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  1. Article ; Online: Advent and maturation of regenerative medicine.

    Mhashilkar, Abner M / Atala, Anthony

    Current stem cell research & therapy

    2012  Volume 7, Issue 6, Page(s) 430–445

    Abstract: The field of regenerative medicine (RM), encompassing stem cell (SC) technologies, therapeutics, tissue engineering (TE), biomaterials, scaffolds and other enabling technologies provides a wide gamut of tools and tracks to combat, manage and hopefully ... ...

    Abstract The field of regenerative medicine (RM), encompassing stem cell (SC) technologies, therapeutics, tissue engineering (TE), biomaterials, scaffolds and other enabling technologies provides a wide gamut of tools and tracks to combat, manage and hopefully cure serious human and animal injuries, dysfunctions and diseases. This review illustrates the trends that are becoming the major platforms in this field. The last 10 years in itself has seen major definitive observations, including multi-track directives of adult stem cell translational technologies, tissue and organ engineering protocols, iPS cell applications and understanding of the role of cancer stem cells to develop effective anti-cancer regimens. With the rapid advances of RM translational research, further advances are expected to be implemented for personalized repair and curative outcomes. RM future is bright although laden with challenges of global fragmentation which needs coherent consolidation, stringent cost and time effective regulation and long-term funding mechanisms, so clinical and diagnostic solutions are realized and recognized to combat unmet medical needs.
    MeSH term(s) Adult Stem Cells/physiology ; Animals ; Biocompatible Materials/therapeutic use ; Humans ; Neoplasms/therapy ; Neoplastic Stem Cells/physiology ; Regenerative Medicine/trends ; Stem Cell Transplantation/methods ; Tissue Engineering ; Tissue Scaffolds/statistics & numerical data ; Translational Medical Research ; Wounds and Injuries/therapy
    Chemical Substances Biocompatible Materials
    Language English
    Publishing date 2012-11-22
    Publishing country United Arab Emirates
    Document type Journal Article ; Review
    ZDB-ID 2251937-3
    ISSN 2212-3946 ; 1574-888X
    ISSN (online) 2212-3946
    ISSN 1574-888X
    DOI 10.2174/157488812804484657
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  2. Article ; Online: Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont.

    Bennuru, Sasisekhar / Cotton, James A / Ribeiro, Jose M C / Grote, Alexandra / Harsha, Bhavana / Holroyd, Nancy / Mhashilkar, Amruta / Molina, Douglas M / Randall, Arlo Z / Shandling, Adam D / Unnasch, Thomas R / Ghedin, Elodie / Berriman, Matthew / Lustigman, Sara / Nutman, Thomas B

    mBio

    2016  Volume 7, Issue 6

    Abstract: Onchocerciasis (river blindness) is a neglected tropical disease that has been successfully targeted by mass drug treatment programs in the Americas and small parts of Africa. Achieving the long-term goal of elimination of onchocerciasis, however, ... ...

    Abstract Onchocerciasis (river blindness) is a neglected tropical disease that has been successfully targeted by mass drug treatment programs in the Americas and small parts of Africa. Achieving the long-term goal of elimination of onchocerciasis, however, requires additional tools, including drugs, vaccines, and biomarkers of infection. Here, we describe the transcriptome and proteome profiles of the major vector and the human host stages (L1, L2, L3, molting L3, L4, adult male, and adult female) of Onchocerca volvulus along with the proteome of each parasitic stage and of its Wolbachia endosymbiont (wOv). In so doing, we have identified stage-specific pathways important to the parasite's adaptation to its human host during its early development. Further, we generated a protein array that, when screened with well-characterized human samples, identified novel diagnostic biomarkers of O. volvulus infection and new potential vaccine candidates. This immunomic approach not only demonstrates the power of this postgenomic discovery platform but also provides additional tools for onchocerciasis control programs.
    Importance: The global onchocerciasis (river blindness) elimination program will have to rely on the development of new tools (drugs, vaccines, biomarkers) to achieve its goals by 2025. As an adjunct to the completed genomic sequencing of O. volvulus, we used a comprehensive proteomic and transcriptomic profiling strategy to gain a comprehensive understanding of both the vector-derived and human host-derived parasite stages. In so doing, we have identified proteins and pathways that enable novel drug targeting studies and the discovery of novel vaccine candidates, as well as useful biomarkers of active infection.
    MeSH term(s) Animals ; Onchocerca volvulus/chemistry ; Onchocerca volvulus/genetics ; Onchocerca volvulus/growth & development ; Proteome ; Symbiosis ; Transcriptome ; Wolbachia/chemistry ; Wolbachia/genetics ; Wolbachia/growth & development
    Chemical Substances Proteome
    Language English
    Publishing date 2016-11-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.02028-16
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  3. Article: Cytokine- and chemokine-based gene therapy for cancer.

