tbuckley/cabot-search huggingface dataset:
Should Bilateral Internal Thoracic Artery Grafting Be Used in Elderly Patients Undergoing Coronary Artery Bypass Grafting
Authors: BenjaminMedalion, RephaelMohr, OsnatFrid, GideonUretzky, NachumNesher, YosefPaz, AmirKramer, DmitryPevni
Journal: Circulation (2013)

Background—Although bilateral internal thoracic artery grafting is associated with improved survival, the use of this technique in the elderly is controversial because of their increased surgical risk and shorter life expectancy. The purpose of this study was to evaluate the effect of age on outcome of patients undergoing bilateral internal thoracic artery grafting. Methods and Results—Between 1996 and 2001, 1714 consecutive patients underwent skeletonized bilateral internal thoracic artery grafting, of whom 748 were ≤65 years of age, 688 were between 65 and 75 years of age, and 278 were ≥75 years of age. Operative mortality of the 3 age groups (1.2%, 4.1%, and 5.8%, respectively) was lower than the logistic EuroSCORE predicted mortality (3.9%, 6.5%, and 9.3%, respectively; P<0.001). There were no significant differences among the groups in occurrence of sternal infection (1.3%, 2.6%, and 1.4%, respectively; P=0.171). Mean follow-up was 11.5 years. Kaplan–Meier 10-year survival for patients ≤65, 65 to 75,...
Abstract 4030: Loss of E-cadherin expression is a critical step for peritoneal metastasis of gastric cancer with sub-serosal invasion
Authors: Shingo Togano, Masakazu Yashiro, Kenji Kuroda, Tomohisa Okuno, Yuichiro Miki, Kosei Hirakawa, Masaichi Ohira
Journal: Cancer Research (2018)

Abstract Background: Peritoneal metastasis is the most frequent type of metastasis in gastric cancer. However, the actual mechanisms responsible for this metastasis are not understood clearly. The process of peritoneal metastasis requires some steps including the detachment of cancer cells from the primary tumor. E-cadherin, a calcium-dependent cell-cell adhesion molecule, is known to mediate intercellular adhesion. We examined the correlation between peritoneal metastasis of gastric cancer and reduced E-cadherin expression. Methods: A total of 694 gastric cancer cases of which were resected at our department was enrolled in this study. The expression of E-cadherin of gastric cancer cells was evaluated by immunohistochemical staining. We analyzed the correlation between the E-cadherin expression and clinicopathological features. A case with less than 50% of E-cadherin expression was defined as E-cadherin negative. Results: Among the 694 cases, 232 cases were E-cadherin negative. 171 cases developed peritoneal metastasis. Among the 171cases, 88cases were E-cadherin negative. E-cadherin-negative cancer was significantly (p&amp;lt;0.0001) associated with peritoneal metastasis. The 5-year survival rate of patients with E-cadherin-negative cancer (48.1%) was poor, in compared to that with E-cadherin-positive tumor (62.8%), while a multivariate analysis did not show significant difference. A multivariate analysis of sub-serosal invasion tumors (T3 stage tumor) indicated that only E-cadherin-negative was significantly associated with peritoneal metastasis (p=0.0005). Conclusion: The loss of E-cadherin is a critical step in the promotion of cancer cells to a more malignant phenotype. E-cadherin is a useful prognostic factor for peritoneal metastasis in gastric carcinoma with sub-serosal tumor. Citation Format: Shingo Togano, Masakazu Yashiro, Kenji Kuroda, Tomohisa Okuno, Yuichiro Miki, Kosei Hirakawa, Masaichi Ohira. Loss of E-cadherin expression is a critical step for peritoneal metastasis of gastric cancer with sub-serosal invasion [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 4030.
Abstract 064: The Lipoxigenase Inhibitor Nordihydroguaiaretic Acid Prevents the Development of Hypoxia-Induced Pulmonary Hypertension in Mice
Authors: AndreaIorga, GabrielWong, DeniseMai, JingyuanLi, SalilSharma, MansourehEghbali
Journal: Circulation Research (2013)

