tbuckley/cabot-search huggingface dataset:
Importance of Pressure Recovery for the Assessment of Aortic Stenosis by Doppler Ultrasound
Authors: JuliaNiederberger, HeinrichSchima, GeraldMaurer, HelmutBaumgartner
Journal: Circulation (1996)

Background Pressure recovery has been shown to occur distal to aortic stenoses in experimental and clinical studies. However, its clinical relevance in this setting has not yet been evaluated. Methods and Results To address the hypothesis that pressure recovery can cause significant differences between Doppler and catheter gradients in aortic stenosis and to examine the effects of aortic size, aortic valve area, and direction of the stenotic jet on these differences, stenoses with valve areas from 0.5 to 1.25 cm2 and aortic diameters from 1.8 to 5.0 cm were studied in a pulsatile flow model. Jets entered the aorta centrally or eccentrically with angles of 15°, 30°, or 45°. Overall, good correlation was found between Doppler and catheter gradients. However, when the various combinations of orifices and aortas were analyzed separately, slopes varied from 1.0 to 1.86, and the Doppler-catheter gradient differences ranged from −2 (small valve area with a large aorta) to 66 mm Hg (80% overestimation by Doppler ...
Fine Particulate Air Pollution and Adverse Birth Outcomes: Effect Modification by Regional Nonvolatile Oxidative Potential
Authors: Éric Lavigne, Richard T. Burnett, David M. Stieb, Greg J. Evans, Krystal J. Godri Pollitt, Hong Chen, David van Rijswijk, Scott Weichenthal
Journal: Environmental Health Perspectives (2018)

Background: Prenatal exposure to fine particulate matter air pollution with aerodynamic diameter ≤2.5μm (PM2.5) has been associated with preterm delivery and low birth weight (LBW), but few studies have examined possible effect modification by PM2.5 oxidative potential. Objectives: The aim of this study was to evaluate if regional differences in the oxidative potential of PM2.5 modify the relationship between PM2.5 and adverse birth outcomes. Methods: A retrospective cohort study was conducted using 196,171 singleton births that occurred in 31 cities in the province of Ontario, Canada, from 2006 to 2012. Daily air pollution data were collected from ground monitors, and city-level PM2.5 oxidative potential was measured. We used random-effects meta-analysis to combine the estimates of effect from regression models across cities on preterm birth, term LBW, and term birth weight and used meta-regression to evaluate the modifying effect of PM2.5 oxidative potential. Results: An interquartile increase (2.6 μg/m3) in first-trimester PM2.5 was positively associated with term LBW among women in the highest quartile of glutathione (GSH)-related oxidative potential [odds ratio (OR)=1.28; 95% confidence interval (CI): 1.10, 1.48], but not the lowest quartile (OR=0.99; 95% CI: 0.87, 1.14; p-interaction=0.03). PM2.5 on the day of delivery also was associated with preterm birth among women in the highest quartile of GSH-related oxidative potential [hazard ratio (HR)=1.02; 95% CI: 1.01, 1.04], but not the lowest quartile [HR=0.97; 95% CI: 0.95, 1.00; p-interaction=0.04]. Between-city differences in ascorbate (AA)-related oxidative potential did not significantly modify associations with PM2.5. Conclusions: Between-city differences in GSH-related oxidative potential may modify the impact of PM2.5 on the risk of term LBW and preterm birth. https://doi.org/10.1289/EHP2535
Abstract 19183: Responsive Intravenous Oxygen Microparticles Improve Survival From Asphyxial Cardiac Arrest
Authors: Yifeng Peng, Raymond P Seekell, Alexis R Cole, Jemima R Lamothe, Andrew T Lock, Xiaoqi Tang, John N Kheir, Brian Polizzotti
Journal: Circulation (2017)

Introduction: In-hospital cardiac arrest is precipitated by severe hypoxemia in 45% of cases, a subset of patients who suffer severe neurologic injury. Favorable outcomes requires the immediate rev...
Effect of electrochemotherapy with IV bleomycin on complete response in a preclinical brain tumor study.
Authors: Birgit Agerholm-Larsen, Helle K. Iversen, Jakob M. Moller, Per Ibsen, Kurt S. Jensen, Mette Linnert, Julie Gehl
Journal: Journal of Clinical Oncology (2012)

