tbuckley/cabot-search huggingface dataset:
Experimental Reversal of Capillary Blood Flow
Authors: Rayheimbecker, Vivienthomas, Alfredblalock
Journal: Circulation (1951)

Beck, Sciaroni and others have made clinical and experimental attempts to reverse the direction of flow of blood across the capillary bed by the anastomosis of arteries and veins. The present authors have shown by the microscopic observation of capillaries in acute experiments on cats, dogs and rabbits that a reversal of blood flow in mesenteric capillaries will occur following the connection of an artery to a vein provided the collateral arteries and veins are obstructed. Furthermore, it was shown that blood flowing in a reverse direction through capillaries loses oxygen.
Abstract 809: Afatinib restrains K-RAS driven lung tumorigenesis
Authors: Herwig P. Moll, Klemens Pranz, Monica Musteanu, Luka Brcic, Helmut Popper, Judit Moldvay, Balázs Dome, Emilio Casanova
Journal: Cancer Research (2018)

Abstract Lung cancer is still the leading cause of cancer deaths worldwide. While it is well documented that patients suffering from epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) benefit from (EGFR) inhibition, there are still no successful targeted therapies for oncogenic mutations in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene available. Indeed, based on clinical trials using first generation EGFR tyrosine kinase inhibitors (TKI) it became a doctrine that K-RAS mutations drive resistance to EGFR inhibition in non-small cell lung cancer (NSCLC). Conversely, we demonstrate here that EGFR signaling is engaged in K-RAS driven lung tumorigenesis both in human and in mice. Genetic mouse models revealed that deletion of Egfr quenches mutant K-ras activity and transiently reduces tumor growth. However, EGFR inhibition initiates a resistance mechanism which involves non-EGFR ERBB family members. This escape mechanism not only clarifies the disappointing outcome of first generation TKI in clinical trials, but also suggests therapeutic potential of pan-ERBB inhibitors. Indeed, by using several experimental models, including genetically engineered mouse models, (patient derived-) xenografts and in vitro experiments, we demonstrate that the FDA approved pan-ERBB inhibitor afatinib formidably reduces K-RAS driven lung tumorigenesis, whereas first generation TKI erlotinib and gefitinib remained ineffective in our models. Altogether, our data strongly suggests revisiting the potential of EGFR TKI in clinical trials for the treatment of K-RAS mutated NSCLC, with a particular focus on pan-ERBB inhibitors, which are readily available. Citation Format: Herwig P. Moll, Klemens Pranz, Monica Musteanu, Luka Brcic, Helmut Popper, Judit Moldvay, Balázs Dome, Emilio Casanova. Afatinib restrains K-RAS driven lung tumorigenesis [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 809.
Abstract 5570: Analytical and clinical validation of blood-based NGS panel for detection of genomic alterations in DNA repair pathways
Authors: Xiaohong Wang, Jianjun Yu
Journal: Cancer Research (2018)

Abstract Response to DNA-damaging agents, such as PARP inhibitors (PARPi), is associate with homologous recombination deficiency (HRD). In fact, patients with advanced breast, prostate, and ovarian cancers who carry harmful mutations in BRCA1/2 have benefited greatly from olaparib, niraparib, and rucaparib as reported in multiple clinical trials. However, current available assays either require tumor biopsy which may be of insufficient quantity or unobtainable or only examine very limited genes such as BRCA1, BRCA2, and ATM from patient blood. We recently developed a blood-based NGS panel to accurately detect genomic alterations in 51 genes related to DNA damage and repair. With in-house proprietary ultra-sensitive DeepSeaTM(Deterministic, Efficient, Precise, Sensitive Algorithm) variant detection algorithm, analytical performance was rigorously assessed via serial dilutions of reference materials and also further validated by clinical plasma samples in prostate, ovarian, lung and breast cancer. Key words: cfDNA, DNA damage repair, PARP, BRCA1, BRCA2, liquid biopsy, biomarker Citation Format: Xiaohong Wang, Jianjun Yu. Analytical and clinical validation of blood-based NGS panel for detection of genomic alterations in DNA repair pathways [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 5570.
Abstract 5739: Targeting EZH2 histone methyltransferase activity alleviates inflammatory bowel disease
Authors: Haixia Long, Jie Zhou, Zhongyu Wang, Shuo Huang, Bo Zhu
Journal: Cancer Research (2018)

