tbuckley/cabot-search huggingface dataset:
Abstract 4181: Oncogenic microRNA-183 induces cell growth and motility through down-regulation of Dkk-3 and SMAD4 in bladder cancer.
Authors: Koji Ueno, Hiroshi Hirata, Varahram Shahryari, Yuichiro Tanaka, Z. Laura Tabatabai, Yuji Hinoda, Rajvir Dahiya
Journal: Cancer Research (2013)

Abstract Introduction and Objective : The purpose of this study was to carry out functional analysis of oncogenic microRNA-183 and identify their specific target genes in bladder cancer. Methods : Expression levels of miR-183 in bladder normal/cancer tissues and bladder cancer cell lines were confirmed using real-time PCR. To examine the function of miR-183, cell growth, and migration were performed using UM-UC-3 cells because the miR-183 expression level was highest among bladder cancer cell lines. To search for target genes of miR-183, we used a target scan algorithm and performed Dkk-3 and SMAD4 3’UTR luciferase assays. To analyze whether Dkk-3 and SMAD4 affect cell growth and motility, Dkk-3 and SMAD4 expressing plasmids were transfected into UM-UC-3 cells and cell growth and motility were performed. Results: Expression of miR-183 in cancer bladder tissues was significantly up-regulated compared to normal bladder tissues. MiR-183 expression was significantly higher in the pT3+4 tissues than in pT1+2 tissues. Higher miR-183 expression was significantly associated with shorter survival. MiR-183 increased cell growth and migration abilities in UM-UC-3 cells. MiR-183 decreased 3’UTR luciferase activity of Dkk-3 and SMAD4. Cell growth and motility was significantly decreased in Dkk-3 and SMAD4 transfected cells compared with control cells. Conclusions : MiR-183 is a oncogenic microRNA in bladder cancer through down-regulation of Dkk-3 and SMAD4. Citation Format: Koji Ueno, Hiroshi Hirata, Varahram Shahryari, Yuichiro Tanaka, Z. Laura Tabatabai, Yuji Hinoda, Rajvir Dahiya. Oncogenic microRNA-183 induces cell growth and motility through down-regulation of Dkk-3 and SMAD4 in bladder cancer. [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 4181. doi:10.1158/1538-7445.AM2013-4181
A Dose-Dependent Increase in Mortality with Vesnarinone among Patients with Severe Heart Failure
Authors: Jay N. Cohn, Sidney O. Goldstein, Barry H. Greenberg, Beverly H. Lorell, Robert C. Bourge, Brian E. Jaski, Sidney O. Gottlieb, Frank McGrew, David L. DeMets, Bill G. White
Journal: New England Journal of Medicine (1998)

Vesnarinone, an inotropic drug, was shown in a short-term placebo-controlled trial to improve survival markedly in patients with severe heart failure when given at a dose of 60 mg per day, but there was a trend toward an adverse effect on survival when the dose was 120 mg per day. In a longer-term study, we evaluated the effects of daily doses of 60 mg or 30 mg of vesnarinone, as compared with placebo, on mortality and morbidity.
High Liver FDG Uptake on PET/CT in Patient With Lymphoma Diagnosed With Hereditary Hemochromatosis
Authors: Jose R. Infante, Manuel Moreno, Juan I. Rayo, Justo Serrano, Maria L. Dominguez, Lucia Garcia
Journal: Clinical Nuclear Medicine (2015)

Hereditary hemochromatosis is an autosomal recessive disorder of iron metabolism resulting in toxic accumulation of iron in vital organs. We present a 64-year-old white man with non-Hodgkin lymphoma treated with high-dose chemotherapy and stem cell transplant that was subsequently diagnosed with hereditary hemochromatosis. F-FDG PET/CT was performed as routine follow-up and showed a pathological finding of homogeneous increased liver glucose metabolism. Increased FDG avidity in the liver suggested the presence of damage caused by hemochromatosis.
Abstract P4-12-01: A nomogram based on clinical, imaging and histological data to predict the risk of upgrades to malignancy at surgery in biopsy-diagnosed premalignant lesions of the breast
Authors: C Uzan, C Mazouni, C Balleyguier, M-C Mathieu, M Ferchiou, S Delaloge
Journal: Cancer Research (2012)

