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malignant melanoma prevention

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https://www.readbyqxmd.com/read/28723576/an-atlas-of-human-regulatory-t-helper-like-cells-reveals-features-of-th2-like-tregs-that-support-a-tumorigenic-environment
#1
Leena Halim, Marco Romano, Reuben McGregor, Isabel Correa, Polychronis Pavlidis, Nathali Grageda, Sec-Julie Hoong, Muhammed Yuksel, Wayel Jassem, Rosalind F Hannen, Mark Ong, Olivia Mckinney, Bu'Hussain Hayee, Sophia N Karagiannis, Nicholas Powell, Robert I Lechler, Estefania Nova-Lamperti, Giovanna Lombardi
Regulatory T cells (Tregs) play a pivotal role in maintaining immunological tolerance, but they can also play a detrimental role by preventing antitumor responses. Here, we characterized T helper (Th)-like Treg subsets to further delineate their biological function and tissue distribution, focusing on their possible contribution to disease states. RNA sequencing and functional assays revealed that Th2-like Tregs displayed higher viability and autocrine interleukin-2 (IL-2)-mediated activation than other subsets...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28713672/bap1-a-tumor-suppressor-gene-driving-malignant-mesothelioma
#2
REVIEW
Mitchell Cheung, Joseph R Testa
Like cancer generally, malignant mesothelioma (MM) is a genetic disease at the cellular level. DNA copy number analysis of mesothelioma specimens has revealed a number of recurrent sites of chromosomal loss, including 3p21.1, 9p21.3, and 22q12.2. The key inactivated driver genes located at 9p21.1 and 22q12.2 were discovered two decades ago as being the tumor suppressor loci CDKN2A and NF2, respectively. Only relatively recently was the BAP1 gene determined to be the driver gene at 3p21.1 that is somatically inactivated...
June 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28697174/uv-radiation-promotes-melanoma-dissemination-mediated-by-the-sequential-reaction-axis-of-cathepsins-tgf-%C3%AE-1-fap-%C3%AE
#3
Petra Wäster, Kyriakos Orfanidis, Ida Eriksson, Inger Rosdahl, Oliver Seifert, Karin Öllinger
BACKGROUND: Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-α is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-α is not yet completely revealed. METHODS: Expression of FAP-α was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs...
July 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28692051/transcriptional-regulation-of-ataxia-telangiectasia-and-rad3-related-protein-by-activated-p21-activated-kinase-1-protects-keratinocytes-in-uv-b-induced-premalignant-skin-lesions
#4
S Beesetti, J Mavuluri, R P Surabhi, T M Oberyszyn, K Tober, R S Pitani, L D Joseph, G Venkatraman, S K Rayala
Sun-induced skin lesions, in particular actinic keratosis, are generally considered as premalignant skin lesions that can progress into squamous cell carcinoma (SCC) and invasive SCC if left untreated. Therefore, understanding the molecular mechanisms by which the ultraviolet-B (UV-B)-exposed cells are being protected and the signaling pathways that promote the progression of certain premalignant skin lesions to malignant lesions will permit us to prevent or cure skin cancers. In the current study, we found that phospho-p21-activated kinase-1 (Pak1) and Pak1 expression was high in clinical samples of sunlight-induced premalignant skin lesions assessed by immunohistochemistry...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28680742/modulation-of-mhc-class-i-surface-expression-in-b16f10-melanoma-cells-by-methylseleninic-acid
#5
Claudia Lennicke, Jette Rahn, Jürgen Bukur, Falko Hochgräfe, Ludger A Wessjohann, Rudolf Lichtenfels, Barbara Seliger
The essential trace element selenium (Se) might play a role in cancer prevention as well as for cancer therapy. Its metabolite methylselenol is able to kill cells through distinct mechanisms including induction of reactive oxygen species, DNA damage and apoptosis. Since methylselenol affects innate immune responses by modulating the expression of NKG2D ligands, the aim of this study was to determine whether the methylselenol generating compound methylseleninic acid (MSA) influences the expression of the MHC class I surface antigens and growth properties thereby reverting immune escape...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679300/the-emerging-role-of-immune-checkpoint-based-approaches-in-aml-and-mds
#6
Prajwal Boddu, Hagop Kantarjian, Guillermo Garcia-Manero, James Allison, Padmanee Sharma, Naval Daver
The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases...
