tbuckley/cabot-search huggingface dataset:
Abstract 1590: Taxifolin suppresses UV-induced skin carcinogenesis by targeting EGFR and PI3-K
Authors: Naomi Oi, Hanyong Chen, Myoung Ok Kim, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2012)

Abstract Skin cancer is one of the most commonly diagnosed cancers in United States. Taxifolin (3, 3′, 4′, 5, 7-pentahydroxy-flavanone, (2R,3R)-dihydroquercetin), which is found in many citrus fruits such as grapefruits and oranges, has been studied for multiple biological effects. However, the molecular mechanisms and direct target of taxifolin in skin cancer chemoprevention are unclear. Here we show that taxifolin suppresses UV-induced skin carcinogenesis by directly targeting epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3-K). In silico computer screening results suggest that EGFR and PI3-K are potential targets for taxifolin. In vitro and ex vivo pull-down assay data revealed that taxifolin indeed directly interacts with EGFR and PI3-K at the ATP-binding pocket, and inhibited their kinase activities in vitro. UVB-induced phosphorylation of EGFR and Akt were substantially suppressed by taxifolin in mouse skin epidermal JB6 P+ cells. Taxifolin also suppressed UVB-induced phosphorylation of mitogen-activated protein kinases (MAPKs) and cyclooxygenase-2 (COX-2) expression. Importantly, topical treatment with taxifolin to the dorsal skin significantly suppressed tumor incidence, multiplicity and volume in a solar UV-induced skin carcinogenesis mouse model. Further analysis of the solar UV-exposed mouse skin showed that the taxifolin-treated group had a substantial reduction in solar UV-induced phosphorylation of EGFR and Akt. These results suggest that taxifolin exerts potent chemopreventive activity against UV-induced skin carcinogenesis by targeting EGFR and PI3-K. 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 1590. doi:1538-7445.AM2012-1590
A3.23 Alterations in the distribution and pro-inflammatory activity of peripheral blood monocytes and dendritic cells subpopulations in systemic sclerosis
Authors: Tiago Carvalheiro, Sara Horta, Mariana Santiago, Maria João Salvador, José António Pereira da Silva, Artur Paiva
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic sclerosis (SSc) is a connective tissue disease characterised by immune and fibrotic abnormalities. Important observations suggest monocytes and dendritic cells (DCs) involvement in SSc, including abnormalities in differentiation, recruitment, trafficking, activation and an enhanced pro-fibrotic phenotype that could be important factors in the disease pathogenesis. <h3>Objectives</h3> Evaluate the frequency of monocytes subpopulations (CD16<sup>-</sup> and CD16<sup>+</sup> monocytes) and DCs subsets (myeloid – mDC, CD16<sup>+</sup>CD14<sup>-/low</sup> DCs and plasmacytoid DCs – pDCs) and their functional ability to produce chemokines (CXCL10, CCL4 and IL-8) in SSc patients. <h3>Materials and Methods</h3> The study enrolled 43 SSc patients, 30 with limited cutaneous subtype (lSSc) and 13 with diffuse cutaneous subtype (dSSc). A further subdivision was made based upon clinical parameters of disease duration and organ involvement. The healthy control group (HC) included 20 age and gender matched individuals. Immunophenotyping of peripheral blood DC and monocytes subpopulations was assessed by flow cytometry and their functional characterisation was performed after LPS plus IFN-g stimulation. <h3>Results</h3> We observed an increased frequency and absolute number of CD16<sup>+</sup> monocytes in SSc patients, particularly in the lSSc group. These changes were more pronounced in patients with longer disease duration (&gt;10 yrs). Concerning the DCs subsets, no differences were observed between the SSc subtypes and HG. Patients without pulmonary fibrosis demonstrated a higher frequency and absolute number of CD16<sup>+</sup>CD14<sup>-/low</sup> DCs than HG, while the differences were not statistically significant between patients with pulmonary fibrosis and HC. Patients with SSc for more than 10 years, demonstrated an increased frequency and absolute value of CD16<sup>+</sup>CD14<sup>-/low</sup> DCs in comparison to HG. Without <i>in vitro</i> stimulation, we observed an increased frequency of CD16<sup>+</sup>CD14<sup>-/low</sup> DCs and mDCs expressing CCL4 and CXCL10, particularly in dSSc subtype. After <i>in vitro</i> stimulus, a higher frequency of CD16<sup>+</sup>CD14<sup>-/low</sup> DCs expressing IL-8 in dSSc subtype was observed. Moreover, the frequency of monocytes, CD16<sup>+</sup>CD14<sup>-/low</sup> DCs and mDCs expressing IL-8 and the frequency of CD16<sup>+</sup>CD14<sup>-/low</sup> DCs and mDCS expressing CCL4 was higher in patients with pulmonary fibrosis than in HC. <h3>Conclusions</h3> Important alterations were observed in the frequency/absolute number of circulating monocytes and DCs subsets and their functional ability to produce chemokines in SSc patients, which seem to be related to disease duration and to pulmonary fibrosis.
