tbuckley/cabot-search huggingface dataset:
Abstract 2678: Targeting prostate cancer metastasis with novel small molecule agonists of EphA2
Authors: Bingcheng Wang, Aaron Petty
Journal: Cancer Research (2015)

Abstract During tumor progression, EphA2 receptor can gain ligand-independent pro-oncogenic functions due to Akt activation and reduced ephrin-A ligand engagement. The effects can be reversed by ligand stimulation, which triggers the intrinsic tumor suppressive signaling pathways of EphA2 including inhibition of PI3/Akt and Ras/ERK pathways. These observations argue for development of small molecule agonists for EphA2 as potential tumor intervention agents. Through virtual screening and cell-based assays, we report here the identification and characterization of doxazosin as a novel small molecule agonist for EphA2 and EphA4, but not for other Eph receptors tested. NMR studies revealed extensive contacts of doxazosin with EphA2/A4, recapitulating both hydrophobic and electrostatic interactions recently found in the EphA2/ephrin-A1 complex. Clinically used as an α1-adrenoreceptor antagonist (Cardura®) for treating hypertension and benign prostate hyperplasia, doxazosin activated EphA2 independent of α1-adrenoreceptor. Similar to ephrin-A1, doxazosin inhibited Akt and ERK kinase activities in an EphA2-dependent manner. Treatment with doxazosin triggered EphA2 receptor internalization, and suppressed haptotactic and chemotactic migration of prostate cancer, breast cancer, and glioma cells. Moreover, in an orthotopic xenograft model, doxazosin reduced distal metastasis of human prostate cancer cells and prolonged survival in recipient mice. More potent and selective derivatives of doxazosin have been developed with enhanced efficacy against prostate cancer and glioblastoma. To our knowledge, this is the first example of small molecule agonists of a receptor tyrosine kinase that is capable of inhibiting malignant behaviors in vitro and in vivo. Citation Format: Bingcheng Wang, Aaron Petty. Targeting prostate cancer metastasis with novel small molecule agonists of EphA2. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2678. doi:10.1158/1538-7445.AM2015-2678
Still No Migraine Relief for Kids
Authors: Anita Slomski
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
PO31FRACTAL ANALYSIS OF PREOPERATIVE IMAGING AS A TOOL FOR PREDICTING PROGNOSIS IN GLIOBLASTOMA MULTIFORMAE – PRELIMINARY RESULTS
Authors: Marcin Czyz, Hesham Radwan, Alexis M. Demopoulos, Christopher G. Filippi, Michael Schulder
Journal: Neuro-Oncology (2015)

INTRODUCTION: The fractal analysis objectively quantifies the geometric complexity of structures in unitless measure index. We hypothesise it may reflect the degree of malignancy in glioblastoma multiformae (GBM). METHOD: A group of 33 patients with postoperative diagnosis of GBM were retrospectively enrolled into the study. Preoperative brain MR (T1-weighted post-gadolinium) were processed and analyzed to determine the average and maximum fractal dimension (FD and FDmax) of the inner and outer surface of the contrast enhancing part of the tumour. Box-count method and ImageJ 1.49 software were used. Corellations between fractal dimensions and: 1) demographics; 2) immunohistochemical characteristics; 3) progression free (PFS) and overal survival (OS); 4) tumour volume were determined by mean of nonparametric tests. RESULTS: There were 8 women and 25 men in the study group, mean age was 67 ± 10 years. Fractal analysis was possible to be perfomed in all cases with good inter-observer reproducibility (Kappa >0.80). The median FD was 1.2550 (IQR 0.0897) and FDmax 1.3848 (IQR 0.1057). There was a statisticaly significant Spearman Rank correlation between fractal dimensions and Ki-67 index (-0.44 and -0.52 for FD and FDmax respectively). Both FD and FDmax were significantly (Fi2; p < 0.05) correlated with: age, tumor volume, PFS, OS, and Phosphohistone-H3 index but not with the expression of neurofilaments, p53, GFAP, EGFR and IDH-1. CONCLUSION: Fractal analysis of the preoperative MR images may pottentially act as an adjunct in determing the degree of malignancy and prognosis in GBM. Further studies on a wider cohort of patients are warranted.
Abstract 3070: MicroRNA-155 directly targets PDCD4 and activates BIC promoter through AP-1 dependent transcription to replenish miR-155 expression in SAS cells
Authors: shabir A. zargar, Devarajan Karunagaran
Journal: Cancer Research (2015)

