tbuckley/cabot-search huggingface dataset:
Abstract 168: TMEM8A 1080A&gt;G Polymorphism in a 3’UTR MicroRNA Target Site Influences Aerobic Capacity in Health Individuals: the HUNT Study
Authors: Gustavo J Silva, Marcio A Afonso de Almeida, Anja Bye, Hamid el Azzouzi, John Blangero, Ulrik Wisløff
Journal: Circulation Research (2013)

Large-scale epidemiological studies demonstrate that aerobic fitness, measured as maximal oxygen uptake (VO 2max ), is the single best predictor for cardiovascular mortality in both healthy individuals and patients with cardiovascular disease. However, the genetic basis for aerobic capacity has remained unknown. A genome-wide associative study was conducted in 1500 healthy men from the Nord-Trøndelag Health (HUNT3) study in order to identify SNPs located at microRNA target sites associated to VO 2max . VO 2max was directly measured using a treadmill ramp protocol. The following bioinformatics approach were adopted: first, 2,393,543 conserved microRNA binding sites were initially selected from the TargetScan database out of 25,847,058 already identified in the human genome; second, among 60,480,978 SNPs described in the dbSNP, 388,110 SNPs are located in 3’UTRs and only 0.26% (1000 SNPs) were represented in the Illumina Human Cardio-Metabo (200k) chip. We identified a significant (p=0.003142) SNP (rs540, MAF=0.4131), located in the 3’UTR of the transmembrane protein 8A (TMEM8A) gene, associated with VO 2max . TMEM8A is a five membrane-spanning domain, non-globin gene entrapped in the globin pathway. Accordingly, two microRNAs (hsa-miR-190 and hsa-miR-190b) can potentially bind the original variant of the TMEM8A 3’UTR. Interestingly, in the polymorphic variant (G(1080)) these microRNAs are not predicted anymore, and, curiously, five other microRNAs can now bind it (hsa-let-7a-3p, hsa-let-7f-2-3p, hsa-let-7b-3p, hsa-miR-300 and hsa-miR-381). Our data shows for the first time a SNP that can potentially influence microRNA gene expression regulation associated to aerobic capacity in a large population study.
PD-L1 expression and tumor infiltrating lymphocytes (TIL) in brain metastases (BM) of small cell lung cancer (SCLC).
Authors: Anna Sophie Berghoff, Gerda Ricken, Dorothee Wilhelm, Orsolya Rajky, Georg Widhalm, Karin Dieckmann, Peter Birner, Rupert Bartsch, Christoph Zielinski, Matthias Preusser
Journal: Journal of Clinical Oncology (2016)

8563 Background: Novel insights in the pathobiology of SCLC BM are needed for development of new treatment strategies. Methods: TIL subsets (CD3+, CD8+, CD45RO+, FOXP3+ and PD-1+) and expression of PD-L1 was studied in a series of 32 SCLC BM specimens and 4 matched primary tumor specimens using immunohistochemistry. Results: TIL infiltration was present in 30/32 (93.8%) BM specimens. CD3+ TILs were observed in 30/32 (93.8%) BM specimens, CD8+ TILs in 25/32 (78.1%), CD45RO+ TILs in 15/32 (46.9%), FOXP3+ TILs in 15/32 (46.9%) and PD-1+ TILs in 1/32 (3.1%) BM specimens. Dense infiltration with CD45RO+ TILs was associated with a significantly longer median survival time (11 months; 95% CI 0.000- 26.148) as compared to absence of CD45RO+ TILs (5 months; 95% CI 0.966- 9.034; p = 0.007; log rank test). Membranous PD-L1 on tumor cells was observed in 24/32 (75.0%) BM specimens, 11/32 (34.4%) cases presented with membranous PD-L1 expression in over 5% of viable BM tumor cells. PD-L1 expression on tumor infiltrating macrophages was observed in 9/32 (28.1%) specimens and on TILs in 8/32 (25.0%). Among matched primary tumors, all (4/4; 100%) specimens showed TIL infiltration, while PD-L1 expression found in only 1/4 (25.0%) specimen. Conclusions: TIL infiltration and PD-L1 expression are frequently observed in SCLC BM. Presence of CD45RO+ memory T-cells in SCLC BM seems to be associate with favorable survival times. Therefor, our data shows that SCLC BM have an immune active microenvironment that may be targetable by immune-modulating drugs.
A Risk Stratification Model Using Quantification of Circulating Plasma Cells in Multiple Myeloma Prior to Autologous Stem Cell Transplantation in the Era of Novel Agents
Authors: Rajshekhar Chakraborty, Eli Muchtar, Shaji Kumar, Dragan Jevremovic, Francis K Buadi, David Dingli, Angela Dispenzieri, Suzanne R. Hayman, William J Hogan, Prashant Kapoor, Martha Q. Lacy, Nelson Leung, Morie A. Gertz
Journal: Blood (2016)
DRAK2 a Novel Effector of Apoptosis is Modulated by Cyclooxygenase 2 in Colorectal Cancer
Authors: GA Doherty, SM Byrne, SC Austin, GM Scully, EW Kay, FE Murray, DJ Fitzgerald
Journal: Endoscopy (2004)

