tbuckley/cabot-search huggingface dataset:
Abstract 2294: Customizable weighted DNA copy-number networks inform oncogenic pathway alterations and chemoresistance risk
Authors: Joe Ryan Delaney, Dwayne G. Stupack
Journal: Cancer Research (2018)

Abstract Cancer is driven by mutations of many types: single nucleotide variants, insertion-deletion events within coding exons, and prolific DNA copy-number alterations (CNAs). CNAs have been often viewed as a passenger event due to seemingly inconsistent patterns between tumors and a large fraction of the genome altered, preventing traditional statistical analysis. Here, we present a tool which incorporates phenotypic data including haploinsufficiency and triploproficiency of genes and protein-protein interaction studies, which enables the identification of consistently altered pathways in cancer. This tool, HAPTRIG (for HAPloinsufficient and TRIplosensitive Gene) can be used with RNA, log2 CNA, absolute CNA data, or any other normalized gene-level data. As part of the pathway scoring process, control CNA networks are generated to provide a permuted-genome control, enabling detection of alterations in very heterogeneous cancer backgrounds. The customizable gene-scores which build these networks allow prioritization of altered network hubs: single genes which have exceptional influence within an altered pathway, facilitating hypothesis-testing in cell and animal models. A beta-version was validated in a recent publication from our lab to better predict tumor suppressor genes and oncogenes than Gene Set Enrichment Analysis, and additionally identified targetable pathway hubs which improved murine treatment in ovarian cancer chemo-resistant models. However, its applicability was limited in the beta. Now HAPTRIG can work with any user-supplied human dataset, not just TCGA samples, is an order of magnitude faster, able to run in parallel processors for unlimited speed improvement, and can produce pan-pathway outputs. The tool can use expected background rates from permuted data or compare to a second control dataset, which can be used to compare altered CNA pathways in tumor subtypes or unusual alterations of RNA compared to CNAs, among many other possibilities. We provide this tool for free community use online and in App form, so molecular biologists without bioinformatics training may produce well-informed hypotheses. We find that altered CNA pathways can predict chemoresistance risk groups within tumor types. A tumor suppressor gene hub was found to accelerate tumorigenesis upon deletion in a spontaneous mouse model. Overall, HAPTRIG represents a user-friendly tool to better understand a whole new landscape of tumor mutations: that of copy number alterations. Citation Format: Joe Ryan Delaney, Dwayne G. Stupack. Customizable weighted DNA copy-number networks inform oncogenic pathway alterations and chemoresistance risk [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 2294.
Linear Cryoablation of the Left Atrium Versus Pulmonary Vein Cryoisolation in Patients With Permanent Atrial Fibrillation and Valvular Heart Disease
Authors: FiorenzoGaita, RiccardoRiccardi, DomenicoCaponi, DipenShah, LuciaGarberoglio, LauraVivalda, AlessandroDulio, AndreaChiecchio, EricManasse, RobertoGallotti
Journal: Circulation (2005)

Background— The aim of this study was to clarify the role of pulmonary vein isolation (PVI) alone versus left atrial linear lesions in the treatment of permanent atrial fibrillation (AF) in patients with left atrial dilatation and valvular disease. The primary end point was to assess the persistence of sinus rhythm (SR) off antiarrhythmic drugs (AADs) at 2-year follow-up and to correlate clinical outcome with surgical results validated with electroanatomic mapping (EAM). Methods and Results— A total of 105 patients with permanent AF undergoing valve surgery were assigned to 3 different groups: in groups “U” and “7,” left atrial linear cryoablation was performed, whereas in group “PV” patients, anatomic cryoisolation of pulmonary veins only was performed. In groups U and 7, SR was achieved in 57% of patients, whereas it was achieved in 20% of PV patients during 2-year follow-up. In the first 51 patients, the ablation schemes were validated with EAM. The EAM showed that the U lesion was never obtained: in 5...
Abstract 9970: Androgen Deprivation Therapy by Surgical Castration, Gonadotropin Releasing Hormone Receptor Agonists or Antagonists and the Development of Atherosclerosis in Apoe-deficient Mice
Authors: Christian Bo Poulsen, Martin Bødtker Mortensen, Wolfgang Koechling, Charlotte Brandt Sørensen, Jacob Fog Bentzon
Journal: Circulation (2015)