PTH-151 The Implications for new to follow-up Ratios Based on Diagnoses Encountered in Gastroenterology Outpatient Services: Abstract PTH-151 Table 1
Authors: K Clark, A Bond, A Thuraisingam
Journal: Gut (2013)

<h3>Introduction</h3> ‘Better Care, Better Values’ highlighted the importance of outpatient new to follow up ratios (NFRs) (1). Trusts are encouraged to reduce NFRs or may perform unpaid activity. This has implications for patient care, yet can conflict with Speciality guidelines for follow up. There are no published data on the diagnostic case-mix attending secondary care Gastroenterology appointments nor are any diagnostic data available from Hospital Episode Statistics (HES) for outpatient-based specialties. <h3>Methods</h3> We performed a retrospective audit of all Gastroenterology follow-up patients attending Wirral University Teaching Hospital (catchment population 360,000) during a 3-month period. All clinic letters were identified from the hospital IT system and the following information obtained. Number of new and follow up attendances per Consultant-led clinic Primary diagnosis for each follow-up encounter Appointment outcome- further follow up or discharge Discharge rate per diagnosis Number seen in dedicated Specialist Nurse clinics <h3>Results</h3> - 675 new and 1622 follow up appointments were seen by Medical Staff (Consultant, Registrar or SHO) giving an overall NFR of 1:2.4 516 patients were seen in Nurse-led clinics NFR and diagnostic case-mix varied by Consultant team Table 1 shows the diagnostic case-mix and outcomes <h3>Conclusion</h3> Almost 40% of secondary care follow up patients are seen with IBD or chronic liver disease. Fewer of these patients are discharged than patients with other diagnoses. In order to improve NFRs we now have primary care discharge pathways for stable patients with coeliac disease and limited colitis. Additional pathways are planned but diagnostic case-mix appears to be a major determinant of NFRs and should be taken into consideration when NFR targets are set. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> NHS Institute for Innovation and Improvement. Converting the potential into reality: 10 steps a provider can take to realise the benefits of Better Care, Better Value indicators.
Simultaneous Transmission of Human Immunodeficiency Virus and Hepatitis C Virus from a Needle-Stick Injury
Authors: Renée Ridzon, Kathleen Gallagher, Carol Ciesielski, Eric E. Mast, Michael B. Ginsberg, Betty Jo Robertson, Chi-Cheng Luo, Alfred DeMaria
Journal: New England Journal of Medicine (1997)

Human immunodeficiency virus type 1 (HIV) and hepatitis C virus (HCV) are blood-borne viruses that pose occupational hazards to health care workers exposed to the blood of infected patients. As of June 1996, 51 documented and 108 possible cases of occupationally acquired HIV infection had been reported to the Centers for Disease Control and Prevention (CDC).1 The estimated risk of acquiring HIV infection after percutaneous exposure to blood from an HIV-infected patient is 0.3 percent.2 Recommendations for follow-up after occupational exposure to HIV-infected blood include HIV-antibody testing at the time of exposure and periodically for at least six months thereafter. . . .
THIRD GENERATION DUAL SOURCE COMPUTED TOMOGRAPHY FOR EVALUATION OF PATIENTS PRIOR TO TRANSCATHETER AORTIC VALVE REPLACEMENT: COMPREHENSIVE IMAGING WITH AN ULTRA LOW-DOSE OF CONTRAST AGENT
Authors: Mohamed Marwan, Stephan Achenbach, Michaela Hell, Annika Schuhbaeck, Soeren Gauss, Daniel Bittner, Monique Troebs
Journal: Journal of the American College of Cardiology (2015)
TCTAP A-172 Feasibility and Safety of Right Heart Catheterization via Arteriovenous Shunts in Patients on Maintenance Hemodialysis: A Prospective Study
Authors: Jui-Cheng Kuo, Mu-Yang Hsieh, Lin Lin, Ren-Huei Wang, Chih-Cheng Wu
Journal: Journal of the American College of Cardiology (2015)
Abstract 1272: Myeloid leukemia cell lines suppress T cell activation and proliferation.
