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Melanoma: HELP
Articles by Sancy A. Leachman
Based on 62 articles published since 2008
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Between 2008 and 2019, S. Leachman wrote the following 62 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial Individualizing follow-up for patients with early-stage melanoma. 2011

Sondak, Vernon K / Leachman, Sancy A. · ·J Clin Oncol · Pubmed #22067394.

ABSTRACT: -- No abstract --

2 Review Integrating Skin Cancer-Related Technologies into Clinical Practice. 2017

Winkelmann, Richard R / Farberg, Aaron S / Glazer, Alex M / Cockerell, Clay J / Sober, Arthur J / Siegel, Daniel M / Leachman, Sancy A / High, Whitney A / Markowitz, Orit / Berman, Brian / Pariser, David M / Goldenberg, Gary / Rosen, Theodore / Rigel, Darrell S. ·Department of Dermatology, OhioHealth, 75 Hospital Drive STE 250, Athens, OH 4570, USA. · Department of Dermatology, Icahn School of Medicine at Mt. Sinai, 1425 Madison Avenue, Floor 2, New York, NY 10029, USA. · National Society for Cutaneous Medicine, 35 East 35th Street #208, New York, NY 10016, USA. · Department of Dermatology, The University of Texas Southwestern Medical Center, 5939 Harry Hines Boulevard. 4th Floor, Suite 100, Dallas, TX 75390, USA. · Department of Dermatology, Harvard Medical School, 50 Staniford Street, 2nd Floor, Boston, MA 02114, USA. · Department of Dermatology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. · Department of Dermatology, OHSU Knight Cancer Institute, Oregon Health & Science University, 3303 S.W. Bond Avenue, Portland, OR 97239, USA. · Department of Dermatology & Pathology, University of Colorado School of Medicine, 12635 E Montview Boulevard, Bioscience Park, Suite 160, Aurora, CO 80045, USA. · Department of Dermatology, Mount Sinai Medical Center, 5 E 98th Street, FL 5, New York, NY 10029, USA. · Department of Dermatology, University of Miami Miller School of Medicine, 2925 Aventura Boulevard, Suite 205, Aventura, FL 33180, USA. · Department of Dermatology, Eastern Virginia Medical School, 6160 Kempsville Circle, Suite 200A, Norfolk, VA 23502, USA. · Department of Dermatology, Baylor College of Medicine, 1977 Butler Street, Suite E6.200, Houston, Texas 77030, USA. · Department of Dermatology, NYU School of Medicine, 35 East 35th Street #208, New York, NY 10016, USA. Electronic address: dsrigel@prodigy.net. ·Dermatol Clin · Pubmed #28886814.

ABSTRACT: Early diagnosis and treatment of melanoma improve survival. New technologies are emerging that may augment the diagnosis, assessment, and management of melanoma but penetrance into everyday practice is low. In the current health care climate, greater emphasis will be placed on the incorporation of technology for clinically suspicious pigmented lesions to facilitate better, more cost-effective management.

3 Review Assessing Genetic Expression Profiles in Melanoma Diagnosis. 2017

Leachman, Sancy A / Mengden Koon, Stephanie / Korcheva, Veselina B / White, Kevin P. ·Melanoma and Skin Cancer Program, Department of Dermatology, OHSU Knight Cancer Institute, Oregon Health & Science University, 3303 SW Bond Avenue, Portland, OR 97239, USA. Electronic address: leachmas@ohsu.edu. · Department of Dermatology, Oregon Health & Science University, 3303 SW Bond Avenue, Portland, OR 97239, USA. ·Dermatol Clin · Pubmed #28886810.

ABSTRACT: Most melanocytic tumors can be characterized as a benign nevus or a melanoma by a trained pathologist using traditional histopathological methods. However, a minority demonstrates ambiguous features and continues to be a diagnostic challenge. Genetic expression profiling (GEP) assays have been developed in an effort to resolve this dilemma. These assays measure mRNA levels of specified genes using reverse transcription quantitative polymerase chain reaction technology. The development of GEP assays, methodology, challenges associated with GEP validation and testing, and the suitability of a currently available GEP test for clinical use are reviewed.

4 Review Operable Melanoma: Screening, Prognostication, and Adjuvant and Neoadjuvant Therapy. 2017

Tarhini, Ahmad A / Lorigan, Paul / Leachman, Sancy. ·From the University of Pittsburgh, Pittsburgh, PA; University of Manchester, Manchester, United Kingdom; Oregon Health & Science University, Portland, OR. ·Am Soc Clin Oncol Educ Book · Pubmed #28561661.

ABSTRACT: The importance of reducing the numbers of patients with late-stage melanoma, identifying which patients are most likely to progress, and treating these patients at the earliest possible stage cannot be overemphasized. Improved screening of patients prior to diagnosis has the advantage of identifying early-stage disease that is for the most part treatable by surgical methods. The process of melanoma screening is rapidly evolving through population-based programs, mobile health technologies, and advanced imaging tools. For patients with newly diagnosed melanoma, accurately estimating disease prognosis has important implications for management and follow-up. Prognostic factors are individual host- or tumor-related factors or molecules that correlate with genetic predisposition and clinical course. These include clinical covariates and host and tumor proteomic/genomic markers that allow the prognostic subclassification of patients. Adjuvant therapy for high-risk surgically resected melanoma targets residual micrometastatic disease with the goal of reducing the risk of relapse and mortality. In the United States, three regimens have achieved regulatory approval for adjuvant therapy, including high-dose interferon alpha, pegylated interferon alpha, and ipilimumab at 10 mg/kg. Phase III trials have reported benefits in relapse-free survival (all regimens) and overall survival (high-dose interferon alpha and ipilimumab). The management of locally/regionally advanced melanoma may benefit from neoadjuvant therapy, which is the subject of several ongoing studies. Recent studies have shown promising clinical activity and yielded important biomarker findings and mechanistic insights.

5 Review A systematic review of interventions to improve adherence to melanoma preventive behaviors for individuals at elevated risk. 2016

Wu, Yelena P / Aspinwall, Lisa G / Conn, Bridgid M / Stump, Tammy / Grahmann, Bridget / Leachman, Sancy A. ·Division of Public Health, Department of Family and Preventive Medicine, University of Utah, USA; Huntsman Cancer Institute, USA. Electronic address: yelena.wu@utah.edu. · Huntsman Cancer Institute, USA; Department of Psychology, University of Utah, USA. · Department of Pediatrics, Division of Adolescent and Young Adult Medicine, Children's Hospital Los Angeles, USA. · Department of Psychology, University of Utah, USA. · Division of Public Health, Department of Family and Preventive Medicine, University of Utah, USA. · Huntsman Cancer Institute, USA; Department of Dermatology, Oregon Health & Science University, USA. ·Prev Med · Pubmed #27090434.

