tbuckley/cabot-search huggingface dataset:
Abstract 4193: TNF-α dynamically modulates genome-wide cross-regulation of cRel, ΔNp63 and TAp73 promoter binding and gene expression in head and neck cancer: TP53 and NFκB ChIP-Seq in HNSCC
Authors: Han Si, Hai Lu, Xinping Yang, Minyoung Jang, Jeffery Burnett, Sean Davis, Hong-wei Sun, Wenming Xiao, Lai Wei, Paul Meltzer, Carter Van Waes, Zhong Chen
Journal: Cancer Research (2012)

Abstract We previously showed that cRel, ΔNp63, and TAp73, members of NF-kappaB and TP53 transcription factor (TF) families, together regulate broad biological processes critical for inflammation and cancer survival. However, the underlying molecular mechanisms explaining the global cross-regulation of transcriptome and interactive signal network have not been revealed. Here, we demonstrate that inflammatory cytokine TNF-α induces a dynamic, genome-wide increase in cRel and ΔNp63 chromatin occupancy after replacing TAp73 binding activity, using Illumina Next Generation ChIP-sequencing and fitting the data into a dynamic Poisson distribution model integrated in MACS. Globally, significant binding peaks (p&amp;lt;10-5) were highly enriched in promoter regions (∼10%). These binding peaks further showed significant enrichment around transcription starting sites (±2000bp), and co-localized peaks for any of the two TFs were prevalent within a distance of ∼200 bp. De novo motif search using Gibbs Sampler indicated that cRel and ΔNp63 bound to p53 motifs while TAp73 binding switched from p53 to AP1 motifs when treated with TNF-α. Motifs from these TFs also co-localized within ∼200 bp. Binding activities of individual transcription factors were validated by ChIP-PCR and oliogo-ELISA based binding assays. In addition, TNF-α modulated 1050 differentially expressed genes detected by microarray, of which one-third exhibited binding activity for at least one TF, and 73 genes were identified with co-binding activities for the three TFs simultaneously. Ingenuity Systems Pathway Analysis (IPA) and Gene Ontology revealed that these genes are enriched in cancer-related transcription factors and signaling pathways. Our data suggest a novel mechanism of genome-wide replacement of TAp73 by cRel and ΔNp63, supporting cross-regulation and interactive network between NF-kappaB and TP53 families. 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 4193. doi:1538-7445.AM2012-4193
Abstract 3146: The involvement of Foxp3 or CD34 expression and tumor lymphocyte infiltration in the prognosis of breast carcinoma patients
Authors: María J. Rico, Viviana R. Rozados, Carlos M. Alasino, Eduardo Roggero, Ana L. Nocito, O Graciela Scharovsky
Journal: Cancer Research (2011)

Abstract Breast cancer is a heterogeneous disease with different known biological subclasses some of which are associated with immune cell infiltration. Studies in mice have shown that thymus-derived CD4+CD25+ regulatory T cells (Treg; FOXP3+ lymphocytes) inhibit the antitumor immune response. The presence of inflammatory cells may represent an immune response to the tumor, but could also potentially exhibit pro-tumor effects including stimulation of tumor invasion or angiogenesis. Angiogenesis has an important role in the progression of breast cancer. Microvessel density has been found to be strongly associated with features of tumor aggression as larger size and poor differentiation. It was observed that different characteristics of tumors like immune cells infiltration, number of Tregs and blood vessels density would be useful tools to anticipate the response to the therapy. The aim of this study was to analyze different cellular characteristics of primary tumors of patients with breast cancer and their relationship to the response to therapy. Samples of breast carcinomas (Stage I and II) (n=14) were analyzed. Foxp3 and CD34 expression was determined immunohistochemically on formalin-fixed, parafin-embedded tumor sections. Also, peritumor and intratumor lymphocytes infiltration was evaluated by hematoxylin-eosin staining. For quantification in 20 high magnification fields, a 0 (nule expression) to 6 (high expression) score was utilized. Confocal microcopy for Foxp3 was also used. Lymphocytes were mainly found in the intratumor (IT) area. Twelve over 14 patients (DF) that had a disease free survival of approximately 5 years showed an IT score for lymphocyte infiltration [median (range): 4 (2-6)] higher than that of 2/14 patients that relapsed (R) [2 (2-2)], p&amp;lt;0.05. For Foxp3 expressing lymphocytes, the IT score was low in DF [2 (0-6)] and R [2 (2-2)] patients. Interestingly, some tumor cells were Foxp3+. Vascular density, evaluated through CD34 expression, was low [DF: 2 (1-4); R: (1-2)]. The relationship between the presence of Tregs cells, and the vascular density in the intratumor area, with prognosis is still controversial. Our present results show that Foxp3+ or CD34 IT expression could not predicts patients prognosis. Disease free patients showed higher intratumor lymphocyte infiltration than relapsed patients, a fact that could reflect the involvement of the host anti-tumor immune response. 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 3146. doi:10.1158/1538-7445.AM2011-3146
A Novel Approach to Cancer Therapy Using an Oncolytic Herpes Virus to Package Amplicons Containing Cytokine Genes
Authors: John F. Carew, David A. Kooby, Marc W. Halterman, Se-Heon Kim, Howard J. Federoff, Yuman Fong
Journal: Molecular Therapy (2001)

