tbuckley/cabot-search huggingface dataset:
Managing Barrett's oesophagus
Authors: S. J. Spechler
Journal: BMJ (2003)

<h3>Summary</h3> The UAS/GAL4 system is the most used method In <i>Drosophila melanogaster</i> for directing the expression of a gene of interest to a specific tissue. However, the ability to control the temporal activity of GAL4 with this system is very limited. This study constructed and characterized Tet-off GAL80 transgenes designed to allow temporal control of GAL4 activity in aging adults. By placing GAL80 under the control of a Tet-off promoter, GAL4 activity is regulated by the presence or absence of tetracycline in the diet. Almost complete inhibition of the expression of UAS transgenes during the pre-adult stages of the life cycle is obtained by using four copies and two types of Tet-off GAL80 transgenes. Upon treatment of newly emerged adults with tetracycline, induction of GAL4 activity is observed but the level of induction is influenced by the concentration of the inducer, the age, the sex and the anatomical location of the expression. The inhibition of GAL4 activity and the maintenance of induced expression is altered in old animals. This study reveals that the repressive ability of GAL80 is affected by the age and sex of the animal which is a major limitation to regulate gene expression with GAL80 in aged <i>Drosophila</i>.
Persistent Prothrombotic State in Atrial Fibrillation Despite Use of Novel Oral Anti-Coagulants
Authors: Jeffrey Liles, Christopher Wanderling, Abigail M Otto, Jordan Liles, Debra Hoppensteadt, Daneyal Syed, Sallu Jabati, Mushabbar Syed, Jawed Fareed
Journal: Blood (2016)
Immunomodulatory Interventions Based on Minimal Residual Disease before and after Transplantation for Childhood Acute Lymphoblastic Leukemia
Authors: Adriana Balduzzi, Lucia Di Maio, Daniela Silvestri, Simona Songia, Giulia Prunotto, Sonia Bonanomi, Attilio Rovelli, Andrea Biondi, Giovanni Cazzaniga, Maria Grazia Valsecchi
Journal: Blood (2016)
Chemotherapy in Addition to Supportive Care Improves Survival in Advanced Non–Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 16 Randomized Controlled Trials
Journal: Journal of Clinical Oncology (2008)

Purpose Since our individual patient data (IPD) meta-analysis (MA) of supportive care and chemotherapy for non–small-cell lung cancer (NSCLC), published in 1995, many trials have been completed. An updated, IPD MA has been carried out to assess newer regimens and determine conclusively the effect of chemotherapy. Methods Systematic searches for randomized controlled trials (RCTs) were undertaken, followed by central collection, checking, and reanalysis of updated IPD. Results from RCTs were combined to calculate individual and pooled hazard ratios (HRs). Results Data were obtained from 2,714 patients from 16 RCTs. There were 1,293 deaths among 1,399 patients assigned supportive care and chemotherapy and 1,240 among 1,315 assigned supportive care alone. Results showed a significant benefit of chemotherapy (HR, 0.77; 95% CI, 0.71 to 0.83; P ≤ .0001), equivalent to a relative increase in survival of 23% or an absolute improvement in survival of 9% at 12 months, increasing survival from 20% to 29%. There was no clear evidence that this effect was influenced by the drugs used (P = .63) or whether they were used as single agents or in combination (P = .40). Despite changes in patient demographics, the effect of chemotherapy in recent trials did not differ from those included previously (P = .77). There was no clear evidence of a difference or trend in the relative effect of chemotherapy across patient subgroups. Conclusion This MA of chemotherapy in the supportive care setting demonstrates conclusively that chemotherapy improves overall survival in all patients with advanced NSCLC. Therefore, all patients who are fit enough and wish to receive chemotherapy should do so.
Induction of apoptosis in human prostate cancer cells by α-TEA through Fas signaling pathway
Authors: Li Jia, Weiping Yu, Pei Wang, Bob G. Sanders, Kimberly Kline
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