ABSTRACT: BACKGROUND AND OBJECTIVES: To examine the effectiveness of behavioral interventions for melanoma prevention targeted to individuals at elevated risk due to personal and/or family history. METHODS: Through literature searches in 5 search databases (through July 2014), 20 articles describing 14 unique interventions focused on melanoma prevention among individuals at elevated risk for the disease were identified. Interventions targeting only patients undergoing active treatment for melanoma were excluded. RESULTS: The average study quality was moderate. The majority of interventions (6 out of 9, 66% of studies) led to improvements in one or more photoprotective behaviors, particularly for improvements in use of protective clothing (3 out of 5, 60% of studies), and frequency and/or thoroughness of skin self-examinations (9 out of 12, 75%). Fewer interventions (5 out of 14, 36%) targeted uptake of total body skin examinations (60% led to improvements). Also, fewer interventions targeted all three preventive behaviors (5 out of 14, 36%). CONCLUSIONS: Findings suggest that future interventions should aim to improve adherence across multiple preventive behaviors, over a longer time period (past 8months post-intervention), and target high-risk children. Studies should include adequate sample sizes to investigate moderators and mediators of intervention effectiveness. Interventions may be strengthened by new techniques, such as incorporating family members (e.g., to improve thoroughness of skin self-examinations) and eHealth technology.

6 Review Familial skin cancer syndromes: Increased melanoma risk. 2016

Ransohoff, Katherine J / Jaju, Prajakta D / Tang, Jean Y / Carbone, Michele / Leachman, Sancy / Sarin, Kavita Y. ·Department of Dermatology, Stanford University Medical Center, Stanford, California. · Department of Thoracic Oncology, University of Hawaii Cancer Center, Honolulu, Hawaii. · Department of Dermatology, Oregon Health and Science University, Portland, Oregon. · Department of Dermatology, Stanford University Medical Center, Stanford, California. Electronic address: ksarin@stanford.edu. ·J Am Acad Dermatol · Pubmed #26892652.

ABSTRACT: 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.

7 Review Methods of Melanoma Detection. 2016

Leachman, Sancy A / Cassidy, Pamela B / Chen, Suephy C / Curiel, Clara / Geller, Alan / Gareau, Daniel / Pellacani, Giovanni / Grichnik, James M / Malvehy, Josep / North, Jeffrey / Jacques, Steven L / Petrie, Tracy / Puig, Susana / Swetter, Susan M / Tofte, Susan / Weinstock, Martin A. ·Department of Dermatology and Knight Cancer Institute, Oregon Health and Science University, 3303 SW Bond Avenue, CH16D, Portland, OR, 97239, USA. leachmas@ohsu.edu. · Department of Dermatology and Knight Cancer Institute, Oregon Health and Science University, 3125 SW Sam Jackson Park Road, L468R, Portland, OR, 97239, USA. cassidyp@ohsu.edu. · Department of Dermatology, Emory University School of Medicine, 1525 Clifton Road NE, 1st Floor, Atlanta, GA, 30322, USA. schen2@emory.edu. · Department of Dermatology and Arizona Cancer Center, University of Arizona, 1515 N Campbell Avenue, Tucson, AZ, 85721, USA. ccuriel@email.arizona.edu. · Department of Dermatology, Harvard School of Public Health and Massachusetts General Hospital, Landmark Center, 401 Park Drive, 3rd Floor East, Boston, MA, 02215, USA. ageller@hsph.harvard.edu. · Laboratory of Investigative Dermatology, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA. daniel.gareau@rockefeller.edu. · Department of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, Modena, Italy. giovanni.pellacani@unimore.it. · Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Room 912, BRB (R-125), 1501 NW 10th Avenue, Miami, FL, 33136, USA. grichnik@miami.edu. · Melanoma Unit, Dermatology Department, Hospital Clinic Barcelona, Villarroel 170, 08036, Barcelona, Spain. jmalvehy@clinic.ub.es. · University of California, San Francisco, 1701 Divisadero Street, Suite 280, San Francisco, CA, 94115, USA. jeffrey.north@ucsf.edu. · Department of Biomedical Engineering and Dermatology, Oregon Health and Science University, 3303 SW Bond Avenue, CH13B, Portland, OR, 97239, USA. jacquess@ohsu.edu. · Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Avenue, CH13B, Portland, OR, 97239, USA. petrie@ohsu.edu. · Melanoma Unit, Dermatology Department, Hospital Clinic Barcelona, Villarroel 170, 08036, Barcelona, Spain. spuig@clinic.ub.es. · Department of Dermatology/Cutaneous Oncology, Stanford University, 900 Blake Wilbur Drive, W3045, Stanford, CA, 94305, USA. sswetter@stanford.edu. · Department of Dermatology, Oregon Health and Science University, 3303 SW Bond Avenue, CH16D, Portland, OR, 97239, USA. toftes@ohsu.edu. · Departments of Dermatology and Epidemiology, Brown University, V A Medical Center 111D, 830 Chalkstone Avenue, Providence, RI, 02908, USA. maw@brown.edu. ·Cancer Treat Res · Pubmed #26601859.

ABSTRACT: Detection and removal of melanoma, before it has metastasized, dramatically improves prognosis and survival. The purpose of this chapter is to (1) summarize current methods of melanoma detection and (2) review state-of-the-art detection methods and technologies that have the potential to reduce melanoma mortality. Current strategies for the detection of melanoma range from population-based educational campaigns and screening to the use of algorithm-driven imaging technologies and performance of assays that identify markers of transformation. This chapter will begin by describing state-of-the-art methods for educating and increasing awareness of at-risk individuals and for performing comprehensive screening examinations. Standard and advanced photographic methods designed to improve reliability and reproducibility of the clinical examination will also be reviewed. Devices that magnify and/or enhance malignant features of individual melanocytic lesions (and algorithms that are available to interpret the results obtained from these devices) will be compared and contrasted. In vivo confocal microscopy and other cellular-level in vivo technologies will be compared to traditional tissue biopsy, and the role of a noninvasive "optical biopsy" in the clinical setting will be discussed. Finally, cellular and molecular methods that have been applied to the diagnosis of melanoma, such as comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), will be discussed.

