Tarek Kashour

Hôpital St-Boniface Hospital, Winnipeg, Manitoba, Canada

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Publications (18)54.66 Total impact

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    ABSTRACT: Adipose tissue stromal fraction (ASF) contains multipotent cells capable of differentiation towards several lineages and may be used for the treatment of various degenerative diseases. However, the multipotent cells within ASF have not been fully characterized. In this study we have attempted to characterize stem cells in the ASF obtained through serial dilution. Five single-cell clones were studied. It was found that the single-cell clones exhibited slight but significant differences in proliferative capacity and differentiation potential. We conclude that ASF houses different subtypes of stem cells.
    Canadian Journal of Physiology and Pharmacology 08/2012; 90(9):1295-301. DOI:10.1139/y2012-094 · 1.56 Impact Factor
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    ABSTRACT: This study assessed the potential therapeutic efficacy of adipose-derived stem cells (ASCs) on infarcted hearts. Myocardial infarction was induced in rat hearts by occlusion of the left anterior descending artery (LAD). One week after LAD occlusion, the rats were divided into three groups and subjected to transplantation of ASCs or transplantation of cell culture medium (CCM) or remained untreated. During a 1-mo recovery period, magnetic resonance imaging showed that the ASC-treated hearts had a significantly greater left ventricular (LV) ejection fraction and LV wall thickening than did the CCM-treated and untreated hearts. The capillary density in infarct border zone was significantly higher in the ASC-treated hearts than in the CCM-treated and untreated hearts. However, only 0.5% of the ASCs recovered from the ASC-treated hearts were stained positive for cardiac-specific fibril proteins. It was also found that ASCs under a normal culture condition secreted three cardiac protective growth factors: vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1. Results of this study suggest that ASCs were able to improve cardiac function of infarcted rat hearts. Paracrine effect may be the mechanism underlying the improved cardiac function and increased capillary density.
    AJP Heart and Circulatory Physiology 08/2009; 297(3):H1020-31. DOI:10.1152/ajpheart.01082.2008 · 4.01 Impact Factor
  • Farrukh Hussain, Tarek S Kashour, Ivan Barac
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    ABSTRACT: Simultaneous valvular, pericardial and myocardial involvement from chronic rheumatic heart disease is a rare phenomenon. We describe a novel patient with simultaneous aortic stenosis, mitral stenosis, constrictive pericarditis and pathologic myocardial rheumatic involvement. Lessons and pitfalls of the catheterization hemodynamics for concomitant multivalvular disease and constrictive physiology are outlined. Echocardiographic, computed tomographic (CT) imaging and pathologic findings are presented for the pancardiac involvement in this case.
    International journal of cardiology 01/2009; 131(1):e28-30. DOI:10.1016/j.ijcard.2007.07.054 · 6.18 Impact Factor
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    ABSTRACT: The objectives of this study were (1) to determine whether superparamagnetic iron oxide (SPIO) affects viability, transdifferentiation potential and cell-factor secretion of adipose-derived stem cells (ASCs); and (2) to determine whether SPIO-enhanced magnetic resonance (MR) imaging highlights living stem cells. Rat ASCs were incubated in SPIO-containing cell culture medium for 2 days. The SPIO-treated ASCs were then subjected to adipogenic, osteogenic and myogenic transdifferentiation. Expression of vascular endothelial growth factor, hepatocyte growth factor and insulin-like growth factor 1 by the SPIO-treated ASCs was measured using reverse transcription polymerase chain reaction. Cell viability was assessed using trypan blue stain. For in vivo experiments, SPIO-labeled ASCs were injected into 10 rat hearts. The hearts were monitored using MRI. We found that survival rate of the ASCs cultured in the SPIO-containing medium was very high (97-99%). The SPIO-treated ASCs continued to express specific markers for the three types of transdifferentiation. Expression of the cell factors by the ASCs was not affected by SPIO. Signal voids on MR images were associated with the living SPIO-labeled ASCs in the rat hearts. We conclude that SPIO does not affect viability, transdifferentiation potential or cell-factor secretion of ASCs. MRI mainly highlights living SPIO-labeled stem cells.
