tbuckley/cabot-search huggingface dataset:
SAT0306 Radiographic changes in patients with early psoriatic arthritis:
Authors: M. Khraishi, R. Aslanov, E. Rampakakis, A. Duong, J.S. Sampalis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Psoriatic arthritis (PsA) disease duration and severity of joint inflammation significantly affect the radiographic outcome which can be used as a prognostic factor for PsA progression. <h3>Objectives</h3> To describe the radiographic changes in early PsA (EPsA), defined as &lt;2 years since symptom onset. <h3>Methods</h3> EPsA patients were assessed at a rheumatology clinic specializing in PsA. Standard clinical and laboratory assessments, including conventional radiography of peripheral (hands, wrists and feet) and sacroiliac joints were conducted. Radiographic changes were classified as normal, abnormal-not clinically relevant, and abnormal-clinically relevant. <h3>Results</h3> A total of 81 patients with EPsA (mean (SD) disease duration =1.0 (0.8) years) were included in this analysis. The most common joint involvement was polyarticular (60.5% of patients) presentation (symmetric or asymmetric) and Distal Interphalangeal Predominant (DIP) involvement (56.8% of patients). Among the 81 patients, radiographic damage (clinically relevant) was identified in 23 (28.4%) patients, of whom 9 (39.1%) had changes in 2 joints and 7 (30.4%) in ≥3 joints. The vast majority of these patients (73.9%) experienced joint damage within the 1st year of symptoms. The observed radiographic changes included new bone formation (often interpreted by radiologists as degenerative), slight-to-moderate narrowing of the joint space, and marginal and central bone erosions. Overall, 14 (17.3%) patients had clinically relevant abnormalities in hands (10 (71.4%) in both hands), 11 (13.6%) in feet (9 (81.8%) in both legs), 4 (4.9%) in sacroiliac joints, and 1 (1.2%) in wrists. Follow-up (12-18 months) information was available for 68 patients. Among these, 7 (10.3%) patients displayed radiographic progression and 61 (89.7%) remained stable. Radiographic progression included worsening of joint erosion and space narrowing in patients with [2 (28.6%)] or without [5 (71.4%)] prior clinically relevant abnormalities. <h3>Conclusions</h3> Radiographic damage was detected in 28% of EPsA patients, the vast majority of whom acquired the damage as early as the 1st year of symptom onset. The increased incidence of axial and DIP joint involvement are in agreement with previous studies showing that they represent the most common sites in PsA. Radiographic progression was only observed in 10% of patients highlighting the importance of early PsA diagnosis and intervention. <h3>Disclosure of Interest</h3> None Declared
1024 IDENTIFICATION OF SERUM PROTEOGLYCANS AS PROGNOSTIC BIOMARKERS IN PATIENTS WITH HEPATOCELLULAR CARCINOMA AND ALCOHOLIC CIRRHOSIS
Authors: J.C. Nault, E. Guyot, C. Laguillier, S. Chevret, N. Ganne-Carrie, G. N'Kontchou, M. Beaugrand, O. Seror, J.-C. Trinchet, P. Lasalle, N. Charnaux, M. Delhedde, A. Sutton, P. Nahon
Journal: Journal of Hepatology (2012)
892 CLAUDIN-1 GENE VARIANTS AND SUSCEPTIBILITY TO HEPATITIS C INFECTION IN HIV-1 INFECTED INTRAVENOUS DRUG USERS (AN ANRS CASE-CONTROL STUDY)
Authors: J. Ghosn, O. Alibeu, S. Sahali, Y. Quertainmont, L. Meyer, D. Salmon, M. Mole, J.-F. Delfraissy, M. Misrahi
Journal: Journal of Hepatology (2012)
Abstract 2450: Resistance of CD44+ hepatocellular carcinoma cancer stem cellsto immune effector responses
Authors: Shanshan Wan, Linda Vatan, Diane M. Simeone, Ilona Kryczek, Weiping Zou, Theodore H. Welling
Journal: Cancer Research (2011)

Abstract Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide. There is little therapy for advanced disease and recurrence rates can be as high as 50% following resection. Evidence in several tumor types suggests that cancer stem cells (CSCs) contribute to tumorigenicity, therapeutic resistance and recurrence, however the HCC CSC phenotype remains to be completely defined. HCC recurrence is influenced by the degree of immune response in the tumor microenvironment. Therefore, we aimed to characterize HCC-CSCs phenotype and investigate the interaction between CSCs and immune cell subsets. To identify a dominant CSC population in HCC, we examined several putative CSC markers, including CD44, CD90, CD133 and EpCAM on primary human resected HCCs (n=6), HCC xenografts (n=2), and HCC cell lines (n=3) using flow cytometry. Cells from all sources