tbuckley/cabot-search huggingface dataset:
Abstract 976: CUDC-101, a hybrid molecular targeted agent, reverses multiple mechanisms of drug resistance.
Authors: Kenneth K.W. To, Daniel C. Poon, XG Chen, Ge Lin, Li-wu Fu
Journal: Cancer Research (2013)

Abstract CUDC-101, a hybrid molecular targeted agent, reverses multiple mechanisms of drug resistance CUDC-101 is a potent molecular targeted anticancer agent, rationally designed to simultaneously inhibit HDAC, EGFR and HER2. It exhibits potent antiproliferative and proapoptotic activities in both in vitro and in vivo assays and it is currently in Phase 1b clinical trial. Multidrug resistance (MDR) is a major unresolved obstacle to successful cancer chemotherapy. It is often associated with increased ABC transporters-mediated efflux of substrate anticancer drugs out of the cell. Platinum (Pt)-based anticancer drugs, exemplified by cisplatin and oxaliplatin, are the mainstay of treatment for most solid cancers. However, resistance to Pt anticancer drugs develops rapidly upon their administration, which can be caused by overexpression of MDR transporters and activated DNA repair mechanisms. We investigated the potentiation effect of CUDC-101 on the anticancer activity of conventional cytotoxic drugs in MDR cells with overexpression of various ABC transporters and in Pt-resistant cancer cells. CUDC-101 was found to increase the cytotoxicity and accumulation of substrate anticancer drugs in MPR-1 (doxorubicin) and MRP-2 (methotrexate) overexpressing cells, while no effect was observed in the parental sensitive cells. Mechanistically, CUDC-101 was found to inhibit MRP-1 and MRP-2 efflux function, probably by acting as an uncompetitive inhibitor and interfering with their ATPase activity. In Pt-resistant cancer cells, CUDC-101 appears to circumvent the resistance through inhibition of both MRP-2 and other DNA repair-mediated mechanisms. The combinations of CUDC-101 with cisplatin or oxaliplatin were found to display synergistic cytotoxic effect in cisplatin- or oxaliplatin-resistant cancer cell lines, respectively. Upon the concomitant administration of CUDC-101, cellular accumulation of Pt drugs and formation of DNA-Pt adducts were found to be increased whereas expression levels of DNA repair genes (e.g. ERCC1) was inhibited in Pt-resistant cells. The data advocates further development of CUDC-101 as a novel MDR reversal agent for use in combination cancer chemotherapeutic regimens. Citation Format: Kenneth K.W. To, Daniel C. Poon, XG Chen, Ge Lin, Li-wu Fu. CUDC-101, a hybrid molecular targeted agent, reverses multiple mechanisms of drug resistance. [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 976. doi:10.1158/1538-7445.AM2013-976
Abstract LB-333: Metabolic imaging of cancer using nanostructure-initiator mass spectrometry
Authors: Matthew P. Greving, Cathy Zhang, Zhengming Yan, Mary E. Spilker, Wenlin Li, Gary Siuzdak, Peter J. O'Brien
Journal: Cancer Research (2011)

