The Experts below are selected from a list of 99 Experts worldwide ranked by ideXlab platform
Motohiro Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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tumor specific antivascular effect of tzt 1027 Soblidotin elucidated by magnetic resonance imaging and confocal laser scanning microscopy
Cancer Science, 2007Co-Authors: Tsugitaka Natsume, Junichi Watanabe, Kenji Ogawa, Kazuhiko Yasumura, Motohiro KobayashiAbstract:TZT-1027 (Soblidotin), an antimicrotubule agent, has previously been evaluated in terms of its antivascular effects. In this study, Evans blue perfusion, magnetic resonance imaging (MRI), and confocal laser scanning microscopy (CLSM) were utilized to further elucidate the antivascular effect of TZT-1027 in female nude mice and rats bearing human breast tumor MX-1, as well as in female Sprague-Dawley rats that developed breast tumors induced by dimethylbenz(a)anthracene (DMBA). Therapeutic doses of TZT-1027 caused nearly complete regression of implanted MX-1 tumors in nude mice and rats as well as DMBA-induced tumors in rats. The perfusion in MX-1 tumor implanted in nude mice was drastically reduced within 30 min after TZT-1027 administration and was completely inhibited after 6 h or more, although not reduced in normal tissue of kidney. The study using MRI demonstrated that rich blood flow within tumors was remarkably reduced 1-3 h after TZT-1027 administration both in nude rats bearing MX-1 tumors and in rats with DMBA-induced tumors. Furthermore, the study with CLSM in nude mice bearing MX-1 tumors revealed a disruption of tumor microvessels at 1 h and a destruction of tumor microvessel network at 3 h after TZT-1027 administration. In contrast, these types of vascular disorders were not observed in heart and kidney. These results suggest that TZT-1027 specifically damages tumor vasculatures, leading to extensive tumor necrosis within tolerable dose range, and confirms earlier observations that TZT-1027 exerts a considerable antivascular effect in addition to an excellent cytotoxic effect.
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Antiangiogenic activity of TZT-1027 (Soblidotin) on chick chorioallantoic membrane and human umbilical vein endothelial cells.
In vivo (Athens Greece), 2007Co-Authors: Junichi Watanabe, Tsugitaka Natsume, Yoshio Endo, Nami Shimada, Takuma Sasaki, Motohiro KobayashiAbstract:Background: TZT-1027 (Soblidotin), a microtubule- depolymerizing agent, has antivascular activity which disrupts newly formed tumor vasculature. In this study, it was investigated whether TZT-1027 has also antiangiogenic activity preventing neovascularization. Materials and Methods: Antiangiogenic activities were evaluated in vivo in a chick embryo chorioallantoic membrane (CAM) assay and in vitro in a tube formation assay on human umbilical vein endothelial cells (HUVEC). RT-PCR and skimmed milk zymography analyses were performed to clarify the involvement of angiogenesis-related proteolytic enzymes and transcription factors. Results: TZT-1027 at doses of 0.01 and 0.06 Ig/egg showed potent antiangiogenic activities in the CAM assay (80% and 100% inhibition, respectively), with no lethal toxicity to the chick embryo. TZT-1027 at doses of 0.01-10 ng/mL prevented
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The inhibitory effect of docetaxel and p38 MAPK inhibitor on TZT-1027 (Soblidotin)-induced antivascular activity.
Anticancer research, 2007Co-Authors: Junichi Watanabe, Tsugitaka Natsume, Motohiro KobayashiAbstract:BACKGROUND: TZT-1027 (Soblidotin), a microtubule (MT)-depolymerizing agent, has antivascular activity through the disruption of microtubules in vascular endothelial cells. Our aim was to elucidate the mechanism of TZT-1027-induced antivascular activity by investigating the impact of various inhibitors. MATERIALS AND METHODS: The inhibitory effects on TZT-1027-induced antivascular activity were evaluated by a tumor perfusion study in mice bearing Colon26 tumors and a vascular permeability study on human umbilical vein endothelial cells monolayer. Western blotting analyses were performed to verify the mechanism of antivascular activity. RESULTS: Pretreatment with docetaxel and SB220025, a p38 mitogen-activated protein kinase (MAPK) inhibitor, significantly suppressed the TZT-1027-induced reduction of tumor perfusion and increase in vascular permeability. Gross findings showed that SB220025 visibly attenuated the TZT-1027-induced widespread hemorrhage in tumors. Western blotting analyses revealed that TZT-1027 induced the phosphorylation of p38 MAPK only slightly compared to hydrogen peroxide, and that docetaxel and SB220025 increased the acetylation of alpha-tubulin an effect opposite to that of TZT-1027. CONCLUSION: TZT-1027-induced antivascular activity was abolished by docetaxel through the stabilization of microtubules, and by p38 MAPK inhibitor not only through the regulation of the p38 MAPK pathway, but also through the direct stabilization of microtubules, similar to docetaxel.
