The Experts below are selected from a list of 948 Experts worldwide ranked by ideXlab platform
Yolanda N Mageto - One of the best experts on this subject based on the ideXlab platform.
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treatment of idiopathic pulmonary fibrosis with a new Antifibrotic Agent pirfenidone results of a prospective open label phase ii study
American Journal of Respiratory and Critical Care Medicine, 1999Co-Authors: Ganesh Raghu, W C Johnson, Diane Lockhart, Yolanda N MagetoAbstract:Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of unknown etiology and fatal outcome. Currently available therapies are ineffective and associated with significant adverse effects. Pirfenidone, a new, investigational Antifibrotic Agent, was evaluated for its tolerability and usefulness in terminally ill patients with advanced IPF. Consecutive patients with IPF and deterioration despite conventional therapy or who were unable to tolerate or unwilling to try conventional therapy were treated with oral pirfenidone. Treatment was administered on a compassionate basis (open-label). Fifty-four patients were followed for mortality, change in lung function, and adverse effects. Their mean age was 62, mean duration of symptoms 4.6 yr, and time since lung biopsy was 3.2 yr. Conventional therapy was discontinued in 38 of 46 patients; the other eight were able to decrease their prednisone dosage and eight had no previous conventional treatment. One- and 2-yr survival was 78% (95% CI 66%, 89%) ...
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treatment of idiopathic pulmonary fibrosis with a new Antifibrotic Agent pirfenidone results of a prospective open label phase ii study
American Journal of Respiratory and Critical Care Medicine, 1999Co-Authors: Ganesh Raghu, W C Johnson, Diane Lockhart, Yolanda N MagetoAbstract:Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of unknown etiology and fatal outcome. Currently available therapies are ineffective and associated with significant adverse effects. Pirfenidone, a new, investigational Antifibrotic Agent, was evaluated for its tolerability and usefulness in terminally ill patients with advanced IPF. Consecutive patients with IPF and deterioration despite conventional therapy or who were unable to tolerate or unwilling to try conventional therapy were treated with oral pirfenidone. Treatment was administered on a compassionate basis (open-label). Fifty-four patients were followed for mortality, change in lung function, and adverse effects. Their mean age was 62, mean duration of symptoms 4.6 yr, and time since lung biopsy was 3.2 yr. Conventional therapy was discontinued in 38 of 46 patients; the other eight were able to decrease their prednisone dosage and eight had no previous conventional treatment. One- and 2-yr survival was 78% (95% CI 66%, 89%) and 63% (95% CI 50%, 76%), respectively. Patients whose lung functions had deteriorated prior to enrollment appeared to stabilize after beginning treatment. Adverse effects were relatively minor. The results of this study are encouraging. Pirfenidone is a promising new treatment for IPF that is well tolerated.
David J Riley - One of the best experts on this subject based on the ideXlab platform.
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liposome encapsulation improves the effect of Antifibrotic Agent in rat lung fibrosis
American Journal of Respiratory and Critical Care Medicine, 1994Co-Authors: G J Poiani, J K Choe, J D Fox, M J Greco, David J RileyAbstract:We studied whether the therapeutic efficacy of the Antifibrotic Agent cis-4-hydroxy-L-proline (cHyp) in preventing bleomycin-induced pulmonary fibrosis in rats is enhanced by intratracheal delivery in liposomes. Dual-radiolabeled liposomes were used to study the distribution and stability of liposomes after intratracheal instillation. Lung retention was > 20% 1 wk after intratracheal instillation of 9 mumol phospholipid, and liposomes were intact as indicated by the ratio of the lipid and aqueous-phase markers remaining unchanged. For the fibrosis study, groups of rats were instilled with 1.2 U bleomycin (Bleo) and treated 1 and 2 wk later by single intratracheal instillation of test compounds. The control group received 0.3 ml saline (Bleo/sal). The treated groups received 9 mumol phospholipid in 0.3 ml of the following liposome preparations: empty liposomes (Bleo/lip), liposomes and 100 mg/kg of free unencapsulated cHyp (Bleo/lip/cHyp), and 100 mg/kg of liposome-encapsulated cHyp (Bleo/lip-cHyp). At 3 wk, fibrosis (mg hydroxyproline/g weight lung) by groups was as follows: control, 2.6 +/- 0.1 (SEM); Bleo/sal, 3.2 +/- 0.1, Bleo/lip, 3.2 +/- 0.1, and Bleo/lip/cHyp, 3.1 +/- 0.1, p < 0.05 compared with control; Bleo/lip-cHyp, 2.6 +/- 0.1, p < 0.05 compared with Bleo/sal, n = 3 to 6. Histologic grading of fibrosis did not show decreased fibrosis in the Bleo/lip-cHyp group, probably because of the focal nature of the fibrotic lesions. We conclude that cHyp encapsulated in liposomes prevents bleomycin-induced fibrosis by biochemical measurements. Delivery of Antifibrotic Agents to the lung in carrier vehicles promotes retention and may enhance their efficacy in treating bleomycin-induced pulmonary fibrosis.
