Chato Taher

Publications (2)20.83 Total impact

• Article: Frequent detection of human cytomegalovirus in neuroblastoma: A novel therapeutic target?

  Nina Wolmer-Solberg, Ninib Baryawno, Afsar Rahbar, Dieter Fuchs, Jenny Odeberg, Chato Taher, Vanessa Wilhelmi, Jelena Milosevic, Abdul-Aleem Mohammad, Tommy Martinsson, Baldur Sveinbjörnsson, John Inge Johnsen, Per Kogner, Cecilia Söderberg-Nauclér
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  ABSTRACT: Neuroblastoma is the most common and deadly tumor of childhood, where new therapy options for patients with high-risk disease are highly warranted. Human cytomegalovirus (HCMV) is prevalent in the human population and has recently been implicated in different cancer forms where it may provide mechanisms for oncogenic transformation, oncomodulation and tumour cell immune evasion. Here we show that the majority of primary neuroblastomas and neuroblastoma cell lines are infected with HCMV. Our analysis show that HCMV immediate-early protein was expressed in 100% of 36 primary neuroblastoma samples, and HCMV late protein was expressed in 92%, However, no infectious virus was detected in primary neuroblastoma tissue extracts. Remarkably, all six human neuroblastoma cell lines investigated contained CMV DNA and expressed HCMV proteins. HCMV proteins were expressed in neuroblastoma cells expressing the proposed stem cell markers CD133 and CD44. When engrafted into NMRI nu/nu mice, human neuroblastoma cells expressed HCMV DNA, RNA and proteins but did not produce infectious virus. The HCMV-specific antiviral drug valganciclovir significantly reduced viral protein expression and tumor cell growth both in vitro and in vivo. These findings indicate that HCMV is important for the pathogenesis of neuroblastoma and that anti-viral therapy may be a novel adjuvant treatment option for children with neuroblastoma. © 2013 Wiley Periodicals, Inc.
  International Journal of Cancer 05/2013; · 5.44 Impact Factor
• Article: Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target.

  Ninib Baryawno, Afsar Rahbar, Nina Wolmer-Solberg, Chato Taher, Jenny Odeberg, Anna Darabi, Zahidul Khan, Baldur Sveinbjörnsson, O-M FuskevÅg, Lova Segerström, Magnus Nordenskjöld, Peter Siesjö, Per Kogner, John Inge Johnsen, Cecilia Söderberg-Nauclér
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  ABSTRACT: Medulloblastomas are the most common malignant brain tumors in children. They express high levels of COX-2 and produce PGE2, which stimulates tumor cell proliferation. Human cytomegalovirus (HCMV) is prevalent in the human population and encodes proteins that provide immune evasion strategies and promote oncogenic transformation and oncomodulation. In particular, HCMV induces COX-2 expression; STAT3 phosphorylation; production of PGE2, vascular endothelial growth factor, and IL-6; and tumor formation in vivo. Here, we show that a large proportion of primary medulloblastomas and medulloblastoma cell lines are infected with HCMV and that COX-2 expression, along with PGE2 levels, in tumors is directly modulated by the virus. Our analysis indicated that both HCMV immediate-early proteins and late proteins are expressed in the majority of primary medulloblastomas. Remarkably, all of the human medulloblastoma cell lines that we analyzed contained HCMV DNA and RNA and expressed HCMV proteins at various levels in vitro. When engrafted into immunocompromised mice, human medulloblastoma cells induced expression of HCMV proteins. HCMV and COX-2 expression correlated in primary tumors, cell lines, and medulloblastoma xenografts. The antiviral drug valganciclovir and the specific COX-2 inhibitor celecoxib prevented HCMV replication in vitro and inhibited PGE2 production and reduced medulloblastoma tumor cell growth both in vitro and in vivo. Ganciclovir did not affect the growth of HCMV-negative tumor cell lines. These findings imply an important role for HCMV in medulloblastoma and suggest HCMV as a novel therapeutic target for this tumor.
  The Journal of clinical investigation 09/2011; 121(10):4043-55. · 15.39 Impact Factor