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https://www.readbyqxmd.com/read/29760563/durvalumab-a-potential-maintenance-therapy-in-surgery-ineligible-non-small-cell-lung-cancer
#1
REVIEW
Michael R Shafique, Lary A Robinson, Scott Antonia
Lung cancer is the most common cancer worldwide and the most common cause of cancer-related death. Non-small-cell lung cancer comprises ~87% of newly diagnosed cases of lung cancer, and nearly one-third of these patients have stage III disease. Despite improvements in the treatment of stage IV lung cancer, particularly with the introduction and dissemination of checkpoint inhibitors, very little progress has been made in the treatment of stage III lung cancer. In this article, we discuss the general staging criteria and treatment options for stage III lung cancer...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29731394/tumor-mutational-burden-and-efficacy-of-nivolumab-monotherapy-and-in-combination-with-ipilimumab-in-small-cell-lung-cancer
#2
Matthew D Hellmann, Margaret K Callahan, Mark M Awad, Emiliano Calvo, Paolo A Ascierto, Akin Atmaca, Naiyer A Rizvi, Fred R Hirsch, Giovanni Selvaggi, Joseph D Szustakowski, Ariella Sasson, Ryan Golhar, Patrik Vitazka, Han Chang, William J Geese, Scott J Antonia
Durable responses and encouraging survival have been demonstrated with immune checkpoint inhibitors in small-cell lung cancer (SCLC), but predictive markers are unknown. We used whole exome sequencing to evaluate the impact of tumor mutational burden on efficacy of nivolumab monotherapy or combined with ipilimumab in patients with SCLC from the nonrandomized or randomized cohorts of CheckMate 032. Patients received nivolumab (3 mg/kg every 2 weeks) or nivolumab plus ipilimumab (1 mg/kg plus 3 mg/kg every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks)...
April 21, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29688290/gestational-age-is-dimensionally-associated-with-structural-brain-network-abnormalities-across-development
#3
Rula Nassar, Antonia N Kaczkurkin, Cedric Huchuan Xia, Aristeidis Sotiras, Marieta Pehlivanova, Tyler M Moore, Angel Garcia de La Garza, David R Roalf, Adon F G Rosen, Scott A Lorch, Kosha Ruparel, Russell T Shinohara, Christos Davatzikos, Ruben C Gur, Raquel E Gur, Theodore D Satterthwaite
Prematurity is associated with diverse developmental abnormalities, yet few studies relate cognitive and neurostructural deficits to a dimensional measure of prematurity. Leveraging a large sample of children, adolescents, and young adults (age 8-22 years) studied as part of the Philadelphia Neurodevelopmental Cohort, we examined how variation in gestational age impacted cognition and brain structure later in development. Participants included 72 preterm youth born before 37 weeks' gestation and 206 youth who were born at term (37 weeks or later)...
April 21, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29657128/genomic-features-of-response-to-combination-immunotherapy-in-patients-with-advanced-non-small-cell-lung-cancer
#4
Matthew D Hellmann, Tavi Nathanson, Hira Rizvi, Benjamin C Creelan, Francisco Sanchez-Vega, Arun Ahuja, Ai Ni, Jacki B Novik, Levi M B Mangarin, Mohsen Abu-Akeel, Cailian Liu, Jennifer L Sauter, Natasha Rekhtman, Eliza Chang, Margaret K Callahan, Jamie E Chaft, Martin H Voss, Megan Tenet, Xue-Mei Li, Kelly Covello, Andrea Renninger, Patrik Vitazka, William J Geese, Hossein Borghaei, Charles M Rudin, Scott J Antonia, Charles Swanton, Jeff Hammerbacher, Taha Merghoub, Nicholas McGranahan, Alexandra Snyder, Jedd D Wolchok
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent of PD-L1 expression and the strongest feature associated with efficacy in multivariable analysis...
April 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29607448/silicone-wristbands-compared-with-traditional-polycyclic-aromatic-hydrocarbon-exposure-assessment-methods
#5
Holly M Dixon, Richard P Scott, Darrell Holmes, Lehyla Calero, Laurel D Kincl, Katrina M Waters, David E Camann, Antonia M Calafat, Julie B Herbstman, Kim A Anderson
Currently there is a lack of inexpensive, easy-to-use technology to evaluate human exposure to environmental chemicals, including polycyclic aromatic hydrocarbons (PAHs). This is the first study in which silicone wristbands were deployed alongside two traditional personal PAH exposure assessment methods: active air monitoring with samplers (i.e., polyurethane foam (PUF) and filter) housed in backpacks, and biological sampling with urine. We demonstrate that wristbands worn for 48 h in a non-occupational setting recover semivolatile PAHs, and we compare levels of PAHs in wristbands to PAHs in PUFs-filters and to hydroxy-PAH (OH-PAH) biomarkers in urine...
