tbuckley/cabot-search huggingface dataset:
AB0347 Validation of the clinical remission criteria in rheumatoid arthritis at keio immunotherapy center
Authors: Y. Kaneko, M. Kuwana, H. Kameda, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Remission has become the realistic goal in rheumatoid arthritis (RA) with the advent of new therapy including biologic agents. In 2011 ACR/EULAR has developed new definition of remission in RA which can presumably reflect the residual disease activity more accurately. However there is little information regarding the validity and the feasibility of the new definition in clinical practice. <h3>Objectives</h3> To clarify the performance of ACR/EULAR remission criteria we investigated the prevalence and agreement between remission definitions at KIC (Keio Immunotherapy Center) cohort where RA patients were treated with biologic agents. <h3>Methods</h3> RA patients who were treated with biologic agents available in Japan for more than two months at KIC as of April 2011 were cross-sectionally included in this analysis. Remission rates were calculated based on 4 definitions: DAS28&lt;2.6, SDAI≤3.3, CDAI≤2.8 and ACR/EULAR (Boolean-based) which requires the complete fulfillment of the follwings; TJC≤1 SJC≤1, patient global (PtGH) ≤1 on a 10cm VAS scale and CRP ≤1mg/dl. It was also examined which variable was more attributed the cause of not-fulfillment of Boolean-based to. <h3>Results</h3> A total of 319 subjects were analyzed; 85% were female, mean (SD) age was 56 (14) years old and mean disease duration was 124 (114) months and mean treatment duration with the current biologic agents was 18 (17) months. Most were RF positive (76%) and anti-CCP antibody positive (72%). One hundred twenty three patients were treated with infliximab, 86 with etanercept, 30 with adalimumab, 66 with tocilizumab and 17 with abatacept. Remission was identified in 56% using DAS28, 47% by SDAI, 43% by CDAI, 33% by Boolean-based. The mean (max) swollen joint count in remission patients was 0.55 (5) by DAS28, 0.23 (2) by SDAI, 0.19 (2) by CDAI, and 0.17 (1) by Boolean-based. When three variables in Boolean-based were ≤1, the other variable was PtGH in 77%, SJC in 18%, TJC in 3% and CRP in 2%. <h3>Conclusions</h3> In daily clinical practice Boolean-based criteria was the most stringent among other clinical remission definitions and neverthless was an achievable goal with biologic agents. <h3>Disclosure of Interest</h3> None Declared
29 BODY FAT DISTRIBUTION AND RISK FACTORS FOR FIBROSIS IN PATIENTS WITH ALCOHOLIC LIVER DISEASE
Authors: S. Naveau, A.-S. Dobrin, A. Balian, M. Njiké-Nakseu, P. Nohra, A. Asnacios, S. Prevot, G. Perlemuter
Journal: Journal of Hepatology (2012)
Abstract 5619: Drugging the “undrugable” DNA-binding domain of STAT3 for inhibition of cancer cell migration and invasion
Authors: Wei Huang, Jian-Ting Zhang
Journal: Cancer Research (2012)