Abstract Objective: Inflammation plays crucial roles in the pathogenesis of inflammatory bowel disease (IBD). Enhancer of zeste homolog 2 (EZH2)-mediated trimethylation of histone 3 lysine 27 (H3K27m3) is critical to immune regulation. However, evidence is lacking to address the effect of EZH2 enzyme's activity on intestinal immune responses during IBD. This study aimed to explore the effects of targeting EZH2 methyltransferase activity on IBD progression in mice. Design: EZH2's enzymatic activity inhibitor GSK343 or GSK126 were delivered by intravenous injection to C57BL/6 mice at the onset, or during the ongoing of IBD, induced by dextran sodium sulfate (DSS). Azoxymethane (AOM)/DSS protocol was applied to trigger colitis-associated colorectal cancer (CAC). Immune cells in the colon of colitis mice were analyzed by flow cytometry, immunofluorescence staining and myeloid-derived suppressor cells (MDSCs) deletion experiments. We differentiated mouse hematopoietic progenitor cells (HPCs) into MDSCs in vitro to investigate the effect of GSK343 on MDSCs generation. Results: Inhibition of EZH2 activity significantly attenuated IBD-related symptoms and inflammation, substantially delaying the onset of CAC. Injection of GSK343 increased the number of functional MDSCs in the colons during IBD. Deletion of MDSCs abrogated the protective effects of GSK343 on IBD. Moreover, inhibition of EZH2 activity promoted the generation of MDSCs from HPCs. Conclusion: Inhibition of EZH2 activity alleviates DSS-induced colitis by promoting MDSC development, and might serve as a new therapeutic strategy to treat IBD. Additionally, EZH2 inhibition enhances MDSC generation, therefore, EZH2 enzymatic inhibitors now in clinical trials for cancer treatment may hinder beneficial anticancer immunity responses. Citation Format: Haixia Long, Jie Zhou, Zhongyu Wang, Shuo Huang, Bo Zhu. Targeting EZH2 histone methyltransferase activity alleviates inflammatory bowel disease [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 5739.
Detection of Fibrous Cap in Atherosclerotic Plaque by Intravascular Ultrasound by Use of Color Mapping of Angle-Dependent Echo-Intensity Variation
Authors: TakafumiHiro, TakashiFujii, KyounoriYasumoto, TakashigeMurata, AkihiroMurashige, MasunoriMatsuzaki
Journal: Circulation (2001)

Background—The thickness of the fibrous cap is a major determinant in the vulnerability of atherosclerotic plaque to rupture. It has been demonstrated that intravascular ultrasound (IVUS) backscatter from fibrous tissue is strongly dependent on the ultrasound beam angle of incidence. This study investigated the feasibility of using a new IVUS color mapping technique representing the angle-dependent echo-intensity variation to determine the thickness of the fibrous cap in atherosclerotic plaque. Methods and Results—Nineteen formalin-fixed noncalcified human atherosclerotic plaques from necropsy were imaged in vitro with a 30-MHz IVUS catheter. The IVUS catheter was moved coaxially relative to the plaque. The images showing maximum and minimum echo intensity of the plaque surface were selected to calculate the angle-dependent echo-intensity variation. A colorized representation of the echo-intensity variation in the plaque was obtained from the 2 IVUS images. A clearly bordered area with large variation in ...
Serial Angioscopic Evidence of Incomplete Neointimal Coverage After Sirolimus-Eluting Stent Implantation
Authors: MasakiAwata, Jun-ichiKotani, MasaakiUematsu, TakakazuMorozumi, TetsuyaWatanabe, ToshinariOnishi, OsamuIida, FusakoSera, ShinsukeNanto, MasatsuguHori, SeikiNagata
Journal: Circulation (2007)

