Growth suppression of established human osteosarcoma lung metastases in mice by aerosol gene therapy with PEI-p53 complexes.

Abstract:

:Lung metastases are a frequent complication of osteosarcoma and a treatment that would reduce the severity of this complication would be of great benefit to patients. We have used a formulation consisting of polyethyleneimine (PEI) and a p53 gene administered in aerosol to treat established lung micrometastases as a model of human osteosarcoma in nude mice. The SAOS-LM6 cell line, a metastatic derivative of the p53 null SAOS-2 line, expresses high levels of p53 protein after in vitro transfection with PEI-p53 complexes as determined by ELISA, and transfection with both p53wt and the p53 variant, p53-CD(1-366) in vitro, results in a marked inhibition of SAOS-LM6 cell proliferation. Aerosol delivery of plasmid DNA containing either the p53 gene or a p53-CD(1-366) variant gene formulated with PEI to mice resulted in highly significant reductions in the numbers and size of tumors (P<.001), the total number of tumor foci in the lungs (P<.001) and the size of individual tumor nodules in treated animals compared to untreated, PEI only-treated and PEI-CAT-treated control animals. The different tissues examined did not reveal any signs of toxicity or inflammation after repeated exposure to PEI-DNA. The aerosol delivery of PEI-based formulations of p53 or synthetic p53 variant genes represents a promising new strategy for the treatment of established human osteosarcoma lung metastases. The noninvasive nature of aerosol delivery coupled with low toxicity also make this therapeutic approach potentially appropriate for combination therapy with either radio- or chemotherapy.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Densmore CL,Kleinerman ES,Gautam A,Jia SF,Xu B,Worth LL,Waldrep JC,Fung YK,T'Ang A,Knight V

doi

10.1038/sj.cgt.7700343

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

619-27

issue

9

eissn

0929-1903

issn

1476-5500

journal_volume

8

pub_type

杂志文章
  • Her-2 expression regulated by downregulation of miR-9 and which affects chemotherapeutic effect in breast cancer.

    abstract::This study aimed to identify microRNAs (miRs), the deregulated expression of which leads to the activation of oncogenic pathways in human breast cancer (BC). miRs are classes of endogenous, small, noncoding RNAs that regulate gene expression aberrantly in human tumor tissues. A total of 39 out of 123 tumoral and match...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2014.82

    authors: Sun G,Sun L,Liu Y,Xing H,Wang K

    更新日期:2017-05-01 00:00:00

  • Use of the EGP-2/Ep-CAM promoter for targeted expression of heterologous genes in carcinoma derived cell lines.

    abstract::EGP-2, also known as Ep-CAM, is expressed at high levels on the surface of most carcinomas and is therefore considered an attractive target for anticancer strategies. To explore the mechanisms regulating the expression of EGP-2, sequences 3.4 kb upstream of the transcription start site were isolated and assayed for th...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700725

    authors: McLaughlin PM,Trzpis M,Kroesen BJ,Helfrich W,Terpstra P,Dokter WH,Ruiters MH,de Leij LF,Harmsen MC

    更新日期:2004-09-01 00:00:00

  • Correction to: Schwannoma gene therapy by adeno-associated virus delivery of the pore-forming protein Gasdermin-D.

    abstract::The original version of this Article contained an error in the spelling of the author Ahmed Abdelanabi, which was incorrectly given as Abdelanabi Ahmed. This has now been corrected in both the PDF and HTML versions of the Article. ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41417-019-0096-8

    authors: Ahmed SG,Abdelanabi A,Doha M,Brenner GJ

    更新日期:2020-04-01 00:00:00

  • Genetically marking human cells--results of the first clinical gene transfer studies.

    abstract::The rapid development of both knowledge and techniques in molecular biology have made it possible to engineer genetic constructs and transfer them into cells of individuals with various diseases. Such gene therapies may alleviate or perhaps even cure diseases for which no adequate treatment now exists. One potential a...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:

    authors: Cai Q,Rubin JT,Lotze MT

    更新日期:1995-06-01 00:00:00

  • Generation of an adenoviral vector containing an addition of a heterologous ligand to the serotype 3 fiber knob.

