tbuckley/cabot-search huggingface dataset:
PWE-095 Faecal Calprotectin Is Useful In Predicting Long Term Disease Recurrence In Post-operative Crohn’s
Authors: R Perowne, C Lamb, RA Speight, M Price, J Mansfield
Journal: Gut (2014)

<h3>Introduction</h3> The concept of using faecal biomarkers to predict prognosis and direct treatment in patients with Crohn's disease is attractive but long term follow-up data is lacking. A cohort of 51 patients with previous ileal resections for Crohn's disease provided a one-off stool sample for faecal calprotectin (FC). These patients were followed up for 5 years to assess whether FC could predict disease progression in the long term. <h3>Methods</h3> Patients were identified from a database of patients who had participated in a previous study evaluating the use of FC in post-operative Crohn's. Patients were included in the study if they had been followed up for at least 5 years after the initial FC was recorded. Case notes were reviewed retrospectively and information on the need for escalation of medical therapy or for further surgery for disease recurrence was recorded. A FC of more than 200 was taken as the cut-off value for evidence of active inflammation. Statistical analysis was performed using Prism 6 (GraphPad Software, San Diego, USA). <h3>Results</h3> 17 patients had a FC ≥ 200 (median 751, IQR 593–916). Of these 13 required either escalation of medical treatment and/or further surgery over the 5 year follow-up period. 34 patients had a FC &lt;200 (median 18, IQR 4–71). Of these 11 required treatment escalation and/or surgery. A FC of ≥200 correlated significantly with need for escalation of medical treatment and/or further surgery over a 5 year follow up (p 0.003). <h3>Conclusion</h3> A FC of less than 200 predicts a better prognosis in patients with post-op Crohn's disease over a prolonged (5 year) period and could therefore potentially be used to stratify treatment and target early intervention. <h3>Disclosure of Interest</h3> None Declared.
TCT-758 Age Alone Should Not Preclude Surgery: Contemporary Outcomes after Aortic Valve Replacement in Nonagenarians
Authors: Halit Yerebakan, Isaac George, Bindu Kalesan, Tamim Nazif, Jacob Kriegel, Hiroo Takayama, Michael Argenziano, Yoshifumi Naka, Allan Stewart, Susheel Kodali, Craig Smith, Mathew Williams
Journal: Journal of the American College of Cardiology (2013)
THE FINAL RESULTS OF THE IXCELL-DCM TRIAL: TRANSENDOCARDIAL INJECTION OF IXMYELOCEL-T IN PATIENTS WITH ISCHEMIC DILATED CARDIOMYOPATHY
Authors: Timothy D. Henry, Arshed Quyyumi, Gary Schaer, R. David Anderson, Catalin Toma, Cara East, David Recker, Ann Remmers, James Goodrich, Amit Patel
Journal: Journal of the American College of Cardiology (2016)
Abstract 1862: NY-ESO-1 and clinicopathological features in ovarian cancer
Authors: Charlotte R. Topka, Wafic M. ElMasri, Clara E. Magyar, Min Song, Oliver Dorigo
Journal: Cancer Research (2012)

