Publications by authors named "Azouz A"

51 Publications

Corrigendum to "Synthesis and biological evaluations of new nitric oxide-anti-inflammatory drug hybrids" [Bioorg Med Chem Lett (2017) 4358-4369].

Bioorg Med Chem Lett 2018 02 31;28(4):839. Epub 2018 Jan 31.

Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.

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http://dx.doi.org/10.1016/j.bmcl.2018.01.024DOI Listing
February 2018

Discovery of a COX-2 selective inhibitor hit with anti-inflammatory activity and gastric ulcer protective effect.

Future Med Chem 2017 10 27;9(16):1899-1912. Epub 2017 Oct 27.

Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Sakaka, Aljouf 2014, Kingdom of Saudi Arabia.

Aim: A novel series of 2-arylimino-5-arylidenethiazolidin-4-ones 12a-n were synthesized and all the target compounds were fully characterized by IR, H NMR, C NMR, mass spectroscopy and elemental analysis. Materials & methods: All the target compounds were evaluated for their COX inhibition by enzyme immunoassay kit and in vivo anti-inflammatory activity.

Results: Tested compounds were found more potent inhibitors of COX-2 (IC = 0.54-3.14 µM) than COX-1 (IC = 4.97-11.52 µM). The ulcerogenic liability of compounds 12(d, e, f, h, k, m) was performed and showed gastric safety more than or comparable to celecoxib.

Conclusion: In addition, docking study of the most potent and selective compound 12h into COX-2 active site revealed that this target compound assumed interactions and binding pattern similar to that of as a cocrystallized ligand bromocelecoxib (S-58).
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http://dx.doi.org/10.4155/fmc-2017-0115DOI Listing
October 2017

Synthesis and biological evaluations of new nitric oxide-anti-inflammatory drug hybrids.

Bioorg Med Chem Lett 2017 09 13;27(18):4358-4369. Epub 2017 Aug 13.

Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.

Three novel series of nitroso derivatives (11-15), isoxazolopyrazoles (17a-c) and isoxazolo[3,4-d]pyridazines (18a-c) were prepared from the hydroxyimoyl chloride 10. In vitro COX1⧹2 inhibition activities were evaluated, both of 17b and 18a proved a promising inhibitory activity with IC=1.12, 0.78μM in sequent. Carrageenan induced Paw edema, ulcer liability, nitric oxide (NO) release and histopathological study were determined. Most of the prepared compounds showed excellent activities. Reactions of 2-aminopyridine and enaminone with hydroxyimoyl chloride 10 were investigated and proved by 2D NMR. Molecular docking for most active compounds was operated giving a hint for compound-receptor interactions.
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http://dx.doi.org/10.1016/j.bmcl.2017.08.023DOI Listing
September 2017

Novel tetrazole and cyanamide derivatives as inhibitors of cyclooxygenase-2 enzyme: design, synthesis, anti-inflammatory evaluation, ulcerogenic liability and docking study.

J Enzyme Inhib Med Chem 2017 Dec;32(1):805-820

c Pathology Department, Faculty of Veterinary Medicine , Beni Suef University , Beni Suef , Egypt.

Nineteen new compounds containing tetrazole and/or cyanamide moiety have been designed and synthesised. Their structures were confirmed using spectroscopic methods and elemental analyses. Anti-inflammatory activity for all the synthesised compounds was evaluated in vivo. The most active compounds 4c, 5a, 5d-f, 8a and b and 9a and b were further investigated for their ulcerogenic liability and analgesic activity. Pyrazoline derivatives 9b and 8b bearing trimethoxyphenyl part and SONH or SOMe pharmacophore showed equal or nearly the same ulcerogenic liability (UI: 0.5, 0.75, respectively), to celecoxib (UI: 0.50). Most of tested compounds showed potent central and/or peripheral analgesic activities. Histopathological investigations were done to evaluate test compounds effect on rat's gastric tissue. The obtained results were in consistent with the in vitro data on COX evaluation. Docking study was also done for all the target compounds inside COX-2-active site.
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http://dx.doi.org/10.1080/14756366.2017.1326110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445242PMC
December 2017

Synthesis, anti-inflammatory, cyclooxygenases inhibitions assays and histopathological study of poly-substituted 1,3,5-triazines: Confirmation of regiospecific pyrazole cyclization by HMBC.