Abstract Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors, and its activation is associated with high histological grade and advanced cancer stage. STAT3 has been shown to play important roles in multiple aspects of cancer aggressiveness including migration, invasion, survival, self-renewal, angiogenesis, and tumor-cell immune evasion by regulating the expression of multiple downstream target genes. Thus, inhibiting STAT3 promises an attracting strategy for treatment of advanced tumors with metastatic potential. Recently, using in-silico screening of a virtual compound database by docking onto the DNA-binding site of human STAT3, our laboratory identified specific STAT3 inhibitors that can disrupt DNA binding activity of STAT3 and inhibit STAT3-dependent cancer cell proliferation. In this study, we further characterized these STAT3 inhibitors and demonstrated that these inhibitors suppressed migration and invasion of both breast and lung cancer cells by inhibiting STAT3-dependent expression of metalloproteinase-2, -9 and vascular endothelial growth factor which are known to promote and enhance tumor metastasis. Taken together, we conclude that it is possible to inhibit STAT3 by targeting its DNA binding domain for discovery of anticancer therapeutics and for treatment of metastatic cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5619. doi:1538-7445.AM2012-5619
AB0469 Patient-Oriented Decision of Early Treatment of Rheumatoid Arthritis with Combination of Triple Conventional Disease Modifying Anti-Rheumatic Drugs or Tumor Necrosis Factor Inhibitors and Methotrexate (Prospective, Open-Label Clinical Trial)
Authors: M. Okada, H. Matsuno, C. Abe, K. Katayama, M. Kondo, A. Sagawa, K. Yamasaki, M. Kishimoto, T. Matsubara
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Early optimization of conventional disease modifying anti-rheumatic drugs (cDMARD) treatment is imperative as delay of biologics in certain patients potentially leads to irreversible functional disability. Bucillamine (BUC) is a unique cDMARD available in Japan in the past twenty years which was recently shown to augment the efficacy of methotrexate (MTX) and salazosulfapyridine (SASP) when they are administered together. <h3>Objectives</h3> We examined the early institution of the triple combination therapy (TriD) before judging requirement of combination therapy of TNF inhibitors and methotrexate (TNFI) in daily practice setting. <h3>Methods</h3> One hundred fourteen patients of early rheumatoid arthritis with worse prognosis based on the activity and known prognostic factors were incorporated in the study from 26 institutions belonging to Japan Association of Rheumatologists in Private practice (JARP). After careful informed consent, all patients by themselves decided to receive TriD therapy or TNFI therapy. Primary endpoint is average DAS28 score at 6 and 12 months, and secondary endpoint is clinical remission rate, functional remission rate and serum MMP-3 value at 3, 6 and 12 months, and modified Total Sharp Score at 12 months. <h3>Results</h3> Fifty four patients and 30 patients completed 1 year treatment in TriD group and TNFI group, respectively, and both groups had significant improvement over the 12 months period. Mean DAS28 were comparable in TriD and TNFI groups at baseline 4.90±0.99 and 5.23±1.2 (p=0.13), 3.43±1.41 and 3.43±1.41 at 6 months, and 3.31±1.37 and 3.07±1.4 (p=0.39) at 12 months, respectively. The change between baseline and 12 months in the EULAR response rate and the CDAI were also similar in the two groups. There were no significant between group differences in the changes of modified Sharp score at 12 months as 4.2±6.6 in TriD and 3.8±8.4 in TNFI (p=0.86) at 12 months. <h3>Conclusions</h3> With sufficient instruction and discussion between patients and physician, patients with active rheumatoid arthritis despite conventional DMARD therapy could choose either TriD or TNFI, appropriately. Patients-oriented decisions significantly reduced the cost of treatment without affecting the clinical and radiological outcome. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1939
Dietary Cadmium Exposure and Risk of Breast, Endometrial, and Ovarian Cancer in the Women’s Health Initiative
Authors: Scott V. Adams, Sabah M. Quraishi, Martin M. Shafer, Michael N. Passarelli, Emily P. Freney, Rowan T. Chlebowski, Juhua Luo, Jaymie R. Meliker, Lina Mu, Marian L. Neuhouser, Polly A. Newcomb
Journal: Environmental Health Perspectives (2014)

In vitro and animal data suggest that cadmium, a heavy metal that contaminates some foods and tobacco plants, is an estrogenic endocrine disruptor. Elevated estrogen exposure is associated with breast, endometrial, and ovarian cancer risk.We examined the association between dietary cadmium intake and risk of these cancers in the large, well-characterized Women's Health Initiative (WHI).A total of 155,069 postmenopausal women, 50-79 years of age, who were enrolled in the WHI clinical trials or observational study, participated in this study. We estimated dietary cadmium consumption by combining baseline food frequency questionnaire responses with U.S. Food and Drug Administration data on food cadmium content. Participants reported incident invasive breast, endometrial, or ovarian cancer, and WHI centrally adjudicated all cases through August 2009. We applied Cox regression to estimate adjusted hazard ratios (HRs) and 95% CIs for each cancer, comparing quintiles of energy-adjusted dietary cadmium intake.Over an average of 10.5 years, 6,658 invasive breast cancers, 1,198 endometrial cancers, and 735 ovarian cancers were reported. We observed no statistically significant associations between dietary cadmium and risk of any of these cancers after adjustment for potential confounders including total dietary energy intake. Results did not differ in any subgroup of women examined.We found little evidence that dietary cadmium is a risk factor for breast, endometrial, or ovarian cancers in postmenopausal women. Misclassification in dietary cadmium assessment may have attenuated observed associations.
412 PREVALENCE, VIROLOGICAL AND CLINICAL CHARACTERISTICS OF CHRONIC HEPATITIS DELTA VIRUS INFECTION (CHD) IN ROMANIA
Authors: L. Gheorghe, I.E. Csiki, S. Iacob, A. Trifan, M. Grigorescu, A. Motoc, A. Suceveanu, M. Curescu, F. Caruntu, I. Sporea, C. Brisc, I. Rogoveanu, L. Tugui, A. Alexandrescu
Journal: Journal of Hepatology (2013)
Abstract 1240: The role of hematopoietic protein kinases in GBM
Authors: Gerald E. Moncayo, Michal Grzmil, Yuhua Wang, Stephan Frank, Adrian Merlo, Hemmings A. Brian
Journal: Cancer Research (2012)

