tbuckley/cabot-search huggingface dataset:
Abstract IA01: PARP inhibitors as single agents and in combinations for ovarian cancer: What lies ahead?
Authors: Ursula A. Matulonis
Journal: Clinical Cancer Research (2018)

Abstract Poly (ADP ribose) polymerase (PARP) inhibitors are an exciting and promising new class of anticancer drugs. Initial clinical trials of PARP inhibitors began over a decade ago following the discovery that PARP inhibitors in vitro had heightened anticancer activity in BRCA mutated cancer cells compared to BRCA wild-type cells. PARP inhibitor clinical development has taken several strategies, including single-agent and combination testing. Single-agent PARP inhibitors have been used as either primary treatment of recurrent ovarian cancer or as maintenance treatment following anticancer response after platinum-based chemotherapy. Three PARP inhibitors are now FDA approved for recurrent ovarian cancer, all as single agents: 1) olaparib for patients with recurrent germline BRCA mutated ovarian cancer who have received 3 or more prior lines of chemotherapy and also as maintenance therapy post-platinum therapy for patients with platinum sensitive recurrence who are in response to platinum-based chemotherapy and regardless of BRCA or tumor HR status; 2) rucaparib for patients with BRCA mutated ovarian cancer (either deleterious tumor or germline mutation) who have received at least 2 prior lines of chemotherapy; and 3) niraparib for platinum-sensitive recurrent ovarian cancer patients as maintenance therapy who are in response to platinum-based chemotherapy and regardless of BRCA or tumor HR status. Because of the myelosuppression observed with PARP inhibitors, combining these agents with chemotherapy has been difficult and has required lowering the doses of either the PARP inhibitor and/or the chemotherapy agents and often abbreviating the treatment schedule; several negative phase III studies have been reported. Combining PARP inhibitors with biologic agents is another strategy currently being tested in clinical trials and one that avoids overlapping toxicities. The combination of the PARP inhibitor olaparib and the antivascular endothelial growth factor receptor agent cediranib has shown promising phase II results against olaparib alone, especially in BRCA wild-type ovarian cancer. These results have led to phase III studies comparing the olaparib and cediranib combination to standard therapies (NCT02502266 and NCT02446600). Other studies are under way testing PARP inhibitors with other biologic agents such as immunotherapy agents and other targeted agents such as ATR inhibitors, PI3 kinase inhibitors, and heat shock protein 90 inhibitors. Citation Format: Ursula A. Matulonis. PARP inhibitors as single agents and in combinations for ovarian cancer: What lies ahead? [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 IA01.
Abstract LB-328: Influence of radiation on the evolution of orthotopic xenografts initiated from glioblastoma stem-like cells
Authors: Joseph H. McAbee, Barbara H. Rath, Kevin A. Camphausen, Philip J. Tofilon
Journal: Cancer Research (2018)

Abstract Glioblastoma (GBM) is the most common and malignant primary adult brain cancer with a median survival of 15 months despite treatment with surgical resection followed by chemo-radiotherapy. By examining changes that occur following irradiation of brain tumor xenografts initiated from glioma stem-like cells (GSCs), this study seeks to better understand the impact of radiotherapy on GBM evolution. Therefore, we intracranially implanted CD133+ NSC11 cells, a well-documented GSC line, into nude mice. After 21 days, bioluminescence imaging was performed to confirm the presence of tumor prior to randomization into control and radiation therapy groups (3x5Gy). Following treatment, brain samples were collected at various time points out to morbidity to investigate changes in tumor morphology and histology. Further, tumors from morbid mice (control and 3x5Gy) were collected for viral integration site analysis (VISA). Initial survival analysis demonstrated a significant survival advantage for mice undergoing radiation therapy (+34.2 days) compared to controls. On gross examination of morphology at morbidity, brains bearing irradiated tumors contained tumor tissue that was softer, more adherent to the skull, and more likely to efface olfactory bulb(s) than control tumor brains. H&amp;E staining demonstrated that irradiated tumors were more dense/compact and did not grow as infiltrative as tumors from control mice. These histological changes were followed up with VISA to determine whether certain clones were responsible for this difference. VISA revealed that irradiated tumors were heterogeneously enriched for clones with different integration sites when compared to control tumors and in vitro tumor lines. Heat map analysis of the number of clones present in each sample demonstrated that control tumors harbor fewer clones than in vitro lines and that radiated tumors harbor the fewest clones of all. Initial data also revealed that various doses of radiation (3x5Gy or 10x5Gy) can provide very similar selection pressures to limit the number of clones. Our results demonstrate that radiation, a treatment component for almost all glioblastoma patients, can have wide-ranging effects on the evolution of this dynamic tumor. In particular, the pressures imposed by radiation treatment seem to lead to the selection of a reduced number of clones. This selection may have future implications for tumor evolution and the treatment of recurrent GBM. Citation Format: Joseph H. McAbee, Barbara H. Rath, Kevin A. Camphausen, Philip J. Tofilon. Influence of radiation on the evolution of orthotopic xenografts initiated from glioblastoma stem-like cells [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 LB-328.
Abstract 133: Synergistic effect between natural killer cells and anysomycin against hepatocellular carcinoma cells
Authors: Chang Hoon Lee, Miok Kim, Kyung Won Lee
Journal: Cancer Research (2018)

