tbuckley/cabot-search huggingface dataset:
Abstract 16828: Genetic Deletion of Integrin Alpha1Beta1 Protect Against Aortic Rupture by Modulating CCl21 in Angiotensin Il-induced Abdominal Aortic Aneurysm
Authors: Toru Miyoshi, Tomoko Yonezawa, Kazufumi Nakamura, Masashi Yoshida, Satoshi Akagi, Hiroshi Ito
Journal: Circulation (2016)

Introduction:  Abdominal aortic aneurysm (AAA) is a common disease characterized by chronic inflammation and degradation of extracellular matrix. Integrin alpha1beta1 is a major collagen receptor that is expressed on activated monocytes and involved as well as smooth muscle cells and fibroblasts. The homeostatic chemokines, CCL19 and CCL21 and their receptor CCR7, have recently been linked to atherogenesis.   Purpose:  We investigated the role of integrin alpha1beta1 using murine angiotensin II-induced AAA model in which alpha1 integrin was deficient.   Methods:  Apolipoprotein E -/- mice that were either alpha1 +/+ or alpha1 -/-, were infused with either saline or angiotensin II (1000 ng/kg per minute) for 28 days via mini-osmotic pumps.   Results:  Deficiency in integrin aplha1 tended to reduce the incidence of AAA (69% [alpha1 +/+] and 37% [alpha1 -/-], p= 0.12), but external diameters did not differ between the two groups; 1.6 ± 0.3 mm [alpha1 +/+] vs. 1.7 ± 0.7 mm [alpha1 -/-], p=NS, respectively). Interestingly, Kaplan-Meir survival curves revealed that the alpha1 -/- mice (n=36) were decreased in death due to aortic rupture compared to the alpha1 +/+ mice (n=36) (p=0.04). Zymography also showed the decrease in MMP-9 activity in aortae at day 7 in alpha1 -/- mice. Quantitative real time PCR showed that the decrease in TNF-alpha and the increase in collagen 1 expression in aortae at day 7 in alpha1 -/- mice. Of note, the increase in CCL21 at day 7 was significantly reduced in the alpha1-/- mice. In vitro experiments, CCL21 induced MMP9 from vascular smooth muscle cells.   Conclusions:  Integrin alpha1beta1 is involved in susceptibility to aortic rupture in angiotensin II-induced AAA by the suppression of inflammation and the augmentation of collagen synthesis.
The Role of FDG PET in Diabetic Myonecrosis
Authors: Guillaume Chaussé, Gad Abikhzer
Journal: Clinical Nuclear Medicine (2017)

A 66-year-old man with poorly controlled type 2 diabetes was admitted for acute bilateral calf pain in the context of coronary artery disease, chronic renal failure, and peripheral neuropathy. Lower-extremity Doppler ultrasound excluded deep vein thrombosis. FDG-PET was performed to exclude a suspected infection because of elevated white blood cells and inflammatory markers but normal creatinine kinase levels. PET scan demonstrated intense bilateral calf muscle and left thigh muscle uptake, which in combination with the patient's history was consistent with diabetic myonecrosis, a rare end-stage complication of diabetes. The patient was managed conservatively, and pain resolved following a typical self-limited course.
Genome-Wide Association Study Identifies a New Locus at 7q21.13 Associated with Hepatitis B Virus–Related Hepatocellular Carcinoma
Authors: Yuanfeng Li, Yun Zhai, Qingfeng Song, Haitao Zhang, Pengbo Cao, Jie Ping, Xinyi Liu, Bingqian Guo, Guanjun Liu, Jin Song, Ying Zhang, Aiqing Yang, Hongbo Yan, Liang Yang, Ying Cui, Yilong Ma, Jinliang Xing, Xizhong Shen, Taotao Liu, Hongxin Zhang, Jiaze An, Jin-Xin Bei, Weihua Jia, Longli Kang, Lijun Liu, Dongya Yuan, Zhibin Hu, Hongbing Shen, Lei Lu, Xuan Wang, Hua Li, Fuchu He, Hongxing Zhang, Gangqiao Zhou
Journal: Clinical Cancer Research (2017)

