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familial melanoma

Maomao Zhang, Julie S Di Martino, Robert L Bowman, Nathaniel R Campbell, Sanjeethan C Baksh, Theresa Simon-Vermot, Isabella S Kim, Pearce Haldeman, Chandrani Mondal, Vladimir Yong-Gonzalez, Mohsen Abu-Akeel, Taha Merghoub, Drew R Jones, Xiphias Ge Zhu, Arshi Arora, Charlotte E Ariyan, Kivanc Birsoy, Jedd D Wolchok, Katherine S Panageas, Travis J Hollmann, Jose Javier Bravo-Cordero, Richard M White
Advanced, metastatic melanomas frequently grow in subcutaneous tissues and portend a poor prognosis. Though subcutaneous tissues are largely composed of adipocytes, the mechanisms by which adipocytes influence melanoma are poorly understood. Using in vitro and in vivo models, we find that adipocytes increase proliferation and invasion of adjacent melanoma cells. Additionally, adipocytes directly transfer lipids to melanoma cells, which alters tumor cell metabolism. Adipocyte-derived lipids are transferred to melanoma cells through the FATP/SLC27A family of lipid transporters expressed on the tumor cell surface...
June 14, 2018: Cancer Discovery
Aki Fujiwara-Kuroda, Tatsuya Kato, Takehiro Abiko, Takahiro Tsuchikawa, Noriaki Kyogoku, Masaomi Ichinokawa, Kimitaka Tanaka, Takehiro Noji, Yasuhiro Hida, Kichizo Kaga, Yoshiro Matsui, Hiroaki Ikeda, Shinichi Kageyama, Hiroshi Shiku, Satoshi Hirano
Melanoma antigen family A4 (MAGEA4), a cancer/testis antigen, is overexpressed and is thus an immunotherapy target in various malignant tumors, including non-small cell lung cancer. However, whether MAGEA4 induces or inhibits the apoptosis of lung cancer cells remains controversial, as is its prognostic significance, particularly since there is no reliable method with which to detect MAGEA4 specifically. In this study, we optimized assay conditions to detect MAGEA4 based on cells transiently transfected with MAGEA genes, and found that MAGEA4 was expressed in four of eight non-small cell lung cancer cell lines, and in 25...
May 31, 2018: International Journal of Oncology
Valeria Caneparo, Santo Landolfo, Marisa Gariglio, Marco De Andrea
Absent in melanoma 2 (AIM2)-like receptors (ALRs) are a newly characterized class of pathogen recognition receptors (PRRs) involved in cytosolic and nuclear pathogen DNA recognition. In recent years, two ALR family members, the interferon (IFN)-inducible protein 16 (IFI16) and AIM2, have been linked to the pathogenesis of various autoimmune diseases, among which systemic lupus erythematosus (SLE) has recently gained increasing attention. SLE patients are indeed often characterized by constitutively high serum IFN levels and increased expression of IFN-stimulated genes due to an abnormal response to pathogens and/or incorrect self-DNA recognition process...
2018: Frontiers in Immunology
Bhuvanasundar Renganathan, Vinoth Durairaj, Dogan Can Kirman, Paa Kow A Esubonteng, Swee Kim Ang, Ruowen Ge
Inhibiting tumor angiogenesis is a well-established approach for anticancer therapeutic development. A Disintegrin-like and Metalloproteinase with ThromboSpondin Motifs 5 (ADAMTS5) is a secreted matrix metalloproteinase in the ADAMTS family that also functions as an anti-angiogenic/anti-tumorigenic molecule. Its anti-angiogenic/anti-tumorigenic function is independent from its proteinase activity, but requires its first thrombospondin type 1 repeat (TSR1). However, it is not known if recombinant TSR1 (rTSR1) can function as an anticancer therapeutic...
