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Trial sequence analysis

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https://www.readbyqxmd.com/read/28433602/folfoxiri-regimen-for-metastatic-colorectal-cancer-a-systematic-review-and-meta-analysis
#1
Frederico Leal, Fernanda Proa Ferreira, Andre Deeke Sasse
INTRODUCTION: Cytotoxic chemotherapy is the mainstay treatment for metastatic colorectal cancer (mCRC). Fluoropyrimidines, oxaliplatin, and irinotecan are the most active drugs; however, their optimal sequencing has not yet been established. Some evidence has shown that upfront treatment with 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI regimen) can improve outcomes for patients with mCRC. MATERIALS AND METHODS: We performed a systematic search in electronic databases...
March 24, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28430172/ezh2-alterations-in-follicular-lymphoma-biological-and-clinical-correlations
#2
S Huet, L Xerri, B Tesson, S Mareschal, S Taix, L Mescam-Mancini, E Sohier, M Carrère, J Lazarovici, O Casasnovas, L Tonon, S Boyault, S Hayette, C Haioun, B Fabiani, A Viari, F Jardin, G Salles
The histone methyltransferase EZH2 has an essential role in the development of follicular lymphoma (FL). Recurrent gain-of-function mutations in EZH2 have been described in 25% of FL patients and induce aberrant methylation of histone H3 lysine 27 (H3K27). We evaluated the role of EZH2 genomic gains in FL biology. Using RNA sequencing, Sanger sequencing and SNP-arrays, the mutation status, copy-number and gene-expression profiles of EZH2 were assessed in a cohort of 159 FL patients from the PRIMA trial. Immunohistochemical (IHC) EZH2 expression (n=55) and H3K27 methylation (n=63) profiles were also evaluated...
April 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28429470/meta-analysis-combining-parallel-and-cross-over-trials-with-random-effects
#3
François Curtin
Meta-analysis can necessitate the combination of parallel and cross-over trial designs. Because of the differences in the trial designs and potential biases notably associated with the crossover trials, one often combines trials of the same designs only, which decreases the power of the meta-analysis. To combine results of clinical trials from parallel and cross-over designs, we extend the method proposed in an accompanying study to account for random effects. We propose here a hierarchical mixed model allowing the combination of the 2 types of trial designs and accounting for additional covariates where random effects can be introduced to account for heterogeneity in trial, treatment effect, and interactions...
April 21, 2017: Research Synthesis Methods
https://www.readbyqxmd.com/read/28428729/the-risk-of-bias-in-randomized-controlled-trials-in-otorhinolaryngology-hardly-any-improvement-since-1950
#4
Jeroen P M Peters, Inge Stegeman, Wilko Grolman, Lotty Hooft
BACKGROUND: Randomized Controlled Trials (RCTs) represent the most valuable study design to evaluate the effectiveness of therapeutic interventions. However, flaws in design, conduct, analysis, and reporting of RCTs can cause the effect of an intervention to be under- or overestimated. These biased RCTs may be included in literature reviews. To make the assessment of Risk of Bias (RoB) consistent and transparent, Cochrane published a RoB tool, with which RoB is assessed per item as "low", "unclear" or "high"...
2017: BMC Ear, Nose, and Throat Disorders
https://www.readbyqxmd.com/read/28427160/biomarker-analysis-of-the-phase-3-torch-trial-for-first-line-erlotinib-versus-chemotherapy-in-advanced-non-small-cell-lung-cancer-patients
#5
Lucia Kim, Mauro Saieg, Massimo Di Maio, Ciro Gallo, Charles Butts, Fortunato Ciardiello, Ronald Feld, Dengxiao Cheng, Vittorio Gebbia, Marco Angelo Burgio, Yasmin Alam, Simona Signoriello, Antonio Rossi, Natasha Leighl, Paolo Maione, Alessandro Morabito, Geoffrey Liu, Ming-Sound Tsao, Francesco Perrone, Cesare Gridelli
BACKGROUND: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. METHODS: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424669/inferring-microbial-interactions-in-the-gut-of-the-hong-kong-whipping-frog-polypedates-megacephalus-and-a-validation-using-probiotics
#6
Francis Cheng-Hsuan Weng, Grace Tzun-Wen Shaw, Chieh-Yin Weng, Yi-Ju Yang, Daryi Wang
The concerted activity of intestinal microbes is crucial to the health and development of their host organisms. Investigation of microbial interactions in the gut should deepen our understanding of how these micro-ecosystems function. Due to advances in Next Generation Sequencing (NGS) technologies, various bioinformatic strategies have been proposed to investigate these microbial interactions. However, due to the complexity of the intestinal microbial community and difficulties in monitoring their interactions, at present there is a gap between the theory and biological application...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28423702/experience-with-precision-genomics-and-tumor-board-indicates-frequent-target-identification-but-barriers-to-delivery
