tbuckley/cabot-search huggingface dataset:
PTH-080 Risk Profile For Non-alcoholic Fatty Liver Disease (nafld) In A Paediatric Specialist Care Setting
Authors: FWD Tai, Y Derwa, S Naik, W Alazawi
Journal: Gut (2014)

<h3>Introduction</h3> Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver dysfunction in adults. Much less is known about this disease in children, although obesity and metabolic dysfunction are believed to be risk factors. In England the prevalence rates of obesity in children in Reception classes (age 4) and Year 6 (age 11) are 10.8% and 22.4% <sup>[1]</sup> respectively in 2012/13. In inner city populations such as those served by The Royal London Hospital (RLH), these rates are even higher (12.3% to 13.2% in Reception and 22.9% to 27.3%<sup>1</sup> in Year 6). Our aims were to determine the prevalence of NAFLD in our specialist clinics in our unit and to identify key characteristics of children with NAFLD. <h3>Methods</h3> Clinical records of patients who attended specialist paediatric Hepatology and Metabolic clinics at RLH in 2012 were reviewed. We recorded demographic information, serum biochemistry (abnormal ALT- females &gt;35 U/L, males &gt;40 U/L), liver screening tests, hepatic ultrasound results and insulin resistance (HOMA-IR) were calculated. <h3>Results</h3> Twelve of 155 patients (8%) (7/62 Hepatology (11%), 5/93 Metabolic (5%) clinics) had evidence of hepatic steatosis on ultrasound. The mean BMI percentile in the Hepatology clinic for NAFLD patients was the 93<sup>rd</sup> (vs 63<sup>rd</sup> in non-NAFLD patients, P = 0.005), whereas all patients in the metabolic clinic (irrespective of NAFLD) had BMI above 3.5 standard deviations for age. The mean age of patients with NAFLD was similar to that of patients without NAFLD (12.5 vs. 12.1 years), and there was no significant difference in the proportion of males with NAFLD compared to children without. All NAFLD patients had elevated ALT (mean 93, range 38–168). Nine patients with normal ALT (mean 16, range 12–23) had undergone abdominal ultrasound and none of these had signs of steatosis. The mean HOMA-IR in those with radiological evidence of steatosis was significantly greater than those with normal ultrasound (7.64 vs. 3.37, p = 0.005). Only two patients had a liver biopsy, both of which showed advanced fibrosis. Nine patients in the metabolic clinic (10%) with elevated ALT (mean 59, range 36–115) had not had a liver screen or ultrasound. <h3>Conclusion</h3> Paediatric NAFLD is common in this setting and is associated with raised BMI and elevated insulin resistance. All patients with raised ALT, and none with normal ALT, had steatosis on ultrasound in our cohort. This highlights the importance of screening for liver disease including the use of ultrasonography in at-risk patients with abnormal liver chemistry. There is a need for an evidence-based algorithm to guide liver investigation and referral in children with deranged LFTs. <h3>Reference</h3> 1 Health and Social Care Information Centre. National Child Measurement Programme – England, 2012–13 school year [NS]. 2013; http://www.hscic.org.uk <h3>Disclosure of Interest</h3> None Declared.
P4-07-08: Subsets and Molecular Signatures of Circulating Tumor Cells in Breast Cancer Brain Metastasis.
Authors: D Marchetti, L Zhang, M Wetzel, T Zaidi, L Ridgway, W Schoeber, W He, MD Groves, RL Katz
Journal: Cancer Research (2011)

