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Dirk Schadendorf, James Larkin, Jedd Wolchok, F Stephen Hodi, Vanna Chiarion-Sileni, Rene Gonzalez, Piotr Rutkowski, Jean-Jacques Grob, C Lance Cowey, Christopher Lao, John Wagstaff, Margaret K Callahan, Michael A Postow, Michael Smylie, Pier Francesco Ferrucci, Reinhard Dummer, Andrew Hill, Fiona Taylor, Javier Sabater, Dana Walker, Srividya Kotapati, Amy Abernethy, Georgina V Long
BACKGROUND: Nivolumab, a monoclonal antibody of immune checkpoint programmed death 1 on T cells (PD-1), combined with ipilimumab, an immune checkpoint cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, as combination therapy on the one hand and nivolumab as monotherapy on the other, have both demonstrated improved efficacy compared with ipilimumab alone in the CheckMate 067 study. However, the combination resulted in a higher frequency of grade 3/4 adverse events (AEs), which could result in diminished health-related quality of life (HRQoL)...
June 22, 2017: European Journal of Cancer
C Lance Cowey, Lisa Mahnke, Janet Espirito, Christoph Helwig, Dina Oksen, Murtuza Bharmal
AIM: This retrospective study of patients in the USA with metastatic Merkel cell carcinoma (mMCC) aimed to assess patient responses to second-line and later (2L+) and first-line (1L) chemotherapy. PATIENTS & METHODS: Out of 686 patients with MCC identified in The US Oncology Network, 20 and 67 patients with mMCC qualified for the 2L+ and 1L study, respectively; the primary analysis population was restricted to immunocompetent patients. RESULTS: In the 2L+ primary analysis population, objective response rate (ORR) was 28...
June 13, 2017: Future Oncology
Shaveta Mulla, Susan Stirling, Sarah Cowey, Rosie Close, Sara Pullan, Rosalind Howe, Lynne Radbone, Paul Clarke
OBJECTIVE: To compare in two epochs of differing phosphate provision serum calcium, phosphate, potassium, and sodium concentrations and the frequency of abnormality of these electrolytes and of sepsis in preterm infants who received an optimised higher amino acid-content formulation. DESIGN AND SETTING: Retrospective cohort study at a single tertiary-level neonatal unit. PATIENTS: Preterm infants given parenteral nutrition (PN) in the first postnatal week during two discrete 6-month epochs in 2013-2014...
April 29, 2017: Archives of Disease in Childhood. Fetal and Neonatal Edition
C L Cowey, L Mahnke, J Espirito, P Fox, C Helwig, D Oksen, M Bharmal
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Anne Rowat, Alex Pollock, Bridget St George, Eileen Cowey, Joanne Booth, Maggie Lawrence
AIM: To determine the top 10 research priorities specific to stroke nursing. BACKGROUND: It is important that stroke nurses build their research capability and capacity. This project built on a previous James Lind Alliance prioritization project, which established the shared stroke research priorities of stroke survivors, carers and health professionals. DESIGN: Research priority setting project using James Lind Alliance methods; a survey for interim prioritization and a consensus meeting for final priority setting...
November 2016: Journal of Advanced Nursing
Lijo John, C Lance Cowey
For decades, no cancer therapy had been shown to improve average survival in metastatic melanoma. Two critical events have occurred, the discovery of melanoma driver mutation subsets and the discovery of immune checkpoint inhibitors, which have allowed for the development of modern, effective therapies. These findings have facilitated a rapid emergence of novel therapeutics for the disease with multiple FDA approvals in the last several years. The drugs vemurafenib, trametinib, and dabrafenib, which inhibit the commonly mutated BRAF pathway, have been approved based on improvements in survival outcomes...
September 2015: Dermatology and Therapy
Simiao Wu, Mansur A Kutlubaev, Ho-Yan Y Chun, Eileen Cowey, Alex Pollock, Malcolm R Macleod, Martin Dennis, Elizabeth Keane, Michael Sharpe, Gillian E Mead
BACKGROUND: Post-stroke fatigue (PSF) is a common and distressing problem after stroke. The best ways to prevent or treat PSF are uncertain. Several different interventions can be argued to have a rational basis. OBJECTIVES: To determine whether, among people with stroke, any intervention reduces the proportion of people with fatigue, fatigue severity, or both; and to determine the effect of intervention on health-related quality of life, disability, dependency and death, and whether such intervention is cost effective...
