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, each of which expresses Fas on the cell surface. Infection of Adeno-Fas induced apoptosis in each glioma cell line. In U251 cells and A-172 cells that express the same level of Fas as a result of infection with Adeno-Fas, a much higher percentage of U251 cells underwent apoptosis than did A-172 cells. This suggests that each glioma cell line has its own threshold of Fas expression, above which apoptosis is induced, and that the constitutive expression of Fas is below the level of this threshold. It was found that the constitutive expression of the anti-apoptotic gene Bcl-X(L) is higher in A-172 cells than in U251 cells. Adenovirus-mediated transduction of the Bcl-X(L) gene into U251 cells effectively suppressed Adeno-Fas-mediated apoptosis. These data indicate that the Bcl-X(L) gene is one of the important determinants of the threshold for Fas-mediated apoptosis. When U251 and U-373 MG cells were transduced with the Fas gene controlled by the myelin basic protein promoter, which had been shown to be active in gliomas but not in neural tissues, the cells underwent markedly enhanced apoptosis. Taken together, these results indicate that the overexpression of Fas alone induced apoptosis in each glioma cell line. The degree of Fas-mediated apoptosis was attenuated by the expression of an anti-apoptotic gene, Bcl-X(L). The adenovirus-mediated induction of Fas gene controlled by a tissue-specific promoter (e.g., myelin basic protein promoter) would be a promising therapeutic approach for malignant glioma.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Shinoura N,Ohashi M,Yoshida Y,Kirino T,Asai A,Hashimoto M,Hamada Hdoi
10.1038/sj.cgt.7700110subject
Has Abstractpub_date
2000-02-01 00:00:00pages
224-32issue
2eissn
0929-1903issn
1476-5500journal_volume
7pub_type
杂志文章abstract::We exploited the differential activation of hypoxia-inducible factor (HIF)-dependent gene expression in tumors versus normal tissue for the design of a targeted oncolytic herpes simplex virus type-1 (HSV-1). A gene that is essential for viral replication, infected cell polypeptide 4 (ICP4), was placed under the regula...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.62
更新日期:2011-02-01 00:00:00
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
doi:10.1038/sj.cgt.7700021
更新日期:1999-03-01 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
abstract::A number of monoclonal antibodies (mAbs) have been studied for their ability to enhance immune responses. Although these antibodies are effective in pre-clinical and clinical studies, they are costly and have occasionally been associated with adverse effects such as autoimmunity and cytokine storm. Numerous studies ha...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2009.39
更新日期:2009-12-01 00:00:00
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
doi:10.1038/sj.cgt.7700069
更新日期:1999-11-01 00:00:00
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:
更新日期:1996-07-01 00:00:00
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
更新日期:2008-02-01 00:00:00
abstract::The effect of local and systemic delivery of the angiostatin gene on human melanoma growth was studied in nude mice. Liposome-coated plasmids carrying the cDNA coding for murine and human angiostatin (CMVang and BSHang) were injected weekly, locally or systemically, in mice transplanted with melanoma cells. The treatm...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700331
更新日期:2001-07-01 00:00:00
abstract::A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 ce...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
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
更新日期:2012-01-01 00:00:00
abstract::Myeloid leukemia (ML) is heterogeneous cancer classified by abnormal growth of myeloid cells due to genetic aberrations and mutations. It is generally categorized by clonal disorders of hematopoietic stem cells and differentiation. The molecular mechanism behind the myeloid malignancies is not yet known, but recent se...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/s41417-018-0025-2
更新日期:2018-08-01 00:00:00
abstract::Cisplatin (DDP)-based strategies are the first-line treatment for cancers; however, resistance to DDP remains a major obstacle to cancer treatment. The current study set out to investigate the effects of microRNA-181c (miR-181c) on the resistance of ovarian cancer cells to DDP. Ovarian cancer-associated miRs as well a...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-0195-6
更新日期:2020-07-07 00:00:00
abstract::Immune checkpoint inhibition (ICI) has revolutionized cancer treatment, and produced durable responses in many cancer types. However, there remains a subset of patients that do not respond despite their tumors exhibiting PD-L1 expression, which highlights the need for additional biomarkers relevant to response. Here, ...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/s41417-020-0174-y
更新日期:2020-12-01 00:00:00
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
doi:10.1038/sj.cgt.7700226
更新日期:2000-09-01 00:00:00
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
doi:10.1038/sj.cgt.7700453
更新日期:2002-04-01 00:00:00
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
更新日期:2004-12-01 00:00:00
abstract::We examined whether novel cytokines, interleukin (IL)-21 and IL-23, that were expressed in tumors could produce antitumor effects in the inoculated mice. Human pancreatic cancer AsPC-1 cells were retrovirally transduced with murine IL-21 or IL-23 (p19-linked p40) gene (AsPC-1/IL-21, AsPC-1/IL-23) and were injected int...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700630
更新日期:2003-10-01 00:00:00
abstract::The DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) is epigenetically silenced in some tumors by MGMT gene promoter methylation. MGMT-hypermethylated solid tumors have enhanced susceptibility to the cytotoxic effects of alkylating chemotherapy such as temozolomide, compared with non-methylated tumors. ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2017.27
更新日期:2017-08-01 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::We have described three potential adenovirus type 5 (Ad5)-based replication-competent cancer gene therapy vectors named KD1, KD3, and VRX-007. All three vectors overexpress an Ad5 protein named Adenovirus Death Protein (ADP, also named E3-11.6 K protein). ADP is required for efficient lysis of Ad5-infected cells and s...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700555
更新日期:2003-03-01 00:00:00
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
doi:10.1038/cgt.2010.22
更新日期:2010-09-01 00:00:00
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
更新日期:2013-07-01 00:00:00
abstract::Sodium iodide symporter (NIS) reporter gene imaging is an excellent technology for noninvasive cell fate determination in living animals unless the NIS-transduced cells reside in perigastric organs such as the spleen, liver, diaphragm, omentum, pancreas, perigastric lymph nodes or perigastric tumor deposits. Here we r...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2013.57
更新日期:2013-11-01 00:00:00
abstract::Various therapeutic approaches toward killing glioma cells by inducing apoptosis have been developed, but these approaches are often hampered by anti-apoptotic mechanisms. In this study, we attempted to develop a technique that overrides the resistance toward apoptosis in glioma cells. To date, p53- and Fas-mediated a...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700160
更新日期:2000-05-01 00:00:00
abstract::Replication-selective oncolytic viruses are being developed for human cancer therapy. We previously developed an attenuated adenovirus (OBP-301, Telomelysin), in which the human telomerase reverse transcriptase promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site. OBP-301...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.57
更新日期:2012-11-01 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::A phase l study using intravesical Ad-IFNαSyn3 for patients with bacillus Calmette-Guérin-resistant superficial bladder cancer showed a complete remission (CR) of 43% at 90 days after treatment with high levels of interferon-α (IFNα) being produced. Ad-IFNα kills bladder cancer cells by two apoptotic and one necrotic ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2014.1
更新日期:2014-03-01 00:00:00
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
更新日期:2018-08-01 00:00:00
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
更新日期:1999-07-01 00:00:00
abstract::Current oncolytic viruses exert only limited antitumor activity on their own. There is a need to increase their oncolytic capability. We evaluated the effect of a differentiating reagent, hexamethylene bisacetamide (HMBA), on the antitumor activity of a gamma(1)34.5-deficient herpes simplex virus type 1 (HSV-1) R849 f...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700957
更新日期:2006-08-01 00:00:00