The Experts below are selected from a list of 72 Experts worldwide ranked by ideXlab platform
Hui Dong - One of the best experts on this subject based on the ideXlab platform.
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s2010 Purinergic P2Y2 Receptor and ca2 mediated proliferation of human pancreatic epithelial cancer cells
Gastroenterology, 2009Co-Authors: Jimmy Y.c. Chow, Ki-nam Shim, Tiffany A. Ornelas, John M. Carethers, Hui DongAbstract:Angiogenesis is a key step in the progression toward and maintenance of a malignant phenotype. Interaction between CXC ligands and CXC Receptors are associated with specific angiogenic or angiostatic activity. CXCL5 [epithelial neutrophil activating peptide-78], a CXC ligand, shares the same Receptor (CXCR2) with the known angiogenic CXC chemokine, CXCL8 [Interleukin-8]. The precise role of CXCL5 in pancreatic cancer has yet to be defined. The mRNA and protein levels of CXCL5 were analyzed by real time PCR and immunohistochemistry in six human pancreatic cancer cell lines, and 17 human pancreatic cancers with matched normal pancreas. CXCL5 mRNA and protein were detectable in all six human pancreatic cancer cell lines, and CXCL5 mRNA level was increased in cancer tissue compared to normal pancreas tissue in 14 out of 17 (82.4%) patients. A majority (66.7%) of the high CXCL5 mRNA expression cancers were poorly differentiated. Tumors with elevated CXCL5 mRNA were two-fold larger by volume. Immunohistochemistry confirmed most of cancer specimens (77.3%) overexpressed CXCL5 compared to normal tissue. The microvascular density was significantly higher in tumors with high CXCL5 levels compared to low CXCL5 expressing tumors (p=0.02). For In Vitro functional analysis of CXCL5, human umbilical vascular endothelial cells (HUVEC) were treated with exogenous recombinant human (rh) CXCL5[ENA-78]. We observed a dose dependent increase in HUVEC growth in response to rhCXCL5[ENA-78] treatment (p<0.02). This response was specific to the ligand given that rhCXCL5[ENA-78] in combination with antibody to CXCL5[ENA-78] or its Receptor, CXCR2, blocked HUVEC growth (IgG served as control) (p<0.02). Conditioned media from pancreatic cancer cells (ASPC-1, BxPC-3 and Capan-2) significantly stimulated HUVEC growth (p<0.01). The induction of HUVEC growth by pancreatic cancer cell media was blocked by antibody treatment to CXCL5[ENA-78] or CXCR2 (p<0.03). Finally, pancreatic cancer cell conditioned media and rhCXCL5[ENA-78] both stimulated capillary tube formation, and tubule formation was inhibited by antibody treatment to CXCL5[ENA-78] or CXCR2. These findings indicate that CXCL5 is constitutively expressed in the majority of human pancreatic cancers. The expression correlates with microvascular density, tumor volume, and differentiation. CXCL5 potently stimulated endothelial cell growth and tube formation. Specific blockade of CXCL5 may be a novel and effective therapeutic option in patients with pancreatic cancer.
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S2010 Purinergic P2Y2 Receptor and CA2+-Mediated Proliferation of Human Pancreatic Epithelial Cancer Cells
Gastroenterology, 2009Co-Authors: Jimmy Y.c. Chow, Ki-nam Shim, Tiffany A. Ornelas, John M. Carethers, Hui DongAbstract:Angiogenesis is a key step in the progression toward and maintenance of a malignant phenotype. Interaction between CXC ligands and CXC Receptors are associated with specific angiogenic or angiostatic activity. CXCL5 [epithelial neutrophil activating peptide-78], a CXC ligand, shares the same Receptor (CXCR2) with the known angiogenic CXC chemokine, CXCL8 [Interleukin-8]. The precise role of CXCL5 in pancreatic cancer has yet to be defined. The mRNA and protein levels of CXCL5 were analyzed by real time PCR and immunohistochemistry in six human pancreatic cancer cell lines, and 17 human pancreatic cancers with matched normal pancreas. CXCL5 mRNA and protein were detectable in all six human pancreatic cancer cell lines, and CXCL5 mRNA level was increased in cancer tissue compared to normal pancreas tissue in 14 out of 17 (82.4%) patients. A majority (66.7%) of the high CXCL5 mRNA expression cancers were poorly differentiated. Tumors with elevated CXCL5 mRNA were two-fold larger by volume. Immunohistochemistry confirmed most of cancer specimens (77.3%) overexpressed CXCL5 compared to normal tissue. The microvascular density was significantly higher in tumors with high CXCL5 levels compared to low CXCL5 expressing tumors (p=0.02). For In Vitro functional analysis of CXCL5, human umbilical vascular endothelial cells (HUVEC) were treated with exogenous recombinant human (rh) CXCL5[ENA-78]. We observed a dose dependent increase in HUVEC growth in response to rhCXCL5[ENA-78] treatment (p
James D. Stockand - One of the best experts on this subject based on the ideXlab platform.