    Magnetic Resonance Imaging 01/2009; 27(1):108-19. DOI:10.1016/j.mri.2008.05.013 · 2.02 Impact Factor
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    ABSTRACT: Pulmonic valvular stenosis represents the most frequent cause of right ventricular outflow obstruction. Transthoracic echocardiography is the imaging modality of choice in the diagnosis, evaluation and longitudinal follow-up of individuals with pulmonic stenosis (PS). Although valvular PS is usually diagnosed by two-dimensional imaging, Doppler echocardiography allows for the quantification of severity of the valvular lesion. In patients with limited acoustic windows, computed tomography and cardiac magnetic resonance imaging may provide complementary anatomical characterization of the pulmonic annulus and valve prior to percutaneous balloon valvuloplasty.
    Echocardiography 03/2008; 25(2):231-5. DOI:10.1111/j.1540-8175.2007.00609.x · 1.25 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder, due to excess amyloid-beta peptide (Abeta). TGF-beta1 and beta-catenin signaling pathways have been separately implicated in modulating Abeta-neurotoxicity. However, the underlying mechanisms remain unclear. Here, we report that TGF-beta1 and nuclear Smad7 and beta-catenin levels were markedly upregulated in cortical brain regions of the TgCRND8 mice, a mouse model of familial Alzheimer's disease. Coimmunoprecipitation of cortical brain tissue lysates revealed an interaction between Smad7 and beta-catenin. This interaction which was significantly enhanced in the TgCRND8 mice was also associated with an increase in TCF/LEF DNA-shift binding activity. TCF/LEF reporter gene activity was significantly increased in mouse primary cortical neuronal cultures (MCN) from the TgCRND8 mice, compared to controls. Interestingly, exposure of MCN to Abeta(1-42) led to an increase in TGF-beta1 and nuclear levels of both beta-catenin and Smad7. Furthermore, addition of TGF-beta1 to the MCN caused an increase in apoptosis and Smad7 levels. When Smad7 or beta-catenin levels were reduced by siRNA, TGF-beta1-induced apoptosis was suppressed, indicating that both Smad7 and beta-catenin are required for TGF-beta1-induced neurotoxicity. Since Abeta(1-42)-induced TGF-beta1, we suggest that TGF-beta1 may amplify Abeta(1-42)-mediated neurodegeneration in AD via Smad7 and beta-catenin interaction and nuclear localization.
    Neuroscience Letters 02/2008; 430(1):81-6. DOI:10.1016/j.neulet.2007.10.025 · 2.06 Impact Factor
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    ABSTRACT: Saphenous vein graft interventions carry a significant risk of adverse events. We present a case in which a free left internal thoracic artery (LITA to the LAD) had been anastomosed to a saphenous vein graft (SVG) to an obtuse marginal (OM) as its proximal anastomosis. Due to surgical iatrogenic injury during a subsequent aortic valve replacement, the proximal portion of this dual graft was resected in error and then repaired using an interposed vein graft (vein patch). We present the first known case of percutaneous intervention to an interposition vein graft stenosis with left main equivalent anatomy. Virtual histology (VH) and grey scale intravascular ultrasound (IVUS) were utilized to visualize plaque characteristics in this novel lesion.
    International journal of cardiology 12/2007; 122(2):179-81. DOI:10.1016/j.ijcard.2006.11.067 · 6.18 Impact Factor
  • Farrukh Hussain, Tarek Kashour, Roger Philipp
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    ABSTRACT: Stent dislodgement or loss in a coronary artery carries significant risks of infarction, thrombosis and requirement for emergency bypass surgery. Even with the advent of premounted stents, stent loss can occasionally occur, especially when performing intervention in calcified and tortuous anatomy. Multiple stent retrieval/stent exclusion techniques have been described to overcome this dreaded complication. We describe the first case of deploying a dislodged stent using a buddy wire technique with both wires through the center of the dislodged stent, and subsequent use of the small balloon technique to successfully deploy a dislodged stent in a heavily calcified and tortuous circumflex artery.