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Comparison of the antivascular and cytotoxic activities of TZT-1027 (Soblidotin) with those of other anticancer agents.
Anti-cancer drugs, 2007Co-Authors: Junichi Watanabe, Tsugitaka Natsume, Motohiro KobayashiAbstract:TZT-1027 (Soblidotin), a microtubule-depolymerizing agent exerts both a direct cytotoxic activity against cancer cells and an indirect antivascular activity against tumor vascular endothelial cells. We compared both activities of TZT-1027 with those of various anticancer agents having different mechanisms of action, including vinca alkaloids, a vascular targeting agent, a taxane and nonmicrotubule-binding agents. In the MTT assay, TZT-1027 most potently inhibited the growth of both murine colon C26 cancer cells and human umbilical vein endothelial cells, implying its potent antivascular activity against tumor vasculature in addition to its cytotoxic activity against cancer cells. Treatment with 0.1 microg/ml TZT-1027 significantly enhanced vascular permeability in human umbilical vein endothelial cell monolayers and a single intravenous administration of 2 mg/kg TZT-1027 significantly reduced the perfusion of Colon26 tumors implanted into mice, with efficacies superior to vinca alkaloids and comparable to a known vascular targeting agent. These results strongly suggest that TZT-1027 exerts marked antivascular activity. Next, to clarify the mechanism of the antivascular activity, we have taken a novel approach, and analyzed the relationships among human umbilical vein endothelial cells cytotoxicity, vascular permeability and tumor perfusion, on the basis of efficacies of each agent. Analyses revealed strong and significant correlations, and indicated that the vascular endothelial cell damage leads to endothelial barrier dysfunction and, thereby, tumor vascular shutdown. In summary, TZT-1027 was verified to have not only an excellent cytotoxic activity, but also an attractive antivascular activity through the induction of damage to vascular endothelial cells. We believe that these dual activities may make TZT-1027 useful for treating solid tumors.
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Tumor‐specific antivascular effect of TZT‐1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy
Cancer Science, 2007Co-Authors: Tsugitaka Natsume, Junichi Watanabe, Kenji Ogawa, Kazuhiko Yasumura, Motohiro KobayashiAbstract:TZT-1027 (Soblidotin), an antimicrotubule agent, has previously been evaluated in terms of its antivascular effects. In this study, Evans blue perfusion, magnetic resonance imaging (MRI), and confocal laser scanning microscopy (CLSM) were utilized to further elucidate the antivascular effect of TZT-1027 in female nude mice and rats bearing human breast tumor MX-1, as well as in female Sprague-Dawley rats that developed breast tumors induced by dimethylbenz(a)anthracene (DMBA). Therapeutic doses of TZT-1027 caused nearly complete regression of implanted MX-1 tumors in nude mice and rats as well as DMBA-induced tumors in rats. The perfusion in MX-1 tumor implanted in nude mice was drastically reduced within 30 min after TZT-1027 administration and was completely inhibited after 6 h or more, although not reduced in normal tissue of kidney. The study using MRI demonstrated that rich blood flow within tumors was remarkably reduced 1-3 h after TZT-1027 administration both in nude rats bearing MX-1 tumors and in rats with DMBA-induced tumors. Furthermore, the study with CLSM in nude mice bearing MX-1 tumors revealed a disruption of tumor microvessels at 1 h and a destruction of tumor microvessel network at 3 h after TZT-1027 administration. In contrast, these types of vascular disorders were not observed in heart and kidney. These results suggest that TZT-1027 specifically damages tumor vasculatures, leading to extensive tumor necrosis within tolerable dose range, and confirms earlier observations that TZT-1027 exerts a considerable antivascular effect in addition to an excellent cytotoxic effect.