Abstract Ovarian cancer ranks fifth in cancer deaths among women and the American Cancer Society estimates that in the US about 15,460 women will die from this disease in 2011. NY-ESO-1 is an 18 kDa member of the cancer/testis 6 antigen family which is thought to play a role in germ cell differentiation. In healthy adults, NY-ESO-1 is restricted to the testis. NY-ESO-1 expression has been found in various malignant neoplasms, including melanomas, neuroblastomas, soft tissue sarcomas, and carcinomas from the breast and endometrium. To further delineate the role of NY-ESO-1 in epithelial ovarian cancer, we constructed a tissue microarray of archived formalin-fixed paraffin-embedded paired tumor and normal control specimens from ovarian cancer patients. NY-ESO-1 expression was correlated with clinicopathologic features and overall survival. Specimens were collected from 242 patients who underwent cytoreductive surgery for ovarian cancer between 1989 and 2009. Immunohistochemical staining was performed with mouse monoclonal antibody clone E978 specific for NY-ESO-1. Stained slides were digitized with the Aperio ScanScope XT and images were analyzed using DEFINENS Tissue Studio software. Histological scores (H-scores) based on intensity of NY-ESO-1 staining and percent positive cells were calculated for all specimens. Positive NY-ESO-1 expression was found in 21% of papillary serous carcinomas, 18% of endometrioid carcinomas, and 20% of clear cell carcinomas. Ovarian cancer tissue had significantly higher H-scores compared to normal tissue controls from the same patients. H-scores increased with increasing FIGO stage and grade of the tumors. Caucasians had higher H-scores compared to African Americans and Asians. H-scores did not correlate with overall survival. Similarly, no differences in overall survival based on NY-ESO-1 expression levels were detected when patients were stratified by their histologic subtype. In conclusion, NY-ESO-1 is expressed in all histologic subtypes of epithelial ovarian cancer but not in normal tissues, therefore making it an ideal candidate for the development of targeted therapeutic approaches in ovarian cancer. 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 1862. doi:1538-7445.AM2012-1862
Implications of Extracellular Vesicle Transfer on Cellular Heterogeneity in Cancer: What Are the Potential Clinical Ramifications?
Authors: Anoek Zomer, Jacco van Rheenen
Journal: Cancer Research (2016)

The functional and phenotypic heterogeneity of tumor cells represents one of the greatest challenges in the successful treatment of cancer patients, because it increases the risk that certain individual tumor cells possess the ability to, for example, metastasize or to tolerate cytotoxic drugs. This heterogeneity in cellular behavior is driven by genetic and epigenetic changes and environmental differences. Recent studies suggest that an additional layer of complexity of tumor heterogeneity exists, based on the ability of cells to share functional biomolecules through local and systemic transfer of extracellular vesicles (EV), with profound effects on cellular behavior. The transfer of functional biomolecules between various populations of tumor cells and between tumor cells and nontumor cells has large consequences for both the tumor cells and the microenvironment that support the cellular behavior of tumor cells, and therefore for the clinical outcome of cancer. Here, we discuss the latest findings on EV transfer and the potential implications of EV-mediated local and systemic transmission of phenotypic behavior, particularly in the context of tumor heterogeneity, metastatic disease, and treatment response. Cancer Res; 76(8); 2071-5. ©2016 AACR.
Abstract 5102: Increased plasma levels of MAPRE1, an APC interacting protein, preceding a diagnosis of colorectal cancer
Authors: Jon Ladd, Tina B. Buson, Melissa M. Johnson, Qing Zhang, Sharon J. Pitteri, Hong Wang, Ross L. Prentice, Samir Hanash
Journal: Cancer Research (2011)

