tbuckley/cabot-search huggingface dataset:
MiR-424 and miR-155 deregulated expression in cytogenetically normal acute myeloid leukaemia: correlation with NPM1 and FLT3 mutation status
Authors: Isabella Faraoni, Serena Laterza, Davide Ardiri, Claudia Ciardi, Francesco Fazi, Francesco Lo-Coco
Journal: Journal of Hematology & Oncology (2012)

MicroRNA have a central role in normal haematopoiesis and are deregulated in acute myeloid leukaemia (AML). The purpose of the study was to investigate by qRT-PCR the expression of miRNAs involved in myeloid differentiation (miR-424, miR-155, miR-223, miR-17-5p) in 48 patients with cytogenetically normal AML well characterized for NPM1 and/or FLT3 mutations. Three types of normalization were used for the data validation. We found that miR-424 was down-modulated in AMLs with NPM1mutA regardless of FLT3 status. On the contrary, miR-155 showed up-regulation in patients with FLT3 internal tandem duplications (ITD) with or without NPM1 mutations. No significant associations were found by analyzing miR-223 and miR-17-5p in relation to FLT3 and NPM1 status. This study supports the view that major genetic subsets of CN-AML are associated with distinct miRNA signatures and suggests that miR-424 and miR-155 deregulation is involved in the pathogenesis of CN-AML with NPM1 and FLT3-ITD mutations, respectively.
The 1+1 Trial
Authors: Dietmar Bänsch, Frank Steffgen, Gerian Grönefeld, Christian Wolpert, Dirk Böcker, Ralph-Uwe Mletzko, Wolfgang Schöls, Karlheinz Seidl, Michael Piel, Feifan Ouyang, Stefan H. Hohnloser, Karl-Heinz Kuck
Journal: Circulation (2004)

Background— The tachycardia detection interval (TDI) in implantable cardioverter/defibrillators (ICDs) is conventionally programmed according to the slowest documented ventricular tachycardia (VT), with a safety margin of 30 to 60 ms. With this margin, VTs above the TDI may occur. However, longer TDIs are associated with an increased risk of inappropriate therapy. We hypothesized that patients with slow VTs (&lt;200 bpm) may benefit from a long TDI and a dual-chamber detection algorithm compared with a conventionally programmed single-chamber ICD. Methods and Results— Patients with VTs &lt;200 bpm were implanted with a dual-chamber ICD that was randomly programmed to a dual-chamber algorithm and a TDI of ≥469 ms or to a single-chamber algorithm with a TDI 30 to 60 ms above the slowest documented VT cycle length and the enhancement criteria of cycle length variation and acceleration. The primary combined end point was the number of all inappropriate therapies, VTs above the TDI, and VTs with significant therapy delay (&gt;2 minutes). After 6 months, a crossover analysis was performed. Total follow-up was 1 year. One hundred two patients were included in the study. The programmed TDI was 500±36 ms during the dual-chamber phase and 424±63 ms during the single-chamber phase. For the primary end point (inappropriate therapies, VTs above the TDI, or VTs with detection delay), a moderate superiority of the dual-chamber mode was found: Mann-Whitney estimator=0.6661; 95% CI, 0.5565 to 0.7758; P =0.0040. Conclusions— Dual-chamber detection with a longer TDI improves VT detection and does not increase the rate of inappropriate therapies despite a considerable increase in tachycardia burden.
Gene Therapy with Secretory Leukoprotease Inhibitor Promoter-Controlled Replication-Competent Adenovirus for Non-Small Cell Lung Cancer
Authors: Makoto Maemondo, Yasuo Saijo, Ko Narumi, Toshiaki Kikuchi, Kazuhiro Usui, Ryushi Tazawa, Kunio Matsumoto, Toshikazu Nakamura, Katsunori Sasaki, Minoru Takahashi, Yoshiro Niitsu, Toshihiro Nukiwa
Journal: Cancer Research (2004)

