tbuckley/cabot-search huggingface dataset:
Abstract 2631: Analysis of PI3K pathway genes in bladder cancer
Authors: Didem Seven, Hatice Tigli, Nur Buyru
Journal: Cancer Research (2012)

Abstract Bladder cancer is the most common cancer of the urinary tract and is the ninth the most common cancer among men. Its incidence directly increases with age, it rarely occurs before the age of 50 and it is three to four times more common in men compared to women. Although there is now exclusive information on bladder cancer genetics, epigenetics and gene expression, several questions remain unanswered. Global profiling via expression and genomic microarray technologies may provide answers to some of the outstanding questions. Many studies have assessed the status of known oncogenes and tumor suppressor genes and have investigated common chromosomal alterations to identify novel genomic events in bladder cancer. The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays critical role in cell growth, proliferation, and apoptosis. As a result of genomic alterations and loss of some tumor suppressor genes signaling through this pathway is commonly altered in many types of cancer including bladder. In the present study, our interest was focused on the expression analysis of some critical genes in this pathway. For this purpose, expression of seven genes (mTOR, KRAS, PIK3CA, TSC1, STK11, Rheb, PTEN and AKT1) acting in this pathway was analyzed in 35 matched bladder tumor and non-cancerous tissue samples by quantitative RT-PCR. Expression of all genes except PIK3CA and PTEN were similar for the normal bladder and tumor tissue. We observed downregulated expression of PTEN and PIK3CA genes in bladder tumors. The median PTEN mRNA levels in non-cancerous and tumor tissue samples were 2.11 and 0.35, respectively and the difference between the two groups was statistically significant (p=0.00). PIK3CA was also downregulated in the tumor tissues. Tumor tissue samples displayed 6.62 fold decrease in PIK3CA expression compared to normal tissue samples (p=0.002). On the other hand, slightly decreased Rheb mRNA expression was also observed in tumor tissue compared to the non-cancerous tissue. However, the difference expression levels of Rheb between two groups was not statistically significant. Our result indicate that, PI3K pathway has an important function in bladder cancer progression with the contribution of more than one gene in this pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2631. doi:1538-7445.AM2012-2631
Catheterization of the Splenic Artery for Portal Venography
Authors: James J. Pollard, Robert A. Nebesar
Journal: New England Journal of Medicine (1964)

SHORTLY after Abeatici and Campi,1 in 1951, introduced direct percutaneous splenic puncture as a method of performing splenoportal venography in dogs this became the standard roentgenographic method of demonstrating the portal venous system in man. The usual indication for this examination is the evaluation of portal hypertension. Demonstration of portal-vein patency is essential before surgical shunting procedures performed in an attempt to alleviate the danger of hemorrhage from varices secondary to the hypertension. Less common indications for splenoportography include the demonstration of varices, liver masses and, occasionally, invasion of the splenic or portal vein by tumor.Direct puncture of the . . .
Abstract 3059: The Tmeff2 protein functions as a tumor suppressor and interacts with Sarcosine dehydrogenase
Authors: Ryan Overcash, Xiaofei Chen, Mitchel Harris, Donald Hoffman, Maria J. Ruiz-Echevarria
Journal: Cancer Research (2010)

