The Experts below are selected from a list of 203922 Experts worldwide ranked by ideXlab platform
Radu O Minea - One of the best experts on this subject based on the ideXlab platform.
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abstract a14 a novel integrin targeted Therapeutic Agent for prostate cancer with anti tumor anti angiogenic activity
Cancer Research, 2012Co-Authors: Francis S Markland, Stephen Swenson, Jacek Pinski, Qingcai Wang, Radu O MineaAbstract:Contortrostatin (CN), an anti-invasive/anti-angiogenic protein and member of the disintegrin family is a homodimeric protein that was isolated from southern copperhead snake venom. CN displayed potent antitumor activity against human prostate cancer (PC) xenografts in nude mice (The Prostate 70:1359, 2010). However, a major obstacle to the clinical translation of CN was the dependence on snake venom as the commercial source of the protein. To directly address this problem, we produced a recombinant version of CN, called vicrostatin (VCN), which is as active as native CN both in vitro and in vivo. The antitumor activity of VCN is based on its high affinity interaction with integrins αvβ3, αvβ5, and α5β1. These integrins are involved in invasion not only of cancer cells, but also of vascular endothelial cells. This diverse mechanism of action provides VCN with a distinct advantage over many other antiangiogenic Agents, which act on a single angiogenic pathway. In our new studies using VCN as therapy for PC, we employed an intravenous (i.v.) delivery system using a neutral unilamelar liposome formulation, suitable for clinical use, to encapsulate VCN (LVCN). LVCN was found to have a circulatory half-life of ∼22 hours whereas unencapsulated VCN has a half-life of ∼30 minutes. An important feature in the design of VCN is a carboxylterminal sequence alteration that produces ∼13-fold higher affinity (as compared to CN) for integrin α5β1, which has been shown to be over-expressed on angiogenic endothelial cells and on PC cell lines. Based on our previous in vivo efficacy results with a liposomal formulation of CN in breast and prostate cancer, we hypothesized that i.v. delivery of LVCN should be clinically relevant and lead to passive accumulation of VCN in the tumor. The increased circulatory residence time provided by liposomal encapsulation is critical to the biological efficacy of LVCN; by comparison naked VCN at the same dose has very limited activity in cancer xenograft models. In an experimental bone metastasis model, CWR22 prostate cancer cells were injected into a drilled hole in one tibia of nude mice. LVCN was injected i.v. at 100μg per dose twice per week. LVCN showed ∼80% inhibition of tumor growth. Thus, i.v. liposomal delivery leads to accumulation of LVCN in the metastatic tumor bed in nude mice where the disintegrin exerts its potent anti-tumor and anti-angiogenic activity without apparent side effects or immune recognition. In conclusion, we have shown that a liposomal formulation of VCN exerts significant anti-tumor activity in an experimental bone metastasis model of PC. In future studies, we will examine combination therapy employing VCN and chemotherapy in xenograft and bone metastasis models of PC. Citation Format: Francis S. Markland, Jr., Jacek Pinski, Stephen Swenson, Qingcai Wang, Radu Minea. A novel integrin-targeted Therapeutic Agent for prostate cancer with antitumor/antiangiogenic activity [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A14.
