tbuckley/cabot-search huggingface dataset:
Biomarker correlates from the randomized phase 2 trial of the PARP inhibitor olaparib (O) with or without the antiangiogenic TKI cediranib (C) in recurrent platinum-sensitive ovarian cancer (NCT01116648).
Authors: Jung-min Lee, Joyce Liu, Peter L. Choyke, Osama Elbuluk, Ismail B. Turkbey, Jane B. Trepel, Min-Jung Lee, Liang Cao, Nicole D. Houston, Nicolas Gordon, William Douglas Figg, William Thomas Barry, Ursula Matulonis, Michael J. Birrer, Percy Ivy, Elise C. Kohn
Journal: Journal of Clinical Oncology (2014)

5535 Background: O and C have single agent activity in recurrent platinum-sensitive high-grade serous ovarian cancer (HGSOC). A multi-institutional phase 2 open label study evaluated the efficacy of O with or without C in HGSOC pts. We hypothesized O+C combination may yield greater inhibition in tumor vascularity and VEGF pathways than O alone and these changes may correlate with response rate (RR) and progression-free survival (PFS). Methods: A self-selected subset of eligible pts were randomized 1:1 to O (400mg capsules BID) or O+C (O 200 mg capsules BID; C 30 mg daily). No prior anti-angiogenic therapy in the recurrent setting or prior PARPi was allowed. Blood samples were collected at baseline and day 3 to measure circulating endothelial cells (CEC: nucleated CD133-CD146+CD31+CD45-), circulating endothelial progenitor cells (CPC: viable nucleated CD133+, CD146-, CD31+ CD45 - or dim), plasma for cytokine concentrations of IL-6, IL-8, VEGF, and sVEGFR-2. DCE-MRI obtained at baseline and day 3 on therapy were evaluated for changes of Ktrans and Kepas a result of decreases in angiogenesis. Results: The clinical cohort and results of the full trial will be presented independently. 13 pts (median age 53 yr [32-70]; 7pts on O, 6pts on O+C) had paired correlative studies including DCE-MRI (10pts), CEC/CPC (10pts), and cytokine measurements (12pts). Median PFS with RR for O and O+C were 11mo, 57% and 14mo, 83%, respectively for this subset. Pts on O+C had a greater decrease in IL-8 and a median 3.5 fold increase in CEC compared to O alone (p=0.016 and 0.013, respectively). The increase of CEC pretreatment to day 3 was correlated with PFS>6mo in 6 pts on O+C (p=0.011, 95%CI 0.47-0.99, R2=0.91). Pre-day3 Ktrans and Kep did not correlate with RR or PFS in either arm. Conclusions: Significant changes of IL-8 concentration and CEC number with O+C suggest greater inhibition in angiogenesis compared with O alone. Further studies of this combination with prospectively planned validation of these potential predictive biomarkers may yield information to focus therapy to HGSOC pts who may best respond. Clinical trial information: NCT01116648.
Modelled health benefits of a sugar-sweetened beverage tax across different socioeconomic groups in Australia: A cost-effectiveness and equity analysis
Authors: Anita Lal, Ana Maria Mantilla-Herrera, Lennert Veerman, Kathryn Backholer, Gary Sacks, Marjory Moodie, Mohammad Siahpush, Rob Carter, Anna Peeters
Journal: PLoS Medicine (2017)