Abstract Background: Circulating tumor cells (CTCs) represent the “seeds” of intractable brain metastatic breast cancer (BMBC); however, properties of CTCs targeting the brain remain elusive. For example, the FDA-approved CTC platform (CellSearch™, Veridex, LLC) detects only CTCs positive for epithelial cell adhesion molecule (EpCAM) and cytokeratins (CKs), but is unable to capture any other CTC subtypes or analyze biomarkers of brain-homing CTCs. We hypothesized that profiling CTCs from BMBC patients might result in the identification of brain-colonizing CTC signatures. Materials and Methods: We employed CellSearch™ and a novel technology that uses analysis of specific antigenic markers by immunofluorescence, coupled with detecting gene amplification by fluorescence in situ hybridization on the same cells; and quantification of the signal via automated scanning (FICTION; BioView Duet-3™ system). Results: We established that our approach was feasible by performing CTC analyses on peripheral blood mononuclear cells isolated from BMBC patients or patients not possessing overt metastatic disease. We detected a differential gene amplification for human epidermal growth factor receptor1 and 2 (EGFR and HER2, respectively). Second, the number of EpCAM-positive CTCs visualized by the BioView™ platform was at least three orders of magnitude higher than one obtained from CellSearch™ CTC analyses using the same specimen. Third, we identified the presence of CTCs positive for CKs but negative for EpCAM. Conversely, high levels of prometastatic heparanase, in conjunction with the expression of aldehyde dehydrogenase-1 (ALDH1), a known cancer stem-cell marker, were detected in CTCs from BMBC patients; with a correlation between heparanase, ALDH1, and high EGFR amplification. Finally, extensive flow cytometric/FACS analyses validated the presence of CTC subsets negative for EpCAM and CD45, a hematolymphoid marker, however enriched for heparanase/ALDH1 expression. Discussion: These findings indicate that the BioView™ platform not only captures more EpCAM-positive CTCs than CellSearch™ but also allows the detection of novel CTC subtypes possessing varying EpCAM levels. Importantly, they suggest that profiling CTC subtypes in patients with BMBC can be relevant towards the discovery of BMBC founder CTCs. Work is ongoing to further characterize these CTC subtypes, and to assess their abilities to metastasize to brain in xenotransplantation studies using immunodeficient mice. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-08.
P51 * PREPARATION OF ASIATIC ACID LOADED NANOPARTICLES FOR DELIVERY ACROSS THE BLOOD BRAIN BARRIER AND ITS EFFECTS ON GLIOBLASTOMA CELLS IN VITRO
Authors: F. Thakor, P. J. Welsby, K.-W. Wan, G. Welsby
Journal: Neuro-Oncology (2014)

INTRODUCTION: Drug delivery across tight junctions of the blood brain barrier poses a significant challenge to glioma treatment. Biodegradable nanoparticles (NPs) formulated with poly-ɛ-caprolactone were prepared to investigate sustained delivery of asiatic acid (AA). METHOD: Blank & drug-loaded NPs were prepared by the solvent displacement method using a two-phase system consisting of acetone & water; drug (AA or cisplatin) was dissolved in the organic phase. NPs were characterised for stability, encapsulation efficiency, biodegradation & rate of drug release. The IC50 values for AA & cisplatin in SVGP12 and U87-MG cell lines were also established. RESULTS: Blank NPs were produced in the range of 131-148nm ( Day 0: 133 ± 2; Day 60: 142 ± 5), with AA- loaded particles in the range of 150-151nm ( Day 0: 153 ± 3; Day 60: 150 ± 1). NPs had a negative surface charge of -17 ± 1 mV to -31 ± 3 mV and -20 ± 1 mV to -30 ± 1 mV for blank & AA-loaded NPs, respectively. Polydispersity index was <1 demonstrating a monodisperse, uniform polymer was created. NPs were stable for a minimum of 60 days. AA-loaded NPs had a drug loading efficiency of 28 ± 1.2%, showing a sustained drug release in phosphate buffered saline at pH 7.4 & pH 5.5 over 24hrs. An enhanced drug release of 65 ± 4% at the end of 24hrs along with NP degradation was observed in the presence of lipase. The IC50 values for AA & cisplatin at 48hrs were 67mM & 10mM for SVGP12 and 50mM & 7mM for U87-MG cells respectively. CONCLUSION: This study provides a method for the preparation of stable, monodispersed NPs containing AA, showing a sustained drug release. Future work will examine the ability of the NPs to cross the blood brain barrier using an in vitro model system.
SAT0431 In de quervain’s with a separate epb, us-guided injection is more effective than a manual technique
Authors: K. Kume, K. Amano, S. Yamada, K. Hatta, N. Kuwaba, K. Amano
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> De Quervain's disease (dQD) is a stenosing tenosynovitis of the first compartment of the wrist, which is formed by the tendons of the abductor pollicis longus (APL) and extensor pollicis brevis (EPB).There are two types of dQD. Type I dQD is characterized by a tight constriction of both tendons by a clear loop-shaped retinaculum with no evidence of septation between the two tendons. Type II dQD is characterized by an evident septation, and the retinaculum compresses only the EPB.Intra-sheath steroid injection is one of the best therapeutic approaches to dQD. However, in some cases (15–20%) it is not sufficiently effective. Intra-sheath injection failure is probably due to the presence of septation. We hypothesized that, in case of injection failure due to septation, a US-guided injection targeting the EPB might be effective. <h3>Objectives</h3> We compared US-guided injection, targeting the EPB in dQDwith septation, to clinical injection. <h3>Methods</h3> Forty-four wrists were randomly allocated to US-guided or manual (non-US-guided) injection. We conducted questionnaires related to subjective symptoms (wrist pain by 100 mm VAS) at baseline and 4 weeks after injection. All patients with worsening dQD disease activity at 4 weeks were allowed to switch to surgery (the patient's choice).The primary outcome was a reduction in wrist pain (VAS) from baseline to 4 weeks in each group. The secondary outcome was the proportion of patients who switched to surgery within 6 weeks after injection in each group. <h3>Results</h3> At 4 weeks, pain was significantly reduced in both groups. Pain on the 100 mm visual analogue scale (VAS) for the US group was 80.3 (SD 19.6) mm at baseline and 25.6 (SD 15.1) mm at 4 weeks after injection (<i>p</i>=0.004). Values for the manual group were 78.0 (SD 18.5) mm at baseline and 58.2 (SD 21.9) mm at 4 weeks after injection (<i>p</i>=0.04). Pain on the VAS showed a more significant decrease in the US-guided than in the manual injection group (<i>p</i>=0.0007) from baseline to 4 weeks after injection. Only two patients in the US group and nine in manual group required surgery. The ratio of surgeries to total number was significantly lower in the US than the manual group (<i>p</i>&lt;0.01; Chi-square test). <h3>Conclusions</h3> The results of this study suggest US-guided injection targeting the EPB in dQD patients with septation is more effective than manual injection. <h3>References</h3> Volpe A, Pavoni M, Marchetta A, et al. Ultrasound differentiation of two types of de Quervain's disease: the role of retinaculum. Ann Rheum Dis. 2010, 69: 938–9. <h3>Disclosure of Interest</h3> None Declared
Visible peritoneal catheter during colonscopy
Authors: S. Mahady, M. Bourke
Journal: Endoscopy (2011)

