tbuckley/cabot-search huggingface dataset:
596. Radiosensitization of Gliomas Using Lentiviral Vectors Expressing Antisense ATM
Authors: Teong L. Chuah, David G. Walker, Ming Q. Wei, Shaun P. Scott, Martin F. Lavin
Journal: Molecular Therapy (2004)

INTRODUCTION: Gliomas are the commonest primary brain tumour of which death is due to failure to control the growth of the tumour. Effective therapies for malignant gliomas remain elusive and even with the best therapeutic modalities currently available, a prognosis of less than one year, as for the glioblastoma multiforme, is appalling. The ATM gene, which is mutated in the disease ataxia-telangiectasia (A-T), is implicated in response to radiation-induced DNA damage, leading to profound radiosensitivity. By taking advantage of the extreme radiosensitivity conferred by reduced levels of ATM, a method of reducing the levels of ATM within radioresistant glioma cells such as the glioblastoma multiforme would be very beneficial, especially if it could transform the radioresistant tumour to radiosensitive. Concurrently, advances in science have demonstrated that the lentivirus is one of the most effective method of delivering genes into quiescent cells. By producing safe non-replicating lentivirus, containing the ATM antisense knockout, malignant gliomas can be sensitised to radiotherapy. In conjunction with surgery, this strategy will provide an enhanced therapeutic intervention especially in the case of the glioblastoma multiforme where the tumour is untreatable.
Fatty acid metabolism in cancer cells: Differential inhibitory effects of epigallocatechin (EGCG) and C75
Authors: Teresa Puig, Alejandro Vázquez-Martín, Pedro Marrero, Gemma Casals, Jordi Pétriz, Joana Relat, Diego Haro, Javier A. Menéndez, María Luz López-Rodríguez, Maria Vilanova, Ramon Colomer
Journal: Clinical Cancer Research (2006)

B28   Endogenous fatty acid metabolism is crucial to maintain the cancer cell malignant phenotype. We and others have shown that blocking the activity of fatty acid synthase (FASN), a lipogenic multienzyme that catalyzes the final step in the de novo fatty acid synthesis, either alone or in combination with chemoterapy or monoclonal antibodies, has potential as an anticancer strategy. The pharmacologic FASN inhibitors, cerulenin and its synthetic derivative C75, show a structurally-related weight-loss induction in experimental animals, which limits in clinical development. Other compounds that block FASN activity include (-)-epigallocatechin-3-gallate (EGCG), triclosan and orlistat.We have tested whether there are differential effects of EGCG in comparison with C75 on fatty acid metabolism (FASN, and carnitine palmitoyltransferase-1 [CPT-1], a component of the shuttle system which allows entry of long-chain fatty acids into the mitochondrial matrix for subsequent oxidation), and on cellular and molecular effects in three metastatic breast cancer cell lines MDA-MB-231, MCF-7 and SK-Br3, which are models of low, moderate and high levels of FAS, respectively. EGCG and C75 had comparable effects in blocking FASN, producing a dose- and time-dependent decrease in the viability of metastatic breast cancer cell lines MDA-MB-231, MCF-7 and SK-Br3 (directly dependent on cell FAS levels); causing a decrease in the active forms of oncoprotein HER2, AKT and ERK1/2, and inducing apoptosis (as assessed by cleavage of PARP and flow cytometry using Annexin V conjugated to Alexa Fluor 488 and propidium iodide).We observed, in contrast, clear differential effects between EGCG and C75 on CPT-1 activity. While EGCG has either no effect or a moderate reduction in CPT-1 activity, C75 stimulated CPT-1 activity (up to 125 %). Our results with EGCG show that pharmacologically inhibition of FAS can occur uncoupled from the stimulation of CPT-1, and thus avoid the weight-loss pathways. We are now evaluating the combination of EGCG with chemotherapy and monoclonal antibodies.
CLINICAL EXPERIMENTS WITH MIXTURES OF STANDARD AND PROTAMINE ZINC INSULINS
Authors: Helmuth Ulrich
Journal: Annals of Internal Medicine (1941)

