tbuckley/cabot-search huggingface dataset:
Abstract P5-08-06: Differential effects of eribulin on key transcription factors snail and slug
Authors: R Kaul, AL Risinger, SL Mooberry
Journal: Cancer Research (2019)

Abstract Microtubule targeting agents (MTAs) are a mainstay in the treatment of breast cancer and a growing body of evidence demonstrates that they have non-mitotic effects that contribute to their anticancer actions. Even after decades of clinical use, there is much to still be learned about the mechanisms of action these drugs, and differences among them, for optimal utility. MTAs rapidly alter microtubule dynamics, often within minutes, leading to significant changes in oncogenic cellular signaling. We evaluated the early effects of eribulin on key oncogenic signaling pathways following a 2 h incubation using clinically relevant concentrations and compared the effects to those initiated by other MTAs. These studies led to the identification of novel mechanisms by which MTAs disrupt oncogenic signaling and contribute to the reversal of epithelial to mesenchymal transition (EMT), including unanticipated differences among drugs. The TGF-β-mediated expression of the Snail transcription factor is a key driver pathway of EMT in breast cancer. The effects of eribulin and other MTAs on TGF-β-induced, Smad-dependent expression of Snail were evaluated. Our results show that eribulin and vinorelbine, but not paclitaxel or ixabepilone, inhibit the ability of TGF-β to promote the transcriptional induction of Snail by impeding the nuclear transport of Smad2/3 proteins in 4 triple-negative breast cancer cell lines. This study begins to explain how microtubule disruption might contribute to the eribulin-mediated EMT reversal observed in vitro, in vivo, and in patients. Slug is another member of the Snail family of transcription factors that plays a central role in breast cancer EMT. Although Snail and Slug are often grouped together due to functional similarities, it is becoming increasingly clear that Slug has an independent role in regulating stemness and cancer cell survival during partial EMT. In contrast to our findings with Snail, eribulin and vinorelbine, but not paclitaxel or ixabepilone, induced Slug expression independent of TGF-β stimulation in a subset of triple-negative breast cancer cell lines. Studies are ongoing to identify the molecular pathways and consequences of eribulin and vinorelbine-induced Slug induction, which might begin to identify biomarkers of patient response to different MTAs. This work highlights the multifaceted nature of MTA-mediated effects on EMT-associated signaling pathways in breast cancer cells and prompts a reevaluation of their differential efficacy in tumors with distinct molecular profiles. These studies are supported by Eisai Inc. Citation Format: Kaul R, Risinger AL, Mooberry SL. Differential effects of eribulin on key transcription factors snail and slug [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-08-06.
Abstract 225: Comparison of Myocardial Infarction and Congestive Heart Failure Induced Through Interventional Ischemia Reperfusion Injury in Yorkshire (Domestic), Yucatan, and Göttingen Swine
Authors: Christopher A Drummond, Randy Pielemeier, Jenifer Sweet, Jennifer DeVries, Janelle Gesaman, Mark LaBar, Gayle Nugent, Mark D Johnson
Journal: Circulation Research (2018)

Swine are important translational research models for developing and gaining regulatory approval for novel therapies for heart failure. Three swine species in particular are utilized in these studies, the Domestic Yorkshire (DY), Yucatan Minipigs (Yuc), and Göttingen minipigs (Gott). Selecting the right swine breed is important to the translational success of novel therapies and is the source of debate in the field. The current study compared interventionally induced Ischemia-reperfusion injury (IRI), a method that mimics clinical myocardial infarction and subsequent heart failure, in these breeds. Interventional IRI was induced by occluding the Left Anterior Descending Coronary Artery for 90 minutes using a PTCA balloon placed distal to the first diagonal branch. Yuc have the highest rate of survival of the three breeds following a 90 min occlusion (81%; 56 out of 69), Gott survival was 70% (28 out of 40), and DY survival was 57% (75 out of 131). Assessment of serum levels of Cardiac Troponin I (CTnI) revealed significant increases in this parameter that peak at 3 hrs following occlusion. Gott have the highest levels at 122ng/mL, followed by Yuc (99ng/mL), and DY (85ng/mL) at this time point. Functionally, all three breeds displayed an Ejection Fraction assessed by echocardiography of less than 40%, with Gott having the lowest mean, followed by Yuc, and DY. These levels remain low or decrease slightly over 1 to 4 months. Magnetic Resonance imaging demonstrates infarct sizes are approximately 25% of the left ventricle following 1 month and decreasing over time to 22% at 2 months post and 13% 4 months post. Additionally, all three species lose their hemodynamic responsiveness to dobutamine challenge following IRI. All three breeds respond similarly to IRI functionally and structurally, and they develop the clinical features of congestive heart failure, the main distinguishing factor in the current study was survival of the IRI procedure. Based on this data, factors such as rate of body weight gain in relation to the ability to obtain functional endpoints, availability, and other practical considerations should drive the selection of breed for translational studies.
Resistance exercise training improves mucociliary clearance in subjects with COPD: A randomized clinical trial
Authors: B.S.A. Silva, D. Ramos, G.N. Bertolini, A.P.C.F. Freire, M.R. Leite, C.A. Camillo, L.A. Gobbo, E.M.C. Ramos
Journal: Pulmonology (2019)

