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 oligonucleotide (ODN20) conjugated to high molecular weight monomethoxy polyethylene glycol (MPEG) to inhibit the expression of the Ki-ras gene and the proliferation of pancreatic cancer cells. The conjugate, MPEG ODN20, was designed to form a triplex with a critical pur/pyr sequence located in the promoter of the Ki-ras gene. To make the conjugate resistant to endogenous and exogenous nucleases, five phosphorothioate linkages were introduced in its backbone. Confocal microscopy and FACS experiments showed that MPEG ODN20 had a higher capacity to penetrate the cell membranes and accumulate in the nucleus of Panc-1 cells than ODN20. Incubation of Panc-1 cells with MPEG ODN20 reduced specifically the levels of Ki-ras mRNA and RAS protein p21RAS. A single-dose administration of MPEG ODN20 was sufficient to inhibit cell proliferation by about 50% compared with control. By contrast, the antiproliferative activity of the unconjugated ODN20 analog was found to be not significant. Band-shift and footprinting experiments showed that MPEG ODN20 formed a weak triplex (Kd approximately 1.5 microM at 37 degrees C, 50 mM Tris-acetate, pH 7.4, 10 mM NaCl, 10 mM MgCl2, 5 mM spermidine) with the Ki-ras pyr/pur motif, suggesting that its bioactivity can hardly be mediated by a triplex-based mechanism. Here, we provide evidence that, in vitro, ODN20 and MPEG ODN20 competitively inhibit the binding to the Ki-ras pur/pyr motif of a nuclear protein, suggesting that the activity of MPEG ODN20 occurs with an aptameric mechanism. The biological implications of this study are discussed.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Cogoi S,Ballico M,Bonora GM,Xodo LEdoi
10.1038/sj.cgt.7700722subject
Has Abstractpub_date
2004-07-01 00:00:00pages
465-76issue
7eissn
0929-1903issn
1476-5500pii
7700722journal_volume
11pub_type
杂志文章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
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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::Direct intratumoral injection of a lipid/DNA complex encoding an allogeneic major histocompatibility complex (MHC) class I molecule leads to regression of both an immunogenic murine tumor and also melanoma lesions in some patients. We have sought to understand the mechanism(s) for this augmentation of antitumor activi...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
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
doi:10.1038/s41417-019-0084-z
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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
更新日期:2020-09-01 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::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
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journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
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更新日期:2018-06-01 00:00:00
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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
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journal_title:Cancer gene therapy
pub_type: 杂志文章
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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::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
更新日期:2003-01-01 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::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
doi:10.1038/cgt.2012.33
更新日期:2012-08-01 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::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
更新日期:2014-07-01 00:00:00
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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
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700995
更新日期:2007-01-01 00:00:00
abstract::Stathmin is the founding member of a family of microtubule-destabilizing proteins that have a critical role in the regulation of mitosis. Stathmin is expressed at high levels in breast cancer and its overexpression is linked to disease progression. Although there is a large body of evidence to support a role for stath...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2013.21
更新日期:2013-05-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7701079
更新日期:2007-11-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
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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::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::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: 杂志文章,撤回出版物
doi:10.1038/s41417-019-0158-y
更新日期:2020-02-01 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::The use of genetically modified tumor cells as vaccines has been successful in numerous animal models of grafted syngenic tumors and has provided the groundwork for many clinical trials of gene therapy in cancer patients. To investigate the real efficacy of ex vivo gene therapy-based vaccines, we used transgenic mice ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2014.59
更新日期:2014-12-01 00:00:00
abstract::Mortality due to colorectal cancer (CRC) is high and is associated with the development of liver metastases. Approximately 40% of human CRCs harbor an activating mutation in the KRAS oncogene. Tumor cells with activated KRAS are particularly sensitive to Reovirus T3D, a non-pathogenic oncolytic virus. The efficacy of ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700949
更新日期:2006-08-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2011.47
更新日期:2011-10-01 00:00:00
abstract::Transfer of genes to the gastrointestinal epithelium would be advantageous from investigational and therapeutic standpoints. Efficient transfer of DNA to the intestinal epithelial cells, however, has been problematic with conventional viral and nonviral vectors. As an alternative, we have utilized molecular conjugate ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00