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Molecular mechanisms underlying fibrosis and elastin destruction in childhood interstitial lung diseases

Research Abstract
Objective This study aimed to evaluate fibrosis and elastin destruction in childhood interstitial lung disease (chILD) patients. Methods Sixty patients and twenty healthy children were recruited. On admission, evaluation of chILD severity was made using Fan chILD score. Participants provided urine and blood samples. Plasma levels of transforming growth factor (TGF)-β1, connective tissue growth factor (CCN2), soluble factor related apoptosis (sFas) and long non-coding RNAs and urinary levels of desmosine/urinary creatinine (UDes/UCr) were measured. Results In patients, clinical findings were crackles (100.00%), tachypnea (65.00%), cardiomegaly (45.00%), digital clubbing (43.30%), cough (33.00%), cyanosis (26.70%), hepatomegaly (28.30%) and wheezes (23.30%). Categorizing of the patients with Fan chILD clinical score revealed that most patients 33.30% scored (3, symptomatic with abnormal saturation/cyanosis during exercise) then 28.30% scored (5, symptomatic with clinical and echocardiographic features of pulmonary hypertension), 18.30% scored (2, symptomatic with normal room air saturations), 15.00% scored (1, asymptomatic) and 5.00% scored (4, symptomatic with abnormal room air saturation/cyanosis at rest). TGF-β1, CCN2, sFas, lncrRNA-2700086A05Rik relative gene expression and UDes/UCr levels were higher in patients than controls (P = 0.002, P = 0.001, P = 0.001, P = 0.001, P = 0.001, respectively). In patients, significant positive correlations were found between TGF-β1 and CCN2, sFas, UDes/UCr; between CCN2 and both sFas and UDes/UCr; between UDes/UCr and sFas. Morbidity and mortality rates were 46.70% and 10.00%, respectively. Conclusion Markers of fibrosis (TGF-β1, sFas, CCN2) and elastin destruction (UDes/UCr) were increased in chILD especially in patients with long disease duration. So blockage of their pathways signals may offer novel therapeutic targets. Abbreviations ARDS, acute respiratory distress syndrome; AECs, alveolar epithelial cells; BMI, body mass index; CXR, chest X-ray; chILD, childhood interstitial lung disease; CPI, chronic pneumonitis of infancy; CCN2, connective tissue growth factor; CT, critical threshold; ECM, extracellular matrix; DIP, desquamative interstitial pneumonitis; DAD, diffuse alveolar damage; EMT, epithelial-mesenchymal transition; ERS, European Respiratory Society; HRCT, high-resolution computed tomography; lncRNAs, long non-coding RNAs; LIP, lymphocytic interstitial pneumonia; NSIP, idiopathic interstitial pneumonias; IPF, interstitial pulmonary fibrosis; OP, organizing pneumonia; PAP, pulmonary alveolar proteinosis; sFas, soluble factor related apoptosis; TGF-β1, transforming growth factor-β1; UDes/UCr, urinary levels of desmosine/urinary creatinine; UIP, usual interstitial pneumonia
Research Authors
Enas A. Hamed, M.D.a, , , Mostafa M. El-Saieda, Khaled Saada, Hazem Abu-Zeid Yousefb, Amany O. Mohamedc, Dina Sabryd
Research Journal
Pathophysiology
Research Pages
NULL
Research Publisher
NULL
Research Rank
1
Research Vol
NULL
Research Website
NULL
Research Year
2016

Molecular mechanisms underlying fibrosis and elastin destruction in childhood interstitial lung diseases

Research Abstract
Objective This study aimed to evaluate fibrosis and elastin destruction in childhood interstitial lung disease (chILD) patients. Methods Sixty patients and twenty healthy children were recruited. On admission, evaluation of chILD severity was made using Fan chILD score. Participants provided urine and blood samples. Plasma levels of transforming growth factor (TGF)-β1, connective tissue growth factor (CCN2), soluble factor related apoptosis (sFas) and long non-coding RNAs and urinary levels of desmosine/urinary creatinine (UDes/UCr) were measured. Results In patients, clinical findings were crackles (100.00%), tachypnea (65.00%), cardiomegaly (45.00%), digital clubbing (43.30%), cough (33.00%), cyanosis (26.70%), hepatomegaly (28.30%) and wheezes (23.30%). Categorizing of the patients with Fan chILD clinical score revealed that most patients 33.30% scored (3, symptomatic with abnormal saturation/cyanosis during exercise) then 28.30% scored (5, symptomatic with clinical and echocardiographic features of pulmonary hypertension), 18.30% scored (2, symptomatic with normal room air saturations), 15.00% scored (1, asymptomatic) and 5.00% scored (4, symptomatic with abnormal room air saturation/cyanosis at rest). TGF-β1, CCN2, sFas, lncrRNA-2700086A05Rik relative gene expression and UDes/UCr levels were higher in patients than controls (P = 0.002, P = 0.001, P = 0.001, P = 0.001, P = 0.001, respectively). In patients, significant positive correlations were found between TGF-β1 and CCN2, sFas, UDes/UCr; between CCN2 and both sFas and UDes/UCr; between UDes/UCr and sFas. Morbidity and mortality rates were 46.70% and 10.00%, respectively. Conclusion Markers of fibrosis (TGF-β1, sFas, CCN2) and elastin destruction (UDes/UCr) were increased in chILD especially in patients with long disease duration. So blockage of their pathways signals may offer novel therapeutic targets. Abbreviations ARDS, acute respiratory distress syndrome; AECs, alveolar epithelial cells; BMI, body mass index; CXR, chest X-ray; chILD, childhood interstitial lung disease; CPI, chronic pneumonitis of infancy; CCN2, connective tissue growth factor; CT, critical threshold; ECM, extracellular matrix; DIP, desquamative interstitial pneumonitis; DAD, diffuse alveolar damage; EMT, epithelial-mesenchymal transition; ERS, European Respiratory Society; HRCT, high-resolution computed tomography; lncRNAs, long non-coding RNAs; LIP, lymphocytic interstitial pneumonia; NSIP, idiopathic interstitial pneumonias; IPF, interstitial pulmonary fibrosis; OP, organizing pneumonia; PAP, pulmonary alveolar proteinosis; sFas, soluble factor related apoptosis; TGF-β1, transforming growth factor-β1; UDes/UCr, urinary levels of desmosine/urinary creatinine; UIP, usual interstitial pneumonia
Research Authors
Enas A. Hamed, M.D.a, , , Mostafa M. El-Saieda, Khaled Saada, Hazem Abu-Zeid Yousefb, Amany O. Mohamedc, Dina Sabryd
Research Department
Research Journal
Pathophysiology
Research Member
Research Pages
NULL
Research Publisher
NULL
Research Rank
1
Research Vol
NULL
Research Website
NULL
Research Year
2016

Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment

Research Abstract
The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.
Research Authors
Ahmed A. Markeb, Nagwa A. El-Maali, Douaa M. Sayed, Amany Osama, Mohamed A. Y. Abdel-Malek, Amen H. Zaki, Mostafa E. A. Elwanis, and James J. Driscoll
Research Journal
International Journal of Breast Cancer
Research Pages
8 pages
Research Publisher
Hindawi Publishing Corporation
Research Rank
1
Research Vol
Volume 2016 (2016), Article ID 7549372,
Research Website
NULL
Research Year
2016

Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment

Research Abstract
The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.
Research Authors
Ahmed A. Markeb, Nagwa A. El-Maali, Douaa M. Sayed, Amany Osama, Mohamed A. Y. Abdel-Malek, Amen H. Zaki, Mostafa E. A. Elwanis, and James J. Driscoll
Research Journal
International Journal of Breast Cancer
Research Pages
8 pages
Research Publisher
Hindawi Publishing Corporation
Research Rank
1
Research Vol
Volume 2016 (2016), Article ID 7549372,
Research Website
NULL
Research Year
2016

Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment

Research Abstract
The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.
Research Authors
Ahmed A. Markeb, Nagwa A. El-Maali, Douaa M. Sayed, Amany Osama, Mohamed A. Y. Abdel-Malek, Amen H. Zaki, Mostafa E. A. Elwanis, and James J. Driscoll
Research Department
Research Journal
International Journal of Breast Cancer
Research Member
Research Pages
8 pages
Research Publisher
Hindawi Publishing Corporation
Research Rank
1
Research Vol
Volume 2016 (2016), Article ID 7549372,
Research Website
NULL
Research Year
2016

Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment

Research Abstract
The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.
Research Authors
Ahmed A. Markeb, Nagwa A. El-Maali, Douaa M. Sayed, Amany Osama, Mohamed A. Y. Abdel-Malek, Amen H. Zaki, Mostafa E. A. Elwanis, and James J. Driscoll
Research Journal
International Journal of Breast Cancer
Research Pages
8 pages
Research Publisher
Hindawi Publishing Corporation
Research Rank
1
Research Vol
Volume 2016 (2016), Article ID 7549372,
Research Website
NULL
Research Year
2016

Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment

Research Abstract
The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.
Research Authors
Ahmed A. Markeb, Nagwa A. El-Maali, Douaa M. Sayed, Amany Osama, Mohamed A. Y. Abdel-Malek, Amen H. Zaki, Mostafa E. A. Elwanis, and James J. Driscoll
Research Journal
International Journal of Breast Cancer
Research Pages
8 pages
Research Publisher
Hindawi Publishing Corporation
Research Rank
1
Research Vol
Volume 2016 (2016), Article ID 7549372,
Research Website
NULL
Research Year
2016

Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment

Research Abstract
The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.
Research Authors
Ahmed A. Markeb, Nagwa A. El-Maali, Douaa M. Sayed, Amany Osama, Mohamed A. Y. Abdel-Malek, Amen H. Zaki, Mostafa E. A. Elwanis, and James J. Driscoll
Research Journal
International Journal of Breast Cancer
Research Pages
8 pages
Research Publisher
Hindawi Publishing Corporation
Research Rank
1
Research Vol
Volume 2016 (2016), Article ID 7549372,
Research Website
NULL
Research Year
2016

Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment

Research Abstract
The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.
Research Authors
Ahmed A. Markeb, Nagwa A. El-Maali, Douaa M. Sayed, Amany Osama, Mohamed A. Y. Abdel-Malek, Amen H. Zaki, Mostafa E. A. Elwanis, and James J. Driscoll
Research Journal
International Journal of Breast Cancer
Research Pages
8 pages
Research Publisher
Hindawi Publishing Corporation
Research Rank
1
Research Vol
Volume 2016 (2016), Article ID 7549372,
Research Website
NULL
Research Year
2016
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