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Ververis K Rodd AL Tang MM El-Osta A Karagiannis TC 《Cellular and molecular life sciences : CMLS》2011,68(24):4101-4114
Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid
(Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that
histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies
such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies,
involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified
that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in
cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase
inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes.
Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors
tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained
nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight
the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination
therapies for cancer. 相似文献
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Raja S. Vasireddy Tom C. Karagiannis Assam El-Osta 《Cellular and molecular life sciences : CMLS》2010,67(2):291-294
The central dogma in radiation biology is that nuclear DNA is the critical target with respect to radiosensitivity. In accordance
with the theoretical expectations, and in the absence of a conclusive model, the general consensus in the field has been to
view chromatin as a homogeneous template for DNA damage and repair. This paradigm has been called into question by recent
findings indicating a disparity in γ-irradiation-induced γH2AX foci formation in euchromatin and heterochromatin. Here, we
have extended those studies and provide evidence that γH2AX foci form preferentially in actively transcribing euchromatin
following γ-irradiation. 相似文献
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DNA damage repair and transcription 总被引:2,自引:0,他引:2
Berardi P Russell M El-Osta A Riabowol K 《Cellular and molecular life sciences : CMLS》2004,61(17):2173-2180
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