2069 Background: Electrochemotherapy (ECT) describes enhanced chemotherapeutic drug uptake after cell membranes have been made transiently permeable due to application of an electric field to the tumor. ECT is routinely used to treat skin metastases, with high response rates after once-only treatment. We have developed an electrode for use in the brain, both a rodent model and an electrode for clinical use. The aim of the present study was to evaluate ECT using intravenous (iv) bleomycin in a rat brain tumor model. Methods: Sprague Dawley male rats (7-11 week old) were inoculated with rat glial cell derived tumor cells (N32) through a burr hole in the skull. When tumors appeared on MRI, animals were allocated to ECT (iv bleomycin and local electric pulses), iv bleomycin only, iv bleomycin with placement of electrodes (no pulses), or no treatment. Bleomycin was injected iv in the tail vein (600µL, 3 IU/µL) and electrode deployment was made through the burr hole into the brain tissue. Electrochemotherapy parameters were 32 pulses, 100V, 100µs, 1Hz. Tumor size was determined based on contrast enhanced area from MR scans. Kaplan-Meyer events were defined as termination due to extensive tumor progression prior to end of the three independent experiments performed. Immuno-histo-pathology was performed after termination to verify MRI findings. Results: In 88% of the animals (14 of 16) treated with electrochemotherapy we found complete response (no tumor), validated by MRI and immuno-histo-pathology, whereas bleomycin only, bleomycin and electrodes, and no treatment showed progression in 11 out of 13 control animals. A Kaplan-Meier plot showed a pronounced improved survival for the ECT group as compared to controls within 3 weeks from treatment (p&lt;0.001). Treatment was well tolerated. Conclusions: The present data suggest that electrochemotherapy with iv injection of bleomycin is a new promising treatment for brain tumors. In a clinical study using iv bleomycin and electrochemotherapy for brain metastases ( www.clinicaltrials.gov , ID:NCT01322100) the first patient has just been treated successfully with ECT, indicating feasibility of the approach in the clinical setting.
Abstract 3656: Detecting MSI in plasma: Implications for early detection of lynch associated tumors
Authors: Preethi Srinivasan, Christina Tran, Jonathan Reichel, Juber Ahamad Patel, Maysun Hasan, Fanli Meng, Xiaohong Jing, Sumit Middha, Ahmet Zehir, Rona D. Yaeger, Diane Reidy, Dana Tsui, Zsofia Stadler, Michael F. Berger
Journal: Cancer Research (2018)

Abstract Lynch Syndrome (LS) is characterized by germline mutations in mismatch repair pathway genes. The increased cancer susceptibility risk in these patients and the association of these tumors with microsatellite instability (MSI) provides a transformative opportunity for early detection of cancer in these patients. The presence of microsatellite unstable DNA fragments or zygosity changes of the MMR mutations in the plasma of LS patients is predictive of the presence of cancer. Here we describe an approach to detect MSI from plasma cell-free DNA (cfDNA) of LS associated cancer patients. First, to determine the background rate of MSI in cfDNA of microsatellite stable patients, we screened plasma samples collected from a large number of advanced cancer patients using MSK-IMPACT, a custom sequencing assay targeting 468 cancer genes encompassing ~1.5 megabases. MSK-IMPACT is approved by the NYS Department of Health and authorized by the FDA for clinical testing, including MSI assessment based on more than 1,000 microsatellite regions covered by the assay, and has been used to profile more than 20,000 patients at our institution. We were also able to confirm the ability to detect MSI in cfDNA in a small cohort of plasma samples collected from patients with MSI High tumors, and determine thresholds to delineate MSI from MSS cases from plasma. Using MSK-IMPACT, we detected MSI in the plasma of four patients with advanced MSI-H cancer, including one with confirmed LS. Three of these were patients with confirmed MSI signature from tumor tissue (one prostate cancer and two colorectal cancers. The fourth patient with prostate cancer had no tissue available for sequencing, though MSI was independently confirmed. To improve the sensitivity to detect MSI in patients with earlier stage disease where the fraction of tumor-derived cfDNA is lower, we have developed a novel targeted panel with optimized sequencing process and informatics, incorporating a set of highly informative microsatellite regions as well as SNPs to assess tumor-specific zygosity changes in mismatch repairs pathway genes. Through this work, we demonstrate the ability of our assay to detect MSI in plasma cfDNA with high sensitivity. Citation Format: Preethi Srinivasan, Christina Tran, Jonathan Reichel, Juber Ahamad Patel, Maysun Hasan, Fanli Meng, Xiaohong Jing, Sumit Middha, Ahmet Zehir, Rona D. Yaeger, Diane Reidy, Dana Tsui, Zsofia Stadler, Michael F. Berger. Detecting MSI in plasma: Implications for early detection of lynch associated 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 3656.
One-Year Coronary Bypass Graft Patency
Authors: PetrWidimsky, ZbynekStraka, PetrStros, KarelJirasek, JaroslavDvorak, JanVotava, LiborLisa, TomasBudesinsky, MiroslavKolesar, TomasVanek, PetrBrucek
Journal: Circulation (2004)

