Endostatin therapy reveals a U-shaped curve for antitumor activity.

Abstract:

:Developing continuous systemic delivery of endostatin has been a goal of many laboratories. We have employed a method of gene therapy utilizing different viral constructs. Here, we report that a new serotype of adeno-associated viruses, which incorporates canine endostatin, provides dose-dependent transgene expression in the circulation after intramuscular injection in mice. Elevated levels of endostatin remained stable in the circulation for at least 4 months. In vitro assays determined that the protein expressed was biologically active. Antitumor activities of the above construct demonstrated a U-shape curve, where the maximum activity was observed within a certain critical concentration range. These data suggest that an optimum dose range may be required to achieve therapeutic efficacy in large animal models.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Tjin Tham Sjin RM,Naspinski J,Birsner AE,Li C,Chan R,Lo KM,Gillies S,Zurakowski D,Folkman J,Samulski J,Javaherian K

doi

10.1038/sj.cgt.7700938

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

619-27

issue

6

eissn

0929-1903

issn

1476-5500

pii

7700938

journal_volume

13

pub_type

杂志文章
  • Combining CAR T cells and the Bcl-2 family apoptosis inhibitor ABT-737 for treating B-cell malignancy.

    abstract::B-cell malignancies upregulate the B-cell lymphoma 2 (Bcl-2) family inhibitors of the intrinsic apoptosis pathway, making them therapy resistant. However, small-molecule inhibitors of Bcl-2 family members such as ABT-737 restore a functional apoptosis pathway in cancer cells, and its oral analog ABT-263 (Navitoclax) h...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2013.35

    authors: Karlsson H,Lindqvist AC,Fransson M,Paul-Wetterberg G,Nilsson B,Essand M,Nilsson K,Frisk P,Jernberg-Wiklund H,Loskog A

    更新日期:2013-07-01 00:00:00

  • Transcellular transfer of active HSV-1 thymidine kinase mediated by an 11-amino-acid peptide from HIV-1 Tat.

    abstract::Suicide gene therapy using herpes simplex virus type-1 (HSV-1) thymidine kinase (TK) is a widely exploited approach for gene therapy of cancer and other hyperproliferative disorders. Despite its popularity, clinical success has been so far hampered mostly by the relative inefficiency of TK gene transfer and its limite...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700526

    authors: Tasciotti E,Zoppè M,Giacca M

    更新日期:2003-01-01 00:00:00

  • Endostatin gene therapy delivered by attenuated Salmonella typhimurium in murine tumor models.

    abstract::Salmonella typhimurium (hereafter S. typhimurium), as Gram-negative facultative anaerobic bacteria, are good candidates for cancer therapy and delivering therapeutic antitumor agents. However, it is necessary to reduce the virulence of such bacteria and enhance their tumor-targeting ability, and their immunostimulator...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-018-0021-6

    authors: Liang K,Liu Q,Li P,Han Y,Bian X,Tang Y,Kong Q

    更新日期:2018-08-01 00:00:00

  • Murine neuroblastoma vaccines produced by retroviral transfer of MHC class II genes.

    abstract::Malignant tumors express tumor-related antigens, but effective antitumor immunity does not occur in the primary host. One hypothesis is that there is insufficient stimulation of T-cell responses due to ineffective antigen presentation. An approach to overcome these deficiencies is to modify tumor cells to express majo...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Hock RA,Reynolds BD,Tucker-McClung CL,Heuer JG

    更新日期:1996-09-01 00:00:00

  • Author Correction: BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction.

    abstract::All animal experiments were approved by the Animal Care and Use Committee (ACUC), Louisiana State University Health Science Center and not The People's Hospital of Liaoning Province as indicated in the original version of the Article. The PDF and HTML versions of the Article have been modified accordingly. ...