8 Review Addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi: Pigmented Lesion Subcommittee consensus statement. 2015

Kim, Caroline C / Swetter, Susan M / Curiel-Lewandrowski, Clara / Grichnik, James M / Grossman, Douglas / Halpern, Allan C / Kirkwood, John M / Leachman, Sancy A / Marghoob, Ashfaq A / Ming, Michael E / Nelson, Kelly C / Veledar, Emir / Venna, Suraj S / Chen, Suephy C. ·Pigmented Lesion Clinic and Cutaneous Oncology Program, Department of Dermatology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts. · Pigmented Lesion and Melanoma Program, Department of Dermatology, Stanford University Medical Center, Palo Alto, California3Dermatology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California. · Pigmented Lesion Clinic and Multidisciplinary Cutaneous Oncology Program, Division of Dermatology, Department of Medicine, University of Arizona, Tucson. · Melanoma Program, Department of Dermatology, Miller School of Medicine, University of Miami, Miami, Florida. · Pigmented Lesion Clinic, Departments of Dermatology and Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City. · Pigmented Lesion Clinic, Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. · Melanoma Program, University of Pittsburgh Cancer Institute, Department of Medicine, Dermatology and Translational Science, University of Pittsburgh, Pittsburgh, Pennsylvania. · Melanoma and Cutaneous Oncology Program, Department of Dermatology, Oregon Health and Science University, Portland. · Pigmented Lesion Clinic, Department of Dermatology, University of Pennsylvania, Philadelphia. · Pigmented Lesion Clinic, Department of Dermatology, Duke University Medical Center, Durham, North Carolina. · Center for Research and Grants, Baptist Health South Florida, Miami. · Skin Oncology and Melanoma Center, Department of Medicine, MedStar Washington Cancer Institute and Georgetown University Medical Center, Washington, DC. · Melanoma and Pigmented Lesion Clinic, Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia15Division of Dermatology, Atlanta Veterans Administration Medical Center, Decatur, Georgia. ·JAMA Dermatol · Pubmed #25409291.

ABSTRACT: IMPORTANCE: The management of clinically atypical nevi/dysplastic nevi (CAN/DN) is controversial, with few data to guide the process. Management recommendations for DN with positive histologic margins were developed by the Delphi method to achieve consensus among members of the Pigmented Lesion Subcommittee (PLS) of the Melanoma Prevention Working Group (MPWG) after reviewing the current evidence. OBJECTIVES: To outline key issues related to the management of CAN/DN: (1) biopsies of CAN and how positive margins arise, (2) whether incompletely excised DN evolve into melanoma, (3) current data on the outcomes of DN with positive histologic margins, (4) consensus recommendations, and (5) a proposal for future studies, including a large-scale study to help guide the management of DN with positive margins. EVIDENCE REVIEW: The literature, including recent studies examining management and outcomes of DN with positive margins between 2009 to 2014, was reviewed. FINDINGS: A consensus statement by the PLS of the MPWG following review of the literature, group discussions, and a structured Delphi method consensus. CONCLUSIONS AND RELEVANCE: This consensus statement reviews the complexities of management of CAN/DN. A review of the literature and 2 rounds of a structured Delphi consensus resulted in the following recommendations: (1) mildly and moderately DN with clear margins do not need to be reexcised, (2) mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than reexcised, and (3) observation may be a reasonable option for management of moderately DN with positive histologic margins without clinically apparent residual pigmentation; however, more data are needed to make definitive recommendations in this clinical scenario.

9 Review Melanocortins and the melanocortin 1 receptor, moving translationally towards melanoma prevention. 2014

Abdel-Malek, Zalfa A / Swope, Viki B / Starner, Renny J / Koikov, Leonid / Cassidy, Pamela / Leachman, Sancy. ·Department of Dermatology, University of Cincinnati, United States. Electronic address: abdelmza@uc.edu. · Department of Dermatology, University of Cincinnati, United States. · Department of Dermatology, Oregon Health Sciences University, United States. ·Arch Biochem Biophys · Pubmed #25017567.

ABSTRACT: Beginning in the last decade of the twentieth century, the fields of pigment cell research and melanoma have witnessed major breakthroughs in the understanding of the role of melanocortins in human pigmentation and the DNA damage response of human melanocytes to solar ultraviolet radiation (UV). This began with the cloning of the melanocortin 1 receptor (MC1R) gene from human melanocytes and the demonstration that the encoded receptor is functional. Subsequently, population studies found that the MC1R gene is highly polymorphic, and that some of its variants are associated with red hair phenotype, fair skin and poor tanning ability. Using human melanocytes cultured from donors with different MC1R genotypes revealed that the alleles associated with red hair color encode for a non-functional receptor. Epidemiological studies linked the MC1R red hair color variants to increased melanoma risk. Investigating the impact of different MC1R variants on the response of human melanocytes to UV led to the important discovery that the MC1R signaling activates antioxidant, DNA repair and survival pathways, in addition to stimulation of eumelanin synthesis. These effects of MC1R were absent in melanocytes expressing 2 MC1R red hair color variants that result in loss of function of the receptor. The importance of the MC1R in reducing UV-induced genotoxicity in melanocytes led us to design small peptide analogs of the physiological MC1R agonist α-melanocortin (α-melanocyte stimulating hormone; α-MSH) for the goal of utilizing them for melanoma chemoprevention.

10 Review Melanocytes as instigators and victims of oxidative stress. 2014

Denat, Laurence / Kadekaro, Ana L / Marrot, Laurent / Leachman, Sancy A / Abdel-Malek, Zalfa A. ·L'OREAL Research and Innovation, Aulnay-sous-Bois, France. · Department of Dermatology, University of Cincinnati, Cincinnati, Ohio, USA. · Department of Dermatology, Oregon Health Sciences University, Portland, Oregon, USA. · Department of Dermatology, University of Cincinnati, Cincinnati, Ohio, USA. Electronic address: abdelmza@uc.edu. ·J Invest Dermatol · Pubmed #24573173.

ABSTRACT: Epidermal melanocytes are particularly vulnerable to oxidative stress owing to the pro-oxidant state generated during melanin synthesis, and to the intrinsic antioxidant defenses that are compromised in pathologic conditions. Melanoma is thought to be oxidative stress driven, and melanocyte death in vitiligo is thought to be instigated by a highly pro-oxidant state in the epidermis. We review the current knowledge about melanin and the redox state of melanocytes, how paracrine factors help counteract oxidative stress, the role of oxidative stress in melanoma initiation and progression and in melanocyte death in vitiligo, and how this knowledge can be harnessed for melanoma and vitiligo treatment.

11 Review Survival is not the only valuable end point in melanoma screening. 2012

Curiel-Lewandrowski, Clara / Kim, Caroline C / Swetter, Susan M / Chen, Suephy C / Halpern, Allan C / Kirkwood, John M / Leachman, Sancy A / Marghoob, Ashfaq A / Ming, Michael E / Grichnik, James M / Anonymous1021005. ·Division of Dermatology, Department of Medicine, University of Arizona, Tucson, Arizona, USA. ·J Invest Dermatol · Pubmed #22336950.