Eur J Med Chem 2017 Feb 23;127:10-21. Epub 2016 Dec 23.

Department of Pathology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, 62514, Egypt.

Three novel triazines series were prepared. These series are pyrazolines (4a and 4b), pyrazoles (6a, 6b and 8a-d) and isoxazoles (7a and 7b). Such series were designed as COX-2 inhibitors. All compounds were characterized by using spectroscopic methods and elemental analysis. Regarding COX-2, compounds 5b, 4a and 3b were the most active with IC in the range of 0.55-0.87 μM. Most of synthesized compounds were relatively more potent to celecoxib (0.78 μM), diclofenac (2.94 μM) and indomethacin (7.24 μM). A molecular modeling study was performed for the most active compounds. Histopathological evaluation also was done to estimate the safety of compounds. Finally, structure elucidation of pyrazole 8 was studied by 2D NMR.
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http://dx.doi.org/10.1016/j.ejmech.2016.12.030DOI Listing
February 2017

Synthesis, Cyclooxygenase Inhibition, Anti-Inflammatory Evaluation, and Ulcerogenic Liability of New 1,3,5-Triarylpyrazoline Derivatives Possessing a Methanesulfonyl Pharmacophore.

Arch Pharm (Weinheim) 2016 Oct 7;349(10):801-807. Epub 2016 Sep 7.

Faculty of Pharmacy, Department of Pharmacology and Toxicology, Beni-Suef University, Beni-Suef, Egypt.

A new series of 1,3,5-triarylpyrazolines 13a-l was synthesized and all prepared compounds were evaluated for their in vitro COX-1/COX-2 inhibitory activity and in vivo anti-inflammatory activity. All test compounds were more selective for the COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compound 13h was the most COX-2 selective compound (COX-2 selectivity index (SI) = 10.23) and the most potent anti-inflammatory derivative (ED  = 60.1 µmol/kg) in comparison with celecoxib (COX-2 SI = 9.29 and ED  = 81.4 µmol/kg). All screened compounds were less ulcerogenic (ulcer indexes (UI) = 0.33-1.33) than aspirin (UI = 2.33) and comparable to celecoxib (UI = 0.33).
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http://dx.doi.org/10.1002/ardp.201600145DOI Listing
October 2016

Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1-phenylpyrazolo[3,4-d]pyrimidine derivatives.

J Enzyme Inhib Med Chem 2016 22;31(sup2):6-12. Epub 2016 May 22.

a Department of Pharmaceutical Organic Chemistry , Beni-Suef University , Beni-Suef , Egypt , and.

A new group of 1-phenylpyrazolo[3,4-d]pyrimidine derivatives 14a-d-21 were synthesized from 2-(6-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)acetohydrazide (12). All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity and ulcerogenic liability. All the target compounds were more potential in inhibiting COX-2 than COX-1. Compounds having pyrazolyl moiety in a hybrid structure with pyrazolo[3,4-d]pyrimidine scaffold (14a-d, 16 and 17) showed higher edema inhibition percentage activities (34-68%) and the 5-aminopyrazole derivative (14c, ED=87.9 μmol/kg) was the most potent one > celecoxib (ED=91.9 μmol/kg). While, the in vivo potent compounds (14a-d, 16, 17 and 21) caused variable ulceration effect (ulcer index= 0.33-4.0) comparable to that of celecoxib (ulcer index= 0.33), the pyrazol-3-one derivative (16) and the acetohydrazide (21) were the least ulcerogenic derivatives showing the same ulcerogenic potential of celecoxib.
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http://dx.doi.org/10.1080/14756366.2016.1186018DOI Listing
February 2017

Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8(+) T cells.

Nat Commun 2015 May 8;6:7089. Epub 2015 May 8.

WELBIO and Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies 6041, Belgium.

