tbuckley/cabot-search huggingface dataset:
Abstract LB-324: Methylation-associated silencing of miR-193a-3p promotes ovarian cancer aggressiveness via targeting GRB7
Authors: Kangmei Chen, Hextan YS Ngan, David W. Chan
Journal: Cancer Research (2017)

Abstract The human growth factor receptor-bound protein-7 (GRB7) is a pivotal mediator involved in receptor tyrosine kinase signaling and governing diverse cellular processes. We and others have reported that GRB7 is frequently upregulated and associated with the progression of human cancers. Clinicopathological analysis has shown that the overexpressed GRB7 is correlated with high grade and metastatic ovarian cancers. However, the molecular mechanisms leading to the upregulation of GRB7 remain largely unknown. In this study, we propose that the epigenetic modification of GRB7 at the post-transcriptional level may be a crucial factor leading to GRB7 upregulation in ovarian cancers. We found that the protein level of GRB7 was much higher than its mRNA levels in a subset of ovarian cancer cell lines, indicating aberrant post-transcriptional alterations in GRB7. Using an in silico study, we identified miR-193a-3p and its isoform, miR-193b-3p, by specifically targeting the conserved site (GGCCAGT) at position 332-338 in the 3’ UTR (length: 387) of the human GRB7 gene. QPCR and western blot analyses revealed that only the expression levels of miR-193a-3p but not miR-193b-3p were inversely correlated in ovarian cancer cell lines accompanied with high levels of GRB7 protein levels. Further biochemical analyses using luciferase reporter assays in combination with mutational analyses identified miR-193a-3p specifically targeting GRB7 3’UTR, confirming miR-193a-3p, instead of its isoform miR-193b-3p, has a more important role in GRB7 post-transcriptional regulation in ovarian cancer cells. Constitutive expression or knockdown of miR-193a-3p could significantly alter GRB7 expression, as well as oncogenic capacities of ovarian cancer cells such as cell growth, cell migration and cell invasion. Importantly, we observed that there was a significant stepwise decrease of miR-193a-3p expression from low to high grade ovarian cancers, and was inversely correlated with GRB7 expressions. Intriguingly, treatment with the DNA methyl transferase inhibitor (5’-Aza-dc) could restore the expression of miR-193a-3p, suggesting the epigenetic inhibition of miR-193a-3p is clinically relevant. Importantly, such epigenetic alteration may be the clue leading to overexpression of GRB7 in ovarian cancer cells. Taken together, our findings suggest that epigenetically silencing of miR-193a-3p upregulates GRB7 and contribute to ovarian cancer aggressiveness in tumor progression. Citation Format: Kangmei Chen, Hextan YS Ngan, David W. Chan. Methylation-associated silencing of miR-193a-3p promotes ovarian cancer aggressiveness via targeting GRB7 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-324. doi:10.1158/1538-7445.AM2017-LB-324
<i>Notes from the Field:</i> Measles Outbreak at a United States Immigration and Customs Enforcement Facility ― Arizona, May–June 2016
Authors: Heather Venkat, Ahmed M. Kassem, Chia-ping Su, Clancey Hill, Evan Timme, Graham Briggs, Kenneth Komatsu, Susan Robinson, Rebecca Sunenshine, Manisha Patel, Diana Elson, Paul Gastañaduy, Shane Brady, Jessica Rigler, Cara Christ, Eugene Livar, Lisa Villarroel, Rosa Lira, Corey Tarango, Teresa Jue, Sara Imholte Johnston, Don Herrington, Karen Lewis, Harmony Duport, Peter Kelly, Krista Anheluk, Irene Ruberto, Jennifer Pistole, Kristen Herrick, Jabette Franco, Samuel Packard, Christopher Reimus, Marcela Salinas, Tammy Sylvester, Ron Klein, Karen Rose, Karen Zabel, Jennifer Adair, Marcus Castle, Bob England, Edith Lederman, Geri Tagliaferri, Jennifer Freiman, Bessie Padilla, Herman Auhl, Paul Rota, Carole Hickman, Jessica Leung, Sun Bae Sowers, Sara Mercader, William Slanta, Kathryn Fitzpatrick, Jessica Escobar
Journal: MMWR Morbidity and Mortality Weekly Report (2017)
Erratum: Mutation of the gene in a family with optic nerve colobomas, renal anomolies and vesicoureteral reflux (Nature Genetics (1995) 9 (358- 364))
Authors: P. Sanyanusin, Lisa A Schimmenti, L. A. McNoe, T. A. Ward, Mary Ella M Pierpont, M. J. Sullivan, W. B. Dobyns, M. R. Eccles
