The Experts below are selected from a list of 105 Experts worldwide ranked by ideXlab platform
M T Santamarina - One of the best experts on this subject based on the ideXlab platform.
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Oral pharmacological treatments for parasitic diseases of rainbow trout Oncorhynchus mykiss. II: Gyrodactylus sp.
Diseases of Aquatic Organisms, 1998Co-Authors: J. L. Tojo, M T SantamarinaAbstract:A total of 24 drugs were evaluated as regards their efficacy for oral treatment of gyrodactylosis in rainbow trout Oncorhynchus mykiss. In preliminary trials, all drugs were supplied to infected fish at 40 g per kg of feed for 10 d. Twenty-two of the drugs tested (aminosidine, amprolium, benznidazole, bithionol, chloroquine, diethylcarbamazine, flubendazole, levamisole, mebendazole, metronidazole, niclosamide, nitroxynil, oxibendazole, Parbendazole, piperazine, praziquantel, ronidazole, secnidazole, tetramisole, thiophanate, toltrazuril and trichlorfon) were ineffective. Triclabendazole and nitroscanate completely eliminated the infection. Triclabendazole was effective only at the screening dosage (40 g per kg of feed for 10 d), while nitroscanate was effective at dosages as low as 0.6 g per kg of feed for 1 d.
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Oral pharmacological treatments for parasitic diseases of rainbow trout Oncorhynchus mykiss. III: Ichthyobodo necator
Diseases of Aquatic Organisms, 1998Co-Authors: J. L. Tojo, M T SantamarinaAbstract:A total of 32 drugs were evaluated as regards their efficacy for oral treatment of Ichthyobodo necator infestation of rainbow trout. In preliminary trials, all drugs were supplied to infected fish at 40 g per kg of feed for 10 d. The majority of the drugs tested (1,3-di-6-quinolylurea, aminosidine, amprolium, benznidazole, bithionol, chloroquine, diethylcarbamazine, dimetridazole, diminazene aceturate, febantel, flubendazole, ketoconazole, levamisole, mebendazole, netobimin, niclosamide, niridazole, nitroscanate, nitroxynil, oxibendazole, Parbendazole, piperazine, praziquantel, ronidazole, sulphaquinoxaline, tetramisole, thiophanate, toltrazuril and trichlorfon) were ineffectdive. Metronidazole and secnidazole were 100% effective (unlike the other nitroimidazoles tested, namely dimetridazole, benznidazole and ronidazole). The non-carbamate benzimidazole triclabendazole was likewise 100% effective.
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Oral pharmacological treatments for parasitic diseases of rainbow trout Oncorhynchus mykiss. I: Hexamita salmonis
Diseases of Aquatic Organisms, 1998Co-Authors: J. L. Tojo, M T SantamarinaAbstract:Abstract Various drugs were evaluated as regards efficacy for the treatment of Hexamita salmonis infection in rainbow trout. The results confirm the efficacy of nitroimidazoles: infection was completely eradicated not only by metronidazole (which has been recommended previously for the treatment of hexamitosis), but also by benznidazole, ronidazole and secnidazole, which have not been assayed previously. The non-nitroimidazoles albendazole, aminosidine, diethylcarbamazine and nitroscanate also completely eliminated infection. The remaining non-nitroimidazoles tested (amprolium, bithionol, febantel, flubendazole, levamisole, netobimin, niclosamide, nitroxynil, oxibendazole, Parbendazole, piperazine, praziquentel, tetramisole, thiophanate, toltrazuril, trichlorfon and triclabendazole) were not effective.
Johannes P.t.m. Van Leeuwen - One of the best experts on this subject based on the ideXlab platform.
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Using the Connectivity Map to discover compounds influencing human osteoblast differentiation.
