tbuckley/cabot-search huggingface dataset:
P09.58 Quality of randomized controlled trials reporting in the treatment of adult high grade gliomas
Authors: M. P. Tardy, J. Gal, E. Chamorey, F. Almairac, F. Van den bos, P. Bondiau, E. Saada-Bouzid
Journal: Neuro-Oncology (2017)

Introduction: Randomized Controlled Trial (RCTs) is the gold standard to objectively assess the effect of a treatment. The RCTs methodology must be particularly rigorous to achieve strong evidence of efficiency. To help improve the quality of RCTs, a group of experts established a list of recommendations, adopted by most international journals, called the CONSORT (CONsolidated Standards of Reporting Trials) Statement. First published in 1996, it was actualised in 2001 and 2010. In this study, we assessed the implementation of the CONSORT Statement criteria in the field of adult high grade gliomas. We also aimed to identify criteria associated with higher quality of RCTs. METHODS: We searched PUBMED to retrieve all RCTs concerning high grade gliomas published between the 1st January 1990 and the 1st March 2016. The quality of these RCTs was assessed by completing a modified CONSORT Score containing 33 items. This work was done independently by two investigators and every discordance was resolved by consensus. We also extracted data that seemed relevant to assess the quality of RCTs. Results: Eighty-four published RCTs were identified. The median CONSORT Score was 19 (range: 3-30). Items were not equally reported and items regarding the method of randomization, the blinding or the accessibility of the protocol were reported in less than 25% of RCTs which could raise important biases and led to inappropriate interpretation of the results. However, the CONSORT Score constantly improved over the years. Before the onset of the CONSORT Statement in 1996, the median CONSORT Score was 13 (range: 4-19) whereas it was equal to 18 (range: 3-26) for the period 1996-2004 and equal to 22 (range: 6-30) after 2005. A higher CONSORT Score was observed when RCTs were published in journal with impact factor above 10 (24 vs 17, p<0.001). RCTs that enrolled more than 200 patients had a significantly higher CONSORT Score (20.6 vs 16.4, p=0.004). CONCLUSION: This study demonstrated a continuous improvement over the years of the CONSORT Score of published RCTs in the field of high grade gliomas. We identified three factors associated with a better report of RCTs: the date of publication, the impact factor of the journal and the number of patients included in the study.
P07.02 Trials of a personalized peptide vaccine (ITK-1) for patients with recurrent or progressive glioblastoma (GBM)
Authors: T. Fujimaki, K. Itoh, M. Terasaki, Y. Narita, Y. Arakawa, K. Sugiyama, R. Nishikawa, T. Aoki, T. Kumabe, M. Nagane
Journal: Neuro-Oncology (2017)

Immunotherapy trials for glioblastoma (GBM) have some effects but the efficacy was limited, some because of the low immunogenicity and diverse antigens for GBMs. Personalized selection of suitable peptides for patients is one way to conquer this problem. We conducted serial series of clinical trials with 14 kinds of vaccine candidates (ITK-1) in patients with advanced cancers. Here we report our phase I results of ITK-1 in GBM and also introduce the trial design of phase III in GBM which is on-going. (Phase I) Twelve HLA-A-24 positive patients were enrolled from 8 Japanese hospitals. The dose escalation trial was conducted to determine safety and tolerability of ITK-1 peptides (at 1mg, 3mg, 5mg), however because of a dose limiting toxicity (injection site skin reaction) in another ITK-1 phase I trial for advanced prostate cancer, patients with 5mg dose was skipped or discontinued. No serious adverse drug reactions were observed. By analysis of intention to treat, two patients displayed PR, 5 SD and 5 PD by WHO criteria. The PFS rate at 6 months was 16.7%. Median OS from registration was 10.6 months. (Phase III) Based on the phase I trial, phase III trial is on-going. GBM patients refractory or recurrence after standard initial TMZ-radiation treatment were enrolled. The multi-institutional trial are conducting under IRB approval of each institutes and written informed consents from the patients and/or responsible relatives. HLA-A24 positive patients receive peptide vaccine (3mg/1.5ml) or placebo with selected 2 to 4 subcutaneous injection once weekly in total 12 times at the first course. At the second to twenty course, peptide vaccine or placebo is administered biweekly. Patients were randomly assigned (2: 1) to receive relevant peptides or placebo and both arms were under best supportive care. No other chemotherapy, immunotherapy nor radiotherapy are allowed. The primary endpoint is OS and secondary endpoints includes survival rates at 12 month, objective tumor response, immune responses and PFS. A total of 90 cases were registered and the results will be open by June 2017. So far we do not experience serious side effects, excluding one case of pulmonary embolus. Overall survival of all cases (both vaccine and placebo arms together) from registration is 8.4 months.