Abstract Pdcd4 (programmed cell death 4) has been demonstrated to be a tumor suppressor gene and is expressed at higher levels during apoptosis. PDCD4 is down regulated in a subset of oral cancers (tongue and buccal cavity) and an association between its down-regulation by miR-21 and tumorigenesis and invasion in oral carcinoma has been demonstrated. In this study we show that miR-155 directly targets PDCD4 in SAS (tongue squamous carcinoma) cells. We demonstrate a positive feedback loop between miR-155 expression and AP-1 dependent transcription through the down regulation of PDCD4. Analysis of miR-155 promoter (BIC) showed the presence of NF-κB and AP-1 (c-Jun and c-Fos) transcription factor binding sites and PDCD4 is known to inhibit AP-1 dependent transcription. Ectopic expression of PDCD4 in SAS cells drastically reduced the BIC promoter activity via inhibition of AP-1 dependent transcription and down regulated the levels of miR-155. We also generated the Lentiviral based miR-155 sponge stable cells to down regulate miR-155 in SAS cells, and found an increase in PDCD4 protein levels. The activity of BIC promoter was relatively low in miR-155 sponge stable cells compared to control sponge stable cells as analyzed by a dual luciferase reporter assay. We have also seen the reduced rate of proliferation in miR-155 sponge stable cells compared to control sponge stable cells. Thus our data show that miR-155 directly targets PDCD4 and consequently activates AP-1 dependent transcription in BIC promoter and increasing the levels of miR-155. Citation Format: shabir A. zargar, Devarajan Karunagaran. MicroRNA-155 directly targets PDCD4 and activates BIC promoter through AP-1 dependent transcription to replenish miR-155 expression in SAS cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3070. doi:10.1158/1538-7445.AM2015-3070
221. Staurosporine Increases Lentiviral Transduction of Human CD34+ Cells
Authors: Melissa Bonner, Gretchen Lewis, Lauryn Christiansen, Dakota Campbell, Christopher Tipper, Amanda Hamel, Seema Shah, Holly Horton, Olivier Negre, Gabor Veres, Philip Gregory
Journal: Molecular Therapy (2016)

Lentiviral vector (LVV) mediated transduction of CD34+ hematopoietic stem and progenitor cells holds tremendous promise for the treatment of monogenic diseases of the blood. Critical to the success of this ex vivo gene therapy approach is the generation of a sufficient proportion of gene-modified cells. Here we investigated the potential of staurosporine, a protein kinase inhibitor, to enhance the transduction of LVVs in mobilized peripheral blood CD34+ cells both in vitro and in vivo. Staurosporine treatment has been previously demonstrated to increase HIV-1 integration in metaphase-arrested cells and shown to cause chromatin relaxation in metaphase cells (Manioui et al., Virology 2004). Additionally, in a separate study staurosporine treatment led to a 150% increase in transduction of CAp24+ CD4+ T cells (Permanyer et al., PLoS One 2013). Staurosporine increases vector copy number (VCN) approximately 2-fold when added to human mobilized peripheral blood (mPB) CD34+ enriched cells prior to transduction. The mechanism of this VCN improvement was investigated using the BLAM assay and a 1.5-fold improvement in viral entry was demonstrated. This effect was observed in at least six different mPB CD34+ cell lots that had various levels of transducibility. Interestingly, the effect of increased LVV transduction was most striking with low transducing cell lots and the effect diminished in higher transducing cell lots. Staurosporine treatment did not affect viability of cells post-transduction and there was no difference in in vitro colony formation in staurosporine-treated cells compared to vehicle-treated cells. NSG mice transplanted with cells transduced in the presence of 400 nM or 800 nM staurosporine demonstrated a statistically significant 3-fold and 4-fold increase in VCN in human CD45+ cells in bone marrow at 4 months post-transplantation compared to vehicle-treated cells. Importantly, there was no significant difference in engraftment nor any observed lineage-bias between groups. Based on these observations, the use of staurosporine to enhance LVV transduction of human CD34+ cells is a promising method to improve the potential therapeutic benefit of gene therapy drug products.
Pla a 2 and Pla a 3 reactivities identify plane tree-allergic patients with respiratory symptoms or food allergy
Authors: E. Scala, L. Cecchi, D. Abeni, E. C. Guerra, L. Pirrotta, M. Locanto, M. Giani, R. Asero
Journal: Allergy (2017)