Abstract Although advances in the clinical management of hepatocellular carcinoma (HCC) have been made, HCC is the second leading cause of cancer-related death worldwide. Currently, there are limited treatment options for advanced HCC. Therefore, novel treatment strategies for HCC are required. Here, we described a promising anti-tumor effect of anisomycin, which not only had direct killing effects but also enhanced a natural killer cell-mediated immunotherapeutic effect in HCC. To better elucidate the anti-tumor mechanisms of anisomycin, we performed a genome-scale analysis of gene expression profiles. We found that anisomycin treatment of HCC differentially regulated a broad range of immune regulation-associated genes; among them, we found that CD58, which was significantly increased on anisomycin treated HCC cells was one of the critical components for natural killer cell-mediated immunotherapeutic effect enhanced by anisomycin. Notably, this is the first report for synergistic effect of anisomycin in combination with NK cell therapy as a potential therapeutic option for HCC. Citation Format: Chang Hoon Lee, Miok Kim, Kyung Won Lee. Synergistic effect between natural killer cells and anysomycin against hepatocellular carcinoma cells [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 133.
Myocarditis in Acute Infectious Diseases
Authors: Irvingfine, Henrybrainerd, Mauricesokolow
Journal: Circulation (1950)

Serial clinical and electrocardiographic studies were carried out on 84 patients suffering from a variety of acute infectious diseases. About one-third were found to have myocarditis on the basis of abnormal electrocardiograms. Abnormal physical findings were usually present. Evidence of congestive heart failure was uncommon. A group of patients subjected to artificial fever therapy did not manifest similar abnormalities.
Role of Afadin in Vascular Endothelial Growth Factor– and Sphingosine 1-Phosphate–Induced Angiogenesis
Authors: HidetoTawa, YoshiyukiRikitake, MotonoriTakahashi, HisayukiAmano, MuneakiMiyata, SeimiSatomi-Kobayashi, MitsuoKinugasa, YuichiNagamatsu, TakashiMajima, HisakazuOgita, JunMiyoshi, Ken-ichiHirata, YoshimiTakai
Journal: Circulation Research (2010)

Rationale: Angiogenesis contributes to physiological and pathological conditions, including atherosclerosis. The Rap1 small G protein regulates vascular integrity and angiogenesis. However, little is known about the effectors of Rap1 involved in angiogenesis. It is not known whether afadin, an adherens junction protein that connects immunoglobulin-like adhesion molecule nectins to the actin cytoskeleton and binds activated Rap1, plays a role in angiogenesis. Objective: We investigated the role of endothelial afadin in angiogenesis and attempted to clarify the underlying molecular mechanism. Methods and Results: Treatment of human umbilical vein endothelial cells (HUVECs) with vascular endothelial growth factor (VEGF) and sphingosine 1-phosphate (S1P) induced the activation of Rap1. Activated Rap1 regulated intracellular localization of afadin. Knockdown of Rap1 or afadin by small interfering RNA inhibited the VEGF- and S1P-induced capillary-like network formation, migration, and proliferation, and increas...
Development and characterization of DNAzyme candidates demonstrating significant efficiency against human rhinoviruses
Authors: Daniel P. Potaczek, Sebastian D. Unger, Nan Zhang, Styliani Taka, Sven Michel, Nesibe Akdağ, Feng Lan, Markus Helfer, Christoph Hudemann, Markus Eickmann, Chrysanthi Skevaki, Spyridon Megremis, Anne Sadewasser, Bilal Alashkar Alhamwe, Fahd Alhamdan, Mübeccel Akdis, Michael R. Edwards, Sebastian L. Johnston, Cezmi A. Akdis, Stephan Becker, Claus Bachert, Nikolaos G. Papadopoulos, Holger Garn, Harald Renz
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 17088: Permanence of Pulmonary Vein Isolation Using Cryoballoon Observed in Repeat Left Atrial Ablation
Authors: AlbertChiu, MuhanadAl-Zubaidi, WilberSu
Journal: Circulation (2014)

