The Experts below are selected from a list of 48165 Experts worldwide ranked by ideXlab platform
Jennifer M Golas - One of the best experts on this subject based on the ideXlab platform.
-
ski 606 a src abl inhibitor with in vivo activity in colon Tumor Xenograft models
Cancer Research, 2005Co-Authors: Jennifer M Golas, Judy Lucas, Carlo Etienne, Carolyn Discafani, Latha Sridharan, Erwin R Boghaert, K T Arndt, Diane H Boschelli, Craig TitschAbstract:Src up-regulation is a common event in human cancers. In colorectal cancer, increased Src levels are an indicator of poor prognosis, and progression to metastatic disease is associated with substantial increases in Src activity. Therefore, we examined the activity of SKI-606, a potent inhibitor of Src and Abl kinases, against colon Tumor lines in vitro and in s.c. Tumor Xenograft models. SKI-606 inhibited Src autophosphorylation with an IC50 of ∼0.25 μmol/L in HT29 cells. Phosphorylation of Tyr925 of focal adhesion kinase, a Src substrate, was reduced by similar concentrations of inhibitor. Antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC50s, 1.5 and 2.5 μmol/L, respectively), although submicromolar concentrations of SKI-606 inhibited HT29 cell colony formation in soft agar. SKI-606 also caused loosely aggregated Colo205 spheroids to condense into compact spheroids. On oral administration to nude mice at the lowest efficacious dose, peak plasma concentrations of ∼3 μmol/L, an oral bioavailability of 18%, and a t 1/2 of 8.6 hours were observed. SKI-606 was orally active in s.c. colon Tumor Xenograft models and caused substantial reductions in Src autophosphorylation on Tyr418 in HT29 and Colo205 Tumors. SKI-606 inhibited HT29 Tumor growth on once daily administration, whereas twice daily administration was necessary to inhibit Colo205, HCT116, and DLD1 Tumor growth. These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer.
-
ski 606 a src abl inhibitor with in vivo activity in colon Tumor Xenograft models
Cancer Research, 2005Co-Authors: Jennifer M Golas, Judy Lucas, Carlo Etienne, Carolyn Discafani, Latha Sridharan, Erwin R Boghaert, K T Arndt, Diane H Boschelli, Craig TitschAbstract:Src up-regulation is a common event in human cancers. In colorectal cancer, increased Src levels are an indicator of poor prognosis, and progression to metastatic disease is associated with substantial increases in Src activity. Therefore, we examined the activity of SKI-606, a potent inhibitor of Src and Abl kinases, against colon Tumor lines in vitro and in s.c. Tumor Xenograft models. SKI-606 inhibited Src autophosphorylation with an IC(50) of approximately 0.25 micromol/L in HT29 cells. Phosphorylation of Tyr(925) of focal adhesion kinase, a Src substrate, was reduced by similar concentrations of inhibitor. Antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC(50)s, 1.5 and 2.5 micromol/L, respectively), although submicromolar concentrations of SKI-606 inhibited HT29 cell colony formation in soft agar. SKI-606 also caused loosely aggregated Colo205 spheroids to condense into compact spheroids. On oral administration to nude mice at the lowest efficacious dose, peak plasma concentrations of approximately 3 micromol/L, an oral bioavailability of 18%, and a t(1/2) of 8.6 hours were observed. SKI-606 was orally active in s.c. colon Tumor Xenograft models and caused substantial reductions in Src autophosphorylation on Tyr(418) in HT29 and Colo205 Tumors. SKI-606 inhibited HT29 Tumor growth on once daily administration, whereas twice daily administration was necessary to inhibit Colo205, HCT116, and DLD1 Tumor growth. These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer.
Craig Titsch - One of the best experts on this subject based on the ideXlab platform.
