Efficient delivery of liposome-mediated MGMT-siRNA reinforces the cytotoxity of temozolomide in GBM-initiating cells.

Abstract:

:Glioblastoma multiforme (GBM) is one of the most formidable brain tumors with a mean survival period of approximately 12 months. To date, a combination of radiotherapy and chemotherapy with an oral alkylating agent, temozolomide (TMZ), has been used as first-line therapy for glioma. However, the efficacy of chemotherapy for treating GBM is very limited; this is partly because of the high activity levels of the DNA repair protein O⁶-methylguanine-DNA methyltransferase (MGMT) in tumor cells, which creates a resistant phenotype by blunting the therapeutic effect of alkylating agents. Thus, MGMT may be an important determinant of treatment failure and should be considered as a suitable target for intervention, in an effort to improve the therapeutic efficacy of TMZ. In this study, we showed that small-interfering RNA (siRNA)-based downregulation of MGMT could enhance the chemosensitivity of malignant gliomas against TMZ. Notably, TMZ-resistant glioma-initiating cells with increased DNA repair and drug efflux capabilities could be efficiently transduced with MGMT-siRNA by using a novel liposome, LipoTrust. Accordingly, such transduced glioma-initiating cells could be sensitized to TMZ in both in vitro and in vivo tumor models. Taken together, this study provides an experimental basis for the clinical use of such therapeutic combinations.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Kato T,Natsume A,Toda H,Iwamizu H,Sugita T,Hachisu R,Watanabe R,Yuki K,Motomura K,Bankiewicz K,Wakabayashi T

doi

10.1038/gt.2010.88

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

1363-71

issue

11

eissn

0969-7128

issn

1476-5462

pii

gt201088

journal_volume

17

pub_type

杂志文章
  • Disruption of integrin-dependent adhesion and survival of endothelial cells by recombinant adenovirus expressing isolated beta integrin cytoplasmic domains.

    abstract::We explored the possibility of using a genetic approach to inhibit integrin-mediated endothelial cell adhesion and survival. We constructed recombinant adenoviruses (Ads) expressing chimeric proteins consisting of the cytoplasmic and transmembrane domains of integrin beta1 (CH1), beta3 (CH3) or the beta1 transmembrane...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301236

    authors: Oguey D,George PW,Rüegg C

    更新日期:2000-08-01 00:00:00

  • Adenoviral gene transfer into the normal and injured spinal cord: enhanced transgene stability by combined administration of temperature-sensitive virus and transient immune blockade.

    abstract::This study characterized gene transfer into both normal and injured adult rat dorsal spinal cord using first (E1-/E3-) or second (E1-/E2A125/E3-, temperature-sensitive; ts) generation of replication-defective adenoviral (Ad) vectors. A novel immunosuppressive regimen aimed at blocking CD4/CD45 lymphocytic receptors wa...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300774

    authors: Romero MI,Smith GM

    更新日期:1998-12-01 00:00:00

  • Efficient adventitial gene delivery to rabbit carotid artery with cationic polymer-plasmid complexes.

    abstract::Different lipids and cationic polymers were tested in vitro for their ability to transfect rabbit aortic smooth muscle cells and human endothelial cells with lacZ marker gene. Toxicity of the complexes was evaluated with MTT assay. Selected plasmid-polymer complexes with different charge ratios were then tested for in...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300800

    authors: Turunen MP,Hiltunen MO,Ruponen M,Virkamäki L,Szoka FC Jr,Urtti A,Ylä-Herttuala S

    更新日期:1999-01-01 00:00:00

  • Multi-subtype gp160 DNA immunization induces broadly neutralizing anti-HIV antibodies.

    abstract::A highly desirable feature for an human immunodeficiency virus type 1 (HIV-1) vaccine is the ability to induce broadly reactive anti-envelope antibodies that can neutralize primary HIV-1 isolates. Two immunizations with an HIV-1 envelope-encoding plasmid together with recombinant granulocyte-macrophage colony-stimulat...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302275

    authors: Rollman E,Hinkula J,Arteaga J,Zuber B,Kjerrström A,Liu M,Wahren B,Ljungberg K