July 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28676162/skin-and-composite-grafting-techniques-in-facial-reconstruction-for-skin-cancer
#7
REVIEW
Michael J Brenner, Jeffrey S Moyer
Skin and composite grafting provide effective resurfacing and reconstruction for cutaneous defects after excision of the malignancy. The goal is to restore a natural appearance and function while preventing distortion of the eyelid, nose, or lips. With careful planning and attention to aesthetic subunits, the surgeon can camouflage incisions and avoid blunting aesthetically sensitive sulci. The surgical plan is also informed by the pathology, as basal or squamous cell carcinomas removed by Mohs micrographic excision have different prognostic and logistical considerations from melanoma...
August 2017: Facial Plastic Surgery Clinics of North America
https://www.readbyqxmd.com/read/28654937/handheld-in-vivo-reflectance-confocal-microscopy-for-the-diagnosis-of-eyelid-margin-and-conjunctival-tumors
#8
Elisa Cinotti, Aurélie Singer, Bruno Labeille, Damien Grivet, Pietro Rubegni, Catherine Douchet, Frédéric Cambazard, Gilles Thuret, Philippe Gain, Jean Luc Perrot
Importance: The clinical diagnosis of conjunctival and eyelid margin tumors is challenging, and new noninvasive imaging techniques could be valuable in this field. Objective: To assess the diagnostic accuracy of handheld in vivo reflectance confocal microscopy (IVCM) for the diagnosis of eyelid margin and conjunctival tumors. Design: A prospective observational study was conducted at University Hospital of Saint-Etienne from January 2, 2011, to December 31, 2016 (inclusion of patients until December 31, 2015, and follow-up until December 31, 2016)...
June 22, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28615821/pyogenic-granuloma-like-lesion-in-children-should-we-wait
#9
Lai Kuan Chooi, Arman Zaharil Mat Saad, Shamala Durairajanayagam
Malignant melanoma is a potentially lethal cutaneous malignancy. Melanoma in paediatrics is rare as compared to adult melanoma. The clinicopathological characteristics of paediatric melanoma are different from adult melanoma, and the presence of melanoma mimics which occurs frequently in children (Spitz naevi) resulted in diagnosis uncertainty. We reported a 9-year-old girl who presented with a slow-growing, pyogenic granuloma-like lesion which was diagnosed with melanoma. It is important to have a high index of suspicion in paediatric skin lesion that would usually be deemed benign...
January 2017: Indian Journal of Plastic Surgery: Official Publication of the Association of Plastic Surgeons of India
https://www.readbyqxmd.com/read/28614305/bap1-regulates-ip3r3-mediated-ca-2-flux-to-mitochondria-suppressing-cell-transformation
#10
Angela Bononi, Carlotta Giorgi, Simone Patergnani, David Larson, Kaitlyn Verbruggen, Mika Tanji, Laura Pellegrini, Valentina Signorato, Federica Olivetto, Sandra Pastorino, Masaki Nasu, Andrea Napolitano, Giovanni Gaudino, Paul Morris, Greg Sakamoto, Laura K Ferris, Alberto Danese, Andrea Raimondi, Carlo Tacchetti, Shafi Kuchay, Harvey I Pass, El Bachir Affar, Haining Yang, Paolo Pinton, Michele Carbone
BRCA1-associated protein 1 (BAP1) is a potent tumour suppressor gene that modulates environmental carcinogenesis. All carriers of inherited heterozygous germline BAP1-inactivating mutations (BAP1(+/-)) developed one and often several BAP1(-/-) malignancies in their lifetime, mostly malignant mesothelioma, uveal melanoma, and so on. Moreover, BAP1-acquired biallelic mutations are frequent in human cancers. BAP1 tumour suppressor activity has been attributed to its nuclear localization, where it helps to maintain genome integrity...