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paracrine regulation of the epithelial na channel in the mammalian collecting duct by Purinergic P2Y2 Receptor tone
Journal of Biological Chemistry, 2008Co-Authors: Oleh Pochynyuk, Vladislav Bugaj, Timo Rieg, Paul A. Insel, Elena Mironova, Volker Vallon, James D. StockandAbstract:Growing evidence implicates a key role for extracellular nucleotides in cellular regulation, including of ion channels and renal function, but the mechanisms for such actions are inadequately defined. We investigated Purinergic regulation of the epithelial Na+ channel (ENaC) in mammalian collecting duct. We find that ATP decreases ENaC activity in both mouse and rat collecting duct principal cells. ATP and other nucleotides, including UTP, decrease ENaC activity via apical P2Y2 Receptors. ENaC in collecting ducts isolated from mice lacking this Receptor have blunted responses to ATP. P2Y2 couples to ENaC via PLC; direct activation of PLC mimics ATP action. Tonic regulation of ENaC in the collecting duct occurs via locally released ATP; scavenging endogenous ATP and inhibiting P2 Receptors, in the absence of other stimuli, rapidly increases ENaC activity. Moreover, ENaC has greater resting activity in collecting ducts from P2Y2-/- mice. Loss of collecting duct P2Y2 Receptors in the knock-out mouse is the primary defect leading to increased ENaC activity based on the ability of direct PLC stimulation to decrease ENaC activity in collecting ducts from P2Y2-/- mice in a manner similar to ATP in collecting ducts from wild-type mice. These findings demonstrate that locally released ATP acts in an autocrine/paracrine manner to tonically regulate ENaC in mammalian collecting duct. Loss of this intrinsic regulation leads to ENaC hyperactivity and contributes to hypertension that occurs in P2Y2 Receptor-/- mice. P2Y2 Receptor activation by nucleotides thus provides physiologically important regulation of ENaC and electrolyte handling in mammalian kidney.
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Paracrine Regulation of the Epithelial Na+ Channel in the Mammalian Collecting Duct by Purinergic P2Y2 Receptor Tone
The Journal of biological chemistry, 2008Co-Authors: Oleh Pochynyuk, Vladislav Bugaj, Timo Rieg, Paul A. Insel, Elena Mironova, Volker Vallon, James D. StockandAbstract:Growing evidence implicates a key role for extracellular nucleotides in cellular regulation, including of ion channels and renal function, but the mechanisms for such actions are inadequately defined. We investigated Purinergic regulation of the epithelial Na+ channel (ENaC) in mammalian collecting duct. We find that ATP decreases ENaC activity in both mouse and rat collecting duct principal cells. ATP and other nucleotides, including UTP, decrease ENaC activity via apical P2Y2 Receptors. ENaC in collecting ducts isolated from mice lacking this Receptor have blunted responses to ATP. P2Y2 couples to ENaC via PLC; direct activation of PLC mimics ATP action. Tonic regulation of ENaC in the collecting duct occurs via locally released ATP; scavenging endogenous ATP and inhibiting P2 Receptors, in the absence of other stimuli, rapidly increases ENaC activity. Moreover, ENaC has greater resting activity in collecting ducts from P2Y2-/- mice. Loss of collecting duct P2Y2 Receptors in the knock-out mouse is the primary defect leading to increased ENaC activity based on the ability of direct PLC stimulation to decrease ENaC activity in collecting ducts from P2Y2-/- mice in a manner similar to ATP in collecting ducts from wild-type mice. These findings demonstrate that locally released ATP acts in an autocrine/paracrine manner to tonically regulate ENaC in mammalian collecting duct. Loss of this intrinsic regulation leads to ENaC hyperactivity and contributes to hypertension that occurs in P2Y2 Receptor-/- mice. P2Y2 Receptor activation by nucleotides thus provides physiologically important regulation of ENaC and electrolyte handling in mammalian kidney.