Junichi Watanabe - One of the best experts on this subject based on the ideXlab platform.
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tumor specific antivascular effect of tzt 1027 Soblidotin elucidated by magnetic resonance imaging and confocal laser scanning microscopy
Cancer Science, 2007Co-Authors: Tsugitaka Natsume, Junichi Watanabe, Kenji Ogawa, Kazuhiko Yasumura, Motohiro KobayashiAbstract:TZT-1027 (Soblidotin), an antimicrotubule agent, has previously been evaluated in terms of its antivascular effects. In this study, Evans blue perfusion, magnetic resonance imaging (MRI), and confocal laser scanning microscopy (CLSM) were utilized to further elucidate the antivascular effect of TZT-1027 in female nude mice and rats bearing human breast tumor MX-1, as well as in female Sprague-Dawley rats that developed breast tumors induced by dimethylbenz(a)anthracene (DMBA). Therapeutic doses of TZT-1027 caused nearly complete regression of implanted MX-1 tumors in nude mice and rats as well as DMBA-induced tumors in rats. The perfusion in MX-1 tumor implanted in nude mice was drastically reduced within 30 min after TZT-1027 administration and was completely inhibited after 6 h or more, although not reduced in normal tissue of kidney. The study using MRI demonstrated that rich blood flow within tumors was remarkably reduced 1-3 h after TZT-1027 administration both in nude rats bearing MX-1 tumors and in rats with DMBA-induced tumors. Furthermore, the study with CLSM in nude mice bearing MX-1 tumors revealed a disruption of tumor microvessels at 1 h and a destruction of tumor microvessel network at 3 h after TZT-1027 administration. In contrast, these types of vascular disorders were not observed in heart and kidney. These results suggest that TZT-1027 specifically damages tumor vasculatures, leading to extensive tumor necrosis within tolerable dose range, and confirms earlier observations that TZT-1027 exerts a considerable antivascular effect in addition to an excellent cytotoxic effect.
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Antiangiogenic activity of TZT-1027 (Soblidotin) on chick chorioallantoic membrane and human umbilical vein endothelial cells.
In vivo (Athens Greece), 2007Co-Authors: Junichi Watanabe, Tsugitaka Natsume, Yoshio Endo, Nami Shimada, Takuma Sasaki, Motohiro KobayashiAbstract:Background: TZT-1027 (Soblidotin), a microtubule- depolymerizing agent, has antivascular activity which disrupts newly formed tumor vasculature. In this study, it was investigated whether TZT-1027 has also antiangiogenic activity preventing neovascularization. Materials and Methods: Antiangiogenic activities were evaluated in vivo in a chick embryo chorioallantoic membrane (CAM) assay and in vitro in a tube formation assay on human umbilical vein endothelial cells (HUVEC). RT-PCR and skimmed milk zymography analyses were performed to clarify the involvement of angiogenesis-related proteolytic enzymes and transcription factors. Results: TZT-1027 at doses of 0.01 and 0.06 Ig/egg showed potent antiangiogenic activities in the CAM assay (80% and 100% inhibition, respectively), with no lethal toxicity to the chick embryo. TZT-1027 at doses of 0.01-10 ng/mL prevented
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The inhibitory effect of docetaxel and p38 MAPK inhibitor on TZT-1027 (Soblidotin)-induced antivascular activity.
Anticancer research, 2007Co-Authors: Junichi Watanabe, Tsugitaka Natsume, Motohiro KobayashiAbstract:BACKGROUND: TZT-1027 (Soblidotin), a microtubule (MT)-depolymerizing agent, has antivascular activity through the disruption of microtubules in vascular endothelial cells. Our aim was to elucidate the mechanism of TZT-1027-induced antivascular activity by investigating the impact of various inhibitors. MATERIALS AND METHODS: The inhibitory effects on TZT-1027-induced antivascular activity were evaluated by a tumor perfusion study in mice bearing Colon26 tumors and a vascular permeability study on human umbilical vein endothelial cells monolayer. Western blotting analyses were performed to verify the mechanism of antivascular activity. RESULTS: Pretreatment with docetaxel and SB220025, a p38 mitogen-activated protein kinase (MAPK) inhibitor, significantly suppressed the TZT-1027-induced reduction of tumor perfusion and increase in vascular permeability. Gross findings showed that SB220025 visibly attenuated the TZT-1027-induced widespread hemorrhage in tumors. Western blotting analyses revealed that TZT-1027 induced the phosphorylation of p38 MAPK only slightly compared to hydrogen peroxide, and that docetaxel and SB220025 increased the acetylation of alpha-tubulin an effect opposite to that of TZT-1027. CONCLUSION: TZT-1027-induced antivascular activity was abolished by docetaxel through the stabilization of microtubules, and by p38 MAPK inhibitor not only through the regulation of the p38 MAPK pathway, but also through the direct stabilization of microtubules, similar to docetaxel.
