Jessica Saliba - Academia.edu (original) (raw)
Papers by Jessica Saliba
Diagnosis, Management and Modeling of Neurodevelopmental Disorders, 2021
La leucemie myeloide chronique (LMC) est une maladie myeloproliferative, resultant d'une tran... more La leucemie myeloide chronique (LMC) est une maladie myeloproliferative, resultant d'une translocation reciproque entre les chromosomes 9 et 22, donnant naissance a une kinase de fusion a activite continue, la BCR-ABL. Les inhibiteurs de la tyrosine kinase (ITK) sont le traitement de choix de la LMC, mais ces inhibiteurs n'offrent pas de cure radicale aux patients, qui, une fois le traitement interrompu, presentent une rechute et une exacerbation de leur condition. En plus, les patients peuvent developper une resistance ou une intolerance aux ITK, d'ou la necessite de nouvelles modalites therapeutiques. Les imidazoquinoxalines sont de nouveaux composes a visee anticancereuse, dont la structure est basee sur celle de l'imiquimod, un immunomodulateur connu. EAPB0203, un compose du groupe des imidazo[1,2-α]quinoxalines, a fait preuve d'un pouvoir anticancereux sur des cellules de melanome, in vitro et in vivo, ainsi que sur des cellules de leucemie liee au virus HTL...
Cancers, 2019
Loss of connexin-mediated cell-cell communication is a hallmark of breast cancer progression. Pan... more Loss of connexin-mediated cell-cell communication is a hallmark of breast cancer progression. Pannexin1 (PANX1), a glycoprotein that shares structural and functional features with connexins and engages in cell communication with its environment, is highly expressed in breast cancer metastatic foci; however, PANX1 contribution to metastatic progression is still obscure. Here we report elevated expression of PANX1 in different breast cancer (BRCA) subtypes using RNA-seq data from The Cancer Genome Atlas (TCGA). The elevated PANX1 expression correlated with poorer outcomes in TCGA BRCA patients. In addition, gene set enrichment analysis (GSEA) revealed that epithelial-to-mesenchymal transition (EMT) pathway genes correlated positively with PANX1 expression. Pharmacological inhibition of PANX1, in MDA-MB-231 and MCF-7 breast cancer cells, or genetic ablation of PANX1, in MDA-MB-231 cells, reverted the EMT phenotype, as evidenced by decreased expression of EMT markers. In addition, PANX1...
Cancers, 2019
Connexins regulate multiple cellular functions and are considered tumor suppressors. Connexin43 (... more Connexins regulate multiple cellular functions and are considered tumor suppressors. Connexin43 (Cx43) is frequently down-regulated in breast tumors. However, Cx43 regulation during cancer onset and metastasis is complex and context-dependent. We investigated the effect of Cx43 over-expression or knock-down on the metastatic potential of MDA-MB-231 breast cancer cells in vitro and in vivo and in human breast cancer tissues. MDA-MB-231 cells over-expressing (Cx43D) or down-regulating Cx43 (shCx43) were generated and used in proliferation, migration, and invasion assays. The regulation of genes/proteins implicated in progression, invasion and metastasis was assessed in vitro and in immune-compromized mice injected with MDA-MB-231, Cx43D or shCx43 cells. Primary tumor onset/growth, metastasis and overall survival of these animals was monitored and evaluated. In addition, Cx43 expression in human breast carcinoma samples was assessed by qPCR. Cx43 over-expression increased protein level...
