and immunotherapy. We have demonstrated in mice that intravenous administration of vesicular stomatitis virus (VSV) expressing defined tumor-associated antigens (TAAs) generates systemic immune responses capable of clearing established tumors. Therefore, in the present preclinical study, we tested whether the combination of systemic VSV-mediated antigen delivery and SABR would be effective against oligometastatic disease. Methods and Materials: We generated a model of oligometastatic melanoma in C57BL/6 immunocompetent mice and then used a combination of SABR and systemically administered VSV-TAA viral immunotherapy to treat both local and systemic disease. Results: Our data showed that SABR generates excellent control or cure of local, clinically detectable, and accessible tumor through direct cell ablation. Also, the immunotherapeutic activity of systemically administered VSV-TAA generated T-cell responses that cleared subclinical metastatic tumors. We also showed that SABR induced weak T-cell-mediated tumor responses, which, particularly if boosted by VSV-TAA, might contribute to control of local and systemic disease. In addition, VSV-TAA therapy alone had significant effects on control of both local and metastatic tumors. Conclusions: We have shown in the present preliminary murine study using a single tumor model that this approach represents an effective, complementary

  19. Quantile uncertainty and value-at-risk model risk.

    Science.gov (United States)

    Alexander, Carol; Sarabia, José María

    2012-08-01

    This article develops a methodology for quantifying model risk in quantile risk estimates. The application of quantile estimates to risk assessment has become common practice in many disciplines, including hydrology, climate change, statistical process control, insurance and actuarial science, and the uncertainty surrounding these estimates has long been recognized. Our work is particularly important in finance, where quantile estimates (called Value-at-Risk) have been the cornerstone of banking risk management since the mid 1980s. A recent amendment to the Basel II Accord recommends additional market risk capital to cover all sources of "model risk" in the estimation of these quantiles. We provide a novel and elegant framework whereby quantile estimates are adjusted for model risk, relative to a benchmark which represents the state of knowledge of the authority that is responsible for model risk. A simulation experiment in which the degree of model risk is controlled illustrates how to quantify Value-at-Risk model risk and compute the required regulatory capital add-on for banks. An empirical example based on real data shows how the methodology can be put into practice, using only two time series (daily Value-at-Risk and daily profit and loss) from a large bank. We conclude with a discussion of potential applications to nonfinancial risks. © 2012 Society for Risk Analysis.

  20. The European approach to in-transit melanoma lesions

    NARCIS (Netherlands)

    Hoekstra, H. J.

    The biological behavior of melanoma is unpredictable. Three to five per cent of melanoma patients will develop in-transit lesions and the median time to recurrence ranges between 13-16 months. At the time of recurrence the risk of occult nodal metastasis, with clinically negative regional lymph

  1. Germline MC1R variants and BRAF mutant melanoma.

    Science.gov (United States)

    Hacker, Elke; Hayward, Nicholas K

    2008-10-01

    Recent studies have demonstrated that melanocortin-1 receptor (MC1R) variants increase the risk of melanomas harboring BRAF mutations. This finding provides insight into the relationship between host genotype and selection for somatic mutation type. Additional larger studies are required in diverse populations to further examine the interaction between MC1R and BRAF in different melanoma subtypes.

  2. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  3. Up-Regulation of Hepatoma-Derived Growth Factor Facilities Tumor Progression in Malignant Melanoma

    Science.gov (United States)

    Kung, Mei-Lang; Liu, Li-Feng; Kuo, Lai-Hsin; Kuo, Hsiao-Mei; Chen, San-Cher; Chan, Elsa C.; Wu, Chieh-Shan; Tai, Ming-Hong; Liu, Guei-Sheung

    2013-01-01

    Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF) is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200) showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn) expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16–F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma. PMID:23536873

  4. Adjuvant therapy with high dose vitamin D following primary treatment of melanoma at high risk of recurrence: a placebo controlled randomised phase II trial (ANZMTG 02.09 Mel-D).

    Science.gov (United States)

    Saw, Robyn P M; Armstrong, Bruce K; Mason, Rebecca S; Morton, Rachael L; Shannon, Kerwin F; Spillane, Andrew J; Stretch, Jonathan R; Thompson, John F

    2014-10-24

    Patients with primary cutaneous melanomas that are ulcerated and >2 mm in thickness, >4 mm in thickness and those with nodal micrometastases at diagnosis, have few options for adjuvant treatment. Recent studies have suggested a role for vitamin D to delay melanoma recurrence and improve overall prognosis. This is a pilot placebo-controlled randomised phase II trial to assess the feasibility, safety and toxicity of an oral loading dose of Vitamin D (500,000 IU) followed by an oral dose of 50,000 IU of Vitamin D monthly for 2 years in patients who have been treated for cutaneous melanoma by wide excision of the primary. Patients aged 18-79 years who have completed primary surgical treatment and have Stage IIb, IIc, IIIa (N1a, N2a) or IIIb (N1a, N2a) disease are eligible for randomisation 2:1 to active treatment or placebo. The primary endpoints are sufficiency of dose, adherence to study medication and safety of the drug. The secondary endpoints are participation and progression free survival. The study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, protocol number X09-0138. Effective, non-toxic adjuvant therapy for high risk primary melanoma is not currently available. Favorable outcomes of this phase II study will form the basis for a multi-centre phase III study to assess whether the addition of oral high-dose vitamin D therapy in patients who have completed primary treatment for melanoma and are at high risk of recurrence will: 1. prolong time to recurrence within 5 years 2. improve overall survival at 5 years and 3. be both safe and tolerable. 62 patients have been randomised since the study commenced in December 2010. Target accrual for the study has been met with 75 patients randomised between December 2010 and August 2014.The Mel-D trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG 02.09) TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN

  5. Gliotoxin Targets Nuclear NOTCH2 in Human Solid Tumor Derived Cell Lines In Vitro and Inhibits Melanoma Growth in Xenograft Mouse Model

    Directory of Open Access Journals (Sweden)

    Rainer Hubmann

    2017-07-01

    Full Text Available Deregulation of NOTCH2 signaling is implicated in a wide variety of human neoplasias. The current concept of targeting NOTCH is based on using gamma secretase inhibitors (GSI to regulate the release of the active NOTCH intracellular domain. However, the clinical outcome of GSI remains unsatisfactory. Therefore we analyzed human solid tumor derived cell lines for their nuclear NOTCH activity and evaluated the therapeutic potential of the NOTCH2 transactivation inhibitor gliotoxin in comparison to the representative GSI DAPT. Electrophoretic mobility shift assays (EMSA were used as a surrogate method for the detection of NOTCH/CSL transcription factor complexes. The effect of gliotoxin on cell viability and its clinical relevance was evaluated in vitro and in a melanoma xenograft mouse model. Cell lines derived from melanoma (518A2, hepatocellular carcinoma (SNU398, HCC-3, Hep3B, and pancreas carcinoma (PANC1 express high amounts of nuclear NOTCH2. Gliotoxin efficiently induced apoptosis in these cell lines whereas the GSI DAPT was ineffective. The specificity of gliotoxin was demonstrated in the well differentiated nuclear NOTCH negative cell line Huh7, which was resistant to gliotoxin treatment in vitro. In xenotransplanted 518A2 melanomas, a single day dosing schedule of gliotoxin was well tolerated without any study limiting side effects. Gliotoxin significantly reduced the tumor volume in early (83 mm3 vs. 115 mm3, p = 0.008 as well as in late stage (218 mm3 vs. 576 mm3, p = 0.005 tumor models. In conclusion, NOTCH2 appears to be a key target of gliotoxin in human neoplasias and gliotoxin deserves further evaluation as a potential therapeutic agent in cancer management.