Authors: Kazushi Tanimoto, Sawa Ito, Samantha Miner, Pawel Muranski, Nancy F. Hensel, J. Joseph Melenhorst, A. John Barrett
Journal: Cancer Research (2013)

Abstract In preliminary experiments to develop the K562 human leukemia cell line as an artificial antigen presenting cell we found that K562 cells strongly inhibited T cell proliferation. To explore this phenomenon further we tested CD4+CD25- T cells from healthy donor PBMC as targets of proliferation suppression. Targets were co-cultured with 3 chronic myeloid leukemia (CML) derived cell lines (K562, BV173 and CML1 established from a CML patient in our laboratory), two monocytic leukemia derived cell lines (THP-1 and U937), the myeloid leukemia derived cell line (KG1a) and the Burkitt lymphoma cell line (Daudi). To evaluate early activation, CD154 expression was tested by flow cytometry 16h after stimulation with CD3/CD28 beads. T cell proliferation was tested by CFSE dilution in T cells stimulated for 72h. All myeloid lines blocked CD154 expression (10.9-62.8% of control at 1:8 target: suppressor ratio). In CFSE proliferation assay, K562, KG1a, CML1, THP-1 and U937 induced comparable suppression (28.4-93.9%, at 1:8 ratio). In contrast, BV173 and Daudi cells were the least suppressive (4.96-23.0%, P&amp;lt;0.01). Strikingly, CML1 cell line and THP-1 showed more suppressive effect on T cell proliferation than CD4+CD25+CD127- autologous regulatory T cell (Treg). Our result showed that myeloid leukemia cell lines but not B cells strongly inhibit both T cell activation and T cell proliferation. Suppression of proliferation was greatest in acute myeloid and monocytic leukemia derived lines. These data indicate that myeloid lekemia cell lines exhibit features of myeloid-derived suppressor cells (MDSC) which can induce T cell tolerance to tumors. Our findings raise the possibility that myeloid leukemias may actively evade immune control through T cell suppression. We plan to use such cell lines to further define the mechanism of MDSC related T cell suppression. Citation Format: Kazushi Tanimoto, Sawa Ito, Samantha Miner, Pawel Muranski, Nancy F. Hensel, J. Joseph Melenhorst, A. John Barrett. Myeloid leukemia cell lines suppress T cell activation and proliferation. [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 1272. doi:10.1158/1538-7445.AM2013-1272
Informed Consent for Comparative Effectiveness Trials
Authors: Ahmed Elsayyad
Journal: New England Journal of Medicine (2014)

To the Editor: We reject the argument by Faden et al. (Feb. 20 issue)1 that certain research with randomized assignment of interventions can be conducted without the consent of patients. Whether or not these studies are embedded in the routine processes of medical care, randomization equals research, and such studies are subject to all of the standard requirements for research, including approval by an institutional review board and patient consent. Patients have the right to choose whether to participate after they have been informed about the interventions, risks, and potential benefits and alternatives, irrespective of the risk levels of the interventions. Patients are the ultimate arbiters of what is done to them. Integrated consent, as proposed by Kim and Miller in the same issue of the Journal,2 is fine in theory but difficult in practice. Few studies involve the comparison of agents delivered in the same way with similar side effects. In most research settings, written disclosure of the treatments being compared, including their risks and potential benefits, is necessary. Written documentation of the patient’s agreement to be a research subject remains essential.