CD8(+) T-cell memory phenotype and function are acquired after antigen-driven activation. Memory-like cells may also arise in absence of antigenic exposure in the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription factor for the development of these unconventional memory cells. Herein, we show that type I interferon signalling in CD8(+) T cells directly activates Eomes gene expression. Consistent with this observation, the phenotype, function and age-dependent expansion of 'virtual memory' CD8(+) T cells are strongly affected in absence of type I interferon signalling. In addition, type I interferons induce a sustained expansion of 'virtual memory' CD8(+) T cells in an Eomes-dependent fashion. We further show that the development of 'innate thymic' CD8(+) T cells is dependent on the same pathway. In conclusion, we demonstrate that type I interferon signalling in CD8(+) T cells drives Eomes expression and thereby regulates the function and homeostasis of memory-like CD8(+) T cells.
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http://dx.doi.org/10.1038/ncomms8089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432629PMC
May 2015

Advances in three-dimensional rapid prototyping of microfluidic devices for biological applications.

Biomicrofluidics 2014 Sep 16;8(5):052112. Epub 2014 Oct 16.

Insight Centre for Data Analytics, National Centre for Sensor Research, Dublin City University , Dublin, Ireland.

The capability of 3D printing technologies for direct production of complex 3D structures in a single step has recently attracted an ever increasing interest within the field of microfluidics. Recently, ultrafast lasers have also allowed developing new methods for production of internal microfluidic channels within the bulk of glass and polymer materials by direct internal 3D laser writing. This review critically summarizes the latest advances in the production of microfluidic 3D structures by using 3D printing technologies and direct internal 3D laser writing fabrication methods. Current applications of these rapid prototyped microfluidic platforms in biology will be also discussed. These include imaging of cells and living organisms, electrochemical detection of viruses and neurotransmitters, and studies in drug transport and induced-release of adenosine triphosphate from erythrocytes.
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http://dx.doi.org/10.1063/1.4898632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4241764PMC
September 2014

Focussed ion beam serial sectioning and imaging of monolithic materials for 3D reconstruction and morphological parameter evaluation.

Analyst 2014 Jan 25;139(1):99-104. Epub 2013 Oct 25.

Irish Separation Science Cluster, National Centre for Sensor Research, Dublin City University, Glasnevin, Dublin 9, Ireland.

A new characterisation method, based on the utilisation of focussed ion beam-scanning electron microscopy (FIB-SEM), has been employed for the evaluation of morphological parameters in porous monolithic materials. Sample FIB serial sectioning, SEM imaging and image processing techniques were used to extract the pore boundaries and reconstruct the 3D porous structure of carbon and silica-based monoliths. Since silica is a non-conducting material, a commercial silica monolith modified with activated carbon was employed instead to minimise the charge build-up during FIB sectioning. This work therefore presents a novel methodology that can be successfully employed for 3D reconstruction of porous monolithic materials which are or can be made conductive through surface or bulk modification. Furthermore, the 3D reconstructions were used for calculation of the monolith macroporosity, which was in good agreement with the porosity values obtained by mercury intrusion porosimetry (MIP).
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http://dx.doi.org/10.1039/c3an01827jDOI Listing
January 2014

Breast lymphoma complicating anti-tumor necrosis factor therapy in rheumatoid arthritis.

Clin Breast Cancer 2011 Dec 12;11(6):413-6. Epub 2011 May 12.

Department of Medicine, University of Tennessee Health Science Center, 956 Court Avenue, Memphis, TN 38163, USA.

The relationship between anti-TNF therapy and development of lymphoma in Rheumatoid arthritis (RA) patients is controversial. However lymphomas of unusual types and sites have been reported among RA patients receiving anti-TNF therapy. Primary lymphoma of the breast is a rare entity and has never been reported to occur among RA patients taking anti-TNF therapy. This is the first case of primary lymphoma of the breast reported among RA patients on anti-TNF therapy. Rheumatoid arthritis patients currently on anti-TNF therapy should undergo routine gynecological examination.
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http://dx.doi.org/10.1016/j.clbc.2011.01.001DOI Listing
December 2011

Epigenetic plasticity of hTERT gene promoter determines retinoid capacity to repress telomerase in maturation-resistant acute promyelocytic leukemia cells.

