The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Domenico Rotilio - One of the best experts on this subject based on the ideXlab platform.
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inhibition of gelatinase a mmp 2 by batimastat and captopril reduces tumor growth and lung metastases in mice bearing lewis lung carcinoma
International Journal of Cancer, 1999Co-Authors: Cesaria Prontera, Cosmo Rossi, Barbara Mariani, Andreina Poggi, Domenico RotilioAbstract:We have examined the effects of the synthetic Matrix Metalloproteinase Inhibitor, batimastat (BB-94) and the angiotensin-converting enzyme Inhibitor, captopril, on Metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramuscularly in syngeneic C57BL/6 mice. The effect of BB-94 and captopril on the survival of the 3LL-tumor-bearing mice was also examined. Here we report that captopril treatment resulted in decreased transcription and protein levels of gelatinase A by 3LL cells. Both BB-94 and captopril also prevented substrate degradation by gelatinase A and B released in conditioned medium by cultured cells. Treatment of tumor-bearing animals with BB-94 (i.p.) or captopril (in drinking water) resulted in significant inhibition of the mean tumor volume (25 and 33% respectively) and of the mean lung metastasis number (26 and 29% respectively). When both agents were given, they acted in synergy, resulting in 51 and 80% inhibition of tumor growth and metastasis. The survival time of the mice treated with both BB-94 and captopril was also significantly longer compared with the groups treated with each agent alone or with the vehicle. Our data support the hypothesis of an essential role of Metalloproteinase(s) in the metastatic process. Moreover, blockade of invasion, angiogenesis and other processes mediated by Metalloproteinases may underlie the anti-tumor and anti-metastatic effect of BB-94 and captopril and their combination. It is conceivable that this combination could be tested in selected clinical conditions as an adjuvant modality to cytotoxic therapy.
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inhibition of gelatinase a mmp 2 by batimastat and captopril reduces tumor growth and lung metastases in mice bearing lewis lung carcinoma
International Journal of Cancer, 1999Co-Authors: Cesaria Prontera, Cosmo Rossi, Barbara Mariani, Andreina Poggi, Domenico RotilioAbstract:We have examined the effects of the synthetic Matrix Metalloproteinase Inhibitor, batimastat (BB-94) and the angiotensin-converting enzyme Inhibitor, captopril, on Metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramuscularly in syngeneic C57BL/6 mice. The effect of BB-94 and captopril on the survival of the 3LL-tumor-bearing mice was also examined. Here we report that captopril treatment resulted in decreased transcription and protein levels of gelatinase A by 3LL cells. Both BB-94 and captopril also prevented substrate degradation by gelatinase A and B released in conditioned medium by cultured cells. Treatment of tumor-bearing animals with BB-94 (i.p.) or captopril (in drinking water) resulted in significant inhibition of the mean tumor volume (25 and 33% respectively) and of the mean lung metastasis number (26 and 29% respectively). When both agents were given, they acted in synergy, resulting in 51 and 80% inhibition of tumor growth and metastasis. The survival time of the mice treated with both BB-94 and captopril was also significantly longer compared with the groups treated with each agent alone or with the vehicle. Our data support the hypothesis of an essential role of Metalloproteinase(s) in the metastatic process. Moreover, blockade of invasion, angiogenesis and other processes mediated by Metalloproteinases may underlie the anti-tumor and anti-metastatic effect of BB-94 and captopril and their combination. It is conceivable that this combination could be tested in selected clinical conditions as an adjuvant modality to cytotoxic therapy. Int. J. Cancer 81:761–766, 1999. © 1999 Wiley-Liss, Inc.
Tschirhart Eric - One of the best experts on this subject based on the ideXlab platform.