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Abstract A14: A novel integrin-targeted Therapeutic Agent for prostate cancer with anti-tumor/anti-angiogenic activity
Cancer Research, 2012Co-Authors: Francis S Markland, Stephen D. Swenson, Jacek Pinski, Qingcai Wang, Radu O MineaAbstract:Contortrostatin (CN), an anti-invasive/anti-angiogenic protein and member of the disintegrin family is a homodimeric protein that was isolated from southern copperhead snake venom. CN displayed potent antitumor activity against human prostate cancer (PC) xenografts in nude mice (The Prostate 70:1359, 2010). However, a major obstacle to the clinical translation of CN was the dependence on snake venom as the commercial source of the protein. To directly address this problem, we produced a recombinant version of CN, called vicrostatin (VCN), which is as active as native CN both in vitro and in vivo. The antitumor activity of VCN is based on its high affinity interaction with integrins αvβ3, αvβ5, and α5β1. These integrins are involved in invasion not only of cancer cells, but also of vascular endothelial cells. This diverse mechanism of action provides VCN with a distinct advantage over many other antiangiogenic Agents, which act on a single angiogenic pathway. In our new studies using VCN as therapy for PC, we employed an intravenous (i.v.) delivery system using a neutral unilamelar liposome formulation, suitable for clinical use, to encapsulate VCN (LVCN). LVCN was found to have a circulatory half-life of ∼22 hours whereas unencapsulated VCN has a half-life of ∼30 minutes. An important feature in the design of VCN is a carboxylterminal sequence alteration that produces ∼13-fold higher affinity (as compared to CN) for integrin α5β1, which has been shown to be over-expressed on angiogenic endothelial cells and on PC cell lines. Based on our previous in vivo efficacy results with a liposomal formulation of CN in breast and prostate cancer, we hypothesized that i.v. delivery of LVCN should be clinically relevant and lead to passive accumulation of VCN in the tumor. The increased circulatory residence time provided by liposomal encapsulation is critical to the biological efficacy of LVCN; by comparison naked VCN at the same dose has very limited activity in cancer xenograft models. In an experimental bone metastasis model, CWR22 prostate cancer cells were injected into a drilled hole in one tibia of nude mice. LVCN was injected i.v. at 100μg per dose twice per week. LVCN showed ∼80% inhibition of tumor growth. Thus, i.v. liposomal delivery leads to accumulation of LVCN in the metastatic tumor bed in nude mice where the disintegrin exerts its potent anti-tumor and anti-angiogenic activity without apparent side effects or immune recognition. In conclusion, we have shown that a liposomal formulation of VCN exerts significant anti-tumor activity in an experimental bone metastasis model of PC. In future studies, we will examine combination therapy employing VCN and chemotherapy in xenograft and bone metastasis models of PC. Citation Format: Francis S. Markland, Jr., Jacek Pinski, Stephen Swenson, Qingcai Wang, Radu Minea. A novel integrin-targeted Therapeutic Agent for prostate cancer with antitumor/antiangiogenic activity [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A14.
Xin Du - One of the best experts on this subject based on the ideXlab platform.
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mesoporous silica nanoparticles with organo bridged silsesquioxane framework as innovative platforms for bioimaging and Therapeutic Agent delivery
Biomaterials, 2016Co-Authors: Xin Du, Xiaoyu Li, Lin Xiong, Xueji Zhang, Freddy Kleitz, Shizhang QiaoAbstract:Mesoporous silica material with organo-bridged silsesquioxane frameworks is a kind of synergistic combination of inorganic silica, mesopores and organics, resulting in some novel or enhanced physicochemical and biocompatible properties compared with conventional mesoporous silica materials with pure Si-O composition. With the rapid development of nanotechnology, monodispersed nanoscale periodic mesoporous organosilica nanoparticles (PMO NPs) and organo-bridged mesoporous silica nanoparticles (MSNs) with various organic groups and structures have recently been synthesized from 100%, or less, bridged organosilica precursors, respectively. Since then, these materials have been employed as carrier platforms to construct bioimaging and/or Therapeutic Agent delivery nanosystems for nano-biomedical application, and they demonstrate some unique and/or enhanced properties and performances. This review article provides a comprehensive overview of the controlled synthesis of PMO NPs and organo-bridged MSNs, physicochemical and biocompatible properties, and their nano-biomedical application as bioimaging Agent and/or Therapeutic Agent delivery system.
Tararaj Dharakul - One of the best experts on this subject based on the ideXlab platform.
