tbuckley/cabot-search huggingface dataset:
A prospective comparison of ER, PR, Ki67 and gene expression in paired sequential core biopsies of primary, untreated breast cancer.
Authors: Alastair Mark Thompson, Sirwan M. Hadad, Lee Jordan, Pankaj Roy, Colin Purdie, Takayuki Iwamoto, Lajos Pusztai, Stacy L. Moulder
Journal: Journal of Clinical Oncology (2015)

578 Background: Sequential biopsy of breast cancer is increasingly favoured to assess biomarker effects and drug efficacy. The “window of opportunity” in the preoperative setting is recognised as advantageous to test biomarker changes in response to therapeutic agents in previously untreated cancers. However, tissue sampling over time could confound biomarker effects. This study tested the consistency over time of paired, sequential biomarker measurements on primary, operable breast cancer in the absence of drug therapy. Methods: Immunohistochemistry was performed for ER, PR and Ki67 on paired preoperative/operative tumor samples taken from untreated patients within 2 weeks of each other. Additionally, microarray analysis on mRNA extracted from formalin fixed paraffin embedded cores was performed using Affymetrix based arrays on paired core biopsies analysed using Ingenuity Pathway Analysis (IPA) and Gene Set Analysis (GSA). Results: In 41 core/resection pairs, the recognised trend to lower ER, PR and Ki67 score on resected material was confirmed: concordance for ER, PR and Ki67 without switch in status by Allred or Quickscore was 90%, 74% and 80% respectively. However, in 23 paired core samples (diagnostic core v on table core), Ki67 using a cut off of 13.25% was concordant in 22/23 (96%) and differences in ER and PR immunohistochemistry by Allred or Quickscore between the pairs did not impact hormone receptor status. IPA and GSA demonstrated substantial gene expression changes between paired cores at the mRNA level, including under expression of ER pathway analysis, despite the absence of drug intervention. Conclusions: This study addresses the potential impact of sampling effects over time in the context of preoperative (window of opportunity) trials. Sequential core biopsy of primary breast cancer (but not core versus resection) was consistent and may be appropriate to assess the effects of drug therapy in vivo on ER, PR and Ki67 using immunohistochemistry. Conversely, studies including mRNA expression may require non-treatment controls to distinguish therapeutic from biopsy differences.
A pharmacokinetic/pharmacodynamic approach to evaluating the safety of zebularine in non-human primates
Authors: William D. Johnson, J. Brooks Harder, Jennifer Naylor, David L. McCormick, Carol J. Detrisac, Elizabeth R. Glaze, Joseph E. Tomaszewski
Journal: Cancer Research (2006)