Leukemia 2010 Mar 14;24(3):613-22. Epub 2010 Jan 14.

INSERM UMR-S 1007, Paris, France.

The expression of hTERT gene, encoding the catalytic subunit of telomerase, is a feature of most cancer cells. Changes in the chromatin environment of its promoter and binding of transcriptional factors have been reported in differentiating cells when its transcription is repressed. However, it is not clear whether these changes are directly involved in this repression or only linked to differentiation. In a maturation-resistant acute promyelocytic leukemia (APL) cell line (NB4-LR1), we have previously identified a new pathway of retinoid-induced hTERT repression independent of differentiation. Using a variant of this cell line (NB4-LR1(SFD)), which resists to this repression, we show that although distinct patterns of histone modifications and transcription factor binding at the proximal domain of hTERT gene promoter could concur to modulate its expression, this region is not sufficient to the on/off switch of hTERT by retinoids. DNA methylation analysis of the hTERT promoter led to the identification of two distinct functional domains, a proximal one, fully unmethylated in both cell lines, and a distal one, significantly methylated in NB4-LR1(SFD) cells, whose methylation was further re-enforced by retinoid treatment. Interestingly, we showed that the binding to this distal domain of a known hTERT repressor, WT1, was defective only in NB4-LR1(SFD) cells. We propose that epigenetic modifications targeting this distal region could modulate the binding of hTERT repressors and account either for hTERT reactivation and resistance to retinoid-induced hTERT downregulation.
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http://dx.doi.org/10.1038/leu.2009.283DOI Listing
March 2010

Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis.

Blood 2009 Apr 30;113(14):3172-81. Epub 2009 Jan 30.

Department of Molecular Biology, University of Bergen, Bergen, Norway.

Retinoids triggers differentiation of acute promyelocytic leukemia (APL) blasts by transcriptional regulation of myeloid regulatory genes. Using a microarray approach, we have identified a novel retinoid-responsive gene (CXXC5) encoding a nuclear factor, retinoid-inducible nuclear factor (RINF), that contains a CXXC-type zinc-finger motif. RINF expression correlates with retinoid-induced differentiation of leukemic cells and with cytokine-induced myelopoiesis of normal CD34(+) progenitors. Furthermore, short hairpin RNA (shRNA) interference suggests for this gene a regulatory function in both normal and tumoral myelopoiesis. Interestingly, RINF localizes to 5q31.3, a small region often deleted in myeloid leukemia (acute myeloid leukemia [AML]/myelodysplasia [MDS]) and suspected to harbor one or several tumor suppressor gene.
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http://dx.doi.org/10.1182/blood-2008-07-170035DOI Listing
April 2009

Hepatic colorectal cancer metastases: imaging initial steps of formation in mice.

Radiology 2007 Jun 12;243(3):703-11. Epub 2007 Apr 12.

Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, West Clinical Center-CC302B, 1 Deaconess Rd, Boston, MA 02215, USA.

Purpose: To prospectively use optical imaging to study the cell-specific mechanisms of entrapment and subsequent growth of two human colon cancer cell lines differing in their propensity to form hepatic metastases.

Materials And Methods: In this Animal Care Committee-approved study, intravital optical imaging was performed in exteriorized livers of three groups of mice after intrasplenic inoculation of human colon cancer cells. Group 1 mice (control group; n=12) received a cell-maintaining solution only. Groups 2 and 3 (n=12 in each) were administered poorly (MIP-101 colon cancer cells) or highly (CX-1 colon cancer cells) metastatic cells. Imaging was performed on postinoculation days 0, 1, 3, and 6 to document sites and mechanisms of tumor cell entrapment and presence and sites of endothelial cell activation and of tumor cell interactions with systemic macrophages and Kupffer cells. Fluorescence intensity of Kupffer cells was compared by using the Mann-Whitney test. Immunohistochemistry served as the reference standard for all in vivo observations.

