tbuckley/cabot-search huggingface dataset:
Abstract 2429: HIF-1α repressed glycerol-3-phosphate shuttle to reduce oxidative stress in liver cancer
Authors: Shuo ZHANG, Robin Kit-Ho LAI, David Kung-Chun CHIU, Iris Mingjing XU, Aki Pui Wah TSE, Chun-Ming WONG, Irene Oi Lin NG, Carmen Chak Lui WONG
Journal: Cancer Research (2018)

Abstract Liver cancer is the fifth most prevalent and third most common cancer globally. Hepatocellular carcinoma (HCC), arises from hepatocytes, accounts for more than 80% of liver cancer. HCC cells undergo extensive metabolic rewiring to support their uncontrolled growth. HCC cells encounter extremely high level of oxidative stress which is mostly generated in the electron transport chain. Reactive oxygen species (ROS) rapidly accumulate in the electron transport chain (ETC) during hypoxia due to inadequate electron transfer to O2 in the ETC. The glycerol phosphate (GP) shuttle plays an important role to transfer electron source (NADH) from cytoplasm to mitochondria to initiate the ETC. The GP shuttle is mediated by glycerol 3 phosphate dehydrogenase (GPD) which converts dihydroxyacetone phosphate to glycerol 3 phosphate (G3P) through the oxidation of NADH to NAD+. This contributes to ATP production in the mitochondria. Here, we reported that hypoxia-inducible factor 1 (HIF-1) acts as a transcriptional repressor instead of an activator to suppress transcription of an important ETC component of the glycerol phosphate shuttle (GPD) to reduce activity of the GP shuttle, thereby reducing oxidative stress. GPD expression was significantly reduced under hypoxic condition. Surprisingly, knockout, knockdown, or inhibition of HIF-1 restored GPD expression in hypoxia. GPD expression was significantly under-expressed in tumorous as compared to non-tumorous liver tissues in 91 HCC patients of our center by 2.67 fold. TCGA database containing 49 HCC patients echoed with our in-house data. Downregulation of GPD was associated with poor cellular differentiation and overall survival in HCC patients. Stable overexpression of GPD1 in multiple HCC cell lines increased the levels of G3P as well as NAD+, which is crucial to lactate dehydrogenase (LDHA) activity. GPD overexpression altered mitochondrial activity, ROS levels, and suppressed HCC cell proliferation. Taken together, this study showed that the HIF-1 negatively controls key component of the GP shuttle to maximize HCC growth. Citation Format: Shuo ZHANG, Robin Kit-Ho LAI, David Kung-Chun CHIU, Iris Mingjing XU, Aki Pui Wah TSE, Chun-Ming WONG, Irene Oi Lin NG, Carmen Chak Lui WONG. HIF-1α repressed glycerol-3-phosphate shuttle to reduce oxidative stress in liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2429.
Abstract 17014: Prognosis of Patients With Reduced Left Ventricular Function Undergoing Catheter Ablation for Atrial Fibrillation:From Kansai Plus Atrial Fibrillation (KPAF) Registry
Authors: Hajime Fujimoto, Nozomi Toyokawa, Satoshi Sakai, Hiroki Yano, Kazutaka Nogi, Atsushi Iwai, Yukihiro Hashimoto, Megumi Suzuki, Hajime Iwama, Takehito Nakai, Naofumi Doi, Kaeko Hirai, Masaki Naito, Satoshi Shizuta, Takeshi Kimura, Kobori Atsushi, Koichi Inoue, Kazuaki Kaitani, Takeshi Morimoto, Toshiya Kurotobi, Itsuro Morishima, Takeshi Shirayama, Katsunori Okajima, Kazuhiro Satomi, Yukei Higashi, Shigeru Ikeguchi, Hirosuke Yamaji, Yumie Matsui, Minoru Horie, Makoto Ito, Yuko Nakazawa, Takenori Yao, Kengo F. Kusano, Wataru Shimizu, Shiro Kamakura
Journal: Circulation (2017)

