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https://www.readbyqxmd.com/read/28648699/prognostic-factors-and-outcomes-in-metastatic-uveal-melanoma-treated-with-programmed-cell-death-1-or-combined-pd-1-cytotoxic-t-lymphocyte-antigen-4-inhibition
#1
Markus V Heppt, Lucie Heinzerling, Katharina C Kähler, Andrea Forschner, Michael C Kirchberger, Carmen Loquai, Markus Meissner, Friedegund Meier, Patrick Terheyden, Beatrice Schell, Rudolf Herbst, Daniela Göppner, Felix Kiecker, David Rafei-Shamsabadi, Sebastian Haferkamp, Margit A Huber, Jochen Utikal, Mirjana Ziemer, Irmgard Bumeder, Christiane Pfeiffer, Susanne G Schäd, Christoph Schmid-Tannwald, Julia K Tietze, Thomas K Eigentler, Carola Berking
BACKGROUND: Uveal melanoma (UM) is an ocular malignancy with high potential for metastatic spread. In contrast to cutaneous melanoma, immunotherapy has not yet shown convincing efficacy in patients with UM. Combined immune checkpoint blockade with checkpoint programmed cell death-1 (PD-1) and checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibition has not been systematically assessed for UM to date. PATIENTS AND METHODS: Patients with metastatic UM treated with either PD-1 inhibitor monotherapy or combined PD-1 inhibitor and ipilimumab (an anti-CTLA-4 monoclonal antibody) were included from 20 German skin cancer centres...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28648515/-history-of-cutaneous-melanoma-from-laennec-s-melanosis-to-the-end-of-20th-century
#2
J Chevallier
No abstract text is available yet for this article.
June 22, 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/28647616/photodynamic-therapy-in-dermatology-beyond-non-melanoma-cancer-an-update
#3
REVIEW
Xiang Wen, Yong Li, Michael R Hamblin
Photodynamic therapy (PDT) employs a photosensitizer (PS) and visible light in the presence of oxygen, leading to production of cytotoxic reactive oxygen species, which can damage the cellular organelles and cause cell death. In dermatology PDT has usually taken the form of topical application of a precursor in the heme biosynthesis pathway, called 5-aminolevulinic acid (or its methyl ester), so that an active PS, protoporphyrin IX accumulates in the skin. As PDT enhances dermal remodeling and resolves chronic inflamation, it has been used to treat cutaneous disorders include actinic keratoses, acne, viral warts, skin rejuvenation, psoriasis, localized scleroderma, some non-melanoma skin cancers and port-wine stains...
June 21, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28646613/novel-tmc8-splice-site-mutation-in-epidermodysplasia-verruciformis-and-review-of-hpv-infections-in-patients-with-the-disease
#4
E Imahorn, Z Yüksel, I Spoerri, G Gürel, C Imhof, Z N Saraçoğlu, A E Koku Aksu, P L Rady, S K Tyring, W Kempf, P H Itin, B Burger
BACKGROUND: Epidermodysplasia verruciformis (EV) is a genodermatosis leading to infections with cutaneous HPV, persistent plane warts and a high rate of non-melanoma skin cancer (NMSC). Biallelic loss-of-function mutations in TMC6 and TMC8 are known to be causative. OBJECTIVE: The aim of this study was to report EV-causing mutations in four patients with EV and to give an overview of all described EV patients. PATIENTS AND METHODS: We investigated four patients with classical features of EV from two families...
June 24, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28645859/discovery-of-a-novel-pan-raf-inhibitor-with-potent-anti-tumor-activity-in-preclinical-models-of-braf-v600e-mutant-cancer
#5
Sung Pyo Hong, Soon Kil Ahn
AIMS: BRAF mutations, especially BRAF V600E, are a frequent occurrence in malignant melanomas. The BRAF inhibitors are used as the care standard for BRAF-mutant metastatic melanomas. However, melanomas rapidly develop resistance to BRAF inhibitors after a median response duration of 6months, and the subsequent rapid development of cutaneous toxicity is enhanced by the paradoxical activation of CRAF. In this study, we discovered a potent and selective pan-RAF inhibitor: INU-152. The goal of this study was to investigate whether the inhibition of pan-RAF with INU-152 completely disrupts the MAPK pathway in cancer cells bearing BRAF or RAS mutations...