Purpose: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In China, chronic hepatitis B virus (HBV) infection remains the major risk factor for HCC. In this study, we performed a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci contributing to susceptibility to HBV-related HCC.Experimental Design: GWAS scan is performed in a collection of 205 HBV-related HCC trios (each trio includes an affected proband and his/her both parents), and 355 chronic HBV carriers with HCC (cases) and 360 chronic HBV carriers without HCC (controls), followed by two rounds of replication studies totally consisting of 3,796 cases and 2,544 controls.Results: We identified a novel association signal within the CDK14 gene at 7q21.13 (index rs10272859, OR = 1.28, P = 9.46 × 10-10). Furthermore, we observed that the at-risk rs10272859[G] allele was significantly associated with higher mRNA expression levels of CDK14 in liver tissues. Chromosome conformation capture assays in liver cells confirmed that a physical interaction exists between the promoter region of CDK14 and the risk-associated SNPs in strong linkage disequilibrium with the index rs10272859 at 7q21.13. This index rs10272859 also showed significant association with the survival of HCC patients.Conclusions: Our findings highlight a novel locus at 7q21.13 conferring both susceptibility and prognosis to HBV-related HCC, and suggest the CDK14 gene to be the functional target of the 7q21.13 locus. Clin Cancer Res; 24(4); 906-15. ©2017 AACR.
Protein Kinase Cδ modulates migration and invasiveness of prostate carcinoma cells
Authors: Sourabh Kharait, Rajiv Dhir, Douglas Lauffenburger, Alan Wells
Journal: Cancer Research (2006)

1808   Background: Transformation of tumor cells into an invasive phenotype is driven by growth factor-induced motility. Overexpression of certain growth factor receptors including the EGF receptor (EGFR) is commonly noted in such progressive tumors. However, the intracellular molecular switches are only now being identified. The Protein Kinase C (PKC) family has been implicated in a variety of tumors including those of prostate and breast due to their role in cell proliferation, migration and invasion. The novel δ isoform of Protein Kinase C (PKCδ) has been shown to regulate EGFR-mediated fibroblast transcellular contractility during motility. We hypothesized that PKCδ mediates motility of prostate cancer cells via regulation of myosin light chain filament activation and that targeting contractility of tumor cells by abrogating PKCδ, can be explored as a novel therapeutic avenue in limiting prostate cancer invasiveness. Methods: We utilized two invasive prostate tumor cell lines, DU145 overexpressing wildtype human EGFR cells (DU145 WT) and PC3 cells, to conduct our studies. Using pharmacological (rottlerin) and molecular biological (RNAi) approaches, we abrogated PKCδ activity and/or decreased its protein levels in the cells. Under these conditions we assessed the migratory and invasive potential of cells  in vitro.  In addition, we surveyed a panel of human prostate tumors for level of activation and location of the phosphorylated form of PKCδ. Results & Discussion: We found that PKCδ is directly activated downstream of EGFR signaling in both prostate cancer lines. Rottlerin and siRNA to PKCδ also significantly decreased EGF induced migration and  in vitro  invasion through Matrigel of both DU145 WT and PC3 cells. PKCδ inhibition also decreased activation status of the regulatory myosin light chain (MLC) filament. Using immunoblotting of prostate tissue lysates, we showed that total PKCδ protein levels are higher in prostate tumor specimens as compared to normal prostate specimens. These findings were identical to that of overexpression of PKCδ in prostate cancer cell lines (PC3 and DU145 WT) as compared to normal prostate epithelial cells. In addition, immunohistochemical staining of prostate cancer tissue specimens for activated (phosphorylated) PKCδ showed statistically higher levels in cancerous tissue as compared to benign normal tissue or normal tissue adjacent to the tumor. Activated PKCδ was seen both at cytoplasmic as well as nuclear locale in prostate cancer cells but not in normal prostate cells (in tissue sections). Thus PKCδ is a crucial mediator of prostate tumor cell motility and invasiveness and newer therapeutic approaches that abrogate PKCδ activity can be explored as therapeutic avenues in prostate cancer therapy.
Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function
Authors: Guoying Yu, Argyris Tzouvelekis, Rong Wang, Jose D Herazo-Maya, Gabriel H Ibarra, Anup Srivastava, Joao Pedro Werneck de Castro, Giuseppe DeIuliis, Farida Ahangari, Tony Woolard, Nachelle Aurelien, Rafael Arrojo e Drigo, Ye Gan, Morven Graham, Xinran Liu, Robert J Homer, Thomas S Scanlan, Praveen Mannam, Patty J Lee, Erica L Herzog, Antonio C Bianco, Naftali Kaminski
Journal: Nature Medicine (2017)
A novel nitroreductase-enhanced MRI contrast agent and its potential application in bacterial imaging
Authors: Yun Liu, Leilei Zhang, Marc Nazare, Qingqiang Yao, Hai-Yu Hu
Journal: Acta Pharmaceutica Sinica B (2017)