Elastic tubing was recently investigated as an alternative to the conventional resistance training (RT) in chronic obstructive pulmonary disease (COPD). The effects of RT on the mucociliary system have not yet been reported in the literature. The aim of this study was to evaluate the effects of two RT programs on mucociliary clearance in subjects with COPD. Twentyeight subjects with COPD were randomly allocated by strata, according to individual strength of lower limbs, to defined groups: conventional resistance training (GCT) or resistance training using elastic tubing (GET). Nineteen subjects (GET: n = 9; GCT: n = 10) completed the study and were included in the analysis. The measurement of vital signs (blood pressure, heart rate and respiratory rate), lung function (spirometry) and the primary outcome mucociliary clearance analysis (saccharin transit time test (STT)) were performed before and after the 12 weeks of RT. In relation to the mucociliary transportability analysis, no differences were observed between the baseline evaluations of the training groups (p = 0.05). There was a significant reduction in the STT values in both training groups, GET (10.64 ± 5.06 to 6.01 ± 4.91) and GCT (12.07 ± 5.10 to 7.36 ± 2.54) with p = 0.03. However, no differences between groups were observed on the magnitude of SST changes after interventions (GET: −43.51%; GCT: −38.94%; p = 0.97). The present study demonstrated that both RT with elastic tubing and conventional training with weights promoted similar gains in the mucociliary transportability of subjects with COPD.
UTILITY OF CARDIAC MRI AND LATE GADOLINIUM ENHANCEMENT IN NEW ONSET BIVENTRICULAR HEART FAILURE: A CASE OF A YOUNG FEMALE WITH ACQUIRED HYPERCOAGULABLE STATE AND NORMAL CORONARY ARTERIES
Authors: Elizabeth Hill, Christopher Vanichsarn, Aparajit Venkateswaran, Phong Hu, Malhar Patel, Jorge Gonzalez
Journal: Journal of the American College of Cardiology (2019)
Abstract GS3-03: Effects of prolonging adjuvant aromatase inhibitor therapy beyond five years on recurrence and cause-specific mortality: An EBCTCG meta-analysis of individual patient data from 12 randomised trials including 24,912 women
Authors: R Gray
Journal: Cancer Research (2019)

