tbuckley/cabot-search huggingface dataset:
Clinical and Prognostic Usefulness of Supine Bicycle Exercise Echocardiography in the Functional Evaluation of Patients Undergoing Elective Percutaneous Transluminal Coronary Angioplasty
Authors: ArmandoDagianti, SalvatoreRosanio, MariaPenco, AlessandraDagianti, SusannaSciomer, MonicaTocchi, LucianoAgati, FrancescoFedele
Journal: Circulation (1997)

Background Supine bicycle exercise echocardiography (SBEE) has never been used before and early after percutaneous transluminal coronary angioplasty (PTCA) for assessing the functional outcome of the procedure and predicting late restenosis. Methods and Results We selected 76 subjects with stable angina, normal wall motion at rest, and exercise-induced wall-motion abnormalities before PTCA. SBEE with peak exercise imaging and the use of a 16-segment, four-grade score model was performed 54±15 hours after PTCA. No exercise-related adverse events occurred. Patients were grouped according to SBEE results: group 1 (n=35, 46%) with negative exercise ECG and echo; group 2 (n=19, 25%) with a positive exercise ECG but normal echo; and group 3 (n=22, 29%) with a positive exercise echo with either a positive (n=7, 32%) or negative (n=15, 68%) ECG. Exercise performance significantly improved in all groups. In group 3, peak wall-motion score index decreased from 1.27±0.11 before to 1.15±0.06 after PTCA (P<.05), and d...
Molecular imaging of T cell co-regulator factor B7-H3 with <sup>89</sup>Zr-DS-5573a
Authors: Ingrid Julienne Georgette Burvenich, Sagun Parakh, Fook-Thean Lee, Nancy Guo, Zhanqi Liu, Hui Kong Gan, Angela Rigopoulos, Graeme Joseph O'Keefe, Sylvia Jie Gong, Yit Wooi Goh, Henri Tochon-Danguy, Fiona Elizabeth Scott, Masakatsu Kotsuma, Kenji Hirotani, Giorgio Senaldi, Andrew Mark Scott
Journal: Theranostics (2018)

B7-H3 is a transmembrane protein widely expressed in a variety of cancers and has been shown to play a role in anti-tumor immunity.This study aims to develop a molecular imaging probe to identify B7-H3 expression in tumors and to develop 89 Zr-DS-5573a as a theranostic that could aid patient selection in clinical Phase I studies.Methods: The anti-B7-H3 humanised monoclonal antibody DS-5573a was labeled with zirconium-89 ( 89 Zr-), and assessed for radiochemical purity, immunoreactivity (Lindmo analysis), antigen binding affinity (Scatchard analysis), and serum stability in vitro.In vivo biodistribution and imaging studies were performed with positron emission tomography and magnetic resonance imaging (PET/MRI) studies to identify and quantitate 89 Zr-DS-5573a tumor uptake in a B7-H3-positive breast cancer model (MDA-MB-231) and a B7-H3-negative murine colon cancer model (CT26).Imaging and biodistribution studies were also performed in MDA-MB-231 tumor-bearing SCID mice in the absence and presence of therapeutic DS-5573a antibody dose (3 mg/kg DS-5573a).Results: 89 Zr-DS-5573a showed high and specific binding to B7-H3-expressing MDA-MB-231 cells (immunoreactivity on day 0, 75.0 ± 2.9%), and low binding to B7-H3-negative CT26 cells (immunoreactivity on day 0, 10.85 ± 0.11%) in vitro. 89Zr-DS-5573a demonstrated good serum stability in vitro with 57.2 ± 2.0% of immunoreactivity remaining on day 7.In vivo biodistribution studies showed high uptake of 89 Zr-DS-5573a in B7-H3-expressing MDA-MB-231 tumor-bearing mice, achieving 32.32 ± 6.55 %ID/g on day 7 post injection in BALB/c nu/nu mice and 25.76 ± 1.79 %ID/g in SCID mice, with minimal evidence of non-specific uptake in normal tissues, and excellent tumor localization on PET/MRI.In a combined imaging/therapy study, receptor saturation was demonstrated in tumors responding to therapy.Conclusion: 89 Zr-DS-5573a demonstrates specific and prolonged targeting of B7-H3-expressing tumors in vivo.Saturation of binding sites was demonstrated in tumors responding to DS-5573a therapy.These results indicate that 89 Zr-DS-5573a has potential to target B7-H3-expressing tumors in cancer patients.Furthermore 89 Zr-DS-5573a has the potential to provide important insights into T cell biology through its specific binding to B7-H3.
Vascular Endothelial–Cadherin Tyrosine Phosphorylation in Angiogenic and Quiescent Adult Tissues
Authors: NathalieLambeng, YannWallez, ChristineRampon, FrancineCand, GeorgesChristé, DanielleGulino-Debrac, IsabelleVilgrain, PhilippeHuber
Journal: Circulation Research (2005)