Nitroreductases (NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide (NADH) as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study,
Non-isothermal dehydration kinetic study of aspartame hemihydrate using DSC, TGA and DSC-FTIR microspectroscopy
Authors: Wei-hsien Hsieh, Wen-ting Cheng, Ling-chun Chen, Shan-yang Lin
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Three thermal analytical techniques such as differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) using five heating rates, and DSC-Fourier Transform Infrared (DSC-FTIR) microspectroscopy using one heating rate, were used to determine the thermal characteristics and the dehydration process of aspartame (APM) hemihydrate in the solid state. The intramolecular cyclization process of APM anhydrate was also examined. One exothermic and four endothermic peaks were observed in the DSC thermogram of APM hemihydrate, in which the exothermic peak was due to the crystallization of some amorphous APM caused by dehydration process from hemihydrate to anhydride. While four endothermic peaks were corresponded to the evaporation of absorbed water, the dehydration of hemihydrate, the diketopiperazines (DKP) formation via intramolecular cyclization, and the melting of DKP, respectively. The weight loss measured in TGA curve of APM hemihydrate was associated with these endothermic peaks in the DSC thermogram. According to the Flynn–Wall–Ozawa (FWO) model, the activation energy of dehydration process within 100–150 °C was about 218 ± 11 kJ/mol determined by TGA technique. Both the dehydration and DKP formation processes for solid-state APM hemihydrate were markedly evidenced from the thermal-responsive changes in several specific FTIR bands by a single-step DSC-FTIR microspectroscopy.
Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women
Authors: Gerald Gartlehner, Sheila V. Patel, Cynthia Feltner, Rachel Palmieri Weber, Rachel Long, Kelly Mullican, Erin Boland, Linda Lux, Meera Viswanathan
Journal: JAMA (2017)