Introduction: Adjuvant treatment of prostate cancer often involves androgen deprivation therapy (ADT) by orchiectomy (Orx), gonadotropin releasing hormone (GnRH) receptor agonists or GnRH receptor antagonists. Clinical studies of men with preexisting atherosclerotic disease, have indicated that cardiovascular event rates differs between different types of ADT, suggesting that not only testosterone deficiency, but also direct effects of ADT on processes in the atherosclerotic plaque may be involved. Immune cell GnRH receptors have been implicated as potential mediators. In the present study, we compared the effects of common types of ADT on de-novo atherosclerosis in mice. Methods: Chow-fed Apoe-deficient mice (n=121) were allocated to Orx and/or monthly injections with the GnRH receptor agonist leuprolide (0.5 mg s.c.), the GnRH receptor antagonist degarelix (0.5 mg s.c.) or saline starting from 8 weeks of age (n=19-21 in each group). At 26 weeks of age, the burden of atherosclerosis was quantified by en face analysis of the Oil red O-stained aortic arch and in histological sections of the aortic root. Bone marrow-derived macrophages and splenocytes were incubated in the presence of leuprolide (10 -6 mol/L) or degarelix (10 -6 mol/L). Data is shown as mean ± sem, *p&lt;0.05, **p&lt;0.01. Results: All types of ADT augmented hypercholesterolemia and atherosclerosis with no significant differences in the size of the effect (Figure A-B). In Orx mice, the addition of leuprolide, but not degarelix, led to further increases in plasma total cholesterol and in atherosclerosis in the aortic root (D), but not the aortic arch (C). Plaque necrosis was unaffected by ADT. No effects of the drugs on macrophage cytokine secretion or splenocyte proliferation were observed. Conclusions: ADT did not exert differential effects on the development of atherosclerosis in the Apoe-deficient mice. A pro-atherogenic, possibly cholesterol-mediated, effect of leuprolide was seen in Orx mice.
Abstract 18299: Development of a Regional STEMI Management Guideline Significantly Increases Fibrinolytic Therapy Prior to Emergent Transfer for Percutaneous Intervention
Authors: David A Wampler, Steven R Bailey, Eric Epley, Cheryl Baker, Dudley Wait, Craig Cooley, Jorge A Alvarez
Journal: Circulation (2017)

Introduction: PCI is established as definitive care for STEMI. This therapy is rarely available in rural hospitals. The Southwest Texas Regional Advisory Council developed a STEMI Management Guidel...
Abstract 19059: Thermodilution-derived Coronary Blood Flow Pattern Immediately After Coronary Intervention as a Predictor of Long-term Clinical Outcomes in Patients With ST-segment Elevation Myocardial Infarction
Authors: MasashiFukunaga, KenichiFujii, MachikoNishimura, TetsuoHorimatsu, TenSaita, AkinoriSumiyoshi, HirotoTamaru, KojiroMiki, TakahiroImanaka, TohruMasuyama
Journal: Circulation (2014)

Background: We reported that coronary blood flow (CBF) can be evaluated by analyzing thermodilution curve that is measured with a single pressure sensor/thermistor-tipped guidewire in the cardiac catheterization laboratory during percutaneous coronary intervention (PCI). Bimodal shape of thermodilution curve was associated with microvascular damage and predictors of left ventricular functional recovery after ST-segment elevation myocardial infarction (STEMI). However it is unknown whether the bimodal shape of thermodilution curve predicts mortality and re-hospitalization for heart failure in long term period for patients experiencing STEMI. Methods: Between September 2009 and August 2012, 97 consecutive patients with a first STEMI were prospectively enrolled in this study. Using a pressure sensor/thermistor-tipped guidewire, CBF pattern was assessed from the thermodilution-curves after successful PCI at maximum hyperemia. CBF pattern was classified into 3 groups according to the shape of thermodilution cu...
Low-Density Lipoprotein Cholesterol Concentrations and Death Due to Intraparenchymal Hemorrhage
Authors: HiroyukiNoda, HiroyasuIso, FujikoIrie, ToshimiSairenchi, EmikoOhtaka, MikioDoi, YokoIzumi, HitoshiOhta
Journal: Circulation (2009)