Introduction: It has been reported that mortality in atrial fibrillation (AF) patients with reduced left ventricular ejection fraction (EF) is commonly high. However, the efficacy and safety of cat...
Rat Lungworm Infection Associated with Central Nervous System Disease — Eight U.S. States, January 2011–January 2017
Authors: Eugene W. Liu, Brian S. Schwartz, Nicholas D. Hysmith, John P. DeVincenzo, Derek T. Larson, Ryan C. Maves, Debra L. Palazzi, Chelsea Meyer, Haidee T. Custodio, Mariejane M. Braza, Roukaya Al Hammoud, Suchitra Rao, Yvonne Qvarnstrom, Michael J. Yabsley, Richard S. Bradbury, Susan P. Montgomery
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Angiostrongyliasis is caused by infection and migration to the brain of larvae of the parasitic nematode Angiostrongylus cantonensis, or rat lungworm. Adult A. cantonensis reside in the lungs of the definitive wild rodent host, where they produce larvae passed in feces, which are then ingested by snails and slugs (gastropods). Human infection typically occurs when gastropods containing mature larvae are inadvertently ingested by humans. Although human infection often is asymptomatic or involves transient mild symptoms, larval migration to the brain can lead to eosinophilic meningitis, focal neurologic deficits, coma, and death. The majority of cases of human angiostrongyliasis occur in Asia and the Pacific Islands, including Hawaii, but autochthonous and imported cases have been reported in the continental United States (1,2), underscoring the importance of provider recognition to ensure prompt identification and treatment. The epidemiologic and clinical features of 12 angiostrongyliasis cases in the continental United States were analyzed. These cases were identified through A. cantonensis polymerase chain reaction (PCR) testing (3) of cerebrospinal fluid (CSF) submitted to CDC from within the continental United States. Six cases were likely a result of autochthonous transmission in the southern United States. All 12 patients had CSF pleocytosis and eosinophilia, consistent with eosinophilic meningitis. Health care providers need to be aware of the possibility of angiostrongyliasis in patients with eosinophilic meningitis, especially in residents in the southern United States or persons who have traveled outside the continental United States and have a history of ingestion of gastropods or contaminated raw vegetables.
Independent and Incremental Prognostic Value of 201Tl Lung Uptake at Rest in Patients With Severe Postischemic Left Ventricular Dysfunction
Authors: ClaudioMarcassa, MicheleGalli, ClaudioBaroffio, ErmannoEleuteri, RiccardoCampini, PantaleoGiannuzzi
Journal: Circulation (2000)

Background—An elevated 201Tl lung uptake after stress is related to an adverse prognosis. Methods and Results—The functional and prognostic significance of resting 201Tl lung uptake was assessed in 124 consecutive patients with ischemic heart disease and ejection fraction ≤35% undergoing rest-redistribution tomography to evaluate myocardial viability. 201Tl lung uptake significantly correlated with pulmonary wedge pressure (r=0.66; P 0.61 best separated patients with and without events (ROC area under curve 0.82). Event-free survival was significantly lower in patients with L/H >0.61 (P 0.61 (χ2=10.8; P<0.001) and a restrict...
Abstract 61: miR-28 Induces Oxidative Stress via Nrf2 in Right Ventricular Failure but not in Left Ventricular Failure
Authors: SushmaReddy, Dong-QingHu, MingmingZhao, EddieBlay, GiovanniFajardo, DanielBernstein
Journal: Circulation Research (2014)