Background— The time course of neointimal formation after stent implantation has not been studied extensively by angioscopy in the drug-eluting stent era. Methods and Results— Serial angioscopic findings at first follow-up (3.6±1.1 months), second follow-up (10.5±1.6 months), and third follow-up (21.2±2.2 months) after stent implantation were compared between sirolimus-eluting stents (SES, n=17) and bare-metal stents (BMS, n=11). Neointimal coverage, thrombus, and presence of yellow plaques underneath the stents were assessed. Neointimal coverage was graded as follows: grade 0, stent struts were fully visible; grade 1, struts bulged into the lumen, although they were covered; grade 2, struts were embedded by the neointima but were seen translucently; or grade 3, struts were fully embedded and invisible. Neointimal coverage was remarkably different between SES and BMS at each follow-up point. Neointimal coverage grade was 1.1±0.5 in SES versus 2.9±0.3 in BMS at the first follow-up (P<0.0001), 1.1±0.5 in SE...
Tools for Evaluating and Improving Causal Inference
Authors: Mark D. Huffman, Laine E. Thomas
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
Subcutaneous panniculitis-like T-cell lymphoma: Clinical features, therapeutic approach, and outcome in a case series of 16 patients
Authors: Ingrid López-Lerma, Yeray Peñate, Fernando Gallardo, Rosa M. Martí, Josune Mitxelena, Isabel Bielsa, Virginia Velasco-Tamariz, Juan I. Yanguas-Bayona, Pedro Sánchez-Sambucety, Vicente García-Patos, Pablo L. Ortiz-Romero, Ramón M. Pujol, Teresa Estrach
Journal: Journal of the American Academy of Dermatology (2018)
Abstract 134: Dysbiosis of gut microbiota in chronic stressed patients with endometriosis
Authors: Jing Xu, Yu Kang, Yinhua Yu
Journal: Cancer Research (2018)

Abstract Although endometriosis is a benign disease, it has malignant characters such as invasion and migration. Besides, there is an endometrial type of ovarian cancer, which means endometriosis is similar to malignant disease at some extent. Existing researches showed that patients with endometriosis often have high level of chronic stress. Furthermore, chronic stress can promote the growth of endometriosis by activating the β-adrenergic signaling pathway. Gut microbiota is reported to be related to the stress level through the gut-brain axis. So we wonder whether gut microbiota is associated with chronic stress level in endometriosis patients, which may provide a new clinical intervention method to improve prognosis. We grouped the endometriosis patients into stress group and control group with GAD-7 and PHQ-9 questionnaires and collected patients' fecal and tissues samples. Gut microbiota compositions were analyzed by the 16SrRNA gene sequencing-based method and we performed Immunohistochemistry (IHC) to detect the activation of inflammatory pathways in endometriosis tissues. We found that in patients with endometriosis, dysbiosis of gut microbiota is associated with patients' stress levels and Paraprevotella, Odoribacter, Veillonell and Ruminococcus show significant differences with reduced levels in chronic stressed endometriosis patients group, which represents a disease-specific change of gut microbiota on the genus level. Besides, compared to the control group, the expression level of inflammatory cytokines, NF-κB p65 and COX-2, increased in the chronic stressed patients group, which means that dysbiosis of gut microbiota may active the inflammatory pathway of gut-brain axis. In conclusion, we found new disease-specific changes of gut microbiota in chronic stressed patients with endometriosis, which can be a new examination target of chronic stress level and may provide an adjuvant therapy method for clinical psychological intervention, reducing the stress level and improving the prognosis of endometriosis patients. Citation Format: Jing Xu, Yu Kang, Yinhua Yu. Dysbiosis of gut microbiota in chronic stressed patients with endometriosis [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 134.
A Simple Geometric Analysis of Cardiac Potentials as Recorded at Points Close to the Heart
Authors: Manuelgardberg
Journal: Circulation (1954)