Abstract Tmeff2 is a gene with an expression profile limited to the brain and the prostate but shown to be frequently upregulated in prostate cancer. It encodes a type I transmembrane protein with a short cytoplasmic tail containing a potential G-protein activation domain and an extracellular domain containing two follistatin (FS) modules and an epidermal growth factor-like (EGF) domain. Although these features are suggestive of a function in signal transduction, the role of the Tmeff2 in prostate cancer, or the mechanism(s) that lead to its overexpression during the disease are unclear. In the present study, we evaluated the functional role of Tmeff2 in prostate tumorigenesis. To investigate the function of the gene, Tmeff2 was overexpressed in TRAMP C1 murine prostate cancer cells and HEK293T cells, and the effects of overexpression on cellular growth and tumorigenicity were assessed. Tmeff2 overexpression in HEK293T cells almost completely abolished the ability of these cells to form colonies in soft agar and resulted in a 20-30% reduction in proliferation rates in these and TRAMP C1 cells, indicating that the gene may function as a tumor suppressor in prostate cancer cells. Moreover, although TMEFF2 overexpression alone did not induce apoptosis, it sensitized these cell lines to staurosporine or rapamycin-induced apoptosis, causing nearly a three-fold increase in the percentage of apoptotic cells. In order to assess the molecular mechanism(s) by which Tmeff2 may suppress cellular growth and tumorigenicity, we screened Tmeff2 affinity complexes by mass spectrometry to search for candidate functional partner(s) of Tmeff2. Our results showed an interaction with Sarcosine Dehydrogenase (SARDH) an enzyme involved in the metabolism of sarcosine. This interaction was further confirmed by co-immunoprecipitation analysis. Importantly, sarcosine has recently been described as a biomarker for prostate cancer as it was shown to be highly increased in prostate and metastatic prostate cancer. In addition, it may also play a role in the biology of the cancer since it promotes cell invasion when added to benign prostate epithelial cells. In summary, the results presented here suggest that Tmeff2 functions as a tumor suppressor for prostate cancer. Its interaction with SARDH may represent a mechanism by which Tmeff2 modulates tumorigenicity by altering the levels of sarcosine. Further analyses are necessary to determine the value of Tmeff2 as a prognostic marker. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3059.
A3.3 An Immunological Window of Opportunity Defines the Ability of Early RA Patient to Achieve Remission with First Anti-Rheumatic Treatment
Authors: Agata Burska, Rekha Parmar, Yasser El-Sherbiny, Jehan El Jawhari, Paul Emery, Frederique Ponchel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> The therapeutic goal for patients with rheumatoid arthritis (RA) is clinical remission. This is best achieved by early diagnosis followed by appropriate therapeutic intervention. RA is associated with dys-regulation of T-cell subsets early in the disease with naïve cells and regulatory T-cell losses and acquisition of abnormal subset in realtion with inflammation (IRC). Our aim was to test the hypothesis that T-cell subset quantification can predict the achievement of clinical remission in patients with early RA. <h3>Materials and Methods</h3> T-cell subsets (naive, Treg and IRC) were quantified using flow cytometry in 108 DMARDs-naïve, early RA patients (&lt;24 months) symptom duration commencing methot-rexate MTX or MTX + anti-tumour necrosis factor agents (anti-TNF) and in 105 healthy controls (HC). The primary outcome assessed was remission (DAS28 &lt; 2.6). The pilot analysis was performed on frozen PBMC obtained from 38 RA patients and 35 HC. These results were validated using fresh blood samples on a cohort of 70 RA patients and 70 HC. <h3>Results</h3> In the pilot study, T-cell subset analysis in early RA confirmed immune dysregulation compared to HC with reduced frequency of naïve CD4+ T-cells and Treg and increased IRC (all p &lt; 0.001) compared to HC. Naive T-cell above median was associated with remission (p = 0.001). In the validation study, 50 patients were treated with MTX and showed the same relationship with naïve cell frequency above median being associated with remission (p = 0.011). Individual analysis on each patient's naïve cell frequency deviation from expected (using 70 HC) demonstrated that "normal" naïve cell frequency (observed in 30 patients) was associated with remission whereas reduced naïve cell frequency was more frequently observed in patients with poor response to MTX (p = 0.03). Patients with poor immunological status were not prevented to achieve remission when treated with MTX + anti-TNF (n = 20 including 10 patients with normal and 10 with reduced naïve cells) raising the rate of remission from 20% in the MTX group (n = 4 of the 20 patients with reduced naïve cells at baseline) to 60% in the MTX + anti-TNF group (n = 6 of the 10 patients). <h3>Conclusions</h3> These data show that baseline naïve T-cell subset analysis has a value in predicting early RA MTX treatment outcome. Immunological analysis could be used in conjunction with clinical/serological features to predict response to MTX and select the most appropriate therapy at disease presentation.
Postgenomics and genetic essentialism
Authors: Ilan Dar-Nimrod
Journal: Behavioral and Brain Sciences (2012)

