tbuckley/cabot-search huggingface dataset:
Abstract 343: High-throughput screening of multiple protein kinase inhibitor using polymeric nanoparticles
Authors: Eunsung Jun, Jong-Ho Kim, In-Seop So, In-San Kim
Journal: Cancer Research (2010)

Abstract Protein kinase play pivotal regulatory roles in most cell communication and metabolic pathways. Inhibitors of protein kinases not only hold great promise as therapeutic agents for many diseases, especially cancer, but are also of profound utility in the characterization of signaling pathways because of the centrality of protein phosphorylation as a regulatory process. Therefore, sensitive and widely applicable detection of protein kinase activity will provide a valuable tool to screen protein kinase inhibitors in drug discovery. We previously reported that self-assembled poly-ion complexes (PICs) containing kemptide, protein kinase A specific peptide motif, recognize the phosphorylation of kemptide by protein kinase A by recovery of fluorescence. In this research we found kinase specific substrate peptide with phage display which an efficient primary screening method to detect protein-protein interaction because of its relatively easy, rapid and massive recovery and analysis. Kinase substrate peptide library was made with phage and then library is displayed on capsid protein of phage. After kinase reaction, the phage clones are selected, recovered, and amplified for next round of bio-panning. The candidate clones are selected according for at least 4th round of bio-panning and the resultant peptides are analyzed for specificity. To prepare PICs, found peptide was conjugated with polyehtyleneimine (PEI) labeled with cyanine 5.5 (cy5.5). PICs consisting of peptide and cy5.5 chemically conjugated PEI and poly-L-aspartic acid showed significant fluorescent signal recovery in presence of protein kinase while they hardly showed fluorescent signal in absence of protein kinase. In addition, fluorescent signal did not recover with protein kinase inhibitor even though protein kinase was present. We tried to apply highthroughput screening to perform chemical library screening with 384-well plate. While wells without protein kinase showed strong fluorescent signal, wells containing protein kinase inhibitors represented no fluorescent signal, which is fully consistent with previous results and our expects. We conclude that this system is applied to highthroughput screening systems targeting protein kinase inhibitors. 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 343.
Reversal of Blood Flow through the Vertebral Artery and Its Effect on Cerebral Circulation
Authors: Martin Reivich, H. Edward Holling, Brooke Roberts, James F. Toole
Journal: New England Journal of Medicine (1961)

WE have recently studied 2 patients with symptoms of cerebral ischemia in whom a reversal of blood flow through the left vertebral artery was demonstrated. In both cases the anatomic lesion producing the reversal of blood flow was a stenosis of the left subclavian artery proximal to the origin of the vertebral artery. The cause of the reversed flow in these circumstances can be attributed to a fall of pressure distal to the stenosis below that at the vertebral-basilar junction so that the pressure gradient in the vertebral artery is reversed. We had not previously encountered this phenomenon and were . . .
Usefulness of F-18 FDG PET/CT as One-Stop-Shop Imaging Modality for Diagnosis of Occult Primary and Estimation of Disease Burden in Patients With Intraocular Masses
Authors: Kuruva Manohar, Bhagwant Rai Mittal, Pandurang Kulkarni, Navneet Singh, Anish Bhattacharya, Amod Gupta
Journal: Clinical Nuclear Medicine (2012)

Metastases are the most common intraocular malignancy. Determination of the primary site and entire burden of disease as a part of initial staging is important in choosing the most appropriate management strategy. F-18 FDG PET/CT can demonstrate primary neoplasms and the whole-body total burden of disease. We present 2 cases of intraocular metastases from lung carcinoma where F-18 FDG PET/CT was useful as one-stop-shop imaging modality in detection of the primary and in assessment of total disease burden.
Abstract LB-243: microRNA mimics: siRNA lessons apply. miRNA mimics exhibit a significant off-target effect that is cell-line, length and dose dependent.
Authors: Mae A. Goldgraben, Anna Git, Oscar Rueda, Carlos Caldas
Journal: Cancer Research (2013)