    journal_title:Cancer gene therapy

    pub_type: 已发布勘误

    doi:10.1038/s41417-019-0082-1

    authors: Yao Z,Yang S,Zhao H,Yang H,Jiang X

    更新日期:2019-07-01 00:00:00

  • Mdr1 promoter-driven tumor necrosis factor-alpha expression for a chemotherapy-controllable combined in vivo gene therapy and chemotherapy of tumors.

    abstract::Cancer gene therapy approaches are often designed as single-agent treatments; however, greater therapeutic effect might be obtained if combined with an established conventional treatment regimen such as chemotherapy. In this context, conditional promoters are useful tools, because they may be induced by therapeutic mo...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700196

    authors: Walther W,Stein U,Fichtner I,Alexander M,Shoemaker RH,Schlag PM

    更新日期:2000-06-01 00:00:00

  • Cancer gene therapy: an awkward adolescence.

    abstract::At the Eleventh International Conference on Gene Therapy of Cancer (December 12-14, 2002, San Diego, CA) progress on using gene transfer technology to treat cancer was presented. Although there is as yet no cancer gene therapy being marketed, considerable progress has been made in defining likely strategies and likely...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.cgt.7700602

    authors: Gottesman MM

    更新日期:2003-07-01 00:00:00

  • CRISPR/Cas9 genome editing technology significantly accelerated herpes simplex virus research.

    abstract::Herpes simplex viruses (HSVs) are important pathogens and ideal for gene therapy due to its large genome size. Previous researches on HSVs were hampered because the technology to construct recombinant HSVs were based on DNA homology-dependent repair (HDR) and plaque assay, which are inefficient, laborious, and time-co...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/s41417-018-0016-3

    authors: Wang D,Wang XW,Peng XC,Xiang Y,Song SB,Wang YY,Chen L,Xin VW,Lyu YN,Ji J,Ma ZW,Li CB,Xin HW

    更新日期:2018-06-01 00:00:00

  • Treatment of cholangiocarcinoma with oncolytic herpes simplex virus combined with external beam radiation therapy.

    abstract::Replication-competent oncolytic herpes simplex viruses (HSV), modified by deletion of certain viral growth genes, can selectively target malignant cells. The viral growth gene gamma(1)34.5 has significant homology to GADD34 (growth arrest and DNA damage protein 34), which promotes cell cycle arrest and DNA repair in r...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700890

    authors: Jarnagin WR,Zager JS,Hezel M,Stanziale SF,Adusumilli PS,Gonen M,Ebright MI,Culliford A,Gusani NJ,Fong Y

    更新日期:2006-03-01 00:00:00

  • Recombinant interferon alpha2a synergistically enhances ganciclovir-mediated tumor cell killing in the herpes simplex virus thymidine kinase system.

    abstract::The herpes simplex virus thymidine kinase (HSV-TK) gene is being developed in the treatment of many different types of tumors. The HSV-TK gene sensitizes tumor cells to the antiviral drug ganciclovir (GCV) and mediates the bystander effect in which unmodified tumor cells are killed as well. Although this approach has ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700063

    authors: Whartenby KA,Darnowski JW,Freeman SM,Yurasha K,Calabresi P

    更新日期:1999-09-01 00:00:00

  • Adenovirus-mediated herpes simplex virus thymidine kinase gene therapy in BT4C rat glioma model.

    abstract::Adenovirus (Adv)-mediated herpes simplex virus thymidine kinase (adv/tk) gene therapy combined with ganciclovir (GCV) medication is a promising approach for the treatment of malignant glioma. However, optimal administration and the effect of possible adjuvant treatments have not been fully examined. In the present stu...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700515

    authors: Tyynelä K,Sandmair AM,Turunen M,Vanninen R,Vainio P,Kauppinen R,Johansson R,Vapalahti M,Ylä-Herttuala S

    更新日期:2002-11-01 00:00:00

  • The chicken chorioallantoic membrane tumor assay as model for qualitative testing of oncolytic adenoviruses.

