Dermatology Commons^™

Treatment Of Lipomas And Diffuse Lipomatosis With Ndyag 1064 Nm Laser And Their Impact On The Quality Of Life, Valeriu Ardeleanu, Liliana Florina Andronache, Florentina Gherghiceanu, Stana Paunica, Cristian Balalau, Anca Pantea Stoian

Journal of Mind and Medical Sciences

Lipomas, the most common type of benign tumours, are generally developed from adipose tissue and present an incidence of 2.1 per 1000 inhabitants. In addition to lipomas, at least three other maladies of the adipose tissue lead patients to consult a doctor, especially for aesthetic purposes: multiple familial lipomatosis, diffuse congenital lipomatosis, and adiposa doloris. Unlike lipomas, these maladies are characterized by numerous lipomas, encapsulated or not, of different sizes, symmetrical or not, which may appear in the neck, limbs, or the trunk, sometimes being painful. The life quality of these patients is affected, not only from an aesthetic point …

The Effect Of A Sun Damage Simulation Photography App On The Skin-Protective Behavior Intentions Of Women With Children Age 18 Or Younger, James Bowlds

DNP Projects

Abstract

Background: Skin cancer is the most common form of cancer diagnosed in the U.S. annually, despite being a largely preventable disease through the limitation of ultraviolet radiation exposure. Attempts to decrease its incidence have focused on appearance-based interventions. These have been effective at improving sun-protective behaviors among various subpopulations including people of color. Anecdotal observations suggest mothers more frequently utilize sun protection for their children than on themselves.

Purpose: The purpose of this project was to gain an understanding of the sun protection practices and beliefs of Caucasian and African American mothers, to assess the response to an appearance-based …

Treatment Of Basal Cell Carcinoma With Vismodegib, Sunitha Johns, Katlyn Brown, Emily Loudermilk, Crystal Zheng, Anh Dao Le, Sophocles Chrissobolis

Pharmacy and Wellness Review

The most prevalent nonmelanoma skin cancers are basal cell carcinoma (BCC) and locally advanced basal cell carcinoma (aBCC). Current, effective first-line treatments for BCC aim to remove and destroy cancerous skin cells through excision surgery, Mohs surgery, radiation therapy and cryotherapy, while treatment of aBCC remains limited. An emerging treatment option for aBCC that promotes tumor size reduction is vismodegib, a pharmaceutical product approved in 2012 by the U.S. Food and Drug Administration (FDA). Vismodegib was approved for the treatment of aBCC, metastasized HCC (mBCC) or recurrent BCC after surgery as well as for use in adults who are not …

Trametinib And Dabrafenib: New Agents For Advanced Stage Melanoma, Kelsey Weisenburger, Kevin Krivanek, Armond Cosiano, Kasie Bellmann, Mark E. Olah

Pharmacy and Wellness Review

Melanoma, the deadliest form of skin cancer, is caused primarily by exposure to ultraviolet radiation. Tumor formation occurs early in disease progression and can easily metastasize. The development of the disease can be described by one of four stages, characterized by tumor size and risk of spreading. The B-rafprotein plays an important role in cell proliferation and has the ability to develop a mutation for continuous activation, resulting in uncontrolled cell growth. Sixty percent of melanomas possess a V600E mutation in the BRAF gene. Recently, drug developers have turned the focus of melanoma treatments toward preventing the activation of the …

Pigmented Melanoma Cell Migration Study On Murine Syngeneic B16f10 Melanoma Cells Or Tissue Transplantation Models, Maria-Cristina Predoi, Ion Mîndrilă, Sandra Alice Buteică, Ovidiu Marcel Mărginean, Bogdan Mîndrilă, Mihaela Niculescu

Journal of Mind and Medical Sciences

Melanoma is a lethal form of skin cancer with poor prognosis, especially due to the early metastatic feature. Recent studies have shown that the melanin pigment influences the nanomechanical properties and, therefore, the metastatic behavior of the melanoma cells. We aimed to study the growth of subcutaneously transplanted syngeneic melanoma tissue in female C57BL/6 mice harvested from a mouse with a four-week B16F10 melanoma. Also, we studied the effect of the melanin pigment loading on the peritumoral migratory abilities of melanoma cells. Even when the syngeneic transplant was different (cultured cells vs. tumor tissue), the morphological features and the tumor …