A simple geometric method is employed to investigate the theoretically expected potentials at an electrode close to the heart as a dipole moves about in an area in the chest occupied by the heart. The considerable error resulting from the assumption that the dipole remains at the center of a geometric frame of reference is thus disclosed. It is pointed out that errors in polarity which occur cannot be compensated for by alteration of the characteristics of the recording device. It is suggested that such errors account for the finding by spatial vectorcardiographers that many normal QRS loops point forward, a finding which does not correlate well with the Gardberg-Ashman hypothesis of ventricular accession. It is further suggested that the limb leads are not free of these effects and that exaggeration of the electrical rotation of the heart is thus accounted for. It is further pointed out that derivation of precordial potentials from vector loops or vice versa is not permissible.
Is the Extracardiac Conduit the Preferred Fontan Approach for Patients With Univentricular Hearts?
Authors: Brian Kogon
Journal: Circulation (2012)

W ith improvements in technology, operative technique, and critical care medicine, more and more children with congenital heart disease are surviving into adulthood.As they age, these patients are providing physicians with new challenges, and we are realizing the long-term consequences of our previous interventions.This oftentimes has changed the mode of treatment for subsequent children.
Abstract 4847: Evaluation of the combination of olaparib and cediranib in small-cell lung cancer cells
Authors: Naoto Morikawa, Monique B. Nilsson, Irene Guijarro, You-Hong Fan, Alissa Poteete, John V. Heymach
Journal: Cancer Research (2018)

Abstract Metastatic Small cell lung cancer (SCLC) is exceptionally lethal, having a median survival of 9-10 months from the time of diagnosis and a 5 year survival rate of less than 2 percent. More effective treatment approaches to SCLC are desperately needed. Poly ADP-ribose polymerase (PARP) inhibitor such as olaparib exploit the concept of synthetic lethality by selectively targeting cancer cells with defective DNA repair pathways. Preclinical data indicates that SCLC cell lines overexpress PARP and are sensitive to PARP inhibition, and PARP inhibitors show promise in the clinical setting of SCLC. The identification of combination regimens that potentiate the efficacy of PARP inhibition would be of great clinical value. Recent findings indicate that olaparib and the vascular endothelial growth factor receptor (VEGFR) inhibitor, cediranib, is an effective therapeutic combination in patients with BRCA wild-type ovarian cancer. Therefore, we evaluated the efficacy of the olaparib and cediranib combinations in SCLC models. Human SCLC cell lines, NCI-H841, H526, COR-L24 and murine SCLC cell line TKOmTmG were sensitive to olaparib or cediranib therapy in vitro as determined by Cell Titer Glo® assay. Moreover, a significantly greater effect on cell viability was observed when olaparib and cediranib were used in combination. Likewise, in H841 xenograft models, single agent treatment of olaparib or cediranib inhibited tumor growth, and combination treatment of olaparib plus cediranib induced tumor regression. Western blot analysis indicated that treatment with cediranib or the combination of olaparib and cediranib induced PD-L1 protein expression both in vivo and in vitro. In TKOmTmG xenograft model in syngeneic mice, programmed death-ligand 1 (PD-L1) inhibitor plus olaparib or olaparib/cediranib combination resulted in superior combined efficacy compared to the respective single agent therapies in terms of tumor growth inhibition. These data indicate that olaparib plus cediranib may be an effective therapeutic strategy for the treatment of SCLC. Further study is warranted to understand the mechanism of action and clinical activity. Citation Format: Naoto Morikawa, Monique B. Nilsson, Irene Guijarro, You-Hong Fan, Alissa Poteete, John V. Heymach. Evaluation of the combination of olaparib and cediranib in small-cell lung 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 4847.
Cellular Basis for the Normal T Wave and the Electrocardiographic Manifestations of the Long-QT Syndrome
Authors: Gan-XinYan, CharlesAntzelevitch
Journal: Circulation (1998)