    abstract::As an initial assessment of the feasibility of employing the adenovirus serotype 3 (Ad3) fiber knob as a locale for introducing a tropism-modifying motif, we generated an adenoviral vector containing a six-histidine tag genetically fused to the carboxy-terminus of the Ad3 fiber knob. The heterologous tag proved to be ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700543

    authors: Uil TG,Seki T,Dmitriev I,Kashentseva E,Douglas JT,Rots MG,Middeldorp JM,Curiel DT

    更新日期:2003-02-01 00:00:00

  • Targeted-simultaneous expression of Gas1 and p53 using a bicistronic adenoviral vector in gliomas.

    abstract::The targeted expression of transgenes is one of the principal goals of gene therapy, and it is particularly relevant for the treatment of brain tumors. In this study, we examined the effect of the overexpression of human gas1 (growth arrest specific 1) and human p53 cDNAs, both under the transcriptional control of a p...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7701076

    authors: Benítez JA,Arregui L,Vergara P,Segovia J

    更新日期:2007-10-01 00:00:00

  • Cytokine-armed vaccinia virus infects the mesothelioma tumor microenvironment to overcome immune tolerance and mediate tumor resolution.

    abstract::Intratumoral (i.t.) administration of cytokine genes expressed by viral vectors represents a rational approach that induces cytokine secretion at the site they are needed, and i.t. vaccinia virus (VV) has shown promise in mesothelioma patients. However, we and others have shown that the mesothelioma tumor microenviron...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2009.85

    authors: Jackaman C,Nelson DJ

    更新日期:2010-06-01 00:00:00

  • Gene therapy for castration-resistant prostate cancer cells using JC polyomavirus-like particles packaged with a PSA promoter driven-suicide gene.

    abstract::Prostate cancer is the second most common cancer in men globally. Prostate cancer patients at advanced stages are usually treated with androgen deprivation therapy (ADT). However, with disease progression, it often becomes the incurable castration-resistant prostate cancer (CRPC). JC polyomavirus (JCPyV) is a human DN...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-019-0083-0

    authors: Lin MC,Wang M,Chou MC,Chao CN,Fang CY,Chen PL,Chang D,Shen CH

    更新日期:2019-07-01 00:00:00

  • Antiproliferative activity of a triplex-forming oligonucleotide recognizing a Ki-ras polypurine/polypyrimidine motif correlates with protein binding.

    abstract::The Ki-ras gene is frequently mutated and/or overexpressed in human cancer. Since it is suspected to play a key role in the pathogenesis of many tumors, there is interest to search for strategies aiming at the specific inhibition of this oncogene. In this paper, we investigated the capacity of a 20 mer G-rich oligonuc...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700722

    authors: Cogoi S,Ballico M,Bonora GM,Xodo LE

    更新日期:2004-07-01 00:00:00

  • Comparative assessment of TCRBV diversity in T lymphocytes present in blood, metastatic lesions, and DTH sites of two melanoma patients vaccinated with an IL-7 gene-modified autologous tumor cell vaccine.

    abstract::A phase I clinical trial using autologous, IL-7 gene-modified tumor cells in patients with disseminated melanoma has been recently completed. Although no major clinical responses were observed, increased antitumor cytotoxicity was measured in postvaccine peripheral blood lymphocytes in a subset of treated patients. To...

    journal_title:Cancer gene therapy

    pub_type: 临床试验,杂志文章

    doi:10.1038/sj.cgt.7700435

    authors: Carsana M,Tragni G,Nicolini G,Bersani I,Parmiani G,Anichini A,Sun YS,Möller P,Schadendorf D,Sensi ML

    更新日期:2002-03-01 00:00:00

  • Canarypox virus expressing wild type p53 for gene therapy in murine tumors mutated in p53.

