tbuckley/cabot-search huggingface dataset:
Abstract 2663: Preclinical pharmacokinetic characterizations and human pharmacokinetic prediction of AMG 900, an orally available small molecule inhibitor of aurora kinases
Authors: Liyue Huang, Xuhai Be, Loren Berry, Wei-Jiang Pan, Zhiyang Zhao, Min-Hwa Jasmine Lin
Journal: Cancer Research (2010)

Abstract Introduction: AMG 900 is a small molecule being developed as an orally administered, highly potent and selective pan-aurora kinase inhibitor. AMG 900 is currently undergoing phase 1 clinical evaluation in patients with advanced solid tumors. The objectives of the studies were to characterize single dose pharmacokinetics (PK) of AMG 900 in preclinical species and use the preclinical PK data to predict its human PK. Methods: Following a single intravenous and oral administration of AMG 900 to mice, rats, dogs, and monkeys, blood samples were collected and processed for plasma by centrifugation. AMG 900 plasma concentrations were determined by LC-MS/MS. Non-compartmental analysis of the concentration - time data was performed to calculate PK parameters of AMG 900. Human PK were predicted based on data from preclinical species using the simple allometric scaling method assuming a human body weight of 60 kg. Results: AMG 900 exhibited low (mouse, monkey and dog) to moderate (rat) clearance in the species evaluated. The volume of distribution at steady state was less than 0.5 L/kg across species. Following intravenous administration, the compound had terminal elimination half-life ranging from 0.6 to 2.4 hours. AMG 900 was well absorbed in fasted animals across species with an oral bioavailability ranging from 31% to 104%. The clearance and volume of distribution at steady state in humans were predicted to be 0.03 L/hr/kg and 0.1 L/kg, respectively, with the predicted half-life to be approximately 2.3 hours. Bioavailability after oral administration of AMG 900 was predicted to be 75%, calculated from the mean values observed in non-clinical species. Conclusion: AMG 900 exhibits good PK properties in preclinical species and it was predicted to have low clearance and good oral bioavailability in human. Available PK results from the on-going phase 1 trial are consistent with the allometric scaling predictions. 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 2663.
SAT0059 Inhibition of CIP2A facilitate C-MYC independent apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis
Authors: J. Lee, J.W. Hwang, J.W. Noh, E.-J. Park, B. Huang, J.K. Ahn, J. Kim, H.-S. Cha, E.-M. Koh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that leads to cellular proliferation in cancer cells by stabilizing c-Myc protein. The effect of CIP2A in stabilizing c-Myc by inhibition of protein phosphatase 2A activity is a prerequisite step in tumor cell growth and in vivo tumor formation. We have previously shown that CIP2A is expressed in RA FLS and its expression is strongly associated with histopathological synovitis score and invasive function of RA FLS. However, the effect of CIP2A in association with c-Myc on the apoptosis of RA FLS is unknown. <h3>Objectives</h3> This study was undertaken to investigate the effect of CIP2A and c-myc on the apoptosis of RA FLS and to determine the signaling pathway through which dysfunctional apoptosis is facilitated. <h3>Methods</h3> Proliferation and apoptotic activity of RA FLS following treatment with CIP2A siRNA or control siRNA were analyzed using MTT assays and Cell Death Detection ELISA kit. c-Myc expression from RA FLS after treatment with CIP2A siRNA or control at 3, 6, 9 days interval was also determined using Western blot analysis. To evaluate which signal transduction pathways were engaged in apoptosis, caspase-3 activity and phosphorylation of the Akt kinase were also analyzed by Western blot. <h3>Results</h3> Survival of RA FLS as measured by MTT assay was significantly lower in CIP2A siRNA -treated group compared to control after 7 days (n=5, each, p=0.0221). Apoptosis of RA FLS as measured by DNA fragmentation was significantly higher in CIP2A siRNA treated group compared to control when incubated for 3, 6 and 9 days (p=0.029, p=0.021, p=0.043, respectively). C-Myc expression measured by Western blot did not change during the incubation period. Apoptosis of CIP2A siRNA-treated RA FLS was induced by activation of caspase-3 and dephosphorylation of Akt kinase, but these findings were not observed in the control siRNA-treated RA FLS. <h3>Conclusions</h3> Our data show that CIP2A expression in RA FLS is an important mediator of dysfunctional apoptosis that is independent of c-Myc stabilization. CIP2A may induce dysfunctional apoptosis of RA FLS by activation of Akt and deactivation of caspase-3. These results warrant further investigation of CIP2A as a potential pathogenetic factor and therapeutic target in RA. <h3>Disclosure of Interest</h3> None Declared
Linked Databases Help Researchers Track Costs, Care Patterns, Outcomes
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Linked Databases Help Researchers Track Costs, Care Patterns, Outcomes Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 3, 2 February 1994, Pages 168–169, https://doi.org/10.1093/jnci/86.3.168 Published: 02 February 1994
FRI0166 Ankylosing Spondylitis Associated ERAP1 Variants Alter the Unfolded Protein Response
Authors: N. Haroon, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Endoplasmic reticulum aminopeptidase 1 (ERAP1) has recently been identified to be strongly associated with HLA-B27 positive AS. We have shown that ERAP1 variants cause changes in free heavy chain (FHC) expression on peripheral blood mononuclear cells from HLA-B27 positive patients as well as on B27-expressing C1R cells by <i>in vitro</i> assays. Unfolding of HLA-B27 and the formation of FHC can cause the release of inflammatory cytokines by triggering the unfolded protein response (UPR). <h3>Objectives</h3> To generate an <i>in vitro</i> system with HLA-B27 expressing C1R (B-lymphoblastoid) cells that express different ERAP1 varaints. Using this system we will tested if ERAP1 variants asociated with AS can result in increase in UPR. <h3>Methods</h3> Endogenous ERAP1 was silenced in C1R-HLA-B27 cells with ERAP1-shRNA (C1R<sup>ERAP1sh</sup>). C1R cells with stable ERAP1-shRNA expression were identified by GFP expression and were selected with puromycin. Scrambled sequence shRNA was used as control. Western blot (WB) for ERAP1 suppression was done using ERAP1 antibody. We then transfected either the common variant ERAP1 (ERAP1<sup>WT</sup>) or one of the two AS-associated ERAP1 variants, K528R or Q730E into the C1R<sup>ERAP1sh</sup> cells. Lentivirus expression vector alone was used as control and exogenous ERAP1 expression was tracked with HA-tag. Stable cells expressing ERAP1<sup>WT</sup> or ERAP1-variants were selected by hygromycin. UPR was measured using PCR for spliced variants of XBP-1 and by qRT-PCR and western blot for BiP, CHOP and ATF-6. <h3>Results</h3> Almost all C1R cells that were selected by antibiotics were GFP positive indicating stable ERAP1-shRNA expresion. Using WB we noted more than 90% suppression of ERAP1 and more than 75% suppression by qRT-PCR in C1R<sup>ERAP1sh</sup>, compared to the cells with scrambled-sequence shRNA. Anti-HA WB showed uniform strong expression of ERAP1<sup>WT</sup> and variant forms of ERAP1 in the respective cell lines. Spliced XBP1, a marker of UPR, was upregulated in the C1R<sup>ERAP1sh</sup> cells. Re-introduction of ERAP1 (C1R-ERAP1<sup>WT</sup> cells) reduces the UPR response while C1R-ERAP1<sup>K528R</sup> and C1R-ERAP1<sup>Q730E</sup> cells expressing the ERAP1 variants had higher UPR activation compared to C1R-ERAP1<sup>WT</sup> cells. Other UPR markers including BiP, CHOP and ATF6 expression followed the same pattern with AS-associated variants leading to higher UPR. <h3>Conclusions</h3> ERAP1 suppression leads to increased UPR. AS-associated ERAP1-variants, which are known to have reduced function, leads to more UPR compared to the common variant of ERAP1. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5951
Analysis of percutaneous transhepatic cholangioscopy-related complications and the risk factors for those complications
Authors: H.-C. Oh, S. Lee, T. Lee, S. Kwon, S. Lee, D.-W. Seo, M.-H. Kim
Journal: Endoscopy (2007)