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New biological investigations on 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate as anti-angiogenic agent
2010Co-Authors: Hemmer Marc, Kempen Isabelle, De Tullio Pascal, Frankenne Francis, Lambert Vincent, Blacher Silvia, Bueb Jean-luc, Foidart Jean-michel, Noël Agnès, Tschirhart EricAbstract:The development of blood vessels inside tumors is required to provide the nutrients and oxygen needed for tumor growth and to allow the spread of cancer cells at a distance to form metastasis. Angiogenesis is also implicated in ocular diseases like age-related macular degeneration. The present work describes the potential anti-angiogenic properties of a coumarinic derivative, 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate (IK9), previously described as a potent Inhibitor of HT 1080 fibrosarcoma cell invasion in vitro and tumor growth in vivo. In vivo, ex vivo, and in vitro models were used to delineate the anti-angiogenic properties of IK9. The anti-angiogenic effect of IK9 was demonstrated in vivo in a choroidal neovascularization mice model and additionally ex vivo in a rat aortic ring assay where it was more active than the known Matrix Metalloproteinase Inhibitor Ro 28-2653. IK9 did not affect apoptosis, proliferation, or endothelial cell invasiveness in vitro. These findings suggest a complex mechanism of action of the compound via direct or indirect effects on endothelial cell properties. This study identifies IK9 as a new potent Inhibitor of angiogenesis and suggests its potential use as a therapeutic agent
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New Biological Investigations on 3-Bromophenyl 6-Acetoxymethyl-2-oxo-2H-1-Benzopyran-3-Carboxylate as Anti-angiogenic Agent
'Wiley', 2010Co-Authors: Hemmer M., Kempen Isabelle, De Tullio Pascal, Frankenne Francis, Lambert Vincent, Blacher Silvia, Bueb Jean-luc, Foidart Jean-michel, Noël Agnès, Tschirhart EricAbstract:peer reviewedaudience: researcher, professional, student, popularizationThe development of blood vessels inside tumors is required to provide the nutrients and oxygen needed for tumor growth and to allow the spread of cancer cells at a distance to form metastasis. Angiogenesis is also implicated in ocular diseases like age-related macular degeneration. The present work describes the potential anti-angiogenic properties of a coumarinic derivative, 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate (IK9), previously described as a potent Inhibitor of HT 1080 fibrosarcoma cell invasion in vitro and tumor growth in vivo. In vivo, ex vivo, and in vitro models were used to delineate the anti-angiogenic properties of IK9. The anti-angiogenic effect of IK9 was demonstrated in vivo in a choroidal neovascularization mice model and additionally ex vivo in a rat aortic ring assay where it was more active than the known Matrix Metalloproteinase Inhibitor Ro 28-2653. IK9 did not affect apoptosis, proliferation, or endothelial cell invasiveness in vitro. These findings suggest a complex mechanism of action of the compound via direct or indirect effects on endothelial cell properties. This study identifies IK9 as a new potent Inhibitor of angiogenesis and suggests its potential use as a therapeutic agent
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New Biological Investigations on 3-Bromophenyl 6-Acetoxymethyl-2-oxo-2H-1-Benzopyran-3-Carboxylate as Anti-angiogenic Agent
2010Co-Authors: Hemmer M., Kempen Isabelle, De Tullio Pascal, Frankenne Francis, Lambert Vincent, Blacher Silvia, Bueb Jean-luc, Foidart Jean-michel, Noël Agnès, Tschirhart EricAbstract:The development of blood vessels inside tumors is required to provide the nutrients and oxygen needed for tumor growth and to allow the spread of cancer cells at a distance to form metastasis. Angiogenesis is also implicated in ocular diseases like age-related macular degeneration. The present work describes the potential anti-angiogenic properties of a coumarinic derivative, 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate (IK9), previously described as a potent Inhibitor of HT 1080 fibrosarcoma cell invasion in vitro and tumor growth in vivo. In vivo, ex vivo, and in vitro models were used to delineate the anti-angiogenic properties of IK9. The anti-angiogenic effect of IK9 was demonstrated in vivo in a choroidal neovascularization mice model and additionally ex vivo in a rat aortic ring assay where it was more active than the known Matrix Metalloproteinase Inhibitor Ro 28-2653. IK9 did not affect apoptosis, proliferation, or endothelial cell invasiveness in vitro. These findings suggest a complex mechanism of action of the compound via direct or indirect effects on endothelial cell properties. This study identifies IK9 as a new potent Inhibitor of angiogenesis and suggests its potential use as a therapeutic agent.Peer reviewe
Cosmo Rossi - One of the best experts on this subject based on the ideXlab platform.