Abstract Background: Population-based mammography screening has resulted in the increased detection of suspicious, non-palpable lesions that require histopathological assessment. When a “pre-malignant” lesion, such as lobular carcinoma in situ (LCIS), atypical ductal or lobular hyperplasia (ADH and ALH) or flat epithelial atypia (FEA), is discovered on the primary biopsy, a surgical excision is recommended due to the risk of underestimation of the lesion. DCIS or invasive carcinoma is finally retrieved in 10–30% of the patients, meaning a large part receive unnecessary surgery. The aim of this study was to define a nomogram integrating clinical, imaging and histological data to predict for the risk of underestimation of the lesion. Intentionally, we decided to include all the premalignant lesions which implied the same management, whereas most of the previous models of the literature are focused in only one or another type of atypia. Patients and Methods: We collected complete clinical, radiological and double-reading histological data on all patients with a diagnosis of pure atypical lesion (CLIS, ADH, ALH, FEA) on image-guided biopsy performed at the One-Stop Unjt of our breast care center from 2004 to 2011. Univariate and multivariate logistic regression analyses were used to develop a model predicting for the presence of DCIS or invasive carcinoma on the final surgical sample, and build a nomogram. This nomogram was evaluated on a training set of 205 patients treated at IGR. Results: 205 patients were eligible for the study. Of these 205 patients, 50 cancers (24.4%) were diagnosed at definitive surgery (21 DCIS, 20 ductal and 9 lobular invasive carcinoma). Univariate analysis retrieved age (p = 0.03), number of biopsy cores (p = 0.02) and type of radiological anomalies (p = 0.02) as factors associated with cancer at surgery. The presence of microcalcifications on biopsies of limit significance was included in the multivariate analysis (p = 0.09). The final most informative nomogram included information on patient age (p = 0.03), type of radiological anomalies (p = 0.02) and number of biopsy cores (p = 0.04). The predictive accuracy of the nomogram was 0.71 and 0.68 in the training set before and after bootstrapping, respectively. The calibration of the nomogram was good. The sensitivity, specificity, positive predictive value, and negative predictive values were 68%, 73%, 45%, and 88%, respectively. Conclusion: This nomogram could help identify a subset of patients with premalignant disease for whom surgery could be spared and who would be eligible for exclusive clinical follow-up. A validation study is currently undergoing in an external dataset. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-01.
Primary Tumor Volume Measured by FDG PET and CT in Nasopharyngeal Carcinoma
Authors: Guang-Uei Hung, Iuan-Sheng Wu, Hong-Shen Lee, Weir-Chiang You, Hui-Chuan Chen, Mu-Kuan Chen
Journal: Clinical Nuclear Medicine (2011)

