tbuckley/cabot-search huggingface dataset:
Regulation of GLI Underlies a Role for BET Bromodomains in Pancreatic Cancer Growth and the Tumor Microenvironment
Authors: Yinshi Huang, Sabikun Nahar, Akifumi Nakagawa, Maite G. Fernandez-Barrena, Jennifer A. Mertz, Barbara M. Bryant, Curtis E. Adams, Mari Mino-Kenudson, Kate N. Von Alt, Kevin Chang, Andrew R. Conery, Charlie Hatton, Robert J. Sims, Martin E. Fernandez-Zapico, Xingpeng Wang, Keith D. Lillemoe, Carlos Fernández-del Castillo, Andrew L. Warshaw, Sarah P. Thayer, Andrew S. Liss
Journal: Clinical Cancer Research (2016)

Abstract Purpose: The initiation, progression, and maintenance of pancreatic ductal adenocarcinoma (PDAC) results from the interplay of genetic and epigenetic events. While the genetic alterations of PDAC have been well characterized, epigenetic pathways regulating PDAC remain, for the most part, elusive. The goal of this study was to identify novel epigenetic regulators contributing to the biology of PDAC. Experimental Design: In vivo pooled shRNA screens targeting 118 epigenetic proteins were performed in two orthotopic PDAC xenograft models. Candidate genes were characterized in 19 human PDAC cell lines, heterotopic xenograft tumor models, and a genetically engineered mouse (GEM) model of PDAC. Gene expression, IHC, and immunoprecipitation experiments were performed to analyze the pathways by which candidate genes contribute to PDAC. Results: In vivo shRNA screens identified BRD2 and BRD3, members of the BET family of chromatin adaptors, as key regulators of PDAC tumor growth. Pharmacologic inhibition of BET bromodomains enhanced survival in a PDAC GEM model and inhibited growth of human-derived xenograft tumors. BET proteins contribute to PDAC cell growth through direct interaction with members of the GLI family of transcription factors and modulating their activity. Within cancer cells, BET bromodomain inhibition results in downregulation of SHH, a key mediator of the tumor microenvironment and canonical activator of GLI. Consistent with this, inhibition of BET bromodomains decreases cancer-associated fibroblast content of tumors in both GEM and xenograft tumor models. Conclusions: Therapeutic inhibition of BET proteins offers a novel mechanism to target both the neoplastic and stromal components of PDAC. Clin Cancer Res; 22(16); 4259–70. ©2016 AACR.
Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for relapsed non-Hodgkin's lymphoma: blood and bone marrow progenitor growth studies. A phase II Eastern Cooperative Oncology Group Trial
Authors: HM Lazarus, J Andersen, MG Chen, D Variakojis, EG Mansour, D Oette, CA Arce, MM Oken, SL Gerson
Journal: Blood (1991)
Abstract 66: Unique Cardiac Fibroblast Expression Profiles in Pathological and Physiological Hypertrophy
Authors: Janet K Lighthouse, Lissette S Velasquez, Eric M Small
Journal: Circulation Research (2014)

The heart undergoes hypertrophic growth in response to both physiological and pathological stimuli. Pathological hypertrophy results from various humoral, mechanical, or ischemic insults, and often leads to cardiac fibrosis, diminished contractility, and heart failure. In contrast, physiological hypertrophy is an adaptive response to the excessive demands of exercise or pregnancy and does not lead to fibrosis. We hypothesized that cardiac fibroblasts, the main cellular source of extracellular matrix in the heart, exhibit distinct expression profiles in physiological or pathological remodeling that influence the divergent fibrotic response. To investigate these differences, we obtained the expression profile of cardiac fibroblasts isolated from mice subjected to swim training, pressure-overload induced cardiac remodeling, or myocardial infarction by RNA-sequencing. Although we observed cardiac growth in all conditions, pressure-overload induced hypertrophy and myocardial infarction induced the predicted fibrotic gene expression signature, which was absent in physiological hypertrophy. Utilizing these validated datasets, we identified novel genes and molecular pathways that are differentially expressed in physiological and pathological hypertrophic remodeling and will correlate transcriptional programs with altered gene profiles. Fibroblast gene expression profiles in pathological and physiological are expected to lead to diagnostic or prognostic markers of fibrotic remodeling as well as genes that may serve as novel therapeutic strategies to prevent or reverse cardiac fibrosis.
Abstract 17139: Cathepsin S Deficiency Attenuates AngiotensinII-induced Abdominal Aortic Aneurysm Without Altering Hypertension in ApoE Knockout Mice
Authors: Chanwoo Kim, Dongju Son, Noah Albert-Grill, Sandeep Kumar, Hanjoong Jo
Journal: Circulation (2011)

