tbuckley/cabot-search huggingface dataset:
Abstract 5403: Pro-apoptotic properties of Bag-1 peptides in the control of prostate cancer cell growth
Authors: Danilo Maddalo
Journal: Cancer Research (2011)

Abstract Purpose of the study: The purpose of the study is to identify sequence(s) in Bag-1 proteins responsible for growth inhibition and to eventually derive a short peptide for cancer therapy. Introduction: Bag-1 family of proteins consists of four members (Bag- 1L, 1M, 1 and 1S) originating from different translation-initiation sites on the same mRNA. Clinical reports have shown a dual role of the Bag-1 proteins in tumor progression and in the inhibition of tumor growth. In this work we have identified a 19 amino acid sequence in the Bag-1 proteins that reduces prostate cancer cell growth ex vivo and in vivo. Experimental procedures: Inhibition of prostate cancer cell growth was analyzed in clonogenic assay and in athymic nude mouse xenograft models. Histological analysis for apoptosis was carried out on paraffin-embedded tumor samples. Structural analyses were carried out by NMR and circular dichroism. Interaction partners of the Bag-1 peptides were analyzed by GST-pull down and by co-immunoprecipitation assays. Significance of cellular levels of glucose-regulated proteins (GRP) 75 and 78 for the growth inhibitory action of the peptide was demonstrated by RNA interference experiments. Results: Overexpression of Bag-1 proteins in 22Rv.1 prostate tumor cells reduced the growth of these cells in a colony forming assay. A study making use of several deletion mutants identified a 69 amino acid Bag-1 sequence as responsible for the growth inhibition. NMR and circular dichroism studies showed this peptide to be unstructured but it nonetheless interacted with the substrate binding domain of GRP 75 and 78. The cellular levels of the GRPs were shown by RNA interference studies to be essential for the action of the peptide. Overexpression of the peptide in the 22Rv1 cells decreased growth in proliferation assay and in xenograft tumor models. The decreased growth in vivo was demonstrated to be due to apoptosis of the Bag-1 peptide expressing cells as showed by immuohistochemical analysis. The growth inhibitory activity could be narrowed down to a 7 amino acid core within a 19 amino acid Bag-1 peptide sequence. Amino acid exchanges in the core region impaired binding of the peptide to the GRPs and inhibition of tumor cell growth. Colony formation assay using a wide panel of prostate cells showed that the 19 amino acid peptide inhibits growth of only malignant but not benign cells and this correlates with the level of expression of the two GRP target proteins in the cells. Conclusion: Together these results demonstrate that a short peptide sequence derived from Bag-1 proteins that binds GRP75/78 specifically inhibits the growth of prostate cancer cells. 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 5403. doi:10.1158/1538-7445.AM2011-5403
ANTIPLATELET AND ANTITHROMBOTIC THERAPY IN ATRIAL FIBRILLATION PATIENTS IN THE SETTING OF ACUTE CORONARY SYNDROME AND/OR AFTER PERCUTANEOUS CORONARY INTERVENTION: EVIDENCE FROM META-ANALYSIS
Authors: Karam Ayoub, Ramez Nairooz, Ahmed Almomani, Meera Marji, Hakan Paydak, Waddah Maskoun
Journal: Journal of the American College of Cardiology (2016)
PWE-114 Does gastrointestinal infection trigger coeliac disease?: Abstract PWE-114 Table 1
Authors: K Evans, S M Barrett, A Smythe, D S Sanders, A Arnout
Journal: Gut (2012)