Pulmonary hypertension (PH) is a chronic lung disease characterized by progressively elevated pulmonary arterial pressures and severe pulmonary vascular remodeling resulting from interactions between oxidized lipoprotein deposition and increased endothelial proliferation. Previously we have shown increased plasma levels of biological oxidation products such as hydroxyoctadecadienoic acids (HODEs) and hydroxyeicosatetraenoic acids (HETEs) in the rat monocrotaline model of PH. Here we investigated the role of HETEs and HODEs in the development of PH and whether their inhibition with the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) attenuates the progression of PH. Mice were placed in a hypoxic chamber with O2 concentrations of ≤10% for 21 days and either left untreated to develop PH (n=7) or treated with NDGA daily (10mg/kg/day, i.p., n=4) from day 1. Direct RV catheterization was terminally performed to record RV pressure (RVP). Pulmonary arteriolar thickening and oxidized lipid deposition were ...
Abstract 836: ISU104, a fully human anti-ErbB3 antibody, overcomes acquired cetuximab resistance
Authors: Miyoung Kim, Youngmi Hur, Mirim Hong, Youngsoo Sohn, Kum-Joo Shin, Kyungyong Kim, Seung-Beom Hong, Kum-Joo Shin, Donggoo Bae
Journal: Cancer Research (2018)

Abstract ErbB3 is noted as one of major causes of acquired cetuximab resistance in colorectal and head and neck cancers. ErbB3 causes activation of alternative signaling pathways that bypass the original target and sustained PI3K/AKT activation, and these are associated with cetuximab resistance. We confirmed the induced ErbB3 activation by the cetuximab treatment in FaDu head and neck squamous-cell carcinoma (HNSCC) xenograft model. Immunoblot analysis was shown that twice weekly 10 mg/kg of cetuximab treatment upregulated ErbB3 expression and phosphorylation even though tumor growth was well controlled. To investigate whether ErbB3 activation by ligand, heregulin (HRG,) might induce cetuximab resistance, two cetuximab-sensitive colorectal cancer cell lines, DiFi and LIM1215, were treated 0-25 ng/mL of HRG. HRG induced dose-dependent cetuximab resistance in cell proliferation assay, and this was reversed via ISU104 treatment. To evaluate if ISU104 could overcome resistance to cetuximab in vivo, acquired cetuximab-resistant FaDu xenograft model was established. Tumors that had acquired resistance to 5 mg/kg of cetuximab treatment were significantly regressed by replaced treatment of ISU104 alone (10 mg/kg) or combination treatment of ISU104 and cetuximab, while mice continued on cetuximab only showed uncontrolled tumor growth like vehicle-treated group. Our results suggest that ISU104 effectively overcomes cetuximab resistance and may provide clinical benefit to cetuximab-resistant patients. Citation Format: Miyoung Kim, Youngmi Hur, Mirim Hong, Youngsoo Sohn, Kum-Joo Shin, Kyungyong Kim, Seung-Beom Hong, Kum-Joo Shin, Donggoo Bae. ISU104, a fully human anti-ErbB3 antibody, overcomes acquired cetuximab resistance [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 836.
Activation of Cardiac Aldosterone Production in Rat Myocardial Infarction
Authors: Jean-SébastienSilvestre, ChristopheHeymes, AbdeslamOubénaïssa, ValérieRobert, BrigitteAupetit-Faisant, AlainCarayon, BernardSwynghedauw, ClaudeDelcayre
Journal: Circulation (1999)

Background—This study analyzed the regulation and the role of the cardiac steroidogenic system in myocardial infarction (MI). Methods and Results—Seven days after MI, rats were randomized to untreated infarcted group or spironolactone- (20 and 80 mg · kg−1 · d−1), losartan- (8 mg · kg−1 · d−1), spironolactone plus losartan–, and L-NAME– (5 mg · kg−1 · d−1) treated infarcted groups for 25 days. Sham-operated rats served as controls. In the noninfarcted myocardium of the left ventricle (LV), MI raised aldosterone synthase mRNA (the terminal enzyme of aldosterone synthesis) by 2.0-fold and the aldosterone level by 3.7-fold. Conversely, MI decreased 11β-hydroxylase mRNA (the terminal enzyme of corticosterone synthesis) by 2.4-fold and the corticosterone level by 1.9-fold. MI also induced a 1.9-fold increase in cardiac angiotensin II level. Such cardiac regulations were completely prevented by treatment of the infarcted heart with losartan. The MI-induced collagen deposition in noninfarcted LV myocardium was p...
Efficacy and Safety of Further Lowering of Low-Density Lipoprotein Cholesterol in Patients Starting With Very Low Levels
Authors: Marc S. Sabatine, Stephen D. Wiviott, KyungAh Im, Sabina A. Murphy, Robert P. Giugliano
Journal: JAMA Cardiology (2018)