Nine hundred and thirty-nine rPla a 1, nPla a 2, and rPla a 3 ImmunoCAP ISAC reactors were studied. nPla a 2pos MUXF3pos but Pla a 1/2neg subjects were excluded from the study because they were cross-reactive carbohydrate determinant reactors. Among the 764 remaining participants, 71.9% were Pla a 3pos, 54.1% Pla a 2pos, and 10.9% Pla a 1pos. Among Pla a 3 reactors, 89.6% were Pru p 3pos and 86.8% Jug 3pos, but the strongest IgE recognition relationship was observed between Pla a 3 and Jug r 3. Distinctive clinical subsets could be documented among plane tree-allergic patients. Pla a 3 reactors had both local and systemic food-induced reactions, but lower past respiratory symptoms occurrence. Pla a 2 reactivity was associated with respiratory symptoms but inversely related to systemic reactions to food. Cosensitization to Pla a 2 and Pla a 3 was associated with a lower past incidence of severe food-induced reactions.
Hospital volume and adverse events following esophageal endoscopic submucosal dissection in Japan
Authors: Hiroyuki Odagiri, Hideo Yasunaga, Hiroki Matsui, Shigeru Matsui, Kiyohide Fushimi, Mitsuru Kaise
Journal: Endoscopy (2016)

<b>Background and study aims</b> Esophageal endoscopic submucosal dissection (ESD) has gradually acquired popularity as a minimally invasive surgery for early cancers not only in Japan, but also in other countries. However, most reported outcomes have been based on relatively small samples of patients from specialized centers. Therefore, the association between hospital volume and the rate of adverse events following esophageal ESD has been poorly understood. <b>Patients and methods</b> Using a nationwide administrative database in Japan, we identified patients who underwent esophageal ESD between 1 July 2007 and 31 March 2013. Hospital volume was defined as the number of esophageal ESD procedures performed per year at each hospital and was categorized into quartiles. <b>Results</b> In total, 12 899 esophageal ESD procedures at 699 institutions were identified during the study period. Perforation and perforation-related disorders were observed in 422 patients (3.3 %), and one patient died after perforation. There was a significant association between a lower hospital volume and a higher proportion of adverse events following esophageal ESD. Although not statistically significant, a similar tendency was observed in the occurrence of blood transfusion within 1 week after ESD and all-cause in-hospital death. Multivariable logistic regression analysis showed that hospitals with very high case volumes were less likely to experience adverse events following esophageal ESD than hospitals with very low volumes. <b>Conclusions</b> The proportion of perforation and perforation-related disorders following esophageal ESD was permissibly low, and there was a linear association between higher hospital volume and lower rates of adverse events following esophageal ESD.
Abstract 148: Transcriptome sequencing reveals PCAT5 - new ERG-regulated non-coding transcript in prostate cancer
Authors: Antti Ylipää, Kati Kivinummi, Matti Annala, Annika Kohvakka, Leena Latonen, Mauro Scaravilli, Kimmo Kartasalo, Simo-Pekka Leppänen, Serdar Karakurt, Janne Seppälä, Olli Yli-Harja, Teuvo L.J. Tammela, Wei Zhang, Tapio Visakorpi, Matti Nykter
Journal: Cancer Research (2015)