Background— Off-pump coronary bypass surgery has become a widely used technique during recent years. However, limited data are available with regard to 1-year patency of bypass grafts implanted on the beating heart in unselected consecutive bypass surgery candidates. The aim of this study was to compare 1-year angiographic patency of bypass grafts done on the beating heart (off pump) with those done classically (on pump). Methods and Results— The PRAGUE-4 trial randomized 400 consecutive nonselected cardiac surgery candidates into group A (on pump; n=192) and group B (off pump; n=208). One-year follow-up coronary angiography was done in 255 patients. The arterial graft patency after 1 year was 91% in both groups. Saphenous graft patency was 59% (on pump) versus 49% (off pump; P=NS). Saphenous graft patency per patient was lower in the off-pump group: 0.7 patent anastomosis per patient versus 1.1 patent anastomosis in the on-pump group (P<0.01). There were 46% on-pump patients with all grafts patent versus...
Abstract 544: Characterization of serine/threonine kinase LASK2 as a biomarker and therapeutic target for lung cancer
Authors: Yataro Daigo, Atsushi Takano, Yusuke Nakamura
Journal: Cancer Research (2018)

Abstract As the number of lung cancer patients responding well to standard therapies is still small, further development of new anti-cancer drugs with minimum risk of adverse event and highly sensitive cancer biomarkers is urgently awaited. We have been developing new molecular therapies targeting oncoproteins with their companion biomarkers by screening system as follows; i) To identify up-regulated genes in 120 lung cancers by the gene expression microarray representing 27,648 genes, ii) To verify the candidate genes for their low expression in 23 normal tissues, iii) To validate the clinicopathological significance of their protein expression by tissue microarray covering hundreds of non-small cell lung cancers (NSCLCs), iv) To verify whether they are essential for the growth/invasion of cancer cells by siRNAs. During this process, we selected dozens of druggable oncoproteins with various enzymatic activities, and identified activation of serine/threonine kinase LASK2 (lung cancer-associated kinase 2) in the majority of various histological types of lung cancers, but not in normal tissues except testis. Immunohistochemical analysis showed that strong LASK2 positivity was an independent prognostic factor for patients with NSCLC (P&amp;lt;0.0001). Suppression of LASK2 expression with its siRNAs inhibited growth of lung cancer cells. The enhanced cellular proliferation by introduction of LASK2 in mammalian cells also supported its oncogenic function in vitro and in mice model. Induction of LASK2 appeared to increase the levels of phosphorylation of oncogenic signal proteins for lung cancer such as MAPK. The data suggest that LASK2 is a candidate prognostic biomarker and possible therapeutic target for lung cancers. Citation Format: Yataro Daigo, Atsushi Takano, Yusuke Nakamura. Characterization of serine/threonine kinase LASK2 as a biomarker and therapeutic target for lung 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 544.
Abstract 5016: A unique ex vivo drug evaluation model: 3D co-cultured system with tumor, stroma and blood microvessels
Authors: Yuki Takahashi, Kei Tsukamoto, Shiro Kitano, Shinji Irie, Michiya Matsusaki, Satoshi Nagayama, Ryohei Katayama, Eiji Shinozaki, Naoya Fujita
Journal: Cancer Research (2018)