Analysis of basophil activation in patients with aspirin-exacerbated respiratory disease
Authors: Chihiro Mitsui, Keiichi Kajiwara, Emiko Ono, Kentaro Watai, Hiroaki Hayashi, Yosuke Kamide, Yuma Fukutomi, Kiyoshi Sekiya, Takahiro Tsuburai, Kazuhiko Yamamoto, Masami Taniguchi
Journal: Journal of Allergy and Clinical Immunology (2017)
Initial Safety and Efficacy Results of a Second-Generation Humanized Anti-CD20 Antibody, IMMU-106 (hA20), in Non-Hodgkin’s Lymphoma.
Authors: Franck Morschhauser, John P. Leonard, Bertrand Coiffier, Marie-Odile Petillon, Morton Coleman, Amina Bahkti, Puja Sapra, Nick Teoh, William A. Wegener, Ivan D. Horak, David M. Goldenberg
Journal: Blood (2005)
P09.56 Comparison of the effect of different treatment strategies within discrepant health-care systems on survival of glioblastoma patients
Authors: P. Stavrinou, A. Kalyvas, S. Katsigiannis, C. Hamisch, B. Krischek, G. Stranjalis, R. Goldbrunner
Journal: Neuro-Oncology (2017)

OBJECTIVE: Although interdisciplinary, longitudinal treatment of glioblastoma patients is standard-of-care for most countries, its effect on glioblastoma patients survival has not been quantified. The goal of this study was to examine survival in similar cohorts of glioblastoma patients from two university hospitals with different treatment strategies functioning within two completely different healthcare systems. METHODS: We retrospectively analyzed two matched cohorts from a university hospital in Greece (188 patients) and Germany (189 patients). In both centers patients were treated with surgery followed by radiochemotherapy according to the stupp protocol. In case of recurrence, Greek patients were treated rather conservatively and further therapeutic decisions were made solely by the primary treating physician whereas German patients were treated more aggressively, with an individual strategy that was developed within an interdisciplinary tumorboard. The primary endpoint was progression-free and overall survival. Groups were compared using the Kaplan-Meier method for survival estimates. Results: Both groups were comparable with respect to baseline parameters. Only 17% of Greek patients versus 88% of German patients received second line treatment. Progression-free survival was similar for both patient cohorts (PFSGreece=9,9 months vs PFSGermany=9,0 months, p=0,37). Median survival was 12 months (95% CI, 9,4-14,5) and 16,6 months (95% CI, 13,3-19.8) for Greek and German patients respectively (p=0,02). CONCLUSION: Treatment steered by a neurooncological tumorboard, functioning within a well financed-health care system and favoring second-line treatment for recurrent glioblastomas was associated with significantly better overall survival.