Abstract Longitudinal blood collections from cohort studies provide the means to search for proteins associated with disease processes prior to diagnosis. We have investigated pre-diagnostic plasma samples to determine quantitative differences in plasma protein between subjects subsequently diagnosed with colorectal cancer (CRC) and matched controls that remain cancer free during an 18 month period of active follow-up. In-depth quantitative proteomic profiling was performed on 90 pre-diagnostic plasma samples. Experiments compared nine pools each consisting of plasma aliquots from 10 CRC subjects diagnosed within 18 months after blood draw and 10 matched controls. MAPRE1 was confirmed in a set of 58 pairs of plasma from newly diagnosed CRC cases and controls using enzyme linked immunosorbent assay (ELISA). MAPRE1 was further tested by ELISA in a second independent set of 100 pre-diagnostic CRC plasma samples diagnosed within 18 months after blood draw and 100 matched controls. Proteomic analysis of pre-diagnostic plasma samples collected prior to diagnosis of CRC yielded a set of proteins with elevated concentrations (p &amp;lt;0.05) in cases compared to control that included MAPRE1 which is a binding partner for APC. MAPRE1 and carcinoembryonic antigen (CEA) were assayed by ELISA in newly diagnosed CRC samples, yielding equally significant elevation (p &amp;lt;0.05) among cases relative to controls for each protein with areas under the curve (AUCs) of 0.778 and 0.782, respectively. Further testing in an independent set of pre-diagnostic samples confirmed predictive value of MAPRE1 by receiver operator characteristic (ROC) achieving an AUC of 0.675 within 7 months of diagnosis. This is the first reported evidence of elevated circulating levels of MAPRE1 in colorectal cancer patient plasma. Plasma levels increased with development of CRC. Because of MAPRE1's interaction with adenomatous polyposis coli protein (APC), a known target of mutation in a majority of CRC, increased circulating levels of MAPRE1 may be an early indicator of CRC development. 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 5102. doi:10.1158/1538-7445.AM2011-5102
Abstract 1339: Inhibition of chitinase-3-like-1 protein to suppress angiogenesis and enhance immune response in a mammary tumor model
Authors: Stephania Libreros, Ramon Garcia-Areas, Vijaya L. Iragavarapu-Charyulu
Journal: Cancer Research (2010)

Abstract The purpose of this study is to determine whether inhibition of Chitinase-3-like 1 protein reduces the expression of angiogenic chemokines in macrophages while enhancing IFN-γ production in T cells. It is known that tumors can induce the upregulation of angiogenic and extracellular matrix degrading molecules. Tumor growth is often accompanied by immunosuppression. Our previous studies using the DA-3 mammary adenocarcinoma mouse model has shown that with tumor progression there is a profound down-regulation of interferon-gamma (IFN-γ), a crucial molecule involved in anti-tumor response. Additionally, angiogenic chemokines such as Monocyte Chemoattractant Protein-1 (CCL2/MCP-1) and Matrix Metalloproteinase-9 (MMP-9) are upregulated with mammary tumor growth. CCL2/MCP-1 is a known inflammatory chemoattractant for T cells and macrophages, and we have evidence that this molecule downregulates IFN-γ by the T lymphocytes. Recent studies have linked tumor progression with upregulation of Chitinase-3-like-1 protein (CHI3L1) in human breast cancer patients and that macrophages express this molecule during inflammatory processes. Our studies using DA-3 mammary breast cancer model indicate that CHI3L1 is expressed by DA-3 tumor cells. Expression of CHI3L1 in macrophages has been linked with upregulation of angiogenic chemokine, CCL2/MCP-1. Our studies indicate that macrophages from mammary tumor-bearing mice express higher levels of CHI3L1 compared to normal control mice and also secrete CCL2/MCP-1. We hypothesize that inhibition of CHI3L1 will suppress the production of CCL2/MCP-1 and enhance IFN-γ production in mammary tumor-bearing mice. One of the known ligands for CHI3L1 is chitin microparticle. Our in vitro studies of cultured splenocytes from normal and 5-week mammary tumor-bearing mice with chitin micro-particles revealed down-regulation of CHI3L1 and upregulation of IFN-γ. Therefore, it is expected that in vivo blocking of CHI3L1 with chitin microparticles will have a favorable anti-tumor response by inhibiting the production of angiogenic chemokines, metalloproteinase, MMP-9 and enhancing the production of IFN-γ. The results from these studies may provide new avenues for cancer treatment. 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 1339.
AB0018 A multifaceted approach to select target genes for resequencing in rheumatoid arthritis
Authors: S.-Y. Bang, Y.-J. Na, D. Kim, J.-Y. Choi, S.-M. Ahn, H.-S. Lee, S.-C. Bae
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The common disease rare variant hypothesis states that disease etiology is caused collectively by multiple rare variants. Although many studies including genome-wide association study (GWAS) until recently have shown disease susceptibility genes associated with rheumatoid arthritis (RA), causal variants underlying these findings have not yet been identified. <h3>Objectives</h3> We used a comprehensive approach to select genes for targeted resequencing in rheumatoid arthritis (RA). <h3>Methods</h3> One of the critical components for success lies in the selection of target regions or genes, which are associated with common variants from GWAS for resequencing. We integrate multi-layered approaches for targeted resequencing in RA combining RA-related biological pathways, text-mining and animal model approach as well as experiment data such as GWAS, linkage study, and candidate study. <h3>Results</h3> In the experimental data approach, we selected 106 genes from previously known variants such as linkage study and candidate study, 155 genes from Korean RA/systemic lupus erythematosus (SLE) GWAS, and 519 genes from immunochip of Korean RA. In the pathway based approach, we selected 18 genes from sharing common pathways among the RA-related pathways. In the text mining approach, we obtained 65 genes using Gene Relationhips Across Implicated Loci (GRAIL). In the animal model approach, we obtained 8 homology genes from Mouse Genome Informatics (MGI) database (Fig 1). <h3>Image/graph</h3> <h3>Conclusions</h3> When put together, 684 target genes were selected for resequencing. By applying targeted resequencing, we could extend the results of successful GWAS and pinpoint disease-causing genes in genomic regions initially identified by GWASs. Rare and common variants discovered by resequencing potential risk genes will help unravel the causality of RA disease risks. <h3>Disclosure of Interest</h3> None Declared
Abstract 2783: Mammotrophic hormone score and risk of postmenopausal breast cancer
Authors: Shelley S. Tworoger, Heather Eliassen, Bernard Rosner, Susan E. Hankinson
Journal: Cancer Research (2010)