ABSTRACT: -- No abstract --

12 Review Genetics of pigmentation and melanoma predisposition. 2010

Pho, L N / Leachman, S A. ·Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA. ·G Ital Dermatol Venereol · Pubmed #20197744.

ABSTRACT: About 5-10% of human cutaneous malignant melanoma is hereditary and known to involve rare germline mutations in highly penetrant, autosomal dominant genes. These genes are important in cell cycle control but are not responsible for all familial cases of melanoma. Epidemiologic studies have linked specific phenotypic traits including fair skin, light-colored eyes, and poor tanning ability to melanoma risks. The ability to visually discern and define pigmentary phenotypes in humans and in animal models has permitted elucidation of many genes involved in pigmentation and melanin biosynthesis. Additional genetic epidemiological studies have recently identified a subset of these pigmentation genes that are associated with risk for melanoma and other cutaneous malignancies as well as photosensitivity. Genome-wide association studies (GWAS) have unveiled single nucleotide polymorphisms (SNPs) or genetic variants in MC1R, TPCN2, ASIP, KITLG, NCKX5, TYR, IRF4, OCA2, and TYRP1 pigmentation genes. These findings emphasize the contribution of pigmentation pathways to melanoma predisposition and tumorigenesis through gene-environment interactions. Since pigmentation genes in the melanin synthesis pathway also confer risk for cutaneous malignancy, a better understanding of the operative molecular mechanisms involved in this relationship has the potential to impact individual risk assessment for cutaneous malignant melanoma in the future. This paper is an overview of our current understanding of pigmentation gene modifications that have been associated with melanoma risk and how these genes can enrich clinical management, prevention, and early detection of malignant melanoma.

13 Review Selection criteria for genetic assessment of patients with familial melanoma. 2009

Leachman, Sancy A / Carucci, John / Kohlmann, Wendy / Banks, Kimberly C / Asgari, Maryam M / Bergman, Wilma / Bianchi-Scarrà, Giovanna / Brentnall, Teresa / Bressac-de Paillerets, Brigitte / Bruno, William / Curiel-Lewandrowski, Clara / de Snoo, Femke A / Debniak, Tadeusz / Demierre, Marie-France / Elder, David / Goldstein, Alisa M / Grant-Kels, Jane / Halpern, Allan C / Ingvar, Christian / Kefford, Richard F / Lang, Julie / MacKie, Rona M / Mann, Graham J / Mueller, Kurt / Newton-Bishop, Julia / Olsson, Håkan / Petersen, Gloria M / Puig, Susana / Rigel, Darrell / Swetter, Susan M / Tucker, Margaret A / Yakobson, Emanuel / Zitelli, John A / Tsao, Hensin. ·Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112-5550, USA. sancy.leachman@hci.utah.edu ·J Am Acad Dermatol · Pubmed #19751883.

ABSTRACT: Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of melanoma can be specifically attributed to pathogenic germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the small proportion of patients who benefit most from referral to a genetics specialist for consideration of genetic testing for CDKN2A, we have reviewed available published studies of CDKN2A mutation analysis in cohorts with invasive, cutaneous melanoma and found variability in the rate of CDKN2A mutations based on geography, ethnicity, and the type of study and eligibility criteria used. Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family. The work summarized in this review should help identify individuals who are appropriate candidates for referral for genetic consultation and possible testing.

14 Clinical Trial A Phase II Randomized Placebo-Controlled Trial of Oral N-acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative Stress In Vivo. 2017

Cassidy, Pamela B / Liu, Tong / Florell, Scott R / Honeggar, Matthew / Leachman, Sancy A / Boucher, Kenneth M / Grossman, Douglas. ·Department of Dermatology, Oregon Health & Science University, Portland, Oregon. doug.grossman@hci.utah.edu cassidyp@ohsu.edu. · Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon. · Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah. · Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah. · Department of Dermatology, Oregon Health & Science University, Portland, Oregon. · Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah. · Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah. doug.grossman@hci.utah.edu cassidyp@ohsu.edu. · Department of Oncological Sciences, University of Utah Health Sciences Center, Salt Lake City, Utah. ·Cancer Prev Res (Phila) · Pubmed #27920018.

ABSTRACT: Oxidative stress plays a role in UV-induced melanoma, which may arise from melanocytic nevi. We investigated whether oral administration of the antioxidant N-acetylcysteine (NAC) could protect nevi from oxidative stress in vivo in the setting of acute UV exposure. The minimal erythemal dose (MED) was determined for 100 patients at increased risk for melanoma. Patients were randomized to receive a single dose (1,200 mg) of NAC or placebo, in double-blind fashion, and then one nevus was irradiated (1-2 MED) using a solar simulator. One day later, the MED was redetermined and the irradiated nevus and a control unirradiated nevus were removed for histologic analysis and examination of biomarkers of NAC metabolism and UV-induced oxidative stress. Increased expression of 8-oxoguanine, thioredoxin reductase-1, and γ-glutamylcysteine synthase modifier subunit were consistently seen in UV-treated compared with unirradiated nevi. However, no significant differences were observed in these UV-induced changes or in the pre- and postintervention MED between those patients receiving NAC versus placebo. Similarly, no significant differences were observed in UV-induced changes between subjects with germline wild-type versus loss-of-function mutations in the melanocortin-1 receptor. Nevi showed similar changes of UV-induced oxidative stress in an open-label post-trial study in 10 patients who received NAC 3 hours before nevus irradiation. Thus, a single oral dose of NAC did not effectively protect nevi from UV-induced oxidative stress under the conditions examined. Cancer Prev Res; 10(1); 36-44. ©2016 AACR.

15 Clinical Trial A phase I study of intratumoral ipilimumab and interleukin-2 in patients with advanced melanoma. 2016

Ray, Abhijit / Williams, Matthew A / Meek, Stephanie M / Bowen, Randy C / Grossmann, Kenneth F / Andtbacka, Robert H I / Bowles, Tawnya L / Hyngstrom, John R / Leachman, Sancy A / Grossman, Douglas / Bowen, Glen M / Holmen, Sheri L / VanBrocklin, Matthew W / Suneja, Gita / Khong, Hung T. ·Division of Oncology, Huntsman Cancer Institute-University of Utah, Salt Lake City, UT, USA. · Department of Pathology, University of Utah, Salt Lake City, UT, USA. · School of Medicine, University of Utah, Salt Lake City, UT, USA. · Section of Surgical Oncology, Division of General Surgery Huntsman Cancer Institute-University of Utah, Salt Lake City, UT, USA. · Department of General Surgery, Intermountain Medical Center, Murray, UT, USA. · Department of Dermatology, Oregon Health & Science University-Knight Cancer Institute, Portland, OR, USA. · Department of Radiation Oncology, University of Utah, Salt Lake City, UT, USA. ·Oncotarget · Pubmed #27391442.