    更新日期:2004-07-01 00:00:00

  • Effects of dose, intervention time, and radionuclide on sodium iodide symporter (NIS)-targeted radionuclide therapy.

    abstract::The sodium iodide symporter (NIS) mediates iodide uptake into thyrocytes and is the molecular basis of thyroid radioiodine therapy. We previously have shown that NIS gene transfer into the F98 rat gliomas facilitated tumor imaging and increased survival by radioiodine. In this study, we show that: (1) the therapeutic ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302147

    authors: Shen DH,Marsee DK,Schaap J,Yang W,Cho JY,Hinkle G,Nagaraja HN,Kloos RT,Barth RF,Jhiang SM

    更新日期:2004-01-01 00:00:00

  • Antimonocyte chemoattractant protein-1 gene therapy reduces experimental in-stent restenosis in hypercholesterolemic rabbits and monkeys.

    abstract::In-stent restenosis results exclusively from neointimal hyperplasia due to mechanical injury and a foreign body response to the prosthesis. Inflammation mediated by monocyte chemoattractant protein-1 (MCP-1) might therefore underlie in-stent restenosis. We recently devised a new strategy for anti-MCP-1 gene therapy by...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302288

    authors: Ohtani K,Usui M,Nakano K,Kohjimoto Y,Kitajima S,Hirouchi Y,Li XH,Kitamoto S,Takeshita A,Egashira K

    更新日期:2004-08-01 00:00:00

  • Transduction of human macrophages using a stable HIV-1/HIV-2-derived gene delivery system.

    abstract::We have previously established a stable HIV-1 packaging cell line, psi 422, which yielded high titers of an HIV-1 vector capable of efficiently transducing CD4+ cells. In order to increase the safety of this gene delivery system, we have now replaced the HIV-1 vector with an HIV-2 vector to abolish any risk of homolog...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300563

    authors: Corbeau P,Kraus G,Wong-Staal F

    更新日期:1998-01-01 00:00:00

  • Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc 'spacer' domain in the extracellular moiety of chimeric antigen receptors avoids 'off-target' activation and unintended initiation of an innate immune response.

    abstract::Chimeric antigen receptors (CARs, immunoreceptors) are frequently used to redirect T cells with pre-defined specificity, in particular towards tumour cells for use in adoptive immunotherapy of malignant diseases. Specific targeting is mediated by an extracellularly located antibody-derived binding domain, which is joi...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.91

    authors: Hombach A,Hombach AA,Abken H

    更新日期:2010-10-01 00:00:00

  • Human adipose tissue-derived mesenchymal stromal cells as vehicles for tumor bystander effect: a model based on bioluminescence imaging.

    abstract::Human adipose tissue mesenchymal stromal cells (AMSCs) share common traits, including similar differentiation potential and cell surface markers, with their bone marrow counterparts. Owing to their general availability, higher abundance and ease of isolation AMSCs may be convenient autologous delivery vehicles for loc...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2008.176

    authors: Vilalta M,Dégano IR,Bagó J,Aguilar E,Gambhir SS,Rubio N,Blanco J

    更新日期:2009-04-01 00:00:00

  • Bypassing tumor-specific and bispecific antibodies: triggering of antitumor immunity by expression of anti-FcgammaR scFv on cancer cell surface.

    abstract::We have developed a novel immunostimulatory molecule against tumor cells, composed of an anti-FcgammaRIII (CD16) scFv fused to the platelet-derived growth factor receptor (PDGFR) transmembrane region. This fusion molecule was stably expressed on the tumor cell surface and retained the ability of the parental antibody ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301575

    authors: Gruel N,Fridman WH,Teillaud JL

    更新日期:2001-11-01 00:00:00

  • Lipofection of cultured mouse muscle cells: a direct comparison of Lipofectamine and DOSPER.

