tbuckley/cabot-search huggingface dataset:
CHOLINESTERASE GENE EXPRESSION AND SERUM LEVELS PREDICT 6 YEAR MAJOR ADVERSE CARDIAC EVENTS FOLLOWING CORONARY ANGIOGRAPHY
Authors: Yaron Arbel, Shani Shenhar-Tsarfaty, Ilan Freidson, Ariel Finkelstein, Shlomo Berliner, Shmuel Banai, Gad Keren, Hermona Soreq
Journal: Journal of the American College of Cardiology (2016)
The Changing Concepts of Guillain–Barré Syndrome
Authors: Charles F. Bolton
Journal: New England Journal of Medicine (1995)

Guillain–Barré syndrome1,2 is a leading cause of acute paralysis. It occurs worldwide, in patients of all ages and both sexes. The weakness develops in a matter of days, sometimes with frightening rapidity and severity. Thirty percent of patients require treatment in critical care units, where ingenuity and resources are taxed to their maximum, and the stress on the patient and family is enormous. Nonetheless, modern management has reduced the mortality rate from 30 to 3 percent, and 75 percent of patients recover completely in 6 to 12 months.Guillain–Barré syndrome has traditionally been regarded as a poorly understood immune-mediated . . .
Delayed Tc-99m Sestamibi Washout in Graves’ Disease
Authors: KOTTEKKATTU K. BALAN, ANDREW H. BALTROP, GORDON C. WISHART
Journal: Clinical Nuclear Medicine (2003)

BALAN, KOTTEKKATTU K. M.D., F.R.C.P.I.; BALTROP, ANDREW H. F.R.C.S., F.R.C.R.; WISHART, GORDON C. M.D., F.R.C.S. Author Information
Abstract 186: NER factor XPC enhances DNA damage-induced apoptosis independently of p53 function
Authors: Qi-En Wang, Chunhua Han, Keisha Milum, Altaf A. Wani
Journal: Cancer Research (2011)

Abstract Xeroderma Pigmentosum complementation group C (XPC) is a 940-aa protein engaged in the DNA damage recognition during nucleotide excision repair (NER). It was reported that one of the XPC polymorphisms, Lys939Gln, is associated to cancer predisposition, although this variant did not affect NER. Thus, another mechanism must exist to contribute to this cancer susceptibility. In addition, this XPC genetic polymorphism correlates with the failure of imatinib treatment in patients with chronic myeloid leukemia. We reasoned that XPC must be influencing other functions unrelated to DNA repair. Here, we demonstrated that XPC can enhance the apoptosis induced by various DNA damaging agents, including ionizing radiation (IR), ultraviolet light (UV), cisplatin, and etoposide. In addition, XPC-mediated apoptosis is independent of p53, as reflected by the findings that knock-down of XPC expression compromised the UV or IR-induced apoptosis in p53-deficient Li-Fraumeni Syndrome (LFS) MDAH041 and HCT116 cell lines, while having no influence on apoptosis in their p53-proficient counterparts. Also, in response to UV irradiation, XPC deficiency did not affect the mitochondrial cytochrome c release or had only slight effect on the activation of caspase-3. However, XPC deficiency compromised the UV-induced activation of caspase-9. Therefore, XPC seems to function downstream of mitochondrial membrane permeabilization (MMP) and upstream of caspase-9 activation during DNA damage-induced apoptosis. We further demonstrated that XPC deficiency impaired the UV-induced caspase-2 activation, as reflected by reduced cleavage of long isoform of caspase-2 (CASP-2L) in XP-C cells compared to XPC-restored XP-C cells following UV irradiation. Meanwhile, the short isoform of caspase-2 (CASP-2S) was found to be induced in XP-C cells at early times following UV irradiation, while it remained unchanged in XPC-restored XP-C cells. Given that caspase 2 gene generates both proapoptotic (CASP-2L) and antiapoptotic (CASP-2S) isoforms by alternative splicing, our data suggest that XPC enhances DNA damage-induced apoptosis by inhibiting the production of anti-apoptotic CASP-2S via regulation of the alternative splicing of caspase-2. (Supported by NIH grants CA93413, ES2388 and ES12991). 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 186. doi:10.1158/1538-7445.AM2011-186
Abstract LB-426: Delphinidin suppresses ultraviolet B-induced cyclooxygenases-2 expression through inhibition of MAPKK4 and PI-3 kinase
Authors: Nam Joo Kang, Jung Yeon Kwon, Jong-Eun Kim, Sung-Keun Jung, Mun Kyung Hwang, Hyong Joo Lee, Ki Won Lee, Yong-Seok Heo, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2010)