ABSTRACT: PURPOSE: Intratumoral interleukin-2 (IL-2) is effective but does not generate systemic immunity. Intravenous ipilimumab produces durable clinical response in a minority of patients, with potentially severe toxicities. Circulating anti-tumor T cells activated by ipilimumab may differ greatly from tumor-infiltrating lymphocytes activated by intratumoral ipilimumab in phenotypes and functionality. The objective of this study was to primarily assess the safety of intratumoral ipilimumab/IL-2 combination and to obtain data on clinical efficacy. RESULTS: There was no dose limiting toxicity. While local response of injected lesions was observed in 67% patients (95% CI, 40%-93%), an abscopal response was seen in 89% (95% CI, 68%-100%). The overall response rate and clinical benefit rate by immune-related response criteria (irRC) was 40% (95% CI, 10%-70%) and 50% (95% CI, 19%-81%), respectively. Enhanced systemic immune response was observed in most patients and correlated with clinical responses. EXPERIMENTAL DESIGN: Twelve patients with unresectable stages III/IV melanoma were enrolled. A standard 3+3 design was employed to assess highest tolerable intratumoral dose of ipilimumab and IL-2 based on toxicity during the first three weeks. Escalated doses of ipilimumab was injected into only one lesion weekly for eight weeks in cohorts of three patients. A fixed dose of IL-2 was injected three times a week into the same lesion for two weeks, followed by two times a week for six weeks. CONCLUSIONS: Intratumoral injection with the combination of ipilimumab/IL-2 is well tolerated and generates responses in both injected and non-injected lesions in the majority of patients.

16 Clinical Trial A randomized, double-blind, placebo-controlled phase II clinical trial of lovastatin for various endpoints of melanoma pathobiology. 2014

Linden, Kenneth G / Leachman, Sancy A / Zager, Jonathan S / Jakowatz, James G / Viner, Jaye L / McLaren, Christine E / Barr, Ronald J / Carpenter, Philip M / Chen, Wen-Pin / Elmets, Craig A / Tangrea, Joseph A / Lim, Sung-Jig / Cochran, Alistair J / Meyskens, Frank L. ·Department of Dermatology and The Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, 101 The City Drive, Orange, CA 92868. kglinden@uci.edu. ·Cancer Prev Res (Phila) · Pubmed #24614012.

ABSTRACT: On the basis of large cardiovascular clinical trials of lipid-lowering agents that showed a considerable decrease in the incidence of primary melanomas in the active agent arm, we have carried out a randomized, double-blind clinical trial examining the impact of lovastatin on various biomarkers of melanoma pathogenesis. Subjects with at least two clinically atypical nevi were randomized to receive oral lovastatin or placebo for a 6-month period. Clinical, histopathologic, and molecular biomarkers were evaluated for change in the two groups. Eighty subjects were randomized, evaluable, and included in the analyses. Lovastatin showed no benefit in comparison with placebo in the primary endpoint of decreasing the level of histopathologic atypia, nor in any of the secondary endpoints of decreasing clinical atypia, impact on nevus number, nor in showing significant changes in any of the molecular biomarkers. There were no significant differences in adverse event profiles for lovastatin compared with placebo. The lovastatin arm did show a significant and considerable decrease in total serum cholesterol and serum low-density lipoprotein (LDL) levels compared with placebo, an expected result. This finding bolsters confidence in subject compliance. Given the results of this trial, it is concluded that if lovastatin were to lower the incidence of melanoma, it would appear not to be doing so by reversing atypia of precursor atypical nevi over the 6-month time frame studied. Further research into the pathogenesis of melanoma and in other potential chemopreventive agents is needed.

17 Article Identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria. 2019

Gastman, Brian R / Gerami, Pedram / Kurley, Sarah J / Cook, Robert W / Leachman, Sancy / Vetto, John T. ·Department of Plastic Surgery, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio. · Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Skin Cancer Institute, Northwestern University Lurie Comprehensive Cancer Center, Chicago, Illinois. · Castle Biosciences, Inc, Friendswood, Texas. · Castle Biosciences, Inc, Friendswood, Texas. Electronic address: rcook@castlebiosciences.com. · Department of Dermatology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon. · Division of Surgical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon. ·J Am Acad Dermatol · Pubmed #30081113.

ABSTRACT: BACKGROUND: A substantial number of patients who relapse and die from cutaneous melanoma (CM) are categorized as being at low risk by traditional staging factors. The 31-gene expression profile (31-GEP) test independently stratifies metastatic risk of patients with CM as low (Class 1, with 1A indicating lowest risk) or high (Class 2,with 2B indicating highest risk). OBJECTIVE: To assess risk prediction by the 31-GEP test within 3 low-risk (according to the American Joint Committee on Cancer) populations of patients with CM: those who are sentinel lymph node (SLN) negative, those with stage I to IIA tumors, and those with thin (≤1 mm [T1]) tumors. METHODS: A total of 3 previous validation studies provided a nonoverlapping cohort of 690 patients with 31-GEP results, staging information, and survival outcomes. Kaplan-Meier and Cox regression analysis were performed. RESULTS: The results included the identification of 70% of SLN-negative patients who experienced metastasis as Class 2, the discovery of reduced recurrence-free survival for patients with thin tumors and Class 2B biology compared with that of those with Class 1A biology (P < .0001); and determination of the 31-GEP test as an independent predictor of risk compared with traditional staging factors in patients with stage I to IIA tumors. LIMITATIONS: Diagnoses spanned multiple versions of pathologic staging criteria. CONCLUSIONS: The 31-GEP test identifies high-risk patients who are likely to experience recurrence or die of melanoma within low-risk groups of subpopulations of patients with CM who have SLN-negative disease, stage I to IIA tumors, and thin tumors.

