tbuckley/cabot-search huggingface dataset:
Papillary Muscle Perfusion Pattern
Authors: PaoloVoci, FedericoBilotta, QuintilioCaretta, CorradoMercanti, BenedettoMarino
Journal: Circulation (1995)

Background The pathogenesis of posterior papillary muscle dysfunction is poorly understood. We hypothesized that papillary muscle perfusion pattern may explain the higher prevalence of posterior papillary muscle dysfunction after myocardial infarction. Methods and Results Twenty patients were monitored by transesophageal echocardiography during coronary surgery. Superselective coronary graft injections of 0.2 to 0.5 mL of sonicated albumin microbubbles were performed to assess graft patency and papillary muscle perfusion. Thirty-five graft injections were analyzed: 13 in the right coronary artery, 15 in an obtuse marginal branch, 1 in the left anterior descending coronary artery, and 6 in the first diagonal branch. The posterior papillary muscle was opacified in 16 patients, 11 from the right coronary artery and 5 from one obtuse marginal branch. In 10 of 16 patients (63%), the papillary muscle was perfused by one vessel, while in 6 of 16 (37%), it was perfused by two vessels. The anterior papillary muscl...
Impact of Percutaneous Device Implantation for Closure of Patent Foramen Ovale on Valve Insufficiencies
Authors: JochenWöhrle, MatthiasKochs, JochenSpiess, ThorstenNusser, VinzenzHombach, NicoMerkle
Journal: Circulation (2009)

Background— In patients with percutaneous device implantation for closure of patent foramen ovale (PFO), a 10% incidence of new or worsened aortic regurgitation within 12 months has been reported with echocardiography. Cardiac magnetic resonance imaging is a powerful noninvasive tool to quantify volume and fraction of valve insufficiencies. We studied the acute and long-term impact of percutaneous device implantation for PFO closure on valve insufficiencies in cardiac magnetic resonance imaging. Methods and Results— Sequential cardiac magnetic resonance imaging studies were performed in 102 patients with cryptogenic ischemic events. Cardiac magnetic resonance imaging was performed before PFO closure, the day after device implantation, and at 12 months of follow-up. There was no difference in volumetric and hemodynamic parameters before PFO closure compared with 12 months of follow-up. With a cutoff for relevant regurgitation fraction of 5%, there were no statistically significant differences in regurgitat...
Abstract 2059: Alcohol enhances estrogen-responsive breast cancer neovascularization
Authors: Natalie C. Cruz, Rachana Maniyar, Robert Suriano
Journal: Cancer Research (2018)

Abstract The pleiotropic effects of estrogen in breast cancer development have been observed at both the initiation and progression phases. Interestingly, alcohol, as a dietary component, has been observed to possess estrogenic activity, but the synergistic interaction between alcohol and estrogen and its cellular targets remains undefined. Our previous study identified neovascularization as a cellular target of estrogen that was mediated by the mobilization of bone marrow-derived endothelial progenitor cells (BM-EPCs) and their subsequent incorporation within the tumor mass. The present study was undertaken to define the synergistic interaction between estrogen and alcohol using a cell culture model. To examine the effects of both estrogen and alcohol on breast cancer progression, we developed an in vitro model using the murine mammary tumor cell line, TG1-1, and the murine endothelial cell line, SVEC4-10. Neovascularization was assayed by the tubulogenesis and scratch wound assays as well as quantitating the expression of various provasculogenic markers. Conditioned media, generated by culturing the murine mammary cancer cell line, TG1-1, in estrogen and ethanol, was observed to enhance tubule formation and migration of the murine endothelial cell line, SVEC4-10. In addition, the TG1-1 conditioned media enhanced the prosurvival MAP kinase-signaling pathway in SVEC4-10 cells. Presumably, the observed enhancement of both endothelial cell tubulogenesis and migration is in part attributed to provasculogenic proteins secreted by TG1-1 cells. In order to address this, Western blot analysis using TG1-1 cell lysates indicated an increase in VEGF, MMP-9, and eNOS expression in presence of alcohol and estrogen. As a whole, our data suggest that both estrogen and alcohol function to enhance expression of key provasculogenic molecules in breast cancer cells, which in turn modulates the morphologic, migratory, and survival properties of endothelial cells. Citation Format: Natalie C. Cruz, Rachana Maniyar, Robert Suriano. Alcohol enhances estrogen-responsive breast cancer neovascularization [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 2059.
Abstract 16924: Adherence and Persistence to Statin Therapy in a Veteran Population
Authors: KendraMorotti, JulioLopez, MichaelHarvey, VanessaVaupel, ArthurSwislocki, DavidSiegel
Journal: Circulation (2014)