There are two promising herpes viral-based anticancer strategies: one involves replication-defective viruses to transfer therapeutic transgenes, and the other involves replication-conditional oncolytic viruses, which selectively infect and destroy cancer cells directly. This study examines a novel dual herpesvirus preparation, which combines the immunostimulatory effects of amplicon-mediated IL2 expression with direct viral-induced oncolysis. The oncolytic virus G207 was used as the helper virus to package a herpes simplex virus (HSV)-amplicon vector carrying the gene IL2 (HSV-IL2), yielding a single preparation with two complementary modes of action. In vivo comparison was carried out in a syngeneic squamous cell carcinoma flank tumor model. We directly injected established tumors with HSV-IL2, G207, G207 mixed with HSV-IL2, or G207-packaged HSV-amplicon carrying the IL2 transgene (G207[IL2]). Significant inhibition of tumor growth was seen at 2 weeks in the G207[IL2]-treated tumors relative to controls (0.57+/-0.44 cm(3) versus 39.45+/-5.13 cm(3), P<0.00001), HSV-IL2 (20.97+/-4.60 cm(3)), and the G207 group (7.71+/-2.10 cm(3)). This unique use of a replication-conditional, oncolytic virus to package a replication-incompetent amplicon vector demonstrates impressive efficacy in vitro and in vivo, and avoids the theoretical concerns of recombination with reversion to wild type.
Covered stent placement is a treatment option for anastomotic leakage after gastric bypass surgery
Authors: JA Arroyo-Vàzquez, S Karhu, M Bergström, PO Park
Journal: Endoscopy (2012)

Introduction: One of the most feared complications after Laparoscopic Gastric Bypass (LGBP) surgery is leakage of the gastro-entero anastomosis, often leading to re-operation with high morbidity. Endoscopic treatment with covered self-expandable metal stents (SEMS) has been proposed as a treatment for these leakages.
The Ratio of 18F-FDG Activity Uptake Between the Right and Left Ventricle in Patients With Pulmonary Hypertension Correlates With the Right Ventricular Function
Authors: Tao Yang, Lei Wang, Chang-Ming Xiong, Jian-Guo He, Yan Zhang, Qing Gu, Zhi-hui Zhao, Xin-Hai Ni, Wei Fang, Zhi-Hong Liu
Journal: Clinical Nuclear Medicine (2014)