Abstract Background: Prostate cancer (PC) is the second most common cancer among men. Most PC-related deaths are due to invasive tumors that are treated with therapies inhibiting androgen production or androgen receptor (AR) activity. After an initial response, tumors invariably progress to castration resistant prostate cancers (CRPCs) for which no effective cure exists. Methods and Results: We used transcriptome sequencing to study fresh-frozen tissue specimens from 12 benign prostatic hyperplasias (BPHs), 28 PCs, and 13 CRPCs. Reference-based transcriptome assembly uncovered 145 previously unannotated intergenic PC and CRPC associated long non-coding transcripts (lncRNAs) or isoforms. One third of the transcripts were CRPC-specific. We showed that one of the novel transcripts, Prostate Cancer Associated Transcript 5 (PCAT5), expressed in half of the tumors, was likely regulated by ERG, the key transcription factor in ∼50% of prostate cancers. Genome-wide expression analysis of a PCAT5-positive prostate cancer cell line after PCAT5 knockdown suggested significant alterations in proliferation pathways. In vitro validation of the pathway alterations revealed concordantly dramatic effects in phenotype: stalling of cell growth, migration, invasion, and colony forming potential, and increase in the rate of apoptosis. Conclusions: We identified the key differences between PC and CRPC in transcriptome level, and validated the oncogenic potential of a novel lncRNA in ERG-positive prostate cancers, PCAT5. Our study presents a number of putative lncRNA biomarkers for CRPC, and opportunities for therapeutic intervention. Citation Format: Antti Ylipää, Kati Kivinummi, Matti Annala, Annika Kohvakka, Leena Latonen, Mauro Scaravilli, Kimmo Kartasalo, Simo-Pekka Leppänen, Serdar Karakurt, Janne Seppälä, Olli Yli-Harja, Teuvo L.J. Tammela, Wei Zhang, Tapio Visakorpi, Matti Nykter. Transcriptome sequencing reveals PCAT5 - new ERG-regulated non-coding transcript in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 148. doi:10.1158/1538-7445.AM2015-148
Phase 3b UPFRONT Study: Interim Results From a Community Practice-Based Prospective Randomized Trial Evaluating Three Bortezomib-Based Regimens in Elderly, Newly Diagnosed Multiple Myeloma Patients.
Authors: Ruben Niesvizky, James Reeves, Ian W Flinn, Robert M. Rifkin, Billy Clowney, Nashat Gabrail, Vijay R. Phooshkooru, Veena Charu, Christopher H. Chay, Deyanira Corzo, Rachel Neuwirth, Robert F. Manges, Thomas A. Warr
Journal: Blood (2009)
Low-Dose Administration of Recombinant IL-2 Following T Cell Depleted Bone Marrow Transplantaion Induces Expansion of CD4+CD25+ FOXP3+ Regulatory T Cells in Vivo.
Authors: Emmanuel Zorn, Despina Lista, Haesook Kim, Roberto Bellucci, Christine Canning, Robert J. Soiffer, Jerome Ritz
Journal: Blood (2004)
A Rare Genetic Polymorphism in C5 Confers Poor Response to the Anti-C5 Monoclonal Antibody Eculizumab by Nine Japanese Patients with PNH
Authors: Jun-ichi Nishimura, Masaki Yamamoto, Shin Hayashi, Kazuma Ohyashiki, Kiyoshi Ando, Hideyoshi Noji, Kunio Kitamura, Tetsuya Eto, Toshihiko Ando, Masayoshi Masuko, Hirohiko Shibayama, Masakazu Hase, Li Lan, Paul Tamburini, Johji Inazawa, Taroh Kinoshita, Yuzuru Kanakura
Journal: Blood (2012)
Predicting Poor Peripheral Blood Stem Cell Mobilization in Multiple Myeloma (MM) Using Initial Peripheral CD34 Counts: Developing Target-Based Cut-Points for Early Intervention.
Authors: Shirshendu Sinha, Dennis A. Gastineau, William J. Hogan, Ivana N Micallef, Francis K. Buadi, David Dingli, Angela Dispenzieri, Morie A. Gertz, Carl Greiner, Suzzane Hayman, David J. Inwards, Patrick B. Johnston, Martha Q. Lacy, Mark R. Litzow, Luis F. Porrata, Jeffrey Winters, Shaji Kumar
Journal: Blood (2009)
MPTH-15MOLECULAR RECLASSIFICATION OF CNS-PRIMITIVE NEUROECTODERMAL TUMORS INTO WELL-KNOWN AND NOVEL TUMOR ENTITIES
Authors: Dominik Sturm, Brent Orr, Volker Hovestadt, David T. W. Jones, David Capper, Peter Lichter, Andrey Korshunov, Stefan Pfister, David Ellison, Marcel Kool
Journal: Neuro-Oncology (2015)

CNS-primitive neuroectodermal tumors (CNS-PNETs) are poorly differentiated embryonal tumors with early onset and aggressive clinical behavior. Histological diagnosis is complicated by morphological heterogeneity and divergent differentiation. Recent studies suggest the existence of molecular subgroups of CNS-PNETs sharing biological characteristics with other CNS tumors. To investigate this we have analyzed 301 fresh-frozen or paraffin-embedded CNS-PNET samples using DNA methylation (n = 301) and expression (n = 76) arrays. (Epi-)genetic profiles of CNS-PNETs were compared to >200 reference cases of other pediatric and adult brain tumors representing more than 20 well-known entities. DNA methylation and gene expression patterns segregated brain tumors by histological entities and molecular subgroups. Solely, CNS-PNET profiles showed a significant overlap with various well-defined entities, including AT/RT, ETMR, high-grade glioma, medulloblastoma, ependymoma, and others. When screening CNS-PNETs with profiles highly resembling other entities, hallmark genetic alterations of these, such as amplification of 19q13.42, mutations in IDH1 or H3F3A, or mutations/deletions of the SMARCB1 locus, were frequently detected. Also, established protein markers, such as INI-1, LIN28A, and OLIG2, confirmed the reclassification of these CNS-PNETs. Strikingly, a subset (∼25%) of CNS-PNETs, which could not be reclassified, segregated into at least five distinct molecular subgroups, each with its own characteristic pattern of DNA-methylation, copy number aberrations, gene expression, and recurrent mutations. Extending our clustering cohort to include larger series of non CNS PNET tumours, we identified additional brain tumors from various entities to resemble DNA methylation and mutation patterns of these five new molecular subgroups. The correct classification of CNS-PNETs based solely on histology remains challenging. The majority of cases can reliably be reclassified using molecular markers, indicating that a significant proportion of CNS-PNETs represents a variety of other brain tumor subtypes. The remaining CNS PNETs comprise five novel tumour groups with distinct molecular features that overlap with tumors previously diagnosed as non PNETs.
Reconstitution of Neutrophil NADPH Oxidase Activity in Murine X-CGD Following Transplantation of Retrovirus-Transduced Marrow: Potential Impact of Submyeloablative Conditioning.
Authors: Mohammed Sadat, Cecilia Barese, Nancy Pech, W. Scott Goebel, Mervin C. Yoder, Sean Mooney, Kenneth Cornetta, Manuel Grez, Mary C. Dinauer
Journal: Blood (2005)
PWE-012 Colonoscopic adverse events in St Mark's bowel cancer screening experience: Abstract PWE-012
Authors: S Gupta, M E Vance, N Suzuki, C Fraser, B P Saunders, S Thomas-Gibson
Journal: Gut (2010)