1309  DB67 (7-tert-butyldimethylsilyl-10-hydroxycamptothecin; NSC 708298) is a camptothecin analog that has high intrinsic potency against topoisomerase I and impressive anticancer activity both in vitro and in vivo. In preparation for clinical trials, the toxicity of DB67 was investigated in groups of male and female beagle dogs (2/sex/group) and Fischer rats (10/sex/group) given single iv bolus doses of DB67 or vehicle once daily for 5 consecutive days for 2 cycles (Days 1-5 and Days 8-12). DB67 was formulated as a solution in cremophor EL:ethanol:saline (12.5:12.5:75). No mortality was observed for dogs given doses of 0.25 or 0.375 mg/kg/day (5 or 7.5 mg/m2/day) (total dose/cycle: 1.25 or 1.88 mg/kg; 25 or 37.6 mg/m2). Drug-related clinical signs of gastrointestinal toxicity included decreased food consumption and body weight loss. Drug-related clinical pathological changes observed during the dose period included neutropenia, lymphopenia, and anemia. Mean blood concentrations of DB67 at 2 minutes after dosing were similar on Days 8 and 12 and were 370 ng/mL (773 nM) and 406 ng/mL (848 nM) for dogs in the 0.25 mg/kg/day dose group, and 478 ng/mL (998 nM) and 510 ng/mL (1066 nM) for dogs in the 0.375 mg/kg/day dose group. Possible drug-related histopathological changes observed on Day 13, but not on Day 40, were limited to decreased lymphocytes in the thymus for dogs given 0.25 or 0.375 mg/kg/day. For rats given 0.5, 1, or 3 mg/kg/day (3, 6, or 18 mg/m2/day) (total dose/cycle: 5, 10, or 30 mg/kg; 30, 60, or 180 mg/m2), a no effect dose level was not observed. Mortality occurred for 2/10 rats in the vehicle control group and 1/10 rats in the 1 mg/kg/day dose group. Dose-related hematopoietic toxicity (including decreased RBC, HGB, HCT, reticulocytes, platelets, WBC, neutrophils, and/or lymphocytes) and potential drug-related decreases in BUN, creatinine, ALP, ALT, total protein, and albumin were observed. Dose-related histopathological lesions that were observed for rats necropsied on Days 10-13, but not for rats necropsied on Day 42, included lesions in the bone marrow (atrophy of blood-forming elements) and thymus (lymphocyte depletion) of animals in the 0.5, 1, and 3 mg/kg/day dose groups. Vehicle-induced lesions were also observed on Day 11 or 13 in the brain (focal malacia), spleen (cytoplasmic vacuolization of macrophages), and kidneys (eosinophilic cytoplasmic crystals in the proximal tubules); these lesions were either absent (kidney) or present in an attenuated form on Day 42. No sex-related differences in toxicity were observed for dogs or rats given DB67. The toxicity of DB67 appeared to be reversible in both dogs and rats. (Supported by NCI Contract N01-CM-42201).
Human TH17 cell development requires processing of dendritic cell–derived CXCL8 by neutrophil elastase
Authors: Yuri Souwer, Tom Groot Kormelink, Esther W. Taanman-Kueter, Femke J. Muller, Toni M.M. van Capel, Domonkos V. Varga, Yotam E. Bar-Ephraim, Marcel B.M. Teunissen, S. Marieke van Ham, Taco W. Kuijpers, Diana Wouters, Linde Meyaard, Esther C. de Jong
Journal: Journal of Allergy and Clinical Immunology (2018)
Disproportionate Right Ventricular Dysfunction and Poor Survival in Group 3 Pulmonary Hypertension
Authors: Kurt W. Prins, Lauren Rose, Stephen L. Archer, Marc Pritzker, E. Kenneth Weir, Felipe Kazmirczak, Jeffrey R. Misialek, Thenappan Thenappan
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau
Authors: Joseph McInnes, Keimpe Wierda, An Snellinx, Laura Bounti, Yu-Chun Wang, Ilie-Cosmin Stancu, Nuno Apóstolo, Kris Gevaert, Ilse Dewachter, Tara L. Spires-Jones, Bart De Strooper, Joris De Wit, Lujia Zhou, Patrik Verstreken
Journal: Neuron (2018)
Gastric endoscopic submucosal dissection using the “pulley clip with elastic line” method
Authors: Tatsuma Nomura, Akira Kamei, Shinya Sugimoto
Journal: Endoscopy (2018)

Visibility of the submucosa is important for safe and quick gastric endoscopic submucosal dissection (ESD) [1] [2] [3] [4]. Thus, we have developed a new efficient traction method called the “pulley clip with elastic line” method (PEM).
Measles-mumps-rubella and other measles-containing vaccines do not increase the risk for inflammatory bowel disease
Authors: R Davis, P Kramarz, K Bohlke, P Benson, R Thompson, J Mullooly, S. Black, H Shinefield, E Lewis, J Ward, S Marcy, E Eriksen, Frank DeStefano, R Chen
Journal: JAMA Pediatrics (2001)
Targeting Siglec-7: A Novel Immunotherapeutic Approach to Potentiate the Cytotoxic Functions of Natural Killer Cells Against Multiple Myeloma
Authors: John Daly, Tony Duggan, Jinsong Hu, Alessandro Natoni, Subhashis Sarkar, Lucy Kirkham-McCarthy, Cian McEllistrim, Janusz Krawczyk, Michael O'Dwyer
Journal: Blood (2017)
Molecular characterization of a novel drug candidate with anti-angiogenesis and anti-cancer activity in prostate cancer
Authors: Ehlen Asa, Cecilia Brunhoff, Pirkko Harkonen, Johanna Tuomela, Heather Liao, Jenny L. Persson
Journal: Cancer Research (2007)