    abstract::Oncolytic adenoviruses are promising anticancer agents. To study and optimize their tumor-killing potency, genuine tumor models are required. Here we describe the use of the chicken chorioallantoic membrane (CAM) tumor model in studies on oncolytic adenoviral vectors. Suspensions of human melanoma, colorectal carcinom...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2011.68

    authors: Durupt F,Koppers-Lalic D,Balme B,Budel L,Terrier O,Lina B,Thomas L,Hoeben RC,Rosa-Calatrava M

    更新日期:2012-01-01 00:00:00

  • Application of RNA-sequencing to identify transcriptome modification by DCLK1 in colorectal cancer cells.

    abstract::Doublecortin-like kinase 1 (DCLK1) is a cancer stem cell marker for the colorectal cancer (CRC). It plays critical roles in the oncogenesis, progression, and metastasis of CRC. DCLK1 can be an intriguing therapeutic target for CRC treatment. However, the molecular mechanism of how DCLK1 functions is unclear currently....

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-019-0144-4

    authors: Li L,Mei H,Commey ANA

    更新日期:2020-09-01 00:00:00

  • Alternative splicing as a novel of means of regulating the expression of therapeutic genes.

    abstract::In order to determine the potential of alternative splicing as a means of targeting the expression of therapeutic genes to tumor cells in vivo, a series of episomal plasmid-based "splice-activated gene expression" (pSAGE) vectors was generated, which contain minigene cassettes composed of various combinations of the t...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700427

    authors: Hayes GM,Carpenito C,Davis PD,Dougherty ST,Dirks JF,Dougherty GJ

    更新日期:2002-02-01 00:00:00

  • Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus.

    abstract::Although gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers, few studies have explored this possibility for uterine cervical cancer. MN/CA9 is a transmembrane glycoprotein that was first identified in the human cervical carcinoma cell line, HeLa. Since MN/CA9 ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700732

    authors: Lim HY,Ahn M,Chung HC,Gardner TA,Kao C,Lee SJ,Kim SJ

    更新日期:2004-08-01 00:00:00

  • Adenovirus-mediated overexpression of Fas induces apoptosis of gliomas.

    abstract::Gliomas express a higher amount of Fas than normal brain tissue. It is of interest to know whether expression of the Fas receptor is unfavorable to the antiapoptotic pathways in gliomas. In this study, we introduced the Fas gene via an adenovirus vector (Adeno-Fas) into the A-172, U251, and U-373 MG glioma cell lines,...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700110

    authors: Shinoura N,Ohashi M,Yoshida Y,Kirino T,Asai A,Hashimoto M,Hamada H

    更新日期:2000-02-01 00:00:00

  • Screening siRNAs targeting a novel gene (HA117) and the development of a derivative recombinant adenovirus delivery system.

    abstract::A novel gene, HA117, was discovered in our previous work. Using the pSOS-HUS vector method which we designed at previous study, we screened for small interfering RNAs (siRNAs) that targeted HA117. The pSOS-HUS siRNA screening results were verified and a delivery system was developed that contained a recombinant adenov...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2011.32

    authors: Zheng GH,Luo Q,Jin XQ,Guo YX,Xu YH

    更新日期:2011-09-01 00:00:00

  • Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers.

    abstract::Infection with high-risk types (type 16 or type 18) of human papillomaviruses (HPVs) increases a patient's risk of cervical cancer. Given the importance of the cervix and the severe side effects resulting from traditional cancer therapies, this study aimed to achieve targeted inhibition of viral oncogenes in tumor cel...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2010.38

    authors: Chang JT,Kuo TF,Chen YJ,Chiu CC,Lu YC,Li HF,Shen CR,Cheng AJ

    更新日期:2010-12-01 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

  • 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

  • Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors.

    abstract::p53 mutations are common genetic alterations in human cancer. Gene transfer of a wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of a replication-defective adenoviral expression vector containing wt p53 was c...

    journal_title:Cancer gene therapy

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1038/sj.cgt.7700214

    authors: Dummer R,Bergh J,Karlsson Y,Horowitz JA,Mulder NH,Huinink DTB,Burg G,Hofbauer G,Osanto S