Abstract Effects of prolonging adjuvant aromatase inhibitor therapy beyond five years on recurrence and cause-specific mortality: an EBCTCG meta-analysis of individual patient data from 12 randomised trials including 24,912 women Background: Five years of endocrine therapy with tamoxifen and/or an aromatase inhibitor is highly effective in reducing the risk of recurrence but a substantial risk remains after treatment discontinuation. Continuing treatment with an aromatase inhibitor may mitigate this risk. Methods: We sought individual patient data for meta-analysis from 12 randomised trials that compared 3-5 years of aromatase inhibitor versus no further treatment after five or more years of endocrine therapy. Primary outcomes were recurrence, and breast cancer mortality. Predefined subgroup comparisons were or prior endocrine therapy (tamoxifen alone, tamoxifen then AI, AI alone), site of recurrence (distant, local, contralateral), age, nodal status, tumour size, grade, and period of follow-up (yrs 0-1, 2-5, 5-9, 10+). Five trials randomised 2-3 years prior to treatment divergence and the primary analyses included only women who were recurrence and second primary cancer free and still alive at the point of treatment divergence. Results: Data have so far been received on 7,488 women (100% of those randomised) in trials of extended AI following tamoxifen alone, 10,796 women (82% 0f 13,192 randomised) following prior tamoxifen then AI, and 959 (23% of 4,229 randomised) following AI alone. Preliminary analyses including 1,617 breast cancer recurrences and 854 breast cancer deaths confirm a 35% reduction in recurrence with extended AI following tamoxifen alone but suggest a more moderate reduction after prior AI therapy. Data from two trials (NSABP B-42 &amp; N-SAS BC 05) contributing ˜5666 women should be available before SABCS to allow definitive analyses. Conclusion: This meta-analysis will provide the most reliable possible summary of the available evidence to inform clinicians on the efficacy of extending AI therapy compared to stopping AI after about 5 years of endocrine therapy in preventing disease recurrence and death from breast cancer, both overall and in different categories of women. Citation Format: Gray R, Early Breast Cancer Trialists' Collaborative Group. Effects of prolonging adjuvant aromatase inhibitor therapy beyond five years on recurrence and cause-specific mortality: An EBCTCG meta-analysis of individual patient data from 12 randomised trials including 24,912 women [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS3-03.
Management of OTRs in a dermatological surgical clinic
Authors: K. Papier, L.G. Gordon, K. Khosrotehrani, N. Isbel, S. Campbell, A. Griffin, A.C. Green
Journal: British Journal of Dermatology (2019)

People who undergo organ transplantation are more likely to develop skin cancers, due to long‐term immunosuppressive therapy. This is especially concerning for organ transplant recipients (OTRs) living in Queensland, Australia, where skin cancer is more common than elsewhere. In an attempt to address the extreme skin cancer problem in OTRs living in Queensland, a dedicated Transplant Skin Clinic was established in Brisbane. This study aimed to describe the performance of this new clinic, the first of its kind in Queensland, Australia. Clinic attendees were invited to complete two surveys, supplied three months apart, about their health and personal characteristics, and permission was obtained to access participating attendees’ hospital records for details on detected and treated skin cancers over the same three‐month period. In total, the authors recruited 101 clinic patients into the study. Over the three months, the authors found that 615 skin lesions were detected in the clinic. Of these, 55 were referred for treatment outside the clinic and 478 were treated in clinic, mostly (78%) with surgery. Of the lesions treated in clinic, 268 were confirmed to be skin cancers, equivalent to nearly 3 skin cancers per patient over the three months. On average, the clinic staff successfully treated one skin cancer for every 1.4 skin lesions they surgically removed. In conclusion, this study found that the clinic is detecting, and efficiently treating, a large number of skin cancers in OTRs and thus effectively contributing to the control of the skin cancer burden in OTRs living in Queensland.
Abstract 558: Melatonin Exerts Cardioprotective Effects Under Chronic Neuropathic Pain Through Rip1-rip3-mlkl and Rip3-camkii Pathway Mediating Myocardial Necroptosis in Ischemia Reperfusion Injury
Authors: Zheng Yang, Chen Li, Han Xue, Yishi Wang, Heng Ma
Journal: Circulation Research (2018)