Background A sugar-sweetened beverage (SSB) tax in Mexico has been effective in reducing consumption of SSBs, with larger decreases for low-income households. The health and financial effects across socioeconomic groups are important considerations for policy-makers. From a societal perspective, we assessed the potential cost-effectiveness, health gains, and financial impacts by socioeconomic position (SEP) of a 20% SSB tax for Australia. Methods and findings Australia-specific price elasticities were used to predict decreases in SSB consumption for each Socio-Economic Indexes for Areas (SEIFA) quintile. Changes in body mass index (BMI) were based on SSB consumption, BMI from the Australian Health Survey 2011–12, and energy balance equations. Markov cohort models were used to estimate the health impact for the Australian population, taking into account obesity-related diseases. Health-adjusted life years (HALYs) gained, healthcare costs saved, and out-of-pocket costs were estimated for each SEIFA quintile. Loss of economic welfare was calculated as the amount of deadweight loss in excess of taxation revenue. A 20% SSB tax would lead to HALY gains of 175,300 (95% CI: 68,700; 277,800) and healthcare cost savings of AU$1,733 million (m) (95% CI: $650m; $2,744m) over the lifetime of the population, with 49.5% of the total health gains accruing to the 2 lowest quintiles. We estimated the increase in annual expenditure on SSBs to be AU$35.40/capita (0.54% of expenditure on food and non-alcoholic drinks) in the lowest SEIFA quintile, a difference of AU$3.80/capita (0.32%) compared to the highest quintile. Annual tax revenue was estimated at AU$642.9m (95% CI: $348.2m; $1,117.2m). The main limitations of this study, as with all simulation models, is that the results represent only the best estimate of a potential effect in the absence of stronger direct evidence. Conclusions This study demonstrates that from a 20% tax on SSBs, the most HALYs gained and healthcare costs saved would accrue to the most disadvantaged quintiles in Australia. Whilst those in more disadvantaged areas would pay more SSB tax, the difference between areas is small. The equity of the tax could be further improved if the tax revenue were used to fund initiatives benefiting those with greater disadvantage.
Expanded Phenotypic and Genetic Heterogeneity in the Clinical Spectrum of FPD-AML: Lymphoid Malignancies and Skin Disorders Are Common Features in Carriers of Germline RUNX1 Mutations
Authors: Anna L Brown, Christopher N Hahn, Catherine Carmichael, Ella Wilkins, Milena Babic, Chan-Eng Chong, Xiao-Chun Li, Joelle Michaud, Ping Cannon, Nicola Poplawski, Meryl Altree, Kerry Phillips, Louise Jaensch, Miriam Fine, Andreas W Schreiber, Jinghua Feng, Lesley Rawlings, Cassandra Vakulin, Carolyn Butcher, Richard D'Andrea, Ian D Lewis, Nigel Patton, Cecily Forsyth, Sally Mapp, Helen Mar Fan, Rachel Susman, Sue Morgan, Julian Cooney, Mark S Currie, Uday R. Popat, Kenneth Bradstock, April D. Sorrell, Carolyn J. Owen, Marshall S Horwitz, Devendra Hiwase, Alwin Krämer, Stefan Fröhling, Lucy A Godley, Jane E Churpek, Hamish S Scott
Journal: Blood (2016)
Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients with Impaired Renal Function: Efficacy Analysis of PrE1003, a Precog Study
Authors: Joseph Mikhael, Judi Manola, Sagar Lonial, Brendan M Weiss, Kurt Oettel, Suzanne R. Hayman, Abraham S. Kanate, S. Vincent Rajkumar
Journal: Blood (2016)
Evaluation of the Radiance planning system for breast fibrosis after intraoperative radiotherapy as a boost in breast conserving surgery.
Authors: XueRui Li, Elena Sperk, Frank Schneider, Sven Clausen, Christel Weiss, Frederik Wenz
Journal: Journal of Clinical Oncology (2016)

e12534 Background: Intraoperative radiotherapy (IORT) is a convenient and effective treatment for some breast cancer patients. IORT as a boost followed by conventional external radiotherapy has less radiation-induced fibrosis than whole breast radiotherapy, but the percentage of higher-grade fibrosis (II ̊-III ̊) still ranges between 25 - 38% after IORT as a boost. Currently, it is not possible to plan the radiation therapy process beforehand for IORT. Radiance planning System is a new simulation and planning tool for IORT. The purpose of this project is to validate the planning software Radiance System for IORT boost patients by creating dose-volume-histograms for the skin at risk and to find the affecting factors for fibrosis after IORT as a boost. Methods: 42 cases were enrolled into replanning and analysis and distributed into two groups: 14 cases with fibrosis in group A and 28 cases without fibrosis in group B. The replanning data including breast volume, seroma volume, skin volume, skin dose, applicator size and 50% dose-volume were planned successfully using Radiance System. Univariate and multivariate analyses were done for the patients’ basic characteristic, radiotherapy data and replanning data. Results: In the univariate analysis, seroma volume and skin volume were associated with a trend towards the risk of fibrosis (p < 0.1), whereas applicator size and 50% dose-volume were significantly associated with higher grade fibrosis (p < 0.05). In the multivariate analysis, the independent prognostic factor for fibrosis was the applicator size (p = 0.0565, OR 3.85, 95%CI 0.963 - 15.384). Conclusions: An increase of the applicator size of 1cm increased the risk of fibrosis 3.85 times after IORT as a boost in breast cancer. The results suggest that excessive expansion of the clear margin during breast conserving surgery will obviously increase the risk for fibrosis after IORT. Secondly, the planning software Radiance system was validated and can be used as an evaluation and documentation tool for post-planning of IORT for breast cancer.
Prothèses oesophagiennes expansives (POE) avec ou sans dispositif anti-reflux (DAR): résultats d'une étude nationale prospective multicentrique randomisée
Authors: M Le Rhun, E Ben Soussan, E Coron, A Le Sidaner, T Barrioz, D Coumaros, JM Nguyen, B Vedrenne, P Bichard, C Boustière, F Prat
Journal: Endoscopy (2006)

