tbuckley/cabot-search huggingface dataset:
Abstract 202: Tocopherols inhibit the dietary carcinogen PhIP-induced prostate carcinogenesis in a CYP1A-humanized mouse model.
Authors: Guangxun Li, Hong Wang, Anna B. Liu, Jayson X. Chen, Mao-Jung Lee, Chung S. Yang
Journal: Cancer Research (2013)

Abstract γ-TmT, a tocopherol mixture that is rich in γ-tocopherol (γ-T), containing 56.8% γ-T, 24.3% δ-T, 13.0% α-T and 1.5% β-T, has been shown to inhibit colon, lung, mammary and prostate tumorigenesis in our previous studies, whereas α-T was ineffective. The present work investigated the inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced prostate carcinogenesis in CYP1A-humanized (hCYP1A) mice by γ-TmT. Male hCYP1A mice, maintained on the AIN93M diet or the same diet supplemented with 0.3% γ-TmT, were treated with a dose of PhIP (200 mg/kg, i.g.). At week 40 after PhIP treatment, all mice developed high-grade prostate intraepithelial neoplasia (hgPIN) in the dorso-lateral glands. The hgPIN was associated with elevated levels of 8-oxo-deoxyguanosine (8-oxo-dG), DNMT1, COX-2 and p-AKT, as well as with loss of expression of the tumor suppressor PTEN, E-cadherin, GSTP1 and Nrf2 in the dorso-lateral glands. In the γ-TmT group, the number of glands with hgPIN (per 100 glands) was significantly lower than the control group (14.6 ± 4.87 vs. 34.81 ± 3.87, p &amp;lt; 0.01). The γ-TmT treatment also prevented the elevation of 8-oxo-dG, COX-2 and p-AKT and the loss of PTEN and Nrf2. The γ-TmT treatment significantly increased the plasma levels of γ-T and δ-T (to 1.7 and 0.8 μM, respectively) as well as their side-chain degradation metabolites, carboxyethyl hydroxychromans and carboxymethylbutyl hydroxychromans (to 2.6-4.0 μM, higher than their parent tocopherols). In a short-term experiment, PhIP-treatment elevated levels of 8-oxo-dG, γH2AX and DNMT1, and caused gene expression changes in several p53-associated genes, including p53bp1, p21WAF1/CIP1, cyclin D1, Bax, Igf1 and cyclinG1 at 1 and/or 3 days after PhIP treatment. Dietary γ-TmT treatment partially prevented the elevation of 8-oxo-dG, γH2AX and DNMT1. This action may contribute to the prostate cancer preventive effect of tocopherols. The presently observed inhibitory activities of γ-TmT against prostate carcinogenesis are hypothesized to be due to the decrease of oxidative stress and inhibition of AKT phosphorylation by γ- and δ-tocopherols, and this hypothesis remains to be tested further (supported by NIH grants CA159361 &amp; CA133021). Citation Format: Guangxun Li, Hong Wang, Anna B. Liu, Jayson X. Chen, Mao-Jung Lee, Chung S. Yang. Tocopherols inhibit the dietary carcinogen PhIP-induced prostate carcinogenesis in a CYP1A-humanized mouse model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 202. doi:10.1158/1538-7445.AM2013-202
Authors' reply to Bjerrum and colleagues
Authors: P. Little, M. Moore
Journal: BMJ (2013)

Bjerrum and colleagues query the generalisability of our trial sample, stating that 697 patients were approached over two and a half years.1 2 They also question the cut-off value of the clinical score used to determine whether a rapid antigen detection test (RADT) should be used.