Objectives: Chronic pain is not an isolated pathophysiological symptom, myocardial ischemic/reperfusion injury contributes significantly to morbidity and mortality among people reporting chronic pain. However, the related mechanisms remain elusive. TNF-α triggered necroptosis contributes a lot to MI/R in jury and RIP3 plays an important role during this process under chronic pain condition. Melatonin has analgesia and cardioprotective effects, which may regulate necroptosis in chronic pain related MI/R injury. The aim of this study was to investigate the roles of melatonin in MI/R injury under chronic pain condition and the underlying mechanism. Methods: In this study, chronic neuropathic pain was induced by spared nerve injury (SNI) model. RIP3 KO and wild-type (WT) littermates were subjected to MI/R in vivo. Melatonin was administrated to mice 10 minutes before reperfusion. Results: SNI-WT mice manifested enhanced nociception and TNF-α induced necroptosis. SNI increased RIP1-RIP3 necrosome formation provoked RIP1-RIP3-MLKL and RIP3-CaMKII signaling, which led to exacerbated MI/R injury and higher mortality compared with control-WT mice. Chronic pain induced susceptibility to MI/R injury was decreased by RIP3 deficiency associated with impaired RIP1-RIP3-MLKL and RIP3-CaMKII signaling. Melatonin treatment in SNI-WT mice showed inhibited necroptosis and decreased TNF-α elevation and ROS production. RIP3 was also inhibited by melatonin treatment followed with impaired MLKL and CaMKII activation, which subsequently decreased MI/R injury (impaired serum LDH level, minimized infarct size and elevated cardiac function). Conclusions: These results suggested that chronic pain rendered cardiomyocytes more susceptible to MI/R injury. RIP3 plays an important role in mediating necroptosis in response to MI/R injury under chronic pain condition. Melatonin treatment could inhibited TNF-α triggered necroptosis and downregulated RIP3 mediating MLKL and CaMKII signaling which alleviated ROS production and cardiomyocytes death.
Abstract 552: Harnessing the Versatility of PLGA Nanoparticles for Targeted Cre-Mediated Recombination
Authors: Ngoc Nguyen, Cheng-Han Chen, Yulong Zhang, Peng Zhao, Benjamin Wu, Reza Ardehali
Journal: Circulation Research (2018)

The Cre/LoxP recombinase system has emerged as an important tool for the generation of conditional somatic mouse mutants. This method enables spatial control of gene activity in almost any tissue, providing new avenues for studying gene function and establishing animal models of human diseases. A major technical advance was the development of ligand-dependent Cre recombinases that are activated by tamoxifen. While this advance has paved the way for temporally-controlled developmental studies previously deemed impractical, the generation of tissue-specific transgenic mouse lines can be time-consuming and costly. Herein, we design a ‘smart’, biocompatible, and biodegradable nanoparticle system that can be actively targeted to specific cell types in vivo through surface conjugation of antibodies. We provide proof-of-principle for successful delivery of macromolecules and plasmid DNA. Importantly, we demonstrate that these ‘smart’, tamoxifen-loaded nanoparticles can be precisely targeted to cells of interest in vivo to bind and activate Cre recombinase, resulting in tissue-specific Cre activation. This system provides a simple, yet powerful approach to induce recombination in a ubiquitious Cre system for a time- and cost-effective strategy to generate new transgenic mouse lines.
<i>CHEK2</i> Alleles Predispose to Renal Cancer in Poland—In Reply
Authors: Maria I. Carlo, Semanti Mukherjee, Kenneth Offit
Journal: JAMA Oncology (2019)

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 Oncology 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 Oncology journal
ACHIEVEMENT OF GUIDELINE DIRECTED MEDICAL THERAPY GOALS IN COMPLEX HIGHER-RISK (AND INDICATED) PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION
Authors: Andre Cheng, Anurag Deeconda, Darshan Doshi, Dimitrios Karmpaliotis, Manish Parikh, Tamim Nazif, Ziad Ali, Philip Green, Sahil Parikh, Torsten P. Vahl, Susheel Kodali, Michael Collins, Gregg Stone, Martin Leon, Jeffrey Moses, Ajay Kirtane
Journal: Journal of the American College of Cardiology (2019)
ABLATION OF VENTRICULAR TACHYCARDIA IN PATIENTS WITH SEVERE HEART FAILURE IS ASSOCIATED WITH LOWER VENTRICULAR TACHYCARDIA RECURRENCE, MORTALITY, OR HEART FAILURE READMISSION COMPARED TO MEDICAL THERAPY ALONE
Authors: Natalie Beck, Peter Sauer, Alexis Tumolo, Amneet Sandhu, Matthew Zipse, Ryan Borne, Duy Nguyen, Joseph Schuller, Ryan Aleong, Christine Tompkins, Paul Varosy, Michael Rosenberg, Prateeti Khazanie, Natasha Altman, Andreas Brieke, William Cornwell, Eugene Wolfel, Amrut Ambardekar, Larry Allen, Wendy S. Tzou
Journal: Journal of the American College of Cardiology (2019)
Abstract 12672: Follistatin-Like 1 is a Regenerative Factor That Promotes Revascularization and Muscle Regeneration in Models of Peripheral Artery Disease
Authors: Koji Ohashi, Noriyuki Ouchi, Kenneth Walsh
Journal: Circulation (2010)

