Increased expression of heat shock protein 70 (HSP70) in the brain has been extensively documented in association with a variety of insults, including ischemia, and is suggested to play a role in cell survival and recovery after ischemic injury. To more directly assess the protective role of HSP70 during ischemic brain damage, we used transgenic mice overexpressing the rat HSP70 (HSP70tg mice). In contrast to wild‐type (wt) littermates, high levels of HSP70 messenger RNA and protein were detected in brains of HSP70tg mice under normal conditions, and immunohistochemical analysis revealed primarily neuronal expression of HSP70. Heterozygous HSP70tg mice and their wt littermates were subjected to permanent focal cerebral ischemia by intraluminal blockade of the middle cerebral artery. Cerebral infarction after 6 hours of ischemia, as evaluated by Nissl staining, was significantly less in HSP70tg mice compared with wt mice. This reduction in infarction volume in HSP70tg mice was not attributable to an altered cardiovascular anatomy or to initial differences in body temperature or hemodynamic parameters. The HSP70tg mice were still protected against cerebral infarction 24 hours after permanent focal ischemia. The data suggest that HSP70 can markedly protect the brain against ischemic damage and that approaches aimed at inducing HSP70 may lead to new therapeutic interventions in cerebrovascular injuries. Ann Neurol 2000;47:782–791

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GP125/CD98 is a heterodimeric 125-kDa glycoprotein, which consists of an 85-kDa heavy chain (hc) and a 40-kDa light chain (lc), and is strongly expressed on the cell surface of various tumor cells, irrespective of their tissue of origin. We have recently demonstrated that overexpression of the CD98hc cDNA causes malignant transformation of NIH3T3 cells. To investigate the function of the extracellular domain of CD98hc in cell proliferation and malignant transformation, we established two NIH3T3-derived clones transfected with human truncated CD98hc cDNAs, and compared their characteristics with parental NIH3T3 and clones transfected with full-length CD98hc cDNA. Truncated as well as full-length CD98hc-transfected clones grew to a higher saturation density than control cells. E ciency of colony formation in soft agar was augmented in all CD98hc-transfected clones, and the degrees of augmented colony formation of the transfectants expressing fulllength CD98hc of 529 a.a. or truncated CD98hc of 418 a.a. were reduced by anti-human CD98hc antibodies, while that of the transfectant expressing truncated CD98hc of 237 a.a. lacking the epitopes recognized by anti-human CD98hc antibodies was not a ected by the addition of antibodies. CD98hc-transfected clones developed tumors in athymic mice, and tumor growth of truncated CD98hc-transfected clones was faster than that of full-length CD98hc-transfected clones. Oncogene (2000) 19, 6209 ± 6215.

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Antigen challenge and Ca-dependent agonist treatment increased Cl ion transport via the overexpression of TMEM16A in goblet cell metaplasia in a guinea-pig asthma model. TMEM16A inhibitors may be useful for the treatment of hyper-secretion in asthma.

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Our previous study showed that adhesion molecule with immunoglobulin like domain 2 (AMIGO2) is a pivotal driver gene of liver metastasis via regulating tumor cell adhesion to liver endothelial cells in mouse models. The aim of the present study was to clarify the role of AMIGO2 in liver metastasis in patients the colorectal cancer (CRC). Two human CRC cell lines, Caco-2 (AMIGO2-low) and HCT116 (AMIGO2-high), were used in this study. AMIGO2-overexpressing Caco-2 and AMIGO2-knockdown HCT116 cells were generated by transfection with an AMIGO2 expression vector or AMIGO2 small interfering RNA, respectively. Cell proliferation, invasion and adhesion to human liver endothelial cells were examined in in vitro studies. Immunohistochemical analysis was also performed to evaluate the association between AMIGO2 expression and liver metastasis in patients with CRC. In vitro studies revealed that cell proliferation, invasion and adhesion to liver endothelial cells were accelerated by upregulation of AMIGO2 expression, but suppressed by downregulation of AMIGO2 expression in human CRC cells. Immunohistochemical analysis using clinical CRC specimens revealed that AMIGO2 expression was associated with the frequency of liver metastasis (P<0.01), but not that of pulmonary metastasis (P=0.611) and peritoneal dissemination (P=0.909). In addition, AMIGO2 expression levels in tumor cells were significantly higher in liver metastatic foci than primary lesions (P=0.012). In conclusion, the present results indicated that AMIGO2 expression may contribute to the formation of liver metastasis in CRC.