tbuckley/cabot-search huggingface dataset:
Abstract P309: Vulnerabilities to Health Disparities and Statin Use in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: Praful Schroff, Christopher M Gamboa, Raegan W Durant, Asikhame Oikeh, Joshua S Richman, Monika M Safford
Journal: Circulation (2016)

Introduction: Statins reduce the incidence of major cardiovascular disease events, but many individuals do not receive them. The AHRQ National Healthcare Disparities Report identifies several vulnerable populations, but few studies have examined statin use from the perspective of the presence of multiple vulnerabilities in the same individual. Hypothesis: A greater number of vulnerabilities is associated with lower statin use. Methods: This study used data from the REGARDS study, which included 30,239 adults of age 45 and older recruited between 2003 and 2007 from the 48 contiguous US states. Baseline data included a 45-minute telephone interview and an in-home visit. Vulnerabilities included older age, black race, being a woman, rural/small city residence, area level poverty, Southeastern residence, and lack of health insurance. Prevalence ratios were estimated from Poisson models and adjusted for factors influencing health services utilization (education, awareness of hyperlipidemia, medication adherence, cigarette smoking, depressive symptoms, obesity, high-density lipoprotein cholesterol, physical functioning and Adult Treatment Panel III Framingham Risk Group). Results: The study sample included 18,047 individuals of mean age 65.8 years with indications for statin therapy; 41.7% were black, 50.8% were women, 8.7% lived in a rural area/small city, 25.2% lived in areas with &gt;25% of residents living below the Federal poverty line, 55.0% lived in the Southeastern states and 6% did not have health insurance. Older age, being black, being a woman, area level poverty, and health insurance were significantly associated with lower statin use. Statin use decreased as the number of vulnerabilities increased. Conclusions: A greater burden of healthcare disparity vulnerabilities was associated with a graded pattern of lower statin use. Individuals with multiple vulnerabilities have the greatest risk of under treatment and should be targeted for intervention.
Abstract 16802: Efficacy and Safety of Cryoballoon versus Radiofrequency Ablation for Atrial Fibrillation: A Meta-analysis of Randomized Clinical Trials
Authors: Marwan Saad, Ramez Nairooz, Islam Y Elgendy, Amgad Mentias, Akram Y Elgendy, Amr F Barakat, Ahmed Abuzaid, Ahmed N Mahmoud, Asif Sewani, Waddah Maskoun, Sanjeev Saksena
Journal: Circulation (2016)

Background: The comparative efficacy and safety of cryoballoon (CB) ablation vis-a-vis radiofrequency (RF) ablation for pulmonary vein (PV) isolation in atrial fibrillation (AF) is unclear. Objecti...
Abstract 4089: Establishment and long-term in vitro culture of organoids derived from human biliary tract carcinomas
Authors: Yoshimasa Saito, Toshihide Muramatsu, Yuko Sugiyama, Ryoei Uchida, Ryo Furukawa, Nao Yoshikawa, Tomoko Yamaguchi, Yae Kanai, Hidetsugu Saito
Journal: Cancer Research (2018)

Abstract Background Biliary tract carcinomas (BTCs) are epithelial malignancies arising in the region between the intrahepatic bile ducts and the ampulla of Vater at the distal end of the common bile duct. Although patients with inoperable BTCs generally receive a chemotherapy regimen of gemcitabine and cisplatin, the effect of these drugs is limited and the 5-year survival rates of patients are very low. The newly developed 3D culture system known as “organoid culture” allows long-term expansion of stem cells into budding cyst-like structures (organoids) with properties resembling those of the original tissues. The aim of this study is to establish in vitro preclinical models for patients with BTCs using the organoid culture technology. Methods We established organoids using cancer tissues obtained from patients with BTCs. Alterations of genome, gene expression profiles including microRNAs and drug sensitivity were analyzed in BTC organoids. Results We were successful in establishment and long-term in vitro culture of five organoid lines derived from human BTCs including intrahepatic cholangiocarcinoma, gallbladder cancer and neuroendocrine carcinoma of the ampulla of Vater. These BTC organoids can be stably cultured over a year, whereas organoids derived from non-cancer bile duct and gallbladder tissues ceased proliferating after 15 passages or six months. H&amp;E staining and immunohistochemistry of BTC organoids and the primary tissues demonstrated that BTC organoids closely recapitulate the histopathological features of the primary tumors. The tumor suppressor microRNA miR-34a was suppressed in organoids derived from one case of intrahepatic cholangiocarcinoma, and enforced expression of miR-34a markedly suppressed the growth of these organoids with down-regulation of its target oncogenes. We also examined the effect of the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR) on BTC organoids. Treatment with 5-Aza-CdR suppressed the proliferation of all BTC organoids by inducing an anti-viral immune response including activation of interferon-responsive genes. Conclusions Studies using organoids derived from various BTC cases could potentially pave the way for development of precision medicine for patients with BTCs. These preclinical models for refractory cancers may fill the gap between basic cancer research and patients trials and allow personalized cancer therapy. Citation Format: Yoshimasa Saito, Toshihide Muramatsu, Yuko Sugiyama, Ryoei Uchida, Ryo Furukawa, Nao Yoshikawa, Tomoko Yamaguchi, Yae Kanai, Hidetsugu Saito. Establishment and long-term in vitro culture of organoids derived from human biliary tract carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4089.
Abstract 276: Targeting cancer stem cells with chemopreventive agents for breast cancer prevention
Authors: Naing Lin Shan, Jeffrey Yang, Min Ji Bak, Joseph Wahler, Nanjoo Suh
Journal: Cancer Research (2018)