    abstract::Cationic lipid-DNA complexes (lipoplexes) have been widely used as gene transfer vectors which avoid the adverse immunogenicity and potential for viraemia of viral vectors. With the long-term aim of gene transfer into skeletal muscle in vivo, we describe a direct in vitro comparison of two commercially available catio...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300604

    authors: Dodds E,Dunckley MG,Naujoks K,Michaelis U,Dickson G

    更新日期:1998-04-01 00:00:00

  • Stable rAAV-mediated transduction of rod and cone photoreceptors in the canine retina.

    abstract::Recombinant adeno-associated virus (rAAV) vectors are attractive candidates for the treatment of inherited and acquired retinal disease. Although rAAV vectors are well characterized in rodent models, a prerequisite to their clinical application in human patients is the thorough evaluation of their efficacy and safety ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301990

    authors: Bainbridge JW,Mistry A,Schlichtenbrede FC,Smith A,Broderick C,De Alwis M,Georgiadis A,Taylor PM,Squires M,Sethi C,Charteris D,Thrasher AJ,Sargan D,Ali RR

    更新日期:2003-08-01 00:00:00

  • T cell activation with systemic agonistic antibody versus local 4-1BB ligand gene delivery combined with interleukin-12 eradicate liver metastases of breast cancer.

    abstract::We have shown that interleukin-12 (IL-12) generated a strong, albeit transient, anti-tumor response, mostly mediated by natural killer (NK) cell. T cell participation, in addition to NK cells, was essential for persistence of the anti-tumor response. Ligation of 4-1BB, a co-stimulatory receptor expressed on activated ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301687

    authors: Martinet O,Divino CM,Zang Y,Gan Y,Mandeli J,Thung S,Pan PY,Chen SH

    更新日期:2002-06-01 00:00:00

  • Pseudotyping of Moloney leukemia virus-based retroviral vectors with simian immunodeficiency virus envelope leads to targeted infection of human CD4+ lymphoid cells.

    abstract::In view of our recent findings that a truncated form of the envelope (Env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) was efficiently incorporated into MoMLV particles, we studied the generation of Moloney murine leukemia virus (MoMLV)/simian immunodeficiency virus (SIV) pseudotypes. Unlike HIV-1, bot...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300603

    authors: Indraccolo S,Minuzzo S,Feroli F,Mammano F,Calderazzo F,Chieco-Bianchi L,Amadori A

    更新日期:1998-02-01 00:00:00

  • Protein transduction by pseudotyped lentivirus-like nanoparticles.

    abstract::A simple, efficient and reproducible method to transduce proteins into mammalian cells has not been established. Here we describe a novel protein transduction method based on a lentiviral vector. We have developed a method to package several thousand foreign protein molecules into a lentivirus-like nanoparticle (LENA)...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2011.38

    authors: Aoki T,Miyauchi K,Urano E,Ichikawa R,Komano J

    更新日期:2011-09-01 00:00:00

  • Cationic liposome-mediated gene transfer.

    abstract::Direct gene transfer for the treatment of human diseases requires a vector which can be administered efficiently, safely and repeatedly. Cationic liposomes represent one of the few examples that can meet these requirements. Currently, more than a dozen cationic liposome formulations have been reported. These liposomes...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:

    authors: Gao X,Huang L

    更新日期:1995-12-01 00:00:00

  • Heart-targeted adeno-associated viral vectors selected by in vivo biopanning of a random viral display peptide library.

    abstract::Selection of targeted vectors from virus display peptide libraries is a versatile and efficient approach to improve vector specificity and efficiency. This strategy has been used to target various cell types in vitro. Here, we report the screening of an adeno-associated virus type 2 (AAV2) display peptide library in v...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.44

    authors: Ying Y,Müller OJ,Goehringer C,Leuchs B,Trepel M,Katus HA,Kleinschmidt JA