Abstract Metabolic adaptation is critical for the development and progression of cancer, and may influence the sensitivity of tumor cells to chemotherapy. Tumor metabolic profiling provides insights into those processes, but most quantitative methods are relatively limited in terms of assay sensitivity and spatial resolution, and by necessity focus on cultured cells, explanted tumors, or tissue extracts. Nanostructure-initiator Mass Spectrometry (NIMS) is a mass-based imaging technique that requires no sample preparation or extraction, and provides unbiased characterization of tissue metabolites in situ at low micron resolution. Seeking mechanistic insights and biomarkers of drug response, we used NIMS to profile xenobiotic- and cell-intrinsic metabolism in cultured Burkitt's lymphoma cells and breast cancer xenograft tumors treated with Rapamycin (RAPA) and Docetaxel (DOC), respectively. In both systems, non-radioactive fluorothymidine (FLT) metabolism was monitored as an indicator of cell proliferation, since FLT phosphorylation by thymidine kinase occurs mainly in G1-S phase cells. Rapamycin, FLT, and phosphorylated FLT metabolites were readily detected in Raji cells. RAPA, a starvation mimetic, induced dramatic alterations in metabolome of Raji cells 30, 60, and 90 minutes after treatment. Significant changes in cellular energetic- and biosynthetic intermediates were seen, including elevations in D-glucose (p=0.071); stearic acid (p=0.089); uridine monophosphate (p=0.002); N-Acetyl-L-glutamic acid (p=0.033); tiglyglycine (p=0.011); and isobutyryl carnitine (p=0.037). NIMS analysis of tumor tissues and normal liver from SCID-Beige mice implanted with MDA-MB-231 tumors showed FLT metabolite distribution consistent with that expected for proliferating cells. DOC induced derangement in that distribution and in endogenous metabolite profiles when compared to vehicle treatment. NIMS metabolomics thus allows simultaneous quantification of drug exposure, drug metabolism, and broad metabolic responses to treatment with single cell resolution. Metabolic discrimination of tissues, as with NIMS, is increasingly used to inform our understanding of pathology and to identify endogenous biomarkers. The approach described here, where differences in xenobiotic metabolism are used as landmarks of proliferating tumor cells in situ, offers novel tools for translating in vitro findings into a deeper understanding of tumor responses to therapy. 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 LB-333. doi:10.1158/1538-7445.AM2011-LB-333
SAT0516 Megacapillaries as Detected by Nailfold Videocapillaroscopy in a Cohort of Patients with Acrocyanosis.
Authors: R. Irace, G. Cuomo, L. Pirro, G. Valentini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with acrocyanosis are known to display a capillaroscopic pattern characterised by normal/mild reduction of capillary density, microhemorrhages, asymmetrical capillary ectasias with greater width of venular loop and capillary thrombosis (1). At the best of our knowledge, one small series study only as so far reported the occurrence of megacapillaries (i.e. giant capillary: homogeneously enlarged loops with a diameter &gt;50µm) in patients with acrocyanosis (2). <h3>Objectives</h3> To investigate the presence of megacapillaries in a cohort of patients with acrocyanosis <h3>Methods</h3> We enrolled 71 consecutive patients attending the Videocapillaroscopy Outpatient clinicof the Second University of Naples from 1st January 2011 to 1st June 2012 (median age 45 years, range 18-70) diagnosed to have acrocyanosis (i.e. persistent, symmetrical and painful cyanosis of extremities, triggered by cold, often associated to hyperhidrosis) and 35 control patients affected by osteoarthritis. Nailfold videocapillaroscopy was carried out with optical probes of 200X (VideoCap 2.5). <h3>Results</h3> Megacapillaries (maximal loop width 80 µm) were detected in 14 out of 71 patients (19%). In 12 and 2 patients a mean score of 1 (less than 4 megacapillaries / mm) and of 2 (≥4 megacapillaries ≤ 6 / mm) was registered, respectively. In all patients the capillaroscopic alterations already described in patients with acrocyanosis were found : mild reduction of capillary density (mean capillary number 7±1/mm), asymmetrical capillary ectasias with greater width of venular loop, microhemorrhages, capillary thrombosis. In controls rare ectasias were the only capillaroscopic alterations detected. <h3>Conclusions</h3> Our study confirms the possible occurrence of megacapillaries in a larger cohort of patients with acrocyanosis. It suggests the need of a careful clinical approach in order to make differential diagnosis between acrocyanosis and Raynaud's Phenomenon. The patients enrolled will be prospectically followed-up to assess the changes of capillaroscopic scores overtime. <h3>References</h3> Kurklinsky et al. Vasc Med 2011 16(4):288-301 Monticone et a J Am Acad Dermatol 2000; 42:787-90 Davis E. Adv Microcirc 1982 ;10:101-119 <h3>Disclosure of Interest</h3> None Declared
Potential of a HDR image processing sensor for optimized visualisation in NOTES interventions
Authors: M Falkinger, A Schneider, D Wilhelm, J Jakob, W Endreß, H Feußner
Journal: Endoscopy (2012)