Les POE améliorent la qualité de vie des patients atteints de cancer oesophagien inopérable. Leur positionnement trans-cardial favorise le reflux trans-prothétique et ses complications. Des dispositifs anti-reflux ont été commercialisés mais leur efficacité reste controversée. Les buts de cette étude prospective randomisée étaient 1) d'évaluer l'apport du DAR par la recherche et la quantification d'un éventuel reflux transprothétique 2) de comparer les POE avec et sans DAR dans les symptômes de reflux, la qualité de vie, le traitement de la dysphagie et les complications éventuelles.
Abstract 318: Heterogeneous Remodeling in Diabetic Hearts Leads to Sudden Cardiac Death
Authors: Siva K Panguluri, Jared Tur, Srinivas Tipparaju
Journal: Circulation Research (2012)

Diabetes increases propensity to sudden cardiac death. Although ion channels were implicated, the precise mechanisms leading to arrhythmias remain unclear. We hypothesized that the diabetic heart undergoes heterogeneous remodeling leading to arrhythmogenic substrate and sudden cardiac death. For this, we investigated the expression of cardiac specific microRNAs, key transcriptional factors and their target gene in right (RV) and left ventricle (LV). TaqMan and SYBR green qRT-PCR was used to estimated the transcriptional data and Western blots/ELISA for protein profiles. Our data clearly suggests that miR-1-1a (1.6±0.021; p≤0.00067) and miR-301 (1.36±0.02; p≤0.0201) were up-regulated in epicardium of left ventricle (LV-epi), whereas miR-1-1a (2.9±0.59; p≤0.027), miR-133a (3.7±0.19; p ≤ 0.041) and miR-301 (3.6±0.26; p-value ≤ 0.037) were up-regulated in RV of diabetic (db/db) mice (n=3) hearts compared with wild type (n=3). Out of 30 genes tested we confirmed down-regulation of 14 genes (with p≤0.05) including transcriptional factors NFkB2, GATA6, Irx5, Ezh-2, Six-1, CtBP, SiRT1; ion channels Kv4.2, Scn1b and Scn5a and its protein chaperon Kchip-2, whereas Mef2c was up-regulated significantly in LV-epi in diabetic mice. Similarly, 11 genes including Kv4.2, Mef2c, GATA4, GATA6, Pitx2c, Scn1b, Kchip-2, SiRT1, Nampt and MMP-9 were down-regulated (p≤0.05), whereas 9 genes such as Irx5, Kv2.1, Kv4.3, NFkB1, NFkB2, MHC7, CtBP, NNt, and G6PD were up-regulated significantly in RV of diabetic mice. The Ingenuity Pathway Analysis of the differentially expressed genes in heart revealed hypertrophy, arrhythmias, proliferation, and failure as top toxicology networks in LV-epi, whereas cardiac hypertrophy, hepatic stellate cell activation, oxidative stress, PPAR mediated gene activation, fibrosis and necrosis are among top toxicology networks in RV. The role of miR’s along with transcriptional factors down-regulating Kv4.2 in diabetic LV may be consistent with the idea that repolarization reserve is decreased in diabetic hearts. Moreover, regional differences in potassium current may play vital role in regulating function. These data suggest that the ion channel remodeling in left and right ventricles are modulated via different mechanisms.
Cardiovascular Disease and Type 2 Diabetes: Has the Dawn of a New Era Arrived?
Authors: Muhammad Abdul-Ghani, Ralph A. DeFronzo, Stefano Del Prato, Robert Chilton, Rajvir Singh, Robert E.J. Ryder
Journal: Diabetes Care (2017)