Abstract Traditional lay perceptions of genetics are plagued with essentialist biases leading to some unfortunate consequences. Changes in the scientific understanding of heredity in general, and in genotype–phenotype relationships more specifically, provide a vital basis for shifting public understanding of genetics. Facilitating postgenomic literacy among the public has the potential to have translational implications in diminishing deleterious attitudes, beliefs, and behaviors.
BLOOD LACTATE LEVEL AT CORONARY CARE UNIT CAN PREDICT SHORT-TERM PROGNOSIS AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE MYOCARDIAL INFARCTION
Authors: Hirohide Matsuura, Nehiro Kuriyama, Tatsuya Nakama, Makoto Furugen, Hiroshi Koiwaya, Akihiko Matsuyama, Keiichi Ashikaga, Nozomi Watanabe, Yoshisato Shibata
Journal: Journal of the American College of Cardiology (2016)
The National Institute of Environmental Health Sciences: a perspective.
Authors: E Y James, G M Kingman
Journal: Environmental Health Perspectives (1978)

This paper attempts to place the programs of the National Institute of Environmental Health Sciences into correct perspective in relation to the other Federal environmental programs. Its goal is to illuminate the field of environmental health as a new field in science that confronts a wide variety of complex and diverse issues. It is unrealistic to believe these issues can somehow be rendered less complex and diverse. What is hoped is that the Institute will contribute to providing the tools which will make is possible for us to develop principles leading to an understanding of the underlying problems. Then we should be able to build a base for effective public health programs for the years ahead, years that should prove to be as eventful and challenging as those just past.
The Sequelae of<i>Haemophilus influenzae</i>Meningitis in School-Age Children
Authors: H. Gerry Taylor, Elaine L. Mills, Antonio Ciampi, Roxane du Berger, Gordon V. Watters, Ronald Gold, Noni MacDonald, Richard H. Michaels
Journal: New England Journal of Medicine (1990)

Previous data on the consequences of Haemophilus influenzae type b meningitis for school-age children have been inconsistent, and much of the information on risk factors has been inconclusive. The present study was designed to evaluate the sequelae of this disease with a protocol for the comprehensive assessment of neuropsychological function.
AB0643 The Ψ-Reuma Project: Role of Early and Recent Life Events on Systemic Sclerosis (SSC) Clinical Presentation and Course
Authors: F. Rotella, F. Pietrini, L. Lelli, S. Guiducci, S. Bellando-Randone, J. Blagojevic, G. Lepri, C. Bruni, M. Matucci-Cerinic, C. Faravelli
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Stressful Life Events (SLEs) may play a role in the etiopathogenesis of autoimmune diseases, especially during childhood (<i>early</i> SLEs) and in the year prior to the onset of the disease (<i>recent</i> SLEs). Such a deleterious effect of stressful events seems to be mediated by the inadequate responsiveness to stressors and to chronic inflammation due to a dysregulation of the Hypothalamic-Pituitary-Adrenal axis (HPA axis). Few studies have addressed the relationship between SLEs and SSc and none of them evaluated the effect of both <i>early</i> and <i>recent</i> life events. <h3>Objectives</h3> The aims of the present study were to explore the multiple effects of stress on SSc onset and course, and to evaluate the impact of pain perception and health-related quality of life on patients with SSc. <h3>Methods</h3> 110 consecutive SSc patients were enrolled. The assessment included a face-to-face interview and the administration of self-reported questionnaires evaluating pain perception and quality of life (Short Form (36) Health Survey (SF-36), Brief Pain Inventory (BPI), Childhood Experience of Care and Abuse Questionnaire and Florence Psychiatric Interview). Clinical status was assessed by modified Rodnan Skin Score and Raynaud Condition Score, nailfold videocapillaroscopy and instrumental examination of internal organs. <h3>Results</h3> Compared to a group of matched controls (n=110), a higher proportion of patients reported at least one Stressful Life Events (56.3% vs 34.5%, p&lt;0.01). All <i>early</i> life events were more frequently reported by SSc patients, even though a significantly difference was obtained only for "loss of mother" and for "sexual abuse" (13.6% vs 5.4%, p&lt;0.05 and 16.4% vs 8.2%, p&lt;0.05, respectively). Patients displayed a worse quality of life and a higher pain perception (all the subscales of SF-36 and of BPI were significantly different between the two groups, p&lt;0.01). SSc patients, with a significant clinical worsening (33.6%), reported more frequently the occurrence of severe <i>recent</i> life events compared to patients without a significant clinical worsening (54.0% vs 26.0% p&lt;0.05). <h3>Conclusions</h3> <i>Early</i> SLEs can be considered potential risk factors for the onset of SSc. The occurrence of <i>recent</i> SLEs may have a role in the course of the disease, being linked to a significant clinical worsening. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4998
Abstract 3968: MicroRNA-34a inhibits proliferation and invasion by targeting c-Myc in prostate cancer cells
Authors: Soichiro Yamamura, Sharanjot Saini, Shahana Majid, Hiroshi Hirata, Koji Ueno, Guoren Deng, Yuichiro Tanaka, Peter Carroll, Rajvir Dahiya
Journal: Cancer Research (2011)

