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https://www.readbyqxmd.com/read/28097822/synthetic-lethality-emerging-targets-and-opportunities-in-melanoma
#1
REVIEW
Nicola Thompson, David Adams, Marco Ranzani
Great progress has been made in the treatment of melanoma through use of targeted therapies and immunotherapy. One approach that has not been fully explored is synthetic lethality, which exploits somatically acquired changes, usually driver mutations, to specifically kill tumour cells. We outline the various approaches that may be applied to identify synthetic lethal interactions and define how these interactions may drive drug discovery efforts. This article is protected by copyright. All rights reserved.
January 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28067894/unexpected-uvr-and-non-uvr-mutation-burden-in-some-acral-and-cutaneous-melanomas
#2
Robert V Rawson, Peter A Johansson, Nicholas K Hayward, Nicola Waddell, Ann-Marie Patch, Serigne Lo, John V Pearson, John F Thompson, Graham J Mann, Richard A Scolyer, James S Wilmott
Ultraviolet radiation (UVR) mutagenesis causes nearly all cutaneous melanomas, however, since UVR signatures are largely absent in acral melanoma, as well as melanoma in sun-protected sites, the cause of these melanomas is unknown. Whole-genome sequencing data generated as part of the Australian Melanoma Genome Project was supplemented with a detailed histopathological assessment with the melanomas then classified as UVR or non-UVR related, based on their mutation signatures. The clinicopathological characteristics of melanomas with mutation signatures for their subtype were compared...
January 9, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28060373/small-round-blue-cell-tumors-of-the-sinonasal-tract-a-differential-diagnosis-approach
#3
Lester Dr Thompson
One of the most challenging diagnostic categories within tumors of the sinonasal tract is the small round blue cell tumors. Biopsies are usually small and limited, resulting in considerable diagnostic difficulty for practicing surgical pathologists. These tumors share several overlapping histologic and immunophenotypic findings while also showing considerable variation within and between cases. Specific tumor site of origin, imaging findings, and clinical findings must be combined with the histology and pertinent ancillary studies if the correct diagnosis is to be reached...
January 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27829101/clinical-features-associated-with-individuals-at-higher-risk-of-melanoma-a-population-based-study
#4
Caroline G Watts, Christine Madronio, Rachael L Morton, Chris Goumas, Bruce K Armstrong, Austin Curtin, Scott W Menzies, Graham J Mann, John F Thompson, Anne E Cust
Importance: The identification of a subgroup at higher risk of melanoma may assist in early diagnosis. Objective: To characterize melanoma patients and the clinical features associated with their melanomas according to patient risk factors: many nevi, history of previous melanoma, and family history of melanoma, to assist with improving the identification and treatment of a higher-risk subgroup. Design, Setting, and Participants: The Melanoma Patterns of Care study was a population-based observational study of physicians' reported treatment of 2727 patients diagnosed with an in situ or invasive primary melanoma over a 12-month period from October 2006 to 2007 conducted in New South Wales...
January 1, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/27824739/effect-of-the-lymphocyte-to-monocyte-ratio-on-the-clinical-outcome-of-chemotherapy-administration-in-advanced-melanoma-patients
#5
Alexey A Leontovich, Roxana S Dronca, Wendy K Nevala, Michael A Thompson, Lisa A Kottschade, Leonid V Ivanov, Svetomir N Markovic
Skin cancer affects more individuals in the USA than any other malignancy and malignant melanoma is particularly deadly because of its metastatic potential. Melanoma has been recognized as one of the most immunogenic malignancies; therefore, understanding the mechanisms of tumor-immune interaction is key for developing more efficient treatments. As the tumor microenvironment shows an immunosuppressive action, immunotherapeutic agents promoting endogenous immune response to cancer have been tested (interleukin-2, anticytotoxic-T-lymphocyte-associated antigen 4, and antiprogrammed cell death protein 1 monoclonal antibodies) as well as combinations of cytotoxic chemotherapy agents and inhibitors of angiogenesis (taxol/carboplatin/avastin)...
