tbuckley/cabot-search huggingface dataset:
EpCAM-Regulated Transcription Exerts Influences on Nanomechanical Properties of Endometrial Cancer Cells That Promote Epithelial-to-Mesenchymal Transition
Authors: Ya-Ting Hsu, Pawel Osmulski, Yao Wang, Yi-Wen Huang, Lu Liu, Jianhua Ruan, Victor X. Jin, Nameer B. Kirma, Maria E. Gaczynska, Tim Hui-Ming Huang
Journal: Cancer Research (2016)

Abstract Overexpression of epithelial cell adhesion molecule (EpCAM) has been implicated in advanced endometrial cancer, but its roles in this progression remain to be elucidated. In addition to its structural role in modulating cell-surface adhesion, here we demonstrate that EpCAM is a regulatory molecule in which its internalization into the nucleus turns on a transcription program. Activation of EGF/EGFR signal transduction triggered cell-surface cleavage of EpCAM, leading to nuclear internalization of its cytoplasmic domain EpICD. ChIP-seq analysis identified target genes that are coregulated by EpICD and its transcription partner, LEF-1. Network enrichment analysis further uncovered a group of 105 genes encoding functions for tight junction, adherent, and cell migration. Furthermore, nanomechanical analysis by atomic force microscopy revealed increased softness and decreased adhesiveness of EGF-stimulated cancer cells, implicating acquisition of an epithelial–mesenchymal transition (EMT) phenotype. Thus, genome editing of EpCAM could be associated with altering these nanomechanical properties towards a less aggressive phenotype. Using this integrative genomic–biophysical approach, we demonstrate for the first time an intricate relationship between EpCAM-regulated transcription and altered biophysical properties of cells that promote EMT in advanced endometrial cancer. Cancer Res; 76(21); 6171–82. ©2016 AACR.
A prospective phase II study of single-agent gemcitabine at prolonged constant infusion at 10mg/m<sup>2</sup>/min rate (PCI-G) in first-line treatment of elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): The MILES-2G study
Authors: E. De Maio, A. Morabito, S. Barbera, S. F. Robbiati, E. Piazza, L. Brancaccio, F. Rosetti, P. Foa, C. Verusio, C. Gridelli
Journal: Journal of Clinical Oncology (2006)

7125 Background: Single-agent chemotherapy is the standard treatment for elderly pts with advanced NSCLC, following the results of the ELVIS and MILES-1 trials. Some hints that infusing gemcitabine at a fixed dose rate of 10 mg/m 2 /minute can optimize its pharmacokinetics have been reported. A prospective phase 2 study was conducted to describe activity and toxicity of PCI-G. Methods: Advanced (stage IV or IIIb with supraclavear nodes or pleural effusion) NSCLC pts, aged &gt;70, PS 0–1, were eligible. 51 patients were required according to a single-stage phase 2 design to have 90% confidence in estimating a 25% ±10% response rate. Response was assessed with RECIST; toxicity was coded with NCI-CTC. Results: From October 2002 to June 2003, 51 pts were enrolled. 26 pts (51%) were older than 75 years. Two complete and seven partial responses were observed, for an overall response rate of 17.6% (95% exact CI: 8–31). The median progression-free survival was 16 wks (95% CI: 11–21) and the median overall survival was 41 wks (95% CI: 28–51). Two toxic deaths were recorded (1 bronchial bleeding and 1 hepatic toxicity). Other relevant toxicities were (% of pts): grade 3–4 neutropenia (11.8%), grade 3 thrombocytopenia (5.9%), grade 3 pulmonary toxicity (3.9%) and grade 3 liver toxicity (3.9%); platelet transfusion, grade 3 anemia, RBC transfusion, non-neutropenic infection, and grade 4 neurotoxicity were all reported in one pt each. Conclusions: In this phase 2 prospective study dedicated to elderly pts with advanced NSCLC, PCI-G was not sufficiently active to warrant further investigation. No significant financial relationships to disclose.
Is Justification of Animal Research Necessary?
Authors: Andrew N. Rowan
Journal: JAMA (1993)