Abstract In light of the great success of siRNA reagents in modern research, similar reagents have also become increasingly popular to study miRNAs in cancer biology. To explore the endogenous function of a particular miRNA in fine-tuning target protein translation, synthetic mimics are transfected into host cells either to examine the effect of a candidate target 3′UTR on the expression of a reporter, or to identify new targets using microarray technology. Such studies typically employ a proprietary commercial universal negative control, whose suitability is taken for granted. Methods: We transfected commercial miRNA mimics into a large panel of breast cancer cell lines (BT549, Cama1, HCC1500, MCF7, MDAMB134, MDAMB231 MDAMB436, MFM223, SUM159, ZR75-1) to identify endogenous targets of miR-155 using microarray analysis. ‘Seed’ and passenger-strand mutants were integrated into the study as additional controls. Results: The resulting list of differentially-expressed genes often reflects a saturation of transcripts pertaining to a strong immune response to the transfected double-stranded RNA (dsRNA). Different cell lines exhibit variable sensitivity to dsRNA mimics, evident as the induction of the interferon pathway and apoptosis. Using custom variants of the mimics we show that this sequence-independent response is predominantly length-dependent and dose-dependent. Moreover, a substantial part of the remaining, seemingly sequence-specific response could be attributed to the passenger strand, assumed to be inert. Conclusions and future work: Commercial miRNA mimics may have significant off-target effects that require careful controls to account for the phenotypes under study. In particular, ‘seed’ mutants rather than universal negative controls are of essence. Additionally, alternative methods of transient miRNA over-expression are currently under investigation to validate targets identified to date. Taken together, these lessons have significant implications for all areas of cancer biology where synthetic mimic transfections are a means for investigating the functional role of miRNAs in the cell. Citation Format: Mae A. Goldgraben, Anna Git, Oscar Rueda, Carlos Caldas. microRNA mimics: siRNA lessons apply. miRNA mimics exhibit a significant off-target effect that is cell-line, length and dose dependent. [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 LB-243. doi:10.1158/1538-7445.AM2013-LB-243
416 CELLULAR IMMUNE RESPONSE FOLLOWING HUMAN FETAL LIVER-DERIVED STEM CELLS TRANSPLANTATION IN CASE OF DECOMPENSATED LIVER CIRRHOSIS
Authors: M.A. Habeeb, A.A. Khan, G. Sivaram, A. Bardia, G. Srinivas, T. Avinashraj, G. Pande
Journal: Journal of Hepatology (2012)
DD-03 * THE NATURALLY OCCURRING STEROID, WITHAFERIN A, IN SYNERGISTIC CONCERT WITH HER2/EGFR INHIBITORS ABROGATES PROLIFERATION OF HUMAN GLIOBLASTOMA CELL CULTURES AT NANOMOLAR CONCENTRATIONS
Authors: E. Chang, T. Abbasi, A. D'Souza, G. Gowrishankar, P. Mallick, S. S. Gambhir
Journal: Neuro-Oncology (2014)