A 54-year-old woman with a past history of IgA nephropathy, chronic renal failure, and hypertension was referred for outpatient colonoscopy to investigate a history of change in bowel habit with intermittent diarrhea. Non-invasive investigations including stool tests had failed to find a cause.
P191 With A Low Incidence Of Drug-induced Hepatitis, Should We Be Offering Latent Tb Treatment To More Patients Over The Age Of 35?
Authors: P. Howlett, N. Lungu, W. Owen, R. Breen, L. Baker
Journal: Thorax (2014)

<h3>Introduction</h3> NICE guidelines recommend patients &gt;35 yrs at risk of tuberculosis (TB) on screening, but without active disease, should not be offered latent TB infection (LTBI) treatment unless a healthcare worker, or HIV positive. This is based on perceived risks of drug-induced hepatitis, and reduced diagnostic sensitivity of LTBI in &gt;35’s. 3 months Rifampicin/Isoniazid (3RH) is commonly used however in a review of LTBI treatment, only one Hong-Kong based study found 1766/100,000 (n = 170) had symptomatic hepatitis or alanine aminotransferase (ALT) &gt;250 IU (Grade 3 hepatitis).<sup>1</sup> Prompted by improved sensitivity of LTBI case finding with interferon gamma testing, and local case of active TB in a contact &gt;35 yrs, we studied whether those &gt;35 yrs with LTBI, treated with 3RH experienced greater hepatotoxicty than <h3>Method</h3> We retrospectively analysed electronic patient records detailing LTBI patient treatments from June 2008–2013 from two hospitals, collecting baseline clinical data and ALT level &gt;2 weeks into treatment. <h3>Results</h3> Of 270 eligible patients, 151 had complete results and were included. 98/151 (65%) were 35 yrs (range 35–75), of whom 32 (60%) were male. Only 3 patients (2 males) developed ALT &gt;250 IU/L (rate of 1,987/100,000), all patients were symptomatic and required treatment cessation. Ages were 31, 32 and 52 yrs and the single female patient was pregnant starting treatment. None required admission and all liver function returned to normal following cessation. <h3>Discussion</h3> This study, although small, provides a similar rate of hepatitis (defined &gt;250 IU/L or symptoms) to the only previous study using the 3RH regimen and shows no age specific differences in ALT results. In light of this, we raise the question; with increasing rates of TB in the UK, a large proportion of which is attributable to latent infection, should we be offering LTBI treatment to more patients &gt;35 yrs? This study suggests the need, and provides important information for, planning a larger study to help answer this question. <h3>Reference</h3> Ormerod <i>et al</i>. BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-a Thorax 2005;60:800–805
From Dancing to Debilitated
Authors: Brian A. Houston, P. Elliott Miller, Lisa M. Rooper, Paul J. Scheel, Allan C. Gelber
Journal: New England Journal of Medicine (2016)