<h3>Introduction</h3> The incidence of polyps requiring therapy is higher in Bowel Cancer Screening (BCS) compared to the symptomatic population. The current BCS patient information leaflets quote “heavy” bleeding risk of 1:150 and perforation 1:1500. <h3>Methods</h3> To assess all complications 2006–2009. Data were collected prospectively. Additional information was retrieved from the screening team. <h3>Result</h3> 1253 procedures were performed in this period. 583 patients had 1625 polyps requiring polypectomy. There were eight (0.6%) reported adverse events and five (0.4%), recalled by screening team (Abstract 012). <h3>Conclusion</h3> Less than 1:500 patients undergoing polypectomy required transfusion. Overall bleeding risk (including small bleeds without transfusion) was ∼1:80 patients requiring polypectomy. Admission risk was 0.6%. Perforation risk was ∼1:1200 colonoscopies and ∼1:600 patients requiring polypectomy. No patients required surgery or prolonged admission, with no procedure related mortality. Despite a higher therapeutic load in the BCS cohort, the risk of significant complications was within acceptable ranges.
ERCC1 and class III β-tubulin expression in chemotherapy-naive advanced non-small cell lung cancer patients treated with cisplatin and vinorelbine.
Authors: S. Park, J. C. Park, Y. J. Yang
Journal: Journal of Clinical Oncology (2011)

e21010 Background: The excision repair cross-complementation group 1 (ERCC1) and class III β-tubulin are suggested to be associated with resistance to cisplatin and vinorelbine, respectively. Methods: We evaluated the effects of ERCC1 and class III β-tubulin expression in the aspect of treatment response and survival in chemotherapy-naïve advanced non-small cell lung cancer (NSCLC) patients treated with cisplatin and vinorelbine. Results: Protein expression of ERCC1 and class III β-tubulin was evaluated immunohistochemically in tumor samples taken from 49 patients. High expression of ERCC1 and class III β-tubulin was found in 24 and 29 patients, respectively. High expression of ERCC1 and class III β-tubulin was associated with poor response rate compared with low expression (17% vs 48%, P = 0.03; 21% vs 50%, P = 0.03, respectively). High expression of class III β-tubulin was significantly associated with shorter overall survival (OS) (P = 0.041). With this combination, patients with low expression of both ERCC1 and class III β-tubulin had longer median OS (132 weeks, P = 0.007) than patients with high expression of either ERCC1 or class III β-tubulin. Multivariate analysis revealed that high expression of ERCC1 (HR = 2.554, P = 0.025) and class III β-tubulin (HR = 3.109, P = 0.013) were independent prognostic markers for shorter OS. Conclusions: ERCC1 and class III β-tubulin were both predictive and prognostic factors in advanced NSCLC patients treated with cisplatin and vinorelbine chemotherapy and might be useful biomarkers in decision making of chemotherapy.
<i>Notes from the Field:</i> Outbreak of <i>Escherichia coli</i> O157 Infections Associated with Goat Dairy Farm Visits — Connecticut, 2016
Authors: Mark Laughlin, Kelly Gambino-Shirley, Paul Gacek, Quyen Phan, Lauren Stevenson, Alexandra Mercante, Jocelyn Mullins, Laura Burnworth, Anna Blackstock, Jafar H Razeq, Matthew Cartter, Megin Nichols
Journal: MMWR Morbidity and Mortality Weekly Report (2016)