The prognostic value of CT-derived primary tumor volume in patients with nasopharyngeal carcinoma (NPC) has been demonstrated in our previous serial studies. The purpose of the present study is to compare the primary tumor volume measured by FDG PET and traditional CT in NPC, and to ascertain their prognostic value.From 2007 to 2008, 32 patients with newly diagnosed NPC were prospectively studied. All patients underwent a CT scan, followed by a FDG PET/CT scan. CT-derived primary tumor volume (VolumeCT) was measured using the summation-of-area technique. PET-volume was measured using 3 methods: delineating the contour of tumor with the threshold of standardized uptake value (SUV) ≧2.5 (Volume2.5), ≧40% of maximal SUV (Volume40%), and ≧50% of maximal SUV (Volume50%). The primary tumor volumes derived from the 4 methods, VolumeCT, Volume2.5, Volume40%, and Volume50%, were compared. Univariate Cox regression was used to identify the above parameters as prognosticators.The volumes derived from the VolumeCT, Volume2.5, Volume40%, and Volume50% methods were 16.48 ± 12.46 cm(3), 25.87 ± 16.96 cm(3), 13.66 ± 6.90 cm(3), and 8.25 ± 4.52 cm(3), respectively. There was decent correlation between VolumeCT and Volume2.5 (r = 0.64, P = 0.0001), and Volume2.5 was systemically larger than VolumeCT. No significant difference was noted between VolumeCT and Volume40% (P = 0.24), but the correlation was poor (r = 0.15, P = 0.39). For VolumeCT and Volume50%, the difference was significant (P = 0.0006) and the correlation was poor (r = 0.23, P = 0.20). Larger tumor volumes presented as VolumeCT, Volume2.5, and Volume50% were associated with shorter overall survival.PET-derived primary tumor volumes are substantially different from CT-derived tumor volumes, only decent correlation is noted between VolumeCT and Volume2.5. Volume2.5 and Volume50% seem to be reasonable alternatives for VolumeCT in predicting the patient outcomes.
Abstract 3424: Slug-mediated epithelial mesenchymal transition in lung cancer cells
Authors: Tamura Daisuke, Tokuzo Arao, Tomoyuki Nagai, Kazuyuki Furuta, Kazuko Sakai, Kanae Kudo, Hiroyasu Kaneda, Keiichi Aomatsu, Yoshihiko Fujita, Kazuko Matsumoto, Yoshikazu Kotani, Yoshihiro Nishimura, Nagahiro Saijo, Kazuto Nishio
Journal: Cancer Research (2011)

Abstract Epithelial-Mesenchymal Transition (EMT) has been classified as a unique process by which epithelial cells undergo mesenchymal phenotype leading to increased motility and invasion. The aim of this study was to elucidate the biological functions of Slug/Snail2 in lung cancer cells. We introduced Slug gene into several lung cancer cell line (A549, Ma1, and H1299) and established stable cell lines. Overexpression of Slug clearly mediated the EMT-related morphological changes including the cell scattering and the elongation of cell-shape. Real-time RT PCR and Western blot demonstrated that overexpression of Slug markedly downregulated the mRNA levels and protein levels of E-cadherin, while mesenchymal marker, N-cadherin, fibronectin 1 and vimentin, were upregulated. In addition to these changes, Slug enhanced the cellular migration activity and the cellular anchorage independent growth activity. Finally, we examined the Slug-mediated EMT on drug sensitivity to several anti-cancer dugs. Interestingly, Slug-overexpressing cells increased the drug sensitivity to only tubulin-binding agents such as vinorelbine, vincristine, and paclitaxel in vitro. Microarray analysis revealed that Slug downregulates tubulin beta 3 or 4 expression. Luciferase promoter assay showed that Slug directly down-regulates tubulin beta 4 expression at the transcription level. These results suggested that Slug-mediated sensitivity to tubulin-binding agents may be involved in expression changes of tubulin beta 3 or 4.In conclusion, we found that overexpression of Slug mediates EMT and change of drug sensitivity to tubulin-binding agents, presumably via downregulations of tubulin beta 3 and 4 in lung 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 3424. doi:10.1158/1538-7445.AM2011-3424
Uptake and Blood Level of Radioactive Iodine in Hyperthyroidism
Authors: Robert A. Newburger, Solomon Silver, Stephen B. Yohalem, Sergei Feitelberg
Journal: New England Journal of Medicine (1955)