    abstract::The antitumor activity of a recombinant canarypox virus expressing wild type murine p53 (ALVAC-p53) was investigated in two murine syngeneic tumors harboring an endogenous p53 mutation (CMS4 and TS/A). Direct intratumor injections of ALVAC-p53 in CMS4 pre-established subcutaneous tumors induced total tumor regression ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700279

    authors: Odin L,Favrot M,Poujol D,Michot JP,Moingeon P,Tartaglia J,Puisieux I

    更新日期:2001-02-01 00:00:00

  • Tumor-selective drug activation: a GDEPT approach utilizing cytochrome P450 1A1 and AQ4N.

    abstract::Drug metabolizing transgene products, which activate bioreductive cytotoxins, can be used to target treatment-resistant hypoxic tumors. The prodrug AQ4N is bioreduced in hypoxic cells by cytochrome P450s (CYPs) to the cytotoxin AQ4. Previously we have shown that intra-tumoral injection of CYP3A4 and CYP2B6 transgenes ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700933

    authors: Yakkundi A,McErlane V,Murray M,McCarthy HO,Ward C,Hughes CM,Patterson LH,Hirst DG,McKeown SR,Robson T

    更新日期:2006-06-01 00:00:00

  • Efficient transfer of PSA and PSMA cDNAs into DCs generates antibody and T cell antitumor responses in vivo.

    abstract::Gene therapy for prostate cancer may be realized through transduction of whole genes, such as PSA or PSMA, into immunotherapeutic dendritic cells (DCs). An oncoretroviral vector encoding human PSMA and a bicistronic oncoretroviral vector encoding human PSA and cell surface CD25 cDNAs were constructed. Remarkably, tran...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700810

    authors: Medin JA,Liang SB,Hou JW,Kelley LS,Peace DJ,Fowler DH

    更新日期:2005-06-01 00:00:00

  • E6AP gene suppression and characterization with in vitro selected hammerhead ribozymes.

    abstract::E6AP was originally identified as the ubiquitin-protein ligase involved in human papillomavirus (HPV) E6-mediated p53 degradation and has since been shown to act as an E3 ubiquitin-protein ligase in the ubiquitination of several other protein substrates. To further define E6AP function at the molecular and cellular le...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700623

    authors: Kim Y,Cairns MJ,Marouga R,Sun LQ

    更新日期:2003-09-01 00:00:00

  • Expression of costimulatory molecules: B7 and ICAM up-regulation after treatment with a suicide gene.

    abstract::The herpes simplex virus thymidine kinase gene (HSV-TK) in combination with ganciclovir (GCV), is currently being used in gene therapy-based clinical trials for cancer treatment. Its therapeutic effect is based on a "bystander effect" whereby HSV-TK gene-modified tumor cells are toxic to nearby unmodified tumor cells ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Ramesh R,Munshi A,Abboud CN,Marrogi AJ,Freeman SM

    更新日期:1996-11-01 00:00:00

  • Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population.

    abstract::This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG gro...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2017.13

    authors: Yang HW,Lei P,Xie YC,Han ZL,Li D,Wang SH,Sun ZL

    更新日期:2017-06-01 00:00:00

  • Mesenchymal stem cell: a new horizon in cancer gene therapy.

    abstract::Cancer is one of the main problems in public health worldwide. Despite rapid advances in the diagnosis and treatment of cancer, the efficacy of current treatment strategies is still limited. There are promising new results in animal models whereby mesenchymal stem cells (MSCs) can be used as vehicles for targeted ther...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/cgt.2016.35

    authors: Mohammadi M,Jaafari MR,Mirzaei HR,Mirzaei H

    更新日期:2016-09-01 00:00:00

  • Immune properties of recombinant vaccinia virus encoding CD154 (CD40L) are determined by expression of virally encoded CD40L and the presence of CD40L protein in viral particles.