Abdominal aortic aneurysm (AAA) formation is characterized by weakening of the vessel wall, followed by progressive expansion and eventual rupture of the diseased aortic segment. Extracellular matrix remodeling contributes importantly to the pathogenesis of cardiovascular diseases such as atherosclerosis and abdominal aortic aneurysms. The cysteine protease, cathepsin is one of the most potent mammalian elastases and collagenases, which were highly expressed in the AAA wall compared to that in healthy arteries. Here, we examined the hypothesis that Cat S and Cat K plays a key role in AAA formation. When infused with Angiotensin II (Ang II; 1 μg/kg/min) using osmotic pumps for 28 days, 69% of ApoE KO mice (9 of 13 mice), 75% of Cat K_ApoE DKO (6 of 8 mice) and only 7% of Cat S_ApoE DKO (1 of 13 mice) developed AAA as determined by increases in abdominal aorta diameter by more than two-fold above control. In mice infused with angiotensin II, mortality due to aortic rupture occurred more frequently in ApoE KO mice (4 of 13 mice; 30%) compared to Cat K_ApoE DKO mice (1 of 8mice; 12.5%) and Cat S_ApoE DKO mice (1 of 13 mice; 7%). AngII infusion also significantly increased systemic blood pressure (155-165 mmHg) in ApoE KO mice (n=13), Cat K_ApoE DKO (n=8) and Cat S_ApoE DKO (n=13) mice but, there are no significant difference between the groups. Our results showed that Cat K gene deficiency does not affect AAA development while Cat S gene deficiency dramatically prevented Ang II-induced AAA formation without altering hypertension. These data suggest that Cat S plays a central role in AAA development. Targeting the Cat S may lead to an important therapeutic intervention for preventing AAA formation
Carcinogenic Effect of N -Nitrosohexamethylenimine in Syrian Golden Hamsters 2
Authors: J. Althoff, A. Cardesa, P. Pour, U. Mohr
Journal: JNCI Journal of the National Cancer Institute (1973)

Syrian golden hamsters were treated subcutaneously with N-nitrosohexamethylenimine (N-6-MI). Tumors of the respiratory system were found, and the trachea appeared to be the main target organ. Neoplasms of the nasal cavities were mostly adenocarcinomas, whereas the morphologic patterns of tracheal tumors were similar to the papillary polyps induced by diethylnitrosamine. The lungs had a low tumor incidence.
Performance of diagnostic tests in an intensive follow-up protocol for patients with American Joint Committee on Cancer (AJCC) stage IIB, IIC, and III localized primary melanoma: A prospective cohort study
Authors: Sebastian Podlipnik, Cristina Carrera, Marcelo Sánchez, Pedro Arguis, Maria L. Olondo, Ramon Vilana, Ramon Rull, Sergi Vidal-Sicart, Antonio Vilalta, Carles Conill, Josep Malvehy, Susana Puig
Journal: Journal of the American Academy of Dermatology (2016)
Pilot study on transient bacteremia and blood stream infections after invasive dental procedures in patients with cancer and central venous catheters.
Authors: Z. Shahid, S. Z. Usmani, L. Choquette, R. Lalla, R. D. Bona
Journal: Journal of Clinical Oncology (2010)

e19575 Background: There is no consensus among cancer centers on whether or not to administer antibiotic prophylaxis to cancer patients with long-term central venous catheters (CVCs) before a dental procedure to prevent transient bacteremia and potentially, a blood stream infection (BSI). To our knowledge, there are no epidemiological studies or national or international guidelines that have looked at the incidence of transient bacteremia and/or BSI in patients who have cancer and a CVC. Methods: This prospective, IRB-approved, pilot study will evaluate 30 subjects undergoing a standardized dental cleaning procedure (without antibiotic prophylaxis) for development of transient bacteremia or established BSI. Blood cultures will be drawn before, 20 minutes, 30 minutes and 24 hours post-procedure initiation. Periodontal health will be measured pre-procedure in order to correlate possible poor periodontal status with increased rate of positive blood culture or BSI. The data will be reported as the cumulative incidence rates for bacteremia at all time-points after procedure initiation, with exact binomial 95% confidence intervals. Results: 9 subjects have been recruited to the study. Only 2 out of 36 blood cultures (4 per subject) were positive. Both positive cultures were taken 20 minutes after initiating the dental cleaning. The organisms identified were Streptococcus mutans and Prevotella species, which are both oral commensals. Conclusions: Preliminary results demonstrate that transient bacteremia rates in patients with cancer with CVCs appear comparable to previous reports in a population of individuals without cancer. The patients with the two positive blood cultures did not develop BSI. The present work is innovative, because this will be the first study, to our knowledge, that examines the natural history of transient bacteremia in patients with cancer who have long term CVCs. This work is being supported by the University of Connecticut Health Center/HERA Foundation Seed Grant and the University of Connecticut Health Center/General Clinical Research Center (NIH M01R006192). No significant financial relationships to disclose.
Abstract 1079: Modulation of Atherosclerotic Plaque Characteristics by Minocycline: An Evaluation by Molecular Imaging of Matrix Metalloprotainase (MMP) Expression
Authors: Satoru Ohshima, Shinichiro Fujimoto, Hironori Nakagami, Nezam Haider, Jun Zhou, Mariana K Osako, Ai Fujimoto, Jie Zhu, Navneet Narula, Toyoaki Murohara, Artiom Petrov, Ryuichiro Morishita, Jagat Narula
Journal: Circulation (2008)

