tbuckley/cabot-search huggingface dataset:
Abstract 5241: Clinical relevance of circulating tumor DNA in plasma from pancreatic cancer patients
Authors: Kjersti Tjensvoll, Morten Lapin, Tove Buhl, Satu Oltedal, Katrine Steen-Ottosen Berry, Bjørnar Gilje, Jon Arne Søreide, Millind Javle, Oddmund Nordgård, Rune Smaaland
Journal: Cancer Research (2015)

Abstract Background: Circulating tumor DNA (ctDNA) may originate from necrotic or apoptotic tumor cells in the primary tumor, metastatic lesions or in the circulation. There is evidence that the ctDNA level may reflect the total tumor burden in a patient. We wanted to investigate whether changes in the ctDNA level might be used to monitor disease progression in pancreatic cancer patients with locally or advanced disease. Methods: Blood samples (9 mL in EDTA tubes) were collected from 15 prospectively recruited patients with locally advanced and/or metastatic pancreatic cancer before initiation of treatment, and subsequently every month during chemotherapy. The samples were processed by LymphoprepTM (Axis Shield) density centrifugation before plasma DNA isolation using the QIAamp Circulating Nucleic Acid kit (Qiagen). A high-fidelity polymerase-based PNA clamp PCR method (Gilje et al., 2008, Oltedal et al., 2010) was then used for the detection of KRAS mutations in exon 12 and 13, as a surrogate marker for ctDNA. KRAS mutations have previously been reported to be present in &amp;gt;90% of the pancreatic cancers. Plasma samples from 29 healthy individuals were also analysed as a reference group for the PNA clamp PCR method. The results were compared with conventional biochemical and radiological monitoring measures. Results: The majority of the patients (80%) had metastatic disease and they were treated either by gemcitabine or FOLFORINOX. Nine (60%) patients had a positive KRAS status in the plasma samples obtained before initiation of chemotherapy, indicating presence of ctDNA. Moreover, 11 of the 15 included patients had ≥2 follow-up samples, and in several of these patients the ctDNA level changed substantially during the course of chemotherapy. In total, 17/38 (44.7%) patient samples were positive for plasma DNA KRAS mutations during chemotherapy. Changes in the ctDNA level seemed to correspond both to radiological follow-up data and changes in CA19-9 for several patients. Analyses of the total plasma DNA fraction with regard to disease monitoring, gave more inconclusive results in this small pilot study. Conclusion: Our pilot study gives support to the hypothesis that ctDNA may be used as a marker for monitoring treatment efficacy and disease progression in pancreatic cancer patients. This will be further investigated. Citation Format: Kjersti Tjensvoll, Morten Lapin, Tove Buhl, Satu Oltedal, Katrine Steen-Ottosen Berry, Bjørnar Gilje, Jon Arne Søreide, Millind Javle, Oddmund Nordgård, Rune Smaaland. Clinical relevance of circulating tumor DNA in plasma from pancreatic cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5241. doi:10.1158/1538-7445.AM2015-5241
P3-027: Anti-tumor efficacies of liposomal honokiol combined with cisplatin in lewis lung cancer and human a 549 lung cancer models
Authors: Qiqi Jiang, Lin-Yu Fan, Guang-Li Yang, Min-Hai Tang, Hao-Yu Ye, Wen-Li Hou, Jia Hu, Zheng-Hua Zhong, Xiang Chen, Yong-Bing Xu, Xia Li, Li-Juan Chen, Xiu-Hong Nie, Xiu-Yi Zhi, Yu-Quan Wei
Journal: Journal of Thoracic Oncology (2007)
The lymph node ratio as prognostic factor in patients with stage III rectal cancer treated with total mesorectal excision and postoperative chemoradiotherapy
Authors: Y. Kim, J. Kim, E. Choi, S. Ahn, S. Lee, J. Kim, C. Yu, T. Kim, H. Chang, J. Lee, M. Ryu
Journal: Journal of Clinical Oncology (2008)