INTRODUCTION: Withaferin A, a steroidal lactone that is isolated from the winter cherry (Withania sominifera), confers abrogatory effects on proliferating cancer cells. This is achieved, partly though Withaferin A's ability to retard angiogenesis along with VEGF and calcium signaling. At the level of transcription, Withaferin A inhibits both Nfkb and Sp1 Transcription factor activity. In glioblastomas, Withaferin A promotes cytotoxicity by impinging on Akt/mTOR-associated transduction pathways. In this report, we probe the relationship of Withaferin A with Her2- and EGFR-directed signaling (through the use of receptor-targeted inhibitors such as Afatinib and Lapatinib) in human glioblastomas. METHODS: Human parietal-cortical glioblastoma cells (pcGBM2, GBM39, LN229) were derived from primary tumors. Genomic material (both RNA and DNA) was isolated via standardized methods so as to study the mutational and expression status of relevant gene targets (PTEN, p53, MGMT, EGFRvIII). Proliferative potential of these cells was assessed by the alamar blue bioassay. RESULTS: The human glioblastomas studied displayed both wild-type and mutant p53. Both MGMT and PTEN expressions were usually suppressed. Expression of EGFRvIII was highly variegated with both wild type and vIII receptors being present. GBM39 expressed EGFRvIII levels 20-fold higher than pcGBM2. Growth of GBM39 and pcGBM2 were inhibited by Withaferin A with an IC50 of 0.3 + /-0.05 µM. The EGFR inhibitors, Afatinib and Lapatinib, abrogated glioblastoma growth at IC50s of 4.5/-1.0 uM and 18.0 + /-2.0 uM respectively. Inclusion of 0.15 µM, 0.3 µM and 0.6 µM of Withaferin A on top of Afatinib or Lapatinib resulted in dose-dependent, 2 to 4-fold sensitization of glioblastomas to the Her2/EGFR inhibitors. Addition of the Akt inhibitor, BKM120 to Afatinib and Withaferin A did not add further to the sensitization. CONCLUSIONS: The results suggest that Withaferin A exerts an inhibitory effect on glioblastoma proliferation and that it provides a synergistic effect on inhibition when co-administered with Afatinib or Lapatinib.
P474 CLINICAL OUTCOMES OF PATIENTS WITH PORTAL HYPERTENSION NOT DUE TO CIRRHOSIS: A SINGLE-CENTRE EXPERIENCE
Authors: S. Gioia, E.G. Onori, C. Marzano, S. Angeloni, F. Cerini, I. Pentassuglio, S. Nardelli, M. Merli, A.F. Attili, O. Riggio
Journal: Journal of Hepatology (2014)
MR-06 * MicroRNA SIGNATURE ASSOCIATED WITH POOR OUTCOME OF GLIOBLASTOMA PATIENTS
Authors: M. Smrcka, J. Sana, R. Lakomy, P. Fadrus, P. Slampa, L. Kren, M. Svoboda, M. Hajduch, O. Slaby
Journal: Neuro-Oncology (2014)