-
ski 606 a src abl inhibitor with in vivo activity in colon Tumor Xenograft models
Cancer Research, 2005Co-Authors: Jennifer M Golas, Judy Lucas, Carlo Etienne, Carolyn Discafani, Latha Sridharan, Erwin R Boghaert, K T Arndt, Diane H Boschelli, Craig TitschAbstract:Src up-regulation is a common event in human cancers. In colorectal cancer, increased Src levels are an indicator of poor prognosis, and progression to metastatic disease is associated with substantial increases in Src activity. Therefore, we examined the activity of SKI-606, a potent inhibitor of Src and Abl kinases, against colon Tumor lines in vitro and in s.c. Tumor Xenograft models. SKI-606 inhibited Src autophosphorylation with an IC50 of ∼0.25 μmol/L in HT29 cells. Phosphorylation of Tyr925 of focal adhesion kinase, a Src substrate, was reduced by similar concentrations of inhibitor. Antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC50s, 1.5 and 2.5 μmol/L, respectively), although submicromolar concentrations of SKI-606 inhibited HT29 cell colony formation in soft agar. SKI-606 also caused loosely aggregated Colo205 spheroids to condense into compact spheroids. On oral administration to nude mice at the lowest efficacious dose, peak plasma concentrations of ∼3 μmol/L, an oral bioavailability of 18%, and a t 1/2 of 8.6 hours were observed. SKI-606 was orally active in s.c. colon Tumor Xenograft models and caused substantial reductions in Src autophosphorylation on Tyr418 in HT29 and Colo205 Tumors. SKI-606 inhibited HT29 Tumor growth on once daily administration, whereas twice daily administration was necessary to inhibit Colo205, HCT116, and DLD1 Tumor growth. These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer.
-
ski 606 a src abl inhibitor with in vivo activity in colon Tumor Xenograft models
Cancer Research, 2005Co-Authors: Jennifer M Golas, Judy Lucas, Carlo Etienne, Carolyn Discafani, Latha Sridharan, Erwin R Boghaert, K T Arndt, Diane H Boschelli, Craig TitschAbstract:Src up-regulation is a common event in human cancers. In colorectal cancer, increased Src levels are an indicator of poor prognosis, and progression to metastatic disease is associated with substantial increases in Src activity. Therefore, we examined the activity of SKI-606, a potent inhibitor of Src and Abl kinases, against colon Tumor lines in vitro and in s.c. Tumor Xenograft models. SKI-606 inhibited Src autophosphorylation with an IC(50) of approximately 0.25 micromol/L in HT29 cells. Phosphorylation of Tyr(925) of focal adhesion kinase, a Src substrate, was reduced by similar concentrations of inhibitor. Antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC(50)s, 1.5 and 2.5 micromol/L, respectively), although submicromolar concentrations of SKI-606 inhibited HT29 cell colony formation in soft agar. SKI-606 also caused loosely aggregated Colo205 spheroids to condense into compact spheroids. On oral administration to nude mice at the lowest efficacious dose, peak plasma concentrations of approximately 3 micromol/L, an oral bioavailability of 18%, and a t(1/2) of 8.6 hours were observed. SKI-606 was orally active in s.c. colon Tumor Xenograft models and caused substantial reductions in Src autophosphorylation on Tyr(418) in HT29 and Colo205 Tumors. SKI-606 inhibited HT29 Tumor growth on once daily administration, whereas twice daily administration was necessary to inhibit Colo205, HCT116, and DLD1 Tumor growth. These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer.
Marco Presta - One of the best experts on this subject based on the ideXlab platform.