  6. Model risk analysis for risk management and option pricing

    NARCIS (Netherlands)

    Kerkhof, F.L.J.

    2003-01-01

    Due to the growing complexity of products in financial markets, market participants rely more and more on quantitative models for trading and risk management decisions. This introduces a fairly new type of risk, namely, model risk. In the first part of this thesis we investigate the quantitative

  7. The role of BRAF mutation in patients with high-risk malignant melanoma treated with high-dose adjuvant interferon therapy.

    Science.gov (United States)

    Akman, Tulay; Oztop, Ilhan; Baskin, Yasemin; Akbarpour, Mahdi; Unal, Olcun Umit; Oflazoglu, Utku; Ellidokuz, Hulya; Lebe, Banu

    2015-01-01

    Data regarding the prognostic importance of BRAFV600 tumor mutations in high-risk, non-metastatic, stage 2 and 3 malignant melanoma (MM) patients are controversial. There is not sufficient information in the medical literature regarding the reliability of BRAF mutations as a predictive factor in prognosis and adjuvant treatment decision issues in this patient group. The data of 50 operated high-risk, non-metastatic, stage 2B/2C and 3 MM patients who received high-dose interferon alfa-2b therapy were evaluated retrospectively. BRAF mutations were analyzed by using microarray-based molecular methods. The associations between BRAF mutations and both clinicopathological characteristics and survival were assessed. Of the 50 patients, 52 % was female and 48 % was male, and the median age was 51.5 years. Twenty-three (46 %) and 27 (54 %) patients had stage 2B/2C and stage 3 disease, respectively. BRAF mutation was detected in 21 patients. The median overall survival (OS) was 58.1 months, whereas the median disease-free survival (DFS) was 22.7 months. When the OS and DFS were compared according to the BRAF mutation status, no difference was detected between the two groups. BRAF mutations were detected more frequently in tumors with mitosis and ulceration; however, no statistically significant difference was observed in other clinicopathological parameters. In conclusion, it is not appropriate to use BRAF mutations as a prognostic and predictive marker for selecting the treatment and assessing its outcomes in patients with early stage, high-risk MM.

  8. IRF4 rs12203592 functional variant and melanoma survival.

    Science.gov (United States)

    Potrony, Miriam; Rebollo-Morell, Aida; Giménez-Xavier, Pol; Zimmer, Lisa; Puig-Butille, Joan Anton; Tell-Marti, Gemma; Sucker, Antje; Badenas, Celia; Carrera, Cristina; Malvehy, Josep; Schadendorf, Dirk; Puig, Susana

    2017-04-15

    Inherited genetic factors may modulate clinical outcome in melanoma. Some low-to-medium risk genes in melanoma susceptibility play a role in melanoma outcome. Our aim was to assess the role of the functional IRF4 SNP rs12203592 in melanoma prognosis in two independent sets (Barcelona, N = 493 and Essen, N = 438). Genotype association analyses showed that the IRF4 rs12203592 T allele increased the risk of dying from melanoma in both sets (Barcelona: odds ratio [OR] = 6.53, 95% CI 1.38-30.87, Adj p = 0.032; Essen: OR = 1.68, 95% CI 1.04-2.72, Adj p = 0.035). Survival analyses only showed significance for the Barcelona set (hazard ratio = 4.58, 95% CI 1.11-18.92, Adj p = 0.036). This SNP was also associated with tumour localization, increasing the risk of developing melanoma in head or neck (OR = 1.79, 95% CI 1.07-2.98, Adj p = 0.032) and protecting from developing melanoma in the trunk (OR = 0.59, 95% CI 0.41-0.85, Adj p = 0.004). These findings suggest for the first time that IRF4 rs12203592 plays a role in the modulation of melanoma outcome and confirms its contribution to the localization of the primary tumour. © 2017 UICC.

  9. Assessment of PALB2 as a candidate melanoma susceptibility gene.

    Directory of Open Access Journals (Sweden)

    Lauren G Aoude

    Full Text Available Partner and localizer of BRCA2 (PALB2 interacts with BRCA2 to enable double strand break repair through homologous recombination. Similar to BRCA2, germline mutations in PALB2 have been shown to predispose to Fanconi anaemia as well as pancreatic and breast cancer. The PALB2/BRCA2 protein interaction, as well as the increased melanoma risk observed in families harbouring BRCA2 mutations, makes PALB2 a candidate for melanoma susceptibility. In order to assess PALB2 as a melanoma predisposition gene, we sequenced the entire protein-coding sequence of PALB2 in probands from 182 melanoma families lacking pathogenic mutations in known high penetrance melanoma susceptibility genes: CDKN2A, CDK4, and BAP1. In addition, we interrogated whole-genome and exome data from another 19 kindreds with a strong family history of melanoma for deleterious mutations in PALB2. Here we report a rare known deleterious PALB2 mutation (rs118203998 causing a premature truncation of the protein (p.Y1183X in an individual who had developed four different cancer types, including melanoma. Three other family members affected with melanoma did not carry the variant. Overall our data do not support a case for PALB2 being associated with melanoma predisposition.

  10. Biodistribution dosimetric study of radiopharmaceutical 99mTc Ixolaris in mice for melanoma diagnosis by molecular image and translational model for human beings

    International Nuclear Information System (INIS)

    Soriano, Sarah Canuto Silva

    2015-01-01

    The labeling of Ixolaris with 99m Tc was developed by Barboza et.al. (2013) aiming its use primarily in glioblastoma and after in melanoma diagnosis, a less common but very aggressive cancer and with high mortality rate. Preliminary tests on animals have proven its effectiveness of labeling but a dosimetric study to human clinical trials should be performed. This study aimed to: (1) determine the biokinetic model for the radiotracer 99m Tc-Ixolaris in mice by imaging dosimetry method; and (2) estimate the absorbed and effective dose resulting from the use of a new radiopharmaceutical for melanoma and metastases diagnosis in human beings, since a dosimetric study of new radiopharmaceuticals in animals is necessary to test them subsequently in humans and apply for registration in ANVISA. According to SPECT images, was found a latency period of 15 to 21 days for the development of lung metastasis in mice. Three C57BL6 mice, one control animal, and two animals with induced cell line B16-F10 murine melanoma were tested. The 99m Tc-Ixolaris radiopharmaceutical was administered intravenously in a caudal vein, and SPECT images were acquired 0.5 h, 1.5 h, 2.5 h, 3.5 h and 24 h post-administration for analysis and biodistribution quantification. The biokinetic model was determined and thus, obtained cumulative activity in order to estimate the absorbed dose in each organ. The mass and metabolic differences between mice and humans were considered and used to extrapolate the data acquired at different scales. Based on dose factors provided by the software MIRDOSE and Olinda (S factor), absorbed doses in irradiated target organs were calculated for the source organs, and finally the effective dose was estimated. The results indicate that for diagnostic exams conducted in human melanoma patients by administering approximately 25.7 MBq the estimated effective dose was 4.3 mSv. Comparing with effective doses obtained in other diagnostic techniques with 99m Tc, a range of effective

  11. α-Pinene isolated from Schinus terebinthifolius Raddi (Anacardiaceae) induces apoptosis and confers antimetastatic protection in a melanoma model.