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targeted small interfering rna immunoliposomes as a promising Therapeutic Agent against highly pathogenic avian influenza a h5n1 virus infection
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: Kannika Khantasup, Phikulthong Kopermsub, Kridsada Chaichoun, Tararaj DharakulAbstract:ABSTRACT This study describes a proof-of-concept study on the use of small interfering RNA (siRNA)-immunoliposomes as a Therapeutic Agent against H5N1 influenza virus infection. siRNA specific for influenza virus nucleoprotein (NP) mRNA was employed as the key antiviral Agent to inhibit viral replication in this study. A humanized single-chain Fv antibody (huscFv) against the hemagglutinin (HA) of H5N1 highly pathogenic avian influenza virus (HPAI) was used as the targeting molecule to HA of H5N1 virus, which is abundantly expressed on the surface of infected cells (the HA target cells). The huscFv was applied to cationic polyethylene glycol-conjugated 3β-[N-(N′,N′-dimethylaminoethane) carbamoyl] cholesterol–dioleoylphosphatidyl ethanolamine (PEGylated DC-Chol–DOPE) liposomes to generate immunoliposomes for siRNA delivery. The immunoliposomes were shown to specifically bind HA-expressing Sf9 cells and demonstrated enhanced siRNA transfection efficiency. The siRNA transfection efficiency was significantly reduced after preincubation of the HA target cells with an excess amount of free huscFv. These results therefore demonstrated that the enhanced siRNA delivery by use of immunoliposomes was mediated via targeting by huscFv. Furthermore, the siRNA silencing effect was more pronounced when the immunoliposomes were administered 6 to 12 h post-H5N1 infection in MDCK cells compared with the nontargeted liposomes. This proof-of-concept study may contribute to the future design and development of an siRNA delivery system for combating viral infectious diseases in humans.
Yuan Li - One of the best experts on this subject based on the ideXlab platform.
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ebosin a potential Therapeutic Agent for rheumatoid arthritis and autoinflammatory syndromes
Cellular & Molecular Immunology, 2018Co-Authors: Yang Zhang, Lifei Wang, Yuan LiAbstract:Ebosin: a potential Therapeutic Agent for rheumatoid arthritis and autoinflammatory syndromes
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wogonin as a targeted Therapeutic Agent for ebv lymphoma cells involved in lmp1 nf κb mir 155 pu 1 pathway
BMC Cancer, 2017Co-Authors: Xue Wu, Jumah Masoud Mohammad Salmani, Rong Fu, Zhewei Chen, Yuan Li, Haijun Zhang, Ke Yang, Fei Wang, Baoan ChenAbstract:Wogonin is an encouraging choice for clinical use owing to its potent anti-tumor and anti-inflammatory effects with the high safety profile. However, wogonin for targeted therapy of lymphoma was not well addressed. In this study, we focused on its anticancer effect alongside with the underlying mechanisms for targeted therapy in EBV-positive lymphoma. This will facilitate its introduction to clinical use, which is planned in the near future. Cell proliferation was studied by CCK8. Flow cytometry was used to analyze the apoptosis and the cycle arrest of cells. Further, we also used immunofluorescent staining to detect the morphologic changes of the apoptotic cells. The expression of LMP1/miR-155/p65/pp65/PU.1 was evaluated by quantitative real-time PCR (qRT-PCR) and western blot, while that of NF-κB was analyzed by EMSA. At last, immunohistochemical staining was applied to assess the expression of target proteins and relevant molecules. In vitro, wogonin induced the apoptosis of Raji cells by downregulating the expression of NF-κB through LMP1/miR-155/NF-κB/PU.1 pathway, which was in a dose and time-dependent manner. In vivo, wogonin could suppress tumor growth, associated with the downregulation of ki67, p65 and upregulation of PU.1. Wogonin could suppress tumor growth and induce cell apoptosis by inhibiting the expression of NF-κB. Taken these findings, we concluded that wogonin could be a potential targeted Therapeutic Agent for EBV-positive lymphoma with the expression of LMP1 through the pathway of LMP1/NF-κB/miR-155/PU.1.
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Wogonin as a targeted Therapeutic Agent for EBV (+) lymphoma cells involved in LMP1/NF-κB/miR-155/PU.1 pathway.