OS06.1 Genome-wide association study reveals specific differences in genetic susceptibility to glioblastoma and non-glioblastoma
Authors: B. S. Melin, B. Kinnersley, Q. Ostrom, J. S. Barnholtz-Sloan, M. R. Wrensch, R. B. Jenkins, R. S. Houlston, M. L. Bondy
Journal: Neuro-Oncology (2017)

Background: Glioma accounts for around 27% of all primary brain tumors and is responsible for approximately 13,000 cancer-related deaths in the US each year. Glioma tumors can be broadly classified into glioblastoma (GBM) and lower-grade non-GBM. Typically gliomas have a poor prognosis irrespective of medical care, with the most common form, GBM, having a five-year survival rate of only 5%. While genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, individual studies have had limited power to identify risk loci. Methods: We performed the largest GWAS in glioma to date, comprising a meta-analysis of existing GWAS (6,405 cases, 14,100 controls) as well as new GWAS from the Glioma International Case Control Consortium (GICC; 4,572 cases and 3,286 controls) and University of California, San Francisco (UCSF)-Mayo (1,519 cases, 804 controls), totalling 12,496 cases and 18,190 controls. Results: We identified five new loci for GBM at 1p31.3 (rs12752552, near JAK1, P=2.04 × 10–9, odds ratio (OR)=1.22), 11q14.1 (rs11233250, P=9.95 × 10-10, OR=1.24), 16p13.3 (rs2562152, near MPG, P=1.93x10-8, OR=1.21), 16q12.1 (rs10852606, HEATR3, P=1.29 × 10–11, OR=1.18), 22q13.1 (rs2235573, P=1.76 × 10-10, OR=1.15) and eight for non-GBM at 1q32.1 (rs4252707, MDM4, P=3.34 × 10–9, OR=1.19), 1q44 (rs12076373, AKT3, P=2.63 × 10-10, OR=1.23), 2q33.3 (rs7572263, near IDH1, P=2.18 × 10-10, OR=1.20), 3p14.1 (rs11706832, LRIG1l, P=7.66 × 10–9, OR=1.15), 10q24.33 (rs11598018, OBFC1, P=3.39 × 10–8, OR=1.14), 11q21 (rs7107785, P=3.87 × 10-10, OR=1.16), 14q12 (rs10131032, P=5.07x10-11, OR=1.33) and 16p13.3 (rs3751667, P=2.61 × 10–9, OR=1.18). Case-only analyses confirmed the specificity of 11q14.1, 16p13.3 and 22q13.1 ­associations for GBM and 1q44, 2q33.3, 3p14.1, 11q21 and 14q12 for non-GBM tumors. In the combined meta-analysis, among previously published glioma risk SNPs, those for all glioma at 17p13.1 (TP53), GBM at 5p15.33 (TERT), 7p11.2 (EGFR), 9p21.3 (CDKN2B-AS1) and 20q13.33 (RTEL1) and for non-GBM at 8q24.21 (CCDC26), 11q23.2, 11q23.3 (PHLDB1) and 15q24.2 (ETFA) showed even greater evidence for association. SNPs at 10q25.2 and 12q12.1 for non-GBM tumors retained genome-wide significance (i.e. P<5.0x10-8). Associations at the previously reported 3q26.2 (near TERC) and 12q23.33 (POLR3B) loci for GBM did not retain statistical significance. Conclusions: Our findings substantiate genetic susceptibility to GBM and non-GBM being highly distinct, consistent with their distinctive molecular profiles presumably resulting from different etiological pathways. Functional analyses should lead to further insights into the biological basis of the different glioma histologies. Such information can inform gene discovery initiatives and therefore have a measurable impact on the successful development of new therapeutic agents.