    Science.gov (United States)

    Matsuo, Alisson L; Figueiredo, Carlos R; Arruda, Denise C; Pereira, Felipe V; Scutti, Jorge A Borin; Massaoka, Mariana H; Travassos, Luiz R; Sartorelli, Patricia; Lago, João H G

    2011-07-29

    Malignant melanoma is one the most aggressive types of cancer and its incidence has gradually increased in the last years, accounting for about 75% of skin cancer deaths. This poor prognosis results from the tumor resistance to conventional drugs mainly by deregulation of apoptotic pathways. The aim of this work was to investigate the cell death mechanism induced by α-pinene and its therapeutic application. Our results demonstrated that α-pinene was able to induce apoptosis evidenced by early disruption of the mitochondrial potential, production of reactive oxygen species, increase in caspase-3 activity, heterochromatin aggregation, DNA fragmentation and exposure of phosphatidyl serine on the cell surface. Most importantly, this molecule was very effective in the treatment of experimental metastatic melanoma reducing the number of lung tumor nodules. This is the first report on the apoptotic and antimetastatic activity of isolated α-pinene. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Credit Risk Evaluation : Modeling - Analysis - Management

    OpenAIRE

    Wehrspohn, Uwe

    2002-01-01

    An analysis and further development of the building blocks of modern credit risk management: -Definitions of default -Estimation of default probabilities -Exposures -Recovery Rates -Pricing -Concepts of portfolio dependence -Time horizons for risk calculations -Quantification of portfolio risk -Estimation of risk measures -Portfolio analysis and portfolio improvement -Evaluation and comparison of credit risk models -Analytic portfolio loss distributions The thesis contributes to the evaluatio...

  13. A Quantitative Software Risk Assessment Model

    Science.gov (United States)

    Lee, Alice

    2002-01-01

    This slide presentation reviews a risk assessment model as applied to software development. the presentation uses graphs to demonstrate basic concepts of software reliability. It also discusses the application to the risk model to the software development life cycle.

  14. TCTP as a therapeutic target in melanoma treatment.

    Science.gov (United States)

    Boia-Ferreira, M; Basílio, A B; Hamasaki, A E; Matsubara, F H; Appel, M H; Da Costa, C R V; Amson, R; Telerman, A; Chaim, O M; Veiga, S S; Senff-Ribeiro, A

    2017-08-22

    Translationally controlled tumour protein (TCTP) is an antiapoptotic protein highly conserved through phylogeny. Translationally controlled tumour protein overexpression was detected in several tumour types. Silencing TCTP was shown to induce tumour reversion. There is a reciprocal repression between TCTP and P53. Sertraline interacts with TCTP and decreases its cellular levels. We evaluate the role of TCTP in melanoma using sertraline and siRNA. Cell viability, migration, and clonogenicity were assessed in human and murine melanoma cells in vitro. Sertraline was evaluated in a murine melanoma model and was compared with dacarbazine, a major chemotherapeutic agent used in melanoma treatment. Inhibition of TCTP levels decreases melanoma cell viability, migration, clonogenicity, and in vivo tumour growth. Human melanoma cells treated with sertraline show diminished migration properties and capacity to form colonies. Sertraline was effective in inhibiting tumour growth in a murine melanoma model; its effect was stronger when compared with dacarbazine. Altogether, these results indicate that sertraline could be effective against melanoma and TCTP can be a target for melanoma therapy.

  15. Staging of cutaneous melanoma

    NARCIS (Netherlands)

    P. Mohr (P.); A.M.M. Eggermont (Alexander); A. Hauschild (Axel); A. Buzaid (A.)

    2009-01-01

    textabstractThe American Joint Committee on Cancer (AJCC) staging of cutaneous melanoma is a continuously evolving system. The identification of increasingly more accurate prognostic factors has led to major changes in melanoma staging over the years, and the current system described in this review

  16. Uveal melanoma: estimating prognosis.

    Science.gov (United States)

    Kaliki, Swathi; Shields, Carol L; Shields, Jerry A

    2015-02-01

    Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  17. Uveal melanoma: Estimating prognosis

    Directory of Open Access Journals (Sweden)

    Swathi Kaliki

    2015-01-01

    Full Text Available Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  18. Bronchial malignant melanoma.

    Science.gov (United States)

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E

    1980-01-01

    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  19. Does hormone replacement therapy and use of oral contraceptives increase the risk of non-melanoma skin cancer?

    DEFF Research Database (Denmark)

    Birch-Johansen, Fatima; Jensen, Allan; Olesen, Anne Braae

    2012-01-01

    We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women.......We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women....

  20. Melanoma do aparelho ungueal Nail apparatus melanoma

    Directory of Open Access Journals (Sweden)

    Ignez Regina dos Santos Muri Mendonça

    2004-10-01

    Full Text Available O melanoma do aparelho ungueal é apresentação relativamente rara dessa neoplasia, muitas vezes diagnosticada como nevo juncional, hematoma subungueal ou mesmo onicomicose. Esse fato leva a um atraso no diagnóstico e, conseqüentemente, na instituição da terapêutica específica, contribuindo para agravar o prognóstico de uma doença que por si só já é muito agressiva. Os autores relatam um caso de melanoma no primeiro quirodáctilo esquerdo de uma paciente negra com evolução de um ano, ressaltando a importância de avaliar certos critérios clínicos para obter o diagnóstico em fases mais precoces da doença.Nail apparatus melanoma is a rare presentation of melanoma and may be misdiagnosed as junctional nevus, subungual hematoma or onychomycosis. This fact often leads initially to inappropriate treatment and significant delays in appropriately managing such an aggressive disease. The authors report a case of melanoma on the left thumb of a black patient evolving for a year. Emphasis was placed on the importance of assessing certain clinical characteristics in order to reach an early diagnosis.

  1. Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

    Directory of Open Access Journals (Sweden)

    Iván Márquez-Rodas

    Full Text Available Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain.An observational study conducted by the Spanish Group of Melanoma (GEM analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments.In all, 1047 patients were analyzed, and 69 (6.6% fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma. Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%. Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups.Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.