In the Cholesterol Treatment Trialists Collaboration (CTTC), in patients starting with low-density lipoprotein cholesterol (LDL-C) levels of approximately 3.4 mmol/L (131.5 mg/dL), there was a 22% reduction in major vascular events per 1-mmol/L (38.7-mg/dL) lowering of LDL-C. The magnitude of clinical benefit of further LDL-C lowering in patients already with very low LDL-C levels remains debated.To evaluate efficacy and safety of further lowering LDL-C levels in patient populations presenting with median LDL-C levels of 1.8 mmol/L (70 mg/dL) or less.The CTTC was used for statin data. For nonstatin therapy, Medline database was searched (2015-April 2018). Key inclusion criteria were a randomized, double-blind, controlled cardiovascular outcome trial of LDL-C lowering with data in populations starting with LDL-C levels averaging 1.8 mmol/L (70 mg/dL) or less.Two authors independently extracted data into standardized data sheets, and data were analyzed using meta-analysis.The risk ratio (RR) of major vascular events (a composite of coronary heart death, myocardial infarction, ischemic stroke, or coronary revascularization) per 1-mmol/L (38.7-mg/dL) reduction in LDL-C level.In the subgroup of patients from the CTTC meta-analysis of statins with a mean LDL-C in the control arm of 1.7 mmol/L (65.7 mg/dL), 1922 major vascular events occurred and the RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C was 0.78 (95% CI, 0.65-0.94). For 3 trials of nonstatin LDL-C-lowering therapies added to statins, there were 50 627 patients, the median LDL-C in the control arms ranged from 1.6 mmol/L to 1.8 mmol/L (63 mg/dL to 70 mg/dL), and 9570 major vascular events occurred. Nonstatin therapy lowered LDL-C by 0.3 to 1.2 mmol/L (11 mg/dL to 45 mg/dL), and the RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C was 0.79 (95% CI, 0.70-0.88). For statins and nonstatins combined, the RR was 0.79 (95% CI, 0.71-0.87; P < .001). Low-density lipoprotein cholesterol lowering was not associated with an increased risk of serious adverse events, myalgias and/or myositis, elevation in the level of aminotransferases, new-onset diabetes, hemorrhagic stroke, or cancer.There is a consistent relative risk reduction in major vascular events per change in LDL-C in patient populations starting as low as a median of 1.6 mmol/L (63 mg/dL) and achieving levels as low as a median of 0.5 mmol/L (21 mg/dL), with no observed offsetting adverse effects. These data suggest further lowering of LDL-C beyond the lowest current targets would further reduce cardiovascular risk.
Abstract 19043: Left Atrial Structural Remodeling With Ventricular Assist Device
Authors: Amrish Deshmukh, Emeka Anyanwu, Nir Uriel, Valluvan Jeevanandam, Roderick Tung, Cevher Ozcan
Journal: Circulation (2016)

Introduction: Left ventricular assist devices (LVAD) have become the mainstay of therapy for patients with advanced heart failure, both as bridge to transplantation or as destination therapy. Although LVAD are associated with significant ventricular remodeling, its impact on left atrial (LA) remodeling is not known. Hypothesis: LVAD may have a significant impact on atrial remodeling through alteration in atrial filling pressures and perfusion. Methods: All patients who underwent LVAD implantation from 2008 to 2015 were included. Medical records and electrocardiograms were abstracted to determine baseline characteristics and arrhythmia incidence. Echocardiograms before and after the LVAD implantation were reviewed for LA size and volume. LA sizes were graded from 0 to 3 (0=normal, 1=mildly enlarged, 2=moderately enlarged and 3=severely enlarged). Results: A total of 331 consecutive patients were followed for a median of 331 days. Mean age was 57.8±12.8 years, 256 (77.3%) were male, mean left ventricular ej...
Abstract 2831: Collateral lethality: A new target for personalized oncology
Authors: Yu-Hsi Lin, Naima Hammoudi, Nikunj Satani, Jeffrey Ackroyd, Sunada Khadka, Dimitra Georgiou, Joe Marszalek, Yuting Sun, Marina Protopopova, Maria E. Di Francesco, Barbara Czako, Alan Y. Wang, Ronald A. DePinho, Florian L. Muller
Journal: Cancer Research (2018)

