Oncolytic virotherapy for osteosarcoma using midkine promoter-regulated adenoviruses.


:Oncolytic virotherapy using adenoviruses has potential therapeutic benefits for a variety of cancers. We recently developed MOA5, a tumor-specific midkine promoter-regulated oncolytic vector based on human adenovirus serotype 5 (Ad5). We modified the binding tropism of MOA5 by replacing the cell-binding domain of the Ad5 fiber knob with that from another adenovirus serotype 35 (Ad35); the resulting vector was designated MOA35. Here we evaluated the therapeutic efficacies of MOA5 and MOA35 for human osteosarcoma. Midkine mRNA expression and its promoter activity was significantly high in five human osteosarcoma cell lines, but was restricted in normal cells. Very low levels of adenovirus cellular receptor coxsackievirus/adenovirus receptor (CAR) (Ad5 receptor) expression were observed in MNNG-HOS and MG-63 cells, whereas high levels of CAR expression were seen in the other osteosarcoma cell lines. By contrast, CD46 (Ad35 receptor) was highly expressed in all osteosarcoma cell lines. Infectivity and in vitro cytocidal effect of MOA35 was significantly enhanced in MNNG-HOS and MG-63 cells compared with MOA5, although the cytocidal effects of MOA5 were sometimes higher in high CAR-expressing cell lines. In MG-63 xenograft models, MOA35 significantly enhanced antitumor effects compared with MOA5. Our findings indicate that MOA5 and MOA35 allow tailored virotherapy and facilitate more effective treatments for osteosarcoma.


Cancer Gene Ther


Cancer gene therapy


Takagi-Kimura M,Yamano T,Tagawa M,Kubo S




Has Abstract


2014-03-01 00:00:00














  • Recombinant vaccinia virus GLV-1h68 is a promising oncolytic vector in the treatment of cholangiocarcinoma.

    abstract::Although early stage cholangiocarcinoma (CC) can be cured by surgical extirpation, the options for treatment of advanced stage CC are very few and suboptimal. Oncolytic virotherapy using replication-competent vaccinia virus (VACV) is a promising new strategy to treat human cancers. The ability of oncolytic VACV GLV-1h...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Pugalenthi A,Mojica K,Ady JW,Johnsen C,Love D,Chen NG,Aguilar RJ,Szalay AA,Fong Y

    更新日期:2015-12-01 00:00:00

  • Preclinical full-scale evaluation of dendritic cells transfected with autologous tumor-mRNA for melanoma vaccination.

    abstract::Most cancer vaccines to date have made use of common tumor antigens or allogenic cancer cell lines. The majority of tumor antigens may, however, be unique patient-specific antigens. Dendritic cells (DCs) are the most potent antigen-presenting cells known. The present report is a full-scale preclinical evaluation of au...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Kyte JA,Kvalheim G,Aamdal S,Saebøe-Larssen S,Gaudernack G

    更新日期:2005-06-01 00:00:00

  • Neuregulin receptor-mediated gene transfer by human epidermal growth factor receptor 2-targeted antibodies and neuregulin-1.

    abstract::The human epidermal growth factor receptors 2, 3, and 4 (HER2, HER3, and HER4, respectively) are frequently overexpressed in many human cancers, and therefore may be potential targets for receptor-mediated gene transfer. To evaluate this possibility, we constructed a series of HER-targeted gene transfer vehicles by co...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Kern JA,Wakita R,Sliwkowski MX

    更新日期:1999-11-01 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


    authors: Jackaman C,Nelson DJ

    更新日期:2010-06-01 00:00:00

  • Regression of primary hepatocarcinoma in cancer-prone transgenic mice by local interferon-gamma delivery is associated with macrophages recruitment and nitric oxide production.

    abstract::The clinical potential of tumor therapies must be evaluated using animal models closely resembling human cancers. We investigated the impact of locally delivered interferon-gamma (IFN-gamma) on primary hepatocarcinoma spontaneously developed by T-SV40 transgenic mice. A single intratumor injection of adenovirus IFN-ga...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Baratin M,Ziol M,Romieu R,Kayibanda M,Gouilleux F,Briand P,Leroy P,Haddada H,Rénia L,Viguier M,Guillet JG

    更新日期:2001-03-01 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


    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

  • 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


    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

  • Correction: Specific driving of the suicide E gene by the CEA promoter enhances the effects of paclitaxel in lung cancer.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Cancer gene therapy

    pub_type: 已发布勘误


    authors: Ballesteros ARR,Hernández R,Perazzoli G,Cabeza L,Melguizo C,Vélez C,Prados J

    更新日期:2020-06-01 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


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

    更新日期:2014-07-01 00:00:00

  • 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


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

    更新日期:2017-05-01 00:00:00

  • Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells.

