tbuckley/cabot-search huggingface dataset:
Abstract 825: Molecular mechanisms of regulation of cytochrome P4501A enzymes by 3-methylcholanthrene (MC) in micein vivo
Authors: Bhagavatula Moorthy, Jiang Weiwu, Lihua Wang, Chun Chu, Sudha R. Kondraganti, Paramahamsa Maturu
Journal: Cancer Research (2015)

Abstract 3-Methylcholanthrene (MC) is one of the most potent polycyclic aromatic hydrocarbons (PAHs) present in cigarette smoke, diesel exhausts, and charcoal broiled meats, etc. Cytochrome P450 (CYP)1A enzymes play key roles in the activation of PAHs to carcinogenic metabolites. We previously showed persistent induction of CYP1A enzymes by MC in vivo. In this study, we tested the hypothesis that MC elicits persistent induction of CYP1A1 in vivo by sustained transcriptional activation of the CYP1A1 promoter. Thirty two C57B6 (WT) mice were divided into two groups. Group I was treated with vehicle corn oil (CO) (8ml/kg) and group II was treated with a single dose of MC (100 μmol/kg), i.p. Four animals from each group were sacrificed at 6, 12, 24, and 48 h after MC withdrawal. The mRNA levels, protein content and enzyme activities of CYP1A1 were determined by real-time PCR, Western blotting, and fluorimetry, respectively at different time points. In addition, the binding of MC-AHR-AHR nuclear translocator (ARNT) to the AHREs on the CYP1A1 promoter region were determined by chromatin immunoprecipitation (ChIP) assay. The translocation of AHR was also analyzed by immunofluorescence. The ChIP experiments indicated that transcriptional activation of CYP1A1 was most pronounced at 6 h, followed by 12 h, but declined at later time points. On the other hand, the expression of CYP1A1 at the mRNA, protein and enzyme levels persisted for up to 48 h both in lung and liver tissues. These results suggest that transcriptional activation of CYP1A1 at 6-12 h is sufficient to result in sustained induction of CYP1A mRNA and protein expression for up to 48 h. Isolation of the immunoprecipitated promoter fragment (containing the xenobiotic response elements), which binds to the MC-AHR complex, followed by 32P-postlabeling revealed the formation of MC-DNA adducts, suggesting that DNA adducts are sequence-specific and target the CYP1A1 promoter. Our results suggest that DNA adducts might play a role in regulation of CYP1A1 by MC, a phenomenon that may be of relevance to PAH-mediated carcinogenesis. Citation Format: Bhagavatula Moorthy, Jiang Weiwu, Lihua Wang, Chun Chu, Sudha R. Kondraganti, Paramahamsa Maturu. Molecular mechanisms of regulation of cytochrome P4501A enzymes by 3-methylcholanthrene (MC) in mice in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 825. doi:10.1158/1538-7445.AM2015-825
Ileocutaneous fistula with distal ileal narrowing treated with an esophageal stent
Authors: Amir Kashani, Shirin Towfigh, Laith Jamil
Journal: Endoscopy (2015)

A 70-year-old man was referred to our institute for endoscopic management of an enterocutaneous fistula that had developed following surgical repair of a ventral hernia. A previous surgical approach had failed, as shown by imaging before and after surgery ([Fig. 1]).
Suppression of Thyrotropin (H-TSH) in Serums of Patients with Myxedema of Varying Etiology Treated with Thyroid Hormones
Authors: Gerald E. Cotton, Colum A. Gorman, William E. Mayberry
Journal: New England Journal of Medicine (1971)

Abstract Patients with myxedema and high thyrotropin (h-TSH) levels were given levothyroxine (l-T4) orally in doses increasing stepwise from 0.025 to 0.2 mg per day at 3-week intervals. The serum h-TSH response was similar regardless of etiology of the myxedema. In all but one patient, h-TSH levels were suppressed to normal at 0.2 mg per day, but at lower doses, many patients still had increased h-TSH levels when total and free T4 levels were normal. h-TSH was correlated with dose of T4 (r equals -0.99), total T4 (r equals -0.99), and free T4 (r equals -1.0). Five patients were given levo-tri-iodothyronine (l-T3) orally in doses increasing each week by 25 μg daily to 100 μg per day; serum h-TSH levels became normal in all patients with 100 μg per day but not with 75 μg per day. For T3 suppression tests, 75 μg per day is not sufficient for routine use. Serum h-TSH levels appear to offer the best means of diagnosing hypothyroidism and assessing adequacy of thyroid-hormone therapy.
Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia
Authors: T Iwai, S Yokota, M Nakao, T Okamoto, M Taniwaki, N Onodera, A Watanabe, A Kikuta, A Tanaka, K Asami, I Sekine, H Mugishima, Y Nishimura, S Koizumi, Y Horikoshi, J Mimaya, S Ohta, K Nishikawa, A Iwai, T Shimokawa, M Nakayama, K Kawakami, T Gushiken, N Hyakuna, N Katano, M Tsurusawa, T Fujimoto
Journal: Leukemia (1999)
LONG TERM IMPACT OF PROXIMAL LEFT ANTERIOR DESCENDING ARTERY LESIONS IN PATIENTS WITH THREE-VESSEL AND/OR LEFT-MAIN CORONARY ARTERY DISEASE: A PATIENT-LEVEL POOLED ANALYSIS OF 3280 PATIENTS FROM THE SYNTAX, PRECOMBAT AND BEST TRIALS
Authors: Rafael Cavalcante, Yohei Sotomi, Cheol Whan Lee, Jung-Min Ahn, Pannipa Suwannsom, Yaping Zeng, Yoshinobu Onuma, Seung-Jung Park, Patrick Serruys
Journal: Journal of the American College of Cardiology (2016)
HEALTH STATUS AFTER TRANSCATHETER OR SURGICAL AORTIC VALVE REPLACEMENT IN HIGH-RISK PATIENTS WITH SEVERE AORTIC STENOSIS: RESULTS FROM THE COREVALVE US PIVOTAL TRIAL
Authors: Suzanne Arnold, Matthew Reynolds, Kaijun Wang, Elizabeth Magnuson, Suzanne Baron, Khaja Chinnakondepalli, Michael Reardon, Peter Tadros, George Zorn, Brijeshwar Maini, Mubashir Mumtaz, John Brown, Robert Kipperman, David Adams, Jeffrey Popma, David Cohen
Journal: Journal of the American College of Cardiology (2015)
P386 Th17 EFFECTOR CELLS MAY BE INVOLVED IN THE BILE DUCT DAMAGE CHARACTERISTIC OF AUTOIMMUNE SCLEROSING CHOLANGITIS
Authors: R. Liberal, C.R. Grant, Y. Ma, M.A. Heneghan, G. Mieli-Vergani, D. Vergani, M.S. Longhi
Journal: Journal of Hepatology (2014)
Abstract 2734: Genome-wide analysis of direct Nkx3.1 target genes
Authors: Monica Logan, Philip Anderson, Sarki Abdulkadir
Journal: Cancer Research (2011)

Abstract NKX3.1 is an androgen-regulated, prostate-specific tumor suppressor gene that is essential for development and maintenance of the prostate gland. Loss of Nkx3.1 expression results in the formation of premalignant lesions called prostatic intraepithelial neoplasia lesions (PIN). With additional mutations, these PIN lesions will progress to invasive carcinoma and eventually to metastatic disease in which there is currently no effective treatment. The specific mechanism(s) by which Nkx3.1 suppresses prostate tumorigenesis remains unknown. Previous gene expression profiling studies in Nkx3.1-deficient mouse prostates have shown aberrant expression of many genes that may be involved in prostate tumorigenesis. However, it is unknown whether these genes are direct targets of Nkx3.1 in vivo. To identify direct Nkx3.1 target gens, we used chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) to identify Nkx3.1 binding sites in the genomes of a human prostate cancer cell line (LNCaP) as well as the normal mouse prostate. We obtained 7 to 15 million uniquely mapped tags each from Nkx3.1 ChIP-seq using LNCaP cells or Nkx3.1+/+, Nkx3.1+/−, and Nkx3.1−/− mouse prostates. This led to the identification of about 8000 Nkx3.1 binding sites in the genome (the Nkx3.1 cistrome). The binding site data were integrated with gene expression profiling results from Nkx3.1 mutant mice to yield a core set of “direct” Nkx3.1 target genes. One gene in particular that is upregulated in Nkx3.1 mutant mice and in human prostate tumors and bound by Nkx3.1 in our ChIP-Seq studies is the receptor activity modifying