Journal of cellular physiology, 2018Co-Authors: Andrea M. Brum, Jeroen Van De Peppel, Cindy S. Van Der Leije, Marijke Schreuders-koedam, Marco Eijken, Linh Nguyen, Abidin Aliev, Tarini Gajadien, Anke Van Kerkwijk, Johannes P.t.m. Van LeeuwenAbstract:Osteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. Identification of factors influencing osteoblast differentiation and bone formation is very important. Previously, we identified Parbendazole to be a novel compound that stimulates osteogenic differentiation of human mesenchymal stromal cells (hMSCs), using gene expression profiling and bioinformatic analyzes, including the Connectivity Map (CMap), as an in-silico approach. The aim for this paper is to identify additional compounds affecting osteoblast differentiation using the CMap. Gene expression profiling was performed on hMSCs differentiated to osteoblasts using Illumina microarrays. Our osteoblast gene signature, the top regulated genes 6 hr after induction by dexamethasone, was uploaded into CMap (www.broadinstitute.org/cmap/). Through this approach we identified compounds with gene signatures positively correlating (withaferin-A, calcium folinate, amylocaine) or negatively correlating (salbutamol, metaraminol, diprophylline) to our osteoblast gene signature. All positively correlating compounds stimulated osteogenic differentiation, as indicated by increased mineralization compared to control treated cells. One of three negatively correlating compounds, salbutamol, inhibited dexamethasone-induced osteoblastic differentiation, while the other two had no effect. Based on gene expression data of withaferin-A and salbutamol, we identified HMOX1 and STC1 as being strongly differentially expressed . shRNA knockdown of HMOX1 or STC1 in hMSCs inhibited osteoblast differentiation. These results confirm that the CMap is a powerful approach to identify positively compounds that stimulate osteogenesis of hMSCs, and through this approach we can identify genes that play an important role in osteoblast differentiation and could be targets for novel bone anabolic therapies.
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Connectivity Map-based discovery of Parbendazole reveals targetable human osteogenic pathway
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Andrea M. Brum, Jeroen Van De Peppel, Cindy S. Van Der Leije, Marijke Schreuders-koedam, Marco Eijken, Bram C. J. Van Der Eerden, Johannes P.t.m. Van LeeuwenAbstract:Osteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. In this study, we have identified pathways that stimulate differentiation of bone forming osteoblasts from human mesenchymal stromal cells (hMSCs). Gene expression profiling was performed in hMSCs differentiated toward osteoblasts (at 6 h). Significantly regulated genes were analyzed in silico, and the Connectivity Map (CMap) was used to identify candidate bone stimulatory compounds. The signature of Parbendazole matches the expression changes observed for osteogenic hMSCs. Parbendazole stimulates osteoblast differentiation as indicated by increased alkaline phosphatase activity, mineralization, and up-regulation of bone marker genes (alkaline phosphatase/ALPL, osteopontin/SPP1, and bone sialoprotein II/IBSP) in a subset of the hMSC population resistant to the apoptotic effects of Parbendazole. These osteogenic effects are independent of glucocorticoids because Parbendazole does not up-regulate glucocorticoid receptor (GR) target genes and is not inhibited by the GR antagonist mifepristone. Parbendazole causes profound cytoskeletal changes including degradation of microtubules and increased focal adhesions. Stabilization of microtubules by pretreatment with Taxol inhibits osteoblast differentiation. Parbendazole up-regulates bone morphogenetic protein 2 (BMP-2) gene expression and activity. Cotreatment with the BMP-2 antagonist DMH1 limits, but does not block, Parbendazole-induced mineralization. Using the CMap we have identified a previously unidentified lineage-specific, bone anabolic compound, Parbendazole, which induces osteogenic differentiation through a combination of cytoskeletal changes and increased BMP-2 activity.
J. L. Tojo - One of the best experts on this subject based on the ideXlab platform.
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Oral pharmacological treatments for parasitic diseases of rainbow trout Oncorhynchus mykiss. II: Gyrodactylus sp.
Diseases of Aquatic Organisms, 1998Co-Authors: J. L. Tojo, M T SantamarinaAbstract:A total of 24 drugs were evaluated as regards their efficacy for oral treatment of gyrodactylosis in rainbow trout Oncorhynchus mykiss. In preliminary trials, all drugs were supplied to infected fish at 40 g per kg of feed for 10 d. Twenty-two of the drugs tested (aminosidine, amprolium, benznidazole, bithionol, chloroquine, diethylcarbamazine, flubendazole, levamisole, mebendazole, metronidazole, niclosamide, nitroxynil, oxibendazole, Parbendazole, piperazine, praziquantel, ronidazole, secnidazole, tetramisole, thiophanate, toltrazuril and trichlorfon) were ineffective. Triclabendazole and nitroscanate completely eliminated the infection. Triclabendazole was effective only at the screening dosage (40 g per kg of feed for 10 d), while nitroscanate was effective at dosages as low as 0.6 g per kg of feed for 1 d.
