tbuckley/cabot-search huggingface dataset:
Hepatocyte nuclear factor 4α-nuclear factor-κB feedback circuit modulates liver cancer progression
Authors: Bei-Fang Ning, Jin Ding, Jiao Liu, Chuan Yin, Wen-Ping Xu, Wen-Ming Cong, Qing Zhang, Fei Chen, Tao Han, Xing Deng, Pei-Qin Wang, Cai-Feng Jiang, Jun-Ping Zhang, Xin Zhang, Hong-Yang Wang, Wei-Fen Xie
Journal: Hepatology (2014)

Hepatocyte nuclear factor 4α (HNF4α) is a liver enriched transcription factor and is indispensable for liver development. However, the role of HNF4α in hepatocellular carcinoma (HCC) progression remains to be elucidated. We report that reduced HNF4α expression correlated well with the aggressive clinicopathological characteristics of HCC and predicted poor prognosis of patients. HNF4α levels were even lower in metastatic HCCs, and ectopic HNF4α expression suppressed the metastasis of hepatoma cells both in vitro and in vivo . Forced HNF4α expression attenuated the expression and nuclear translocation of RelA (p65) and impaired NF-κB activation through an IKK-independent mechanism. Blockage of RelA robustly attenuated the suppressive effect of HNF4α on hepatoma cell metastasis. MicroRNA (miR)-7 and miR-124 were transcriptionally up-regulated by HNF4α, which repressed RelA expression by way of interaction with RelA-3′ untranslated region (UTR). In addition, nuclear factor kappa B (NF-κB) up-regulated the expression of miR-21 in hepatoma cells, resulting in decreased HNF4α levels through down-regulating HNF4α-3′UTR activity. Conclusions : Collectively, an HNF4α-NF-κB feedback circuit including miR-124, miR-7, and miR-21 was identified in HCC, and the combination of HNF4α and NF-κB exhibited more powerful predictive efficiency of patient prognosis. These findings broaden the knowledge of hepatic inflammation and cancer initiation/progression, and also provide novel prognostic biomarkers and therapeutic targets for HCC. (Hepatology 2014;60:1607-1619)
Effects of Breast Augmentation on Accuracy of Mammography
Authors: Deborah J. Steiner, Robert G. Schwager, Don J. Lewittes
Journal: JAMA (2004)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Endothelin receptor B (ETBR) dependent GM-CSF mRNA stabilization explains the higher efficacy of bosentan vs. ambrisentan in the reduction of GM-CSF release from human airway smooth muscle cells (HASMCs)
Authors: David Jungck, Juergen Knobloch, Katja Urban, Erich Stoelben, Justus Strauch, Juergen Behr, Andrea Koch
Journal: European Respiratory Journal (2011)

Introduction: TNFα and GM-CSF are pivotal in chronic inflammatory airway diseases and lung fibrosis. TNFα-induced Endothelin-1 (ET-1) release is required for full TNFα induced GM-CSF transcription in HASMCs suggesting anti-inflammatory potential of endothelin receptor antagonists (ERA). The MAP-Kinase ERK protects GM-CSF mRNA from degradation. Ambrisentan (ETAR blocker) and bosentan (dual blocker) are available for PAH therapy.

Aim: We compared the anti-inflammatory potential of bosentan vs. ambrisentan.

Methods: HASMC culture, qRT-PCR, ELISA.

Results: TNFα and ET-1 induce transcription and release of ET-1 and GM-CSF (each p<0.05). Bosentan reduces GM-CSF release more efficiently than ambrisentan (p<0.01; EC50: 4.5 vs. 11×10-8M; EMAX: 63.7 vs. 54.8% reduction; n=9) but both block GM-CSF transcription similarly. Specific ETBR inhibition (BQ 788) also reduces GM-CSF mRNA. Combined blocking of ETAR (ambrisentan) and ERK activity (PD 098059) leads to a greater reduction of GM-CSF release than single inhibition (each p<0.05). In the presence of actinomycin D which blocks gene transcription bosentan leads to a significantly greater reduction of GM-CSF mRNA than ambrisentan (p<0.01).

