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Hypoxia inducible factor‐１α（HIF‐１α）and histone deacetylase（HDAC）expressions in gastrointestinal cancer, especially intrahepatic cholangiocarcinoma and pancreas cancer, significantly reflect on the malignant potential of these cancers, and are significantly associated with patient’s prognosis. It has also been shown that HIF‐１α is deacetylated and stabilized by nucleosome remodeling and histone deacetylation （NuRD） complex, consisting of HDAC and metastasis-associated gene‐１（MTA１）, leading to angiogenesis. More recently, it has been reported that HIF‐１α induces tumorigenesis and ultimately cancer stemness through epithelial-mesenchymal transition （EMT）. Therefore, HIF‐１α may be one of the master molecules of cancer progression, and it is expected that novel therapeutic strategies will be devised by controlling the signaling pathway of HIF‐１α in hypoxic condition of gastrointestinal cancer.

Pancreaticobiliary maljunction（PBM）is the congenital malformation that the junction of the pancreatic and bile ducts is located outside of the duodenal wall anatomically, so sphincter function preventing to mix the bile and pancreatic juice does not act. In PBM, the mutual reflux of bile and pancreatic juice induces various diseases and becomes the cause of biliary tract cancer generation. PBM is divided into PBM with the biliary dilatation and PBM without the biliary dilatation. From the perspective of carcinogenesis, surgery to separate the pancreatic juice and bile by excision of extrahepatic biliary tract and hepaticojejunostomy is commonly performed in the former, the treatment of the latter is controversial, for instance ; the only cholecystectomy should be performed and excision of extrahepatic biliary tract is unnecessary or excision of extrahepatic biliary tract and hepaticojejunostomy should be done. In addition, histone acetylation and histone deacetylation is one of the important regulatory mechanism of gene transcription, the error of the balance between histone acetyltransferase（HAT）and histone deacetylase（HDAC）leads to carcinogenesis. In other words, HDAC has a carcinogenic potential. Overexpression of HDAC was found in the both resected gallbladder and bile duct mucosa of infant PBM patient with the biliary dilatation performed the excision of extrahepatic biliary tract and hepaticojejunostomy in our department. Appropriate treatment for PBM has not been established yet, but even infant case with PBM has carcinogenesis potential just like this case. In conclusion, further accumulation of cases including PBM without the biliary dilatation was thought to be essential though the excision of extrahepatic biliary tract and hepaticojejunostomy still seems to be required for infant PBM patient with the biliary dilatation.

Histone deacetylase（ HDAC） is an enzyme that catalyzes the deacetylation of lysine residues in histone proteins. The HDAC plays important roles in realizing the histone code, changing the epigenetic condition and regulating the gene expression in eukaryote. Inhibition of HDAC induces anticancer effects such as induction of apoptosis or cell-cycle arrest in many cancer cells. Therefore, HDAC inhibition is one of the new prospective treatments of cancer. This review describes about the basic and clinical information of the HDAC inhibition focused on anticancer effects.

SIR2 and its homologues are newly identified nicotinamide adenine dinucleotide （NAD）-dependent histone deacetylases. Yeast （Saccharomyces cerevisiae） SIR2 silences transcription at silent mating loci, teromeres and ribosomal DNA （rDNA）, and that also suppresses recombination in rDNA. Yeast and mammalian SIR2 homologue （SIR2 alpha） was found to specifically deacetylate acetylated lysine residues of histone H3 and H4 in a NAD-dependent manner. The deacetylation of histones has been identified as important for silencing. Interestingly, increase in dosages of SIR2 gene extended the life span in yeast and Caenorhabditis elegans. Although recent studies showed that Sir2 alpha directly binds and deacetylates p53 to repress p53-dependent apoptosis, the distribution and physiological functions of SIR2 family in mammals still remain to be elucidated. We found that SIR2 alpha and SIR3, both of which are mammalian SIR2 homologues, are expressed in neural stem cells. The expression of these SIRs promptly disappeared after differentiation. We assume that these SIRs may play a significant role in the proliferation and/or differentiation of neural stem cells.