The Experts below are selected from a list of 1743 Experts worldwide ranked by ideXlab platform

Steven M Albelda - One of the best experts on this subject based on the ideXlab platform.

  • Surgical cytoreduction restores the antitumor efficacy of a Listeria monocytogenes vaccine in malignant pleural Mesothelioma.
    Immunology Letters, 2015
    Co-Authors: Gregory T. Kennedy, Brendan F. Judy, Pratik Bhojnagarwala, Edmund K. Moon, Zvi G. Fridlender, Steven M Albelda, Sunil Singhal
    Abstract:

    Abstract Recent studies suggest that immunotherapy may offer a promising treatment strategy for early-stage malignant pleural Mesothelioma (MPM), but advanced tumor burden may limit the efficacy of immunotherapy. Therefore, we hypothesized that surgical cytoreduction could restore the efficacy of vaccine-based immunotherapy for MPM. We developed a murine model of MPM through transduction of a Mesothelioma Cell Line with mesothelin. We used this model to evaluate the efficacy of a Listeria monocytogenes vaccine expressing mesothelin. Tumor growth was significantly inhibited at four weeks in animals vaccinated two weeks prior to tumor Cell inoculation as compared to those given an empty vector control (1371 ± 420 mm 3 versus 405 ± 139 mm 3 ; p 3 versus 309 ± 173 mm 3 ; p 3 versus 1047 ± 258 mm 3 ; p

  • Activation of the Nucleotide Oligomerization Domain Signaling Pathway by the Non-bacterially Derived Xanthone Drug 5′6-Dimethylxanthenone-4-acetic Acid (Vadimezan)
    The Journal of biological chemistry, 2010
    Co-Authors: Guanjun Cheng, Zvi G. Fridlender, Jing Sun, Liang-chuan S. Wang, Lai-ming Ching, Steven M Albelda
    Abstract:

    The cytosolic nucleotide-binding oligomerization domain 1 (NOD1)/CARD4 and NOD2/CARD15 proteins are members of NOD-like receptors recognizing specific motifs within peptidoglycans of both Gram-negative and Gram-positive bacteria. NOD1 and NOD2 signal via the downstream adaptor serine/threonine kinase RIP2/CARDIAK/RICK to initiate NF-κB activation and the release of inflammatory cytokines/chemokines. In this report, we show that 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a Cell-permeable, small molecule that has anti-tumor activity, can also activate NOD1 and NOD2. This was demonstrated: 1) by using human embryonic kidney epithelial (HEK) 293 Cells transfected with a NF-κB reporter plasmid in combination with NOD1 or NOD2 expression plasmids; 2) by inhibiting DMXAA-induced chemokine (CXCL10) mRNA and protein production in the AB12 Mesothelioma Cell Line using a pharmacological inhibitor of RICK kinase, SB20358; and 3) by using small interfering RNA to knock down NOD2 and lentiviral short hairpin RNA to knock down RICK. These findings expand the potential ligands for the NOD-like receptors, suggesting that other xanthone compounds may act similarly and could be developed as anti-tumor agents. This information also expands our knowledge on the mechanisms of action of the anti-tumor agent DMXAA (currently in clinical trials) and may be important for its biological activity.

  • Gene therapy using adenovirus carrying the herpes simplex-thymidine kinase gene to treat in vivo models of human malignant Mesothelioma and lung cancer.
    American journal of respiratory cell and molecular biology, 1995
    Co-Authors: Harry C. Hwang, W R Smythe, A A Elshami, John C. Kucharczuk, Kunjlata M. Amin, John P. Williams, Leslie A. Litzky, Larry R. Kaiser, Steven M Albelda
    Abstract:

    Previous studies have shown adenoviral transfer of the herpes simplex virus thymidine kinase (HSVtk) gene followed by the anti-viral drug ganciclovir (GCV) can be used to successfully treat established human Mesothelioma tumors growing within the peritoneal cavities of severe combined immune deficient (SCID) mice. These findings raised a number of questions important to the applicability, efficiency, and safety of this treatment strategy. In this report, we have further characterized the use of recombinant adenovirus carrying the HSVtk gene to treat Mesothelioma and other localized malignancies. Our results indicate that the Ad.RSVtk/GCV system is effective in causing tumor regression in animals inoculated with another Mesothelioma Cell Line and a lung cancer Cell Line and that animals with bulky disease can be successfully treated. Effects are seen at a wide range of virus doses and significant anti-tumor activity is present at doses of ganciclovir that are clinically achievable. Finally, this treatment ...