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liposome entrapped Antifibrotic Agent prevents collagen accumulation in hypertensive pulmonary arteries of rats
Circulation Research, 1992Co-Authors: George J Poiani, Carol A Tozzi, Frank J Wilson, J D Fox, J M Sumka, Bonnie Peng, Weichi Liao, David J RileyAbstract:We studied the therapeutic efficacy of an intravenously injected Antifibrotic Agent encapsulated in liposomes on inhibiting collagen accumulation in hypertensive blood vessels. cis-4-Hydroxy-L-proline (cHyp) in liposomes was injected into rats exposed to 10% O2, and drug effect was evaluated by measuring right ventricular pressure and hydroxyproline content of the pulmonary artery. Right ventricular pressure was 11 +/- 1 mm Hg (mean +/- SEM) 5 days after a single intravenous injection of 200 mg/kg cHyp in liposomes compared with 14 +/- 1 mm Hg in rats injected with empty liposomes; hydroxyproline content was also reduced by cHyp treatment (87 +/- 6 versus 107 +/- 7 micrograms per vessel) (p less than 0.05 for both, n = 6-9). Injections of cHyp in liposomes every 5 days partially prevented hypertension and vascular collagen accumulation during a 3-week exposure to hypoxia, and the dose required was one tenth the dose of unencapsulated cHyp. Therapeutic doses of cHyp in liposomes injected for 6 months affected tensile properties of main pulmonary artery and aorta, but there were no apparent histological effects on other organs. Liposomes injected intravenously were identified in pulmonary artery endothelial cells. The prolonged effect of a single injection of cHyp in liposomes may be due to uptake of the liposomes by the endothelium. Liposome delivery of drugs to the arterial wall may be useful in the study and treatment of hypertensive vascular disease.
Mutsuo Taiji - One of the best experts on this subject based on the ideXlab platform.
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amelioration of established diabetic nephropathy by combined treatment with smp 534 Antifibrotic Agent and losartan in db db mice
Nephron Experimental Nephrology, 2006Co-Authors: Eiji Sugaru, Tsutomu Nakagawa, Michiko Onokishino, Jun Nagamine, Teruhisa Tokunaga, Makoto Kitoh, Ewan W Hume, Ryu Nagata, Mutsuo TaijiAbstract:Background/Aims: Diabetic nephropathy is the main cause of end-stage renal disease. Previously we have demonstrated that SMP-534 (an Antifibrotic Agent) prevents the development of
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enhanced effect of combined treatment with smp 534 Antifibrotic Agent and losartan in diabetic nephropathy
American Journal of Nephrology, 2006Co-Authors: Eiji Sugaru, Tsutomu Nakagawa, Michiko Onokishino, Jun Nagamine, Teruhisa Tokunaga, Makoto Kitoh, Ewan W Hume, Ryu Nagata, Mutsuo TaijiAbstract:Background/Aims: Diabetic nephropathy is now the most common cause of end-stage renal disease. It is also clear that the current therapy, angiotensin II blockage, cannot prevent the
Ganesh Raghu - One of the best experts on this subject based on the ideXlab platform.
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treatment of idiopathic pulmonary fibrosis with a new Antifibrotic Agent pirfenidone results of a prospective open label phase ii study
American Journal of Respiratory and Critical Care Medicine, 1999Co-Authors: Ganesh Raghu, W C Johnson, Diane Lockhart, Yolanda N MagetoAbstract:Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of unknown etiology and fatal outcome. Currently available therapies are ineffective and associated with significant adverse effects. Pirfenidone, a new, investigational Antifibrotic Agent, was evaluated for its tolerability and usefulness in terminally ill patients with advanced IPF. Consecutive patients with IPF and deterioration despite conventional therapy or who were unable to tolerate or unwilling to try conventional therapy were treated with oral pirfenidone. Treatment was administered on a compassionate basis (open-label). Fifty-four patients were followed for mortality, change in lung function, and adverse effects. Their mean age was 62, mean duration of symptoms 4.6 yr, and time since lung biopsy was 3.2 yr. Conventional therapy was discontinued in 38 of 46 patients; the other eight were able to decrease their prednisone dosage and eight had no previous conventional treatment. One- and 2-yr survival was 78% (95% CI 66%, 89%) ...