Aims: Cyclooxygenase 2 (COX-2) is over-expressed in the majority of colorectal tumours, and cancer cells that express COX-2 appear to be rendered resistant to apoptosis. The mechanisms by which COX-2 modulates apoptosis have not been well characterised, however we have identified DRAK2, a pro-apoptotic serine/threonine kinase, as regulated by COX-2 in cancer cells.
Flexible Sigmoidoscopy and Double Contrast Barium Enema in Patients with Large Bowel Symptoms – Diagnostic Yield
Authors: I Paul, GC Beattie, O Gilchrist, WJ Campbell
Journal: Endoscopy (2004)

Introduction: Flexible sigmoidoscopy (FS) combined with double contrast barium enema (DCBE) provides pancolonic imaging in patients with large bowel symptoms. The aim of this study was to assess the diagnostic yield of colorectal pathology in patients undergoing both FS and DCBE.
FDA pulls opioid from market over misuse concerns
Authors: Owen Dyer
Journal: BMJ (2017)

The US Food and Drug Administration has asked Endo Pharmaceuticals to withdraw its Opana ER formulation of oxymorphone amid concerns over a mounting epidemic of opioid misuse. It is the first time the FDA has made such a request, which could require court action to enforce.

The Dublin based drug manufacturer did not immediately say whether it would comply. Endo said in a statement that it is “reviewing the request and is evaluating the full range of potential options.”

The FDA’s request sent Endo’s shares tumbling 13.4% on Wall Street. The request was foreshadowed in March, when an FDA …
The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC
Authors: P N Aguiar, L A Perry, J Penny-Dimri, H Babiker, H Tadokoro, R A de Mello, G L Lopes
Journal: Annals of Oncology (2017)

Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection.We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment.We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were $155 605 and $187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was $215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was $98 421. Patient selection also reduced the budget impact of immunotherapy.The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved.
Abstract P276: Cardiac-Specific Knockout NF-kB Mice Resist Dysfunction Induced by Global Ischemia-Reperfusion
Authors: Xiu Q Zhang, Ling Li, Yubin Deng, Lensey Scott, Craig Selzman
Journal: Circulation Research (2011)