    abstract::Let-7 miRNAs are involved in carcinogenesis and tumor progression through their roles in maintaining differentiation and normal development. However, there is little research focusing on the effects of let-7 on Wnt-activated self-renewal of breast cancer stem cells. By analyzing the expression levels of let-7 family m...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Sun X,Xu C,Tang SC,Wang J,Wang H,Wang P,Du N,Qin S,Li G,Xu S,Tao Z,Liu D,Ren H

    更新日期:2016-04-01 00:00:00

  • The role of natural killer cells in combinatorial anti-cancer therapy using Sindbis viral vectors and irinotecan.

    abstract::Oncolytic viruses (OVs) have shown great anti-cancer potential in animal models, but only modest success in early clinical trials. A better understanding of the mechanisms underlining OV efficacy is needed to resolve this discrepancy. In the clinic, OV therapy will likely be combined with traditional chemotherapy, und...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Granot T,Meruelo D

    更新日期:2012-08-01 00:00:00

  • microRNA-let-7e in serum-derived exosomes inhibits the metastasis of non-small-cell lung cancer in a SUV39H2/LSD1/CDH1-dependent manner.

    abstract::Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Accumulating research has highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the clinical significance of seru...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Xu S,Zheng L,Kang L,Xu H,Gao L

    更新日期:2020-12-09 00:00:00

  • T-cell-dependent antitumor effects produced by CD40 ligand expressed on mouse lung carcinoma cells are linked with the maturation of dendritic cells and secretion of a variety of cytokines.

    abstract::CD40/CD40 ligand (CD40L) interaction plays an essential role in cell-mediated immune responses. We examined whether expression of CD40L in murine lung carcinoma (A11) cells could produce antitumor effects. The proliferation rate in vitro of A11 cells transfected with the murine CD40L gene (A11/CD40L) was not different...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Tada Y,O-Wang J,Yu L,Shimozato O,Wang YQ,Takiguchi Y,Tatsumi K,Kuriyama T,Takenaga K,Sakiyama S,Tagawa M

    更新日期:2003-06-01 00:00:00

  • Adenovirus-mediated p16INK4 gene transfer significantly suppresses human breast cancer growth.

    abstract::The p16INK4 tumor suppressor gene encodes a protein that inhibits cyclin-dependent kinase 4, and its homologous deletion is common in human breast cancer. p16INK4 gene transfer has been reported to be efficacious in inducing growth inhibition of various human tumors such as brain, lung, prostate, and esophageal cancer...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Campbell I,Magliocco A,Moyana T,Zheng C,Xiang J

    更新日期:2000-09-01 00:00:00

  • Clinical characteristics and prognostic analysis of multiple primary malignant neoplasms in patients with lung cancer.

    abstract::Retrospective analysis of data from 14,528 lung cancer patients with multiple primary malignant neoplasm (MPMN) revealed that 2.5% (364/14,528) were MPMN cases and 96.2% (350/364) were diagnosed with two primary malignancies, 3.6% (13/364) with three primary malignancies, and 0.3% (1/364) with four primary malignancie...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Wang H,Hou J,Zhang G,Zhang M,Li P,Yan X,Ma Z

    更新日期:2019-11-01 00:00:00

  • Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study.

    abstract::Treatment of metastatic tumors with engineered adenoviruses that replicate selectively in tumor cells is a new therapeutic approach in cancer. Systemic administration of these oncolytic adenoviruses lack metastatic targeting ability. The tumor stroma engrafting property of intravenously injected mesenchymal stem cells...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: García-Castro J,Alemany R,Cascalló M,Martínez-Quintanilla J,Arriero Mdel M,Lassaletta A,Madero L,Ramírez M

    更新日期:2010-07-01 00:00:00

  • Lipid-coated polyplexes for targeted gene delivery to ovarian carcinoma cells.

    abstract::A nonviral gene delivery vector has been developed in our laboratory based on the cationic polymer, poly(2-(dimethylethylamino)ethyl methacrylate) (p(DMAEMA)). p(DMAEMA)-based polyplexes have been successfully used for the transfection of OVCAR-3 cells in vitro. However, these polyplexes were unable to transfect OVCAR...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Mastrobattista E,Kapel RH,Eggenhuisen MH,Roholl PJ,Crommelin DJ,Hennink WE,Storm G

    更新日期:2001-06-01 00:00:00

  • In vivo manipulation of interleukin-2 expression by a retroviral tetracycline (tet)-regulated system.

    abstract::We have used the tetracycline (tet)-regulated system as described previously to evaluate the applicability of controlled gene expression in cancer gene therapy. As a model gene, we used the human interleukin-2 (IL-2) gene, which has been placed under the transcriptional control of the tetO/promoter. Human melanoma cel...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Pitzer C,Schindowski K,Pomer S,Wirth T,Zöller M

    更新日期:1999-03-01 00:00:00

  • Targeting HSV-1 virions for specific binding to epidermal growth factor receptor-vIII-bearing tumor cells.