777 

α-TEA is a nonhydrolyzable ether analogue of RRR-α-tocopherol. It has been shown to inhibit cell proliferation and induce apoptosis in human breast and ovarian cancer cells. In our study, the apoptosis-inducing potential of α-TEA was investigated in LNCaP and PC-3 GFP human prostate cancer cells. Both cell lines were sensitive to α-TEA induced apoptosis. 72 h treatment with 40 μM α-TEA caused 95% and 68% apoptosis in LNCaP and PC-3 GFP cells, respectively. The mechanisms underlying α-TEA induced apoptosis were investigated. The activation of caspases and JNK is important for α-TEA induced apoptosis. Chemical caspase and JNK inhibitors, and dominant negative JNK inhibited apoptosis induced by α-TEA. Fas mRNA and protein levels were elevated in both LNCaP and PC-3 GFP cells treated with α-TEA. PC-3 GFP cells are sensitive to Fas-mediated apoptosis, while LNCaP cells are resistant. α-TEA treatment enhanced Fas-mediated apoptosis in PC-3 GFP cells and sensitized Fas-resistant LNCaP cells to Fas-mediated apoptosis. α-TEA induced apoptosis can be blocked by Fas neutralizing antibody. Supported by CA59739, ESO2784 and the Foundation for Research.
Comparison of Patterns and Outcomes of Liver Resection for Hepatocellular Carcinoma: East vs West
Authors: Tian Yang, Parissa Tabrizian, Han Zhang, Wan-Yee Lau, Jun Han, Zhen-Li Li, Zheng Wang, Meng-Chao Wu, Sander Florman, Myron E. Schwartz, Feng Shen
Journal: Clinical Gastroenterology and Hepatology (2017)
Resin infiltration of deproteinised natural occlusal subsurface lesions improves initial quality of fissure sealing
Authors: Andrej M Kielbassa, Ina Ulrich, Rita Schmidl, Christoph Schüller, Wilhelm Frank, Vanessa D Werth
Journal: International Journal of Oral Science (2017)

The aim of this ex vivo study was to evaluate the infiltration capability and rate of microleakage of a low-viscous resin infiltrant combined with a flowable composite resin (RI/CR) when used with deproteinised and etched occlusal subsurface lesions (International Caries Detection and Assessment System code 2). This combined treatment procedure was compared with the exclusive use of flowable composite resin (CR) for fissure sealing. Twenty premolars and 20 molars revealing non-cavitated occlusal carious lesions were randomly divided into two groups and were meticulously cleaned and deproteinised using NaOCl (2%). After etching with HCl (15%), 10 premolar and 10 molar lesions were infiltrated (Icon/DMG; rhodamine B isothiocyanate (RITC)-labelled) followed by fissure sealing (G-ænial Flo/GC; experimental group, RI/CR). In the control group (CR), the carious fissures were only sealed. Specimens were cut perpendicular to the occlusal surface and through the area of the highest demineralisation (DIAGNOdent pen, KaVo). Using confocal laser-scanning microscopy, the specimens were assessed with regard to the percentage of caries infiltration, marginal adaption and internal integrity. Within the CR group, the carious lesions were not infiltrated. Both premolar (57.9%±23.1%) and molar lesions (35.3%±22.1%) of the RI/CR group were uniformly infiltrated to a substantial extent, albeit with significant differences (P=0.034). Moreover, microleakage (n=1) and the occurrence of voids (n=2) were reduced in the RI/CR group compared with the CR group (5 and 17 specimens, respectively). The RI/CR approach increases the initial quality of fissure sealing and is recommended for the clinical control of occlusal caries.
Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide
Authors: D.E. Rathkopf, M.R. Smith, C.J. Ryan, W.R. Berry, N.D. Shore, G. Liu, C.S. Higano, J.J. Alumkal, R. Hauke, R.F. Tutrone, M. Saleh, E. Chow Maneval, S. Thomas, D.S. Ricci, M.K. Yu, C.J. de Boer, A. Trinh, T. Kheoh, R. Bandekar, H.I. Scher, E.S. Antonarakis
Journal: Annals of Oncology (2017)
Donor pulmonary intravascular nonclassical monocytes recruit recipient neutrophils and mediate primary lung allograft dysfunction
Authors: Zhikun Zheng, Stephen Chiu, Mahzad Akbarpour, Haiying Sun, Paul A. Reyfman, Kishore R. Anekalla, Hiam Abdala-Valencia, Daphne Edgren, Wenjun Li, Daniel Kreisel, Farida V. Korobova, Ramiro Fernandez, Alexandra McQuattie-Pimentel, Zheng J. Zhang, Harris Perlman, Alexander V. Misharin, G. R. Scott Budinger, Ankit Bharat
Journal: Science Translational Medicine (2017)