Background: Cryoballoon ablation using Arctic Front Advance (AFA) (Medtronic, Minneapolis, MN) has been used for the treatment of atrial fibrillation (AF). Permanence of pulmonary vein isolation (PVI) has not been established, particularly correlating to reduced dosing strategies and to time-to-isolation during PVI. Methods: A single center retrospective chart review of 644 patients who had undergone prior AF ablation using AFA was examined (195 paroxysmal, 335 persistent, and 114 long-standing persistent). Dosing of 3 minutes and repeat ablation at 2 minutes were utilized. In addition, termination with temperature <-55 C were utilized to minimize collateral injury. 73 of 644 patients underwent repeat ablation, where previous procedural characteristics and the status of PVI at the time of repeat ablation were analyzed. Results: 73 of 644 patients (11.3%) underwent repeat ablation for left atrial arrhythmias (6 paroxysmal, 28 persistent, 39 long-standing persistent) with time to repeat ablation 1.5 month t...
Abstract 128: More Effective Chest Compression and Less Rescuer Fatigue in Cardiopulmonary Resuscitation with Leg-Foot Compression with a Footstool
Authors: TakejiSaitoh, MisakiOkada, HiroshiSatoh, ToshiyaAkai, ToshiakiMochizuki, HironaoHozumi, YoshiakiTakahashi, MasashiNozawa, HideharuHayashi, AtsutoYoshino
Journal: Circulation (2014)

Background: Conventional hands-on chest compression in cardiopulmonary resuscitation (CPR) is often inadequate because of rescuer fatigue. This study aimed to investigate the potential of a novel method of CPR by leg-foot compression with a footstool in terms of the efficacy in chest compression and rescuer fatigue. Methods: We prospectively enrolled 21 medical workers competent in basic life support, and measured their height, weight, body surface area, and sole size. They performed CPR to a manikin for 2 minutes by conventional hands-on compression (HO), leg-foot compression (LF1), and leg-foot compression with a footstool (LF2). We analyzed the compression depth in the manikin, changes in the rescuer’s vital signs, and the modified Borg scale scores after the trials. Results: The prevalence of compression depth equal or ≧ 5 cm was larger in LF2 (median, inter-quartile range: 93%, 81-100%) than in HO (9%, 0-57%; p < 0.01) and LF1 (28%, 11-47%; p < 0.01). The increase in heart rate and modified Borg scal...
Patient factors and satisfaction in the choice of contralateral prophylactic mastectomy.
Authors: Amanda Kathleen Arrington, Karin London, Steven L. Chen, Courtney Vito, John H Yim, Rebecca A. Nelson, Laura Kruper
Journal: Journal of Clinical Oncology (2012)

1117 Background: The percentage of women undergoing contralateral prophylactic mastectomy (CPM) has more than doubled in recent years. The underlying reasons patients choose CPM have not been fully evaluated. Our objective was to survey patients who have undergone a unilateral mastectomy with or without CPM to identify reasons surrounding their decisions. Methods: After obtaining IRB approval, a 30-question cross-sectional validated survey was mailed to 691 patients who underwent mastectomy from 1972 to 2011 and are receiving treatment or surveillance at City of Hope. The questionnaire queried the factors behind the choice of surgery for each patient. Demographic questions were included and patient charts were also reviewed. Results: The overall response rate was 53% (N=368). Patients were classified into those who underwent mastectomy with CPM (N=139, 38%) and those who underwent mastectomy without CPM (no-CPM) (N=229, 62%). Of returned surveys, the median age was 50; 24% of patients reported a family history of breast cancer (42% CPM vs. 13% no-CPM, p&lt;0.0001) and 80% of patients had education beyond the high school level (87% CPM vs. 77% no-CPM, p=0.013). PM patients reported being “very concerned” about breast cancer more often than no-CPM patients (46% vs. 34%, p=0.033).The primary reasons for CPM were: concern of recurrence (55%), cosmetic symmetry (27%), physician recommendation (17%), and unclear pre-operative imaging (9%). When questioned about regrets, the top response was decreased sensation (26%). Although 81% of CPM patients were “very satisfied” with their decision, 32% of no-CPM patients reported the same level of satisfaction with their decision (p&lt;0.0001). For no-CPM patients, the primary reasons for the choice of no-CPM was physician advice and “monitoring is sufficient”; with 18% of the responders still considering a CPM. Conclusions: Patients’ perceived risk of contralateral breast cancer is the primary reason for CPM. CPM patients tend to be more satisfied with their decision compared to no-CPM patients. This may be related to the active decision-making thought processes and education necessary to choose CPM. Further patient education is warranted to minimize the risk of regret in making this decision.
Abstract 10937: Coronary Characteristic in Patients With Impaired Glucose Tolerance
Authors: Keishi Suzuki, Hitoshi Takano, Atsushi Tanita, Hideto Sangen, Yuuki Nakamura, Keisuke Inui, Yoshiaki Kubota, Rie Aoyama, Shunichi Nakamura, Shuhei Tara, Koji Murai, Yuukichi Tokita, Kuniya Asai, Wataru Shimizu
Journal: Circulation (2015)