Introduction: A relative cardiovascular risk reduction of 25-35% has been reported in patients that have started statins for elevated cholesterol; yet many patients fail to consistently take these medications as directed. Our study evaluated factors that impact adherence to and persistence with statin therapy. Methods: This retrospective study analyzed data extracted from a VA database encompassing 6 facilities in Northern California, Northern Nevada and Hawaii for patients newly prescribed statin medication between July 1, 2007 and December 31, 2012. Patient demographics, co-morbidities, prescription record information, and time on therapy were collected. Adherence to statin therapy was determined using the mean possession ratio (MPR), calculated as the total days’ supply of medication dispensed divided by the total number of days in the intended treatment period. Persistence was defined as whether a patient continued to refill their statin prescription, with non-persistence occurring when a given patien...
Abstract 5182: Activity and clinical relevance of autotaxin and lysophosphatidic acid pathways in high-grade serous carcinoma
Authors: Hadil Onallah, Claes G Trope, Thea E. Hetland Falkenthal, Ben Davidson, Reuven Reich
Journal: Cancer Research (2018)

Abstract Lysophosphatidic acid (LPA) is a bioactive phospholipid with mitogenic and growth factor-like activities affecting cell invasion, cancer progression and drug resistance. It is produced mainly by Autotaxin and acts on six G protein-coupled receptors, LPAR1-6. LPA has recently been implicated as a growth factor present in ascites of ovarian cancer patients. However, mitogenic pathways stimulated by LPA via its receptors are still far uncharacterized. Here we show that three LPA receptors are involved in the progression of the malignancy by the activation of both AKT and ERK pathways. We analyzed a set of 155 samples of high grade serous ovarian carcinoma (HGSC) from the three different anatomic sites of the disease. Results show that LPAR2 mRNA was overexpressed in HGSC cells in effusions compared to solid lesions, with opposite findings for LPAR3 and LPAR6 mRNA and ATX protein that was found mainly in exosomes. LPAR3 levels were significantly higher in pre-chemotherapy effusions compared to post-chemotherapy specimens (p=0.025). Higher expression of LPAR1 (p=0.037), LPAR2 (p=0.025) and LPAR5 (p=0.021) was significantly associated with shorter overall survival. Furthermore, we combined 3D (spheroids) and 2D cell culture models with gene editing using the CRISPR/Cas9 method for LPAR2, LPAR3 and LPAR6 and tested the effects of their silencing in vitro using OVCAR3 and ES2 cell lines. The p-ERK/ERK ratio was significantly elevated in LPAR3KO OVCAR3 cells cultured both in 2D and 3D form. Yet, LPAR2KO OVCAR3 cells expressed low levels of p-ERK/ERK in the 3D form, suggesting that LPAR3 inhibits p-ERK activity downstream, while LPAR2 activates it. ES2 LPAR2KO cells expressed elevated levels of p-AKT/AKT ratio in both the 2D and 3D forms. OVCAR3 LPAR6KO had low p-AKT/AKT ratio when cultured in 2D, but high ratio in the 3D form. LPAR KO further inhibited ovarian cancer invasion and motility.Our results demonstrate, for the first time, significant changes in LPARs' mRNA levels and Autotaxin protein levels with changes in anatomic sites of the disease that correlate to clinic-pathological parameters. Our study identifies a specific molecular machinery triggered by LPA and its' receptors that modulate tumor and can serve as therapeutic targets in this malignancy. Citation Format: Hadil Onallah, Claes G Trope, Thea E. Hetland Falkenthal, Ben Davidson, Reuven Reich. Activity and clinical relevance of autotaxin and lysophosphatidic acid pathways in high-grade serous carcinoma [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 5182.
Abstract 84: Identification of HNRNPLL as a novel metastasis suppressor of colorectal cancer
Authors: Masahiro Aoki, Eiichi Sasaki, Kenya Kimura, Koji Komori, Yasuhiro Shimizu, Yasushi Yatabe, Keiichiro Sakuma
Journal: Cancer Research (2018)