Abstract Secretory leukoprotease inhibitor (SLPI) is highly expressed in almost all non-small cell lung cancers (NSCLCs), but not in the majority of other tumor types. In an attempt to create a specific gene therapy for NSCLC, we constructed AdSLPI.E1AdB, an adenovirus vector with a double expression cassette consisting of E1A driven by the SLPI promoter gene followed by E1B-19K under the control of the cytomegalovirus (CMV) promoter that can selectively replicate only in NSCLC cells. Infection with AdSLPI.E1AdB yielded E1A protein expression and adenovirus replication resulting in a &amp;gt;100-fold increase of the virus titers only in SLPI-producing NSCLC cells (A549, H358, and HS24 cells). In contrast, neither E1A protein nor replication was detected in non-SLPI-producing HepG2 cells. Treatment with AdSLPI.E1AdB significantly inhibited the proliferation of NSCLC cells in vitro in a dose-dependent manner, whereas the cell growth of HepG2 or normal human bronchial epithelial cells was not affected by AdSLPI.E1AdB infection. Direct injection of AdSLPI.E1AdB into A549 and H358 tumors in nude mice resulted in a marked reduction in tumor growth compared with controls (A549, 57%, P &amp;lt; 0.02; H358, 67%, P &amp;lt; 0.03). Histological examination revealed the replication of AdSLPI.E1AdB and strong induction of necrosis and apoptosis. In addition, we evaluated the combination of AdSLPI.E1AdB and AdCMV.NK4 encoding NK4 protein, which has strong antiangiogenic activity. E1A expressed by AdSLPI.E1AdB trans-acts on the replication of AdCMV.NK4 and thus increases the expression of NK4. Injection of these two vectors into H358 tumors resulted in a more striking reduction of tumor growth compared with single injection of each vector. These results suggest that AdSLPI.E1AdB could provide a selective therapeutic modality for NSCLC and that the combination of AdSLPI.E1AdB and AdCMV.NK4 may be a more effective gene therapy for NSCLC.
White Matter Integrity and Cognitive Impairment in First-Episode Psychosis
Authors: Rocío Pérez-Iglesias, Diana Tordesillas-Gutiérrez, Philip K. McGuire, Gareth J. Barker, Roberto Roiz-Santiañez, Ignacio Mata, Enrique Marco de Lucas, Jose Manuel Rodríguez-Sánchez, Rosa Ayesa-Arriola, Jose L. Vazquez-Barquero, Benedicto Crespo-Facorro
Journal: American Journal of Psychiatry (2010)

Objective Impaired cognitive function has been identified as a core feature of schizophrenia. However, a significant proportion of patients do not show any cognitive deficits. The aim of this study was to assess if there were differences in white matter integrity between patients with and without cognitive impairment. Method A diffusion tensor imaging study and neurocognitive assessment were conducted in 49 patients with first-episode psychosis and 41 healthy comparison subjects. Subjects were assessed using the Continuous Performance Test, the Grooved Pegboard Test, the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B. For each test, the patient sample was subdivided according to performance, with those scoring more than one standard deviation below the normative mean categorized as impaired. For each cognitive domain, white matter fractional anisotropy in deficit and nondeficit subgroups was compared using a voxel-based analysis. A nonparametric statistical method, controlling for multiple comparisons, was applied. Results Impairment on the Trail Making Test Part B was associated with reduced fractional anisotropy in the right/left anterior thalamic radiation and inferior fronto-occipital fasciculus, forceps minor, and left superior and inferior longitudinal fasciculi. Patients exhibiting Grooved Pegboard Test impairment showed reduced fractional anisotropy in the forceps minor, inferior fronto-occipital fasciculus, anterior thalamic radiation, and corticospinal and corticopontine tracts. Impaired performance on the Rey Auditory Verbal Learning Test and Continuous Performance Test was not associated with significant differences in fractional anisotropy. Conclusion Deficits in executive and motor functioning in patients with first-episode psychosis are associated with reductions in white matter integrity in the major fasciculi that connect the frontal and temporal cortices as well as in pathways connecting cortical and subcortical regions. Their presence at the onset of illness, in minimally medicated patients, indicates that these findings are not attributable to effects of chronic illness or its treatment.
TM-11 * METABOLOMIC ANALYSIS OF GLIOBLASTOMA MULTIFORME UPON ARGININE DEPRIVATION TREATMENT
Authors: J. Langer, F. A. Elustondo, E. C. Y. Chan, H. Antti, E. Want, K. ONeill, N. Syed
Journal: Neuro-Oncology (2014)