June 11, 2018: Cancers
David Turner, Anna G Kondic, Keaven M Anderson, Andrew Robinson, Edward B Garon, Jonathan W Riess, Lokesh Jain, Kapil Mayawala, Jiannan Kang, Scot W Ebbinghaus, Vikram Sinha, Dinesh P de Alwis, Julie A Stone
PURPOSE: To investigate the relationship of pembrolizumab pharmacokinetics (PK) and overall survival (OS) in patients with advanced melanoma and non-small cell carcinoma (NSCLC). EXPERIMENTAL DESIGN: PK dependencies in OS were evaluated across three pembrolizumab studies of either 200mg or 2-10 mg/kg Q3W. Kaplan-Meier (K-M) plots of OS, stratified by dose, exposure, and baseline clearance were assessed per indication and study. A Cox Proportional Hazards model was implemented to explore imbalances of typical prognostic factors in high/low NSCLC CL</SPAN>0 <SPAN style="font-family: Arial, sans-serif;"> subgroups...
June 11, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Anne E Cust, Martin Drummond, Peter A Kanetsky, Alisa M Goldstein, Jennifer H Barrett, Stuart MacGregor, Matthew H Law, Mark M Iles, Minh Bui, John L Hopper, Myriam Brossard, Florence Demenais, John C Taylor, Clive Hoggart, Kevin M Brown, Maria Teresa Landi, Julia A Newton-Bishop, Graham J Mann, D Timothy Bishop
It is unclear to what degree genomic and traditional (phenotypic and environmental) risk factors overlap in their prediction of melanoma risk. We evaluated the incremental contribution of common genomic variants (in pigmentation, nevus and other pathways) and their overlap with traditional risk factors, using data from two population-based case-control studies from Australia (n=1,035) and the UK (n=1,460) that used the same questionnaires. Polygenic risk scores were derived from 21 gene regions associated with melanoma and odds ratios from published meta-analyses...
June 8, 2018: Journal of Investigative Dermatology
Zhen Shi, Bin Lan, Baowei Peng, Xuefeng Wang, Ganggang Zhang, Xiaohu Li, Fang Guo
Malignant melanoma has shown increased incidence and high mortality rate in the last three decades. In this study, we investigated whether combination therapy with ch282-5 (a novel BH3 mimetic) and microwave hyperthermia could display synergistic antitumor effects against melanoma. Our results indicated that combination therapy reduced the viability and proliferation of melanoma cells. Through inhibiting the expression of anti-apoptotic proteins of Bcl-2 and IAP family and activating MAPK proteins, combined hyperthermia enhanced ch282-5-induced apoptosis...
June 7, 2018: Biochemical and Biophysical Research Communications
Marianna Signoretti, Marco J Bruno, Giulia Zerboni, Jan-Werner Poley, Gianfranco Delle Fave, Gabriele Capurso
Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with "familial pancreatic cancer" (FPC) and specific syndromes are limited and heterogeneous. Objective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs. Methods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies...
May 2018: United European Gastroenterology Journal
Azad Saei, Marta Palafox, Touati Benoukraf, Nishi Kumari, Patrick William Jaynes, Prasanna Vasudevan Iyengar, Eva Muñoz-Couselo, Paolo Nuciforo, Javier Cortés, Christopher Nötzel, Nesaretnam Barr Kumarakulasinghe, John Lalith Charles Richard, Zul Fazreen Bin Adam Isa, Brendan Pang, Marta Guzman, Zhou Siqin, Henry Yang, Wai Leong Tam, Violeta Serra, Pieter Johan Adam Eichhorn
RAF kinase inhibitors are clinically active in patients with BRAF (V600E) mutant melanoma. However, rarely do tumors regress completely, with the majority of responses being short-lived. This is partially mediated through the loss of negative feedback loops after MAPK inhibition and reactivation of upstream signaling. Here, we demonstrate that the deubiquitinating enzyme USP28 functions through a feedback loop to destabilize RAF family members. Loss of USP28 stabilizes BRAF enhancing downstream MAPK activation and promotes resistance to RAF inhibitor therapy in culture and in vivo models...
