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Melanoma genetics

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https://www.readbyqxmd.com/read/28814886/a-practical-guide-to-the-handling-and-administration-of-talimogene-laherparepvec-in-europe
#1
REVIEW
Kevin J Harrington, Olivier Michielin, Josep Malvehy, Isabella Pezzani Grüter, Lorna Grove, Anna Lisa Frauchiger, Reinhard Dummer
Talimogene laherparepvec is a herpes simplex virus-1-based intralesional oncolytic immunotherapy and is the first oncolytic virus to be approved in Europe. It is indicated for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (stage IIIB, IIIC, and IVM1a) with no bone, brain, lung, or other visceral disease. Talimogene laherparepvec is a genetically modified viral therapy, and its handling needs special attention due to its deep freeze, cold-chain requirements, its potential for viral shedding, and its administration by direct intralesional injection...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28811978/development-and-characterization-of-naive-single-type-tumor-antigen-specific-cd8-t-lymphocytes-from-murine-pluripotent-stem-cells
#2
Fengyang Lei, Mohammad Haque, Praneet Sandhu, Swetha Ravi, Jianyong Song, Bing Ni, Songguo Zheng, Deyu Fang, Hongyan Jia, Jin-Ming Yang, Jianxun Song
Optimal approaches to differentiate tumor antigen-specific cytotoxic T lymphocytes (CTLs) from pluripotent stem cells (PSCs) remain elusive. In the current study, we showed that combination of in vitro priming through Notch ligands and in vivo development facilitated the generation of tumor Ag-specific CTLs that effectively inhibited tumor growth. We co-cultured the murine induced PSCs (iPSCs) genetically modified with tyrosinase-related protein 2 (TRP2)-specific T cell receptors with OP9 cell line expressing both Notch ligands Delta-like 1 and 4 (OP9-DL1/DL4) for a week before adoptively transferred into recipient C67BL/6 mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28809608/treatment-of-patients-with-metastatic-cancer-using-a-major-histocompatibility-complex-class-ii-restricted-t-cell-receptor-targeting-the-cancer-germline-antigen-mage-a3
#3
Yong-Chen Lu, Linda L Parker, Tangying Lu, Zhili Zheng, Mary Ann Toomey, Donald E White, Xin Yao, Yong F Li, Paul F Robbins, Steven A Feldman, Pierre van der Bruggen, Christopher A Klebanoff, Stephanie L Goff, Richard M Sherry, Udai S Kammula, James C Yang, Steven A Rosenberg
Purpose Adoptive transfer of genetically modified T cells is being explored as a treatment for patients with metastatic cancer. Most current strategies use genes that encode major histocompatibility complex (MHC) class I-restricted T-cell receptors (TCRs) or chimeric antigen receptors to genetically modify CD8(+) T cells or bulk T cells for treatment. Here, we evaluated the safety and efficacy of an adoptive CD4(+) T-cell therapy using an MHC class II-restricted, HLA-DPB1*0401-restricted TCR that recognized the cancer germline antigen, MAGE-A3 (melanoma-associated antigen-A3)...
August 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28806777/a-synthetic-sickness-screen-for-senescence-re-engagement-targets-in-mutant-cancer-backgrounds
#4
Claire J Cairney, Lauren S Godwin, Alan E Bilsland, Sharon Burns, Katrina H Stevenson, Lynn McGarry, John Revie, Jon D Moore, Ceri M Wiggins, Rebecca S Collinson, Clare Mudd, Elpida Tsonou, Mahito Sadaie, Dorothy C Bennett, Masashi Narita, Christopher J Torrance, W Nicol Keith
Senescence is a universal barrier to immortalisation and tumorigenesis. As such, interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however, senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robust senescence inducing agents and an incomplete understanding of the signalling events underlying this complex process. In order to address this issue we undertook a large-scale morphological siRNA screen for inducers of senescence phenotypes in the human melanoma cell line A375P...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28805940/new-and-current-preventive-treatment-options-in-actinic-keratosis
#5
REVIEW
P Arenberger, M Arenbergerova
Actinic keratosis (AK) is a characteristic skin lesion on skin areas of subjects with mainly phototype I and phototype II, or with specific genetic factors and who are exposed to prolonged ultraviolet radiation. AK may be considered a precursor of in situ squamous cell carcinoma (SCC), a type of non-melanoma skin cancer (NMSC). However, it is still not possible to predict which AK lesions will develop into SCC. Early treatment of AK is therefore recommended. Despite the increasing number of patients with AK developing into SCC, to date, there is still no clear suggestion of therapeutic strategy for AK...
