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https://www.readbyqxmd.com/read/28547663/pediatric-predispositional-genetic-risk-communication-potential-utility-for-prevention-and-control-of-melanoma-risk-as-an-exemplar
#1
Yelena P Wu, Darren Mays, Wendy Kohlmann, Kenneth P Tercyak
Predispositional genetic testing among minor children is intensely debated due to the potential benefits and harms of providing this type of genetic information to children and their families. Existing guidelines on pediatric genetic testing state that predispositional testing could be appropriate for minors if preventive services exist that mitigate children's risk for or severity of the health condition in question. We use the example of hereditary melanoma to illustrate the rationale for and potential application of genetic risk communication for an adult-onset cancer to a pediatric population where childhood behaviors may reduce risk of disease later in life...
May 25, 2017: Journal of Genetic Counseling
https://www.readbyqxmd.com/read/28541884/an-incomplete-picture-challenges-of-partial-biopsies-in-large-diameter-atypical-melanocytic-lesions
#2
Lauren C Strazzulla, Hong Wu, Marissa Heller, Caroline C Kim
Large diameter atypical pigmented lesions (LDAPL) can be challenging to diagnose accurately using partial biopsies because of pathologic heterogeneity, while at the same time large excisions of these lesions confer significant morbidity to patients. Consequently, clinicians are often challenged by the management of these lesions. In this case, we describe an elderly patient with a history of multiple basal cell carcinomas, prior melanomas, and a family history of melanoma who presented with an irregularly pigmented brown and dark brown patch on his upper back...
April 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28530548/critical-role-of-rig-i-and-mda5-in-early-and-late-stages-of-tulane-virus-infection
#3
Preeti Chhabra, Priya Ranjan, Theresa Cromeans, Suryaprakash Sambhara, Jan Vinjé
Human noroviruses are a major cause of acute gastroenteritis worldwide, but the lack of a robust cell culture system or small animal model have hampered a better understanding of innate immunity against these viruses. Tulane virus (TV) is the prototype virus of a tentative new genus, Recovirus, in the family Caliciviridae. Its epidemiology and biological properties most closely resemble human norovirus. The host innate immune response to RNA virus infection primarily involves pathogen-sensing toll-like receptors (TLRs) TLR3 and TLR7 and retinoic acid-inducible gene I-like receptor RIG-I and melanoma differentiation associated gene 5 (MDA5)...
May 22, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28526571/the-antiviral-signaling-mediated-by-black-carp-mda5-is-positively-regulated-by-lgp2
#4
Ji Liu, Jun Li, Jun Xiao, Hui Chen, Liang Lu, Xu Wang, Yu Tian, Hao Feng
Melanoma differentiation-associated gene 5 (MDA5) belongs to RIG-I like receptor (RLR) family, which detects cytosolic viral RNA component in immune response. In this study, MDA5 orthologue of black carp (Mylopharyngodon piceus) has been cloned and characterized. The full-length cDNA of black carp MDA5 (bcMDA5) comprises 3244 nucleotides and the predicted bcMDA5 protein contains 984 amino acids. The constitutive transcription of bcMDA5 was extremely low in all the tested tissues, which included gill, skin, muscle, intestine, kidney, spleen, liver and heart...
