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Trial sequence analysis

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https://www.readbyqxmd.com/read/28344988/inspiired-quantification-and-visualization-tools-for-analyzing-integration-site-distributions
#1
Charles C Berry, Christopher Nobles, Emmanuelle Six, Yinghua Wu, Nirav Malani, Eric Sherman, Anatoly Dryga, John K Everett, Frances Male, Aubrey Bailey, Kyle Bittinger, Mary J Drake, Laure Caccavelli, Paul Bates, Salima Hacein-Bey-Abina, Marina Cavazzana, Frederic D Bushman
Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to genomic features and that support numerous user-defined statistical tests...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28343976/prophylactic-cranial-irradiation-versus-observation-in-patients-with-extensive-disease-small-cell-lung-cancer-a-multicentre-randomised-open-label-phase-3-trial
#2
Toshiaki Takahashi, Takeharu Yamanaka, Takashi Seto, Hideyuki Harada, Hiroshi Nokihara, Hideo Saka, Makoto Nishio, Hiroyasu Kaneda, Koichi Takayama, Osamu Ishimoto, Koji Takeda, Hiroshige Yoshioka, Motoko Tachihara, Hiroshi Sakai, Koichi Goto, Nobuyuki Yamamoto
BACKGROUND: Results from a previous phase 3 study suggested that prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs overall survival compared with no prophylactic cranial irradiation in patients with extensive-disease small-cell lung cancer. However, because of the absence of brain imaging before enrolment and variations in chemotherapeutic regimens and irradiation doses, concerns have been raised about these findings. We did a phase 3 trial to reassess the efficacy of prophylactic cranial irradiation in the treatment of extensive-disease small-cell lung cancer...
March 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28343250/apparent-diffusion-coefficient-changes-predict-survival-after-intra-arterial-bevacizumab-treatment-in-recurrent-glioblastoma
#3
Naveen Galla, Gloria Chiang, Shamik Chakraborty, Ranjodh Singh, A John Tsiouris, John Boockvar, Ilhami Kovanlikaya
PURPOSE: Superselective intra-arterial cerebral infusion (SIACI) of bevacizumab (BV) has emerged as a novel therapy in the treatment of recurrent glioblastoma (GB). This study assessed the use of apparent diffusion coefficient (ADC) in predicting length of survival after SIACI BV and overall survival in patients with recurrent GB. METHODS: Sixty-five patients from a cohort enrolled in a phase I/II trial of SIACI BV for treatment of recurrent GB were retrospectively included in this analysis...
March 25, 2017: Neuroradiology
https://www.readbyqxmd.com/read/28341441/neoadjuvant-therapy-versus-upfront-surgery-for-resected-pancreatic-adenocarcinoma-a-nationwide-propensity-score-matched-analysis
#4
Susanna W L de Geus, Mariam F Eskander, Lindsay A Bliss, Gyulnara G Kasumova, Sing Chau Ng, Mark P Callery, Jennifer F Tseng
BACKGROUND: Neoadjuvant therapy is an emerging paradigm in pancreatic cancer care; however, its role for resectable disease remains controversial in the absence of conclusive randomized controlled trials. The purpose of the present study is to assess the impact of neoadjuvant therapy on survival in resected pancreatic cancer patients by clinical stage. METHODS: A retrospective cohort study using the National Cancer Data Base from 2004 to 2012 including nonmetastatic pancreatic adenocarcinoma patients who underwent pancreatectomy and initiated chemotherapy...
March 2017: Surgery
https://www.readbyqxmd.com/read/28339429/comparing-the-efficacy-of-surgery-and-medical-therapy-for-pain-management-in-endometriosis-a-systematic-review-and-meta-analysis
#5
Shahla Chaichian, Ali Kabir, Adolfazl Mehdizadehkashi, Khaled Rahmani, Mehrdad Moghimi, Bahram Moazzami
BACKGROUND: Pain is considered as one of the main symptoms of endometriosis. The treatment for endometriosis remains controversial. OBJECTIVES: The aim of this study is to compare the effect of medical or surgical treatments for pain-relief in patients with endometriosis. STUDY DESIGN: Systematic review and meta-analysis. SETTING: Published papers about evaluating pain treatment in endometriosis in PubMed, Scopus, and Google Scholar...