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Comparison of the antivascular and cytotoxic activities of TZT-1027 (Soblidotin) with those of other anticancer agents.
Anti-cancer drugs, 2007Co-Authors: Junichi Watanabe, Tsugitaka Natsume, Motohiro KobayashiAbstract:TZT-1027 (Soblidotin), a microtubule-depolymerizing agent exerts both a direct cytotoxic activity against cancer cells and an indirect antivascular activity against tumor vascular endothelial cells. We compared both activities of TZT-1027 with those of various anticancer agents having different mechanisms of action, including vinca alkaloids, a vascular targeting agent, a taxane and nonmicrotubule-binding agents. In the MTT assay, TZT-1027 most potently inhibited the growth of both murine colon C26 cancer cells and human umbilical vein endothelial cells, implying its potent antivascular activity against tumor vasculature in addition to its cytotoxic activity against cancer cells. Treatment with 0.1 microg/ml TZT-1027 significantly enhanced vascular permeability in human umbilical vein endothelial cell monolayers and a single intravenous administration of 2 mg/kg TZT-1027 significantly reduced the perfusion of Colon26 tumors implanted into mice, with efficacies superior to vinca alkaloids and comparable to a known vascular targeting agent. These results strongly suggest that TZT-1027 exerts marked antivascular activity. Next, to clarify the mechanism of the antivascular activity, we have taken a novel approach, and analyzed the relationships among human umbilical vein endothelial cells cytotoxicity, vascular permeability and tumor perfusion, on the basis of efficacies of each agent. Analyses revealed strong and significant correlations, and indicated that the vascular endothelial cell damage leads to endothelial barrier dysfunction and, thereby, tumor vascular shutdown. In summary, TZT-1027 was verified to have not only an excellent cytotoxic activity, but also an attractive antivascular activity through the induction of damage to vascular endothelial cells. We believe that these dual activities may make TZT-1027 useful for treating solid tumors.
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Tumor‐specific antivascular effect of TZT‐1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy
Cancer Science, 2007Co-Authors: Tsugitaka Natsume, Junichi Watanabe, Kenji Ogawa, Kazuhiko Yasumura, Motohiro KobayashiAbstract:TZT-1027 (Soblidotin), an antimicrotubule agent, has previously been evaluated in terms of its antivascular effects. In this study, Evans blue perfusion, magnetic resonance imaging (MRI), and confocal laser scanning microscopy (CLSM) were utilized to further elucidate the antivascular effect of TZT-1027 in female nude mice and rats bearing human breast tumor MX-1, as well as in female Sprague-Dawley rats that developed breast tumors induced by dimethylbenz(a)anthracene (DMBA). Therapeutic doses of TZT-1027 caused nearly complete regression of implanted MX-1 tumors in nude mice and rats as well as DMBA-induced tumors in rats. The perfusion in MX-1 tumor implanted in nude mice was drastically reduced within 30 min after TZT-1027 administration and was completely inhibited after 6 h or more, although not reduced in normal tissue of kidney. The study using MRI demonstrated that rich blood flow within tumors was remarkably reduced 1-3 h after TZT-1027 administration both in nude rats bearing MX-1 tumors and in rats with DMBA-induced tumors. Furthermore, the study with CLSM in nude mice bearing MX-1 tumors revealed a disruption of tumor microvessels at 1 h and a destruction of tumor microvessel network at 3 h after TZT-1027 administration. In contrast, these types of vascular disorders were not observed in heart and kidney. These results suggest that TZT-1027 specifically damages tumor vasculatures, leading to extensive tumor necrosis within tolerable dose range, and confirms earlier observations that TZT-1027 exerts a considerable antivascular effect in addition to an excellent cytotoxic effect.
Tsugitaka Natsume - One of the best experts on this subject based on the ideXlab platform.