Jun Shimazaki - One of the best experts on this subject based on the ideXlab platform.
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Effects of diquafosol sodium eye drops on tear film stability in short BUT type of dry eye.
Cornea, 2013Co-Authors: Seika Shimazaki, Hiroyuki Iseda, Murat Dogru, Jun ShimazakiAbstract:Purpose:To investigate the effects of diquafosol sodium (DQS) eye drops, a Purinergic P2Y2 Receptor agonist, on tear film stability in patients with unstable tear film (UTF).Methods:Two prospective studies were conducted. One was an exploratory nonrandomized trial on 39 eyes with dry eye symptoms an
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effects of diquafosol sodium eye drops on tear film stability in short but type of dry eye
Cornea, 2013Co-Authors: Seika Shimazakiden, Hiroyuki Iseda, Murat Dogru, Jun ShimazakiAbstract:PURPOSE: To investigate the effects of diquafosol sodium (DQS) eye drops, a Purinergic P2Y2 Receptor agonist, on tear film stability in patients with unstable tear film (UTF). METHODS: Two prospective studies were conducted. One was an exploratory nonrandomized trial on 39 eyes with dry eye symptoms and short tear film break-up time (BUT), but without epithelial damage. Changes in symptoms, BUT, Schirmer value, and ocular surface fluorescein staining (FS) scores were studied for 3 months. The other was a randomized clinical trial of DQS and artificial tears (AT) in 17 eyes with short BUT. Eyes with decreased Schirmer values (≤ 5 mm) were excluded. Changes in symptoms, BUT, FS scores, and tear film stability using continuous corneal topographic analysis were studied for 4 weeks. RESULTS: In the exploratory study, while Schirmer values were not significantly increased, significant improvements in symptoms and BUT were noted at both 1 and 3 months. In the randomized clinical trial, significant improvements in symptoms were noted in the DQS group, but not in the AT group, at 2 weeks. BUT was significantly prolonged in the DQS group at 4 weeks but not in the AT group. No significant changes were noted in FS scores or tear film stability. CONCLUSIONS: DQS improved subjective symptoms and prolonged BUT in eyes with UTF not associated with low tear secretion and ocular surface epithelial damage. Because many patients who have UTF are refractory to conventional treatments, DQS may offer benefits in the treatment of dry eyes.
Jimmy Y.c. Chow - One of the best experts on this subject based on the ideXlab platform.
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s2010 Purinergic P2Y2 Receptor and ca2 mediated proliferation of human pancreatic epithelial cancer cells
Gastroenterology, 2009Co-Authors: Jimmy Y.c. Chow, Ki-nam Shim, Tiffany A. Ornelas, John M. Carethers, Hui DongAbstract:Angiogenesis is a key step in the progression toward and maintenance of a malignant phenotype. Interaction between CXC ligands and CXC Receptors are associated with specific angiogenic or angiostatic activity. CXCL5 [epithelial neutrophil activating peptide-78], a CXC ligand, shares the same Receptor (CXCR2) with the known angiogenic CXC chemokine, CXCL8 [Interleukin-8]. The precise role of CXCL5 in pancreatic cancer has yet to be defined. The mRNA and protein levels of CXCL5 were analyzed by real time PCR and immunohistochemistry in six human pancreatic cancer cell lines, and 17 human pancreatic cancers with matched normal pancreas. CXCL5 mRNA and protein were detectable in all six human pancreatic cancer cell lines, and CXCL5 mRNA level was increased in cancer tissue compared to normal pancreas tissue