Differential expression of DKK1 in synovial fibroblasts from patients with resolving and early rheumatoid arthritis
Authors: Maria Juarez, Dagmar Scheel Toellner, Lorraine Yeo, Karim Raza, Chris Buckley, Andrew Filer
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Dickkopf related protein 1 (DKK1) is an inhibitor of the Wnt signalling pathway involved in osteoblast growth and differentiation and cell adhesion and invasion in health and disease. In cancer, increased plasma levels of DKK1 have been associated with the osteolytic lesion of multiple myeloma and with tumour invasion and progression in solid tumours. In rheumatoid arthritis (RA) increased DKK1 plasma levels have been shown to correlate with inflammation and bone erosions. Our aim was to study expression of DKK1 in synovial fibroblasts from patients from three different clinical outcome groups: early RA, established RA and resolving arthritis. <h3>Materials and methods</h3> Synovial tissue was obtained from ultrasound guided biopsies done at the time of first presentation to clinic. Resolving (n=8) and early RA (n=12) patients presented with arthritis of less than 3/12 duration and were followed up for 18/12 at which point a diagnostic category was assigned (resolving vs early RA). Established RA (n=9) was defined as RA of &gt;3/12 duration. Synovial fibroblasts from tissue were cultured and mRNA quantified using real-time PCR. Values were expressed as 2<sup>−dCt</sup> relative to glyceraldehyde 3-phosphate dehydrogenase. <h3>Results</h3> DKK1 expression was higher in synovial fibroblasts from patients with early RA than in those from patients with resolving arthritis (0.024 vs 0.009, p&lt;0.005). There was no differential expression of DKK1 in the early RA and established RA groups. <h3>Conclusion</h3> The question of why arthritis resolves in some patients but persists as RA in others is still not resolved. Mechanisms allowing perpetuation of inflammation and joint damage must be in place to allow this. DKK1 is an inhibitor of the Wnt signalling pathway that has been shown to promote cell invasion and imbalance of oestoblast/ostoeclast function in a way that favours bone destruction in cancer. In RA it has been proposed as a biomarker of disease activity and bone erosions. RA synovial fibroblasts have an invasive phenotype and attach to and degrade cartilage causing permanent damage in disease. Our data suggests that DKK1 may be involved in mediation of these actions.
Vascular disease: the next target for local molecular therapeutics
Authors: J McEwan, A Henney, S Humphries
Journal: BMJ (1994)

By the late 1970s, however, disappointment was universal.Departments of community medicine, social medicine, and public health were seen as the "departments of miscellaneous medicine," the soft underbelly of the medical school.They produced socially desirable talk but no hard data.That was in stark contrast to the pilot discipline, epidemiology, which had become widely successful as a method.Some ofthe talk about
PWE-004 Detection of Venous Invasion to Stage Colorectal Cancer
Authors: A K Foulis, C S D Roxburgh, D C McMillan, C H Richards, M Atwan, J H Anderson, T Harvey, P G Horgan
Journal: Gut (2013)

<h3>Introduction</h3> Elastica staining of tumour sections increases the sensitivity of detection of venous invasion in colorectal cancer. We compared the prognostic value of elastica detected venous invasion with that of other pathological features in colorectal tumours. <h3>Methods</h3> This was a single-centre clinical outcome study of pathological variables, including elastica detected venous invasion, in stage I-III electively resected colorectal cancer specimens. <h3>Results</h3> 631 resection specimens, excised between 1997–2009, were analysed (176 retrospectivley and 455 prospectively). The median follow up was 73 months (24–178) and during this time there were 238 deaths (134 from cancer). Venous invasion was detected in 56% of cases and was a stronger predictor of poor long term cancer-specific survival than other pathological features on univariate and multivariate analyses. On multivariate analysis of all cases the hazard ratio (HR) for failure to survive 5 years for venous invasion = 3.94 (95%CI 2.33–6.65, P &lt; 0.001); HR for lymph node involvement = 1.81, (95% CI 1.43–2.30, P &lt; 0.001) and HR for T stage = 1.64 (95%CI 1.16–2.30, P = 0.005). In node negative cases the HR for failure to survive 5 years for venous invasion on multivariate analysis = 3.55 (95%CI 1.81–6.97, P &lt; 0.001) and for T stage was 2.03 (95%CI 1.26–3.28, P = 0.004). Venous invasion strongly related to other high-risk pathological variables. In cases with no venous invasion, no pathological characteristic related to survival other than T stage. When T stage and venous invasion were considered together, patients could be stratified by risk of 5-year cancer mortality from 100–54% in node negative disease and 100–33% in node positive disease. The importance of elastica detected venous invasion can be appreciated from the development of a novel staging system based only on T stage and venous invasion (TVI). This simple TVI system was at least as predictive as the gold standard TNM system when considering all cases, and provided increased prognostic value in both T1 and T2 tumours, as well as in node negative disease. <h3>Conclusion</h3> Sensitive, accurate detection of venous invasion on elastica stained sections improves its prognostic importance such that it becomes a key pathological characteristic, arguably of more importance than nodal status, in determining outcome in patients with colorectal cancer. TVI staging provides a novel and simple method by which venous invasion coupled with T stage can be utilised to predict survival. <h3>Disclosure of Interest</h3> None Declared