Purpose It is known that patients with pulmonary hypertension (PH) can have elevated 18F-FDG uptake in the right ventricle (RV) on PET imaging. This study was designed to assess possible relationship between FDG uptake of ventricles and the function/hemodynamics of the RV in patients with PH. Patients and Methods Thirty-eight patients with PH underwent FDG PET imaging in both fasting and glucose-loading conditions. The standard uptake value (SUVs) corrected for partial volume effect in both RV and left ventricle (LV) were measured. The ratio of FDG uptake between RV to LV (SUVR/L) was calculated. Right heart catheterization and cardiac magnetic resonance (CMR) were performed in all patients within 1 week. The FDG uptake levels by the ventricles were compared with the result form the right heart catheterization and CMR. Results The SUV of RV (SUVR) and SUV of LV were significantly higher in glucose-loading condition than in fasting condition. In both fasting and glucose-loading conditions, SUVR and SUVR/L showed reverse correlation with right ventricular ejection fraction derived from CMR. In addition, in both fasting and glucose-loading conditions, SUVR and SUVR/L showed positive correlations with pulmonary vascular resistance. However, only SUVR/L in glucose-loading condition could independently predict right ventricular ejection fraction after adjusted for age, body mass index, sex, mean right atrial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance (P = 0.048). Conclusions The FDG uptake of RV increases with decreased right ventricular function in patients with PH. Increased FDG uptake ratio between RV and LV might be useful to assess the right ventricular function.
O133 NOVEL PROTEIN MARKERS IDENTIFIED IN BILE AND SERUM ARE ASSOCIATED WITH A DIAGNOSIS OF PRIMARY SCLEROSING CHOLANGITIS, DISEASE SEVERITY, AND TRANSPLANT-FREE SURVIVAL
Authors: M. Vesterhus, A. Holm, J.R. Hov, I.M. Andersen, E. Schrumpf, V. Paulsen, M. Bjørnstad, K. Lundin, S.J.L.B. Zweers, M. Vatn, F.G. Schaap, T. Ueland, H. Røsjø, B. Moum, C.Y. Ponsioen, K.M. Boberg, M. Färkkilä, F. Lund-Johansen, T.H. Karlsen
Journal: Journal of Hepatology (2014)
A Gluten-Free Vegan Meal for Gastric Emptying Scintigraphy
Authors: Vijay Harish Somasundaram, Padma Subramanyam, Shanmuga Sundaram Palaniswamy
Journal: Clinical Nuclear Medicine (2014)

Purpose The aim of this study was to describe the preparation of radiolabeled idli (savory cake) meal for use as an alternate to the egg white sandwich (EWS) meal in gastric emptying scintigraphy (GES). Furthermore, the aim of this study was to establish normal emptying rates for this meal and present our experience in using it in the evaluation of diabetic gastroparesis. Patients and Methods The meal was prepared using a universally available packaged mix labeled with 1 mCi 99mTc sulfur colloid, and the stability of labeling was tested up to 4 hours in simulated gastric fluid. One hundred thirteen healthy volunteers (aged 20–78 years; 54 women, 59 men) underwent GES study using the idli meal. Gastric retention at one-half, 1, 2, and 4 hours after ingestion of the meal was estimated, and the normal limits were set using the fifth and 95th percentile values at each period. Having established its normal emptying rates, the idli meal was further used to evaluate 70 patients suspected with diabetic gastroparesis. Results The idli meal, with a calorific value ≈282 kcal, has a relatively higher fat content (8% of total mass) than EWS. More than 96% of 99mTc sulfur colloid remained bound to the meal after 4 hours suspension in simulated gastric fluid. Gastric retention greater than 30% and greater than 6% at 2 hours and 4 hours, respectively, indicated delayed gastric emptying, whereas retention less than 30% at 1 hour suggested rapid emptying. Among patients suspected with diabetic gastroparesis, delayed gastric emptying was identified in 76%, and rapid emptying was seen in 4.2%. Conclusions Radiolabeled idli meal is a good alternative to EWS meal for routine GES, especially among patients with specific dietary restrictions.
Abstract 4116: Mammary adipocyte-specific metabolic alterations are associated with paracrine effects on mammary tumorigenesis
Authors: Paul A. Volden, Erin L. Wonder, Maxwell N. Skor, Christopher M. Carmean, Honggang Ye, Masha Kocherginsky, Martha K. McClintock, Matthew J. Brady, Suzanne D. Conzen
Journal: Cancer Research (2012)