15003 Background: To analyze the prognostic impact of the lymph node ratio (LNR) on survival in the patients with stage III rectal cancer. Methods: We retrospectively reviewed the data of 431 consecutive patients who underwent total mesorectal excision and postoperative chemoradiotherapy for rectal cancer from 1996 to 2006. Among these patients, 232 had positive lymph nodes (LN) and constituted this analysis. The patients were divided into the following four groups based on quartiles of LNR value: LNR ≤ 0.1 (n=69), ≤ 0.2 (n=49), ≤ 0.4 (n=54), and more than 0.4 (n=60). The association between LNR and survival was evaluated by Kaplan-Meier method and multivariate analysis with covariates including age, gender, T, N stage, carcinoembryonic antigen (CEA) level, histologic differentiation, tumor size, type of operation, number of positive LNs, number of examined LNs, and LNR. Results: The median number of examined and positive LNs were 18, and 3. The median value LNR was 0.20 (range, 0.03–1). There was a strong correlation between the number of positive LNs and LNR (r=0.724, p<0.001). After a median follow-up of 53 months (range, 9–138 months), the actuarial overall survival (OS) and disease-free survival (DFS) at 5 years were 69% and 60%. Five-year survival rate decreased as LNR increased (LNR ≤ 0.1, 89%; LNR ≤ 0.2, 67%; LNR ≤ 0.4, 64%; and LNR > 0.4, 50%, p<0.0001), and LNR was only a significant prognostic factor on stepwise regression analysis (LNR ≤ 0.1, HR=1; LNR ≤ 0.2, HR=1.5, p=0.392; LNR ≤ 0.4, HR=3.0, p=0.018;LNR > 0.4, HR=4.1, p=0.003). In each subgroup of N1 and N2, the prognostic impact on OS of LNR remained (p=0.0323 in N1; p=0.0344 in N2). Conclusions: LNR was the most significant predictors of survival in the patients with stage III rectal cancer who had undergone postoperative chemoratiation. No significant financial relationships to disclose.
P3-097: Regressions 14 days following bevacizumab as a single agent as part of neoadjuvant chemotherapy for resectable non–squamous NSCLC
Authors: Leonard P. James, Valerie Rusch, Binsheng Zhao, Emir Senturk, Lawrence Schwartz, Robert J. Downey, Nabil Rizk, Lee M. Krug, Mark G. Kris, Naiyer A. Rizvi
Journal: Journal of Thoracic Oncology (2007)
THE MULTIFUNCTIONAL PROTEIN E4F1 LINKS P53 TO LIPID METABOLISM AND ADIPOSE TISSUE FUNCTIONS
Authors: Matthieu Lacroix, Laetitia K Linares, Natalia Rueda-rincon, Laurie Gayte, Emilie Blanchet, Rita Derua, Jean-Sebastien Annicotte, Nelly Pirot, Charles Vincent, Florence Bernex, Lluis Fajas, Johan Swinnen, Laurent Le Cam
Journal: Journal of Clinical Investigation (2015)
P2-257: The role of palliative chemotherapy in metastatic non small cell lung cancer with brain metastases
Authors: Daniel W. Wong, Paul Sanghera, Qamar Ghafoor, Jas Kaur, Philippa Howlett, Harriet S. Walters, Stuart I. Collins, Ahmed El Modir, Anula D. Chetiyawardana
Journal: Journal of Thoracic Oncology (2007)
Nearly half of US pediatric trials are unfinished or unpublished, study finds
Authors: Michael McCarthy
Journal: BMJ (2016)

Nearly half of the pediatric randomized clinical trials registered on the US trial registry ClinicalTrials.gov were not completed or their results were not published, a study has found.1

In the study, reported in Pediatrics , Natalie Pica and Florence Bourgeois of Boston Children’s Hospital, Boston, Massachusetts, reviewed pediatric randomized clinical trials, involving children from birth to age 17, that were posted on ClinicalTrials.gov from 2008 to 2010. The researchers found that of the 559 trials registered on the site in this period 104 (19%) were discontinued early. An estimated …
Epigenetics in liver disease: from biology to therapeutics
Authors: Timothy Hardy, Derek A Mann
Journal: Gut (2016)