Abstract Cyclooxygenase-2 (COX-2), a key mediator of inflammation, and its product, prostaglandin E2 (PGE2), enhance carcinogenesis, particularly in skin. Ultraviolet (UV) B is the most carcinogenic component of solar irradiation, and a crucial role of COX-2 in UVB-mediated skin carcinogenesis has been reported. Here, we investigated the effects of delphinidin, an abundant dietary anthocyanin, on UVB-induced COX-2 upregulation and the underlying molecular mechanism. We found that delphinidin suppressed UVB-induced COX-2 expression in JB6 P+ mouse epidermal cells. COX-2 promoter activity and PGE2 production were also suppressed by delphinidin treatment within non-cytotoxic concentrations. Activator protein-1 and nuclear factor- B, crucial transcription factors involved in COX-2 expression, were activated by UVB and delphinidin abolished this activation. UVB-induced phosphorylation of c-Jun N-terminal kinase, p38 kinase and Akt was inhibited by delphinidin. The activities of mitogenactivated protein kinase kinase (MAPKK) 4 and phosphatidylinositol-3 kinase (PI-3K) were inhibited markedly by delphinidin. A pull-down assay using delphinidin-Sepharose beads revealed that delphinidin binds directly with MAPKK4 or PI-3K in a manner that was competitive with adenosine triphosphate. Moreover, in vivo investigations using mouse skin revealed that the upregulation of COX-2 expression, MAPKK4 activity and PI-3K activity induced by UVB was abolished with delphinidin treatment. Collectively, our results demonstrated that delphinidin targets MAPKK4 and PI-3K directly to suppress COX-2 overexpression, suggesting a potential protective role for delphinidin against UVB-mediated skin carcinogenesis. 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 LB-426.
Abstract 4432: Pancreatic normal duct epithelial and cancer cells express an autocrine catecholamine loop that is activated by the α3, 5 and 7 nicotinic acetylcholine receptors
Authors: Mohammed H. Al-Wadei, Hussein A. Al-Wadei, Hildegard M. Schuller
Journal: Cancer Research (2012)

Abstract Pancreatic cancer is the fourth leading cause of cancer deaths in developed countries. Smoking is an established risk factor for this malignancy but the underlying mechanisms are poorly understood. Previous reports have provided evidence that nicotinic acetylcholine receptors (nAChRs) and beta-adrenergic receptors (α-ARs) stimulate the growth and migration of pancreatic cancer cells. But a potential cooperation of these two receptor families in the regulation of pancreatic cancer has not been studied to date. Using two pancreatic cancer cell lines and immortalized pancreatic duct epithelia in vitro, our current data show, that all three cell lines synthesized and released the catecholamine neurotransmitters noradrenaline and adrenaline upon exposure to nicotine and that this activity was regulated by the α3, 5 &amp; 7-nAChRs. In accord with the established function of these catecholamines as α-AR agonists, nicotine-induced cell proliferation was blocked by the α-AR antagonist propranolol. Nicotine-induced proliferation was also abolished by the α7-nAChR antagonist α-bungarotoxin and catecholamine production in response to nicotine was blocked by α3, 5 or 7-nAChR gene knockdown. Moreover, our results show that the nicotinic agonists acetylcholine, nicotine, and its nitrosated carcinogenic derivative NNK induced the phosphorylation of CREB, ERK, Src and AKT and that those responses were inhibited by the beta-blocker, propranolol. Our findings identify this hitherto unknown autocrine catecholamine loop as an important regulatory cascade in pancreatic cancer that may prove a promising new target for cancer intervention. Supported by R01CA042829 and R01CA130888 with the National Cancer Institute. 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 4432. doi:1538-7445.AM2012-4432
Abstract 3187: Nucleolin-induced cap-independent translational pathway involved in Sp1 accumulation in tumorigenesis.
Authors: Tsung-I Hsu, Jan-Jong Hung, Wen-Chang Chang
Journal: Cancer Research (2013)