    abstract::Expression of costimulatory molecules by recombinant poxviruses is a promising strategy for enhancing therapeutic vaccines. CD40-CD40L interactions are critical for conditioning dendritic cells (DC) and priming T- and B-cell immunity. We constructed a vaccinia virus expressing murine CD40L (rV-CD40L) and studied its i...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700762

    authors: Bereta M,Bereta J,Park J,Medina F,Kwak H,Kaufman HL

    更新日期:2004-12-01 00:00:00

  • Receptor-mediated gene delivery using the Fab fragments of anti-epidermal growth factor receptor antibodies: improved immunogene approach.

    abstract::We previously developed the "immunogene" approach toward cancer gene therapy using epidermal growth factor receptor (EGFR)-mediated endocytosis. Here, we describe an improved immunogene system, in which the antigen-binding (Fab) fragments of the monoclonal antibody (Ab) B4G7 against the human EGFR were conjugated with...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Chen J,Gamou S,Takayanagi A,Ohtake Y,Ohtsubo M,Shimizu N

    更新日期:1998-11-01 00:00:00

  • Induction of CAMEL/NY-ESO-ORF2-specific CD8+ T cells upon stimulation with dendritic cells infected with a modified Ad5 vector expressing a chimeric Ad5/35 fiber.

    abstract::Delivery of the full-length tumor antigen might be more successful in immunotherapy than single peptides and has the advantage that patients no longer need to be selected for their HLA type. In this study, we tested the in vitro induction of CAMEL/NY-ESO-ORF2-specific T cells by dendritic cells infected with an adenov...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700674

    authors: Slager EH,van der Minne CE,Goudsmit J,van Oers JM,Kostense S,Havenga MJ,Osanto S,Griffioen M

    更新日期:2004-03-01 00:00:00

  • Improved gene transfer selectivity to hepatocarcinoma cells by retrovirus vector displaying single-chain variable fragment antibody against c-Met.

    abstract::Engineered retroviruses are widely used vectors for cancer gene therapy approaches. However, the ability to target cells of therapeutic interest while controlling the expression of the transferred genes would improve both the efficiency and the safety of viral vectors. In this study, we investigated the ability of a r...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700640

    authors: Nguyen TH,Loux N,Dagher I,Vons C,Carey K,Briand P,Hadchouel M,Franco D,Jouanneau J,Schwall R,Weber A

    更新日期:2003-11-01 00:00:00

  • Alteration of drug chemosensitivity caused by the adenovirus-mediated transfer of the wild-type p53 gene in human lung cancer cells.

    abstract::The aim of the present study is to identify the optimal anticancer agents for use in combination with gene therapy using wild-type (wt) p53 gene transfer. We used adenoviral vectors expressing human wt p53 (AdCAp53) and investigated the effects of wt p53 gene transfer in combination with 12 anticancer agents on a huma...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700096

    authors: Osaki S,Nakanishi Y,Takayama K,Pei XH,Ueno H,Hara N

    更新日期:2000-02-01 00:00:00

  • Tumor gene therapy by MVA-mediated expression of T-cell-stimulating antibodies.

    abstract::Immune responses to tumor-associated antigens are often dampened by a tumor-induced state of immune anergy. Previous work has attempted to overcome tumor-induced T-cell anergy by the direct injection of vectors carrying the genes encoding one of a variety of cytokines. We hypothesised that the polyclonal stimulation o...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700461

    authors: Paul S,Regulier E,Rooke R,Stoeckel F,Geist M,Homann H,Balloul JM,Villeval D,Poitevin Y,Kieny MP,Acres RB

    更新日期:2002-05-01 00:00:00

  • Anticancer activity of oncolytic adenovirus vector armed with IFN-alpha and ADP is enhanced by pharmacologically controlled expression of TRAIL.

    abstract::We have previously described oncolytic adenovirus (Ad) vectors KD3 and KD3-interferon (IFN) that were rendered cancer-specific by mutations in the E1A region of Ad; these mutations abolish binding of E1A proteins to p300/CBP and pRB. The antitumor activity of the vectors was enhanced by overexpression of the Adenoviru...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7701107

    authors: Shashkova EV,Kuppuswamy MN,Wold WS,Doronin K

    更新日期:2008-02-01 00:00:00

  • A "combination oligonucleotide" antisense strategy to downregulate thymidylate synthase and decrease tumor cell growth and drug resistance.