<h3>To the Editor.</h3> —It was a pleasure to see a sophisticated analysis of the two different approaches to animal moral status in a recent issue of<i>JAMA</i>.<sup>1</sup>In the recent scientific literature, most authors who have taken on the philosophers underpinning the modern animal movement have exhibited a distressing lack of scholarship, a tendency to exhibit their own emotional colors, and an obvious ignorance of even relatively basic philosophical argument. Dr Vance does not fall into any of these traps, but neither does he address a major reason that Singer and Regan and the other philosophers have had such an impact on public attitudes. While Singer and Regan expose the weaknesses and inconsistencies in each other's arguments, they do an even better job of exposing the weaknesses of the essentially unexamined status quo position regarding animals. For the most part, animal use by humans is permitted because we find
Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease
Authors: Kaare H Bønaa, Jan Mannsverk, Rune Wiseth, Lars Aaberge, Yngvar Myreng, Ottar Nygård, Dennis W Nilsen, Nils-Einar Kløw, Michael Uchto, Thor Trovik, Bjørn Bendz, Sindre Stavnes, Reidar Bjørnerheim, Alf-Inge Larsen, Morten Slette, Terje Steigen, Ole J Jakobsen, Øyvind Bleie, Eigil Fossum, Tove A Hanssen, Øystein Dahl-Eriksen, Inger Njølstad, Knut Rasmussen, Tom Wilsgaard, Jan E Nordrehaug
Journal: New England Journal of Medicine (2016)

Limited data are available on the long-term effects of contemporary drug-eluting stents versus contemporary bare-metal stents on rates of death, myocardial infarction, repeat revascularization, and stent thrombosis and on quality of life.We randomly assigned 9013 patients who had stable or unstable coronary artery disease to undergo percutaneous coronary intervention (PCI) with the implantation of either contemporary drug-eluting stents or bare-metal stents. In the group receiving drug-eluting stents, 96% of the patients received either everolimus- or zotarolimus-eluting stents. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularization, stent thrombosis, and quality of life.At 6 years, the rates of the primary outcome were 16.6% in the group receiving drug-eluting stents and 17.1% in the group receiving bare-metal stents (hazard ratio, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.66). There were no significant between-group differences in the components of the primary outcome. The 6-year rates of any repeat revascularization were 16.5% in the group receiving drug-eluting stents and 19.8% in the group receiving bare-metal stents (hazard ratio, 0.76; 95% CI, 0.69 to 0.85; P<0.001); the rates of definite stent thrombosis were 0.8% and 1.2%, respectively (P=0.0498). Quality-of-life measures did not differ significantly between the two groups.In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug-eluting stents. (Funded by the Norwegian Research Council and others; NORSTENT ClinicalTrials.gov number, NCT00811772 .).
Determining If Sex Bias Exists in Human Surgical Clinical Research
Authors: Neel A. Mansukhani, Dustin Y. Yoon, Katherine A. Teter, Vanessa C. Stubbs, Irene B. Helenowski, Teresa K. Woodruff, Melina R. Kibbe
Journal: JAMA Surgery (2016)

Sex is a variable that is poorly controlled for in clinical research.To determine if sex bias exists in human surgical clinical research, to determine if data are reported and analyzed using sex as an independent variable, and to identify specialties in which the greatest and least sex biases exist.For this bibliometric analysis, data were abstracted from 1303 original peer-reviewed articles published from January 1, 2011, through December 31, 2012, in 5 surgery journals.Study type, location, number and sex of participants, degree of sex matching of included participants, and inclusion of sex-based reporting, statistical analysis, and discussion of data.Of 2347 articles reviewed, 1668 (71.1%) included human participants. After excluding 365 articles, 1303 remained: 17 (1.3%) included males only, 41 (3.1%) included females only, 1020 (78.3%) included males and females, and 225 (17.3%) did not document the sex of the participants. Although female participants represent more than 50% (n = 57 688 606) of the total number (115 377 213) included, considerable variability existed with the number of male (46 111 818), female (58 805 665), and unspecified (10 459 730) participants included among the journals, between US domestic and international studies, and between single vs multicenter studies. For articles included in the study, 38.1% (497 of 1303) reported these data by sex, 33.2% (432 of 1303) analyzed these data by sex, and 22.9% (299 of 1303) included a discussion of sex-based results. Sex matching of the included participants in the research overall was poor, with 45.2% (589 of 1303) of the studies matching the inclusion of both sexes by 50%. During analysis of the different surgical specialties, a wide variation in sex-based inclusion, matching, and data reporting existed, with colorectal surgery having the best matching of male and female participants and cardiac surgery having the worst.Sex bias exists in human surgical clinical research. Few studies included men and women equally, less than one-third performed data analysis by sex, and there was wide variation in inclusion and matching of the sexes among the specialties and the journals reviewed. Because clinical research is the foundation for evidence-based medicine, it is imperative that this disparity be addressed so that therapies benefit both sexes.
Expert panel recommends that the US cancer “moonshot” focuses on 10 areas
Authors: Michael McCarthy
Journal: BMJ (2016)

