tbuckley/cabot-search huggingface dataset:
Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol
Authors: Howard N. Hodis, Wendy J. Mack, Victor W. Henderson, Donna Shoupe, Matthew J. Budoff, Juliana Hwang-Levine, Yanjie Li, Mei Feng, Laurie Dustin, Naoko Kono, Frank Z. Stanczyk, Robert H. Selzer, Stanley P. Azen
Journal: New England Journal of Medicine (2016)

Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested.
AB0924 Psychological distress symptoms and illness perceptions associated with health-related quality of life in psoriatic arthritis patients
Authors: K. Kotsis, P.V. Voulgari, N. Tsifetaki, M.O. Machado, A.F. Carvalho, F. Creed, T. Hyphantis, A.A. Drosos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Symptoms of psychological distress and illness perceptions influence outcomes in rheumatologic patients. We aimed to assess the prevalence of psychological distress symptoms and illness perceptions in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and to test whether the association between psychological variables and health-related quality of life (HRQoL) was similar in the two forms of arthritis. <h3>Methods</h3> In 83 PsA and 199 RA patients we used the Patient Health Questionnaire (PHQ-9), the Symptom Check-List (SCL-90-R) and the Brief Illness Perception Questionnaire (B-IPQ) to assess psychological variables and the World Health Organization Quality of Life Instrument - Short-Form (WHOQOL-BREF) to assess physical HRQoL. Hierarchical regression models were built to test their independent contribution to Physical HRQoL after adjusting for demographic variables and disease parameters. <h3>Results</h3> The prevalence of major depressive disorder as indicated by a PHQ-9 score ≥10 was 21.7% in PsA, 25.1% in RA, and 36.7% in those PsA patients with polyarthritis. After adjustment for severity of disease and pain, anxiety (b=-0.28) and concern about bodily symptoms attributed to the illness (b=-0.33) were independent correlates of physical HRQoL in PsA. In RA, depression (b=-0.29) and concern about the consequences of the arthritis (b=-0.27) were independent correlates of physical HRQoL. <h3>Conclusions</h3> These findings suggest that psychological factors are important correlates of HRQoL in PsA, as well as in RA. Attention to patients' anxiety and their concern about numerous bodily symptoms attributed to the illness may enable rheumatologists to identify and manage treatable aspects of HRQoL in PsA. <h3>Disclosure of Interest</h3> None Declared
OP0210 Apolipoprotein E Aggravates Inflammation and Joint Destruction in Murine Antigen-Induced Arthritis
Authors: G. Ascone, I. Di Ceglie, W. de Munter, B. Walgreen, A. Sloetjes, P. van Lent, P. van der Kraan
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by severe bone destruction which has been associated with altered lipid metabolism. Apolipoprotein E (Apo E) is a lipoprotein crucial in lipid metabolism, mainly produced by macrophages. Moreover ApoE has been recently described as an important anti-inflammatory mediator regulating innate immunity and bone turnover. <h3>Objectives</h3> In the present study we investigated the role of Apo E in inflammation and bone destruction during antigen-induced arthritis (AIA). <h3>Methods</h3> Experimental arthritis (AIA) was induced by injection of 60 μg mBSA into the right knee joint of ApoE<sup>–/–</sup> and wild type (WT) control mice previously immunized with mBSA/CFA. Joint swelling was measured by uptake of <sup>99m</sup>Technecium (<sup>99m</sup>Tc) and expressed as a ratio of the uptake in right (injected) and the left (non injected) knee joint. Humoral immunity (mBSA antibody titer) was measured by ELISA. Joint inflammation and bone erosion were measured by histological analysis using an arbitrary scale from 0 to 3. TRAP<sup>+</sup> cells were determined using immunohistochemistry. <h3>Results</h3> ApoE<sup>–/–</sup> mice showed significantly less joint swelling at day 1, 3 and 7 after AIA induction compared to WT controls (21%, 17%, 18% lower, respectively). Serum mBSA antibody levels (total IgG, IgG1, IgG2a and IgG2b) are comparable between the two immunized mouse strains. At day 21, histology of the knee joints showed less infiltration of inflammatory cells (25% lower) and decreased bone erosion in the ApoE<sup>–/–</sup> mice compared to WT controls (25% lower from 1.5±0.2 to 1.1 ±0.1). In line with that, ApoE<sup>–/–</sup> mice showed a reduction of the number of osteoclasts present at the area of resorption within the arthritic knee joints (36% lower from 20±4 osteoclasts/section in WT mice to 12±5 in ApoE<sup>–/–</sup> mice), as measured by image analysis of TRAP staining. <h3>Conclusions</h3> ApoE aggravates bone destruction within the knee joints during AIA by increasing influx of inflammatory cells within the synovium and elevating the number of resorbing osteoclasts on the bone surface. <h3>Disclosure of Interest</h3> None declared
S90 Homocystine levels in non-small cell lung cancer
Authors: J. Maguire, V. Kelly, C. Smyth, M. Ledson, M. Walshaw
Journal: Thorax (2010)