in 14 out of 17 (82.4%) patients. A majority (66.7%) of the high CXCL5 mRNA expression cancers were poorly differentiated. Tumors with elevated CXCL5 mRNA were two-fold larger by volume. Immunohistochemistry confirmed most of cancer specimens (77.3%) overexpressed CXCL5 compared to normal tissue. The microvascular density was significantly higher in tumors with high CXCL5 levels compared to low CXCL5 expressing tumors (p=0.02). For In Vitro functional analysis of CXCL5, human umbilical vascular endothelial cells (HUVEC) were treated with exogenous recombinant human (rh) CXCL5[ENA-78]. We observed a dose dependent increase in HUVEC growth in response to rhCXCL5[ENA-78] treatment (p<0.02). This response was specific to the ligand given that rhCXCL5[ENA-78] in combination with antibody to CXCL5[ENA-78] or its Receptor, CXCR2, blocked HUVEC growth (IgG served as control) (p<0.02). Conditioned media from pancreatic cancer cells (ASPC-1, BxPC-3 and Capan-2) significantly stimulated HUVEC growth (p<0.01). The induction of HUVEC growth by pancreatic cancer cell media was blocked by antibody treatment to CXCL5[ENA-78] or CXCR2 (p<0.03). Finally, pancreatic cancer cell conditioned media and rhCXCL5[ENA-78] both stimulated capillary tube formation, and tubule formation was inhibited by antibody treatment to CXCL5[ENA-78] or CXCR2. These findings indicate that CXCL5 is constitutively expressed in the majority of human pancreatic cancers. The expression correlates with microvascular density, tumor volume, and differentiation. CXCL5 potently stimulated endothelial cell growth and tube formation. Specific blockade of CXCL5 may be a novel and effective therapeutic option in patients with pancreatic cancer.
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S2010 Purinergic P2Y2 Receptor and CA2+-Mediated Proliferation of Human Pancreatic Epithelial Cancer Cells
Gastroenterology, 2009Co-Authors: Jimmy Y.c. Chow, Ki-nam Shim, Tiffany A. Ornelas, John M. Carethers, Hui DongAbstract:Angiogenesis is a key step in the progression toward and maintenance of a malignant phenotype. Interaction between CXC ligands and CXC Receptors are associated with specific angiogenic or angiostatic activity. CXCL5 [epithelial neutrophil activating peptide-78], a CXC ligand, shares the same Receptor (CXCR2) with the known angiogenic CXC chemokine, CXCL8 [Interleukin-8]. The precise role of CXCL5 in pancreatic cancer has yet to be defined. The mRNA and protein levels of CXCL5 were analyzed by real time PCR and immunohistochemistry in six human pancreatic cancer cell lines, and 17 human pancreatic cancers with matched normal pancreas. CXCL5 mRNA and protein were detectable in all six human pancreatic cancer cell lines, and CXCL5 mRNA level was increased in cancer tissue compared to normal pancreas tissue in 14 out of 17 (82.4%) patients. A majority (66.7%) of the high CXCL5 mRNA expression cancers were poorly differentiated. Tumors with elevated CXCL5 mRNA were two-fold larger by volume. Immunohistochemistry confirmed most of cancer specimens (77.3%) overexpressed CXCL5 compared to normal tissue. The microvascular density was significantly higher in tumors with high CXCL5 levels compared to low CXCL5 expressing tumors (p=0.02). For In Vitro functional analysis of CXCL5, human umbilical vascular endothelial cells (HUVEC) were treated with exogenous recombinant human (rh) CXCL5[ENA-78]. We observed a dose dependent increase in HUVEC growth in response to rhCXCL5[ENA-78] treatment (p
Ki-nam Shim - One of the best experts on this subject based on the ideXlab platform.