Introduction It is thought that a “second hit” is required to trigger coeliac disease in genetically susceptible individuals. Various infective agents have been postulated as the second hit but there is little evidence to support this. We aimed to establish the recall rate of antecedent gastrointestinal infection in patients with coeliac disease, and the prevalence of undetected coeliac disease in those with stool culture proven gastroenteritis. Methods Group A comprised histologically proven patients with coeliac disease (n=233, 61 male, median 60 years) who were asked to complete a validated questionnaire and then compared to healthy controls (n=219, 79 male, median 46 years), and controls with inflammatory bowel disease (IBD) (n=196, 124 males, median 56 years). Group B were patients with stool culture proven gastroenteritis (n=101, 48 males, median 57 years) who underwent serologic testing for coeliac disease (endomysial antibody [EMA], tissue transglutaminase [tTG], immunoglobulin A [IgA]). They were compared with healthy controls (n=1200, 447 male, median 46 years). Those with positive serology underwent endoscopy and duodenal biopsy. Results In Group A 69/233 (29.6%) with coeliac disease, and 53/196 (27.1%) with IBD reported having a gastrointestinal infection within the 12 months prior to diagnosis. In both diseases this was significantly greater than in healthy controls 15/219 (6.8%) (p<0.0001). In Group B 94/101 (93%) were coeliac antibody negative. The demographics, serology and biopsy results of the seven stool-culture positive subjects with positive coeliac serology are shown in [Abstract PWE-114 table 1][1]. The prevalence of coeliac disease in patients with stool culture positive gastroenteritis was 2.97%. This was higher than in healthy controls (12/1200, 1%) (p=0.10). In Group B the gastroenteritis pathogen was identified as Campylobacter species in 96/101 (95.0%), Salmonella species in 4/101 (4.0%), and Shigella in 1/101 (1.0%). One participant had IgA deficiency. This individual had normal IgG titres, IgG EMA and IgG tTG. View this table: Abstract PWE-114 Table 1 Conclusion Patients with coeliac disease have a recall rate of previous gastrointestinal infection similar to those with inflammatory bowel disease, and significantly greater than healthy controls. In coeliac disease gastrointestinal infection may well be the “second hit” required to trigger disease but further work is required. Competing interests None declared. [1]: #T1
PREDICTORS OF DELAYED WOUND HEALING AFTER ENDOVASCULAR THERAPY IN PATIENTS WITH CRITICAL LIMB ISCHEMIA DUE TO ISOLATED INFRAPOPLITEAL LESIONS
Authors: Osamu Iida, Mitsuyoshi Takahara, Tatsuya Shiraki, Yoshimitsu Soga, Yasutaka Yamauchi, Kisuke Hirano, Daizo Kawasaki, Masahiko Fujiwara, Makoto Utsunomiya, Junichi Tazaki, Terutoshi Yamaoka, Yoshiaki Shintani, Nobuhiro Suematsu, Kenji Suzuki, Yusuke Miyashita, Taketsugu Tsuchiya, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2015)
TCT-191 Health-related quality of life, Functional status and Myocardial ischemia in patients with successful chronic total occlusion recanalization
Authors: Ester Bajo, Beatriz Vaquerizo, Sandra Pujadas, Javier Rosello, Antonio Barros, Faustino Miranda-Guardiola, Marcelo Jimenez Kockar, Francesc Carreras, Juan Cinca, Antonio Serra
Journal: Journal of the American College of Cardiology (2014)
P598Deleterious effects of cardiac aldosterone and exercise in type 2 diabetic mice
Authors: L Fazal, E Polidano, R Merval, G Coutance, C Delcayre, JL Samuel
Journal: Cardiovascular Research (2014)

