Breast cancer encompasses a heterogeneous group of diseases at the molecular level. It is known that chemo-sensitivity of breast cancer depends on its molecular subtype. We investigated the growth inhibitory effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, and the mechanism of this inhibition on four breast cancer cell lines with different molecular subtypes. The growth inhibitory effect of VPA in the four different breast cancer cell lines was investigated. The alteration of levels of p21 WAF1, cleaved caspase-3, acetylated Heat shock protein (Hsp) 90, acetylated Hsp70, and acetylated α-tubulin by VPA was examined in VPA-sensitive, human epidermal receptor 2 (HER2)-overexpressing SKBR3 cells. The cell growth inhibition of breast cancer cell lines was dependent on the dose and exposure time of VPA. The cell growth of HER2-overexpressing SKBR3 cell line was inhibited by VPA to a much greater degree than other cell lines studied. In SKBR3 cell line, VPA upregulated expression of p21 WAF1 and cleaved caspase-3 in the early phase. VPA markedly increased Hsp70 acetylation in a time-dependent manner but did not increase Hsp90 acetylation. Our data demonstrated that VPA inhibited cell proliferation and induced cell cycle arrest and apoptosis of HER2-overexpressing breast cancer cells. This anti-proliferation effect might be the direct function of VPA as an HDAC inhibitor. We propose an alternative mechanism whereby acetylation of Hsp70 disrupts the function of Hsp90 and leads to downregulation of its client proteins, including HER2 that might be the indirect function of VPA, in the sense that non-histone proteins are acetylated.
An 84-year-old man visited our hospital with a chief complaint of a painful mass in the right inguinal region. Based on abdominal computed tomography (CT), a diagnosis of right femoral hernia in which the hernial contents were the intestinal tract was made, but there were no clear findings of intestinal obstruction. Confirmation of the hernial sac at emergency surgery showed that it was filled with dark red ascitic fluid having an unusual odor, with incarceration of the appendix. Appendectomy was performed, and the femoral ring was repaired using McVay's method. Incarceration of the appendix in the hernia sac, or socalled de Garengeot's hernia, has rarely been reported. The possibillity of incarceration of the appendix should be considered in cases of incarcerated hernia without symptoms of intestinal obstruction.
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