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tumor specific antivascular effect of tzt 1027 Soblidotin elucidated by magnetic resonance imaging and confocal laser scanning microscopy
Cancer Science, 2007Co-Authors: Tsugitaka Natsume, Junichi Watanabe, Kenji Ogawa, Kazuhiko Yasumura, Motohiro KobayashiAbstract:TZT-1027 (Soblidotin), an antimicrotubule agent, has previously been evaluated in terms of its antivascular effects. In this study, Evans blue perfusion, magnetic resonance imaging (MRI), and confocal laser scanning microscopy (CLSM) were utilized to further elucidate the antivascular effect of TZT-1027 in female nude mice and rats bearing human breast tumor MX-1, as well as in female Sprague-Dawley rats that developed breast tumors induced by dimethylbenz(a)anthracene (DMBA). Therapeutic doses of TZT-1027 caused nearly complete regression of implanted MX-1 tumors in nude mice and rats as well as DMBA-induced tumors in rats. The perfusion in MX-1 tumor implanted in nude mice was drastically reduced within 30 min after TZT-1027 administration and was completely inhibited after 6 h or more, although not reduced in normal tissue of kidney. The study using MRI demonstrated that rich blood flow within tumors was remarkably reduced 1-3 h after TZT-1027 administration both in nude rats bearing MX-1 tumors and in rats with DMBA-induced tumors. Furthermore, the study with CLSM in nude mice bearing MX-1 tumors revealed a disruption of tumor microvessels at 1 h and a destruction of tumor microvessel network at 3 h after TZT-1027 administration. In contrast, these types of vascular disorders were not observed in heart and kidney. These results suggest that TZT-1027 specifically damages tumor vasculatures, leading to extensive tumor necrosis within tolerable dose range, and confirms earlier observations that TZT-1027 exerts a considerable antivascular effect in addition to an excellent cytotoxic effect.
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Antiangiogenic activity of TZT-1027 (Soblidotin) on chick chorioallantoic membrane and human umbilical vein endothelial cells.
In vivo (Athens Greece), 2007Co-Authors: Junichi Watanabe, Tsugitaka Natsume, Yoshio Endo, Nami Shimada, Takuma Sasaki, Motohiro KobayashiAbstract:Background: TZT-1027 (Soblidotin), a microtubule- depolymerizing agent, has antivascular activity which disrupts newly formed tumor vasculature. In this study, it was investigated whether TZT-1027 has also antiangiogenic activity preventing neovascularization. Materials and Methods: Antiangiogenic activities were evaluated in vivo in a chick embryo chorioallantoic membrane (CAM) assay and in vitro in a tube formation assay on human umbilical vein endothelial cells (HUVEC). RT-PCR and skimmed milk zymography analyses were performed to clarify the involvement of angiogenesis-related proteolytic enzymes and transcription factors. Results: TZT-1027 at doses of 0.01 and 0.06 Ig/egg showed potent antiangiogenic activities in the CAM assay (80% and 100% inhibition, respectively), with no lethal toxicity to the chick embryo. TZT-1027 at doses of 0.01-10 ng/mL prevented
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The inhibitory effect of docetaxel and p38 MAPK inhibitor on TZT-1027 (Soblidotin)-induced antivascular activity.
Anticancer research, 2007Co-Authors: Junichi Watanabe, Tsugitaka Natsume, Motohiro KobayashiAbstract:BACKGROUND: TZT-1027 (Soblidotin), a microtubule (MT)-depolymerizing agent, has antivascular activity through the disruption of microtubules in vascular endothelial cells. Our aim was to elucidate the mechanism of TZT-1027-induced antivascular activity by investigating the impact of various inhibitors. MATERIALS AND METHODS: The inhibitory effects on TZT-1027-induced antivascular activity were evaluated by a tumor perfusion study in mice bearing Colon26 tumors and a vascular permeability study on human umbilical vein endothelial cells monolayer. Western blotting analyses were performed to verify the mechanism of antivascular activity. RESULTS: Pretreatment with docetaxel and SB220025, a p38 mitogen-activated protein kinase (MAPK) inhibitor, significantly suppressed the TZT-1027-induced reduction of tumor perfusion and increase in vascular permeability. Gross findings showed that SB220025 visibly attenuated the TZT-1027-induced widespread hemorrhage in tumors. Western blotting analyses revealed that TZT-1027 induced the phosphorylation of p38 MAPK only slightly compared to hydrogen peroxide, and that docetaxel and SB220025 increased the acetylation of alpha-tubulin an effect opposite to that of TZT-1027. CONCLUSION: TZT-1027-induced antivascular activity was abolished by docetaxel through the stabilization of microtubules, and by p38 MAPK inhibitor not only through the regulation of the p38 MAPK pathway, but also through the direct stabilization of microtubules, similar to docetaxel.