March 2017: Pain Physician
https://www.readbyqxmd.com/read/28336267/association-analysis-of-polymorphism-in-kiss1-gene-with-reproductive-traits-in-goats
#6
Mahmoud S El-Tarabany, Asmaa W Zaglool, Akram A El-Tarabany, Ashraf Awad
Understanding the genetic information of related genes is helpful for the selection and breeding course through marker assisted selection. The aim of the current study was to detect polymorphisms of the KiSS1 gene in 137 animals, including Baladi, Zaraibi and Damascus goat breeds by PCR-RFLP, and DNA sequencing and to investigate the association between these variants and reproductive traits. Comparison of the nucleotide sequence indicated the substitution of T with A at position 121 (T121A) in the intron 1 of the KiSS1 gene in all goat breeds...
March 18, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28334435/withdrawn-radioisotopes-for-metastatic-bone-pain
#7
REVIEW
Marta Roqué I Figuls, Maria José Martinez-Zapata, Martin Scott-Brown, Pablo Alonso-Coello
BACKGROUND: This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates. OBJECTIVES: To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival...
March 23, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28334365/effect-of-kit-and-pdgfra-mutations-on-survival-in-patients-with-gastrointestinal-stromal-tumors-treated-with-adjuvant-imatinib-an-exploratory-analysis-of-a-randomized-clinical-trial
#8
Heikki Joensuu, Eva Wardelmann, Harri Sihto, Mikael Eriksson, Kirsten Sundby Hall, Annette Reichardt, Jörg T Hartmann, Daniel Pink, Silke Cameron, Peter Hohenberger, Salah-Eddin Al-Batran, Marcus Schlemmer, Sebastian Bauer, Bengt Nilsson, Raija Kallio, Jouni Junnila, Aki Vehtari, Peter Reichardt
Importance: Little is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor α (PDGFRA) mutations. Objective: To investigate the effect of KIT and PDGFRA mutations on recurrence-free survival (RFS) in patients with gastrointestinal stromal tumors (GISTs) treated with surgery and adjuvant imatinib. Design, Setting, and Participants: This exploratory study is based on the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28331964/the-hypomorphic-tert-a1062t-variant-is-associated-with-increased-treatment-related-toxicity-in-acute-myeloid-leukemia
#9
Anna Both, Jürgen Krauter, Frederik Damm, Felicitas Thol, Gudrun Göhring, Michael Heuser, Oliver Ottmann, Michael Lübbert, Mohammed Wattad, Lothar Kanz, Günter Schlimok, Aruna Raghavachar, Walter Fiedler, Hartmut Kirchner, Wolfram Brugger, Brigitte Schlegelberger, Gerhard Heil, Arnold Ganser, Katharina Wagner
Hypomorphic germline variants in TERT, the gene encoding the reverse transcriptase component of the human telomerase complex, occur with a frequency of 3-5% in acute myeloid leukemia. We analyzed the clinical and prognostic impact of the most common TERT A1062T variant in younger patients with acute myeloid leukemia intensively treated within two prospective multicenter trials. Four hundred and twenty patients (age 17-60 years) were analyzed for the TERT A1062T variant by direct sequencing. Fifteen patients (3...
March 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28331002/personalized-in-vitro-and-in-vivo-cancer-models-to-guide-precision-medicine
#10
Chantal Pauli, Benjamin D Hopkins, Davide Prandi, Reid Shaw, Tarcisio Fedrizzi, Andrea Sboner, Verena Sailer, Michael Augello, Loredana Puca, Rachele Rosati, Terra J McNary, Yelena Churakova, Cynthia Cheung, Joanna Triscott, David Pisapia, Rema Rao, Juan Miguel Mosquera, Brian Robinson, Bishoy M Faltas, Brooke E Emerling, Vijayakrishna K Gadi, Brady Bernard, Olivier Elemento, Himisha Beltran, Francesca Demichelis, Christopher J Kemp, Carla Grandori, Lewis C Cantley, Mark A Rubin
Precision medicine is an approach that takes into account the influence of individuals' genes, environment, and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform that integrates whole-exome sequencing with a living biobank that enables high-throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an Institutional Review Board-approved clinical trial...