Abstract MicroRNA-34a (miR-34a), a potent p53 mediator, has been reported to function as a tumor suppressor. The proto-oncogene c-Myc regulates cell proliferation and transformation both transcriptionally and non-transcriptionally and is frequently deregulated in human cancers. Rho GTPases are small G proteins that regulate various cellular processes, including cytoskeletal dynamics, migration, cell proliferation, apoptosis, and transcription. RhoA has been shown to control cancer metastasis and progression and cross-talk between RhoA and c-Myc has been reported. We studied the functional effects of miR-34a on c-Myc and RhoA in PC-3 prostate cancer cells. Transfection of miR-34a into PC-3 cells strongly inhibited in vitro cell proliferation, in vivo xenograft growth and cell invasion and promoted apoptosis. miR-34a downregulated expression of c-Myc by targeting its 3’ UTR as shown by luciferase reporter assays. miR-34a was also found to repress RhoA expression. Overexpression of c-Myc reversed miR-34a suppression of RhoA expression and invasion, suggesting that miR-34a inhibits invasion by suppressing RhoA through c-Myc. We also found that miR-34a downregulated guanine nucleotide exchange factors (GEFs) which convert inactive GTPases to an active form. Our results demonstrate that miR-34a suppresses malignancy by targeting c-Myc in PC-3 prostate cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3968. doi:10.1158/1538-7445.AM2011-3968
Chronic Pancreatitis and Pancreatic Cancer
Authors: Ellen B. Gold, John L. Cameron
Journal: New England Journal of Medicine (1993)