  • Pleural-based Mesothelioma in immune competent rats: A model to study adenoviral gene transfer
    The Annals of thoracic surgery, 1995
    Co-Authors: John C. Kucharczuk, Steven M Albelda, W. Roy Smythe, Harry C. Hwang, A A Elshami, Kunjlata M. Amin, Leslie A. Litzky, Hong Bing Zhang, James S. Tomlinson, Larry R. Kaiser
    Abstract:

    Background. Despite multimodality approaches, pleural-based malignant Mesothelioma remains a disease with a very poor prognosis. Novel therapeutic strategies such as gene therapy clearly are needed to improve the survival of patients with this neoplasm. To aid in the evaluation of new treatment strategies, animal models that closely mimic human disease are required. This article describes the establishment of a pleural-based model of malignant Mesothelioma in immune-competent Fischer rats. Methods. Via a modified left anterior lateral thorocotomy, a syngeneic malignant Mesothelioma Cell Line, called II-45, was placed into the pleural cavity of Fischer rats. Results. Placement of II-45 Cells into the pleural cavity of Fischer rats results in a model of pleural Mesothelioma that closely resembles the disease seen in patients and is highly reproducible, with animals dying within 1 month. We also demonstrate the feasibility of adenoviral-mediated gene transfer to normal mesothelial Cells lining the pleural cavity, as well as to malignant Cells deep within the substance of pleural-based malignant Mesothelioma. Conclusions. The model described here offers the opportunity to study a variety of new treatment modalities, especially somatic gene transfer, against pleural-based malignant Mesothelioma in an immune competent setting.

  • The role of immunosuppression in the efficacy of cancer gene therapy using adenovirus transfer of the herpes simplex thymidine kinase gene.
    Annals of surgery, 1995
    Co-Authors: A A Elshami, Steven M Albelda, Harry C. Hwang, W R Smythe, John C. Kucharczuk, Kunjlata M. Amin, Leslie A. Litzky, Daniel H. Sterman, Larry R. Kaiser
    Abstract:

    Objective To determine whether the immune system limits or improves the therapeutic efficacy of an adenovirus vector expressing the herpes simplex thymidine kinase (HSVtk) gene in a subcutaneous tumor model. Background Data Enhanced immune reactions against tumors may be therapeutically useful. However, recent studies with adenoviral vectors show that immune responses limit the efficacy and persistence of gene expression. The effect of the immune response on cancer gene therapy with HSVtk gene delivery by an adenovirus vector followed by treatment with ganciclovir is unclear. Methods After adenoviral transduction of a Fischer rat syngeneic Mesothelioma Cell Line with the HSVtk gene in vitro, subcutaneous flank tumors were established. The ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Fischer rats, immunodeficient nude rats, and Fischer rats immunosuppressed with cyclosporin. Results HSVtk/ganciclovir therapy was more effective in nude rats and immunosuppressed Fischer rats than in immunocompetent Fischer rats. Conclusion These results indicate that the immune response against adenovirally transduced Cells limits the efficacy of the HSVtk/ganciclovir system and that immunosuppression appears to be a useful adjunct. These findings have important implications for clinical trials using currently available adenovirus vectors as well as for future vector design.

Larry R. Kaiser - One of the best experts on this subject based on the ideXlab platform.