Abstract Sex hormones and prolactin have been positively associated with risk of breast cancer among postmenopausal women. However two small studies suggested that having multiple hormones above the age-adjusted mean level did not further increase the risk of breast cancer beyond having only one hormone above the mean. This suggests a possible threshold effect, such that these hormones may be permissive with respect to breast cancer growth and an evaluation of hormones levels at the low end of the distribution may be most informative. The goal of this study was to evaluate the combined effect of multiple hormones, including estradiol, estrone, estrone sulfate, testosterone, androstenedione, DHEA, DHEAS, and prolactin, in relation to postmenopausal breast cancer risk. We conducted a nested case-control study in the Nurses' Health Study including cases of postmenopausal breast cancer who were not using postmenopausal hormones at blood collection in 1990 and were diagnosed after blood collection but before June 1, 1998 and their matched controls. We examined the relationship between the number of hormones in which levels were above age- and batch-adjusted means (as determined in controls and referred to as the “hormone score”) and risk of breast cancer overall using conditional logistic regression adjusting for age at menopause, body mass index (BMI) at age 18, history of benign breast disease, and family history of breast cancer. We also examined estrogen receptor (ER) positive cases only using unconditional logistic regression. Overall, 265 cases (189 ER+) and 541 matched controls had measured levels for all eight hormones. The mean hormone score was 4.6 (SD=2.3) in cases and 3.9 (SD=2.4) in controls (p&amp;lt;0.001). There was a statistically significant 16% increase in risk for a one unit increase in the hormone score with risk of breast cancer overall (95% CI: 1.08-1.24, p-trend&amp;lt;0.001) and a 19% increase for ER+ tumors (95% CI: 1.10-1.28, p-trend&amp;lt;0.001). Women with a hormone score of 6-8 versus 0 had a significantly increased risk of breast cancer overall (RR=2.67, 95% CI: 1.26-5.62) and of ER+ disease (RR=5.30, 95% CI: 1.18-15.5). For ER+ tumors, women with a score of 3-5 versus 0 also had an increased risk (RR=3.12, 95% CI: 1.08-9.02). Despite the somewhat small number of cases, our data support that the risk of postmenopausal breast cancer increases linearly as the number of hormones with high levels rises. This suggests that proliferation and other carcinogenic processes may be sensitive to the influence of multiple mammotrophic hormones simultaneously. Further, this information could be used to develop improved risk prediction models. 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 2783.
Abstract 1639: The novel c-MET inhibitor, ARQ 197, shows additive growrh-inhibitory effect with erlotinib through enhanced degradation of c-MET protein via ubiquitin/proteasome pathway
Authors: Tomoko Kanome, Tsuyoki Kadofuku, Toshimitsu Yamaoka, Takashi Hirose, Shiro Akinaga, Mitsuru Adachi, Nagahiro Saijo, Tohru Ohmori
Journal: Cancer Research (2010)

