tbuckley/cabot-search huggingface dataset:
Abstract 1773: Phosphodiesterase 10A: A novel target for selective inhibition of colon tumor cell growth and Wnt/β-catenin signaling
Authors: Nan Li, Kevin Lee, Yaguang Xi, Bing Zhu, Bernary D. Gary, Verónica Ramírez-Alcántara, Evrim Gurpinar, Joshua C. Canzoneri, Alexandra Fajardo, Sara Sigler, John T. Piazza, Xi Chen, Joel Andrews, Wenyan Lu, Yonghe Li, Suzanne Russo, Larry Yet, Adam B. Keeton, William E. Grizzle, Gary A. Piazza
Journal: Cancer Research (2014)

Abstract The cyclic nucleotide phosphodiesterase10A (PDE10) has been studied as a therapeutic target for certain psychiatric and neurological conditions, although a potential role in tumorigenesis has not been reported. Here we report that PDE10 is elevated in human colon tumor cell lines compared with normal colonocytes. Similarly, PDE10 is elevated in colon tumors from human clinical specimens as well as intestinal tumors from the ApcMin/+ mouse model compared with non-involved tissue or normal intestinal mucosa, respectively. An isozyme and tumor-selective role of PDE10 was evident by the ability of specific inhibitors and siRNA knockdown to suppress colon tumor cell growth without significantly affecting the growth of normal colonocytes. Stable knockdown of PDE10 by shRNA also inhibits colony formation and increases doubling time of colon tumor cells. Inhibition of PDE10 results in the selective activation of cGMP/PKG signaling in colon tumor cells to suppress β-catenin levels and T-cell factor (TCF) transcriptional activity. Conversely, ectopic expression of PDE10 in normal and precancerous colonocytes increases proliferation and activates TCF transcriptional activity. These observations demonstrate that PDE10 is essential for colon tumor cell growth and suggest that inhibitors may have therapeutic potential for the treatment or prevention of colorectal cancer. Citation Format: Nan Li, Kevin Lee, Yaguang Xi, Bing Zhu, Bernary D. Gary, Verónica Ramírez-Alcántara, Evrim Gurpinar, Joshua C. Canzoneri, Alexandra Fajardo, Sara Sigler, John T. Piazza, Xi Chen, Joel Andrews, Wenyan Lu, Yonghe Li, Suzanne Russo, Larry Yet, Adam B. Keeton, William E. Grizzle, Gary A. Piazza. Phosphodiesterase 10A: A novel target for selective inhibition of colon tumor cell growth and Wnt/β-catenin signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1773. doi:10.1158/1538-7445.AM2014-1773
Hypoxia regulates the production and activity of glucose transporter-1 and indoleamine 2,3-dioxygenase in monocyte-derived endothelial-like cells: possible relevance to infantile haemangioma pathogenesis
Authors: A. Herbert, H. Ng, W. Jessup, M. Kockx, S. Cartland, S.R. Thomas, P.J. Hogg, O. Wargon
Journal: British Journal of Dermatology (2010)

Journal Article Hypoxia regulates the production and activity of glucose transporter‐1 and indoleamine 2,3‐dioxygenase in monocyte‐derived endothelial‐like cells: possible relevance to infantile haemangioma pathogenesis Get access A. Herbert, A. Herbert Lowy Cancer Research Centre and Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia Search for other works by this author on: Oxford Academic Google Scholar H. Ng, H. Ng Lowy Cancer Research Centre and Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, AustraliaSydney Children's Hospital, Randwick, NSW 2031, Australia Search for other works by this author on: Oxford Academic Google Scholar W. Jessup, W. Jessup Centre for Vascular Research, University of New South Wales, Sydney, NSW 2052, Australia Search for other works by this author on: Oxford Academic Google Scholar M. Kockx, M. Kockx Centre for Vascular Research, University of New South Wales, Sydney, NSW 2052, Australia Search for other works by this author on: Oxford Academic Google Scholar S. Cartland, S. Cartland Centre for Vascular Research, University of New South Wales, Sydney, NSW 2052, Australia Search for other works by this author on: Oxford Academic Google Scholar S.R. Thomas, S.R. Thomas Centre for Vascular Research, University of New South Wales, Sydney, NSW 2052, Australia Search for other works by this author on: Oxford Academic Google Scholar P.J. Hogg, P.J. Hogg Lowy Cancer Research Centre and Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia Philip J. Hogg. E‐mail: p.hogg@unsw.edu.au Search for other works by this author on: Oxford Academic Google Scholar O. Wargon O. Wargon Sydney Children's Hospital, Randwick, NSW 2031, Australia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 2, 1 February 2011, Pages 308–315, https://doi.org/10.1111/j.1365-2133.2010.10086.x Published: 01 February 2011
Abstract 20062: Predicting Sudden Cardiac Death in the General Population: Analysis of the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study
Authors: Rajat Deo, Faye Lopez, Ronit Katz, Selcuk Adabag, Lin Y Chen, Christopher R deFilippi, Aaron R Folsom, Susan R Heckbert, Bryan R Kestenbaum, Suma Konety, Richard A Kronmal, Kristen K Patton, David Siscovick, Nona Sotoodehnia, Michael G Shlipak, Alvaro Alonso
Journal: Circulation (2014)

