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To understand the mechanistic basis for this effect and its potential utility as a TMZ response biomarker, we compared the response of isogenic glioblastoma cell populations differing only in expression of the DNA repair protein MGMT, a TMZ-sensitivity determinant, after exposure to TMZ in vitro and in vivo.
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Because of its limited side effects and proven efficacy, TMZ is a component of the standard therapy for a variety of human brain tumors, and is frequently combined with other experimental agents 2. Viruses are saved from extinction - Creation Myth for the next era.
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So we have to make do with this bathing scene. Reductions in the conversion of 13 C pyruvate to 13 C lactate in in vivo imaging studies of drug-treated tumors have been ascribed to a variety of factors including loss of cellularity, apoptosis-induced PARP activation and depletion of NADH levels, decreased LDH-A expression, and loss of LDH activity.
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This in turn ultimately leads to DNA single strand breaks, activation of sensors of DNA damage, the generation of DNA double strand breaks, and delayed cell death by a combination of senescence and mitotic catastrophe 6 — Candles in the wind Shocking Crashes and Chases.
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Using these cells we show that the TMZ-induced suppression of the conversion of hyperpolarized pyruvate to lactate is uniquely linked to the TMZ-induced DNA damage response via decreased PKM2 expression and intracellular lactate levels, and as such serves as an early monitor of TMZ response in brain tumor cells.
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In addition to identifying the link between TMZ-induced DNA damage and pyruvate metabolism, and defining the mechanism by which this linkage occurs, the present study also has clinical implications. Topless page three girls. Instead, they were associated with a TMZ-induced decrease in the expression and activity of pyruvate kinase PKM2, a glycolytic enzyme that indirectly controls pyruvate metabolism. Nothing feels safe anymore.
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