Results: Whereas both MIP-101 and CX-1 colon cancer cells adhered to periportal Kupffer cells, the CX-1 cells resulted in Kupffer cell activation, evidenced in vivo by increased visible peroxidase activity (P<.05). Only CX-1 cells were associated with subsequent downstream endothelial cell activation, evidenced by in vivo expression of E-selectin. By day 6, regression of periportal MIP-101 tumor growth correlated with ingrowth of systemic macrophages, while CX-1 tumor growth, originating in the outflow venous regions, correlated with translobular migration and ingrowth of activated Kupffer cells.

Conclusion: Formation of hepatic colon cancer metastases is cancer cell-type specific, with cell lines differing in their mechanisms and intrahepatic locations of initial entrapment and Kupffer cell activation and subsequent growth.
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http://dx.doi.org/10.1148/radiol.2432060604DOI Listing
June 2007

Juvenile-onset loss of lipid-raft domains in attractin-deficient mice.

Exp Cell Res 2007 Feb 6;313(4):761-71. Epub 2006 Dec 6.

Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

Mutations at the attractin (Atrn) locus in mice result in altered pigmentation on an agouti background, higher basal metabolic rate and juvenile-onset hypomyelination leading to neurodegeneration, while studies on human immune cells indicate a chemotaxis regulatory function. The underlying biochemical defect remains elusive. In this report we identify a role for attractin in plasma membrane maintenance. In attractin's absence there is a decline in plasma membrane glycolipid-enriched rafts from normal levels at 8 weeks to a complete absence by 24 weeks. The structural integrity of lipid rafts depends upon cholesterol and sphingomyelin, and can be identified by partitioning within of ganglioside GM(1). Despite a significant fall in cellular cholesterol with maturity, and a lesser fall in both membrane and total cellular GM(1), these parameters lag behind raft loss, and are normal when hypomyelination/neurodegeneration has already begun thus supporting consequence rather than cause. These findings can be recapitulated in Atrn-deficient cell lines propagated in vitro. Further, signal transduction through complex membrane receptor assemblies is not grossly disturbed despite the complete absence of lipid rafts. We find these results compatible with a role for attractin in plasma membrane maintenance and consistent with the proposal that the juvenile-onset hypomyelination and neurodegeneration represent a defect in attractin-mediated raft-dependent myelin biogenesis.
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http://dx.doi.org/10.1016/j.yexcr.2006.11.018DOI Listing
February 2007

Immunoinflammatory responses and fibrogenesis.

Med Electron Microsc 2004 Sep;37(3):141-8

Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

In response to injury, tissues adjacent to the damaged area initiate a cascade of inflammatory and matrix remodeling events that are necessary to restore tissue integrity and function. The typical features of such healing effects in adult mammals are deposition of matrix proteins, which mature to scar tissues. In general, the wound healing response demonstrates certain commonalities across organs, but there are also organ-specific mechanisms. Such organ-specific controlled healing and uncontrolled tissue scarring are partly determined by the bioactivities of resident cells and local microenvironments, which are influenced by multiple factors, including the presence of specific types of cytokines (Th1 and Th2), chemokines, growth factors, cell-cell interaction, and reorganization of matrix proteins. In this article, we briefly present the relevance of Th1 and Th2 responses and the significance of interactions between matrix-producing cells and inflammatory cells during granuloma tissue and scar tissue formation.
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http://dx.doi.org/10.1007/s00795-004-0255-2DOI Listing
September 2004

Attractin: cautionary tales for therapeutic intervention in molecules with pleiotropic functionality.

J Environ Pathol Toxicol Oncol 2004 ;23(1):1-11

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.

