tbuckley/cabot-search huggingface dataset:
Abstract 10972: Transthoracic Echocardiography-guided Percutaneous Patent Ductus Arteriosus Occlusion: A New Strategy For Interventional Treatment
Authors: Xiang-Bin Pan, Wen-Bin Ouyang, Shou-Zheng Wang, Yao Liu, Da-Wei Zhang, Feng-Wen Zhang, Kun-Jing Pang, Zhe Zhang, Yi Ge, Sheng-Shou Hu
Journal: Circulation (2015)

Objectives: This prospective single center study investigated the safety and efficacy of percutaneous patent ductus arteriosus (PDA) occlusion using the Amplatzer Duct Occluder II (ADO II) under only guidance of transthoracic echocardiography, which avoids the radiation and contrast agents of traditional PDA occlusion. Methods: From June 2013 to February 2015, 54 consecutive PDA patients (age, 4.6 ± 2.9 years; weight, 18.5 ± 7.5 kg; PDA narrowest diameter, 3.3 ± 1.1 mm) underwent transthoracic echocardiography guided PDA occlusion through the femoral artery. Outpatient follow-up was conducted at 1, 3, and 6 months, and yearly. Results: Echocardiography-guided percutaneous PDA occlusion was successfully performed in 53 patients. The procedure was converted to minimally invasive transthoracic occlusion in one patient due to failure of delivery catheter passage through tortuous PDA. Mean procedure duration was 25.5 ± 7.4 minutes; ADO II diameter averaged 4.7 ± 0.9 mm; 8 cases showed traces of residual shunt immediately after operation; and mean hospital stay was 3.4 ± 0.7 days. There was no occluder migration, hemolysis or pericardial effusion at mean 10.2±4.9 months follow-up. Conclusions: Percutaneous PDA occlusion under only guidance of transthoracic echocardiography appears safe and effective while avoiding radiation and contrast agent use. Legends: A) A suprasternal view showed the tip of pigtail catheter (arrow) faced the aortic end of the PDA. B) The left parasternal long axis view of the pulmonary artery showed that the guide wire (arrow) was located within the main pulmonary artery. C) The release of the occluder at the pulmonary side (arrow). D) The occluder was completely released (arrows point to each side of the occluder). PDA, patent ductus arteriosus; DAO, descending aorta; PA, pulmonary artery; AO, ascending aorta.
Abstract 18200: Intracoronary Delivery of Bioabsorbable Alginate Matrix (IK-5001) Ameliorates Adverse Post-infarction Left Ventricular Remodeling and Improves Left Ventricular Function in a Porcine Model of Reperfused Myocardial Infarction
Authors: Carlos G Santos-Gallego, Belén Picatoste, Ida U Njerve, Kiyotake Ishikawa, Jaime Aguero, Torsten Vahl, Nadjib Hammoudi, Javier Sanz, Jagat Narula, Roger J Hajjar, Martin D Meglasson, Valentin Fuster, Juan J Badimon
Journal: Circulation (2015)

Background: Adverse cardiac remodeling after MI is associated with excessive degradation of the extracellular matrix (ECM). IK-5001 is a low viscosity injectable solution that provides the polysaccharide alginate. After intracoronary injection into the MI area it undergoes phase transition forming a hydrogel which can support the ECM. We hypothesized that administration of alginate post-MI would provide a temporary scaffold and attenuate adverse LV remodeling. Methods: Acute MI was induced in 16 pigs by balloon occlusion of the proximal LAD for 2 hours. Animals randomly received intracoronary alginate or saline 4 days post-MI. LV function and remodeling were evaluated with cardiac MRI, 3D-echo and pressure-volume loops at 1 and 2 months post-MI. Histology and Western blot analysis were performed after 2 months. Results: Both groups had similar LVEF and infarct size 4 days post-MI. Coronary angiography immediately after alginate injection showed no impairment in coronary flow. However, 2 months post-MI, alginate-treated pigs exhibited reduced LV remodeling compared with controls demonstrated by reduced LV end-systolic volume, LV mass and sphericity (Table). Alginate-treated pigs had less cardiomyocyte hypertrophy and decreased interstitial fibrosis. Consistent with this, chronic activation of Akt and ERK was reduced. Alginate pigs also showed lower plasma levels of BNP and aldosterone. Interestingly, after 2 months, alginate pigs showed better systolic LV function: higher LVEF, better contractile reserve with dobutamine, and higher dP/dt. Conclusions: Intracoronary administration of alginate ameliorates adverse post-MI LV remodeling at the anatomical, histological and molecular level, and mitigates neurohormonal activation in a porcine model of MI. Alginate also improves systolic LV function. Intracoronary injection of alginate represents an exciting novel treatment option to reduce post-MI remodeling that merits assessment in clinical studies.
Abstract 18376: Long-term Atherosclerotic Cardiovascular Disease Outcomes Associated With Coronary Artery Calcium
Authors: Joshua D Mitchell, Robert Paisley, Patrick Moon, Todd C Villines
Journal: Circulation (2015)