Knowledge of the fundamental epigenetic mechanisms governing gene expression and cellular phenotype are sufficiently advanced that novel insights into the epigenetic control of chronic liver disease are now emerging. Hepatologists are in the process of shedding light on the roles played by DNA methylation, histone/chromatin modifications and non-coding RNAs in specific liver pathologies. Alongside these discoveries are advances in the technologies for the detection and quantification of epigenetic biomarkers, either directly from patient tissue or from body fluids. The premise for this review is to survey the recent advances in the field of liver epigenetics and to explore their potential for translation by industry and clinical hepatologists for the design of novel therapeutics and diagnostic/prognostic biomarkers. In particular, we present findings in the context of hepatocellular carcinoma, fibrosis and non-alcoholic fatty liver disease, where there is urgent unmet need for new clinical interventions and biomarkers.
Vorinostat in Combination with Pegylated Liposomal Doxorubicin and Bortezomib for Patients with Relapsed/Refractory Multiple Myeloma: Results of a Phase I Study.
Authors: Peter M. Voorhees, Cristina Gasparetto, Kristy L. Richards, Reynaldo Garcia, John S. Strader, Madlyn Ferraro, Jennifer MacLean, Diane Winans, Dominic T. Moore, Andrew Dodd, Matthew C. Foster, Don A. Gabriel, Thomas C. Shea, Jonathan Serody, Hendrik W. van Deventer, Syed Rizvi, Robert Z. Orlowski, David D. Hurd
Journal: Blood (2009)
An updated meta-analysis of calcium channel blockers in the prevention of restenosis after coronary angioplasty
Authors: J Dens, Walter Desmet, Jan Piessens
Journal: Circulation (2001)

Abstract    Background  In 1994, a meta-analysis of 5 small randomized trials reported a 30% reduction in the odds of angiographic restenosis when calcium-channel blockers (CCB) were given after percutaneous coronary intervention. Recently, the results of 2 large similar trials (Nisoldipine In Coronary Artery Disease in Leuven [NICOLE], and Coronary AngioPlasty Amlodipine in REstenosis Study [CAPARES]) were published. An extended meta-analysis including the results of the latter trials was performed.  Methods  A total of 2380 patients were analyzed. Statistical analysis included calculation of odds ratios for each trial, common odds ratio, and homogeneity for treatment effects across trials.  Results  The incidence of angiographic restenosis was 36% in the CCB-treated group and 42% in the placebo group. The odds ratio of restenosis with CCB therapy was 0.78 (95% CI 0.64-0.95) compared with control patients ( P  = .01). Treatment effects were homogeneous across the trials. For the combined end point of death, coronary artery bypass grafting, repeat percutaneous transluminal coronary angioplasty, and myocardial infarction, 126 of 626 events occurred in the CCB group and 191 of 655 in the placebo group (odds ratio 0.61 [95% CI 0.47-0.80],  P   Conclusions  This extended meta-analysis confirmed a reduction in the odds of restenosis and clinical events when CCBs were added to standard therapy after percutaneous coronary intervention. (Am Heart J 2003; 145:404-8.)
Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation
Authors: E Ilker Ozay, Gabriela Gonzalez-Perez, Joe A Torres, Jyothi Vijayaraghavan, Rebecca Lawlor, Heather L Sherman, Daniel T Garrigan, Amy S Burnside, Barbara A Osborne, Gregory N Tew, Lisa M Minter
Journal: Molecular Therapy (2016)

