tbuckley/cabot-search huggingface dataset:
SP0180 Biologics and other inflammatory therapies in finger oa. what have we learned?
Authors: X Chevalier
Journal: Annals of the Rheumatic Diseases (2017)

Hand osteoarthritis (HOA) is the most frequent form of osteoarthritis. A subset of digital hand OA is marked by an "inflammatory" like presentation with painful interphalangeal joints, refractory to NSAIDS and analgesics. This clinical form of OA may be associated with a so called "erosive" radiographic aspect marked by subchondral erosions of the finger joints and ankylosis. Many mediators of inflammation have been involved in the pathogenesis of osteoarthritis such as prostaglandin E2, free radicals and main cytokines (IL1B, IL6, and TNFa). Using Doppler power ultrasonography and magnetic resonance imaging, it has been shown that synovitis is frequently associated with HOA and correlates with pain and with disease progression. Taking all those considerations together, it appears logical to target synovitis in HOA, especially with an erosive form. Because erosive hand OA is a polyarticular disease, the treatment is more systemic than local. Local or oral NSAIDS are out of scope because this presentation focuses on patients with HOA non responders to analgesics and NSAIDS. So far, none of the disease modifying drugs such as methotrexate has proved its efficacy. Regarding biologics, several strategies have been approached. The first biotherapy used in HOA was IL2 receptor plus hydroxychloroquine in a very limited number of patients. Then and more recently, anti-TNFa strategy has been tested in well done RCT, in painful hand OA: one with adalimumab over a year, one with adalimumab 40 mg with 2 sub-cutaneous injections, one using Etanercept (50 mg/week 24 weeks and then 25 mg/week the next 24 weeks). None of those anti-TNFa blockers demonstrated a structural or an analgesic effect. However in the long term trial published by Verbruggen G, the incidence of new erosive lesions was decreased in Adalimumab group compared to placebo, only in a subgroup of patient with clinically inflamed IP joints. Using anti-IL1B strategy, a decrease in pain has been observed in 3 patients using daily subcutaneous injection of Anakinra (100mg) over 3 months ( ). In this Eular meeting a double inhibition of IL-1 Beta and IL-1 Alpha (using a monoclonal antibody directed against both cytokine) failed to demonstrate any benefit compared to placebo injection over 26 weeks. Finally anti-IL6 strategy has been presented in this 2017 Eular meeting in a limited number of patients (n=18) with erosive HOA. Using monthly IV perfusion, the authors showed an improvement in pain level and functional status. Conclusion: though anti-inflammatory strategy in painful HOA is logical, no treatment so far has been able to demonstrate a beneficial effect. Further studies should contemplate either news targets, or new modalities of repeated injections and should be adapted according to the phenotype of pain. <h3>Disclosure of Interest</h3> None declared
P2.02: Thymic Malignancies. A Single Institution Series From 2006-2016
Authors: Flavio L. Cabral, Maria Teresa Ruiz Tsukazan, Jayme O. Rios, Jayme R. Heck, Gabriel M. Schwarcke, Renata M. Rosenthal, Maicon J. Cimarosti, João R. Schmitt, José Antônio Figueiredo Pinto
Journal: Journal of Thoracic Oncology (2016)
新たにスクリーニングしたEGFR/HER2標的ペプチドで官能化したマグネトソームナノ粒子を用いた腫瘍検出【Powered by NICT】
Authors: Xiang Zhichu, Yang Xiaoliang, Xu Junjie, Lai Wenjia, Wang Zihua, Hu Zhiyuan, Tian Jiesheng, Geng Lingling, Fang Qiaojun
Journal: Biomaterials (2017)
中等度冠動脈狭窄病変を有する患者における冠血流予備量比とInstantaneous Wave‐Free Ratio(iFR)の値の比較
Authors: Misawa Toru, Kimura Shigeki, Nakagama Shun, Nakamura Shun, Hayasaka Kazuto, Mizusawa Masafumi, Yamakami Yosuke, Kojima Keisuke, Sagawa Yuichirou, Hishikari Keiichi, Yamao Kazuya, Nakashima Emiko, Nakajima Jun, Tanaka Yasuaki, Ohkubo Kenji, Takagi Katsumasa, Kuwahara Taishi, Hikita Hiroyuki, Takahashi Atsushi, Isobe Mitsuaki
Journal: Circulation (2016)
PTH-015 Prospective Comparison of Fice and I-Scan for In-Vivo Characterisation of Small Colonic Polyps: Abstract PTH-015 Table 1
Authors: P J Basford, G R Longcroft-Wheaton, P Bhandari
Journal: Gut (2013)