Abstract Despite the advances in surgery and chemotherapy for colorectal cancer patients, those with distant metastasis still suffer poor prognosis. Metastasis is a complex process regulated by a number of biomolecules, which can be conceptually divided into metastasis promoters and suppressors. To identify novel targets for prevention and/or therapy of colorectal cancer metastasis, we performed an in vivo shRNA library screen for colorectal cancer metastasis suppressor genes using an orthotopic transplantation model. CMT93 cells, a murine colorectal cancer cell line with poor metastasizing activity, were transduced with lentiviral shRNA library, and then transplanted into the rectum of C57/BL6 mice. Genomic DNA was collected from metastatic lesions, and the integrated shRNAs were retrieved by PCR for sequencing, followed by identification of the candidate genes targeted by the shRNAs. Among 47 candidate genes identified, we focused on Hnrnpll (heterogeneous nuclear ribonucleoprotein L-like) gene encoding a pre-mRNA binding protein involved in pre-mRNA splicing. Hnrnpll knockdown in CMT93 cells significantly increased their matrigel invasion in vitro and lung metastasis in vivo. An RNA-immunoprecipitation analysis identified Cd44 as a candidate target of Hnrnpll. The mRNA level of Cd44 variant 6 (Cd44v6), a splicing variant of Cd44 that had been shown to demarcate colon cancer stem cells driving colon cancer metastasis, was increased by knocking down Hnrnpll in colon cancer cells. Treatment with neutralizing anti-CD44v6 monoclonal antibodies suppressed matrigel invasion of colon cancer cells induced by Hnrnpll knockdown, suggesting that Hnrnpll may suppress invasion and metastasis, at least in part, by modulating the alternative splicing of Cd44. HNRNPLL expression level in colorectal cancer cells was drastically decreased upon induction of epithelial-mesenchymal transition (EMT), accompanied by increased expression of CD44v6. The link between HNRNPLL and EMT was further suggested by immunostaining analysis of clinical samples; colorectal cancer cells with low E-cadherin expression at the invasion front exhibited decreased HNRNPLL expression as compared with those in the tumor center. These results suggest that HNRNPLL is a novel metastasis suppressor in colorectal cancer. Possible mechanisms for regulation of HNRNPLL expression during EMT will also be discussed. Citation Format: Masahiro Aoki, Eiichi Sasaki, Kenya Kimura, Koji Komori, Yasuhiro Shimizu, Yasushi Yatabe, Keiichiro Sakuma. Identification of HNRNPLL as a novel metastasis suppressor of colorectal cancer [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 84.
Angiotensin II Activates Nuclear Transcription Factor κB Through AT1 and AT2 in Vascular Smooth Muscle Cells
Authors: MartaRuiz-Ortega, OscarLorenzo, MónicaRupérez, SvenKönig, BurghardtWittig, JesúsEgido
Journal: Circulation Research (2000)

Abstract—Nuclear factor-κB (NF-κB) regulates many genes involved in vascular physiopathology. We have previously observed in vivo NF-κB activation in injured vessels that diminished by angiotensin-converting enzyme inhibition. In the present work, we investigated the effect of angiotensin II (Ang II) on NF-κB activity in rat vascular smooth muscle cells, evaluating the molecular mechanisms and the specific receptor subtype involved. Ang II increased NF-κB DNA binding (5-fold, 10−9 mol/L at 1 hour; electrophoretic mobility shift assay), nuclear translocation of p50/p65 subunits, and cytosolic inhibitor κBα (IκBα) degradation. Ang II elicited NF-κB–mediated transcription (transfection of a reporter gene) and expression of NF-κB–related genes (monocyte chemoattractant protein-1 and angiotensinogen). AT1 (DUP753) and AT2 (PD123319 and CGP42112) receptor antagonists inhibited Ang II–induced NF-κB DNA binding in a dose-dependent manner (≈85% for each one; 10−5 mol/L at 1 hour). The AT2 agonist p-aminophenylalan...
Stromal Cell–Derived Factor-1α Confers Protection Against Myocardial Ischemia/Reperfusion Injury
Authors: XiaofengHu, ShujingDai, Wen-JianWu, WeiTan, XiaopingZhu, JingyaoMu, YiruGuo, RobertoBolli, GreggRokosh
Journal: Circulation (2007)

Background— Stromal cell–derived factor-1α (SDF-1α) binding to its cognate receptor, CXCR4, regulates a variety of cellular functions such as stem cell homing, trafficking, and differentiation. However, the role of the SDF-1α–CXCR4 axis in modulating myocardial ischemia/reperfusion injury is unknown. Methods and Results— In mice subjected to ischemic preconditioning, myocardial SDF-1α mRNA was found to be increased 3 hours later (P<0.05). Myocardial SDF-1α and CXCR4 mRNA and protein were found to be expressed in both cardiac myocytes and fibroblasts. SDF-1α production increased significantly after 1 or 4 hours of hypoxia and 18 hours of reoxygenation in cultured myocytes (P<0.05) but did not change in fibroblast cultures. In isolated myocytes, CXCR4 activation by SDF-1α resulted in increased phosphorylation of both ERK 1/2 and AKT and decreased phosphorylation of JNK and p38. Cultured myocytes pretreated with SDF-1α were resistant to hypoxia/reoxygenation damage, exhibiting less lactate dehydrogenase rele...
Localization of Optimal Ablation Site of Idiopathic Ventricular Tachycardia from Right and Left Ventricular Outflow Tract by Body Surface ECG
Authors: ShiroKamakura, WataruShimizu, KiyotakaMatsuo, AtsushiTaguchi, KazuhiroSuyama, TakashiKurita, NaohikoAihara, TohruOhe, KatsuroShimomura
Journal: Circulation (1998)