<h3>Importance</h3> Postmenopausal status coincides with increased risks for chronic conditions such as heart disease, osteoporosis, cognitive impairment, or some types of cancers. Previously, hormone therapy was used for the primary prevention of these chronic conditions. <h3>Objective</h3> To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. <h3>Data Sources</h3> MEDLINE, Cochrane Library, EMBASE, and trial registries from June 1, 2011, through August 1, 2016. Surveillance for new evidence in targeted publications was conducted through July 1, 2017. <h3>Study Selection</h3> English-language randomized clinical trials reporting health outcomes. <h3>Data Extraction and Synthesis</h3> Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available. <h3>Main Outcomes and Measures</h3> Beneficial or harmful changes in risks for various chronic conditions. <h3>Results</h3> Eighteen trials (n = 40 058; range, 142-16 608; mean age, 53-79 years) were included. Women using estrogen-only therapy compared with placebo had significantly lower risks, per 10 000 person-years, for diabetes (−19 cases [95% CI, −34 to −3]) and fractures (−53 cases [95% CI, −69 to −39]). Risks were statistically significantly increased, per 10 000 person-years, for gallbladder disease (30 more cases [95% CI, 16 to 48]), stroke (11 more cases [95% CI, 2 to 23]), venous thromboembolism (11 more cases [95% CI, 3 to 22]), and urinary incontinence (1261 more cases [95% CI, 880 to 1689]). Women using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 person-years, for colorectal cancer (−6 cases [95% CI, −9 to −1]), diabetes (−14 cases [95% CI, −24 to −3), and fractures (−44 cases [95% CI, −71 to −13). Risks, per 10 000 person-years, were significantly increased for invasive breast cancer (9 more cases [95% CI, 1 to 19]), probable dementia (22 more cases [95% CI, 4 to 53]), gallbladder disease (21 more cases [95% CI, 10 to 34]), stroke (9 more cases [95% CI, 2 to 19]), urinary incontinence (876 more cases [95% CI, 606 to 1168]), and venous thromboembolism (21 more cases [95% CI, 12 to 33]). <h3>Conclusions and Relevance</h3> Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms. The available evidence regarding benefits and harms of early initiation of hormone therapy is inconclusive.
Photoporation Using Carbon Nanotubes for Intracellular Delivery of Molecules and Its Relationship to Photoacoustic Pressure
Authors: Stefany Y. Holguin, Michael D. Gray, Princeton Joseph, Naresh N. Thadhani, Mark R. Prausnitz
Journal: Advanced Healthcare Materials (2017)

Exposure of carbon-black (CB) nanoparticles to near-infrared nanosecond-pulsed laser energy can cause efficient intracellular delivery of molecules by photoporation. Here, cellular bioeffects of multi-walled carbon nanotubes (MWCNTs) and single-walled carbon nanotubes (SWCNTs) are compared to those of CB nanoparticles. In DU145 prostate-cancer cells, photoporation using CB nanoparticles transitions from (i) cells with molecular uptake to (ii) nonviable cells to (iii) fragmented cells with increasing laser fluence, as seen previously. In contrast, photoporation with MWCNTs causes uptake and, at higher fluence, fragmentation, but does not generate nonviable cells, and SWCNTs show little evidence of bioeffects, except at extreme laser conditions, which generate nonviable cells and fragmentation, but no significant uptake. These different behaviors cannot be explained by photoacoustic pressure output from the particles. All particle types emit a single, ≈100 ns, mostly positive-pressure pulse that increases in amplitude with laser fluence. Different particle types emit different peak pressures, which are highest for SWCNTs, followed by CB nanoparticles and then MWCNTs, which does not correlate with cellular bioeffects between different particle types. This study concludes that cellular bioeffects depend strongly on the type of carbon nanoparticle used during photoporation and that photoacoustic pressure is unlikely to play a direct mechanistic role in the observed bioeffects.
Resistance analysis in patients with genotype 1–6 HCV infection treated with sofosbuvir/velpatasvir in the phase III studies
Authors: Christophe Hezode, Nancy Reau, Evguenia S. Svarovskaia, Brian P. Doehle, Ragavi Shanmugam, Hadas Dvory-Sobol, Charlotte Hedskog, John McNally, Anu Osinusi, Diana M. Brainard, Michael D. Miller, Hongmei Mo, Stuart K. Roberts, Jacqueline G. O'Leary, Stephen D. Shafran, Stefan Zeuzem
Journal: Journal of Hepatology (2017)
TNF-α–induced protein 3 (TNFAIP3) /A20 acts as a master switch in TNF-α blockade–driven IL-17A expression
Authors: Paulo C.M. Urbano, Raúl Aguirre-Gamboa, Angel Ashikov, Bennie van Heeswijk, Anja Krippner-Heidenreich, Henk Tijssen, Yang Li, Valderilio F. Azevedo, Lisa J.T. Smits, Frank Hoentjen, Irma Joosten, Hans J.P.M. Koenen
Journal: Journal of Allergy and Clinical Immunology (2017)
Activity of Brucea javanica oil emulsion against gastric ulcers in rodents
Authors: Qian Li, Linglong Yang, Linlin Fan, Chen Liang, Qiujv Wang, Huimin Wen, Jinwei Dai, Xin Li, Yuyang Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2017)