Abstract Large-scale genomic profiling efforts, such as The Cancer Genome Atlas (TCGA) have painted an unprecedentedly detailed picture of the genetic alterations that underlie carcinogenesis, yet the key challenge remains as to how to turn this information into actionable therapies. Genomic deletions are a frequent event in diverse cancers, which inactivate a limited number of tumor suppressor genes (“driver”-events) but frequently include many chromosomal neighbors as “passengers”, some of which play critical but redundant roles in normal cellular housekeeping. The overall hypothesis we propose to test is that collateral deletions of such “passenger” genes can be utilized as novel targets of synthetic lethality, an idea which we term “collateral lethality." The large number of passenger deleted genes, playing diverse functions in cell homeostasis, offers a rich repertoire of pharmacologically targetable vulnerabilities presenting novel opportunities for the development of personalized anti-neoplastic therapies. We have provided in vitro proof-of-principal of a collaterally deleted glycolytic gene Enolase 1 (ENO1) at the 1p36 tumor suppressor locus in glioblastoma (GBM), that leads to dramatic sensitization to inhibition of the redundant paralogue, ENO2. The next step is to take this concept to the clinic. Our overall goal is to generate a clinical candidate Enolase inhibitor for tumors with ENO1-deletions, like GBM for which there is no other treatment option and the therapeutic benefit could be quite substantial. Citation Format: Yu-Hsi Lin, Naima Hammoudi, Nikunj Satani, Jeffrey Ackroyd, Sunada Khadka, Dimitra Georgiou, Joe Marszalek, Yuting Sun, Marina Protopopova, Maria E. Di Francesco, Barbara Czako, Alan Y. Wang, Ronald A. DePinho, Florian L. Muller. Collateral lethality: A new target for personalized oncology [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 2831.
Abstract 5696: Discovery of putative breast cancer antigens using genomics-driven immunoproteomics
Authors: David K. Han
Journal: Cancer Research (2018)

Abstract Recent advances in cancer immunotherapeutics such as checkpoint inhibitors, chimeric antigen-receptor T cells, and tumor-infiltrating T cells (TIL) are now significantly impacting cancer patients in a positive manner. Although very promising, reports indicate no more than 25% of cases result in complete remission. One of the limitations of these treatments is the identity of cancer antigens in each patient as it is technically challenging to identify cancer antigens in a rapid fashion. Thus, identification of cancer antigens for each patient followed by targeted treatment will likely increase the efficacy of cancer immunotherapies. To achieve this goal, a combined technologies of deep genomic sequencing and personalized immune assessment platform was devised, termed Genomics-Driven Immunoproteomics (GDI). Using this technological platform, we report the discovery of 149 putative tumor antigens from human breast cancer patients. Significant numbers of these cancer antigens arise from single nucleotide variants (SNVs), as well as insertions and deletions that results into frame-shift mutations. We propose a general model of anticancer immunity and suggest that GDI platform may help identify patient-specific tumor antigens in a timely fashion for precision immunotherapies. Citation Format: David K. Han. Discovery of putative breast cancer antigens using genomics-driven immunoproteomics [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 5696.
Cost-Effectiveness of Percutaneous Coronary Intervention With Drug-Eluting Stents Versus Bypass Surgery for Patients With 3-Vessel or Left Main Coronary Artery Disease
Authors: David J. Cohen, Ruben L. Osnabrugge, Elizabeth A. Magnuson, Kaijun Wang, Haiyan Li, Khaja Chinnakondepalli, Duane Pinto, Mouin S. Abdallah, Katherine A. Vilain, Marie-Claude Morice, Keith D. Dawkins, A. Pieter Kappetein, Friedrich W. Mohr, Patrick W. Serruys
Journal: Circulation (2014)