18 Article Frontiers in pigment cell and melanoma research. 2018

Filipp, Fabian V / Birlea, Stanca / Bosenberg, Marcus W / Brash, Douglas / Cassidy, Pamela B / Chen, Suzie / D'Orazio, John A / Fujita, Mayumi / Goh, Boon-Kee / Herlyn, Meenhard / Indra, Arup K / Larue, Lionel / Leachman, Sancy A / Le Poole, Caroline / Liu-Smith, Feng / Manga, Prashiela / Montoliu, Lluis / Norris, David A / Shellman, Yiqun / Smalley, Keiran S M / Spritz, Richard A / Sturm, Richard A / Swetter, Susan M / Terzian, Tamara / Wakamatsu, Kazumasa / Weber, Jeffrey S / Box, Neil F. ·Systems Biology and Cancer Metabolism, Program for Quantitative Systems Biology, University of California Merced, Merced, California. · Department of Dermatology, University of Colorado Denver, Aurora, Colorado. · Department of Dermatology and Dermatopathology, Yale School of Medicine, New Haven, Connecticut. · Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut. · Department of Dermatology, Oregon Health and Science University, Portland, Oregon. · Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey. · Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky. · Mount Elizabeth Medical Centre, Skin Physicians Private Limited, Singapore, Singapore. · Department of Molecular and Cellular Oncogenesis, Wistar Institute, Philadelphia, Pennsylvania. · Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon. · Equipe Labellisée Ligue Contre le Cancer, Normal and Pathological Development of Melanocytes, UMR 3347, CNRS, Institut Curie, Orsay, France. · Lurie Comprehensive Cancer Center, Northwestern University at Chicago, Chicago, Illinois. · Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, California. · Ronald O Perlman Department of Dermatology, New York University Langone Medical Center, New York, New York. · CNB-CSIC, CIBERER-ISCIII, Campus de Cantoblanco, Centro Nacional de Biotecnología, Madrid, Spain. · Department of Tumor Biology, Moffitt Cancer Center, Tampa, Florida. · Human Medical Genetics and Genomics Program, University of Colorado Denver, Aurora, Colorado. · Dermatology Research Centre, University of Queensland Diamantina Institute, University of Queensland, Brisbane, Queensland, Australia. · Department of Dermatology, Stanford University, Palo Alto, California. · Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Japan. · Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York. ·Pigment Cell Melanoma Res · Pubmed #30281213.

ABSTRACT: In this perspective, we identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology. Significantly, this document encapsulates important advances in melanocyte and melanoma research including emerging frontiers in melanoma immunotherapy, medical and surgical oncology, dermatology, vitiligo, albinism, genomics and systems biology, epidemiology, pigment biophysics and chemistry, and evolution.

19 Article Impact of Gene Expression Profiling on Decision-Making in Clinically Node Negative Melanoma Patients after Surgical Staging. 2018

Schuitevoerder, Darryl / Heath, Michael / Cook, Robert W / Covington, Kyle R / Fortino, Jeanine / Leachman, Sancy / Vetto, John T. · ·J Drugs Dermatol · Pubmed #29462228.

ABSTRACT: INTRODUCTION: The surgeon's role in the follow-up of pathologic stage I and II melanoma patients has traditionally been minimal. Melanoma genetic expression profile (GEP) testing provides binary risk assessment (Class 1-low risk, Class 2-high risk), which can assist in predicting metastasis and formulating appropriate follow up. We sought to determine the impact of GEP results on the management of clinically node negative cutaneous melanoma patients staged with sentinel lymph node biopsy (SLNB). METHODS: A retrospective review of prospectively gathered data consisting of patients seen from September 2015 - August 2016 was performed to determine whether GEP class influenced follow-up recommendations. Patients were stratified into four groups based on recommended follow-up plan: Dermatology alone, Surgical Oncology, Surgical Oncology with recommendation for adjuvant clinical trial, or Medical and Surgical Oncology. RESULTS: Of ninety-one patients, 38 were pathologically stage I, 42 stage II, 10 stage III, and 1 stage IV. Combining all stages, GEP Class 1 patients were more likely to be followed by Dermatology alone and less like to be followed by Surgical Oncology with recommendation for adjuvant trial compared to Class 2 patients (P less than 0.001). Among stage 1 patients, Class 1 were more likely to follow up with Dermatology alone compared to Class 2 patients (82 vs. 0%; P less than 0.001). Among stage II patients, GEP Class 1 were more likely to follow up with Dermatology alone (21 vs 0%) and more Class 2 patients followed up with surgery and recommendations for adjuvant trial (36 vs 64%; P less than 0.05). There was no difference in follow up for stage III patients based on the GEP results (P=0.76). CONCLUSION: GEP results were significantly associated with the management of stage I-II melanoma patients after staging with SLNB. For node negative patients, Class 2 results led to more aggressive follow up and management. J Drugs Dermatol. 2018;17(2):196-199.

20 Article Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. 2018

Zager, Jonathan S / Gastman, Brian R / Leachman, Sancy / Gonzalez, Rene C / Fleming, Martin D / Ferris, Laura K / Ho, Jonhan / Miller, Alexander R / Cook, Robert W / Covington, Kyle R / Meldi-Plasseraud, Kristen / Middlebrook, Brooke / Kaminester, Lewis H / Greisinger, Anthony / Estrada, Sarah I / Pariser, David M / Cranmer, Lee D / Messina, Jane L / Vetto, John T / Wayne, Jeffrey D / Delman, Keith A / Lawson, David H / Gerami, Pedram. ·Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 N. McKinley Drive room 4123, Tampa, FL, 33612, USA. · Department of Plastic Surgery, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. · Department of Dermatology, Knight Cancer Institute, Oregon Health & Science University, 3303 S.W. Bond Avenue, Portland, OR, 97239, USA. · Department of Medical Oncology, University of Colorado School of Medicine, 12801 E. 17th Avenue, Aurora, CO, 80045, USA. · Department of Surgical Oncology, The University of Tennessee Health Science Center, 910 Madison, Suite 303, Memphis, TN, 38163, USA. · Department of Dermatology, University of Pittsburgh Medical Center, 3601 Fifth Avenue, Pittsburgh, PA, 15213, USA. · Department of Pathology, University of Pittsburgh Medical Center, 3708 Fifth Avenue, Suite 500.94, Pittsburgh, PA, 15213, USA. · START Center for Cancer Care, 4383 Medical Drive, San Antonio, TX, 78229, USA. · Castle Biosciences, Inc., 820 S. Friendswood Drive, Suite 201, Friendswood, TX, 77546, USA. · Dermatology North Palm Beach, 840 U.S. Highway Number One, North Palm Beach, FL, 33408, USA. · Research & Development, Kelsey Research Foundation, 5615 Kirby Drive, Suite 660, Houston, TX, 77005, USA. · Affiliated Dermatology, 20401 North 73rd Street, Suite 230, Scottsdale, AZ, 85255, USA. · Pariser Dermatology Specialists, Virginia Clinical Research, Inc., 6160 Kempsville Circle, Suite 200A, Norfolk, VA, 23502, USA. · Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA, 23501-1980, USA. · Department of Sarcoma Medical Oncology, Seattle Cancer Care Alliance, 825 Eastlake Avenue E, Seattle, WA, 98109, USA. · Department of Anatomic Pathology, Moffitt Cancer Center, 10920 N. McKinley Drive, Tampa, FL, 33612, USA. · Division of Surgical Oncology, Knight Cancer Institute, Oregon Health & Science University, 3303 S.W. Bond Avenue, Portland, OR, 97239, USA. · Department of Surgical Oncology, Northwestern University Feinberg School of Medicine, 251 East Huron Street, Chicago, IL, 60611, USA. · Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 1600, Chicago, IL, 60611, USA. · Skin Cancer Institute, Northwestern University, Lurie Comprehensive Cancer Center, 420 East Superior Street, Chicago, IL, 60611, USA. · Department of Surgery, Emory University Winship Cancer Institute, 1364 Clifton Road NE, Atlanta, GA, 30322, USA. · Department of Hematology and Medical Oncology, Emory University Winship Cancer Institute, 550 Peachtree Street NE, Atlanta, GA, 30308, USA. · Skin Cancer Institute, Northwestern University, Lurie Comprehensive Cancer Center, 420 East Superior Street, Chicago, IL, 60611, USA. pgerami1@nm.org. · Departments of Dermatology and Pathology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Arkes 1600, Chicago, IL, 60611, USA. pgerami1@nm.org. ·BMC Cancer · Pubmed #29402264.