A 69-year-old man with a history of hypertension, hyperlipidemia, gastroesophageal reflux, and adult-onset diabetes mellitus presented with fatigue and a 14-kg unintentional weight loss over the preceding year.
Abstract LB-241: Targeting cancer cells and anti-tumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma in vivo
Authors: Jianmin Qin
Journal: Cancer Research (2012)

Abstract BACKGROUND and AIMS: In vitro and in vivo studies have showed that brucine can inhibit the growth of liver cancer cells and animals with bearing cancer, and may be a promising anti-cancer drugs. However, high toxicity, poor water solubility, short half-life, narrow therapeutic window, close therapeutic and toxic dose limit its clinical application in malignant tumor treatment. In this study, we report on the preparation, in vivo disrtibution and anti-tumor effect of the brucine immuno-nanoparticles. METHODS: Anionic polymerization and chemical modification technology was used to prepare carboxylated polyethylene glycol-poly lactic acid copolymer carrier material, phacoemulsification technology was employed to prepare carboxylated polyethylene glycol-polylactic acid copolymer brucine nanoparticles and chemical coupling technology was utilized to develop anti-human AFP McAb-polyethylene glycol-poly lactic acid copolymer brucine immuno-nanoparticles. The nude mice in situ transplanted liver cancer model was established by surgical technique, and the brucine immuno-nanoparcitles was injected by caudal vein at indicated time. The liver and kidney function and AFP level were assayed, and the anti-tumor effect was observed after intravenous administration of the brucine immuno-nanoparticles.RESULTS: This results showed that in vivo application of brucine immuno-nanoparticles caused temporary liver and kidney functions damage and significantly reduced AFP secretion. Brucine immuno-nanoparticles had good slow releasing and tumor targeting properties. The brucine immuno-nanoparticles inhibited CD34 expression and angiogenesis of tumor tissues, induced tumor apoptosis, and inhibited tumor growth. CONCLUSIONS: The brucine immuno-nanoparticles has good tumor targeting and obvious anti-tumor effects, and is a promising targeted drug for liver cancer therapy in the future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-241. doi:1538-7445.AM2012-LB-241
Unintentional Intra-arterial Injection of a Bone-imaging Agent
Authors: GOULD A. ANDREWS, JOSEPH L. THEOCHEUNG, ELLEN ANDREWS, KENNETH R. TYLER
Journal: Clinical Nuclear Medicine (1980)

The inadvertent intra-arterial injection of a dose of Tc-99m-MDP is reported. Limited quantitative studies were done on the distribution pattern. More extensive investigations of cases of this type may yield useful data on the behavior of radiopharmaceuticals.
Abstract C30: p53-independent 8-amino-adenosine mediated breast cancer cell death
Authors: Alla Polotskaia, Jill Bargonetti
Journal: Cancer Research (2011)

Abstract Nucleoside analogues are routinely used as breast cancer chemotherapeutics however which death pathways they trigger in the various subtypes of breast cancer, based on the p53 biomarker status, has not been adequately assessed. Here we compare the effectiveness of the novel compound 8-amino-adenosine to gemcitabine (a commonly used nucleoside analogue for the treatment of breast cancer). Gemcitabine requires functional wild-type p53 to work as a cytotoxic drug and we asked if 8-amino-adenosine could act as a cytotoxic agent independently of p53. We found that regardless of the p53-status, 8-amino-adenosine was highly cytotoxic in a panel of breast cancer cell lines. 8-amino-adenosine was a more effective cytotoxic agent than either gemcitabine or etoposide in the breast cancer cell line MCF-7 (having wild-type p53) or MDA-MB-468 and T47-D, (having oncogenic mutant p53) as well as with the cell line MDA-MB-231 (highly metastatic containing mutant p53). Importantly, in the presence of wild-type p53, in contrast to the outcomes with gemcitabine and etoposide, 8-amino-adenosine did not increase transcription of the p53 target gene p21 or protein levels of either p53 or p21. The death pathway mediated by 8-amino-adenosine in MCF-7 cells was apoptotic as the pan-caspase inhibitor ZVAD blocked cell death and PARP cleavage. Additionally, knockdown of functional p53 by inducible shRNA did not inhibit 8-amino-adenosine mediated cell death, further supporting a p53-independent death pathway. Interestingly, the death pathway mediated by 8-amino-adenosine in the metastatic cell line MDA-MB-231 (containing mutant p53) correlated with an increase in LC3-II and no PARP cleavage, suggesting an increase in autophagy. In conclusion, 8-amino-adenosine is cytotoxic to breast cancer cells with non-functional p53 and may be an effective treatment of breast cancer regardless of the status of the p53 biomarker. Acknowledgement: We thank Steven T. Rosen, Mala Shanmugam and Nancy Krett for the 8-amino-adenosine compound and valuable discussions. The Breast Cancer Research Foundation supported this work. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C30.
Abstract 1394: Beta-cryptoxanthin suppresses cancer cell motility and angiogenesis via inhibiting alpha 7-nicotinic acetylcholine receptor-mediated PI3K pathway
Authors: Benchun Miao, Xiang-Dong Wang
Journal: Cancer Research (2011)