Relating The Gut Metagenome And Metatranscriptome To Immunotherapy Responses In Melanoma Patients., Brandilyn A. Peters, Melissa Wilson, Una Moran, Anna Pavlick, Allison Izsak, Todd Wechter, Jeffrey S. Weber, Iman Osman, Jiyoung Ahn

Department of Medical Oncology Faculty Papers

BACKGROUND: Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community.

METHODS: In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression.

RESULTS: Higher …

Slc36a1-Mtorc1 Signaling Drives Acquired Resistance To Cdk4/6 Inhibitors., Akihiro Yoshida, Yiwen Bu, Shuo Qie, John Wrangle, E. Ramsay Camp, E. Starr Hazard, Gary Hardiman, Renée De Leeuw, Karen E. Knudsen, J. Alan Diehl

Department of Cancer Biology Faculty Papers

The cyclin-dependent kinase 4/6 (CDK4/6) kinase is dysregulated in melanoma, highlighting it as a potential therapeutic target. CDK4/6 inhibitors are being evaluated in trials for melanoma and additional cancers. While beneficial, resistance to therapy is a concern, and the molecular mechanisms of such resistance remain undefined. We demonstrate that reactivation of mammalian target of rapamycin 1 (mTORC1) signaling through increased expression of the amino acid transporter, solute carrier family 36 member 1 (SLC36A1), drives resistance to CDK4/6 inhibitors. Increased expression of SLC36A1 reflects two distinct mechanisms: (i) Rb loss, which drives SLC36A1 via reduced suppression of E2f; (ii) fragile X …

Guidance Of Sentinel Lymph Node Biopsy Decisions In Patients With T1-T2 Melanoma Using Gene Expression Profiling., John T. Vetto, Eddy C. Hsueh, Brian R. Gastman, Larry D. Dillon, Federico A. Monzon, Robert W. Cook, Jennifer Keller, Xin Huang, Andrew Fleming, Preston Hewgley, Pedram Gerami, Sancy Leachman, Jeffrey D. Wayne, Adam C. Berger, Martin D. Fleming

Department of Surgery Faculty Papers

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity?

PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted <5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively.

RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors.

CONCLUSION: The 31-gene expression profile test identifies patients …

High Density Of Tumor-Associated Macrophage Staining Correlates With Poor Clinicopathologic Markers In Head And Neck Squamous Cell Carcinoma: A Meta-Analysis, Alexander Knops, Ba, Ayan Kumar, Bs, Brian Swendseid, Md, Ubaldo E. Martinez-Outshoorn, Md, Larry Harshyne, Phd, Nancy Philp, Phd, Ulrich Rodeck, Md, Phd, Christopher Snyder, Adam Luginbuhl, Md, David Cognetti, Md, Jennifer Johnson, Md, Joseph Curry, Md

Phase 1

Background: Head and neck squamous cell carcinoma (HNSCC) develops within a complex cellular microenvironment that promotes tumor growth, but also represents many potential therapeutic targets. Macrophage presence within that environment has been implicated in the growth, aggression, and persistence of HNSCC. Current literature reports variable degrees of association between tumor-associated macrophage (TAMs) density and clinicopathologic markers of disease.Inconsistent findings may result from grouping of TAM subtypes, which include both M1 (pro-inflammatory) and M2 (immunosuppressive). Our aim is to define the prognostic significance of the phenotypes of tumor-associated macrophages in HNSCC.