Journal: Nature Genetics (1996)
Concussion education: a randomised trial with undergraduate students
Authors: Tara Kobitowich, Martin Mrazik
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate optimal methods for educating individuals about concussions. Design Prospective randomised controlled trial. Setting University setting. Participants 162 undergraduate students. Intervention Students from a university participant pool were randomly assigned to one of three conditions: 1) control group (CN); 2) internet group (IG); 3) presentation group (PG). All subjects completed the knowledge concussion questionnaire (18 questions) in the concussion knowledge section of the questionnaire published by Rosenbaum &amp; Arnett (2014). Subjects completed a pretest and a posttest. The IG was provided with 3 websites and given 30 minutes to review this material. The PG group was involved in a 45 minute interactive lecture from a neuropsychologist. Main outcome measure Concussion knowledge. Main results A repeated measures ANOVA suggested a significant interaction between group and time F (2, 159)=30.2, p&lt;0.001. The PG demonstrated significantly higher scores at posttest compared with both the IG and CN groups [(F (2, 159)=12.6, p&lt;0.001 although all groups presented with improved scores at the posttest interval compared with the pretest. Post-hoc pairwise comparison at posttest interval between CN and IG groups did not reach statistical significance (p=0.50). Specific items suggested inaccurate information about concussions may be common in the undergraduate population. Conclusions There are many methods used to educate athletes about concussions. As expected, an interactive presentation about concussions was more effective at improving concussion knowledge than reviewing information from the internet. Results also suggested the importance of clarifying existing myths about concussions Conflicts There were no conflicts to declare. Competing interests None.
Immune Correlates of GM-CSF and Melanoma Peptide Vaccination in a Randomized Trial for the Adjuvant Therapy of Resected High-Risk Melanoma (E4697)
Authors: Lisa H. Butterfield, Fengmin Zhao, Sandra Lee, Ahmad A. Tarhini, Kim A. Margolin, Richard L. White, Michael B. Atkins, Gary I. Cohen, Theresa L. Whiteside, John M. Kirkwood, David H. Lawson
Journal: Clinical Cancer Research (2017)

Purpose: E4697 was a multicenter intergroup randomized placebo-controlled phase III trial of adjuvant GM-CSF and/or a multiepitope melanoma peptide vaccine for patients with completely resected, high-risk stage III/IV melanoma.Experimental Design: A total of 815 patients were enrolled from December 1999 to October 2006 into this six-arm study. GM-CSF was chosen to promote the numbers and functions of dendritic cells (DC). The melanoma antigen peptide vaccine (Tyrosinase368-376 (370D), gp100209-217 (210M), MART-127-35) in montanide was designed to promote melanoma-specific CD8+ T-cell responses.Results: Although the overall RFS and OS were not significantly improved with the vaccine or GM-CSF when compared with placebo, immunomodulatory effects were observed in peripheral blood and served as important correlates to this therapeutic study. Peripheral blood was examined to evaluate the impact of GM-CSF and/or the peptide vaccine on peripheral blood immunity and to investigate potential predictive or prognostic biomarkers. A total of 11.3% of unvaccinated patients and 27.1% of vaccinated patients developed peptide-specific CD8+ T-cell responses. HLA-A2+ patients who had any peptide-specific CD8+ T-cell response at day +43 tended to have poorer OS in univariate analysis. Patients receiving GM-CSF had significant reduction in percentages of circulating myeloid dendritic cells (mDC) and plasmacytoid DC (pDC) at day +43. In a subset of patients who received GM-CSF, circulating myeloid-derived suppressor cells (MDSC), and anti-GM-CSF-neutralizing antibodies (Nabs) were also modulated. The majority of patients developed anti-GM-CSF Nabs, which correlated with improved RFS and OS.Conclusions: The assessment of cellular and humoral responses identified counterintuitive immune system changes correlating with clinical outcome. Clin Cancer Res; 23(17); 5034-43. ©2017 AACR.