<h3>Introduction</h3> In-vivo characterisation of small colonic polyps has been reported using several technologies but with few prospective comparisons between them. We aimed to compare the accuracy of Flexible Spectral Imaging Colour Enhancement (FICE) and i-Scan in the assessment of polyps &lt; 10mm. In addition the relationship between accuracy of white light assessment (WL) and resolution of endoscope was assessed. <h3>Methods</h3> Patients undergoing screening colonoscopy through the UK BCSP were prospectively recruited. All procedures were performed by a single endoscopist with extensive experience in in-vivo diagnosis. For the FICE group Fujinon 410,000 pixel CCD and 650,000 pixel CCD colonoscopes were used with an EPX 4400 processor. For the i-Scan group Pentax 1.2 Megapixel colonoscopes were used with an EPKi processor. All polyps &lt; 10mm were assessed sequentially using white light endoscopy (WL) and either FICE or i-Scan before resection. Predicted histology was recorded with both modalities and compared to the final histopathological diagnosis. In-vivo characterisation accuracy was analysed based on the resolution of the endoscopes used; standard definition - SD (410K pixel), high definition – HD (650K pixel) and HD+ (1.2M pixel). <h3>Results</h3> In the FICE group 293 polyps of mean size 4.7mm were assessed in 170 patients. In the i-Scan group 209 polyps of mean size 4.3mm were assessed in 84 patients. There was no significant difference in WL accuracy between SD and HD endoscopes (70% vs 72.7%, p = 0.606), however accuracy was significantly higher with the HD+ 1.2megapixel CCD endoscopes (93.3%) compared to both the SD (70.0%, p = 0.0001) and HD (72.7%, p = 0.0001) endoscopes. Sensitivity was significantly greater with FICE using an HD endoscope compared to an SD endoscope (92.6% vs 83.3%, p = 0.048). Overall accuracy was significantly greater with HD+ i-Scan (94.7%) than SD FICE (82.7%, p = 0.0003) and HD FICE (88.8%, p = 0.0439). The use of FICE improved accuracy from 70.0% with WL to 82.7% (p = 0.014) and from 72.7% with WL to 88.8% (p &lt; 0.001) for SD and HD endoscopes respectively. Only a minor gain over WL was seen with addition of iScan (93.3% to 94.7%, p = 0.68). <h3>Conclusion</h3> Only a small, non-significant gain in WL accuracy is seen between a 410K pixel SD endoscope and a 650K pixel HD endoscope. However diagnostic accuracy with WL improves significantly with a 1.2 megapixel endoscope. FICE significantly improves accuracy when used with an SD or HD endoscope but the very high WL accuracy of a 1.2 megapixel endoscope allows no significant additional improvement with i-Scan. <h3>Disclosure of Interest</h3> None Declared.
Where is the evidence for general intelligence in nonhuman animals?
Authors: Ludwig Huber
Journal: Behavioral and Brain Sciences (2017)

Abstract This commentary contrasts evolutionary plausibility with empirical evidence and cognitive continuity with radiation and convergent evolution. So far, neither within-species nor between-species comparisons on the basis of rigorous experimental and species-appropriate tests substantiate the claims made in the target article. Caution is advisable on meta-analytical comparisons that primarily rely on publication frequencies and overgeneralizations (from murids and primates to other nonhuman animals).
Ascorbic Acid Content of Tumors and Homologous Normal Tissues
Authors: William van B. Robertson
Journal: JNCI Journal of the National Cancer Institute (1943)

