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Thompson melanoma

Antoneicka L Harris, Samantha E Lee, Louis K Dawson, Laura A Marlow, Brandy H Edenfield, William F Durham, Thomas J Flotte, Michael Thompson, Daniel L Small, Aidan J Synnott, Svetomir N Markovic, John A Copland
Patient-derived tumor xenograft (PDTX) mouse models were used to discover new therapies for naïve and drug resistant BRAF V600E -mutant melanoma. Tumor histology, oncogenic protein expression, and antitumor activity were comparable between patient and PDTX-matched models thereby validating PDTXs as predictive preclinical models of therapeutic response in patients. PDTX models responsive and non-responsive to BRAF/MEK standard of care (SOC) therapy were used to identify efficacious combination therapies. One such combination includes a CDK4/6 inhibitor that blocks cell cycle progression...
February 16, 2018: Oncotarget
Catherine M Olsen, Nirmala Pandeya, Bridie S Thompson, Jean Claude Dusingize, Penelope M Webb, Adele C Green, Rachel E Neale, David C Whiteman
Background: Risk stratification can improve the efficacy and cost-efficiency of screening programs for early detection of cancer. We sought to derive a risk stratification tool for melanoma that was suitable for the general population using only self-reported information. Methods: We used melanoma risk factor information collected at baseline from QSKIN, a prospective cohort study of Queensland adults age 40 to 69 years at recruitment (n = 41 954). We examined two separate outcomes: 1) invasive melanomas and 2) all melanomas (invasive + in situ) obtained through data linkage to the cancer registry...
March 11, 2018: Journal of the National Cancer Institute
Joshua Arbesman, Sairekha Ravichandran, Pauline Funchain, Cheryl L Thompson
Identifying novel melanoma genetic risk factors informs screening and prevention efforts. Mutations in the phenylalanine hydroxylase gene (the causative gene in phenylketonuria) lead to reduced pigmentation in untreated phenylketonuria patients, and reduced pigmentation is associated with greater melanoma risk. Therefore, we sought to characterize the relationship between phenylketonuria carrier status and melanoma risk. Using National Newborn Screening Reports, we determined the United States phenylketonuria/hyperphenylalanemia carrier frequency in Caucasians to be 1...
February 23, 2018: Pigment Cell & Melanoma Research
Michael J Sladden, Omgo E Nieweg, Julie Howle, Brendon J Coventry, John F Thompson
Definitive management of primary cutaneous melanoma consists of surgical excision of the melanoma with the aim of curing the patient. The melanoma is widely excised together with a safety margin of surrounding skin and subcutaneous tissue, after the diagnosis and Breslow thickness have been established by histological assessment of the initial excision biopsy specimen. Sentinel lymph node biopsy should be discussed for melanomas ≥ 1 mm thickness (≥ 0.8 mm if other high risk features) in which case lymphoscintigraphy must be performed before wider excision of the primary melanoma site...
February 19, 2018: Medical Journal of Australia
Samuel S Zagarella, Michael J Sladden, Catalin M Popescu, Michael E Bigby
No abstract text is available yet for this article.
February 7, 2018: Australasian Journal of Dermatology
Joshua R Veatch, Sylvia M Lee, Matthew Fitzgibbon, I-Ting Chow, Brenda Jesernig, Thomas Schmitt, Ying Ying Kong, Julia Kargl, A McGarry Houghton, John A Thompson, Martin McIntosh, William W Kwok, Stanley R Riddell
T cells specific for neoantigens encoded by mutated genes in cancers are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, most neoantigens result from random mutations and are patient specific, and some cancers contain few mutations to serve as potential antigens. We describe a patient with stage IV acral melanoma who obtained a complete response following adoptive transfer of tumor infiltrating lymphocytes (TIL). Tumor exome sequencing surprisingly revealed less than 30 somatic mutations, including oncogenic BRAF V600E...
January 23, 2018: Journal of Clinical Investigation
Michael B Atkins, F Stephen Hodi, John A Thompson, David McDermott, Wen-Jen Hwu, Donald P Lawrence, Nancy A Dawson, Deborah Jean Lee Wong, Shailender Bhatia, Marihella James, Lokesh Jain, Seth Robey, Xinxin Shu, Blanca Homet Moreno, Rodolfo F Perini, Toni K Choueiri, Antoni Ribas
PURPOSE: Pembrolizumab, ipilimumab, and pegylated interferon alfa-2b (PEG-IFN) monotherapy are active against melanoma and renal cell carcinoma (RCC). We explored the safety and preliminary antitumor activity of pembrolizumab combined with either ipilimumab or PEG-IFN in patients with advanced melanoma or RCC. EXPERIMENTAL DESIGN: The phase 1b KEYNOTE-029 study (, NCT02089685) included independent pembrolizumab plus reduced-dose ipilimumab and pembrolizumab plus PEG-IFN cohorts...