consistently showed discrete populations of CD44+ cells (2-40%), while other common CSC markers showed significant heterogeneity. CD44+ cells isolated from HCC xenografts or HepG2 cells by fluorescence-activated cell sorting (FACS) demonstrated enhanced tumorigenic potential with as little as 100 cells implanted into NOD-SCID/IL-2Rgnull mice compared to no tumor from 100 CD44− cells. CD44+ cells were also able to produce heterogenic tumor mass in vivo. Moreover, CD44+ cells demonstrated increased sphere forming capacity in serum free media (2 fold, p&amp;lt;0.05), and increased resistance to the chemotherapeutic agents cisplatin and doxorubicin in vitro. Additionally, CD44+ HCC cells were resistant to effector cytokines such as IFNγ and TNFα and effector responses during co-culture with anti-CD3/anti-CD28 activated T cells from healthy donor PBMCs. CD44+ HCC cells had 2-fold increased expression of B7-H1, a co-inhibitory molecule for T cells, when compared to non-CSCs during exposure to activated T cells or effector cytokine IFNγ, suggesting a possible mechanism of resistance to immune effectors in the HCC microenvironment. In conclusion, CD44 discriminates for the HCC CSC as evidenced by CD44+ subset demonstrating enhanced tumorigenicity, sphere forming capacity and resistance to chemotherapeutic agents. CD44+ CSC are also resistant to activated T cells and effector cytokines suggesting that microenvironmental factors related to immune response may be important for HCC recurrence or progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2450. doi:10.1158/1538-7445.AM2011-2450
A Study of Tobacco Carcinogenesis. XX. Role of Catechol as a Major Cocarcinogen in the Weakly Acidic Fraction of Smoke Condensate&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn4"&gt;4&lt;/xref&gt;
Authors: S S Hecht, S Carmella, H Mori, D Hoffmann
Journal: JNCI Journal of the National Cancer Institute (1981)

The weakly acidic fraction of cigarette smoke condensate was fractionated by preparative high-pressure liquid chromatography into major subfractions I-IV. Major subfractions II and III were fractionated further into subfractions A-J. Subfractions A-J were tested for cocarcinogenicity on the skin of noninbred Ha:ICR Swiss albino mice by application with 0.003% benzo[a]pyrene. Subfractions A-C and F-J showed significant cocarcinogenic activity; subfractions A, F, and H were the most active. Catechol was a major component of subfraction A and was also detected in subfractions B-D and F. Major components of the other subfractions included hydroquinone (B), coniferyl alcohol (C and H), hydroxyphenyl alcohols (D), alkyl-2-hydroxy-2-cyclopenten-1-ones (C, D, and F), hydroxyacetophenones (F), phenolic cyano compounds (F), and fatty acids (F). The results demonstrate the importance of catechol as a cocarcinogen in the weakly acidic fraction of cigarette smoke condensate and indicate the presence of other cocarcinogens.
Predicting ventilation distribution: A model of coupled acinar dynamics and pressure distribution in the conducting airways
Authors: David Kay
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

 In an asymmetric structure during bronchoconstriction complex flow patterns including convective pendelluft emerged. (Fig. 3)  The variation of acinar volume during a respiratory cycle was influenced by gravitational potential, so that it increased in the lower, gravitationally-dependent regions. Thus, the ventilation rate increased down the craniocaudal axis. Alteration of acinar properties had a large influence on ventilation patterns. (Fig. 4)  The dynamic pressure of acinar units was affected by both pleural pressure variation and airway pressure distribution. The propagation of a pressure wave was altered by a bronchoconstriction. (Fig. 5)  The flow rate in constricted airways decreased. Tidal volume in the constricted lung was reduced by 16.7%. (Fig. 6)  Flow in severely constricted branches not only affected the flow in subsequent branches but also attenuated the dynamics of the acini and caused an increased flow rate in neighbouring branches.3 (Fig. 7) Background
Case 26-2012
Authors: Mark S. Drapkin, Ravi S. Kamath, Ji Yeon Kim
Journal: New England Journal of Medicine (2012)

A 70-year-old woman was admitted to this hospital because of intermittent fevers and new-onset back and leg pain. Imaging of the lumbar spine revealed abnormalities in the vertebral bodies adjacent to the L5–S1 disk space. A diagnostic result was received.