Plasma homocystine level is the most sensitive marker of sub-clinical folate deficiency. Elevated levels of homocystine have been associated with several pathologies, particularly vascular and cardiac disease. Patients with lung cancer are frequently elderly and may have insufficient intake of folate. Sub-clinical folate deficiency may lead to increased morbidity during chemotherapy and radiotherapy, and possibly reduced response rates to both treatment modalities. We have measured plasma homocystine levels in 460 patients with a diagnosis of non-small cell lung cancer who were referred to our lung cancer unit between 2005 and 2009. Two hundred and fifty-six patients were male, 204 were female. The median age was 71. 22% of patients were PS 0-1, 35% PS2 and 43% PS3. The local laboratory reference range for homocystine is ≤15 μmol/l. 43% of patients had elevated plasma levels of homocystine at diagnosis. In 35% the level was between 15.1 and 25 μmol/l, and in 8% the homocystine level was greater than 25 μmol/l. Patients with elevated plasma homocystine levels had inferior median and 1 year survival rates, both for stage III disease (464 vs 356 days ms, 1 year survival 65% vs 47%) and stage IV disease (212 vs 190 days ms, 1 year 30% vs 21%). The finding of elevated homcystine levels in 43% of newly diagnosed patients with non-small cell lung cancer is of potentially profound significance, as this implies that there could be a possible therapeutic benefit from folate and B12 supplementation before and during treatment for this group of patients with non- small cell lung cancer.
Abstract 2385: Evidence and actions for nuclear localization of vascular endothelial growth factor receptor 1 (VEGFR1) in endothelial and cancer cells
Authors: Li-Wha Wu
Journal: Cancer Research (2010)

Abstract Abstract: Vascular endothelial growth factor receptor 1 (VEGFR1) is a receptor tyrosine kinase (RTK) predominantly expressed in endothelial cells. Recent studies have shown that VEGFR1 is also expressed in several types of human cancer cells, and its expression correlates with cancer progression. Moreover, higher VEGFR1 expression worsened the outcome of lung cancers, breast cancer, and pancreatic cancer patients following cancer treatment. A new mode of signal transduction mediated by RTK is through internationalization of ligand-bound receptor rather than through activation of intracellular signaling cascades by the interaction of ligand and receptor on the cell surface. Epidermal growth factor receptor is the prototype for such new mode of action. One previous study has shown that VEGFR1 was colocalized with nuclear STAT1 in chronic lymphocytic leukemia B cells treated with VEGF-A, indicating a possible role for VEGFR-1 in the nucleus. Consistent with the notion, we found that the intracellular domain of VEGFR1 behaved as a transcriptional activator in yeast two-hybrid system. Second, VEGFR1 could shuttle between cytosol and nucleus following VEGF-A treatment in endothelial cells. Third, nuclear and cytosolic fractionation indicated the presence of VEGFR1 in the nuclear compartment of oral cancer and human endothelial cells. We thus hypothesized that VEGFR1 might harbor a nuclear localization signal (NLS) in the protein. Using a cytosolic protein pyruvate kinase fused with green fluorescent protein (GFP) and the putative NLS derived from VEGFR1 together with serial deletions and fluorescence microscopy, we were able to alter the subcellular location of pyruvate kinase fusion protein. Moreover, mutations of crucial arginine or lysine residues in the putative NLS significantly reduced the nuclear presence of VEGFR1 in the transfected cells. More studies are needed to address the molecules involved in nuclear transport of VEGFR1 and the target DNA sequence recognized by nuclear VEGFR1. The functional consequence of VEGFR1 localization in different subcellular compartments will be also studied by the use of oral cancer cells as a model. 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 2385.
Abstract 5078: The NCI-NIST-FDA effort to develop fitness-for-purpose biospecimen assessment standards: Development of quality assessment metrics and standards for optimal biospecimen utilization
Authors: Richard Aragon, Anthony Dickherber, David Litwack, Jimmie Vaught, Carolyn Compton
Journal: Cancer Research (2011)