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beneficial effects of batimastat bb 94 a Matrix Metalloproteinase Inhibitor in rat experimental colitis
Digestion, 2001Co-Authors: Pierluigi Di Sebastiano, Fabio F Di Mola, Luciano Artese, Cosmo Rossi, Giuseppe Mascetta, Heinz Pernthaler, Paolo InnocentiAbstract:Background and Aims: Matrix Metalloproteinases (MMPs) represent a group of enzymes that regulate cell-Matrix composition playing a major role in the inflammatory response. In the pr
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inhibition of gelatinase a mmp 2 by batimastat and captopril reduces tumor growth and lung metastases in mice bearing lewis lung carcinoma
International Journal of Cancer, 1999Co-Authors: Cesaria Prontera, Cosmo Rossi, Barbara Mariani, Andreina Poggi, Domenico RotilioAbstract:We have examined the effects of the synthetic Matrix Metalloproteinase Inhibitor, batimastat (BB-94) and the angiotensin-converting enzyme Inhibitor, captopril, on Metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramuscularly in syngeneic C57BL/6 mice. The effect of BB-94 and captopril on the survival of the 3LL-tumor-bearing mice was also examined. Here we report that captopril treatment resulted in decreased transcription and protein levels of gelatinase A by 3LL cells. Both BB-94 and captopril also prevented substrate degradation by gelatinase A and B released in conditioned medium by cultured cells. Treatment of tumor-bearing animals with BB-94 (i.p.) or captopril (in drinking water) resulted in significant inhibition of the mean tumor volume (25 and 33% respectively) and of the mean lung metastasis number (26 and 29% respectively). When both agents were given, they acted in synergy, resulting in 51 and 80% inhibition of tumor growth and metastasis. The survival time of the mice treated with both BB-94 and captopril was also significantly longer compared with the groups treated with each agent alone or with the vehicle. Our data support the hypothesis of an essential role of Metalloproteinase(s) in the metastatic process. Moreover, blockade of invasion, angiogenesis and other processes mediated by Metalloproteinases may underlie the anti-tumor and anti-metastatic effect of BB-94 and captopril and their combination. It is conceivable that this combination could be tested in selected clinical conditions as an adjuvant modality to cytotoxic therapy.
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inhibition of gelatinase a mmp 2 by batimastat and captopril reduces tumor growth and lung metastases in mice bearing lewis lung carcinoma
International Journal of Cancer, 1999Co-Authors: Cesaria Prontera, Cosmo Rossi, Barbara Mariani, Andreina Poggi, Domenico RotilioAbstract:We have examined the effects of the synthetic Matrix Metalloproteinase Inhibitor, batimastat (BB-94) and the angiotensin-converting enzyme Inhibitor, captopril, on Metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramuscularly in syngeneic C57BL/6 mice. The effect of BB-94 and captopril on the survival of the 3LL-tumor-bearing mice was also examined. Here we report that captopril treatment resulted in decreased transcription and protein levels of gelatinase A by 3LL cells. Both BB-94 and captopril also prevented substrate degradation by gelatinase A and B released in conditioned medium by cultured cells. Treatment of tumor-bearing animals with BB-94 (i.p.) or captopril (in drinking water) resulted in significant inhibition of the mean tumor volume (25 and 33% respectively) and of the mean lung metastasis number (26 and 29% respectively). When both agents were given, they acted in synergy, resulting in 51 and 80% inhibition of tumor growth and metastasis. The survival time of the mice treated with both BB-94 and captopril was also significantly longer compared with the groups treated with each agent alone or with the vehicle. Our data support the hypothesis of an essential role of Metalloproteinase(s) in the metastatic process. Moreover, blockade of invasion, angiogenesis and other processes mediated by Metalloproteinases may underlie the anti-tumor and anti-metastatic effect of BB-94 and captopril and their combination. It is conceivable that this combination could be tested in selected clinical conditions as an adjuvant modality to cytotoxic therapy. Int. J. Cancer 81:761–766, 1999. © 1999 Wiley-Liss, Inc.