Methods: We conducted a meta-analysis of the existing publications investigating …

Metformin Clinical Trial In Hpv+ And Hpv- Head And Neck Squamous Cell Carcinoma: Impact On Cancer Cell Apoptosis And Immune Infiltrate., Joseph M. Curry, Jennifer Johnson, Mehri Mollaee, Patrick Tassone, Dev Amin, Alexander Knops, Diana Whitaker Menezes, My Mahoney, Andrew P. South, Ulrich Rodeck, Tingting Zhan, Larry A. Harshyne, Nancy Philp, Adam J. Luginbuhl, David Cognetti, Madalina Tuluc, Ubaldo E. Martinez-Outshoorn, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Metformin, an oral anti-hyperglycemic drug which inhibits mitochondrial complex I and oxidative phosphorylation has been reported to correlate with improved outcomes in head and neck squamous cell carcinoma (HNSCC) and other cancers. This effect is postulated to occur through disruption of tumor-driven metabolic and immune dysregulation in the tumor microenvironment (TME). We report new findings on the impact of metformin on the tumor and immune elements of the TME from a clinical trial of metformin in HNSCC. Methods: Human papilloma virus-(HPV-) tobacco+ mucosal HNSCC samples (n = 12) were compared to HPV+ oropharyngeal squamous cell carcinoma (OPSCC) samples (n …

Biological Therapy In The Treatment Of Melanoma, Simona Roxana Georgescu, Mihaela Roxana Ioghen, Maria Isabela Sarbu, Alexandra-Florentina Ion, Ela Ghita, Cristina-Iulia Mitran, Madalina-Irina Mitran, Vasile Benea, Mircea Tampa

Journal of Mind and Medical Sciences

Melanoma is one of the most aggressive tumors and its incidence is on the rise. The low rates of survival in metastatic melanoma has led to the development of new drugs for this type of patient, such as biological therapy which has shown remarkable results. This therapy is based on stimulation of the immune system to fight tumoral cells through: injection of cytokines with immunomodulatory properties (interleukin-2, alpha-interferon), vaccination with tumor antigens or immune cells that process tumor antigens, adoptive immunotherapy, inhibition of immune checkpoints (PD-1, CTLA-4), inhibition or stimulation of immune modulator molecules (OX-40, LAG-3), inhibition of signaling pathways …

A Preexisting Rare Pik3ca E545k Subpopulation Confers Clinical Resistance To Mek Plus Cdk4/6 Inhibition In Nras Melanoma And Is Dependent On S6k1 Signaling, Gabriele Romano, Pei-Ling Chen, Ping Song, Jennifer L. Mcquade, Roger J. Liang, Mingguang Liu, Whijae Roh, Dzifa Y. Duose, Fernando C.L. Carapeto, Jun Li, Jessica L.F. Teh, Andrew A. Aplin, Merry Chen, Jianhua Zhang, Alexander J. Lazar, Michael A. Davies, P. Andrew Futreal, Rodabe N. Amaria, David Y. Zhang, Jennifer A. Wargo, Lawrence N. Kwong

Department of Cancer Biology Faculty Papers

Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS- mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA ^E545K mutation as conferring drug resistance. We demonstrate that PIK3CA ^E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA ^E545K being nonuniformly distributed. This resistant population rapidly expanded after the initiation of MEKi + CDK4i therapy and …

Optimizing Vaccine Immunotherapy For Prostate Cancer, G. Hattier, E. K. Bongiorno, C. Portocarrero, Trevor R. Baybutt, Adam E. Snook, U. Rodeck

Sigma Xi Student Research Day

Introduction: Treatment options for metastatic prostate cancer are limited and cures are rare. In other cancers immunotherapy has shown remarkable efficacy in certain patient subsets particularly when combined with other treatment modalities. Our previous work showed that combining radiation and vaccine therapy slows the growth of syngeneic prostate cancer in mice more effectively than single modality treatment arms. Here we tested the hypothesis that addition of immune checkpoint inhibitors targeting the PD1/PD-L1 axis further improves efficacy of the dual radiation/vaccine treatment.