protein 1 (RAMP1) gene. Ramp1 is a single transmembrane protein that is required for trafficking of the calcitonin gene-related peptide (CGRP) receptor to the plasma membrane. The CGRP receptor binds CGRP, a neuropeptide that has been shown to promote cancer progression. Current studies are focused on whether RAMP1 expression in human prostate cancer cells function to promote tumorigenesis. Given that Ramp1 is localized to the plasma membrane, data from my project may provide support for investigating Ramp1 as a therapeutic target for prostate cancer or for imaging prostate lesions. 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 2734. doi:10.1158/1538-7445.AM2011-2734
P5-14-20: Neoadjuvant Chemotherapy (NCT) in 466 Patients for Operable Breast Cancer: The Prognostic Value of SBR Grade Variation.
Authors: C Abrial, M-A Mouret-Reynier, Q Wang-Lopez, X Durando, E Thivat, I Raoelfils, P Gimbergues, Praagh-Doreau I Van, J-M Nabholtz, P Chollet, F Penault-Llorca
Journal: Cancer Research (2011)

Abstract Purpose of the study: In a new database harbouring the patients of several prospective phase II neoadjuvant trials (fec 50–100, net, tncf, taxotere/tncf, taxotere alone), the predictive value of tumour factors (SBR grade, RH, Her2, Ki-67 and cycline D1) was studied in 466 women with stage II-III operable breast cancer treated between 1991 and 2006. Patients and methods: Median age of the patients was 48 years [27-76]. Median diameter of the invasive tumour was 40 mm [10-130]. 382 (82%) patients had a canalar, 57 (12.2%) a lobular, 14 (3%) a mixed or invasive carcinoma, 3 (0.6%) neoplasic cells only and 10 (2.2%) another carcinoma. Before chemotherapy, 33% were grade III SBR. The median number of NCT courses was 6 [1-8] followed by a surgery for 98%, a radiotherapy for 93%, an adjuvant chemotherapy (20%) and/or a hormonotherapy (56%). Results: Overall response rate was 73% (18% complete). The complete pathological response (pCR) rate was 17.2% according to Chevallier's classification. On 455 patients operated, 324 (71%) had a conservative surgery. On 390 patients with an axillary dissection, 195 (50%) had involved nodes (median number: 2 [1-20]). After a median follow-up of 135 months, DFS and actuarial survival at 120 months were 61.9% and 73%, respectively. After chemotherapy, we found a significant variation for SBR grade ***: there was five fold more patients for whom we observed a down grading of the SBR grade (grade 2/3 to grade 1) than up grading (grade 1 to grade 2/3), p=6.1.10−6. For patients in objective response, we observed a significant decrease of SBR grade (p=1.7.10−3). Moreover, the variation of SBR grade was also pronostic. Indeed, the disesase-free survival for patients who presented a SBR down grading after chemotherapy was significantly better (p=0.031) compared to patients for whom SBR grade remained stable or was in up grading. There was a tendancy for overall survival (p=0.15). Conclusion: Down grading of SBR grade appears linked to response and so may constitute a parameter of better prognostic. At the opposite, up grading of SBR grade is an adverse prognostic factor. To conclude, it is interesting to emphasize that SBR grade variations can be assessed when patients are not in pCR, ie plays a complementary role. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-20.