Objective: Peripheral artery disease (PAD) is a major unmet clinical need that is caused by the obstruction of major arteries and accompanied by the degeneration of muscle in the affected limb. Thu...
Abstract 478: Small Molecule ICG-001, Sodium Butyrate, and Retinoic Acid Enhanced Direct Cardiac Reprogramming of Induced Cardiomyocytes (iCMs)
Authors: Vivek P Singh, JayaPratap Pinnamaneni, Megumi Mathison, Deepthi Sanagasetti, Sonal Somvanshi, Aarthi Pugazenthi, Lina Yang, Davis So, Kai Wang, Jianchang Yang, Todd K Rosengart
Journal: Circulation Research (2018)

Background: Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells (iCMs) in situ represents a promising strategy for cardiac regeneration. A combination of three cardiac transcription factors Gata4, Mef2c and Tbx5 (GMT), and microRNAs can convert fibroblasts into iCMs, albeit with low efficiency in vitro . We aimed to increase the efficiency, maturation and speed of direct reprogramming using a unique combination of small molecules, in combination with previously identified reprogramming transcription factors, that we selected and combined in a cocktail specifically formulated to effect optimal impact on the aspects of reprogramming pathways thought to represent “roadblocks” or points of opportunity in these pathways. Methods: We screened a variety of such candidate compounds in primary rat/human cardiac fibroblast. Cardiac reprogramming was induced by lentivirus encoding Gata4, Mef2c and Tbx5 plus small molecules, and the presence of iCM was confirmed 10 days later by QRT-PCR, IFs and FACS analysis for the activation of endogenous cardiac troponin T (cTnT). Results: After validating and optimizing the dose and conditions for adding small molecules to the reprogramming cocktail, we treated GMT-overexpressing fibroblast with a combination of sodium butyrate (SB, 1mM; HDAC inhibitor), ICG-001(1μM; WNT inhibitor), and retinoic acid (RA, 1μM). We found that that a combination of SB, ICG-001, and RA significantly increased GMT-induced reprogramming efficiency to 22 % cTnT + iCMs from primary rat cardiac fibroblasts compared to 8% in the presence of single compounds and 3.5% without any added small molecule compound alone. QRT-PCR and IFs, analysis shows that a combination of the SB, ICG-001, and RA increased cTnT gene expression 4-6 fold when added to GMT-overexpressing rat cardiac fibroblasts. We also demonstrated that combined addition of SB, ICG-001, and RA increased cardiac fibroblast reprogramming efficiency 4 fold when added to GMTHM plus miR-590-overexpressing human cardiac fibroblasts. Conclusions: Thus, HDAC and WNT inhibitors along with RA, jointly accelerate GMT-induced cardiac reprogramming from rat/human cardiac fibroblasts and pave the way for new translational approaches for cardiac regeneration.
Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout
Authors: Tilman Jobst-Schwan, Charlotte A. Hoogstraten, Caroline M. Kolvenbach, Johanna Magdalena Schmidt, Amy Kolb, Kaitlyn Eddy, Ronen Schneider, Shazia Ashraf, Eugen Widmeier, Amar J. Majmundar, Friedhelm Hildebrandt
Journal: Kidney International (2019)
Bubble-Wrapping Halloween
Authors: Niko Yiannakoulias
Journal: JAMA Pediatrics (2019)

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 Pediatrics 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 Pediatrics journal
SOLUBLE LECTIN-LIKE OXIDIZED LOW-DENSITY LIPOPROTEIN RECEPTOR-1 IS ASSOCIATED WITH SUBCLINICAL CORONARY ARTERY DISEASES IN PSORIASIS
Authors: Amit Dey, Ranjitha Gaddipati, Youssef Elnabawi, Emily Ongstad, Aditya Goyal, Justin Rodante, Aparna Sajja, Alexander Sorokin, Heather Teague, Milena Aksentijevich, Noor Khalil, Aarthi Reddy, Harry Choi, Jenis Argueta-Amaya, Parag Shukla, Yvonne Baumer, Aditya Joshi, Veit Sandfort, Martin Playford, Marcus Chen, David Bluemke, Sotirios Karathanasis, Joel Gelfand, Ruchi Gupta, Nehal Mehta
Journal: Journal of the American College of Cardiology (2019)