Methods: Mice were injected with tumor cells expressing human prostate specific antigen (TPSA-23). The mice were divided into six …

Randomized Phase Ii Trial Of Autologous Dendritic Cell Vaccines Versus Autologous Tumor Cell Vaccines In Metastatic Melanoma: 5-Year Follow Up And Additional Analyses., Robert O. Dillman, Andrew N Cornforth, Gabriel I Nistor, Edward F Mcclay, Thomas T Amatruda, Carol Depriest

Articles, Abstracts, and Reports

BACKGROUND: Despite improved survival following checkpoint inhibitors, there is still a potential role for anti-cancer therapeutic vaccines. Because of biological heterogeneity and neoantigens resulting from each patient's mutanome, autologous tumor may be the best source of tumor-associated antigens (TAA) for vaccines. Ex vivo loading of autologous dendritic cells with TAA may be associated with superior clinical outcome compared to injecting irradiated autologous tumor cells. We conducted a randomized phase II trial to compare autologous tumor cell vaccines (TCV) and autologous dendritic cell vaccines (DCV) loaded with autologous TAA.

METHODS: Short-term autologous tumor cell lines were established from metastatic tumor. Vaccines …

A Comprehensive Patient-Derived Xenograft Collection Representing The Heterogeneity Of Melanoma., Clemens Krepler, Katrin Sproesser, Patricia Brafford, Marilda Beqiri, Bradley Garman, Min Xiao, Batool Shannan, Andrea Watters, Michela Perego, Gao Zhang, Adina Vultur, Xiangfan Yin, Qin Liu, Ioannis N Anastopoulos, Bradley Wubbenhorst, Melissa A. Wilson, Wei Xu, Giorgos Karakousis, Michael Feldman, Xiaowei Xu, Ravi Amaravadi, Tara C. Gangadhar, David E. Elder, Lauren E. Haydu, Jennifer A. Wargo, Michael A. Davies, Yiling Lu, Gordon B. Mills, Dennie T. Frederick, Michal Barzily-Rokni, Keith T. Flaherty, Dave S. Hoon, Michael Guarino, Joseph J. Bennett, Randall W. Ryan, Nicholas J. Petrelli, Carol L. Shields, Mizue Terai, Takami Sato, Andrew E. Aplin, Alexander Roesch, David Darr, Steve Angus, Rakesh Kumar, Ensar Halilovic, Giordano Caponigro, Sebastien Jeay, Jens Wuerthner, Annette Walter, Matthias Ocker, Matthew B. Boxer, Lynn Schuchter, Katherine L Nathanson, Meenhard Herlyn

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint …

Predictors Of Responses To Immune Checkpoint Blockade In Advanced Melanoma., N Jacquelot, M P Roberti, D P Enot, S Rusakiewicz, N Ternès, S Jegou, D M Woods, A L Sodré, M Hansen, Y Meirow, M Sade-Feldman, A Burra, S S Kwek, C Flament, M Messaoudene, C P M Duong, L Chen, B S Kwon, A C Anderson, V K Kuchroo, B Weide, F Aubin, C Borg, S Dalle, O Beatrix, M Ayyoub, B Balme, G Tomasic, A M Di Giacomo, M Maio, D Schadendorf, I Melero, B Dréno, A Khammari, R Dummer, M Levesque, Yoshinobu Koguchi, L Fong, M Lotem, M Baniyash, H Schmidt, I M Svane, G Kroemer, A Marabelle, S Michiels, A Cavalcanti, M J Smyth, J S Weber, A M Eggermont, L Zitvogel

Articles, Abstracts, and Reports

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, …

The Prognostic Importance Of Scalp Location In Primary Head And Neck Melanoma., Junko Ozao-Choy, Daniel W Nelson, Jason Hiles, Stacey L Stern, Jeong Lim Yoon, Myung Shin Sim, Mark Faries

Articles, Abstracts, and Reports

BACKGROUND AND OBJECTIVES: For patients with cutaneous melanoma, primary tumors located in the head and neck is associated with poor outcomes. The reason for this difference and whether it is applicable to all locations within the head and neck remains unclear. We hypothesized that scalp melanoma is uniquely distinguished from other anatomic sites and is independently responsible for the poor prognosis of head and neck melanoma.