  2. Associations between childhood height and morphologically different variants of melanoma in adulthood.

    Science.gov (United States)

    Meyle, Kathrine Damm; Gamborg, Michael; Hölmich, Lisbet Rosenkrantz; Baker, Jennifer Lyn

    2016-11-01

    Melanoma subtypes have different aetiological characteristics. Child height is positively associated with adult melanoma; however, a clarification of associations with specific melanoma variants is necessary for an improved understanding of risk factors underlying the histologic entities. This study investigated associations between childhood height and future development of cutaneous melanoma variants. A cohort study of 316,193 individuals from the Copenhagen School Health Records Register, with measured heights at ages 7-13 years who were born from 1930 to 1989. Melanoma cases were identified via linkage to the national Danish Cancer Registry and subdivided into subtypes. Cox proportional hazards regressions were performed. A total of 2223 cases of melanoma distributed as 60% superficial spreading melanoma (SSM), 27.5% melanoma not otherwise specified (NOS), 8.5% nodular melanoma (NM), and 2% lentigo maligna melanoma (LMM). The remaining rare melanoma forms were not analysed. Childhood height was positively and significantly associated with SSM, melanoma NOS, and NM, but not LMM, in adulthood. Per height z-score at age 13 years, the hazard ratios were 1.20 (95% confidence intervals [CI]: 1.13-1.27) for SSM, 1.19 (95% CI: 1.09-1.29) for melanoma NOS, and 1.21 (95% CI: 1.04-1.41) for NM. Further, growth patterns were linked to the melanoma variants with persistently tall children having an increased risk of developing SSM, melanoma NOS, or NM. Childhood height is positively associated with the majority of the melanoma variants. These results suggest that the underlying processes contributing to childhood height and growth patterns interconnect early-life events with the predisposition to melanomagenesis in adulthood. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Peptide-Targeted Radionuclide Therapy for Melanoma

    Science.gov (United States)

    Miao, Yubin; Quinn, Thomas P.

    2011-01-01

    Melanocortin-1 receptor (MC1-R) and melanin are two attractive melanoma-specific targets for peptide-targeted radionuclide therapy for melanoma. Radiolabeled peptides targeting MC1-R/melanin can selectively and specifically target cytotoxic radiation generated from therapeutic radionuclides to melanoma cells for cell killing, while sparing the normal tissues and organs. This review highlights the recent advances of peptide-targeted radionuclide therapy of melanoma targeting MC1R and melanin. The promising therapeutic efficacies of 188Re-(Arg11)CCMSH (188Re-[Cys3,4,10, d-Phe7, Arg11]-α-MSH3-13), 177Lu- and 212Pb-labeled DOTA-Re(Arg11)CCMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[ReO-(Cys3,4,10, d-Phe7, Arg11)]-α-MSH3-13) and 188Re-HYNIC-4B4 (188Re-hydrazinonicotinamide-Tyr-Glu-Arg-Lys-Phe-Trp-His-Gly-Arg-His) in preclinical melanoma-bearing models demonstrate an optimistic outlook for peptide-targeted radionuclide therapy for melanoma. Peptide-targeted radionuclide therapy for melanoma will likely contribute in an adjuvant setting, once the primary tumor has been surgically removed, to treat metastatic deposits and for treatment of end-stage disease. The lack of effective treatments for metastatic melanoma and end stage disease underscores the necessity to develop and implement new treatment strategies, such as peptide-targeted radionuclide therapy. PMID:18387816

  4. Simultaneous purifying selection on the ancestral MC1R allele and positive selection on the melanoma-risk allele V60L in south Europeans.

    Science.gov (United States)

    Martínez-Cadenas, Conrado; López, Saioa; Ribas, Gloria; Flores, Carlos; García, Oscar; Sevilla, Arrate; Smith-Zubiaga, Isabel; Ibarrola-Villaba, Maider; Pino-Yanes, Maria del Mar; Gardeazabal, Jesús; Boyano, Dolores; García de Galdeano, Alicia; Izagirre, Neskuts; de la Rúa, Concepción; Alonso, Santos

    2013-12-01

    In humans, the geographical apportionment of the coding diversity of the pigmentary locus melanocortin-1 receptor (MC1R) is, unusually, higher in Eurasians than in Africans. This atypical observation has been interpreted as the result of purifying selection due to functional constraint on MC1R in high UV-B radiation environments. By analyzing 3,142 human MC1R alleles from different regions of Spain in the context of additional haplotypic information from the 1000 Genomes (1000G) Project data, we show that purifying selection is also strong in southern Europe, but not so in northern Europe. Furthermore, we show that purifying and positive selection act simultaneously on MC1R. Thus, at least in Spain, regions at opposite ends of the incident UV-B radiation distribution show significantly different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair), with higher frequency of V60L at those regions of lower incident UV-B radiation. Besides, using the 1000G south European data, we show that the V60L haplogroup is also characterized by an extended haplotype homozygosity (EHH) pattern indicative of positive selection. We, thus, provide evidence for an adaptive value of human skin depigmentation in Europe and illustrate how an adaptive process can simultaneously help to maintain a disease-risk allele. In addition, our data support the hypothesis proposed by Jablonski and Chaplin (Human skin pigmentation as an adaptation to UVB radiation. Proc Natl Acad Sci U S A. 2010;107:8962-8968), which posits that habitation of middle latitudes involved the evolution of partially depigmented phenotypes that are still capable of suitable tanning.

  5. Cutaneous manifestations associated with melanoma.

    Science.gov (United States)

    Vyas, Ritva; Selph, Jacqueline; Gerstenblith, Meg R

    2016-06-01

    Melanoma is a malignancy most commonly arising from the skin; therefore, primary melanoma characteristics are usually the first cutaneous manifestations of melanoma. Cutaneous metastases, which can occur locally or diffusely, are important to detect in a timely manner as treatments for advanced melanoma that impact survival are now available. Melanoma can be associated with local or diffuse pigmentation changes, including depigmentation associated with the leukodermas and hyperpigmentation associated with diffuse melanosis cutis. The leukodermas occur frequently, illustrate the immunogenic nature of melanoma, and may impact prognosis. Paraneoplastic syndromes in association with melanoma are rare, though can occur. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Malignant melanoma – etiopathogenesis, clinical picture, diagnosis and patient management

    International Nuclear Information System (INIS)

    Murarova, Z.; Borecka, D.

    2016-01-01

    Malignant melanoma belongs to the most malignant and aggressive tumors due to its fast growing metastasis. Despite the fact that the incidence of melanoma has been on the increase for the past years and mortality to low and medium risk melanoma has decreased, the mortality of aggressive fast growing high risk melanomas has been stable. Diagnosis of “typical” melanomas, fulfilling ABCDEF criteria, usually does not cause any problems. Particular attention should be paid to the problems of fast growing melanomas, which are very similar to benign lesions at the beginning so they are often detected too late. Melanomas have two extreme properties: on one edge of the spectrum there are patients with small and thin skin lesions, who are usually completely cured by wide surgical excision. On the other edge of the spectrum there are patients with generalized metastatic disease. In these patients the treatment options are very limited and the probability to survive is about 6-9 months. The most significant factor for survival is the early melanoma detection. (author)

  7. Statistical models for competing risk analysis

    International Nuclear Information System (INIS)

    Sather, H.N.