MicroRNAs (miRs) are crucial regulators of cardiac remodeling in left ventricular hypertrophy and failure (LVH/LVF). However, there is minimal data on their role in right ventricular hypertrophy and failure (RVH/RVF), a risk for patients with congenital heart disease or pulmonary hypertension. Utilizing a murine model of RVH/RVF, we have described RV-specific overexpression of miR-28, not found in LVH/LVF. We used this model to evaluate miR-28 regulation of its downstream target Nrf2, a master regulator of antioxidant defenses, and a potential mechanism of the enhanced susceptibility of the RV to fail under pressure overload. Methods: miR-28 and Nrf2 gene and protein expression and ROS production and antioxidant defenses were assessed at 10d in RVH/RVF (pulmonary artery banding) and LVH/LVF (aortic banding). miR-28 was overexpressed in HEK293 cells and Nrf2 and ROS production assessed. Plasma miRs were also profiled. Results: Mice developed RVH by d4, at which time miR-28 was not increased vs. sham, and R...
Abstract 4181: Simultaneous inhibition of the Wnt/B-catenin and Ras pathways by KY1022 effectively suppresses tumor initiation and progression of colorectal cancer
Authors: Eun Ji Ro, Jeong-Ha Hwang, Yong-Hee Cho, Kang-Yell Choi
Journal: Cancer Research (2018)

Abstract APC (80-90%) and K-Ras (40-50%) mutations frequently occur in human colorectal cancer (CRC) and these mutations cooperatively accelerate tumorigenesis including metastasis. In addition, both B-catenin and Ras levels are highly increased in CRC, especially in metastatic CRC (mCRC). Targeting these signaling pathways may therefore be an ideal strategy for treating mCRC; however, therapeutics targeting both of these pathways have not been developed because the mechanisms regulating these pathways are not well understood. Based on our recent identification of the B-catenin destruction complex-mediated Ras protein stability mechanism, we screened a small-molecule library to identify compounds that destabilize both B-catenin and Ras proteins via inhibition of the Wnt/B-catenin pathway. Among the effective small molecules destabilizing both B-catenin and Ras proteins via inhibition of the Wnt/β-catenin pathway, we characterized KY1022, a small molecule that most effectively inhibits EMT, an initial process of metastasis. As shown by in vitro and in vivo studies using APCMin/+/K-RasG12DLA2 mice, KY1022 effectively suppressed the development of mCRC at an early stage of tumorigenesis. Our results suggest that a small molecular approach degrading both B-catenin and Ras via inhibition of the Wnt/B-catenin signaling would be an ideal strategy for treatment of CRC including mCRC. Citation Format: Eun Ji Ro, Jeong-Ha Hwang, Yong-Hee Cho, Kang-Yell Choi. Simultaneous inhibition of the Wnt/B-catenin and Ras pathways by KY1022 effectively suppresses tumor initiation and progression of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4181.
Sequencing of Circulating Cell-free DNA during Pregnancy
Authors: Diana W. Bianchi, Rossa W.K. Chiu
Journal: New England Journal of Medicine (2018)

Interview with Dr. Diana Bianchi on the use of cell-free DNA testing to screen for fetal chromosome abnormalities. (12:19)Download Advances in DNA sequencing have facilitated a change in the method used to screen for fetal chromosome trisomies. This review describes the basis and development of the method.
Abstract 2068: Single-cell RNA-seq profiling of the transcriptional response to Rb loss in the retinoblastoma cell of origin
Authors: Sunhye Lee, Hardeep P. Singh, Martin Triska, Kevin T. Stachelek, Maxwell M. Bay, Brendan H. Grubbs, Matthew E. Thronton, Haoze Hu, Neil I. Segil, Michael A. Bonaguidi, David Cobrinik
Journal: Cancer Research (2018)

