E-viri
Recenzirano
Odprti dostop
-
GuhaSarkar, Dwijit; Neiswender, James; Su, Qin; Gao, Guangping; Sena‐Esteves, Miguel
Molecular oncology, February 2017, Letnik: 11, Številka: 2Journal Article
The highly invasive property of glioblastoma (GBM) cells and genetic heterogeneity are largely responsible for tumor recurrence after the current standard‐of‐care treatment and thus a direct cause of death. Previously, we have shown that intracranial interferon‐beta (IFN‐β) gene therapy by locally administered adeno‐associated viral vectors (AAV) successfully treats noninvasive orthotopic glioblastoma models. Here, we extend these findings by testing this approach in invasive human GBM xenograft and syngeneic mouse models. First, we show that a single intracranial injection of AAV encoding human IFN‐β eliminates invasive human GBM8 tumors and promotes long‐term survival. Next, we screened five AAV‐IFN‐β vectors with different promoters to drive safe expression of mouse IFN‐β in the brain in the context of syngeneic GL261 tumors. Two AAV‐IFN‐β vectors were excluded due to safety concerns, but therapeutic studies with the other three vectors showed extensive tumor cell death, activation of microglia surrounding the tumors, and a 56% increase in median survival of the animals treated with AAV/P2‐Int‐mIFN‐β vector. We also assessed the therapeutic effect of combining AAV‐IFN‐β therapy with temozolomide (TMZ). As TMZ affects DNA replication, an event that is crucial for second‐strand DNA synthesis of single‐stranded AAV vectors before active transcription, we tested two TMZ treatment regimens. Treatment with TMZ prior to AAV‐IFN‐β abrogated any benefit from the latter, while the reverse order of treatment doubled the median survival compared to controls. These studies demonstrate the therapeutic potential of intracranial AAV‐IFN‐β therapy in a highly migratory GBM model as well as in a syngeneic mouse model and that combination with TMZ is likely to enhance its antitumor potency. Our study shows that species‐matched interferon‐beta (IFN‐β) gene therapy by locally administered adeno‐associated viral vectors (AAV) is an effective therapeutic approach for treating both highly invasive human glioblastoma and syngeneic mouse glioblastoma in mouse orthotopic models. We also show that combination treatment with AAV‐IFN‐β and temozolomide (TMZ) provides enhanced therapeutic benefit if AAV‐IFN‐β is administered prior to TMZ.
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.