Conclusion: Following TNFa-induced ET-1 release, ETAR induces GM-CSF transcription and ETBR signals via ERK to protect GM-CSF mRNA from degradation. This can explain why bosentan reduces TNFα induced GM-CSF release more effectively than ambrisentan. Thus, bosentan may be superior in the therapy of early stages of chronic airway diseases by preventing the establishment of inflammation.
815. Investigation into the Frequency of Post-Integrative Gene Silencing Using a Non-Selective Sleeping Beauty Transposition System
Authors: Sonia Moreno, Florian Sack, Colin Smith, Luisa Lopez-Fuertes, Antonio J. Vila-Coro, Sven A. König-Merediz, Burghardt Wittig, Matthias Schroff, Manuel Schmidt, Marcos Timon
Journal: Molecular Therapy (2004)

Plasmid vectors currently used for DNA vaccination contain many sequences including antibiotic resistance genes which are not needed for the vaccine and that can potentially be dangerous for the host, i.e. in inducing allergic responses. We have developed linear, covalently-closed minimalistic vectors (MIDGE) containing only the expression cassette. MIDGE are a safe and more efficient alternative to plasmids at inducing protective immune responses in DNA vaccination protocols (i.e. hepatitis or leishmania models). More importantly, MIDGE vectors can be chemically modified at both ends by the specific linking of peptides, proteins, sugars, antibodies, biotin etc. We performed experiments to evaluate the effect of the covalent attachment of a short peptide of 11 aminoacids (Pro-Lys-Lys-Lys-Arg-Lys-Val-Glu-Asp-Pro-Tyr) to the MIDGE, a new vector type termed MIDGE-TH 1P. MIDGE-TH1P led to a drastic enhancement of antigenicity, lowered the necessary amount of DNA for detection of antibody response and an earlier onset of measurable antibody titers in vivo. In further mice experiments a pronounced shift of the cytokine profile accompanying the response towards the TH1 type was detected: MIDGE-TH1P resulted in a higher IgG2a/IgG1 ratio, a strong induction of IFN-γ producing antigen-specific CD8+ and more IFN-γ producing CD4+ T-cells compared to plain MIDGE and plasmid vectors. In vitro stimulation of both mouse and human PBMCs confirmed the TH1 shift as measured by the increased production of IL12p40 induced by MIDGE-TH1P vectors (in comparison to plain MIDGE and plasmid as well). These advantages are recently being exploited in several applications where a quicker immune response and/or a TH1-type response are required. Although the mechanism underlying these effects is still unknown, preliminary evidence suggests a direct activation of dendritic cells by this linear DNA-peptide structure as the most likely candidate.
Endemic fungal infections caused by Cryptococcus neoformans and Penicillium marneffei in patients infected with human immunodeficiency virus and treated with highly active anti-retroviral therapy
Authors: H.-Y. Sun, M.-Y. Chen, C.-F. Hsiao, S.-M. Hsieh, C.-C. Hung, S.-C. Chang
Journal: Clinical Microbiology and Infection (2006)
Depsipeptide (FR901228): A Novel Therapeutic Agent With Selective, In Vitro Activity Against Human B-Cell Chronic Lymphocytic Leukemia Cells
Authors: John C. Byrd, Charlotte Shinn, Rajani Ravi, Carl R. Willis, Jamie K. Waselenko, Ian W. Flinn, Nancy A. Dawson, Michael R. Grever
Journal: Blood (1999)
Coeliac disease specific antigen found
Authors: Abi Berger
Journal: BMJ (2000)

The discovery of a coeliac disease specific antigen could offer a new route for treatment of the condition. Dr Robert Anderson and his colleagues at the Institute of Molecular Medicine in Oxford have identified a peptide in wheat that elicits a specific immune response in people with coeliac disease.

If this immune response could be blocked, then the need to stick to a gluten free diet could become obsolete (Nature Medicine 2000;6:337-42).

Dr Anderson, a gastroenterologist, and his team set out to find the toxic part of the gluten molecule. It is already known that gluten can be separated into …
Cardiac mechano-electric coupling: a role in regulating normal function of the heart?: Figure 1
Authors: T. Alexander Quinn
Journal: Cardiovascular Research (2015)

This editorial refers to ‘Synchronization of repolarization by mechano-electrical coupling in the porcine heart’ by T. Opthof et al ., doi:10.1093/cvr/cvv140. 

At the most basic level, the heart is an electrically controlled pump. As such, our attention tends to focus on the feed-forward mechanisms by which cardiac excitation, occurring through co-ordinated ion channel activity, leads to the calcium signal necessary for contraction. Yet, it is becoming clear that the heart is intrinsically regulated, including feedback from its mechanical state to ion channel function, electrical conduction, and calcium–myofilament interactions. This essential aspect of intra-cardiac regulation, originally termed Mechano-Electric Feedback, is now more generally known as Mechano-Electric Coupling (MEC).1

MEC might seem to be an evolutionary quirk or physiological epiphenomenon. It is now understood, however, to be important in numerous cardiac diseases, for instance contributing to the electrophysiological effects of non-uniform contraction, the reduced arrhythmia threshold accompanying atrial or ventricular enlargement, and the impact of pulmonary vein loading on atrial fibrillation.2 Yet this says nothing about its importance in the healthy heart. Does MEC play a role in regulating normal cardiac function?