Regarding patient recruitment, 697 refers to the second phase: an estimated 1944 patients were approached during the whole two and a half years, although this …
Case 39-2007
Authors: Melissa M. Burnett, Mary S. Huang, Rania M. Seliem
Journal: New England Journal of Medicine (2007)

A 5-month-old girl was seen in the pediatric dermatology clinic because of a rash. At the age of 3 months, a red papule had developed on her cheek, followed by a generalized eruption. She was well except for the skin lesions. A diagnostic procedure was performed.
P206 Changes In Indices Derived From Multibreath Washout (mbw) Following Treatment With Ivacaftor In Patients With Cystic Fibrosis
Authors: K. Harman, S. Irving, K. Bayfield, C. Saunders, E. Spearing, J. Davies
Journal: Thorax (2014)

<h3>Background</h3> Lung clearance index (LCI) is a measure of gas mixing inhomogeneity derived from multi-breath wash (MBW) out techniques, which has been shown to be more sensitive than conventional spirometry/ FEV<sub>1</sub>. The potentiator, Ivacaftor, led to improvement in LCI in patients with mild cystic fibrosis (CF) lung disease however its utility as an outcome measure in more severe disease requires further investigation. Whilst LCI reflects overall ventilation heterogeneity, analysis of the phase III slopes of successive breaths in the MBW; known as Sacin and Scond; are thought to reflect the ventilation heterogeneity generated at branch points in the acinar and conductive lung zones respectively. This study aimed to explore changes in the indices derived from analysis of MBW following a year of treatment with Ivacaftor. <h3>Method</h3> A prospective study was performed between March 2013 and April 2014 on patients with the G551D mutation and eligible for clinically prescribed Ivacaftor. MBW (Innocor SF6 technique) and spirometry were performed immediately prior to commencing Ivacaftor, and at a clinic visit following 9–12 months therapy. FEV<sub>1</sub> is calculated using Stanojevic references and all data are expressed as mean (SD). Paired data were analysed with a Wilcoxon rank sum test and correlations with Spearman’s rank correlation. The null hypothesis was rejected at p &lt; 0.05. <h3>Results</h3> 8 patients were enrolled with ages ranging from 6–27 years. FEV<sub>1</sub> increased from 68.7 (17.2)% before treatment to 80.1 (16.3)% after 9–12 months (p1 and LCI did not correlate with each other. <h3>Discussion</h3> Patients prescribed Ivacaftor demonstrated improvements in both conventional FEV<sub>1</sub> and the newer measure of LCI; improvement was not limited to patients with milder disease and was seen throughout the group. In this study, the phase III slope measures did not appear to add further value to the LCI. It is possible that this reflects under powering in this small group; further data will be obtained.
Abstract 5276: CXCL7/CXCR2 axis and invasion
Authors: Minghuan Yu, Mary A. Kosir
Journal: Cancer Research (2010)

Abstract Introduction: The CXCL7/CXCR2 axis interfaces with matrix molecules whereby the chemokine CXCL7 binds heparan sulfate and the G-protein-linked receptor CXCR2. CXCL7-transfected breast cells acquire the ability to invade through Matrigel. The purpose of this study was to test the effect of inhibition of heparan sulfate binding and CXCR2 binding on invasion. Methods: Stably transfected breast cells (MCF10AT) were tested with CXCL7-siRNA, and a specific CXCR2 antagonist (SB225002). Inhibition was verified by real time PCR and heparanase ELISA assay. Matrigel invasion assays were performed. Results: SB225002 and CXCL7 siRNA blocked invasion through Matrigel as compared to controls (p&amp;lt;0.01), and CXCL7 siRNA significantly decreased heparanase activity (p&amp;lt;0.01). Conclusion: Interfering with either heparan sulfate binding by CXCL7 or its binding to CXCR2 leads to decreased invasion through Matrigel. 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 5276.
Childhood Obesity and Coronary Heart Disease
Authors: Albert P. Rocchini
Journal: New England Journal of Medicine (2011)