BMC Cancer, 2017Co-Authors: Xue Wu, Jumah Masoud Mohammad Salmani, Rong Fu, Zhewei Chen, Yuan Li, Haijun Zhang, Ke Yang, Fei Wang, Baoan ChenAbstract:Wogonin is an encouraging choice for clinical use owing to its potent anti-tumor and anti-inflammatory effects with the high safety profile. However, wogonin for targeted therapy of lymphoma was not well addressed. In this study, we focused on its anticancer effect alongside with the underlying mechanisms for targeted therapy in EBV-positive lymphoma. This will facilitate its introduction to clinical use, which is planned in the near future. Cell proliferation was studied by CCK8. Flow cytometry was used to analyze the apoptosis and the cycle arrest of cells. Further, we also used immunofluorescent staining to detect the morphologic changes of the apoptotic cells. The expression of LMP1/miR-155/p65/pp65/PU.1 was evaluated by quantitative real-time PCR (qRT-PCR) and western blot, while that of NF-κB was analyzed by EMSA. At last, immunohistochemical staining was applied to assess the expression of target proteins and relevant molecules. In vitro, wogonin induced the apoptosis of Raji cells by downregulating the expression of NF-κB through LMP1/miR-155/NF-κB/PU.1 pathway, which was in a dose and time-dependent manner. In vivo, wogonin could suppress tumor growth, associated with the downregulation of ki67, p65 and upregulation of PU.1. Wogonin could suppress tumor growth and induce cell apoptosis by inhibiting the expression of NF-κB. Taken these findings, we concluded that wogonin could be a potential targeted Therapeutic Agent for EBV-positive lymphoma with the expression of LMP1 through the pathway of LMP1/NF-κB/miR-155/PU.1.
Francis S Markland - One of the best experts on this subject based on the ideXlab platform.
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abstract a14 a novel integrin targeted Therapeutic Agent for prostate cancer with anti tumor anti angiogenic activity
Cancer Research, 2012Co-Authors: Francis S Markland, Stephen Swenson, Jacek Pinski, Qingcai Wang, Radu O MineaAbstract:Contortrostatin (CN), an anti-invasive/anti-angiogenic protein and member of the disintegrin family is a homodimeric protein that was isolated from southern copperhead snake venom. CN displayed potent antitumor activity against human prostate cancer (PC) xenografts in nude mice (The Prostate 70:1359, 2010). However, a major obstacle to the clinical translation of CN was the dependence on snake venom as the commercial source of the protein. To directly address this problem, we produced a recombinant version of CN, called vicrostatin (VCN), which is as active as native CN both in vitro and in vivo. The antitumor activity of VCN is based on its high affinity interaction with integrins αvβ3, αvβ5, and α5β1. These integrins are involved in invasion not only of cancer cells, but also of vascular endothelial cells. This diverse mechanism of action provides VCN with a distinct advantage over many other antiangiogenic Agents, which act on a single angiogenic pathway. In our new studies using VCN as therapy for PC, we employed an intravenous (i.v.) delivery system using a neutral unilamelar liposome formulation, suitable for clinical use, to encapsulate VCN (LVCN). LVCN was found to have a circulatory half-life of ∼22 hours whereas unencapsulated VCN has a half-life of ∼30 minutes. An important feature in the design of VCN is a carboxylterminal sequence alteration that produces ∼13-fold higher affinity (as compared to CN) for integrin α5β1, which has been shown to be over-expressed on angiogenic endothelial cells and on PC cell lines. Based on our previous in vivo efficacy results with a liposomal formulation of CN in breast and prostate cancer, we hypothesized that i.v. delivery of LVCN should be clinically relevant and lead to passive accumulation of VCN in the tumor. The increased circulatory residence time provided by liposomal encapsulation is critical to the biological efficacy of LVCN; by comparison naked VCN at the same dose has very limited activity in cancer xenograft models. In an experimental bone metastasis model, CWR22 prostate cancer cells were injected into a drilled hole in one tibia of nude mice. LVCN was injected i.v. at 100μg per dose twice per week. LVCN showed ∼80% inhibition of tumor growth. Thus, i.v. liposomal delivery leads to accumulation of LVCN in the metastatic tumor bed in nude mice where the disintegrin exerts its potent anti-tumor and anti-angiogenic activity without apparent side effects or immune recognition. In conclusion, we have shown that a liposomal formulation of VCN exerts significant anti-tumor activity in an experimental bone metastasis model of PC. In future studies, we will examine combination therapy employing VCN and chemotherapy in xenograft and bone metastasis models of PC. Citation Format: Francis S. Markland, Jr., Jacek Pinski, Stephen Swenson, Qingcai Wang, Radu Minea. A novel integrin-targeted Therapeutic Agent for prostate cancer with antitumor/antiangiogenic activity [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A14.