Background— Few studies have examined the association between low levels of low-density lipoprotein (LDL) cholesterol and risk of intraparenchymal hemorrhage. Methods and Results— A total of 30 802 men and 60 417 women, 40 to 79 years of age with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993 under the auspices of the Ibaraki Prefectural Health Study. Systematic mortality surveillance was performed through 2003, and 264 intraparenchymal hemorrhage deaths were identified. LDL cholesterol levels were calculated with the Friedewald formula. Persons with LDL cholesterol ≥140 mg/dL had half the sex- and age-adjusted risk of death due to intraparenchymal hemorrhage of those with LDL cholesterol <80 mg/dL. After adjustment for cardiovascular risk factors, the multivariable hazard ratio compared with persons with LDL cholesterol <80 mg/dL was 0.65 (95% CI 0.44 to 0.96) for those with LDL cholesterol 80 to 99 mg/dL, 0.48 (0.32 to 0.71) for 100 to 119 mg/dL, 0.50 (0....
A synthetic polymeric biolubricant imparts chondroprotection in a rat meniscal tear model
Authors: Michel Wathier, Benjamin A. Lakin, Benjamin G. Cooper, Prashant N. Bansal, Alison M. Bendele, Vahid Entezari, Hideki Suzuki, Brian D. Snyder, Mark W. Grinstaff
Journal: Biomaterials (2018)
The Value of Registries for Rare Diseases
Authors: Robert J. Hinchliffe, Janet T. Powell
Journal: Circulation (2014)

B acterial infections of the aorta are rare.The label mycotic aneurysm is misleading because mycoses or fungal infections of the aorta are even more rare.The management of bacterial infections of the aorta has always been considered difficult, largely because they frequently herald aortic rupture, and the outcomes of traditional surgery have been poor.Historically, these patients were managed by surgical resection of the aneurysm, debridement of the infected tissue, and revascularization using in situ or extra-anatomic techniques with either prosthetic or, less commonly, autologous grafts.However, the results of such surgery have been disappointing, with many patients being considered unfit to withstand the rigors of such major intervention and, therefore, palliated.Others have died as a result of the attempted curative surgery or had late infectious complications.
Abstract IA20: Autophagy in alveolar soft part sarcomagenesis
Authors: Kevin B. Jones
Journal: Clinical Cancer Research (2018)

Abstract Altered metabolism is considered to be one of the new hallmarks of cancer. Autophagy is one major avenue of altered cancer metabolism, enabling cell survival under metabolic stress and promoting chemoresistance. The nuclear localization of MiTF/TFE3 family transcription factors has associated with upregulated transcription of autophagy genes in pancreatic cancer. Alveolar soft part sarcoma is a rare but deadly soft-tissue sarcoma, with a predilection for adolescent and young adult victims. Alveolar soft part sarcoma is noteworthy for its resistance to traditional cytotoxic chemotherapies. It consistently associates with a t(X;17) chromosomal translocation that produces the ASPSCR1-TFE3 target gene, bearing the DNA-binding domain from TFE3 and protein interaction domains from ASPSCR1. We have demonstrated that conditional expression of ASPSCR1-TFE3 is sufficient to drive alveolar soft part sarcomagenesis in the mouse with complete penetrance. Mouse tumors recapitulate human alveolar soft part sarcoma histology and transcriptomes faithfully. While direct targets of ASPSCR1-TFE3 have been studied in a renal cell carcinoma cell line, they have not been studied in alveolar soft part sarcoma. We report not only the first genome-wide localization of the ASPSCR1-TFE3 oncoprotein on chromatin from alveolar soft part sarcoma cell lines and mouse tumors, but also its association with actively transcribed genes. Among these are found many genes related to autophagy, especially those related specifically to the nutrient responsive pathways that drive autophagy. We demonstrate high expression of autophagy-related lysosomes and proteins at baseline conditions in human tumors and cell lines and mouse tumors. We also demonstrate active autophagic flux even in the absence of stress conditions. Inhibition of autophagy has no apparent impact on the survival of alveolar soft part sarcoma cells alone, but profoundly impacts their protein degradation pathways and the availability of amino acids for protein assembly in stress. Inhibition of autophagy strongly synergizes with chemotherapy to kill alveolar soft part sarcoma cells, suggesting it was a source mechanism for resistance. We have therefore demonstrated the direct targets of ASPSCR1-TFE3 in alveolar soft part sarcomas, including a number of autophagy genes that are expressed in these tumors, independently from nutrient deprivation or stress, rendering cells particularly resistant to many therapy-induced stresses. Citation Format: Kevin B. Jones. Autophagy in alveolar soft part sarcomagenesis [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA20.
MASTL induces Colon Cancer progression and Chemoresistance by promoting Wnt/β-catenin signaling
Authors: Srijayaprakash Babu Uppada, Saiprasad Gowrikumar, Rizwan Ahmad, Balawant Kumar, Bryan Szeglin, Xi Chen, J. Joshua Smith, Surinder K. Batra, Amar B. Singh, Punita Dhawan
Journal: Molecular Cancer (2018)