    Chada, Sunil / Ramesh, Rajagopal / Mhashilkar, Abner M

    Current opinion in molecular therapeutics

    2003  Volume 5, Issue 5, Page(s) 463–474

    Abstract: Cytokines are protein/glycoprotein messengers of the immune system and have distinct autocrine and paracrine functions to modulate immunity. Recombinant cytokine proteins have been employed as biological drugs for cancer, viral and autoimmune targets. ... ...

    Abstract Cytokines are protein/glycoprotein messengers of the immune system and have distinct autocrine and paracrine functions to modulate immunity. Recombinant cytokine proteins have been employed as biological drugs for cancer, viral and autoimmune targets. Unfortunately, systemic delivery of pharmacological doses of proteins often results in severe side effects and toxicities. As these therapeutic proteins tend to have very short half-lives and are complex to manufacture and deliver, many investigators are evaluating the genetic delivery of cytokine genes. Here, some of the promising cytokines currently under investigation for cancer therapies are examined, including interleukin (IL)-2, IL-4, IL-12, IL-24, interferon (IFN)-alpha, IFN beta, IFN gamma, granulocyte-monocyte colony-stimulating factor and tumor necrosis factor (TNF)-alpha. Chemokines are smaller chemotactic cytokines which induce migration of leukocytes, activate inflammatory responses, and are implicated in the regulation of tumor development and growth. Chemokines can modulate tumor growth via regulation of tumor-associated angiogenesis, by activation of host immunological responses or by direct inhibition of tumor cell proliferation. In this review, chemokines that have been proposed as antitumor drugs will be discussed, including Glu-Leu-Arg (ELR)-negative chemokines such as IP-10, MCP-3, MIG and SDF-1 alpha from the human CXC and C-C chemokine families.
    MeSH term(s) Animals ; Chemokines/genetics ; Chemokines/therapeutic use ; Clinical Trials as Topic ; Cytokines/genetics ; Cytokines/therapeutic use ; Genetic Therapy ; Humans ; Neoplasms/genetics ; Neoplasms/therapy
    Chemical Substances Chemokines ; Cytokines
    Language English
    Publishing date 2003-10
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 2022273-7
    ISSN 1464-8431
    ISSN 1464-8431
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5272: Show issues Location:
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  4. Article: Technology evaluation: StealthVector (HIV) Enzo.

    Günzburg, W / Mhashilkar, A M / Hindi, M

    Current opinion in molecular therapeutics

    1999  Volume 1, Issue 5, Page(s) 651–657

    Abstract: Efficient inhibition of human immunodeficiency virus-1 (HIV-1) replication with intracellularly expressed antiviral genes would be an important step toward clinical gene therapy for HIV-1 disease. Enzo Biochem is investigating and developing antisense ... ...

    Abstract Efficient inhibition of human immunodeficiency virus-1 (HIV-1) replication with intracellularly expressed antiviral genes would be an important step toward clinical gene therapy for HIV-1 disease. Enzo Biochem is investigating and developing antisense genes as a potential gene therapy approach against a variety of conditions including acquired immunodeficiency syndrome (AIDS), cancer and hepatitis. The subsidiary of Enzo Biochem, Enzo Therapeutics, utilized its StealthVector technology and initiated phase I trials in July 1998 [291511,307156]. StealthVector, which is comprised of independent antisense sequences directed against two functional HIV-1 regions, is involved in regulation of gene expression soon after HIV infection, transactivation response (TAR) and tat/rev. StealthVector localizes primarily in the cell nucleus, where it could be most effective in inhibiting viral growth.
    MeSH term(s) Biotechnology ; DNA, Antisense/genetics ; DNA, Antisense/therapeutic use ; Genetic Therapy/adverse effects ; Genetic Therapy/methods ; Genetic Vectors ; HIV Infections/therapy ; HIV-1/genetics ; Humans
    Chemical Substances DNA, Antisense
    Language English
    Publishing date 1999-10
    Publishing country England
    Document type Clinical Trial ; Clinical Trial, Phase I ; Journal Article ; Review
    ZDB-ID 2022273-7
    ISSN 1464-8431
    ISSN 1464-8431
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  5. Article: Tumor suppressor MDA-7/IL-24 selectively inhibits vascular smooth muscle cell growth and migration.

