tbuckley/cabot-search huggingface dataset:
Simultaneous inactivation of TP53 and loss of PTEN diminish response to targeted therapy in V600EBRAF mutant melanoma
Authors: Elena Galvani, Kelly Brooks, Franziska Baenke, Maria Romina Girotti, Gabriela Gremel, Amit Kumar Mandal, Amaya Viros, Clare McManus, Matthew Smith, Kok Haw Jonathan Lim, Rebecca J Lee, Alberto Fusi, Paul C Lorigan, Richard Marais
Journal: Journal of Thoracic Oncology (2015)
“¿Tuviste gripe la semana pasada?” Una encuesta telefónica para evaluar la prevalencia de la gripe en la población sueca
Authors: L Payne, S Kühlmann-Berenzon, K Ekdahl, J Giesecke, L Högberg, P Penttinen
Journal: Eurosurveillance (2005)

La vigilancia centinela infraestima muchas veces el verdadero peso de la gripe en una poblacion porque ese sistema se basa en las consultas en centros medicos. Se realizo una encuesta telefonica en la poblacion sueca para evaluar el peso de la gripe a nivel nacional, durante una semana en la estacion gripal 2004-2005. Se seleccionaron de modo aleatorio numeros de telefono de lineas fijas. Se contacto con los hogares correspondientes y sus habitantes fueron encuestados sobre la gripe entre el 14 y el 20 de Febrero (semana 7 de 2005). Tambien se les hicieron preguntas sobre su estatus vacunal en relacion a la gripe, sobre los sintomas y el impacto de la enfermedad en su vida diaria. Se estimo asi en un 7,7% la prevalencia auto-definida durante la semana 7. Aplicando como definicion de caso de sindrome gripal “tos-fiebre-dolores musculares”, la prevalencia bajo al 3,6%. La encuesta proporciono una mejor medida del peso de la enfermedad en la poblacion que la estimada unicamente por el sistema de vigilancia centinela.
An Element of Unsteadiness
Authors: Danielle L. Saly, Ursula C. Brewster, Gordon K. Sze, Elan D. Louis, Anushree C. Shirali
Journal: New England Journal of Medicine (2017)

A 61-year-old woman presented with a 3-day history of increasingly unsteady gait and an inability to stand. She had a history of numbness and tingling in her hands and feet over the previous year.
Abstract #2676: Anthocyanins isolated from meoru (Vitis coignetiae Pulliat) inhibit the invasion of human hepatoma cells by the suppression of NF-KB activation
Authors: Won Sup Lee, Dong Yeok Shin, Seok Hyun Kim, Gyu Young Chai, Irina Tsoy, Hye Jung Kim, Sung Joong Lee, Chung Ho Rye, Gi Young Kim, Ho Sung Kang, Sung Chul Shin, Yung Hyun Choi
Journal: Cancer Research (2009)

Meoru (Vitis coignetiae Pulliat) has been used as a remedy for inflammatory diseases and cancers. It contains lots of anthocyanins, which belong to a class of flavonoids exhibiting antioxidant and anti-inflammatory actions as well as a variety of chemotherapeutic effects. We isolated anthocyanins from meoru. In this study, we investigated the anti-cancer activity of anthocyanins isolated from meoru (AIMs). We tested anti-cancer effects of AIMs on human hepatoma cells, Hep3B cells expressing hepatitis virus B antigen. AIMs inhibited in a dose-dependent manner the invasion of Hep3B cells through a Matrigel-coated chamber. AIMs inhibit TNF-\#945;-induced NF-\#954;B activity and I\#954;B\#945; phosphorylation. In Hep3B cells, anthocyanins also inhibited expression of MMP-2 and MMP-9 which are regulated by NF-\#954;B activity. AIMs also inhibited TNF-\#945;-stimulated invasion of Hep3B cells. Taken together, the results of this study indicate that the anthocyanins isolated from meoru have anti-invasive effects on human hepatoma Hep3B cells at least in part by the inhibition of NF-\#954;B activation. This study suggests that AIMs might be the helpful phytochemicals for the management of human hepatitis B associated hepatoma. Keywords: anthocyanins, cancer, MMP-2, MMP-9, invasion, Hep3B cell, NF-\#954;B * This study was supported by a grant from the National RD 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2676.
A selective Aurora B kinase inhibitor with potent anticancer activity either as a single agent or in combination with irinotecan (CPT-11) in colon cancer cells
Authors: Jayasree Nair, Gary Schwartz
Journal: Cancer Research (2008)