3281   PA-105 is a newly identified 610 Dalton small molecule compound. The anti-cancer activities of PA-105 and its targeted signaling pathways in prostate cancer have been studied. Treatment of androgen-dependent prostate cancer cell line LNCaP cells and androgen-independent DU-145 cell lines resulted in a dose-dependent inhibition of the cellular proliferation. This was coupled with a cell cycle arrest at G0/G1 phases and a down-regulation of the expression of several critical cell cycle regulatory proteins including cyclin A2, CDK1 and CDK2. Interestingly, treatment of PA-105 also led to a dose-dependent inhibition of the expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2, but not VEGF receptor 1 in LNCaP cells and DU-145 cells. In addition, there was a significant increase in the rate of apoptosis in PA-105 treated DU-145 cells compared to the controls. Further, in vitro toxicity study revealed that PA-105 had no toxic effect on benign prostate endothelial cells.  To investigate the effect of PA-105 on metastatic prostate cancers in an  in vivo  model, we generated tumor xenograft mice baring DU145 tumors. The animals were treated with PA-105 or PBS for one month. The expression of cell cycle regulatory proteins, Bcl 2, VEGF and VEGF receptor 2 were determined. In agreement with our observations obtained from cell line studies, expression of CDK1 and CDK2 was down regulated in 4 out of 6 tumor xenografts treated with PA-105 compared with controls. In the majority of tumor xenografts treated with PA-105, VEGF expression was inhibited at both mRNA and protein levels as measured by real-time quantitative RT-PCR and ELISA assay. Furthermore, immunohistochemical analysis revealed that the decreased expression of VEGF and VEGF receptor 2, and this was coupled with the decreased tumor vacuolization and tumor cell density in PA-105 treated animals. Our tumor xenograft model validated a potential role of PA-105 on anti-angiogenesis and anti-cancer activities in prostate cancer.  Our results suggest that PA-105 has specific activities of anti-angiogenesis and anti-cancer in hormone-refractory metastatic prostate cancer cells. Further, PA-105 may target cancer cells via cell cycle regulatory pathways and VEGF receptor 2-mediated pathways.
Re: Giorgio Gandaglia, Stephen A. Boorjian, William P. Parker, et al. Impact of Postoperative Radiotherapy in Men with Persistently Elevated Prostate-specific Antigen After Radical Prostatectomy for Prostate Cancer: A Long-term Survival Analysis. Eur Urol 2017;72:910–7
Authors: Mustafa Z. Temiz, Huseyin Besiroglu
Journal: European Urology (2018)
Endoscopic clipping prior to n-butyl-2-cyanoacrylate injection for gastric varices with a large gastrorenal shunt
Authors: Huixian Li, Dong Ye, Derun Kong
Journal: Endoscopy (2018)

Gastric variceal obturation with cyanoacrylate has been proven to be an effective treatment for gastric varices with a shunt [1]. However, there may be complications after the treatment, such as systemic embolism [2], which can be severe and even fatal. With the aim of reducing the risk of complications, we here report on the use of endoscopic clipping prior to n-butyl-2-cyanoacrylate injection as a therapy to obliterate gastric varices with a large gastrorenal shunt.
Preoperative exercise halves the postoperative complication rate in patients with lung cancer: a systematic review of the effect of exercise on complications, length of stay and quality of life in patients with cancer
Authors: Daniel Steffens, Paula R Beckenkamp, Mark Hancock, Michael Solomon, Jane Young
Journal: British Journal of Sports Medicine (2018)

Objective To investigate the effectiveness of preoperative exercises interventions in patients undergoing oncological surgery, on postoperative complications, length of hospital stay and quality of life. Design Intervention systematic review with meta-analysis. Data sources MEDLINE, Embase and PEDro. Eligibility criteria for selecting studies Trials investigating the effectiveness of preoperative exercise for any oncological patient undergoing surgery were included. The outcomes of interest were postoperative complications, length of hospital stay and quality of life. Relative risks (RRs), mean differences (MDs) and 95% CI were calculated using random-effects models. Results Seventeen articles (reporting on 13 different trials) involving 806 individual participants and 6 tumour types were included. There was moderate-quality evidence that preoperative exercise significantly reduced postoperative complication rates (RR 0.52, 95% CI 0.36 to 0.74) and length of hospital stay (MD −2.86 days, 95% CI −5.40 to −0.33) in patients undergoing lung resection, compared with control. For patients with oesophageal cancer, preoperative exercise was not effective in reducing length of hospital stay (MD 2.00 days, 95% CI −2.35 to 6.35). Although only assessed in individual studies, preoperative exercise improved postoperative quality of life in patients with oral or prostate cancer. No effect was found in patients with colon and colorectal liver metastases. Conclusions Preoperative exercise was effective in reducing postoperative complications and length of hospital stay in patients with lung cancer. Whether preoperative exercise reduces complications, length of hospital stay and improves quality of life in other groups of patients undergoing oncological surgery is uncertain as the quality of evidence is low. PROSPEROregistration number
Abstracts cont.
Authors: J Garcı ´a-Campos, D Domingo, T Alarco ´n, E Aznar, J Dı ´az-Regan ˜o ´n, M Lo ´pez-, Brea Madrid, P Piqueres, Y Moreno, A Jimenez, J Herna ´ndez, M Ferru ´s Valencia, J Weile, M Susa, T Bachmann, C Stuttgart, D Akbulut, K Grant, M Brett, J London, L Vitorino, R De Sousa, L Ze ´-Ze, F Bacellar, R Lisbon, K Martienssen, A Becker, D Forster, K Pelz, A Sander, E Kniehl, M Porro, M Correnti, M Urrestarazu, J Vivas, M Avila, D Ortiz, V Lecuna, R Pin ˜ero, M Caracas, San Cristo´bal, N Montiel, J Navarro, J Prada, J De, La Torre, A Arco, C De Sola, I Lopez Marbella
Journal: Clinical Microbiology and Infection (2004)
Hepatitis B : Clonal evolution of hepatitis B virus resistant to Lamivudine, adefovir and entecavir during therapy with Lamivudine and adefovir (초)
Authors: Hye Lim Ju, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang Hyub Han, Weon Sang S Ro
Journal: Clinical and Molecular Hepatology (2011)
Abstract 68: p38 MAP Kinase Regulates Chamber Specific Postnatal Remodelling of Cardiac Ventricles
Authors: Tomohiro Yokota, Jin Li, Qing Zhang, Yichen Ding, Kevin Sung, Christoph Rau, Vincent Ren, Susumu Minamisawa, Tzung Hsiai, Rajan Kulkarni, Xinshu Xiao, Yibin Wang
Journal: Circulation Research (2016)

