Regulation of the actin cytoskeleton may play a crucial role in cell motility and cancer invasion. We have produced a monoclonal antibody (NCC- Lu-632, IgM, k) reactive with an antigenic protein that is upregulated upon enhanced cell movement. The cDNA for the antigen molecule was found to encode a novel isoform of nonmuscle α-actinin. This isoform (designated actinin-4) was concentrated in the cytoplasm where cells were sharply extended and in cells migrating and located at the edge of cell clusters, but was absent from focal adhesion plaques or adherens junctions, where the classic isoform (actinin-1) was concentrated. Actinin-4 shifted steadily from the cytoplasm to the nucleus upon inhibition of phosphatidylinositol 3 kinase or actin depolymerization. The cytoplasmic localization of actinin-4 was closely associated with an infiltrative histological phenotype and correlated significantly with a poorer prognosis in 61 cases of breast cancer. These findings suggest that cytoplasmic actinin-4 regulates the actin cytoskeleton and increases cellular motility and that its inactivation by transfer to the nucleus abolishes the metastatic potential of human cancers.

BACKGROUND.Effective treatment options are limited for patients with cutaneous angiosarcoma (AS). Docetaxel, a member of the taxane family of drugs, reportedly has been effective in the treatment of lung, head and neck, and breast cancers. Another taxane drug, paclitaxel, reportedly had unique activity in the treatment of AS of the scalp and neck and acquired immunodeficiency syndrome‐related Kaposi sarcoma. Therefore, the authors hypothesized that docetaxel may be of value in the treatment of cutaneous AS that is resistant to conventional therapy. However, there were only 3 case reports of the successful treatment of AS in elderly patients using docetaxel in combination with surgery and radiotherapy.METHODS.This was a retrospective trial. After written informed consent was obtained, docetaxel was administered intravenously at a dose of 25 mg/m2 for 1 hour weekly over a period of 8 weeks on the basis of previous reports. This treatment regimen was received by 9 patients with cutaneous AS who were treated at Kobe University Hospital between January 2003 and October 2006.RESULTS.Six of the 9 patients who received treatment achieved major responses, including 2 complete responses and 4 partial responses. Neutropenia and peripheral neuropathy were not prominent, although severe radiation dermatitis enhanced by the docetaxel was observed in 3 patients. There were no deaths attributable to this therapy.CONCLUSIONS.The current study demonstrated that docetaxel was effective in patients with cutaneous AS. Cancer 2007. © 2007 American Cancer Society.

Long term effect of the growing instability of the bone-implant interface due to bone resorption at the interface is a problem for the implants, including bioactive ceramics. Zn2+ -containing tricalcium phosphate (ZnTCP) is a material which may overcome this problem. The present study aims to clarify whether Zn2+ -containing tricalcium phosphate (ZnTCP) ceramics with a Zn2+ content of 0.316 (ZnTCP316) and 0.633 (ZnTCP633) wt % suppress resorption by mature osteoclasts in vitro. Suppression would be due to an increase in the number of apoptotic osteoclasts and the inhibition of the resorbing activity of osteoclasts, the latter being the major mechanism of the suppression. The number of apoptotic osteoclasts was significantly 6.3 times higher with ZnTCP633 than with tricalcium phosphate ceramic (TCP) after 24-h culture. The net contribution to resorption of this change in apoptotic cell numbers is much smaller than that of the change in resorbing activity. The osteoclasts cultured on ZnTCP formed fewer actin rings than those cultured on the TCP. The mRNA expression of CAII and cathepsin K/OC2 in the osteoclasts on ZnTCP633 was downregulated 0.5-fold and 0.6-fold, respectively, compared with that on the TCP. The volume of resorption pits was downregulated 0.4-fold in the ZnTCP633 than that in TCP. These results suggest that ZnTCPs suppressed the resorbing activity of mature osteoclasts probably through a local increase in the level of Zn2+. Bone substitutes or coating layers containing ZnTCP would be promising biomaterials from the viewpoint of counteracting osteoclastic bone resorption at the bone-implant interface.

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