Vascular endothelial–cadherin (VE-cadherin) plays a key role in angiogenesis and in vascular permeability. The regulation of its biological activity may be a central mechanism in normal or pathological angiogenesis. VE-cadherin has been shown to be phosphorylated on tyrosine in vitro under various conditions, including stimulation by VEGF. In the present study, we addressed the question of the existence of a tyrosine phosphorylated form of VE-cadherin in vivo, in correlation with the quiescent versus angiogenic state of adult tissues. Phosphorylated VE-cadherin was detected in mouse lung, uterus, and ovary but not in other tissues unless mice were injected with peroxovanadate to block protein phosphatases. Remarkably, VE-cadherin tyrosine phosphorylation was dramatically increased in uterus and ovary, and not in other organs, during PMSG/hCG-induced angiogenesis. In parallel, we observed an increased association of VE-cadherin with Flk1 (VEGF receptor 2) during hormonal angiogenesis. Additionally, Src kin...
Abstract 17891: NF-κB Signaling Plays a Crucial and Detrimental Role in Cardiomyocyte Senescence
Authors: Sheng Ye, Guangming Cheng, Jiafeng Lin, Xing Chen, Lin Zhao, Anweshan Samanta, Magdy Girgis, Arash Davani, Yanjuan Yang, Jeryl Hauptman, Robert Vincent, Buddhadeb Dawn
Journal: Circulation (2016)

Introduction: Emerging evidence indicates that senescent cardiomyocytes are responsible for the development of cardiac dysfunction in aging heart. Evidence also indicates that NF-κB activity increa...
Assessing the Credibility of Findings From Nonrandomized Studies of Interventions
Authors: Luke A. McGuinness, Julian P. T. Higgins, Jonathan A. C. Sterne
Journal: JAMA Cardiology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Yakov Brand: Soviet and Russian cardiac surgeon and TV anchor
Authors: Boleslav Lichterman
Journal: BMJ (2018)

Yakov Beniaminovich Brand was born into a Jewish family. His father was a military dermatologist and his mother a surgeon. “When I was 3 years old, my mother started taking me to her hospital since there was nobody to stay at home with me,” he recalled. “I am convinced that growing up in a surgical department is as romantic as growing up backstage or on a film set. My mother’s patients loved me. They taught me not only grammar but also how to play the guitar.” Brand grew up in Odessa, a vibrant cosmopolitan city on the Black Sea in Ukraine.

During his school years, Brand worked in a studio theatre as a puppet mover. His acting abilities came to the fore at a summer camp of the factory where his uncle was employed. Only the children of factory employees were allowed to go, and Brand played the part of his uncle’s son every summer. He viewed himself as a spy in another country and never revealed his real name to the others. He aspired to be a film actor, but he failed his entrance exams at the …
Abstract 767: Identification of cell surface proteins expressed exclusively on mutant KRas-dependent cancer cells
Authors: Vijayendra Agrawal, Bin Fang, Eric A. Welsh, John Koomen, Said M. Sebti
Journal: Cancer Research (2018)