June 20, 2017: Life Sciences
https://www.readbyqxmd.com/read/28642816/safe-and-effective-administration-of-t-vec-in-a-patient-with-heart-transplantation-and-recurrent-locally-advanced-melanoma
#6
Gustavo Schvartsman, Kristen Perez, Jill E Flynn, Jeffrey N Myers, Hussein Tawbi
BACKGROUND: Immunotherapy plays a key role in the treatment of metastatic melanoma. Patients with autoimmune conditions and/or on immunosuppressive therapy due to orthotropic transplants, however, are systematically excluded from clinical trials. Talimogene laherparepvec (T-VEC) is the first oncolytic virus to be approved by the FDA for cancer therapy. To our knowledge, this is the first report of T-VEC being administered in the setting of an organ transplant recipient. CASE PRESENTATION: Here we present the case of a patient with recurrent locally advanced cutaneous melanoma receiving salvage T-VEC therapy in the setting of orthotropic heart transplantation...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28642245/a-reporter-mouse-model-for-in-vivo-tracing-and-in-vitro-molecular-studies-of-melanocytic-lineage-cells-and-their-diseases
#7
Melissa Crawford, Valerie Leclerc, Lina Dagnino
Alterations in melanocytic lineage cells give rise to a plethora of distinct human diseases, including neurocristopathies, cutaneous pigmentation disorders, loss of vision and hearing, as well as melanoma. Understanding the ontogeny and biology of melanocytic cells, as well as how they interact with their surrounding environment, are key steps in the development of therapies for diseases that involve this cell lineage. Efforts to culture and characterize primary melanocytes from normal or genetically engineered mouse models have at times yielded contrasting observations...
June 22, 2017: Biology Open
https://www.readbyqxmd.com/read/28640877/identification-of-c-ebp%C3%AE-as-a-novel-target-of-the-hpv8-e6-protein-regulating-mir-203-in-human-keratinocytes
#8
Anna M Marthaler, Marta Podgorska, Pascal Feld, Alina Fingerle, Katrin Knerr-Rupp, Friedrich Grässer, Hans Smola, Klaus Roemer, Elke Ebert, Yoo-Jin Kim, Rainer M Bohle, Cornelia S L Müller, Jörg Reichrath, Thomas Vogt, Magdalena Malejczyk, Sławomir Majewski, Sigrun Smola
Patients suffering from Epidermodysplasia verruciformis (EV), a rare inherited skin disease, display a particular susceptibility to persistent infection with cutaneous genus beta-human papillomavirus (beta-HPV), such as HPV type 8. They have a high risk to develop non-melanoma skin cancer at sun-exposed sites. In various models evidence is emerging that cutaneous HPV E6 proteins disturb epidermal homeostasis and support carcinogenesis, however, the underlying mechanisms are not fully understood as yet. In this study we demonstrate that microRNA-203 (miR-203), a key regulator of epidermal proliferation and differentiation, is strongly down-regulated in HPV8-positive EV-lesions...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28640512/a-major-responder-to-ipilimumab-and-nivolumab-in-metastatic-uveal-melanoma-with-concomitant-autoimmunity
#9
Pui Ying Chan, Peter Hall, Gordon Hay, Victoria M L Cohen, Peter W Szlosarek
The use of immune checkpoint inhibition has led to major improvements in outcome for patients with metastatic cutaneous melanoma. The combination of ipilimumab and nivolumab has demonstrated greater activity over single agent immunotherapy in phase III trials. Clinical trials of combination CTLA-4 and PD-1 inhibition are underway in uveal melanoma, for which there are currently no data. Here, we present the case of a 74-year-old male patient with metastatic uveal melanoma, who was treated with a combination of ipilimumab and nivolumab...
June 22, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28639409/anti-pd-1-antibodies-in-metastatic-uveal-melanoma-a-treatment-option
#10
Carolin Bender, Alexander Enk, Ralf Gutzmer, Jessica C Hassel
Uveal melanomas (UMs) are a rare form of cancer with clinical and pathological characteristics distinct from cutaneous melanomas. Ipilimumab has shown efficacy and safety in the treatment of metastatic UM. This provides a rationale for treatment with other immune checkpoint inhibitors. This is a retrospective review of 15 patients with metastatic UM treated between June 2014 and February 2016, who received treatment with the anti-PD-1 Abs pembrolizumab or nivolumab. Patients were treated at two German university hospitals...