Abstract Glioblastoma multiforme (GBM) is the most common and deadly form of brain cancer. Despite intensive research the median survival of GBM remains at 1 year, with less than 10 % of patients surviving over 5 years. Our analysis of fresh GBM, secondary GBM, high grade astrocytoma, oligodendroglioma, normal brain and normal human astrocytes showed increased expression of 19 novel protein kinases in GBM and targets previously associated with gliomagenesis (e.g. EGFR or PDGF). Two of these kinases which are mainly expressed in hematopoietic cells were the cytoplasmic kinases SYK and LYN. We confirmed the overexpression in GBM tumours and cell lines through western blot and immunohistochemistry analysis. More importantly, SYK expression was derived from the GBM tumours and not from infiltrating leukocytes as shown through colocalization with GFAP, and not with CD45. SYK was found strongly activated at the membrane after EGF and treatment with three specific small molecule inhibitors and siRNA targeting SYK strongly blocked proliferation and migration of GBM cells. This was confirmed through wtSYK and kinase dead SYK overexpression. In addition, SYK phosphorylation was found to be cell cycle regulated after synchronization. Due to our preliminary results we will test the therapeutic potential of SYK inhibitors and epistatic kinase interactions on our xenograft model measuring the efficacy of therapeutics crossing the blood brain barrier with the ultimate goal of discovering alternative treatments for GBM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1240. doi:1538-7445.AM2012-1240
Risk of Colorectal Cancer in the Families of Patients with Adenomatous Polyps
Authors: Sidney J. Winawer, Ann G. Zauber, Hans Gerdes, Michael J. O'Brien, Leonard S. Gottlieb, Stephen S. Sternberg, John H. Bond, Jerome D. Waye, Melvin Schapiro, Joel F. Panish, Robert C. Kurtz, Moshe Shike, Frederick W. Ackroyd, Edward T. Stewart, Mark Skolnick, D. Timothy Bishop
Journal: New England Journal of Medicine (1996)

The adenoma–adenocarcinoma sequence in colorectal cancer suggests an increased risk of colorectal cancer in the families of patients with adenomatous polyps.
Carotid Cavernous Fistula
Authors: Sudhir Venkataramaiah, Kamath Sriganesh
Journal: New England Journal of Medicine (2014)

A 26-year-old man who had had blunt trauma to the head 2 months earlier presented with rapidly progressive swelling, pain, and diminishing vision in the left eye. The physical examination of the left eye revealed chemosis, pulsating proptosis, and an ulcerated cornea.
Panel recommends that assisted suicide be legalised in Canada
Authors: C. Dyer
Journal: BMJ (2011)

Assisted suicide and voluntary euthanasia should be legalised in Canada, an expert panel set up by the Royal Society of Canada has concluded after a two year study.

“We are recommending that the criminal code be changed in such a way as to permit physician assisted suicide and voluntary euthanasia,” said Udo Schuklenk, a bioethicist from Queen’s University in Kingston, Ontario, who chaired the panel of six Canadian and international experts.

