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Immunohistochemical Characterization and Sensitivity to Human Adenovirus Serotypes 3, 5, and 11p of New Cell Lines Derived from Human Diffuse Grade II to IV Gliomas

Niittykoski, Minna (author)
Univ Eastern Finland, AI Virtanen Inst Mol Sci, Biotechnol & Mol Med, Kuopio, Finland.
zu Fraunberg, Mikael von und (author)
Kuopio Univ Hosp, NeuroCtr, Kuopio, Finland.;Univ Eastern Finland, Inst Clin Med, Neurosurg, Kuopio, Finland.
Martikainen, Miika (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi
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Rauramaa, Tuomas (author)
Univ Eastern Finland, Inst Clin Med, Pathol, Kuopio, Finland.;Kuopio Univ Hosp, Dept Pathol, Kuopio, Finland.
Immonen, Arto (author)
Kuopio Univ Hosp, NeuroCtr, Kuopio, Finland.;Univ Eastern Finland, Inst Clin Med, Neurosurg, Kuopio, Finland.
Koponen, Susanna (author)
Kuopio Univ Hosp, NeuroCtr, Kuopio, Finland.
Leinonen, Ville (author)
Kuopio Univ Hosp, NeuroCtr, Kuopio, Finland.;Univ Eastern Finland, Inst Clin Med, Neurosurg, Kuopio, Finland.
Vaha-Koskela, Markus (author)
Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
Zhang, Qiwei (author)
Southern Med Univ, Guangzhou, Guangdong, Peoples R China.
Kuhnel, Florian (author)
Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany.
Mei, Ya-Fang (author)
Umeå universitet,Institutionen för klinisk mikrobiologi,Umea Univ, Dept Clin Microbiol, Umea, Sweden.
Yla-Herttuala, Seppo (author)
Univ Eastern Finland, AI Virtanen Inst Mol Sci, Biotechnol & Mol Med, Kuopio, Finland.
Jaaskelainen, Juha E. (author)
Kuopio Univ Hosp, NeuroCtr, Kuopio, Finland.;Univ Eastern Finland, Inst Clin Med, Neurosurg, Kuopio, Finland.
Hinkkanen, Ari (author)
Univ Eastern Finland, AI Virtanen Inst Mol Sci, Biotechnol & Mol Med, Kuopio, Finland.
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Univ Eastern Finland, AI Virtanen Inst Mol Sci, Biotechnol & Mol Med, Kuopio, Finland Kuopio Univ Hosp, NeuroCtr, Kuopio, Finland.;Univ Eastern Finland, Inst Clin Med, Neurosurg, Kuopio, Finland. (creator_code:org_t)
ELSEVIER SCIENCE INC, 2017
2017
English.
In: Translational Oncology. - : ELSEVIER SCIENCE INC. - 1944-7124 .- 1936-5233. ; 10:5, s. 772-779
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • BACKGROUND: Oncolytic adenoviruses show promise in targeting gliomas because they do not replicate in normal brain cells. However, clinical responses occur only in a subset of patients. One explanation could be the heterogenic expression level of virus receptors. Another contributing factor could be variable activity of tumor antiviral defenses in different glioma subtypes. METHODS: We established a collection of primary low-passage cell lines from different glioma subtypes (3 glioblastomas, 3 oligoastrocytomas, and 2 oligodendrogliomas) and assessed them for receptor expression and sensitivity to human adenovirus (HAd) serotypes 3, 5, and 11p. To gauge the impact of antiviral defenses, we also compared the infectivity of the oncolytic adenoviruses in interferon (IFN)-pretreated cells with IFN-sensitive Semliki Forest virus (SFV). RESULTS: Immunostaining revealed generally low expression of HAd5 receptor CAR in both primary tumors and derived cell lines. HAd11p receptor CD46 levels were maintained at moderate levels in both primary tumor samples and derived cell lines. HAd3 receptor DSG-2 was reduced in the cell lines compared to the tumors. Yet, at equal multiplicities of infection, the oncolytic potency of HAd5 in vitro in tumor-derived cells was comparable to HAd11p, whereas HAd3 lysed fewer cells than either of the other two HAd serotypes in 72 hours. IFN blocked replication of SFV, while HAds were rather unaffected. CONCLUSIONS: Adenovirus receptor levels on glioma-derived cell lines did not correlate with infection efficacy and may not be a relevant indicator of clinical oncolytic potency. Adenovirus receptor analysis should be preferentially performed on biopsies obtained perioperatively.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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