  • Gene therapy using adenovirus carrying the herpes simplex-thymidine kinase gene to treat in vivo models of human malignant Mesothelioma and lung cancer.
    American journal of respiratory cell and molecular biology, 1995
    Co-Authors: Harry C. Hwang, W R Smythe, A A Elshami, John C. Kucharczuk, Kunjlata M. Amin, John P. Williams, Leslie A. Litzky, Larry R. Kaiser, Steven M Albelda
    Abstract:

    Previous studies have shown adenoviral transfer of the herpes simplex virus thymidine kinase (HSVtk) gene followed by the anti-viral drug ganciclovir (GCV) can be used to successfully treat established human Mesothelioma tumors growing within the peritoneal cavities of severe combined immune deficient (SCID) mice. These findings raised a number of questions important to the applicability, efficiency, and safety of this treatment strategy. In this report, we have further characterized the use of recombinant adenovirus carrying the HSVtk gene to treat Mesothelioma and other localized malignancies. Our results indicate that the Ad.RSVtk/GCV system is effective in causing tumor regression in animals inoculated with another Mesothelioma Cell Line and a lung cancer Cell Line and that animals with bulky disease can be successfully treated. Effects are seen at a wide range of virus doses and significant anti-tumor activity is present at doses of ganciclovir that are clinically achievable. Finally, this treatment ...

  • Pleural-based Mesothelioma in immune competent rats: A model to study adenoviral gene transfer
    The Annals of thoracic surgery, 1995
    Co-Authors: John C. Kucharczuk, Steven M Albelda, W. Roy Smythe, Harry C. Hwang, A A Elshami, Kunjlata M. Amin, Leslie A. Litzky, Hong Bing Zhang, James S. Tomlinson, Larry R. Kaiser
    Abstract:

    Background. Despite multimodality approaches, pleural-based malignant Mesothelioma remains a disease with a very poor prognosis. Novel therapeutic strategies such as gene therapy clearly are needed to improve the survival of patients with this neoplasm. To aid in the evaluation of new treatment strategies, animal models that closely mimic human disease are required. This article describes the establishment of a pleural-based model of malignant Mesothelioma in immune-competent Fischer rats. Methods. Via a modified left anterior lateral thorocotomy, a syngeneic malignant Mesothelioma Cell Line, called II-45, was placed into the pleural cavity of Fischer rats. Results. Placement of II-45 Cells into the pleural cavity of Fischer rats results in a model of pleural Mesothelioma that closely resembles the disease seen in patients and is highly reproducible, with animals dying within 1 month. We also demonstrate the feasibility of adenoviral-mediated gene transfer to normal mesothelial Cells lining the pleural cavity, as well as to malignant Cells deep within the substance of pleural-based malignant Mesothelioma. Conclusions. The model described here offers the opportunity to study a variety of new treatment modalities, especially somatic gene transfer, against pleural-based malignant Mesothelioma in an immune competent setting.

  • The role of immunosuppression in the efficacy of cancer gene therapy using adenovirus transfer of the herpes simplex thymidine kinase gene.
    Annals of surgery, 1995
    Co-Authors: A A Elshami, Steven M Albelda, Harry C. Hwang, W R Smythe, John C. Kucharczuk, Kunjlata M. Amin, Leslie A. Litzky, Daniel H. Sterman, Larry R. Kaiser
    Abstract:

    Objective To determine whether the immune system limits or improves the therapeutic efficacy of an adenovirus vector expressing the herpes simplex thymidine kinase (HSVtk) gene in a subcutaneous tumor model. Background Data Enhanced immune reactions against tumors may be therapeutically useful. However, recent studies with adenoviral vectors show that immune responses limit the efficacy and persistence of gene expression. The effect of the immune response on cancer gene therapy with HSVtk gene delivery by an adenovirus vector followed by treatment with ganciclovir is unclear. Methods After adenoviral transduction of a Fischer rat syngeneic Mesothelioma Cell Line with the HSVtk gene in vitro, subcutaneous flank tumors were established. The ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Fischer rats, immunodeficient nude rats, and Fischer rats immunosuppressed with cyclosporin. Results HSVtk/ganciclovir therapy was more effective in nude rats and immunosuppressed Fischer rats than in immunocompetent Fischer rats. Conclusion These results indicate that the immune response against adenovirally transduced Cells limits the efficacy of the HSVtk/ganciclovir system and that immunosuppression appears to be a useful adjunct. These findings have important implications for clinical trials using currently available adenovirus vectors as well as for future vector design.