The first evidence that MEC may be important for cardiac auto-regulation came 100 years ago, with Francis Arthur Bainbridge's observation that right-atrial distension in anaesthetized dogs results in an acute increase in heart rate. …
Abstract 2968: FTY720 inhibits mutant Kras-induced lung cancer via disrupting Stat3-S1PR1 vicious cycle and downregulating tumor PD-L1 expression
Authors: Hsuan-Heng Yeh, Tsung-I Hsu, Jan-Jong Hung, Wen-Pin Su, Wu-Chou Su
Journal: Cancer Research (2014)

Abstract Aberrant activation of signal transducer and activator of transcription 3 (Stat3) occurs in many cancers and plays a critical role in tumor progression. The system that Stat3-induced Sphingosine-1-phosphate receptor 1 (S1PR1) expression and the S1P-S1PR1 pathway reciprocally regulate Stat3 activity was considered a major positive feedback loop for persistent Stat3 activation in cancer cells and the cells of tumor microenvironment. Tumor cells expressing the ligand for the receptor programmed death-1 (PD-1), PD-L1, have been shown to increase apoptosis of antigen-specific human T-cell to evade the immune system. In this study, we determined the influence of disrupting Stat3-S1PR1 vicious cycle on tumor formation and PD-L1 expression in lung cancer. We have established mutant Kras-induced lung cancer mice model and found that Stat3 phosphorylation was elevated in tumor tissues of lung cancer. Treatment of lung cancer cells with AG490 (JAK2 inhibitor) inhibited Stat3 activation and AG490 administration to the mice decreased the numbers of lung cancer nodules, indicating that blockage of Stat3 activation could inhibit mutant Kras-induced lung cancer in mice. Similar effects were also detected by using Stat3 inhibitor, S3I-201. We found that lung cancer cells expressed more pStat3 showed higher PD-L1 expression levels than that of lower pStat3 expressing cells. Inhibition of Stat3 activation by AG490 decreased PD-L1 expression in vitro and in vivo, indicating that PD-L1 expression could be regulated by Stat3. Moreover, FTY720 (S1P antagonist) could inhibit S1PR1 expression, down-regulate Stat3 activity, pJAK1 expression and inhibit IL-6 secretion in lung cancer cell lines and causes inhibition of the mutant Kras-induced lung cancer in mice. Furthermore, FTY720 administration dose-dependently suppressed tumor PD-L1 expression in mice lung cancer tissues. Taken together, our study indicated that FTY720 could suppress mutant Kras induced-lung cancer formation via inhibiting persistent Stat3 activation and down-regulating tumor PD-L1 expression. Citation Format: Hsuan-Heng Yeh, Tsung-I Hsu, Jan-Jong Hung, Wen-Pin Su, Wu-Chou Su. FTY720 inhibits mutant Kras-induced lung cancer via disrupting Stat3-S1PR1 vicious cycle and downregulating tumor PD-L1 expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2968. doi:10.1158/1538-7445.AM2014-2968
A Randomized Trial of Rosuvastatin in the Prevention of Venous Thromboembolism
Authors: Robert J. Glynn, Eleanor Danielson, Francisco A.H. Fonseca, Jacques Genest, Antonio M. Gotto, John J.P. Kastelein, Wolfgang Koenig, Peter Libby, Alberto J. Lorenzatti, Jean G. MacFadyen, Børge G. Nordestgaard, James Shepherd, James T. Willerson, Paul M Ridker
Journal: New England Journal of Medicine (2009)