TCT-394 Optical Coherence Tomography- versus Angiography-guided Percutaneous Coronary Intervention with Biolimus-eluting Stent Implantation in Patients with Myocardial Infarction: Dynamic Malapposition Patterns and Strut Coverage at 6 Months. The OCTACS Trial
Authors: Lisbeth Antonsen, Per Thayssen, Akiko Maehara, Henrik S. Hansen, Anders Junker, Knud N. Hansen, Karsten T. Veien, Mikkel Hougaard, Lisette Okkels Jensen
Journal: Journal of the American College of Cardiology (2014)
Abstract 2439: Association of antigen processing machinery components and CD8+ T-cell infiltration in breast cancer brain metastasis
Authors: Yan Liu, Yoshihiro Komohara, Natalie Domenick, Craig Horbinski, Ronald Hamilton, Soldano Ferrone, Hideho Okada
Journal: Cancer Research (2011)

Abstract Purpose: Defects in human leukocyte antigen (HLA) class I antigen processing machinery (APM) component expression can have a negative impact on the clinical course of tumors and the response to T cell-based immunotherapy. Since brain metastases of breast cancer are of increasing clinical significance and only scant information is available about the expression of APM component abnormalities in these lesions, the APM component expression and CD8+ T cell infiltration pattern was analyzed in primary breast and metastatic brain lesions of breast cancer. Experimental design: Immunohistochemistry was performed to evaluate the expression of APM components HLA class I heavy chain, β2-microglobulin, tapasin, antigen peptide transporter (TAP)1, TAP2, LMP2 and calnexin. Results: Comparison of unpaired 50 primary and 33 brain metastases showed lower expression of β2-microglobulin, TAP1, TAP2 and calnexin in the brain lesions. Although no significant differences were found in APM component scores between primary breast and brain lesions in 15 paired cases, primary breast lesions of which patients eventually developed brain metastases showed lower levels of β2-microglobulin, TAP1 and calnexin compared with newly diagnosed breast lesions without brain metastases. Furthermore, the extent of CD8+ T cell infiltration was significantly higher in the newly diagnosed breast lesions compared with the ones of which the patients developed brain metastases, and was positively associated with the expression of TAP1 and calnexin. Conclusions: Our data suggest that patients with low or defective TAP1 or calnexin in the primary breast cancers may be at higher risks for developing brain metastases due to the reduced immunosurveillance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2439. doi:10.1158/1538-7445.AM2011-2439
Abstract 1513: Pre-clinical evaluation of two oncolytic viral vectors expressing IFNβ in treatment of thoracic cancer: Vaccinia virus versus vesicular stomatitis virus
Authors: Liang-Chuan Steve Wang, Valia Saloura, Edward Alexander, Guanjun Cheng, Veena Kapoor, Richard Vile, Stephen H. Thorne, Stuart N. Isaacs, Steven M. Albelda
Journal: Cancer Research (2010)

Abstract Rationale: Given recent success in delivering interferon-beta (IFNβ) using replication incompetent adenovirus in patients with malignant pleural effusions, we hypothesized that vectors that could replicate (inducing oncolysis) and express IFNβ at high level would be more effective. Both vaccinia virus (VV) and vesicular stomatitis (VSV) expressing mouse IFNβ have been constructed in a manner to improve their safety and efficacy as oncolytic vectors. In this study, we evaluated these two oncolytic vectors in different murine thoracic cancer models for clinical translation. Experimental procedures: We compared the efficacy of VVIFNβ and VSVIFNβ to kill 3 mouse lung cancer and 4 mouse mesothelioma lines in vitro over a 5 day-period assessing cell viability by MTT assay. The amount of IFNβ produced by these two vectors were measured with ELISA. The viral replication in infected mice was assessed by measuring viral titers in both immunocompetent and immunodeficient mice bearing an IFN-non-responsive AB12 tumor, following intratumoral injection of either vector at 108 pfu/mouse. To assess their anti-tumor activity, the two vectors were also given at 108 pfu/mouse intratumorally in mice bearing two lung cancer tumors on their flanks. Results: The replication of VSVIFNβ and its killing ability was limited in some of the tumor lines. This appeared to be due to an intact IFN response pathway. In contrast, VVIFNβ was able to kill all of the tumor lines. In culture, VSV replicates faster than VV, which resulted in faster cell killing (in susceptible cell lines), but with less IFNβ production. The amount of IFNβ production by VVIFNβ was comparable with AdIFNβ over a 5 day period. VVIFNβ-infected immunodeficient mice showed minimal or no toxicity when given virus intravenously, while all 5 mice infected with VSVIFNβ developed neurotoxicity within a week. In the TC-1 lung cancer model, VVIFNβ caused tumor regression, while VSVIFNβ and AdIFNβ were completely ineffective. In a second model using LKRM2, all 3 viral vectors were equivalent. The anti-tumor effect of VVIFNβ was shown to be mainly CD8 dependant, as depletion of CD8 with antibody dampened the tumor growth inhibition from 48% to 20%. Conclusions: Overall, VVIFNβ appears to be a better oncolytic vector than VSVIFNβ for a number of reasons: 1) it is safer, 2) it is able to replicate in vitro and in vivo in almost every cell line tested, 3) it induces longer and larger IFNβ production, and 4) it can potentially be given intravenously. 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 1513.