2304   AZD1152 is a novel, selective inhibitor of Aurora B that targets cell division in proliferating tumor cells. Clonogenic assay revealed an IC-50 of 20 nM in the colon cancer cell line HCT-116 with target inhibition (reduction of phosphorylation of histone H3 ser10) observed at this concentration by western blot and immunofluorescence. Irrespective of the p53 status of the cell line, AZD1152 induced its antiproliferative effect by inhibiting cytokinesis with endoreduplication of chromosomes. At a concentration of 100 nM AZD1152 induced all the cells to undergo polyploidy followed by significant apoptosis. AZD1152 also showed tumor suppression/ regression in mice bearing HCT-116 tumors in a dose dependent manner. However, 3 weeks after the therapy the tumors showed an increased proliferation rate and regrowth. Combination studies were done with the topoisomerase II poison CPT-11 and its active metabolite SN-38. In vitro studies showed a synergistic effect with SN-38. A close examination revealed an antagonistic effect when SN-38 was given prior to AZD1152. This was associated with SN-38 induced G2 cell cycle arrest and a decrease in AZD1152 induced polyploidy. In contrast, the reverse sequence of AZD1152 followed by SN-38 was most effective with persistence of the polyploid phenotype and increased apoptosis. This was confirmed using annexin V+, and DAPI staining, as well as western blot using PARP cleavage. This was next evaluated in tumor bearing mice. As expected the effect of tumor suppression/ regression against the HCT-116 xenografts was greatest in the combination therapy as compared with either single agent AZD1152 or CPT-11 therapy. The sequence of drug administration favored AZD1152 followed by CPT-11, though even the reverse sequence was better than either agent alone. In conclusion,  AZD1152 is a potent inhibitor of cell growth in proliferating colon cancer cells, both as a single agent and in combination with CPT-11. Studies suggest that administration sequence may influence the outcome when an Aurora B kinase inhibitor is co-administered with a topoisomerase inhibitor. Supported by AstraZeneca.
Abstract 15482: Recovery of Histone Methylation and Cardiac Function by Prolonged Left Ventricular Assist Device Support, Predominantly by Pulsatile Flow Device, in Advanced Heart Failure
Authors: Emiko Ito, Shigeru Miyagawa, Satsuki Fukushima, Yasushi Yoshikawa, Shunsuke Saito, Keitaro Domae, Akima Harada, Maki Takeda, Koichi Toda, Yoshiki Sawa
Journal: Circulation (2016)

Background:  It was reported that pulsatile flow left ventricular assist device (PF-LVAD) is more likely to induce reverse remodeling of the LV than continuous flow one (CF-LVAD), while underlying mechanism remains unclear. Epigenetic modification such as histone methylation has been suggested to be an important upstream signal to determine function and/or fate of cardiac tissue. We hypothesized that histone methylation may be associated with reverse LV remodeling under the LVAD support, dependent upon the type of the LVAD.   Methods:  This study enrolled 15 patients (7 PF-LVAD and 8 CF-LVAD) who institutionally completed “bridge-to-transplantation” by 2.7±1.2 years and 2.0±0.7 years of the LVAD support, respectively. Transmural tissue of the LV apex was sampled at the time of the LVAD implant and the transplant surgery.   Results:  Ejection fraction predominantly increased in the PF-LVAD group, compared to that in the CF-LVAD group (18.4±9.4% to 28.1±11.1% vs 17.6±3.8% to 16.6±4.0%,  P   P   P   P     Conclusion:  Functional recovery in advanced cardiac failure occurred predominantly under the PF-LVAD support compared to that under the CF-LVAD support, in association with recovery of histone methylation in the LV cardiomyocytes, suggesting that pulsatile flow is important in reverse LV remodeling at least in part  via  epigenetic modification.
Comprehensive Genomic Profiling (CGP) of Thymic Gland Carcinomas
Authors: J.S. Ross, P. Vanden Borre, N. Almog, A.B. Schrock, J. Chung, J.-A. Vergilio, J. Suh, S. Ramkissoon, E. Severson, S. Daniel, S.M. Ali, V.A. Miller, P.J. Stephens, J.A. Elvin, L.M. Gay
Journal: Annals of Oncology (2017)
Multicenter Validation of Enhancer of Zeste Homolog 2 Expression as an Independent Prognostic Marker in Localized Clear Cell Renal Cell Carcinoma
Authors: Thai Huu Ho, Payal Kapur, Jeanette E. Eckel-Passow, Alana Christie, Richard W. Joseph, Daniel J. Serie, John C. Cheville, R. Houston Thompson, Farrah Homayoun, Vandana Panwar, James Brugarolas, Alexander S. Parker
Journal: Journal of Clinical Oncology (2017)