Percutaneous transhepatic cholangioscopy (PTC) is being increasingly used for patients with biliary tract diseases. The aim of this study was to assess the safety of this procedure, and we systematically analyzed PTC-related complications and the risk factors for those complications.A total of 364 patients who underwent PTC were included in the study. The initial diagnoses, the indications for PTC, the complications that occurred during the procedures, and the risk factors for these complications were retrospectively analyzed.The overall incidence of complications was 12.9 % for percutaneous transhepatic biliary drainage (PTBD), 12.8 % for tract dilation, and 6.9 % for tract maturation. Complications developed in 58/848 PTC sessions (6.9 %). Cholangitis and bacteremia were associated with PTBD and tract dilation, catheter migration and blockage with tract maturation, and bile duct injury with PTC. Mild complications occurred in 80 patients (22.2 %) during the preparation stages and in 43 sessions (5.1 %) during the PTC itself. Severe complications, including severe hemobilia, hemoperitoneum, rupture of the sinus tract, and ductal injury developed in 17 patients (4.7 %) during the preparation period, and in 15 patients (4.1 %) during PTC. The overall incidence of severe complications along the entire course was 8.2 % (30/364 patients). No patient died or required surgery. Intraductal manipulations, such as electrohydraulic lithotripsy or balloon dilation, and the first session of PTC were risk factors for procedure-related complications.PTC is a relatively safe and well-tolerated method for treating certain biliary tract diseases. Meticulous patient selection and a cooperative team approach are required in order to minimize the incidence of complications and to provide effective management.
Abstract 2698: Alternative expression of <i>E2F1</i>, <i>EZH2</i> and <i>SUZ12</i> response for the invasive progression of superficial bladder cancers.
Authors: Se-Ra Lee, Yun-Gil Roh, In-Sun Chu, Young Il Yeom, Sun-Hee Leem
Journal: Cancer Research (2013)