-
the zebrafish Tumor Xenograft angiogenesis assay
Nature Protocols, 2007Co-Authors: Stefania Nicoli, Marco PrestaAbstract:Zebrafish (Danio rerio) represents a powerful model system in cancer research. Recent observations have shown the possibility to exploit zebrafish to investigate Tumor angiogenesis, a pivotal step in cancer progression and target for anti-Tumor therapies. Novel genetic tools and high resolutionin vivo imaging techniques are also becoming available in zebrafish. It is anticipated that zebrafish will represent an important tool for chemical discovery and gene targeting in Tumor angiogenesis. Here we describe a method to study Tumor angiogenesis in zebrafish (Danio rerio) based on the injection of proangiogenic mammalian Tumor cells into the perivitelline space of zebrafish embryos at 48 h post-fertilization. Within 24–48 h, proangiogenic Tumor grafts induce a neovascular response originating from the developing sub-intestinal vessels. Angiogenesis inhibitors added to the fish water or to the injected cell suspension prevent Tumor-induced neovascularization. Also, gene inactivation by antisense morpholino oligonucleotide injection in zebrafish embryos may allow the rapid identification of genes involved in Tumor angiogenesis. The assay represents a novel tool for investigating Tumor angiogenesis and for antiangiogenic drug discovery.
K T Arndt - One of the best experts on this subject based on the ideXlab platform.
-
ski 606 a src abl inhibitor with in vivo activity in colon Tumor Xenograft models
Cancer Research, 2005Co-Authors: Jennifer M Golas, Judy Lucas, Carlo Etienne, Carolyn Discafani, Latha Sridharan, Erwin R Boghaert, K T Arndt, Diane H Boschelli, Craig TitschAbstract:Src up-regulation is a common event in human cancers. In colorectal cancer, increased Src levels are an indicator of poor prognosis, and progression to metastatic disease is associated with substantial increases in Src activity. Therefore, we examined the activity of SKI-606, a potent inhibitor of Src and Abl kinases, against colon Tumor lines in vitro and in s.c. Tumor Xenograft models. SKI-606 inhibited Src autophosphorylation with an IC50 of ∼0.25 μmol/L in HT29 cells. Phosphorylation of Tyr925 of focal adhesion kinase, a Src substrate, was reduced by similar concentrations of inhibitor. Antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC50s, 1.5 and 2.5 μmol/L, respectively), although submicromolar concentrations of SKI-606 inhibited HT29 cell colony formation in soft agar. SKI-606 also caused loosely aggregated Colo205 spheroids to condense into compact spheroids. On oral administration to nude mice at the lowest efficacious dose, peak plasma concentrations of ∼3 μmol/L, an oral bioavailability of 18%, and a t 1/2 of 8.6 hours were observed. SKI-606 was orally active in s.c. colon Tumor Xenograft models and caused substantial reductions in Src autophosphorylation on Tyr418 in HT29 and Colo205 Tumors. SKI-606 inhibited HT29 Tumor growth on once daily administration, whereas twice daily administration was necessary to inhibit Colo205, HCT116, and DLD1 Tumor growth. These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer.
-
ski 606 a src abl inhibitor with in vivo activity in colon Tumor Xenograft models
Cancer Research, 2005Co-Authors: Jennifer M Golas, Judy Lucas, Carlo Etienne, Carolyn Discafani, Latha Sridharan, Erwin R Boghaert, K T Arndt, Diane H Boschelli, Craig TitschAbstract:Src up-regulation is a common event in human cancers. In colorectal cancer, increased Src levels are an indicator of poor prognosis, and progression to metastatic disease is associated with substantial increases in Src activity. Therefore, we examined the activity of SKI-606, a potent inhibitor of Src and Abl kinases, against colon Tumor lines in vitro and in s.c. Tumor Xenograft models. SKI-606 inhibited Src autophosphorylation with an IC(50) of approximately 0.25 micromol/L in HT29 cells. Phosphorylation of Tyr(925) of focal adhesion kinase, a Src substrate, was reduced by similar concentrations of inhibitor. Antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC(50)s, 1.5 and 2.5 micromol/L, respectively), although submicromolar concentrations of SKI-606 inhibited HT29 cell colony formation in soft agar. SKI-606 also caused loosely aggregated Colo205 spheroids to condense into compact spheroids. On oral administration to nude mice at the lowest efficacious dose, peak plasma concentrations of approximately 3 micromol/L, an oral bioavailability of 18%, and a t(1/2) of 8.6 hours were observed. SKI-606 was orally active in s.c. colon Tumor Xenograft models and caused substantial reductions in Src autophosphorylation on Tyr(418) in HT29 and Colo205 Tumors. SKI-606 inhibited HT29 Tumor growth on once daily administration, whereas twice daily administration was necessary to inhibit Colo205, HCT116, and DLD1 Tumor growth. These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer.