Donor nonclassical monocytes mediate primary lung allograft dysfunction by recruiting neutrophils via MyD88-dependent production of CXCL2.
Trastuzumab-related cardiotoxicity in patients with non-limiting cardiac comorbidity.
Authors: Rossella Martinello, Paolo Becco, Patrizia Vici, Mario Airoldi, Lucia Del Mastro, Ornella Garrone, Carla Barone, Laura Pizzuti, Alessia D'Alonzo, Elisa Bellini, Andrea Milani, Alessandro Bonzano, Filippo Montemurro
Journal: Journal of Clinical Oncology (2017)

e12043 Background: Significant and symptomatic cardiac comorbidity (CC) is a contraindication to adjuvant trastuzumab (T) in breast cancer patients (pts). However, some pts with asymptomatic, non-limiting CC and normal baseline left ventricular ejection fraction (LVEF) receive T in the clinical practice. We sought to describe the tolerability of T in these pts. Methods: Retrospective analysis of pts with baseline asymptomatic non-limiting CC receiving adjuvant T with chemotherapy (CT) at 6 Institutions between Jul 2006 and Jan 2016. Results: Thirty-seven patients HER2-positive, operable BC at high risk of relapse BC were studied. Median age was 64y (range 36-82, 80% post-menopausal), median baseline LVEF was 61% (range 50-85%) and median BMI 26 (18-42, obesity 22%). Thirteen patients (35%) received T with adjuvant anthracycline and taxane-based, 19 (51%) taxane-based and 3 (8%) other adjuvant CT regimens (13 pts sequential, 22 pts concomitant with CT) and 2 (5%) with endocrine therapy. Prior non-limiting CC was ischemic heart disease (35%), valvular disease (30%), atrial fibrillation (19%), conduction disorders (13%), aortic aneurism (3%), and other (19%). Nine (29%) pts experienced TRC: congestive heart failure (1 pt, 3%), LVEF reduction (6 pts, 16%) and rhythm disturbances (1 pt, 3%). TRC occurred in pts with ongoing multiple cardiovascular risk factors (i.e. obesity and hypertension). Seven pts discontinued T because of TRC (19%), 5 permanently (14%) and 2 temporarily (5%). These latter pts, were able to resume and complete T after TRC resolution. At the end of adjuvant treatment, all pts showed LVEF within normal limits, except one of those who experienced a TRC (last FU value 46 %). Conclusions: This is the first analysis of TRC in pts receiving adjuvant T in the presence prior non-limiting CC. Despite the small size, our analysis shows that T is feasible in these pts and most of the TRC events were reversible at T withdrawal. Caution is needed in pts with significant ongoing cardiovascular risk factors, but when adjuvant T is deemed beneficial on breast cancer outcomes, non-limiting CC should not preclude treatment.
Abstract 196: Cardiotrophin-1 Promotes Physiologic Cardiac Hypertrophy
Authors: Lynn A Megeney, Mohammad Abdul-Ghani, Colin Suen, Duncan J Stewart
Journal: Circulation Research (2015)