Abstract A superficial bladder cancer is a noninvasive cancer that is presented as a good prognosis after receiving treatment, and noninvasive. However, about 20∼50% of superficial bladder cancer patients progressed to invasive tumor which represent the poor survival rates within 5 years. In previous study, we addressed if the transcriptional characteristics of the superficial bladder cancer could be used as predictive biomarkers for the progression of superficial tumors to invasive ones. Using gene expression data from 165 bladder cancer patients, we identified a gene expression signature that could predict the likelihood of progression to invasive tumors. Gene network analyses of the signature revealed that E2F1 and its downstream effectors EZH2 and SUZ12 could be important mediators for the invasive and metastatic progression of superficial tumors. In this study, we investigated how these genes may affect the invasive and metastatic progression of superficial tumors. We investigated the invasive ability by these genes in two groups of bladder cancer cell lines: One group (UC5 and UC9) has a superficial signature of bladder cancer, and the other group (EJ and 5637) has an invasive signature of bladder cancer. We examined the effects of overexpression or siRNA inhibition of these genes on cell growth, migration and invasion in bladder cancer cell lines. We will report the results estimating the roles of these genes for the invasive and metastatic progression in bladder cancer cell lines. Citation Format: Se-Ra Lee, Yun-Gil Roh, In-Sun Chu, Young Il Yeom, Sun-Hee Leem. Alternative expression of E2F1, EZH2 and SUZ12 response for the invasive progression of superficial bladder cancers. [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 2698. doi:10.1158/1538-7445.AM2013-2698
Directions and beliefs of self-presentational bias
Authors: David C. Funder
Journal: Behavioral and Brain Sciences (2011)

Abstract The target article tends to conflate self-deception and self-enhancement, but biased self-presentation can be negative as well as positive. Self-deceiving self-diminishers may be depressed and non-self-deceiving self-diminishers may project false modesty. The article's otherwise brilliant argument for the advantages of self-deceptive self-enhancement for deceiving others may underemphasize the risks it entails for poor decision making.
Abstract P2-02-08: 3-Tesla MRI Is More Useful for the Evaluation of Intraductal Spreading Area of Breast Cancer: A Comparative Study with Conventional 1.5-Tesla MRI
Authors: H Tanaka, M Kubo, T Kamitani, H Yamamoto, K Shirahane, M. Tanaka
Journal: Cancer Research (2010)