    abstract::Thymidylate synthase (TS) catalyzes de novo production of thymidylate for DNA synthesis and cell proliferation. As such, TS has been a target of antitumor chemotherapy for many years. Our laboratory has identified several antisense oligodeoxynucleotides (ODNs) that downregulate TS mRNA and protein, inhibit cell prolif...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700566

    authors: Berg RW,Ferguson PJ,Vincent MD,Koropatnick DJ

    更新日期:2003-04-01 00:00:00

  • Lipofection indirectly increases expression of endogenous major histocompatibility complex class I molecules on tumor cells.

    abstract::Direct intratumoral injection of a lipid/DNA complex encoding an allogeneic major histocompatibility complex (MHC) class I molecule leads to regression of both an immunogenic murine tumor and also melanoma lesions in some patients. We have sought to understand the mechanism(s) for this augmentation of antitumor activi...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Fox BA,Drury M,Hu HM,Cao Z,Huntzicker EG,Qie W,Urba WJ

    更新日期:1998-09-01 00:00:00

  • Employment of microarray analysis to characterize biologic differences associated with tropism-modified adenoviral vectors: utilization of non-native cellular entry pathways.

    abstract::In this study, we have applied high-density oligonucleotide microarray technology to characterize biologic changes associated with adenoviral vector-mediated target cell infection. We infected a human melanoma cell line, M21, with the tropism-modified vectors, Ad5lucRGD and Ad5/3luc1. In addition, we infected the M21 ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700776

    authors: Volk AL,Rivera AA,Page GP,Salazar-Gonzalez JF,Nettelbeck DM,Matthews QL,Curiel DT

    更新日期:2005-02-01 00:00:00

  • Antitumor effects of non-replicative herpes simplex vectors expressing antiangiogenic proteins and thymidine kinase on Lewis lung carcinoma establishment and growth.

    abstract::There is growing evidence that combinations of antiangiogenic proteins with other antineoplastic treatments such as chemo- or radiotherapy and suicide genes-mediated tumor cytotoxicity lead to synergistic effects. In the present work, we tested the activity of two non-replicative herpes simplex virus (HSV)-1-based vec...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7701058

    authors: Berto E,Bozac A,Volpi I,Lanzoni I,Vasquez F,Melara N,Manservigi R,Marconi P

    更新日期:2007-09-01 00:00:00

  • Phase I trial of interferon-gamma (IFN-gamma) retroviral vector administered intratumorally to patients with metastatic melanoma.

    abstract:BACKGROUND:Interferon-gamma (IFN-gamma) gene/retroviral vector cell vaccinations have generated protective responses from unmodified tumor cell challenges as well as a regression of established tumors in animal models. The purpose of this trial was to determine the feasibility and safety of a direct intratumoral inject...

    journal_title:Cancer gene therapy

    pub_type: 临床试验,杂志文章

    doi:10.1038/sj.cgt.7700019

    authors: Nemunaitis J,Fong T,Robbins JM,Edelman G,Edwards W,Paulson RS,Bruce J,Ognoskie N,Wynne D,Pike M,Kowal K,Merritt J,Ando D

    更新日期:1999-07-01 00:00:00

  • Fusion protein from RGD peptide and Fc fragment of mouse immunoglobulin G inhibits angiogenesis in tumor.

    abstract::Targeting tumor vasculature represents an interesting approach for the treatment of solid tumors. The alpha v beta 3 integrins have been found to be specifically associated with angiogenesis in tumors. By using bacteriophage display technology, Ruoslahti et al found that a group of peptides containing the RGD (Arg-Gly...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700707

    authors: Li J,Ji J,Holmes LM,Burgin KE,Barton LB,Yu X,Wagner TE,Wei Y

    更新日期:2004-05-01 00:00:00