Controversy persists regarding the extent of shared pathways between arterial and venous thrombosis and whether treatments of known efficacy for one disease process have consistent benefits for the other. Observational studies have yielded variable estimates of the effect of statin therapy on the risk of venous thromboembolism, and evidence from randomized trials is lacking.We randomly assigned 17,802 apparently healthy men and women with both low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to receive rosuvastatin, 20 mg per day, or placebo. We followed participants for the first occurrence of pulmonary embolism or deep-vein thrombosis and performed analyses of the data on an intention-to-treat basis.During a median follow-up period of 1.9 years (maximum, 5.0), symptomatic venous thromboembolism occurred in 94 participants: 34 in the rosuvastatin group and 60 in the placebo group. The rates of venous thromboembolism were 0.18 and 0.32 event per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio with rosuvastatin, 0.57; 95% confidence interval [CI], 0.37 to 0.86; P=0.007); the corresponding rates for unprovoked venous thromboembolism (i.e., occurring in the absence of a known malignant condition, trauma, hospitalization, or surgery) were 0.10 and 0.17 (hazard ratio, 0.61; 95% CI, 0.35 to 1.09; P=0.09) and for provoked venous thromboembolism (i.e., occurring in patients with cancer or during or shortly after trauma, hospitalization, or surgery), 0.08 and 0.16 (hazard ratio, 0.52; 95% CI, 0.28 to 0.96; P=0.03). The rates of pulmonary embolism were 0.09 in the rosuvastatin group and 0.12 in the placebo group (hazard ratio, 0.77; 95% CI, 0.41 to 1.45; P=0.42), whereas the rates of deep-vein thrombosis only were 0.09 and 0.20, respectively (hazard ratio, 0.45; 95% CI, 0.25 to 0.79; P=0.004). Consistent effects were observed in all the subgroups examined. No significant differences were seen between treatment groups in the rates of bleeding episodes.In this trial of apparently healthy persons, rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism. (ClinicalTrials.gov number, NCT00239681.)
STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients
Authors: V Gouilleux-Gruart, F Gouilleux, C Desaint, JF Claisse, JC Capiod, J Delobel, R Weber-Nordt, I Dusanter-Fourt, F Dreyfus, B Groner, L Prin
Journal: Blood (1996)
Abstract 3896: The Hippo coactivator YAP1 upregulates SOX9 and endows cancer stem cell properties in non-transformed cells and esophageal cancer cells
Authors: Shumei Song, Jaffer A. Ajani, Soichiro Honjo, Dipen M. Maru, Qiongrong Chen, Jiankang Jin, Ailing W. Scott, Todd R. Heallen, Lianchun Xiao, Wayne L. Hofstetter, Brian Weston, Jeffrey H. Lee, Roopma Wadhwa, Kazuki Sudo, James F. Martin, John R. Stroehlein, Mien-Chie Hung, Randy L. Johnson
Journal: Cancer Research (2014)

Abstract Cancer stem cells are proposed to initiate and maintain tumor growth. Dysregulation of normal stem cell signaling may lead to the generation of cancer stem cells (CSCs), however, the molecular determinants of this process remain poorly understood. Here we show that the transcriptional co-activator YAP1 through direct regulation of SOX9 promotes the generation of CSCs and that the inhibition of YAP1 and SOX9 attenuates CSC formation. SOX9 transcripts and expression are upregulated upon YAP1 activation and several lines of evidence indicate that SOX9 is a direct target of YAP1. The Chromatin Immunoprecipitation analysis and luciferase assays demonstrate direct binding of YAP1 to the SOX9 promoter through a conserved TEAD binding site. Mutation of this site abrogates transcriptional regulation of SOX9 by YAP1 and Tead2. Functional studies demonstrate that YAP1 regulation of SOX9 is necessary and sufficient to confer CSC properties and tumorigenesis in vitro and in vivo. The small molecule inhibitor of YAP1, Verteporfin (VP) significantly blocks CSC self-renewal properties in cells with high YAP1 and a high proportion of the CSC marker aldehyde dehydrogenase 1 (ALDH1) indicating that VP targets the CSC population. These data identify YAP1 as a driver of esophageal cancer (EC) stem cells, in part, by regulation of SOX9 and suggest that pharmacological inhibition of YAP1 may be an effective means of specifically targeting EC stem cells. Citation Format: Shumei Song, Jaffer A. Ajani, Soichiro Honjo, Dipen M. Maru, Qiongrong Chen, Jiankang Jin, Ailing W. Scott, Todd R. Heallen, Lianchun Xiao, Wayne L. Hofstetter, Brian Weston, Jeffrey H. Lee, Roopma Wadhwa, Kazuki Sudo, James F. Martin, John R. Stroehlein, Mien-Chie Hung, Randy L. Johnson. The Hippo coactivator YAP1 upregulates SOX9 and endows cancer stem cell properties in non-transformed cells and esophageal cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3896. doi:10.1158/1538-7445.AM2014-3896
Abstract 19570: Diastolic Anterior Leaflet Tethering Contributes to Functional Mitral Stenosis after Restrictive Mitral Valve Annuloplasty
Authors: Philippe B Bertrand, David Verhaert, Christophe J Smeets, Frederik H Verbrugge, Lars Grieten, Wilfried Mullens, Herbert Gutermann, Robert A Dion, Robert A Levine, Pieter M Vandervoort
Journal: Circulation (2014)