Abstract Epidemiologic studies show that increased dietary intake or higher blood levels of one specific carotenoid, beta-cryptoxanthin (BCX), is strongly associated with a reduced risk of lung cancer. However, the biological activities and molecular targets by which BCX functions as a chemopreventive agent against lung cancer are poorly understood. Recent studies show that both nicotine and nicotinic acetylcholine receptors (nAChRs) play crucial roles in cancer cell survival, proliferation, migration, invasion and angiogenesis. In particular, alpha 7-nAChR is the main subunit mediating the effects of nicotine in lung carcinogenesis. Here we report that BCX suppresses cancer cell motility and angiogenesis by inhibiting the expression of alpha 7-nAChR and its mediated PI3K pathway in vitro. Similar to MG624, an alpha 7-nAChR-specific antagonist, BCX significantly inhibited migration and invasion of alpha 7-nAChR positive lung cancer cells and endothelial cells in both transwell and wound healing assays, but both MG624 and BCX were inactive in alpha 7-nAChR negative cells. Moreover, BCX and MG624 were synergized in suppressing cell migration due to the fact that BCX, but not MG624, is effective at suppressing alpha 7-nAChR at both mRNA expression and protein levels. Furthermore, the inhibition of cell migration by BCX was attenuated in PTEN-deficient U87MG cells or MCF-7 cells which express constitutively active PI3K. BCX also effectively inhibited nicotine and PNU282987, an alpha 7-nAChR-specific agonist-stimulated cell migration, endothelial cell tube formation and microvessel outgrowth in an aortic ring model. Immunocytochemistry analysis showed that BCX effectively suppressed actin reorganization, lamellipodia and stress fiber formation induced by overexpression of wild type PI3K downstream molecules Rac and Rho, while constitutively active Rac and Rho attenuated the inhibition of cell migration by BCX. Moreover, BCX suppressed activities of matrix metalloproteinase (MMP)-2 and MMP9, two downstream molecules of alpha 7-nAChR/PI3K. Conclusively, these data demonstrate that BCX can inhibit cancer cell motility and angiogenesis by suppressing alpha 7-nAChR expression and its downstream PI3K pathway. This could be one of the potential mechanisms for the chemopreventive effect of BCX against lung cancer (Supported by NIH R01CA104932). 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 1394. doi:10.1158/1538-7445.AM2011-1394
Impairment of Cardiac Function in Patients with Pectus Excavatum, with Improvement after Operative Correction
Authors: G. David Beiser, Stephen E. Epstein, Morris Stampfer, Robert E. Goldstein, Stanton P. Noland, Sidney Levitsky
Journal: New England Journal of Medicine (1972)

Although pectus excavatum is thought to impair cardiac performance, no consistent hemodynamic abnormalities have been identified. We hypothesized that cardiac function might be impaired during upright exercise when the heart descends into the pectus deformity. Catheterization of the right side of the heart in six patients with pectus excavatum gave normal results, and the hemodynamic response to supine exercise was normal. In contrast, cardiac output (CO) during intense upright exercise was low in two patients, at the lower limits of normal in one, and low normal in two. The CO and stroke-volume responses to mild upright exercise also differed from normal. After operative repair in three patients, CO during intense upright exercise increased an average of 38 per cent, and hemodynamic responses to mild upright exercise also changed toward normal. No alterations occurred in the response to supine exercise. Thus, pectus excavatum can reduce the pumping capacity of the heart during upright exercise, and hemodynamic improvement occurs after surgical correction.