June 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28637727/a-protocol-for-prospective-studies-of-25-hydroxyvitamin-d-leptin-and-body-mass-index-in-relation-to-cutaneous-melanoma-incidence-and-survival
#11
Jo Steinson Stenehjem, Tom K Grimsrud, Judith R Rees, Linda Vos, Ronnie Babigumira, Marit B Veierød, Trude Eid Robsahm
INTRODUCTION: The incidence and mortality rates of cutaneous melanoma (CM) are increasing among fair-skinned populations worldwide. Ultraviolet radiation (UVR) is the principal risk factor for CM, but is also the main source of 25-hydroxyvitamin D (25(OH)D), which has been associated with reduced risk and better prognosis of some cancer types. However, both low and high 25(OH)D levels have been associated with increased risk of CM. Obesity as measured by body mass index (BMI) is associated with risk of several cancers and has also been suggested as a risk factor for CM, and may also be related to insufficient 25(OH)D and/or high leptin levels...
June 21, 2017: BMJ Open
https://www.readbyqxmd.com/read/28637487/the-nf1-somatic-mutational-landscape-in-sporadic-human-cancers
#12
REVIEW
Charlotte Philpott, Hannah Tovell, Ian M Frayling, David N Cooper, Meena Upadhyaya
BACKGROUND: Neurofibromatosis type 1 (NF1: Online Mendelian Inheritance in Man (OMIM) #162200) is an autosomal dominantly inherited tumour predisposition syndrome. Heritable constitutional mutations in the NF1 gene result in dysregulation of the RAS/MAPK pathway and are causative of NF1. The major known function of the NF1 gene product neurofibromin is to downregulate RAS. NF1 exhibits variable clinical expression and is characterized by benign cutaneous lesions including neurofibromas and café-au-lait macules, as well as a predisposition to various types of malignancy, such as breast cancer and leukaemia...
June 21, 2017: Human Genomics
https://www.readbyqxmd.com/read/28635133/critical-role-of-glioma-associated-oncogene-homolog-1-in-maintaining-invasive-and-mesenchymal-like-properties-of-melanoma-cells
#13
I Ketut Gunarta, Rong Li, Ryota Nakazato, Ryusuke Suzuki, Jambaldorj Boldbaatar, Takeshi Suzuki, Katsuji Yoshioka
Cutaneous melanoma is the most aggressive form of skin cancer. This aggressiveness appears to be due to the cancer cells' ability to reversibly switch between phenotypes with non-invasive and invasive potentials, and microphthalmia-associated transcription factor (MITF) is known to play a central role in this process. The transcription factor glioma-associated oncogene homolog 1 (GLI1) is a component of the canonical and noncanonical sonic hedgehog pathways. Although GLI1 has been suggested to be involved in melanoma progression, its precise role and the mechanism underlying invasion remain unclear...
June 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28635084/primary-tumor-sites-in-relation-to-ultraviolet-radiation-exposure-and-skin-visibility-correlate-with-survival-in-cutaneous-melanoma
#14
Daniela Gordon, Johan Hansson, Sandra Eloranta, Max Gordon, Peter Gillgren, Karin E Smedby
The prognostic value of detailed anatomic site and ultraviolet radiation (UVR) exposure patterns has not been fully determined in cutaneous melanoma. Thus, we reviewed medical records for detailed site in a population-based retrospective Swedish patient cohort diagnosed with primary invasive melanoma 1976 - 2003 (n=5,973). We followed the patients from date of diagnosis until death, emigration or December 31(st) 2013, and evaluated melanoma-specific survival by subsite in a multivariable regression model adjusting for established prognostic factors...
June 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28634549/a-qualitative-study-of-quality-of-life-concerns-following-a-melanoma-diagnosis
#15
Rachel I Vogel, Lori G Strayer, Rehana L Ahmed, Anne Blaes, DeAnn Lazovich
The goal of this study was to identify a relevant and inclusive list of quality of life issues among long-term survivors of melanoma. Individuals diagnosed with stage I-III cutaneous melanoma and had survived 1-5 years, ages 18-65 years at diagnosis, were recruited. Five focus groups were conducted with 33 participants in total. Discussions centered on participants' experiences at diagnosis, as well as ongoing physical, emotional, and social concerns, and behavioral changes since diagnosis. The majority of participants reported shock, fear, and feeling overwhelmed at the time of diagnosis...