April 2, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29601185/lead-diversification-at-the-nanomole-scale-using-liver-microsomes-and-quantitative-nuclear-magnetic-resonance-spectroscopy-application-to-phosphodiesterase-2-inhibitors
#6
R Scott Obach, Gregory S Walker, Raman Sharma, Stephen Jenkinson, Tuan P Tran, Antonia F Stepan
In this report, we describe a method whereby lead molecules can be converted into several new analogues each using liver microsomes. Less than 1 micromole of substrate is incubated with liver microsomes (mouse, rat, hamster, guinea pig, rabbit, dog, monkey, or human) to produce multiple products which are isolated and analyzed by quantitative cryomicroprobe NMR (qNMR) spectroscopy. The solutions from qNMR analysis were then used as stocks that were diluted into biochemical assays. Nine human phosphodiesterase-2 (PDE2) inhibitors yielded 36 new analogues...
March 30, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29599543/corrigendum-assessing-national-biodiversity-trends-for-rocky-and-coral-reefs-through-the-integration-of-citizen-science-and-scientific-monitoring-programs
#7
Rick D Stuart-Smith, Graham J Edgar, Neville S Barrett, Amanda E Bates, Susan C Baker, Nicholas J Bax, Mikel A Becerro, Just Berkhout, Julia L Blanchard, Daniel J Brock, Graeme F Clark, Antonia T Cooper, Tom R Davis, Paul B Day, J Emmett Duffy, Thomas H Holmes, Steffan A Howe, Alan Jordan, Stuart Kininmonth, Nathan A Knott, Jonathan S Lefcheck, Scott D Ling, Amanda Parr, Elisabeth Strain, Hugh Sweatman, Russell Thomson
[This corrects the article DOI: 10.1093/biosci/biw180.].
August 1, 2017: Bioscience
https://www.readbyqxmd.com/read/29570421/five-year-follow-up-of-nivolumab-in-previously-treated-advanced-non-small-cell-lung-cancer-results-from-the-ca209-003-study
#8
Scott Gettinger, Leora Horn, David Jackman, David Spigel, Scott Antonia, Matthew Hellmann, John Powderly, Rebecca Heist, Lecia V Sequist, David C Smith, Philip Leming, William J Geese, Dennis Yoon, Ang Li, Julie Brahmer
Purpose In two phase III studies, nivolumab, a programmed death-1 (PD-1) inhibitor antibody, improved overall survival (OS) versus docetaxel in pretreated advanced non-small-cell lung cancer (NSCLC). We report 5-year follow-up results from an early phase I study of nivolumab in this patient population and describe characteristics of 5-year survivors. Patients and Methods Patients with pretreated, advanced NSCLC received nivolumab 1, 3, or 10 mg/kg every 2 weeks in 8-week cycles for up to 96 weeks. OS from the time of first dose was estimated by the Kaplan-Meier method...
March 23, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29515795/a-phase-1-2-study-of-adenovirus-p53-transduced-dendritic-cell-vaccine-in-combination-with-indoximod-in-metastatic-solid-tumors-and-invasive-breast-cancer
#9
Hatem Soliman, Fatema Khambati, Hyo S Han, Roohi Ismail-Khan, Marilyn M Bui, Daniel M Sullivan, Scott Antonia
Background: Indoleamine 2, 3-dioxygenase is an enzyme that causes immunosuppression in tumors. Indoximod inhibits the indoleamine 2, 3-dioxygenase pathway and enhances immunologic responses to dendritic cell (DC) vaccines preclinically. Adenovirus p53 (Ad.p53) is used to generate DC vaccines against p53. A phase-1/2 trial of indoximod with Ad.p53-DC vaccine was conducted. Materials and Methods: The phase-1 study combined 7 indoximod dose levels with < 6 Ad.p53-DC vaccinations every 2 weeks...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29456790/late-stage-microsomal-oxidation-reduces-drug-drug-interaction-and-identifies-phosphodiesterase-2a-inhibitor-pf-06815189
#10
Antonia F Stepan, Tuan P Tran, Christopher J Helal, Maria S Brown, Cheng Chang, Rebecca E O'Connor, Michael De Vivo, Shawn D Doran, Ethan L Fisher, Stephen Jenkinson, David Karanian, Bethany L Kormos, Raman Sharma, Gregory S Walker, Ann S Wright, Edward X Yang, Michael A Brodney, Travis T Wager, Patrick R Verhoest, R Scott Obach
Late-stage oxidation using liver microsomes was applied to phosphodiesterase 2 inhibitor 1 to reduce its clearance by cytochrome P450 enzymes, introduce renal clearance, and minimize the risk for victim drug-drug interactions. This approach yielded PF-06815189 ( 2 ) with improved physicochemical properties and a mixed metabolic profile. This example highlights the importance of C-H diversification methods to drug discovery.