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Oral pharmacological treatments for parasitic diseases of rainbow trout Oncorhynchus mykiss. III: Ichthyobodo necator
Diseases of Aquatic Organisms, 1998Co-Authors: J. L. Tojo, M T SantamarinaAbstract:A total of 32 drugs were evaluated as regards their efficacy for oral treatment of Ichthyobodo necator infestation of rainbow trout. In preliminary trials, all drugs were supplied to infected fish at 40 g per kg of feed for 10 d. The majority of the drugs tested (1,3-di-6-quinolylurea, aminosidine, amprolium, benznidazole, bithionol, chloroquine, diethylcarbamazine, dimetridazole, diminazene aceturate, febantel, flubendazole, ketoconazole, levamisole, mebendazole, netobimin, niclosamide, niridazole, nitroscanate, nitroxynil, oxibendazole, Parbendazole, piperazine, praziquantel, ronidazole, sulphaquinoxaline, tetramisole, thiophanate, toltrazuril and trichlorfon) were ineffectdive. Metronidazole and secnidazole were 100% effective (unlike the other nitroimidazoles tested, namely dimetridazole, benznidazole and ronidazole). The non-carbamate benzimidazole triclabendazole was likewise 100% effective.
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Oral pharmacological treatments for parasitic diseases of rainbow trout Oncorhynchus mykiss. I: Hexamita salmonis
Diseases of Aquatic Organisms, 1998Co-Authors: J. L. Tojo, M T SantamarinaAbstract:Abstract Various drugs were evaluated as regards efficacy for the treatment of Hexamita salmonis infection in rainbow trout. The results confirm the efficacy of nitroimidazoles: infection was completely eradicated not only by metronidazole (which has been recommended previously for the treatment of hexamitosis), but also by benznidazole, ronidazole and secnidazole, which have not been assayed previously. The non-nitroimidazoles albendazole, aminosidine, diethylcarbamazine and nitroscanate also completely eliminated infection. The remaining non-nitroimidazoles tested (amprolium, bithionol, febantel, flubendazole, levamisole, netobimin, niclosamide, nitroxynil, oxibendazole, Parbendazole, piperazine, praziquentel, tetramisole, thiophanate, toltrazuril, trichlorfon and triclabendazole) were not effective.
Andrea M. Brum - One of the best experts on this subject based on the ideXlab platform.
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Using the Connectivity Map to discover compounds influencing human osteoblast differentiation.
Journal of cellular physiology, 2018Co-Authors: Andrea M. Brum, Jeroen Van De Peppel, Cindy S. Van Der Leije, Marijke Schreuders-koedam, Marco Eijken, Linh Nguyen, Abidin Aliev, Tarini Gajadien, Anke Van Kerkwijk, Johannes P.t.m. Van LeeuwenAbstract:Osteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. Identification of factors influencing osteoblast differentiation and bone formation is very important. Previously, we identified Parbendazole to be a novel compound that stimulates osteogenic differentiation of human mesenchymal stromal cells (hMSCs), using gene expression profiling and bioinformatic analyzes, including the Connectivity Map (CMap), as an in-silico approach. The aim for this paper is to identify additional compounds affecting osteoblast differentiation using the CMap. Gene expression profiling was performed on hMSCs differentiated to osteoblasts using Illumina microarrays. Our osteoblast gene signature, the top regulated genes 6 hr after induction by dexamethasone, was uploaded into CMap (www.broadinstitute.org/cmap/). Through this approach we identified compounds with gene signatures positively correlating (withaferin-A, calcium folinate, amylocaine) or negatively correlating (salbutamol, metaraminol, diprophylline) to our osteoblast gene signature. All positively correlating compounds stimulated osteogenic differentiation, as indicated by increased mineralization compared to control treated cells. One of three negatively correlating compounds, salbutamol, inhibited dexamethasone-induced osteoblastic differentiation, while the other two had no effect. Based on gene expression data of withaferin-A and salbutamol, we identified HMOX1 and STC1 as being strongly differentially expressed . shRNA knockdown of HMOX1 or STC1 in hMSCs inhibited osteoblast differentiation. These results confirm that the CMap is a powerful approach to identify positively compounds that stimulate osteogenesis of hMSCs, and through this approach we can identify genes that play an important role in osteoblast differentiation and could be targets for novel bone anabolic therapies.