Chemotherapeutic agents that modulate cell cycle checkpoints and/or tumor-specific pathways have shown immense promise in preclinical and clinical studies aimed at anti-cancer therapy. MASTL (Greatwall in Xenopus and Drosophila), a serine/threonine kinase controls the final G2/M checkpoint and prevents premature entry of cells into mitosis. Recent studies suggest that MASTL expression is highly upregulated in cancer and confers resistance against chemotherapy. However, the role and mechanism/s of MASTL mediated regulation of tumorigenesis remains poorly understood. We utilized a large patient cohort and mouse models of colon cancer as well as colon cancer cells to determine the role of Mastl and associated mechanism in colon cancer. Here, we show that MASTL expression increases in colon cancer across all cancer stages compared with normal colon tissue (P < 0.001). Also, increased levels of MASTL associated with high-risk of the disease and poor prognosis. Further, the shRNA silencing of MASTL expression in colon cancer cells induced cell cycle arrest and apoptosis in vitro and inhibited xenograft-tumor growth in vivo. Mechanistic analysis revealed that MASTL expression facilitates colon cancer progression by promoting the β-catenin/Wnt signaling, the key signaling pathway implicated in colon carcinogenesis, and up-regulating anti-apoptotic proteins, Bcl-xL and Survivin. Further studies where colorectal cancer (CRC) cells were subjected to 5-fluorouracil (5FU) treatment revealed a sharp increase in MASTL expression upon chemotherapy, along with increases in Bcl-xL and Survivin expression. Most notably, inhibition of MASTL in these cells induced chemosensitivity to 5FU with downregulation of Survivin and Bcl-xL expression. Overall, our data shed light on the heretofore-undescribed mechanistic role of MASTL in key oncogenic signaling pathway/s to regulate colon cancer progression and chemo-resistance that would tremendously help to overcome drug resistance in colon cancer treatment.
Good Clinical Practice in Diagnosis of Vulvovaginal Symptoms
Authors: Orna Reichman, Jack D. Sobel
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Studies on the Renal Circulation and Renal Function in Mitral Valvular Disease
Authors: Larswerkö, Edvardasvarnauskas, Janek, Hôrjebucht, Bengtthomasson, Jonasbergström, Haraldeliasch
Journal: Circulation (1954)

In a study of the nature of the renal changes in patients with mitral stenosis, lowered renal function and reduced renal circulation the effect of Apresoline, given during heart catheterization to 12 patients with mitral stenosis of varying severity, was studied. The drug was found to increase renal blood flow (and decrease arterial blood pressure), showing that the renal changes in mitral stenosis are reversible. The two effects of Apresoline were shown to be independent of each other.
Abstract 378: Stat3 promotes ovarian cancer by modulating the energy metabolism and develops drug resistance in patients
Authors: Vaishnavi Raja, Shailendra Giri, Sharif Sakr, Miriana Hijaz, Raymond Quiles, Adnan R. Munkarah, Ramandeep Rattan
Journal: Cancer Research (2018)