Abstract The US Congress, through recent health care reform legislation, has directed the National Institutes of Health (NIH) to formulate a more aggressive strategy by which to translate scientific discoveries directly into the development of novel therapeutic and diagnostic capabilities. The National Cancer Institute (NCI) seeks to facilitate these efforts by targeting specific bottlenecks caused by the lack of standardization, quality metrics, and comparative benchmarks for research and clinical biospecimens used throughout the relevant discovery and validation pipelines. Many of the bottlenecks that currently impede routes to more effective biomarker discovery as well as drug, biologic and device development are impeded by a current lack of standards surrounding the research biospecimens used to advance this type of research. The National Institutes of Standards and Technology (NIST), the Food and Drug Administration (FDA) and the NCI have engaged in an interagency effort to develop fitness-for-purpose quality assessment tools and metrics for the research biospecimens used by the clinical research, diagnostics, and technology development communities. An interagency workshop was convened consisting of biomedical and biospecimen scientists, standards/metrology scientists, commercial assay developers, experimental design and research methods experts, statisticians, and regulatory scientists that are among the leaders in their field. Subsequent to that workshop, a number of specimen quality assessment metric development projects were initiated to target metrics and standards that would have a significant impact on the development pipelines for diagnostics and therapeutics development, including the incorporation of certain regulatory efficiencies that could potentially accelerate development. The NCI would like to present these ongoing projects and share ideas for future biospecimen quality assessment standards development projects for the cancer research, diagnostics, and technology development communities. Progress in designing such projects and preliminary results from experiments discussed in the October workshop will thus be described. 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 5078. doi:10.1158/1538-7445.AM2011-5078
British Society of Gastroenterology policy and processes for the development of guidelines
Authors: Tony CK Tham, Dermot Gleeson, Simon M Greenfield, Adam Harris, Simone Cort
Journal: Gut (2015)

We refer to two recently published guidelines in this journal from the British Society of Gastroenterology (BSG) on coeliac disease1 and Barretts oesophagus.2 We describe our BSG policy on the production of guidelines, which sets a sufficiently high quality benchmark such that we have been awarded National Institute of Health and Care Excellence (NICE) accreditation for our production process.3 The full policy and advice document are available on our website.4

Most guidelines are commissioned by the BSG clinical services and standards committee (CSSC). The formulation of guidelines are driven by a Guideline Development Group (GDG), include a writing committee, members of which are recognised authorities in the field, and others representing a range of relevant expertise, …
Abstract 2761: Co-administration of the short-chain sphingolipid N-octanoyl-glucosylceramide improves doxorubicin therapy by enhancing intracellular drug accumulation in vivo
Authors: Albert J. van Hell, Gerben Koning, Jos Jonkers, Marcel Verheij
Journal: Cancer Research (2012)