ABSTRACT: BACKGROUND: The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients. METHODS: This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival. RESULTS: The 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively (P < 0.001). The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each). GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each). CONCLUSIONS: The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual's risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.

21 Article Genetic test reporting of CDKN2A provides informational and motivational benefits for managing melanoma risk. 2018

Aspinwall, Lisa G / Stump, Tammy K / Taber, Jennifer M / Drummond, Danielle M / Kohlmann, Wendy / Champine, Marjan / Leachman, Sancy A. ·Department of Psychology, University of Utah, Salt Lake City, UT, USA. · Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. · Oregon Health and Science University, Portland, OR, USA. ·Transl Behav Med · Pubmed #29385581.

ABSTRACT: A CDKN2A/p16 mutation confers 28%-67% lifetime melanoma risk, a risk that may be moderated by ultraviolet radiation exposure. The aim of this study was to test whether melanoma genetic counseling and test disclosure conferred unique informational, motivational, or emotional benefits compared to family history-based counseling. Participants included were 114 unaffected members of melanoma-prone families, ages 16-69, 51.8% men, 65.8% with minor children or grandchildren. Carriers (n = 28) and noncarriers (n = 41) from families with a CDKN2A mutation were compared to no-test controls (n = 45) from melanoma-prone families without an identifiable CDKN2A mutation. All participants received equivalent counseling about melanoma risk and management; only CDKN2A participants received genetic test results. Using newly developed inventories, participants rated perceived costs and benefits for managing their own and their children's or grandchildren's melanoma risk 1 month and 1 year after counseling. Propensity scores controlled for baseline family differences. Compared to no-test controls, participants who received test results (carriers and noncarriers) reported feeling significantly more informed and prepared to manage their risk, and carriers reported greater motivation to reduce sun exposure. All groups reported low negative emotions about melanoma risk. Parents reported high levels of preparedness to manage children's risk regardless of group. Carrier parents reported greater (but moderate) worry about their children's risk than no-test control parents. Women, older, and more educated respondents reported greater informational and motivational benefits regardless of group. Genetic test results were perceived as more informative and motivating for personal sun protection efforts than equivalent counseling based on family history alone.

22 Article Management strategies of academic pigmented lesion clinic directors in the United States. 2018

Nelson, Kelly C / Grossman, Douglas / Kim, Caroline C / Chen, Suephy C / Curiel-Lewandrowski, Clara N / Grichnik, James M / Kirkwood, John M / Leachman, Sancy A / Marghoob, Ashfaq A / Swetter, Susan M / Venna, Suraj S / Ming, Michael E. ·Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah. · Department of Dermatology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts. · Department of Dermatology, Emory University, Atlanta, Georgia; Division of Dermatology, Atlanta Veterans Affairs Medical Center, Decatur, Georgia. · University of Arizona Cancer Center, Tucson, Arizona. · Scully-Welsh Cancer Center, Indian River Medical Center, Vero Beach, Florida. · University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Department of Dermatology, Oregon Health Sciences University, Portland, Oregon. · Dermatology Service, Memorial Sloan Kettering Skin Cancer Center, Hauppage, New York. · Department of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center, Stanford, California; Cancer Institute, Stanford, California; Dermatology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California. · Inova Schar Cancer Institute, Department of Medicine, Virginia Commonwealth University, Fairfax, Virginia. · Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: michael.ming@uphs.upenn.edu. ·J Am Acad Dermatol · Pubmed #29307637.

ABSTRACT: -- No abstract --

23 Article Melanoma risk assessment based on relatives' age at diagnosis. 2018

Wu, Yelena P / Kohlmann, Wendy / Curtin, Karen / Yu, Zhe / Hanson, Heidi A / Hashibe, Mia / Parsons, Bridget G / Wong, Jathine / Schiffman, Joshua D / Grossman, Douglas / Leachman, Sancy A. ·Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. yelena.wu@utah.edu. · Departments of Dermatology and Oncological Sciences, University of Utah, Salt Lake City, UT, USA. yelena.wu@utah.edu. · Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. · Department of Medicine, University of Utah, Salt Lake City, UT, USA. · Department of Surgery, University of Utah, Salt Lake City, UT, USA. · Division of Public Health, Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT, USA. · Department of Pediatrics, University of Utah, Salt Lake City, UT, USA. · Departments of Dermatology and Oncological Sciences, University of Utah, Salt Lake City, UT, USA. · Department of Dermatology, Oregon Health and Science University, Portland, OR, USA. ·Cancer Causes Control · Pubmed #29243179.

ABSTRACT: PURPOSE: The aim of this study was to determine risk for melanoma among individuals who have a first- or second-degree relative with a history of melanoma, based on the unaffected individual's age and age at diagnosis of the relative. METHODS: The study employed a case-control design using a statewide database linked with a Surveillance Epidemiology and End Results cancer registry. A population-based sample of individuals who received at least one diagnosis of first primary, malignant melanoma (n = 14,281), as well as their first- and second-degree relatives, was included. Control individuals with no history of melanoma (n = 70,889) were matched to cases on birth year, gender, race/ethnicity, and county at birth. RESULTS: Risk for melanoma among relatives of melanoma patients declined with relative's age and age at diagnosis. Individuals between ages 40 and 49 who are first-degree relatives of melanoma patients diagnosed between ages 40 and 49 had the greatest risk for melanoma compared with individuals without a first-degree relative with a melanoma history (HR 4.89; 95% CI 3.11-7.68). Increased melanoma risk among second-degree relatives of patients was typically lower than that for first-degree relatives. CONCLUSIONS: Risk for melanoma, at earlier ages than expected, is increased among relatives of individuals with a history of melanoma, particularly if the melanoma case was diagnosed at a young age. Further research on the relationship between age at diagnosis and relative's melanoma risk could inform melanoma screening recommendations for individuals with a family history of the disease.