METHODS: Query and analysis of a prospectively maintained melanoma database of all patients treated for primary cutaneous melanoma from 1971 to 2010.

RESULTS: Of 11 384 patients identified, 7% (n = 799) of lesions …

Impact Of Time Between Diagnosis And Slnb On Outcomes In Cutaneous Melanoma., Daniel W Nelson, Stacey Stern, David E Elashoff, Robert Elashoff, John F Thompson, Nicola Mozzillo, Omgo E Nieweg, Harald J Hoekstra, Alistair J Cochran, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Hypothetically, delay between melanoma diagnosis and SLNB could affect outcomes, either adversely by allowing growth and dissemination of metastases, or beneficially by allowing development of an anti-melanoma immune response. Available data are conflicting about the effect of SLNB delay on patient survival. Our objective was to determine whether delay between initial diagnosis and SLNB affects outcomes in patients with cutaneous melanoma.

STUDY DESIGN: We performed query and analysis of a large prospectively maintained database of patients with primary cutaneous melanomas undergoing SLNB. An independent dataset from MSLT-1 (Multicenter Selective Lymphadenectomy Trial-1) was used for validation. Primary outcomes included disease-free …

Is Pregnancy-Associated Melanoma Associated With Adverse Outcomes?, Maris S Jones, Jihey Lee, Stacey L Stern, Mark Faries

Articles, Abstracts, and Reports

BACKGROUND: Melanoma is the most common malignancy encountered during pregnancy. Conflicting data have led to ongoing confusion regarding pregnancy-associated melanoma (PAM) in the media and among the public. The objective of this study was to better characterize both the clinical presentation of PAM and its prognostic implications.

STUDY DESIGN: Female patients of reproductive age, with stage 0 to IV cutaneous melanoma, were identified from our prospectively maintained database. Clinical and histopathologic factors were analyzed with appropriate statistical methods. Univariable and then multivariable analysis were used on matched data to compare disease-free survival (DFS), overall survival (OS), and melanoma-specific survival (MSS) …

Divergence Of Camp Signalling Pathways Mediating Augmented Nucleotide Excision Repair And Pigment Induction In Melanocytes, Erin M. Wolf Horrell, Stuart G. Jarrett, Katharine M. Carter, John A. D'Orazio

Markey Cancer Center Faculty Publications

Loss‐of‐function melanocortin 1 receptor (MC1R) polymorphisms are common in UV‐sensitive fair‐skinned individuals and are associated with blunted cAMP second messenger signalling and higher lifetime risk of melanoma because of diminished ability of melanocytes to cope with UV damage. cAMP signalling positions melanocytes to resist UV injury by upregulating synthesis of UV‐blocking eumelanin pigment and by enhancing the repair of UV‐induced DNA damage. cAMP enhances melanocyte nucleotide excision repair (NER), the genome maintenance pathway responsible for the removal of mutagenic UV photolesions, through cAMP‐activated protein kinase (protein kinase A)‐mediated phosphorylation of the ataxia telangiectasia‐mutated and Rad3‐related (ATR) protein on the S435 …

Pathologists' Diagnosis Of Invasive Melanoma And Melanocytic Proliferations: Observer Accuracy And Reproducibility Study., Joann G Elmore, Raymond L Barnhill, David E Elder, Gary M Longton, Margaret S Pepe, Lisa M Reisch, Patricia A Carney, Linda J Titus, Heidi D Nelson, Tracy Onega, Anna N A Tosteson, Martin A Weinstock, Stevan R Knezevich, Michael W Piepkorn

Articles, Abstracts, and Reports

No abstract provided.

