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 study, we examined the efficacy of adv/tk/GCV gene therapy in a syngeneic BT4C rat malignant glioma model, either as a single administration or given as three injections during three consecutive days. The effect of combined adv-mediated macrophage colony-stimulating factor (MCSF) and adv/tk gene transfer was also studied. BT4C malignant glioma cells were injected into the right corpus callosum of BDIX rats (n=112). Before gene therapy, the presence of tumors was verified by MRI. The rats were divided into eight groups as follows: group I (n=20) received a single adv/tk gene transfer (total dose 4x10(8) pfu) and GCV treatment for 14 days; group II (n=5) received the same gene transfer without GCV; group III (n=28) received three adv/tk injections (total dose 4x10(8) pfu) on three consecutive days and GCV for 14 days; group IV (n=5) received three similar adv/tk injections without GCV medication; group V (n=13) received three adv/MCSF injections (total dose 2x10(8) pfu) on three consecutive days and GCV medication; group VI (n=12) received three adv/tk and adv/MCSF (total dose 6x10(8) pfu) injections on three consecutive days followed by GCV medication; and group VII (n=12) the same treatment without GCV. Group VIII (n=17) consisted of wild-type BT4C malignant glioma tumors without any treatment. Treatment effect and tissue responses were characterized by general histology, immunohistochemistry, MRI, and survival of the study groups. The best treatment effect and survival was found in rats treated with adv/tk gene transfer once a day for three consecutive days (P<.05). No improvement of the treatment effect was seen after the combined adv/tk and adv/MCSF gene transfer compared with the repeated adv/tk gene transfer. The results show that 20% of the rats can be cured (survival >6 months) after optimized adv/tk gene therapy. It is concluded that repeated intratumoral administration of adv/tk is a promising approach for the treatment of malignant glioma tumors in vivo.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Tyynelä K,Sandmair AM,Turunen M,Vanninen R,Vainio P,Kauppinen R,Johansson R,Vapalahti M,Ylä-Herttuala Sdoi
10.1038/sj.cgt.7700515subject
Has Abstractpub_date
2002-11-01 00:00:00pages
917-24issue
11eissn
0929-1903issn
1476-5500journal_volume
9pub_type
杂志文章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
doi:10.1038/cgt.2016.3
更新日期:2016-04-01 00:00:00
abstract::In this study, we investigated the safety and efficacy in cancer patients of a single intra-tumor injection of recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene (AdV/TK) followed by systemic administration of ganciclovir (GCV). In 18 patients with malignant tumors refractory to standard...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2009.19
更新日期:2009-09-01 00:00:00
abstract::Gastric cancer is the fourth most common type of cancer. Liver-intestine cadherin (CDH17) has been found to be involved in the proliferation and apoptosis of gastric cancer cells. Cisplatin is one of the most widely used antineoplastic agents in the treatment of solid tumor and hematological malignancies. However, the...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-017-0001-2
更新日期:2018-02-01 00:00:00
abstract::Glioblastoma (GBM) is known as a tumor type, which arises from astrocytes. Several studies indicated that GBM tumor cells are malignant. This is because of the fact that they consist of different cell types, which are reproducing very quickly and are also supported by a large network of blood vessels. The correct iden...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2016.48
更新日期:2016-12-01 00:00:00
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:
更新日期:1998-11-01 00:00:00
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
更新日期:2003-07-01 00:00:00
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
更新日期:2017-05-01 00:00:00
abstract::The human papillomaviruses (HPVs) are a diverse group of infectious agents, some of which are a causative agent of human cancers. Cervical cancer and oral cancer are closely associated with specific types of HPV, and the tumors grow only if there is continual expression of the viral E6 and E7 genes. Evidence from in v...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.cgt.7700926
更新日期:2006-05-01 00:00:00
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
更新日期:2013-02-01 00:00:00
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
更新日期:2004-08-01 00:00:00
abstract::Mammary carcinomas that develop in C3 (1)/SV40 T- antigen (TAg) transgenic mice have lost the p53-mediated induction of p21, leading to increased cellular proliferation and significant elevations of cyclins and Cdks. To test whether p21 could serve as a target for anticancer therapy for this mammary cancer model, a re...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700275
更新日期:2001-01-01 00:00:00
abstract::Angiogenesis is among the most important mechanisms that helps cancer cells to survive, grow and undergo metastasis. Therefore, inhibiting angiogenesis will suppress tumor growth. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are believed to be important players of angiogenesis. The goal of this s...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.76
更新日期:2017-01-01 00:00:00
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
更新日期:2005-02-01 00:00:00
abstract::We have examined the effect of adenoviruses expressing soluble transforming growth factor receptorII-Fc (sTGFβRIIFc) in a 4T1 mouse mammary tumor bone metastasis model using syngeneic BALB/c mice. Infection of 4T1 cells with a non-replicating adenovirus, Ad(E1-).sTβRFc, or with two oncolytic adenoviruses, Ad.sTβRFc an...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.41
更新日期:2012-09-01 00:00:00
abstract::Breast cancer is the most common cause of cancer-related death worldwide, thus remaining a crucial health problem among women despite advances in conventional therapy. Therefore, new alternative strategies are needed for effective diagnosis and treatment. One approach is the use of oncolytic viruses for gene-directed ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.49
更新日期:2011-01-01 00:00:00
abstract::Angiogenesis is a requirement for solid tumor growth. Therefore, inhibition of this neovascularization is one mechanism by which restoration of wtp53 function may lead to tumor regression. Here we report that adenoviral vector-mediated wild-type p53 transduction results in growth inhibition of squamous cell carcinoma ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700361
更新日期:2001-10-01 00:00:00
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
更新日期:2003-04-01 00:00:00
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
更新日期:2005-06-01 00:00:00
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
更新日期:2004-09-01 00:00:00
abstract::The tumor-suppressive role of Farnesoid X receptor (FXR) in colorectal tumorigenesis supports restoring FXR expression as a novel therapeutic strategy. However, the complicated signaling network and tumor heterogeneity hinder the effectiveness of FXR agonists in the clinical setting. These difficulties highlight the i...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00239-8
更新日期:2020-10-13 00:00:00
abstract::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 ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2014.7
更新日期:2014-03-01 00:00:00
abstract::One of the challenges of oncolytic virotherapy is the inability to easily track or monitor virus activity during treatment. Here we describe the construction and functional characterization of Ad/hTC-GFP-E1, an oncolytic virus whose transgenes GFP and E1A are both under the control of a synthetic promoter (hTC). This ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700944
更新日期:2006-07-01 00:00:00
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
更新日期:2001-02-01 00:00:00
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
更新日期:2011-09-01 00:00:00
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:
更新日期:1996-11-01 00:00:00
abstract::Fusion of the 5' half of the Ewing's sarcoma (ES) gene EWS with the DNA-binding domain of several transcription factors has been detected in many human tumors. The t(11;22)(q24;q12) chromosomal translocation is specifically linked to ES and primitive neuroectodermal tumors and results, in the majority of cases, in the...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700220
更新日期:2000-08-01 00:00:00
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
更新日期:2000-07-01 00:00:00
abstract::Replication-competent adenoviruses (Ads) were used for oncolytic virotherapy soon after they were discovered. Recently mutated and genetically engineered Ads have been shown to selectively lyse tumor cells. We have split the human Ad type 5 genome into two defective viruses that complement each other only in certain t...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700001
更新日期:1999-01-01 00:00:00
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
更新日期:1999-09-01 00:00:00
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
doi:10.1038/s41417-020-0166-y
更新日期:2020-06-01 00:00:00