Ascorbic Acid Content of Tumors and Homologous Normal Tissues William van B. Robertson William van B. Robertson research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 3, December 1943, Pages 321–328, https://doi.org/10.1093/jnci/4.3.321 Published: 01 December 1943
The real-world experience with nivolumab in previously treated patients with advanced non small cell lung cancer (NSCLC): A Galician Lung Cancer Group clinical practice.
Authors: MC Areses, Rosario Garcia Campelo, Jorge García González, Francisco Javier Afonso, Martin Emilio Lazaro, Begoña Campos, Cristina Azpitarte, Margarita Amenedo, Lucía Santomé, David Arias Ron, Guillermo Alonso-Jaudenes, Francisco Baron, Rocio Vilchez, Joaquin Casal, Natalia Fernandez, Iria Carou, Joaquin Mosquera, Urbano Anido, Jesus Garcia Mata, Jose-luis Firvida
Journal: Journal of Clinical Oncology (2017)

e20564 Background: Nivolumab, was the first checkpoint inhibitor to show a survival benefit in previously treated patients with advanced NSCLC in two randomized trials (CheckMate 017 and 057). Experience in routine clinical practice may differ from that seen in a controlled clinical trial. This is an observational study that represents the real-world experience. Methods: Elegibility criteria included, histologically confirmed NSCLC stage IIIB vs IV, evaluable disease and at least one prior therapy. Patients received nivolumab 3 mg/kg IV (60 min) every 2 weeks until progressive disease or unacceptable toxicity. The aim of the study was to report the efficacy and safety profile of Nivolumab in pretreated patients with advanced NSCLC of our everyday clinical practice. The exploratory assessments include response rate (RR), progression-free survival (PFS), overall survival (OS) and treatment related adverse events (AEs). Results: From August 2015 to January 2017, with a median follow time of 18 months, 188 patients were enrolled from 9 different centers. Patients demographics were: median age 62 years, 44 female and 144 male; 17 never smoker and 171 former or current smoker; 105 adenocarcinoma, 7 large-cell carcinoma, 66 squamous, 3 adenosquamous and 7 NSCLC; 61 stage IIIB and 129 stage IV; 42 with central nervous system metastasis; and 70 received 2 or more prior therapy lines. Among 156 patients evaluated, 1,3% had CR, 28,2% PR, 29,7% SD and 40,8% PD. At the time of database lock, the median of PFS was 2.9 IC 95% (2,3-3.4) and OS was 12,8 IC 95% (9,2-16,4). The evaluation of PFS and OS by baseline characteristics doesn´t revealed statistical significance. Grade 1-2 treatment related adverse events (AEs) occurred in 58% of the patients: asthenia (22%), rash (14%), diarrhea (8%), anorexia (7%), endocrine (6%) and neumonitis (1,5%). Grade 3-4 AEs occurred in 5 patients; (3) diarrhea and (2) neumonitis and there were 3 treatment-related deaths. Conclusions: This study represents the real-word experience with nivolumab and the results are consistent with those previously reported in the CheckMate 017 and 057 trials.
Exercise rehabilitation programs for the treatment of claudication pain. A meta-analysis
Authors: A. W. Gardner
Journal: JAMA (1995)