June 22, 2017: Nature
https://www.readbyqxmd.com/read/28611307/review-oncolytic-virotherapy-updates-and-future-directions
#11
REVIEW
Christos Fountzilas, Sukeshi Patel, Devalingam Mahalingam
Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or non-resectable melanoma...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28584020/kit-d816v-induces-src-mediated-tyrosine-phosphorylation-of-mitf-and-altered-transcription-program-in-melanoma
#12
Bengt Phung, Julhash U Kazi, Alicia Lundby, Kristin Bergsteinsdottir, Jianmin Sun, Colin R Goding, Göran Jönsson, Jesper V Olsen, Eiríkur Steingrímsson, Lars Rönnstrand
The oncogenic D816V mutation of the KIT receptor is well characterized in systemic mastocytosis and acute myeloid leukemia. Although KIT(D816V) has been found in melanoma, its function and involvement in this malignancy is not understood. Here we show that KIT(D816V) induces tyrosine phosphorylation of MITF through a triple protein complex formation between KIT, MITF, and SRC family kinases. In turn, phosphorylated MITF activates target genes that are involved in melanoma proliferation, cell-cycle progression, suppression of senescence, survival, and invasion...
June 5, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28573821/overexpression-of-the-human-antigen-r-suppresses-the-immediate-paradoxical-proliferation-of-melanoma-cell-subpopulations-in-response-to-suboptimal-braf-inhibition
#13
Marylise Fernandez, Hedwig Sutterlüty-Fall, Christoph Schwärzler, Sylvain Lemeille, Wolf-Henning Boehncke, Rastine Merat
Tumor plasticity and the heterogeneous response of melanoma cells to targeted therapies are major limits for the long-term efficacy of this line of therapy. Targeting tumor plasticity is theoretically possible through the modulation of the expression of RNA-binding proteins which can affect many different compensatory mechanisms of the adaptive response of malignant cells to targeted therapies. Human antigen R (HuR) is a modulator of gene expression and a transacting factor in the mRNA-processing machinery used in the cell stress response, and is a potential target for reducing tumor plasticity...
July 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28572258/immunotherapy-for-breast-cancer-what-are-we-missing
#14
EDITORIAL
Robert H Vonderheide, Susan M Domchek, Amy S Clark
The recent demonstration of modest single-agent activity of programmed death-ligand 1 (PD-L1) and programmed death receptor-1 (PD-1) antibodies in patients with breast cancer has generated hope that breast cancer can be made amenable to immunotherapy. Depending on the subtype of breast cancer, it is now clear in both primary and metastatic disease that the extent of tumor-infiltrating T cells is not only prognostic for survival but predictive of response to nonimmune, standard therapies. Despite these findings, immune cytolytic activity in spontaneous breast tumors, the burden of nonsynonymous tumor mutations, and the predicted load of neoepitopes-factors linked to response to checkpoint blockade in other malignancies-are all relatively modest in breast cancer compared with melanoma or lung cancer...
June 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28537531/clinical-features-of-nivolumab-induced-thyroiditis-a-case-series-study
#15
Ichiro Yamauchi, Yoriko Sakane, Yorihide Fukuda, Toshihito Fujii, Daisuke Taura, Masakazu Hirata, Keisho Hirota, Yohei Ueda, Yugo Kanai, Yui Yamashita, Eri Kondo, Masakatsu Sone, Akihiro Yasoda, Nobuya Inagaki
BACKGROUND: The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. It consists of the PD-1 receptor and its two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Nivolumab is an anti-PD-1 monoclonal antibody approved for malignant melanoma, advanced non-small cell lung cancer, and advanced renal cell carcinoma in Japan. Thyrotoxicosis and hypothyroidism have both been reported in international Phase 3 studies and national post-marketing surveillance of nivolumab in Japan...