THE most widely applied technic involving the use of radioactive iodine in the diagnosis of hyperthyroidism is the measurement of the thyroid uptake after the oral administration of tracer doses. The size of the tracer and the time at which the uptake is measured have been varied by individual observers. Most determinations, however, are made at twenty-four hours after the tracer dose even though in some patients maximum accumulation will not have occurred at that time, whereas in others the peak uptake may have taken place at an earlier period. In spite of these limitations the measurement of the twenty-four-hour . . .
Abstract 5448: The tricyclic anti-depressant amitriptyline inhibits D-cyclin transactivation and induces myeloma cell apoptosis by inhibiting histone deacetylases
Authors: Xinliang Mao, Wenjie Wang, Biyin Cao, Zhihua Li, Rose Hurren, Suzanne Trudel, Aaron D. Schimmer
Journal: Cancer Research (2010)

Abstract D-cyclins are universally dysregulated in multiple myeloma and contribute to the pathogenesis and chemoresistance of this disease. To identify novel pharmaceutical inhibitors of cyclin D transactivation, we compiled and screened a library of on-patent and off-patent drugs using NIH 3T3 cells stably expressing the Cyclin D2 promoter-driving a luciferase reporter gene. From this screen we identified the tricyclic antidepressant amitriptyline as a novel inhibitor of Cyclin D2 transactivation. In secondary assays, Amitriptyline reduced expression of cyclins D1, D2, and D3 in myeloma cell lines at low micromolar concentrations across a variety of transforming events including c-maf over-expression (JJN3, KMS11, My5 cells), FGFR3 translocation (KMS11, OPM2 cells), and cyclin D1 translocation (KMS12 cells). Consistent with its effects on D-cyclin expression, amitriptyline arrested cells in the G0/G1 phase of the cell cycle at concentrations associated with its ability to decrease D-cyclins. Decreased cyclin D expression and G1 arrest can induce apoptosis. Therefore we tested the effects of amitriptyline on cell viability. Myeloma cell lines were treated with increasing concentrations of Amit and cell viability was measured by the MTS assay. Amitriptyline reduced the viability of myeloma cells with an IC50 &amp;lt; 20 uM within 72hr. In addition, the combination of amitriptyline and dexamethasone synergistically induced cell death. Cell death and apoptosis were confirmed by Annexin V and PI staining and were associated with activation of Caspase-3 and Poly(ADP-ribose)Polymerase (PARP) as detected by immunoblotting. To understand the mechanism by which amitryptiline inhibits D-cyclin transactivation and induces cell death, we examined the effects of this compound on HDAC levels and activity. By immunoblotting, treatment with amitriptyline increased levels of acetyl-Histone 3 in myeloma cell lines. Furthermore amitriptyline decreased levels of HDACs 3, 6, 7 and 8 in examined cell lines with a concentration consistent with the cell death and cyclin D2 inhibition. Thus, in summary, amitriptyline inhibits D-cyclin transactivation in myeloma cells that is associated with reductions in HDAC levels. Given the preclinical activity of amitriptyline in myeloma, this work highlights a potential therapeutic strategy for this disease. 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 5448.
CRYPTOGENIC STROKE AND UNDERLYING ATRIAL FIBRILLATION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROL TRIALS
Authors: Muhammad Afzal, Arun Kanmanthareddy, Sampath Gunda, Donita Atkins, Madhu Reddy, Moustapha Atoui, Jayasree Pillarisetti, Buddhadeb Dawn, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2015)
Establishing transvaginal NOTES for gynecological and surgical indications: benefits, limits, and patient experience
Authors: A. Hackethal, J. Sucke, F. Oehmke, K. Münstedt, W. Padberg, H.-R. Tinneberg
Journal: Endoscopy (2010)