Article1 January 1941CLINICAL EXPERIMENTS WITH MIXTURES OF STANDARD AND PROTAMINE ZINC INSULINSHELMUTH ULRICH, M.D., F.A.C.P.HELMUTH ULRICH, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-7-1166 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptEvanescent action is one of the major disadvantages of standard insulin. Protamine zinc insulin overcomes this difficulty. Its absorption from the site of injection is slow; its therapeutic action is prolonged. But precisely because of its retarded action, short periods of post-prandial hyperglycemia and glycosuria are common with its use. If separate additional injections of standard insulin are given for the purpose of eliminating this objectionable feature, then one of the major advantages of protamine zinc insulin, a reduction in the number of injections, is partly or wholly lost.Mixtures of the two forms of insulin in the same syringe...Bibliography1. CAMPBELLFLETCHERKERR WRAARB: Protamine insulin in the treatment of diabetes mellitus, Am. Jr. Med. Sci., 1936, cxcii, 589. CrossrefGoogle Scholar2. GRAHAM G: The use of a mixture of ordinary and protamine insulin, Acta med. Scand. (Supplement), 1938, xc, 54. Google Scholar3. Queries and Minor Notes, Jr. Am. Med. Assoc., 1939, cxii, 871. Google Scholar4. CAMPBELL WR: Some difficulties in the use of the insulins in diabetic practice, Bull. New York Acad. Med., 1939, xv, 579. Google Scholar5. PECK FB: Personal communication. Google Scholar6. CAMPBELL WR: Personal communication. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*Received for publication September 23, 1939.From the Evans Memorial of the Massachusetts Memorial Hospitals, Boston, Mass. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byInsulin Preparations with Prolonged EffectPrepared insulin mixtures in the treatment of the severe diabetic patientInsulin mixturesInsulin mixturesExperience with insulin mixturesCLINICAL TRIAL OF DI-INSULINEffective Insulin Timing in Diabetes MellitusInsulin Mixtures and ModificationsGlobin insulin: a clinical studyDISORDERS OF THE NEWBORNLIVER NECROSIS AFTER TRILENE ANÆSTHESIAINSULIN MIXTURES 1 January 1941Volume 14, Issue 7Page: 1166-1179KeywordsHyperglycemiaInsulinProtaminesZinc ePublished: 1 December 2008 Issue Published: 1 January 1941 PDF downloadLoading ...
Masked polycythemia vera diagnosed according to WHO and BCSH classification
Authors: Tiziano Barbui, Jürgen Thiele, Alessandra Carobbio, Heinz Gisslinger, Guido Finazzi, Elisa Rumi, Maria Luigia Randi, Alessandro M. Vannucchi, Bettina Gisslinger, Leonhard Müllauer, Marco Ruggeri, Alessandro Rambaldi, Ayalew Tefferi
Journal: American Journal of Hematology (2013)

Polycythemia vera (PV) is currently diagnosed by the World Health Organization (WHO) criteria regarding hemoglobin (HB) levels and JAK2V617F and related mutations or by the British Committee for Standards in Haematology (BCSH) guidelines predominantly based on hematocrit (HCT) values (&gt;52% in men and &gt;48% in women) in JAK2 mutated patients. We examined clinical features at diagnosis and outcome in 397 mutated PV patients showing a bone marrow (BM) morphology conforming with the WHO descriptions but including also cases with a HB level &lt;18.5 g/dL in males (range 16.0–18.4) and &lt;16.5 g/dL in females (range 15.0–16.4). These patients were regarded as masked PV (mPV) comprising 140 (35%) cases of our cohort. A comparison with the BCSH criteria based on HCT levels revealed a decrease of mPV patients to 59 (15%). In both classification systems, mPV patients were more males, presented more frequently with higher platelet counts, and increased BM reticulin fibrosis. A worsening of overall survival was documented in mPV patients in comparison with overt PV following the WHO ( P = 0.011) as well as the BCSH ( P = 0.0019) criteria. Risk factors for inferior survival in mPV were age &gt;65 years and white blood cell count &gt;15 × 10 9 /L. Without these risk factors mPV patients had the same survival as overt PV suggesting that a fraction of patients with HB lower than that required for WHO diagnosis should still be considered as overt PV. This study has established the existence of mPV by two different classification systems based on either HB or HCT threshold values. Am. J. Hematol. 89:199–202, 2014. © 2013 Wiley Periodicals, Inc.
Abstract 3915: Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target
Authors: Nabil Amirouchene-Angelozzi, Fariba Nemati, David Gentien, May-Linda Lepage, André Nicolas, Jordan Madic, Amaury Dumont, Guillaume Carita, Jaques Camonis, Laurence Desjardins, Nathalie Cassoux, Sophie Piperno-Neumann, Pascale Mariani, Xavier Sastre, Didier Decaudin, Sergio Roman-Roman
Journal: Cancer Research (2014)