    1976-08-01

    Research results on three new models for potential applications in competing risks problems. One section covers the basic statistical relationships underlying the subsequent competing risks model development. Another discusses the problem of comparing cause-specific risk structure by competing risks theory in two homogeneous populations, P1 and P2. Weibull models which allow more generality than the Berkson and Elveback models are studied for the effect of time on the hazard function. The use of concomitant information for modeling single-risk survival is extended to the multiple failure mode domain of competing risks. The model used to illustrate the use of this methodology is a life table model which has constant hazards within pre-designated intervals of the time scale. Two parametric models for bivariate dependent competing risks, which provide interesting alternatives, are proposed and examined

  8. Environmental modeling and health risk analysis (ACTS/RISK)

    National Research Council Canada - National Science Library

    Aral, M. M

    2010-01-01

    ... presents a review of the topics of exposure and health risk analysis. The Analytical Contaminant Transport Analysis System (ACTS) and Health RISK Analysis (RISK) software tools are an integral part of the book and provide computational platforms for all the models discussed herein. The most recent versions of these two softwa...

  9. UVB: suscetibilidade no melanoma maligno UVB: susceptibility in malignant melanoma

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2010-12-01

    Full Text Available FUNDAMENTOS: Está bem definido que a radiação ultravioleta provoca depleção imunológica na pele, permitindo o desenvolvimento de tumores cutâneos malignos. A maioria dos pacientes de cânceres da pele não melanomas são considerados UVB-suscetíveis. OBJETIVOS: Estudar a UVB-suscetibilidade nos pacientes com melanoma maligno e se este é um fator de risco para o desenvolvimento desse câncer. MÉTODOS: Foram selecionados 88 voluntários divididos em dois grupos: grupo-controle saudável (n=61 e grupo de portadores de melanoma (n=27, todos identificados de acordo com os critérios: tipo histológico, nível de invasão, fotótipos de pele, sexo e idade. A suscetibilidade à radiação ultravioleta B (UVB foi medida pela reação de hipersensibilidade ao contato com o difenciprone nos voluntários sensibilizados em áreas previamente irradiadas. RESULTADOS: A suscetibilidade à radiação UVB foi de 81,5% nos pacientes com melanoma maligno e de 31,2% no grupo-controle. O risco de um indivíduo desenvolver o melanoma maligno foi 9,7 vezes maior do que nos indivíduos UVB-resistentes. CONCLUSÕES: A UVB-suscetibilidade pode ser considerada um fator de risco importante para o desenvolvimento do melanoma maligno.BACKGROUND: It is well established that UV radiation provokes an immunological depletion in the skin, enabling the development of malignant cutaneous tumors. Most nonmelanoma skin cancer patients are considered to be UVB-susceptible. OBJECTIVE: To study the behavior of UVB- susceptibility in malignant melanoma (MM patients and whether this is a risk factor to the development of MM. METHODS: Eighty-eight volunteers were selected and divided into two groups: healthy control group (n = 61 and MM group (n = 27, which were identified according to the following clinical criteria: histopathological type, level of invasion, skin phototype, sex and age. Susceptibility to ultraviolet B (UVB radiation was measured by the onset of a contact

  10. Risk matrix model for rotating equipment

    Directory of Open Access Journals (Sweden)

    Wassan Rano Khan

    2014-07-01

    Full Text Available Different industries have various residual risk levels for their rotating equipment. Accordingly the occurrence rate of the failures and associated failure consequences categories are different. Thus, a generalized risk matrix model is developed in this study which can fit various available risk matrix standards. This generalized risk matrix will be helpful to develop new risk matrix, to fit the required risk assessment scenario for rotating equipment. Power generation system was taken as case study. It was observed that eight subsystems were under risk. Only vibration monitor system was under high risk category, while remaining seven subsystems were under serious and medium risk categories.

  11. Yessotoxin, a Marine Toxin, Exhibits Anti-Allergic and Anti-Tumoural Activities Inhibiting Melanoma Tumour Growth in a Preclinical Model.

    Directory of Open Access Journals (Sweden)

    Araceli Tobío

    Full Text Available Yessotoxins (YTXs are a group of marine toxins produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. They may have medical interest due to their potential role as anti-allergic but also anti-cancer compounds. However, their biological activities remain poorly characterized. Here, we show that the small molecular compound YTX causes a slight but significant reduction of the ability of mast cells to degranulate. Strikingly, further examination revealed that YTX had a marked and selective cytotoxicity for the RBL-2H3 mast cell line inducing apoptosis, while primary bone marrow derived mast cells were highly resistant. In addition, YTX exhibited strong cytotoxicity against the human B-chronic lymphocytic leukaemia cell line MEC1 and the murine melanoma cell line B16F10. To analyse the potential role of YTX as an anti-cancer drug in vivo we used the well-established B16F10 melanoma preclinical mouse model. Our results demonstrate that a few local application of YTX around established tumours dramatically diminished tumour growth in the absence of any significant toxicity as determined by the absence of weight loss and haematological alterations. Our data support that YTX may have a minor role as an anti-allergic drug, but reveals an important potential for its use as an anti-cancer drug.

  12. Dermoscopic evaluation of nodular melanoma.

    Science.gov (United States)

    Menzies, Scott W; Moloney, Fergal J; Byth, Karen; Avramidis, Michelle; Argenziano, Giuseppe; Zalaudek, Iris; Braun, Ralph P; Malvehy, Josep; Puig, Susana; Rabinovitz, Harold S; Oliviero, Margaret; Cabo, Horacio; Bono, Riccardo; Pizzichetta, Maria A; Claeson, Magdalena; Gaffney, Daniel C; Soyer, H Peter; Stanganelli, Ignazio; Scolyer, Richard A; Guitera, Pascale; Kelly, John; McCurdy, Olivia; Llambrich, Alex; Marghoob, Ashfaq A; Zaballos, Pedro; Kirchesch, Herbert M; Piccolo, Domenico; Bowling, Jonathan; Thomas, Luc; Terstappen, Karin; Tanaka, Masaru; Pellacani, Giovanni; Pagnanelli, Gianluca; Ghigliotti, Giovanni; Ortega, Blanca Carlos; Crafter, Greg; Ortiz, Ana María Perusquía; Tromme, Isabelle; Karaarslan, Isil Kilinc; Ozdemir, Fezal; Tam, Anthony; Landi, Christian; Norton, Peter; Kaçar, Nida; Rudnicka, Lidia; Slowinska, Monika; Simionescu, Olga; Di Stefani, Alessandro; Coates, Elliot; Kreusch, Juergen

    2013-06-01

    Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. To determine the dermoscopy features of NM. Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. Predominantly hospital-based clinics from 5 continents. Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. When

  13. Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: role of adipokines.

