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Efficient human int...
Efficient human interferon-alpha gene transfer to neuroendocrine tumor cells with long-term and stable expression
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- Liu, Minghui (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Onkologisk endokrinologi,Kjell Öberg
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- Kilarski, Witold W. (författare)
- Uppsala universitet,Institutionen för genetik och patologi
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- Gerwins, Pär (författare)
- Uppsala universitet,Institutionen för genetik och patologi,Institutionen för medicinsk biokemi och mikrobiologi
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- Öberg, Kjell (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Onkologisk endokrinologi,Kjell Öberg
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- Zhou, Yinghua (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Onkologisk endokrinologi,Kjell Öberg
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visa färre...
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(creator_code:org_t)
- 2006-05-31
- 2005
- Engelska.
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 82:5-6, s. 264-73
- Relaterad länk:
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Interferon (IFN)-alpha has been used in the treatment of neuroendocrine (NE) tumors; however, the feasibility of IFN-alpha gene therapy has not been evaluated in NE tumor cells. In this study, human IFN-alpha2 (hIFN-alpha2) gene has been transferred into a NE tumor cell line BON. hIFN-alpha2-expressing BON cells were subcutaneously inoculated in nude mice. The results demonstrated that hIFN-alpha2 exerted significant antiproliferative effects on NE tumor cell lines (BON and LCC18) and other tumor cell lines (CA46 and SW480) as well as porcine aorta cell line. Furthermore, hIFN-alpha2 demonstrated its antineovascular activity in mice tumor and a direct antiangiogenic effect in chicken chorioallantoic membrane assay. hIFN-alpha2-expressing BON cells had a stable and long-term expression. Mice implanted with hIFN-alpha2-expressing BON cells showed a lower incidence, a delayed development and a significantly longer doubling time of the tumor compared to both wild-type (WT) and vector group. In addition, IFN-alpha significantly inhibited cell adhesion of WT BON cells. hIFN-alpha2-expressing BON tumors had a high level of hIFN-alpha2 protein. Finally, mice implanted with a mixture of WT and hIFN-alpha2-expressing BON cells (1:1) presented a delayed tumor development and had an even lower incidence of tumors than those implanted with hIFN-alpha2-expressing BON cells only. The doubling time of tumor was also longest in the mixture group. Our data suggest that hIFN-alpha2 gene therapy might be possible to be used as a new treatment for NE tumor patients. Further studies on the regulation of hIFN-alpha expression are needed, especially in combination with other cytokines, which could lead to a better understanding and improvements of hIFN-alpha gene therapy.
Nyckelord
- Actins/analysis
- Animals
- Cell Adhesion/drug effects/physiology
- Cell Differentiation
- Cell Line; Tumor
- Cell Movement/drug effects/physiology
- Cytoskeleton/chemistry/pathology
- Gene Expression Regulation; Neoplastic/*genetics/physiology
- Gene Therapy
- Gene Transfer Techniques
- Humans
- Immunohistochemistry
- Interferon-alpha/analysis/*genetics/physiology/therapeutic use
- Mice
- Mice; Nude
- Neoplasm Invasiveness/physiopathology
- Neovascularization; Pathologic/drug therapy
- Neuroendocrine Tumors/*genetics/pathology/therapy
- Recombinant Proteins/analysis/genetics
- Swine
- Time Factors
- eIF-2 Kinase/analysis/genetics/physiology
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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