Background—Idiopathic ventricular tachycardia (VT) is known to arise from the right ventricular (RV) and left ventricular outflow tracts (LVOT). However, reliable noninvasive methods to localize the optimum ablation site for VT have not been reported. Methods and Results—Body surface maps (BSM) and 12-lead ECGs were investigated in 35 VTs from the RVOT and 5 VTs from the LVOT in which the origin was confirmed during the ablation procedure. The RVOT was classified into 8 subdivisions with the use of a 3-dimensional anatomic relation: anterior (A)–posterior (P), right (R)–left (L), and superior (S)–inferior (I). On the BSM, the following 3 indexes differentiated each location of the origin, with a diagnostic accuracy of 88% (A-P), 92% (R-L), and 77% (S-I): (1) the location of the minimum at the early-to-mid QRS (right, A; left, P), (2) the isopotential distribution in the left shoulder area after 30 ms of QRS (positive, R; negative, L), and (3) the downward moving time of the minimum at the early-to-mid QRS...
Abstract 17833: Traditional Group Feedback is Better Than Technology-Assisted Individual Feedback During Simulation-Based Medical Education for Advanced Cardiac Life Support!
Authors: N. Gurukripa Kowlgi, Edgar Naut, Rahul Mutneja, Demytra Mitsis, Mamta Shah, Omar Shahbaz, Shounak Majumder
Journal: Circulation (2016)

Introduction: Simulation based medical education (SBME) is a key component of Advanced Cardiac Life Support (ACLS) training. Delivering effective feedback efficiently is critical in SBME. There is ...
Long-term Relapse of Type 2 Diabetes After Roux-en-Y Gastric Bypass: Prediction and Clinical Relevance
Authors: Jean Debédat, Nataliya Sokolovska, Muriel Coupaye, Simona Panunzi, Rima Chakaroun, Laurent Genser, Garance de Turenne, Jean-Luc Bouillot, Christine Poitou, Jean-Michel Oppert, Matthias Blüher, Michael Stumvoll, Geltrude Mingrone, Séverine Ledoux, Jean-Daniel Zucker, Karine Clément, Judith Aron-Wisnewsky
Journal: Diabetes Care (2018)

OBJECTIVE Roux-en-Y gastric bypass (RYGB) induces type 2 diabetes remission (DR) in 60% of patients at 1 year, yet long-term relapse occurs in half of these patients. Scoring methods to predict DR outcomes 1 year after surgery that include only baseline parameters cannot accurately predict 5-year DR (5y-DR). We aimed to develop a new score to better predict 5y-DR. RESEARCH DESIGN AND METHODS We retrospectively included 175 RYGB patients with type 2 diabetes with 5-year follow-up. Using machine learning algorithms, we developed a scoring method, 5-year Advanced-Diabetes Remission (5y-Ad-DiaRem), predicting longer-term DR postsurgery by integrating medical history, bioclinical data, and antidiabetic treatments. The scoring method was based on odds ratios and variables significantly different between groups. This score was further validated in three independent RYGB cohorts from three European countries. RESULTS Compared with 5y-DR patients, patients who had relapsed after 5 years exhibited more severe type 2 diabetes at baseline, lost significantly less weight during the 1st year after RYGB, and regained more weight afterward. The 5y-Ad-DiaRem includes baseline (diabetes duration, number of antidiabetic treatments, and HbA1c) and 1-year follow-up parameters (glycemia, number of antidiabetic treatments, remission status, 1st-year weight loss). The 5y-Ad-DiaRem was accurate (area under the receiver operating characteristic curve [AUROC], 90%; accuracy, 85%) at predicting 5y-DR, performed better than the Diabetes Remission score (DiaRem) and the Advanced-DiaRem (AUROC, 81% and 84%; accuracy, 79% and 78%, respectively), and correctly reclassified 13 of 39 patients misclassified with the DiaRem. The 5y-Ad-DiaRem robustness was confirmed in the independent cohorts. CONCLUSIONS The 5y-Ad-DiaRem accurately predicts 5y-DR and appears relevant to identify patients at risk for relapse. Using this score could help personalize patient care after the 1st year post-RYGB to maximize weight loss, limit weight regains, and prevent relapse.
Abstract 18425: Characteristics and Outcomes of Patients With Aortic Stenosis and Chronic Kidney Disease Not on Dialysis
Authors: Krishna K Patel, Shailee Shah, Susana Arrigain, Stacey Jolly, Jesse Schold, Sankar Navaneethan, Brian P Griffin, Joseph V Nally, Milind Y Desai
Journal: Circulation (2016)