Introduction: Current risk assessment guidelines focus on prevention of atherosclerotic cardiovascular disease (ASCVD), which includes stroke as a primary outcome variable. The long-term (&gt;10 year) relationship of coronary artery calcium (CAC) scoring with stroke has not been previously reported, a limitation cited by the guidelines. Further, large-scale, long-term outcomes studies following CAC are limited. We sought to define the long-term relationship of CAC for stroke and myocardial infarction (MI) in a large screening cohort. Methods: We retrospectively identified 24,246 subjects (mean age 50±8; 70.5% men) without ASCVD or malignancy who underwent CAC scoring (Agatston) at Walter Reed Medical Center from 1997-2009. Subjects were assessed for the primary outcomes of MI and stroke and the secondary outcome of late (&gt;90 days post CAC) coronary revascularization. Outcomes were extracted from the military data repository, a comprehensive healthcare database that captures care provided within and outside of the military healthcare system, and then analyzed using Cox proportional hazard multivariate stepwise regression controlling for baseline risk factors. Results: With a mean follow-up of 11.3±3.6 years there were 546 MI, 947 strokes and 843 late coronary revascularizations. Compared to subjects with no CAC, the adjusted hazard ratios (aHR) for MI were 2.09 (95% CI, 1.68-2.60), 2.01 (1.78-2.28) and 1.91 (1.72-2.11) for CAC scores of 1-100, 101-400 and &gt;400, respectively. CAC of 1-100 was not predictive of stroke compared to no CAC. The aHRs of incident stroke were 1.15 (1.03-1.28) and 1.23 (1.13-1.33) for CAC scores of 101-400 and &gt;400. CAC was strongly associated with late coronary revascularizations. CAC explained the most variance in models for MI and late revascularization and was the third most important predictor for stroke behind age and hypertension. Conclusion: In patients without ASCVD, CAC was a stronger independent predictor of incident MI and late coronary artery revascularization as compared to stroke over one of the longest follow-up intervals reported to date. Advanced CAC (&gt;100) was a modest independent predictor of stroke during the study period. These results support the role of CAC for the prediction of incident ASCVD outcomes.
An Incidental Finding of Subcutaneous Hemangioma During 99mTcO4 Salivary Gland Scintigraphy
Authors: Zhen Zhao, Yu Chen, Bin Liu
Journal: Clinical Nuclear Medicine (2018)

A 43-year-old woman with papillary thyroid cancer prepared for I ablation after total thyroidectomy. With a history of type 2 diabetes for 10 years, she recently presented with periodontitis, candidiasis, and mouth dryness. TcO4 scintigraphy was ordered to evaluate function of the salivary glands. The scintigraphy incidentally found a focal TcO4 uptake in the left supraclavicular region. The subsequent neck ultrasonography showed a hypoechoic soft tissue mass with heterogeneous hypervascularity, suggestive of hemangioma.
Abstract 3990: Clinicopathologic findings and in vitro efficacy of MYC-targeting agentsin NUT midline carcinoma
Authors: Soyeon Kim, Minsun Jung, Heae Surng Park, Sun Och Yoon, Soon Won Hong, Weon-Seo Park, Bhumsuk Keam, Hyun Jik Kim, Dong-Wan Kim, Young Tae Kim, Dae Seong Heo, Tae Min Kim, Yoon Kyung Jeon
Journal: Cancer Research (2018)