Inhibition Of Age-Related Therapy Resistance In Melanoma By Rosiglitazone-Mediated Induction Of Klotho., Reeti Behera, Amanpreet Kaur, Marie R. Webster, Suyeon Kim, Abibatou Ndoye, Curtis H. Kugel, Gretchen M. Alicea, Joshua Wang, Kanad Ghosh, Phil Cheng, Sofia Lisanti, Katie Marchbank, Vanessa Dang, Mitchell Levesque, Reinhard Dummer, Xiaowei Xu, Meenhard Herlyn, Andrew E. Aplin, Alexander Roesch, Cecilia Caino, Dario C. Altieri, Ashani T. Weeraratna

Department of Cancer Biology Faculty Papers

Purpose: Aging is a poor prognostic factor for melanoma. We have shown that melanoma cells in an aged microenvironment are more resistant to targeted therapy than identical cells in a young microenvironment. This is dependent on age-related secreted factors. Klotho is an age-related protein whose serum levels decrease dramatically by age 40. Most studies on klotho in cancer have focused on the expression of klotho in the tumor cell. We have shown that exogenous klotho inhibits internalization and signaling of Wnt5A, which drives melanoma metastasis and resistance to targeted therapy. We investigate here whether increasing klotho in the aged microenvironment …

Completion Dissection Or Observation For Sentinel-Node Metastasis In Melanoma., Mark Faries, John F Thompson, Alistair J Cochran, Robert H Andtbacka, Nicola Mozzillo, Jonathan S Zager, Tiina Jahkola, Tawnya L Bowles, Alessandro Testori, Peter D Beitsch, Harald J Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W J M Wouters, Michael S Sabel, Edward A Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R Rossi, Rogerio I Neves, Steven D Trocha, Frances Wright, David R Byrd, Maurice Matter, Eddy Hsueh, Alastair Mackenzie-Ross, Douglas B Johnson, Patrick Terheyden, Adam C Berger, Tara L Huston, Jeffrey D Wayne, B Mark Smithers, Heather B Neuman, Schlomo Schneebaum, Jeffrey E Gershenwald, Charlotte E Ariyan, Darius C Desai, Lisa Jacobs, Kelly M Mcmasters, Anja Gesierich, Peter Hersey, Steven D Bines, John M Kane, Richard J Barth, Gregory Mckinnon, Jeffrey M Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A Hoefer, James M Lewis, Randall Scheri, Mark C Kelley, Omgo E Nieweg, R Dirk Noyes, Dave S B Hoon, He-Jing Wang, David A Elashoff, Robert M Elashoff

Articles, Abstracts, and Reports

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear.

METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis.

RESULTS: Immediate completion …

The Skin Cancer Health Crisis And Recommended Intervention Methods, Blaire Brooks

Senior Theses

Despite the increasing research connecting UVR exposures to skin cancer, rates of skin cancer are rising. Skin cancer is now the most common form of cancer and there are significant health care costs associated with treating the cases (Balk et al., 2013). As a result, the United States needs greater initiatives to increase educational programs, physician counseling, and political action regarding ultraviolet exposure and incidence of skin cancer. Evaluation of the types of skin cancer, perceptions of tanning, and current regulations and recommendations are required in order to form the initiatives to combat the growth of skin cancer.

Systematic Analysis Of Whole Exome Sequencing Determines Ret G691s Polymorphism As Germline Variant In Melanoma, Brent J. Smith Jr, Jennifer D. Hintzsche, Carol M. Amato, Aik-Choon Tan, Keith R. Wells, Allison J. Applegate, Rita T. Gonzalez, Jodie R. Barr, William A. Robinson

Marshall Journal of Medicine

Abstract

The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by glial cell derived neutrotrophic factor (GDNF). Previous studies have found that a single nucleotide polymorphism (SNP), RETp (G691S), in the juxtamembrane domain enhances the signaling pathway and promotes tumor growth by GDNF in pancreatic and thyroid cancer in addition to melanoma. It is uncertain however whether this SNP is a germline variant or somatic mutation. A prior study reported that the RETp variant was a germline SNP in desmoplastic and non-desmoplastic melanomas. In the present study, we examined both melanoma tissue samples and matching peripheral blood DNA …

Thin Melanoma With Nodal Involvement: Analysis Of Demographic, Pathologic, And Treatment Factors With Regard To Prognosis., Giorgos Karakousis, Phyllis A Gimotty, Edmund K Bartlett, Myung-Shin Sim, Madalyn G Neuwirth, Douglas Fraker, Brian J Czerniecki, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Although only a small proportion of thin melanomas result in lymph node metastasis, the abundance of these lesions results in a relatively large absolute number of patients with a diagnosis of nodal metastases, determined by either sentinel lymph node (SLN) biopsy or clinical nodal recurrence (CNR).

