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 proliferation, and sensitize cells to TS-directed chemotherapeutic drugs. Based on our observation that targeting distinct regions of the TS mRNA with a variety of antisense molecules resulted in differential effects on TS mRNA levels, it was hypothesized that use of multiple ODNs targeting distinct noncontiguous regions would result in synergistic or antagonistic interactions. In this study, we report that some combinations of TS antisense ODNs were more effective at reducing TS mRNA abundance and inhibiting cell proliferation than the individual ODNs used alone. However, in contrast to the effects on cell proliferation, the enhanced sensitivity to anti-TS chemotherapeutic drugs (i.e., raltitrexed and 5-fluorodeoxyuridine) that is achieved by treatment with individual ODNs was not further augmented by combined ODN treatment. This suggests that ODNs targeting TS mRNA inhibit an alternative function of TS mRNA or protein, distinct from thymidylate production. The results are evidence that the novel use of multiple antisense ODNs that target different regions of the same mRNA represents a general strategy to improve antisense effectiveness.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Berg RW,Ferguson PJ,Vincent MD,Koropatnick DJdoi
10.1038/sj.cgt.7700566subject
Has Abstractpub_date
2003-04-01 00:00:00pages
278-86issue
4eissn
0929-1903issn
1476-5500pii
7700566journal_volume
10pub_type
杂志文章abstract：:ING4 as a member of inhibitor of growth (ING) tumor suppressor family has potent inhibitory effects on a variety of tumors. Interleukin-24 (IL-24), a cytokine-tumor suppressor, also shows broad-spectrum and tumor-specific antitumor activities. In this report, we constructed an ING4/IL-24 bicistronic adenovirus (Ad-ING...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2011.31
更新日期：2011-09-01 00:00:00
abstract：:The ability of viruses to readily infect tumor cells both in vitro and in vivo has resulted in their study as antitumor agents through a variety of strategies. Replicating and conditionally replicating viruses and recombinant viruses encoding genes for toxins and/or prodrugs have been studied for their direct antitumo...
journal_title：Cancer gene therapy
pub_type： 杂志文章,评审
doi：10.1038/sj.cgt.7700538
更新日期：2002-12-01 00:00:00
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：:Endothelial cells and endothelial cell precursors encoding a therapeutic gene have induced antitumor responses in preclinical models. Culture of peripheral blood provides a rich supply of autologous, highly proliferative endothelial cells, also referred to as blood outgrowth endothelial cells (BOECs). The aim of this ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2010.42
更新日期：2010-12-01 00:00:00
abstract：:Over the past several years we have obtained considerable evidence indicating that adenoviruses-expressing interferon α (Ad-IFNα) can overcome resistance to the IFNα protein itself. Since cancer cells infected with Ad-IFNα also show high perinuclear cytoplasmic IFNα expression, we were interested in whether endoplasmi...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2011.26
更新日期：2011-09-01 00:00:00
abstract：:Using our model to grow superficial human bladder cancer in the mouse bladder, we have found that the polyamide compound, Syn3, when injected intravesically for 1 hour at 1 mg/mL on two consecutive days, markedly increases rAd-beta-gal intravesical gene transfer and expression. This enhanced transgene expression was m...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700488
更新日期：2002-08-01 00:00:00
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
更新日期：2010-12-01 00:00:00
abstract：:We have constructed and tested five recombinant adenoviruses (Ads) that express a variety of immunomodulators, including CD40 ligand (CD40L), a potent costimulator of several components of the immune system. We demonstrate that CD40L expressed from Ad in K1735 mouse melanoma cells leads to a strong reduction in tumori...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700475
更新日期：2002-07-01 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：:The present study was designed to investigate the upstream transcription factors (TFs) and the signature genes in cholangiocarcinoma (CCA), providing better clues on the regulatory mechanisms and therapeutic applications. Gene expression data sets of CCA were searched in the Gene Expression Omnibus database for integr...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2016.64
更新日期：2016-12-01 00:00:00
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
doi：10.1038/sj.cgt.7700492
更新日期：2002-10-01 00:00:00
abstract：:Recurrent fusion genes (FGs) with clinical significances in leukemias are mainly mutually exclusive, and the coexistence of different FGs has been rarely reported. In this study, we retrospectively analyzed the incidence, genetic characteristics, and prognosis of leukemias with concurrent pathogenic FGs, which commonl...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-019-0147-1
更新日期：2020-02-01 00:00:00
abstract：:MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. In this study, we investigate whether let-7b acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers. We analyzed the expression of let-7b in 60 pair-matched gastric neoplastic and adjacent ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2014.75
更新日期：2015-04-01 00:00:00
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
更新日期：2007-09-01 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：:T cells can be reprogrammed to redirect specificity to tumor-associated antigens (TAAs) through the enforced expression of chimeric antigen receptors (CARs). The prototypical CAR is a single-chain molecule that docks with TAA expressed on the cell surface and, in contrast to the T-cell receptor complex, recognizes tar...