July 2, 2015: Cochrane Database of Systematic Reviews
Patricia M LoRusso, Scott A Boerner, Mary Jo Pilat, Karen M Forman, Clarice Y Zuccaro, Jeffrey A Kiefer, Winnie S Liang, Sally Hunsberger, Bruce G Redman, Svetomir N Markovic, Aleksandar Sekulic, Alan H Bryce, Richard W Joseph, C Lance Cowey, Leslie Anne Fecher, Jeffrey Alan Sosman, Paul B Chapman, Gary K Schwartz, David W Craig, John D Carpten, Jeffrey M Trent
Targeted therapies and immunotherapies have led to significant improvements in the treatment of advanced cancers, including metastatic melanoma. However, new strategies are desperately needed to overcome therapeutic resistance to these agents, as well as to identify effective treatment approaches for cancer patients that fall outside major targetable mutational subtypes (e.g., non-V600 BRAF melanoma). One such strategy is to extend the paradigm of individually tailored, molecularly targeted therapy into a broader spectrum of melanoma patients, particularly those bearing tumors without commonly recognized therapeutic targets, as well as having failed or were ineligible for immunotherapy...
August 2015: Molecular Cancer Therapeutics
James Larkin, Vanna Chiarion-Sileni, Rene Gonzalez, Jean Jacques Grob, C Lance Cowey, Christopher D Lao, Dirk Schadendorf, Reinhard Dummer, Michael Smylie, Piotr Rutkowski, Pier F Ferrucci, Andrew Hill, John Wagstaff, Matteo S Carlino, John B Haanen, Michele Maio, Ivan Marquez-Rodas, Grant A McArthur, Paolo A Ascierto, Georgina V Long, Margaret K Callahan, Michael A Postow, Kenneth Grossmann, Mario Sznol, Brigitte Dreno, Lars Bastholt, Arvin Yang, Linda M Rollin, Christine Horak, F Stephen Hodi, Jedd D Wolchok
BACKGROUND: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. METHODS: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone...
July 2, 2015: New England Journal of Medicine
Devin B Terhune, Elizabeth Murray, Jamie Near, Charlotte J Stagg, Alan Cowey, Roi Cohen Kadosh
Phosphenes are illusory visual percepts produced by the application of transcranial magnetic stimulation to occipital cortex. Phosphene thresholds, the minimum stimulation intensity required to reliably produce phosphenes, are widely used as an index of cortical excitability. However, the neural basis of phosphene thresholds and their relationship to individual differences in visual cognition are poorly understood. Here, we investigated the neurochemical basis of phosphene perception by measuring basal GABA and glutamate levels in primary visual cortex using magnetic resonance spectroscopy...
November 2015: Cerebral Cortex
Eileen Cowey, Lorraine N Smith, David J Stott, Christine H McAlpine, Gillian E Mead, Mark Barber, Matthew Walters
BACKGROUND: Death after stroke is common, but little is known about end-of-life care processes in acute stroke units. AIM: (1) To identify family and health-care worker perceptions of an end-of-life care pathway for patients who die after acute stroke. (2) To determine whether patients with fatal stroke judged to require an end-of-life care pathway differ from patients with fatal stroke who die without introduction of such a pathway. DESIGN: Mixed methods study integrating qualitative semistructured interviews with quantitative casenote review...
March 2015: Palliative Medicine
R E Passingham, A Chung, B Goparaju, A Cowey, L M Vaina
Humans have a sophisticated knowledge of the actions that can be performed with objects. In an fMRI study we tried to establish whether this depends on areas that are homologous with the inferior parietal cortex (area PFG) in macaque monkeys. Cells have been described in area PFG that discharge differentially depending upon whether the observer sees an object being brought to the mouth or put in a container. In our study the observers saw videos in which the use of different objects was demonstrated in pantomime; and after viewing the videos, the subject had to pick the object that was appropriate to the pantomime...
September 25, 2014: Brain Research
Sara D Robinson, Joyce A O'Shaughnessy, C Lance Cowey, Kartik Konduri
Somatic BRAF mutations have been reported in 1-4% of non-small cell lung cancer (NSCLC), primarily in adenocarcinomas with the BRAF (V600E) mutation in about 50% of the cases. The role of BRAF mutation in NSCLC and the treatment for tumors with such mutations is still evolving. Our patient had metastatic NSCLC with metastases to her brain. Due to the BRAF (V600E) mutation in her tumor and her poor functional status, we offered her off-label treatment with vemurafenib, a BRAF inhibitor approved for use in metastatic melanoma...