2017: Journal of Skin Cancer
https://www.readbyqxmd.com/read/28632148/claw-foot-a-case-report
#16
Alessandro Innocenti, Francesco Ciancio, Cecilia Taverna, Sara Tanini, Aurelio Portincasa, Domenico Parisi, Marco Innocenti, Vincenzo De Giorgi
A cutaneous horn could be defined as a conical projection on the surface of skin made of cornified material and resembling an animal horn. These lesions most commonly affect light-skinned men aged between 50 to 89 years and usually appear in sun exposed areas. Radiation, chronic irritation and even human papilloma virus-2 infection may be precipitating factors. More than half of the cases originate from either malignant or premalignant lesions, therefore the base of the lesion must be carefully examined histologically...
June 8, 2017: Annali Italiani di Chirurgia
https://www.readbyqxmd.com/read/28630054/slc45a2-a-melanoma-antigen-with-high-tumor-selectivity-and-reduced-potential-for-autoimmune-toxicity
#17
Jungsun Park, Amjad H Talukder, Seonah Lim, Kwanghee Kim, Ke Pan, Brenda Melendez, Sherille D Bradley, Kyle Jackson, Jahan S Khalili, Junmei Wang, Caitlin Creasy, Bih-Fang Pan, Scott E Woodman, Chantale Bernatchez, David Hawke, Patrick Hwu, Kyung-Mi Lee, Jason Roszik, Gregory Lizee, Cassian Yee
Cytotoxic T lymphocyte (CTL)-based immunotherapies have had remarkable success at generating objective clinical responses in patients with advanced metastatic melanoma.  Although the melanocyte differentiation antigens (MDAs) MART-1, PMEL, and tyrosinase were among the first melanoma tumor-associated antigens identified and targeted with immunotherapy, expression within normal melanocytes of the eye and inner ear can elicit serious autoimmune side effects, thus limiting their clinical potential as CTL targets...
June 19, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28629629/association-between-lithium-use-and-melanoma-risk-and-mortality-a-population-based-study
#18
Maryam M Asgari, Andy J Chien, Ai Lin Tsai, Bruce Fireman, Charles P Quesenberry
Laboratory studies show lithium, an activator of the Wnt/ß-catenin signaling pathway, slows melanoma progression, but no published epidemiologic studies have explored this association. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n=2,213,848) from 1997-2012 to examine the association between lithium use and melanoma risk. Lithium exposure (n=11,317) was assessed from pharmacy databases, serum lithium levels were obtained from electronic laboratory databases, and incident cutaneous melanomas (n= 14,056) were identified from an established cancer registry...
June 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28628689/aggressive-skin-cancers-occurring-in-patients-treated-with-the-janus-kinase-inhibitor-ruxolitinib
#19
Adam B Blechman, Christine E Cabell, Christine H Weinberger, Anna Duckworth, Justin J Leitenberger, Fiona O Zwald, Mark A Russell
<p>The Food and Drug Administration approved Ruxolitinib in 2011 for the treatment of primary myelofibrosis. Five-year safety data showed a higher incidence of skin cancer in patients treated with Ruxolitinib compared to best available therapy for myelofibrosis. This report presents a series of five patients with history of myelofibrosis treated with Ruxolitinib who subsequently developed numerous skin cancers with aggressive biological behavior. Each patient in this report was treated by a Mohs surgeon affiliated with an academic institution...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28628677/impact-of-a-31-gene-expression-profiling-test-for-cutaneous-melanoma-on-dermatologists-clinical-management-decisions
#20
Aaron S Farberg, Alex M Glazer, Richard White, Darrell S Rigel
<p>Importance: Current guidelines for cutaneous malignant melanoma (CMM) provide general recommendations regarding surveillance while indicating that management should be tailored to patients' individual probability of recurrence. A 31-gene expression profile (31-GEP) test to predict metastatic risk has been previously validated, and classifies patients as either Class 1 (low risk) or Class 2 (high risk).</p> <p>Objective: To determine the impact of the 31-GEP test's result on clinical decision-making...
May 1, 2017: Journal of Drugs in Dermatology: JDD
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