Hyperglycemia is the major risk factor for microvascular complications in patients with type 2 diabetes (T2D). However, cardiovascular disease (CVD) is the principal cause of death, and lowering HbA1c has only a modest effect on reducing CVD risk and mortality. The recently published LEADER and SUSTAIN-6 trials demonstrate that, in T2D patients with high CVD risk, the glucagon-like peptide 1 receptor agonists liraglutide and semaglutide reduce the primary major adverse cardiac events (MACE) end point (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) by 13% and 24%, respectively. The EMPA-REG OUTCOME, IRIS (subjects without diabetes), and PROactive (second principal end point) studies also demonstrated a significant reduction in cardiovascular events in T2D patients treated with empagliflozin and pioglitazone. However, the benefit of these four antidiabetes agents (liraglutide, semaglutide, empagliflozin, and pioglitazone) on the three individual MACE end points differed, suggesting that different underlying mechanisms were responsible for the reduction in cardiovascular events. Since liraglutide, semaglutide, pioglitazone, and empagliflozin similarly lower the plasma glucose concentration but appear to reduce CVD risk by different mechanisms, there emerges the intriguing possibility that, if used in combination, the effects of these antidiabetes agents may be additive or even multiplicative with regard to cardiovascular benefit.
Predictors of Coronary Heart Disease Events Among Asymptomatic Persons With Low Low-Density Lipoprotein Cholesterol
Authors: Ron Blankstein, Matthew J. Budoff, Leslee J. Shaw, David C. Goff, Joseph F. Polak, Joao Lima, Roger S. Blumenthal, Khurram Nasir
Journal: Journal of the American College of Cardiology (2011)
Abstract P268: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Myocardial Ischemia/Reperfusion Injury
Authors: Kazuhiro Nagaoka, Tetsuya Matoba, Kaku Nakano, Kenji Sunagawa, Kensuke Egashira
Journal: Circulation Research (2011)

Background: In acute myocardial infarction, early myocardial reperfusion is the most effective therapeutic strategy. The reperfusion, however, induces ischemia-reperfusion (I/R) injury that paradoxically cancels the beneficial effects of reperfusion. Statins are known to activate reperfusion injury salvage kinase (RISK) pathway, but its efficacy is not enough to be used as cardioprotective therapy. Local delivery of statins might optimize cardioprotective effects of statins. Hence we tested the hypothesis that nanoparticle (NP)-mediated delivery of pitavastatin into ischemic myocardium at the time of reperfusion ameliorates myocardial I/R injury. Methods and Results: In a rat model of 30-min ischemia followed by reperfusion, significant FITC signals were detected in cardiomyocytes within infarct areas after intravenous (IV) injection of FITC-NP at the time of reperfusion ( Figure A). No significant FITC signals were noted after IV injection of FITC only. IV injection of pitavastatin-NP that contained 1.0 mg/kg pitavastatin at reperfusion reduced infarct size ( Figure B). The therapeutic effects of pitavastatin-NP were associated with activation of RISK pathway such as Akt signals in the reperfused myocardium. Wortmannin blunted the therapeutic effects of pitavastatin-NP (Figure B). On the other hand, no therapeutic effects were noted after IV injection of pitavastatin alone (1.0, 10 mg/kg). Conclusions: In I/R injury, NPs were delivered selectively into reperfused myocardium possibly via enhanced permeability and retension effects. NP-mediated delivery of pitavastatin at the time of reperfusion reduced myocardial infarct size by activating RISK pathway.
Cetuximab or Bevacizumab With First-Line Chemotherapy in Advanced <i>KRAS</i> Wild-Type Colorectal Cancer
Authors: Christopher H. Lieu, Wells A. Messersmith
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Exercise training during anthracycline-based chemotherapy for breast cancer.
Authors: Steve Fraser, Ashley Bigaran, Steve Selig, Andre LaGerche
Journal: Journal of Clinical Oncology (2017)