Scientific Reports, 2017
Electronic cigarettes (e-cigarettes) are promoted as low-risk alternatives to combustible cigaret... more Electronic cigarettes (e-cigarettes) are promoted as low-risk alternatives to combustible cigarettes. However, the effects of chronic inhalation of potential toxicants emitted by ecigarettes remain largely unexamined. It is conceivable that smoking-induced chronic diseases result in cellular injury, in the absence of effective repair by stem cells. This study evaluates the effect of cigarette and e-cigarette aerosol extracts on the survival and differentiation of bone marrow-derived mesenchymal stem cells (MSCs). MSC growth and osteogenic differentiation were examined after exposure to smoke extracts. Data revealed detrimental effects of both cigarette and e-cigarette extracts on MSC morphology and growth. Levels and activity of alkaline phosphatase, an osteogenic marker, decreased and induction of osteoblastic differentiation was impaired. Both smoke extracts prevented osteogenic differentiation from progressing, evident by decreased expression of terminal osteogenic markers and mineralization. Elevated levels of reactive oxygen species (ROS) were detected in cells exposed to smoke extracts. Moreover, decreased differentiation potential was concomitant with severe down-regulation of Connexin 43 expression, leading to the loss of gap junction-mediated communication, which together with elevated ROS levels, could explain decreased proliferation and loss of differentiation potential. Hence, e-cigarettes present similar risk as combustible cigarettes with respect to tissue repair impairment. The detrimental impact of cigarette smoking on health is amply documented and ranges from oral diseases 1 , to systemic malfunction, inflammation 2 , infertility 3,4 , cancer and abnormal cell differentiation and tissue repair 1. Awareness has been raised among smokers and policy-makers, and has resulted in proactive measures aiming at curbing cigarette smoking. Controversially, waterpipe smoking is gaining popularity worldwide, alongside another globally spreading phenomenon, the use of electronic cigarette (e-cigarette) or "vaping" 5. E-cigarettes are often claimed to be a safer alternative to conventional tobacco products and are sometimes marketed as a smoking cessation tool. Some research has suggested a decrease in the disease burden of e-cigarette vaping, compared to combustible cigarette smoking 6. However, e-cigarette liquids have been reported to be cytotoxic 7,8 , and e-cigarette aerosol emissions have been shown to exert negative effects in animal models 9-14. Nevertheless, partly due to the recent emergence of the e-cigarette, there is a lack of information on its long-term effects on health and studies on e-cigarette safety are not yet conclusive. Combustible cigarette smoke compromises cell growth and tissue repair 1,15,16 ; however, the impact of e-cigarette aerosols on cell differentiation and tissue repair has not been studied. A stable epithelial layer with a relatively slow cell turnover rate lines the respiratory tract 17. Upon injury, progenitor and stem cells are recruited to repair damaged tissues. However, smokers develop chronic conditions, from long-term exposure to smoke, suggesting impaired tissue healing and remodelling. Previously, we explored the effect of waterpipe smoke on alveolar type II-derived cells 18 and on endothelial cells 19 , detailing cytotoxic, mutagenic, inflammatory and anti-proliferative effects. The onset of systemic inflammation and the compromised
Genes, 2018
Understanding the mechanisms that govern nervous tissues function remains a challenge. In vitro t... more Understanding the mechanisms that govern nervous tissues function remains a challenge. In vitro two-dimensional (2D) cell culture systems provide a simplistic platform to evaluate systematic investigations but often result in unreliable responses that cannot be translated to pathophysiological settings. Recently, microplatforms have emerged to provide a better approximation of the in vivo scenario with better control over the microenvironment, stimuli and structure. Advances in biomaterials enable the construction of three-dimensional (3D) scaffolds, which combined with microfabrication, allow enhanced biomimicry through precise control of the architecture, cell positioning, fluid flows and electrochemical stimuli. This manuscript reviews, compares and contrasts advances in nervous tissues-on-a-chip models and their applications in neural physiology and disease. Microplatforms used for neuro-glia interactions, neuromuscular junctions (NMJs), blood-brain barrier (BBB) and studies on brain cancer, metastasis and neurodegenerative diseases are addressed. Finally, we highlight challenges that can be addressed with interdisciplinary efforts to achieve a higher degree of biomimicry. Nervous tissue microplatforms provide a powerful tool that is destined to provide a better understanding of neural health and disease.
Journal of biological regulators and homeostatic agents
Integrins can modulate the infiltration of inflammatory cells and the secretion of various inflam... more Integrins can modulate the infiltration of inflammatory cells and the secretion of various inflammatory mediators, essential players in the pathogenesis of colitis. This study explores the role of beta2 and beta3 integrin signaling and their possible role in experimental colitis. A total of 160 adult male Sprague-Dawly rats were divided into 4 equal groups: methylcellulose, bacteria, iodoacetamide and iodoacetamide plus bacteria. Clinical symptoms and signs of colitis were checked daily and colonic tissues were biopsied on days 3, 14, 28, and 56 post induction. Histological studies along with histochemical analysis and polymerase chain reaction of beta2, beta3 and alphavbeta3 were performed according to standard procedures. The symptoms and signs were consistent with previously reported data on active colitis. The highest expression of beta3 integrin was in the combined treatment mostly on platelets, endothelial and inflammatory cells. In the same group, the expression of alphavbeta...