INTRODUCTION: Treatment of glioblastoma (GBM) remains challenging, and metabolic targeting opens novel treatment approaches. Arginine is a semi-essential amino-acid that plays a central role in various proliferative cellular reactions. Argininosuccinate synthetase-1 (ASS1) is the rate-limiting enzyme of de novo arginine synthesis, and methylation specific silencing of ASS1 exerts an auxotrophic dependency for extracellular arginine in GBM, amongst other cancers. We have identified that ASS1-silenced GBM cell lines targeted by arginine-deprivation therapy through pegylated arginine deiminase (ADI-PEG20) resulted in arrested proliferation as well as autophagy, highlighting the key role of arginine in GBM cell proliferation. Consequences of arginine deprivation by ADI-PEG20 were analysed with an untargeted metabolomics approach, with the aim of identifying novel metabolic targets for therapy in ASS1 positive and negative cells. METHODS: ASS1 positive and negative GBM cell lines were exposed to arginine deprivation by ADI-PEG20, and samples for 1H NMR and GC/TOF-MS metabolic analysis were prepared, and the data was processed according to established protocols. This included data analysis via principal component analysis (PCA) using SIMCA-P software, and further multi- and uni-variate studies were performed in MATLAB as well as Graphpad Prism. RESULTS: 1H NMR and GC/TOF-MS analysis, via PCA, revealed separation in the metabolic profiles between ADI-PEG20 treated and non-treated GBM cell lines, particularly striking in ASS1-deficient cell lines. OPLS-DA analysis of 1H NMR data highlighted discriminant metabolites including intermediates of the arginine metabolism, such as decreases in creatine and choline levels, not previously linked to arginine deprivation. Functional investigations demonstrated that creatine was able to promote proliferation in GBM cell lines. CONCLUSIONS: We have identified differentially altered metabolic pathways in GBM as a result of arginine deprivation that are involved in proliferation, including creatine. Changes observed in GBM lines showed potential to use metabolic profiles for monitoring treatment response, and open new avenues for therapies.
Circuits for Skilled Reaching and Grasping
Authors: Bror Alstermark, Tadashi Isa
Journal: Annual Review of Neuroscience (2012)