Objective.  —To identify the components of exercise rehabilitation programs that were most effective in improving claudication pain symptoms in patients with peripheral arterial disease.  Data Sources.  —English-language articles were identified by a computer search using Index Medicus and MEDLINE, followed by an extensive bibliography review.  Study Selection.  —Studies were included if they provided the mean or individual walking distances or times to the onset of claudication pain and to maximal pain during a treadmill test before and after rehabilitation.  Data Extraction.  —Walking distances and times and characteristics of the exercise programs were independently abstracted by two observers.  Data Synthesis.  —Thirty-three English-language studies were identified, of which 21 met the inclusion criteria. Overall, following a program of exercise rehabilitation, the distance (mean±SD) to onset of claudication pain increased 179% from 125.9±57.3 m to 351.2±188.7 m ( P  P  P   Conclusions.  —The optimal exercise program for improving claudication pain distances in patients with peripheral arterial disease uses intermittent walking to near-maximal pain during a program of at least 6 months. Such a program should be part of the standard medical care for patients with intermittent claudication.  ( JAMA . 1995;274:975-980)
Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial
Authors: Dirk Sibbing, Dániel Aradi, Claudius Jacobshagen, Lisa Gross, Dietmar Trenk, Tobias Geisler, Martin Orban, Martin Hadamitzky, Béla Merkely, Róbert Gábor Kiss, András Komócsi, Csaba A Dézsi, Lesca Holdt, Stephan B Felix, Radoslaw Parma, Mariusz Klopotowski, Robert H G Schwinger, Johannes Rieber, Kurt Huber, Franz-Josef Neumann, Lukasz Koltowski, Julinda Mehilli, Zenon Huczek, Steffen Massberg, Radoslaw Parma, Zofia Parma, Maciej Lesiak, Anna Komosa, Zenon Huczek, Lukasz Koltowski, Michal Kowara, Bartosz Rymuza, Mariusz Klopotowski, Lukasz Malek, Daniel Aradi, Gábor Veress, András Döme Dézsi, Béla Merkely, Árpád Lux, Róbert Gábor Kiss, Judit Papp, Andrea Kovács, Csaba András Dézsi, Sayour Amer, Zoltán Ruzsa, Szilárd Róna, András Komócsi, Renáta Ili, Imre Ungi, Ferenc Nagy, Robert Zweiker, Gábor Tóth-Gayor, Kurt Huber, Paul Haller, Wolfgang von Scheidt, Andreas Blüthgen, Franz-Josef Neumann, Dietmar Trenk, Stefan Leggewie, Hans Ulrich Kreider-Stempfle, Thomas Remp, Kaffer Kara, Andreas Mügge, Alexander Wutzler, Stephan Fichtlscherer, Andreas M. Zeiher, Florian Seeger, Martin Hinterseer, Andreas König, Susanne Lederle, Claudius Jacobshagen, Frauke Czepluch, Lars Maier, Wolfgang Schillinger, Samuel Sossalla, Astrid Hummel, Stephan Felix, Mahir Karakas, Karsten Sydow, Tanja Rudolph, Marcel Halbach, Tommaso Gori, Thomas Münzel, Andreas May, Carsten-Manuel Gerstenberg, David Pilecky, Johannes Rieber, Markus Deichstetter, Dirk Sibbing, Julinda Mehilli, Lisa Gross, Stefan Kääb, Anja Löw, Martin Orban, Matthias Orban, Stefan Sattler, Sabine Deuschl, Daniel Teupser, Lesca Holdt, Harald Mudra, Thomas Räder, Torsten Schütz, Felix Vahldiek, Dimitar Divchev, Hüseyin Ince, Christoph A Nienaber, Henning Radunski, Peter Boekstegers, Jan Horstkotte, Ralf Mueller, Tobias Geisler, Karin Müller, Robert Schwinger, Oliver Rasp
Journal: The Lancet (2017)
BMS-582664, a dual inhibitor of VEGF and FGF signaling pathways, induces growth suppression and apoptosis in mouse models of hepatocellular carcinoma
Authors: Huynh Hung, Fargnoli Joseph, Ayers Mark, Soo Chee, Chow Pierce, Tran Evelyn
Journal: Clinical Cancer Research (2007)

A31  Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with no effective treatment for most individuals who succumb to this neoplasm. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived endothelial growth factor (PDGF) released from the tumor itself, inflammatory cells, and/or tumor stromal cells participate in the growth, neovascularization, invasiveness, and metastatic potential of HCC. In this study subcutaneous human HCC xenografts were used to determine the in vivo anti-neoplastic activity of a dual inhibitor of VEGF and FGF signaling pathways, BMS-582664. We report that BMS-582664 significantly suppressed tumor growth of six HCC xenograft lines. BMS-582664-induced growth inhibition was associated with increased apoptosis, reduction in microvessel density, inhibition of cell proliferation, and down-regulation of cell cycle regulators, including cyclin D1, Cdk-2, Cdk-4, cyclin B1, and phospho-c-Myc. Our study provides a strong rationale for clinical investigation of BMS-582664 in patients with HCC.
Trends in Financial Access to Prescription Drugs Among Cancer Survivors
Authors: Felisa Gonzales, Zhiyuan Zheng, K. Robin Yabroff
Journal: JNCI Journal of the National Cancer Institute (2017)