Gynecologists have been performing transvaginal surgery for over a century and consequently the transvaginal approach was advocated for establishing natural orifice transluminal endoscopic surgery (NOTES) in gynecological and surgical practice. From 2008 the NOTES alternative has been offered to selected patients. Transvaginal cholecystectomies were intended in 13 patients and completed in 12. Various additional procedures were performed. All surgical procedures and postoperative courses were uneventful. The mean operating time for transvaginal cholecystectomy only was 88.4 minutes (standard deviation [SD] 17.3). A questionnaire was posted to the patients after a mean follow-up of 8.5 months. Patients primarily chose transvaginal NOTES because of the lack of scarring. Vaginal sensation was not affected. Patients perceived transgastric, transvesical, and transrectal surgery to be less acceptable approaches. The feasibility of transvaginal NOTES was proven for different indications. Patients' experiences and perceptions concerning transvaginal NOTES were excellent.
A simple tissue-handling technique performed in the endoscopy suite improves histologic section quality and diagnostic accuracy for serrated polyps
Authors: Shannon Morales, Carol Bodian, Susan Kornacki, Robert Rouse, Robert Petras, Nicholas Rouse, Lawrence Cohen, Neville Bamji, Kenneth Miller, Roy Soetikno, Tonya Kaltenbach, James Aisenberg
Journal: Endoscopy (2013)

<b>Background and study aims</b>: Surveillance intervals after colonoscopic resection of serrated polyps are partially predicated on the histology of the polyp(s) removed during the index exam. Histologic discrimination between sessile serrated adenomas/polyps (SSA/P) and hyperplastic polyps is challenging. We devised and tested a simple tool – an envelope – that gastroenterologists can integrate into routine colonoscopy practice to address this problem. <b>Methods:</b> In the "modified protocol," immediately after polypectomy each serrated polyp was flattened and enclosed in a paper envelope before being placed in formalin. In the pathology laboratory, each polyp was sectioned after processing. A two-site, prospective, randomized, single-blinded trial was performed to compare this modified protocol with the conventional protocol. Serrated polyps located proximal to the splenic flexure and 5 – 20 mm in diameter were included. A novel orientation score that measured the number of well-oriented crypts per unit area of polyp (higher orientation score = better orientation) was validated. Orientation score, SSA/P diagnosis rate, and inter-pathologist agreement were measured. <b>Results</b>: A total of 375 polyps were enrolled, of which 264 were identified for analysis. The mean orientation scores in the modified and conventional protocol groups were 3.11 and 1.13, respectively (<i>P</i> < 0.0001). SSA/Ps were diagnosed in 103/135 cases (76.3 %) in the modified protocol group vs. 54/129 (41.9 %) in the conventional protocol group (<i>P</i> < 0.0001). Inter-pathologist agreement was higher with the modified than the conventional protocol (77.0 % vs. 62.8 %; <i>P</i> = 0.015). <b>Conclusion</b>: Standard polyp handling techniques may be sub-optimal for interpretation of serrated polyps resected at colonoscopy, and may lead to inadvertent histologic "under-grading" of many lesions. Our intervention improved histopathologic interpretation and increased the SSA/P diagnosis rate.
Medical-Imaging Stewardship in the Accountable Care Era
Authors: Daniel J. Durand, Jonathan S. Lewin, Scott A. Berkowitz
Journal: New England Journal of Medicine (2015)