Subjective: Nuclear factor Kappa B (NF-kB) is a pluripotent transcriptional factor that has been implicated as mediator of cardiac injury after ischemia-reperfusion (IR). Multiple approaches have been used to target inhibition of NF-kB, yet these strategies are often non-specific. P65-NF-kB exists as a heterodimer with its p50 subunit and is the dominant transcriptional subunit of NF-kB. In order to better understand its role in the heart, we have recently generated mice that have cardiomyocyte (CMC) specific deletion of p65 NF-kB and hypothesized that these animals would be protected from ischemic stress. Methods: Transgenic mice were generated with (WT) or without CMC p65 (KO). NF-kB p65 expression was assessed with Western Blots. We subjected the mice to global IR using Langendorf system with baseline 20 min, ischemia 45 min and reperfusion 60 min. Cardiac contractile functional recovery was analyzed using rate pressure product (RPP), contractility (+dp/dt), and relaxation (-dp/dt). Infarct size was assessed with TTC staining. LDH and CK were measured in reperfused solutions. Results: 1. No differences were found between groups of WT (n=7) and KO (n=8) in body weight and heart weight. 2. KO mice express significant less cardiac-specific NF-kB p65. 3. During reperfusion, RPP, +dp/dt, -dp/dt recovery to base line were all better in p65 KO mice (RPP: 0.841±0.074 in KO vs 0.635±0.080 in WT; +dp/dt: 0.997±0.096 in KO vs 0.731±0.108 in WT; -dp/dt: 0.869±0.096 in KO vs 0.630±0.090 in WT; p&lt;0.05 respectively). 4. After ischemia, both LDH and CK release were markedly less in solutions collected from p65 KO heart (LDH: 45.2±28.0 u/L; CK: 28.1±23.6 u/L) than those in p65 WT heart (LDH: 143.2±25.9 u/L; CK: 107.2±26.2 u/L; p,0.01 respectively). 5. TTC staining shown significant less necrotic tissue in KO heart vs WT heart (0.314±0.052 vs 0.653±0.061, p&lt;0.05). Conclusion: CMC-specific knockout NF-kB p65 mice have improved cardiac recovery function, less heart necrosis, and decreased CMC injury compared to WT after global heart ischemia. These studies confirm many of the previous studies suggesting a protective role for anti-NF-kB strategies for ischemia. It furthermore provides a template to further define the mechanisms of p65-NF-kB afforded cardioprotection.
An Audit of the Biopsy Protocol for Barretts Eosophagus – Need to Improve Compliance to Guidelines?
Authors: S Sebastian, A Qasim, R McLoughlin, O Rathore, P Crotty, H O'Connor, C O'Morain, M Buckley
Journal: Endoscopy (2004)

Introduction: Guidelines exist regarding the number and interval of endoscopic biopsies for surveillance of Barrett's esophagus. However, the data on compliance is widely variable. We aimed to audit the Barrett's biopsy protocol practice at our institution.
Pattern of Central Nervous System (CNS) Involvement in Adult Acute Myeloid Leukemia (AML) and Its Impact on Outcome
Authors: Maria Ilaria Del Principe, Francesco Buccisano, Stefano Soddu, Luca Maurillo, Mariagiovanna Cefalo, Alfonso Piciocchi, Giovangiacinto Paterno, Chiara Sarlo, Gottardo De Angelis, Vittorio Forte, Maria Irno Consalvo, Daniela Fraboni, Eleonora De Bellis, Annagiulia Zizzari, Mariadomenica Divona, Giuseppe Sconocchia, Maria Teresa Voso, Giovanni Del Poeta, Francesco Lo Coco, Sergio Amadori, William Arcese, Adriano Venditti
Journal: Blood (2016)
Erythrocyte Mean Corpuscular Volume (MCV) Correlation with Thiopurine Methyl Transferase (TPMT) Activity in Inflammatory Bowel Disease (IBD) Patients Receiving Azathioprine (AZA)/6-Mercaptopurine (6MP)
Authors: A Qasim, R McLoughlin, S Sebastian, M Buckley, H O'Connor, C O'Morain
Journal: Endoscopy (2004)

Background: Azathioprine/6-mercaptopurine therapy leads to variable degree of change in the mean red cell corpuscular volume (MCV). This variability may be related to thiopurine methyl transferase (TPMT) activity of individual patients.
Extended Duration of Anti-Thymocyte Globulin (ATG) Administration May Reduce the Risk of Graft-Versus-Host Disease in Patients with Aplastic Anemia Undergoing Matched-Related Allogeneic Peripheral Blood Stem Cell Transplantation
Authors: Laura A. Zider, Amanda N. Seddon, Sunita Nathan, John J. Maciejewski, Jamile M. Shammo, Gorgun Akpek
Journal: Blood (2016)
Non-invasive monitoring of airway inflammation after specific bronchoprovocation test with cat allergen in asthmatic patients
Authors: I. Badiu, S. Pizzimenti, G. Guida, E. Heffler, B. Culla, S. Mietta, S. Sciascia, G. Racca, F. Molinaro, E. Maggio, G. Rolla, C. Bucca, L. Brussino
Journal: European Respiratory Journal (2009)
Histiocytoid Sweet Syndrome and Myelodysplastic Syndrome
Authors: Marie Dominique Vignon-Pennamen, Amélie Osio, Maxime Battistella
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
A phase I/IB study of paclitaxel in combination with VS-6063, a focal adhesion kinase (FAK) inhibitor, in patients (pts) with advanced ovarian cancer.
Authors: Suzanne Fields Jones, Kathleen N. Moore, Manish R. Patel, Jeffrey R. Infante, Anne Poli, Mitchell Keegan, Mahesh Padval, Howard A. Burris
Journal: Journal of Clinical Oncology (2013)