Objective of the Study: Since current NOTES endoscopes have a very narrow and poorly illuminated field of view, it is inevitable to optimize the visualization of the operation field and build a basis for further developments in NOTES-surgery. Typical effects are the overexposure of near objects and the underexposure of distant structures, as well as bright areas in the centre and poorly illuminated areas in the periphery. Consistent illumination and sharp clear structures would help for orientation and to ensure safe operation.
AB0962 Ankle Tendon Involvement in Patients with Spondylarthritis
Authors: F. Vreju, B. Chisalau, I. Cojocaru Gofita, M. Ivan, C. Criveanu, M. Florea, A. Rosu, P. Ciurea
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Management of spondylarthritis (SA) has evolved lately, in part due to new biologic therapies and part because of the new imaging techniques that can depict earlier involvement in joints and tendons. <h3>Objectives</h3> to evaluate, by ultrasonography (US), the prevalence and type of the ankle tendons involvement in patients with spondylarthritis. <h3>Methods</h3> Thirty-four patients with SA and ankle pain were included in the study (12 with ankylosing spondylitis - AS, 11 with psoriatic arthritis - PsA and 11 with reactive arthritis -ReA). Twenty healthy age-matched controls without inflammatory diseases were examined as well. The US evaluation included the anterior scan, the medial malleolar, lateral malleolar and posterior scan, for the evaluation of the following tendons: anterior tibialis tendon, extensor halux tendon and extensor common tendons, posterior tibialis tendon, flexor digitorum tendon and flexor hallux tendon, brevis and longus peroneous tendon and Achilles tendon. The presence of US findings indicative of tenosynovitis and tendon damage was investigated. <h3>Results</h3> Tenosynovitis in at least one site, was statistically significant more frequent in patients with SA than in controls (58,82% vs 10,00%, p&lt;0,001). Between patients with SA, it was more frequent in PsA patients (72,72%), followed by ReA patients (63,63%), compared to those with AS (41,66%). The most frequently involved tendon was tibialis posterior tendon in PsA and ReA patients and Achilles tendon in AS patients. We found partial or complete tears of the tendons in 3 patients from control group (15%) and 4 patients with SA (11,76%). <h3>Conclusions</h3> This study reveals the high frequency of ankle tendon involvement in patients with spondylarthritis and can guide the further assessment in the evaluation of those patients in daily practice. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5719
P579Novel insights into the regulatory mechanisms of scn5a expression
Authors: A Tarradas, M Pinsach-Abuin, O Llora, P Beltran-Alvarez, R Brugada, S Pagans
Journal: Cardiovascular Research (2014)

Brugada Syndrome (BrS) is a life-threating arrhythmogenic disease associated with a high risk of Sudden Cardiac Death. Genetic alterations in SCN5A, which encodes the alpha subunit of the cardiac voltage-gated sodium channel (Nav1.5), are the most common cause of BrS. Nav1.5 channel is responsible for the rapid influx of sodium ions that initiate the propagation of the action potential in cardiomyocytes. However, mutations in SCN5A gene only explain 20-25% of the cases with BrS. Our working hypothesis is that a deregulation of SCN5A expression could cause BrS and explain, at least in part, some cases of BrS with no mutation identified. Nevertheless, little is known regarding the regulation of SCN5A expression. Therefore, it is the goal of this study to gain insight into the molecular mechanisms that regulate SCN5A expression at the transcriptional level, and how alterations of these mechanisms contribute to cardiac arrhythmias.
Abstract 4177: Detection of mir-449 and mir-let-7g expression in Taiwan paired hepatocellular carcinoma.
Authors: Yu-Jing Zhang, Hui-Chen Wu, Jing Shen, Ming-Whei Yu, Regina M. Santella
Journal: Cancer Research (2013)