March 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28327926/genomic-characterisation-of-her2-positive-breast-cancer-and-response-to-neoadjuvant-trastuzumab-and-chemotherapy-results-from-the-acosog-z1041-alliance-trial
#11
R Lesurf, O L Griffith, M Griffith, J Hundal, L Trani, M A Watson, R Aft, M J Ellis, D Ota, V J Suman, F Meric-Bernstam, A M Leitch, J C Boughey, G Unzeitig, A U Buzdar, K K Hunt, E R Mardis
Background: HER2 ( ERBB2 ) gene amplification and its corresponding overexpression are present in 15-30% of invasive breast cancers. While HER2-targeted agents are effective treatments, resistance remains a major cause of death. The American College of Surgeons Oncology Group Z1041 trial (NCT00513292) was designed to compare the pathologic complete response (pCR) rate of distinct regimens of neoadjuvant chemotherapy and trastuzumab, but ultimately identified no difference [1]. Patients and methods: In supplement to tissues from 37 Z1041 cases, 11 similarly treated cases were obtained from a single institution study (NCT00353483)...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28326079/differences-in-ureolytic-bacterial-composition-between-the-rumen-digesta-and-rumen-wall-based-on-urec-gene-classification
#12
Di Jin, Shengguo Zhao, Nan Zheng, Dengpan Bu, Yves Beckers, Stuart E Denman, Christopher S McSweeney, Jiaqi Wang
Ureolytic bacteria are key organisms in the rumen producing urease enzymes to catalyze the breakdown of urea to ammonia for the synthesis of microbial protein. However, little is known about the diversity and distribution of rumen ureolytic microorganisms. The urease gene (ureC) has been the target gene of choice for analysis of the urea-degrading microorganisms in various environments. In this study, we investigated the predominant ureC genes of the ureolytic bacteria in the rumen of dairy cows using high-throughput sequencing...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28325297/engineering-of-pedf-expressing-primary-pigment-epithelial-cells-by-the-sb-transposon-system-delivered-by-pfar4-plasmids
#13
Gabriele Thumann, Nina Harmening, Cécile Prat-Souteyrand, Corinne Marie, Marie Pastor, Attila Sebe, Csaba Miskey, Laurence D Hurst, Sabine Diarra, Martina Kropp, Peter Walter, Daniel Scherman, Zoltán Ivics, Zsuzsanna Izsvák, Sandra Johnen
Neovascular age-related macular degeneration (nvAMD) is characterized by choroidal blood vessels growing into the subretinal space, leading to retinal pigment epithelial (RPE) cell degeneration and vision loss. Vessel growth results from an imbalance of pro-angiogenic (e.g., vascular endothelial growth factor [VEGF]) and anti-angiogenic factors (e.g., pigment epithelium-derived factor [PEDF]). Current treatment using intravitreal injections of anti-VEGF antibodies improves vision in about 30% of patients but may be accompanied by side effects and non-compliance...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28320635/safety-and-efficacy-of-multipotent-adult-progenitor-cells-in-acute-ischaemic-stroke-masters-a-randomised-double-blind-placebo-controlled-phase-2-trial
#14
David C Hess, Lawrence R Wechsler, Wayne M Clark, Sean I Savitz, Gary A Ford, David Chiu, Dileep R Yavagal, Ken Uchino, David S Liebeskind, Alexander P Auchus, Souvik Sen, Cathy A Sila, Jeffrey D Vest, Robert W Mays
BACKGROUND: Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. METHODS: We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA...
March 17, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28318817/clinical-and-mutational-characteristics-of-duchenne-muscular-dystrophy-patients-based-on-a-comprehensive-database-in-south-china
#15
Dan-Ni Wang, Zhi-Qiang Wang, Lei Yan, Jin He, Min-Ting Lin, Wan-Jin Chen, Ning Wang
The development of clinical trials for Duchenne muscular dystrophy (DMD) in China faces many challenges due to limited information about epidemiological data, natural history and clinical management. To provide these detailed data, we developed a comprehensive database based on registered DMD patients from South China and analysed their clinical and mutational characteristics. The database included DMD registrants confirmed by clinical presentation, family history, genetic detection, prognostic outcome, and/or muscle biopsy...
