In Vitro and In Vivo Preclinical Effects of Type I IFNs on Gliomas

被引:14
作者
Galani, Vasiliki [1 ]
Papadatos, Stamatis S. [2 ]
Alexiou, George [3 ]
Galani, Angeliki [4 ]
Kyritsis, Athanasios P. [3 ,5 ]
机构
[1] Univ Ioannina, Fac Med, Dept Anat Histol Embryol, GR-45110 Ioannina, Greece
[2] Univ Athens, Sotiria Gen Hosp, Athens Sch Med, Dept Internal Med 3, Athens, Greece
[3] Univ Ioannina, Inst Neurosurg, Ioannina, Greece
[4] Univ Patras, Dept Environm & Nat Resources Management, Patras, Greece
[5] Univ Ioannina, Dept Neurol, Fac Med, Ioannina, Greece
关键词
type I IFNs; type II IFNs; gliomas; in vitro preclinical effects; in vivo preclinical effects; BETA GENE-THERAPY; CYTOKINE SIGNALING SOCS; INTERFERON-BETA; CELL-LINES; MALIGNANT GLIOMA; INDUCED APOPTOSIS; DOWN-REGULATION; MELANOMA-CELLS; STEM-CELLS; ALPHA;
D O I
10.1089/jir.2016.0094
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The interferons (IFNs) are a family of cytokines with diverse cellular actions such as control of cell proliferation and regulation of immune responses; therefore, they have been extensively studied as antitumor agents for a variety of malignancies, including gliomas. Type I IFNs exert their antitumor effects either directly, by targeting the tumor cells or the tumor stem cells, or indirectly, by regulating the anticancer activities of the immune system. More specifically, IFN-beta and IFN-alpha exhibit antiproliferative effects by p53 induction, CD8(+) T-lymphocyte and macrophage activation, chemokine secretion, and miR-21 downregulation. In vitro and in vivo studies provide evidence that immunotherapy could have a role in glioma treatment, especially when first-line therapeutic interventions fail to produce durable responses. These effects are more obvious when combining IFN-beta with classical antitumor therapies such as temozolamide, an oral chemotherapeutic, for both newly diagnosed and recurrent gliomas. However, further clinical studies are needed to determine whether IFNs will have a definite place in the management of gliomas.
引用
收藏
页码:139 / 146
页数:8
相关论文
共 91 条
[21]   MicroRNA-145 Targets YES and STAT1 in Colon Cancer Cells [J].
Gregersen, Lea H. ;
Jacobsen, Anders B. ;
Frankel, Lisa B. ;
Wen, Jiayu ;
Krogh, Anders ;
Lund, Anders H. .
PLOS ONE, 2010, 5 (01)
[22]   Interferon-induced mx proteins: Dynamin-like GTPases with antiviral activity [J].
Haller, O ;
Kochs, G .
TRAFFIC, 2002, 3 (10) :710-717
[23]   Interferon-β Induces Loss of Spherogenicity and Overcomes Therapy Resistance of Glioblastoma Stem Cells [J].
Happold, Caroline ;
Roth, Patrick ;
Silginer, Manuela ;
Florea, Ana-Maria ;
Lamszus, Katrin ;
Frei, Karl ;
Deenen, Rene ;
Reifenberger, Guido ;
Weller, Michael .
MOLECULAR CANCER THERAPEUTICS, 2014, 13 (04) :948-961
[24]   Constitutive IFN-α/β signal for efficient IFN-α/β gene induction by virus [J].
Hata, N ;
Sato, M ;
Takaoka, A ;
Asagiri, M ;
Tanaka, N ;
Taniguchi, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 285 (02) :518-525
[25]   MiR-21 expression in the tumor cell compartment holds unfavorable prognostic value in gliomas [J].
Hermansen, Simon Kjaer ;
Dahlrot, Rikke Hedegaard ;
Nielsen, Boye Schnack ;
Hansen, Steinbjorn ;
Kristensen, Bjarne Winther .
JOURNAL OF NEURO-ONCOLOGY, 2013, 111 (01) :71-81
[26]   The complexity of NF-κB signaling in inflammation and cancer [J].
Hoesel, Bastian ;
Schmid, Johannes A. .
MOLECULAR CANCER, 2013, 12
[27]   Induction of MxA gene expression by influenza A virus requires type I or type III interferon signaling [J].
Holzinger, Dirk ;
Jorns, Carl ;
Stertz, Silke ;
Boisson-Dupuis, Stephanie ;
Thimme, Robert ;
Weidmann, Manfred ;
Casanova, Jean-Laurent ;
Haller, Otto ;
Kochs, Georg .
JOURNAL OF VIROLOGY, 2007, 81 (14) :7776-7785
[28]  
Hong YK, 2000, CLIN CANCER RES, V6, P3354
[29]   Enlarged Memory T-Cell Pool and Enhanced Th1-Type Responses in Chronic Myeloid Leukemia Patients Who Have Successfully Discontinued IFN-α Monotherapy [J].
Ilander, Mette ;
Kreutzman, Anna ;
Rohon, Peter ;
Melo, Teresa ;
Faber, Edgar ;
Porkka, Kimmo ;
Vakkila, Jukka ;
Mustjoki, Satu .
PLOS ONE, 2014, 9 (01)
[30]   Human neural stem cells transduced with IFN-β and cytosine deaminase genes intensify bystander effect in experimental glioma [J].
Ito, S. ;
Natsume, A. ;
Shimato, S. ;
Ohno, M. ;
Kato, T. ;
Chansakul, P. ;
Wakabayashi, T. ;
Kim, S. U. .
CANCER GENE THERAPY, 2010, 17 (05) :299-306