February 2017: Melanoma Research
https://www.readbyqxmd.com/read/27779616/prime-boost-using-separate-oncolytic-viruses-in-combination-with-checkpoint-blockade-improves-anti-tumour-therapy
#6
E Ilett, T Kottke, J Thompson, K Rajani, S Zaidi, L Evgin, M Coffey, C Ralph, R Diaz, H Pandha, K Harrington, P Selby, R Bram, A Melcher, R Vile
The anti-tumour effects associated with oncolytic virus therapy are mediated significantly through immune-mediated mechanisms, which depend both on the type of virus and the route of delivery. Here, we show that intra-tumoral oncolysis by Reovirus induced the priming of a CD8+, Th1-type anti-tumour response. By contrast, systemically delivered Vesicular Stomatitis Virus expressing a cDNA library of melanoma antigens (VSV-ASMEL) promoted a potent anti-tumour CD4+ Th17 response. Therefore, we hypothesised that combining the Reovirus-induced CD8+ T cell response, with the VSV-ASMEL CD4+ Th17 helper response, would produce enhanced anti-tumour activity...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27748080/variants-in-autophagy-related-genes-and-clinical-characteristics-in-melanoma-a-population-based-study
#7
Kirsten A M White, Li Luo, Todd A Thompson, Salina Torres, Chien-An Andy Hu, Nancy E Thomas, Jenna Lilyquist, Hoda Anton-Culver, Stephen B Gruber, Lynn From, Klaus J Busam, Irene Orlow, Peter A Kanetsky, Loraine D Marrett, Richard P Gallagher, Lidia Sacchetto, Stefano Rosso, Terence Dwyer, Anne E Cust, Colin B Begg, Marianne Berwick
Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0...
November 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27689254/doctors-recognition-and-management-of-melanoma-patients-risk-an-australian-population-based-study
#8
C M Madronio, B K Armstrong, C G Watts, C Goumas, R L Morton, A Curtin, S W Menzies, G J Mann, J F Thompson, A E Cust
BACKGROUND: Guidelines recommend that health professionals identify and manage individuals at high risk of developing melanoma, but there is limited population-based evidence demonstrating real-world practices. OBJECTIVE: A population-based, observational study was conducted in the state of New South Wales, Australia to determine doctors' knowledge of melanoma patients' risk and to identify factors associated with better identification and clinical management. METHODS: Data were analysed for 1889 patients with invasive, localised melanoma in the Melanoma Patterns of Care study...
December 2016: Cancer Epidemiology
https://www.readbyqxmd.com/read/27686328/value-and-usability-of-unpublished-data-sources-for-systematic-reviews-and-network-meta-analyses
#9
Nicholas James Anthony Halfpenny, Joan Mary Quigley, Juliette Catherine Thompson, David Alexander Scott
Peer-reviewed publications and conference proceedings are the mainstay of data sources for systematic reviews and network meta-analyses (NMA), but access to informative unpublished data is now becoming commonplace. To explore the usefulness of three types of 'grey' literature-clinical trials registries, clinical study reports and data from regulatory authorities-we conducted four case studies. The reporting of outcome data in peer-reviewed publications, the clinical trials registries and the clinical study reports for two clinical trials-one in melanoma, one in juvenile idiopathic arthritis (JIA)-was examined...
September 29, 2016: Evidence-based Medicine
https://www.readbyqxmd.com/read/27598832/single-cell-analysis-of-human-tissues-and-solid-tumors-with-mass-cytometry
#10
Nalin Leelatian, Deon B Doxie, Allison R Greenplate, Bret C Mobley, Jonathan M Lehman, Justine Sinnaeve, Rondi M Kauffmann, Jay A Werkhaven, Akshitkumar M Mistry, Kyle D Weaver, Reid C Thompson, Pierre P Massion, Mary A Hooks, Mark C Kelley, Lola B Chambless, Rebecca A Ihrie, Jonathan M Irish
BACKGROUND: Mass cytometry measures 36 or more markers per cell and is an appealing platform for comprehensive phenotyping of cells in human tissue and tumor biopsies. While tissue disaggregation and fluorescence cytometry protocols were pioneered decades ago, it is not known whether established protocols will be effective for mass cytometry and maintain cancer and stromal cell diversity. METHODS: Tissue preparation techniques were systematically compared for gliomas and melanomas, patient derived xenografts of small cell lung cancer, and tonsil tissue as a control...
