These enzymes do not bind directly to DNA. Bortezomib CAS they are thought to be recruited to dis tinct regions of the genome by sequence specific DNA binding proteins. Class III HDACs is composed of the Sirtuins pro teins 1 7, which are homologous to the yeast Sir2 protein and require NAD for deacetylase activity in contrast to the zinc catalyzed mechanism used by class I and II HDACs. An additional HDAC expressed by higher eukaryotes is a Zn dependent HDAC. This enzyme is phylogenetically different from both class I and class II enzymes and is therefore classified separately as class IV reviewed in. The use of HDAC inhibitors for the treatment of cancer is an area of active investigation. In gliomas, HDACis have been used for the treatment of glioblastoma in combination with radiation therapy and chemother apy.
Some authors have demonstrated that HDACis have a radiosensitizing effect on glioblastoma cells in vitro and in vivo and also seem to be associated with inhi bition of glioma cell growth by both cell cycle arrest and apoptosis. Despite the widespread use of HDACis, the mechanistic implications remain to be elucidated. To this date, there are no studies that demonstrate the sta tus of global HDAC gene expression and protein levels in astrocytomas. The purpose of this study was to evaluate and compare mRNA and protein levels of class I, II and IV of HDACs in low grade and high grade astrocytomas and normal brain tissue and to correlate the findings with the malignancy in astrocytomas. Methods Patients Samples For this study, tumor samples of 43 patients ranging in age from 1.
3 to 79 years were evaluated. The histopathologic diagnoses were 20 low grade gliomas and 23 high grade gliomas. In addition, 11 samples of normal cere bral tissue were analyzed. Frozen tumor and normal spec imens were microdissected. Diagnoses were based on 2007 World Health Organization criteria. For tumor microdissection, tumor samples were placed on a cooled platform and immediately positioned on the cutting base of the cryostat under Tissue Tek. After rapid freezing in liquid nitrogen, the sample was cut and immediately captured on a cover slip, stained with hematoxylin and eosin, and evaluated by image apposition. The area of interest in the original cryopreserved tumor block was then trimmed, and the microdissected sample was transferred to a previously identified tube, which was immediately placed under dry ice.
Prior to initiation, the research here presented was approved by the Research Ethics Committee of the Uni versity Hospital of the Faculty of Medicine of University Batimastat of Sao Paulo, processes number 9375 2003 and 7645 99. The mentioned Committee is in agreement with the Hel sinki Declaration requirements for research carried out on humans. Informed consent was also taken from each patient involved in this project, also in accordance to the Helsinki Declaration.
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