MMP activation in atherosclerotic lesions plays an important role in plaque progression and vulnerability, and is a potential target for plaque stabilization. We evaluated the effectiveness of minocycline (MC) in modulation of plaque characteristics using molecular imaging of MMP expression, compared with fluvastatin (FS). 38 NZW rabbits with experimental atherosclerotic lesions were subjected to in vivo micro SPECT/CT imaging for the assessment of MMP activity using 99mTc-labeled broad spectrum MMP inhibitor (MPI). Atherosclerotic lesions were produced by balloon deendotheliazation of abdominal aorta, and high cholesterol diet for 4 months. Of these, 7 received low dose MC (1.5mg/kg), 7 high dose MC (3mg/kg, N=7), 6 FS (1mg/kg), and 6 combination of low dose MC and FS (MC+FS) in the fourth month, 12 received no intervention (Rx-control). 8 unmanipulated normal chow-fed rabbits were used as disease controls (Dz-control). After in vivo imaging, aortas were explanted for %ID/g MPI uptake, histological characterization, and MMP activity assays. Parallel in vitro studies were performed for the effect of MC and FS on NF-κB, VCAM-1 and MMP-9 expression from cultured TNF-α-stimulated smooth muscle cells and macrophages. Target accumulation of MPI was best visualized in atherosclerotic aorta in Rx-control atherosclerotic rabbits. % ID/g MPI in Rx-control (.10±.04%) was significantly higher than Dz-control (.016±.004%), MC-low (.081±.02%) and high (.045±.01%) dose, FS (.056±.011%), and MC+FS (.049±.005%) rabbits, and showed a significant correlation with histologically and biochemically-verified MMP-2, -9 activity. MC-treated plaques showed marked reduction in inflammation and increase in smooth muscle content. In vitro cell culture confirmed that NF-κB and VCAM-1 expression in activated VSMC were reduced by MC, and that MMP-9 expression in activated macrophage was also inhibited by MC. The present study demonstrates that MC is equally effective as FS in modulation of plaque characteristics, and that molecular imaging can characterize various biologic processes in vivo and allows for the study of the efficacy of targeted interventions.
ASiT’s concerns about views expressed in the Nuffield Trust report on emergency general surgery
Authors: Elizabeth Elsey, Rhiannon Harries, Adam Williams
Journal: BMJ (2016)

The Association of Surgeons in Training (ASiT) is concerned about views expressed in the Nuffield Trust report on emergency general surgery.

Data quoted in relation to general surgery trainee operative experience at completion of training imply that all trainees expressing a “general surgery” specialist interest meet the Joint Committee for Surgical Training minimum operative …
P0692 : PKC/AP-1 signaling drives transcription of interferon-stimulated genes and exerts potent antiviral activity against hepatitis C and E viruses
Authors: W. Wang, Y. Wang, X. Zhou, Y. Yin, L. Xu, D. Sprengers, H.J. Metselaar, Y. Debing, J. Neyts, M.P. Peppelenbosch, Q. Pan
Journal: Journal of Hepatology (2015)
Prognostic versus predictive value of EML4-ALK translocation in metastatic non-small cell lung cancer.
Authors: A. T. Shaw, B. Yeap, D. B. Costa, B. J. Solomon, E. L. Kwak, A. T. Nguyen, K. Bergethon, J. A. Engelman, A. J. Iafrate
Journal: Journal of Clinical Oncology (2010)