Abstract BACKGROUND: Plasma membranes are a effective barrier that prevent exogenous therapeutics, including cytostatic drugs, to reach their intracellular targets and become active. Membrane traversal of most drugs is therefore sub-optimal and remains a major limitation for clinical efficacy. We identified a well-defined class of short-chain lipids that modulate the plasma membrane and facilitate the cellular accumulation of amphiphilic drugs, including doxorubicin. RESULTS: A liposomal co-formulation of the short-chain lipid N-octanoylglucosylceramide (GC) and doxorubicin was applied in a genetically engineered mouse (GEM) breast tumor model (Wcre;Cdh1F/F;Trp53F/F). These tumors, which are resistant to a variety of conventional and biological cytostatic therapies, responded to doxorubicin treatment when combined with the membrane modulation strategy. Co-administration of GC generated a sustained anti-tumor response and significantly improved overall survival (30 days versus 11 days for control; p &amp;lt; 0.005). Using a nuclear isolation procedure, we showed that the presence of GC enhanced the intracellular tumor accumulation in vivo by a factor 1.9 (p &amp;lt; 0.05). In contrast, the accumulation within normal heart tissue was not elevated. The latter data are in agreement with in vitro experiments using cultured cardiac myocytes. When compared to either clinically available formulations of doxorubicin (free or PEGylated liposomal doxorubicin) a favorable efficacy, pharmacokinetic and toxicity profile was obtained by co-formulation of GC with doxorubicin. CONCLUSION: The short-chain sphingolipid GC improves the therapeutic ratio in multi-drug resistant GEM breast tumors by enhancing the intracellular tumor accumulation of doxorubicin while limiting normal tissue exposure. 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 2761. doi:1538-7445.AM2012-2761
TCTAP A-156 The Impact of Abnormal Admission Glycemic Level on In-Hospital Mortality in Non-Diabetic Patients Undergoing Percutaneous Coronary Intervention
Authors: Harris Ngow, Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Shaopeng Xu, Jabar Ali, Ji Bak Kim, Cheol Ung Choi, Eung Ju Kim, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2015)
ASSOCIATION OF BLOOD TYPES WITH BLEEDING AND THROMBOEMBOLIC EVENTS IN PATIENTS RECEIVING CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICES
Authors: Michael Andrew Pfeffer, Amanda Bennett, Krista Marz, Lisa Tichenor, Mandy Bourgeois, Kayla Cusachs, Monchel Young, Sapna Desai, Stacy Mandras, Hamang Patel, Clement Eiswirth, Patrick Campbell, Hector Ventura, Selim Krim
Journal: Journal of the American College of Cardiology (2016)
Abstract 3170: Early detection and follow up of head and neck squamous cell carcinoma – A longitudinal serum based biomarker study
Authors: Ethan Soudry, Mariana Brait, Bao-Ling Adam, Christine Gourin, David Sidransky
Journal: Cancer Research (2011)

Abstract Head and neck squamous cell carcinoma (HNSCC) accounts for more than 37,000 new cases in the US each year. More than half of the patients present in an advanced stage, which confers a poor prognosis. However if detected early this cancer maybe highly curable. Currently there is no biomarker in clinical practice for early detection or prognosis prediction. Many studies are attempting to discover potential biomarkers in tissue, saliva and serum. Promoter methylation suppresses gene expression in cancer and several candidates have been demonstrated to be cancer specific biomarkers. Increased mitochondrial content is another feature that has been demonstrated related to cancer. Our goal is to validate potential biomarkers previously described by our group and others to be linked to HNSCC, in serum samples from a cohort of patients with longitudinal follow up and a subset of normal subjects’ samples. We assessed mitochondrial DNA content (Cox I and Cox II) and methylation status of EDNRB and KIF1a by quantitative PCR in an evaluation set of samples consisting of 75 pre and post treatment serum samples from HNSCC patients and from 11 healthy cancer-free subjects. In tumors, the observed methylation frequencies were 17%, 22% for EDNRB and KIF1a, respectively. There was no observed methylation for EDNRB and KIF1a in normal samples. Increased mitochondrial DNA content was observed in 54% and 59% of the HNSCC samples, by COX1 and COX2, respectively. And no increased content was noted in the normal set. Combining all the markers and analyzing as a panel (at least one positive), we obtained a sensitivity of 83% with specificity of 100%. When we compared post treatment samples to pre treatment samples, we noticed a decreased mitochondrial DNA content in patients without recurrence, and an increase in patients that recurred, however, due to the small number of samples, these associations needs to be confirmed. Our findings indicate that a serum based panel that includes mitochondrial DNA content analysis and cancer specific methylation markers may serve as a high quality detection tool for HNSCC, as well as recurrence prediction. Validation of these preliminary data is ongoing in a larger independent cohort with comprehensive clinical and follow up data. 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 3170. doi:10.1158/1538-7445.AM2011-3170
Separation of I-131-Positive Juxtagastric Metastatic Thyroid Carcinoma From the Stomach by Simultaneous Dual-Isotope Imaging With I-131 and Tc-99m Pertechnetate
Authors: SHINSAKU TSUCHIMOCHI, MASAYUKI NAKAJO, YUICHI HINO, YOSHIAKI NAKABEPPU, NOBORU FUKUSHIMA, TOYOTSUGU KIKU
Journal: Clinical Nuclear Medicine (1999)

