Connexins have long been believed to suppress tumour development during carcinogenesis by exerting gap junctional intercellular communication (GJIC). Although GJIC is abrogated in hepatocellular carcinoma (HCC), connexin32 (Cx32) protein tends to remain expressed in cytoplasm, but not in cell-cell contact areas; thus, it is incapable of forming gap junctions. Hypothesising that cytoplasmic Cx32 protein that has accumulated in HCC should have its proper functions, which are independent of GJIC, we established an inducible expression system of Cx32 in human HuH7 HCC cells, which were unable to support the formation of Cx32-mediated gap junctions, so that Cx32 protein could be overexpressed by doxycycline (Dox) withdrawal. Although the established clone HuH7 Tet-off Cx32 cells exhibited a 4-fold increase in Cx32 expression after Dox withdrawal, none of them were dyecoupled, and Cx32 protein was retained in the Golgi apparatus. However, the proliferation rate of the HuH7 Tet-off Cx32 cells was significantly higher in the Dox-free medium than in the Doxsupplemented one. Transwell assays also revealed that Dox withdrawal enhanced serum-stimulated motility and invasiveness into Matrigel of the HuH7 Tet-off Cx32 cells. Furthermore, when HuH7 Tet-off Cx32 cells were xenografted into the liver of SCID mice, only the mice to which no Dox was administered developed metastatic lesions, indicating that overexpression of cytoplasmic Cx32 protein induced metastasis of HuH7 cells. Our results suggest that, while Cx32-mediated GJIC suppresses the development of HCCs, cytoplasmic Cx32 protein exerts effects favourable for HCC progression, such as invasion and metastasis, once the cells have acquired a malignant phenotype. ' 2007 Wiley-Liss, Inc.

This study was aimed to clarify some ambiguities in the interpretation of proton magnetic resonance spectroscopy (1H-MRS) of meningiomas. The cases of 31 meningioma patients (27 benign and 4 nonbenign meningiomas) that underwent single-voxel 1H-MRS (PRESS sequence, TR/TE = 2,000 ms/68, 136, 272 ms) were retrospectively analyzed. To verify the findings of in-vivo study, phantoms were measured, and pathological sections of 11 patients were reviewed. All meningiomas demonstrated increased choline and decreased creatine, except for a lipomatous meningioma that only displayed a prominent lipid (Lip) peak. Alanine (Ala) and lactate (Lac) coexisted in eight cases, indicating an alternative pathway of energy metabolism in meningiomas. They partially overlapped with each other and demonstrated a triplet-like spectral pattern, which was consistent with phantom study. Glutamine/glutamate (Glx) was helpful for the recognition of meningioma when Ala was absent. N-acetyl compounds(NACs) were observed in nine cases whose voxels were completely limited within the tumors, indicating that meningiomas might have endogenous NACs. Lac was indicative of an aggressive meningioma, although not always a nonbenign one. Lip not only represented micronecrosis in nonbenign meningiomas, but also reflected microcystic changes or fatty degeneration in benign meningiomas. 1H-MRS reflects some distinctive biochemical and pathological changes of meningiomas that might be misinterpreted.

Growing evidence revealed that liver sinusoidal endothelial cells (SEC) play several important roles in physiology and pathology of the liver. It has been well understood that their structural characteristics, such as the membrane sieve and lack of basement membrane, facilitate direct contact of soluble and insoluble serum substances with hepatic parenchymal cells, resulting in enhancement of hepatic metabolic activity. In addition, SEC is now regarded as a member of the scavenger endothelial cells, which have potential to eliminate a variety of macromolecules from the blood circulation by receptor-mediated endocytosis. It is reported that molecules preferentially eliminated by SEC are denatured or modified proteins such as advanced glycation end products, extracellular matrix components including hyaluronic acid, and some lipoproteins. The nature of the scavenger receptors corresponding to these molecules remains to be clarified. Recently, it was noted that SEC has an antigen-presenting function similar to dendritic cells. Taken together, it is suggested that SEC, cooperating with Kupffer cells and hepatic dendritic cells, may partake of immunoregulatory functions in the liver. SEC also plays a pivotal role in the pathological process of ischemia-reperfusion injury following liver surgery and liver transplantation. Thus, it is of importance to elucidate the mechanisms of apoptosis and proliferation of SEC. Recent results on the regulation of growth and apoptotic signaling of SEC are discussed.

These results suggested that COPD of Japanese patients may develop partly because of oxidative stress derived from a shortage of antioxidant nutrients, especially of AA and lycopene, as well as GSH while this may not be the case in both ACOS and BA.

No abstract