Background: Impaired glucose tolerance (IGT) patients are known to have a higher risk of cardiovascular events and their prognosis is reported to be poor. We, therefore, aimed to compare the complexity and vulnerability of coronary artery disease (CAD) among normal glucose tolerance (NGT), IGT and diabetes mellitus (DM). Methods: 232 patients (66.4 ± 12.6 years, 201 male) who received percutaneous coronary intervention for coronary artery disease were enrolled in the present study. All of the patients except those already given the diagnosis of DM underwent 75g oral glucose tolerance test (OGTT). The study cohorts were divided into 3 groups; DM (n=118), IGT (n=67), and NGT (n=47). IGT was defined as 2 hour post-load plasma glucose ≥140mg/dl during the OGTT. The lesion complexity was expressed as SYNTAX score. The vulnerability of coronary plaque was determined by optical coherence tomography (OCT). Results: Glycated hemoglobin (HbA1c) level was significantly higher in DM group (6.7±1.3%) than IGT (5.8±0.3%, P&lt;0.01) or NGT group (5.6±0.3%, P&lt;0.01). The SYNTAX score in IGT group was equivalent to that in DM group (12.7±8.1 vs.11.8±7.8, P = 0.61), and significantly greater than NGT group (10.2±5.8, P&lt;0.05). OCT identified 137 non-target residual plaques in 101 patients. Out of those plaques, 72 plaques contain lipid core (16, 29, and 27 in NGT, IGT and DM groups, respectively). The size of lipid core expressed as mean angles of lipid arc was significantly greater in IGT and DM groups than NGT group (162.0±58.7°, 171.4±59.3° and 130.9±37.7°, respectively, P&lt;0.05). Fibrous cap covering the lipid core in IGT group was equivalent to that in DM group (0.08±0.03mm vs. 0.09±0.03mm, P=0.10), and significantly thinner than NGT group (0.11±0.05mm, P&lt;0.05). Conclusions: The lesion complexity and plaque vulnerability of IGT patients are not inferior to those of DM patients and significantly greater than NTG patients.
Abstract 20162: Comparision of Procedural and 30 Day Outcomes of Roataional vs Orbital Atherectomy in Severely Calcified Coronary Lesions
Authors: AnithaRajamanickam, UsmanBaber, MelissaAquino, SwathiRoy, AnnapoornaKini, SaminSharma
Journal: Circulation (2014)

Introduction: The percutaneous treatment of heavily calcified coronary lesions remains suboptimal and often requires debulking with Rotational Atherectomy (RA) which is often underutilized due to a steep learning curve. Although a novel approach using Orbital Atherectomy (OA) has been introduced, which has an easier set-up and easier learning curve, a comparative assessment of both techniques in real world cohort has not been performed METHODS: Retrospective analysis of our prospectively collected database between October 2013 to May 2014 for patients undergoing atherectomy in heavily calcified lesions at our center retrieved 105 OA and 196 RA procedures RESULTS: There were no significant differences in patient demographics.The maximal stent diameter was significantly larger in OA vs RA (3.41 mm2 vs 3.28 mm2 , p=0.02).There was a trend towards RA showing better Procedural success defined as successful stent deployment with TIMI 3 flow ( 95.9% vs 90.5%, p = 0.06) and Clinical Success which is procedural su...
Smooth Muscle α-Actin Is a Direct Target of Notch/CSL
Authors: MichelaNoseda, YangXinFu, KyleNiessen, FredWong, LindaChang, GraemeMcLean, AlyKarsan
Journal: Circulation Research (2006)