BACKGROUND: It is very important to find new biomarkers which can predict clinical outcomes of glioblastoma (GBM) and help in treatment decissions. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and play key role in pathogenesis of wide range of cancer. Aim of our study is to identify miRNA signature associated with the more aggressive phenotype of GBMs, which will enable sensitive prediction of clinical outcome in GBM patients. METHODS: We determined the expression profile of 667 miRNAs in tumor tissues of 58 patients with primary GBM with completed concomitant chemoradiotherapy with temozolomide and 12 non-malignant brain tissues obtained from patients with drug-resistant anteromedial temporal lobe epilepsy. Methylation status of MGMT promoter (methylation-specific HRM), isocitrate dehydrogenase (IDH1) status (immunohistochemistry) and co-deletion of 1p/19q (FISH) was also evaluated. RESULTS: We have confirmed frequencies of commonly used prognostic biomarkers in GBM patients (MGMT, IDH1, 1p/19q deletion), and observed significant correlation of MGMT methylation status, response to chemoradiotherapy with temozolomide and survival of GBM patients. We have identified specific signature of miRNAs diferentially expressed between GBM tissue and non-tumoral brain tissue from epilepsy surgeries (28 miRNAs, p < 10−10). We have confirmed some previous observations (e.g. up-regulation of miR-21, miR-155, down-regulation of miR-128a, miR-23a) and also identified miRNAs deregulated in GBM tissue which were observed for the first time (e.g. miR-220, miR-328, miR-888, miR-504). More importantly we have found miRNA signature (miR-224, miR-31, miR-454, miR-672, miR-885-5p, miR-432) significantly associated short progression-free survival (p < 10−6) and overall survival (p < 10−6). CONCLUSIONS: These findings indicate that miRNAs play an important role in GBM pathogenesis and may serve not only as promising predictors of therapeutic outcome but also as potential therapeutic targets in GBM patients. Supported by Grant NT13549-4/2012, NT13860-4/2012, NT11214-4/2010, NT13514-4/2012 and NT13581-4 of the Czech Ministry of Health.
AB1442-HPR Fear of movement in ankylosing spondilitis patients: A pilot study
Authors: D. Oskay, I. Düzgün, Z. Tuna, B. Elbasan, Y. Yakut, A. Tufan
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Ankylosing spondilitis (AS) is a chronic, inflammatory disorder characterized by pain and stiffness especially on back and sacroiliac joint. Pain, reduced spine mobility, and decreased physical functioning are the major manifestations of AS. In the literature, the role of fear of movement (kinesiophobia) in musculoskeletal pain disorders has been examined in studies of acute and chronic back pain, and fibromyalgia. The results of these studies tend to support the important contribution of fear of movement in the evaluation of pain, disability, function and QoL and treatment of musculoskeletal disorders. <h3>Objectives</h3> The primary objective of this pilot study was to investigate if AS patients have kinesiophobia or not. The secondary objective of the study was to investigate the effects of kinesiophobia on functional status, quality of life (QoL) of AS patients. <h3>Methods</h3> 36 Participants (18 men, 18 women) who were under a regular follow-up protocol in Gazi Universty Rheumatology Clinic with the diagnosis of AS. Primary outcome measure was kinesiophobia. Evaluation was done using the The Tampa Scale of Kinesiophobia (TSK). Exploratory measures were Bath Ankylosing Spondilitis Disease Activity Index (BASDAI), Bath Ankylosing Spondilitis Functional Index (BASFI), and ankylosing spondilitis quality of life questionnaire (ASQOL). <h3>Results</h3> The mean TSK score of patients was 43.94±6.31 (min-max: 31-59). The most remarkable result was the correlation between TSK score and BASDAI (r: 0.384; p: 0.025), BASFI (r: 0.506; p: 0.002) and ASQOL (r: 0.518; p: 0.002) scores. <h3>Conclusions</h3> Our study is the first clinical study designed to investigate kinesiophobia in AS patients. We conclude that kinesiophobia affect their functional status and quality of life. It also affected by the severity of illness. <h3>References</h3> Kori SH, Miller RP, Todd D. Kinesiophobia: a new view of chronic pain behavior. Pain Management. 1990, 3: 35-43. Vlaeyen JW, Kole-Snijders AM, Boeren RG, et al. Fear of movement/(re)injury in chronic low back pain and its relation to behavioral performance. Pain. 1995; 62: 363-372. Dagfinrud H, Kvien TK, Hagen KB, Nghien FT, Donohue JT. Physiotherapy interventions for ankylosing spondylitis. Dochrana Databased System Reviews. 2008; 23(1): CD002822. La Touche R, Escalante K, Linares MT. Treating non-specific low back pain through to pilates method. J Bodyw Mov Ther. 2008; 12: 364-374 Donzelli S, Di Domencia E, Cova AM, Galetti R, Giınta N. Two different technique in the rehabilitation treatment of low back pain: a randomized clinical trail. Eura Medicophys. 2005; 42: 205-210. Altan L, Korkmaz N, Bingol U, Gunay B. Effect of pilates training on people with ankylozing spondilitis. Arch Phys Med Rehabil 2009 Dec;90(12):1983-8 <h3>Disclosure of Interest</h3> None Declared
Bronchogenic Cyst Causing Unilateral Ventilation-Perfusion Mismatch
Authors: DANIEL F. WORSLEY, ROBERT D.A. JOHNSON, J. STEPHEN KWONG
Journal: Clinical Nuclear Medicine (1996)

A 24-year-old woman presented with dysphagia and shortness of breath. Ventilation-perfusion lung imaging demonstrated global reduction in perfusion with normal ventilation in the entire right lung. CT and MRI showed a large subcarinal mass compatible with a bronchogenic or esophageal duplication cyst. Histologic examination after surgical excision revealed findings typical for a bronchogenic cyst. Previous case reports of bronchogenic cysts detected with scintigraphy have documented complete absence of perfusion and matched ventilation-perfusion defects within the right lung. This case report demonstrates a bronchogenic cyst that caused reduced perfusion with normal ventilation within the right lung (unilateral ventilation-perfusion mismatch). Although pulmonary embolism may cause a unilateral ventilation-perfusion mismatch, other conditions that cause extrinsic compression of central pulmonary vasculature also need to be considered in patients with this scintigraphic finding.
SINUS RHYTHM HEART RATE POST ATRIAL FIBRILLATION ABLATION MAY PREDICT OUTCOMES POST ABLATION
Authors: Ammar M. Killu, Alan Sugrue, Vaibhav Vaidya, Kristi Monahan, Charles Lenz, Vidhushei Yogeswaran, Philip Y. Sun, David Hodge, Peter Brady, Paul Friedman, Douglas Packer, Samuel Asirvatham
Journal: Journal of the American College of Cardiology (2016)
Abstract 521: Active sonic hedgehog signaling between androgen independent human prostate cancer cells and normal/benign but not cancer-associated prostate stromal cells
Authors: Katsumi Shigemura, Wen-chin Haung, Haiyen Zhau, Xiangyan Li, Masuo Yamashita, Akinobu Gotoh, Soichi Arakawa, Leland Chung, Masato Fujisawa
Journal: Cancer Research (2011)