    Chen, Jiyuan / Chada, Sunil / Mhashilkar, Abner / Miano, Joseph M

    Molecular therapy : the journal of the American Society of Gene Therapy

    2003  Volume 8, Issue 2, Page(s) 220–229

    Abstract: Abnormalities in smooth muscle cell (SMC) proliferation and differentiation underlie the pathogenesis of proliferative vascular diseases. MDA-7 (HUGO approved symbol IL24) is a unique gene, originally identified as a tumor suppressor and more recently ... ...

    Abstract Abnormalities in smooth muscle cell (SMC) proliferation and differentiation underlie the pathogenesis of proliferative vascular diseases. MDA-7 (HUGO approved symbol IL24) is a unique gene, originally identified as a tumor suppressor and more recently shown to have cytokine activity. MDA-7/IL24 has been implicated in apoptosis and cellular differentiation in tumor cells and in tumor invasion/metastasis in clinical specimens-properties central to SMC remodeling during proliferative vascular diseases. In this study, we evaluated the effects of overexpressing MDA-7/IL24 in various SMC: the apparently "normal" rat PAC1 cell line, primary human coronary artery SMC, and normal rat aortic SMC. We transduced SMC with adenovirus-mda7 (Ad-mda7) or control virus (Ad-Luc) and assessed cell viability, apoptosis, and migration. Ad-mda7 suppressed PAC1 cell growth in a dose-dependent manner while having no effect on normal primary human coronary artery cells or rat aortic SMC, despite strong expression of the MDA-7 transgene in all SMC. Similarly, Ad-mda7 treatment induced apoptosis in PAC1 cells with essentially no effect on normal coronary and rat aortic SMC. Ad-mda7 also inhibited serum-stimulated PAC1 cell migration. Karyotype analysis of PAC1 cells revealed that they exhibit multiple chromosomal aberrations. Importantly, recombinant MDA-7 did not elicit cell death or STAT-3 activation in PAC1 SMC, suggesting that the effects of Ad-mda7 were mediated through an intracellular pathway. These data demonstrate that Ad-mda7 exhibits selectivity in apoptosis induction and growth suppression in an atypical SMC line, raising new questions pertaining to heterogeneity in SMC death susceptibility.
    MeSH term(s) Adenoviridae/genetics ; Animals ; Apoptosis ; Cell Division ; Cell Movement ; Cells, Cultured ; Gene Expression ; Genes, Tumor Suppressor ; Humans ; Interleukins/genetics ; Interleukins/metabolism ; Myocytes, Smooth Muscle/cytology ; Myocytes, Smooth Muscle/metabolism ; Rats ; Transduction, Genetic
    Chemical Substances Interleukins ; interleukin-24
    Language English
    Publishing date 2003-07-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/s1525-0016(03)00176-x
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    Zs.A 5640: Show issues Location:
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  6. Book ; Online: HEPCloud, an Elastic Hybrid HEP Facility using an Intelligent Decision Support System

    Mhashilkar, Parag / Altunay, Mine / Berman, Eileen / Dagenhart, David / Fuess, Stuart / Holzman, Burt / Kowalkowski, James / Litvintsev, Dmitry / Lu, Qiming / Moibenko, Alexander / Paterno, Marc / Spentzouris, Panagiotis / Timm, Steven / Tiradani, Anthony / Vaandering, Eric / Hover, John / Bejar, Jose Caballero

    2019  

    Abstract: HEPCloud is rapidly becoming the primary system for provisioning compute resources for all Fermilab-affiliated experiments. In order to reliably meet the peak demands of the next generation of High Energy Physics experiments, Fermilab must plan to ... ...