January 22, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Victoria White, Gemma Skaczkowski, Kate Thompson, Helen Bibby, Michael Coory, Ross Pinkerton, Wayne Nicholls, Lisa M Orme, Rachel Conyers, Marianne B Phillips, Michael Osborn, Rosemary Harrup, Antoinette Anazodo
PURPOSE: To examine the care experiences of Australian Adolescents and Young Adults (AYAs) with cancer during a period when youth cancer services (YCS) were developing across the country. METHODS: A cross-sectional, self-report survey completed by 207 recently diagnosed AYAs with cancer, recruited from the population-based cancer registries of Australia's two most populous states. AYAs were 15 to 24 years old when diagnosed with any form of cancer (except melanoma <3 mm or stage I/II)...
January 22, 2018: Journal of Adolescent and Young Adult Oncology
P M Ferguson, G V Long, R A Scolyer, J F Thompson
BACKGROUND: Although surgery for early-stage melanoma offers the best chance of cure, recent advances in molecular medicine have revolutionized the management of late-stage melanoma, leading to significant improvements in clinical outcomes. Research into the genomic drivers of disease and cancer immunology has not only ushered in a new era of targeted and immune-based therapies for patients with metastatic melanoma, but has also provided new tools for monitoring disease recurrence and selecting therapeutic strategies...
January 2018: British Journal of Surgery
Yan Sha, Vladimir Vartanian, Nichole Owen, Stephanie J Mengden Koon, Marcus J Calkins, Courtney S Thompson, Zahra Mirafzali, Sara Mir, Lisa E Goldsmith, Huaping He, Chun Luo, Scott M Brown, Paul W Doetsch, Andy Kaempf, Jeong Y Lim, Amanda K McCullough, R Stephen Lloyd
The molecular basis for ultraviolet (UV) light-induced nonmelanoma and melanoma skin cancers centers on cumulative genomic instability caused by inefficient DNA repair of dipyrimidine photoproducts. Inefficient DNA repair and subsequent translesion replication past these DNA lesions generate distinct molecular signatures of tandem CC to TT and C to T transitions at dipyrimidine sites. Since previous efforts to develop experimental strategies to enhance the repair capacity of basal keratinocytes have been limited, we have engineered the N-terminally truncated form (Δ228) UV endonuclease (UVDE) from Schizosaccharomyces pombe to include a TAT cell-penetrating peptide sequence with or without a nuclear localization signal (NLS): UVDE-TAT and UVDE-NLS-TAT...
January 15, 2018: Scientific Reports
Serigne N Lo, Richard A Scolyer, John F Thompson
BACKGROUND: Counterintuitively, more deaths from melanoma occur among patients with thin (T1) primary melanomas (≤ 1 mm) than among those with thick primary melanoma because the great majority present with T1 tumors. Therefore, it is important to stratify their risk as accurately as possible to guide their management and follow-up. This study sought to explore the relationship between tumor thickness and prognosis for patients with thin primary melanomas. METHODS: A retrospective, single-institution study investigated 6263 patients with cutaneous melanoma (including 2117 T1 cases) who had a minimum follow-up period of 10 years...
January 12, 2018: Annals of Surgical Oncology
Rebecca L Read, Christine M Madronio, Anne E Cust, Chris Goumas, Caroline G Watts, Scott Menzies, Austin M Curtin, Graham Mann, John F Thompson, Rachael L Morton
BACKGROUND: Follow-up practices after diagnosis and treatment of primary cutaneous melanoma vary considerably. We aimed to determine factors associated with recommendations for follow-up setting, frequency, skin surveillance, and concordance with clinical guidelines. METHODS: The population-based Melanoma Patterns of Care study documented clinicians' recommendations for follow-up for 2148 patients diagnosed with primary cutaneous melanoma over a 12-month period (2006/2007) in New South Wales, Australia...
January 3, 2018: Annals of Surgical Oncology
Gemma Skaczkowski, Victoria White, Kate Thompson, Helen Bibby, Michael Coory, Ross Pinkerton, Lisa M Orme, Rachel Conyers, Marianne B Phillips, Michael Osborn, Rosemary Harrup, Antoinette Anazodo
OBJECTIVE: To examine the relationship between the cancer care experiences of adolescents and young adults (AYAs) and their quality of life. METHODS: 209 AYAs completed a cross-sectional, self-report survey distributed through the population-based cancer registries in two Australian states (New South Wales and Victoria). Eligible AYAs were diagnosed at 15-24 years old with any cancer (excluding early stage melanoma) and were 3-24 months post-diagnosis. Questions examined whether particular care experiences occurred for the patient at different points in the cancer care pathway, including diagnosis, treatment, inpatient care and at the end of treatment...