    Science.gov (United States)

    Malvi, Parmanand; Chaube, Balkrishna; Pandey, Vimal; Vijayakumar, Maleppillil Vavachan; Boreddy, Purushotham Reddy; Mohammad, Naoshad; Singh, Shivendra Vikram; Bhat, Manoj Kumar

    2015-03-01

    Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well as progression. Although a few studies have attempted to understand the relationship between obesity and melanoma, the consequences of controlling body weight by reducing adiposity on cancer progression is not well understood. By employing animal models of obesity, we report that controlling obesity either by orlistat treatment or by restricting caloric intake significantly slows down melanoma progression. The diminished tumor progression was correlated with decreased fat mass (adiposity) in obese mice. Obesity associated factors contributing to tumor progression were decreased in the experimental groups compared to respective controls. In tumors, protein levels of fatty acid synthase (FASN), caveolin (Cav)-1 and pAkt, which are tumor promoting molecules implicated in melanoma growth under obese state, were decreased. In addition, increased necrosis and reduction in angiogenesis as well as proliferative markers PCNA and cyclin D1 were observed in tumors of the orlistat treated and/or calorically restricted obese mice. We observed that growth of melanoma cells cultured in conditioned medium (CM) from orlistat-treated adipocytes was reduced. Adipokines (leptin and resistin), via activating Akt and modulation of FASN as well as Cav-1 respectively, enhanced melanoma cell growth and proliferation. Together, we demonstrate that controlling body weight reduces adipose mass thereby diminishing melanoma progression. Therefore, strategic means of controlling obesity by reduced caloric diet or with antiobesity drugs treatment may render obesity-promoted tumor progression in check and prolong survival of patients. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Patient and Oncology Nurse Preferences for the Treatment Options in Advanced Melanoma: A Discrete Choice Experiment.

    Science.gov (United States)

    Liu, Frank Xiaoqing; Witt, Edward A; Ebbinghaus, Scot; DiBonaventura Beyer, Grace; Basurto, Enrique; Joseph, Richard W

    2017-10-25

    Understanding the perceptions of patients and oncology nurses about the relative importance of benefits and risks associated with newer treatments of advanced melanoma can help to inform clinical decision-making. The aims of this study were to quantify and compare the views of patients and oncology nurses regarding the importance of attributes of treatments of advanced melanoma. A discrete choice experiment (DCE) was conducted in US-based oncology nurses and patients diagnosed with advanced melanoma. Patients and nurses were enlisted through online panels. In a series of scenarios, respondents had to choose between 2 hypothetical treatments, each with 7 attributes: mode of administration (MoA), dosing schedule (DS), median duration of therapy (DoT), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and grade 3 or 4 adverse events (AEs). Hierarchical Bayesian logistic regression models were used to estimate preference weights. A total of 200 patients with advanced melanoma and 150 oncology nurses participated. The relative importance estimates of attributes by patients and nurses, respectively, were as follows: OS, 33% and 28%; AEs, 29% and 26%; ORR, 25% and 27%; PFS, 12% and 15%; DS, 2% and 3%; DoT, 0% and 0%; and MoA, 0% and 0%. Both patients and oncology nurses valued OS, ORR, and AEs as the most important treatment attributes for advanced melanoma, followed by PFS, whereas DS, DoT, and MoA were given less value in their treatment decisions. Oncology nurses and patients have similar views on important treatment considerations for advanced melanoma, which can help build trust in shared decision-making.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  15. Descriptive models of perceived risk

    OpenAIRE

    Wang, Yitong; Keller, L. Robin; Simon, Jay

    2010-01-01

    Risk plays a central role in decision making. Accordingly, risk has been a popular research topic for more than four decades. Finding a generic definition of risk is hard, since this term is used in many areas such as economics, political science, management science, and medical research. However, one thing in common is that risk is always related to both the negative outcomes and uncertainty. In addition, we know that risk is normally subjective and constructed ...

  16. Models for assessing and managing credit risk

    Directory of Open Access Journals (Sweden)

    Neogradi Slađana

    2014-01-01

    Full Text Available This essay deals with the definition of a model for assessing and managing credit risk. Risk is an inseparable component of any average and normal credit transaction. Looking at the different aspects of the identification and classification of risk in the banking industry as well as representation of the key components of modern risk management. In the first part of the essay will analyze how the impact of credit risk on bank and empirical models for determining the financial difficulties in which the company can be found. Bank on the basis of these models can reduce number of approved risk assets. In the second part, we consider models for improving credit risk with emphasis on Basel I, II and III, and the third part, we conclude that the most appropriate model and gives the best effect for measuring credit risk in domestic banks.

  17. Risk assessment models in the tourism sector

    Directory of Open Access Journals (Sweden)

    Simanavicius Arturas

    2015-05-01

    Full Text Available One of the most prominent contemporary success stories is tourism. This industry began to significantly increase only in 1960, and during the last 50 years, tourism revenues and number of outgoing people have increased by a number of times. Therefore, the tourism sector is highly attractive to new business initiation and development of its dynamic growth, new activities, new trends and technologies, new markets and rapid changes. Purpose of the article - to analyze the prevailing risks in the tourism sector and to identify the business risk assessment models. Scientists pay big attention to risk analysis. A series of risk analysis theoretical, methodological and practical studies are made, but for the tourism risk scientistseconomists do not pay attention in practice. Tourism risk assessment models, analyzed in the article, showed their adaptability to tourism industry. Performed tourism economic risk assessment models showed that in the tourism risk classification it is appropriate to use a procedural approach, which is related to the tourism product identification stages. It would be logical to link the identification of risks to the tourism services in stages, as in each stage prevails certain risk groups The aim of the article - to analyze the tourism risk assessment models and on the basis of analysis to develop further tourism risk assessment model. Article originality is associated with the prepared tourism risk assessment model that is versatile and can be used in different countries in assessing the risks of tourism.

  18. In vivo overexpression of tumstatin domains by tumor cells inhibits their invasive properties in a mouse melanoma model

    International Nuclear Information System (INIS)

    Pasco, Sylvie; Ramont, Laurent; Venteo, Lydie; Pluot, Michel; Maquart, Francois-Xavier; Monboisse, Jean-Claude

    2004-01-01

    Our previous studies demonstrated that a synthetic peptide encompassing residues 185-203 of the noncollagenous (NC1) domain of the α3 chain of type IV collagen, named tumstatin, inhibits in vitro melanoma cell proliferation and migration. In the present study, B16F1 melanoma cells were stably transfected to overexpress the complete tumstatin domain (Tum 1-232) or its C-terminal part, encompassing residues 185-203 (Tum 183-232). Tumstatin domain overexpression inhibited B16F1 in vitro cell proliferation, anchorage-independent growth, and invasive properties. For studying the in vivo effect of overexpression, representative clones were subcutaneously injected into the left side of C57BL6 mice. In vivo tumor growth was decreased by -60% and -56%, respectively, with B16F1 cells overexpressing Tum 1-232 or Tum 183-232 compared to control cells. This inhibitory effect was associated with a decrease of in vivo cyclin D1 expression. We also demonstrated that the overexpression of Tum 1-232 or Tum 183-232 induced an in vivo down-regulation of proteolytic cascades involving matrix metalloproteinases (MMPs), especially the production or activation of MMP-2, MMP-9, MMP-13, as well as MMP-14. The plasminogen activation system was also altered in tumors with a decrease of urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) and a strong increase of plasminogen activator inhibitor-1 (PAI-1). Collectively, our results demonstrate that tumstatin or its C-terminal antitumor fragment, Tum 183-232, inhibits in vivo melanoma progression by triggering an intracellular transduction pathway, which involves a cyclic AMP (cAMP)-dependent mechanism