Qatar Foundation Annual Research Forum Proceedings, 2011
International Journal of Cancer, 2013
Diagnosis, Management and Modeling of Neurodevelopmental Disorders, 2021
La leucemie myeloide chronique (LMC) est une maladie myeloproliferative, resultant d'une tran... more La leucemie myeloide chronique (LMC) est une maladie myeloproliferative, resultant d'une translocation reciproque entre les chromosomes 9 et 22, donnant naissance a une kinase de fusion a activite continue, la BCR-ABL. Les inhibiteurs de la tyrosine kinase (ITK) sont le traitement de choix de la LMC, mais ces inhibiteurs n'offrent pas de cure radicale aux patients, qui, une fois le traitement interrompu, presentent une rechute et une exacerbation de leur condition. En plus, les patients peuvent developper une resistance ou une intolerance aux ITK, d'ou la necessite de nouvelles modalites therapeutiques. Les imidazoquinoxalines sont de nouveaux composes a visee anticancereuse, dont la structure est basee sur celle de l'imiquimod, un immunomodulateur connu. EAPB0203, un compose du groupe des imidazo[1,2-α]quinoxalines, a fait preuve d'un pouvoir anticancereux sur des cellules de melanome, in vitro et in vivo, ainsi que sur des cellules de leucemie liee au virus HTL...
Cancers, 2019
Loss of connexin-mediated cell-cell communication is a hallmark of breast cancer progression. Pan... more Loss of connexin-mediated cell-cell communication is a hallmark of breast cancer progression. Pannexin1 (PANX1), a glycoprotein that shares structural and functional features with connexins and engages in cell communication with its environment, is highly expressed in breast cancer metastatic foci; however, PANX1 contribution to metastatic progression is still obscure. Here we report elevated expression of PANX1 in different breast cancer (BRCA) subtypes using RNA-seq data from The Cancer Genome Atlas (TCGA). The elevated PANX1 expression correlated with poorer outcomes in TCGA BRCA patients. In addition, gene set enrichment analysis (GSEA) revealed that epithelial-to-mesenchymal transition (EMT) pathway genes correlated positively with PANX1 expression. Pharmacological inhibition of PANX1, in MDA-MB-231 and MCF-7 breast cancer cells, or genetic ablation of PANX1, in MDA-MB-231 cells, reverted the EMT phenotype, as evidenced by decreased expression of EMT markers. In addition, PANX1...
Cancers, 2019
Connexins regulate multiple cellular functions and are considered tumor suppressors. Connexin43 (... more Connexins regulate multiple cellular functions and are considered tumor suppressors. Connexin43 (Cx43) is frequently down-regulated in breast tumors. However, Cx43 regulation during cancer onset and metastasis is complex and context-dependent. We investigated the effect of Cx43 over-expression or knock-down on the metastatic potential of MDA-MB-231 breast cancer cells in vitro and in vivo and in human breast cancer tissues. MDA-MB-231 cells over-expressing (Cx43D) or down-regulating Cx43 (shCx43) were generated and used in proliferation, migration, and invasion assays. The regulation of genes/proteins implicated in progression, invasion and metastasis was assessed in vitro and in immune-compromized mice injected with MDA-MB-231, Cx43D or shCx43 cells. Primary tumor onset/growth, metastasis and overall survival of these animals was monitored and evaluated. In addition, Cx43 expression in human breast carcinoma samples was assessed by qPCR. Cx43 over-expression increased protein level...