June 7, 2018: Journal of Experimental Medicine
Kyle M LaPak, Dennis C Vroom, Ayush A Garg, Xiangnan Guan, John L Hays, Jonathan W Song, Christin E Burd
The overexpression and hyperactivity of p21-activated serine/threonine kinases (PAKs) is known to facilitate tumorigenesis; however, the contribution of cancer-associated PAK mutations to tumor initiation and progression remains unclear. Here, we identify p21-activated serine/threonine kinase 5 (PAK5) as the most frequently altered PAK family member in human melanoma. More than 60% of melanoma-associated PAK5 gene alterations are missense mutations, and distribution of these variants throughout the protein coding sequence make it difficult to distinguish oncogenic drivers from passengers...
May 22, 2018: Oncotarget
Aline Hantute-Ghesquier, Aurélien Haustrate, Natalia Prevarskaya, V'yacheslav Lehen'kyi
Members of the TRPM ("Melastatin") family fall into the subclass of the TRP channels having varying permeability to Ca2+ and Mg2+ , with three members of the TRPM family being chanzymes, which contain C-terminal enzyme domains. The role of different TRPM members has been shown in various cancers such as prostate cancer for mostly TRPM8 and TRPM2, breast cancer for mostly TRPM2 and TRPM7, and pancreatic cancer for TRPM2/7/8 channels. The role of TRPM5 channels has been shown in lung cancer, TRPM1 in melanoma, and TRPM4 channel in prostate cancer as well...
June 7, 2018: Pharmaceuticals
Ken Noguchi, Toros A Dincman, Annamarie C Dalton, Breege V Howley, Buckley J McCall, Bidyut K Mohanty, Philip H Howe
Interleukin-like EMT Inducer (ILEI,FAM3C) is a secreted factor that contributes to the epithelial-to-mesenchymal transition (EMT), a cell biological process that confers metastatic properties to a tumor cell. However, very little is known about how ILEI is regulated. Here we demonstrate that ILEI is anin vivo regulator of melanoma invasiveness and is transcriptionally up-regulated by the upstream stimulatory factor-1 (USF-1), an E- box-binding, basic-helix-loop-helix family transcription factor. shRNA-mediated knockdown of ILEI in melanoma cell lines attenuated lung colonization but not primary tumor formation...
June 5, 2018: Journal of Biological Chemistry
Lin Zheng, Yum-Shing Wong, Mumin Shao, Shiying Huang, Fochang Wang, Jianping Chen
9,11-Dehydroergosterol peroxide [9(11)-DHEP] is an important steroid from medicinal mushroom, which has been reported to exert antitumor activity in several tumor types. However, the role of 9(11)‑DHEP toward the malignant melanoma cells has not been investigated. In the present study, the steroid from Ganoderma lucidum was purified on a submerged culture, and its antitumor mechanisms on A375 human malignant melanoma cells was investigated by MTT, flow cytometry and western blotting. The studies demonstrated that apoptotic mechanisms of the steroid were caspase‑dependent and mediated via the mitochondrial pathway...
May 17, 2018: Molecular Medicine Reports
Limin Cai, Jing Liu, Yu Wang, Hongxiao Chen, Yanli Ma, Yanhua Wang, Yongchen Wang
Melanoma, is a highly aggressive and the most lethal form of skin cancer, and is known to be resistant to current therapeutic modalities. Interferon (IFN)-α2b is an immunostimulatory cytokine and is used to treat melanoma by inhibiting proliferation and promoting apoptosis of cells. However, there is a need to improve the efficacy of IFN-α2b. Inhibitor of growth family member 4 (ING4) has been reported to function as a tumor suppressor and is involved in regulating cell cycle progression, apoptosis, cell migration and invasion...
June 2018: Oncology Letters
Wei Li, Ru Hong, Lan-Tian Lai, Qiman Dong, Peiling Ni, Rosi Chelliah, Mehnaz Huq, Siti Nadirah Binte Ismail, Udita Chandola, Zhiwei Ang, Bingqing Lin, Xin Chen, Lingyi Chen, Li-Feng Zhang
Xist (inactivated X chromosome specific transcript) is a prototype long non-coding RNA (lncRNA) in charge of epigenetic silencing of one X chromosome in each female cell in mammals. In a genetic screen, we identify Mageb3, and its homologs Mageb1 and Mageb2 as genes functionally required for Xist-mediated gene silencing. Mageb1-3 are previously uncharacterized genes belonging to the MAGE (melanoma-associated antigen) gene family. Mageb1-3 are expressed in undifferentiated ES cells and early stages of in vitro differentiation, a critical time window of X chromosome inactivation...