Introduction: Scarcity of microvessels and deregulation of the renin-angiotensin-aldosterone system contribute to the development of heart failure in diabetes. We showed that cardiac aldosteronism inhibits the onset of cardiomyopathy in type 1 diabetic mice by preventing capillary rarefaction (Messaoudi, 2009). Another promising therapeutic approach to prevent diabetic heart disease is exercise training (Ex). Exercise is beneficial in diabetic cardiomyopathy in human and experimentally. Thus, the objective of the study was to determine whether cardiac aldosterone-induced angiogenesis in type 2 diabetes (D) is used to meet the energy demand associated with Ex, and to identify the mechanisms involved. Methods: 3 weeks old mice overexpressing cardiac aldosterone system (AS) and their controls (WT) were made diabetic by enriched fat and sucrose diet. After 4 months of diet, diabetic mice and their controls were subjected to 2 months of Ex on treadmill (3 sessions/week). Results: Cardiac function was not affected by Ex. The Ex led to cardiac hypertrophy in AS-D-Ex mice (+15 % in AS-D-Ex vs AS-D, P<0.01) while it improved the basic parameters of WT-D-Ex vs WT-D (body weight: -15 %, blood glucose: -15%, resistance to insulin:-50%). Interestingly, the Ex revealed a defect in AS mice: the cumulative distance traveled by AS mice, with or without type 2 D was 30% lower than in WT mice (p < 0.01). In addition, a 75% mortality was observed in AS mice (diabetic or not) submitted to the Ex, in contrast to WT mice. These results demonstrate that AS mice, unfit to Ex, developed a pathological hypertrophy. In contrast to the observed baseline responses, the Ex did not phosphorylate and thus did not activated the Akt pathway in AS-D-Ex mice (NS vs AS-D), signing the absence of activation of the physiological pathway of cardiac hypertrophy. Conclusion: These results demonstrate a deleterious effect of cardiac aldosteronism in response to Ex, regardless of diabetic context, thus underlining that the microangiogenesis observed in the AS-D mice prevented neither the inability to Ex nor mortality. This suggests that the proangiogenic effect of cardiac hyperaldosteronism associated with type 2 diabetes is not enough to cope with this overload of cardiac output associated with the physical exercise.
Abstract 5727: B vitamins and reduced risk of lung cancer among 900 cases and 1800 controls from the EPIC cohort study
Authors: Paul J. Brennan, Mattias Johansson, Caroline Relton, Stein Emil Vollset, Oivind Midttun, Ottar Nygard, Per Mange Ueland, Paolo Vineis
Journal: Cancer Research (2010)

Abstract Background: B-vitamins including folate help to ensure DNA integrity and the regulation of gene expression and may be associated with subsequent reduced cancer risk. One previous cohort study among smokers identified a substantial protective effect for vitamin B6 on lung cancer. Methods: The EPIC study population included 385,747 participants from 23 centres in ten countries who completed a dietary questionnaire and provided a blood sample at recruitment between 1992 and 2000. 899 lung cancer cases were identified by 2006, with an average follow-up of 5 years, and matched to 1,770 controls for country, sex, date of birth and time of blood collection. Circulating concentrations were measured for four specific B-vitamins (B2, B6, folate and B12) as well as methionine, homocysteine and cotinine. Results: After adjusting for matching variables and cotinine, a substantial decreasing risk for lung cancer was seen for increasing levels of B6 (relative risk of 4th vs 1st quartile [RR] = 0·44, with 95% confidence interval [CI] 0·33-0·60; p for trend [ptrend]&amp;lt;0·000001), as well as for methionine (RR=0·52, CI 0·39-0·69; ptrend&amp;lt;0·000001). Similar and consistent decreases in risk were observed for never, former and current smokers, indicating that results were not due to a smoking associated artifact. The magnitude of risk was also constant with increasing length of follow-up, indicating the effects were not explained by pre-clinical disease. A decrease in risk was also seen for folate, (RR=0·68, CI 0·51-0·90; ptrend=0·001), although this was apparent only for former and current smokers. When participants were classified by median levels of both methionine and B6, having above median levels of both resulted in a substantial decrease in lung cancer risk overall (RR=0·41, CI 0·31-0·54), as well as separately among never (RR=0·36, CI 0·18-0·71), former (RR=0·51, CI 0·34-0·76), and current smokers (RR=0·42 CI 0·27-0·65). Interpretation: Higher serum levels of both vitamin B6 and methionine were associated with a substantial decrease in lung cancer risk on average 5 years later, indicating that they, or strongly related dietary factors, have an important effect on future lung cancer development. Increased knowledge of protective factors for lung cancer over and above tobacco cessation could make a significant contribution to disease prevention, particularly in former and never smokers. 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 5727.
LONG-TERM STATIN USE FOLLOWING RE-INITIATION AMONG MEDICARE BENEFICIARIES WITH CORONARY HEART DISEASE
Authors: John N. Booth, Lisandro Colantonio, Robert Rosenson, Monika Safford, Ligong Chen, Meredith Kilgore, Todd Brown, Emily Levitan, Benjamin Taylor, Ricardo Dent, Keri Monda, Paul Muntner
Journal: Journal of the American College of Cardiology (2016)
Abstract LB-434: Baseline serum adrenal androgens are prognostic and predictive of overall survival (OS) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC): Results of the COU-AA-301 phase 3 randomized trial
Authors: Charles Ryan, Jinhui Li, Thian Kheoh, Howard I. Scher, Arturo Molina
Journal: Cancer Research (2012)