First discovered as a circulating secreted molecule expressed by activated T lymphocytes, attractin was examined as a potential marker of immune activity. The discovery that a transmembrane form not only controls neuropeptide regulation of hair pigmentation in animals but also affects basal metabolism led to proposals that attractin may also be an extracellular target amenable for the development of obesity-regulating drugs. Examination of several animal mutants used as models ofjuvenile-onset neurodegeneration revealed mutations at the attractin locus as the cause, and the reassessment of earlier attractin mutants demonstrated that neurodegeneration, alterations in pigmentation regulation, and basal metabolic rate were common to all the allelic variants. The presentation and severity of the symptoms differ depending upon the mutation, and some may be variably penetrant even within an allelic line. In this report, we review our rapidly altering perception of the functional activity of attractin with each further addition to its sphere of physiological involvement. We further reappraise our concepts of the subcellular location of attractin, leading to a new proposal that provides a unifying mechanism for attractin's pleiotropic activities. Progress in elucidating each new aspect of attractin function provides a case study in the evolution of possible therapeutic interventions as well as illuminating some of the pitfalls of studying molecular pathways isolated from the whole organism physiology.
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http://dx.doi.org/10.1615/jenvpathtoxoncol.v23.i1.10DOI Listing
March 2004

Factors regulating the progression of hypertensive nephrosclerosis.

Contrib Nephrol 2003 ;139:173-86

Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Mass., USA.

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http://dx.doi.org/10.1159/000071743DOI Listing
October 2003

SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates.

Nat Immunol 2003 Apr 24;4(4):366-74. Epub 2003 Mar 24.

Department of Haematology, Division of Investigative Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.

Src kinase-associated phosphoprotein of 55 kDa (SKAP-55; encoded by SCAP1) is a T cell adaptor protein of unknown function that contains a pleckstrin homology and an SH3 domain. Here we show that SKAP-55 regulates integrin-mediated adhesion and conjugate formation between T cells and antigen-presenting cells (APCs). SKAP-55 enhances adhesion to fibronectin and intercellular adhesion molecule-1 (ICAM-1), colocalizes with actin at the T cell-APC synapse and promotes the clustering of lymphocyte-associated antigen-1 (LFA-1). Enhanced conjugation is comparable to that induced by adhesion and degranulation-promoting adaptor protein (ADAP), a binding partner of SKAP-55, and is abrogated by deletion of the SKAP-55 SH3 domain. Conjugate formation is accompanied by the translocation of SKAP-55 to membrane rafts, an event that is regulated by both LFA-1 and T cell receptor ligation. Our findings identify a mechanism by which SKAP-55 modulates T cell responses to antigen.
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http://dx.doi.org/10.1038/ni913DOI Listing
April 2003

Cytotoxic T lymphocyte antigen 4 and CD28 modulate cell surface raft expression in their regulation of T cell function.

J Exp Med 2001 Dec;194(11):1675-81

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Coreceptors CD28 and cytotoxic T lymphocyte antigen (CTLA)-4 have opposing effects on TcR/CD3 activation of T cells. While CD28 enhances and CTLA-4 inhibits activation, the underlying molecular basis of these effects has yet to be established. In this context, ganglioside and cholesterol enriched membrane microdomains (rafts, GEMs) serve as centers of signaling in T cells. Although CD28 can promote TcR/raft colocalization, evidence is lacking on whether the surface expression of membrane rafts can be targeted by CTLA-4 in its modulation of T cell responses. In this study, we demonstrate that both CD28 and CTLA-4 profoundly alter the surface expression of membrane rafts during T cell activation. While CD28 increased expression and the number of peripheral T cells induced to express surface rafts in response to TcR ligation, CTLA-4 potently inhibited both TcR and TcR x CD28 induced raft expression on the surface of T cells. Consistent with this, CD28 increased the presence of the linker of activated T cells (LAT) in purified membrane rafts, while CTLA-4 coligation effectively blocked this increase. Further, the reversal of the CTLA-4 block with CD3/CD28 ligation was accompanied by an increase in surface raft expression and associated LAT. Our observations demonstrate for the first time that CTLA-4 targets the release of rafts to the surface of T cells, and provides a mechanism for the opposing effects of CD28 and CTLA-4 on costimulation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193535PMC
http://dx.doi.org/10.1084/jem.194.11.1675DOI Listing
December 2001

[The incidence of locoregional recurrences of breast cancer after surgery and radiation].

Rontgenpraxis 1992 Jun;45(6):191-5

Klinik und Poliklinik für Strahlentherapie-Radioonkologie, Universität Münster.

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June 1992
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