METHODS: Independent cohorts with thin melanoma and either SLN metastasis or CNR were identified at two melanoma referral centers. At both centers, SLN metastasis patients were included. At center 1, the CNR cohort included patients with initial negative clinical nodal evaluation followed by CNR. At center 2, the CNR cohort was restricted to …

Atr Mutations Promote The Growth Of Melanoma Tumors By Modulating The Immune Microenvironment., Chi-Fen Chen, Rolando Ruiz-Vega, Priya Vasudeva, Francisco Espitia, Tatiana B Krasieva, Sebastien De Feraudy, Bruce J Tromberg, Sharon Huang, Chad P Garner, Jie Wu, Dave S B Hoon, Anand K Ganesan

Articles, Abstracts, and Reports

Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet somehow suppress the immune response to facilitate continued growth. In this study, we identify a subset of human melanomas that have loss-of-function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA damage and is required for cellular proliferation. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T cell recruitment and increased recruitment of macrophages known to spur tumor invasion. Taken together, these studies identify a mechanism by which melanoma cells modulate the immune …

The Influence Of Tumor Regression, Solar Elastosis, And Patient Age On Pathologists' Interpretation Of Melanocytic Skin Lesions., Linda Titus, Raymond L Barnhill, Jason P Lott, Michael W Piepkorn, David E Elder, Paul D Frederick, Heidi D Nelson, Patricia A Carney, Stevan R Knezevich, Martin A Weinstock, Joann G Elmore

Articles, Abstracts, and Reports

It is not known whether patient age or tumor characteristics such as tumor regression or solar elastosis influence pathologists' interpretation of melanocytic skin lesions (MSLs). We undertook a study to determine the influence of these factors, and to explore pathologist's characteristics associated with the direction of diagnosis. To meet our objective, we designed a cross-sectional survey study of pathologists' clinical practices and perceptions. Pathologists were recruited from diverse practices in 10 states in the United States. We enrolled 207 pathologist participants whose practice included the interpretation of MSLs. Our findings indicated that the majority of pathologists (54.6%) were influenced toward …

Ladarixin, A Dual Cxcr1/2 Inhibitor, Attenuates Experimental Melanomas Harboring Different Molecular Defects By Affecting Malignant Cells And Tumor Microenvironment., Daria Marley Kemp, Alyson Pidich, Mary Larijani, Rebecca Jonas, Elizabeth Lash, Takami Sato, Mizue Terai, Maria De Pizzol, Marcello Allegretti, Olga Igoucheva, Vitali Alexeev

Department of Dermatology and Cutaneous Biology Faculty Papers

CXCR1 and CXCR2 chemokine receptors and their ligands (CXCL1/2/3/7/8) play an important role in tumor progression. Tested to date CXCR1/2 antagonists and chemokine-targeted antibodies were reported to affect malignant cells in vitro and in animal models. Yet, redundancy of chemotactic signals and toxicity hinder further clinical development of these approaches. In this pre-clinical study we investigated the capacity of a novel small molecule dual CXCR1/2 inhibitor, Ladarixin (LDX), to attenuate progression of experimental human melanomas. Our data showed that LDX-mediated inhibition of CXCR1/2 abrogated motility and induced apoptosis in cultured cutaneous and uveal melanoma cells and xenografts independently of the …

Insights Into Local Tumor Microenvironment Immune Factors Associated With Regression Of Cutaneous Melanoma Metastases By, Junbao Yang, Maris S Jones, Romela Irene Ramos, Alfred A Chan, Agnes F Lee, Leland J Foshag, Peter A Sieling, Mark Faries, Delphine J Lee

Articles, Abstracts, and Reports

No abstract provided.