Abstract Retinoblastoma is a rare childhood tumor initiated by biallelic inactivation of the RB1 gene and loss of functional retinoblastoma (Rb) protein. The tumors are thought to originate in cone photoreceptor precursors since Rb knockdown induces cone precursor proliferation and elicits cone-precursor-derived retinoblastoma-like tumors in orthotopic grafts. The identification of the retinoblastoma cell of origin and the authentic initiating mutation presents an opportunity to define the detailed molecular mechanisms controlling malignant transformation of a human cancer. In this project, we seek to define the transcriptional and epigenetic cell state transitions that follow Rb depletion as post-mitotic human cone precursors are induced to re-enter the cell cycle. Prospectively isolated cone precursors were transduced with lentivirus carrying either of three RB1 shRNAs or a SCR control shRNA and then re-isolated by FACS. Single cell RNA-sequencing (scRNA-seq) was performed at multiple time points over 15 days by generating full-length cDNAs corresponding to polyadenylated RNAs followed by sequencing. Among the 572 individual cells that passed quality control, an average of 6.6 million mapped reads and ~21,000 genes (~93,000 transcript isoforms) were detected per transcriptome. In addition, 300 cells per shRNA group were evaluated for genome-wide open chromatin using uATAC-seq at day 0 and 15. Cell transcriptomes were pseudotemporally ordered using “Waterfall” in order to define cellular trajectories and corresponding transcriptomic responses to Rb loss. Using transcriptomic, epigenetic, and network analyses, we define cell state transitions and identify potential mediators of such transitions, that are associated with the initiation of retinoblastoma development. Citation Format: Sunhye Lee, Hardeep P. Singh, Martin Triska, Kevin T. Stachelek, Maxwell M. Bay, Brendan H. Grubbs, Matthew E. Thronton, Haoze Hu, Neil I. Segil, Michael A. Bonaguidi, David Cobrinik. Single-cell RNA-seq profiling of the transcriptional response to Rb loss in the retinoblastoma cell of origin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2068.
Abstract 14561: Intra Left Ventricular Pressure Gradient Obtained by Vector Flow Mapping is Useful to Assess Left Ventricular Suction and Relaxation
Authors: Kazuaki Wakami, Shinro Saiki, Yu Kawada, Keisuke Muto, Junki Yamamoto, Hiroshi Fujita, Toshihiko Goto, Tomonori Sugiura, Hidekatsu Fukuta, Nobuyuki Ohte
Journal: Circulation (2016)

Background: Inertia force of late systolic aortic flow (IF) that is generated by good left ventricular (LV) systolic function enhances LV relaxation. We investigated whether the intra-LV pressure g...
Abstract 285: Osteopontin Deficiency Ameliorates Heart Failure with Preserved Ejection Fraction Pathology by Upregulating Mitochondrial 2-Oxoglutarate Dehydrogenase Like Enzyme
Authors: Keyvan Yousefi, Wen Ding, Lina A Shehadeh
Journal: Circulation Research (2017)

HFpEF is an increasingly prevalent syndrome associated with impaired myocardial energetics, for which no etiologic therapy is available. Osteopontin (OPN) is a matricellular protein that is upregulated in the circulation of HFpEF patients, and reported to induce mitochondrial stress in rodent cardiomyocytes. Here we evaluate the role of circulating OPN in regulating myocardial function in the nephrotic Col4a3-/- mouse model of HFpEF. We performed extensive cardiac, biochemical and mitochondrial analyses of the Col4a3-/- mouse and found a striking HFpEF phenotype. We showed OPN levels were elevated in Col4a3-/- mice (FC=2.1, n=6; p<.01). Col4a3-/- mice were hypertensive, had diastolic dysfunction, myocyte hypertrophy and interstitial fibrosis - all of which were ameliorated in Col4a3-/-OPN-/- mice (n=5-20; p<.05). Col4a3-/- hearts had dysmorphic mitochondria (EM), lowered antioxidant capacity as a 50% reduction in GSH/GSSG ratio (n=6; p<.05) and lower protein levels of mitochondrial respiratory complexes I...
Interleukin-10 Expression Mediated by an Adeno-Associated Virus Vector Prevents Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats
Authors: TakayukiIto, TakashiOkada, HiroshiMiyashita, TatsuyaNomoto, MutsukoNonaka-Sarukawa, RyosukeUchibori, YoshikazuMaeda, MasashiUrabe, HiroakiMizukami, AkihiroKume, MasafumiTakahashi, UichiIkeda, KazuyukiShimada, KeiyaOzawa
Journal: Circulation Research (2007)