Scientific Reports, 2017
Electronic cigarettes (e-cigarettes) are promoted as low-risk alternatives to combustible cigaret... more Electronic cigarettes (e-cigarettes) are promoted as low-risk alternatives to combustible cigarettes. However, the effects of chronic inhalation of potential toxicants emitted by ecigarettes remain largely unexamined. It is conceivable that smoking-induced chronic diseases result in cellular injury, in the absence of effective repair by stem cells. This study evaluates the effect of cigarette and e-cigarette aerosol extracts on the survival and differentiation of bone marrow-derived mesenchymal stem cells (MSCs). MSC growth and osteogenic differentiation were examined after exposure to smoke extracts. Data revealed detrimental effects of both cigarette and e-cigarette extracts on MSC morphology and growth. Levels and activity of alkaline phosphatase, an osteogenic marker, decreased and induction of osteoblastic differentiation was impaired. Both smoke extracts prevented osteogenic differentiation from progressing, evident by decreased expression of terminal osteogenic markers and mineralization. Elevated levels of reactive oxygen species (ROS) were detected in cells exposed to smoke extracts. Moreover, decreased differentiation potential was concomitant with severe down-regulation of Connexin 43 expression, leading to the loss of gap junction-mediated communication, which together with elevated ROS levels, could explain decreased proliferation and loss of differentiation potential. Hence, e-cigarettes present similar risk as combustible cigarettes with respect to tissue repair impairment. The detrimental impact of cigarette smoking on health is amply documented and ranges from oral diseases 1 , to systemic malfunction, inflammation 2 , infertility 3,4 , cancer and abnormal cell differentiation and tissue repair 1. Awareness has been raised among smokers and policy-makers, and has resulted in proactive measures aiming at curbing cigarette smoking. Controversially, waterpipe smoking is gaining popularity worldwide, alongside another globally spreading phenomenon, the use of electronic cigarette (e-cigarette) or "vaping" 5. E-cigarettes are often claimed to be a safer alternative to conventional tobacco products and are sometimes marketed as a smoking cessation tool. Some research has suggested a decrease in the disease burden of e-cigarette vaping, compared to combustible cigarette smoking 6. However, e-cigarette liquids have been reported to be cytotoxic 7,8 , and e-cigarette aerosol emissions have been shown to exert negative effects in animal models 9-14. Nevertheless, partly due to the recent emergence of the e-cigarette, there is a lack of information on its long-term effects on health and studies on e-cigarette safety are not yet conclusive. Combustible cigarette smoke compromises cell growth and tissue repair 1,15,16 ; however, the impact of e-cigarette aerosols on cell differentiation and tissue repair has not been studied. A stable epithelial layer with a relatively slow cell turnover rate lines the respiratory tract 17. Upon injury, progenitor and stem cells are recruited to repair damaged tissues. However, smokers develop chronic conditions, from long-term exposure to smoke, suggesting impaired tissue healing and remodelling. Previously, we explored the effect of waterpipe smoke on alveolar type II-derived cells 18 and on endothelial cells 19 , detailing cytotoxic, mutagenic, inflammatory and anti-proliferative effects. The onset of systemic inflammation and the compromised
Genes, 2018
Understanding the mechanisms that govern nervous tissues function remains a challenge. In vitro t... more Understanding the mechanisms that govern nervous tissues function remains a challenge. In vitro two-dimensional (2D) cell culture systems provide a simplistic platform to evaluate systematic investigations but often result in unreliable responses that cannot be translated to pathophysiological settings. Recently, microplatforms have emerged to provide a better approximation of the in vivo scenario with better control over the microenvironment, stimuli and structure. Advances in biomaterials enable the construction of three-dimensional (3D) scaffolds, which combined with microfabrication, allow enhanced biomimicry through precise control of the architecture, cell positioning, fluid flows and electrochemical stimuli. This manuscript reviews, compares and contrasts advances in nervous tissues-on-a-chip models and their applications in neural physiology and disease. Microplatforms used for neuro-glia interactions, neuromuscular junctions (NMJs), blood-brain barrier (BBB) and studies on brain cancer, metastasis and neurodegenerative diseases are addressed. Finally, we highlight challenges that can be addressed with interdisciplinary efforts to achieve a higher degree of biomimicry. Nervous tissue microplatforms provide a powerful tool that is destined to provide a better understanding of neural health and disease.
Journal of biological regulators and homeostatic agents
Integrins can modulate the infiltration of inflammatory cells and the secretion of various inflam... more Integrins can modulate the infiltration of inflammatory cells and the secretion of various inflammatory mediators, essential players in the pathogenesis of colitis. This study explores the role of beta2 and beta3 integrin signaling and their possible role in experimental colitis. A total of 160 adult male Sprague-Dawly rats were divided into 4 equal groups: methylcellulose, bacteria, iodoacetamide and iodoacetamide plus bacteria. Clinical symptoms and signs of colitis were checked daily and colonic tissues were biopsied on days 3, 14, 28, and 56 post induction. Histological studies along with histochemical analysis and polymerase chain reaction of beta2, beta3 and alphavbeta3 were performed according to standard procedures. The symptoms and signs were consistent with previously reported data on active colitis. The highest expression of beta3 integrin was in the combined treatment mostly on platelets, endothelial and inflammatory cells. In the same group, the expression of alphavbeta...
Qatar Foundation Annual Research Forum Proceedings, 2011
International Journal of Cancer, 2013