The post-natal heart retains a remarkable adaptive capacity, which matches growth of the myocardium to increased physical demands. The beneficial form of myocardial growth is referred to as physiologic hypertrophy, and derives from a compensatory response to conditions that require increased blood volumes such as pregnancy and chronic exercise training. Despite the clear benefits associated with this form of adaptation, the molecular mechanism(s) that initiate or sustain such cardiac remodeling remain obscure. As such, identification of factors that promote physiologic hypertrophy will be of considerable interest to both cardiac biologists and clinicians. Here, we have begun to explore the role of the cytokine, cardiotrophin 1 (CT-1) as a central mediator of physiologic hypertrophy. We demonstrate that primary cardiomyocytes treated with recombinant human CT-1 protein engage a physiologic growth response, adding sarcomeres in series, a cellular/molecular change that is fully reversible with the removal of CT-1. This physiologic hypertrophy response to CT-1 is dominant, as CT-1 administration overrides the pathologic hypertrophy associated with agonists such as phenylephrine. In vivo delivery of human CT-1 protein leads to a rapid (14 days) alteration in the structure of the rat heart, with volume and wall dimension increases characteristic of exercise adaptation, changes that are fully reversible upon cessation of CT-1 treatment. In addition, CT-1 administration mitigates right heart failure in a model of pulmonary arterial hypertension, and sustains cardiac function in the post infarct rat heart. Finally, gene expression analysis revealed that CT-1 treatment leads to up-regulation of angiogenic factors within cardiomyocytes, suggesting that this cytokine engages a paracrine signaling mechanism to ensure that myocardial growth is matched by a robust angiogenesis.
Abstract 93: Sestrin2 Mediates the LKB1-AMPK Signaling Cascade in the Ischemic Heart
Authors: Alex Morrison, Chao Tong, Jun Hee Lee, Michael Karin, Ji Li
Journal: Circulation Research (2012)

Background:   AMP-activated Protein Kinase (AMPK) has emerged as a pertinent stress-activated kinase shown to have substantial cardioprotective capabilities against myocardial ischemia/reperfusion (I/R) injury. The regulation of AMPK in the ischemic and reperfused heart is critical to the development of new therapeutic strategies. We hypothesized that a novel stress-inducible protein, sestrin2, mediates AMPK activation in the ischemic heart.    Methods and Results:   C57BL/6 mice were subjected to left anterior descending coronary artery occlusion for different time points of ischemia and I/R in order to detect the signaling activity in the left ventricle. The kinetics of AMPK phosphorylation at Thr 172  of the α catalytic subunit appears brief and bell-shaped, peaking around 10 min (3.6-fold  vs.  sham,  p  vs.  sham,  p  172 ) (10 min), suggesting the interaction of LKB1 with sestrin2 initiates the phosphorylation of AMPK in this complex. Furthermore, sestrin2 knock out hearts demonstrate impaired ischemic AMPK activation and higher sensitivity to I/R-induced injury as compared to wild type hearts ( p     Conclusions:  Here we show for the first time evidence of a unique mechanism that sestrin2 is a stress-induced scaffold protein that mediates the activation of AMPK in the ischemic myocardium  via  a time-dependent interaction with LKB1. Moreover, sestrin2 deficiency leads to blunted ischemic AMPK activation and increased sensitivity to ischemic insults.
포스터전시 : 간암 세포에서 실리비닌(Silibinin)과 게피티닙(Gefitinib) 복합 치료의 효과 (초)
Authors: 박수철, 최수진, 최윤정, 노진경, 강민수, 노금엽, 조성인, 남승범, 김연주, 양기영, 김진, 이재철, 한철주, 김유철, 정용진, 이상협
Journal: Clinical and Molecular Hepatology (2010)
Frequency and compliance of specific immunotherapy in patients with allergic rhinitis from two German Federal States
Authors: G. Balakirski, M. Bas, L. Kaiser, H. F. Merk, Z. Hajdu, W. Dott, Stefani Roeseler, J. M. Baron, H.-G. Muecke, H. Bier, A. Chaker, S. Gerdsen, K. Czaja, U. Strassen, W. Straff, C. Hoeflich
Journal: Allergy (2015)
Alpha1-Antichymotrypsin Present in Therapeutic C1-Inhibitor Products Competes with Selectin - Sialyl LewisX Interaction
Authors: Ruchira Engel, Laura Delvasto Nunez, Dorina Roem, Gerard van Mierlo, Stephanie Holst, Marinus H.J. Van Oers, Manfred Wuhrer, Diana Wouters, Sacha Zeerleder
Journal: Blood (2015)
CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease
Authors: Su Yang, Renbao Chang, Huiming Yang, Ting Zhao, Yan Hong, Ha Eun Kong, Xiaobo Sun, Zhaohui Qin, Peng Jin, Shihua Li, Xiao-Jiang Li
Journal: Journal of Clinical Investigation (2017)