Background: Left ventricle (LV) and right ventricle (RV) in mouse heart undergo dramatically different chamber-specific remodeling after birth, leading to rapid increase in LV vs. RV chamber size. However, the underlying regulatory mechanism mediating chamber specific remodeling process remains enigmatic. Results and Methods: In neonatal mouse heart, p38 MAP kinase activity is dynamically activated in a chamber specific manner. p38 activity is specifically elevated in RV comparing to LV at E18.5, postnatal day 3 (P3) and P7 stages whereas p38 activity is lower in both ventricles at P0 and P1. In mouse heart with cardiomyocyte specific-knockout of p38α and β (p38ab-cdKO), total p38 activity was diminished in both chambers. The p38ab-cdKO mice had significant neonatal lethality associated with RV specific chamber enlargement and significant increase in both RV wall thickness (RVW) and inner diameter of RV (RVID) as early as P3. Interestingly, p38 inactivation suppressed myocyte apoptotic activity specifically in RV while increased RV myocyte proliferation and hypertrophy during neonatal period. Unexpectedly, RNA-seq results implicated Xbp1 mediated transcriptional regulation significantly contributing to p38 dependent transcriptome reprogramming in RV. Indeed, IRE1α expression in neonatal cardiomyocyte is sufficient to induce proliferation in vitro. Furthermore, knockdown of Xbp1 blunted p38 inhibition-induced myocyte proliferation, suggesting that IRE1a/Xbp1 mediate p38 signaling in neonatal myocyte proliferation. Conclusion: Chamber-specific remodeling in neonatal heart involves temporally regulated and RV specific p38 MAP kinase activity. RV specific myocyte proliferation and hypertrophy concurrent with RV specific programmed myocyte death is orchestrated by two innate stress-response pathways, p38 and Xbp1.
Seasonality and geographical spread of respiratory syncytial virus epidemics in 15 European countries, 2010 to 2016
Authors: Eeva K Broberg, Matti Waris, Kari Johansen, René Snacken, Pasi Penttinen
Journal: Eurosurveillance (2018)

Respiratory syncytial virus (RSV) is considered the most common pathogen causing severe lower respiratory tract infections among infants and young children. We describe the seasonality and geographical spread of RSV infection in 15 countries of the European Union and European Economic Area. We performed a retrospective descriptive study of weekly laboratory-confirmed RSV detections between weeks 40/2010 and 20/2016, in patients investigated for influenza-like illness, acute respiratory infection or following the clinician's judgment. Six countries reported 4,230 sentinel RSV laboratory diagnoses from primary care and 14 countries reported 156,188 non-sentinel laboratory diagnoses from primary care or hospitals. The median length of the RSV season based on sentinel and non-sentinel surveillance was 16 (range: 9-24) and 18 (range: 8-24) weeks, respectively. The median peak weeks for sentinel and non-sentinel detections were week 4 (range: 48 to 11) and week 4.5 (range: 49 to 17), respectively. RSV detections peaked later (r = 0.56; p = 0.0360) and seasons lasted longer with increasing latitude (r = 0.57; p = 0.0329). Our data demonstrated regular seasonality with moderate correlation between timing of the epidemic and increasing latitude of the country. This study supports the use of RSV diagnostics within influenza or other surveillance systems to monitor RSV seasonality and geographical spread.
MR-PheWAS: exploring the causal effect of SUA level on multiple disease outcomes by using genetic instruments in UK Biobank
Authors: Xue Li, Xiangrui Meng, Athina Spiliopoulou, Maria Timofeeva, Wei-Qi Wei, Aliya Gifford, Xia Shen, Yazhou He, Tim Varley, Paul McKeigue, Ioanna Tzoulaki, Alan F Wright, Peter Joshi, Joshua C Denny, Harry Campbell, Evropi Theodoratou
Journal: Annals of the Rheumatic Diseases (2018)