July 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28536525/immune-checkpoint-in-glioblastoma-promising-and-challenging
#16
REVIEW
Jing Huang, Fangkun Liu, Zhixiong Liu, Hui Tang, Haishan Wu, Qianni Gong, Jindong Chen
Glioblastoma (GBM) is a severe malignant brain cancer with poor overall survival. Conventional intervention remains dismal to prevent recurrence and deterioration of GBM cell. Recent years have witnessed exciting breakthroughs in novel immune strategies, especially checkpoint inhibitors, some of which have become adjuvant setting after standard of care in melanoma. Several clinical trials of checkpoint inhibitors are ongoing in glioblastoma and other brain carcinomas. Plus, synergistic combinations of checkpoint inhibitors with conventional therapy strategies-radiotherapy, temozolomide, bevacizumab, and corticosteroids are now being exploited and applied in clinical settings...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28533998/ipilimumab-as-a-cause-of-severe-pan-colitis-and-colonic-perforation
#17
Raj Shah, Danielle Witt, Talal Asif, Fahad F Mir
Ipilimumab is a human monoclonal antibody that functions as a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor that is used to treat malignant melanoma. Due to ipilimumab's removal of immune regulation, specifically through the inactivation of CTLA-4, it is commonly associated with inflammatory and autoimmune events. Gastrointestinal (GI) related immune-related adverse events such as diarrhea occur in 29% of patients with 7.6% of patients specifically suffering from colitis. We describe a case of colonic perforation with ipilimumab use...
April 20, 2017: Curēus
https://www.readbyqxmd.com/read/28529451/role-of-epigenetics-in-uveal-melanoma
#18
REVIEW
Yongyun Li, Renbing Jia, Shengfang Ge
Uveal melanoma (UM) is a severe human malignancy with a high mortality rate that demands continued research into new and alternative forms of prevention and treatment. The emerging field of epigenetics is beginning to unfold an era of contemporary approaches to reducing the risk and improving the clinical treatment of UM. Epigenetic changes have a high prevalence rate in cancer, are reversible in nature, and can lead to cancer characteristics even in mutation-free cells. The information contained in this review highlights and expands on the main mechanisms of epigenetic dysregulation in UM tumorigenesis, progression and metastasis, including microRNA expression, hypermethylation of genes and histone modification...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28528541/melanoma-frequency-among-symmetrical-spitzoid-looking-lesions-a-retrospective-study
#19
Claudia Costa, Matteo Megna, Milena Cappello, Maddalena Napolitano, Giuseppe Monfrecola, Massimiliano Scalvenzi
BACKGROUND: Many efforts have been spent attempting to define clinical, histopathological and molecular markers for differential diagnosis of Spitz nevus and melanoma. Dermoscopy has been widely used but it may be not always sufficient. METHODS: A retrospective study was performed evaluating Spitzoid-looking lesions showing symmetry at clinical and dermoscopic examination in patients ≥ 12 years attending our Clinic from 2004 to 2014. Demographic, clinical and dermoscopic data were assessed for each lesion in order to highlight the most common characteristics which could help the differential diagnosis between Spitz nevus and melanoma when clinical or dermoscopic asymmetry is lacking...
May 16, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28526240/endocrine-actions-of-vitamin-d-in-skin-relevance-for-photocarcinogenesis-of-non-melanoma-skin-cancer-and-beyond
#20
REVIEW
Jörg Reichrath, Roman Saternus, Thomas Vogt
The skin represents a pivotal organ for the human body's vitamin D endocrine system, being both the site of ultraviolet (UV)-B-induced vitamin D synthesis and a target tissue for the pluripotent effects of 1,25(OH)2D3 and other biologically active vitamin D metabolites. As many other steroid hormones, 1,25(OH)2D3 exerts its effects via two independent signal transduction pathways: the classical genomic and the non-genomic pathway. While non-genomic effects of 1,25(OH)2D3 are in part exerted via effects on intracellular calcium, genomic effects are mediated by the vitamin D receptor (VDR)...
May 16, 2017: Molecular and Cellular Endocrinology
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