Abstract Mutant KRas is a major contributor to human oncogenesis and confers resistance to therapy. Identification of cell surface proteins that are expressed exclusively in mutant KRas-driven tumors could lead to novel approaches for diagnosing and treating mutant KRas-dependent tumors. To this end, we used a biotinylation/mass spectrometry approach to capture cell surface proteins from mutant KRas-dependent and -independent human cancer cells. KRas was depleted from both mutant KRas-dependent and -independent cells, and the cells were subjected to cell surface protein biotinylation using EZ-Link Sulfo-NHS-SS-Biotin reagent and captured via neutravidin column. The efficiency of cell surface protein capture was confirmed by the presence of membrane proteins EGFR, IGF1R and absence of cytosolic proteins RhoGDIa in biotin-pull down fractions (western blot analysis). Mass spectrometric and proteomics analyses of biotinylated proteins yielded 20 highly probable hits with very high expression in mutant KRas-dependent cells and very low expression in mutant KRas-independent cells. Upon KRas depletion, the level of these proteins was significantly reduced in mutant KRas-dependent cells (up to 25 fold) but not in mutant KRas-independent cells. Currently, we are analyzing these 20 hits to determine if any of these are required for the survival of mutant KRas-dependent cells. Results from these studies have the potential to lead to novel approaches for diagnosing and treating mutant KRas-driven cancers. Citation Format: Vijayendra Agrawal, Bin Fang, Eric A. Welsh, John Koomen, Said M. Sebti. Identification of cell surface proteins expressed exclusively on mutant KRas-dependent cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 767.
Abstract 3355: Clock genes DEC1 and BMAL1 regulate the expression of stem cell marker genes Sox2 and c-Myc in cervical cancer
Authors: Fuyuki Sato, Yasueru Muragaki
Journal: Cancer Research (2018)

Abstract It has been reported that abnormalities of clock genes are associated with tumor progression. Clock genes CLOCK, BMAL1/2, Differentiated embryonic chondrocyte gene (DEC)1/2, PER1/2/3 and CRY1/2 play important roles in the regulation of cell proliferation, cell cycle, apoptosis, epithelial to mesenchymal transition (EMT) and metastasis. We have shown that DEC1 is highly expressed in pancreatic cancer and oral cancer cells compared with non-tumor cells. However, the expression of clock genes is not well understood in cervical cancer. In this study, we focused on the expression of DEC1, DEC2 and BMAL1 in human cervical cancer tissues, examining their expression in biopsy and surgical resection samples by immunohistochemistry. As a result, DEC1 was strongly positive in tumor cells compared with adjacent non-tumor cells. Especially, the positive cells were observed in the front lesions of the tumors, suggesting that DEC1 is associated with invasion. The positive staining of vimentin was also observed in the same lesions where DEC1 was positive. On the other hand, no obvious significant difference in DEC2 expression was observed between tumor cells and non-tumor cells. For BMAL1, we found a week staining in the tumor cells compared with non-tumor cells. In addition, we examined the expression of stem cell marker Sox2 and c-Myc in cancer tissues. They were highly expressed in tumor cells compared with the adjacent non-tumor cells. Furthermore, Sox2 was expressed in metastatic lesions higher than the primary sites. These results suggest that clock genes DEC1 and BMAL1 may promote progression of cervical cancer, regulating Sox2 and c-Myc expression. Citation Format: Fuyuki Sato, Yasueru Muragaki. Clock genes DEC1 and BMAL1 regulate the expression of stem cell marker genes Sox2 and c-Myc in cervical 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 3355.
Loss of Matrix Metalloproteinase-9 or Matrix Metalloproteinase-12 Protects Apolipoprotein E–Deficient Mice Against Atherosclerotic Media Destruction but Differentially Affects Plaque Growth
Authors: AernoutLuttun, EstherLutgens, AnnManderveld, KatleenMaris, DésiréCollen, PeterCarmeliet, LieveMoons
Journal: Circulation (2004)