Abstract In rodent models of breast cancer, chronic social stress from isolated housing is associated with increased mammary tumor growth. Interestingly, in several diverse mouse strains, social isolation is also associated with increased expression of the key metabolic genes Acaca, Hk2 and Acly in the adipocyte fraction of the mammary gland. We hypothesized that these gene expression changes would be associated with increased mammary fat glucose metabolism, lipid synthesis, and secretion of paracrine growth promoting adipokines. We found that increased metabolic gene expression in mammary fat did indeed increase both lipid metabolism and leptin secretion from the mammary adipocytes of isolated mice. Surprisingly, visceral fat metabolism and systemic metabolic parameters were unchanged in social isolates, suggesting an effect of social stress that is specific to the mammary fat depot. When mouse mammary cancer cells were treated with culture media derived from the incubation of isolated versus group-housed mouse mammary adipose tissue, the mammary fat secretome of social isolates resulted in significantly increased cancer cell proliferation compared to mammary fat from grouped mice. Current experiments are designed to elucidate the metabolic factors promoting tumor cell proliferation in the mammary fat derived from the stressed animals. We propose a model wherein social isolation and the ensuing heightened neuroendocrine response significantly alters mammary adipocyte metabolism and associated adipokine secretion, thereby potentiating estrogen-independent mammary tumor growth. These studies have implications for understanding the environmental, endocrine, and molecular risk factors associated with estrogen receptor-negative breast cancer. DOD W81XWH-11-1-014901, NIH/NIDDK T32 DK087703, NIH R01CA148814 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 4116. doi:1538-7445.AM2012-4116
SAT0186 Abnormal Videofluoroscopy Swallow study Finding in Inflammatory Myopathy Patient with Dysphagia as Predictor of Prognosis
Authors: H.W. Kim, H. Kim, S.H. Chang, B.M. Oh, E.Y. Lee
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Previous reports of dysphagia in patients with inflammatory myopathy (IM) have been focused on detection, intervention and rehabilitation. However, whether dysphagia with abnormal videofluoroscopy swallow study (VFSS) findings is in relation to clinical manifestations and treatment response is not known. <h3>Objectives</h3> We hypothesized that clinical entities in IM patients with dysphagia would be distinct from non-dysphagia patients and abnormal VFSS finding could be a predictor of prognosis. <h3>Methods</h3> Total 236 patients with IM were reviewed in this study. Of them, the patients with dysphagia were evaluated with clinical functional scale, VFS scale, new VFSS scale, and American Speech-Language-Hearing Association National Outcome Measurement System swallowing scale. VFSS score was categorized into oral, pharyngeal and esophageal phase based on modified Logemann's methods. Association between VFSS scale and serum creatinine kinase (CK), clinical findings, or treatment response were analyzed. <h3>Results</h3> Among 236 IM patients, 28 patients had IM related dysphagia (26 with dermatomyositis, 1 polymyositis and 1 inclusion body myositis). Ten male and 18 female with mean age of 42.7 were included. Dysphagia was a presenting symptom in 5 patients (17.9%) and rest of patients developed dysphagia in average 221 days later. The VFSS results showed more prevalent abnormalities in pharyngeal phase than oral phase (n=26 vs. n=9). Baseline CK level was higher in delayed laryngeal elevation and epiglottic closure (LEEC) patients than in normal LEEC patients (473.8 ± 415.6 mg/dl vs 3931.7 ± 5532.3 mg/dl, p=0.008) (Figure 1). There was no correlation in total VFSS score with baseline CK level. Intravenous immunoglobulin were significantly more prescribed in delayed LEEC patients than in normal LEEC patients (OR=10.7, p=0.047). Frequency of pulmonary involvement and malignancy were significantly different between patients with dysphagia and patients without dysphagia (7.1% vs 40.4%, p&lt;0.001, 35.7% vs 9.6%, p=0001, respectively) (Table 1). <h3>Conclusions</h3> Abnormal VFSS findings in IM Patients with dysphagia were more prominent in pharyngeal phases than oral phases. Delayed LEEC was associated with higher baseline CK level and use of intravenous immunoglobulin. IM patients with dysphagia showed lower pulmonary involvement and higher malignancy. These results indicate that dysphagia in IM is not only a localized symptom or disabling condition, but also a predictor of prognosis. <h3>Acknowledgements</h3> None <h3>Disclosure of Interest</h3> None Declared
REASONS FOR INABILITY TO COMPLETE ULTRAMARATHONS: A MULTICENTER STUDY
Authors: M Khodaee, J Spittler, P Basset, K Vanbaak, JC Hill, I San Millán, MD Hoffman
Journal: British Journal of Sports Medicine (2014)