TPS2620 Background: Blockade of FAK reduces tumor growth and metastasis through inhibition of tumor cell survival, proliferation and invasion as well as tumor angiogenesis. Furthermore, treatment with FAK inhibitors reduces the proportion of cancer stem cells (CSCs) in a dose dependent manner while paclitaxel treatment enriches for CSCs. (Kolev VN San Antonio Breast Cancer Symposia 2012 abstr P6-11-09). The ability of CSCs to survive exposure to chemotherapy but remain susceptible to novel drugs suggests a unique therapeutic approach whereby standard of care chemotherapy may be sequentially combined with targeted drugs to kill surviving CSCs and thus prevent tumor recurrence and metastasis. VS-6063 (previously PF-04554878) is a potent oral inhibitor of FAK and proline-rich tyrosine-kinase -2. The phase I first-in-man trial explored doses ranging from 12.5 -750 mg twice daily (BID). (Jones SF J Clin Oncol 2011 29:1 suppl; abstr 3002) Dose-limiting toxicities consisted of headache, fatigue, and unconjugated hyperbilirubinemia at various dose levels. A maximum tolerated dose was not defined, but doses &gt; 100 mg BID consistently yielded concentrations above the preclinically predicted minimal efficacious concentration. Seven pts demonstrated stable disease lasting approximately 6 months or greater, including 3 heavily-pretreated ovarian cancer pts (2 platinum resistant). Methods: Pts with advanced or refractory ovarian cancer (≤ 4 prior regimens) will be enrolled. In the phase I portion, VS-6063 is administered continuously at a starting dose of 200mg BID with paclitaxel 80 mg/m 2 on days 1, 8, and 15 every 28 days, and will be escalated to 400mg BID if tolerated. Pharmacokinetics will be analyzed. An additional 15 pts with biopsiable disease will be enrolled at the recommended dose. A 10-day run-in with VS-6063 alone will be used to obtain paired tumor biopsies in order to examine the effects on pFAK expression, CSCs, and other biomarkers. Patients will continue treatment until disease progression. Clinical trial information: NCT01778803.
Treat ER<sup>+</sup>ight: Canadian prospective observational study in post-menopausal HR<sup>+</sup>HER2<sup>-</sup> advanced breast cancer women—First interim analysis (IA).
Authors: Cristiano Ferrario, Nadia Califaretti, Catherine Doyle, Susan Faye Dent, Josee-Anne Roy, Sabrina R. Perri, Stephen K. L. Chia
Journal: Journal of Clinical Oncology (2017)

1067 Background: Treat ER + ight is the first Canadian real-world study enrolling patients (pts) previously exposed to NSAI therapy and currently receiving endocrine therapy (ET) alone or in combination with targeted therapy (ET+TT). Methods: This first planned IA describes baseline parameters and adverse event (AE) prevention strategies adopted by 16 centers since Feb 2016 upon enrolling pts initiating ET or ET+TT. Results: See Table.Conclusions: This IA suggests that pts initiating ET+TT are younger, have a better ECOG status, mostly visceral disease and receive more prophylactic/proactive AE prevention therapies. Insights into real-world dosing and sequence will be presented. Clinical trial information: NCT02753686. [Table: see text]
Airway inflammation and inhaled corticosteroids in COPD
Authors: Sukhwinder Singh Sohal, Mathew Suji Eapen, Chris Ward, Eugene Haydn Walters
Journal: European Respiratory Journal (2017)