    Abstract HEPCloud is rapidly becoming the primary system for provisioning compute resources for all Fermilab-affiliated experiments. In order to reliably meet the peak demands of the next generation of High Energy Physics experiments, Fermilab must plan to elastically expand its computational capabilities to cover the forecasted need. Commercial cloud and allocation-based High Performance Computing (HPC) resources both have explicit and implicit costs that must be considered when deciding when to provision these resources, and at which scale. In order to support such provisioning in a manner consistent with organizational business rules and budget constraints, we have developed a modular intelligent decision support system (IDSS) to aid in the automatic provisioning of resources spanning multiple cloud providers, multiple HPC centers, and grid computing federations. In this paper, we discuss the goals and architecture of the HEPCloud Facility, the architecture of the IDSS, and our early experience in using the IDSS for automated facility expansion both at Fermi and Brookhaven National Laboratory.

    Comment: 8 pages
    Keywords Computer Science - Distributed ; Parallel ; and Cluster Computing
    Publishing date 2019-04-18
    Publishing country us
    Document type Book ; Online
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  7. Article: Activation of the Fas-FasL signaling pathway by MDA-7/IL-24 kills human ovarian cancer cells.

    Gopalan, Began / Litvak, Anya / Sharma, Sikha / Mhashilkar, Abner M / Chada, Sunil / Ramesh, Rajagopal

    Cancer research

    2005  Volume 65, Issue 8, Page(s) 3017–3024

    Abstract: The tumor-suppressive activity of melanoma differentiation-associated gene-7 (mda-7), also known as interleukin 24 (IL-24), has been shown in a spectrum of human cancer cells in vitro and in vivo. However, mechanisms responsible for antitumor activity of ...

    Abstract The tumor-suppressive activity of melanoma differentiation-associated gene-7 (mda-7), also known as interleukin 24 (IL-24), has been shown in a spectrum of human cancer cells in vitro and in vivo. However, mechanisms responsible for antitumor activity of mda-7 in human ovarian cancer cells have not been identified. We investigated the therapeutic activity and underlying mechanisms of adenovirus-mediated mda-7 gene (Ad-mda7) transfer in human ovarian cancer cells. Ad-mda7 treatment resulted in overexpression of MDA-7/IL-24 protein in both ovarian cancer and normal ovarian epithelial cells. However, Ad-mda7 significantly (P = 0.001) inhibited cell proliferation and induced apoptosis only in tumor cells and not in normal cells. Studies addressing the mechanism of action of Ad-mda7-induced tumor cell apoptosis revealed early activation of the transcription factors c-Jun and activating transcription factor 2, which in turn stimulated the transcription of an immediate downstream target, the death-inducer Fas ligand (FasL), and its cognate receptor Fas. Associated with the activation of Fas-FasL was the activation of nuclear factor kappaB and induction of Fas-associated factor 1, Fas-associated death domain, and caspase-8. Promoter-based reporter gene analyses showed that Ad-mda7 specifically activated the Fas promoter. Inhibition of Fas using small interfering RNA resulted in a significant decrease in Ad-mda7-mediated tumor cell death. Additionally, blocking of FasL with NOK-1 antibody abrogated Ad-mda7-mediated apoptosis. Collectively, these results show that Ad-mda7-mediated killing of human ovarian cancer cells involves activation of the Fas-FasL signaling pathway, a heretofore unrecognized mediator of MDA-7 apoptosis induction.
    MeSH term(s) Adenoviridae/genetics ; Apoptosis/genetics ; Apoptosis/physiology ; Cell Cycle/genetics ; Cell Cycle/physiology ; Cell Line, Tumor ; Cell Proliferation ; Fas Ligand Protein ; Female ; Gene Transfer Techniques ; Genes, Tumor Suppressor ; Genetic Therapy/methods ; Humans ; Interleukins/biosynthesis ; Interleukins/genetics ; Membrane Glycoproteins/antagonists & inhibitors ; Membrane Glycoproteins/biosynthesis ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/physiology ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/therapy ; Promoter Regions, Genetic ; Signal Transduction ; fas Receptor/biosynthesis ; fas Receptor/genetics ; fas Receptor/physiology
    Chemical Substances FASLG protein, human ; Fas Ligand Protein ; Interleukins ; Membrane Glycoproteins ; fas Receptor ; interleukin-24
    Language English
    Publishing date 2005-04-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-04-3758
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    Uh III Zs.135/5: Show issues Location:
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  8. Article ; Online: Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont

    Sasisekhar Bennuru / James A. Cotton / Jose M. C. Ribeiro / Alexandra Grote / Bhavana Harsha / Nancy Holroyd / Amruta Mhashilkar / Douglas M. Molina / Arlo Z. Randall / Adam D. Shandling / Thomas R. Unnasch / Elodie Ghedin / Matthew Berriman / Sara Lustigman / Thomas B. Nutman

    mBio, Vol 7, Iss 6, p e02028-

    2016  Volume 16

    Abstract: Onchocerciasis (river blindness) is a neglected tropical disease that has been successfully targeted by mass drug treatment programs in the Americas and small parts of Africa. Achieving the long-term goal of elimination of onchocerciasis, however, ... ...

    Abstract Onchocerciasis (river blindness) is a neglected tropical disease that has been successfully targeted by mass drug treatment programs in the Americas and small parts of Africa. Achieving the long-term goal of elimination of onchocerciasis, however, requires additional tools, including drugs, vaccines, and biomarkers of infection. Here, we describe the transcriptome and proteome profiles of the major vector and the human host stages (L1, L2, L3, molting L3, L4, adult male, and adult female) of Onchocerca volvulus along with the proteome of each parasitic stage and of its Wolbachia endosymbiont (wOv). In so doing, we have identified stage-specific pathways important to the parasite’s adaptation to its human host during its early development. Further, we generated a protein array that, when screened with well-characterized human samples, identified novel diagnostic biomarkers of O. volvulus infection and new potential vaccine candidates. This immunomic approach not only demonstrates the power of this postgenomic discovery platform but also provides additional tools for onchocerciasis control programs.
    Keywords Science ; Q ; Microbiology ; QR1-502
    Subject code 572
    Language English
    Publishing date 2016-11-01T00:00:00Z
    Publisher American Society for Microbiology
    Document type Article ; Online
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  9. Article: Combinatorial synergy induced by adenoviral-mediated mda-7 and Herceptin in Her-2+ breast cancer cells.

    Bocangel, D / Zheng, M / Mhashilkar, A / Liu, Y / Ramesh, R / Hunt, K K / Chada, S

    Cancer gene therapy

    2006  Volume 13, Issue 10, Page(s) 958–968

    Abstract: The melanoma differentiation-associated gene-7 (mda-7) is a member of the interleukin-10 cytokine family and a novel tumor suppressor gene. Adenoviral-mediated mda-7 (Ad-mda7) gene transfer has tumor-specific growth inhibitory and proapoptotic effects in ...