Judy Lucas - One of the best experts on this subject based on the ideXlab platform.
-
ski 606 a src abl inhibitor with in vivo activity in colon Tumor Xenograft models
Cancer Research, 2005Co-Authors: Jennifer M Golas, Judy Lucas, Carlo Etienne, Carolyn Discafani, Latha Sridharan, Erwin R Boghaert, K T Arndt, Diane H Boschelli, Craig TitschAbstract:Src up-regulation is a common event in human cancers. In colorectal cancer, increased Src levels are an indicator of poor prognosis, and progression to metastatic disease is associated with substantial increases in Src activity. Therefore, we examined the activity of SKI-606, a potent inhibitor of Src and Abl kinases, against colon Tumor lines in vitro and in s.c. Tumor Xenograft models. SKI-606 inhibited Src autophosphorylation with an IC50 of ∼0.25 μmol/L in HT29 cells. Phosphorylation of Tyr925 of focal adhesion kinase, a Src substrate, was reduced by similar concentrations of inhibitor. Antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC50s, 1.5 and 2.5 μmol/L, respectively), although submicromolar concentrations of SKI-606 inhibited HT29 cell colony formation in soft agar. SKI-606 also caused loosely aggregated Colo205 spheroids to condense into compact spheroids. On oral administration to nude mice at the lowest efficacious dose, peak plasma concentrations of ∼3 μmol/L, an oral bioavailability of 18%, and a t 1/2 of 8.6 hours were observed. SKI-606 was orally active in s.c. colon Tumor Xenograft models and caused substantial reductions in Src autophosphorylation on Tyr418 in HT29 and Colo205 Tumors. SKI-606 inhibited HT29 Tumor growth on once daily administration, whereas twice daily administration was necessary to inhibit Colo205, HCT116, and DLD1 Tumor growth. These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer.
-
ski 606 a src abl inhibitor with in vivo activity in colon Tumor Xenograft models
Cancer Research, 2005Co-Authors: Jennifer M Golas, Judy Lucas, Carlo Etienne, Carolyn Discafani, Latha Sridharan, Erwin R Boghaert, K T Arndt, Diane H Boschelli, Craig TitschAbstract:Src up-regulation is a common event in human cancers. In colorectal cancer, increased Src levels are an indicator of poor prognosis, and progression to metastatic disease is associated with substantial increases in Src activity. Therefore, we examined the activity of SKI-606, a potent inhibitor of Src and Abl kinases, against colon Tumor lines in vitro and in s.c. Tumor Xenograft models. SKI-606 inhibited Src autophosphorylation with an IC(50) of approximately 0.25 micromol/L in HT29 cells. Phosphorylation of Tyr(925) of focal adhesion kinase, a Src substrate, was reduced by similar concentrations of inhibitor. Antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC(50)s, 1.5 and 2.5 micromol/L, respectively), although submicromolar concentrations of SKI-606 inhibited HT29 cell colony formation in soft agar. SKI-606 also caused loosely aggregated Colo205 spheroids to condense into compact spheroids. On oral administration to nude mice at the lowest efficacious dose, peak plasma concentrations of approximately 3 micromol/L, an oral bioavailability of 18%, and a t(1/2) of 8.6 hours were observed. SKI-606 was orally active in s.c. colon Tumor Xenograft models and caused substantial reductions in Src autophosphorylation on Tyr(418) in HT29 and Colo205 Tumors. SKI-606 inhibited HT29 Tumor growth on once daily administration, whereas twice daily administration was necessary to inhibit Colo205, HCT116, and DLD1 Tumor growth. These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer.