Obesity is the most common nutritional problem among children in both developed and underdeveloped countries. Despite efforts over the past decade to prevent and control obesity, data from the 2003–2006 National Health and Nutrition Examination Surveys (NHANES) show that 16.3% of children and adolescents, 2 to 19 years of age, are obese (i.e., have a body-mass index [BMI] above the 95th percentile for age and sex).1 There is strong epidemiologic evidence that obesity in childhood is associated with an increased incidence of atherosclerosis in adulthood. Postmortem studies have shown that obesity in childhood and adolescence is associated with increased evidence . . .
AB0565 Can Color Doppler Ultrasound BE Used to Monitor Treatment Response in Large Vessel GIANT Cell Arteritis?
Authors: A. Diamantopoulos, G. Haugeberg, G. Myklebust
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> On ultrasound examinations large vessel vasculitis (LVV) has been reported to be present in up to 37% of giant cell arteritis (GCA) patients. In these patients, the axillary arteries are reported to be affected as high as 98% <sup>1,2</sup>. No consensus exists on how to evaluate treatment response in LVV. Color Doppler ultrasound (CDUS) yields a high sensitivity and specificity to diagnose GCA <sup>1</sup>. <h3>Objectives</h3> The aim of this study was to examine if CDUS of the axillary arteries could be used to monitor treatment response in LVV-GCA. <h3>Methods</h3> Patients with new onset or relapsing GCA (positive ultrasound of the temporal artery and typical clinical picture) and with axillary arteritis were prospectively recruited in this study. The intima media complex (IMC) thickness of the axillary artery was measured at the active disease phase (and before treatment initiation) and after the patients had achieved clinical remission. C-reactive protein (CRP) and prednisolone dose were also registered. Appropriate statistical tests were applied and p values &lt;0.05 were considered as significant <h3>Results</h3> Ten patients (nine females, one male) were evaluated (eight with relapsing and one with new-onset disease) with a mean (SD) age of 63 years (25). The mean start dose of prednisolone was 18.0 mg. The mean time between the active phase and remission was 3.1 months (4.1), mean CRP was reduced by 23.5 mg/dl (95% CI 7.5-39.4, p=0.01) and prednisolone by 6.5 mg (95% CI 0.9-12.1, p=0.02). On the CDUS examinations, a mean reduction of IMC thickness of 0.6 mm (95% CI 0.2-1.0, p=0.004) in the right axillary and 0.7 mm (95% CI 0.2-1.2, p=0.009) in the left axillary arteries were measured. <h3>Conclusions</h3> CDUS of the axillary arteries seems to be a useful tool to monitor treatment response in LVV-GCA. Thus, CDUS of the large vessels has the potential to be used for the assessment of disease activity in LVV-GCA patients. These promising results have to be confirmed in larger cohorts of patients. <h3>References</h3> Diamantopoulos AP, Haugeberg G, Hetland H, Soldal DM, Bie R, Myklebust G. The diagnostic value of color Doppler ultrasonography of temporal arteries and large vessels in giant cell arteritis: A consecutive case series. Arthritis care &amp; research 2013. Schmidt WA, Seifert A, Gromnica-Ihle E, Krause A, Natusch A. Ultrasound of proximal upper extremity arteries to increase the diagnostic yield in large-vessel giant cell arteritis. Rheumatology (Oxford) 2008;47:96-101. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3844
Bleomycin-Induced Alveolitis Detected by FDG Positron Emission Tomography
Authors: SHARON F. HAIN, ANDREW D. BEGGS
Journal: Clinical Nuclear Medicine (2002)

From The Clinical PET Centre, Guy’s and St. Thomas’ Hospital, Guy’s, King’s and St. Thomas’ School of Medicine, London, United Kingdom Received for publication October 10, 2001. Revision accepted December 24, 2001. Correspondence: Sharon F. Hain, The Clinical PET Centre, St. Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom. E-mail: [email protected]
Case 29-2015
Authors: Steven K. Feske, Marcia Goldberg, David M. Dudzinski, Ramon Gilberto Gonzalez, Alexandra E. Kovach
Journal: New England Journal of Medicine (2015)