Abstract 1151: Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis.
Authors: Jeroen A C M Goos, Veerle M H Coupé, Begoña Diosdado, Pien M. Delis-van Diemen, Cemile Karga, Jeroen A.M. Beliën, Beatriz Carvalho, M. Petrousjka van den Tol, Henk M W Verheul, Albert A. Geldof, Gerrit A. Meijer, Otto S. Hoekstra, Remond J A Fijneman
Journal: Cancer Research (2013)

Abstract Introduction: Approximately half of all colorectal cancer (CRC) patients die as a consequence of metastases. Hemihepatectomy, occasionally in combination with radiofrequency ablation (RFA), is the only curative treatment available for patients with CRC liver metastases (CRCLM). Patient eligibility is based on established prognostic clinicopathological variables, however, 70% of patients still die within 5 years indicating that better prognostic markers are needed. Aurora kinase A (AURKA) is a driver of 20q gain-associated tumor progression and is associated with disease recurrence in stage III CRC patients. AIM: This study aimed to investigate the prognostic value of AURKA protein expression in liver metastases of CRC patients who underwent hemihepatectomy with curative intent. Patients and Methods: Tissue microarrays (TMAs) were generated from formalin-fixed paraffin-embedded CRCLM of 507 patients who underwent hemihepatectomy in the Netherlands between 1990 and 2010. Matched primary CRC tissue was collected of 234 patients. TMAs were stained for AURKA by immunohistochemistry, nuclear expression of neoplastic cells was assessed and subsequently associated with patient overall survival (OS) in a training and validation set. Results: High AURKA expression in CRCLM was associated with poor OS in a univariate analysis (HRR 1.68; 95%CI 1.04-2.73; P=0.03) and upon correction for established prognostic clinicopathological variables (HRR 1.77; 95%CI 1.02-3.08; P=0.04). Furthermore, AURKA expression in liver metastases was correlated to its expression in corresponding primary CRC (P=0.0002). Conclusion and Discussion: AURKA protein expression is a molecular biomarker with prognostic value for CRC patients with liver metastasis, independent of established clinicopathological variables. This study opens novel opportunities to investigate AURKA inhibitors for personalized therapy. Citation Format: Jeroen A C M Goos, Veerle M H Coupé, Begoña Diosdado, Pien M. Delis-van Diemen, Cemile Karga, Jeroen A.M. Beliën, Beatriz Carvalho, M. Petrousjka van den Tol, Henk M W Verheul, Albert A. Geldof, Gerrit A. Meijer, Otto S. Hoekstra, Remond J A Fijneman. Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1151. doi:10.1158/1538-7445.AM2013-1151
Abstract 4859: Ultra-sensitive detection of rare mutants by droplet digital PCR with conventional TaqMan assays
Authors: Benjamin Hindson, Austin So, Ryan Koehler, Camille Troup, Nick Heredia, George Karlin-Neumann, Serge Saxonov, Helen White
Journal: Cancer Research (2012)

Abstract Molecular tests for genetic mutations play an important role in the diagnosis of cancer. Somatic mutations that drive the pathological features of most tumors have increasing promise as biomarkers for cancer prognosis and therapeutic efficacy. The detection of somatic mutations poses an analytical challenge due to the heterogeneous nature of most samples, where a gene carrying a mutation may differ from the highly abundant wild type sequence by only a single nucleotide. Although a variety of methods exist for mutation analysis, many have poor selectivity and fail to detect mutant sequence below 1 in 100 wildtype sequences. Methods that provide better discrimination and quantitation of somatic mutations are desirable. Here we present a simple strategy using droplet digital™ PCR (ddPCR™) for the detection of somatic mutations with high selectivity and sensitivity. Based on the simple principle of sample partitioning into water-in-oil microdroplets, this ddPCR method increases the abundance of a mutant DNA sequence up to 20,000 times compared to an equivalent bulk PCR reaction. Using