    Abstract The melanoma differentiation-associated gene-7 (mda-7) is a member of the interleukin-10 cytokine family and a novel tumor suppressor gene. Adenoviral-mediated mda-7 (Ad-mda7) gene transfer has tumor-specific growth inhibitory and proapoptotic effects in a broad spectrum of cancer cells. In breast cancer cells, adenoviral-induced mda-7 expression triggers antiproliferative effects by downregulation of survival signals, such as Bcl-2 and Akt. The anti-human epidermal growth factor receptor-2 (Her-2) monoclonal antibody, Trastuzumab (Herceptin), increases the sensitivity of Her-2/neu-overexpressing breast cancer cells to chemotherapeutic agents and radiotherapy. In this study, we evaluate the effects of treatment with Ad-mda7 and Herceptin combination therapy in a panel of Her-2/neu-overexpressing cell lines, and in established tumors in nude mice. Compared to individual treatments, the combination of Ad-mda7 and Herceptin elicits supra-additive antitumor activity in Her-2/neu-overexpressing tumor cell lines: increased cell death, cell cycle block and apoptosis. The Ad-mda7 and Herceptin interaction was shown to be synergistic by isobologram analysis. Ad-mda7 does not alter cell surface Her-2/neu levels, but the combination of Ad-mda7+Herceptin results in increased expression of cell surface E-cadherin with concomitant translocation of beta-catenin from the nucleus to the cell membrane. In vivo, the combination of Ad-mda7 and Herceptin showed significantly increased antitumor activity (P<0.003) against Her-2/neu-overexpressing tumors. These data suggest that the combination of Ad-mda7 with Herceptin may be a novel therapy for breast cancer patients whose tumors overexpress Her-2/neu. The observed synergistic effect may improve treatment options for otherwise poorly responsive, Her-2-positive, breast cancer patients.
    MeSH term(s) Adenoviridae/genetics ; Animals ; Antibodies, Monoclonal/genetics ; Antibodies, Monoclonal, Humanized ; Blotting, Western ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation ; Fluorescent Antibody Technique ; Genetic Vectors ; Humans ; Interleukins/genetics ; Mice ; Mice, Nude ; Trastuzumab
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Interleukins ; interleukin-24 ; Trastuzumab (P188ANX8CK)
    Language English
    Publishing date 2006-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 1212513-1
    ISSN 0929-1903
    ISSN 0929-1903
    DOI 10.1038/sj.cgt.7700972
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    Zs.A 4125: Show issues Location:
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  10. Article: Ectopic production of MDA-7/IL-24 inhibits invasion and migration of human lung cancer cells.

    Ramesh, Rajagopal / Ito, Isao / Gopalan, Began / Saito, Yuji / Mhashilkar, Abner M / Chada, Sunil

    Molecular therapy : the journal of the American Society of Gene Therapy

    2004  Volume 9, Issue 4, Page(s) 510–518

    Abstract: We have previously observed the suppression of lung tumor growth in response to overexpression of melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24; approved gene symbol IL24) in vitro and in vivo. MDA-7/IL-24 exerts its tumor- ... ...

    Abstract We have previously observed the suppression of lung tumor growth in response to overexpression of melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24; approved gene symbol IL24) in vitro and in vivo. MDA-7/IL-24 exerts its tumor-suppressive effects by multiple mechanisms, including the activation of the caspase cascade and the inhibition of angiogenesis. In this study, we used an adenoviral vector (Ad-mda7) to examine the effect of the ectopic production of MDA-7/IL-24 on cell migration and invasion by human non-small-cell lung carcinoma cells. Lung tumor cells (H1299 and A549) treated in vitro with Ad-mda7 migrated and invaded less than cells treated with phosphate-buffered saline (PBS) or Ad-Luc (vector control). MDA-7/IL-24 inhibited migration and invasion by down-regulating the production of phosphatidylinositol 3-kinase/protein kinase B, focal adhesion kinase, and matrix metalloproteinase-2 and -9 relative to PBS and Ad-Luc. Furthermore, tumor cells treated with Ad-mda7 ex vivo or with DOTAP:Chol-mda7 complex in vivo formed significantly fewer tumors in an experimental lung metastasis model. These results show that MDA-7/IL-24 inhibits invasion and migration by lung cancer cells by down-regulating proteins associated with these processes, resulting in reduced metastasis. Thus, Ad-mda7 should be considered a therapeutic agent that can inhibit primary tumor growth and prevent metastasis.
    MeSH term(s) Adenoviridae/genetics ; Caspases/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Survival ; Down-Regulation ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; Gelatin/chemistry ; Gene Transfer Techniques ; Genes, Tumor Suppressor ; Genetic Therapy/methods ; Humans ; Immunoblotting ; Interleukins/biosynthesis ; Luciferases/metabolism ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis/prevention & control ; Neovascularization, Pathologic ; Phosphatidylinositol 3-Kinases/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Resting Phase, Cell Cycle ; Time Factors
    Chemical Substances Interleukins ; Proto-Oncogene Proteins ; interleukin-24 ; Gelatin (9000-70-8) ; Luciferases (EC 1.13.12.-) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Focal Adhesion Kinase 1 (EC 2.7.10.2) ; Focal Adhesion Protein-Tyrosine Kinases (EC 2.7.10.2) ; PTK2 protein, human (EC 2.7.10.2) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Caspases (EC 3.4.22.-) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
    Language English
    Publishing date 2004-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2004.01.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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