Introduction: We sought to study the mortality among patients with aortic stenosis (AS) &chronic kidney disease (CKD) not on dialysis, & compared them to CKD patients with no AS. Methods: We studie...
Mortality From Thoracic Aortic Diseases and Associations With Cardiovascular Risk Factors
Authors: DavidSidloff, EdwardChoke, PhilipStather, MatthewBown, JohnThompson, RobertSayers
Journal: Circulation (2014)

Background—Temporal trends in mortality from thoracic aortic disease are unclear. This study examined trends in mortality from thoracic aortic aneurysm (TAA) and aortic dissection (AD) with the aim of identifying associations with trends in established cardiovascular risk factors. Methods and Results—TAA and AD mortality (1994–2010) using International Classification of Diseases codes was extracted from the World Health Organization mortality database and age standardized. World Health Organization InfoBase and International Mortality and Smoking Statistics provided risk factor data. Eighteen World Health Organization member states were included (Europe=13, Australasia=2, North America=2, Asia=1). Ecological regression was performed of temporal trends in cardiovascular risk factors (1946–2010) and independent correlations to mortality trends. TAA and AD mortality trends show substantial heterogeneity but are generally declining. TAA mortality has increased in Hungary, Romania, Japan, and Denmark, and AD m...
Abstract 1931: Targeting master neuronal transcription factor BRN2 in neuroendocrine prostate cancer
Authors: Daksh Thaper, Ravi Munuganti, Shaghayegh Norouzi, Sahil Kumar, Soojin Kim, Kriti Singh, Sepideh Vahid, Jennifer Bishop, Amina Zoubeidi
Journal: Cancer Research (2018)

Abstract Introduction: Resistance to newly developed androgen receptor pathway inhibitors (ARPIs), such as Enzalutamide (ENZ), rapidly emerges and patients generally die within two years. In particular, a subset of patients who relapse following ARPI therapy exhibit lineage switching whereby tumours shed their dependence on AR signaling and emerge with neuroendocrine features. These tumours, termed treatment induced neuroendocrine prostate cancer (t-NEPC), carry an extremely poor prognosis and, to date, treatment remains decades old cytotoxic chemotherapy which carries a short-lived response at the cost of significant toxicity. Therefore, targeted therapies for this deadly disease are desperately needed. Thus, the need to develop targeted treatments for this devastating disease is of paramount importance. Recently our group identified the neural transcription factor BRN2 as a major clinically relevant driver of NEPC and aggressive tumor growth, both in vitro and in vivo, suggesting targeting BRN2 is a promising strategy to prevent neuroendocrine differentiation or treat NEPC. Methods: Study the effects of BRN2 inhibition using siRNA and CRISPR K/O models. Results: Inhibition of BRN2 by siRNA and by CRISPR/Cas9 knockout drastically reduced cell proliferation in 42DENZR (NEPC) cell lines. This data was re-capitulated in human NEPC NCI-H660 cells. Loss of BRN2 initiated drastic epigenetic changes in NEPC cell lines as well as in G1 arrest through up-regulation of CDKN1A/1B. This was confirmed using our first in field BRN2 inhibitors. Targeting BRN2 also lead to downregulation several known targets in NEPC like EZH2, AURKA, SOX2 and Peg10. Conclusion: No therapies exist for highly lethal NEPC. Hence, the described work aims to verify BRN2 as a central driver of NEPC, and lay the pre-clinical foundation for the integration of targeted therapies into the treatment landscape to improve survival and quality of life for patients suffering from deadly form of prostate cancer. Citation Format: Daksh Thaper, Ravi Munuganti, Shaghayegh Norouzi, Sahil Kumar, Soojin Kim, Kriti Singh, Sepideh Vahid, Jennifer Bishop, Amina Zoubeidi. Targeting master neuronal transcription factor BRN2 in neuroendocrine prostate cancer [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 1931.