    The Journal of invasive cardiology 07/2007; 19(6):E160-2. · 1.57 Impact Factor
  • Journal of Molecular and Cellular Cardiology 06/2007; 42(6). DOI:10.1016/j.yjmcc.2007.03.210 · 5.22 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) is characterized by cognitive decline due to excess amyloid beta peptide (Abeta), neurofibrillary tangles, and neuronal loss. Abeta promotes neuronal apoptosis in AD by activating glycogen synthase kinase-3beta (GSK-3beta), leading to degradation of beta-catenin and inactivation of Wnt signaling. beta-Catenin interacts with the T-cell factor (TCF)/Lymphoid enhancer factor (LEF)-nuclear complex to mediate Wnt signaling and cell survival. Statins are associated with decreased prevalence of AD. Lovastatin has been shown to decrease the production of Abeta and to promote neuronal survival. The mechanisms of how statins promote neuronal survival are unclear. We propose that the neuroprotective effect of lovastatin may be due to inactivation of GSK-3beta activity, resulting in induction of Wnt signaling. Here, we report that lovastatin prevented Abeta-induced apoptosis in human SK-NSH cells. This was accompanied by reduction in active GSK-3beta, and increased nuclear translocation of beta-catenin, TCF-3, and LEF-1. Lovastatin treatment induced an increase in TCF/LEF-chloramphenicol acetyl transferase (CAT) gene reporter activity. More importantly, beta-catenin and TCF were required for the neuroprotective function of lovastatin. Our results suggest that lovastatin protects neuronal cells from Abeta-induced apoptosis and causes reduction in GSK-3beta activity, resulting in activation of Wnt signaling.
    Neuroscience Letters 03/2007; 412(3):211-6. DOI:10.1016/j.neulet.2006.07.045 · 2.06 Impact Factor
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    ABSTRACT: Ostial coronary disease presents a challenge from multiple perspectives with regard to percutaneous intervention. We present a novel case of a technically challenging ostial right coronary artery calcified lesion with a bar of calcium at the aorto-ostial junction which prevented intubation with multiple guiding catheters. We describe the use of a buddy wire as a technique for focused-force angioplasty with slow incremental balloon inflation of increasing diameter for plaque modification prior to stenting in a situation where rotational atherectomy and cutting balloon angioplasty were not an option.
    The Journal of invasive cardiology 01/2007; 18(12):E298-301. · 1.57 Impact Factor
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    ABSTRACT: Transforming growth factor beta (TGF-beta) is a biologically multipotent regulatory protein implicated in functions that include the regulation of cellular growth, differentiation, extracellular matrix formation, and wound healing. It also plays a role in the pathologies of Alzheimer's disease, cancer and autoimmune disorders. TGF-beta modulates gene expression by affecting transcriptional activation and mRNA turnover rate. Steady-state mRNA levels depend on both the transcriptional activity and mRNA half-life. The stability of mRNA can be modified by the binding of trans-acting factors to cis-elements on the message. These can protect the mRNA from cleavage by RNAses, or they may promote mRNA cleavage. Changes in mRNA stability can lead to changes in the proteome and subsequently in cellular metabolism. The SMAD family of proteins has been implicated in the transduction of the TGF-beta signal, where they regulate transcriptional activity. This review attempts to provide new insights into the role played by TGF-beta in the regulation of mRNA turnover.
    Growth Factors 04/2006; 24(1):1-11. DOI:10.1080/08977190500365995 · 3.09 Impact Factor
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    Sat Sharma, Tarek Kashour, Roger Philipp
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    ABSTRACT: Secondary pulmonary arterial hypertension (SPAH) is an adverse outcome of a variety of systemic disorders. These include collagen vascular diseases, chronic thromboembolism, human immunodeficiency virus, portopulmonary hypertension, and other diseases. Progression of SPAH may persist despite stabilization of the causative disease, thereby contributing to the poor quality of life and unfavorable survival in these patients. Treatment of the underlying cause and oxygen supplementation may alleviate symptoms, but no specific therapy to treat SPAH currently exists. Endothelin receptor blockade with bosentan has been shown to be beneficial in the treatment of primary pulmonary hypertension, but efficacy of this therapy in SPAH has not been established. We describe a case series of 6 patients with disparate causes of SPAH, who benefited from endothelin receptor blockade therapy. The causes of SPAH included collagen vascular disease (scleroderma) (1); systemic lupus erythematosus (2); chronic thromboembolic disease (2); and granulomatous vasculitis from sarcoidosis (1). Therapy with bosentan led to improvements in symptoms, New York Heart Association functional class, and walking distance in all patients. Distance walked in 6 minutes increased from a mean of 151.67 +/- 69.30 m at baseline to 314.83 +/- 89.09 m after an average of 14 months of bosentan treatment. Pulmonary arterial pressure decreased in most but not all 6 patients on follow-up echocardiography. This case series suggests a role for endothelin receptor blockade therapy in SPAH and should generate further interest in pharmacologic management of SPAH. A prospective controlled clinical trial of bosentan in SPAH is urgently needed.
    Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital 02/2005; 32(3):405-10. · 0.63 Impact Factor
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    ABSTRACT: Rat H9c2 cardiomyoblasts can proliferate and maintain an undifferentiated state in the presence of serum. These cardiomyoblasts have been used as a cellular model to study myogenic differentiation after serum withdrawal. Here, we examined the effects of lithium, a known inhibitor of glycogen synthase kinase-3beta and activator of Wnt pathway in myogenic differentiation. We show that in the presence of serum, lithium induced the differentiation of H9c2 cells as measured by multinucleated myotube formation and expression of the muscle-specific proteins, myogenin and skeletal alpha-actin. This differentiation was preceded by nuclear accumulation of beta-catenin, which was associated with increased Tcf/Lef-dependent transcription. We also observed that lithium mediated the activation of phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target Akt. Inhibition of PI3-kinase by LY294002 and over-expression of dominant-negative PI3-kinase caused a marked reduction in beta-catenin levels. This inhibition was associated with decreased beta-catenin-Tcf/Lef-dependent transcription, lack of multinucleated myotube formation, and expression of the muscle-specific proteins. In contrast, expression of dominant-negative Akt failed to inhibit the effects of lithium. We conclude that the capacity of lithium to overcome the inhibitory effects of serum and to induce the differentiation of H9c2 cardiomyoblasts is mediated, in part, by the stabilization and nuclear translocation of beta-catenin in a PI3-kinase-dependent but Akt-independent manner. Once activated, beta-catenin then interacts with the Lef/Tcf complex to regulate expression of myogenic-inducing genes.
    Journal of Molecular and Cellular Cardiology 09/2003; 35(8):937-51. DOI:10.1016/S0022-2828(03)00176-7 · 5.22 Impact Factor
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    ABSTRACT: The association of familial Alzheimer's disease (FAD) with mutations in Alzheimer's amyloid precursor protein (APP) suggests important functions for APP in the central nervous system. Mutations in APP impair its function to confer resistance to apoptosis in cells under stress, and this may contribute to neurodegeneration in Alzheimer's disease (AD) brain, but the mechanisms involved are unknown. We examined the role of the late Simian virus 40 transcription factor (LSF), in anti-apoptotic APP pathways. We show that in APP-deficient B103 cells, expression of wild-type human APP (hAPPwt), but not of FAD-mutant APP, inhibited staurosporine (STS)-induced apoptosis. This inhibition was further enhanced by expression of LSFwt, although LSFwt alone was not sufficient to inhibit STS-induced apoptosis. In contrast, expression of dominant-negative LSF led to a marked increase in STS-induced cell death that was significantly blocked by hAPPwt. These effects of APP were accompanied by LSF nuclear translocation and dependent gene transcription. The activation of LSF is dependent on the expression of hAPPwt and is inhibited by the expression of dominant-negative forms of either phosphoinositide 3-kinase or Akt. These results demonstrate that LSF activation is required for the neuroprotective effects of APP via phosphoinositide 3-kinase/Akt signalling. Alterations in this pathway by aberrations in APP and/or LSF could promote neuronal loss in AD brain, due to secondary insults. Thus a link is established between APP and LSF and AD.
    Biochemical Journal 04/2003; 370(Pt 3):1063-75. DOI:10.1042/BJ20021197 · 4.78 Impact Factor
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    ABSTRACT: Ribonucleotide reductase is an enzyme that is essential for DNA synthesis and repair. It is composed of 2 dimeric proteins called R1 and R2 that are both necessary for enzymatic activity that reduces ribonucleotides to deoxyribonucleotides. This is the rate-limiting reaction that provides a supply of precursors for DNA synthesis therefore it is essential for cell proliferation. The importance of understanding the complex regulation of ribonucleotide reductase is emphasized by observations that mechanisms controlling its expression and activity may be altered during malignant cell proliferation which leads to drug resistance, making it a useful target to develop chemotherapeutic compounds in the treatment of cancer. Expression studies with the R1 and R2 genes have provided evidence for a direct role for the components of ribonucleotide reductase in determining malignant potential. Ribonucleotide reductase is regulated by transcriptional activation of gene expression and post-transcriptional mechanisms that alter mRNA message stability. Post-transcriptional regulation of mRNA turnover plays an important role in modulating mRNA steady state levels and therefore directly influences gene expression. The 3'-untranslated region (UTR) of R1 and R2 messages contain sequences that are important in regulating gene expression through changes in message stability. Studies have found that mRNA message stability is mediated by growth factors, cytokines and tumor promoters. Several studies have elucidated signal transduction pathways of tumor promoters, TGF-beta and oxidation/reduction agents. This report reviews how knowledge of these signaling pathways is revealing new insights into how ribonucleotide reductase mRNA binding proteins are important in regulating cellular proliferation, drug resistance and malignancy.