Abstract Hepatocellular carcinoma (HCC) is one of the most common and rapidly fatal human malignancies. In recent decades, it has been increasing in Western, developed countries such as the United States. MicroRNAs (miR) regulate genes involved in diverse biological functions and alterations in miR expression have been linked to the pathogenesis of many malignancies. Some previous studies have reported that miR-449 and miR-let-7g have tumor suppressor functions, but other studies indicate that miR-449 may have more variable functions. In the present study, miR-449 and miR-let-7g expression were measured in 36 Taiwanese paired HCC tumor/adjacent tissues using formalin fixed paraffin embedded samples with real-time RT-PCR. The mean log levels of miR-449 expression in tumor and adjacent non-tumor tissues are -1.14 and -2.65, respectively (p=0.02); for miR-let-7g, the mean log levels of tumor and adjacent non-tumor expression are 5.40 and 5.49 respectively (p=0.87). The relationship between exposure to chemical carcinogens as indicated by levels of polycyclic aromatic hydrocarbon (PAH)-DNA adducts and miR expression was also investigated. The mean log levels of miR449 in tumor tissues with high, moderate and low PAH-DNA adduct levels are -2.27, -2.22 and -0.43, respectively (p=0.02). The log levels of miR449 in tumors with and without cirrhosis are 0.02 and -1.42, respectively (p=0.02). These findings suggest that chemical carcinogen exposure and cirrhosis status may affect miR449 expression in HCC. Larger sample sizes and studies on the underlying mechanisms of miR449 and mir-let-7g expression in HCC are needed. Citation Format: Yu-Jing Zhang, Hui-Chen Wu, Jing Shen, Ming-Whei Yu, Regina M. Santella. Detection of mir-449 and mir-let-7g expression in Taiwan paired hepatocellular carcinoma. [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 4177. doi:10.1158/1538-7445.AM2013-4177
S2 Development Of A Job Exposure Matrix For Soc 2000 Listings To Identify Occupational Causes Of Copd
Authors: S. Sadhra, D. Fishwick, O. Kurmi, H. Chambers, K. Lam, S. Hutchings, D. Jarvis, S. De Matteis, L. Rushton, J. Ayres, P. Cullinan
Journal: Thorax (2014)

<h3>Introduction</h3> Occupational exposures are associated with the presence of a significant proportion of chronic obstructive pulmonary disease (COPD). The majority of the previous population studies have relied on self-reported exposures to vapours, gases, dusts and fumes (VGDF), which could lead to substantial misclassification. We aim to develop an occupational inhalation job exposure matrix (JEM) developed for use specifically with SOC 2000 occupational codes covering a wider range of occupational airborne pollutant types. <h3>Methods</h3> The development of airborne chemical exposure JEM (ACE-JEM) involved a four-stage approach; first, exposure (yes/no) to each of the six different airborne pollutants types (vapours, gases, dusts, fumes, fibres and mists; VGDFFM) was assessed for each of the 353 SOC codes, then three levels of exposure estimates (low, medium and high) (L-JEM1) and four levels of proportion exposed (0–4%, 5–9%, 20–49% and &gt;=50%) (P-JEM2) were assigned to the exposed codes and for each pollutant type. The two P and L JEMs were then combined to produce the final ACE-JEM. The estimated exposure of the 6 pollutant types was expanded to include biological dusts, mineral dusts, metals, diesel fumes and asthmagens. <h3>Results</h3> For L-JEM1 186 (53%) of the codes were assigned as exposed to at least one type of VGDFFM. The most common exposure was dust (40% of all SOC codes) followed by fumes (26%). Over 68% of all codes were assigned as not being exposed to fibres, gases or mists. The pollutant with the highest proportion in the high exposure group was dusts (13%), and 33% of the codes were assigned as exposed to asthmagens. Overall, 53% of the codes were assigned as exposed to CGDF, with 22% assigned as having medium or high exposure to VGDF. <h3>Disccussion</h3> An expert assessment derived JEM has been developed, using a strict set of a priori defined rules. This JEM will assist attribution of possible harmful workplace exposures in future epidemiological studies. The ACE-JEM could also be applied to studies to assess risks of other respiratory diseases, including asthma and extrinsic allergic alveolitis.
Fasting Hypoglycemia in Adults
Authors: Stefan S. Fajans, John C. Floyd
Journal: New England Journal of Medicine (1976)

Fasting hypoglycemia is associated with and caused by a diversity of pathologic states. Elucidation of the pathophysiology and diagnosis of the fasting hypoglycemic states requires an understanding of the many factors that contribute to the maintenance of euglycemia during fasting. We review these and outline how derangements in one or more of the mechanisms that control blood glucose levels lead to hypoglycemia. The physiologic basis for recognizing the fasting hypoglycemias and the application of newer technics and tests for demonstration of basic abnormalities in adults are stressed. Some of the hypoglycemic states encountered in infancy and childhood1 are listed as . . .
Abstract 4960: Circulating miRNAs as noninvasive biomarkers in esophageal adenocarcinoma patients
Authors: Jee Hoon Song, Yulan Cheng, Jian Yang, Wenjing Wu, Yuriko Mori, Alexandru V. Olaru, Moiz Bootwalla, Robert Sharpf, Stephen J. Meltzer
Journal: Cancer Research (2011)