Huntington's disease is a neurodegenerative disorder caused by a polyglutamine repeat in the Huntingtin gene (HTT). Although suppressing the expression of mutant HTT (mHTT) has been explored as a therapeutic strategy to treat Huntington's disease, considerable efforts have gone into developing allele-specific suppression of mHTT expression, given that loss of Htt in mice can lead to embryonic lethality. It remains unknown whether depletion of HTT in the adult brain, regardless of its allele, could be a safe therapy. Here, we report that permanent suppression of endogenous mHTT expression in the striatum of mHTT-expressing mice (HD140Q-knockin mice) using CRISPR/Cas9-mediated inactivation effectively depleted HTT aggregates and attenuated early neuropathology. The reduction of mHTT expression in striatal neuronal cells in adult HD140Q-knockin mice did not affect viability, but alleviated motor deficits. Our studies suggest that non-allele-specific CRISPR/Cas9-mediated gene editing could be used to efficiently and permanently eliminate polyglutamine expansion-mediated neuronal toxicity in the adult brain.
Significant Difference in the Handwritten and Dictated Discharge Notes – Outcome of an Audit on Medical Case Records in a Scottish Private Hospital
Authors: D Debnath, M Hutcheson, JK Hussey
Journal: Endoscopy (2004)

Aim: A comprehensive discharge letter is crucial in liaising with various healthcare personnel. However little is known about the choice of the discharge certificate, more so in the private healthcare. We aimed to assess any difference in the way the discharge letters were recorded by the consultant gastroenterologists and general surgeons in a Scottish private hospital.
Bile salt export pump (BSEP) deficiency is a significant risk factor for both paediatric and adult hepatobiliary malignancy
Authors: A S Knisely, S Strautnieks, A O Scheimann, J Byrne, L Pawlikowska, Y Meier, L N Bull, K Emerick, B Stieger, H Melin-Aldana, B Bilezikci, F Ozcay, A Laszlo, L Tiszlavicz, L Moore, J Raftos, H Arnell, N Papadogiannakis, J Kuszyk, B Fischler, I Jankowska, B Portmann, A Nemeth, J Pawlowska, P Whitington, M Finegold, G Mieli-Vergani, R Thompson
Journal: Hepatology (2005)
Treatment and outcome of 2904 CML patients from the EUTOSpopulation-based registry
Authors: V.S. Hoffmann, M. Baccarani, J. Hasford, F. Castagnetti, F. Di Raimondo, L.F. Casado, A. Turkina, Daniela Žáčková, G. Ossenkoppele, A. Zaritskey, M. Höglund, B. Simonsson, K. Indrak, Z. Sninska, T. Sacha, R. Clark, A. Bogdanovic, A. Hellmann, L. Griskevicius, G. Schubert-Fritschle, D. Sertic, J. Guilhot, S. Lejniece, I. Zupan, S. Burgstaller, P. Koskenvesa, H. Everaus, P. Costeas, D. Lindoerfer, G. Rosti, S. Saussele, A. Hochhaus, R. Hehlmann
Journal: Leukemia (2017)
Detecting bone loss in early breast cancer survivors: The Arm-DXA method.
Authors: Yousuf Al-Farhat, Auth Peter
Journal: Journal of Clinical Oncology (2017)