Background Despite increased ultramarathon participation in recent years, little is known about causes of race incompletion. This study surveyed runners of three 161–168 km ultramarathons in Europe and North America to explore characteristics and issues that affected race performance. Objective Determine human and environmental factors related to failure to complete ultramarathons of ∼161 km in the previous year. Design Observational study using surveys prior to the race. Setting The 2013 Ultra-Trail du Mont-Blanc ® (UTMB ® ) in Europe; Leadville Trail 100 (LT100) and Western States Endurance Run (WSER) in North America. Participants Out of 4 110 race entrants, 2 794 (69%) completed the pre-race survey. Risk factor assessment In this epidemiologic study, we report the incidence of intrinsic and extrinsic factors related to failure to finish of at least one ∼161 km race in the previous year. Main outcome measurements The main outcome measurements were self-reported reasons for not finishing the race. Results Among respondents, about 30% had masters or higher degrees. Out of 2,469 UTMB ® , 1206 LT 100, and 408 WSER entrants, the majority successfully completed the race (68%, 52% and 72%, respectively). Among participants who responded, 18.3% reported they failed to complete an ultramarathon of ∼161km in the past year. The main reasons for dropping out were inability to make the cut off time (23.1%), nausea and/or vomiting (16.5%), injury during the race (16.5%), and an ongoing injury (13.3%). Conclusions We conclude that primary performance-limiting issues in 161–168 km ultramarathons include inability to make the cut off time, nausea and/or vomiting, and injury before and during the race.
Abstract 4715: Activation of lytic cycle of Epstein-Barr virus by suberoylanilide hydroxamic acid affects apoptosis and tumor growth suppression of nasopharyngeal carcinoma
Authors: Alan KS Chiang, Kwai Fung Hui
Journal: Cancer Research (2012)

Abstract Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV). We examined the in vitro and in vivo effects of suberoylanilide hydroxamic acid (SAHA), a FDA-approved histone deacetylase inhibitor, on EBV lytic cycle induction in NPC and investigated the cellular consequences. Micromolar concentrations of SAHA potently induced EBV lytic cycle with replication of EBV DNA, expression of immediate early (Zta and Rta), early (BMRF1) and late (gp350) lytic proteins and production of infectious viral particles in culture supernatants in three of four EBV-positive NPC cell lines. One NPC cell line had abortive EBV lytic cycle (no EBV DNA replication or late lytic protein expression) induction. Same concentrations of SAHA effected enhanced killing of EBV-positive NPC cells in comparison with EBV-negative counterparts, as measured by MTT assay. Increased percentages of annexin V-positive and TUNEL-positive cells and proteolytic cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3, -7 and -9 in EBV-positive versus EBV-negative NPC were also observed. Immunofluorescence staining and flow cytometry showed that the majority of NPC cells (&amp;gt;85%) expressing Zta, BMRF1 or gp350 lytic protein co-expressed cleaved caspase-3. Tracking of expression of EBV lytic protein and cleaved caspase-3 showed that proportion of NPC cells co-expressing EBV lytic protein and cleaved caspase-3 increased over time. Furthermore, knockdown of Zta expression by short-hairpin RNA significantly decreased proteolytic cleavage of caspase-3 in SAHA-treated EBV-positive NPC cells whilst overexpression of Zta induced apoptosis of EBV-positive NPC cells, confirming that lytic cycle induction programmed NPC cells to apoptosis. Interestingly, inhibition of EBV DNA replication and late lytic protein expression by phosphonoformic acid did not impact on SAHA's induced cell death in NPC, suggesting that early rather than late phase of EBV lytic cycle contributed to the apoptotic effect. In vivo effects of SAHA on EBV lytic cycle induction and tumor growth suppression were observed in NPC xenografts established in nude mice. Taken together, our data indicated that activation of lytic cycle from latent cycle of EBV by SAHA effects apoptosis and tumor growth suppression of NPC thereby providing experimental evidence for virus-targeted therapy against EBV-positive cancer. This project is funded by NPC Area of Excellence (AoE/M 06/08 Center for Nasopharyngeal Carcinoma Research) and Epstein-Barr virus research (# 20004525) grants of AKSC. 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 4715. doi:1538-7445.AM2012-4715