AB0458 Better retention rate at 5 years of anti-TNF agents used in conjonction with methotrexate over time in patients with rheumatoid arthritis: Real-life data from rhumadata computarized database
Authors: D. Choquette, J.-P. Raynauld, B. Haraoui, D. Sauvageau
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-TNF agents have been in used in Canada for the last ten years. Although a vast body of clinical experience has been accumulated since that time, there are still areas of uncertainty in their usage. One of them is whether usage in monotherapy has a similar clinical efficacy profile than usage in combination with a DMARDS. Products monograph actually disclosed that both usage are officially indicated base on short term Phase III and Phase IV trials results. <h3>Objectives</h3> The primary objective of this study is to compare the survival rates of two different anti-TNF agents, adalimumab (ADA) and etanercept (ETA) used as first biologic agent with and without associated DMARDS in the treatment of rheumatoid arthritis (RA) using the data coming from the Rhumadata computarized database at the Institute of Rheumatology of Montreal. The secondary objective is to evaluate the influence of baseline demographic and clinical data on the primary outcome. <h3>Methods</h3> Data for all patients with rheumatoid arthritis according to the ACR criteria included in the database since 2005 and exposed for the first time only to an anti-TNF agents were extracted. Only patients exposed to adalimumab and etanercept were included in this analysis to standardize route of administration. Demographics and baseline clinical data are: age, gender, disease duration,tender joint count (TJC), swollen joint count (SJC), disease activity score including DAS 28 ESR and CRP 3-4 variables, CDAI, SDAI, Rheumatoid Factor and Anti-CCP baseline status, ESR and CRP at baseline, HAQ score, VAS fatigue scale, VAS pain Scale, morning stiffness duration, Dmards and glucocorticoid usage. <h3>Results</h3> Data from 249 patients with rheumatoid arthritis are used. 95 and 154 patients were respectively using adalimumab or etanercept. All baseline demagraphic and clinical variables were comparable for both group (performed T-Test=non significant). There was slightly more usage of Dmards with ADA than ETA (89% vs 78%, p=0.02). TJC slightly lower for ETA than ADA (7.3 vs 9.5, p=0.04). There were more female patients in the monotherapy group than in the combination group (75% vs 90%, p=0.01). The 4 year survival rates (Kaplan-Meier survival proportion) for ADA+DMARDS vs ADA mono are respectively 56% and 11% (p=0.03 Log-rank statistic), for ETA+DMARDS vs ETA mono, 67% vs 47% (p=0.007), for combined ETA-ADA+DMARDS vs ETA-ADA MONO, 62% vs 40% (p=0.001) and for ADA or ETA both on MTX, 67% vs 57% (p=0.12). <h3>Conclusions</h3> Combination of etanercept or adalimumab with a traditional DMARDS agent such as methotrexate exhibit a far better survival rate at 4 years than adalimumab or etanercept used in monotherapy. <h3>Disclosure of Interest</h3> None Declared
MS-11 * CLEAR CELL PETRO-CLIVAL MENINGIOMA IN A FIVE YEAR OLD CHILD - HISTOPATHOLOGICAL DIAGNOSIS AND LONG-TERM CLINICAL FOLLOW-UP
Authors: T. Juratli, K. Geiger, T. Lautenschlaeger, M. V. d. Hagen, G. Schackert, M. Kirsch
Journal: Neuro-Oncology (2014)

Intracranial meningiomas are rare in children. We report on a 5 year-old girl who was presented with a one-week history of cephalgia, ataxia, and left sided torticollis. Magnetic resonance imaging (MRI) revealed a dumbbell-shaped homogeneously petro-clival gadolinium-enhancing mass. A staged operative approach was chosen and a complete removal of the tumor was achieved. Due to recurrent tumor progressions, the child underwent several surgeries and two cranial radiations. None of the treatments were efficient enough to stop tumor progression. Consequently, the child died at the age of 14 after further extensive intra- and extracranial tumor progression. The initial histological examinations (at the age of 5 years) revealed a clear cell meningioma WHO grade II with an MIB-1 labeling index <1%, which gradually increased with every recurrence up to 10% by the last progression at the age of 13. Analogically, an increasing over-expression of EGF-, PDGF-, and VEGF-receptors with each recurrence was observed. In reviewing the literature, there have been only 10 reported cases of intracranial clear cell meningioma in children, none of which obtained a serial pathological investigation. The pathologic findings, treatment options, and present understanding of this tumor are discussed in this work.