Abstract Sp1 is a transcriptional factor to regulate numbers genes related to cell proliferation, apoptosis and tumor progression. Previous studies indicate that Sp1 is induced significantly through modulating its transcriptional activity and protein stability. To detail study the level of Sp1 protein and mRNA in tumorigenesis found that Sp1 mRNA was just increased a little, but Sp1 protein was increased dramatically, implying that enhancement of translational activity by nucleion might be important in the Sp1 accumulation in tumor progression. Here we found a Y-shift motif within the 5’-UTR of the Sp1 mRNA, and to study the contribution in Sp1 level found that the 5’-URT could enhance the translational efficiency of Sp1. Using this Y-shift motif as a probe fished the interacted proteins. Several RNA binding proteins were identified by LC/MS/MS, and nucleolin is one of them. To further address the effect of nucleolin in Sp1 induction found that nucleolin overexpression did not alter the level of Sp1 mRNA, but increased the translational activity obviously. In addition, the signal transduction pathway was also studied, and found that EGFR and Kras pathways might be involved in the induction in the cap-independent pathway in Sp1 induction in tumorigenesis. Taken the previous studies and this study together, during tumor formation, several strategies including increasing the transcriptional activity, protein stability and translational efficiency were used to induce the Sp1 level to regulate many oncogenes to enhance the cancer progression. Keywords: Nucleolin, Sp1, Cap-independent pathway, Citation Format: Tsung-I Hsu, Jan-Jong Hung, Wen-Chang Chang. Nucleolin-induced cap-independent translational pathway involved in Sp1 accumulation in tumorigenesis. [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 3187. doi:10.1158/1538-7445.AM2013-3187
P181 Complications from CT guided lung biopsies and risk factors for pneumothorax
Authors: Z. Sheikh, E. Woo, T. Meagher
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> CT guided lung biopsy is a proven diagnostic method for lung cancer. However, traditionally complication rates from this procedure have been high. The aim of our study was to assess current complication rates from this procedure and the determine what possible risk factors may account for these. <h3>Methods</h3> A retrospective cohort of CT guided lung biopsy procedures done between August 2008 and November 2010 were analysed. Patient notes and electronic radiology records (Centricity PACS) were reviewed. Complications of haemorrhage, pneumothorax, and death were recorded and the sample adequacy of biopsy specimens for pathological examination was determined for each procedure. A univariate analysis was performed for determining the risk of post-biopsy pneumothorax and biopsy type (core or FNA), number of co-axial needle passes, needle pleural angle, lesion size, and lesion distance from pleura at point of biopsy, and lesion location (lung or mediastinal). Consequently, a multiple logistic regression analysis was performed on the most significantly correlated risk factors for pneumothorax from the univariate analysis. <h3>Results</h3> Exactly 200 biopsy procedures done in 184 patients were included of which 64% were core biopsies (n=128). The mean age was 69 years (range 31–90 years) with with 79.5% of patients over 65 years old (n=151) and 59.5% of patients male (n=119). Haemorrhage occurred in 2.5% (n=5) and pneumothorax in 17% (n=34) with 5% (n=10) of procedures requiring intercostals chest drain insertion for pneumothorax. No deaths were recorded. A statistically significant higher risk was observed for core biopsy (OR 3.65, p=0.00, 95% CI 1.38 to 9.65) and lesion distance from pleura &gt;2 cm (OR 4.13, p&lt;0.001, 95% CI 1.88 to 9.08). A multivariate analysis showed that the risk was greatest when core biopsies were taken from lesions more than 2 cm from the pleura at point of biopsy (OR 9.14, p&lt;0.001, 95 % CI 2.72 to 30.69). The sample adequacy rate was 95.5% (n=191). <h3>Conclusions</h3> In this recent study all complication rates were found to be lower than that reported in the national survey which is the current standard for BTS guidelines on acceptable complication rates. However, a higher rate of intercostal drain insertion was observed. Lesion distance from pleura at point of biopsy &gt;2 cm and core biopsies were the most significant risk factors for post-biopsy pneumothorax and operators should consider these prior to biopsy. Larger studies are needed to reasses current national complication rates and target complication rates may need to be specified by biopsy type.
Abstract 5335: miR-31 contributes to immortalization and epithelial-mesenchymal transition of oral keratinocyte.
Authors: Hsi-Feng Tu, Pei-Shi Hung, Chung-Ji Liu, Shu-Chuin Lin, Kuo-Wei Chang
Journal: Cancer Research (2013)