February 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29332322/tumor-immunology-and-immune-checkpoint-inhibitors-in-non-small-cell-lung-cancer
#11
REVIEW
Chi Young Jung, Scott J Antonia
Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%-20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer...
January 2018: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29259892/transition-from-early-intervention-program-to-primary-school-in-children-with-autism-spectrum-disorder
#12
Valsamma Eapen, Rachel Grove, Elizabeth Aylward, Annette V Joosten, Scott I Miller, Gerdamari Van Der Watt, Kathryn Fordyce, Cheryl Dissanayake, Jacqueline Maya, Madonna Tucker, Antonia DeBlasio
AIM: To evaluate the characteristics that are associated with successful transition to school outcomes in preschool aged children with autism. METHODS: Twenty-one participants transitioning from an early intervention program were assessed at two time points; at the end of their preschool placement and approximately 5 mo later following their transition to school. Child characteristics were assessed using the Mullen Scales of Early Learning, Vineland Adaptive Behaviour Scales, Social Communication Questionnaire and the Repetitive Behaviour Scale...
November 8, 2017: World Journal of Clinical Pediatrics
https://www.readbyqxmd.com/read/29195718/patient-caregiver-and-physician-perspectives-on-participating-in-a-thoracic-rapid-tissue-donation-program
#13
Gwendolyn P Quinn, Rebecca D Pentz, Teresita Muñoz-Antonia, Theresa A Boyle, Matthew B Schabath, Christie L Pratt, Andrea Shaffer, Luisa F Duarte, Meghan Bowman-Curci, Scott J Antonia, Alberto A Chiappori, Benjamin C Creelan, Jhanelle E Gray, Charles C Williams, Eric B Haura
OBJECTIVE: The collection of posthumous tissue from advanced stage lung cancer patients is beneficial to medical science. Recruiting living patients to a Rapid Tissue Donation Program (RTD) poses several psychosocial challenges and little is known about perceptions of joining this type of program. This study qualitatively examined perceptions of advanced stage lung cancer patients (n=14) participating in a lung cancer RTD program, their NoK (n=11), and physicians (n=6) at the Thoracic Oncology Clinic at H...
November 28, 2017: Patient Education and Counseling
https://www.readbyqxmd.com/read/29179442/a-bayesian-pick-the-winner-design-in-a-randomized-phase-ii-clinical-trial
#14
Dung-Tsa Chen, Po-Yu Huang, Hui-Yi Lin, Alberto A Chiappori, Dmitry I Gabrilovich, Eric B Haura, Scott J Antonia, Jhanelle E Gray
Purpose: Many phase II clinical trials evaluate unique experimental drugs/combinations through multi-arm design to expedite the screening process (early termination of ineffective drugs) and to identify the most effective drug (pick the winner) to warrant a phase III trial. Various statistical approaches have been developed for the pick-the-winner design but have been criticized for lack of objective comparison among the drug agents. Methods: We developed a Bayesian pick-the-winner design by integrating a Bayesian posterior probability with Simon two-stage design in a randomized two-arm clinical trial...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156764/the-neil1-g83d-germline-dna-glycosylase-variant-induces-genomic-instability-and-cellular-transformation
#15
Heather A Galick, Carolyn G Marsden, Scott Kathe, Julie A Dragon, Lindsay Volk, Antonia A Nemec, Susan S Wallace, Aishwarya Prakash, Sylvie Doublié, Joann B Sweasy
Base excision repair (BER) is a key genome maintenance pathway. The NEIL1 DNA glycosylase recognizes oxidized bases, and likely removes damage in advance of the replication fork. The rs5745906 SNP of the NEIL1 gene is a rare human germline variant that encodes the NEIL1 G83D protein, which is devoid of DNA glycosylase activity. Here we show that expression of G83D NEIL1 in MCF10A immortalized but non-transformed mammary epithelial cells leads to replication fork stress. Upon treatment with hydrogen peroxide, we observe increased levels of stalled replication forks in cells expressing G83D NEIL1 versus cells expressing the wild-type (WT) protein...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155933/pd-l1-antibodies-for-ebv-positive-gastric-cancer-going-beyond-pd-l1-expression-and-microsatellite-instability
#16
Khaldoun Almhanna, Scott Antonia
No abstract text is available yet for this article.