7606 Background: The EML4-ALK fusion oncogene represents one of the newest molecular targets in NSCLC. In previous work, we have shown that patients with EML4-ALK-positive NSCLC have distinct clinical and pathologic characteristics. However, the clinical outcome of these patients remains uncertain. Here we present the largest series of EML4-ALK-positive NSCLC patients to date, and the results of a retrospective survival analysis comparing metastatic patients with and without EML4-ALK. Methods: We reviewed the medical records of all NSCLC patients screened for EML4-ALK at MGH. EML4-ALK positivity was established by FISH. EGFR and KRAS mutations were identified either by direct DNA sequencing or by a primer extension-based method (SNaPshot). Clinical characteristics and outcomes were examined according to genotype. Results: Of 477 tumors screened, 43 (9%) harbored ALK rearrangements, 99 (21%) harbored EGFR mutations, and 335 (70%) possessed wild-type ALK and EGFR (WT/WT). Consistent with prior studies, EML4-ALK-positive patients were significantly younger (median age 54 vs 64, p < 0.001) and more likely to be never/light smokers (90% vs 37%, p < 0.001), compared with WT/WT patients. Among patients with metastatic disease, EML4-ALK and EGFR mutant populations showed no difference in overall survival (OS; 1-yr survival 82% vs 81%, p = 0.79); however, both demonstrated a longer OS than WT/WT patients (1-yr survival 66%, p < 0.001). Conclusions: Overall, patients with EML4-ALK-positive NSCLC have a superior outcome compared with WT/WT patients. This superiority may reflect differences in biology, demographic features, or availability of targeted therapies. Our results suggest that EML4-ALK may have prognostic or predictive value for patients with metastatic NSCLC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Gatekeeper Pfizer Biogen Idec, Bristol-Myers Squibb, Daiichi Sankyo, MedImmune, Millennium, Roche, Schering-Plough Novartis, Pfizer
Effect of surface ligand density on cytotoxicity and pharmacokinetic profile of docetaxel loaded liposomes
Authors: Chun Chu, Ping Xu, Haoyue Zhao, Qing Chen, Dawei Chen, Haiyang Hu, Xiuli Zhao, Mingxi Qiao
Journal: Asian Journal of Pharmaceutical Sciences (2016)

Various biotin-modified liposomes incorporated with docetaxel (DTX) were prepared to study the effect of surface biotin density on the pharmacokinetic profile of the liposome. Four types of liposomes such as PEG modified liposome (PDL), 0.5% (mol) biotin modified liposome (0.5BDL), 1% (mol) biotin modified liposome (1BDL) and 2% (mol) biotin modified liposome (2BDL) were prepared using thin film dispersion method. The prepared liposomes were characterized by measuring encapsulation efficiency (EE), particle size, Zeta-potential, physical stability and drug release profiles in vitro. MTT assay was performed to elevate the cytotoxicity of liposomes on MCF-7 cells. In vivo evaluation was further performed to investigate the effect of biotin surface density on the pharmacokinetic profiles. All the prepared liposomes exhibited high encapsulation efficiency, small particle size, narrow particle distribution and sustained release profiles in vitro. In MTT assay, 0.5BDL showed largest tumor cell toxicity, compared with DTX solution. All liposomes containing DTX showed prolonged blood circulation in vivo, and 0.5BDL showed the longest circulation time among the biotin modified liposome. Surface modification of liposome had a negative impact on the circulation of liposomes in the blood, which needs to be considered when designing the ligand mediated targeting delivery systems. A proper amount of biotin liposome with 0.5% molar ratio is expected to produce the best anti-tumor effect.
Imported falciparum malaria in adults: host- and parasite-related factors associated with severity. The French prospective multicenter PALUREA cohort study
Authors: Fabrice Bruneel, Florence Tubach, Jean-Paul Mira, Sandrine Houze, Sebastien Gibot, Marie-Genevieve Huisse, Bruno Megarbane, Christophe Choquet, Philippe Corne, Eric Peytel, Daniel Villers, Christophe Camus, Olivier Bouchaud, Eric Caumes, Pierre-Marie Girard, Fabrice Simon, Antoine Kalloumeh, Carine Roy, Remy Durand, Jacques Le Bras, Sophie Matheron, Michel Wolff
Journal: Intensive Care Medicine (2016)
A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets
Authors: Steven D. Scoville, Bethany L. Mundy-Bosse, Michael H. Zhang, Li Chen, Xiaoli Zhang, Karen A. Keller, Tiffany Hughes, Luxi Chen, Stephanie Cheng, Stephen M. Bergin, Hsiaoyin C. Mao, Susan McClory, Jianhua Yu, William E. Carson, Michael A. Caligiuri, Aharon G. Freud
Journal: Immunity (2016)
Sinus Node and Atrial Arrhythmias
Authors: Roy M. John, Saurabh Kumar
Journal: Circulation (2016)