September 6, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27496110/nccn-guidelines-insights-melanoma-version-3-2016
#11
Daniel G Coit, John A Thompson, Alain Algazi, Robert Andtbacka, Christopher K Bichakjian, William E Carson, Gregory A Daniels, Dominick DiMaio, Ryan C Fields, Martin D Fleming, Brian Gastman, Rene Gonzalez, Valerie Guild, Douglas Johnson, Richard W Joseph, Julie R Lange, Mary C Martini, Miguel A Materin, Anthony J Olszanski, Patrick Ott, Aparna Priyanath Gupta, Merrick I Ross, April K Salama, Joseph Skitzki, Susan M Swetter, Kenneth K Tanabe, Javier F Torres-Roca, Vijay Trisal, Marshall M Urist, Nicole McMillian, Anita Engh
The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.
August 2016: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/27477217/diagnosis-and-clinical-management-of-melanoma-patients-at-higher-risk-of-a-new-primary-melanoma-a-population-based-study-in-new-south-wales-australia
#12
Caroline G Watts, Christine M Madronio, Rachael L Morton, Chris Goumas, Bruce K Armstrong, Austin Curtin, Scott W Menzies, Graham J Mann, John F Thompson, Anne E Cust
BACKGROUND/OBJECTIVES: To describe the method of diagnosis, clinical management and adherence to clinical practice guidelines for melanoma patients at high risk of a subsequent primary melanoma, and compare this with melanoma patients at lower risk. METHODS: The Melanoma Patterns of Care study was a population-based, observational study based on doctors' reported clinical management of melanoma patients in New South Wales, Australia, diagnosed with in situ or invasive melanoma over a 12-month period from October 2006...
August 1, 2016: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/27370683/debate-adjuvant-whole-brain-radiotherapy-or-not-more-data-is-the-wiser-choice
#13
Gerald B Fogarty, Angela Hong, Vinai Gondi, Bryan Burmeister, Kari Jacobsen, Serigne Lo, Elizabeth Paton, Brindha Shivalingam, John F Thompson
Every year 170,000 patients are diagnosed with brain metastases (BMs) in the United States. Traditionally, adjuvant whole brain radiotherapy (AWBRT) has been offered following local therapy with neurosurgery (NSx) and/or stereotactic radiosurgery (SRS) to BMs. The aim is to increase intracranial control, thereby decreasing symptoms from intracranial progression and a neurological death. There is a rapidly evolving change in the radiation treatment of BMs happening around the world. AWBRT is now being passed over in favour of repeat scanning at regular intervals and more local therapies as more BMs appear radiologically, BMs that may never become symptomatic...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27325798/high-ccl27-immunoreactivity-in-supratumoral-epidermis-correlates-with-better-prognosis-in-patients-with-cutaneous-malignant-melanoma
#14
Miguel Martinez-Rodriguez, Alec K Thompson, Carlos Monteagudo
AIMS: It has been proposed that the expression of chemokines and chemokine receptors by melanoma cells may have a role in tumour immune escape. Chemokine CCL27 is reported to be expressed specifically on the epidermal keratinocytes. The implication of CCL27 in cutaneous melanomas is currently unresolved. It has been suggested that CCL27 expression in melanomas can induce antitumoral immunity, and that CCL27 may suppress tumour growth probably due to the local lymphocyte recruitment. METHODS: We studied CCL27 chemokine expression in three different concentric epidermal areas covering the primary cutaneous melanoma in patients with a long clinical follow-up...
January 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27317515/epidemiology-of-genitourinary-melanoma-in-the-united-states-1992-through-2012
#15
Ritva Vyas, Cheryl L Thompson, Homayoun Zargar, Jacqueline Selph, Meg R Gerstenblith
BACKGROUND: Primary melanoma arising in the genitourinary tract is rare and poorly characterized. OBJECTIVES: We sought to describe the epidemiology of genitourinary melanoma in the United States. METHODS: Incident case and population data were obtained for genitourinary melanoma from the Surveillance, Epidemiology, and End Results 13 Registries Database between 1992 and 2012. RESULTS: A total of 817 patients with genitourinary melanoma were identified; most cases occurred in the vulva...