Abstract 1011: Coronary Artery Calcification is More Strongly Associated With Hard Coronary Events Than High-Sensitive C-Reactive Protein in the General Population: Data From the Heinz Nixdorf Recall Study
Authors: Stefan Mohlenkamp, Nils Lehmann, Susanne Moebus, Axel Schmermund, Nico Dragano, Marcus Bauer, Hagen Kalsch, Barbara Hoffmann, Andreas Stang, Martina Broecker-Preuss, Klaus Mann, Johannes Siegrist, Karl-Heinz Jockel, Raimund Erbel
Journal: Circulation (2009)

Background: High sensitive C-reactive protein (hsCRP) and coronary artery calcium (CAC) are both associated with impaired outcome in persons at risk of cardiovascular events. However, their predict...
Stromal-epithelial cell cross-talk in the breast tumour microenvironment elicits changes in tumour epithelial cell gene expression.
Authors: SM Potter, RM Dwyer, MJ Kerin
Journal: Cancer Research (2009)

Abstract Abstract #1053 Introduction Tumour growth &amp; progression in breast cancer is a product of autocrine &amp; paracrine actions of factors secreted by malignant epithelial &amp; stromal populations in the tumour microenvironment. Stromal cells, recognised as prominent modifiers of cancer progression, are thought to play a critical role in controlling neoplastic epithelial cell function. Although chemokines, which are chemotactic cytokines, have been postulated as mediators of stromal-epithelial cell signalling, the precise nature of such intricate interactions remains incompletely understood. The aim of this study was to investigate stromal cell-mediated modification of breast cancer epithelial cells.&amp;#x2028; Methods Two breast cancer cell lines with different hormone receptor profiles (ER+ MDA-MB-231 &amp; ER- T47D) were cultured individually &amp; on confluent monolayers of stromal cells isolated from primary breast tumours. Co-culture supernatants were harvested for chemokine quantitation by ELISA. Following direct co-culture breast cancer epithelial cells were retrieved from mixed populations with EpCAM specific magnetic beads &amp; RNA extracted. Changes in gene expression in epithelial cells resulting from interaction with stromal cells were identified by RQ-PCR using primers for the chemokines Monocyte Chemotactic Protein-1 (MCP-1/CCL2), &amp; Stromal Cell Derived Factor-1α (SDF-1α/CXCL12), as well as their respective receptors, CCR2 &amp; CXCR4. Changes in expression of genes involved in invasion (MMP11 &amp; HER-2) and proliferation (Ki67) were also analysed.&amp;#x2028; Results Expression of CCR2 &amp; CXCR4 was confirmed in epithelial cell lines. Co-cultures of epithelial &amp; stromal cells secreted significantly higher levels of MCP-1 than the cells cultured alone, while the reverse was true of SDF-1α secretion (Table 1). RQ-PCR revealed changes in gene expression of epithelial cells retrieved following co-culture with tumour stromal cells. The highly invasive MDA-MB-231 cells showed upregulation of both CCL2 &amp; CXCL12 genes (2-3 fold increase) following interaction with tumour stromal cells, while the non invasive T47D cells showed downregulation of these genes. Expression of genes specifically associated with invasion, Her2 &amp; MMP11, were elevated (1-2 fold increase) following exposure to tumour stromal cells, with little or no change observed in the proliferative marker Ki67.&amp;#x2028; &amp;#x2028; Conclusion Tumour stromal cells induce altered secretion &amp; expression of tumourigenic chemokines &amp; invasion-associated genes in breast cancer epithelial cells, mediated through direct cell contact. These results further define the tumour promoting role of stromal cells &amp; highlight these interactions as potential therapeutic targets. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1053.