Targeting cellular proteins with antibodies, to better understand cellular signaling pathways in the context of disease modulation, is a fast-growing area of investigation. Humanized antibodies are increasingly gaining attention for their therapeutic potential, but the collection of cellular targets is limited to those secreted from cells or expressed on the cell surface. This approach leaves a wealth of intracellular proteins unexplored as putative targets for antibody binding. Protein kinase Cθ (PKCθ) is essential to T cell activation, proliferation, and differentiation, and its phosphorylation at specific residues is required for its activity. Here we report on the design, synthesis, and characterization of a protein transduction domain mimic capable of efficiently delivering an antibody against phosphorylated PKCθ (Thr538) into human peripheral mononuclear blood cells and altering expression of downstream indicators of T cell activation and differentiation. We used a humanized, lymphocyte transfer model of graft-versus-host disease, to evaluate the durability of protein transduction domain mimic:Anti-pPKCθ modulation, when delivered into human peripheral mononuclear blood cells ex vivo. We demonstrate that protein transduction domain mimic:Antibody complexes can be readily introduced with high efficacy into hard-to-transfect human peripheral mononuclear blood cells, eliciting a biological response sufficient to alter disease progression. Thus, protein transduction domain mimic:Antibody delivery may represent an efficient ex vivo approach to manipulating cellular responses by targeting intracellular proteins.
Interpretation of the evidence for the efficacy and safety of statin therapy
Authors: Rory Collins, Christina Reith, Jonathan Emberson, Jane Armitage, Colin Baigent, Lisa Blackwell, Roger Blumenthal, John Danesh, George Davey Smith, David DeMets, Stephen Evans, Malcolm Law, Stephen MacMahon, Seth Martin, Bruce Neal, Neil Poulter, David Preiss, Paul Ridker, Ian Roberts, Anthony Rodgers, Peter Sandercock, Kenneth Schulz, Peter Sever, John Simes, Liam Smeeth, Nicholas Wald, Salim Yusuf, Richard Peto
Journal: The Lancet (2016)
Moderate Dose Escalation for Advanced Stage Hodgkin’s Disease Using the Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone Scheme and Adjuvant Radiotherapy: A Study of the German Hodgkin’s Lymphoma Study Group
Authors: H. Tesch, V. Diehl, B. Lathan, D. Hasenclever, M. Sieber, U. Rüffer, A. Engert, J. Franklin, M. Pfreundschuh, K.P. Schalk, G. Schwieder, G. Wulf, G. Dölken, P. Worst, P. Koch, N. Schmitz, U. Bruntsch, C. Tirier, U. Müller, M. Loeffler
Journal: Blood (1998)
Early termination of adjuvant therapy for breast and colorectal cancers
Authors: J. Lipscomb, T. W. Gillespie, K. C. Ward, M. Goodman
Journal: Journal of Clinical Oncology (2007)

6610 Background. Recent patterns-of-care studies report that cancer patients often do not complete prescribed therapy, with potentially important implications for clinical outcomes including survival. Yet, little is known about the frequency and determinants of early treatment discontinuation. The aims of this study were to address these issues in a largely rural population of a 33-county region of southwest Georgia. Methods. A total of 3,996 cases of breast, colorectal (CRC), lung, and prostate cancer diagnosed between 2001 and 2003 were identified from the Georgia Comprehensive Cancer Registry, with data collected from medical records by trained abstractors; 3,949 cases were available for analysis. Since completion of adjuvant chemotherapy with a goal of cure may be particularly important, this report focuses on cases treated for stage I and II breast cancer and stage III CRC. Results. Among 854 stage I-II breast cancer cases, 323 (38%) received chemotherapy. In 293 of those cases, treatment was stopped within the first year post-diagnosis. The primary reasons for stopping included treatment completion (86%), significant toxicity (8%), or other clinical reasons (2%). In only seven cases (2%) was treatment discontinued due to patient factors (e.g. refusal or did not return to clinic). Among 179 stage III CRC cases, 124 (69%) received adjuvant chemotherapy; in 117 cases chemotherapy was stopped within 12 months following diagnosis. Clinical reasons for stopping chemotherapy in those 117 cases included treatment completion (67%), toxicity (12%), disease progression (8%), or death (3%). In only 4% of cases was chemotherapy discontinued due to patient refusal, and in 3% of cases a patient was lost to follow up. Conclusions. In this largely rural population, only a small proportion of cases stopped adjuvant chemotherapy early due to patient-attributable factors; most treatment termination was due to clinical indications. Review of practice patterns using only administrative data may not reveal the actual reasons for treatment discontinuation. Further study of underlying factors of early termination is needed to design appropriate interventions to promote completion of prescribed therapy. No significant financial relationships to disclose.
Organisation of Pharmaceutical Producers of India replies to article on India’s health camps
Authors: Ranjana Smetacek
Journal: BMJ (2016)