Abstract Background c-MET, a receptor of hepatocyte growth factor (HGF), is known to be overexpressed in a variety of human cancers. Recently several c-MET inhibitors are being developed as cancer chemotherapy against this compelling molecular target. ARQ 197 is a new small molecule c-MET inhibitor. Since ARQ 197 shows efficient anti-cancer activity without many severe adverse events in Phase I clinical trials, it is expected to be a useful anticancer agent for clinical treatment. This drug is known to bind to c-MET at neighbor area of its ATP binding site and it does not work as an ATP mimic. In this study, we investigated the molecular mechanism of inhibitory effect on c-MET by ARQ 197 in a non-small cell lung cancer cell (NSCLC) line. Materials and Method We established a c-MET-overexpressed NSCLC line, PC-9/MET, by long term exposure of PC-9 cells to EGFR-tyrosine kinase inhibitor. The cytotoxicity of ARQ 197 was measured by MTT assay. The expression of c-MET protein and mRNA were detected by Western blotting analysis and real time RT-PCR method, respectively. In a c-MET degradation analysis, bortezomib was used for inhibition of proteasome. Results ARQ 197 is equally cytotoxic to parental PC-9 and EGFRTKI-resistant PC-9/MET cell line with GI50 values around 200 nM (?). ARQ 197 showed an additive growth- inhibitory effect with erlotinib in PC-9/MET cells as assessed by an Isobologram analysis. In ARQ 197-treated PC-9/MET cells, a clear decrease of phospho c-MET protein as well as phospho AKT and ERK proteins was observed, however, ARQ 197 also induced a down-regulation of c-MET protein in the cells without any effect on c-MET mRNA level. This ARQ 197 induced degradation was reversed by a concomitant treatment with a proteasome inhibitor, bortezomib in the cells. However, bortezomib did not affect cytotoxicity of ARQ 197 in the same cells. Conclusion These data suggest that ARQ 197 may inhibit c-MET through downregulation of this protein in addition to inhibition of its kinase activity. Furthermore, it may enhance c-MET degradation by the ubiquitin/proteasome pathway. These c-MET inhibitory activities by ARQ 197 should be important for the additive combined effect with erlotinib in PC-9/MET cells. 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 1639.
High definition colonoscopy vs. standard video endoscopy for the detection of colonic polyps: a meta-analysis
Authors: V. Subramanian, J. Mannath, C. Hawkey, K. Ragunath
Journal: Endoscopy (2011)

Background and study aims: High definition colonoscopy may improve adenoma detection rates but studies report conflicting results. The aim of this meta-analysis was to compare the diagnostic yield of colonic polyps between high definition colonoscopy and standard video endoscopy (SVE).
Fundamentals of Complementary and Alternative Medicine
Authors: T. J Ryan
Journal: BMJ (1996)

Ed Marc S Micozzi Churchill Livingstone, £19.95, pp 303 ISBN 0443 053 553

With many health services around the world in disarray, mostly for economic reasons, it is worth examining what resources the peoples of the world need, want, and actually use. It is well known that, especially for chronic illness, complementary or alternative medicine is preferred by up to 80% of the population in many developing countries. This is not just in the rural areas of the developing world, where problems of availability, sustainability, and cost explain some of the preference, but also in urban or more technically advanced …