Little is known about the competing effects of increasing prescription drug costs and expansions in insurance coverage on prescription drug access and whether trends vary for adults with and without a cancer history. Using the 2010-2015 National Health Interview Survey, we examined trends in limited prescription drug access, operationalized as forgoing needed prescription drugs because of cost. The percentages of adults age 18 to 64 years with limited prescription drug access decreased over time: predicted margins from multivariable logistic regression models were 13.8% in 2010 vs 8.6% in 2015 for cancer survivors and 11.0% vs 6.8% for adults without a cancer history (adjusted odds ratio [aOR] for trend = 0.89, 95% confidence interval [CI] = 0.88 to 0.90). Access changed little for adults age 65 years and older. Among adults age 18 to 64 years, cancer survivors were more likely than those without a cancer history to report limited access to any prescription drug in all years (aOR from multivariable logistic regression model = 1.45, 95% CI = 1.31 to 1.61). However, trends did not differ by cancer history. Our findings suggest that expansions in health insurance coverage mitigated the effects of growing prescription drug costs to some extent for many individuals with and without a history of cancer.
Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors
Authors: Hana Janouskova, Geniver El Tekle, Elisa Bellini, Namrata D Udeshi, Anna Rinaldi, Anna Ulbricht, Tiziano Bernasocchi, Gianluca Civenni, Marco Losa, Tanya Svinkina, Craig M Bielski, Gregory V Kryukov, Luciano Cascione, Sara Napoli, Radoslav I Enchev, David G Mutch, Michael E Carney, Andrew Berchuck, Boris J N Winterhoff, Russell R Broaddus, Peter Schraml, Holger Moch, Francesco Bertoni, Carlo V Catapano, Matthias Peter, Steven A Carr, Levi A Garraway, Peter J Wild, Jean-Philippe P Theurillat
Journal: Nature Medicine (2017)
β-Adrenergic Signaling in Mice Housed at Standard Temperatures Suppresses an Effector Phenotype in CD8+ T Cells and Undermines Checkpoint Inhibitor Therapy
Authors: Mark J. Bucsek, Guanxi Qiao, Cameron R. MacDonald, Thejaswini Giridharan, Lauren Evans, Brian Niedzwecki, Haichao Liu, Kathleen M. Kokolus, Jason W.-L. Eng, Michelle N. Messmer, Kristopher Attwood, Scott I. Abrams, Bonnie L. Hylander, Elizabeth A. Repasky
Journal: Cancer Research (2017)

The immune context of tumors has significant prognostic value and is predictive of responsiveness to several forms of therapy, including immunotherapy. We report here that CD8+ T-cell frequency and functional orientation within the tumor microenvironment is regulated by β2-adrenergic receptor (β-AR) signaling in host immune cells. We used three strategies-physiologic (manipulation of ambient thermal environment), pharmacologic (β-blockers), and genetic (β2-AR knockout mice) to reduce adrenergic stress signaling in two widely studied preclinical mouse tumor models. Reducing β-AR signaling facilitated conversion of tumors to an immunologically active tumor microenvironment with increased intratumoral frequency of CD8+ T cells with an effector phenotype and decreased expression of programmed death receptor-1 (PD-1), in addition to an elevated effector CD8+ T-cell to CD4+ regulatory T-cell ratio (IFNγ+CD8+:Treg). Moreover, this conversion significantly increased the efficacy of anti-PD-1 checkpoint blockade. These data highlight the potential of adrenergic stress and norepinephrine-driven β-AR signaling to regulate the immune status of the tumor microenvironment and support the strategic use of clinically available β-blockers in patients to improve responses to immunotherapy. Cancer Res; 77(20); 5639-51. ©2017 AACR.
Neoadjuvant dose-dense (DD) concurrent doxorubicin (A) and docetaxel (T) for stage III breast cancer (BC)
Authors: M. Abu-Khalaf, R. Kim, M. Cohenuram, G. Chung, M. Digiovanna, B. Haffty, D. Carter, L. Horvath, F. Tavassoli, B. Burtness
Journal: Journal of Clinical Oncology (2006)