Abstract Breast cancer accounts for one of the most common causes of cancer-related deaths in women. Despite the available treatment modalities to cure breast cancer, therapeutic resistance and recurrence remain major challenges, owing to the culminating evidence of the presence of cancer stem cell subpopulations in breast tumors. The purpose of the study is to identify chemopreventive and dietary compounds that effectively target cancer stem cells to inhibit breast cancer development and progression. The mammosphere culture system has been proven to enrich cancer stem-like cells, and cells from mammospheres are shown to be more tumorigenic in vivo. By culturing mammospheres from breast cancer cell lines, we have shown that 1,25 vitamin D3, a vitamin D3 analog, BXL0124, pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene), tocopherols and triterpenoids (CDDO-Im) decreased the mammosphere forming efficiency (MFE) in a dose-dependent manner. Vitamin D compounds (1,25D3 and BXL0124) decreased the MFE in SUM159, MCF10DCIS and MCF-7 breast cancer cell lines (dose range 1-100 nM). Pterostilbene, a bioactive component of blueberries, effectively decreased the MFE in the MCF-7 cell line. The size of the mammospheres was found to be smaller with increasing concentrations (10-100 μM). Tocopherols significantly decreased estrogen-stimulated MFE in MCF-7 cells (1-10 μM). CDDO-Im, a synthetic triterpenoid derived from natural oleanolic acid, has also been shown to decrease MFE and sphere size in MCF-7 cells (50-100 nM). The effect on the shape of the spheres was also observed, suggesting the differentiation-inducing properties of these compounds. Taken together, we demonstrate that naturally occurring compounds as well as synthetic analogs derived from natural and dietary compounds significantly inhibit sphere forming efficiency and cancer stemness in breast cancer cells. Our study suggests that chemopreventive compounds, 1,25D3, BXL0124, pterostilbene, tocopherols, and CDDO-Im, are agents with the potential to target cancer stem-like cells to prevent breast cancer. Citation Format: Naing Lin Shan, Jeffrey Yang, Min Ji Bak, Joseph Wahler, Nanjoo Suh. Targeting cancer stem cells with chemopreventive agents for breast cancer prevention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 276.
Analysis of Heart-Infiltrating T-Cell Clonotypes in Experimental Autoimmune Myocarditis in Rats
Authors: HaruoHanawa, TakayukiInomata, HirohoSekikawa, ToruAbo, MakotoKodama, TohruIzumi, AkiraShibata
Journal: Circulation Research (1996)

Abstract Experimental autoimmune myocarditis (EAM) resembles the lethal giant cell myocarditis seen in humans, and the recurrent forms lead to dilated cardiomyopathy (DCM). EAM in rats induced by a subcutaneous injection of cardiac myosin has been shown to be a T cell–mediated autoimmune disease. αβ T cells have proved to be important by the observation that antibodies to αβ T-cell receptor (TCR) prevent disease progression. αβ T cells recognize antigenic peptides bound to major histocompatibility (MHC) molecules by αβ TCR, and complementarity determining region 3 (CDR3) is considered the most important region for antigen recognition. To elucidate the nature of this T cell–mediated myocarditis, we analyzed TCR Vβ chains of heart-infiltrating T cells. In the early stage of EAM, none of 22 TCR Vβ chain transcripts seemed to be dominant by reverse transcription–polymerase chain reaction analysis of total RNA and flow cytometric analysis. On the other hand, single-strand conformation polymorphism analysis of ...
Transapical Beating-Heart Mitral Valve Repair With an Expanded Polytetrafluoroethylene Cordal Implantation Device
Authors: James S. Gammie, Peter Wilson, Krzysztof Bartus, Andrzej Gackowski, Judy Hung, Michael N. D’Ambra, Piotr Kolsut, Gregory J. Bittle, Piotr Szymanski, Jerzy Sadowski, Boguslaw Kapelak, Agata Bilewska, Mariusz Kusmierczyk, Mehrdad Ghoreishi
Journal: Circulation (2016)