Abstract Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression by RNA interference and crucial for tumorigenesis. Our previous studies identified miR-31 as an oncogenic miRNA of OSCC, and the increased miR-31 may be contributive to oral carcinogenic process in the early stages. This study further specified the higher miR-31 expression in dysplastic potential malignant disorder (PMD) tissues than non-dysplastic PMD tissues in oral cavity. In addition, miR-31 in the patient's saliva was significantly higher than control subjects. To elucidate the contribution of miR-31 in modulating the extended growth of normal oral keratinocyte, exogenous expression of both miR-31 and hTERT genes were introduced to normal oral keratinocyte (NOK) culture, which led to immortalization of two NOK lines, designated M31OK1 and M31OK3. These immortalized lines exhibited cellular phenotypes lying between NOKs and OSCC cell lines and diminished expression of senescence-associated β-galactosidase. Knockdown of hTERT and/or miR-31 decreased the growth and migration of both lines. M31OK1 also carries p53 gene mutation in codon 273, exhibiting the tolerance to serum-induced senescence, anchorage-independent growth and epithelial-mesenchymal transition (EMT) properties relative to NOK. However, the stemness properties were not increased in M31OK1 in relation to NOKs. Knockdown of miR-31 expression decreased the expression of vimentin and ZEB1 and slightly increased E-cadherin expression in M31OK1 cells. This was correlated with the clinical findings that high miR-31 expression was associated with higher expression of VEGF and lower expression of E-cadherin in PMD tissues. This study concluded that miR-31 may be contributive to early oral carcinogenesis by stimulating factors to facilitate cellular immortalization or by modulating the expression of EMT markers in oral keratinocytes. Citation Format: Hsi-Feng Tu, Pei-Shi Hung, Chung-Ji Liu, Shu-Chuin Lin, Kuo-Wei Chang. miR-31 contributes to immortalization and epithelial-mesenchymal transition of oral keratinocyte. [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 5335. doi:10.1158/1538-7445.AM2013-5335
USE OF ADVANCED THERAPIES FOR ACUTE PULMONARY EMBOLISM AND RELATED OUTCOMES AMONG FEE-FOR-SERVICE MEDICARE BENEFICIARIES FROM 1999 TO 2010
Authors: Behnood Bikdeli, Yun Wang, Karl Minges, Nihar Desai, Nancy Kim, Mayur Desai, John Spertus, Frederick Masoudi, Brahmajee Nallamothu, Samuel Goldhaber, Harlan Krumholz
Journal: Journal of the American College of Cardiology (2015)
Abstract 14587: Proarrhythmic Effects of Ibrutinib, a Clinically Approved Inhibitor of Bruton’S Tyrosine Kinase (BTK) Used in Cancer Therapy
Authors: Tao Yang, Javid J Moslehi, Dan M Roden
Journal: Circulation (2015)

Introduction: Ibrutinib is a novel and potent BTK inhibitor which has been approved for several types of B-cell malignancies. Our meta-analysis of the published clinical trials finds that atrial fibrillation occurs in ~7% of patients after chronic ibrutinib exposure. Ventricular tachycardia has also been reported. Recently, multi-targeted tyrosine kinase inhibitors (TKIs) have been associated with arrhythmias; one implicated mechanism is increased late sodium current (INa-L) after chronic but not acute drug exposure. This effect appears to be mediated by inhibition of PI3Kinase since it is rescued by intra-pipette PIP3, a PI3K effector. Hypothesis: In this study, we tested the hypothesis that chronic exposure to ibrutinib exerts arrhythmogenic effects by this mechanism. Methods: Isolated adult mouse cardiac atrial/ventricular and rabbit ventricular myocytes as well as KCNH2 (HERG/Kv11.1)- or Kv4.3-transfected CHO cells were used for the electrophysiological studies pre- and post-ibrutinib (0.3 μ or 1 μM) acutely (5-10 min) and chronically (5 hrs in myocytes or 48 hrs in CHO cells). In some experiments, 1 μM PIP3 was added into the pipette solution. Results: Chronic but not acute ibrutinib prolonged cardiac action potentials (APs), triggered abnormal APs (EADs and DADs; Figure), and markedly increased cardiac INa-L (1.68±0.27% vs control 0.21±0.04% of peak current, P&lt;0.01) in mouse atrial cells. A similar INa-L increase was also seen in mouse and rabbit ventricular cells. The abnormal APs and increased INa-L were antagonized by adding 1 μM PIP3 into the pipette and by the INa-L blocker ranolazine (10 μM). Ibrutinib has minor and no effects on cardiac HERG and Kv4.3 currents. Conclusion: Ibrutinib, like other TKIs, increased cardiac INa-L, an effect reversed by intracellular PIP3. These data further reinforce the importance of PIP3 signaling as a proximate mechanism leading to arrhythmogenesis by emerging targeted oncology therapies.
P2-10-04: 3D Mapping of Total Choline in Human Breast Cancer Using High-Speed MR Spectroscopic Imaging at 3T: A Feasibility Study.
Authors: S Posse, M Royce, ZR Dayao, T Zhang, C Zhao, L Sillerud, S Lopez, L Casey, SC Eberhardt, L Lomo, S-J Lee, R Rosenberg, A Rajput, P Bolan
Journal: Cancer Research (2011)