May 22, 2018: Journal of Molecular Biology
Seohee Deanne Choi, Mario I D'Souza, Scott W Menzies, Wolfgang Weninger
BACKGROUND/OBJECTIVES: Patients on biologic therapy are thought to be at increased risk of developing non-melanoma skin cancers and melanomas. It is unknown whether biologic therapy alters the natural history of melanocytic naevi. Therefore, a prospective observational study was conducted to determine whether psoriasis patients on biologic therapy develop changes in naevi. METHODS: Clinical and dermoscopic assessment of all melanocytic naevi was performed in 45 psoriasis patients on biologic therapy versus a control cohort of 43 subjects, using sequential digital dermoscopic imaging and total body photography...
May 23, 2018: Australasian Journal of Dermatology
Akihiko Kida, Eishiro Mizukoshi, Toshikatsu Tamai, Takeshi Terashima, Masaaki Kitahara, Kuniaki Arai, Tatsuya Yamashita, Kazumi Fushimi, Masao Honda, Shuichi Kaneko
BACKGROUND & AIMS: Immunotherapy is a promising treatment option for cholangiocarcinoma. We compared cytotoxic T lymphocyte (CTL) responses against several tumor-associated antigen (TAA)-derived epitopes in cholangiocarcinoma patients to identify candidate epitopes for immunotherapy. METHODS: Twenty-six TAAs were selected, and the expression of TAAs in 6 cholangiocarcinoma cell lines and 9 specimens were measured using real-time polymerase chain reaction (PCR)...
May 23, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Elena-Daniela Serban, Francesca Farnetani, Giovanni Pellacani, Maria Magdalena Constantin
Worldwide melanoma incidence and mortality are increasing (1). Despite the ongoing research, advanced melanoma is still incurable; therefore, the most appropriate solution seems to be early detection combined with complete surgical excision (2). Since the diagnostic protocol of suspicious lesions includes a complete excision with safety margins (2), the problem of unnecessary scarring is significant. The real challenge in this case is to have a properly formulated diagnosis before acquiring a biopsy. Currently available non-invasive techniques are coherence tomography, digital dermoscopy, and reflectance confocal microscopy...
April 2018: Acta Dermatovenerologica Croatica: ADC
Mitchell E Fane, Yash Chhabra, Aaron G Smith, Richard A Sturm
The POU domain family of transcription factors play a central role in embryogenesis and are highly expressed in neural crest cells and the developing brain. BRN2 is a class III POU domain protein that is a key mediator of neuroendocrine and melanocytic development and differentiation. While BRN2 is a central regulator in numerous developmental programs, it has also emerged as a major player in the biology of tumourigenesis. In melanoma, BRN2 has been implicated as one of the master regulators of the acquisition of invasive behavior within the phenotype-switching model of progression...
May 21, 2018: Pigment Cell & Melanoma Research
Fani Karagianni, Ching-Ni Njauw, Katerina P Kypreou, Aravela Stergiopoulou, Michaela Plaka, Dorothea Polydorou, Vasiliki Chasapi, Leon Pappas, Ioannis Stratigos, Gregory Champsas, Peter Panagiotou, Helen Gogas, Evangelos Evangelou, Hensin Tsao, Alexander Stratigos, Irene Stefanaki
Approximately 5-10% of melanoma cases occur in a familial context. CDKN2A/CDK4 were the first high-penetrance melanoma genes identified. The aims of this study were to evaluate CDKN2A/CDK4 variants in Greek familial melanoma patients and to correlate the mutational status with specific clinico-epidemiological characteristics. A cross-sectional study was conducted by genotyping CDKN2A/CDK4 variants and selected MC1R polymorphisms in 52 melanoma-prone families. Descriptive statistics were calculated and comparisons were made using the χ2 test, Fisher's exact test and Student's t-test for statistical analysis, as appropriate...
May 18, 2018: Acta Dermato-venereologica
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