May 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28526240/endocrine-actions-of-vitamin-d-in-skin-relevance-for-photocarcinogenesis-of-non-melanoma-skin-cancer-and-beyond
#5
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
https://www.readbyqxmd.com/read/28522750/inhibition-of-mitochondrial-matrix-chaperones-and-anti-apoptotic-bcl-2-family-proteins-empower-antitumor-therapeutic-responses
#6
Georg Karpel-Massler, Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Rolando Perez-Lorenzo, Basil Horst, Matei Banu, Kevin A Roth, Jeffrey N Bruce, Peter Canoll, Dario C Altieri, Markus D Siegelin
Rational therapeutic approaches based on synthetic lethality may improve cancer management. Based on a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy. Our analyses focused on BH3 mimetics that are broad acting (ABT263 and Obatoclax) or selective (ABT199, WEHI-539 and A1210477), along with the established mitochondrial matrix chaperone inhibitor Gamitrinib-TPP...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28516231/molecular-evolution-of-type-ii-mage-genes-from-ancestral-maged2-gene-and-their-phylogenetic-resolution-of-basal-mammalian-clades
#7
Marcos De Donato, Sunday O Peters, Tanveer Hussain, Hectorina Rodulfo, Bolaji N Thomas, Masroor E Babar, Ikhide G Imumorin
Type II melanoma-associated antigens (MAGE) are a subgroup of about a dozen proteins found in various locations in the genome and expressed in normal tissues, thus are not related to cancer as the type I MAGE genes. This gene family exists as a single copy in non-mammals and monotremata, but found as two copies in metatherians and occur as a diverse group in all eutherians. Our studies suggest MAGED2 as the ancestor of this subfamily and the most likely evolutionary history of eutherian type II MAGE genes is hereby proposed based on synteny conservation, phylogenetic relations, genome location, homology conservation, and the protein and gene structures...
May 17, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28513992/immunoregulatory-protein-b7-h3-promotes-growth-and-decreases-sensitivity-to-therapy-in-metastatic-melanoma-cells
#8
Karine Flem-Karlsen, Christina Tekle, Yvonne Andersson, Kjersti Flatmark, Øystein Fodstad, Caroline E Nunes-Xavier
B7-H3 (CD276) belongs to the B7-family of immunoregulatory proteins, and has been implicated in cancer progression and metastasis. In this study, we found that metastatic melanoma cells with knockdown expression of B7-H3 showed modest decrease in proliferation and glycolytic capacity, and were more sensitive to dacarbazine (DTIC) chemotherapy and small-molecule inhibitors targeting MAP kinase (MAPK)- and AKT/mTOR-pathways: vemurafenib (PLX4032; BRAF inhibitor), binimetinib (MEK-162; MEK inhibitor), everolimus (RAD001; mTOR inhibitor) and triciribidine (API-2; AKT inhibitor)...
May 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28503645/immune-checkpoint-inhibitors-an-innovation-in-immunotherapy-for-the-treatment-and-management-of-patients-with-cancer
#9
REVIEW
Jennifer Dine, RuthAnn Gordon, Yelena Shames, Mary Kate Kasler, Margaret Barton-Burke
Cancer survival rates are generally increasing in the United States. These trends have been partially attributed to improvement in therapeutic strategies. Cancer immunotherapy is an example of one of the newer strategies used to fight cancer, which primes or activates the immune system to produce antitumor effects. The first half of this review paper concisely describes the cell mechanisms that control antitumor immunity and the major immunotherapeutic strategies developed to target these mechanisms. The second half of the review discusses in greater depth immune checkpoint inhibitors that have recently demonstrated tremendous promise for the treatment of diverse solid tumor types, including melanoma, non-small cell lung cancer, and others...
April 2017: Asia-Pacific Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28492371/prognostic-value-of-tumoral-expression-of-galectin-9-in-gastric-cancer
#10
Sang Il Choi, Ki Woo Seo, Myeong Cherl Kook, Chan Gyoo Kim, Young Woo Kim, Soo Jeong Cho
BACKGROUND/AIMS: Galectin-9 (Gal-9) is a member of the β-galactoside-binding lectin family. Our previous study revealed that Gal-9 suppresses migration, invasion, and epithelial-mesenchymal transition in gastric cancer cells. Gal-9 was reported to have anti-metastatic activity in patients with malignant melanoma, breast cancer, and hepatocellular carcinoma. Therefore, we aimed to evaluate the prognostic significance of Gal-9 in patients with gastric cancer. MATERIALS AND METHODS: The clinical significance of Gal-9 was explored using clinical and pathological data from 619 patients with gastric cancer who underwent gastrectomy at National Cancer Center, Korea...