An expert panel has recommended that the Obama administration’s cancer “moonshot” focuses its efforts on 10 initiatives, including creating networked databases of patient tumor profiles to facilitate research and treatment, developing a network of cancer immunotherapy clinical trials, and implementing more effective programs for cancer prevention and early detection.1

The moonshot initiative was announced by President Barack Obama in January in his last State of the Union address and is being led by Vice President Joe Biden, whose son, Beau, died of brain cancer …
Heregulin as a novel cetuximab-resistace factor in colorectal cancer.
Authors: K. Yonesaka, I. Okamoto, T. Satoh, K. Takeda, M. Takada, K. Nishio, M. Fukuoka, N. Saijo, P. A. Janne, K. Nakagawa
Journal: Journal of Clinical Oncology (2010)

e14044 Background: Cetuximab, anti-EGFR monoclonal antibody, is one of the treatment option for metastatic colorectal cancer (mCRC). And now we could predict the efficacy of cetuximab with KRAS gene status. However, all patients (pts) ultimately acquire the resistance to cetuximab, and we do not understand the mechanism underlying there. Here we investigated for elucidating how to acquire cetuximab resistance thorough the treatemant in cancer. Methods: We established A431ER, cetuximab resistant subline, from parental A431, which was sensitive to cetuximab. And we screened out a resistant factor for cetuximab by the comparison between two cell lines using phospho receptor tyrosine kinase (RTK) array, immunoblotting and ELISA. Clinical relevance for a novel resistant factor was evaluated among mCRC pts treated with cetuximab based therapy. Plasma level of heregulin was measured by ELISA. KRAS gene was directly sequenced at codon 12 and 13 of exon 2. Results: Phospho-RTK array detected potently phosphorylated ErbB2 and ErbB3 in A431ER than A431. And immunoblotting and ELISA showed that aberrant expression of heregulin (HRG), a ligand for Erb3, induced phosphorylation of those receptors. Growth inhibition assay showed that HRG could induce resistance to cetuximab in vitro. In the 60 pts with mCRC, HRG expressed variously (median 2,002, range 274 to 17,260 pg/mL). Plasma level of HRG was significantly greater among pts with progressive disease (n = 23, median 5,763 pg/mL) than pts developed SD or PR (n = 19, median 1,441 pg/mL, p = 0.0001) through the cetuximab treatment. Progression-free survival was longer in HRG low group (n = 30, HRG < 2,000 pg/mL) than HRG high group (n = 30, HRG > 2,000 pg/mL) (MST 154 vs. 42 days, HR 0.23 [95%CI 0.11-0.48]; p < 0.0001). And also overall survival was longer in HRG low group than HRG high group (MST 214 vs. 104 days, HR 0.29 [95%CI 0.13-0.67]; p = 0.0037). HRG plasma level did not significantly related with KRAS gene status. Further HRG plasma level was significantly elevated following acquired resistance to cetuximab (n = 8, pre-805 vs. post 1627 pg/mL, p = 0.0093). Conclusions: HRG induced both de novo and acquired resistance in mCRC. We suggest HRG plasma level could be predictive biomarker for cetuximab. No significant financial relationships to disclose.
Fatal acute respiratory distress syndrome with diffuse alveolar damage: donor lymphocyte infusion imputability?
Authors: Colombe Saillard, Magali Bisbal, Antoine Sannini, Laurent Chow-Chine, Jean-Paul Brun, Samia Harbi, Sabine Furst, Didier Blaise, Maria Paciencia, Véronique Secq, Djamel Mokart
Journal: European Respiratory Journal (2016)