24 Article A novel educational intervention targeting melanoma risk and prevention knowledge among children with a familial risk for melanoma. 2018

Wu, Yelena P / Nagelhout, Elizabeth / Aspinwall, Lisa G / Boucher, Kenneth M / Parsons, Bridget G / Kohlmann, Wendy / Kaphingst, Kimberly A / Homburger, Sheila / Perkins, Ryan D / Grossman, Douglas / Harding, Garrett / Leachman, Sancy A. ·Department of Dermatology, University of Utah, 30 North 1900 East, 4A330, Salt Lake City, UT 84132; Huntsman Cancer Institute, 2000 Circle of Hope, Rm 4509, Salt Lake City, UT 84112, USA. Electronic address: Yelena.Wu@utah.edu. · Department of Dermatology, University of Utah, 30 North 1900 East, 4A330, Salt Lake City, UT 84132. · Department of Psychology, University of Utah, 380 South 1530 East, Room 502, Salt Lake City, UT 84112, USA. · Huntsman Cancer Institute, 2000 Circle of Hope, Rm 4509, Salt Lake City, UT 84112, USA. · Huntsman Cancer Institute, 2000 Circle of Hope, Rm 4509, Salt Lake City, UT 84112, USA; Department of Communication, University of Utah,255 S Central Campus Drive, Room 2400, Salt Lake City, UT 84112, USA. · Genetic Science Learning Center, University of Utah, 515 100 S, Salt Lake City, UT 84102, USA. · Huntsman Cancer Institute, 2000 Circle of Hope, Rm 4509, Salt Lake City, UT 84112, USA; Department of Dermatology & Knight Cancer Institute, Oregon Health & Science University,3303 SW Bond Avenue, Portland, OR 97239, USA. · Department of Dermatology & Knight Cancer Institute, Oregon Health & Science University,3303 SW Bond Avenue, Portland, OR 97239, USA. ·Patient Educ Couns · Pubmed #29078964.

ABSTRACT: OBJECTIVE: To examine the acceptability of and preliminary effects associated with a novel educational intervention for children at elevated risk for melanoma. The intervention incorporated information on mechanisms through which melanoma preventive behaviors mitigate risk for melanoma and was delivered to parents and children concurrently. METHODS: Twenty-two parents (with a personal history of melanoma or spouse with a history of melanoma) and 33 children (mean age 11.8 years) were asked to complete questionnaires immediately prior to and after an educational session and at a one-month follow-up. RESULTS: Both parents and children endorsed that the educational materials were acceptable. Knowledge about melanoma risk and preventive and screening behaviors increased significantly. Children's perceived risk for melanoma increased significantly, while parents' perceptions of children's risk started at a higher level and remained constant. There were significant increases in reported engagement in sun protective behaviors. CONCLUSION: The educational intervention shows promise in terms of its acceptability and effects on participant knowledge, perceived risk, and engagement in melanoma preventive behaviors. PRACTICE IMPLICATION: Children at elevated risk for melanoma and their parents may benefit from receiving educational information on their disease risk and strategies for prevention and screening.

25 Article SCF-KIT signaling induces endothelin-3 synthesis and secretion: Thereby activates and regulates endothelin-B-receptor for generating temporally- and spatially-precise nitric oxide to modulate SCF- and or KIT-expressing cell functions. 2017

Chen, Lei L / Zhu, Jing / Schumacher, Jonathan / Wei, Chongjuan / Ramdas, Latha / Prieto, Victor G / Jimenez, Arnie / Velasco, Marco A / Tripp, Sheryl R / Andtbacka, Robert H I / Gouw, Launce / Rodgers, George M / Zhang, Liansheng / Chan, Benjamin K / Cassidy, Pamela B / Benjamin, Robert S / Leachman, Sancy A / Frazier, Marsha L. ·Department of Sarcoma, University of Texas M D Anderson Cancer Center, Houston, Texas, United States of America. · Department of Epidemiology, University of Texas M D Anderson Cancer Center, Houston, Texas, United States of America. · ARUP Laboratories, Salt Lake City, Utah, United States of America. · Research Information Services & Technology, University of Texas M D Anderson Cancer Center, Houston, Texas, United States of America. · Pathology, University of Texas M D Anderson Cancer Center, Houston, Texas, United States of America. · Vel-Lab Research, Missouri City, Texas, United States of America. · Department of Surgery, University of Utah, Salt Lake City, Utah, United States of America. · Department of Internal Medicine, University of Utah, Salt Lake City, Utah, United States of America. · Department of Hematology & Oncology, The Second Hospital of Lanzhou University, Lanzhou, Gansu, P. R. China. · Department of Biology, University of Utah, Salt Lake City, Utah, United States of America. · Department of Dermatology, University of Utah, Salt Lake City, Utah, United States of America. · Graduate School of Biomedical Sciences, University of Texas M D Anderson Cancer Center, Houston, Texas, United States of America. ·PLoS One · Pubmed #28880927.

ABSTRACT: We demonstrate that SCF-KIT signaling induces synthesis and secretion of endothelin-3 (ET3) in human umbilical vein endothelial cells and melanoma cells in vitro, gastrointestinal stromal tumors, human sun-exposed skin, and myenteric plexus of human colon post-fasting in vivo. This is the first report of a physiological mechanism of ET3 induction. Integrating our finding with supporting data from literature leads us to discover a previously unreported pathway of nitric oxide (NO) generation derived from physiological endothelial NO synthase (eNOS) or neuronal NOS (nNOS) activation (referred to as the KIT-ET3-NO pathway). It involves: (1) SCF-expressing cells communicate with neighboring KIT-expressing cells directly or indirectly (cleaved soluble SCF). (2) SCF-KIT signaling induces timely local ET3 synthesis and secretion. (3) ET3 binds to ETBR on both sides of intercellular space. (4) ET3-binding-initiated-ETBR activation increases cytosolic Ca2+, activates cell-specific eNOS or nNOS. (5) Temporally- and spatially-precise NO generation. NO diffuses into neighboring cells, thus acts in both SCF- and KIT-expressing cells. (6) NO modulates diverse cell-specific functions by NO/cGMP pathway, controlling transcriptional factors, or other mechanisms. We demonstrate the critical physiological role of the KIT-ET3-NO pathway in fulfilling high demand (exceeding basal level) of endothelium-dependent NO generation for coping with atherosclerosis, pregnancy, and aging. The KIT-ET3-NO pathway most likely also play critical roles in other cell functions that involve dual requirement of SCF-KIT signaling and NO. New strategies (e.g. enhancing the KIT-ET3-NO pathway) to harness the benefit of endogenous eNOS and nNOS activation and precise NO generation for correcting pathophysiology and restoring functions warrant investigation.

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