September 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28802505/soft-tissue-tumors-of-uncertain-histogenesis-a-review-for-dermatopathologists
#6
REVIEW
Darya Buehler, Paul Weisman
The mesenchymal tumors discussed herein represent a heterogeneous group of neoplasms with distinctive morphologic, immunophenotypic, and molecular genetic features. These uncommon tumors often arise in the dermis and subcutis and can pose a major diagnostic challenge to dermatopathologists because they closely mimic melanoma, carcinoma, fibrous histiocytoma, schwannoma, or granulomatous inflammation. This article reviews the clinical presentation, histopathology, differential diagnosis, and diagnostic pitfalls of epithelioid sarcoma, clear cell sarcoma, perivascular epithelioid cell tumor, ossifying fibromyxoid tumor, pleomorphic hyalinizing angiectatic tumor, and hemosiderotic fibrolipomatous tumor...
September 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/28802494/toward-a-molecular-genetic-classification-of-spitzoid-neoplasms
#7
REVIEW
Michael T Tetzlaff, Alexandre Reuben, Steven D Billings, Victor G Prieto, Jonathan L Curry
The histopathologic spectrum of Spitzoid neoplasms includes Spitz nevi, atypical Spitz tumors, and Spitzoid melanomas. Advances in molecular genetics have evolved to the point that Spitzoid lesions can now be reasonably classified according to their distinctive molecular-genetic alterations: Spitzoid lesions with (1) 11p amplification and/or HRAS mutations; (2) isolated loss of 6q23 by fluorescence in situ hybridization (FISH); (3) homozygous deletion of 9p21 by FISH; (4) BAP1 loss and BRAFV600 E mutation; (5) translocations involving any of a number of different oncogenic kinase drivers, including ROS1, ALK, NTRK1, NTRK3, MET, BRAF, and RET; and (6) TERT promoter mutations...
September 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/28801942/cancer-risk-in-different-generations-of-middle-eastern-immigrants-to-california-1988-2013
#8
Clara Ziadeh, Argyrios Ziogas, Hoda Anton-Culver
The objective of this study is to compare cancer risk among different generations of Middle Eastern (ME) immigrants and Non-Hispanic Whites (NHW) in California between 1988 and 2013. We used data from the California Cancer Registry to identify invasive primary incident cancer cases in three population groups: a) first generation ME immigrants, b) second or subsequent generations ME immigrants, and c) NHW. Proportional Incidence Ratio (PIR) was used to compare cancer risk of the 15 selected most common cancers in the 3 population groups taking into consideration time since immigration for first generation ME immigrants...
August 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28801919/familial-associations-of-female-breast-cancer-with-other-cancers
#9
Guoqiao Zheng, Hongyao Yu, Akseli Hemminki, Asta Försti, Kristina Sundquist, Kari Hemminki
Familial risks of breast cancer (BC) are well established but whether BC clusters with other, i.e. discordant, cancers is less certain but of interest for the identification of common genetic and possible environmental factors contributing to a general cancer susceptibility. We apply a novel approach to search for familial associations of BC with other (discordant) cancers based on the Swedish Family-Cancer Database. Relative risks (RRs) were calculated for BC in families with increasing numbers of patients with discordant cancer X, and conversely, familial RRs for cancer X in families with increasing numbers of BC patients...
August 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28800028/current-status-and-future-direction-in-the-management-of-malignant-melanoma
#10
Patrick Gladfelter, Noureldien H E Darwish, Shaker A Mousa
The incidence of malignant melanoma is increasing rapidly on a global scale. Although some types of melanoma, for example primary cutaneous melanoma, can be managed by surgery, metastatic melanoma cannot and it has a high mortality rate. Both oncogene and immune-targeted strategies have shown marked efficacy in some patients, but their effect on overall survival is still variable. Therefore, newer therapeutic approaches are needed. Fortunately, new advances in molecular medicine have led to an understanding of an individual patient's cancer at the genomic level...