Intercellular signaling mediated by Notch receptors is essential for proper cardiovascular development and homeostasis. Notch regulates cell fate decisions that affect proliferation, survival, and differentiation of endothelial and smooth muscle cells. It has been reported that Jagged1–Notch interactions may participate in endocardial cushion formation by inducing endothelial-to-mesenchymal transformation. Here, we show that Notch directly regulates expression of the mesenchymal and smooth muscle cell marker smooth muscle α-actin (SMA) in endothelial and vascular smooth muscle cells via activation of its major effector, CSL. Notch/CSL activation induces SMA expression during endothelial-to-mesenchymal transformation, and Notch activation is required for expression of SMA in vascular smooth muscle cells. CSL directly binds a conserved cis element in the SMA promoter, and this consensus sequence is required for Notch-mediated SMA induction. This is the first evidence of the requirement for Notch activation ...
Synergistic Neovascularization by Mixed Transplantation of Early Endothelial Progenitor Cells and Late Outgrowth Endothelial Cells
Authors: Chang-HwanYoon, JinHur, Kyung-WooPark, Ji-HyunKim, Choon-SooLee, Il-YoungOh, Tae-YounKim, Hyun-JaiCho, Hyun-JaeKang, In-HoChae, Han-KwangYang, Byung-HeeOh, Young-BaePark, Hyo-SooKim
Journal: Circulation (2005)

Background— Two types of cells are cultured from the human peripheral blood, early endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs), as previously reported. Here, we further characterize these cells, especially with respect to their different origins and functions both in vitro and in vivo. We also investigated whether the combination of these different cell types shows synergism during neovascularization. Methods and Results— Early EPCs were heterogeneously made up of both CD14+ monocyte-derived cells, which secrete cytokines, and CD14−-derived cells, which contain high levels of CD34+KDR+ cells. OECs were cultured almost exclusively from CD14− cells, not CD14+ cells, and were distinct from mature endothelial cells in terms of proliferation potential, KDR+ expression level, and telomerase activity. A portion of cells from CD14− cells and early EPCs produced rapidly proliferating, capillary-forming cells in both the Matrigel plug and the ischemic hind limb similar to OECs. Early ...
Abstract 1365: NR1D1 enhances reactive oxygen species-induced DNA damage by inhibition of PARP1
Authors: Na-Lee Ka, Tae-Young Na, Mi-Ock Lee
Journal: Cancer Research (2018)

Abstract Breast cancer is the most commonly diagnosed cancer in women worldwide. Cancer cells produce higher levels of intracellular reactive oxygen species (ROS) than their normal counterparts, because of their accelerated metabolism, mitochondrial dysfunction, and antioxidant deficit. The oxidative stress in cancer cells may provide clinical benefits, which can be associated with a better response to anticancer therapies. Therefore, identifying the regulatory pathway of oxidative stress in cancer cells is important in the development of therapeutic targets that enhance sensitivity to ROS-generating anticancer therapies. In this study, we identified that nuclear receptor subfamily 1, group D, member 1 (NR1D1; Rev-erbα) inhibited DNA repair of ROS-induced DNA damage in breast cancer cells. NR1D1 interacted with poly(ADP-ribose) polymerase 1 (PARP1) and subsequently inhibited catalytic activity of PARP1. NR1D1 enhanced accumulation of oxidative DNA damage, which increased sensitivity of breast cancer cells to the ROS-induced cell death. Our findings suggest that NR1D1 may provide better therapeutic options for breast cancer treatment, especially in those patients treated with ROS-inducing chemotherapeutic agents. Citation Format: Na-Lee Ka, Tae-Young Na, Mi-Ock Lee. NR1D1 enhances reactive oxygen species-induced DNA damage by inhibition of PARP1 [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 1365.
Abstract 18591: Relationship Between Gut Microbiota, Inflammation and Congestion Among Advanced Heart Failure Patients
Authors: Ryan T Demmer, Pauline N Trinh, Amelia M Zuver, Duygu Onat, Nasrin Akter, Eugene A Royzman, Joseph K Nwokocha, Autumn Clemons, Francesco Castagna, Alberto Pinsino, Arthur R Garan, Veli K Topkara, Danielle L Brunjes, Koji Takeda, Hiroo Takayama, Yoshifumi Naka, Maryjane A Farr, Anne-Catrin Uhlemann, Paolo C Colombo, Melana Yuzefpolskaya
Journal: Circulation (2017)

Introduction: Circulating biomarkers of congestion and inflammation correlate with poor clinical outcomes in heart failure (HF). Splanchnic venous congestion may alter intestinal barrier function a...