Abstract PURPOSE: Uveal melanoma is the most common primary tumor of the eye in adults. There is no standard adjuvant treatment to prevent metastases and no effective therapy in the metastatic setting. Relevant models of uveal melanoma are necessary to preclinical assessment of drugs activity. The goal of this study was to develop cell lines recapitulating the genetic landscape of uveal melanoma and identify therapeutic approaches for treatment using in vitro and in vivo models. EXPERIMENTAL DESIGN: Tumors samples from patients or patient-derived xenografts were put into culture.The cell lines obtained were characterized for chromosomal alterations and reported recurrent mutations. They were tested for sensitivity to a selected panel of drugs including the mTOR inhibitor Everolimus. We assessed mTOR signaling activation in the cell lines and evaluated the effect of Everolimus in patient-derived xenografts. RESULTS: We established seven uveal melanoma cell lines. All display either GNAQ or GNA11 activating mutations, three harbor BAP1 mutations, and one an EIF1AX mutation. No cell line exhibits SF3B1 mutations. mTOR pathway was shown to be activated in these cells. Everolimus reduced viability of the cell lines and significantly delayed in vivo tumor growth of 4 patient-derived xenografts. CONCLUSIONS: Our established panel of uveal melanoma cell lines represents a relevant preclinical tool for the study of this disease. Our in vitro and in vivo data suggest that mTOR inhibition with Everolimus, most probably in combination with other agents, may be considered as a therapeutic option for the management of uveal melanoma. Citation Format: Nabil Amirouchene-Angelozzi, Fariba Nemati, David Gentien, May-Linda Lepage, André Nicolas, Jordan Madic, Amaury Dumont, Guillaume Carita, Jaques Camonis, Laurence Desjardins, Nathalie Cassoux, Sophie Piperno-Neumann, Pascale Mariani, Xavier Sastre, Didier Decaudin, Sergio Roman-Roman. Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3915. doi:10.1158/1538-7445.AM2014-3915
Abstract 14958: Global Longitudinal Strain is a Superior Predictor of All-cause Mortality Compared to Left Ventricular Ejection Fraction in Male Patients with Heart Failure and Without Atrial Fibrillation
Authors: Morten Sengeløv, Tor Biering-Sørensen, Peter Godsk Jørgensen, Niels Eske Bruun, Thomas Fritz-Hansen, Jan Bech, Flemming Javier Olsen, Jacob Sivertsen, Jan Skov Jensen
Journal: Circulation (2014)