Introduction: Restrictive mitral valve annuloplasty (RMA) for secondary mitral regurgitation (MR) might cause functional (mitral) stenosis, yet underlying pathophysiological mechanisms remain debated. Hypothesis: Diastolic restriction of the anterior leaflet (AL) opening, due to papillary muscle tethering, plays a key role in the inflow obstruction after RMA. Increasing AL opening during exercise is associated with greater mitral valve area (MVA). Methods: Consecutive RMA patients (n=39, 63±11 years, 77% male) performed a symptom-limited (supine) bicycle exercise test with stepwise Doppler echocardiography and respiratory gas analysis. Diastolic AL opening angle (3-chamber view, Figure A), transmitral flow rate, mean transmitral gradient, and effective MVA were assessed at rest and during peak exercise. Results: At rest, effective MVA (1.5±0.4cm2) correlated moderately to the AL opening angle (68±10°) (r=0.4, p=0.014; Figure B). During exercise, effective MVA increased significantly to 2.0±0.5cm2 (p&lt;0.001), with a stronger correlation to AL opening angle (r=0.6, p&lt;0.001; Figure B). After stratification of the population into tertiles according to increase in AL opening angle during exercise (&lt;=0°, 0-4° and &gt;4° AL angle increase, respectively), a higher increase was significantly associated with greater effective MVA during exercise (p=0.013, Figure C). Patients with AL opening angle &lt;69° at rest (median) and without dynamic AL angle increase of &gt;4° (n=13) had a significantly lower maximal oxygen uptake compared to patients with AL opening angle at rest above the median or a greater dynamic AL angle increase with exercise (n=22) (VO2max 12.5±2.8 versus 16.4±4.7 mL/kg/min, p=0.005). Conclusions: Diastolic restriction of AL opening plays a key role in functional mitral stenosis after RMA for secondary MR. Increasing AL opening at rest, or better AL opening reserve during exercise, are associated with higher MVA and improved exercise capacity.
Abstract 13425: Nanoparticle-Mediated Monocyte-Selective Delivery of Pitavastatin Inhibits Monocyte Activation and Attenuates Plaque Destabilization and Rupture in ApoE-Deficient Mice
Authors: Shunsuke Katsuki, Tetsuya Matoba, Kaku Nakano, Kei Sato, Kenji Sunagawa, Kensuke Egashira
Journal: Circulation (2010)
Observations on Rheumatic Pancarditis and Infective Endocarditis
Authors: W. S. Thayer
Journal: Annals of Internal Medicine (1931)

Article1 September 1931Observations on Rheumatic Pancarditis and Infective EndocarditisW. S. THAYER, M.D., F.A.C.P.W. S. THAYER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-5-3-247 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWe now know that the endocarditis of rheumatism on which so much stress has been laid in the past is but one of the manifestations of a general process, the most important feature of which, though often not the most prominent, is the cardiac disease. This cardiac disease is a general involvement of the heart in which valvular affections, acute, subacute and chronic, often, but by no means always, play a relatively important part. Indeed in the more acute and not infrequently in the more chronic forms of the malady the changes in the muscle or in the pericardium are... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Baltimore, Md.*Presented at the Baltimore meeting of the American College of Physicians, March 23, 1931.†The Gibson Lectures, Edinb. Med. Jr., 1931, n. s., xxxviii, 237-265, 307-334. In this article numerous references to the literature may be found which have not been included in this communication. For further references the reader is referred to the admirable monograph of Lemierre and Deschamps: Les endocarditis infectieuses, diagnostic et traitement, 1930, 8°, G. Doin et Cie., 1930. Nextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPurulent pneumococcal pericarditisLeft-sided valvular active infective endocarditisPathologische Anatomie der Endocarditis Septica IV. MITTEILUNG DIE MYOCARDVERAENDERUNGENEndokarditis lentaRheumatic manifestations in subacute bacterial endocarditis in children 1 September 1931Volume 5, Issue 3Page: 247-255KeywordsCardiovascular therapyEndocarditisHeart diseasesMusclesPericardium ePublished: 1 December 2008 Issue Published: 1 September 1931 PDF downloadLoading ...