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 stathmin in breast cancer progression, the validity of stathmin as a viable therapeutic target for breast cancer has not been investigated. Here, we used a bicistronic adenoviral vector that co-expresses green fluorescent protein and a ribozyme that targets stathmin messenger RNA in preclinical breast cancer models with different estrogen receptor (ER) status. We examined the effects of anti-stathmin ribozyme on the malignant phenotype of breast cancer cells in vitro and in xenograft models in vivo both as a single agent and in combination with chemotherapeutic agents. Adenovirus-mediated gene transfer of anti-stathmin ribozyme resulted in a dose-dependent inhibition of proliferation and clonogenicity associated with a G2/M arrest and increase in apoptosis in both ER-positive and ER-negative breast cancer cell lines. This inhibition was markedly enhanced when stathmin-inhibited breast cancer cells were exposed to low concentrations of taxol, which resulted in virtually complete loss of the malignant phenotype. Interestingly, breast cancer xenografts treated with low doses of anti-stathmin therapy and taxol showed regression in a majority of tumors, while some tumors stopped growing completely. In contrast, combination of anti-stathmin ribozyme and adriamycin resulted in only a modest inhibition of growth in vitro and in breast cancer xenografts in vivo. Although inhibition of tumor growth was observed in both the combination treatment groups compared with groups treated with single agent alone, combination of anti-stathmin therapy and taxol had a more profound inhibition of tumorigenicity, as both agents target the microtubule pathway. Clinically, these findings are highly relevant because taxol is one of the most active chemotherapeutic agents in breast cancer. These studies provide the proof-of-principle that stathmin provides an attractive molecular target, which could serve as a primary focus of novel approaches to breast cancer.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Miceli C,Tejada A,Castaneda A,Mistry SJdoi
10.1038/cgt.2013.21subject
Has Abstractpub_date
2013-05-01 00:00:00pages
298-307issue
5eissn
0929-1903issn
1476-5500pii
cgt201321journal_volume
20pub_type
杂志文章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
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journal_title:Cancer gene therapy
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journal_title:Cancer gene therapy
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doi:10.1038/sj.cgt.7700096
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journal_title:Cancer gene therapy
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journal_title:Cancer gene therapy
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更新日期:2006-10-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
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journal_title:Cancer gene therapy
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更新日期:2000-11-01 00:00:00
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journal_title:Cancer gene therapy
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doi:10.1038/sj.cgt.7700394
更新日期:2001-11-01 00:00:00
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journal_title:Cancer gene therapy
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更新日期:2015-08-01 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:2016-02-01 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::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
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700938
更新日期:2006-06-01 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:2000-08-01 00:00:00
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journal_title:Cancer gene therapy
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doi:10.1038/s41417-020-00282-5
更新日期:2021-01-07 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700899
更新日期:2006-03-01 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
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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::To investigate a novel suicide gene for nasopharyngeal carcinoma (NPC) therapy, the yCDglyTK gene was constructed by fusing yeast cytosine deaminase (CD) and herpes simplex type 1 thymidine kinase. The expression of the yCDglyTK gene was detected by RT-PCR and Western blotting, and its bioactivity was demonstrated by ...
journal_title:Cancer gene therapy
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doi:10.1038/sj.cgt.7700728
更新日期:2004-12-01 00:00:00
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pub_type: 已发布勘误
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journal_title:Cancer gene therapy
pub_type: 杂志文章
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更新日期:2010-09-01 00:00:00
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journal_title:Cancer gene therapy
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更新日期:1996-03-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0103-0
更新日期:2020-05-01 00:00:00
abstract::The clinical potential of tumor therapies must be evaluated using animal models closely resembling human cancers. We investigated the impact of locally delivered interferon-gamma (IFN-gamma) on primary hepatocarcinoma spontaneously developed by T-SV40 transgenic mice. A single intratumor injection of adenovirus IFN-ga...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700285
更新日期:2001-03-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.75
更新日期:2013-01-01 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: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
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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
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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