Background: Degenerative mitral valve (MV) disease is a common cause of severe mitral regurgitation (MR) and accounts for the majority of MV operations. Conventional MV surgery requires cardiopulmonary bypass, aortic cross-clamping, cardioplegia, and a thoracotomy or sternotomy and, therefore, is associated with significant disability, risks, and unpredictable rates of MV repair. Transesophageal echocardiography–guided beating-heart MV repair with expanded polytetrafluoroethylene cordal insertion has the potential to significantly reduce surgical morbidity. We report the first-in-human clinical experience with a novel preformed expanded polytetrafluoroethylene knot implantation device (Harpoon TSD-5) designed to treat degenerative MR. Methods: Through a small left thoracotomy, the device was inserted into the heart and guided by transesophageal echocardiography to the ventricular surface of the prolapsed leaflet. Multiple expanded polytetrafluoroethylene cords were anchored in the leaflet and then adjusted to the correct length to restore MV leaflet coaptation and secured at the epicardium. Results: Eleven patients with posterior leaflet prolapse and severe MR, with mean±SD age of 65±13 years and mean ejection fraction of 69±7%, were treated with 100% procedural success. Immediate postprocedural mean MR grade was trace. At 1 month, the mean MR grade was mild with significant decreases in end-diastolic volume (139 to 107 mL; P =0.03) and left atrial volume (118 to 85 mL; P =0.04). Conclusions: A novel device used for beating-heart image-guided MV repair demonstrates a significant reduction in MR with favorable left ventricular and left atrial reverse remodeling. This approach has the potential to decrease invasiveness and surgical morbidity. Further follow-up is necessary to assess long-term efficacy. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT02432196.
Clinical Manifestations of the Unperforated Aortic Sinus Aneurysm
Authors: Israelsteinberg, Nathanielfinby
Journal: Circulation (1956)

There are no diagnostic features for the recognition of unperforated aortic sinus aneurysms except for a grade 3 to 4 cardiac murmur. Linear or massive calcifications in the intracardiac portion of the root of the aorta continuous with the linear calcifications of the ascending aorta sometimes occurs in syphilitic aortic sinus aneurysms. Accordingly, a high index of suspicion and angiocardiography are advocated in order to establish the diagnosis during life. Surgical repair of a localized congenital aortic sinus aneurysm through the right atrial approach seems feasible if there are no serious complicating aortic or cardiac lesions. The diffuse unruptured aneurysmal congenital and syphilitic aortic sinus aneurysms are better left alone. If rupture occurs, surgical repair, even though heroic, should be attempted.
A Population-Based Study of the Bidirectional Association Between Obstructive Sleep Apnea and Type 2 Diabetes in Three Prospective U.S. Cohorts
Authors: Tianyi Huang, Brian M. Lin, Meir J. Stampfer, Shelley S. Tworoger, Frank B. Hu, Susan Redline
Journal: Diabetes Care (2018)

OBJECTIVE Multiple lines of evidence support a complex relationship between obstructive sleep apnea (OSA) and diabetes. However, no population-based study has evaluated the potential bidirectional association between these two highly prevalent disorders. RESEARCH DESIGN AND METHODS We followed 146,519 participants from the Nurses' Health Study (NHS; 2002–2012), Nurses’ Health Study II (NHSII; 1995–2013), and Health Professionals Follow-up Study (HPFS; 1996–2012) who were free of diabetes, cardiovascular disease, and cancer at baseline. Cox proportional hazards models were used to estimate hazard ratios (HRs) for developing diabetes according to OSA status. In parallel, we used similar approaches to estimate risk of developing OSA according to diabetes status among 151,194 participants free of OSA, cardiovascular disease, and cancer at baseline. In all three cohorts, diagnoses of diabetes and OSA were identified by validated self-reports. RESULTS Similar results were observed across the three cohorts. In the pooled analysis, 9,029 incident diabetes cases were identified during follow-up. After accounting for potential confounders, the HR (95% CI) for diabetes was 2.06 (1.86, 2.28) comparing those with versus without OSA. The association was attenuated but remained statistically significant after further adjusting for waist circumference and BMI (HR 1.37 [95% CI 1.24, 1.53]), with the highest diabetes risk observed for OSA concomitant with sleepiness (1.78 [1.13, 2.82]). In the second analysis, we documented 9,364 incident OSA cases during follow-up. Compared with those without diabetes, the multivariable HR (95% CI) for OSA was 1.53 (1.32, 1.77) in individuals with diabetes. Adjustment for BMI and waist circumference attenuated the association (1.08 [1.00, 1.16]); however, an increased risk was observed among those with diabetes who used insulin compared with those without diabetes (1.43 [1.11, 1.83]), particularly among women (1.60 [1.34, 1.89]). CONCLUSIONS OSA is independently associated with an increased risk of diabetes, whereas insulin-treated diabetes is independently associated with a higher risk of OSA, particularly in women. Clinical awareness of this bidirectional association may improve prevention and treatment of both diseases. Future research aimed at elucidating the mechanisms that underlie each association may identify novel intervention targets.
Varicose Veins and Deep Venous Thrombosis—Reply
Authors: Shyue-Luen Chang, Pei-Chun Chen
Journal: JAMA (2018)