    更新日期:2000-07-01 00:00:00

  • Use of targeted cationic liposomes in enhanced DNA delivery to cancer cells.

    abstract::Cationic liposomes are considered to be safe vectors for gene transfer, but they are less efficient at delivering DNA to cells when compared with retroviral vectors. Cationic liposomes complexed with DNA were targeted to specific cells in vitro by means of monoclonal antibodies (mAbs) or ligands associated with the li...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Kao GY,Change LJ,Allen TM

    更新日期:1996-07-01 00:00:00

  • Chimeric Antigen Receptor-modified T cells targeting EphA2 for the immunotherapy of paediatric bone tumours.

    abstract::Chimeric Antigen Receptor (CAR) T-cell therapy, as an approved treatment option for patients with B cell malignancies, demonstrates that genetic modification of autologous immune cells is an effective anti-cancer regimen. Erythropoietin-producing Hepatocellular receptor tyrosine kinase class A2 (EphA2) is a tumour ass...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-020-00221-4

    authors: Hsu K,Middlemiss S,Saletta F,Gottschalk S,McCowage GB,Kramer B

    更新日期:2020-09-01 00:00:00

  • Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to tamoxifen through upregulation of TIMP3.

    abstract::Aberrantly expressed microRNAs (miRNAs) are involved in breast tumorigenesis. It is still unclear if and how miRNAs-221/222 are implicated in breast cancer and the resistance to estrogen receptor modulator tamoxifen. We investigated the roles and mechanisms of miR-221/222 in breast cancer cells, particularly in modula...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2014.29

    authors: Gan R,Yang Y,Yang X,Zhao L,Lu J,Meng QH

    更新日期:2014-07-01 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

  • A novel gene transfer strategy that combines promoter and transgene activities for improved tumor cell inhibition.

    abstract::Typically, gene transfer strategies utilize a promoter/transgene arrangement that treat these elements independently and do not offer any interplay between them. Our goal was to establish a promoter/transgene combination that would result in improvement in both expression and therapeutic effect by utilizing the transc...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700846

    authors: Strauss BE,Bajgelman MC,Costanzi-Strauss E

    更新日期:2005-12-01 00:00:00

  • Recent developments in oncolytic adenovirus-based immunotherapeutic agents for use against metastatic cancers.

    abstract::Recurrent or metastatic cancer in most cases remains an incurable disease, and thus alternative treatment strategies, such as oncolytic virotherapy, are of great interest for clinical application. Oncolytic adenoviruses (Ads) have many advantages as virotherapeutic agents and have been safely employed in the clinics. ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/cgt.2012.95

    authors: Choi IK,Yun CO

    更新日期:2013-02-01 00:00:00

  • Regulation of melanoma malignancy by the RP11-705C15.3/miR-145-5p/NRAS/MAPK signaling axis.

    abstract::Melanoma is a common lethal skin cancer. Dissecting molecular mechanisms driving the malignancy of melanoma may uncover potential therapeutic targets. We previously identified miR-145-5p as an important tumor-suppressive microRNA in melanoma. Here, we further investigated the roles of long non-coding RNAs (lncRNAs) in...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-020-00274-5

    authors: Chen XJ,Liu S,Han DM,Han DZ,Sun WJ,Zhao XC

    更新日期:2020-12-14 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

  • CLEC5A expressed on myeloid cells as a M2 biomarker relates to immunosuppression and decreased survival in patients with glioma.

    abstract::Glioma is the most common tumor in the central nervous system that portends a poor prognosis. Key genes negatively related to survival may provide targets for therapy to improve the outcome of glioma. Here, we report a protein-coding gene CLEC5A, which is the top 1 gene by univariate Cox regression analysis of 524 pri...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-019-0140-8

    authors: Tong L,Li J,Choi J,Pant A,Xia Y,Jackson C,Liu P,Yi L,Boussouf E,Lim M,Yang X

    更新日期:2020-09-01 00:00:00