Background— The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial demonstrated that in patients with 3-vessel or left main coronary artery disease, coronary artery bypass graft surgery (CABG) was associated with a lower rate of cardiovascular death, myocardial infarction, stroke, or repeat revascularization compared with percutaneous coronary revascularization with drug-eluting stents (DES-PCI)). The long-term cost-effectiveness of these strategies is unknown. Methods and Results— Between 2005 and 2007, 1800 patients with left main or 3-vessel coronary artery disease were randomized to CABG (n=897) or DES-PCI (n=903). Costs were assessed from a US perspective, and health state utilities were evaluated with the EuroQOL questionnaire. A patient-level microsimulation model based on the 5-year in-trial data was used to extrapolate costs, life expectancy, and quality-adjusted life expectancy over a lifetime horizon. Although initial procedural costs were $3415 per patient lower with CABG, total hospitalization costs were $10 036 per patient higher. Over the next 5 years, follow-up costs were higher with DES-PCI as a result of more frequent hospitalizations, revascularization procedures, and higher medication costs. Over a lifetime horizon, CABG remained more costly than DES-PCI, but the incremental cost-effectiveness ratio was favorable ($16 537 per quality-adjusted life-year gained) and remained &lt;$20 000 per quality-adjusted life-year in most bootstrap replicates. Results were consistent across a wide range of assumptions about the long-term effect of CABG versus DES-PCI on events and costs. In patients with left main disease or a SYNTAX score ≤22, however, DES-PCI was economically dominant compared with CABG, although these findings were less certain. Conclusions— For most patients with 3-vessel or left main coronary artery disease, CABG is a clinically and economically attractive revascularization strategy compared with DES-PCI. However, among patients with less complex disease, DES-PCI may be preferred on both clinical and economic grounds. Clinical Trial Registration— URL: www.clinicaltrials.gov . Unique identifier: NCT00114972.
Abstract 5797: BET inhibitor synthetic lethality in malignant peripheral nerve sheath tumors
Authors: Jonathan M. Cooper, Amish J. Patel, Zhiguo Chen, Chung-Ping Liao, Kun Chen, Yong Wang, Lu Q. Le
Journal: Cancer Research (2018)

Abstract BET bromodomain inhibitors have emerged as a promising therapy for numerous cancer types in pre-clinical studies, but molecular indicators of tumor response are lacking. Through modeling tumor evolution by studying genetic lesions underlying the development of Neurofibromatosis Type 1 (NF1)-associated Malignant Peripheral Nerve Sheath Tumors (MPNST), a lethal sarcoma with no effective medical treatment, we identified a BRD4 dependency that serves as a controlled model system to delineate mechanisms of sensitivity or resistance to BET bromodomain inhibitors in this disease. In this study, we show that loss of NF1 and p53 is associated with increased BRD4 protein levels and partial sensitivity to BET inhibition in MPNST. Strikingly, genetic depletion of BRD4 profoundly sensitizes MPNST cells to diverse BET inhibitors in culture and in vivo, while wild-type cells are spared. Collectively, genetic and pharmacological inhibition of BRD4 reveals that BET inhibitor resistance in MPNST requires wild-type BRD4 to support growth in a bromodomain-independent manner. Our findings provide a framework for understanding BET inhibitor sensitivity and resistance within distinct molecular subsets of MPNST. In addition, discovery that a synthetic lethality exists between BET inhibition and reduced BRD4 levels nominates a BRD4-low patient subpopulation as that which might best respond to a BET inhibitor therapeutic strategy for MPNST. Citation Format: Jonathan M. Cooper, Amish J. Patel, Zhiguo Chen, Chung-Ping Liao, Kun Chen, Yong Wang, Lu Q. Le. BET inhibitor synthetic lethality in malignant peripheral nerve sheath tumors [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 5797.
Abstract 19348: A Panel of Free Circulating miRNAs (miR-1, miR-21, miR-133a, miR-208a and miR-499) May Be Used as Biomarkers to Discriminate Between Different Clinical Types of Coronary Artery Disease: Stable Coronary Artery Disease, Unstable Angina and Non-ST-Elevation Myocardial Infarction
Authors: Dawid Miskowiec, Piotr Lipiec, Karolina Kupczynska, Michal Simiera, Marcin Ojrzanowski, Blazej Michalski, Karina Wierzbowska-Drabik, Paulina Wejner-Mik, Ewa Szymczyk, Jaroslaw D Kasprzak
Journal: Circulation (2016)

Introduction: Some studies reported utility of microRNAs in ST-elevation myocardial infarction diagnosis, whereas their diagnostic value in non-ST elevation acute coronary syndrome (NSTE-ACS) still remains unclear. Hypothesis: We hypothesized that the altered expression of 5 circulating miRs (miR-1, miR-21, miR-133a, miR-208a, miR-499) allows to differentiate NSTE-ACS from stable coronary artery disease (SCAD). Methods: The prospective, single-center observational study was composed of 72 patients (pts) with NSTE-ACS with symptoms onset <24h before the hospital admission and 34 pts with SCAD as controls. Blood was sampled twice in the NSTE-ACS group (at admission and 4h after) and once in SCAD. Unstable angina (UA) vs NSTEMI diagnosis was based on the troponin 99th percentile rule. Relative expression of miRs were calculated using the ΔΔCt method after normalization to the cel-miR-39 spiked-in control. The mean value of miRs’ relative expression from two time samples in NSTE-ACS pts were used for further ...