A 38-year-old pregnant woman presented with headache and visual symptoms. MRI of the brain revealed multiple small infarcts, with no thrombosis. Anemia and eosinophilia were present, as was abnormal endocardial material on echocardiography. Diagnostic tests were performed.
Endoscopic full thickness resection of gastric subepithelial tumors (EndoResect Study)
Authors: C Schlag, D Wilhelm, S von Delius, H Feussner, A Meining
Journal: Endoscopy (2012)

Objective of the study: Endoscopic resection of gastric subepithelial tumors (SETs) bears a high risk of perforation. New techniques such as use of the OTSC®-clip may enable secure endoscopic closure of perforations but have not systematically been analysed. Hence, we aimed to evaluate the feasibility of endoscopic resection of small gastric SETs using a grasp-and-snare technique followed by OTSC®-closure of the gastric wall if necessary.
Abstract 4328: Phenotypic selection for identification of functional antibodies and development of high throughput screening assays.
Authors: Carl Hay, Steven Rust, Erin Sult, Lori Clarke, Kim Rosenthal, Sandrine Guillard, David Lowne, Matt Flynn, Lutz Jermutus, Ralph Minter, Robert Hollingsworth, Kris Sachsenmeier
Journal: Cancer Research (2013)

Abstract Discovery of therapeutic antibodies requires the continued identification of tractable targets, and we have employed a phenotypic screening strategy to this end. In this study, antibodies from phage display libraries were screened for their abilities to inhibit MDA-MB-231 (‘triple negative’) breast cancer cells. The screening cascade included tests for specific cell binding, antibody internalization, and cytotoxicity as an antibody-drug conjugate. Targets of these antibodies then were identified using immunoprecipitation and mass spectrometry, and confirmed by showing diminished antibody binding after siRNA-mediated knockdown of the putative target gene. One target was identified as NT5E (also known as CD73), a 5’-ectonucleotidase. NT5E catalyzes the conversion of adenosine monophosphate to adenosine, and its function has been linked with immunity, angiogenesis, and cancer. To screen for additional inhibitors of this target, a novel, high-throughput ectonucleotidase assay was developed. NT5E activity is typically assayed either by high performance liquid chromatography or by quantification of free phosphate using malachite green, and neither of these methods is suitable for high-throughput screening. One inhibitory antibody was found to significantly slow growth of MDA-MB-231 xenograft tumors in mice. In summary, our phenotypic screening approach provides a mechanism for rapidly discovering and evaluating new antibody targets and is being used to accelerate the discovery of new cancer drugs. Citation Format: Carl Hay, Steven Rust, Erin Sult, Lori Clarke, Kim Rosenthal, Sandrine Guillard, David Lowne, Matt Flynn, Lutz Jermutus, Ralph Minter, Robert Hollingsworth, Kris Sachsenmeier. Phenotypic selection for identification of functional antibodies and development of high throughput screening assays. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4328. doi:10.1158/1538-7445.AM2013-4328
HER2 and HER3 in HPV+ and HPV− HNSCC—Letter
Authors: Jean-Pascal Machiels, Rachel Galot, Sandra Schmitz
Journal: Clinical Cancer Research (2016)