Abstract Purpose: NUT midline carcinoma (NMC) is an aggressive and poorly differentiated carcinoma defined by chromosomal rearrangements of NUT gene, which is fused to the BET family genes (BRD3/4). Although NMC is extremely rare and mostly reported in a Western population, clinico-pathologic findings of Asian NMC patients are not well studied. Here, we performed the clinicopathologic analysis of Korean NMC cases and in vitro efficacy of MYC-targeting agents against patient-derived NMC cell lines. Experimental Design: A total of 12 NMC patients (3 thoracic and 9 head and neck origins) were collected in Korean multi-centers by immunohistochemistry (IHC) and fluorescence in situ hybridization for NUT. IHC staining was performed for c-MYC, p53, EGFR, HER2, and PD-L1. NMC cell lines (SNU-2972-1, SNU-3178S, HCC2429, and Ty-82) were exposed to MYC-targeting agents including BET (I-BET, OTX-015, and AZD5153) and HDAC (vorinostat, romidepsin, panobinostat, and CUDC-907) inhibitors. Cell viability assays were performed and IC50 values were determined. Results: Primary sites of tumor included sinonasal area (n=7), salivary gland (n=2), and thorax/lung (n=3). The median age was 47.5 years (range, 8-73 years) with equal male-to-female ratio. NUT immunostaining showed diffuse positivity in all except for one who had focal NUT positivity. C-MYC and p53 were expressed in all evaluated cases. PD-L1 expression was observed only in a patient (8.3%). Seven of 12 patients died at 3-24 months (median, 9 months) after diagnosis. Long-term survivor was observed in one patient with stage IV NMC who received mass excision plus metastasectomy followed by 6 cycles of docetaxel plus cisplatin and radiotherapy (survival &amp;gt; 27 months). Although BET and HDAC inhibitors showed limited in vitro efficacies against NMC cells, a dual HDAC/PI3K inhibitor, CDUC-907 exhibited the most potent efficacy with the IC50 of 6.2 to 9 pmol/L. Conclusions: Korean NMC patients pursued grave prognosis like Western patients except one long-term survivor who received tri-modality treatments. Dual HDAC/PI3K inhibitor might be promising in NMC treatment. Citation Format: Soyeon Kim, Minsun Jung, Heae Surng Park, Sun Och Yoon, Soon Won Hong, Weon-Seo Park, Bhumsuk Keam, Hyun Jik Kim, Dong-Wan Kim, Young Tae Kim, Dae Seong Heo, Tae Min Kim, Yoon Kyung Jeon. Clinicopathologic findings and in vitro efficacy of MYC-targeting agentsin NUT midline 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 3990.
Vasculoprotective Role of Inducible Nitric Oxide Synthase at Inflammatory Coronary Lesions Induced by Chronic Treatment With Interleukin-1β in Pigs in Vivo
Authors: YoshihiroFukumoto, HiroakiShimokawa, ToshiyukiKozai, ToshiakiKadokami, KouichiKuwata, YoshikazuYonemitsu, TakeshiKuga, KensukeEgashira, KatsuoSueishi, AkiraTakeshita
Journal: Circulation (1997)

Background We recently developed a porcine model in which chronic, local treatment with interleukin-1β (IL-1β) causes coronary arteriosclerotic changes and hyperconstrictive responses. Inflammatory cytokines are known to induce inducible NO synthase (iNOS) in the vascular smooth muscle. This study was designed to examine whether or not the production of NO by iNOS has a protective or deleterious effect on the coronary artery in vivo. Methods and Results A segment of the porcine coronary artery was aseptically wrapped with cotton mesh absorbing IL-1β suspension. We inhibited both eNOS and iNOS activity by cotreatment with L-NAME (a nonspecific inhibitor of NOS) and iNOS activity alone by aminoguanidine (a selective inhibitor of iNOS). Immunostaining showed that iNOS was absent in the normal coronary artery, whereas it was highly expressed 1 day after the application of IL-1β and thereafter downregulated until 14 days. In contrast, eNOS was well maintained throughout the study period. Two weeks after the op...
Abstract 4281: A family-wide computational analysis of the catalytic domains of the Never In Mitosis A-like kinase (NEK) proteins
Authors: Carline A. Durmus, Shaneen Singh
Journal: Cancer Research (2018)