Francis G Spinale - One of the best experts on this subject based on the ideXlab platform.
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biomaterial based delivery of a small molecule Matrix Metalloproteinase Inhibitor limits adverse biomechanical changes throughout the left ventricle following myocardial infarction
Journal of Cardiac Failure, 2018Co-Authors: William M Torres, Joshua E Mealy, Julia Jacobs, Heather Doviak, Shayne C Barlow, Jason A Burdick, Tarek Shazly, Francis G SpinaleAbstract:Introduction Adverse left ventricular (LV) remodeling following myocardial infarction (MI) involves associated changes in extracellular proteolytic activity and LV biomechanics. This study evaluates how targeted injections of a self-assembling hydrogel (SAgel) loaded with SD-7300, an established Matrix Metalloproteinase Inhibitor (MMPi), impacts regional LV biomechanics post-MI. Hypothesis We hypothesize that delivery of SD-7300 to the MI region will attenuate post-MI changes in biomechanics throughout the LV. Method Mature pigs (25 kg; n=15) were subjected to an ischemia-reperfusion model in which MI is induced by left anterior descending occlusion. At three days post-MI, a subset of pigs were injected with 500μg/mL of SAgel/SD7300 (MI/MMPi; n=7) in a 9 point 100µL array spanning the MI region while the remaining pigs served as controls (MI only; n=8). Peak strain (epeak) and systolic strain rate (γsys), indices of systolic function, were assessed by speckle-tracking echocardiography at baseline and at 28 days post-MI. Regional diastolic myocardial stiffness (Km), an index of diastolic function, was computed from stress-strain relations developed at both time points. Results While global epeak ( Fig 1 A) and global γsys ( Fig 1 B) were reduced at 28 days post-MI in both groups (p Fig 1 C) was significantly lower in the MI/MMPi group relative to MI only in the border zone (3.5 ± 0.4kPa vs. 8.9 ± 1.2kPa, p Conclusions Localized delivery of MMPi mechanically stabilizes the MI region and also impacts border zone and remote myocardial biomechanics over 28 days post-MI. Injectable biomaterials enable the repurposing of an established MMPi for attenuation of post-MI remodeling.
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targeted delivery and controlled release of a small molecule Matrix Metalloproteinase Inhibitor using a self assembling hydrogel following myocardial infarction
Journal of Cardiac Failure, 2018Co-Authors: Joshua E Mealy, William M Torres, Julia Jacobs, Heather Doviak, Shayne C Barlow, Jason A Burdick, Francis G SpinaleAbstract:Background Strategic delivery of biomaterials to the newly formed myocardial infarction (MI) continues to be an area of active investigation and offers the opportunity to reappraise the use of small molecule therapeutics that hold high target specificity but are problematic when systemically delivered. The goal of this study was to examine the effects of late post-MI delivery (3 days post-MI) of a self-assembling hydrogel (SAgel), which had been loaded with a previously characterized Matrix Metalloproteinase Inhibitor (MMPi). Hypothesis Using a minimally invasive (mini-thoracotomy) and an SAgel allowing for targeted myocardial injection array within the MI region of a large animal model as well as localized release of an MMPi, improved LV function and geometry would be demonstrated up to 28 days post-MI. Methods and Results MI was induced in adult pigs (25 kg) by left anterior descending (LAD) catheter balloon occlusion (90 min/then reperfusion) and at 3 days post-MI randomized to MI-SAgel/SD7300 (500 μg/mL; n=7) or saline (MI saline; n=8), whereby the injections were performed in a 9 point 100 uL array within the targeted LAD region. The SAgel adapts fluid-like properties to flow through the syringe (21 Gauge) due to shear forces during injection and rapidly reassembles with encapsulated SD7300 following injection into the MI region. LV ejection fraction (LVEF) and end-diastolic volume (LVEDV) were measured at Baseline (pre-MI) and at 14 and 28 days post-MI by echocardiography. LVEF fell post-MI but was significantly attenuated by SAgel/SD7300 injections. LVEDV increased from Baseline (35±2 mL) in the MI-saline (84+6) and MI-SAgel/SD7300 (64+4 mL groups at 28 days post-MI (p Conclusions This is the first study to demonstrate the feasibility of targeted delivery of a self-assembling injectable gel using a minimally invasive surgical approach at a relevant post-MI time point. Second, targeted delivery of this gel containing an MMPi for sustained local release demonstrated sustained beneficial effects on post-MI remodeling.