Abstract Signal Transducers and Activators of Transcription (STAT) are a group of transcription factors that are known to play a major role in cancer progression. In ovarian cancer, increased STAT3 leads to cancer proliferation in response to cytokines and confers resistance to chemotherapy-induced apoptosis in epithelial malignancies. STAT3 is constitutively activated in patient derived ovarian cancer cells, and increased STAT3 expression is a predictor of poor prognosis. Apart from its function as a transcription factor, recently STAT3 has been shown to modulate mitochondrial function to promote carcinogenesis. The aim of our study was to investigate if STAT3 activation can modulate cellular metabolism of ovarian cancer cells. Stable clones expressing STAT3 were generated in A2780 ovarian cancer cells, along with empty vector clones. Ectopic expression of STAT3 in A2780 ovarian cancer cell line resulted in increased proliferation (p&amp;lt;0.01) and colony formation ability (p&amp;lt;0.001) in vitro and led to large ovarian tumors (p&amp;lt;0.01) compared to parental and vector controls in xenograft mouse model. Bioenergetics profiling showed higher mitochondrial respiration (OCR) and glycolysis (ECAR) in STAT3 clones compared to parental and vector clones. Ratio of ECAR/OCR in the STAT3 overexpressing cells placed them in the ‘metabolically active' phenotype, while parental A2780 and vector clones were in ‘metabolically less active' phenotype. A selective inhibitor of STAT3, STATTIC, inhibited the STAT3 mediated growth of A2780 cells both in vitro (p&amp;lt;0.01) and in vivo (p&amp;lt;0.01). In addition, STATTIC treatments reversed the ‘metabolically active' state of STAT3 overexpressing clones to a ‘lower metabolic state', placing them in the same category as the control cells. In addition, STATTIC inhibited the cell proliferation and modulated bioenergetic phenotype of other ovarian cancer cells lines (PEO4, C200 and OVCAR3) that display a ‘metabolically active' phenotype. Overall, STAT3 can induce metabolic changes in ovarian cancer cells, maybe as survival mechanism and enhances the cellular fitness of the ovarian cancer cell resulting in increased oncogenic abilities. Citation Format: Vaishnavi Raja, Shailendra Giri, Sharif Sakr, Miriana Hijaz, Raymond Quiles, Adnan R. Munkarah, Ramandeep Rattan. Stat3 promotes ovarian cancer by modulating the energy metabolism and develops drug resistance in patients [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 378.
Abstract 15367: Does the Intra-resuscitation Pupillary Light Reflex Predict Return of Spontaneous Circulation or Neurologic Outcome?
Authors: Joshua C Reynolds, Todd Chassee, Mark Fankhauser, Amy Uber
Journal: Circulation (2015)

Objective: We previously demonstrated feasibility of prehospital pupillometry to quantify/qualify the pupillary light reflex (PLR) during resuscitation as a potential neurophysiological marker to guide efforts &amp; provide early neuroprognostication. We now report on the full cohort. Hypothesis: PLR during resuscitation is associated with ROSC &amp; neurologic outcome (following commands [FC]; mRS 0-3 &amp; CPC 1-2) at hospital discharge. Methods: Prospective, observational cohort in which we deployed hand-held pupillometers (NeurOptics, Inc) to EMS-treated OHCA subjects for serial recordings during pulse checks until ROSC, termination, or hospital arrival. We categorized PLR as normal/abnormal/absent with the Neurologic Pupillary Index (NPi), a continuous scale (0-5) combining facets of PLR (e.g. % change, velocity, latency). We abstracted patient data from prehospital &amp; hospital records, tabulated data, estimated test performance, and performed ROC analysis for best NPi &amp; outcomes. Results: From 2/14 - 4/15, 186 subjects were enrolled (61 ± 20 years, 58% male, 41% witnessed, 43% bystander CPR, 25% shockable rhythm). Most (92%) received epi (median 5mg), 12% atropine (median 1mg), 37% defibrillated (median 3.5 attempts). At submission, 173 (96%) had complete follow-up data (44% transported to hospital, 31% ROSC). Of 39 (22%) subjects admitted to hospital (76% hypothermia, 26% cardiac catheterization), 7 survived to discharge with 6 FC &amp; 5 mRS 0-3. Of 1,552 readings attempted (median 7/subject), 39% had usable data &amp; 74% subjects had ≥1 usable reading, Only 15% subjects had PLR during resuscitation. Best NPi &gt; 4.0 classified 92% of FC (LR+ 17; overall AUC 0.69), whereas best NPi &gt; 4.5 classified 98% favorable mRS &amp; CPC (LR+ 67; overall AUC 0.70). Conclusion: A minority of subjects had detectable PLR. Normal PLR was rare, but had high overall classification accuracy for FC, &amp; strong likelihood ratios for ROSC &amp; neurologic outcome. Best NPi had fair test performance by AUC.