Background— Epidemiological and histological evidence implicates proteinases of the matrix metalloproteinase (MMP) family in atherosclerosis and aneurysm formation. We previously indicated a role for urokinase-type plasminogen activator in atherosclerotic media destruction by proteolytic activation of MMPs. However, the role of specific MMPs, such as MMP-9 and MMP-12, in atherosclerosis remains undefined. Methods and Results— MMP-9– or MMP-12–deficient mice were crossed in the atherosclerosis-prone apolipoprotein E–deficient background and fed a cholesterol-rich diet. Mice were killed at 15 or 25 weeks of diet to study intermediate and advanced lesions, respectively. Loss of MMP-9 reduced atherosclerotic burden throughout the aorta and impaired macrophage infiltration and collagen deposition, while MMP-12 deficiency did not affect lesion growth. MMP-9 or MMP-12 deficiency conferred significant protection against transmedial elastin degradation and ectasia in the atherosclerotic media. Conclusions— This st...
Abstract 4541: <i>MET</i> gene copy number gains evaluated by NGS is more predictive than other methods to enrich for papillary RCC patients sensitive to savolitinib, a selective MET inhibitor
Authors: Melanie M. Frigault, Sabina Signoretti, Aleksandra Markovets, Daniel Stetson, William Howat, Martine Roudier, Vincent Haddad, Brian Dougherty, Toni K. Choueiri, J. Carl Barrett
Journal: Cancer Research (2018)

Abstract There is no approved therapy specifically for the treatment of papillary renal cell carcinoma (PRCC). Advances in molecular profiling of PRCC have identified a segment of PRCC with 10% MET mutation rates (Linehan et al 2016). Chromosome 7 gain is a hallmark of PRCC and thought to occur at 50% frequency in PRCC (Jiang et al 1998). We undertook a retrospective analysis of archival tumors to evaluate MET pathway aberrations for correlation with efficacy in a phase II study of savolitinib (volitinib, AZD6094, HMPL-504) in patients with PRCC (NCT02127710). Archival diagnostic tumor samples were mandated for central confirmation of PRCC diagnosis, histological subtyping, and for exploratory biomarker analysis. Eighty-four archival tumors were obtained and profiled using four methods: H&amp;E stain for PRCC histological subtype, immunohistochemistry (IHC) for c-Met protein expression (Ventana, CONFIRM), fluorescent in situ hybridization (FISH) for MET gene amplification (Abbott, VYSIS), and Next Generation Sequencing (NGS) as an orthogonal method for confirmation of MET amplifications, detection of HGF gene amplifications, MET mutations, chromosome 7 ploidy, and other exploratory genomic biomarkers (Foundation Medicine Inc., T7 panel). Eight patients with a confirmed partial response (PR) to savolitinib were used to define MET-driven PRCC. Retrospective analysis demonstrated that only NGS, not IHC, FISH or histological subtype, identified all PRs. NGS detected any one of the following biomarkers alone or in combination in PRs: chromosome 7 copy number gain, MET or HGF gene focal amplification, MET kinase domain mutations. The frequency of these biomarkers in the phase II population were 31.5%, 10%, 1%, and 7.5%, respectively and captured all responders (18% ORR); however, 42% of non-responders (PD and SD) were also classified as MET-driven by NGS. Focal MET amplifications were confirmed with MET FISH testing, but FISH was unable to identify gains in chromosome 7. IHC was not as sensitive as NGS (57% vs 100%) but had a higher specificity. Molecular characterization of MET status was more predictive of response to savolitinib than a classification based on pathology. Citation Format: Melanie M. Frigault, Sabina Signoretti, Aleksandra Markovets, Daniel Stetson, William Howat, Martine Roudier, Vincent Haddad, Brian Dougherty, Toni K. Choueiri, J. Carl Barrett. MET gene copy number gains evaluated by NGS is more predictive than other methods to enrich for papillary RCC patients sensitive to savolitinib, a selective MET inhibitor [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 4541.
Abstract 3202: Radiation increases invasive activity of breast cancer cells via altering lysosome exocytosis
Authors: Ping-Hsiu Wu, Yasuhito Onodera, Amato J. Giaccia, Quynh-Thu Le, Hiroki Shirato, Jin-Min Nam
Journal: Cancer Research (2018)