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treatment of idiopathic pulmonary fibrosis with a new Antifibrotic Agent pirfenidone results of a prospective open label phase ii study
American Journal of Respiratory and Critical Care Medicine, 1999Co-Authors: Ganesh Raghu, W C Johnson, Diane Lockhart, Yolanda N MagetoAbstract:Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of unknown etiology and fatal outcome. Currently available therapies are ineffective and associated with significant adverse effects. Pirfenidone, a new, investigational Antifibrotic Agent, was evaluated for its tolerability and usefulness in terminally ill patients with advanced IPF. Consecutive patients with IPF and deterioration despite conventional therapy or who were unable to tolerate or unwilling to try conventional therapy were treated with oral pirfenidone. Treatment was administered on a compassionate basis (open-label). Fifty-four patients were followed for mortality, change in lung function, and adverse effects. Their mean age was 62, mean duration of symptoms 4.6 yr, and time since lung biopsy was 3.2 yr. Conventional therapy was discontinued in 38 of 46 patients; the other eight were able to decrease their prednisone dosage and eight had no previous conventional treatment. One- and 2-yr survival was 78% (95% CI 66%, 89%) and 63% (95% CI 50%, 76%), respectively. Patients whose lung functions had deteriorated prior to enrollment appeared to stabilize after beginning treatment. Adverse effects were relatively minor. The results of this study are encouraging. Pirfenidone is a promising new treatment for IPF that is well tolerated.
Mandip Singh - One of the best experts on this subject based on the ideXlab platform.
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combination approach of ysa peptide anchored docetaxel stealth liposomes with oral Antifibrotic Agent for the treatment of lung cancer
Molecular Pharmaceutics, 2016Co-Authors: Ketan Patel, Ravi Doddapaneni, Vasanthakumar Sekar, Nusrat Chowdhury, Mandip SinghAbstract:Therapeutic efficacy of nanocarriers can be amplified by active targeting and overcoming the extracellular matrix associated barriers of tumors. The aim of the present study was to investigate the effect of oral Antifibrotic Agent (telmisartan) on tumor uptake and anticancer efficacy of EphA2 receptor targeted liposomes. Docetaxel loaded PEGylated liposomes (DPL) functionalized with nickel chelated phospholipid were prepared using a modified hydration method. DPL were incubated with various concentrations of histidine tagged EphA2 receptor specific peptide (YSA) to optimize particle size, zeta potential, and percentage YSA binding. Cellular uptake studies using various endocytosis blockers revealed that a caveolae dependent pathway was the major route for internalization of YSA anchored liposomes of docetaxel (YDPL) in A549 lung cancer cell line. Hydrodynamic diameter and zeta potential of optimized YDPL were 157.3 ± 11.8 nm and −3.64 mV, respectively. Orthotopic lung tumor xenograft (A549) bearing athymi...
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Combination Approach of YSA Peptide Anchored Docetaxel Stealth Liposomes with Oral Antifibrotic Agent for the Treatment of Lung Cancer
2016Co-Authors: Ketan Patel, Ravi Doddapaneni, Vasanthakumar Sekar, Nusrat Chowdhury, Mandip SinghAbstract:Therapeutic efficacy of nanocarriers can be amplified by active targeting and overcoming the extracellular matrix associated barriers of tumors. The aim of the present study was to investigate the effect of oral Antifibrotic Agent (telmisartan) on tumor uptake and anticancer efficacy of EphA2 receptor targeted liposomes. Docetaxel loaded PEGylated liposomes (DPL) functionalized with nickel chelated phospholipid were prepared using a modified hydration method. DPL were incubated with various concentrations of histidine tagged EphA2 receptor specific peptide (YSA) to optimize particle size, zeta potential, and percentage YSA binding. Cellular uptake studies using various endocytosis blockers revealed that a caveolae dependent pathway was the major route for internalization of YSA anchored liposomes of docetaxel (YDPL) in A549 lung cancer cell line. Hydrodynamic diameter and zeta potential of optimized YDPL were 157.3 ± 11.8 nm and −3.64 mV, respectively. Orthotopic lung tumor xenograft (A549) bearing athymic nude mice treated with oral telmisartan (5 mg/kg) for 2 days showed significantly (p < 0.05) higher uptake of YDPL in tumor tissues compared to healthy tissue. Average lung tumor weight of the YDPL + telmisartan treated group was 4.8- and 3.8-fold lower than that of the DPL and YDPL treated groups (p < 0.05). Substantially lower expression (p < 0.05) of EphA2 receptor protein, proliferating cell nuclear antigen (PCNA), MMP-9, and collagen 1A level with increased E-cadherin and TIMP-1 levels in immunohistochemistry and Western blot analysis of lung tumor samples of the combination group confirmed Antifibrotic effect with enhanced anticancer activity. Active targeting and ECM remodeling synergistically contributed to anticancer efficacy of YDPL in orthotopic lung cancer