Pancreatic cancer is the 5th leading cause of death from cancer and the 11th most common cancer in the United States1; each year 24,000 people die of pancreatic cancer in this country. The incidence of pancreatic cancer increased dramatically several decades ago, but it has remained fairly stable over the past 15 years (9.1 per 100,000). Although the five-year survival rate has improved only slightly in recent years (from 3 percent in 1970 through 1973 to 5.4 percent in 1981 through 1987 among whites and from 2 percent to 4.3 percent during the same periods among blacks), nearly all . . .
THU0502 Ad Promotes the Differentiation of TH17 Cell and Exacerbates Disease Progression in CIA Model via Enhancing TH17 Response
Authors: M. Zhang
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Adiponectin (AD), produced prevalently by adipose tissues, has suggested playing a significant role in chronic inflammation and immune response. The relation between AD and rheumatoid arthritis (RA) has been a topic of much interest recently. We previously reported the high expression of AD in the inflammated joint of RA. Recent studies indicated that circulating adiponectin levels are associated with progressive of radiographic joint destruction in RA, suggesting that AD is involved in bone erosion in RA, but the mechanism remained unclear. We hypothesize that local AD might directly involved in the progression of synovial inflammation and joint destruction in RA by enhancing Th17 cell response. In this study, we will investigate a role of AD on promoting the differentiation of naïve T cell to Th17 cell and bone erosion in collagen-induced arthritis (CIA) mice. <h3>Objectives</h3> To investigate a role of Adiponectin (AD) on promoting the differentiation of naïve T cell to Th17 cell and bone erosion in collagen-induced arthritis (CIA) mice. <h3>Methods</h3> Purified naïve T cells were cultured in anti-CD3 mAb and anti-CD28 mAb precoated with TGF-β, IL-6, IL-23 in the presence and absence of AD (0.1, 1 or 10 μg/ml). After 72 hours of culture, the frequencies of Th17 cells were measured by flow cytometry; the expression of IL-17, ROR-γt, IL-21, IL-22 and IL-23 were determined by real-time PCR and ELISA. Intraarticularly injected of AD 10 μl (1 μg/1 μl) into the knee joint of CIA mice was to analysis the role of AD on CIA development, Th17 cell expression. <h3>Results</h3> The frequencies of Th17 cells were significantly increased with the treatment of AD 10 μg/ml. The expression of IL-17, ROR-γt and IL-23 mRNA were significantly increased upon AD 10 μg/ml stimulation. Consistently with mRNA expression, IL-17 levels were significantly elevated in culture supernatants with 10 μg/ml AD treatments. Intraarticular injection of AD into the knee joint of CIA mice aggravated arthritic development and bone erosion, triggered higher expression of IL-17, IL-22, IL-23 mRNA in CIA model. <h3>Conclusions</h3> These findings identify a role of AD on enhancing the differentiation of Th17 cell and exacerbating disease progression in CIA model via enhancing Th17 response. <h3>References</h3> Jun Deng, Yang Liu, Min Yang. etal. Leptin exacerbates collagen-induced arthritis via enhancing Th17 cell response. 2012. Tan W, Wang F, Zhang M, etal. High adiponectin and adiponectin receptor 1 expression in synovial fluids and synovial tissues of patients with rheumatoid arthritis. Semin Arthritis Rheum. 2009;38(6):420-7. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4176
Abstract 4795: The epigenetic regulation of HPP1 expression in colon cancer
Authors: Jian Wang, Abul Elahi, Jonathan Hernandez, Whalen Clark, Alex Achille, Seto ED, David Shibata
Journal: Cancer Research (2011)

Abstract Background: Tumors often are associated with aberrant epigenetic gene silencing. HPP1, a tumor suppressor gene, is epigenetically silenced by promoter methylation in a number of tumor types including colon cancer however, the contribution of histone acetylation is not clear. Moreover, c-myc interaction with the HPP1 promoter is thought to suppress expression. The purpose of this study is to examine the interplay between c-myc, DNA methylation and histone acetylation in the epigenetic regulation of HPP1 expression. Methods: The HPP1-negative cell line, HCT-116, was treated with the DNA methylation inhibitor 5-aza-2’-deoxycitidine (5-aza-DC) and/or HDAC inhibitors, including sodium butyrate (SB), Vorinostat (SAHA), trichostatin A (TSA), and valproic acid (VPA). Knockdowns of c-Myc and HDAC-3 were performed using siRNA. Protein and mRNA expression of HPP1 were determined by Western Blot and RT-PCR respectively. HPP1 promoter methylation was assessed by real-time methylation-specific PCR. Furthermore, Chromatin immunoprecipitation (ChIP) experiments were used to demonstrate the binding of c-Myc to the HPP1 promoter. Results: 5-aza-DC (0.4uM) as well as the HDAC inhibitors, SB (5mM), TSA (200nM), SAHA (5uM) and VPA (2mM), increased the expression of HPP1 in HCT-116 cells. The treatment of 5-aza-DC in combination with individual HDAC inhibitors resulted in a synergistic effect on increasing HPP1 expression as detected by both RT-PCR and Western blotting. We found that SAHA reduced the expression of HDAC-3 and c-Myc. Concordantly, knockdown of c-Myc and HDAC-3 by siRNA significantly enhanced HPP1 expression. We have also confirmed that c-Myc binds to the HPP1 promoter and its knockdown results in a reduction of HPP1 promoter methylation. Conclusions: These results indicate that c-Myc- and HDAC-3-associated promoter methylation and histone deacetylation contribute to HPP1 epigenetic silencing. Colon cancer cells treated with DNA methylation and HDAC inhibitors can re-express the cancer suppressor gene HPP1. This study supports the conept that 5-aza-DC and HDAC inhibitors represent potentially promising classes of anticancer drugs for the future treatment of colon cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4795. doi:10.1158/1538-7445.AM2011-4795