Purpose Enhancer of zeste homolog 2 (EZH2), a chromatin remodeler, is implicated in the pathogenesis of clear cell renal cell carcinoma (ccRCC). However, the effect of EZH2 on outcomes in localized ccRCC is unclear, and molecular biomarkers are not currently integrated into prognostic models or adjuvant therapy trials. Methods We performed Cox regression to evaluate the association of tumor-based EZH2 gene and protein expression with survival in three independent cohorts: a cohort from The Cancer Genome Atlas (n = 532), a cohort from University of Texas Southwestern Medical Center (n = 122), and a cohort from Mayo Clinic (n = 1,338). Analyses were adjusted for the prognostic stage, size, grade, and necrosis (SSIGN) score as well as within low-, intermediate-, and high-risk SSIGN groups. Results Patients in The Cancer Genome Atlas cohort with EZH2-high gene expression were 1.5 times more likely to experience overall death than patients with EZH2-low expression (95% CI, 1.1 to 2.3; P = .028). Patients in the University of Texas Southwestern Medical Center cohort with EZH2-high protein expression were two times more likely to experience overall death than patients with EZH2-low expression (95% CI, 1.1 to 4.4; P = .034). Similarly, patients in the Mayo Clinic cohort with EZH2-high protein expression were 1.4 times more likely to experience overall death (95% CI, 1.2 to 1.7; P < .001). Patients in the Mayo Clinic cohort with EZH2-high protein expression were nearly two times more likely to experience RCC-specific death (95% CI, 1.5 to 2.6; P < .001); EZH2 protein expression was particularly prognostic among patients with low-risk SSIGN tumors (HR, 6.1; 95% CI, 3.4 to 11.1; P < .001). Conclusion EZH2 expression accurately predicts risk of RCC death beyond existing clinicopathologic models, particularly in low- and intermediate-risk SSIGN tumors. Further studies are required to incorporate molecular biomarkers into surveillance guidelines and adjuvant clinical trials.
Letter by Ma et al Regarding Article, “Depression Treatment and 1-Year Mortality After Acute Myocardial Infarction: Insights From the TRIUMPH Registry (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients’ Health Status)”
Authors: Lei-Lei Ma, Fei-Juan Kong, Jun-Bo Ge
Journal: Circulation (2017)

We congratulate Smolderen et al for their significant work recently published in Circulation about the effects of antidepression therapy in patients hospitalized with a first acute myocardial infarction. 1 The findings of this observational multicenter cohort study indicate that antidepressant therapy appears to fail to improve the adjusted 1-year risk of mortality for depressed patients after myocardial infarction.However, detailed information about antidepressant therapy was not specifically reported in the present study.Consistent with the present study, most clinical studies have failed to demonstrate a cardiovascular benefit from antidepressant treatment.3][4] To our knowledge, only 1 study was performed to compare the cardiovascular effects of different serotonin reuptake inhibitors in depressed patients with ischemic heart disease. 4It was noted that nortriptyline treatment was related to increased serious adverse cardiac events in comparison with paroxetine in depressed patients with ischemic heart disease. 4Furthermore, a preclinical study has shown that chronic treatment with paroxetine but not fluoxetine improved cardiac function and structure in mice after myocardial infarction by inhibiting G-protein-coupled receptor kinase 2. 5 These results suggest that the different antidepressant drugs may produce diverse cardiovascular effects.Therefore, the lack of detailed information about antidepressant therapy in this study makes it confusing to understand whether the negative outcomes are attributable to the ineffectiveness of antidepressant treatment or the disturbance from different antidepressant drugs.
The resilience framework as a strategy to combat stress-related disorders
Authors: Raffael Kalisch, Dewleen G. Baker, Ulrike Basten, Marco P. Boks, George A. Bonanno, Eddie Brummelman, Andrea Chmitorz, Guillén Fernàndez, Christian J. Fiebach, Isaac Galatzer-Levy, Elbert Geuze, Sergiu Groppa, Isabella Helmreich, Talma Hendler, Erno J. Hermans, Tanja Jovanovic, Thomas Kubiak, Klaus Lieb, Beat Lutz, Marianne B. Müller, Ryan J. Murray, Caroline M. Nievergelt, Andreas Reif, Karin Roelofs, Bart P. F. Rutten, David Sander, Anita Schick, Oliver Tüscher, Ilse Van Diest, Anne-Laura van Harmelen, Ilya M. Veer, Eric Vermetten, Christiaan H. Vinkers, Tor D. Wager, Henrik Walter, Michèle Wessa, Michael Wibral, Birgit Kleim
Journal: Nature Human Behaviour (2017)
CNS response to osimertinib in Asian-Pacific patients (pts) with T790M-positive advanced NSCLC: data from an open-label Phase II trial (AURA17)
Authors: C. Zhou, Y. Cheng, Y. Lu, M. Shi, J-Y. Han, M. Wang, S-W. Kim, J. Wang, Y. Chen, Y-L. Wu
Journal: Annals of Oncology (2017)
GW28-e0962 Neutrophil extracellular traps(NETs) was considered to play a key role in disseminated intravascular coagulation(DIC).The chromatin filaments were released by activated polymorphonuclear neutrophil(PMNs) and decorated with granule proteins such as tissue factor(TF). Therefore, we investigated circulating levels of NETs in DIC caused by fulminant myocarditis to analyze coagulation complication severity and predict the outcome.
Authors: Jia Xu, Ye Zhang, Xue Xu, Jinli Liao, Yan Xiong, Hong Zhan
Journal: Journal of the American College of Cardiology (2017)
Abstract 09: Technology Fluency is Not a Barrier to User Adoption of a Mobile Health (mHealth) Wrist-worn Physical Activity (PA) Monitor System: Observations From the Washington, D.C. Cardiovascular (CV) Health and Needs Assessment
Authors: Leah Yingling, Colby Ayers, Marlene Peters-Lawrence, Gwenyth Wallen, Valerie Mitchell, Alyssa Todaro-Brooks, Dana Sampson, Johnetta Saygbe, JaWanna Henry, Samantha Thomas, Joel Adu-Brimpong, Kenneth Wiley, Avis Graham, Lennox Graham, Allan Johnson, Tiffany Powell-Wiley
Journal: Circulation (2016)