  19. Influence of having a home garden on personal UVR exposure behavior and risk of cutaneous malignant melanoma in Denmark

    DEFF Research Database (Denmark)

    Idorn, Luise Winkel; Thieden, Elisabeth; Philipsen, Peter Alshede

    2013-01-01

    . Register study: We collected information from Danish national registers about gender, age, type of home and CMM among persons aged 16-75 in 2002-2006. A total of 5,118 CMM cases were identified. Risk of CMM of the trunk was increased by 46% (p ... of the extremities by 34% (p personal electronic UVR dosimeters measuring time-stamped UVR doses...

  20. Risk of non-melanoma skin cancer in patients with atopic dermatitis treated with oral immunosuppressive drugs

    NARCIS (Netherlands)

    Garritsen, Floor M.; Van Der Schaft, Jorien; van den Reek, Juul M; Politiek, Klaziena; Van Os-Medendorp, Harmieke; van Dijk, Marijke; Hijnen, Dirk J.; De Graaf, Marlies; Bruijnzeel-Koomen, Carla A.; de Jong, Elke M G J; Schuttelaar, Marie-Louise A; De Bruin-Weller, Marjolein S.

    2017-01-01

    There is uncertainty about the risk of developing nonmelanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma (SCC), in patients with atopic dermatitis (AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the

  1. Review of guidance on recurrence risk management for general practitioners in breast cancer, colorectal cancer and melanoma guidelines.

    NARCIS (Netherlands)

    Spronk, I.; Korevaar, J.C.; Burgers, J.S.; Albreht, T.; Schellevis, F.G.

    2017-01-01

    Background. General practitioners (GPs) will face cancer recurrences more frequently due to the rising number of cancer survivors and greater involvement of GPs in the follow-up care. Currently, GPs are uncertain about managing recurrence risks and may need more guidance. Objective. To explore what

  2. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Prause, J.U.

    2002-01-01

    ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology......ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology...

  3. Management of Melanoma Families

    Directory of Open Access Journals (Sweden)

    Wilma Bergman

    2010-04-01

    Full Text Available In this review we have aimed to focus on the clinical management of familial melanoma patients and their relatives. Along this line three major topics will be discussed: (1 management/screening of familial melanoma families: what is advised and what is the evidence thereof; (2 variability of families worldwide with regard to clinical phenotype, including cancer spectrum and likelihood of finding germline mutations and (3 background information for clinicians on the molecular biology of familial melanoma and recent developments in this field.

  4. RISK LOAN PORTFOLIO OPTIMIZATION MODEL BASED ON CVAR RISK MEASURE

    Directory of Open Access Journals (Sweden)

    Ming-Chang LEE

    2015-07-01

    Full Text Available In order to achieve commercial banks liquidity, safety and profitability objective requirements, loan portfolio risk analysis based optimization decisions are rational allocation of assets.  The risk analysis and asset allocation are the key technology of banking and risk management.  The aim of this paper, build a loan portfolio optimization model based on risk analysis.  Loan portfolio rate of return by using Value-at-Risk (VaR and Conditional Value-at-Risk (CVaR constraint optimization decision model reflects the bank's risk tolerance, and the potential loss of direct control of the bank.  In this paper, it analyze a general risk management model applied to portfolio problems with VaR and CVaR risk measures by using Using the Lagrangian Algorithm.  This paper solves the highly difficult problem by matrix operation method.  Therefore, the combination of this paper is easy understanding the portfolio problems with VaR and CVaR risk model is a hyperbola in mean-standard deviation space.  It is easy calculation in proposed method.

  5. The role of depression and personality traits in patients with melanoma: a South-European study.

    Science.gov (United States)

    Gogas, Helen J; Karalexi, Maria A; Dessypris, Nick; Antoniadis, Antonios G; Papadopoulos, Fotis; Petridou, Eleni T

    2017-12-01

    We explored the potential association of depression history and personality, evaluated through a robust questionnaire tool, namely the Eysenck Personality Scale, with disease risk and progression among Greek patients. A total of 106 melanoma patients and their 1 : 1 sex-matched controls were interviewed on the basis of a questionnaire comprising phenotypic, sociodemographic, lifestyle and medical history variables, as well as information on history of lifetime major depression. The Eysenck Personality Questionnaire, measuring the four personality dimensions (extraversion, neuroticism, psychoticism, lie), was thereafter completed. Adjusted odds ratios (ORs) for melanoma risk were derived through multiple logistic regression analyses, whereas potential predictors of survival were explored using Cox proportional hazards models. Sun sensitivity score [OR: 1.55, 95% confidence interval (CI): 1.16-2.06] and major depression history (OR: 5.72, 95% CI: 1.38-23.73) were significantly associated with melanoma, whereas inverse associations of extraversion (OR: 0.90, 95% CI: 0.83-0.97) and psychoticism score (OR: 0.88, 95% CI: 0.78-1.00) were noted. These associations were more pronounced and remained solely among female patients; notably, decreased extraversion (OR: 0.86, 95% CI: 0.76-0.98) and psychoticism score (OR: 0.63, 95% CI: 0.43-0.91), as well as increased depression history (OR: 10.69, 95% CI: 1.43-80.03) were evident. Cox-derived hazard ratios showed nonsignificant associations of depression history and personality with disease outcome. Our data support the hypotheses that depression history and personality are associated with melanoma risk. No effect on survival after cancer diagnosis was observed. If confirmed in future studies, these associations may contribute toward better understanding the etiology of melanoma, enhancing health-related quality of life.

  6. Lifetime prevalence of non-melanoma and melanoma skin cancer in Australian recreational and competitive surfers.

    Science.gov (United States)

    Climstein, Mike; Furness, James; Hing, Wayne; Walsh, Joe

    2016-07-01

    Surfing is one of the most popular outdoor aquatic activities in Australia with an estimated 2.7 million recreational surfers; however, Australia has long been recognized as having the highest incidence of melanoma in the world, and it is the most common type of cancer in young Australians. The aim of this study was to investigate the lifetime prevalence of non-melanoma [basal cell carcinoma (BCC), squamous cell carcinoma (SCC)] and melanoma skin cancers in Australian recreational and competitive surfers. Australian surfers were invited to complete an online surveillance survey to determine the lifetime prevalence of non-melanoma and melanoma skin cancers. A total of 1348 surfers (56.9% recreational) participated in this study, of which 184 surfers reported a skin cancer (competitive n = 96, recreational n = 87). Of non-melanoma and melanoma cancers reported, BCC was the most common (6.8%), followed by melanoma (1.4%) and SCC (0.6%). The relative risk was higher (P skin cancers reported on the face (23.5%), back (16.4%) and arms (12.4%). There were significant trends (P skin cancers between competitive and recreational surfers, as well as significantly (P skin cancers reported in males (14.6%) than females (9.4%). Based upon these findings, individuals who surf are advised to regularly utilize sun protection strategies (avoid peak ultraviolet radiation (10 am-3 pm), rashvest, hat and sunscreen) and primary care physicians are recommended to regularly screen their patients who surf. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Metastatic amelanotic nodular melanoma during pregnancy.