10721 Background: The addition of taxanes to anthracycline therapy results in improved disease-free survival (DFS) in the adjuvant setting, and increased pathologic complete response rates (pCR) in the neoadjuvant setting. DD chemotherapy improves DFS and overall survival (OS). We evaluated neoadjuvant DD concurrent AT. Methods: Eligible patients (pts) with stage III BC were treated with AT q 14 days at 1 of 3 dose levels; L1 = 60 mg/m 2 for both drugs (4 pts), L2 = A 75 mg/m 2 and T 60 mg/m 2 (6 pts) or L3 = 75 mg/m 2 for both drugs (7 pts) × 6 cycles with G-CSF. Dexrazoxane was given after a cumulative dose of 300 mg/m 2 of A. Pts were stratified to post-operative moderate risk (ModR) (≥ partial response, ≤ 3 lymph nodes (LN)) and received adjuvant IV cyclophosphamide (C) 600 mg/m 2 , methotrexate 40 mg/m 2 , 5FU 600 mg/m 2 IV q 21 d × 6 (CMF), or high risk (HiR) (≤ minor response +/or ≥ 4 LN) and received C 3 gm/m 2 q 14 d x 3. Primary endpoints were clinical and pathologic response rates of neoadjuvant AT. Sample size was 42 pts to estimate pCR and provide 90% confidence the true incidence of severe toxicity is &lt;10%. Results: 17 pts with stage III BC were enrolled between 2/1999 and 7/2001; accrual was halted after data on pre-operative trastuzumab were presented. Median age was 50 yrs [range: 34–69]. 3/17 pts (17.6%) had a pCR, and 3 pts had near pCR (residual foci ≤ 1mm), 4/17 (23.5%) had path (-) LN, 7/17 (41%) had a lumpectomy, 7/17 (41%) required dose reductions of AT due to grade 4 neutropenia (5 pts) and grade 3 neuropathy (2 pts). 3 pts required treatment cessation; 1 pt (L2) for prolonged neutropenic fever and 2 pts (L3) for decreased ejection fraction and for acute renal failure. 15 pts were ModR and received adjuvant CMF, 1/2 pts stratified to high dose C declined it and received CMF. Median follow-up is 63 months [range: 28–80] with 13/17 (76.5%) pts surviving, and 12/17 (70.5%) pts surviving and free of disease. Conclusion: Neoadjuvant DD AT every 2 weeks is well-tolerated, with promising activity and survival in locally advanced BC. [Table: see text]
Abstract 11346: A Novel Approach to Vascular Endothelial Cell Dysfunction With 5-Aminoimidazole-4-Carboxamide-3-Ribonucleoside (AICAR) in Cardiovascular Disease
Authors: Christopher T Banek, Jeffrey Gilbert
Journal: Circulation (2013)

Vascular inflammation and decreased endothelial cell (EC) function are common characteristics of cardiovascular disease (CVD) and hypertension. We and others have shown adenosine-monophosphate protein kinase (AMPK)-activators with 5-aminoimidazole-4-carboxamide-3-ribonucleoside (AICAR) treatment can lower blood pressure, ameliorate EC dysfunction, and decrease systemic vascular inflammation in experimental models of hypertension. While the mechanisms by which AICAR improves CV and EC function remain poorly understood, it has been proposed that regulation of endothelin-1 (ET-1) and cell adhesion protein molecules such as intracellular adhesion molecule (ICAM-1) in addition to direct vasoactive effects may play a role. Thus, it was hypothesized AICAR would decrease ICAM-1 and ET-1 expression, and improve EC health and function. Primary human umbilical vascular endothelial cells (HUVECs) (Passages 1-4) were treated with 2mM AICAR +/- an AMPK blocker (100uM Compound C, CC). Media and cell protein extractions were collected for further analysis. Endothelial barrier function, cell adhesion, viability, and migration changes following AICAR treatment were also measured. Vasodilatory effects were measured in virgin (n=4) female Sprague Dawley rats. All animal experimental protocols were approved by the University of Oregon’s IACUC. Increased p-AMPKα/AMPKα (P