December 26, 2017: Psycho-oncology
Evan S Weitman, Matthew Perez, John F Thompson, Robert H I Andtbacka, Jo Dalton, Mona L Martin, Talia Miller, Chad Gwaltney, David Sarson, Eric Wachter, Jonathan S Zager
Locally advanced cutaneous melanoma has marked quality-of-life implications; however, the patient experience of symptom management and subsequent impact on quality of life has not been well described. This study aims to address the impact on patients of advanced cutaneous melanoma through qualitative interviews. Adults with stage IIIB, IIIC, or IV (M1a) cutaneous melanoma were recruited from two cancer centers in the USA and one in Australia. Telephone interviews were conducted to assess how locoregionally advanced cutaneous melanoma impacted everyday life...
December 19, 2017: Melanoma Research
Tristan J Dodds, Serigne Lo, Louise Jackett, Omgo Nieweg, John F Thompson, Richard A Scolyer
Tumor thickness is the strongest predictor of outcome for clinically localized melanoma. Therefore, accurate assessment is critical for appropriate staging, reliable estimation of prognosis, and management. When melanoma extends alongside skin adnexal structures more deeply than the main tumor mass (periadnexal extension), it is currently unknown whether the prognosis is more accurately reflected by the deepest point of periadnexal tumor extension or the main tumor mass. This study sought to address this question...
December 7, 2017: American Journal of Surgical Pathology
Erin K Sykes, Cassandra E McDonald, Shila Ghazanfar, Swetlana Mactier, John F Thompson, Richard A Scolyer, Jean Y Yang, Graham J Mann, Richard I Christopherson
PURPOSE: To validate differences in protein levels between good and poor prognosis American Joint Committee on Cancer (AJCC) stage III melanoma patients and compile a protein panel to stratify patient risk. EXPERIMENTAL DESIGN: Protein extracts from melanoma metastases within lymph nodes in patients with stage III disease with good (n = 16, >4 years survival) and poor survival (n = 14, <2 years survival) were analyzed by selected reaction monitoring (SRM)...
December 11, 2017: Proteomics. Clinical Applications
Eleanor Clancy-Thompson, Lestat Ali, Patrick T Bruck, Mark A Exley, Richard S Blumberg, Glenn Dranoff, Michael Dougan, Stephanie K Dougan
Inhibitor of apoptosis protein (IAP) antagonists are in clinical trials for a variety of cancers, and mouse models show synergism between IAP antagonists and anti-PD-1 immunotherapy. Although IAP antagonists affect the intrinsic signaling of tumor cells, their most pronounced effects are on immune cells and the generation of antitumor immunity. Here, we examined the effects of IAP antagonism on T-cell development using mouse fetal thymic organ culture and observed a selective loss of iNKT cells, an effector cell type of potential importance for cancer immunotherapy...
January 2018: Cancer Immunology Research
Kelly G Paulson, Song Youn Park, Natalie A Vandeven, Kristina Lachance, Hannah Thomas, Aude G Chapuis, Kelly L Harms, John A Thompson, Shailender Bhatia, Andreas Stang, Paul Nghiem
BACKGROUND: Merkel cell carcinoma (MCC) incidence rates are rising and strongly age-associated, relevant for an aging population. OBJECTIVE: Determine MCC incidence in the United States and project incident cases through the year 2025. METHODS: Registry data were obtained from the SEER-18 database, containing 6,600 MCC cases. Age and sex-adjusted projections were generated utilizing US census data. RESULTS: Between 2000-2013, there was a 95% increase in the number of reported MCC cases, compared to 57% for melanoma and 15% for all 'solid' cancers...
November 1, 2017: Journal of the American Academy of Dermatology
Jeffrey E Gershenwald, Richard A Scolyer, Kenneth R Hess, Vernon K Sondak, Georgina V Long, Merrick I Ross, Alexander J Lazar, Mark B Faries, John M Kirkwood, Grant A McArthur, Lauren E Haydu, Alexander M M Eggermont, Keith T Flaherty, Charles M Balch, John F Thompson
Answer questions and earn CME/CNE To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria...
November 2017: CA: a Cancer Journal for Clinicians
Victoria J Mar, Alex J Chamberlain, John W Kelly, William K Murray, John F Thompson
A Cancer Council Australia multidisciplinary working group is currently revising and updating the 2008 evidence-based clinical practice guidelines for the management of cutaneous melanoma. While there have been many recent improvements in treatment options for metastatic melanoma, early diagnosis remains critical to reducing mortality from the disease. Improved awareness of the atypical presentations of this common malignancy is required to achieve this. A chapter of the new guidelines was therefore developed to aid recognition of atypical melanomas...
October 16, 2017: Medical Journal of Australia
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