e12066 Background: Breast cancer survivors who are on adjunct therapy with Aromatase Inhibitors (AIs) or premature menopause due to chemotherapy are known to have an increased risk of osteoporosis and bone fracture. Being at high risk for osteoporosis, these patients should be screened using with dual energy X-ray absorptiometry (DXA) to measure bone mineral density (BMD) according to national guidelines. This study screened the population of patients with early Breast cancer utilizing the Arm-DXA as a user friendly and efficient method. Methods: All Breast cancer patients at the Tolna County Cancer Center, Szekszárd who are diagnosis of early invasive breast cancer were scanned using Arm-DXA during their regular visit to the center. Cancer patients under hormone therapy were scanned annually. Patients who have metastatic disease or known to have osteoporosis were excluded from the study. A total of 431 patients were subject of an arm-DEXA scan for BMD during the period February 2015 to September 2016. Results: Out of the 431 patients, normal T score &gt;-1,5 detected in 223 patients (51,7%), clinically significant osteopenia (CSO) T score -1,5- -2,5 detected in 129 patients (29,9%), and osteoporosis T score &lt; -2,5 detected in 79 patients (18,3%). For the 224 Patients who were under hormone therapy or/and chemotherapy about 29,9% (n: 67) had a CSO, and 20,5% (n:46) had osteoporosis. Conclusions: This study highlights the fact that osteoporosis is under-detected in early breast cancer survivors who are on or after hormone and chemotherapy. About 48% of early breast cancer survivors found to have osteoporosis or clinically significant osteopenia in our study. Our BMD test results shows that half the 224 patients who were under hormone therapy need to take treatment (zoledronic -acid or denosumab ) to prevent bone fracture.
Activation of beta-catenin by mutant FLT3 receptors is mediated by GSK3-beta
Authors: Jingrui Jiang, James Griffin
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

343 

FLT3 is a tyrosine kinase receptor important for normal hematopoiesis, and is also involved in the pathogenesis of hematological malignancies. Mutation of the FLT3 gene is the most prevalent genetic lesion in acute myeloblastic leukemia (AML), most commonly as in frame insertions of variable length (internal tandem duplications, or ITDs) in the juxtamembrane (JM) or missense point mutations in the kinase domain. These activating mutations of FLT3 promote ligand independent proliferation, increase cell survival, and block myeloid differentiation of early hematopoietic cells in mouse model. The Wnt/beta-catenin signaling pathway has recently be shown to participate in the self-renewal of hematopoietic stem cells, and to be constitutively activated in AML patients who harbor FLT3-ITD mutations. In general, the level of beta-catenin is thought to be regulated by a cytosolic destruction complex, in which GSK3-beta is a major component. But GSK3-beta plays a differential role in the regulation of beta-catenin in different cell types. We investigated the mechanism leading to increased beta-catenin found in the cells expressing FLT3-ITD mutations and specially studied the role of GSK3-beta in regulation of beta-catenin and its target genes. We found that activating mutations of FLT3 constitutively inhibited the activity of GSK3-beta and increase total level of beta-catenin in the cells either ectopically expressing FLT3 activating mutations or in the cells derived from AML patient who harbored FLT3-ITD mutations. Further, inhibition of GSK3-beta appears to be mediated by PI3/AKT pathway that is constitutively activated by FLT3 activating mutation. Furthermore, we demonstrated that small molecular inhibitor of FLT3 tyrosine kinase activity reduced phosphorylation of GSK3-beta at serine 9 (phosphorylation at this amino acid will inhibit its kinase activity), decreased total levels of beta-catenin, c-Myc, and cyclin D3. Pharmacological inhibitions of GSK3-beta in AML cells also increased the levels of beta-catenin and its target genes. Finally, stable expression of a dominant negative form of GSK3-beta (dnGSK3-beta) in the Ba/F3-FLT3-ITD cells increased the levels of beta-catenin, c-Myc and cyclin D3 and blocked the down-regulation of theses genes induced by FLT3 inhibitor. Taken together, our data demonstrate that GSK3-beta is critical for mediating the effect of FLT3-ITD on beta-catenin and its target genes, also suggest that GSK3-beta may serve as a nexus for crosstalk of the FLT3 activating mutations and the Wnt pathways.
Leukotrienes
Authors: Marc Peters-Golden, William R. Henderson
Journal: New England Journal of Medicine (2007)

This review of leukotrienes, which are lipid mediators with a broad array of clinical effects, and leukotriene receptors considers the biochemical and physiological aspects of these molecules, examines their roles in asthma and other diseases, and explains the pharmacologic effects of antileukotriene agents.