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Comparison of the antivascular and cytotoxic activities of TZT-1027 (Soblidotin) with those of other anticancer agents.
Anti-cancer drugs, 2007Co-Authors: Junichi Watanabe, Tsugitaka Natsume, Motohiro KobayashiAbstract:TZT-1027 (Soblidotin), a microtubule-depolymerizing agent exerts both a direct cytotoxic activity against cancer cells and an indirect antivascular activity against tumor vascular endothelial cells. We compared both activities of TZT-1027 with those of various anticancer agents having different mechanisms of action, including vinca alkaloids, a vascular targeting agent, a taxane and nonmicrotubule-binding agents. In the MTT assay, TZT-1027 most potently inhibited the growth of both murine colon C26 cancer cells and human umbilical vein endothelial cells, implying its potent antivascular activity against tumor vasculature in addition to its cytotoxic activity against cancer cells. Treatment with 0.1 microg/ml TZT-1027 significantly enhanced vascular permeability in human umbilical vein endothelial cell monolayers and a single intravenous administration of 2 mg/kg TZT-1027 significantly reduced the perfusion of Colon26 tumors implanted into mice, with efficacies superior to vinca alkaloids and comparable to a known vascular targeting agent. These results strongly suggest that TZT-1027 exerts marked antivascular activity. Next, to clarify the mechanism of the antivascular activity, we have taken a novel approach, and analyzed the relationships among human umbilical vein endothelial cells cytotoxicity, vascular permeability and tumor perfusion, on the basis of efficacies of each agent. Analyses revealed strong and significant correlations, and indicated that the vascular endothelial cell damage leads to endothelial barrier dysfunction and, thereby, tumor vascular shutdown. In summary, TZT-1027 was verified to have not only an excellent cytotoxic activity, but also an attractive antivascular activity through the induction of damage to vascular endothelial cells. We believe that these dual activities may make TZT-1027 useful for treating solid tumors.
-
Tumor‐specific antivascular effect of TZT‐1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy
Cancer Science, 2007Co-Authors: Tsugitaka Natsume, Junichi Watanabe, Kenji Ogawa, Kazuhiko Yasumura, Motohiro KobayashiAbstract:TZT-1027 (Soblidotin), an antimicrotubule agent, has previously been evaluated in terms of its antivascular effects. In this study, Evans blue perfusion, magnetic resonance imaging (MRI), and confocal laser scanning microscopy (CLSM) were utilized to further elucidate the antivascular effect of TZT-1027 in female nude mice and rats bearing human breast tumor MX-1, as well as in female Sprague-Dawley rats that developed breast tumors induced by dimethylbenz(a)anthracene (DMBA). Therapeutic doses of TZT-1027 caused nearly complete regression of implanted MX-1 tumors in nude mice and rats as well as DMBA-induced tumors in rats. The perfusion in MX-1 tumor implanted in nude mice was drastically reduced within 30 min after TZT-1027 administration and was completely inhibited after 6 h or more, although not reduced in normal tissue of kidney. The study using MRI demonstrated that rich blood flow within tumors was remarkably reduced 1-3 h after TZT-1027 administration both in nude rats bearing MX-1 tumors and in rats with DMBA-induced tumors. Furthermore, the study with CLSM in nude mice bearing MX-1 tumors revealed a disruption of tumor microvessels at 1 h and a destruction of tumor microvessel network at 3 h after TZT-1027 administration. In contrast, these types of vascular disorders were not observed in heart and kidney. These results suggest that TZT-1027 specifically damages tumor vasculatures, leading to extensive tumor necrosis within tolerable dose range, and confirms earlier observations that TZT-1027 exerts a considerable antivascular effect in addition to an excellent cytotoxic effect.