Abstract Objective In COU-AA-301 the androgen biosynthesis inhibitor abiraterone acetate (AA) significantly increased OS vs placebo (PL) in mCRPC post-docetaxel (HR=0.74; Scher, ASCO 2011). The objective of the current study was to determine the effect of baseline levels of adrenal androgens (testosterone [T], androstenedione [A4], and dehydroepiandrostenedione [DHEA]) on OS in COU-AA-301. Methods COU-AA-301 is a randomized double blind study of AA (1000 mg QD + prednisone [P] 5 mg po BID) vs PL + P. In this post hoc exploratory analysis, the effect of baseline serum androgen levels (T, A4, DHEA) on OS was determined by univariate and multivariate analyses using the Cox proportional hazards regression model. Cut offs for high hormone (HH; above median) and low hormone (LL; below median) levels were used. Pts were stratified by ECOG PS (0-1 vs 2), pain (pain 4-10 [present] vs pain 0-3 [absent]), 1 vs 2 prior chemotherapy regimens, and type of progression (PSA only vs radiographic). Results Higher baseline serum androgens (T, A4, and DHEA) were associated with significantly improved OS, in either univariate or multivariate analysis, adjusting for treatment, other androgens, and other lab parameters (ie, LDH, HGB, ALKP, PSA; all p&amp;lt;0.0001). OS was significantly longer in HH group vs LH group in both AA + P and PL + P arms for T, A4, and DHEA (Table); the longer OS observed with AA + P vs PL + P was observed in both HH and LH groups for T, A4, and DHEA. Conclusions In study COU-AA-301, baseline adrenal androgens were both prognostic and predictive of OS in patients with mCRPC. Pts treated with P alone had longer OS in the HH group vs LH group, suggesting P modulation of the adrenal axis. AA was beneficial in both HH and LH groups, but the effect appeared more pronounced in the HH group. Additional work is underway to further understand the relationship between serum and intratumoral androgens and outcomes. 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 LB-434. doi:1538-7445.AM2012-LB-434
SP0188 Systematic Literature Review: Biological Dmards in Rheumatoid Arthritis
Authors: J. L. Nam
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> A systematic literature review on biological DMARDs for RA was previously undertaken to inform the 2010 EULAR RA management recommendations. This review aims to provide an update on the efficacy of the currently available biological DMARDs from randomised controlled trials (RCTs) and to look at newer biological DMARDs in phase 3 RCTs. <h3>Disclosure of Interest</h3> None Declared
<i>IFI44L</i> promoter methylation as a blood biomarker for systemic lupus erythematosus
Authors: Ming Zhao, Yin Zhou, Bochen Zhu, Mengjie Wan, Tingting Jiang, Qiqun Tan, Yan Liu, Juqing Jiang, Shuaihantian Luo, Yixin Tan, Haijing Wu, Paul Renauer, Maria del Mar Ayala Gutiérrez, Maria Jesús Castillo Palma, Rafaela Ortega Castro, Concepción Fernández-Roldán, Enrique Raya, Raquel Faria, Claudia Carvalho, Marta E Alarcón-Riquelme, Zhongyuan Xiang, Jinwei Chen, Fen Li, Guanghui Ling, Hongjun Zhao, Xiangping Liao, Youkun Lin, Amr H Sawalha, Qianjin Lu
Journal: Annals of the Rheumatic Diseases (2016)

Objective Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker. Methods IFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren's syndrome (pSS) were used for validation. Results Significant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage. Conclusions The methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE.
Headliners: Respiratory Health: Air Pollution Impairs Lung Development in Children
Authors: Jerry Phelps
Journal: Environmental Health Perspectives (2004)

Gauderman WJ, Avol E, Gilliland F, Vora H, Thomas D, Berhane K, McConnell R, Kuenzli N, Lurmann F, Rappaport E, Margolis H, Bates D, Peters J. 2004. The effect of air pollution on lung development from 10 to 18 years of age. N Engl J Med 351(11):1057–1067.