Establishment of a highly sensitive Taqman-based assay for non-invasively detecting biomarkers expressed in circulating tumor cells in human and mouse whole blood.
Authors: Han Ying, Sandra Biroc, Robert Radeke, Jian-ming Gu, Ted Lau, Michael Mamounas
Journal: Cancer Research (2007)

3492  In this study, we developed a Taqman-based RT-PCR assay to quantify circulating tumor cells (CTCs) in human and mouse whole blood. Human gastric cancer cells MKN45 were spiked into whole mouse or human blood and RNA was extracted and analyzed by Taqman RT-PCR with probes specific for a panel of markers, including human Cytokeratin 8 (CK-8), Cytokeratin 18 (CK-18), Cytokeratin 19 (CK-19), cMET and EpCAM. The assay can detect as few as 2-5 cells in 1ml of human or mouse whole blood. The sensitivity of the assay depends on the expression level of the marker used, with CK-18 being the most abundant marker for MKN45 and hence the most sensitive one. To correlate tumor burden with amount of human cancer markers in mouse blood in an animal model, MKN45 cells were implanted i.p. to nude mice, and after 3 weeks peritoneal tumors were excised and weighed and blood analyzed. The amount of CTCs, as measured by Taqman on RNA, tightly correlated (R2 = 0.8893) with tumor burden. To evaluate whether such markers can be used as surrogate markers for predicting treatment efficacy, a set of nude mice bearing MKN45 i.p. tumors was treated with 25 or 75 mg/kg/dose p.o. twice daily for 2 weeks with a potent inhibitor of cMet as well as a potent inhibitor CPT-11. The cMET compound caused a 50% and 90% reduction in tumor burden, whereas CPT-11 caused over 90% tumor reduction. The blood was analyzed and showed a correlated dose-dependent reduction in the markers by the Taqman assay. Our data suggest that human cancer/epithelial markers can be used as surrogate markers for assessing efficacy during anti-cancer drug treatment. Additionally, such markers have potential for patient stratification using non-invasive methods. contact: drhanying@gmail.com
Pharmaceutical-grade Chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT)
Authors: Jean-Yves Reginster, Jean Dudler, Tomasz Blicharski, Karel Pavelka
Journal: Annals of the Rheumatic Diseases (2017)

Objectives Chondroitin sulfate 800 mg/day (CS) pharmaceutical-grade in the management of symptomatic knee osteoarthritis consistent with the European Medicines Agency guideline. Methods A prospective, randomised, 6-month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day)-controlled trial assessing changes in pain on a Visual Analogue Scale (VAS) and in the Lequesne Index (LI) as coprimary endpoints. Minimal-Clinically Important Improvement (MCII), Patient-Acceptable Symptoms State (PASS) were used as secondary endpoints. Results 604 patients (knee osteoarthritis) diagnosed according to American College of Rheumalogy (ACR) criteria, recruited in five European countries and followed for 182 days. CS and celecoxib showed a greater significant reduction in pain and LI than placebo. In the intention-to-treat (ITT) population, pain reduction in VAS at day 182 in the CS group (−42.6 mm) and in celecoxib group (−39.5 mm) was significantly greater than the placebo group (−33.3 mm) (p=0.001 for CS and p=0.009 for celecoxib), while no difference observed between CS and celecoxib. Similar trend for the LI, as reduction in this metric in the CS group (−4.7) and celecoxib group (−4.6) was significantly greater than the placebo group (−3.7) (p=0.023 for CS and p=0.015 for celecoxib), no difference was observed between CS and celecoxib. Both secondary endpoints (MCII and PASS) at day 182 improved significantly in the CS and celecoxib groups. All treatments demonstrated excellent safety profiles. Conclusion A 800 mg/day pharmaceutical-grade CS is superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in symptomatic knee osteoarthritis (OA) patients. This formulation of CS should be considered a first-line treatment in the medical management of knee OA.