The nice experiments performed by Pollock and colleagues showed that Human papillomavirus (HPV) infection coincided with overexpression of HER2 (ERBB2), HER3 (ERBB3), and the associated HER2:HER3 heterodimer and that this may contribute to EGFR therapy resistance. The authors concluded that pan-HER
AB0849 Oxidative Stress, Anti-Oxidant Activity in Patients with Gout
Authors: T.N. Khalfina, A.N. Maksudova
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Gout is an inflammatory arthritis with crystallization of uric acid in joints and tissues. Oxidative stress is prevalent in many diseases and is considered to be an important pathogenic mechanism. <h3>Objectives</h3> exploration of oxidative stress at patients with gout and with/without tophi <h3>Methods</h3> We had compared products of oxidative stress in 33 healthy persons and 2 group of patients with primary gout: 49 patients without tophi and 25- with tophus gout. Levels of plasma and serum lipid peroxidation (LPO), malondialdehyde (MDA) were used as markers of oxidative stress. Superoxide dismutases (SOD), serum total antioxidant status (TAS) were used as markers of antioxidant activity. <h3>Results</h3> patients with gout had significant elevated LPO on the relation to control group, p&lt;0,05, another products in patients didn9t differ from control group. Our test has showed significant difference of LPO, between control group and patients with tophus gout 7,3 [5,7; 9,1] vs 8,8 [7,7; 11,4] per-unit/1 ml, p&lt;0,05, respectively. The MDA, SOD and TAS level in this group of patients didn9t differ from group of control. In comparison patients from fist group (without tophi) not only had higher level of LPO 10,3 [7,9; 16,6] vs 7,3 [5,7; 9,1] per-unit/1 ml, p&lt;0,05, but more higher level of SOD 0,9 [0,7;1,2] vs 0,65 [0,35; 0,82], mkmol/l, p&lt;0,01 and more lower level of TAS 70,6 [53,6; 77,1] vs 80,7 [69,7; 83,3] %, p&lt;0,01. Distinctions between groups of patients were not revealed. <h3>Conclusions</h3> In patients with gout, there is increase of oxidative stress and decrease antioxidant activity especially in patients without tophi. These changes can testify about active inflammation at earlier stages of gout. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5933
Abstract LB-246: Identification of novel direct targets of miR-19a in MCF-7 breast cancer cells
Authors: Hirotaka Kanzaki, Mamoru Ouchida, Sachio Ito, Seiji Tamaru, Hiroko Hanafusa, Yoshimi Jitsumori, Takashi Oka, Kenji Shimizu
Journal: Cancer Research (2010)

Abstract Background: MicroRNAs (miRNAs) are small non-cording RNAs (20-23 nucleotides) that negatively regulate gene expression at post-transcriptional level by interacting with 3′UTRs of their target mRNAs. Aberrant expression of miRNAs in cancer indicates that miRNAs play key roles in human cancers acting as either oncogenes or tumor suppressor genes depending on their targets. The miR-17-92 cluster, including miR-17-5p, -17-3p, -18a, -19a, -20a, -19b and -92-1, located on C13orf25 is well known as oncogenic miRNA, which is overexpressed in lung cancer, malignant lymphoma and breast cancer. However, few data have been collected about the targets of miRNAs, including miR-17-92 cluster, and their roles in tumorigenesis. By using a proteomic approach, we identify novel direct targets of miR-19a. Methods and Results: MiR-17-92 expression profiling was performed in a subset of 32 of cancer cell lines by TanqMan Real-time PCR, and MCF-7 breast cancer cell line was identified as a miR-17-92 cluster overexpressed cell line. To detect candidate target proteins for miR-17-92 cluster, we transfected MCF-7 cell with antisense oligonucleotides against miR-19a, -20a and -92-1 and then performed two-dimensional protein electrophoresis (2-DE) and differential display analysis in protein extracts of MCF-7 which was knocked down of endogenous miR-17-92 by antisense oligonucleotides. Of the 1455 defined valid protein spots, 146 distinct proteins changed 1.5-fold their expression. 135 proteins were identified as candidate target proteins for miR-17-92 cluster by LC-MS/MS. To determine direct targets of miR-17-92, bioinformatics analysis, luciferase assay and western blotting analysis were performed as validation studies. Conclusions: Our results of exhaustive analysis revealed significant differences in the proteomic profile between anti-miR-LNA treated and non-treated MCF-7 breast cancer cell line. Among these candidate target proteins of miR17-92 cluster, we identified novel direct target of miR-19a. To better evaluate the role of miR-19a and the target gene, further studies of gene function are being performed now. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 LB-246.
REDUCED BLOOD PRESSURE LOWERING EFFECT OF CATHETER-BASED RENAL DENERVATION IN PATIENTS WITH ISOLATED SYSTOLIC HYPERTENSION: DATA FROM POOLED SYMPLICITY HTN TRIALS
Authors: Felix Mahfoud, George Bakris, Deepak L. Bhatt, Murray Esler, David Kandzari, Kazuomi Kario, Henry Krum, Giuseppe Mancia, Ashok Seth, Michael Weber, Robert Whitbourn, Michael Boehm
Journal: Journal of the American College of Cardiology (2015)
Abstract IA-20: EMT in tumor invasion and metastasis
Authors: Thomas Brabletz
Journal: Cancer Research (2009)