    abstract::Oncolytic herpes simplex virus (HSV) vectors have been used in early phase human clinical trials as a therapy for recurrent malignant glioblastoma. This treatment proved safe but limited improvements in patient survival were observed. The potency of these vectors might be enhanced by targeting vector infectivity to tu...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Grandi P,Fernandez J,Szentirmai O,Carter R,Gianni D,Sena-Esteves M,Breakefield XO

    更新日期:2010-09-01 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


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

    更新日期:2004-07-01 00:00:00

  • Gene silencing of A-kinase anchor protein 4 inhibits cervical cancer growth in vitro and in vivo.

    abstract::Earlier, we reported an association of A-kinase anchor protein 4 (AKAP4) expression in cervical cancer patient specimens, indicating its implications as an immunotherapeutic target. In this study, we investigated the possible role of AKAP4 in cervical carcinogenesis. AKAP4 messenger RNA and protein expression was asse...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Saini S,Agarwal S,Sinha A,Verma A,Parashar D,Gupta N,Ansari AS,Lohiya NK,Jagadish N,Suri A

    更新日期:2013-07-01 00:00:00

  • Suppressor of cytokine signaling-1 expression by infectivity-enhanced adenoviral vector inhibits IL-6-dependent proliferation of multiple myeloma cells.

    abstract::Multiple myeloma (MM) accounts for 10% of hematological malignant disorders. Its refractory nature indicates the necessity of developing novel therapeutic modalities. Since interleukin 6 (IL-6) is one of the major growth factors for MM cells, we expressed suppressor of cytokine signaling-1 (SOCS-1), one of the blockad...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Yamamoto M,Nishimoto N,Davydova J,Kishimoto T,Curiel DT

    更新日期:2006-02-01 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


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

    更新日期:1996-11-01 00:00:00

  • Enhancement of antitumor immunity by expression of CD70 (CD27 ligand) or CD154 (CD40 ligand) costimulatory molecules in tumor cells.

    abstract::CD70 (CD27 ligand (CD27L)), CD153 (CD30L), and CD154 (CD40L) are members of the tumor necrosis factor family of costimulatory molecules and expressed on the surface of T cells that are important for both T- and B-cell help. We examined the capacity for expression of these tumor necrosis factor family members on tumor ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Couderc B,Zitvogel L,Douin-Echinard V,Djennane L,Tahara H,Favre G,Lotze MT,Robbins PD

    更新日期:1998-05-01 00:00:00

  • Human natural killer cell line modified with a chimeric immunoglobulin T-cell receptor gene leads to tumor growth inhibition in vivo.

    abstract::The gene transfer of tumor-specific chimeric immunoglobulin T-cell receptors (cIgTCRs) combining antibody-like specificity with the effector cell function could be an attractive tool in immunotherapy. In this study, we directed the human natural killer (NK) cell line YT to tumor cells by gene transfer of a cIgTCR with...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Schirrmann T,Pecher G

    更新日期:2002-04-01 00:00:00

  • Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin.

    abstract::Sarcomas, or tumors of connective tissue, represent roughly 20% of childhood cancers. Although the cure rate for sarcomas in general has significantly improved in the last 10 years, there continue to be subgroups that are difficult to treat. High-grade or metastatic soft-tissue sarcomas and rhabdomyosarcomas (RMS) of ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Ganjavi H,Gee M,Narendran A,Freedman MH,Malkin D

    更新日期:2005-04-01 00:00:00

  • p53 alone or in combination with antisense cyclin D1 induces apoptosis and reduces tumor size in human melanoma.

    abstract::Melanoma incidence is growing at a faster rate than any other human malignancy. Wild-type (wt) p53 is important in both G(1) and G(2) cell cycle arrest, and cyclin D1 (CD1) is necessary for G(1)-->S progression in melanoma cells. We reported that an adenoviral vector containing wt p53 significantly reduced [(3)H]thymi...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Sauter ER,Takemoto R,Litwin S,Herlyn M

    更新日期:2002-10-01 00:00:00

  • Calcium-sensing receptor antagonist NPS-2143 suppresses proliferation and invasion of gastric cancer cells.

    abstract::NPS-2143 is a calcium-sensing receptor (CaSR) antagonist that has been demonstrated to possess anticancer activity. To date, the effects of NPS-2143 on gastric cancer (GC) cell growth, motility, and apoptosis have not been investigated. In the present study, we firstly investigated the expression of CaSR in GC tissues...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Zhang ZL,Li ZR,Li JS,Wang SR

    更新日期:2020-08-01 00:00:00

  • Antitumor immune responses mediated by adenoviral GDEPT using nitroreductase/CB1954 is enhanced by high-level coexpression of heat shock protein 70.

    abstract::Gene-directed enzyme prodrug therapy (GDEPT) is a promising approach to local management of cancer through targeted chemotherapy. Killing localized tumors by GDEPT in a manner that induces strong antitumor cellular immune responses might improve local management and allow benefit in disseminated cancer. Here we evalua...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Djeha HA,Todryk SM,Pelech S,Wrighton CJ,Irvine AS,Mountain A,Lipinski KS

    更新日期:2005-06-01 00:00:00