February 21, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28318251/molecular-simulation-studies-on-the-binding-selectivity-of-type-i-inhibitors-in-the-complexes-with-ros1-versus-alk
#16
Yuanxin Tian, Yonghuan Yu, Yudong Shen, Hua Wan, Shan Chang, Tingting Zhang, Shanhe Wan, Jiajie Zhang
ROS1 and ALK are promising targets of anti-cancer drugs for non small cell lung cancer. Since they have 49% amide acid sequence homology in the kinases domain and 77% identity at the ATP binding area, some ALK inhibitors also showed some significant responses for ROS1 in the clinical trial, such as the type-I binding inhibitor crizotinib and PF-06463922. As a newly therapeutic target, selective ROS1 inhibitor is relative rarely. Moreover, the molecular basis for the selectivity of ROS1 versus ALK still remains unclear...
March 20, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28314589/fgfr2-mutations-are-associated-with-poor-outcomes-in-endometrioid-endometrial-cancer-an-nrg-oncology-gynecologic-oncology-group-study
#17
Yvette W Jeske, Shamshad Ali, Sara A Byron, Feng Gao, Robert S Mannel, Rahel G Ghebre, Paul A DiSilvestro, Shashikant B Lele, Michael L Pearl, Amy P Schmidt, Heather A Lankes, Nilsa C Ramirez, Golnar Rasty, Matthew Powell, Paul J Goodfellow, Pamela M Pollock
PURPOSE: Activating FGFR2 mutations have been identified in ~10% of endometrioid endometrial cancers (ECs). We have previously reported that mutations in FGFR2 are associated with shorter disease free survival (DFS) in stage I/II EC patients. Here we sought to validate the prognostic importance of FGFR2 mutations in a large, multi-institutional patient cohort. METHODS: Tumors were collected as part of the GOG 210 clinical trial "Molecular Staging of Endometrial Cancer" where samples underwent rigorous pathological review and had more than three years of detailed clinical follow-up...
March 14, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28302137/mutations-of-crebbp-and-socs1-are-independent-prognostic-factors-in-diffuse-large-b-cell-lymphoma-mutational-analysis-of-the-sakk-38-07-prospective-clinical-trial-cohort
#18
Darius Juskevicius, David Jucker, Dirk Klingbiel, Christoph Mamot, Stephan Dirnhofer, Alexandar Tzankov
BACKGROUND/PURPOSE: Recently, the mutational background of diffuse large B cell lymphoma (DLBCL) has been revealed, identifying specific genetic events that drive lymphomagenesis. However, the prognostic value of these mutations remains to be determined. Prognostic biomarkers in DLBCL are urgently needed, since the current clinical parameter-based factors (e.g., International Prognostic Index (IPI)) are insufficient, particularly in identifying patients with poor prognosis who might benefit from alternative treatments...
March 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28289865/phase-i-single-dose-two-period-and-two-sequence-cross-over-trial-to-evaluate-the-relative-bioavailability-of-two-oral-pimasertib-formulations-in-advanced-cancer-patients
#19
D Mahadevan, Monica Mita, Donald Richards, Edward McClay, Rebecca Suk Heist, A Kumar, S Sundararajan, Aung Naing
PURPOSE: A phase I two-period two sequence cross-over study compared the bioavailability of two pimasertib (MSC1936369B/AS703026) formulations (capsule versus tablet) in advanced cancer patients. METHODS: Patients with advanced solid tumors were randomized to one of two treatment sequences utilizing pimasertib tablet (test; 3 × 20 mg, PO QD) and capsule (standard; 2 × 30 mg, PO QD). The trial comprised a screening and baseline period, two time periods or parts A and B, and a trial extension phase...
March 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28289380/variation-in-event-related-potentials-by-state-transitions
#20
Hiroshi Higashi, Tetsuto Minami, Shigeki Nakauchi
The probability of an event's occurrence affects event-related potentials (ERPs) on electroencephalograms. The relation between probability and potentials has been discussed by using a quantity called surprise that represents the self-information that humans receive from the event. Previous studies have estimated surprise based on the probability distribution in a stationary state. Our hypothesis is that state transitions also play an important role in the estimation of surprise. In this study, we compare the effects of surprise on the ERPs based on two models that generate an event sequence: a model of a stationary state and a model with state transitions...
2017: Frontiers in Human Neuroscience
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