conventional TaqMan chemistries and workflow, selectivities of up to 1/100,000 can readily be achieved in any laboratory. Here we present results on the use of ddPCR for the detection and quantitation of several clinically important mutations, including KRAS, c-KIT D816V and JAK2 from clinical samples such as bone marrow aspirates and FFPE. Results from ddPCR are compared to those of conventional approaches including allele specific real-time PCR and sequencing. This ddPCR method may play an important role in the earlier detection of cancer, monitoring the progress of disease and response to therapeutics. 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 4859. doi:1538-7445.AM2012-4859
OP0250 Exploration of omeract preliminary rheumatoid arthritis (RA) flare domains in a longitudinal observational study:
Authors: E. Lie, T.G. Woodworth, R. Christensen, V. Bykerk, C.O. Bingham, D.E. Furst, E.H. Choy
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The word "flare" is often used to describe episodes of disease worsening in RA, but no established definition of flare in RA currently exists. The OMERACT RA Flare Group has proposed a preliminary working definition of flare. Core domains for assessment of flare have been identified by patients (pts) and health care professionals through Delphi exercises (Pain, Function, Swollen Joints, Tender Joints, Stiffness, Participation, Patient Global Assessment, Self-Management, Fatigue)<sup>1</sup>. <h3>Objectives</h3> To compare changes in RA flare core domain variables in RA pts with and without flare, defined as patient-reported disease worsening. <h3>Methods</h3> Data for the analyses were provided by the NOR-DMARD register, an ongoing longitudinal observational study of pts starting a new DMARD regimen. We restricted the current analyses to pts who considered themselves "improved" or "much improved" at 3 months after start of treatment (answered on a 5-point Likert scale: "much improved" thru "much worse"). Flare was defined as pt-reported worsening at 6 months ("worse" or "much worse"). Additional analyses defined flare based on step-up of DMARD/systemic corticosteroid treatment, or combinations of treatment change and pt-reported worsening. Three-to-6-month changes in variables representing the RA flare core domains, as well as the remaining components of the ACR core set and 3 composite disease activity measures (DAS28, SDAI, CDAI), were compared in the flare/no-flare pts, and expressed as standardized mean differences (SMD) with 95% CI. <h3>Results</h3> Of 1457 pts eligible for analyses, 1195 pts had available 6-month follow-up data (MTX n=727, other non-biologic DMARDs n=224, TNF inhibitor n=229, other biologics n=15). Mean (SD) disease duration 6.3 (9.7) yrs; age 55.0 (13.7) yrs; RF+ 68%; female 71%; baseline DAS28 4.9 (1.4). There were 79 pt-reported flares at 6 months. The overlap with flare defined by treatment change (162 flares) was only 35 patients, indicating that the two flare definitions are different. Only results for pt-reported flare are shown (table) as the SMDs for treatment-related flare were small to moderate. <h3>Conclusions</h3> The working definition of flare based on pt-reported worsening discriminated well between pts with and without worsening in flare domains related to pain and stiffness. Pt-reported flares were sometimes not associated with change in treatment. <h3>References</h3> Bartlett SJ, et al. Consensus Among Patients and Health Care Professionals for Essential Domains to Assess Disease Flares in Rheumatoid Arthritis: Results of Final OMERACT Delphi. Arthritis Rheum 2011;63(suppl):128. <h3>Disclosure of Interest</h3> None Declared
COMPARISON OF PROTECTIVE EFFECT OF ANGIOTENSIN II RECEPTOR BLOCKER AND CALCIUM CHANNEL BLOCKER FOR ENDOTHELIAL VASOMOTOR FUNCTION AFTER EVEROLIMUS-ELUTING STENT IMPLANTATION
Authors: Yasuhiro Aoki, Keishi Ishikawa, Keiichiro Miura, Kazumasa Sugimoto, Takashi Nakayama, Yoshihide Fujimoto, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2015)