Object: Myocardial strain deformation analysis (global strain) may be superior to left ventricular ejection fraction (LVEF) in predicting all-cause mortality in patients with heart failure. Methods: In this retrospective study transthoracic echocardiographic examinations were retrieved from Gentofte Hospital heart failure clinic’s database in 1061 patients. The echocardiographic images were subsequently analyzed and conventional echocardiographic parameters and strain data were obtained. Results: During a median follow-up of 40 months 177 (16.7 %) patient died. Mean LVEF was 23.7 % and mean global strain was -8.12.884 (83.3%) were patients alive at follow-up and mean LVEF was 28.2 % while mean global strain was -9.86 %. The risk of dying increased with decreasing tertile of global strain being approximately three times higher for the patients in the lower tertile compared to the highest tertile (1. tertile vs 3. tertile HR: 3.38 95% CI: 2.3 [[Unable to Display Character: &amp;#8211;]] 5.1), p-value: 0.001. Many of the conventional echocardiographic parameters proved to be predictors of mortality. Global strain remained an independent predictor of mortality in cox proportional-hazards models after adjusting for age, gender, BMI, total cholesterol, heart rate, atrial fibrillation, non-independent diabetes mellitus and conventional echocardiographic parameters (p-value: 0.014, 95% CI: 1.04 [[Unable to Display Character: &amp;#8211;]] 1.37) while ejection fraction proved to be insignificant adjusted for aforementioned characteristics (p-value: 0.81, 95% CI: 0.96 [[Unable to Display Character: &amp;#8211;]] 1.05 Atrial fibrillation modified the relationship between GLS and mortality (p for interaction = 0.023). HR 1.08 (CI 0.97 to 1.19, p=0.150) and HR 1.22 (CI 1.15 to 1.29, p&lt;0.001) per 10 % decrease in GLS for patients with and without atrial fibrillation, respectively. Gender also modified the relationship between mean GLS and mortality (p for interaction = 0.047); HR 1.23 (CI 1.16 to 1.30, p&lt;0.001) and HR 1.09 (CI 0.99 to 1.20, p=0.083) per 10 % decrease in GLS for men and women, respectively. Conclusion: In male patients with systolic heart failure and without atrial fibrillation global strain is an independent predictor of all-cause mortality. Furthermore, global strain proved to be a superior prognosticator when compared to left ventricular ejection fraction.
Evaluation of the impact of writing exercises interventions on quality of life in patients with psoriasis undergoing systemic treatments
Authors: S. Tabolli, L. Naldi, C. Pagliarello, F. Sampogna, C. di Pietro, A. Spagnoli, D. Abeni
Journal: British Journal of Dermatology (2012)

Journal Article Evaluation of the impact of writing exercises interventions on quality of life in patients with psoriasis undergoing systemic treatments Get access S. Tabolli, S. Tabolli IDI‐IRCCS Health Services Research, Via Monti di Creta 104, 00167 Rome, Italy Stefano Tabolli. E‐mail: ste.tab@idi.it Search for other works by this author on: Oxford Academic Google Scholar L. Naldi, L. Naldi Centro Studi GISED, Via Garibaldi 13/15, 24122 Bergamo, Italy Search for other works by this author on: Oxford Academic Google Scholar C. Pagliarello, C. Pagliarello IDI‐IRCCS Health Services Research, Via Monti di Creta 104, 00167 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar F. Sampogna, F. Sampogna IDI‐IRCCS Health Services Research, Via Monti di Creta 104, 00167 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar C. di Pietro, C. di Pietro IDI‐IRCCS Health Services Research, Via Monti di Creta 104, 00167 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar A. Spagnoli, A. Spagnoli IDI‐IRCCS Health Services Research, Via Monti di Creta 104, 00167 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar D. Abeni, D. Abeni IDI‐IRCCS Health Services Research, Via Monti di Creta 104, 00167 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar The Italian Writing Exercise Study Group The Italian Writing Exercise Study Group Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 6, 1 December 2012, Pages 1254–1264, https://doi.org/10.1111/j.1365-2133.2012.11147.x Published: 01 December 2012 Article history Accepted: 03 July 2012 Published: 01 December 2012
Cutting short the path to murine liver cancer models
Authors: Shuyuan Zhang, Sam Wang, Hao Zhu
Journal: Hepatology (2014)

The study of cancer genes in mouse models has traditionally relied on genetically-engineered strains made via transgenesis or gene targeting in embryonic stem cells. Here we describe a new method of cancer model generation using the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system in vivo in wild-type mice. We used hydrodynamic injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs (sgRNAs) to the liver that directly target the tumour suppressor genes Pten (ref. 5) and p53 (also known as TP53 and Trp53) (ref. 6), alone and in combination. CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid accumulation in hepatocytes, phenocopying the effects of deletion of the gene using Cre-LoxP technology. Simultaneous targeting of Pten and p53 induced liver tumours that mimicked those caused by Cre-loxP-mediated deletion of Pten and p53. DNA sequencing of liver and tumour tissue revealed insertion or deletion mutations of the tumour suppressor genes, including bi-allelic mutations of both Pten and p53 in tumours. Furthermore, co-injection of Cas9 plasmids harbouring sgRNAs targeting the β-catenin gene and a single-stranded DNA oligonucleotide donor carrying activating point mutations led to the generation of hepatocytes with nuclear localization of β-catenin. This study demonstrates the feasibility of direct mutation of tumour suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new avenue for rapid development of liver cancer models and functional genomics.
Abstract 1970: Co-culture of 3D tumor spheroids with fibroblasts as an <i>in vitro</i> model for drug resistance study
Authors: Sun-Ah Kim, Hyo-Jeong Kuh
Journal: Cancer Research (2014)