March 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29132271/capgras-syndrome-in-advanced-parkinson-s-disease
#17
Christopher L Groth, Antonia Pusso, Scott A Sperling, Diane S Huss, W Jeffrey Elias, G Frederick Wooten, Matthew J Barrett
Psychosis is common in Parkinson's disease (PD), especially in advanced disease, and can lead to a number of psychotic symptoms, including delusions. One uncommon delusion is Capgras syndrome (CS). The authors report on three PD patients with a history of deep brain stimulation (DBS) who developed this delusion. The anatomic targets in these three patients were the subthalamic nuclei in two patients and the globus pallidus interna in one patient. The length of time between surgery and development of CS varied but was greater than 6 months...
November 14, 2017: Journal of Neuropsychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29111213/prenatal-and-early-life-triclosan-and-paraben-exposure-and-allergic-outcomes
#18
Kathleen Lee-Sarwar, Russ Hauser, Antonia M Calafat, Xiaoyun Ye, George T O'Connor, Megan Sandel, Leonard B Bacharier, Robert S Zeiger, Nancy Laranjo, Diane R Gold, Scott T Weiss, Augusto A Litonjua, Jessica H Savage
BACKGROUND: In cross-sectional studies triclosan and parabens, ubiquitous ingredients in personal care and other products, are associated with allergic disease. OBJECTIVES: We investigated the association between prenatal and early-life triclosan and paraben exposure and childhood allergic disease in a prospective longitudinal study. METHODS: Subjects were enrollees in the Vitamin D Antenatal Asthma Reduction Trial. Triclosan, methyl paraben, and propyl paraben concentrations were quantified in maternal plasma samples pooled from the first and third trimesters and urine samples from children at age 3 or 4 years...
October 27, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29023463/learning-to-tie-the-knot-the-acquisition-of-functional-object-representations-by-physical-and-observational-experience
#19
Emily S Cross, Antonia F de C Hamilton, Nichola Rice Cohen, Scott T Grafton
Here we examined neural substrates for physically and observationally learning to construct novel objects, and characterized brain regions associated with each kind of learning using fMRI. Each participant was assigned a training partner, and for five consecutive days practiced tying one group of knots ("tied" condition) or watched their partner tie different knots ("watched" condition) while a third set of knots remained untrained. Functional MRI was obtained prior to and immediately following the week of training while participants performed a visual knot-matching task...
2017: PloS One
https://www.readbyqxmd.com/read/29023213/nivolumab-versus-docetaxel-in-previously-treated-patients-with-advanced-non-small-cell-lung-cancer-two-year-outcomes-from-two-randomized-open-label-phase-iii-trials-checkmate-017-and-checkmate-057
#20
RANDOMIZED CONTROLLED TRIAL
Leora Horn, David R Spigel, Everett E Vokes, Esther Holgado, Neal Ready, Martin Steins, Elena Poddubskaya, Hossein Borghaei, Enriqueta Felip, Luis Paz-Ares, Adam Pluzanski, Karen L Reckamp, Marco A Burgio, Martin Kohlhäeufl, David Waterhouse, Fabrice Barlesi, Scott Antonia, Oscar Arrieta, Jérôme Fayette, Lucio Crinò, Naiyer Rizvi, Martin Reck, Matthew D Hellmann, William J Geese, Ang Li, Anne Blackwood-Chirchir, Diane Healey, Julie Brahmer, Wilfried E E Eberhardt
Purpose Nivolumab, a programmed death-1 inhibitor, prolonged overall survival compared with docetaxel in two independent phase III studies in previously treated patients with advanced squamous (CheckMate 017; ClinicalTrials.gov identifier: NCT01642004) or nonsquamous (CheckMate 057; ClinicalTrials.gov identifier: NCT01673867) non-small-cell lung cancer (NSCLC). We report updated results, including a pooled analysis of the two studies. Methods Patients with stage IIIB/IV squamous (N = 272) or nonsquamous (N = 582) NSCLC and disease progression during or after prior platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks)...
December 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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