#7
Alan H Bryce, Jan B Egan, Mitesh J Borad, A Keith Stewart, Grzegorz S Nowakowski, Asher Chanan-Khan, Mrinal M Patnaik, Stephen M Ansell, Michaela S Banck, Steven I Robinson, Aaron S Mansfield, Eric W Klee, Gavin R Oliver, Jennifer B McCormick, Norine E Huneke, Colleen M Tagtow, Robert B Jenkins, Kandelaria M Rumilla, Sarah E Kerr, Jean-Pierre A Kocher, Scott A Beck, Martin E Fernandez-Zapico, Gianrico Farrugia, Konstantinos N Lazaridis, Robert R McWilliams
BACKGROUND: The ability to analyze the genomics of malignancies has opened up new possibilities for off-label targeted therapy in cancers that are refractory to standard therapy. At Mayo Clinic these efforts are organized through the Center for Individualized Medicine (CIM). RESULTS: Prior to GTB, datasets were analyzed and integrated by a team of bioinformaticians and cancer biologists. Therapeutically actionable mutations were identified in 65% (92/141) of the patients tested with 32% (29/92) receiving genomically targeted therapy with FDA approved drugs or in an independent clinical trial with 45% (13/29) responding...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421367/ns3-protease-resistance-associated-substitutions-in-liver-tissue-and-plasma-samples-from-patients-infected-by-hepatitis-c-virus-genotype-1a-or-1b
#8
Giulia Morsica, Andrea Andolina, Marco Merli, Emanuela Messina, Hamid Hasson, Adriano Lazzarin, Caterina Uberti-Foppa, Sabrina Bagaglio
The presence of naturally occurring resistance-associated substitutions (RASs) in the HCV-protease domain has been poorly investigated in the liver, the main site of HCV replication. We evaluated the natural resistance of the virus to NS3 protease inhibitors in liver tissue and plasma samples taken from HCV-infected patients. RASs were investigated by means of viral population sequencing in liver tissue samples from 18 HCV-infected patients harbouring genotype 1a or genotype 1b; plasma samples from 12 of these patients were also available for virological investigation...
April 18, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28415679/a-feasibility-study-of-returning-clinically-actionable-somatic-genomic-alterations-identified-in-a-research-laboratory
#9
Natalia Paez Arango, Lauren Brusco, Kenna R Mills Shaw, Ken Chen, Agda Karina Eterovic, Vijaykumar Holla, Amber Johnson, Beate Litzenburger, Yekaterina B Khotskaya, Nora Sanchez, Ann Bailey, Xiaofeng Zheng, Chacha Horombe, Scott Kopetz, Carol J Farhangfar, Mark Routbort, Russell Broaddus, Elmer V Bernstam, John Mendelsohn, Gordon B Mills, Funda Meric-Bernstam
PURPOSE: Molecular profiling performed in the research setting usually does not benefit the patients that donate their tissues. Through a prospective protocol, we sought to determine the feasibility and utility of performing broad genomic testing in the research laboratory for discovery, and the utility of giving treating physicians access to research data, with the option of validating actionable alterations in the CLIA environment. EXPERIMENTAL DESIGN: 1200 patients with advanced cancer underwent characterization of their tumors with high depth hybrid capture sequencing of 201 genes in the research setting...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413823/long-term-predictive-and-feedback-encoding-of-motor-signals-in-the-simple-spike-discharge-of-purkinje-cells
#10
Laurentiu S Popa, Martha L Streng, Timothy J Ebner
Most hypotheses of cerebellar function emphasize a role in real-time control of movements. However, the cerebellum's use of current information to adjust future movements and its involvement in sequencing, working memory, and attention argues for predicting and maintaining information over extended time windows. The present study examines the time course of Purkinje cell discharge modulation in the monkey (Macaca mulatta) during manual, pseudo-random tracking. Analysis of the simple spike firing from 183 Purkinje cells during tracking reveals modulation up to 2 s before and after kinematics and position error...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28411252/prognostic-relevance-of-cd163-and-cd8-combined-with-ezh2-and-gain-of-chromosome-18-in-follicular-lymphoma-a-study-by-the-lunenburg-lymphoma-biomarker-consortium
#11
Wendy B C Stevens, Matias Mendeville, Robert Redd, Andrew J Clear, Reno Bladergroen, Maria Calaminici, Andreas Rosenwald, Eva Hoster, Wolfgang Hiddemann, Philippe Gaulard, Luc Xerri, Gilles Salles, Wolfram Klapper, Michael Phreundschuh, Andrew Jack, Randy D Gascoyne, Yasodha Natkunam, Ranjana Advani, Eva Kimby, Birgitta Sander, Laurie Sehn, Anton Hagenbeek, John Raemaekers, John Gribben, Marie Jose' Kersten, Bauke Ylstra, Edie Weller, Daphne de Jong
In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end-of-spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries; early failure: progression or lymphoma-related death <2 years versus long remission: response duration of >5 years...