Abstract Purpose. Chemotherapeutic failure of human solid tumor is attributed to tumor microenvironmental (TME) factors associated with drug resistance. Three dimensional (3D) tumor spheroid (TS) model is known to be in vivo mimic and has demonstrated its clinical relevancy. Fibroblasts in TME have been shown to play a significant role in drug resistance. The present study was to develop and characterize a co-culture of 3D TS with fibroblasts for human colorectal tumor model. Methods. TS of human colorectal cancer cells (HT-29) was prepared by using liquid overlay method and co-cultured in collagen-coated 24-well plates with colon fibroblasts (CCD-18co) grown in Transwell® inserts. Differentail expression of extracellular matrix (ECM), growth signaling molecules, and microRNAs was analyzed using IHC, ELISA, western blot and qRT-PCR. For miRNA transfection study, changes in motility and drug sensitivity were measured by wound healing assays and APH or MTS assay, respectively. Results. Significant resistance to 5-FU was shown in TS either with or without fibroblasts compared to monolayers. Compared to single culture of TS, co-culture with fibroblast showed 1.3-fold increased outgrowth on collagen gel, indicating increased motility. Cell-to-cell adhesion structures, expression of ECM and active form TGFβ1 were higher in TS-fibroblast co-culture. Expression of several growth- and TME-related factors, such as fibronectin, EGFR, β-catenin and CTGF, was higher in fibroblast co-culture up to the level of HT-29 xenograft tissues. Among miRNAs showing differential expressions, miR-96 showed down-regulation in TS. HT-29 cells transfected with miR-96 showed increase in cell motility, proliferation, and sensitivity to 5-FU, suggesting its potential role in regulation of genes associated with 5-FU resistance. Conclusions. Co-culture of 3D TS-fibroblasts was successfully established and demonstrated in vivo mimic characteristics with respect to presence of adhesion microstructures, expression of ECM and growth signaling molecules, and resistance to 5-FU. MiR-96 showed its potential role in 3D drug resistance which warrants further studies. Citation Format: Sun-Ah Kim, Hyo-Jeong Kuh. Co-culture of 3D tumor spheroids with fibroblasts as an in vitro model for drug resistance study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1970. doi:10.1158/1538-7445.AM2014-1970
Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002)
Authors: S. R. Cairns, J. H. Scholefield, R. J. Steele, M. G. Dunlop, H. J. W. Thomas, G. D. Evans, J. A. Eaden, M. D. Rutter, W. P. Atkin, B. P. Saunders, A. Lucassen, P. Jenkins, P. D. Fairclough, C. R. J. Woodhouse
Journal: Gut (2010)

The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned this update of the 2002 guidance. The aim, as before, is to provide guidance on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer. This guidance provides some new recommendations for those with inflammatory bowel disease and for those at moderate risk resulting from a family history of colorectal cancer. In other areas guidance is relatively unchanged, but the recent literature was reviewed and is included where appropriate.
Clinical Applications of the Interferons, by R Stuart-Harris, R Penny
Authors: D. Isaacs
Journal: BMJ (1997)

R Stuart-Harris, R Penny Chapman&Hall, £79, pp 512 ISBN 0 412 602504

This review is a particularly poignant one for me— “Son of interferon meets son of influenza.” My father, Alick Isaacs, codiscoverer of interferon, spent his formative years in virology in Sheffield, where Charles Stuart-Harris, father of Robin, was his teacher and mentor.

When first described in 1957, interferon was hailed as the antiviral penicillin, the “magic bullet” that would do for viral infections what antibiotics had done for bacterial infections. But hailed by …