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Connectivity Map-based discovery of Parbendazole reveals targetable human osteogenic pathway
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Andrea M. Brum, Jeroen Van De Peppel, Cindy S. Van Der Leije, Marijke Schreuders-koedam, Marco Eijken, Bram C. J. Van Der Eerden, Johannes P.t.m. Van LeeuwenAbstract:Osteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. In this study, we have identified pathways that stimulate differentiation of bone forming osteoblasts from human mesenchymal stromal cells (hMSCs). Gene expression profiling was performed in hMSCs differentiated toward osteoblasts (at 6 h). Significantly regulated genes were analyzed in silico, and the Connectivity Map (CMap) was used to identify candidate bone stimulatory compounds. The signature of Parbendazole matches the expression changes observed for osteogenic hMSCs. Parbendazole stimulates osteoblast differentiation as indicated by increased alkaline phosphatase activity, mineralization, and up-regulation of bone marker genes (alkaline phosphatase/ALPL, osteopontin/SPP1, and bone sialoprotein II/IBSP) in a subset of the hMSC population resistant to the apoptotic effects of Parbendazole. These osteogenic effects are independent of glucocorticoids because Parbendazole does not up-regulate glucocorticoid receptor (GR) target genes and is not inhibited by the GR antagonist mifepristone. Parbendazole causes profound cytoskeletal changes including degradation of microtubules and increased focal adhesions. Stabilization of microtubules by pretreatment with Taxol inhibits osteoblast differentiation. Parbendazole up-regulates bone morphogenetic protein 2 (BMP-2) gene expression and activity. Cotreatment with the BMP-2 antagonist DMH1 limits, but does not block, Parbendazole-induced mineralization. Using the CMap we have identified a previously unidentified lineage-specific, bone anabolic compound, Parbendazole, which induces osteogenic differentiation through a combination of cytoskeletal changes and increased BMP-2 activity.
Nicola Tinari - One of the best experts on this subject based on the ideXlab platform.
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The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer.
Cancers, 2019Co-Authors: Rosalba Florio, Serena Veschi, Viviana Di Giacomo, Sara Pagotto, Simone Carradori, Fabio Verginelli, Roberto Cirilli, Adriano Casulli, Antonino Grassadonia, Nicola TinariAbstract:Pancreatic cancer (PC) is one of the most lethal, chemoresistant malignancies and it is of paramount importance to find more effective therapeutic agents. Repurposing of non-anticancer drugs may expand the repertoire of effective molecules. Studies on repurposing of benzimidazole-based anthelmintics in PC and on their interaction with agents approved for PC therapy are lacking. We analyzed the effects of four Food and Drug Administration (FDA)-approved benzimidazoles on AsPC-1 and Capan-2 pancreatic cancer cell line viability. Notably, Parbendazole was the most potent benzimidazole affecting PC cell viability, with half maximal inhibitory concentration (IC50) values in the nanomolar range. The drug markedly inhibited proliferation, clonogenicity and migration of PC cell lines through mechanisms involving alteration of microtubule organization and formation of irregular mitotic spindles. Moreover, Parbendazole interfered with cell cycle progression promoting G2/M arrest, followed by the emergence of enlarged, polyploid cells. These abnormalities, suggesting a mitotic catastrophe, culminated in PC cell apoptosis, are also associated with DNA damage in PC cell lines. Remarkably, combinations of Parbendazole with gemcitabine, a drug employed as first-line treatment in PC, synergistically decreased PC cell viability. In conclusion, this is the first study providing evidence that Parbendazole as a single agent, or in combination with gemcitabine, is a repurposing candidate in the currently dismal PC therapy.