We read with interest the recent article by Kunz et al . [1] in the European Respiratory Journal ( ERJ ), and the appropriately questioning accompanying editorial by Calverley [2] in the same issue, considering airway inflammation and effects of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD). Understanding COPD pathology is a hugely important area and it is encouraging that leading respiratory journals are recognising this. We would like to suggest that a broader discussion of new insights into COPD pathology might have been appropriate. Thus, a more integrated consideration of overall airway wall cellularity, vascularity, epithelial–mesenchymal transition (EMT) and the effects of ICS on these in COPD is urgently needed to aid discussion of this devastating pathophysiology. There is a need for in-depth discussion of new insights in COPD airway pathogenesis <http://ow.ly/RDFM30bxduu>
Patients with Cystic Fibrosis and a <i>G551D</i> or Homozygous <i>F508del</i> Mutation: Similar Lung Function Decline
Authors: Gregory S. Sawicki, Edward F. McKone, Stefanie J. Millar, David J. Pasta, Michael W. Konstan, Barry Lubarsky, Jeffrey S. Wagener
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Impact of Immune Reconstitution (IR) and Graft-Versus-Host Disease (GvHD) on Clinical Outcomes after Treatment with Donor T Cells Transduced to Express the Herpes Simplex Virus Thymidine-Kinase Suicide Gene (TK cells) in Acute Leukemia Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation (HSCT)
Authors: Fabio Ciceri, Chiara Bonini, Arnon Nagler, Evangelia Yannaki, Maria Teresa Lupo Stanghellini, Attilio Bondanza, Raffaella Greco, Eduardo Olovarria, Eva M. Mischak-Weissinger, Michael Stadler, Donald w. Bunjes, Dietger Niederwieser, Lutz Uharek, Wolfgang Betghe, John F DiPersio, Michele L. Donato, Andrew L. Pecora, Scialini Colombi, Antonio Lambiase, Claudio Bordignon
Journal: Blood (2016)
Loss of thymic innate lymphoid cells leads to impaired thymopoiesis in experimental graft-versus-host disease
Authors: Jarrod A. Dudakov, Anna M. Mertelsmann, Margaret H. O’Connor, Robert R. Jenq, Enrico Velardi, Lauren F. Young, Odette M. Smith, Richard L. Boyd, Marcel R. M. van den Brink, Alan M. Hanash
Journal: Blood (2017)
Abstract 221: miR-19b Protects Myocardial Ischemia Reperfusion Injury
Authors: Dongchao Lv, Shengguang Ding, Ping Chen, Yihua Bei, Chongjun Zhong, Junjie Xiao
Journal: Circulation Research (2015)

Ischemia-reperfusion injury (IRI) following acute myocardial infarction (AMI) has no effective treatment and a poor prognosis. microRNA (miRNA)-19b is a key functional member of miRNA-19-72 cluster family, regulating cellular proliferation, apoptosis, differentiation, and metabolism. Dysregulation of the miR-19b cluster is critically involved in a spectrum of cardiovascular diseases. However, the role of miR-19b in myocardial IRI is unknown. In this study, we found that miR-19b was downregulated in a mouse model of IRI. Meanwhile, about 50% downregulation of miR-19b was detected in H2O2-treated H9C2 cells mimicking myocardial IRI. We also found that overexpression of miR-19b decreased H2O2-induced apoptosis (36.02%±3.92% vs 29.34%±0.79% in nc-mimics vs miR-19b-mimics, respectively) and necrosis (23.11%±1.64% vs 18.76%±0.71% in nc-mimics vs miR-19b-mimics, respectively), and increased proliferation of H9C2 cells in vitro, while downregulation of miR-19b had reverse effects. Furthermore, PTEN, a previously validated target gene of miR-19b, has been found to be negatively regulated by miR-19b at protein levels in H9C2 cells. These data reveal the potential of miR-19b as a therapeutic target for myocardial IRI.
Antithrombotic Therapy and First Myocardial Infarction in Patients With Atrial Fibrillation
Authors: Christina J.-Y. Lee, Jannik L. Pallisgaard, Jonas Bjerring Olesen, Nicholas Carlson, Morten Lamberts, Gunnar H. Gislason, Christian Torp-Pedersen, Axel Brandes, Steen E. Husted, Søren P. Johnsen, Morten L. Hansen
Journal: Journal of the American College of Cardiology (2017)