April 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28410921/a-randomized-trial-to-determine-the-impact-of-a-digestion-resistant-starch-composition-on-the-gut-microbiome-in-older-and-mid-age-adults
#12
Michelle J Alfa, David Strang, Paramjit S Tappia, Morag Graham, Gary Van Domselaar, Jessica D Forbes, Vanessa Laminman, Nancy Olson, Pat DeGagne, David Bray, Brenda-Lee Murray, Brenden Dufault, Lisa M Lix
BACKGROUND: The elderly often have a diet lacking resistant starch (RS) which is thought to lead to gut microbiome dysbiosis that may result in deterioration of gut colonocytes. OBJECTIVE: The primary objective was to assess if elderly (ELD; ≥ 70 years age) had microbiome dysbiosis compared to mid-age (MID; 30-50 years age) adults and then determine the impact of daily consumption of MSPrebiotic(®) (a RS) or placebo over 3 months on gut microbiome composition...
March 31, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28408464/targetable-kinase-gene-fusions-in-high-risk-b-all-a-study-from-the-children-s-oncology-group
#13
Shalini C Reshmi, Richard C Harvey, Kathryn G Roberts, Eileen Stonerock, Amy Smith, Heather Jenkins, I-Ming Chen, Marc Valentine, Yu Liu, Yongjin Li, Ying Shao, John Easton, Debbie Payne-Turner, Zhaohui Gu, Thai Hoa Tran, Jonathan V Nguyen, Meenakshi Devidas, Yunfeng Dai, Nyla A Heerema, Andrew J Carroll, Elizabeth A Raetz, Michael J Borowitz, Brent L Wood, Anne L Angiolillo, Michael J Burke, Wanda L Salzer, Patrick A Zweidler-McKay, Karen R Rabin, William L Carroll, Jinghui Zhang, Mignon L Loh, Charles G Mullighan, Cheryl L Willman, Julie M Gastier-Foster, Stephen P Hunger
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype characterized by genomic alterations that activate cytokine receptor and kinase signaling. We examined the frequency and spectrum of targetable genetic lesions in a retrospective cohort of 1389 consecutively diagnosed childhood B-ALL patients with high-risk clinical features and/or elevated minimal residual disease at the end of remission induction therapy. The Ph-like gene expression profile was identified in 341 of 1389 patients, 57 of which were excluded from additional analysis because of the presence of BCR-ABL1 (n=46) or ETV6-RUNX1 (n=11)...
April 13, 2017: Blood
https://www.readbyqxmd.com/read/28407110/prognostic-and-predictive-value-of-primary-tumour-side-in-patients-with-ras-wild-type-metastatic-colorectal-cancer-treated-with-chemotherapy-and-egfr-directed-antibodies-in-six-randomised-trials
#14
D Arnold, B Lueza, J-Y Douillard, M Peeters, H-J Lenz, A Venook, V Heinemann, E Van Cutsem, J-P Pignon, J Tabernero, A Cervantes, F Ciardiello
Background: There is increasing evidence that metastatic colorectal cancer (mCRC) is a genetically heterogeneous disease and that tumours arising from different sides of the colon (left versus right) have different clinical outcomes. Furthermore, previous analyses comparing the activity of different classes of targeted agents in patients with KRAS wild-type (wt) or RAS wt mCRC suggest that primary tumour location (side), might be both prognostic and predictive for clinical outcome. Methods: This retrospective analysis investigated the prognostic and predictive influence of the localisation of the primary tumour in patients with unresectable RAS wt mCRC included in six randomised trials (CRYSTAL, FIRE-3, CALGB 80405, PRIME, PEAK and 20050181), comparing chemotherapy plus EGFR antibody therapy (experimental arm) with chemotherapy or chemotherapy and bevacizumab (control arms)...