From an evolutionary perspective, it is clear that basic motor functions such as locomotion and posture are largely controlled by neural circuitries residing in the spinal cord and brain-stem. The control of voluntary movements such as skillful reaching and grasping is generally considered to be governed by neural circuitries in the motor cortex that connect directly to motoneurons via the corticomotoneuronal (CM) pathway. The CM pathway may act together with several brain-stem systems that also act directly with motoneurons. This simple view was challenged by work in the cat, which lacks the direct CM system, showing that the motor commands for reaching and grasping could be mediated via spinal interneurons with input from the motor-cortex and brain-stem systems. It was further demonstrated that the spinal interneurons mediating the descending commands for reaching and grasping constitute separate and distinct populations from those involved in locomotion and posture. The aim of this review is to describe populations of spinal interneurons that are involved in the control of skilled reaching and grasping in the cat, monkey, and human.
Her-2-neu Expression and Progression Toward Androgen Independence in Human Prostate Cancer
Authors: S. Signoretti
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Human prostate cancers are initially androgen dependent but ultimately become androgen independent. Overexpression of the Her-2-neu receptor tyrosine kinase has been associated with the progression to androgen independence in prostate cancer cells. We examined the expression of Her-2-neu in normal and cancerous prostate tissues to assess its role in the progression to androgen independence. Methods: Prostate cancer tissue sections were obtained from 67 patients treated by surgery alone (UNT tumors), 34 patients treated with total androgen ablation therapy before surgery (TAA tumors), and 18 patients in whom total androgen ablation therapy failed and who developed bone metastases (androgen-independent [AI] disease). The sections were immunostained for Her-2-neu, androgen receptor (AR), prostate-specific antigen (PSA), and Ki-67 (a marker of cell proliferation) protein expression. Messenger RNA (mRNA) levels and gene amplification of Her-2-neu were examined by RNA in situ hybridization and fluorescent in situ hybridization(FISH), respectively, in a subset of 27 tumors (nine UNT, 11 TAA, and seven AI). All statistical tests were two-sided. Results: Her-2-neu protein expression was statistically significantly higher in TAA tumors than in UNT tumors with the use of two different scoring methods (P = .008 and P = .002). The proportion of Her-2-neu-positive tumors increased from the UNT group (17 of 67) to the TAA group (20 of 34) to the AI group (14 of 18) (P<.001). When compared with UNT tumors, tumor cell proliferation was higher in AI tumors (P = .014) and lower in TAA tumors (P<.001). All tumors expressed AR and PSA proteins. Although Her-2-neu mRNA expression was high in TAA and AI tumors, no Her-2-neu gene amplification was detected by FISH in any of the tumor types. Conclusions: Her-2-neu expression appears to increase with progression to androgen independence. Thus, therapeutic targeting of this tyrosine kinase in prostate cancer may be warranted.
Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer
Authors: Robert N. Jorissen, Peter Gibbs, Michael Christie, Saurabh Prakash, Lara Lipton, Jayesh Desai, David Kerr, Lauri A. Aaltonen, Diego Arango, Mogens Kruhøffer, Torben F. Ørntoft, Claus Lindbjerg Andersen, Mike Gruidl, Vidya P. Kamath, Steven Eschrich, Timothy J. Yeatman, Oliver M. Sieber
Journal: Clinical Cancer Research (2009)

PURPOSE: Colorectal cancer prognosis is currently predicted from pathologic staging, providing limited discrimination for Dukes stage B and C disease. Additional markers for outcome are required to help guide therapy selection for individual patients. EXPERIMENTAL DESIGN: A multisite single-platform microarray study was done on 553 colorectal cancers. Gene expression changes were identified between stage A and D tumors (three training sets) and assessed as a prognosis signature in stage B and C tumors (independent test and external validation sets). RESULTS: One hundred twenty-eight genes showed reproducible expression changes between three sets of stage A and D cancers. Using consistent genes, stage B and C cancers clustered into two groups resembling early-stage and metastatic tumors. A Prediction Analysis of Microarray algorithm was developed to classify individual intermediate-stage cancers into stage A-like/good prognosis or stage D-like/poor prognosis types. For stage B patients, the treatment adjusted hazard ratio for 6-year recurrence in individuals with stage D-like cancers was 10.3 (95% confidence interval, 1.3-80.0; P = 0.011). For stage C patients, the adjusted hazard ratio was 2.9 (95% confidence interval, 1.1-7.6; P = 0.016). Similar results were obtained for an external set of stage B and C patients. The prognosis signature was enriched for downregulated immune response genes and upregulated cell signaling and extracellular matrix genes. Accordingly, sparse tumor infiltration with mononuclear chronic inflammatory cells was associated with poor outcome in independent patients. CONCLUSIONS: Metastasis-associated gene expression changes can be used to refine traditional outcome prediction, providing a rational approach for tailoring treatments to subsets of patients. (Clin Cancer Res 2009;15(24):7642-51).
Psychotherapeutische Behandlung und ärztliche Begutachtung eines Perversen
Authors: H.-J. von Schumann
Journal: Psychotherapy and Psychosomatics (1962)