e12110 Background: Breast Cancer is the most common female malignancy in Australia and worldwide. Medical advancements in breast cancer detection, diagnosis, and treatment have increased the 5 year-survival rate to 90%, so a focus on non-breast cancer related causes of morbidity and mortality have emerged. Anthracycline-chemotherapy has had considerable success in reducing tumour size, cancer recurrence and improving survival rates but significant adverse effects including reductions in VO2peak and cardiac function. Exercise training may provide a treatment option to reduce the cardiotoxic and fitness declines seen in women treated with anthracycline-based chemotherapy. Therefore this study aims to investigate the effects of exercise training for women recently diagnosed with breast cancer undergoing anthracycline chemotherapy Methods: 20 women recently diagnosed with breast cancer were evenly split into either usual care (UC, n = 10, age 49.2 ± 13.4yrs, Ht 164 ± 0.09cm, Wt 77.4 ± 19.7kg, BMI 23.5 ± 5.4) or three months of AEP led aerobic and resistance training designed to reduce the adverse effects of chemotherapy treatment (Ex, n = 10, age 50.9 ± 7.4 yrs, Ht 161 ± 0.09cm, Wt 70.7 ± 23kg, BMI 21.9 ± 6.9). Key measures including cardiac function, VO 2 peak, strength and cancer related fatigue were assessed pre and post intervention. Results: Baseline VO 2 peak (UC 22 ± 6.6 ml/kg/min, Ex UC 26.3 ± 6.7 ml/kg/min were below predicted values. Breast cancer patients tolerated exercise training during chemotherapy treatment and preliminary result suggest a decline in VO 2 peak and cardiac function during chemotherapy treatment and that exercise training was able to ameliorate this. More complete data will be presented at the conference. Conclusions: An Exercise Physiologist led aerobic and resistance training program was well tolerated in women recently diagnosed with breast cancer. The program appears to minimise some of the adverse effects of treatment, notably fitness declines and cardiotoxicity and should be considered in the oncology setting. Clinical trial information: ACTRN1261600160241.
Abstract 130: Epicardial-to-Myocyte Hypertrophic Signaling is Mediated by Epicardial/Mesenchymal Status and Protein Arginine Methyltransferase-1
Authors: Olan Jackson-Weaver, Henry Sucov, Jian Xu
Journal: Circulation Research (2015)

The epithelial-to-mesenchymal transition (EMT) is an important cellular mechanism in a diverse range of biological processes such as development, wound healing, cancer metastasis, and organ fibrosis. Epicardial cells are mesothelial cells lining the outer surface of the heart that are an important progenitor population and a source of growth factors during development. Epicardial cells undergo EMT and invade the myocardium, differentiating into cardiac fibroblasts and coronary smooth muscle cells. Of note, resident fibroblasts of epicardial origin are a major cellular mediator of cardiac fibrosis. Our recent work has established an important function for the protein arginine methyltransferase PRMT1 in EMT. We hypothesized that PRMT1 is required for EMT in a mouse epicardial cell line (MEC-1). We found that PRMT1 is required for a subset of the EMT marker changes in epicardial EMT, such as upregulation of vimentin, fibronectin, and slug, as well as loss of E-cadherin. Furthermore, PRMT1 knockdown reduced MEC-1 migration and invasion, suggesting that PRMT1 is critical for epicardial progenitor function. Epicardial cells secrete a variety of signaling factors that affect cardiomyocyte proliferation and structure. This is a critical component of heart development, and may also affect heart diseases such as hypertophic heart failure. Therefore we assessed whether EMT and PRMT1 affect the paracrine functions of epicardial cells. Co-culture of MEC-1 cells with rat neonatal cardiomyocytes caused cardiomyocyte hypertrophy, and this was enhanced when MEC-1 cells were pre-treated with TGF-β to induce EMT. Interestingly, MEC-1 cells treated with PRMT1 siRNA also induced cardiomyocyte hypertrophy, but TGF-β pre-treatment of these cells did not enhance this effect. In conclusion, epicardial EMT is largely dependent on PRMT1. Epicardial cells also promote cardiomyocyte hypertrophy, which is enhanced in epicardial cells that have undergone PRMT1-mediated EMT towards a mesenchymal fate. These studies establish a role for protein methylation in the EMT process, and could lead to novel treatments for heart failure and other diseases affected by EMT.
The Promise and Opportunities for Screening and Treating Childhood Obesity
Authors: Teresa Quattrin, Denise E. Wilfley
Journal: JAMA Pediatrics (2017)

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