Real-Time Localization of Parathyroid Adenoma during Parathyroidectomy
Authors: Jagadeesan Jayender, Thomas C Lee, Daniel T Ruan
Journal: New England Journal of Medicine (2015)

ly used antifibrotic agent, in inducing remission in patients with idiopathic retroperitoneal fibrosis. 1In addition, biologic therapies such as the B-cell-depleting antibody rituximab and the interleukin-6-receptor blocker tocilizumab induced regression of idiopathic retroperitoneal fibrosis in patients with glucocorticoid-refractory disease. 2,3Glucocorticoids and rituximab are also effective for patients with IgG4-related disease, a systemic fibroinflammatory condition that may encompass retroperitoneal fibrosis. 4We believe that these findings are extremely relevant for the management of retroperitoneal fibrosis and that they provide substantial evidence that targeting inflammation may lead to regression of abnormal fibrosing responses.
FRI0404 Cardiac blocks in systemic sclerosis: prevalence and associated features in the eustar cohort
Authors: G. Cuomo, S. Vettori, M. Iudici, U. Mueller-Ladner, C. Denton, L. Czirják, Y. Allanore, O. Distler, G. Riemekaisten, G. Valentini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cardiac blocks (CBs) (atrioventricular blocks, left bundle branch block, left anterior fascicle block ± right bundle block) are known to reflect myocardial fibrosis in patients with Systemic Sclerosis (SSc). Their prevalence has been already assessed in EUSTAR cohort on 3656 patients (1). Nevertheless, only a few associated features were investigated. <h3>Objectives</h3> To assess the prevalence of CBs in a larger series and investigate associated clinical and therapeutic features. <h3>Methods</h3> Data from 10183 SSc patients (87% females, 13% males; 31% diffuse disease, 69% limited disease); aged from10-91 years-median age 56; with a disease duration ranging from (0.83-76 years - median 9 years) entered in the EUSTAR MEDS-online system, the largest online SSc database in the world, from 2003 to July 2012 were analyzed retrospectively. CBs as well as other epidemiological, clinical and therapeutic aspects were deduced from Minimal Essential Data Set charts. <h3>Results</h3> CBs were detected at enrollment in 968 patients (10%). In univariate analysis CBs were found to be associated with epidemiological [ male sex ( OR 1.6, 1.4-1.9); age &lt;56 (median age at presentation) (OR 1.81, 1.58-2.08)]; clinical [diffuse disease (OR 1.28, 1.12-1.47); anti-Scl-70 positivity (OR 1.45, 1.26-1.60); interstitial lung disease (OR 1.35, 1.05-1.73); tendon friction rubs (OR 1.5; CI 1.2-1.9); articular involvement (OR 2.0, CI 1.7-2.3); renal involvement (OR 2.1, CI 1.5-3.1); and other features reflecting myocardial fibrosis such as an inversion E/A ratio (OR 3.49, 3-4) and LVEF &lt;50% (OR 2.89, 1.68-4.98)] and therapeutic [CCB, ACE inhibitor use]. In multivariate analysis CB were significantly associated with male sex (p&lt;0.0001), anti-Scl70 positivity (p=0.0004) only. <h3>Conclusions</h3> We confirm the already reported association of CCBs with anti-Scl-70 positivity. The detected association with CCB and ACE is likely to reflect confounding for indication. <h3>References</h3> Walker UA, Tyndall A, Czirjak L. Ann Rheum Dis 2007; 66:754-63 <h3>Disclosure of Interest</h3> None Declared