Ashley R. Brown

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Glioblastoma multiforme (GBM) is a devastating brain tumor with poor prognosis and low median survival time. Standard treatment includes radiation and chemotherapy with the DNA alkylating agent temozolomide (TMZ). However, a large percentage of tumors are resistant to the cytotoxic effects of the TMZ-induced DNA lesion O(6)-methylguanine due to elevated(More)
Base excision repair (BER) protein expression is important for resistance to DNA damage-induced cytotoxicity. Conversely, BER imbalance [DNA polymerase beta (Polbeta) deficiency or repair inhibition] enhances cytotoxicity of radiation and chemotherapeutic DNA-damaging agents. Whereas inhibition of critical steps in the BER pathway result in the accumulation(More)
Temozolomide (TMZ) is the preferred chemotherapeutic agent in the treatment of glioma following surgical resection and/or radiation. Resistance to TMZ is attributed to efficient repair and/or tolerance of TMZ-induced DNA lesions. The majority of the TMZ-induced DNA base adducts are repaired by the base excision repair (BER) pathway and therefore modulation(More)
Biomarkers that predict clinical response, tumor recurrence or patient survival are severely lacking for most cancers, particularly for oral and pharyngeal cancer. This study examines whether gene-promoter methylation of tumor DNA correlates with survival and recurrence rates in a population of patients with oral or pharyngeal cancer. The promoter(More)
Alkylating agents induce cell death in wild-type (WT) mouse embryonic fibroblasts (MEFs) by multiple mechanisms, including apoptosis, autophagy and necrosis. DNA polymerase beta (Pol beta) knockout (KO) MEFs are hypersensitive to the cytotoxic effect of alkylating agents, as compared to WT MEFs. To test the hypothesis that Parp1 is preferentially activated(More)
Cellular DNA repair processes are crucial to maintain genome stability and integrity. In DNA base excision repair, a tight heterodimer complex formed by DNA polymerase β (Polβ) and XRCC1 is thought to facilitate repair by recruiting Polβ to DNA damage sites. Here we show that disruption of the complex does not impact DNA damage response or DNA repair.(More)
CYTOTOXICITY* Anbarasi Kothandapani, Venkata Srinivas Mohan Nimai Dangeti, Ashley R. Brown, Lauren A. Banze, Xiao-Hong Wang, Robert W. Sobol and Steve M. Patrick 1. Department of Biochemistry and Cancer Biology, University of Toledo – Health Science Campus, Toledo, OH 43614 2. Department of Pharmacology & Chemical Biology, University of Pittsburgh School of(More)
5-Fluorouracil (5-FU) is a widely utilized cancer chemotherapeutic that causes DNA damage via two mechanisms. Its active metabolite inhibits thymidylate synthase, which deprives cells of TTP and causes the introduction of uracil in DNA. Also, 5-FU is directly incorporated into DNA. Both uracil and 5-FU in DNA are recognized by uracil-DNA glycosylases(More)
BACKGROUND Altered expression of DNA polymerase beta (Pol beta) has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol beta over-expression has not yet been evaluated in a mouse model. METHODOLOGY/PRINCIPAL FINDINGS We have recently developed a novel transgenic mouse model that(More)
The health benefits of sunlight and the risk of skin cancer from UV exposure are still controversial. The literature was analyzed in terms of reviews, controlled and epidemiological studies for the relationships between sunshine exposure and overall cancer mortality, as well as mortality from cancer of the prostate, colon and breast. The residential and/or(More)