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Abstract IA21: Small cell carcinomas of the ovary: Strengths and weaknesses
Authors: Douglas A. Levine
Journal: Clinical Cancer Research (2018)

Abstract Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and very aggressive malignancy that occurs mostly in young women. We and others previously described SCCOHT as a SMARCA4-mutated monogenic disease and unraveled other important molecular features, including apparent universal loss of SMARCA2 through epigenetic silencing. Typically, SMARCA4 and SMARCA2 are redundant catalytic subunits of the SWI/SNF complex and loss of either will result in the overexpression of the other. However, SCCOHT is unique in having concomitant loss of both subunits with restoration of either leading to tumor suppression. Nonetheless, despite these advances in understanding the biology of SCCOHT, there are few effective treatment options and survival rates remain poor. In this presentation we will discuss the role of SMARCA4 and SMARCA2 on tumor growth. We will also present therapeutic options to manipulate SWI/SNF complex dependencies. We will present case histories of patients who have had positive responses to targeted therapies. We will also discuss responses to anti-PD1 immunotherapy and characterize the immune landscape of SCCOHT tumors using quantitative immunofluorescence and gene expression profiling. Unexpectedly for a low mutation burden cancer, the majority of the tumors demonstrated PD-L1 expression with strong associated T-cell infiltration. PD-L1 expression can be detected in both tumor and stromal cells, with macrophages being the most abundant PD-L1 positive cells in some tumors. These findings suggest that although SCCOHT are low-mutational-burden tumors, their immunogenic microenvironment that resembles the landscape of tumors that respond well to treatment with PD-1/PD-L1 blockade. Citation Format: Douglas A. Levine. Small cell carcinomas of the ovary: Strengths and weaknesses. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA21.
Abstract 3085: Epithelial S100A2 reduced upper aerodigestive track carcinogenesis by immunomodulation
Authors: Li-Wha Wu
Journal: Cancer Research (2018)

Abstract Upper aerodigestive track cancer (UATC) including oral and esophageal cancer is the 3rd leading cause of cancer death in the world. Most of these patients demonstrate compromised immunity systems. Myeloid-derived suppressor cells (MDSCs), a population of cells exerting immunosuppressive effects, can sustain cancer progression by providing a pro-tumor microenvironment through the enhancement of T-cell suppressive factors like arginase 1 (ARG1). MDSCs can subsequently facilitate the development of immunosuppressive regulatory T cells (Tregs). Tumor-associated macrophages (TAMs) produce multiple inflammation modulators and are other key players in tumor microenvironment and divided into M1 and M2 phenotypes with specific expression of different cytokines in each type. Several S100 proteins are recently shown to participate in tumor promotion or suppression through both autocrine and least known receptor-mediated paracrine release. RAGE and TLR4, frequently expressed on immune cells, are two known receptors for S100 proteins. Among many S100 proteins, we previously showed a tumor suppressor role of S100A2 in oral cancer. Whether S100A2 functions as a tumor suppressor in mice and plays any role in regulating these immune cell populations during upper aerodigestive track carcinogenesis remains elusive. Due to lack of S100A2 expression in mice, epithelial-specific human S100A2 transgenic mice and their wildtype littermates were used for tumor induction in upper areodigestive track by the co-treatment of 4NQO and arecoline. Epithelial S100A2 significantly repressed tumor formation in esophagus. To understand the involvement of immune cell recruitment in these mice, flow cytometry and qRT-PCR analyses were used. Among the key molecules associated with MDSCs, Tregs and TAMs, S100A2 preferentially induced tumor macrophage polarization to M1 phenotype with a marginal decrease of Tregs recruitment at 7 month post tumor induction. Together, epithelial S100A2 exerts anti-tumor effect in part through differential impact on immune cell recruitment although more studies are needed to underscore the action mechanism. Citation Format: Li-Wha Wu. Epithelial S100A2 reduced upper aerodigestive track carcinogenesis by immunomodulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3085.