Background: Emerging mHealth technologies, like wrist worn PA monitors, offer potential for targeting CV health behaviors among at-risk groups in community-based interventions. It is unknown whether technology fluency impedes user adoption of such mHealth interventions. Methods: A CV health evaluation designed using community-based participatory research principles was conducted in African American, faith-based organizations in Washington D.C. wards with the highest obesity rates (NCT01927783). Participants (n=100) underwent a CV health assessment at a community church and were trained to use an mHealth PA monitor for the ensuing 30-day period. Participants wirelessly uploaded PA data weekly to a data collection hub at a participating church and accessed data online. Users were participants with ≥1 days of data; non-users had zero days of data. A validated Computer-Email-Web fluency self-report instrument captured technology fluency, with skill levels from 1 (no fluency) to 5 (high fluency). Results: Eighty-one participants were users (mean age=60, 78% female); 19 were non-users (mean age=57, 84% female). Users were more likely than non-users to report a lower household income (p=0.01). No differences were noted for computer access (94% vs 94%, p=0.2) or cell phone ownership (88% vs 89%, p=0.2). Technology fluency was similar, with all non-users and 95% of users reporting some level of technology fluency for the 17 surveyed skills (Table). Conclusions: In African-American, faith-based communities in at-risk Washington D.C. areas, lower technology fluency does not appear to impede adoption of this mHealth PA-monitoring system, despite lower socioeconomic status among users. This relationship is likely explained by similar technology access among users and non-users. These findings suggest that an mHealth PA monitoring system using a data collection hub may facilitate a future PA intervention for improved CV health in an at-risk African American community, independent of the population’s technology fluency.
Brief Report: Loss of Muscle Strength Prior to Knee Replacement: A Question of Anatomic Cross‐Sectional Area or Specific Strength?
Authors: Adam G. Culvenor, Felix C. Hamler, Jana Kemnitz, Wolfgang Wirth, Felix Eckstein
Journal: Arthritis & Rheumatology (2017)