    International Journal of Oncology 02/2003; 22(1):21-31. DOI:10.3892/ijo.22.1.21 · 2.77 Impact Factor
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    ABSTRACT: Alzheimer amyloid precursor protein (APP) effectively protects against apoptosis in neuronal cells under stress, but the mechanisms of this anti-apoptotic effect remain largely unknown. Transcription factors act as critical molecular switches in promoting neuronal survival. The myocyte enhancer factor-2 (MEF2) is a transcription factor, and is known to be necessary for neurogenesis and activity-dependent neuronal survival. This study examined the possible role of MEF2 in the anti-apoptotic signaling pathways activated by APP. We report that expression of wild-type human APP (hAPPwt) but not familial Alzheimer's disease mutant APP (FAD-hAPPmut) in APP-deficient rat B103 cells led to a significant increase in the level of phosphorylated MEF2. This differential phosphorylation was dependent on enhanced activation of p38 mitogen-activated protein kinase (p38 MAPK). Also, expression of hAPPwt mediated an increase in MEF2 DNA binding affinity that correlated with p38 MAPK-dependent trans-activation of a MEF2-responsive reporter gene. Furthermore, over-expression of dominant negative MEF2 in hAPPwt-expressing cells enhanced staurosporine-induced apoptosis, in contrast MEF2wt enhanced the capacity of hAPPwt to confer resistance to apoptosis. Thus, MEF2 plays a critical role in APP-mediated signaling pathways that inhibit neuronal apoptosis. A model of anti-apoptotic APP signaling is proposed where APP mediates p38 MAPK-dependent phosphorylation and activation of MEF2. Once activated MEF2 regulates neuronal survival by stimulation of MEF2-dependent gene transcriptions. Alteration of this function by mutations in APP and aberrant APP processing could contribute to neuronal degeneration seen in AD.
    Molecular Brain Research 01/2003; 108(1-2):102-20. DOI:10.1016/S0169-328X(02)00519-3 · 2.00 Impact Factor
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    ABSTRACT: We tested the approach of reversing anticoagulation following PCI and immediate sheath removal in 429 consecutive patients. On completion of the PCI, protamine was administered, and the vascular sheath was immediately removed. Stents were used in 364 patients (85%) and GP IIb/IIIa inhibitors were used in 52 patients (12%). Time to achieve hemostasis was 30 +/- 17 min. Minor groin bleeding occurred in six patients. One patient required repair of femoral pseudoaneurysm. Mean creatine kinase at 8 and 16 hr post-PCI were 129 +/- 35 and 145 +/- 32 units, respectively. Creatine kinase rose to > 3 times normal in 12 out of 350 patients (3.4%). Prior to 48 hr, eight patients (1.9%) required emergency PCI or coronary bypass surgery. Follow-up at 30 days observed no deaths and only three target vessel revascularizations (0.7%). In conclusion, immediate reversal of anticoagulation and sheath removal after PCI is safe and feasible.
    Catheterization and Cardiovascular Interventions 06/2002; 56(2):196-9. DOI:10.1002/ccd.10195 · 2.51 Impact Factor

Publication Stats

240 Citations
54.66 Total Impact Points


  • 2003–2009
    • Hôpital St-Boniface Hospital
      Winnipeg, Manitoba, Canada
    • St. Boniface Hospital Research
      Winnipeg, Manitoba, Canada
  • 2003–2008
    • University of Manitoba
      • Cardiac Sciences Program
      Winnipeg, Manitoba, Canada
  • 2007
    • National Research Council Canada
      • Institute for Biodiagnostics (IBD)
      Ottawa, Ontario, Canada