Abstract Background; Two dimensional single-layer culture still remains the preferred platform for most laboratory preclinical studies, although interaction between cancer and stromal cells has been well reported to be important in tumor progression and resistance against therapies. In order to mimic the patient tumor tissues, ex vivo model which recaptures the tumor microenvironment is required. Methods; Layered 3D stromal tissues were produced by culturing normal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs) coated with extra-cellular matrix (ECM) and natural polysaccharide, namely collagen and heparin. The layered 3D stromal tissues and overlaid tumors were morphologically characterized by HE stain, immunohistochemistry (IHC) and immunofluorescence (IF). Furthermore, drug sensitivity assays were conducted using popular colorectal cancer cell lines, and patient-derived cell lines (PDCs) established in the laboratory of Japanese Foundation for Cancer Research. Cancer cell viability was evaluated by fluorescent labeling, enzymatic dissociation and cell counting analysis. IF with cancer specific markers and imaging analyses were also performed. Results; The 3D stromal tissues including CD31 positive luminal structure were multi-layered (approximately 20 layers), and formation of microvascular network was observed within several days. In comparison with 2D mono-culture or 3D mono/co-cultured spheroid model, decreased drug sensitivities were represented in our 3D co-cultured model. In the simultaneous treatment with cytotoxic anticancer agents and molecular targeted drugs, dose-responses were significantly different between the2D and 3D models. Conclusion; We developed the layered 3D stromal tissue culture system including blood micro-vessels. Drug evaluation with the co-cultured tumors may reflect the drug sensitivity of cancer cells in vivo. Our unique 3D ex vivo model represents a valuable tool for drug development in a fully human cell and matrix microenvironment, and thus testing patient-derived cells and approved compounds also enable better prediction their efficacy. Citation Format: Yuki Takahashi, Kei Tsukamoto, Shiro Kitano, Shinji Irie, Michiya Matsusaki, Satoshi Nagayama, Ryohei Katayama, Eiji Shinozaki, Naoya Fujita. A unique ex vivo drug evaluation model: 3D co-cultured system with tumor, stroma and blood microvessels [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 5016.
Retinoids and Amyotrophic Lateral Sclerosis
Authors: Javier Riancho, Francisco J. Gil-Bea, Adolfo López de Munaín
Journal: JAMA Neurology (2018)

To the Editor We read with great interest the article by Rosenbohm and colleagues. 1 They conducted a case-control study and reported that retinol-binding protein 4 had an inverse association with both risk for amyotrophic lateral sclerosis (ALS) and disease prognosis.Although we agree with the relevance of the reported results and their interpretation, we would like to comment on 2 issues that might also correlate with these findings.First, as the authors indicated in the study, growing evidence shows disturbances in energy metabolism levels in patients with ALS who may experience a shift from glucose to lipid metabolism as the main energy source. 2 Interestingly, ALS is a very complex syndrome from a genotypic and phenotypic perspective.In this line, it has been postulated that causes of the disease could vary depending on the clinical form. 2 In their article, 1 Rosenbohm et al reported that 97 (33.6%), 91 (31.5%), and 73 (25.3%) of the patients had lumbar, bulbar, and cervical onset, respectively, but they did not include this grouping category in the analysis of retinol-binding protein 4 levels. 1n our opinion, because some pathogenic features, as well as several clinical conditions, such as diet, might differ between bulbar and spinal ALS, it would have been interesting to have considered this, for it would might provide further insight into the pathogenesis of the different disease forms.The second issue refers to the potential therapeutic role of retinoids.Because of the absence of an effective modifying disease therapy, there is a pressing need to search for new therapies for ALS.We previously showed that the retinoid agonist bexarotene has clear neuroprotective associations in ALS murine models. 3Traditionally, there are important difficulties in translating basic experimental findings into patients with ALS. 4 However, the study by Rosenbohm et al 1 provides further support for the implication of retinoids in ALS.Also, in line with this concept, Nieves et al 5 conducted a study to evaluate the association between nutrients and ALS course in more than 300 patients with ALS at the initial stages of the disease.Interestingly, it was reported that patients who have caroteneenriched diets exhibited a better prognosis. 5 Altogether, these studies suggest that retinoid pathway activation by bexarotene or other retinoids might be considered in a clinical trial for patients with ALS.
Lateral Zone of Cell-Cell Adhesion as the Major Fluid Shear Stress–Related Signal Transduction Site
Authors: YumikoKano, KazuoKatoh, KeigiFujiwara
Journal: Circulation Research (2000)

Abstract—It has been proposed previously that actin filaments and cell adhesion sites are involved in mechanosignal transduction. In this study, we present certain morphological evidence that supports this hypothesis. The 3D disposition of actin filaments and phosphotyrosine-containing proteins in endothelial cells in situ was analyzed by using confocal microscopy and image reconstruction techniques. Surgical coarctations were made in guinea pig aortas, and the same 3D studies were conducted on such areas 1 week later. Stress fibers (SFs) were present at both basal and apical regions of endothelial cells regardless of coarctation, and several phosphotyrosine-containing proteins were associated with SF ends. Apical SFs had one end attached to the apical cell membrane and the other attached to either the basal membrane or the lateral cell border. Within the coarctation area, the actin filament–containing and vinculin-containing structures became prominent, especially at the apical and the lateral regions. S...
Abstract 5168: Understanding the role of integrins in breast cancer
Authors: Valery Adorno-Cruz, Xia Liu, Huiping Liu
Journal: Cancer Research (2018)