Abstract PURPOSE: To assess the feasibility of quantitative high-speed MR spectroscopic imaging (MRSI) of total Choline (tCho) as an adjunct to dynamic-contrast enhanced (DCE) MRI to improve lesion characterization and monitor treatment response in patients undergoing neoadjuvant chemotherapy. METHOD AND MATERIALS: Seven patients with biopsy-confirmed, infiltrating ductal carcinoma were studied using a clinical 3T MR scanner (Siemens Medical Solutions, Erlangen, Germany) equipped with 8- and 16-channel breast array (Hologic Inc., Bedford, MA). Measurements were performed using PRESS prelocalized 3D Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) using TR/TE=2000ms/135ms, matrix size up to 32×16x8, voxel size=1cc, and total acquisition time of 10 minutes (including water reference scan). Additional data were collected at TE 60 ms to enhance sensitivity for detecting tCho and J-coupled resonances. TE-averaging (8 steps, ΔTE: 2.5 ms) was employed to minimize gradient sideband artifacts. Quantification of tCho in reference to tissue water was performed using spectral fitting and relaxation correction. RESULTS: Strongly elevated tCho with maximum concentration ranging from 0.3 to 4.1 mmol/kg was measured in five patients with single and multi-centric enhancing lesions larger than 2 cc volume (Table 1). The measured tCho concentration in Grade 3 tumors was higher than in lower grade untreated and treated tumors. Strong decreases in tCho concentration were measured in 2 patients undergoing neoadjuvant therapy in a follow-up scan. At short TE an additional resonance was detected that was elevated in enhancing lesions and tentatively assigned to Taurine. Two patients had lesions smaller than 2 cc with surgical clips in which tCho was not detectable due to line broadening. MRSI data sets were preferentially collected before contrast injection, since it increased spectral line width by up to 50%. CONCLUSION: This study demonstrates feasibility of quantitatively mapping tCho in invasive breast carcinoma using high-speed MRSI. The long-term goals are to utilize high-speed MRSI as an early predictor of treatment failure in women undergoing neoadjuvant therapy (i.e. chemotherapy, endocrine therapy or biologic therapy) for breast cancer and to develop an improved screening protocol for high-risk patients. Grant support: 1RC1EB010617-01 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-10-04.
OP0170 Infection Risk by Type and Treatment for Patients with Rheumatoid Arthritis (RA): Table 1.
Authors: K. Michaud, S. Pedro, T. Mikuls, A. Kalil, F. Wolfe
Journal: Annals of the Rheumatic Diseases (2014)

Alcoholic liver disease (ALD) is increasing in incidence in the UK. It is the commonest cause of liver-related deaths, predominantly in people below the age of 60. Alcoholic hepatitis (AH) is an acute form of ALD with high mortality when severe. Jaundice and coagulopathy are clinical hallmarks of severe AH. Histology findings are characterised by parenchymal inflammation and hepatocellular damage although biopsy is only required when diagnostic uncertainty exists; clinical findings are usually sufficient for accurate diagnosis. Patients with AH should be stratified as non-severe or severe using non-invasive scoring systems such as the discriminant function or the Glasgow Alcoholic Hepatitis Score. In patients with non-severe AH, abstinence is the mainstay of treatment, and it is important that steps are taken to help patients stop drinking. Severe AH requires specialist treatment. Consensus guidelines recommend the use of prednisolone although this remains subject to clinical trials. Pentoxifylline may have a survival benefit if corticosteroids are contraindicated. Nutritional support and N-acetylcysteine should be considered for use in conjunction with corticosteroids although evidence of benefit is not conclusive. Patients with severe disease who do not respond to therapy within a week have a very poor outcome. Recent data have shown a survival benefit of liver transplantation in this group although this remains experimental at present. Current and future research should focus on targeted therapies for severe AH and those who fail first-line treatment.
Predominance of influenza A(H1N1)pdm09 virus genetic subclade 6B.1 and influenza B/Victoria lineage viruses at the start of the 2015/16 influenza season in Europe
Authors: Eeva Broberg, Angeliki Melidou, Katarina Prosenc, Karoline Bragstad, Olav Hungnes
Journal: Eurosurveillance (2016)

Influenza A(H1N1)pdm09 viruses predominated in the European influenza 2015/16 season. Most analysed viruses clustered in a new genetic subclade 6B.1, antigenically similar to the northern hemisphere vaccine component A/California/7/2009. The predominant influenza B lineage was Victoria compared with Yamagata in the previous season. It remains to be evaluated at the end of the season if these changes affected the effectiveness of the vaccine for the 2015/16 season.