Abstract Esophageal adenocarcinoma (EAC) is one of the most rapidly increasing cancers in the United States and throughout the developed world. The current primary screening method for EAC is gastrointestinal endoscopy (EGD), and this method is unsuitable and impractical for population-based screening or detection of asymptomatic EAC. Moreover, thus far, only a few reports have described altered miR expression in EAC, none of which were carried out in serum or plasma. We discovered a panel of noninvasive circulating microRNA (miR) biomarkers to promote earlier detection of EAC. We extracted total RNA from serum of each subject and hybridized it to fixed-probe miR microarrays in 12 sera each from EAC patients, subjects with normal EGDs, and 12 matched EAC tissues and normal esophageal tissues from EAC patients. Data was extracted and normalized using Feature Extraction Software 9.3 and GeneSpring software (Agilent) and subsequently analyzed by classification trees, multiple leave-one-out cross-validation, and relative influence plots. We selected the most influential miRs for validation by quantitative RT-PCR assays. Our preliminary miR findings indicate that several miRs show dramatic and significant differences in serum levels between EAC and normal control subjects. An ROC curve assembled based on aggregate data yielded an area under the curve (AUC) = 0.885, with sensitivity = 92% and specificity = 83%. We conclude that a panel consisting of several miRs is likely to discriminate asymptomatic EAC patients from normal subjects, leading to earlier diagnosis and improved prognosis. 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 4960. doi:10.1158/1538-7445.AM2011-4960
ASSOCIATION OF HOSPITAL TEACHING STATUS WITH IN-HOSPITAL MORTALITY OF ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Tanush Gupta, Dhaval Kolte, Sahil Khera, Prakash Harikrishnan, Marjan Mujib, Wilbert Aronow, Diwakar Jain, William Frishman, Sachin Sule, Howard Cooper, Deepak Bhatt, Gregg Fonarow, Julio Panza
Journal: Journal of the American College of Cardiology (2016)
Abstract PD02-02: The effect of HER2 expression on luminal A breast tumors
Authors: RE Ellsworth, AL Valente, CD Shriver
Journal: Cancer Research (2012)

Abstract Background: Luminal A (LumA) tumors are the most common subtype of breast cancer and have been associated with favorable prognosis. Although tumors can be considered LumA if they have &amp;gt;1% expression of ER, negative HER2 status ranges from 0+ (no expression) to 2+ (weak to moderate expression in &amp;gt;10% of cells) without concurrent genomic amplification. It is not clear how moderate levels of HER2 expression influence tumor biology in LumA tumors. Methods: The Clinical Breast Care Project database was queried to identify all hormone receptor positive cases with HER2 status defined as 0+ (n = 89) or 2+/not amplified (n = 154). Clinicopathological characteristics were compared between groups using chi-square analysis. Twenty-five 0+ and 25 2+ tumors were subjected to laser microdissection and hybridized to U133 2.0 microarrays (Affymetrix). Gene expression data was analyzed using Partek Genomics Suite. Results: Age at diagnosis did not differ between patients with no (58.5 years) or moderate (59.3 years) HER2 expression. Patient groups did not differ by ethnicity, tumor stage, grade or size, or lymph node status. Although breast cancer mortality was low, all patients who died of disease (n = 7) had moderate levels of HER2 expression (p = 0.016). At the molecular level, four genes were differentially expressed (p &amp;lt; 0.01, &amp;gt;2x-fold change): ESRRG expressed at significantly higher levels and DHRS2, SCUBE2 and SERPINA6 expressed at significantly lower levels in tumors with moderate HER2 expression. Discussion: LumA (2+) tumors are dissimilar from LumA (0+) tumors. Increased expression of ESRRG has been associated with increased cellular proliferation and tamoxifen resistance, while decreased expression of SCUBE2 and SERPINA6 have been associated with inhibition of growth and proliferation. Together, these molecular differences suggest that LumA tumors with moderate HER2 expression, although classified as HER2 negative, have more aggressive characteristics than those without HER2 expression which may contribute to the significantly higher mortality rate seen in patients with LumA tumors expressing HER2. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD02-02.