Abstract Breast cancer is a highly prevalent disease and the second-leading cancer related death in women. Mortality rates have declined a 38% in recent years thanks to early detection and development of treatments. However, the five year survival rate of patients with a distant metastasis is only 26%. Hence, it is important to identify key players that mediate or promote the migration of cells to other organs. Integrins are cell surface receptors that mediate cell adhesion to the extracellular matrix. They are involved in roles such as cell migration and proliferation. In this project we seek to understand the role of integrin α2 in breast cancer metastasis. It has been previously reported that integrin α2 is a metastasis suppressor of a Her2+ model of breast cancer. However, its role in triple negative breast cancer is unknown. We found the integrin α2 gene (ITGA2) a target of has-miR-206 which controls metastasis and stemness of breast cancer. We hypothesize integrin α2 has a metastasis regulating role in triple negative breast cancer. The triple negative breast cancer cell line, MDA-MB-231 has been used to characterize the role of integrin α2 in migration, cell viability and lung colonization of mice injected though tail vein injection. Lung colonization of breast cancer cells in NSG mice is significantly altered by the knockdown expression of integrin α2. Consistent with the phenotypes in migration and invasion. Taken together, these results suggest integrin α2 regulates breast cancer metastasis through modified cell migration and lung colonization. Citation Format: Valery Adorno-Cruz, Xia Liu, Huiping Liu. Understanding the role of integrins in breast 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 5168.
Intracoronary ST-Segment Shift Soon After Elective Percutaneous Coronary Intervention Accurately Predicts Periprocedural Myocardial Injury
Authors: VruyrBalian, MicheleGalli, ClaudioMarcassa, GianniCecchin, MauriceChild, FabioBarlocco, EttorePetrucci, GiuliaFilippini, RiccardoMichi, MarcoOnofri
Journal: Circulation (2006)

Background— Elevation of cardiac biomarkers after coronary angioplasty (percutaneous coronary intervention [PCI]) reflects periprocedural myocardial damage and is associated with adverse cardiac events. We assessed whether periprocedural myocardial damage that occurs despite successful PCI could be rapidly and easily identified by intracoronary ST-segment recording with the use of a catheter guidewire. Methods and Results— In 108 consecutive stable patients undergoing elective single-vessel PCI, we recorded unipolar ECG from the intracoronary guidewire in the distal coronary before PCI and 2 minutes after the last balloon inflation. After PCI, intracoronary ST-segment shift ≥1 mm from baseline was considered significant. Troponin I levels were measured at baseline and at 8 and 24 hours after intervention, and myocardial damage was defined as troponin I increase above the upper normal value after intervention. All patients had normal cardiac marker values before PCI, and PCI was successful in all (residual...
Study on the Relationship Between Plasma Nitrite and Nitrate Level and Salt Sensitivity in Human Hypertension
Authors: NaotoFujiwara, TomohiroOsanai, TakaatsuKamada, TakeshiKatoh, KokiTakahashi, KenOkumura
Journal: Circulation (2000)

Background—High salt intake suppresses the effect of nitric oxide (NO) in the peripheral resistance vessels in animal models. We tested the hypothesis that the modulation of endogenous NO is related to salt sensitivity in human hypertension. Methods and Results—Inpatients with essential hypertension (n=24) were maintained on a normal-salt diet (12 g/d NaCl) for 3 days, a low-salt diet (2 g), a high-salt diet (20 to 23 g), and a low-salt diet for 7 days. Normotensive subjects (n=16) were maintained on the first 2 salt diets. The hypertensive patients whose average 24-hour blood pressure was increased by >5% by salt loading were assigned to group 1 (n=8) and the others to group 2 (n=16). Nitrate plus nitrite (NOx) was measured by the Griess method, and asymmetrical dimethylarginine (ADMA) by high-performance liquid chromatography. The plasma NOx level during the normal-salt diet was lower in group 1 than in group 2 and the normotensive group. After salt loading, the plasma NOx level was decreased and revers...