Donor lymphocyte infusion (DLI) is increasingly used after allogeneic haematopoietic stem cell transplantation (allo-HSCT), as a pre-emptive or curative immunotherapy of relapsed haematological malignancies, enhancing graft- versus -tumour effects [1]. The main complication is graft- versus -host disease (GVHD), with cumulative incidences of 40–60% and 33–61% for acute and chronic GVHD, respectively, typically developing 32–42 days after DLI [2]. Pulmonary complications after DLI are poorly documented. To our knowledge, there are no cases of diffuse alveolar damage (DAD) [3] after DLI in the literature to date. Here, we report our experience of two cases of acute respiratory distress syndrome (ARDS) with DAD following DLI after allo-HSCT, rapidly extending to fatal pulmonary fibrosis. Submission was approved by our institutional review board and informed consent was obtained. Fatal ARDS with diffuse alveolar damage: donor lymphocyte infusion imputability? <http://ow.ly/WhxP3034P6s> C. Saillard and D. Mokart drafted the manuscript. C. Saillard, M. Bisbal, A. Sannini, L. Chow-Chine, J-P. Brun, S. Harbi, S. Furst, D. Blaise and D. Mokart participated in patient care. M. Paciencia and V. Secq carried out the histological analysis. All authors critically revised the manuscript and approved the final submitted version. D. Mokart had full access to all the data and takes responsibility for the integrity of the data.
Abstract P266: Prevalence and Age-related Trends of Subclinical Cardiovascular Disease Burden in Adult Afro-Caribbean Men From Tobago
Authors: Allison L Kuipers, Iva Miljkovic, J J Carr, James G Terry, Sangeeta Nair, Yaorong Ge, Ryan Cvejkus, Clareann H Bunker, Alan L Patrick, Christina L Wassel, Joseph M Zmuda
Journal: Circulation (2016)