Erratum: Human Oggl, a protein involved in the repair of 8-oxoguanine, is inhibited by nitric oxide (Cancer Research (September 1, 2001) (6388-6393))
Authors: M. Jaiswal, N. F. LaRusso, K. Nishioka, Yusaku Nakabeppu, G. J. Gores
Journal: Cancer Research (2001)
Main drivers of outcome differ between short term and long term in severe alcoholic hepatitis: A prospective study
Authors: Alexandre Louvet, Julien Labreuche, Florent Artru, Alexis Bouthors, Benjamin Rolland, Pierre Saffers, Julien Lollivier, Elise Lemaître, Sébastien Dharancy, Guillaume Lassailly, Valérie Canva‐Delcambre, Alain Duhamel, Philippe Mathurin
Journal: Hepatology (2017)

Understanding the mechanisms of outcome according to the time frame can help optimize the therapeutic development in severe alcoholic hepatitis. We assessed short-term and long-term survival in severe alcoholic hepatitis based on baseline disease severity, extent of therapeutic improvement, long-term influence of alcohol relapse, and their interaction. Data and alcohol consumption were prospectively recorded in 398 patients treated with corticosteroids in the short term (from corticosteroid initiation to 6 months) and long term (from 6 months to maximum follow-up time). Cumulative incidence rate of first alcohol relapse was 25.2%, 33.7%, and 35.2% at 1, 3, and 5 years, respectively. Alcohol relapse (≥30 g/day) was not associated with mortality (P = 0.24) during the short-term period (1,606 patient-months at risk), but the Lille (P < 0.0001) and Model for End-Stage Liver Disease (P < 0.0001) scores were independent prognostic factors. In patients who were alive at 6 months (median follow-up, 42 months; interquartile range 11-88), corresponding to 10,413 patient-months at risk, alcohol consumption (≥30 g/day) was associated with mortality (hazard ratio, 3.9; P < 0.0001). Additional analysis with abstinent patients as a reference showed a dose effect of alcohol on the hazard ratio of death: 2.36 (P = 0.052) for 1-29 g/day, 3.2 (P = 0.003) for 30-49 g/day, 3.51 (P < 0.0001) for 50-99 g/day, and 5.61 (P < 0.0001) for ≥ 100 g/day. The baseline Model for End-Stage Liver Disease score was not predictive of long-term outcome, while Lille score (P = 0.02) and alcohol relapse (P < 0.0001) were independent prognostic factors.This study shows that new therapeutic development for severe alcoholic hepatitis must target liver injury in the short term and alcohol consumption in the long term; thus, health agencies can endorse future study designs adapted to the time frame of factors influencing mortality; with this in mind, drug-targeting mechanisms involved in liver injury should only be tested for the short-term period. (Hepatology 2017;66:1464-1473).
PAINFUL EVALUATION AND INJURY PREVENTION OF LOWER EXTREMITY THROUGH CYCLING DIAGNOSIS SYSTEM DEVELOPMENT: COMPUTATIONAL AND EXPERIMENTAL APPROACHES
Authors: Penny WEN, Bing-Shiang Yang
Journal: British Journal of Sports Medicine (2017)

Background In clinical practices, sports injuries are assessed using radiographic examinations, pain-related inquiries, or palpations, after which prescriptions are issued to patients. Objective By combining anatomy, musculoskeletal simulations, and the concept of sports training, this study demonstrated a system for assessing sports injuries that improves biking strategies and prevents biking injuries. The applicability and accuracy of this study enabled the locations of muscle injuries to be statistically matched with biking strategies. Design We built an instrumented bike which was a conventional road racing bicycle fitted with instruments for measuring the riding parameters: a crank torque sensor, an optical encoder, inclinometer, magnetic and reed switches, and an electromyographic system. Setting A musculoskeletal modelling system of OpenSim (Stanford, CA, USA) was selected to wide use to cyclist. Patients (or Participants) Twelve amateur bikers (12 males; age=26±2 y; height=176±5 cm; body weight=72±7.2 kg) of various ages, heights, and weights were recruited. Interventions (or Assessment of Risk Factors) Cycling strategy suggestion of Patello-femoral and tibial-femoral syndrome. Main Outcome Measurements Acute (Joint reaction) and chronic injury (Joint moment and muscle coordination) were calculated in real-time diagnosis. Results Simulating cycling strategies reduced knee flexion and external rotations of the feet, increasing the force application in the plantar flexion toward the bottom dead center, improving muscle activities at 80°–120° angle, and avoiding excessive slippage improved the VL and VM activities and prevented excessive reaction force in the joints and moment output. Conclusions The system was used to lower the possibility of injuries by providing improved cycling strategies and encouraging active training as well as facilitating sports and sports training performance. Overall, the developed system can be used to predict the possibility of lower limb injuries and lower the occurrence of such injuries.