August 10, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28797232/prognostic-significance-of-braf-and-nras-mutations-in-melanoma-a-german-study-from-routine-care
#11
Markus V Heppt, Timo Siepmann, Jutta Engel, Gabriele Schubert-Fritschle, Renate Eckel, Laura Mirlach, Thomas Kirchner, Andreas Jung, Anja Gesierich, Thomas Ruzicka, Michael J Flaig, Carola Berking
BACKGROUND: Hotspot mutations of the oncogenes BRAF and NRAS are the most common genetic alterations in cutaneous melanoma. Specific inhibitors of BRAF and MEK have shown significant survival benefits in large phase III trials. However, the prognostic significance of BRAF and NRAS mutations outside of clinical trials remains unclear. METHODS: The mutational status of BRAF (exon 15) and NRAS (exon 2 and 3) was determined in melanoma samples of 217 patients with pyrosequencing and Sanger sequencing...
August 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28796414/genetic-variants-in-the-metzincin-metallopeptidase-family-genes-predict-melanoma-survival
#12
Yinghui Xu, Yanru Wang, Hongliang Liu, Qiong Shi, Dakai Zhu, Christopher I Amos, Shenying Fang, Jeffrey E Lee, Terry Hyslop, Xin Li, Jiali Han, Qingyi Wei
Metzincins are key molecules in the degradation of the extracellular matrix and play an important role in cellular processes such as cell migration, adhesion, and cell fusion of malignant tumors, including cutaneous melanoma (CM). We hypothesized that genetic variants of the metzincin metallopeptidase family genes would be associated with CM-specific survival (CMSS). To test this hypothesis, we first performed Cox proportional hazards regression analysis to evaluate the associations between genetic variants of 75 metzincin metallopeptidase family genes and CMSS using the dataset from the genome-wide association study (GWAS) from The University of Texas MD Anderson cancer Center (MDACC) which included 858 non-Hispanic white patients with CM, and then validated in the dataset from the Harvard GWAS study which had 409 non-Hispanic white patients with invasive CM...
August 10, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28777149/malignant-melanoma-presenting-as-thoracic-midline-malignancy-clinicopathologic-and-molecular-features
#13
Keluo Yao, Weiqiang Zhao, Saeed Bajestani, Alejandro Gru, Gregory Otterson, Konstantin Shilo
Because of rarity, clinicopathologic and genomic profiles of noncutaneous malignant melanoma (MM) are not well characterized. In this study, we provide a detailed evaluation of 6 cases of MM presenting as thoracic midline malignancy. The tumors occurred in 6 white patients (5 males and 1 female; medium age, 71.5 y; range, 55 to 81 y). At presentation, the disease was confined to the chest (6/6) with 4 cases subsequently showing brain metastasis. All 6 tumors featured epithelioid and 1 case also spindle cell morphology...
August 2, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#14
REVIEW
Ibrahim Ragab Eissa, Yoshinori Naoe, Itzel Bustos-Villalobos, Toru Ichinose, Maki Tanaka, Wu Zhiwen, Nobuaki Mukoyama, Taishi Morimoto, Noriyuki Miyajima, Hasegawa Hitoki, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28767408/integration-of-genomic-transcriptomic-and-functional-profiles-of-aggressive-osteosarcomas-across-multiple-species
#15
Lara E Davis, Sophia Jeng, Matthew N Svalina, Elaine Huang, Janét Pittsenbarger, Emma L Cantor, Noah Berlow, Bernard Seguin, Atiya Mansoor, Shannon K McWeeney, Charles Keller
In complex, highly unstable genomes such as in osteosarcoma, targeting aberrant checkpoint processes (metabolic, cell cycle or immune) may prove more successful than targeting specific kinase or growth factor signaling pathways. Here, we establish a comparative oncology approach characterizing the most lethal osteosarcomas identified in a biorepository of tumors from three different species: human, mouse and canine. We describe the development of a genetically-engineered mouse model of osteosarcoma, establishment of primary cell cultures from fatal human tumors, and a biorepository of osteosarcoma surgical specimens from pet dogs...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28764308/familial-cancers-of-head-and-neck-region
#16
REVIEW
Reshma Venugopal, Radhika Manoj Bavle, Paremala Konda, Sudhakara Muniswamappa, Soumya Makarla
Cancers that occur in families more often than would be expected by chance are termed as familial cancers. They occur due to an inherited genetic mutation and account for 5%-10% of all cancers. This review article presents some of the common Familial Cancer Syndromes (FCS) such as MEN 2B, hyperparathyroidism-jaw tumour syndrome, familial oral squamous cell carcinoma, melanoma, nasopharyngeal carcinoma, paraganglioma, neurofibroma and other syndromes associated with head and neck region.