I-131 whole-body imaging was performed in a 72-year-old woman with multiple metastases from thyroid follicular carcinoma. Increased activity in the left lower chest mimicked physiologic gastric uptake. To determine whether it was a true-positive lesion, dual-isotope imaging was performed after intravenous administration of Tc-99m pertechnetate. This imaging clearly separated the I-131 in the chest wall metastasis from the physiologic accumulation of Tc-99m pertechnetate in the stomach.
Abstract 1101: Examining the role of the mechanical microenvironment in pancreatic cancer: microrheology studies in 3D tumor models.
Authors: Jonathan P. Celli, Imran Rizvi, Dustin Jones, William Hanna, Tayyaba Hasan
Journal: Cancer Research (2013)

Abstract A growing body of literature points to the importance of the mechanical microenvironment, including rheology (rigidity, viscoelastic properties) of the surrounding extracellular matrix (ECM), as a regulator tumor growth behavior. This is particularly provocative for tumors of the pancreas, which are noted for profound desomplasia characterized by exceptionally dense, collagen-rich, hypovascular, fibrous stroma. While this property of pancreatic tumor stroma has been implicated in drug resistance, and even explored as a therapeutic target (stromal depletion), key questions about the role of the mechanical microenvironment remain unanswered. For example, it is unclear the extent to which this extreme matrix rigidity is driven by the tumorigenic program or what its role is in contributing to the notorious treatment-resistance of these tumors, beyond serving as a physical barrier to drug penetration. In this study we leverage in vitro 3D pancreatic tumor-fibroblast co-culture models combined with particle tracking microrheolgy as a tool to longitudinally probe the mechanical properties of the surrounding ECM during growth and in response to exogenous stimuli. Cultures are prepared by embedding pancreatic cancer cells (PANC-1, AsPC-1 or Capan-1) along with normal human fibroblasts (MRC-5) and (biologically-inert) fluorescent tracer probes in a collagen matrix. The Brownian motion of tracer probes obtained by high-speed digital video microscopy and subsequent offline particle tracking analysis, is used as a reporter of spatio-temporal changes in the viscoelastic properties of ECM. This, combined with our previously introduced high-content quantitative imaging approach for assessment of growth and treatment response in 3D tumor models comprises a platform for mapping of interdependent changes in the matrix mechanics and tumor growth behavior. In this study we correlate changes in matrix stiffness under normal growth, with and without stromal fibroblasts present as signaling partners and TGF-β stimulation. We further explore local mechanical effects by comparing groupings of trajectories of probes proximal and distant from tumor nodules. In ongoing studies we are examining the impact of traditional chemotherapeutics and photodynamic therapy (PDT) on modulation of the mechanical microenvironment and conversely, the impact of ECM rigidity on treatment sensitivity. Citation Format: Jonathan P. Celli, Imran Rizvi, Dustin Jones, William Hanna, Tayyaba Hasan. Examining the role of the mechanical microenvironment in pancreatic cancer: microrheology studies in 3D tumor models. [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 1101. doi:10.1158/1538-7445.AM2013-1101