    Science.gov (United States)

    Jasaitiene, Daiva; Valiukeviciene, Skaidra; Makstiene, Jurgita; Juodzbaliene, Edita Brone

    2008-01-01

    This case report presents a very aggressive course of amelanotic nodular melanoma during pregnancy resulting in death five months after delivery. A 34 year-old Caucasian woman at 19th week of the second pregnancy was diagnosed having amelanotic nodular melanoma (tumor thickness - 2.5 mm) with metastases to the regional right inguinal lymph node. Amelanotic nodular melanoma represents malignant melanocytic tumor of the skin, which clinically mimics a variety of benign and malignant skin conditions and therefore commonly leads to delayed diagnosis. Though primary tumor was excised immediately, other treatment procedures as radical lymphadenectomy and chemotherapy were delayed, and immunotherapy was not given totally. At the 29th week of pregnancy, the woman via naturalem delivered a healthy female child, and the chemotherapy was started. Since pregnancy limits the prescription of immunotherapy and chemotherapy, the prognosis for melanoma during pregnancy detected later than in the second stage is poor and can be illustrated by our reported case. Such patients seems to be at higher risk to develop metastasis of melanoma in the internal organs and occasionally even in the fetus; therefore, they should be timely informed about that.

  8. Melanoma early detection and awareness

    DEFF Research Database (Denmark)

    Wainstein, Alberto; Algarra, Salvador Martin; Bastholt, Lars

    2014-01-01

    Risk factors for melanoma are well known and have guided plans for primary and secondary prevention. The presentation of the disease, however, varies widely depending on the geographic area, ethnicity, and socioeconomic status. For this reason, many countries have developed specific strategies to...... are trying to implement similar measures. Future efforts to further improve the efficacy of preventive strategies should focus on populations that usually escape campaigns, such as elderly men and people with low socioeconomic status. Fast-growing tumors also require specific attention....

  9. Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

    Science.gov (United States)

    2017-06-05

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  10. MODELING CREDIT RISK THROUGH CREDIT SCORING

    OpenAIRE

    Adrian Cantemir CALIN; Oana Cristina POPOVICI

    2014-01-01

    Credit risk governs all financial transactions and it is defined as the risk of suffering a loss due to certain shifts in the credit quality of a counterpart. Credit risk literature gravitates around two main modeling approaches: the structural approach and the reduced form approach. In addition to these perspectives, credit risk assessment has been conducted through a series of techniques such as credit scoring models, which form the traditional approach. This paper examines the evolution of...

  11. Promoting early detection of melanoma during the mammography experience

    Directory of Open Access Journals (Sweden)

    A.K. Rzepecki, BS

    2017-12-01

    Full Text Available Background: Invasive melanoma, a lethal form of skin cancer, is the seventh most common cancer in women. Factors such as a history of indoor tanning or sunburn and a personal or family history of skin cancer increase a woman’s risk of developing a melanoma. Objective: Because the majority of melanomas occur in patients age 40 years or older, which is the age that is recommended for women to begin screening mammograms, the mammogram experience could be used to promote early detection of melanoma by introducing skin self-examinations (SSE to a population of women who are already invested in preventive health. Methods: This was a pilot and feasibility study that was designed to promote the early detection of melanoma among women who undergo a mammogram at the Lynn Sage Breast Center at the Northwestern Medicine/Prentice Women’s Hospital in Chicago, Illinois. The study was conducted in three phases: development of the materials, delivery of the program, and assessment of the program effectiveness. Results: Eighty six percent of women with scheduled mammogram appointments participated in the study (n = 560. Among these women, 68% noticed the SSE information in the changing rooms, 78% thought the information applied to them, and 68% identified with at least one of the risk factors for melanoma. Twenty percent of the patients checked their skin in the changing room, 13% noticed a concerning mole, and 60% of those women who noted a concerning lesion stated their intent to see a dermatologist for further evaluation. Conclusion: A large proportion of the women in our study had risk factors for developing a melanoma and noticed the SSE information in the screening center. Placing an intervention to encourage methods for the early detection of melanoma in an outpatient mammography environment is an effective strategy to increase awareness in a large proportion of at-risk women. Keywords: melanoma, skin self-examination, skin cancer screening

  12. [Melanoma and Human Papillomaviruses: Is There an Outlook for Study?].

    Science.gov (United States)

    Volgareva, G M; Mikhaylova, I N; Golovina, D A

    2016-01-01

    Melanoma is one of the most aggressive human malignant tumors. Its incidence and mortality are growing steadily. Ultraviolet irradiation is the main risk factor for melanoma involved in melanomagenesis. The probability of viral etiology of melanoma has been discussed. Human papillomaviruses (HPV) have been mentioned among candidates for its etiologic agents because some HPV types are the powerful carcinogens causing cervical cancer and other cancers. The review analyses the literature data on the association of melanoma with HPV Several groupsfound HPVin skin melanomas as well as in mucosa; viruses of high oncogenic risk were detected in some cases. For some organs the etiological role of high-risk HPV as inducers of invasive carcinomas is confirmed. These organs require special mention: cervix uteri, vulva, vagina, penis, anal region, and oral cavity. However in the majority of the studies in which viral DNA-positive melanomas were found, testing for viral genome expression was not done while this is the fact of primary importance. HPVare found in normal skin and mucous membranes thus creating justifiable threat of tumor specimen contamination with viral DNA in vivo. There are limited data on aggravation of the disease prognosis in papillomavirus-positive melanomas. However, any systematic observation of a sizeable patient group distinguished by that tumor type has not been performed yet. Viral E6 and E7 oncogenes of high-risk papillomaviruses were shown to be able to transform normal human melanocytes in vitro experiments. Thus, we can assume the presence of the association of melanoma with oncogenic HPV. The clinical significance of this problem is indisputable under the conditions of the steady increase in melanoma incidence and mortality rates in Russia and abroad. The problem requires further study.

  13. Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: Role of adipokines‡

    OpenAIRE

    Malvi, Parmanand; Chaube, Balkrishna; Pandey, Vimal; Vijayakumar, Maleppillil Vavachan; Boreddy, Purushotham Reddy; Mohammad, Naoshad; Singh, Shivendra Vikram; Bhat, Manoj Kumar

    2014-01-01

    Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well