Mounting evidence suggests that exposure to air pollution has long-term effects on lung development in children; reductions in lung function have been observed in studies in Europe and the United States. To further investigate these effects, this NIEHS-supported research team performed a prospective epidemiologic study on 1,759 children from 12 communities in Southern California.

The communities had a wide range of exposures to air pollutants including particulate matter, acid aerosols, ozone, and nitrogen dioxide. The team recruited fourth-graders and performed lung function tests annually for eight years.

Over the eight-year period, decreases in a measurement of lung function known as forced expiratory volume (FEV1) were associated with exposure to nitrogen dioxide, acid aerosols, particulate matter, and elemental carbon. The decreases noted were statistically and clinically significant. For example, the risk of diminished FEV1 was almost five times higher at the highest level of particulate matter exposure than at the lowest level. The magnitude of the effects on development of lung function was comparable to that reported for exposure to maternal smoking.

The authors conclude that these results can be generalized to children living in other parts of the United States that have high air pollution levels. The results indicate that current ambient air pollution levels can have chronic and adverse effects on lung development in children, leading to clinically significant lung function deficits in adulthood. Given the severity of the effects and the importance of lung development as a determinant of morbidity and mortality during adulthood, it is important to continue identifying strategies for reducing air pollution.
Distribution of Abo Blood Groups in Patients with Pernicious Anemia, Gastric Carcinoma and Gastric Carcinoma Associated with Pernicious Anemia
Authors: Lansing C. Hoskins, Helene A. Loux, Anthony Britten, Norman Zamcheck
Journal: New England Journal of Medicine (1965)

THERE is increasing evidence of an association between the ABO blood groups and certain diseases of the upper gastrointestinal tract.1 , 2 This association has been noted with gastric carcinoma and with the gastric atrophy of pernicious anemia, both of which appear to occur more frequently among persons of blood group A than among those of blood group O.As part of studies of the relation between gastric atrophy and gastric carcinoma, we have determined the distribution of ABO blood groups for 158 patients with pernicious anemia, 337 patients with gastric carcinoma and 32 patients with pernicious anemia in whom gastric carcinoma . . .
Abstract 986: Sildenafil potentiates the anticancer activity of paclitaxel in ABCB1-mediated multidrug resistance xenograft model.
Authors: Kamlesh Sodani, Amit K. Tiwari, Chun-ling Dai, Alaa H. Abuznait, Zhi-jie Xiao, Amal Kaddouni, Zhe-Sheng Chen
Journal: Cancer Research (2013)

Abstract The multidrug resistance (MDR) phenotype caused by the overexpression of ATP-binding cassette (ABC) transporters promotes the cellular efflux of a variety of anticancer drugs that may lead to cancer treatment failure. Previous in vitro studies from our group reported sildenafil, a PDE-5 inhibitor, could significantly block the function of ABCB1/P-glycoprotein and reverse ABCB1/P-glycoprotein-mediated MDR. In the current study we investigated the effect of sildenafil on the ABCB1-mediated MDR in vivo. To determine this effect we developed ABCB1-xenograft nude muse model using ABCB1 overexpressing KB-C2 cell line. We found that sildenafil significantly enhanced the chemotherapeutic response of paclitaxel in the ABCB1-xenograft nude mouse model. The combination treatment with sildenafil and paclitaxel attenuated the tumor growth synergistically. In addition, there was no visible toxicity, weight loss or other gross phenotypic changes with combination treatment. The positive effects of sildenafil can be attributed to inhibition of ABCB1-mediated drug efflux. This phenomenon was further supported by increased concentrations of paclitaxel in ABCB1-overexpressing tumors in the combination treatment group compared to paclitaxel alone. In addition, pharmacokinetic analysis showed increase in the plasma paclitaxel concentration in the combination group. These beneficial actions of sildenafil can be considered as viable option for combination therapy with the clinical anticancer drugs that succumb to ABCB1-mediated insensitivity. Citation Format: Kamlesh Sodani, Amit K. Tiwari, Chun-ling Dai, Alaa H. Abuznait, Zhi-jie Xiao, Amal Kaddouni, Zhe-Sheng Chen. Sildenafil potentiates the anticancer activity of paclitaxel in ABCB1-mediated multidrug resistance xenograft model. [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 986. doi:10.1158/1538-7445.AM2013-986