The panel on decision making at the end of life called for a “permissive yet carefully regulated and monitored” system …
Abstract 264: EGFR endocytosis after binding of different ligands
Authors: Lene M. Grøvdal, Lasse Henriksen, Michael V. Grandal, Stine LJ Knudsen, Bo van Deurs
Journal: Cancer Research (2010)

Abstract The EGF receptor (EGFR) is activated by binding of ligand, leading to both signaling and receptor endocytosis. This endocytosis can lead to receptor downregulation, or recycling. Although EGFR regulation has received much attention, most studies have been performed using either EGF or TGFα. We described EGFR endocytosis upon binding of four additional ligands. Even though all ligands induce internalization, degradation of the receptor is dependent on the nature of the ligand bound. We have shown that the different ligands vary in levels of EGFR activation, receptor ubiquitination, and also in pH-stability of receptor-ligand interaction. We found that whereas HB-EGF and betacellulin are strong inducers of EGFR degradation, TGFα and epiregulin mostly allow for recycling of the EGFR. Amphiregulin also allows for recycling of the EGFR, but by a slower pathway. EGF leads to both recycling and degradation of the EGFR. We now show that, in addition to intracellular sorting in endosomes, the mechanism of internalization of the EGFR from the plasma membrane also differs depending on which ligand is bound. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 264.
Development and Progression of Left Ventricular Hypertrophy in Children with Hypertrophic Cardiomyopathy
Authors: Barry J. Maron, Paolo Spirito, Yvonne Wesley, Javier Arce
Journal: New England Journal of Medicine (1986)

Whether the magnitude and distribution of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy are established at birth, or whether they evolve during the first years of life, is unknown. Accordingly, we conducted serial echocardiographic studies in 39 children with a family history or morphologic evidence of hypertrophic cardiomyopathy. The patients were initially evaluated at 4 to 15 years of age (mean, 11) and most recently at 9 to 20 years (mean, 16). During a follow-up period of 2.5 to 6.8 years (mean, 4), the magnitude and extent of preexisting left ventricular hypertrophy markedly increased in 17 patients and the morphologic appearance of the heart evolved from normal to hypertrophic in 5 others. In these 22 patients the left ventricular wall thickness increased strikingly (by 6 to 23 mm, a change of 101 +/- 62 percent); these increases significantly exceeded those expected as a consequence of normal growth (13 +/- 10 percent; P less than 0.001) and were not associated with symptomatic deterioration or related to subaortic obstruction. We conclude that left ventricular hypertrophy may develop or progress spontaneously in patients with hypertrophic cardiomyopathy during childhood, when body growth is considerable. Since echocardiograms may be normal during childhood--before the morphologic features of hypertrophic cardiomyopathy develop--a single echocardiographic examination of young relatives of patients with hypertrophic cardiomyopathy may not exclude this disease.
AB0827 Poor prognostic factors of interdtitial lung disease in juvenile dermatomyositis
Authors: N. Kobayashi, S. Sato, M. Mori, K. Koike, S. Yokota
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Juvenile dermatomyositis (JDM) display differing prevalence of features in comparison with adult-onset dermatomyositis. Because of a few numbers of reports about interstitial lung disease (ILD) in JDM, little is known about the pathogenesis and prognostic factors of ILD in JDM. <h3>Objectives</h3> The aim of this study is to evaluate the clinical manifestiation and prognostic factors of ILD with JDM. <h3>Methods</h3> We retrospectively reviewed the clinical information, laboratory data of severely ill cases who were diagnosed as defined and probable JDM in Japan. The records of 25 patients with ILD were identified. Six cases of them died and 19 patients were alive. ILD is the major cause of death in Japanse JDM patients. Clinical manifestiations and serum IL-18, BAFF and IFNa levels of dead patients were compared with those in alive patients. <h3>Results</h3> All dead cases had acute or subacute ILD and showed mild grade of skin and muscle disorder in compaered with the recovery group. Serum AST, ALT and KL-6 were higher and CK level was lower than those of the recovery cases. The dead cases tend to have the high levels of serum BAFF and IL-18, however, there are no correlation of severity of ILD in ferritin values and serum IFNa levels. Only one case had positive anti-Jo-1 antibody. In almost cases of JDM with ILD, anti-CADM-140/MDA5 antibody is positive and dead cases had a tendency with higher levels of that antibody. The lung pathology of the examples from 4 dead cases is diffuse alveolar damage, suggested existence of prominent blood vessel inflammation. <h3>Conclusions</h3> This study underlines that ILD results in high morbidity in JDM. <h3>Disclosure of Interest</h3> N. Kobayashi Grant/Research support from: Health and Labour Science Research Grant, S. Sato: None Declared, M. Mori Grant/Research support from: Health and Labour Science Research Grant, K. Koike: None Declared, S. Yokota Grant/Research support from: Health and Labour Science Research Grant
Inhibition of 6-phosphofructo-2-kinase suppresses breast tumor growth <i>in vivo</i>.
Authors: B Clem, S Telang, A Clem, U Goswami, J Chesney
Journal: Cancer Research (2009)