Introduction: Most cases of sudden cardiac death (SCD) in the general population occur primarily among persons who do not have any prior history of clinical heart disease. Hypothesis: After evaluating a comprehensive panel of traditional and novel cardiovascular risk factors in two, large, racially diverse, population-based cohorts, we sought to develop a predictive model of SCD among US adults without a history of cardiovascular disease. Methods: We evaluated a series of 26 demographic, clinical, laboratory and electrocardiographic measures in participants who were free of baseline cardiovascular disease in the Atherosclerosis Risk in Communities (ARIC) Study (n=13,677) and the Cardiovascular Health Study (CHS) (n=3,650). Results: After a median follow-up of approximately 13 years, there were a combined total of 318 adjudicated SCD events for analysis. The following 11 risk factors were significant risk factors for SCD after meta-analyzing the findings from each cohort: age (per 5 years; HR 1.32, 95% CI [1.17 - 1.49]), male sex (HR 2.23; 1.70 - 2.93]), African American race (HR 1.62, 1.19 - 2.20), current smoking (HR 2.19, 1.65 - 2.92), low physical activity (HR 1.42, 1.09 - 1.85), hypertension (HR 1.82, 1.37 - 2.42), diabetes (HR 2.49, 1.86 - 3.34), low serum albumin (per 0.3 g/dL decrease; HR 1.38, 1.20 - 1.59), low HDL (&lt;40 mg/dL in men and &lt;50 mg/dL in women; HR 1.37, 1.05 - 1.80), eGFR&lt;60 ml/min/1.73m2 (HR 1.77, 1.16 - 2.71), and a prolonged QTc interval (≥440 milliseconds in men or ≥460 milliseconds in women; HR 2.08, 1.54 - 2.80). Over a 10-year follow-up period, a model combining these risk factors showed good to excellent discrimination for SCD risk (C statistic 0.831 in ARIC and 0.745 in CHS). Serum biomarkers including C-reactive protein (CRP), NT-pro-brain natriuretic peptide (BNP) and high sensitivity troponin T were not significant risk factors and did not enhance SCD risk prediction when added to the final multivariate model. Conclusions: A prediction model including demographic, clinical, laboratory, and electrocardiographic variables provided accurate information on the future SCD risk in middle-aged and elderly populations.
Cell-Cell Interaction in Erythropoiesis
Authors: John J. Rinehart, Esmail D. Zanjani, Benet Nomdedeu, Bobby J. Gormus, Manuel E. Kaplan
Journal: Journal of Clinical Investigation (1978)

Erythroid burst forming units (BFU-E) are proliferative cells present in peripheral blood and bone marrow which may be precursors of the erythroid colony forming cell found in the bone marrow. To examine the possible role of monocyte-macrophages in the modulation of erythropoiesis, the effect of monocytes on peripheral blood BFU-E proliferation in response to erythropoietin was investigated in the plasma clot culture system. Peripheral blood mononuclear cells from normal human donors were separated into four fractions. Fraction-I cells were obtained from the interface of Ficoll-Hypaque gradients (20-30% monocytes; 60-80% lymphocytes); fraction-II cells were fraction-I cells that were nonadherent to plastic (2-10% monocytes; 90-98% lymphocytes); fraction-III cells were obtained by incubation of fraction-II cells with carbonyl iron followed by Ficoll-Hypaque centrifugation (>99% lymphocytes); and fraction-IV cells represented the adherent population of fraction-II cells released from the plastic by lidocaine (>95% monocytes). When cells from these fractions were cultured in the presence of erythropoietin, the number of BFU-E-derived colonies was inversely proportional to the number of monocytes present (r = −0.96, P < 0.001). The suppressive effect of monocytes on BFU-E proliferation was confirmed by admixing autologous purified monocytes (fraction-IV cells) with fraction-III cells. Monocyte concentrations of ≥20% completely suppressed BFU-E activity. Reduction in the number of plated BFU-E by monocyte dilution could not account for these findings: a 15% reduction in the number of fraction-III cells plated resulted in only a 15% reduction in colony formation. These results indicate that monocyte-macrophages may play a significant role in the regulation of erythropoiesis and be involved in the pathogenesis of the hypoproliferative anemias associated with infection and certain neoplasia in which increased monocyte activity and monopoiesis also occur.
Abstract MP87: Circulating sRAGE Levels And The Risk Of Heart Failure
Authors: Mariana Lazo, Lu Shen, Marc K Halushka, Brad C Astor, Casey M Rebholz, Andreea Rawlings, Ron C Hoogeveen, Tina E Brinkley, Christie M Ballantyne, Elizabeth Selvin
Journal: Circulation (2014)