Case Reports| February 10 2010 Psychotherapeutische Behandlung und ärztliche Begutachtung eines Perversen Subject Area: Psychiatry and Psychology H.-J. von Schumann H.-J. von Schumann Aus der Privatklinik für Psychotherapie in Düsseldorf (Leiter: Dr. med. Dr. phil. habil. H.-J. von Schumann) Search for other works by this author on: This Site PubMed Google Scholar Acta Psychotherapeutica et Psychosomatica (1962) 10 (5): 385–393. https://doi.org/10.1159/000285647 Article history Published Online: February 10 2010 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation H.-J. von Schumann; Psychotherapeutische Behandlung und ärztliche Begutachtung eines Perversen. Acta Psychotherapeutica et Psychosomatica 1 May 1962; 10 (5): 385–393. https://doi.org/10.1159/000285647 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsActa Psychotherapeutica et Psychosomatica Search Advanced Search Article PDF first page preview Close Modal This content is only available via PDF. 1962Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.
Nerve blocks enable adequate pain relief during topical photodynamic therapy of field cancerization on the forehead and scalp
Authors: C.B. Halldin, J. Paoli, C. Sandberg, H. Gonzalez, A.-M. Wennberg
Journal: British Journal of Dermatology (2009)

Topical photodynamic therapy (PDT) is an effective method when treating extensive areas of sun-damaged skin with multiple actinic keratoses (AKs) (field cancerization) on areas such as the forehead and scalp, and offers excellent cosmetic outcome. The major side-effect of PDT is the pain experienced during treatment.To investigate whether nerve blocks could provide adequate pain relief during PDT of AKs on the forehead and scalp.Ten men with symmetrically distributed and extensive AKs on the forehead and scalp were included in the study. Prior to PDT one side of the forehead and scalp was anaesthetized by nerve blocks while the other side served as control.The mean visual analogue scale (VAS) score on the anaesthetized side was 1 compared with 6.4 on the nonanaesthetized side during PDT. This difference was significant (P<0.0001), implying that nerve blocks reduce VAS scores during PDT.The results of the study support the use of nerve blocks as pain relief during PDT of field cancerization on the forehead and scalp, although individual considerations must be taken into account to find the most adequate pain-relieving method for each patient.
<i>In vivo</i>Therapeutic Responses Contingent on Fanconi Anemia/BRCA2 Status of the Tumor
Authors: Michiel S. van der Heijden, Jonathan R. Brody, David A. Dezentje, Eike Gallmeier, Steven C. Cunningham, Michael J. Swartz, Angelo M. DeMarzo, G. Johan A. Offerhaus, William H. Isacoff, Ralph H. Hruban, Scott E. Kern
Journal: Clinical Cancer Research (2005)

Abstract Purpose: BRCA2, FANCC, and FANCG gene mutations are present in a subset of pancreatic cancer. Defects in these genes could lead to hypersensitivity to interstrand cross-linkers in vivo and a more optimal treatment of pancreatic cancer patients based on the genetic profile of the tumor. Experimental Design: Two retrovirally complemented pancreatic cancer cell lines having defects in the Fanconi anemia pathway, PL11 (FANCC-mutated) and Hs766T (FANCG-mutated), as well as several parental pancreatic cancer cell lines with or without mutations in the Fanconi anemia/BRCA2 pathway, were assayed for in vitro and in vivo sensitivities to various chemotherapeutic agents. Results: A distinct dichotomy of drug responses was observed. Fanconi anemia–defective cancer cells were hypersensitive to the cross-linking agents mitomycin C (MMC), cisplatin, chlorambucil, and melphalan but not to 5-fluorouracil, gemcitabine, doxorubicin, etoposide, vinblastine, or paclitaxel. Hypersensitivity to cross-linking agents was confirmed in vivo; FANCC-deficient xenografts of PL11 and BRCA2-deficient xenografts of CAPAN1 regressed on treatment with two different regimens of MMC whereas Fanconi anemia–proficient xenografts did not. The MMC response comprised cell cycle arrest, apoptosis, and necrosis. Xenografts of PL11 also regressed after a single dose of cyclophosphamide whereas xenografts of genetically complemented PL11FANCC did not. Conclusions: MMC or other cross-linking agents as a clinical therapy for pancreatic cancer patients with tumors harboring defects in the Fanconi anemia/BRCA2 pathway should be specifically investigated.