    更新日期:2010-08-01 00:00:00

  • Engineering physiologically regulated insulin secretion in non-beta cells by expressing glucagon-like peptide 1 receptor.

    abstract::Glucagon-like peptide 1 (GLP-1) is released from neuroendocrine cells in the intestine in the postprandial state and augments glucose-stimulated insulin secretion from pancreatic beta cells. To develop non-beta cells that exhibit physiologically regulated insulin secretion, we coexpressed the GLP-1 receptor and human ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302055

    authors: Wu L,Nicholson W,Wu CY,Xu M,McGaha A,Shiota M,Powers AC

    更新日期:2003-09-01 00:00:00

  • Effect of tolerance induction to immunodominant T-cell epitopes of Sendai virus on gene expression following repeat administration to lung.

    abstract::Sendai virus (SeV) is able to transfect airway epithelial cells efficiently in vivo. However, as with other viral vectors, repeated administration leads to reduced gene expression. We have investigated the impact of inducing immunological tolerance to immunodominant T-cell epitopes on gene expression following repeate...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302677

    authors: Griesenbach U,Boyton RJ,Somerton L,Garcia SE,Ferrari S,Owaki T,Ya-Fen Z,Geddes DM,Hasegawa M,Altmann DM,Alton EW

    更新日期:2006-03-01 00:00:00

  • Generation of bidirectional hypoxia/HIF-responsive expression vectors to target gene expression to hypoxic cells.

    abstract::Hypoxia initiates an adaptive physiological response in all organisms and plays a role in the pathogenesis of several human diseases. The hypoxia/HIF-inducible factor-1 (HIF-1) transcription factor mediates transcriptional responses to hypoxia by binding to a cis-acting hypoxia-responsive element (HRE) present within ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301605

    authors: Post DE,Van Meir EG

    更新日期:2001-12-01 00:00:00

  • Human PBMC-derived dendritic cells transduced with an adenovirus vectorinduce cytotoxic T-lymphocyte responses against a vector-encoded antigen in vitro.

    abstract::Dendritic cells (DC) are among the most potent antigen-presenting cells known and play an important role in the initiation of antigen-specific T-lymphocyte responses. Several recent studies have demonstrated that DC expressing vector-encoded tumor-associated antigens can induce protective and therapeutic immunity in m...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300899

    authors: Diao J,Smythe JA,Smyth C,Rowe PB,Alexander IE

    更新日期:1999-05-01 00:00:00

  • Liver-directed gene therapy of diabetic rats using an HVJ-E vector containing EBV plasmids expressing insulin and GLUT 2 transporter.

    abstract::Insulin gene therapy in clinical medicine is currently hampered by the inability to regulate insulin secretion in a physiological manner, the inefficiency with which the gene is delivered, and the short duration of gene expression. To address these issues, we injected the liver of streptozotocin-induced diabetic rats ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302644

    authors: Kim YD,Park KG,Morishita R,Kaneda Y,Kim SY,Song DK,Kim HS,Nam CW,Lee HC,Lee KU,Park JY,Kim BW,Kim JG,Lee IK

    更新日期:2006-02-01 00:00:00

  • Intrasplenic transplantation of IL-18 gene-modified hepatocytes: an effective approach to reverse hepatic fibrosis in schistosomiasis through induction of dominant Th1 response.

    abstract::Hepatic fibrosis is a common outcome of chronic liver diseases. In schistosomiasis, chronic parasite egg-induced granuloma formation can lead to fibrosis, which is immunologically characterized by the dominant Th2 response. Recently, it has been shown that gene therapy is an attractive approach for the treatment of he...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301524

    authors: Zhang LH,Pan JP,Yao HP,Sun WJ,Xia DJ,Wang QQ,He L,Wang J,Cao X

    更新日期:2001-09-01 00:00:00

  • Localized adenovirus gene delivery using antiviral IgG complexation.