April 12, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28403795/mesenchymal-stem-cell-derived-extracellular-vesicles-for-renal-repair
#15
Arash A Nargesi, Lilach O Lerman, Alfonso Eirin
Transplantation of autologous mesenchymal stem cells (MSCs) has been shown to attenuate renal injury and dysfunction in several animal models, and its efficacy is currently being tested in clinical trials for patients with renal disease. Accumulating evidence indicates that MSCs release extracellular vesicles (EVs) that deliver genes, microRNAs and proteins to recipient cells, acting as mediators of MSC paracrine actions. In this context, it is critical to characterize the MSC-derived EV cargo to elucidate their potential contribution to renal repair...
April 12, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28403774/pharmacogenetics-of-aromatase-inhibitors-in-endocrine-responsive-breast-cancer-lessons-learnt-from-tamoxifen-and-cyp2d6-genotyping
#16
Karin Jeanne Baatjes, Magda Conradie, Justus Paul Apffelstaedt, Maritha Kotze
BACKGROUND: Genetics play a significant role in drug metabolism of endocrine therapy of breast cancer. These aspects have been studied extensively in patients on tamoxifen, but the pharmacogenetics of aromatase inhibitors are less established. In contrast to the protective effect of tamoxifen, aromatase inhibitors are linked with an increased risk for bone loss and fractures. OBJECTIVE: This review outlines key issues around implementation of pharmacogenetics of cytochrome P450 and tamoxifen as a model for optimal use of aromatase inhibitors in postmenopausal women with estrogen receptor positive breast cancer...
April 12, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28396214/enhancing-links-between-visual-short-term-memory-visual-attention-and-cognitive-control-processes-through-practice-an-electrophysiological-insight
#17
Giorgio Fuggetta, Philip A Duke
The operation of attention on visible objects involves a sequence of cognitive processes. The current study firstly aimed to elucidate the effects of practice on neural mechanisms underlying attentional processes as measured with both behavioural and electrophysiological measures. Secondly, it aimed to identify any pattern in the relationship between Event-Related Potential (ERP) components which play a role in the operation of attention in vision. Twenty-seven participants took part in two recording sessions one week apart, performing an experimental paradigm which combined a match-to-sample task with a memory-guided efficient visual-search task within one trial sequence...
April 7, 2017: Biological Psychology
https://www.readbyqxmd.com/read/28392802/capturing-genomic-evolution-of-lung-cancers-through-liquid-biopsy-for-circulating-tumor-dna
#18
REVIEW
Michael Offin, Jacob J Chabon, Pedram Razavi, James M Isbell, Charles M Rudin, Maximilian Diehn, Bob T Li
Genetic sequencing of malignancies has become increasingly important to uncover therapeutic targets and capture the tumor's dynamic changes to drug sensitivity and resistance through genomic evolution. In lung cancers, the current standard of tissue biopsy at the time of diagnosis and progression is not always feasible or practical and may underestimate intratumoral heterogeneity. Technological advances in genetic sequencing have enabled the use of circulating tumor DNA (ctDNA) analysis to obtain information on both targetable mutations and capturing real-time Darwinian evolution of tumor clones and drug resistance mechanisms under selective therapeutic pressure...
2017: Journal of Oncology
https://www.readbyqxmd.com/read/28392771/find-the-hidden-object-understanding-play-in-psychological-assessments
#19
Alessandra Fasulo, Janhavi Shukla, Stephanie Bennett
Standardized psychological assessments are extensively used by practitioners to determine rate and level of development in different domains of ability in both typical and atypical children. The younger the children, the more likely the trials will resemble play activities. However, mode of administration, timing and use of objects involved are constrained. The purpose of this study is to explore what kind of play is play in psychological assessments, what are the expectations about children's performance and what are the abilities supporting the test activities...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28392237/routine-molecular-point-of-care-testing-for-respiratory-viruses-in-adults-presenting-to-hospital-with-acute-respiratory-illness-respoc-a-pragmatic-open-label-randomised-controlled-trial
#20
Nathan J Brendish, Ahalya K Malachira, Lawrence Armstrong, Rebecca Houghton, Sandra Aitken, Esther Nyimbili, Sean Ewings, Patrick J Lillie, Tristan W Clark
BACKGROUND: Respiratory virus infection is a common cause of hospitalisation in adults. Rapid point-of-care testing (POCT) for respiratory viruses might improve clinical care by reducing unnecessary antibiotic use, shortening length of hospital stay, improving influenza detection and treatment, and rationalising isolation facility use; however, insufficient evidence exists to support its use over standard clinical care. We aimed to assess the effect of routine POCT on a broad range of clinical outcomes including antibiotic use...
April 6, 2017: Lancet Respiratory Medicine
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