Though often essential for diagnosis and management, medical imaging is known for low-value uses and as the single largest source of per-capita radiation exposure. The framework used to reduce overuse of antimicrobial agents can help inform imaging-stewardship efforts.
Nuclear receptor co-factor RIP140 promotes hepatic inflammation in cancer cachexia
Authors: Anja Krones-Herzig, Mauricio Berriel Diaz, Inka Zschiedrich, Alexandros Vegiopoulos, Stephan Herzig
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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The excessive loss of body energy stores represents a hallmark of several tumor entities such as pancreatic, colon, or lung cancer. Inflammatory reactions are intimately linked to wasting hypermetabolism under these conditions. However, the molecular basis for cross-talk between metabolic and inflammatory pathways remains largely enigmatic. Therefore, this study aimed at the identification of transcriptional checkpoints for aberrant energy homeostasis during cancer cachexia. Here we show that the expression of nuclear receptor co-factor RIP140 was induced in livers of tumor-bearing, cachectic mice, correlating with a previously unrecognized invasion of macrophages into cachectic liver tissue, and a loss of circulating lipid energy substrates and body weight. Remarkably, liver-specific disruption of RIP140 expression in tumor-bearing animals prevented these cachectic phenotypes -at least in part- through the inhibition of nuclear factor (NF) kappaB-dependent pro-inflammatory genes, identified here as direct RIP140 targets. By triggering inflammatory dyslipidemia via hepatic macrophage recruitment and pro-inflammatory gene expression, the induction of RIP140 in the liver provides a molecular rationale for inter-tissue communication and wasting metabolism in cancer cachexia. Inhibition of hepatic RIP140 transcriptional activity might, thereby, provide an attractive adjunct scheme in the treatment of this condition.
PTU-238 Prep, no prep or more prep? a prospective randomised study comparing two bowel preparation regimes with no preparation on quality of capsule endoscopy
Authors: N Maqboul, A Murugananthan, T Hong, J French, R Chen
Journal: Gut (2012)

<h3>Introduction</h3> Capsule endoscopy (CE) is a widely used method for evaluation of the small bowel. However it does have limitations; visualisation of the small bowel mucosa is often impaired due to the presence of food residue, air bubbles and bile pigments.<sup>1</sup> The effect of bowel preparation on improving visualisation of the small bowel varies<sup>2</sup> and is inconvenient for patients.<sup>3</sup> We aimed to prospectively evaluate the effects of two different bowel preparations on visualisation of the small bowel and on overall diagnostic yield compared with standard dietary changes. <h3>Methods</h3> 51 patients (26 male/25 female; mean age 60.7 years) were randomised into three groups using the sealed envelope technique. Indications for CE were iron deficiency anaemia, obscure GI bleeding (occult and overt) and anaemia. Group 1 (n=19): Clear fluid day before procedure. Overnight fast. Group 2 (n=12): Clear fluid day before procedure. 2L PEG in afternoon of day prior to procedure. Overnight fast. Group 3 (n=20): Clear fluid day before procedure. 1L PEG and 1 sachet Picoprep in afternoon of day prior to procedure. Overnight fast. CE were viewed by a single blinded examiner and adequacy of bowel preparation according to three categories (&gt;80% visualisation; 50%–80% visualisation). <h3>Results</h3> <h3>Conclusion</h3> Our findings are in keeping with a recent meta-analysis which has shown no difference in CE completion rates, GTT and SBTT with purgative preparation.<sup>4</sup> Our study shows a trend towards better caecal completion rates with bowel preparation involving PEG and Picoprep, but these results did not reach statistical significance. Overall diagnostic yield was similar in all three groups. Liquid diet, in combination with fasting, prior to CE is generally better tolerated by patients<sup>3</sup> and our findings would support this as adequate preparation for CE. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Park SC</b>, Keum B, Seo YS, <i>et al.</i> Effect of bowel preparation with polyethylene glycol on quality of capsule endoscopy. <i>Dig Dis Sci</i> 2011;<b>56</b>:1769–75. 2. <b>Dai N</b>, Gubler C, Hengstler P, <i>et al.</i> Improved capsule endoscopy after bowel preparation. <i>Gastrointest Endosc</i> 2005;<b>61</b>:28–35. 3. <b>Pons Beltrán V</b>, González Suárez B, González Asanza C, <i>et al.</i> Evaluation of different bowel preparations for small bowel capsule endoscopy: a prospective, randomised, controlled study. <i>Dig Dis Sci</i> 2011;<b>56</b>:2900–5. 4. <b>Rokkas T</b>, Papaxoinis K, Triantafyllou K, <i>et al.</i> Does purgative preparation influence the diagnostic yield of small bowel video capsule endoscopy? : a meta-analysis. <i>Am J Gastroenterol</i> 2009;<b>104</b>:219–27.