Joelving’s article on India’s health camps alleges unethical conduct at these camps, naming several drug companies, including members of the Organisation of Pharmaceutical Producers of India (OPPI).1 I am writing on behalf of these OPPI member companies.

Our companies do not control how health camps are conducted. Healthcare professionals are at the centre of these camps, which are run in collaboration with government hospitals, non-governmental organisations, civil society representatives, and …
P1-225: Phase II trial of gemcitabine and irinotecan in previously treated patients with small-cell lung cancer
Authors: Yoshio Okano, Atsushi Horiike, Fumiyoshi Ohyanagi, Yukitoshi Satoh, Sakae Okumura, Yuichi Ishikawa, Ken Nakagawa, Takeshi Horai, Makoto Nishio
Journal: Journal of Thoracic Oncology (2007)
First-in-human study of TAS-115, a novel oral MET/VEGFR inhibitor, in patients with advanced solid tumors.
Authors: Nobuaki Matsubara, Kohei Shitara, Yoichi Naito, Yasutoshi Kuboki, Izumi Ohno, Hideaki Takahashi, Hideaki Bando, Takashi Kojima, Nozomu Fuse, Tomoko Yamazaki, Naoki Hirayama, Hidenori Fujita, Toshirou Nishida, Toshihiko Doi
Journal: Journal of Clinical Oncology (2015)