July 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27269940/t-cell-therapy-using-interleukin-21-primed-cytotoxic-t-cell-lymphocytes-combined-with-cytotoxic-t-cell-lymphocyte-antigen-4-blockade-results-in-long-term-cell-persistence-and-durable-tumor-regression
#16
Aude G Chapuis, Ilana M Roberts, John A Thompson, Kim A Margolin, Shailender Bhatia, Sylvia M Lee, Heather L Sloan, Ivy P Lai, Erik A Farrar, Felecia Wagener, Kendall C Shibuya, Jianhong Cao, Jedd D Wolchok, Philip D Greenberg, Cassian Yee
PURPOSE: Peripheral blood-derived antigen-specific cytotoxic T cells (CTLs) provide a readily available source of effector cells that can be administered with minimal toxicity in an outpatient setting. In metastatic melanoma, this approach results in measurable albeit modest clinical responses in patients resistant to conventional therapy. We reasoned that concurrent cytotoxic T-cell lymphocyte antigen-4 (CTLA-4) checkpoint blockade might enhance the antitumor activity of adoptively transferred CTLs...
June 6, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27242164/combined-il-21-primed-polyclonal-ctl-plus-ctla4-blockade-controls-refractory-metastatic-melanoma-in-a-patient
#17
Aude G Chapuis, Sylvia M Lee, John A Thompson, Ilana M Roberts, Kim A Margolin, Shailender Bhatia, Heather L Sloan, Ivy Lai, Felecia Wagener, Kendall Shibuya, Jianhong Cao, Jedd D Wolchok, Philip D Greenberg, Cassian Yee
Adoptive transfer of peripheral blood-derived, melanoma-reactive CD8(+) cytotoxic T lymphocytes (CTLs) alone is generally insufficient to eliminate bulky tumors. Similarly, monotherapy with anti-CTLA4 infrequently yields sustained remissions in patients with metastatic melanoma. We postulated that a bolus of enhanced IL-21-primed polyclonal antigen-specific CTL combined with CTLA4 blockade might boost antitumor efficacy. In this first-in-human case study, the combination successfully led to a durable complete remission (CR) in a patient whose disease was refractory to both monoclonal CTL and anti-CTLA4...
June 27, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27226502/major-changes-in-systemic-therapy-for-advanced-melanoma
#18
John A Thompson
Over the past 5 years, a host of new agents have radically changed the therapeutic landscape in advanced melanoma; gone are the days when the only active agents were interferon and dacarbazine. Nearly 25 years ago, few patients with stage IV melanoma reached 2-year survival; today, these survival curves have risen substantially. At the NCCN 21st Annual Conference, John A. Thompson, MD, discussed updates with longer duration of patient follow-up for immune checkpoint therapies. He also reviewed some of the newer approvals in advanced melanoma, including the combination of ipilimumab and nivolumab, high-dose ipilimumab, the oncolytic virus therapy talimogene laherparepvec, and the molecularly targeted combination of the BRAF and MEK inhibitors vemurafenib and cobimetinib...
May 2016: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/27182556/t-cell-bim-levels-reflect-responses-to-anti-pd-1-cancer-therapy
#19
Roxana S Dronca, Xin Liu, Susan M Harrington, Lingling Chen, Siyu Cao, Lisa A Kottschade, Robert R McWilliams, Matthew S Block, Wendy K Nevala, Michael A Thompson, Aaron S Mansfield, Sean S Park, Svetomir N Markovic, Haidong Dong
Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1(+)CD11a(hi)CD8(+)) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti-PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti-PD-1 therapy...
May 5, 2016: JCI Insight
https://www.readbyqxmd.com/read/27092829/pd-1-blockade-in-melanoma-a-promising-start-but-a-long-way-to-go
#20
EDITORIAL
Shailender Bhatia, John A Thompson
No abstract text is available yet for this article.
April 19, 2016: JAMA: the Journal of the American Medical Association
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