Objective To determine whether loss in thigh muscle strength prior to knee replacement is caused by reductions of muscle strength in the anatomic cross‐sectional area or by reductions of specific strength. Methods All 100 of the participants in the Osteoarthritis Initiative who underwent knee replacement and whose medical records included data on thigh isometric muscle strength and magnetic resonance imaging ( MRI ) (58 women, and 42 men, mean ± SD age 65 ± 8 years, mean ± SD body mass index [ BMI ] 29 ± 5 kg/m 2 ) were matched with a control (no knee replacement) for age, sex, height, BMI , and radiographic severity. Thigh muscle anatomic cross‐sectional area was determined by MRI at the research visit before knee replacement (time 0) and 2 years before time 0 (time −2). Specific strength (strength/anatomic cross‐sectional area) was calculated, and the measures were compared by conditional logistic regression (i.e., odds ratio [ OR ] per standard deviation). ORs adjusted for pain ( OR adj ) and 95% confidence intervals (95% CI s) were also calculated. Results Knee replacement cases had significantly smaller extensor (but not flexor) anatomic cross‐sectional areas than controls at time 0 (women, OR adj 1.89 [95% CI 1.05–3.90]; men, OR adj 2.22 [95% CI 1.04–4.76]), whereas no significant differences were found at time −2. Women who had knee replacement showed lower levels of extensor specific strength than controls at time 0 ( OR 1.59 [95% CI 1.02–2.50]), although this difference was not observed in men and did not maintain significance after adjustment for pain ( OR adj 1.22 [95% CI 0.71–2.08]). Female cases lost significantly more extensor specific strength between time −2 and time 0 than controls ( OR adj 3.76 [95% CI 1.04–13.60]), whereas no significant differences were noted at time −2, or in men. Conclusion Prior to knee replacement, a significant reduction in knee extensor strength appears to occur in women through 2 mechanisms: one driven by pain (loss of specific strength) and one independent of pain (loss of muscle anatomic cross‐sectional area). Men who underwent knee replacement showed significantly reduced levels of extensor anatomic cross‐sectional area, but not significantly lower strength or specific strength.
A phase II study of TAS-102 for advanced/recurrent esophageal cancer refractory/intolerable to standard therapies
Authors: T. Kojima, H. Kasai, T. Tsushima, H. Hara, Y. Mori, R. Ishihara, K. Kato, S. Hironaka, K. Mukai, O. Kikuchi, K. Enomoto, H. Tada, R. Uozumi, A. Kawaguchi, M. Muto
Journal: Annals of Oncology (2017)
Patient commentary: the current model has failed
Authors: Emma Robertson
Journal: BMJ (2017)

The cost of cancer drugs is skyrocketing: prices of cancer drugs increased by 10% every year between 1995 and 2013.1 More and more we’re seeing cancer drugs being priced off the NHS—as is the case with secondary breast cancer drug palbociclib, currently under review after it was rejected by NICE earlier this year because of cost.

Another really hard burden to bear for patients is that so many …
DNA methylation and histone modifications in regulating chromatin structure and gene expression in colorectal cancer
Authors: Yutaka Kondo, Lanlan Shen, Saira Ahmed, Jean-Pierre Issa
Journal: Cancer Research (2004)

4167   Histone modifications and DNA methylation have been functionally linked to transcription in selected genes in normal to cancer cells. To increase understanding of the interrelations between these two major epigenetic mechanisms, we studied nine residues of histone H3 and H4 and DNA methylation status at 13 loci in two colon cancer cell lines. Chromatin immunoprecipitation (ChIP) assays revealed clear distinctions in the pattern of histone modification between active and silenced genes. Methylation at histone H3 lysine (K) 4 and acetylation at histone H3-K9, H3-K14, H4-K5, H4-K8 and H4-K12 were moderately to substantially higher in active genes than in silenced genes. Among these modifications, levels of methylation on histone H3-K4 and acetylation on histone H3-K9 were most consistently higher in active genes. The average fold of relative precipitated enriched H3-K4 methylation was 1.07 versus 0.38 in active genes versus silenced genes (p
Outcomes of patients with metastatic renal cell carcinoma (mRCC) who were treated with second-line (2L) vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) after first-line (1L) immune checkpoint inhibitor (ICI) therapy
Authors: A.Y. Shah, E.A. Lemke, G. Jianjun, A. Chandamohan, M.T. Campbell, A. Zurita Saavedra, L. Xiao, J. Wang, P.G. Corn, E. Jonasch, P. Sharma, N. Tannir
Journal: Annals of Oncology (2017)
Metabolic and cardiovascular benefits of hydroxychloroquine: exploration in a wider population at high CV risk
Authors: Anil Pareek, Indranil Purkait, Ravi T Mehta, Anu Grover
Journal: Annals of the Rheumatic Diseases (2017)

We complement the authors on their systematic review and meta-analysis on metabolic and cardiovascular (CV) benefits of hydroxychloroquine (HCQ).1 The authors have restricted the meta-analysis to studies comparing HCQ users versus non-users in rheumatoid arthritis (RA). This criterion has precluded the inclusion of many studies where metabolic and CV benefits of HCQ have been reported. We would like to highlight these to add to the significant benefits of this molecule, thus widening the evidence base.

Authors did not include studies comparing HCQ with other disease-modifying antirheumatic drugs (DMARDs) and biologicals. In a study cohort of 13 905 participants, majority of …