A A Elshami - One of the best experts on this subject based on the ideXlab platform.

  • Gene therapy using adenovirus carrying the herpes simplex-thymidine kinase gene to treat in vivo models of human malignant Mesothelioma and lung cancer.
    American journal of respiratory cell and molecular biology, 1995
    Co-Authors: Harry C. Hwang, W R Smythe, A A Elshami, John C. Kucharczuk, Kunjlata M. Amin, John P. Williams, Leslie A. Litzky, Larry R. Kaiser, Steven M Albelda
    Abstract:

    Previous studies have shown adenoviral transfer of the herpes simplex virus thymidine kinase (HSVtk) gene followed by the anti-viral drug ganciclovir (GCV) can be used to successfully treat established human Mesothelioma tumors growing within the peritoneal cavities of severe combined immune deficient (SCID) mice. These findings raised a number of questions important to the applicability, efficiency, and safety of this treatment strategy. In this report, we have further characterized the use of recombinant adenovirus carrying the HSVtk gene to treat Mesothelioma and other localized malignancies. Our results indicate that the Ad.RSVtk/GCV system is effective in causing tumor regression in animals inoculated with another Mesothelioma Cell Line and a lung cancer Cell Line and that animals with bulky disease can be successfully treated. Effects are seen at a wide range of virus doses and significant anti-tumor activity is present at doses of ganciclovir that are clinically achievable. Finally, this treatment ...

  • Pleural-based Mesothelioma in immune competent rats: A model to study adenoviral gene transfer
    The Annals of thoracic surgery, 1995
    Co-Authors: John C. Kucharczuk, Steven M Albelda, W. Roy Smythe, Harry C. Hwang, A A Elshami, Kunjlata M. Amin, Leslie A. Litzky, Hong Bing Zhang, James S. Tomlinson, Larry R. Kaiser
    Abstract:

    Background. Despite multimodality approaches, pleural-based malignant Mesothelioma remains a disease with a very poor prognosis. Novel therapeutic strategies such as gene therapy clearly are needed to improve the survival of patients with this neoplasm. To aid in the evaluation of new treatment strategies, animal models that closely mimic human disease are required. This article describes the establishment of a pleural-based model of malignant Mesothelioma in immune-competent Fischer rats. Methods. Via a modified left anterior lateral thorocotomy, a syngeneic malignant Mesothelioma Cell Line, called II-45, was placed into the pleural cavity of Fischer rats. Results. Placement of II-45 Cells into the pleural cavity of Fischer rats results in a model of pleural Mesothelioma that closely resembles the disease seen in patients and is highly reproducible, with animals dying within 1 month. We also demonstrate the feasibility of adenoviral-mediated gene transfer to normal mesothelial Cells lining the pleural cavity, as well as to malignant Cells deep within the substance of pleural-based malignant Mesothelioma. Conclusions. The model described here offers the opportunity to study a variety of new treatment modalities, especially somatic gene transfer, against pleural-based malignant Mesothelioma in an immune competent setting.

  • The role of immunosuppression in the efficacy of cancer gene therapy using adenovirus transfer of the herpes simplex thymidine kinase gene.
    Annals of surgery, 1995
    Co-Authors: A A Elshami, Steven M Albelda, Harry C. Hwang, W R Smythe, John C. Kucharczuk, Kunjlata M. Amin, Leslie A. Litzky, Daniel H. Sterman, Larry R. Kaiser
    Abstract:

    Objective To determine whether the immune system limits or improves the therapeutic efficacy of an adenovirus vector expressing the herpes simplex thymidine kinase (HSVtk) gene in a subcutaneous tumor model. Background Data Enhanced immune reactions against tumors may be therapeutically useful. However, recent studies with adenoviral vectors show that immune responses limit the efficacy and persistence of gene expression. The effect of the immune response on cancer gene therapy with HSVtk gene delivery by an adenovirus vector followed by treatment with ganciclovir is unclear. Methods After adenoviral transduction of a Fischer rat syngeneic Mesothelioma Cell Line with the HSVtk gene in vitro, subcutaneous flank tumors were established. The ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Fischer rats, immunodeficient nude rats, and Fischer rats immunosuppressed with cyclosporin. Results HSVtk/ganciclovir therapy was more effective in nude rats and immunosuppressed Fischer rats than in immunocompetent Fischer rats. Conclusion These results indicate that the immune response against adenovirally transduced Cells limits the efficacy of the HSVtk/ganciclovir system and that immunosuppression appears to be a useful adjunct. These findings have important implications for clinical trials using currently available adenovirus vectors as well as for future vector design.