Infusion reactions during infliximab treatment are not associated with IgE anti-infliximab antibodies
Authors: Karin A van Schie, Pleuni Ooijevaar-De Heer, Simone Kruithof, Chamaida Plasencia, Teresa Jurado, Dora Pascual Salcedo, Johannan F Brandse, Geert RAM d'Haens, Gerrit Jan Wolbink, Theo Rispens
Journal: Annals of the Rheumatic Diseases (2017)

Controversy exists on the role of IgE antidrug antibodies (IgE-ADA) in infusion reactions (IR) on infliximab treatment, partly due to the lack of a positive control used for assay validation. We sought to (1) develop a robust assay to measure IgE-ADA, including a positive control, (2) determine the association between IgE-ADA and IR and (3) determine the incidence of IgE-ADA in infliximab treated patients.A recombinant human IgE anti-infliximab monoclonal antibody was developed as standard and positive control. With this antibody, we set up a novel robust assay to measure IgE-ADA. IgE-ADA was determined in three retrospective cohorts (n=159) containing IR+ (n=37) and IR- (n=39), and longitudinal sera of 83 spondyloarthritis.IgE-ADA was found in 0/39 IR-, whereas 4/37 (11%) IR+ showed low levels (0.1-0.3 IU/mL, below the 0.35 IU/mL threshold associated with elevated risk of allergic symptoms). All patients who were IgE-ADA positive also had (very) high IgG-ADA levels. The incidence of IgE-ADA in patients with infliximab-treated spondyloarthritis was estimated at less than approximately 1%.IgE-ADA is rarely detected in infliximab-treated patients. Moreover, the absence of IgE-ADA in the majority of IR+ patients suggests that IgE-ADA is not associated with infusion reactions.
Abstract 271: A Novel Functional Role for Plasma miR-30d in Dyssynchronous Heart Failure
Authors: Kirsty Danielson, Yonathan Melman, Bridget Simonson, Andreas Barth, Khalid Chakir, Andre Kleber, Jagmeet Singh, David Kass, Saumya Das
Journal: Circulation Research (2013)

Introduction: We have previously shown that plasma miR-30d level is an independent predictor of echocardiographic response to cardiac resynchronization therapy (CRT) in patients with dyssynchronous heart failure (DHF). We now test the hypothesis that miR-30d is dynamically regulated in cardiomyocytes (CMs) and plays a functional role in DHF. Methods: miR-30d levels were assessed in a canine model of DHF and CRT using qRT-PCR, and potential miR-30d targets were identified using a bioinformatics approach. miR-30d targets were validated in the canine model and in CMs in culture. The regulation and functional role of miR-30d was investigated in CMs in culture using microscopy, western blotting and qRT-pCR. Results: miR-30d is enriched in the coronary sinus compared to peripheral blood in human patients, suggesting a cardiac origin (n=7, p&lt;0.05). In tissue samples from the canine model of DHF, miR-30d levels are highest in the lateral wall, in concert with the greatest wall stress, and decreases with CRT (n=5, p&lt;0.05). Bioinformatics analysis using differential gene expression data and in silico miR target prediction algorithms identified integrin and PI3/Akt signaling pathways as targets of miR-30d. Several targets including MAP4K4 and lims1 were further validated in tissue as well as in cultured CMs (n=4, p&lt;0.05). miR-30d appears to be expressed in CMs, packaged into exosomes and micovesicles, and released in response to pathological rotational stress (n=2). Over-expression of miR-30d in CMs induces cellular hypertrophy with a unique expression signature of cardiac hypertrophy markers most consistent with physiological hypertrophy (n=3, p&lt;0.05). Overexpression of miR-30d appears to be cardioprotective by abrogating TNF-induced increase in MAP4K4 expression (n=4, p&lt;0.05). Conclusions: miR-30d is dynamically regulated in DHF and appears to play an important role in CM biology. Further insight into the role of ‘stretch’-regulated microRNAs such as miR-30d may pave the way for novel therapeutic and diagnostic strategies.