Baseline symptoms are associated with post-concussion symptom frequency and severity in college and high school athletes
Authors: EF Teel, EB Wasserman, JK Register-Mihalik, JP Mihalik
Journal: British Journal of Sports Medicine (2017)

Objective To determine the association between baseline symptoms and symptom frequency and severity one day post-concussion in college and high school athletes. Design Prospective cohort. Setting USA colleges (n=26) and high schools (n=210). Subjects Concussed individuals (n=375; 314 males; 61 females) recruited from a baseline cohort (N=8,905). Intervention Baseline presence or absence for each of the 20 items on a Graded Symptom Checklist (GSC). Outcome measures GSC symptom frequency and severity one day post-concussion. Results Individuals with baseline headache (χ 2 (1)=10.98; P &lt;0.001), fatigue (χ 2 (1)=6.06; P =0.014), sleeping more than usual (χ 2 (1)=16.90; P &lt;0.001), blurred vision (χ 2 (1)=20.48; P &lt;0.001), light/noise sensitivity (χ 2 (1)=4.67; P =0.031), and mental fogginess (χ 2 (1)=6.08; P =0.014) reported these symptoms at a higher frequency post-concussion. Subjects reporting the following baseline symptoms had greater severity of the same symptom post-concussion: headache (Presence: median=2; IQR=1–4; Absence: median=2, IQR=0–3; P =0.004), fatigue (Presence: median=1; IQR=0–3; Absence: median=0, IQR=0–2; P =0.017), sleeping more than usual (Presence: median=1, IQR=0–3; Absence: median=0, IQR=0–0; P &lt;0.001), blurred vision (Presence: median=1; IQR=0–2; Absence: median=0, IQR=0–0; P &lt;0.001), sensitivity to light and noise (Presence: median=1, IQR=0–3; Absence: median=0, IQR=0–1; P =0.010), and fogginess (Presence: median=2, IQR=0–3; Absence: median=0, IQR=0–1; P =0.002). No other symptoms at baseline were associated with post-concussion symptom frequency or severity ( P &gt;0.05). Conclusions Athletes reporting baseline symptoms, particularly those in physical and sleep-related domains, were more likely to report a higher frequency and severity of these same symptoms one day post-concussion. Understanding factors influencing post-concussion symptom recovery may inform clinical decision-making and offer selection criteria for appropriate active recovery strategies. Competing interests None.
Diagnostic Accuracy of Computed Tomography–Derived Fractional Flow Reserve
Authors: Christopher M. Cook, Ricardo Petraco, Matthew J. Shun-Shin, Yousif Ahmad, Sukhjinder Nijjer, Rasha Al-Lamee, Yuetsu Kikuta, Yasutsugu Shiono, Jamil Mayet, Darrel P. Francis, Sayan Sen, Justin E. Davies
Journal: JAMA Cardiology (2017)

Computed tomography-derived fractional flow reserve (FFR-CT) is a novel, noninvasive test for myocardial ischemia. Clinicians using FFR-CT must be able to interpret individual FFR-CT results to determine subsequent patient care.To provide clinicians a means of interpreting individual FFR-CT results with respect to the range of invasive FFRs that this interpretation might likely represent.We performed a systematic review in accordance with guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A systematic search of MEDLINE (January 1, 2011, to 2016, week 2) and EMBASE (January 1, 2011, to 2016, week 2) was performed for studies assessing the diagnostic accuracy of FFR-CT. Title words used were computed tomography or computed tomographic and fractional flow reserve or FFR. Results were limited to publications in peer-reviewed journals. Duplicate studies and abstracts from scientific meetings were removed. All of the retrieved studies, including references, were reviewed.There were 908 vessels from 536 patients in 5 studies included in the analysis. A total of 365 (68.1%) were male, and the mean (SD) age was 63.2 (9.5) years. The overall per-vessel diagnostic accuracy of FFR-CT was 81.9% (95% CI, 79.4%-84.4%). For vessels with FFR-CT values below 0.60, 0.60 to 0.70, 0.70 to 0.80, 0.80 to 0.90, and above 0.90, diagnostic accuracy of FFR-CT was 86.4% (95% CI, 78.0%-94.0%), 74.7% (95% CI, 71.9%-77.5%), 46.1% (95% CI, 42.9%-49.3%), 87.3% (95% CI, 85.1%-89.5%), and 97.9% (95% CI, 97.9%-98.8%), respectively. The 82% (overall) diagnostic accuracy threshold was met for FFR-CT values lower than 0.63 or above 0.83. More stringent 95% and 98% diagnostic accuracy thresholds were met for FFR-CT values lower than 0.53 or above 0.93 and lower than 0.47 or above 0.99, respectively.The diagnostic accuracy of FFR-CT varies markedly across the spectrum of disease. This analysis allows clinicians to interpret the diagnostic accuracy of individual FFR-CT results. In combination with patient-specific factors, clinicians can use FFR-CT to judge when the cost and risk of an invasive angiogram may safely be avoided.
Responses Assigned Using Heavy+Light Chain Assessments Have Better Clinical Correlation with Outcome Than Those Using Current IMWG Criteria for Multiple Myeloma
Authors: Mauricette Michallet, Colette Chapuis-Cellier, Christine Lombard, Mohamad Sobh, Thomas Dejoie, Helene Caillon, Michel Attal, Philippe Moreau, Herve Avet-Loiseau
Journal: Blood (2016)
Abstract 158: Regulation of miR-21 Expression by Acetylation in Myocardial Infarction
Authors: Ludivine Renaud, Harinath Kasiganesan, Erhe Gao, Santhosh K Mani, Jeffrey A Jones, Robert E Stroud, James Chou, Donald R Menick
Journal: Circulation Research (2012)

Cardiovascular diseases are one of the leading causes of morbidity and mortality in the world, underlining the need for innovative therapies and diagnosis. Recent reports have identified microRNAs (miRNAs) as central players in regulating gene expression and showed that several miRNAs are aberrantly expressed in cardiac arrhythmia, hypertrophy, fibrosis, ischemia, vascular atherosclerosis and heart failure. Gene expression is also regulated at the transcriptional level by histone deacetylases (HDACs) under basal and pathological conditions. We previously demonstrated that 1) class I and class II HDACs play an important role in the basal expression and upregulation of the sodium-calcium exchanger (Ncx1) gene in adult cardiomyocytes and pressure-overloaded ventricle and 2) treatment with class I/IIb HDAC inhibitors trichostatin (TSA) or suberoylanilide hydroxamic acid (SAHA) improved ventricular function by suppressing matrix metalloproteinases (MMPs) gene expression in myocardial infarction (MI).Therefore it is possible that protein acetylation regulates the expression of some miRNAs and we hypothesize that HDAC inhibition would attenuate the shift in expression of certain miRNAs that are aberrantly expressed post-MI. In a pilot study, ligation of the left anterior descending (LAD) coronary artery was performed to induce MI with and without SAHA treatment. Because of its misregulation and relevance in cardiac hypertrophy and MI, we examined the expression level of miR-21. qRT-PCR confirmed that miR-21 is increased by 8 fold 7 days post-MI. Interestingly, SAHA treatment significantly attenuated the abnormal expression of miR-21. To our knowledge, it is the first report of the regulation of a miRNA by HDACs in the heart. We anticipate that not only miR-21 but other miRNAs will fall under the same mechanistic control via acetylation. The miR-21 promoter contains binding sites for several transcription factors that get acetylated and we speculate that one or more HDAC mediate the expression of miR-21 by controlling the acetylation state of transcription factors interacting with the miR-21 promoter.