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Abstract A14: A novel integrin-targeted Therapeutic Agent for prostate cancer with anti-tumor/anti-angiogenic activity
Cancer Research, 2012Co-Authors: Francis S Markland, Stephen D. Swenson, Jacek Pinski, Qingcai Wang, Radu O MineaAbstract:Contortrostatin (CN), an anti-invasive/anti-angiogenic protein and member of the disintegrin family is a homodimeric protein that was isolated from southern copperhead snake venom. CN displayed potent antitumor activity against human prostate cancer (PC) xenografts in nude mice (The Prostate 70:1359, 2010). However, a major obstacle to the clinical translation of CN was the dependence on snake venom as the commercial source of the protein. To directly address this problem, we produced a recombinant version of CN, called vicrostatin (VCN), which is as active as native CN both in vitro and in vivo. The antitumor activity of VCN is based on its high affinity interaction with integrins αvβ3, αvβ5, and α5β1. These integrins are involved in invasion not only of cancer cells, but also of vascular endothelial cells. This diverse mechanism of action provides VCN with a distinct advantage over many other antiangiogenic Agents, which act on a single angiogenic pathway. In our new studies using VCN as therapy for PC, we employed an intravenous (i.v.) delivery system using a neutral unilamelar liposome formulation, suitable for clinical use, to encapsulate VCN (LVCN). LVCN was found to have a circulatory half-life of ∼22 hours whereas unencapsulated VCN has a half-life of ∼30 minutes. An important feature in the design of VCN is a carboxylterminal sequence alteration that produces ∼13-fold higher affinity (as compared to CN) for integrin α5β1, which has been shown to be over-expressed on angiogenic endothelial cells and on PC cell lines. Based on our previous in vivo efficacy results with a liposomal formulation of CN in breast and prostate cancer, we hypothesized that i.v. delivery of LVCN should be clinically relevant and lead to passive accumulation of VCN in the tumor. The increased circulatory residence time provided by liposomal encapsulation is critical to the biological efficacy of LVCN; by comparison naked VCN at the same dose has very limited activity in cancer xenograft models. In an experimental bone metastasis model, CWR22 prostate cancer cells were injected into a drilled hole in one tibia of nude mice. LVCN was injected i.v. at 100μg per dose twice per week. LVCN showed ∼80% inhibition of tumor growth. Thus, i.v. liposomal delivery leads to accumulation of LVCN in the metastatic tumor bed in nude mice where the disintegrin exerts its potent anti-tumor and anti-angiogenic activity without apparent side effects or immune recognition. In conclusion, we have shown that a liposomal formulation of VCN exerts significant anti-tumor activity in an experimental bone metastasis model of PC. In future studies, we will examine combination therapy employing VCN and chemotherapy in xenograft and bone metastasis models of PC. Citation Format: Francis S. Markland, Jr., Jacek Pinski, Stephen Swenson, Qingcai Wang, Radu Minea. A novel integrin-targeted Therapeutic Agent for prostate cancer with antitumor/antiangiogenic activity [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A14.