Abstract Most colorectal adenocarcinomas (CRC) have mutations in the APC gene leading to overexpression of the Wnt-pathway effector β-catenin. By acting as a transcriptional activator, nuclear β-catenin is involved in two fundamental processes in embryonic development: epithelial to mesenchymal transition (EMT) and generation of stem cells. We have previously shown, that in particular tumor cells at the invasive front of CRCs accumulate nuclear β-catenin, undergo an EMT and aberrantly express EMT-associated transcriptional repressors, like ZEB1. The amount of such cells strongly correlates with clinical outcome and metastasis formation. We further showed that ZEB1 represses target genes involved in basement membrane formation and epithelial cell polarity. Moreover we report that ZEB1 directly suppresses transcription of members of the miRNA-200 family, which strongly activate epithelial differentiation in pancreatic, colorectal and breast cancer cells. Notably, the EMT-activators TGFβ2 and ZEB1 itself are predominant targets downregulated by these miRNAs. These results indicate that ZEB1 triggers a microRNA-mediated positive feedbackloop, which stabilizes EMT and promotes invasion of cancer cells. In contrast tumor cells in central tumor areas are differentiated and often show membranous, E-cadherin-bound β-catenin. Strikingly, metastases show again a differentiated phenotype and lack nuclear beta-catenin, indicating a mesenchymo-epithelial re-transition (MET) and a regulatory role of the tumor environment during malignant tumor progression. Based on the developmental functions of beta-catenin and our data we propose, that the EMT-associated tumor cells at the invasive front act as “migrating cancer stem cells” which can re-differentiate and, depending on the range of dissemination, give raise to the primary carcinoma and metastases. We suggest that both primary tumors and metastases are derived from a pool of EMT-associated “migrating cancer stem cells” at the tumor host interface. They are defined by strong nuclear beta-catenin accumulation and EMT-phenotype, which gives these epithelial tumor cells a feature driving malignant tumor progression including metastasis: the unusual combination of a migratory and stem cell phenotype. Citation Information: Cancer Res 2009;69(23 Suppl):IA-20.
TCT-9 Racial Disparity With On-Treatment Platelet Reactivity In Patients Undergoing Percutaneous Coronary Intervention
Authors: Lakshmana Pendyala, Salem Badr, Israel Barbash, Fang Chen, Kenneth Kent, Hironori Kitabata, Joshua P. Loh, Marco A. Magalhaes, Sa'ar Minha, Alfazir Omar, Augusto Pichard, Lowell F. Satler, William O. Suddath, Rebecca Torguson, Ron Waksman
Journal: Journal of the American College of Cardiology (2013)
Safety Analysis of Folfox as Adjuvant Chemotherapy for Stage III Colon Cancer in North Japan Multicenter Phase II Study (NORTH/HGCSG1003)
Authors: Takahashi Norihiko, Yuki Satoshi, Fukushima Hiraku, Shichinohe Toshiaki, Sasaki Takahide, Kusumi Takaya, Nakamura Fumitaka, Miyagishima Takuto, Iwanaga Ichiro, Hatanaka Kazuteru, Oomori Kazuyoshi, Misawa Kazuhito, Senmaru Naoto, Iwai Kazuhiro, Koike Masahiko, Shinohara Toshiki, Fukushima Tsuyoshi, Ohno Koichi, Tateyama Miki, Nishimoto Naoki, M. Ito Youichi, Komatsu Yoshito
Journal: Annals of Oncology (2014)