Background—This study probes the cellular basis for the T wave under baseline and long-QT (LQT) conditions using an arterially perfused canine left ventricular (LV) wedge preparation, which permits direct temporal correlation of cellular transmembrane and ECG events. Methods and Results—Floating microelectrodes were used to record transmembrane action potentials (APs) simultaneously from epicardial, M-region, and endocardial sites or subendocardial Purkinje fibers. A transmural ECG was recorded concurrently. Under baseline and LQT conditions, repolarization of the epicardial action potential, the earliest to repolarize, coincided with the peak of the T wave; repolarization of the M cells, the last to repolarize, coincided with the end of the T wave. Thus, the action potential duration (APD) of the longest M cells determine the QT interval and the Tpeak–Tend interval serves as an index of transmural dispersion of repolarization. Repolarization of Purkinje fibers outlasted that of the M cell but failed to r...
Downregulation of Endothelin-1 by Farnesoid X Receptor in Vascular Endothelial Cells
Authors: FengtianHe, JiangLi, YingMu, RamalingaKuruba, ZhengMa, AnnetteWilson, SeanAlber, YuJiang, TroyStevens, SimonWatkins, BrucePitt, WenXie, SongLi
Journal: Circulation Research (2006)

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidney, adrenals, and intestine. FXR may play an important role in the pathogenesis of cardiovascular diseases via regulating the metabolism and transport of cholesterol. In this study, we report that FXR is also expressed in rat pulmonary artery endothelial cells (EC), a “nonclassical” bile acid target tissue. FXR is functional in EC, as demonstrated by induction of its target genes such as small heterodimer partner (SHP) after treatment with chenodeoxycholic acid, a FXR agonist. Interestingly, activation of FXR in EC led to downregulation of endothelin (ET)-1 expression. Reporter assays showed that activation of FXR inhibited transcriptional activation of the human ET-1 gene promoter and also repressed the activity of a heterologous promoter driven by activator protein (AP)-1 response elements. Electrophoretic mobility-shift and chromatin immunoprecipitation assays indicated that FXR reduced...
Abstract 1001: Gut microbiota modulate T cell trafficking into human colorectal cancer
Authors: Eleonora Cremonesi, Valeria Governa, Jesus Garzon, Valentina Mele, Francesca Amicarella, Manuele G. Muraro, Raoul Droeser, Martin Bolli, Julia Slotta-Huspenina, Luigi Terracciano, Paul Zajac, Giulio C. Spagnoli, Serenella Eppenberger-Castori, Klaus-Peter Janssen, Lubor Borsig, Giandomenica Iezzi
Journal: Cancer Research (2018)

Abstract Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related death. CRC infiltration by immune cells, including cytotoxic CD8+ T cells (CTLs), IFN-gamma-producing T-helper 1 cells (Th1), Foxp3+ regulatory T cells (Tregs) and CD16+ MPO+ neutrophils, is associated with favorable prognosis. However, chemokines driving these cell populations into the tumor site, their cellular sources and their microenvironmental triggers remain to be elucidated. Aim: We investigated the chemokine/chemokine receptor network promoting CRC infiltration by immune cells associated to favorable prognosis. Results: CRC infiltration by immune cells was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper 1 cells, and CCL17, CCL22 and CXCL12 for T-helper 1 and regulatory T cells. Most of these chemokine genes were expressed by tumor cells upon exposure to gut bacteria in vitro and in vivo. Indeed, chemokine expression levels were significantly higher in orthotopic xenografts than in intraperitoneal tumors, and were drastically reduced by antibiotic treatment of tumor-bearing mice. Importantly, in human CRC samples, extents of chemokine production and immune cell infiltration was significantly associated with bacterial loads. Conclusion: Gut microbiota stimulates chemokine production by CRC cells, thus favoring T cell recruitment into tumor tissues. Citation Format: Eleonora Cremonesi, Valeria Governa, Jesus Garzon, Valentina Mele, Francesca Amicarella, Manuele G. Muraro, Raoul Droeser, Martin Bolli, Julia Slotta-Huspenina, Luigi Terracciano, Paul Zajac, Giulio C. Spagnoli, Serenella Eppenberger-Castori, Klaus-Peter Janssen, Lubor Borsig, Giandomenica Iezzi. Gut microbiota modulate T cell trafficking into human 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 1001.