Abstract Members of the Never In Mitosis A-like kinase (NEK) proteins are overexpressed in leukemia, breast, ovarian, prostate, and cervical cancers. Overexpression of particular NEK proteins is also implicated in the increased resistance of certain cancer cells to premature senescence due to various cancer treatments. Depending on the cancer cell type, there are NEK members that, when inhibited, either increase the cancer cells' susceptibility to specific drugs or increase their resistance. Structural information and model of action of NEKs is limited to only two members of the family, even though the different members play an important role in human metabolism. The goal of this research is to perform a comprehensive computational analysis of the 11 members of the human NEK protein family. To provide detailed annotations of the NEK family members, the three-dimensional structures of the catalytic domains was modeled using various approaches including template-based modeling, threading, and ab inito techniques. The information gathered from the models was integrated with information obtained from sequence analysis, biophysical characterization including surface electrostatic profiles, and predicted molecular interactions involving NEK members and other proteins/ macromolecules to establish structure-function correlations. Here we present a detailed analysis of the catalytic domains of the 11 NEK proteins and propose interaction and binding partners for each of the individual members of the family. The role of NEKs in the cell cycle, numerous medical disorders, and as potential chemotherapeutic targets underscores the importance of understanding the structure-function relationship of this family of proteins and establishing their mechanism of action, including delineating the differences among the different members of the family, and our study is a step in that direction. Citation Format: Carline A. Durmus, Shaneen Singh. A family-wide computational analysis of the catalytic domains of the Never In Mitosis A-like kinase (NEK) proteins [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 4281.
Abstract 1767: Synergy between intratumoral immunotoxin and systemic anti-CTLA-4 promotes massive inflammation and leads to complete regression of tumors in mice
Authors: Yasmin Leshem, James O'Brien, Yoram Reiter, Ira Pastan
Journal: Cancer Research (2018)

Abstract Background: The immunotoxin SS1P consists of an anti-mesothelin Fv attached to Pseudomonas exotoxin A and kills tumor cells by inhibiting protein synthesis. Because of its unique mechanism of cell killing and unlike other anti-cancer drugs, SS1P does not suppress the immune system. Here we determined if SS1P can cooperate with anti-CTLA-4 to induce anti-tumor immunity and cause tumor regression. Methods: A BALB/c breast cancer cell line was transfected with human mesothelin (66C14-M) and implanted in two different locations. SS1P was injected directly into one tumor and anti-CTLA-4 given IP. Twelve days after treatment initiation, the tumors were harvested and evaluated for immune related gene expression by Nanostring Technologies. A portion of each tumor was sent to pathology and stained for CD8. Results: In mice treated with anti-CTLA-4 and SS1P, complete tumor regressions occurred in 25/30 (86%) SS1P injected tumors and in 16/30 (53%) tumors at the un-injected location. No complete regressions occurred with either drug given separately. This indicates that the combination therapy has a synergistic and systemic anti-tumor effect. Pathological evaluation of injected tumors from combination-treated mice revealed large central abscesses surrounded by a collar of inflammation, containing a mixture of lymphocytes and mononuclear cells. The collar of inflammation was unique to the combination treated mice. Only very small abscesses were observed in tumors from control mice. Immunohistochemistry of tumors from mice treated with SS1P and anti-CTLA-4 showed an increase in CD8+ cells located mainly in the inflammation collar. Analysis of gene expression in tumors from combination-treated mice, compared to PBS-treated tumors, showed that 341/747 (45%) immune transcripts were elevated by 2-fold or more including CD8a, PDL2 and CD56 (8, 15 and 24-fold, respectively). In mice treated with anti-CTLA-4 and PBS, the increase of transcripts was lower: 127/747 (17%) genes. Only 18 out of 747 transcripts (2%) were elevated in the SS1P-treated tumors. This suggests that SS1P by itself does not initiate an inflammatory process. However, SS1P greatly potentiates the inflammatory process initiated by anti-CTLA-4. Conclusions: Combining local SS1P with anti-CTLA-4 promotes massive inflammation that cures injected and un-injected tumors and provides a strong rational to explore this combination therapy in patients. Citation Format: Yasmin Leshem, James O'Brien, Yoram Reiter, Ira Pastan. Synergy between intratumoral immunotoxin and systemic anti-CTLA-4 promotes massive inflammation and leads to complete regression of tumors in mice [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 1767.
Coercivity Determines Magnetic Particle Heating
Authors: Fabian H. L. Starsich, Christian Eberhardt, Andreas Boss, Ann M. Hirt, Sotiris E. Pratsinis
Journal: Advanced Healthcare Materials (2018)