Abstract Background: High quality of space and temporal resolution is demanded from the diagnosis for intraductal spreading area of breast cancer. In our hospital, from April 2007, 3-Tesla (T) MRI was transduced and high resolution dynamic studies for bilateral mammary have been performed. We have reported the accuracy of 3-T MRI in the evaluation of intraductal spreading area of breast cancer at 31st SABCS. At this time, we demonstrate our follow-up data. Methods: We assessed 256 patients with primary breast cancer who underwent the 3-T or 1.5-T breast MRI as pre-operative examination between April, 2007 and February, 2010. Concerning the diagnosis of intraductal spreading area of breast cancer, we weighed 3-T MRI against conventional 1.5-T MRI. Using 1.5-T or 3-T MRI (Achieva, Philips), we injected contrast medium (Magnepist) with 0.2ml/kg body weight in 1ml/sec and photographed five aspects before injection and after injection for every 90 seconds. We obtained fat-sat T1-weighted magnetic resonance image (T1WI), multi-planar reconstruction (MPR) image and standard maximum intensity projection (MIP) image based on T1WI by coronal section, and furthermore slab MIP image with Aquerius net (Terarecon), and we evaluated the enhanced area. Results: 138 cases were examed with 1.5-T MRI, and 118 cases with 3-T MRI. In 1.5-T group, 40 cases (30%) were underestimated, additional resection were required intraoperativelly with cancer-cells positive surgical margin in 18 cases (13%), and surgical margin was positive with carcinoma cells by final pathological findings in 12 cases. In two patients we were forced to changes from breast-conserving surgery to mastectomy, and two cases underwent reoperation (mastectomy) with the diagnosis of widely positive surgical margin. In comparison with 1.5-T MRI group, 16 cases (14%) were underestimated in 3-T MRI group, intraoperative addition resection in eight cases (7%), and surgical margin positive by the final pathological findings in 13 cases, respectively. Conclusions: The concern to enhance an artifact is known on 3-T MRI because it has high resolution. However, it may be more useful rather than1.5-T MRI because of its high resolution, to evaluate the intraductal spreading area of breast cancer and to determine the extent of surgical resection. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-02-08.
RELATIVE ATHEROSCLEROTIC PLAQUE VOLUME BY CT CORONARY ANGIOGRAPHY TRUMPS CONVENTIONAL STENOSIS ASSESSMENT FOR IDENTIFYING FLOW-LIMITING LESIONS
Authors: Nahoko Kato, Satoru Kishi, Armin Zadeh, Frank Rybicki, Shuzou Tanimoto, Jiro Aoki, Masahiko Asami, Mika Watanabe, Yu Horiuchi, Koichi Furui, Masaya Shinohara, Tatsuyuki Kato, Kentaro Yasuhara, Kazuhiro Hara, Kengo Tanabe
Journal: Journal of the American College of Cardiology (2015)
The role of salvage ERCP for the treatment of post-ERCP pancreatitis
Authors: Alberto Murino, Andrea Anderloni, Cesare Hassan, Lorenzo Fuccio, Alesandro Repici
Journal: Endoscopy (2015)

We read with great interest the article by Kerdsirichairat et al. titled “Urgent ERCP with pancreatic stent placement or replacement for salvage of post-ERCP pancreatitis” [1]. The authors reported their experience of performing an urgent endoscopic retrograde cholangiopancreatography (ERCP) to place a pancreatic stent in patients who developed post-ERCP pancreatitis (PEP). PEP was defined by abdominal pain (using the revised Atlanta criteria), serum amylase level at least three times greater than the upper limit of normal, and more than one night of hospitalization (the so-called “Cotton criteria” [2]). Salvage ERCP was attempted 2 hours or more after clinical onset of pain. Compared with before salvage ERCP, the median pain score (P < 0.001), and median amylase (P = 0.003) and lipase (P = 0.001) levels significantly improved 24 hours after the procedure. In addition, systemic inflammatory response syndrome (SIRS) resolved in 24 hours (P < 0.001).
Advanced endoscopic imaging using narrow-band imaging for diagnosis of Whipple's disease
Authors: H. Neumann, K. Mönkemüller, M. Neurath, M. Vieth
Journal: Endoscopy (2012)

Various systemic and gastrointestinal diseases cause mucosal alterations of the duodenum. These include celiac disease, Crohn's disease, congenital enteropathies (e. g. microvillous inclusion disease, tufting enteropathy), and Whipple's disease [1] [2] [3]. Thus careful endoscopic inspection and targeted biopsies are strongly recommended to achieve a correct diagnosis and avoid false reassurance.
PWE-131 Propofol deep sedation for small bowel enteroscopy in elderly patients in a world gastroenterology organising endoscopy training center in Thailand
Authors: S Amornyotin, S Kongphlay
Journal: Gut (2012)