Abstract BACKGROUND: Sonic hedgehog (Shh) signaling plays a pivotal role in stromal-epithelial interaction during normal development but its role in tumor-stromal interaction during carcinogenic progression is less well defined. Since hormone refractory prostate cancer with bone metastasis is difficult to treat, it is crucial to investigate how androgen independent (AI) human prostate cancer cells communicate with their associated stroma. METHODS: Shh and its downstream target transcription factor, Gli1 mRNA, was assessed in vitro by RT-PCR and real time quantitative RT-PCR in co-culture, as cell recombinants under Shh-enriched conditions using AI human C4-2 prostate cancer, and prostate stromal fibroblasts established from normal/benign (NPF) or cancer-associated (CPF) specimens, or human bone marrow stromal (HS27A) cells. In vivo investigation was performed by monitoring serum PSA and immunohistochemical stainings by mouse models bearing chimeric tumors consisting of C4-2 and prostate stromal fibroblast cells. RESULTS: We found that 1) Shh has minimal growth-stimulating effects on prostate cancer or prostate stromal fibroblasts; 2) active Shh signaling was found between AI human prostate cancer and prostate stroma; and 3) osteonectin (ON) is a Gli-1 target gene in benign/normal but not cancer-associated stromal fibrobasts. ON upregulation was observed in co-cultured human prostate stromal cells when in contact with prostate stromal cells. CONCLUSIONS: Based on co-culture and chimeric tumor models, active Shh-mediated signaling was demonstrated between AI human prostate cancer and prostate stroma in a paracrine- and tumor progression-dependent manner. Our study suggests drugs like cyclopamine that interferes with Shh signaling could be beneficial in preventing AI progression of human prostate cancer. 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 521. doi:10.1158/1538-7445.AM2011-521
Osteopetrosis
Authors: FAREEDA AHMED AL-KANDARI, NAFISAH ABDULLA KAZEM, B. DAVID COLLIER, G. M. SHAH SYED
Journal: Clinical Nuclear Medicine (2003)

AHMED AL-KANDARI, FAREEDA M.D.; ABDULLA KAZEM, NAFISAH M.D.; DAVID COLLIER, B. M.D.; SHAH SYED, G. M. M.D. Author Information
TCTAP A-114 Comparison Between High and Low Doses of Subcutaneously Infiltrated Nitroglycerin on Transradial Access for Coronary Procedures
Authors: Babu Ezhumalai, Santhosh Satheesh, Atul Mathur, Bhuvaneswaran K. Panicker, Balachander Jayaraman, Ashok Seth
Journal: Journal of the American College of Cardiology (2015)
BMET-10VASCULOGENIC MIMICRY IN LUNG CANCER BRAIN METASTASIS
Authors: Zhongping Chen
Journal: Neuro-Oncology (2015)

OBJECTIVE: Vasculogenic mimicry (VM) is involved in the process of tumor (including gliomas) initiation and progression. However, the existence and prognostic significance of VM in brain metastases have not been elucidated. In this study, we were trying to detect the presence of VM in brain metastases original from lung cancer, and correlate to patient prognosis. METHODS: The clinical data were retrospectively reviewed in 60 patients received surgical removal for lung cancer brain metastases at our department from 2000 to 2014. The VM was determined by utility of CD34-PAS dual staining. RESULTS: In 60 brain metastatic tumor samples, the VM (PAS positive but CD34 negative channel) were found in 22 cases, and the VM-positive rate in brain metastases was 36.6%. The univariate analysis showed that patient KPS scoring, age and treatment strategy, but not VM, were related with patient survival time. The multivariate analysis indicated that KPS scoring and treatment strategy after brain metastasis surgery were closely related to patient prognosis. CONCLUSION: VM exits in lung cancer brain metastases, but does not associate with patient prognosis. Longer survival of patient was related with KPS scoring (over 70) and treatment strategy after surgery.