Abstract Diseased cell treatment by heating with magnetic nanoparticles is hindered by their required high concentrations. A clear relationship between heating efficiency and magnetic properties of nanoparticles has not been attained experimentally yet due to limited availability of magnetic nanoparticles with varying size and composition. Here, versatile flame aerosol technology is used for the synthesis of 21 types of ferro‐/ferrimagnetic nanocrystals with varying composition, size, and morphology for hyperthermia and thermoablation therapy. Heating efficiency, magnetic hysteresis, and first‐order reversal curves of these materials are compared. The maximum heating performance occurs near the transition from superparamagnetic to single domain state, regardless of particle composition. Most importantly, the ratio between saturation magnetization and coercivity can be linked to the heating properties of magnetic nanoparticles. Magnetic interaction is controlled by changes in the architecture of the nanoparticles and closely analyzed by first‐order reversal curves. Silica‐coated nonstoichiometric Gd‐Zn ferrite exhibits the most promising therapeutic capability at relatively low particle concentrations, as shown in vitro with cancerous prostate cells.
Abstract 11138: Superresolution Studies of Sodium Channels Within Intercalated Disk Microdomains Suggest Novel Arrhythmia Mechanism
Authors: Rengasayee Veeraraghavan, Joyce T Lin, James P Keener, Steven Poelzing, Robert G Gourdie
Journal: Circulation (2015)

Pore-forming (Nav1.5) and auxiliary (β1; SCN1b) subunits of cardiac sodium channels are enriched at the cardiomyocyte intercalated disk (ID). Mathematical models suggest that this may facilitate conduction via ephaptic mechanisms. We recently demonstrated Nav1.5 enrichment (gSTED superresolution microscopy) and close membrane apposition (&lt;10 nm; electron microscopy) within the perinexus, a microdomain surrounding connexin43 (Cx43) gap junctions (GJ). These data identified the perinexus as a candidate structure for the cardiac ephapse. Further studies using gSTED and STORM superresolution microscopy revealed Nav1.5 and β1 enrichment within ID regions not containing dense clusters of Cx43 and N-Cadherin. Notably, both were identified within the perinexus: Overall, 22% of Nav1.5 &amp; β1 were located within perinexal regions while only 2 and 5% respectively overlapped with Cx43 clusters. Importantly, acute interstitial edema (AIE) increased intermembrane distance at perinexal, but not at non-perinexal sites in adult guinea pig myocardium. Functionally, this correlated with decreased transverse conduction velocity (CV-T; 15.2±0.3 vs. 19.6±0.1cm/s) and increased anisotropic ratio (AR; 3.0±0.2 vs. 2.8±0.1) relative to control, in perfused guinea pig ventricles. Nav1.5 blockade (0.5 μM flecainide) by itself decreased CV (18%) without changing AR. However, Nav1.5 inhibition during AIE preferentially decreased CV-T (13.0±0.6cm/s), increased AR (3.3±0.2) and increased spontaneous arrhythmias (7/9 vs. 4/11) compared to AIE alone. Notably, only a computer model including ephaptic coupling and the ID localization of Nav1.5 could recapitulate these results. Next we investigated the role of β1 in ephaptic coupling: Electrical cell-substrate impedance spectroscopy of 1610 cells heterologously overexpressing β1 revealed 3-fold higher paracellular resistance relative to native 1610 cells. These data along with the known cell adhesion function of β1 in neural tissue suggest that β1-mediated adhesion may facilitate close membrane apposition within the perinexus. Taken together, our results identify β1-mediated adhesion as a novel determinant of anisotropic conduction and potential antiarrhythmic target.