Pulmonary arterial hypertension (PAH) is a fatal disease associated with inflammation and pathological remodeling of the pulmonary artery (PA). Interleukin (IL)-10 is a pleiotropic antiinflammatory cytokine with vasculoprotective properties. Here, we report the preventive effects of IL-10 on monocrotaline-induced PAH. Three-week-old Wistar rats were intramuscularly injected with an adeno-associated virus serotype 1 vector expressing IL-10, followed by monocrotaline injection at 7 weeks old. IL-10 transduction significantly improved survival rates of the PAH rats 8 weeks after monocrotaline administration compared with control gene transduction (75% versus 0%, P<0.01). IL-10 also significantly reduced mean PA pressure (22.8±1.5 versus 29.7±2.8 mm Hg, P<0.05), a weight ratio of right ventricle to left ventricle plus septum (0.35±0.04 versus 0.42±0.05, P<0.05), and percent medial thickness of the PA (12.9±0.3% versus 21.4±0.4%, P<0.01) compared with controls. IL-10 significantly reduced macrophage infiltrati...
Sprint Fidelis Lead Fractures in Patients With Cardiac Resynchronization Therapy Devices
Authors: RatikaParkash, BernardThibault, LarrySterns, JohnSapp, AndrewKrahn, MarioTalajic, MarilynnLuce, ElizabethYetisir, PatriciaTheoret-Patrick, GeorgeWells, AnthonyTang
Journal: Circulation (2012)

Background—Using data from the Resynchronization/Defibrillation for Ambulatory Heart Failure (RAFT) study, we examined whether Fidelis lead failure was more common in patients with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (ICD-CRT) than in patients with an ICD only. Methods and Results—All cases of patients who had a right ventricular defibrillation lead revision in the RAFT study were adjudicated for the presence of lead fracture. Criteria for fracture were at least 2 of the following: (1) Impedance rise (>50% or >500 Ω in 1 week), (2) short interval count >10 times per day or 300 times per month, or (3) inappropriate shock caused by noise, verified by stored electrogram. A total of 1798 patients were enrolled into the RAFT study, with a mean follow-up of 40±20 months. There were 818 patients (45.5%) who received a Fidelis lead at the original implantation, 405 with an ICD only and 413 with an ICD-CRT. There were 47 confirmed defibrillation lead fractures; 45 w...
Local Delivery of Imatinib Mesylate (STI571)-Incorporated Nanoparticle Ex Vivo Suppresses Vein Graft Neointima Formation
Authors: SatoshiKimura, KensukeEgashira, KakuNakano, EikoIwata, MihoMiyagawa, HiroyukiTsujimoto, KaoriHara, YoshiakiKawashima, RyujiTominaga, KenjiSunagawa
Journal: Circulation (2008)

Background— Clinical outcome of surgical revascularization using autologous vein graft is limited by vein graft failure attributable to neointima formation. Platelet-derived growth factor (PDGF) plays a central role in the pathogenesis of vein graft failure. Therefore, we hypothesized that nanoparticle (NP)-mediated drug delivery system of PDGF-receptor (PDGF-R) tyrosine kinase inhibitor (imatinib mesylate: STI571) could be an innovative therapeutic strategy. Methods and Results— Uptake of STI571-NP normalized PDGF-induced cell proliferation and migration. Excised rabbit jugular vein was treated ex vivo with PBS, STI571 only, FITC-NP, or STI571-NP, then interposed back into the carotid artery position. NP was detected in many cells in the neointima and media at 7 and 28 days after grafting. Significant neointima was formed 28 days after grafting in the PBS group; this neointima formation was suppressed in the STI571-NP group. STI571-NP treatment inhibited cell proliferation and phosphorylation of the PDGF...
Climate change and sleep: A systematic review of the literature and conceptual framework
Authors: Daniel I. Rifkin, Michael W. Long, Melissa J. Perry
Journal: Sleep Medicine Reviews (2018)