Abstract Abstract #3064 Phosphofructo-1-kinase, a rate-limiting enzyme of glycolysis, is activated in neoplastic cells by fructose-2,6-bisphosphate (Fru-2,6-BP), a product of four 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isozymes (PFKFB1-4). The inducible PFKFB3 isozyme is constitutively expressed by neoplastic cells and required for the high glycolytic rate and anchorage-independent growth of ras-transformed cells. We report that siRNA silencing or small molecule inhibition (3PO) of PFKFB3 causes a decrease in cell proliferation and metabolic flux in several breast cancer cell lines (MDA-MB-231, MDA-MB-468, BT-549, BT-474, SK-BR-3, ZR-75-1, MCF-7, and MCF-10A). Furthermore, 0.075mg/g 3PO administered via intraperitoneal injection suppresses tumor growth in two transgenic mouse models of breast cancer (MMTV-H-ras: 30% inhibition; MMTV-Erbb2(Her2/neu): 60% inhibition). Interestingly, the Her2 positive cell lines (SK-BR-3, BT-549) and the Her2 mouse transgenic model were more susceptible to PFKFB3 inhibition suggesting that the Her2 phenotype may be more sensitive to disruption of glycolytic flux. Taken together, these data support the clinical development of 3PO and other PFKFB3 inhibitors as chemotherapeutic agents against breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3064.
PERSISTENCE OR DEVELOPMENT OF NEW ELECTROCARDIOGRAPHIC LEFT VENTRICULAR HYPERTROPHY BY BOTH CORNELL PRODUCT AND SOKOLOW-LYON VOLTAGE IS ASSOCIATED WITH MARKEDLY INCREASED RISK DURING ANTIHYPERTENSIVE THERAPY
Authors: Peter M. Okin, Darcy Hille, Sverre Kjeldsen, Richard Devereux
Journal: Journal of the American College of Cardiology (2016)
Induction of Partial Synchronization of Leukemia Cells by Continuous Infusion of Low-Dose Methotrexate Followed by Citrovorum Factor
Authors: M. D'INCALCI, E. ERBA, S. SEN, M. L. RABBONE, M. V. PERLANGELI, G. MASERA, V. CONTER
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Induction of Partial Synchronization of Leukemia Cells by Continuous Infusion of Low-Dose Methotrexate Followed by Citrovorum Factor Get access MAURIZIO D'INCALCI, MAURIZIO D'INCALCI * Istituto di Ricerche Farmacologiche “Mario Negri”Milan, Italy *Correspondence to: Dr. Maurizio D'Incalci, Istituto di Ricerche Farmacologiche “Mario Negri,” Via Eritrea 62, 20157 Milan Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar EUGENIO ERBA, EUGENIO ERBA Istituto di Ricerche Farmacologiche “Mario Negri”Milan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar SOUMITRA SEN, SOUMITRA SEN Istituto di Ricerche Farmacologiche “Mario Negri”Milan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar MARIA LETIZIA RABBONE, MARIA LETIZIA RABBONE Università di Milano Ospedale San GeradoMonza, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar MARIA VITTORIA PERLANGELI, MARIA VITTORIA PERLANGELI Università di Milano Ospedale San GeradoMonza, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar GIUSEPPE MASERA, GIUSEPPE MASERA Università di Milano Ospedale San GeradoMonza, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar VALENTINO CONTER VALENTINO CONTER Università di Milano Ospedale San GeradoMonza, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 19, 4 October 1989, Pages 1509–1510, https://doi.org/10.1093/jnci/81.19.1509 Published: 04 October 1989