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28763790/platelets-subvert-t-cell-immunity-against-cancer-via-garp-tgf%C3%AE-axis
#17
Saleh Rachidi, Alessandra Metelli, Brian Riesenberg, Bill X Wu, Michelle H Nelson, Caroline Wallace, Chrystal M Paulos, Mark P Rubinstein, Elizabeth Garrett-Mayer, Mirko Hennig, Daniel W Bearden, Yi Yang, Bei Liu, Zihai Li
Cancer-associated thrombocytosis has long been linked to poor clinical outcome, but the underlying mechanism is enigmatic. We hypothesized that platelets promote malignancy and resistance to therapy by dampening host immunity. We show that genetic targeting of platelets enhances adoptive T cell therapy of cancer. An unbiased biochemical and structural biology approach established transforming growth factor β (TGFβ) and lactate as major platelet-derived soluble factors to obliterate CD4(+) and CD8(+) T cell functions...
May 5, 2017: Science Immunology
https://www.readbyqxmd.com/read/28760732/role-of-nox2-derived-reactive-oxygen-species-in-nk-cell-mediated-control-of-murine-melanoma-metastasis
#18
Ebru Aydin, Junko Johansson, Faisal Hayat Nazir, Kristoffer Hellstrand, Anna Martner
The NADPH oxidase of myeloid cells, NOX2, generates reactive oxygen species (ROS) to eliminate pathogens and malignant cells. NOX2-derived ROS also have been proposed to dampen functions of natural killer (NK) cells and other anti-neoplastic lymphocytes in the microenvironment of established tumors. The mechanisms by which NOX2 and ROS influence the process of distant metastasis have only been partially explored. Here we utilized genetically NOX2-deficient mice and pharmacological inhibition of NOX2 to elucidate the role of NOX2 for the hematogenous metastasis of melanoma cells...
July 31, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28759124/recent-advances-in-uveal-melanoma-treatment
#19
REVIEW
Beatriz Álvarez-Rodríguez, Alfonso Latorre, Christian Posch, Álvaro Somoza
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Recent advances in the understanding of molecular characteristics helped to determine which tumors are most likely to progress. About 50% of patients carrying genetic alterations such as chromosomal aberrations and mutations are at significant risk for metastatic disease of which the majority will succumb to UM within few months. Currently, there is no effective treatment for metastatic uveal melanoma, and we hope this review will encourage researchers and clinicians to work to find a better standard of care...
July 31, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28755520/genetic-variation-in-irf4-expression-modulates-growth-characteristics-tyrosinase-expression-and-interferon-gamma-response-in-melanocytic-cells
#20
Yash Chhabra, Hilary X L Yong, Mitchell E Fane, Arish Soogrim, Wen Lim, Dayana Nur Mahiuddin, Reuben S Q Kim, Melinda Ashcroft, Scott A Beatson, Stephen A Ainger, Darren J Smit, Kasturee Jagirdar, Graeme J Walker, Richard A Sturm, Aaron G Smith
A SNP within intron4 of the Interferon Regulatory Factor4 (IRF4) gene, rs12203592*C/T has been independently associated with pigmentation and age-specific effects on nevus count in European-derived populations. We have characterised the cis-regulatory activity of this intronic region and using human foreskin-derived melanoblast strains we have explored the correlation between IRF4 rs12203592 homozygous C/C and T/T genotypes with TYR enzyme activity, supporting its association with pigmentation traits. Further, higher IRF4 protein levels directed by the rs12203592*C allele were associated with increased basal proliferation but decreased cell viability following UVR, an etiological factor in melanoma development...
July 29, 2017: Pigment Cell & Melanoma Research
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