Although sinus node dysfunction (SND) and atrial arrhythmias frequently coexist and interact, the putative mechanism linking the 2 remain unclear. Although SND is accompanied by atrial myocardial structural changes in the right atrium, atrial fibrillation (AF) is a disease of variable interactions between left atrial triggers and substrate most commonly of left atrial origin. Significant advances have been made in our understanding of the genetic and pathophysiologic mechanism underlying the development and progression of SND and AF. Although some patients manifest SND as a result of electric remodeling induced by periods of AF, others develop progressive atrial structural remodeling that gives rise to both conditions together. The treatment strategy will thus vary according to the predominant disease phenotype. Although catheter ablation will benefit patients with predominantly AF and secondary SND, cardiac pacing may be the mainstay of therapy for patients with predominant fibrotic atrial cardiomyopathy. This contemporary review summarizes current knowledge on sinus node pathophysiology with the broader goal of yielding insights into the complex relationship between sinus node disease and atrial arrhythmias.
R-DHAP Immunochemotherapy Is An Effective Remission-Induction Treatment For CLL Patients With Fludarabine Refractory Disease With Or Without Deletion 17p, Enabling The Majority To Proceed To Allogeneic Stem Cell Transplantation
Authors: Michel Van Gelder, Wendim Ghidey, Martine ED Chamuleau, Jan Cornelissen, Eefke J Petersen, Simon M. G. J. Daenen, Pierre Zachee, Mels Hoogendoorn, Aart Beker, Gert Jan Timmers, Arnon P. Kater, Marinus H.J. Van Oers
Journal: Blood (2013)
First Stage Analysis of Irinotecan, Capecitabine (Xeloda®), and Oxaliplatin (Ixo) As First-Line Treatment of Her2- Metastatic Gastric or Gastroesophageal Junction (Gej) Adenocarcinoma
Authors: J. Spratlin, K. Mulder, C. Brezden-Masley, M.M. Vickers, H. Kennecke, A.L.A. Fields, H. Au, J.A. Maroun
Journal: Annals of Oncology (2014)
Effect of Trypsin on Growth in Several Clones of Tissue Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Pace, Donald M., Aftonomos, Lefkos, Arthur, Walter M.
Journal: JNCI Journal of the National Cancer Institute (1959)

Journal Article Effect of Trypsin on Growth in Several Clones of Tissue Cells Get access Donald M. Pace, Donald M. Pace Institute for Cellular Research, Department of Physiology, University of Nebraska, Lincoln, Nebraska Search for other works by this author on: Oxford Academic PubMed Google Scholar Lefkos Aftonomos, Lefkos Aftonomos Institute for Cellular Research, Department of Physiology, University of Nebraska, Lincoln, Nebraska Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter M. Arthur Walter M. Arthur Institute for Cellular Research, Department of Physiology, University of Nebraska, Lincoln, Nebraska Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 23, Issue 4, October 1959, Pages 655–667, https://doi.org/10.1093/jnci/23.4.655 Published: 01 October 1959 Article history Received: 09 March 1959 Published: 01 October 1959
Abstract 8434: Study of Cardiac Mechanics with a New 3D Echocardiographic Analysis Program
Authors: Jill Panosian, Jiahui Zhang, Helene Houle, Muhammad Ashraf, David J Sahn
Journal: Circulation (2011)

Background: Left ventricular (LV) twist is characterized by apical and basal rotation in opposite directions due to the helical orientation of the myocardial fibers in the normal heart. Methods: We developed a torsion model of pumped fresh pig hearts. A model with a variable-speed motor was used to rotate pig hearts in a water bath. We studied 3 pig hearts; the base of each heart was rotated at 0°, 10°, 15° and 20°, with the apex fixed to avoid translational motion. Stroke volumes (SV) of 40, 60 and 70 ml were used. Three-dimensional images were obtained with a Siemens Acuson SC2000 ultrasound system at maximized frame rates and measured using a new 4D strain and twist analysis program developed by Siemens. Results: Measured apical and basal rotations increased in a pattern similar to the actual rotations. As SVs increased, apical LV rotation also increased accordingly (p &lt; 0.05). Conclusions: Increasing SV in this model correlated with increases in mid level and apical rotation, which can be explained by the helical orientation of myocardial fibers and demonstrated with Siemen's new 4D strain and twist analysis program.