Introduction: Myocardial fibrosis is a key feature of heart failure, and its mechanisms are incompletely understood. It has been postulated that advanced glycation end-products (AGEs) form an etiologic link between diabetes and its vascular complications. Binding of AGEs to the cellular receptor for AGEs (RAGE) induces a state of increased oxidative stress, inflammation and fibrosis. Circulating soluble RAGEs (sRAGE) compete with cellular RAGE for the binding of AGEs which reduces the activation of the AGE-RAGE mediated pro-inflammatory and pro-fibrotic signaling pathways. We hypothesize that low levels of sRAGE will be associated with higher risk of heart failure. Methods: We conducted a prospective analysis of a random subsample of 1,157 participants from the ARIC Study who attended visit 2 (1990-1992). We included participants without a history of heart disease or heart failure, and with measured plasma sRAGE levels. Incident heart failure was defined as death from health failure or hospitalization due to heart failure. Results: In this community-based population (mean age 63 years, 60% women, 78% white), there were 132 incident cases of heart failure during approximately 20 years of follow up. Lower levels of sRAGE were significantly and independently associated with an increased risk of heart failure (Table). Analyses stratified by diabetes status at baseline showed that the risk of heart failure among those in the lowest quartile, compared to those in the upper quartile, was consistent but stronger among persons with diabetes compared to those without diabetes with HR=5.31 (95%CI 1.05-26.76) versus HR=2.50 (95%CI, 1.22-5.13), respectively. We did not observe any significant interactions by race or obesity status. Conclusions: Lower circulating levels of sRAGE are independently associated with the development of heart failure in older adults. These results highlight the pathophysiological role of the AGE-RAGE-sRAGE axis even among persons without diabetes.
Public standards and patients' control: how to keep electronic medical records accessible but private Commentary: Open approaches to electronic patient records Commentary: A patient's viewpoint
Authors: K. D Mandl
Journal: BMJ (2001)

A patient's medical records are generally fragmented across multiple treatment sites, posing an obstacle to clinical care, research, and public health efforts. 1 Electronic medical records and the internet provide a technical infrastructure on which to build longitudinal medical records that can be integrated across sites of care.Choices about the structure and ownership of these records will have profound impact on the accessibility and privacy of patient information.Already, alarming trends are apparent as proprietary online medical record systems are developed and deployed.The technology promising to unify the currently disparate pieces of a patient's medical record may actually threaten the accessibility of the information and compromise patients' privacy. 2 In this article we propose two doctrines and six desirable characteristics to guide the development of online medical record systems.We describe how such systems could be developed and used clinically.
Abstract 1477: Evaluation of microRNA-10b prognostic significance in a prospective cohort of breast cancer patients
Authors: Paola Parrella, Raffaela Barbano, Barbara Pasculli, Andrea Fontana, Massimiliano Copetti, Vanna Maria Valori, Maria Luana Poeta, Giuseppe Perrone, Michelina Coco, Teresa Balsamo, Fabio Pellegrini, Andrea Onetti Muda, Evaristo Maiello, Roberto Murgo, Vito Michele Fazio
Journal: Cancer Research (2014)