Objectives We aimed to investigate the role of serum uric acid (SUA) level in a broad spectrum of disease outcomes using data for 120 091 individuals from UK Biobank. Methods We performed a phenome-wide association study (PheWAS) to identify disease outcomes associated with SUA genetic risk loci. We then implemented conventional Mendelianrandomisation (MR) analysis to investigate the causal relevance between SUA level and disease outcomes identified from PheWAS. We next applied MR Egger analysis to detect and account for potential pleiotropy, which conventional MR analysis might mistake for causality, and used the HEIDI (heterogeneity in dependent instruments) test to remove cross-phenotype associations that were likely due to genetic linkage. Results Our PheWAS identified 25 disease groups/outcomes associated with SUA genetic risk loci after multiple testing correction (P&lt;8.57e-05). Our conventional MR analysis implicated a causal role of SUA level in three disease groups: inflammatory polyarthropathies (OR=1.22, 95% CI 1.11 to 1.34), hypertensive disease (OR=1.08, 95% CI 1.03 to 1.14) and disorders of metabolism (OR=1.07, 95% CI 1.01 to 1.14); and four disease outcomes: gout (OR=4.88, 95% CI 3.91 to 6.09), essential hypertension (OR=1.08, 95% CI 1.03 to 1.14), myocardial infarction (OR=1.16, 95% CI 1.03 to 1.30) and coeliac disease (OR=1.41, 95% CI 1.05 to 1.89). After balancing pleiotropic effects in MR Egger analysis, only gout and its encompassing disease group of inflammatory polyarthropathies were considered to be causally associated with SUA level. Our analysis highlighted a locus ( ATXN2/S2HB3 ) that may influence SUA level and multiple cardiovascular and autoimmune diseases via pleiotropy. Conclusions Elevated SUA level is convincing to cause gout and inflammatory polyarthropathies, and might act as a marker for the wider range of diseases with which it associates. Our findings support further investigation on the clinical relevance of SUA level with cardiovascular, metabolic, autoimmune and respiratory diseases.
Incidence and costs of herpes zoster and postherpetic neuralgia in German adults aged ≥50 years: A prospective study
Authors: Ruprecht Schmidt-Ott, Ulf Schutter, Jörg Simon, Barbara Poulsen Nautrup, Alfred von Krempelhuber, Kusuma Gopala, Anastassia Anastassopoulou, Adrienne Guignard, Desmond Curran, Sean Matthews, Emmanuelle Espié
Journal: Journal of Infection (2018)

ObjectivesHerpes zoster (HZ) mainly affects elderly people and immunocompromised individuals. HZ is usually characterized by a unilateral painful skin rash. Its most common complication, postherpetic neuralgia (PHN), may cause chronic debilitating pain. This study aimed to estimate the HZ incidence in individuals aged ≥50 years in Germany, the proportion of PHN and the economic burden.MethodsFrom 2010 to 2014, HZ patients were recruited when consulting physicians in physician networks covering about 157,000 persons aged ≥50 years. PHN was defined as "worst pain" rated ≥3 on the zoster brief pain inventory persisting or appearing over 90 days after rash onset. Costs were calculated based on medical resource utilization and lost working time.ResultsHZ incidence was estimated as 6.7/1000 person-years, increasing with age to 9.4/1000 in ≥80 year-olds. Among 513 HZ patients enrolled, the proportion of PHN was 11.9%, rising with age to 14.3% in HZ patients ≥80 years. Estimated total cost per HZ patient was €156 from the healthcare system perspective and €311 from the societal perspective.ConclusionsThe study confirmed previous findings that HZ causes a substantial clinical and economic burden in older German adults. It also confirmed the age-related increasing risk of HZ and PHN.