The present study aims to investigate the gastroprotective effect of Brucea javanica oil emulsion (BJOE) in animals. Gastroprotective potential of BJOE was studied on absolute ethanol, aspirin, reserpine and restraint plus water immersion-induced gastric ulcers in mice as well as glacial acetic acid (GAA) and pyloric ligation (PL)-induced gastric ulcers in rats. Except for ulcer scores, total acidity as well as pepsin activity as for the PL-induced gastric ulcer model and ulcer incidence as for the GAA-induced gastric ulcer model were also determined. Histopathological evaluation as for aspirin, reserpine, PL-induced models was conducted. Results showed that BJOE significantly (P < 0.05) reduced ulcer index in the mouse and rat models in a dose-dependent manner. It had significant (P < 0.05) suppressive effect on total activity of gastric juice as well in PL-induced model. Histopathological examination for the stomach samples confirmed the findings in the aspirin, reserpine or PL-induced gastric lesion models, which showed relatively complete mucosa structure and less inflammation. It is concluded that BJOE could be effective on gastric ulcer in rodents and its gastroprotective activity might be related to antioxidant, anti-inflammatory ability and promote gastric mucus secreted. The results may provide beneficial basis for increasing BJOE's clinical indication in future.
Asthma control and action plans
Authors: Andrew Kouri, Louis-Philippe Boulet, Alan Kaplan, Samir Gupta
Journal: European Respiratory Journal (2017)

Arguments over semantics will not advance our common goal of improving AAP uptake <http://ow.ly/rSaq30fRila> We would like to thank I. Amirav and M.T. Newhouse for their correspondence in response to our recent paper, "An evidence-based, point-of-care tool to guide completion of asthma action plans in practice" [1]. They raise an important issue surrounding confusion between the concepts of poor baseline asthma control and acute changes in symptoms that merit activation of the "yellow zone" of the asthma action plan (AAP). Although, contrary to their contention, this discussion does not affect the objective or outcome of our analysis, which was to provide a practical, evidence-based guide to populating the AAP yellow zone, it merits further discussion.
Prohibitin 2 physically interacts with E2F1 and represses transcription
Authors: Smitha Pillai, Srikumar Chellappan
Journal: Cancer Research (2007)