Harry C. Hwang - One of the best experts on this subject based on the ideXlab platform.

  • Gene therapy using adenovirus carrying the herpes simplex-thymidine kinase gene to treat in vivo models of human malignant Mesothelioma and lung cancer.
    American journal of respiratory cell and molecular biology, 1995
    Co-Authors: Harry C. Hwang, W R Smythe, A A Elshami, John C. Kucharczuk, Kunjlata M. Amin, John P. Williams, Leslie A. Litzky, Larry R. Kaiser, Steven M Albelda
    Abstract:

    Previous studies have shown adenoviral transfer of the herpes simplex virus thymidine kinase (HSVtk) gene followed by the anti-viral drug ganciclovir (GCV) can be used to successfully treat established human Mesothelioma tumors growing within the peritoneal cavities of severe combined immune deficient (SCID) mice. These findings raised a number of questions important to the applicability, efficiency, and safety of this treatment strategy. In this report, we have further characterized the use of recombinant adenovirus carrying the HSVtk gene to treat Mesothelioma and other localized malignancies. Our results indicate that the Ad.RSVtk/GCV system is effective in causing tumor regression in animals inoculated with another Mesothelioma Cell Line and a lung cancer Cell Line and that animals with bulky disease can be successfully treated. Effects are seen at a wide range of virus doses and significant anti-tumor activity is present at doses of ganciclovir that are clinically achievable. Finally, this treatment ...

  • Pleural-based Mesothelioma in immune competent rats: A model to study adenoviral gene transfer
    The Annals of thoracic surgery, 1995
    Co-Authors: John C. Kucharczuk, Steven M Albelda, W. Roy Smythe, Harry C. Hwang, A A Elshami, Kunjlata M. Amin, Leslie A. Litzky, Hong Bing Zhang, James S. Tomlinson, Larry R. Kaiser
    Abstract:

    Background. Despite multimodality approaches, pleural-based malignant Mesothelioma remains a disease with a very poor prognosis. Novel therapeutic strategies such as gene therapy clearly are needed to improve the survival of patients with this neoplasm. To aid in the evaluation of new treatment strategies, animal models that closely mimic human disease are required. This article describes the establishment of a pleural-based model of malignant Mesothelioma in immune-competent Fischer rats. Methods. Via a modified left anterior lateral thorocotomy, a syngeneic malignant Mesothelioma Cell Line, called II-45, was placed into the pleural cavity of Fischer rats. Results. Placement of II-45 Cells into the pleural cavity of Fischer rats results in a model of pleural Mesothelioma that closely resembles the disease seen in patients and is highly reproducible, with animals dying within 1 month. We also demonstrate the feasibility of adenoviral-mediated gene transfer to normal mesothelial Cells lining the pleural cavity, as well as to malignant Cells deep within the substance of pleural-based malignant Mesothelioma. Conclusions. The model described here offers the opportunity to study a variety of new treatment modalities, especially somatic gene transfer, against pleural-based malignant Mesothelioma in an immune competent setting.

  • The role of immunosuppression in the efficacy of cancer gene therapy using adenovirus transfer of the herpes simplex thymidine kinase gene.
    Annals of surgery, 1995
    Co-Authors: A A Elshami, Steven M Albelda, Harry C. Hwang, W R Smythe, John C. Kucharczuk, Kunjlata M. Amin, Leslie A. Litzky, Daniel H. Sterman, Larry R. Kaiser
    Abstract:

    Objective To determine whether the immune system limits or improves the therapeutic efficacy of an adenovirus vector expressing the herpes simplex thymidine kinase (HSVtk) gene in a subcutaneous tumor model. Background Data Enhanced immune reactions against tumors may be therapeutically useful. However, recent studies with adenoviral vectors show that immune responses limit the efficacy and persistence of gene expression. The effect of the immune response on cancer gene therapy with HSVtk gene delivery by an adenovirus vector followed by treatment with ganciclovir is unclear. Methods After adenoviral transduction of a Fischer rat syngeneic Mesothelioma Cell Line with the HSVtk gene in vitro, subcutaneous flank tumors were established. The ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Fischer rats, immunodeficient nude rats, and Fischer rats immunosuppressed with cyclosporin. Results HSVtk/ganciclovir therapy was more effective in nude rats and immunosuppressed Fischer rats than in immunocompetent Fischer rats. Conclusion These results indicate that the immune response against adenovirally transduced Cells limits the efficacy of the HSVtk/ganciclovir system and that immunosuppression appears to be a useful adjunct. These findings have important implications for clinical trials using currently available adenovirus vectors as well as for future vector design.

E. Taillandier - One of the best experts on this subject based on the ideXlab platform.

  • Transfer into a Mesothelioma Cell Line of tumor suppressor gene p16 by cholesterol-based cationic lipids.
    Biochimica et Biophysica Acta, 2003
    Co-Authors: S. Piperno-neumann, O. Oudar, P. Reynier, D. Briane, A. Cao, M.c. Jaurand, R. Naejus, M. Kraemer, J.l. Breau, E. Taillandier
    Abstract:

    In this work, the tumor suppressor gene p16 was efficiently transferred into FR Cells isolated from a patient with malignant Mesothelioma using cationic liposomes prepared from trimethyl aminoethane carbamoyl cholesterol (TMAEC-Chol) and triethyl aminopropane carbamoyl cholesterol (TEAPC-Chol). This transfer was performed after preliminary assays were undertaken to find the optimal transfection conditions. Results showed that an efficient transfer of plasmids containing the reporter gene pCMV-beta galactosidase vectorized by TMAEC-Chol/DOPE and TEAPC-Chol/DOPE liposomes into Mesothelioma FR Cells was obtained as assessed by luminometric measurements of beta-galactosidase activity. Cytotoxicity studied by MTT test showed that at concentrations used for this study, the cationic liposomes have no effect on Cell growth. Transfer into Mesothelioma FR Cells of a plasmid construct containing the tumor suppressor gene p16 was carried out with these liposomes. Western blotting and immunofluorescence showed the presence of p16 in treated Cells. An inhibition of Cell growth was observed, indicating that efficient tumor suppressor gene transfer can be performed by using cationic liposomes.

  • Transfer into a Mesothelioma Cell Line of tumor suppressor gene p16 by cholesterol-based cationic lipids
    Biochimica et Biophysica Acta (BBA) - Biomembranes, 2003
    Co-Authors: S. Piperno-neumann, O. Oudar, P. Reynier, D. Briane, A. Cao, M.c. Jaurand, R. Naejus, M. Kraemer, J.l. Breau, E. Taillandier
    Abstract:

    AbstractIn this work, the tumor suppressor gene p16 was efficiently transferred into FR Cells isolated from a patient with malignant Mesothelioma using cationic liposomes prepared from trimethyl aminoethane carbamoyl cholesterol (TMAEC-Chol) and triethyl aminopropane carbamoyl cholesterol (TEAPC-Chol). This transfer was performed after preliminary assays were undertaken to find the optimal transfection conditions. Results showed that an efficient transfer of plasmids containing the reporter gene pCMV-β galactosidase vectorized by TMAEC-Chol/DOPE and TEAPC-Chol/DOPE liposomes into Mesothelioma FR Cells was obtained as assessed by luminometric measurements of β-galactosidase activity. Cytotoxicity studied by MTT test showed that at concentrations used for this study, the cationic liposomes have no effect on Cell growth. Transfer into Mesothelioma FR Cells of a plasmid construct containing the tumor suppressor gene p16 was carried out with these liposomes. Western blotting and immunofluorescence showed the presence of p16 in treated Cells. An inhibition of Cell growth was observed, indicating that efficient tumor suppressor gene transfer can be performed by using cationic liposomes