Differential regulation of 3beta-hydroxysteroid dehydrogenase type II and 17alpha-hydroxylase/lyase P450 in human adrenocortical carcinoma cells by epidermal growth factor and basic fibroblast growth factor

Epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) are pluripotent growth factors that stimulate both the proliferation and steroidogenesis of adrenocortical cells. Here we demonstrate that EGF and bFGF specifically induce mRNA of 3beta-hydroxysteroid dehydrogenase type II (3betaHSD II) and suppress that of 17alpha-hydroxylase/lyase P450 (CYP17) in human adrenocortical H295R cells. The induction of 3betaHSD II mRNA did not occur until 6 h after the growth factor treatment and was completely abolished in the presence of a protein synthesis inhibitor, cycloheximide (CHX), suggesting that the induction required de novo protein synthesis. The CYP17 mRNA suppression began at almost the same time as the induction of the 3betaHSD II mRNA. Interestingly, the CYP17 mRNA level was increased by the CHX treatment. Both the 3betaHSD II and CYP17 mRNAs were repressed by treatment with a calmodulin kinase II (CaMK II) inhibitor, KN-93, and were enhanced by a mitogen-activated protein kinase (MAPK) inhibitor, PD98059. The PD98059-mediated induction of the 3betaHSD II mRNA was completely blocked by the CHX treatment. Interestingly, treatment with EGF in the presence of both PD98059 and CHX produced a greater increase in the CYP17 mRNA than did treatment in the presence of PD98059 alone. These results suggest that CHX-sensitive factor(s) and CaMK II- and MAPK-signaling pathways may have important roles in both induction of 3betaHSD II and suppression of CYP17 by EGF or bFGF in H295R cells.     

Determining Timing of Hepatectomy for Colorectal Cancer with Distant Metastasis According to Imaging-Based Tumor Shrinkage Ratio

Background: The optimal timing of surgical resection of liver metastasis remains controversial, and guidelines regarding the upper limits of operative indications have not yet been defined. Surgical indication for metastasis from colorectal cancer (CLM) based on results of preoperative chemotherapy and RNF8 was investigated. Methods: Differences in CLM size on CT were evaluated as shrinkage rate/day by dividing tumor shrinkage rates by the interval in days between CT. Levels of RNF8 of resected colorectal cancer and CLM frozen specimen were detected. Results: When the cut line for shrinkage rate at 12 weeks was set at 0.35%, disease-free survival was significantly better in patients with a shrinkage rate >0.35% vs. ≤0.35% (p=0.003). RNF8 expression was significantly higher in Tis (p=0.001). In liver metastasis, RNF8 expression level was significantly lower in patients with partial response to FOLFOX than with stable disease, (p=0.017). Conclusions: A strategy of FOLFOX administration for 12 weeks to patients with low RNF8 expression and hepatectomy planned after 4 weeks rest may be accepted as the best therapeutic option for treating CLM.     

Presence of a translational stop codon in the precore region of HBVDNA in the HBeAg positive stage of chronic Hepatitis B

This work was Supported by a Grant-in-Aid for Scientific Research(B) from the Ministry of Education, Science and Culture, No 63480203.     

Serum levels of S-glutathionylated proteins as a risk-marker for arteriosclerosis obliterans.

BACKGROUND: Oxidative stress plays a role in the development of chronic peripheral arterial disease (PAD) because under these conditions redox regulation is impaired, inducing the S-glutathionylation of proteins. A method of estimating the levels of S-glutathionylated proteins has been developed using biotinylated glutathione S-transferase, which allows the study of their crucial role in the oxidative stress-related progression of PAD. METHODS AND RESULTS: The serum levels of S-glutathionylated proteins were examined in 41 patients with arteriosclerosis obliterans (ASO) and 38 age-matched non-ASO patients using biotinylated glutathione S-transferase. The levels were higher in the patients with ASO, even early on, and positively correlated with the ankle/brachial index. In vitro, the levels of S-glutathionylated proteins were reduced in the presence of glutathione and glutaredoxin. CONCLUSIONS: Serum levels of S-glutathionylated proteins are a sensitive risk-marker for ASO at an early stage.     

Immunocytochemical study of peptidylarginine deiminase: localization of its immunoreactivity in prolactin cells of female rat pituitaries

We have performed an immunocytochemical study of peptidylarginine deiminase (EC 3.5.3.15) in rat pituitaries. Male and female rat pituitaries were fixed by brief transcardial perfusion of Bouin Hollande Sublimate solution. Immunoperoxidase staining of cryosections obtained from female pituitaries with an antiserum to rat skeletal muscle peptidylarginine deiminase yielded specific staining of numerous cells in the pars distalis. In contrast, few immunopositive cells were noted in the pars distalis of male pituitaries. At least some of the immunopositive cells in female pars distalis were also stained with an antiserum to rat PRL. No such coincidence of immunoreactivities was noted when antisera to other anterior pituitary hormones were used. Biochemical and immunocytochemical examination of peptidylarginine deiminase during the pregnant period revealed its marked depletion on day 7 and its substantial restoration on day 14, showing apparently negative correlation with the known changes in the secretory activities of lactotrophs. This and the female-dominant occurrence of peptidylarginine deiminase in lactotrophs suggest significant involvement of the enzyme in the function of lactotrophs.