Introduction: Cardiovascular disease (CVD) is the leading cause of death throughout the world and age-adjusted rates of CVD mortality in Trinidad and Tobago are estimated to be ~2x those of the US. Given the drastic differences in culture and urbanization between Tobago and the US, we started the Tobago Heart Health Study to evaluate several aspects of subclinical CVD within a sample of men from an existing longitudinal study on the island. Hypothesis: We assessed the hypothesis that subclinical CVD burden in adult Afro-Caribbean men would be low overall, but that the burden would be substantially greater in the oldest men. Methods: We have preliminary data on subclinical CVD measures from 140 men, including carotid plaque from B-mode ultrasound, coronary artery calcification (CAC) and pericardial fat from computed tomography, and ankle-brachial index (ABI) and brachial-ankle pulse-wave velocity (baPWV) from automated waveform analysis. To assess the burden of multiple adverse measures, we calculated a subclinical CVD score (range 0-5) by summing the prevalence of the following: any carotid plaque, any CAC, highest quintile of pericardial fat, lowest quintile of ABI, or highest quintile of baPWV. For all subclinical variables of interest, we calculated means(SD) or frequencies, as appropriate, and identified age trends by testing for linear trends with age grouped as &lt;60 years (n=56), 60-69 years (n=59) or ≥70 years (n=30). Results: The men were aged 53-88 years (mean(SD): 64(9) years) and the prevalence of hypertension, diabetes, smoking, moderate alcohol intake, and sedentary behavior were 64%, 26%, 5%, 18% and 52%, respectively. Sixteen percent of men had any carotid plaque and 25% had any CAC. Mean ABI was 1.1(0.1), mean baPWV was 1696(388)cm/s and mean pericardial fat was 41.4(27.6)cm3. Only 56% had ≥1 adverse subclinical CVD measure (23% with 1, 21% with 2, 10% with 3, 2% with 4, 0 with 5). Men in the oldest age group had significantly more carotid plaque, more CAC, lower ABI, higher baPWV and more pericardial fat compared to the younger age groups (all p&lt;0.05). Mean(SD) subclinical CVD score was 0.6(0.8) in men &lt;60 years, 0.8(0.9) in men aged 60-69 years, and 2.2(1.0) in men aged ≥70 years (p&lt;0.001). Greater age remained a significant predictor of subclinical CVD score after adjustment for hypertension, diabetes, smoking, alcohol intake and physical activity (p&lt;0.001). Conclusions: Subclinical CVD burden was low in this sample of 140 Afro-Caribbean men from Tobago. However, prevalence of adverse subclinical CVD measures greatly increased over the age of 70. It will be important to assess the impact of this aging-related subclinical burden on clinical CVD and cardiovascular mortality risks in adult Afro-Caribbean men in future studies.
A Case-Matched Analysis Comparing Lenalidomide After Autologous or After Allogeneic Stem Cell Transplantation Demonstrates a Survival Advantage in Allografted Myeloma Patients
Authors: Vittorio Montefusco, Francesco Spina, Elena Zamagni, Benedetto Bruno, Francesca Gay, Francesca Patriarca, Giorgia Saporiti, Monica Galli, Claudia Crippa, Lucia Farina, Anna Maria Cafro, Angelo Michele Carella, Paolo Corradini
Journal: Blood (2012)
Sensitivity of Acute Leukemia Cells to Cytarabine Is a Correlate of Cellular es Nucleoside Transporter Site Content Measured by Flow Cytometry With SAENTA-Fluorescein
Authors: Wendy P. Gati, Alan R.P. Paterson, Loree M. Larratt, A. Robert Turner, Andrew R. Belch
Journal: Blood (1997)
Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations
Authors: Loren C. Denlinger, Brenda R. Phillips, Sima Ramratnam, Kristie Ross, Nirav R. Bhakta, Juan Carlos Cardet, Mario Castro, Stephen P. Peters, Wanda Phipatanakul, Shean Aujla, Leonard B. Bacharier, Eugene R. Bleecker, Suzy A. A. Comhair, Andrea Coverstone, Mark DeBoer, Serpil C. Erzurum, Sean B. Fain, Merritt Fajt, Anne M. Fitzpatrick, Jonathan Gaffin, Benjamin Gaston, Annette T. Hastie, Gregory A. Hawkins, Fernando Holguin, Anne-Marie Irani, Elliot Israel, Bruce D. Levy, Ngoc Ly, Deborah A. Meyers, Wendy C. Moore, Ross Myers, Maria Theresa D. Opina, Michael C. Peters, Mark L. Schiebler, Ronald L. Sorkness, W. Gerald Teague, Sally E. Wenzel, Prescott G. Woodruff, David T. Mauger, John V. Fahy, Nizar N. Jarjour
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined.To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.Baseline data from the NHLBI Severe Asthma Research Program (SARP)-3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (≥3). Replication of a multivariable model was performed with data from the SARP-1 + 2 cohort.Of 709 subjects in the SARP-3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency in SARP-3; bronchodilator responsiveness also discriminated exacerbation proneness from asthma severity. In the SARP-3 multivariable model, blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency (rate ratios [95% confidence interval], 1.6 [1.2-2.1] for every log unit of eosinophils, 1.3 [1.1-1.4] for every 10 body mass index units, and 1.2 [1.1-1.4] for every 10% increase in bronchodilatory responsiveness). Chronic sinusitis and gastroesophageal reflux were also associated with exacerbation frequency (1.7 [1.4-2.1] and 1.6 [1.3-2.0]), even after adjustment for multiple factors. These effects were replicated in the SARP-1 + 2 multivariable model.EPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 01760915).
CDC Grand Rounds: Public Health Strategies to Prevent Preterm Birth
Authors: Carrie K. Shapiro-Mendoza, Wanda D. Barfield, Zsakeba Henderson, Arthur James, Jennifer L. Howse, John Iskander, Phoebe G. Thorpe
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Preterm birth (delivery before 37 weeks and 0/7 days of gestation) is a leading cause of infant morbidity and mortality in the United States. In 2013, 11.4% of the nearly 4 million U.S. live births were preterm; however, 36% of the 8,470 infant deaths were attributed to preterm birth (1). Infants born at earlier gestational ages, especially <32 0/7 weeks, have the highest mortality (Figure) and morbidity rates. Morbidity associated with preterm birth includes respiratory distress syndrome, necrotizing enterocolitis, and intraventricular hemorrhage; longer-term consequences include developmental delay and decreased school performance. Risk factors for preterm delivery include social, behavioral, clinical, and biologic characteristics (Box). Despite advances in medical care, racial and ethnic disparities associated with preterm birth persist. Reducing preterm birth, a national public health priority (2), can be accomplished by implementing and monitoring strategies that target modifiable risk factors and populations at highest risk, and by providing improved quality and access to preconception, prenatal, and interconception care through implementation of strategies with potentially high impact.