Abstract Several prognostic factors are currently used to stratify breast cancer patients based on the risk of disease progression. However, even patients classified as at low risk can progress and die for the disease. MicroRNA-10b (miR-10b) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types including breast cancer. We evaluated the expression of miR-10b in paired tumor and normal specimens obtained from a prospective cohort of breast cancer patients with at least 36 months follow-up enrolled according to the REMARK guidelines (n=150). RNA quality was measured and only samples with RNA Integrity Number (RIN) ≥7.0 were analyzed. The relative expression of miR-10b in tumor as compared to its normal counterpart (RER) was determined by RT-qPCR. miR-10b RERs were higher in the subgroup of patients with synchronous metastases (n=11, Median 0.25; IQR 0.11-1.02) as compared with patients without metastases (n=90, Median 0.09; IQR 0.04-0.29) (p=0.028). In the subgroup of patients without synchronous metastases (n=90), higher miR-10b RERs were associated with increased risk of disease progression and death in both univariable (HR 4.35, p=0.021 and HR 6.02, p=0.015 respectively) and multivariable (HR 13.37, p&amp;lt;0.001, and HR 15.39, p=0.003 respectively) Cox regression models. The addition of miR-10b RERs to the Nottingham Prognostic Index (NPI) provided an improvement in discrimination power and risk reclassification abilities for the clinical outcomes at 36 months. Survival C-indices significantly increased from 0.849 to 0.889 (p=0.009) for OS and from 0.735 to 0.767 (p=0.050) for DFS. Our results provide evidences that the addition of miR-10b RERs to the prognostic factors used in clinical routine could improve the prediction abilities for both overall mortality and disease progression in breast cancer patients. Citation Format: Paola Parrella, Raffaela Barbano, Barbara Pasculli, Andrea Fontana, Massimiliano Copetti, Vanna Maria Valori, Maria Luana Poeta, Giuseppe Perrone, Michelina Coco, Teresa Balsamo, Fabio Pellegrini, Andrea Onetti Muda, Evaristo Maiello, Roberto Murgo, Vito Michele Fazio. Evaluation of microRNA-10b prognostic significance in a prospective cohort of breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1477. doi:10.1158/1538-7445.AM2014-1477
Analysis of genes under the downstream control of the t(8;21) fusion protein AML1-MTG8: overexpression of the TIS11b(ERF-1, cMG1) gene induces myeloid cell proliferation in response to G-CSF
Authors: Hiroyuki Shimada, Hitoshi Ichikawa, Sawako Nakamura, Rieko Katsu, Mitsuteru Iwasa, Issay Kitabayashi, Misao Ohki
Journal: Blood (2000)
Regulation of heparanase expression in breast cancer by estrogen and tamoxifen
Authors: Michael Elkin, Irit Cohen, Bella Maly, Itamar Simon, Israel Vlodavsky, Tamar Peretz
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4367 

Mammalian heparanase (endo-beta-glucuronidase) degrades heparan sulfate, the main polysaccharide component of the extracellular matrix and basement membranes. Heparanase is now recognized as a critical determinant in cancer development, acting via breakdown of extracellular barriers for local invasion and metastasis, as well as release of heparan sulfate bound angiogenic and growth promoting factors, and thus generating a supportive microenvironment that promotes tumor progression and angiogenesis. We demonstrated activation of heparanase gene transcription in breast carcinoma cells by physiological concentrations of estrogen and verified physical association between heparanase gene promoter and estrogen-estrogen receptor (ER) complex, confirming direct regulation of heparanase expression by estrogen. In vivo , exposure to estrogen augmented the levels of heparanase in breast carcinoma cells embedded in Matrigel plugs, and associated with increased plug vascularization. Breast carcinoma tissue microarray analysis revealed a strong correlation between ER status and heparanase expression. It appears that estrogen effects in breast tumorigenesis are not limited solely to the regulation of cell proliferation, and that estrogen may contribute to breast tumor progression also through induction of heparanase expression in the mammary epithelium. This effect could be particularly important at the initial stages of breast tumorigenesis, when more than 70% of all tumors are reportedly ER-positive. Surprisingly, partial ER antagonist tamoxifen, the first line drug in endocrine therapy of breast cancer, exerted estrogen-like stimulatory effect on heparanase gene expression. Chromatin immunoprecipitation assay confirmed tamoxifen-estrogen receptor complex binding to the heparanase promoter and revealed the molecular mechanism of estrogen-like effect of tamoxifen on heparanase expression. Tamoxifen-bound ER recruits to the heparanase promoter ER coactivator AIB1 (SRC-3), thus altering tamoxifen activity from antagonist to agonist. Based on our hypothesis, the estrogen-like effect of tamoxifen on heparanase expression could be responsible, at least in part, for tumor resistance or even progression observed in a substantial fraction of tamoxifen-treated patients with ER-positive breast cancer. Detailed understanding of the mechanism through which estrogen and tamoxifen affect heparanase transcription is expected to provide new insights on breast cancer progression and endocrine therapy resistance, as well as to suggest new strategies for delaying or reversing this process
Emerging trends in hepatocellular carcinoma incidence and mortality
Authors: Basile Njei, Yaron Rotman, Ivo Ditah, Joseph K. Lim
Journal: Hepatology (2014)

