Deregulated expression of HDAC3 in colorectal cancer and its clinical significance.

BACKGROUND: To date, 4 classes of histone deacetylases (HDACs) have been identified in humans. Class I HDACs are zinc-dependent and NAD+-independent enzymes, and include 4 isoforms closely related to yeast RPD3: HDAC1, 2, 3, and 8. OBJECTIVES: The aims of the study were to quantitatively evaluate the expression of HDAC3 in colorectal cancer (CRC) and to correlate its expression levels with clinicopathological parameters. MATERIAL AND METHODS: We characterized expression patterns of HDAC3 as class I HDAC isoforms in a cohort of 48 CRC patients by quantitative (real-time) reverse transcription polymerase chain reaction (RT-PCR). In addition, the potential relationship between HDAC3 expression levels and clinicopathological parameters in patients suffering from CRC was explored. RESULTS: We found that HDAC3 was highly expressed in colorectal tumors compared to normal colorectal tissues (p < 0.05). Furthermore, we found significant correlations between HDAC3 expression levels and tumor differentiation grades (p < 0.05). CONCLUSIONS: In this prospective study we identified a pronounced HDAC3 expression pattern in CRC. Our findings support an important role of HDAC3 as a complementary molecular marker for existing histopathological diagnostic elements; it might also have applications in prognostic and targeted therapy. Furthermore, HDAC3 can be used as a biomarker to differentiate between tumor borders and margins, and it may also be useful for characterizing field cancerization in CRC.

Effects of the flavanone combination hesperetin-naringenin, and orange and grapefruit juices, on airway inflammation and remodeling in a murine asthma model.

We investigated whether flavanones, hesperetin-naringenin, orange, and grapefruit juices reduce airway inflammation and remodeling in murine chronic asthma model. To establish chronic asthma, mice received house dust mite (HDM) for 3 days in 2 weeks, followed by twice per week for 4 weeks. Concurrently, during the last 4 weeks, mice received hesperetin plus naringenin (HN), orange plus grapefruit juice (OGJ), orange juice (OJ), or grapefruit juice (GJ); whereas the asthmatic control (AC) group and non-asthmatic control (NC) group consumed water ad libitum. In histopathological examination, no goblet cells metaplasia was observed in the HN, OJ, and GJ groups; also, intra-alveolar macrophages decreased compared with those of the AC group. Hesperetin plus naringenin significantly decreased subepithelial fibrosis, smooth muscle hypertrophy in airways, and lung atelectasis compared with the AC group. Also, there was a reduction of subepithelial fibrosis in airways in OJ and GJ groups compared with AC group, but it was not noticed in OGJ group. In bronchoalveolar lavage fluid, macrophages numbers decreased in OJ and OGJ groups, whereas eosinophil numbers were increased in OJ group compared with NC group. Our finding revealed that hesperetin plus naringenin ameliorate airway structural remodeling more than orange juice and grapefruit juice in murine model of HDM-induced asthma.