    abstract::Gene therapy with viral vectors has progressed to clinical trials. However, the localization of viral vector delivery to diseased target sites remains a challenge. We tested the hypothesis that an adenoviral vector could be successfully delivered by complexation with a specific antibody that is bound to a biodegradabl...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301452

    authors: Levy RJ,Song C,Tallapragada S,DeFelice S,Hinson JT,Vyavahare N,Connolly J,Ryan K,Li Q

    更新日期:2001-05-01 00:00:00

  • Intrabody-mediated phenotypic knockout of major histocompatibility complex class I expression in human and monkey cell lines and in primary human keratinocytes.

    abstract::Cultured keratinocyte allografts from unrelated donors can be readily grown as sheets in large-scale cell culture and have been used as an immediate skin cover for severely burned patients. Despite the absence of passenger leukocytes and the unlimited amount of material that can be obtained for permanent skin coverage...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301656

    authors: Mhashilkar AM,Doebis C,Seifert M,Busch A,Zani C,Soo Hoo J,Nagy M,Ritter T,Volk HD,Marasco WA

    更新日期:2002-03-01 00:00:00

  • Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery.

    abstract::Adenovirus-mediated gene therapy of experimental hepatocarcinoma is hindered by low transduction efficacy in vivo. We evaluated the extent of gene expression following various routes of administration of recombinant adenovirus AdCMVlacZ in diethylnitrosamine-induced rat hepatocarcinoma. We first characterized the vasc...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300664

    authors: Gérolami R,Cardoso J,Bralet MP,Cuenod CA,Clément O,Tran PL,Bréchot C

    更新日期:1998-07-01 00:00:00

  • MuLV-based vectors pseudotyped with truncated HIV glycoproteins mediate specific gene transfer in CD4+ peripheral blood lymphocytes.

    abstract::Human immunodeficiency virus (HIV) infection ultimately leads to the destruction of the CD4+ lymphocyte subset and the onset of AIDS. In recent years, several gene therapy procedures making use of retroviral vectors that selectively target HIV susceptible cells have been proposed in order to interfere with HIV product...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300646

    authors: Lodge R,Subbramanian RA,Forget J,Lemay G,Cohen EA

    更新日期:1998-05-01 00:00:00

  • Intercellular trafficking and enhanced in vivo antitumour activity of a non-virally delivered P27-VP22 fusion protein.

    abstract::VP22, a structural protein from herpes simplex virus type I, exhibits the unique property of intercellular trafficking. This protein is exported from primary expressing cells and subsequently imported into neighbouring cells. This property is conserved when VP22 is genetically fused to a protein, making it a promising...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301904

    authors: Zavaglia D,Favrot MC,Eymin B,Tenaud C,Coll JL

    更新日期:2003-02-01 00:00:00

  • Localized expression of an anti-TNF single-chain antibody prevents development of collagen-induced arthritis.

    abstract::Although systemic administration of neutralizing anti-TNF antibodies has been used successfully in treating rheumatoid arthritis, there is a potential for side effects. We transduced a collagen reactive T-cell hybridoma with tissue-specific homing properties to assess therapeutic effects of local delivery to inflamed ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301980

    authors: Smith R,Tarner IH,Hollenhorst M,Lin C,Levicnik AU,Fathman CG,Nolan GP

    更新日期:2003-08-01 00:00:00

  • Anti-inflammatory effect of MAPK phosphatase-1 local gene transfer in inflammatory bone loss.

    abstract::Alveolar bone loss associated with periodontal diseases is the result of osteoclastogenesis induced by bacterial pathogens. The mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a critical negative regulator of immune response as a key phosphatase capable of dephosphorylating activated MAPKs. In this st...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.139

    authors: Yu H,Li Q,Herbert B,Zinna R,Martin K,Junior CR,Kirkwood KL

    更新日期:2011-04-01 00:00:00