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s2010 Purinergic P2Y2 Receptor and ca2 mediated proliferation of human pancreatic epithelial cancer cells
Gastroenterology, 2009Co-Authors: Jimmy Y.c. Chow, Ki-nam Shim, Tiffany A. Ornelas, John M. Carethers, Hui DongAbstract:Angiogenesis is a key step in the progression toward and maintenance of a malignant phenotype. Interaction between CXC ligands and CXC Receptors are associated with specific angiogenic or angiostatic activity. CXCL5 [epithelial neutrophil activating peptide-78], a CXC ligand, shares the same Receptor (CXCR2) with the known angiogenic CXC chemokine, CXCL8 [Interleukin-8]. The precise role of CXCL5 in pancreatic cancer has yet to be defined. The mRNA and protein levels of CXCL5 were analyzed by real time PCR and immunohistochemistry in six human pancreatic cancer cell lines, and 17 human pancreatic cancers with matched normal pancreas. CXCL5 mRNA and protein were detectable in all six human pancreatic cancer cell lines, and CXCL5 mRNA level was increased in cancer tissue compared to normal pancreas tissue in 14 out of 17 (82.4%) patients. A majority (66.7%) of the high CXCL5 mRNA expression cancers were poorly differentiated. Tumors with elevated CXCL5 mRNA were two-fold larger by volume. Immunohistochemistry confirmed most of cancer specimens (77.3%) overexpressed CXCL5 compared to normal tissue. The microvascular density was significantly higher in tumors with high CXCL5 levels compared to low CXCL5 expressing tumors (p=0.02). For In Vitro functional analysis of CXCL5, human umbilical vascular endothelial cells (HUVEC) were treated with exogenous recombinant human (rh) CXCL5[ENA-78]. We observed a dose dependent increase in HUVEC growth in response to rhCXCL5[ENA-78] treatment (p<0.02). This response was specific to the ligand given that rhCXCL5[ENA-78] in combination with antibody to CXCL5[ENA-78] or its Receptor, CXCR2, blocked HUVEC growth (IgG served as control) (p<0.02). Conditioned media from pancreatic cancer cells (ASPC-1, BxPC-3 and Capan-2) significantly stimulated HUVEC growth (p<0.01). The induction of HUVEC growth by pancreatic cancer cell media was blocked by antibody treatment to CXCL5[ENA-78] or CXCR2 (p<0.03). Finally, pancreatic cancer cell conditioned media and rhCXCL5[ENA-78] both stimulated capillary tube formation, and tubule formation was inhibited by antibody treatment to CXCL5[ENA-78] or CXCR2. These findings indicate that CXCL5 is constitutively expressed in the majority of human pancreatic cancers. The expression correlates with microvascular density, tumor volume, and differentiation. CXCL5 potently stimulated endothelial cell growth and tube formation. Specific blockade of CXCL5 may be a novel and effective therapeutic option in patients with pancreatic cancer.
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S2010 Purinergic P2Y2 Receptor and CA2+-Mediated Proliferation of Human Pancreatic Epithelial Cancer Cells
Gastroenterology, 2009Co-Authors: Jimmy Y.c. Chow, Ki-nam Shim, Tiffany A. Ornelas, John M. Carethers, Hui DongAbstract:Angiogenesis is a key step in the progression toward and maintenance of a malignant phenotype. Interaction between CXC ligands and CXC Receptors are associated with specific angiogenic or angiostatic activity. CXCL5 [epithelial neutrophil activating peptide-78], a CXC ligand, shares the same Receptor (CXCR2) with the known angiogenic CXC chemokine, CXCL8 [Interleukin-8]. The precise role of CXCL5 in pancreatic cancer has yet to be defined. The mRNA and protein levels of CXCL5 were analyzed by real time PCR and immunohistochemistry in six human pancreatic cancer cell lines, and 17 human pancreatic cancers with matched normal pancreas. CXCL5 mRNA and protein were detectable in all six human pancreatic cancer cell lines, and CXCL5 mRNA level was increased in cancer tissue compared to normal pancreas tissue in 14 out of 17 (82.4%) patients. A majority (66.7%) of the high CXCL5 mRNA expression cancers were poorly differentiated. Tumors with elevated CXCL5 mRNA were two-fold larger by volume. Immunohistochemistry confirmed most of cancer specimens (77.3%) overexpressed CXCL5 compared to normal tissue. The microvascular density was significantly higher in tumors with high CXCL5 levels compared to low CXCL5 expressing tumors (p=0.02). For In Vitro functional analysis of CXCL5, human umbilical vascular endothelial cells (HUVEC) were treated with exogenous recombinant human (rh) CXCL5[ENA-78]. We observed a dose dependent increase in HUVEC growth in response to rhCXCL5[ENA-78] treatment (p