Novel PDGFRB fusions in childhood B- and T-acute lymphoblastic leukemia
Authors: A M Heilmann, A B Schrock, J He, M Nahas, K Curran, N Shukla, S Cramer, L Draper, A Verma, R Erlich, J Ross, P Stephens, V A Miller, S M Ali, J-A Verglio, M S Tallman, T I Mughal
Journal: Leukemia (2017)
ALTERED MRNAS EXPRESSION OF GENES INVOLVED IN CELLULAR IRON HOMEOSTASIS IN LUNG NON SMALL CELLS CARCINOMA
Authors: M Lo Iacono, A Roetto, Monica, M Boero, T Vavala, S Saviozzi, E Bracco, S Novello, M Papotti, Gv Scagliotti
Journal: Journal of Thoracic Oncology (2012)
Gaze-contingent manipulation of the FVF demonstrates the importance of fixation duration for explaining search behavior
Authors: Jochen Laubrock, Ralf Engbert, Anke Cajar
Journal: Behavioral and Brain Sciences (2017)

Abstract Hulleman &amp; Olivers' (H&amp;O's) model introduces variation of the functional visual field (FVF) for explaining visual search behavior. Our research shows how the FVF can be studied using gaze-contingent displays and how FVF variation can be implemented in models of gaze control. Contrary to H&amp;O, we believe that fixation duration is an important factor when modeling visual search behavior.
Analysis of tolerability of intravesical bacillus Calmette-Guérin (BCG) therapy in non-muscle-invasive bladder cancer.
Authors: Jun Miyazaki, Naoki Ishizuka, Shiro Hinotsu, Hideyuki Akaza, Hiroyuki Nishiyama
Journal: Journal of Clinical Oncology (2012)

e15004 Background: Although the effectiveness of BCG intravesical instillation with maintenance therapy (MT) has been shown (Hinotsu S. BJUI 2010), the treatment was not well tolerated. We aimed to characterize adverse events (AEs) affecting tolerability and to study the possible prediction of MT tolerability during the induction therapy (IT) by using data from the previous phase III trial. Methods: Forty-two patients received 81 mg intravesical BCG once weekly for 6 weeks as IT followed by thrice weekly instillations at 3, 6, 12 and 18 months as MT. AEs after each instillation were analyzed. The hazard ratio (HR) and 95% confidence intervals (CI) between the risk of each AE during IT and MT were analyzed by Cox regression. To assess the time between the randomization and the onset of each AE, HR and CI for patients without an AE were measured against those who developed the AE once, using the Wei-Lin-Weissfeld (WLW) Model. The WLW Model allows the analysis of recurrent AEs by controlling within-patient correlations in a marginal Cox model. Results: Fourteen of the 42 patients completed MT, of whom 11 completed as scheduled, and 3 completed with some modifications. For 28 who did not complete, 6 were withdrawn during IT and 22 during MT (of whom 15 had some MT modifications). Among 17 patients who experienced Grade (Gr) 3 AEs, 4 completed the treatment. In total there were 65 Gr3 events. Urinary frequency was most frequent event causing treatment cessation (7/38 events) and hematuria was the most common cause of treatment modification (7/13). The risk of an AE that occurred during IT recurring during MT was high for malaise (HR:3.49), pyrexia (3.33), and difficulty in urination (2.90). The WLW analysis revealed that malaise was relapsed in 18/21 patients (HR:5.81, CI:2.94-11.50, p&lt;0.0001), difficulty in urination in 13/21 (4.56, 1.92-10.84, 0.0006), pyrexia in 14/18 (4.27, 2.18-8.37, &lt;0.0001), hematuria in 36/39 (2.69, 1.79-4.04, &lt;0.0001) and urinary frequency in 35/39 (2.30, 1.38-3.84, 0.0014). Conclusions: Gr3 urinary frequency was the most common cause of treatment cessation. The risk of the recurrent AE during MT will increase in those who develop AEs such as malaise, pyrexia, and difficulty in urination at IT.