Obesity is associated with hypothalamic injury in rodents and humans
Authors: Joshua P. Thaler, Chun-Xia Yi, Ellen A. Schur, Stephan J. Guyenet, Bang H. Hwang, Marcelo O. Dietrich, Xiaolin Zhao, David A. Sarruf, Vitaly Izgur, Kenneth R. Maravilla, Hong T. Nguyen, Jonathan D. Fischer, Miles E. Matsen, Brent E. Wisse, Gregory J. Morton, Tamas L. Horvath, Denis G. Baskin, Matthias H. Tschöp, Michael W. Schwartz
Journal: Journal of Clinical Investigation (2012)
Prognostic value of MACC1 and proficient mismatch repair status for recurrence risk prediction in stage II colon cancer patients: the BIOGRID studies
Authors: U.-P. Rohr, P. Herrmann, K. Ilm, H. Zhang, S. Lohmann, A. Reiser, A. Muranyi, J. Smith, S. Burock, M. Osterland, K. Leith, S. Singh, P. Brunhoeber, R. Bowermaster, J. Tie, M. Christie, H.-L. Wong, P. Waring, K. Shanmugam, P. Gibbs, U. Stein
Journal: Annals of Oncology (2017)
Effect of a pan anti-human alpha-v integrin antibody, CNTO95, on the adhesion, migration and growth of prostate cancer cells in culture and in a mouse model of human prostate cancer bone metastasis
Authors: Tohru Miyagi, Leland W K Chung, Majd Zayzahoon, Jeffrey Nemeth
Journal: Cancer Research (2006)

1168  Introduction and Objective: Integrins αv and β3 or β5 are known to express on the cell surface of cancer and neovascular endothelial cells and are mediating the adhesion, migration, growth and survival of cancer and the growth and tubular formation of the vascular endothelial cells. By targeting αv integrin with a monoclonal pan anti-human αv antibody, CNTO95, it is expected that the growth, adhesion, migration and survival of cancer cells and the new blood vessel formation around cancer tissues must be impaired. Methods: Integrin-dependent adhesion and migration of androgen independent human prostate cancer C4-2B was investigated on vitronectin-coated wells in the presence and absence of CNTO95. The effects of CNTO95 on C4-2B growth (by MTS assay), cell cycle progression and apoptosis (by FACS analysis) were investigated. To evaluate in vivo effect, we inoculated C4-2B into the tibia of athymic BALB/c nu/nu mice and began to treat mice with i.p. injection of CNTO95 at 10mg/kg 3 times per week for 12 weeks. We monitored the growth of C4-2B tumors by measuring serum PSA. Tumor specimens were analyzed by measuring tumor and bone areas. Results: CNTO95 effectively blocked the adhesion and migration of C4-2B cells in a dose-dependent manner. CNTO95 also inhibited the growth of these C4-2B on vitronectin-coated subtratum. FACS analysis demonstrated that CNTO95 arrested cell cycle progression at the G2 interphase and substantial apoptosis was found. Mice experiment showed modest inhibition of serum PSA (AV ±SEM), 201.7±151.5, 294.9±183.7 in treated and control group, respectively (n=5, P=0.36). However, upon histomorphologic analysis, we found a significant reduction of tumor area with a concomitant increase of cortical bone in mice treated with CNTO95. Conclusions: ECM-integrin interaction mediated by αvβ3 or αvβ5 is an attractive therapeutic target for the treatment of prostate cancer bone metastasis in men. In an experimental mouse model, we have shown that a pan anti-human αv antibody, CNTO95, was effective in blocking the growth of prostate tumors in bone and prevented the loss of cortical bone. Because of the low toxicity observed using this antibody therapy, targeting ECM-integrin interaction can be used in conjunction with other cytotoxic therapy, for the treatment of men with hormone refractory prostate cancer bone metastasis.