May 2017: Turkish Journal of Gastroenterology: the Official Journal of Turkish Society of Gastroenterology
https://www.readbyqxmd.com/read/28489985/preclinical-evaluation-of-the-imipridone-family-analogues-of-clinical-stage-anti-cancer-small-molecule-onc201-reveals-potent-anti-cancer-effects-of-onc212
#11
Jessica Wagner, Christina Leah Kline, Marie D Ralff, Avital Lev, Amriti Lulla, Lanlan Zhou, Gary L Olson, Bhaskara Rao Nallaganchu, Cyril H Benes, Joshua E Allen, Varun V Prabhu, Martin Stogniew, Wolfgang Oster, Wafik S El-Deiry
Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene activation. ONC201 is under investigation in multiple clinical trials to treat patients with cancer. Given the unique imipridone core chemical structure of ONC201, we synthesized a series of analogues to identify additional compounds with distinct therapeutic properties. Several imipridones with a broad range of in vitro potencies were identified in an exploration of chemical derivatives...
May 10, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28485764/%C3%A3-kad-kunskap-om-familj%C3%A3-rt-melanom-och-de-bakom%C3%A2-liggande-generna
#12
Hildur Helgadottir, Kari Nielsen, Veronica Höiom
Increased knowledge on familial melanoma and the underlying genetics Approximately 5-10 % of all melanoma patients have close relatives with melanoma. 5-20% of melanoma families have germline mutations in the CDKN2A gene. Swedish CDKN2A mutation carriers have a young median age of onset of melanoma, increased risks of multiple primary melanoma and of tobacco-associated cancers in respiratory and upper digestive tissues, and also worse survival compared to non-carriers. In up to 80% of melanoma families no high risk melanoma associated germline mutations are found...
May 9, 2017: Läkartidningen
https://www.readbyqxmd.com/read/28482042/bap1-mutations-in-high-grade-meningioma-implications-for-patient-care
#13
Ganesh M Shankar, Sandro Santagata
We have recently shown that the BAP1 (BRCA1-associated protein-1) tumor suppressor gene is inactivated in a subset of clinically-aggressive meningiomas that display rhabdoid histomorphology. Immunohistochemistry for BAP1 protein provides a rapid and inexpensive method for screening suspected cases. Notably, some patients with BAP1-mutant meningiomas have germline BAP1 mutations and the BAP1 tumor predisposition syndrome (BAP1-TPDS). It appears that nearly all patients with germline BAP1 mutations develop malignancies by age 55, most frequently uveal melanoma, cutaneous melanoma, pleural or peritoneal malignant mesothelioma or renal cell carcinoma, although other cancers have also been associated with the BAP1-TPDS...
May 8, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28481878/the-ap-1-transcription-factor-fosl1-causes-melanocyte-reprogramming-and-transformation
#14
K Maurus, A Hufnagel, F Geiger, S Graf, C Berking, A Heinemann, A Paschen, S Kneitz, C Stigloher, E Geissinger, C Otto, A Bosserhoff, M Schartl, S Meierjohann
The MAPK pathway is activated in the majority of melanomas and is the target of therapeutic approaches. Under normal conditions, it initiates the so-called immediate early response, which encompasses the transient transcription of several genes belonging to the AP-1 transcription factor family. Under pathological conditions, such as continuous MAPK pathway overactivation due to oncogenic alterations occurring in melanoma, these genes are constitutively expressed. The consequences of a permanent expression of these genes are largely unknown...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28477199/b16-lung-melanoma-model-to-study-the-role-of-th9-cells-in-cancer
#15
Alka Dwivedi, Sushant Kumar, Rahul Purwar
T cell therapy has shown remarkable promise in multiple malignancies including melanoma and Acute Lymphoblastic Leukemia (ALL). Recent data demonstrated the differential efficacy of various subsets of T-helper cells in tumor regression. Th9 cells, the new member of T helper cell family, possess superior anti-tumor activity compared to Th1 and Th2 cells in murine model of melanoma. Therefore, it is important to examine the anti-tumor activity of specific subsets of Th cells in tumor models. Here, we describe the methodology of examining the anti-tumor activity of Th9 cells in murine model of melanoma...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28475458/mda5-associated-neuroinflammation-and-the-singleton-merten-syndrome-two-faces-of-the-same-type-i-interferonopathy-spectrum
#16
Insa Buers, Gillian I Rice, Yanick J Crow, Frank Rutsch
In 1973, Singleton and Merten described a new syndrome in 2 female probands with aortic and cardiac valve calcifications, early loss of secondary dentition, and widened medullary cavities of the phalanges. In 1984, Aicardi and Goutières defined a phenotype resembling congenital viral infection with basal ganglia calcification and increased protein content in the cerebrospinal fluid. Between 2006 and 2012, mutations in 6 different genes were described to be associated with Aicardi-Goutières syndrome, specifically-TREX1, RNASEH2A, RNASEH2B, RNASEH2C, ADAR, and SAMHD1...