Abstract Radiotherapy is a standard treatment for many localized solid cancers. However, previous studies have shown that radiation may increase the invasive activity of cancer cells and potentially distant metastasis. Recently, lysosome exocytosis has been linked to cancer cell invasiveness and progression. In this study, we evaluate the role of lysosome exocytosis on invasive activity of breast cancer cells upon radiation.We used both human and murine breast cancer cell lines (MDA-MB-231 and 4T1). The cells were treated with a single radiation dose of 4 Gy. Cell invasive activity was measured by matrigel chemoinvasion assay. Lysosome exocytosis was quantified by fluorescein isothiocyanate conjugated dextran (FITC-dextran) intake assay, cell-surface lysosomal associated membrane protein 1 (LAMP1) expression and cellular lysosome distribution assay. To validate the lysosome function, lysosome inhibitors, bafilomycin A1 and chloroquine were used. Short hairpin RNA (shRNA) was used to knockdown ARL8B, which is a small GTPase protein that regulates lysosome distribution and exocytosis. The invasive activity and lysosome exocytosis of tested breast cancer cell lines were increased after radiation treatment. Treatment with lysosome inhibitor bafilomycin A1 or chloroquine decreased the invasive activity of cancer cells, with or without radiation treatment. The protein level of ARL8B increased in the lysosome fraction upon radiation. Down-regulation of ARL8B with shRNA led to a decrease in lysosome exocytosis with a concomitant inhibition radiation induced invasive activity of the breast cancer cells without affecting the basal invasiveness. In addition, overexpression of ARL8B increased the invasive activity of breast cancer cells, which was similar to the result obtained after radiation.In summary, radiation enhances lysosome exocytosis in breast cancer cells that can lead to their increased invasive activity. Our findings provide a novel mechanism to understand cancer invasion after radiotherapy and suggest novel approaches to counteract this undesirable effect of radiotherapy in the future. Citation Format: Ping-Hsiu Wu, Yasuhito Onodera, Amato J. Giaccia, Quynh-Thu Le, Hiroki Shirato, Jin-Min Nam. Radiation increases invasive activity of breast cancer cells via altering lysosome exocytosis [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 3202.
Association of dietary macronutrient composition and non-alcoholic fatty liver disease in an ageing population: the Rotterdam Study
Authors: Louise JM Alferink, Jessica C Kiefte-de Jong, Nicole S Erler, Bart J Veldt, Josje D Schoufour, Robert J de Knegt, M Arfan Ikram, Herold J Metselaar, Harry LA Janssen, Oscar H Franco, Sarwa Darwish Murad
Journal: Gut (2018)

Objective A healthy lifestyle is the first-line treatment in non-alcoholic fatty liver disease (NAFLD), but specific dietary recommendations are lacking. Therefore, we aimed to determine whether dietary macronutrient composition is associated with NAFLD. Design Participants from the Rotterdam Study were assessed on (1) average intake of macronutrients (protein, carbohydrate, fat, fibre) using a Food Frequency Questionnaire and (2) NAFLD presence using ultrasonography, in absence of excessive alcohol, steatogenic drugs and viral hepatitis. Macronutrients were analysed using the nutrient density method and ranked (Q1–Q4). Logistic regression analyses were adjusted for sociodemographic, lifestyle and metabolic covariates. Moreover, analyses were adjusted for and stratified by body mass index (BMI) (25 kg/m 2 ). Also, substitution models were built. Results In total, 3882 participants were included (age 70±9, 58% female). NAFLD was present in 1337 (34%) participants of whom 132 were lean and 1205 overweight. Total protein was associated with overweight NAFLD after adjustment for sociodemographic and lifestyle covariates (OR Q4vsQ1 1.40; 95% CI 1.11 to 1.77). This association was driven by animal protein (OR Q4vsQ1 1.54; 95% CI 1.20 to 1.98). After adjustment for metabolic covariates, only animal protein remained associated with overweight NAFLD (OR Q4vsQ1 1.36; 95% CI 1.05 to 1.77). Monosaccharides and disaccharides were associated with lower overall NAFLD prevalence (OR Q4vsQ1 0.66; 95% CI 0.52 to 0.83) but this effect diminished after adjustment for metabolic covariates and BMI. No consistent associations were observed for fat subtypes or fibre. There were no substitution effects. Conclusion This large population-based study shows that high animal protein intake is associated with NAFLD in overweight, predominantly aged Caucasians, independently of well-known risk factors. Contrary to previous literature, our results do not support a harmful association of monosaccharides and disaccharides with NAFLD.