2532 Background: Aberrations in the MET receptor tyrosine kinase pathway occur in various human malignancies (via MET amplification, mutation, or overexpression) driving cell proliferation, survival and metastasis. TAS-115 is a novel oral MET/VEGFR inhibitor with preclinical activity in human tumor models. This dose escalation study evaluates TAS-115 in patients (pts) with advanced solid tumors. Methods: In this Phase I study, the primary objective is to determine the MTD and RD of TAS-115, secondary objectives included safety and tolerability, antitumor activity, and PK. Eligible pts (aged ≥ 20 years, ECOG PS ≤ 1) had tumors that are refractory to standard therapy. The accelerated titration and 3+3 design are used in this study. TAS-115 is administered continuously 21 days in one cycle. Results: Phase I was begun in Oct 2011. The drug formulation has been changed because of the saturation of absorption. Phase I using the new formulation was restarted from Dec 2013. As of Jan 15 2015, 18 pts were enrolled in the dose escalation phase of new formulation (67% male, median age 61 years, 55% PS 0). The numbers of types of tumors were gastrointestinal stromal tumor in 3, gastric in 3, colorectal in 2, bile duct in 2, breast in 2, and others in 6 pts. Pts were treated in 5 dose cohorts of 200-800 mg. DLTs occurred at 800 mg in the 2 pts, which included grade 3 thrombopenia with hemorrhage and grade 3 rash. The frequent drug-related AEs (all grade ≥ 35%) were edema (67%), AST increase (61%), fatigue (56%), ALT increase (50%), rash (50%), leucopenia (44%), neutropenia (39%), thrombopenia (39%). TAS-115 exposure was generally increased with dosage. Mean Cmax and AUClast at 800 mg were 4,910 ng/mL and 39,400 ng*h/mL, respectively, with a mean Tmax of 1.3 hrs and apparent T1/2of 13.7 hrs. Preliminary efficacy was observed in 5 pts. 2 pts maintained SD more than 12 and 24 weeks, respectively, and reduction of SUV in PET was observed in 5 pts. Biomarker analysis including MET status is also evaluated and will be presented. Conclusions: TAS-115 was well tolerated and the safety profile was confirmed up to 800 mg. The ongoing dose escalation is still under evaluation and RP2D will be determined. Clinical trial information: JapicCTI-111645 and 132333 Clinical trial information: JapicCTI-111645 and JapicCTI-132333.
L1-associated genomic regions are deleted in somatic cells of the healthy human brain
Authors: Jennifer A Erwin, Apuã C M Paquola, Tatjana Singer, Iryna Gallina, Mark Novotny, Carolina Quayle, Tracy A Bedrosian, Francisco I A Alves, Cheyenne R Butcher, Joseph R Herdy, Anindita Sarkar, Roger S Lasken, Alysson R Muotri, Fred H Gage
Journal: Nature Neuroscience (2016)
Left atrial appendage occlusion to prevent stroke in sub-optimal warfarin candidates: Current results of the European multicenter registry trial
Authors: E Fischer, H Omran, L Thuesen, M Pichler, E Rowland, A Bartorelli, P Brugada, PW Serruys, Werner Budts, A Ramondo, A Vahanian, P Probst, G Montalescot, JF Piechaud, KH Kuck, W Ruzyllo, J Marco, T Wichter, E Garcia, E Onorato, Y Bayard, S Ostermayer, F Buscheck, M Leetz, H Sievert
Journal: Journal of the American College of Cardiology (2005)
Brief Report: <i>IRF4</i> Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross‐Disease Meta‐Analysis of Genome‐Wide Association Studies
Authors: Elena López‐Isac, Jose‐Ezequiel Martín, Shervin Assassi, Carmen P. Simeón, Patricia Carreira, Norberto Ortego‐Centeno, Mayka Freire, Emma Beltrán, Javier Narváez, Juan J. Alegre‐Sancho, Benjamín Fernández‐Gutiérrez, Alejandro Balsa, Ana M. Ortiz, Miguel A. González‐Gay, Lorenzo Beretta, Alessandro Santaniello, Chiara Bellocchi, Claudio Lunardi, Gianluca Moroncini, Armando Gabrielli, Torsten Witte, Nicolas Hunzelmann, Jörg H. W. Distler, Gabriella Riekemasten, Annette H. van der Helm‐van Mil, Jeska de Vries‐Bouwstra, Cesar Magro‐Checa, Alexandre E. Voskuyl, Madelon C. Vonk, Øyvind Molberg, Tony Merriman, Roger Hesselstrand, Annika Nordin, Leonid Padyukov, Ariane Herrick, Steve Eyre, Bobby P. C. Koeleman, Christopher P. Denton, Carmen Fonseca, Timothy R. D. J. Radstake, Jane Worthington, Maureen D. Mayes, Javier Martín
Journal: Arthritis & Rheumatology (2016)

Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc-RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc-RA loci through an interdisease meta-genome-wide association (meta-GWAS) strategy.The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case-control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls.This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 10(-6) ) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined = 3.29 × 10(-12) ). Analysis of the biologic relevance of the known SSc-RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors.This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.
Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate
Authors: Kristina M Adams Waldorf, Jennifer E Stencel-Baerenwald, Raj P Kapur, Colin Studholme, Erica Boldenow, Jay Vornhagen, Audrey Baldessari, Manjiri K Dighe, Jeff Thiel, Sean Merillat, Blair Armistead, Jennifer Tisoncik-Go, Richard R Green, Michael A Davis, Elyse C Dewey, Marian R Fairgrieve, J Christopher Gatenby, Todd Richards, Gwenn A Garden, Michael S Diamond, Sandra E Juul, Richard F Grant, LaRene Kuller, Dennis W W Shaw, Jason Ogle, G Michael Gough, Wonsok Lee, Chris English, Robert F Hevner, William B Dobyns, Michael Gale, Lakshmi Rajagopal
Journal: Nature Medicine (2016)