Cesaria Prontera - One of the best experts on this subject based on the ideXlab platform.
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inhibition of gelatinase a mmp 2 by batimastat and captopril reduces tumor growth and lung metastases in mice bearing lewis lung carcinoma
International Journal of Cancer, 1999Co-Authors: Cesaria Prontera, Cosmo Rossi, Barbara Mariani, Andreina Poggi, Domenico RotilioAbstract:We have examined the effects of the synthetic Matrix Metalloproteinase Inhibitor, batimastat (BB-94) and the angiotensin-converting enzyme Inhibitor, captopril, on Metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramuscularly in syngeneic C57BL/6 mice. The effect of BB-94 and captopril on the survival of the 3LL-tumor-bearing mice was also examined. Here we report that captopril treatment resulted in decreased transcription and protein levels of gelatinase A by 3LL cells. Both BB-94 and captopril also prevented substrate degradation by gelatinase A and B released in conditioned medium by cultured cells. Treatment of tumor-bearing animals with BB-94 (i.p.) or captopril (in drinking water) resulted in significant inhibition of the mean tumor volume (25 and 33% respectively) and of the mean lung metastasis number (26 and 29% respectively). When both agents were given, they acted in synergy, resulting in 51 and 80% inhibition of tumor growth and metastasis. The survival time of the mice treated with both BB-94 and captopril was also significantly longer compared with the groups treated with each agent alone or with the vehicle. Our data support the hypothesis of an essential role of Metalloproteinase(s) in the metastatic process. Moreover, blockade of invasion, angiogenesis and other processes mediated by Metalloproteinases may underlie the anti-tumor and anti-metastatic effect of BB-94 and captopril and their combination. It is conceivable that this combination could be tested in selected clinical conditions as an adjuvant modality to cytotoxic therapy.
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inhibition of gelatinase a mmp 2 by batimastat and captopril reduces tumor growth and lung metastases in mice bearing lewis lung carcinoma
International Journal of Cancer, 1999Co-Authors: Cesaria Prontera, Cosmo Rossi, Barbara Mariani, Andreina Poggi, Domenico RotilioAbstract:We have examined the effects of the synthetic Matrix Metalloproteinase Inhibitor, batimastat (BB-94) and the angiotensin-converting enzyme Inhibitor, captopril, on Metalloproteinase activity of murine Lewis-lung-carcinoma cells (3LL) in vitro, and on local growth and lung metastasis of the same tumor implanted intramuscularly in syngeneic C57BL/6 mice. The effect of BB-94 and captopril on the survival of the 3LL-tumor-bearing mice was also examined. Here we report that captopril treatment resulted in decreased transcription and protein levels of gelatinase A by 3LL cells. Both BB-94 and captopril also prevented substrate degradation by gelatinase A and B released in conditioned medium by cultured cells. Treatment of tumor-bearing animals with BB-94 (i.p.) or captopril (in drinking water) resulted in significant inhibition of the mean tumor volume (25 and 33% respectively) and of the mean lung metastasis number (26 and 29% respectively). When both agents were given, they acted in synergy, resulting in 51 and 80% inhibition of tumor growth and metastasis. The survival time of the mice treated with both BB-94 and captopril was also significantly longer compared with the groups treated with each agent alone or with the vehicle. Our data support the hypothesis of an essential role of Metalloproteinase(s) in the metastatic process. Moreover, blockade of invasion, angiogenesis and other processes mediated by Metalloproteinases may underlie the anti-tumor and anti-metastatic effect of BB-94 and captopril and their combination. It is conceivable that this combination could be tested in selected clinical conditions as an adjuvant modality to cytotoxic therapy. Int. J. Cancer 81:761–766, 1999. © 1999 Wiley-Liss, Inc.