<h3>Introduction</h3> The aim of the study is to compare and evaluate the clinical efficacy of propofol deep sedation (PDS) for small bowel enteroscopy (SBE) procedure in elderly patients in a teaching hospital in Thailand. <h3>Methods</h3> This study was a retrospective study. All SBE patients were classified into two groups by using age: group 1 (Age &lt;65 years) and group GA (Age ≥65 years). The primary outcome variable of the study was the successful completion of the procedure. Failed procedure is defined as the procedure can not be completed by using PDS technique or sedation-related serious adverse events such as severe hypoxaemia, severe cardiorespiratory instability, are occurred. The secondary outcome variables were sedation-related complications, haemodynamic parameters and mortality rate. <h3>Results</h3> 116 patients underwent SBE procedures by using PDS technique. Premedications were none before the procedure. After matching gender, weight, ASA physical status and indications of procedures, there were 45 patients in group 1 and 28 patients in group 2. There were no significant differences in gender, weight, height, ASA physical status and indications of procedures among the two groups. All procedures were successful completion but one in group 1. Mean dose of propofol, fentanyl and midazolam in both groups was comparable. There were no significant differences in the complication rate, mortality rate and haemodynamic parameters between the two groups. <h3>Conclusion</h3> In the setting of developing country, PDS for SBE procedure in elderly patients by experienced anaesthesiologist with appropriate monitoring were relatively safe and effective. Sedation-related complications in elderly patients are relatively higher than in the younger patients, but not significantly different. <h3>Competing interests</h3> None declared.
Abstract 2696: TMPRSS4 regulates levels of integrin alpha-5 in NSCLC through miR-205 activity.
Authors: Leyre Larzabal, Miriam Redrado, Arrate Lopez de Aberasturi, Paloma Rueda, Maria J. Rodriguez, Lissette Lopez, Luis Montuenga, Alfonso Calvo
Journal: Cancer Research (2013)

Abstract TMPRSS4 is a membrane-anchored protease involved in cell migration and invasion in different cancer types including lung cancer. We have previously shown that TMPRSS4 expression is increased in NSCLC and that its inhibition through shRNA reduces lung metastasis. The goal of the present study was to elucidate molecular mechanisms involved in the protumorigenic role of TMPRSS4 in NSCLC. A knock down strategy and microarray analyses were established to identify genes regulated by TMPRSS4. Among other genes, miR-205 was identified as an overexpressed gene upon TMPRSS4 downregulation. Levels of miR-205 were found to be reduced in NSCLC cells compared to non-malignant cells. miR-205 overexpression promoted the acquisition of an epithelial phenotype with increased E-cadherin and reduced fibronectin expression, probably through the regulation of transcription factors ZEB1 and ZEB2. Furthermore, miR-205 inhibited very significantly (p&amp;lt;0.01) tumor cell migration, invasion and metastasis formation in vivo. A further transcriptional and luciferase assays in miR-205-overexpressing cells identified integrin alpha-5 (a proinvasive protein overexpressed in tumors) as a new miR-205 target in NSCLC. We have therefore demonstrated for the first time a new molecular connection between TMPRSS4 and integrin alpha-5 through miR-205. Citation Format: Leyre Larzabal, Miriam Redrado, Arrate Lopez de Aberasturi, Paloma Rueda, Maria J. Rodriguez, Lissette Lopez, Luis Montuenga, Alfonso Calvo. TMPRSS4 regulates levels of integrin alpha-5 in NSCLC through miR-205 activity. [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 2696. doi:10.1158/1538-7445.AM2013-2696
Early Planar and Early SPECT Tc-99m Sestamibi Imaging
Authors: Isabel Martínez-Rodríguez, Ignacio Banzo, Remedios Quirce, Julio Jiménez-Bonilla, Humberto Portilla-Quattrociocchi, Pamela Medina-Quiroz, María De Arcocha, José Manuel Carril
Journal: Clinical Nuclear Medicine (2011)

To evaluate whether an early protocol (EP) (early planar and early SPECT) with Tc-99m sestamibi could demonstrate the delayed image of the established dual-phase scintigraphy unnecessary without any decrease in sensitivity for the localization of parathyroid adenomas.A study was carried out in 80 consecutive patients with primary hyperparathyroidism (65 women; mean age, 61.8±14.2 years). Final diagnosis by surgery was possible in 79 patients and confirmed parathyroid adenoma in 76 patients, 1 hyperplasic gland in 1 patient, 2 hyperplasic glands in 1 patient, and differentiated thyroid carcinoma in another patient. Ten minutes after intravenous injection of 740 MBq (20 mCi) of Tc-99m sestamibi, a planar image followed by a SPECT and a 2 to 3 hours delayed planar image were acquired. Two sets of images were evaluated, one without (EP) and the other with the delayed image (dual-phase protocol [DPP]). An abnormality rating of 0 to 4 was given to each set and was compared with the final diagnosis.When any focal uptake, no matter the intensity, was considered positive, that is setting the threshold in the abnormality rating 1, 71 of the 76 adenomas were correctly localized by DPP and EP (sensitivity: 93.4%).The delayed planar image could be omitted without any loss in sensitivity for the localization of parathyroid adenomas, and therefore EP could replace DPP.