I. Bodrogi - One of the best experts on this subject based on the ideXlab platform.
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Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative, for the treatment of patients with non-small cell lung cancer
Cancer Chemotherapy and Pharmacology, 2008Co-Authors: J. Horti, E. Juhasz, Z. Monostori, K. Maeda, S. Eckhardt, I. BodrogiAbstract:Purpose The purpose of this phase I study was to evaluate the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), the recommended dose for phase II study, pharmacokinetics, and antitumor activity of TZT-1027 (Soblidotin) in patients with non-small cell lung cancer (NSCLC) when administered every 3–4 weeks. Methods Eligible patients had the following characteristics: stage III/b or IV NSCLC that was refractory to conventional therapy or for which no standard therapy was available; Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2; adequate organ function; and age ≥20 and
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Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative, for the treatment of patients with non-small cell lung cancer
Cancer Chemotherapy and Pharmacology, 2008Co-Authors: J. Horti, E. Juhasz, Z. Monostori, K. Maeda, S. Eckhardt, I. BodrogiAbstract:Purpose The purpose of this phase I study was to evaluate the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), the recommended dose for phase II study, pharmacokinetics, and antitumor activity of TZT-1027 (Soblidotin) in patients with non-small cell lung cancer (NSCLC) when administered every 3–4 weeks.
Shunichi Negoro - One of the best experts on this subject based on the ideXlab platform.
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Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative and inhibitor of tubulin polymerization, which was administered to patients with advanced solid tumors on days 1 and 8 in 3-week courses
Cancer Chemotherapy and Pharmacology, 2007Co-Authors: Kenji Tamura, Kazuhiko Nakagawa, Takayasu Kurata, Taroh Satoh, Toshiji Nogami, Koji Takeda, Shigeki Mitsuoka, Naruo Yoshimura, Shinzoh Kudoh, Shunichi NegoroAbstract:Purpose To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of TZT-1027 (Soblidotin), a dolastatin 10 analogue, in Japanese patients with advanced solid tumors when administered on days 1 and 8 in 3-week courses. Methods Eligible patients had advanced solid tumors that failed to respond to standard therapy or for which no standard therapy was available, and also met the following criteria: prior chemotherapy ≤2 regimens, Eastern Cooperative Oncology Group (ECOG) performance status ≤1, and acceptable organ function. The MTD was defined as the highest dose at which no more than one of six patients experienced a DLT during course 1. Pharmacokinetic samples were collected in courses 1 and 2. Results Eighteen patients were enrolled in the present study. Three doses (1.5, 1.65, and 1.8 mg/m^2) were evaluated. Neutropenia was the principal DLT at doses of 1.65 and 1.8 mg/m^2. In addition, one patient also experienced grade 3 pneumonia with neutropenia, and another patient experienced grade 3 constipation, neuropathy, grade 4 neutropenia, and hyponatremia as DLTs at 1.65 mg/m^2. Phlebitis, the most frequent nonhematological toxicity, was improved by administration of additional saline after TZT-1027 administration. The MTD was 1.5 mg/m^2, at which DLT was not observed in a total of nine patients. The pharmacokinetic profile did not differ from that for the European population. One patient with metastatic esophageal cancer achieved partial response, and each of two patients with non-small cell lung cancer had a minor response. Conclusions When TZT-1027 was administered on days 1 and 8 in 3-week courses to Japanese patients, the MTD was 1.5 mg/m^2 and was lower than the value of 2.4 mg/m^2 in European patients. However, antitumor activity was observed at low doses. TZT-1027 was tolerated well at the MTD, without grade 3 nonhematological toxicities or neutropenia up to grade 2. TZT-1027 is a promising new tubulin polymerization inhibitor that requires further investigation in phase II studies.
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Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative and inhibitor of tubulin polymerization, which was administered to patients with advanced solid tumors on days 1 and 8 in 3-week courses
Cancer Chemotherapy and Pharmacology, 2006Co-Authors: Kenji Tamura, Kazuhiko Nakagawa, Takayasu Kurata, Taroh Satoh, Toshiji Nogami, Koji Takeda, Shigeki Mitsuoka, Naruo Yoshimura, Shinzoh Kudoh, Shunichi NegoroAbstract:Purpose To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of TZT-1027 (Soblidotin), a dolastatin 10 analogue, in Japanese patients with advanced solid tumors when administered on days 1 and 8 in 3-week courses.