From disaster related stress causing insomnia, to poor air quality causing sleep related breathing problems, climate change poses a potentially serious threat to human sleep. We conducted a systematic review evaluating the relationship between climate change and human sleep in the PubMed, Scopus, and Cochrane databases from 1980 through 2017 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria included epidemiologic studies published in English that reported observational population data on human sleep and its relationship to climate change, temperature, extreme weather events and climate related disasters (e.g. hurricanes, floods, and wildfires). We excluded non-human studies, laboratory or experimental physiology studies, commentaries or letters, review articles, and articles on wind turbines. Using a systematic search strategy, 16 studies met the inclusion criteria. Six studies related to the effects of rising temperature, seven studies related to extreme weather events, and three studies related to floods or wildfires. Diminished total sleep times and sleep disruption were most commonly reported, especially among the most vulnerable populations including the elderly and low-income; however, the body of evidence was limited and further well-designed human studies are clearly needed. We present a conceptual framework for identifying the emerging threats of climate change and understanding their respective effects on human sleep.
Abstract 252: Prostate carcinogenesis inhibition through AKT-PKCα signaling pathway by diosmetin
Authors: Rebecca Pakradooni, Ahmad Khalifa, Ilaha Isali, Sanjeev Shukla
Journal: Cancer Research (2018)

Abstract Mammalian target of rapamycin (mTOR) integrates nutrient and mitogen signals to regulate cell growth (increased cell mass and cell size) and cell division. mTOR protein kinase have two different complexes; complex-I contains major component raptor, whereas complex II (insensitive to rapamycin), has major component rictor. Rictor plays a critical role in AKT (Ser-473 phosphorylation), which facilitates phosphorylation of AKT on Thr-308 by PDK1 for full activation. When we genetically disrupted Rictor, it decreased AKT phosphorylation (Ser-473) and impaired PKCα (Ser-657) expressions. Growth factors viz., IGF-1 and IL-6 are the major player in prostate cancers, these increases Rictor expression. We need to have an agent that can modulate kinase activity of AKT and PKCα to inhibit prostate cancer cell growth. Diosmetin (5, 7-Trihydroxy-4′-methoxyflavone) could be such an agent. Diosmetin, a natural flavone present in plant legumes, has anti-mutagenic and anti-allergic properties. Diosmetin inhibited IGF-1 and IL-6 induced rictor expression in LNCaP and PC-3 prostate cancer cells. Diosmetin dose response treatment to these cells inhibited cell growth and induced apoptosis with no significant growth inhibition in normal prostate epithelial cells (RWPE1). Diosmetin treatment to prostate cancer cells modulated cell survival machinery by down regulating key molecules viz., c-Myc, Survivin and XIAP (X-Linked Inhibitor of Apoptosis). Similarly diosmetin (20 and 50μg/animal/day) feeding to nude mice models, which were orthotopically implanted with luciferase tag PC-3 cells in ventral prostate represented significant decrease in tumor volume than control mice. Diosmetin fed tumor bearing mice reduced phosphorylation of Rictor, (Thr-1135), AKT (Ser-473) and PKCα (Ser-657) expressions to inhibit tumor growth significantly. Moreover, luciferase activity of implanted tumor decreased after diosmetin dose response feeding than control mice. Additionally bone radiographic images suggested that diosmetin treatment inhibited homing of PC-3 cells in the bone. These effects were associated with decrease in cyclin D1 expression and their activating partner, cyclin-dependent kinase (cdk) 2 and 4 with concomitant upregulation of p27/KIP1. Further diosmetin treatment induced apoptosis which was evident by increased expression of cleaved caspase-3. We are documenting these evidences for the first time in animal model system that diosmetin acts against potential molecular targets to alter cellular events to elicit anticancer effects in prostate cancer. Citation Format: Rebecca Pakradooni, Ahmad Khalifa, Ilaha Isali, Sanjeev Shukla. Prostate carcinogenesis inhibition through AKT-PKCα signaling pathway by diosmetin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 252.