The rise in incidence of hepatocellular carcinoma (HCC) in the United States has been well documented. The purpose of this analysis was to examine temporal trends in HCC incidence, mortality, and survival within the U.S. population. The Surveillance, Epidemiology, and End Results data were used to examine incidence and incidence-based (IB) mortality in HCC from 1973 to 2011. Secular trends in age-adjusted incidence and IB mortality by sex and cancer stage were characterized using the Joinpoint Regression program. In 1973, HCC incidence was 1.51 cases per 100,000, whereas in 2011, HCC incidence was 6.20 cases per 100,000. Although HCC incidence continues to increase, a slowing of the rate of increase occurs around 2006. In a sensitivity analysis, there was no significant increase in incidence and IB mortality from 2009 to 2011. There was a significant increase in overall median survival from the 1970s to 2000s (2 vs. 8 months; P < 0.001). On multivariable Cox's regression analysis, age, sex, race, tumor grade, stage at diagnosis, lymph/vascular invasion, number of primary tumors, tumor size, and liver transplant were independently associated with mortality.Our results indicate a deceleration in the incidence of HCC around 2006. Since 2009 and for the first time in four decades, there is no increase in IB mortality and incidence rates for HCC in the U.S. population. The nonsignificant increase in incidence and IB mortality in recent years suggest that the peak of the HCC epidemic may be near. A significant survival improvement in HCC was also noted from 1973 to 2010, which seems to be driven by earlier detection of HCC at a curative stage and greater utilization of curative modalities (especially transplant).
Abstract 15285: Notch3 is Required for the Cardiac Adaptation to Hypertension
Authors: Hélène Ragot, Régine Merval, Mathilde Baudet, Evelyne Polidano, Loubina Fazal, Claude Delcayre, Christos Chatziantoniou, Jane-Lise Samuel
Journal: Circulation (2014)

Background:  The Notch3 receptor has a role in the integrity of resistance arteries by controlling the maturation of vascular smooth muscle cells (VSMC). Hypertension in Notch3 null mice (N3-/-) rapidly induced a heart failure. The mechanistic pathways being not defined, we hypothesize that alterations of the coronary tree secondary to Notch3 invalidation might trigger the development of heart failure in response to hypertension.   Methods:  N3-/- and WT C57/Bl6J mice were used. At 11 week of age, WT and N3-/- mice were implanted with Alzet mini-pumps filled with Angiotensin 2 (Ang2, 1μg/kg/min) or NaCl for 28 days (n=15-23/ group).   Results:  Normotensive N3-/- mice showed ventricular hypertrophy (+20%, p   Conclusion:  Altogether, these data demonstrate that Notch3 activation in the VSMC of coronary artery plays a key role in the adaptation of the heart to Ang2- induced hypertension, and in turn in the development of heart failure.
Indoor endotoxin and respiratory symptoms in urban schoolchildren
Authors: Gary Wong, T.F. Leung, Edmund Yung
Journal: European Respiratory Journal (2011)

Background and aim: Endotoxin is a marker of microbial exposure and rural studies suggested it is negatively co-related with asthma. This study aims to determine the relationship of indoor endotoxin and manifestations of respiratory symptoms in urban children in Hong Kong.

Methods: Random sample of schoolchildren aged 7 to 11 years were recruited through the school system. Parents completed the locally validated ISAAC questionnaire with additional questions about the home environment. Random subgroup of subjects was recruited for SPTs and dust samples were collected according to the ISAAC Phase II protocol. Endotoxin levels were log-transformed before analysis.

Results: 3,546 primary schoolchildren were screened with a participation rate of 96%. A random subsample of 1,303 subjects has been skin-tested with 439 also provided mattress dust samples. Among them, 37 (8.4%) had at least one wheezing attack in the past year and 47 (10.7%) had a physician diagnose of asthma. The median (interquartile range) of endotoxin concentration (EU/mg) and load (EU/m2) were 12.9 (6-25) and 547 (230-1,137) in those without current wheeze; they were 34 (19-83) and 1,689 (853-3,301) in those with current wheeze. The differences were significantly different (p< 0.01) adjusted for confounders. Among those with a asthma diagnosis, higher endotoxin level was associated with use of asthma medication in the past year.

Conclusion: Higher level of endotoxin level in this urban sample of schoolchildren is associated with wheezing and increased use of asthma medication among known asthmatics. Further studies are needed to reveal the possible roles of microbial exposure in affecting the development of asthma in urban and rural settings.