Abstract:
:MicroRNAs (miRNAs) were discovered more than a decade ago as noncoding, single-stranded small RNAs (approximately 22 nucleotides) that control the timed gene expression pattern in Caenorhabditis elegans life cycle. A number of these evolutionarily conserved, endogenous miRNAs have been shown to regulate mammalian cell growth, differentiation and apoptosis. miRNAs are multispecific by nature. The individual miRNA is capable of modulating the expression of a network of mRNAs that it binds by imperfect sequence complementarity. Human cancers commonly exhibit an altered expression profile of miRNAs with oncogenic (miR-21, miR-106a and miR-155) or tumor-suppressive (let-7, miR-15a/16, miR-34a and miR-143/145) activity. As consistent with the natural function of miRNAs in specifying cellular phenotype, miRNA-based cancer gene therapy offers the theoretical appeal of targeting multiple gene networks that are controlled by a single, aberrantly expressed miRNA. Reconstitution of tumor-suppressive miRNA, or sequence-specific knockdown of oncogenic miRNAs by 'antagomirs,' has produced favorable antitumor outcomes in experimental models. We discuss pending issues that need to be resolved prior to the consideration of miRNA-based experimental cancer gene therapy. These include the need for definitive mRNA target validation, our incomplete understanding of rate-limiting cellular components that impact the efficiency of this posttranscriptional gene-silencing phenomenon, the possibility for nonspecific immune activation and the lack of a defined, optimal mode of delivery.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Tong AW,Nemunaitis Jdoi
10.1038/cgt.2008.8subject
Has Abstractpub_date
2008-06-01 00:00:00pages
341-55issue
6eissn
0929-1903issn
1476-5500pii
cgt20088journal_volume
15pub_type
杂志文章,评审abstract::Specificity is a prerequisite for systemic gene therapy of hepatocarcinoma. In vitro, the tumor-specific viral death effector Apoptin selectively induces apoptosis in malignant hepatic cells. Intratumoral treatment of xenografted subcutaneous hepatomas with Apoptin results in tumor regression. Here, we report a system...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700985
更新日期:2007-01-01 00:00:00
abstract::RNA interference (RNAi) is a natural cellular regulatory process that inhibits gene expression by transcriptional, post-transcriptional and translational mechanisms. Synthetic approaches that emulate this process (small interfering RNA (siRNA), short hairpin RNA (shRNA)) have been shown to be similarly effective in th...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.35
更新日期:2010-11-01 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::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::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
doi:10.1038/sj.cgt.7700584
更新日期:2003-06-01 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
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::Screening and identifying molecules target to checkpoint pathways has fostered the development of checkpoint-based anticancer strategies. Among these targets, inhibition of chk2 may induce cell death for tumors whose growth depends on enhanced chk2 activity. However, improvement of the potency and specificity of such ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700967
更新日期:2006-10-01 00:00:00
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
doi:10.1038/s41417-020-00216-1
更新日期:2020-12-09 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::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::Gene therapy designed to initiate apoptotic cell death provides a potentially effective method to treat cancer. A prerequisite for this approach is the identification of genes that function in distinct apoptotic pathways. Although apoptotic pathways initiated by receptors such as tumor necrosis factor receptor-1 are w...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700194
更新日期:2000-07-01 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::Poor tumor targeting of oncolytic adenoviruses (OAdv) after systemic administration is considered a major limitation for virotherapy of disseminated cancers. The benefit of using mesenchymal stem cells as cell carriers for OAdv tumor targeting is currently evaluated not only in preclinical models but also in clinical ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0110-1
更新日期:2020-05-01 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
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::Chemotherapy remains the main tool for the treatment of cancers, but is often hampered by tumor cell resistance. In this context, the transfer of genes able to accentuate the effect of anticancer drugs may constitute a useful approach, as exemplified by inactivation of nuclear factor (NF)-kappa B via direct transfer o...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700467
更新日期:2002-06-01 00:00:00
abstract::Arming oncolytic adenoviral vectors with anticancer transgenes that can be expressed in a tumor-selective manner may enable the engineering of vectors with increased potency, while retaining their safety profile. Armed oncolytic adenoviral vectors were constructed in which transgene expression has been linked via modi...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7701093
更新日期:2008-01-01 00:00:00
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,...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700110
更新日期:2000-02-01 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
abstract::Ad-PPE-Fas-c is an adenovector that expresses Fas-c under the control of the modified pre-proendothelin-1 (PPE-1) promoter. Fas-c is a chimeric death receptor containing the extracellular portion of tumour necrosis factor 1 receptor (TNFR1) and the transmembrane and intracellular portion of Fas. We recently demonstrat...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2008.20
更新日期:2008-08-01 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::Replication-competent oncolytic herpes simplex viruses (HSV), modified by deletion of certain viral growth genes, can selectively target malignant cells. The viral growth gene gamma(1)34.5 has significant homology to GADD34 (growth arrest and DNA damage protein 34), which promotes cell cycle arrest and DNA repair in r...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700890
更新日期:2006-03-01 00:00:00
abstract::We present here the updated results after 9 years of the beginning of a trial on canine patients with malignant melanoma. This surgery adjuvant approach combined local suicide gene therapy with a subcutaneous vaccine composed by tumor cells extracts and xenogeneic cells producing human interleukin-2 and granulocyte-ma...
journal_title:Cancer gene therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/cgt.2012.72
更新日期:2012-12-01 00:00:00
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
doi:10.1038/sj.cgt.7700807
更新日期:2005-06-01 00:00:00
abstract::Macrophages plasticity is a key feature in cancer progression. Neoplastic cells can alter their immune functions and orient them into a pro-tumoral phenotype. In this context, we developed a new therapeutic strategy to switch macrophages phenotype and reactivate their anti-tumoral functions. We showed a dual activity ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00286-1
更新日期:2021-01-05 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::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::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::Hepatocellular carcinoma (HCC) recurrence is one of the leading causes of death after orthotopic liver transplantation (OLT). The sixth complement component (C6) is a late-acting complement protein that participates in the assembly of the membrane attack complex, which has an indispensable role in innate and acquired ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.7
更新日期:2016-06-01 00:00:00