August 2014: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Alexandra Arreola, C Lance Cowey, Jonathan L Coloff, Jeffrey C Rathmell, W Kimryn Rathmell
BACKGROUND: Hypoxia Inducible Factors (HIF1α and HIF2α) are commonly stabilized and play key roles related to cell growth and metabolic programming in clear cell renal cell carcinoma. The relationship of these factors to discretely alter cell metabolic activities has largely been described in cancer cells, or in hypoxic conditions, where other confounding factors undoubtedly compete. These transcription factors and their specific roles in promoting cancer metabolic phenotypes from the earliest stages are poorly understood in pre-malignant cells...
2014: PloS One
Lawrence Flaherty, Omid Hamid, Gerald Linette, Lynn Schuchter, Sigrun Hallmeyer, Rene Gonzalez, C Lance Cowey, Anna Pavlick, Fred Kudrik, Brendan Curti, David Lawson, Paul B Chapman, Kim Margolin, Antoni Ribas, David McDermott, Keith Flaherty, Lee Cranmer, F Stephen Hodi, Bann-Mo Day, Rolf Linke, John Hainsworth
PURPOSE: This open-label, multicenter study was designed to allow access to vemurafenib for patients with metastatic melanoma, bridging the time between end of enrollment in the phase III registration trial (December 2010) and commercial availability following US Food and Drug Administration approval of vemurafenib for the treatment of unresectable or metastatic BRAF-mutated melanoma (August 2011). PATIENTS AND METHODS: Eligible patients had metastatic melanoma with a BRAF mutation (detected by the cobas 4800 BRAF V600 Mutation Test)...
January 2014: Cancer Journal
Alan Cowey
No abstract text is available yet for this article.
February 26, 2008: Current Biology: CB
Antoni Ribas, Weijiang Zhang, Ilsung Chang, Keisuke Shirai, Marc S Ernstoff, Adil Daud, C Lance Cowey, Gregory Daniels, Elizabeth Seja, Elizabeth O'Laco, John A Glaspy, Bartosz Chmielowski, Todd Hill, Andrew K Joe, Joseph F Grippo
Vemurafenib is an orally bioavailable BRAF inhibitor approved for the treatment of BRAF(V600) -mutant metastatic melanoma. It is important to understand the effects of a high-fat meal on the pharmacokinetics (PK) of vemurafenib in humans because it is a Biopharmaceutics Classification System Class IV drug and its PK can be altered by food. An open-label, multicenter, randomized, 2-period crossover study was performed to evaluate the effect of food (high-fat meal) on the PK of a single oral dose of vemurafenib...
April 2014: Journal of Clinical Pharmacology
Lucia M Vaina, Sergei Soloviev, Finnegan J Calabro, Ferdinando Buonanno, Richard Passingham, Alan Cowey
We studied patient JS, who had a right occipital infarct that encroached on visual areas V1, V2v, and VP. When tested psychophysically, he was very impaired at detecting the direction of motion in random dot displays where a variable proportion of dots moving in one direction (signal) were embedded in masking motion noise (noise dots). The impairment on this motion coherence task was especially marked when the display was presented to the upper left (affected) visual quadrant, contralateral to his lesion. However, with extensive training, by 11 months his threshold fell to the level of healthy participants...
June 2014: Journal of Cognitive Neuroscience
C B Cowey
The multi-level defence system present in vertebrate cells to protect against chain reactions initiated by free radicals (mainly toxic metabolites of oxygen) is outlined. It comprises superoxide dismutases (Cu-Zn and Mn dependent), glutathione peroxidase (Se dependent), vitamin E and glutathione S-transferase.The protective role of superoxide dismutase (SOD) was demonstrated by studies on trout (Salmo gairdneri) retina (Desrochers and Hoffert 1983). This tissue is subject to very high O2 tensions but has a high resistance to O2 toxicity that is dependent on a high dismutating capacity...
October 1986: Fish Physiology and Biochemistry
M J Walton, C B Cowey, R M Coloso, J W Adron
Three separate studies were performed to determine the dietary requirements of rainbow troutSalmo gairdneri for tryptophan (Trp), lysine (Lys) and arginine (Arg) from both growth and biochemical data. The growth studies were carried out over a 12 week period. From graphical plots of % mean weight gain against % amino acid in diet the following requirement values were obtained, Trp 0.25% diet (0.4% dietary crude protein); Lys 1.9% diet (4.3% dietary protein); and Arg 1.6-1.8% diet (3.6-4% dietary protein). Plasma and liver amino acid concentrations measured 20h after feeding did not prove useful for determination of requirement values...
October 1986: Fish Physiology and Biochemistry
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