journal_title：Cancer gene therapy
pub_type： 杂志文章,评审
doi：10.1038/cgt.2014.69
更新日期：2015-03-01 00:00:00
abstract：:Retroviral replicating vectors (RRVs) have achieved efficient tumor transduction and enhanced therapeutic benefit in a wide variety of cancer models. Here, we evaluated two different RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV), which utilize different cellular recept...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-018-0037-y
更新日期：2019-02-01 00:00:00
abstract：:Cis-diamminedichloroplatinum(II) increased in vivo lipofection efficiency of tumor cells with a target gene, interferon gamma (IFN gamma), in a murine metastatic ovarian carcinoma model. The expression of IFN gamma gene in ascitic tumors reached a peak at day 11 after cisplatin treatment and lasted over 1 week. A loca...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：
更新日期：1997-11-01 00:00:00
abstract：:Mesenchymal stem cells (MSCs) have affinity to tumor sites where they home, affecting their biology and growth. Previously, we have isolated mesenchymal cells from the decidua of the human placenta named as decidua-derived MSCs (DMSCs). The aims of the present study were to investigate the migration capacity of DMSCs ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2012.71
更新日期：2013-01-01 00:00:00
abstract：:Immune-isolation of nonautologous cells with microencapsulation protects these cells from graft rejection, thus allowing the same recombinant therapeutic cell line to be implanted in different recipients. This approach was successful in treating HER2/neu-expressing tumors in mice by delivering an interleukin-2 fusion ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700786
更新日期：2005-04-01 00:00:00
abstract：:We aimed to analyze the association between the distribution of dendritic cells (DC) with expression of tumor-infiltrating T lymphocytes and clinicopathologic parameters with prognosis in epithelial ovarian cancer (EOC). Thirty-three EOC patient samples were surgically resected, and pathology was examined for clinicop...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2015.7
更新日期：2015-03-01 00:00:00
abstract：:Prostate cancer is one of the most commonly diagnosed cancers and the second leading cause of cancer deaths in Americans. The high mortality rate is mainly attributed to the invasiveness and metastasis of advanced prostate cancer. Targeting the molecules involved in metastasis could be an effective mode of treatment f...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2010.16
更新日期：2010-09-01 00:00:00
abstract：:We recently described a novel nonviral/viral vector for gene transfer, the plasmovirus (Noguiez-Hellin P, Robert-le Meur M, Laune S, et al. C R Acad Sci Paris, Sciences de la Vie. 1996;319:45-50; Noguiez-Hellin P, Robert-le Meur M, Salzmann J-L, et al. Proc Natl Acad Sci USA. 1996;93:4175-4180). Plasmoviruses are plas...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:As of January 2005, there were 1020 gene therapy clinical trials ongoing worldwide with 675 or 66.2% devoted to cancer gene therapy. The majority are occurring in the US and Europe (http://www.wiley.co.uk/genetherapy/clinical/). At the present time, to our knowledge there are no trials that employ gene delivery of Fas...
journal_title：Cancer gene therapy
pub_type： 杂志文章,评审
doi：10.1038/sj.cgt.7700965
更新日期：2006-12-01 00:00:00
abstract：:Multiple myeloma (MM) is one of hematological malignancies, characterized by malignant proliferation of plasma cells. Biomarkers play an important role in evaluating the development and prognosis of MM. Ubiquitin-conjugating enzyme E2T (UBE2T) is served to connect with particular E3 ubiquitin ligase to degraded-relate...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-018-0070-x
更新日期：2019-11-01 00:00:00
abstract：:The purpose of this study was to determine the feasibility of cytokine gene delivery to lymphatic tissue using transduced bone marrow-derived cells. MBAE and pBABE retroviral vectors carrying the genes for murine interleukin-4 and the selection marker neomycin phosphotransferase (neo) were used to transduce bone marro...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700204
更新日期：2000-08-01 00:00:00
abstract：:To identify the differentially expressed genes (DEGs) and their transcription factors (TFs) in colorectal cancer (CRC). We performed an integrated analysis of microarray studies. Functional annotation and CRC-specific transcriptional regulatory network construction were performed. Expression of selected DEGs and TFs w...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2017.8
更新日期：2017-06-01 00:00:00
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
更新日期：2007-10-01 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：: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