May 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28473315/4-1bb-enhanced-expansion-of-cd8-til-from-triple-negative-breast-cancer-unveils-mutation-specific-cd8-t-cells
#17
Michiko Harao, Marie-Andrée Forget, Jason Roszik, Hui Gao, Gildy V Babiera, Savitri Krishnamurthy, Jessica A Chacon, Shumin Li, Elizabeth A Mittendorf, Sarah M DeSnyder, Korrene F Rockwood, Chantale Bernatchez, Naoto T Ueno, Laszlo G Radvanyi, Luis Vence, Cara Haymaker, James M Reuben
Triple negative breast cancer (TNBC) highly infiltrated with CD8(+) tumor-infiltrating lymphocytes (TILs) has been associated with improved prognosis. This observation led us to hypothesize that CD8(+) TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8(+) TILs in solid cancers other than melanoma. To overcome this obstacle, we used an agonistic antibody  (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8(+) T cells...
May 4, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28469092/transcriptional-dissection-of-melanoma-identifies-a-high-risk-subtype-underlying-tp53-family-genes-and-epigenome-deregulation
#18
Brateil Badal, Alexander Solovyov, Serena Di Cecilia, Joseph Minhow Chan, Li-Wei Chang, Ramiz Iqbal, Iraz T Aydin, Geena S Rajan, Chen Chen, Franco Abbate, Kshitij S Arora, Antoine Tanne, Stephen B Gruber, Timothy M Johnson, Douglas R Fullen, Leon Raskin, Robert Phelps, Nina Bhardwaj, Emily Bernstein, David T Ting, Georg Brunner, Eric E Schadt, Benjamin D Greenbaum, Julide Tok Celebi
BACKGROUND: Melanoma is a heterogeneous malignancy. We set out to identify the molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. METHODS: We examined transcriptome changes from benign states to early-, intermediate-, and late-stage tumors using a set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions. We utilized a next-generation sequencing platform that enabled a comprehensive analysis of protein-coding and -noncoding RNA transcripts...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28466200/myc-and-raf-key-effectors-in-cellular-signaling-and-major-drivers-in-human-cancer
#19
Eduard Stefan, Klaus Bister
The prototypes of the human MYC and RAF gene families are orthologs of animal proto-oncogenes that were originally identified as transduced alleles in the genomes of highly oncogenic retroviruses. MYC and RAF genes are now established as key regulatory elements in normal cellular physiology, but also as major cancer driver genes. Although the predominantly nuclear MYC proteins and the cytoplasmic RAF proteins have different biochemical functions, they are functionally linked in pivotal signaling cascades and circuits...
May 3, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28459460/magea1-interacts-with-fbxw7-and-regulates-ubiquitin-ligase-mediated-turnover-of-nicd1-in-breast-and-ovarian-cancer-cells
#20
J Zhao, Y Wang, C Mu, Y Xu, J Sang
Melanoma-associated antigen A1 (MAGEA1) is member of the MAGE gene family that is expressed in male germ line cells and placenta under normal physiological conditions. Although MAGEA1's expression levels have been evaluated as one of the cancer testis (CT) antigens for immunotherapy in melanoma and several other cancers, its functional role and signaling mechanisms are largely unknown. In this study, we examined the functional involvement and signaling mechanisms of MAGEA1 in breast and ovarian cancer cells...
May 1, 2017: Oncogene
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