FRI0342 Identification of target antigens of anti-endothelial cell antibodies in patients with anca-associated systemic vasculitis: a proteomic approach
Authors: A. Regent, H. Dib, G. Bussone, N. Tamas, C. Federici, C. Broussard, L. Guillevin, L. Mouthon
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-endothelial cell antibodies (AECA) are frequently detected in anti-neutrophil cytoplasm antibodies (ANCA)-associated systemic vasculitis (AAV) and are considered to play pathological roles but their antigenic specificities are still unknown. <h3>Objectives</h3> We used a proteomic approach combining two-dimensional electrophoresis and immunoblotting to identify the target antigens of AECA in patients with ANCA-associated vasculitis. <h3>Methods</h3> Sera from 30 ANCA-associated vasculitis patients (12 with Granulomatosis with polyangeitis (GPA), 9 with microscopic polyangeitis (MPA), 9 with Churg Strauss syndrome (CSS)), tested in pools of 3 sera, were compared to a sera pool from 12 healthy controls (HC). Serum IgG reactivity was analyzed by use of a 2-D electrophoresis and immunoblotting technique with normal human umbilical vein endothelial cell (HUVEC) antigens. <h3>Results</h3> Serum IgG in the HC sera pool recognized 85 protein spots and serum IgG from patients with AAV recognized 134±65 different protein spots. We focused on protein recognized by at least 3/4 pools of patients with GPA and 2/3 pools of patients with MPA and CSS and not by HC and identified 20, 7 and 8 proteins, respectively. In addition, among the 330 spots recognized by at least one pool of patients with AAV, ten different spots were recognized by at least 6/10 pools. Among identified proteins, IgG reactivity was detected against alpha-enolase, lamin A/C and protein disulfide-isomerase A3. Interestingly, Ingenuity Pathway Analysis revealed that most of these antigens interact with TGF-β and signalling pathways such as Jun and MAPK. <h3>Conclusions</h3> AECA detected in patients with AAV recognize cellular targets playing key roles in cell biology. Target antigens interact with protein and complexes known to play a crucial role in AAV pathophysiology. <b>Disclosure of Interest</b>: None Declared
Abstract 1365: The PAMM (pulmonary assessment of metastatic morbidity) diagnostic: A novel non-invasive method for evaluating lung metastasis in murine models
Authors: Radhika V. Gharpure, Arnulfo Mendoza, John U. Dennis, Chand Khanna
Journal: Cancer Research (2012)

Abstract Metastasis continues to be the most significant problem in the field of cancer. The biological complexity that characterizes metastasis requires relevant experimental systems for its study, necessitating the use of animal models. When using murine models for pulmonary metastasis, it is valuable to conduct longitudinal studies during which progression of metastatic burden in the lung occurs. Current methods for evaluating pulmonary metastatic burden in experimental mice are limited to advanced imaging approaches or to the development of morbidity linked to pulmonary metastasis. Unfortunately, clinical signs of morbidity are often vague and unpredictable. A novel, inexpensive, clinical method to detect advanced metastatic burden in mice before the development of significant morbidity or mortality would be beneficial to the study of metastasis in mice. With this goal in mind we have developed a novel, non-invasive technique for assessing pulmonary metastatic burden in laboratory mice. The PAMM (Pulmonary Assessment of Metastatic Morbidity) test is performed by restraining an awake mouse and gently applying pressure with the index finger under the xiphoid process. This pressure reduces the diaphragmatic component to respiration. Mice with advanced lung metastases will show signs of respiratory distress within 3 seconds of applying this pressure. Application of this method in 4 models of pulmonary metastasis (n=27 mice including sarcoma and mammary carcinoma histologies), amongst 3 independent “users,” yielded 100% positive and 100% negative predictive values that were validated by post mortem examination. In summary, the PAMM method is a simple, inexpensive, reproducible and efficient method to assist in the detection of advanced pulmonary metastasis. This method contributes to the humane care of mice included in longitudinal studies of pulmonary metastasis. 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 1365. doi:1538-7445.AM2012-1365