1241   The two strucurally related proteins prohibitin 1 and prohibitin 2 are involved in multiple cellular functions such as cell cycle regulation, transmembrane signal transduction and cellular senescence. Earlier studies from our lab had shown that prohibitin 1, a potential tumor suppressor protein, binds to Rb and E2F transcription factors and represses E2F1-mediated trannscription via recruitment of transcriptional co-repressors such as N-CoR and histone deacetylase 1 (HDAC1). Prohibitin 2 (PHB2), also known as repressor of estrogen receptor activity (REA), shows extensive homology to prohibitin 1 and has been shown to interact with and inhibit the transcriptional activity of estrogen receptor, MyoD and MEF2. We now present evidence that S-35 labeled Prohibitin 2 can physically interact with Rb and E2F1  in vitro  as seen in GST-binding assays. Furthermore, this interaction was confirmed  in vivo  by immunoprecipitation-western blot analysis in MCF-7 breast cancer cells. Phb2 could also repress E2F1 mediated transcription in transient transfection assays in MCF-7 cells. Attempts were made to determine the region of prohibitin 2 that is involved in transcriptional repression. Toward this purpose deletion mutants of prohibitin 2 expressing amino acid residues 1-171, 170-299 and 226-299 were made. Transient transfection assays were conducted using an E2CAT reporter, which had an E2F1-responsive promoter element from the adenovirus E2 gene fused to a CAT gene. Cotransfection of E2F1 induced this promoter, while full length prohibitin 2 as well as the Phb2 deletion mutant construct containing residues 170-299 effectively repressed E2F1 mediated transcription. However, the prohibitin 2 construct that spanned residues 1-171 and 226-299 did not show transcriptional repression indicating that residues 170-226 are probably involved in transcriptional repression. These results indicate that prohibitin 2 is a novel regulator of E2F1 function and might channel specific signaling cascades to the cell cycle regulatory machinery.
The small molecule CLP257 does not modify activity of the K+–Cl− co-transporter KCC2 but does potentiate GABAA receptor activity
Authors: Ross A Cardarelli, Karen Jones, Lucie I Pisella, Heike J Wobst, Lisa J McWilliams, Paul M Sharpe, Matthew P Burnham, David J Baker, Ilona Chudotvorova, Justine Guyot, Liliya Silayeva, Danielle H Morrow, Niek Dekker, Stephen Zicha, Paul A Davies, Jörg Holenz, Mark E Duggan, John Dunlop, Robert J Mather, Qi Wang, Igor Medina, Nicholas J Brandon, Tarek Z Deeb, Stephen J Moss
Journal: Nature Medicine (2017)
Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000‐patient 15‐year experience
Authors: Riad Salem, Ahmed Gabr, Ahsun Riaz, Ronald Mora, Rehan Ali, Michael Abecassis, Ryan Hickey, Laura Kulik, Daniel Ganger, Steven Flamm, Rohi Atassi, Bassel Atassi, Kent Sato, Al B. Benson, Mary F. Mulcahy, Nadine Abouchaleh, Ali Al Asadi, Kush Desai, Bartley Thornburg, Michael Vouche, Ali Habib, Juan Caicedo, Frank H. Miller, Vahid Yaghmai, Joseph R. Kallini, Samdeep Mouli, Robert J. Lewandowski
Journal: Hepatology (2017)

Yttrium‐90 transarterial radioembolization (TARE) is a locoregional therapy (LRT) for hepatocellular carcinoma (HCC). In this study, we present overall survival (OS) outcomes in a 1,000‐patient cohort acquired over a 15‐year period. Between December 1, 2003 and March 31, 2017, 1,000 patients with HCC were treated with TARE as part of a prospective cohort study. A comprehensive review of toxicity and survival outcomes was performed. Outcomes were stratified by baseline Child‐Pugh (CP) class, United Network for Organ Sharing (UNOS), and Barcelona Clinic Liver Cancer (BCLC) staging systems. Albumin and bilirubin laboratory toxicities were compared to baseline. OS outcomes were reported using censoring and intention‐to‐treat methodologies. All treatments were outpatient, with a median one treatment per patient. Five hundred six (51%) were CP A, 450 (45%) CP B, and 44 (4%) CP C. Two hundred sixty‐three (26%) patients were BCLC A, 152 (15%) B, 541 (54%) C, and 44 (4%) D. Three hundred sixty‐eight (37%) were UNOS T1/T2, 169 (17%) T3, 147 (15%) T4a, 223 (22%) T4b, and 93 (9%) N/M. In CP A patients, censored OS for BCLC A was 47.3 (confidence interval [CI], 39.5‐80.3) months, BCLC B 25.0 (CI, 17.3‐30.5) months, and BCLC C 15.0 (CI, 13.8‐17.7) months. In CP B patients, censored OS for BCLC A was 27 (CI, 21‐30.2) months, BCLC B 15.0 (CI, 12.3‐19.0) months, and BCLC C 8.0 (CI, 6.8‐9.5) months. Forty‐nine (5%) and 110 (11%) patients developed grade 3/4 albumin and bilirubin toxicities, respectively. Conclusion: Based on our experience with 1,000 patients over 15 years, we have made a decision to adopt TARE as the first‐line transarterial LRT for patients with HCC. Our decision was informed by prospective data and incrementally reported demonstrating outcomes stratified by BCLC, applied as either neoadjuvant or definitive treatment. (H epatology 2017).