Irradiation effect on osteoclastogenesis stimulated by breast cancer cells

To examine the effects of carbon ion and gamma ray irradiation on cancer-induced osteoclastogenesis, mouse calvaria MC3T3-E1 cells were cultured with conditioned medium from irradiated and non-irradiated MCF7 human breast cancer cells. The authors examined RANKL and OPG mRNA expression in osteoblastic MC3T3-E1 cells following treatment with conditioned MCF7 medium. Co-cultured MC3T3-E1 and bone marrow cells treated with conditioned medium from irradiated MCF7 cells showed decreased numbers of osteoclasts, assessed using TRAP staining. Conditioned medium from control MCF7 cells elevated the RANKL/OPG mRNA ratio in MC3T3-E1 cells; this effect was suppressed by carbon ion irradiation of the MCF7 cells. These data demonstrate that indirect interactions between breast cancer cells and MC3T3-E1 cells induce osteoclastogenesis in vitro through modulation of RANKL expression and that this process is suppressed by carbon ion irradiation.     

New inhibitors of calpain prevent degradation of cytoskeletal and myelin proteins in spinal cord in vitro

We have determined the effects of the calpain inhibitors AK275 and AK295 upon purified m-calpain and calcium-mediated degradation of neurofilament protein (NFP) in rat spinal cord in vitro. After incubation, the soluble radioactivity and/or extent of myelin basic protein (MBP) or NFP degradation was determined. Fifty percent of caseinolytic activity was inhibited by both inhibitors at 0.6 μM concentration, while more than 90% inhibition was seen at 1.6 μM. In contrast, 37% and 64% inhibition of MBP degradation was seen with AK295 and AK275, respectively, at 10 μM concentration. The extent of NFP degradation in spinal cord was quantified from immunoblot enhanced chemiluminescence. The calcium-mediated breakdown of NFP was inhibited by both AK275 and AK295, and the inhibition was dose-dependent. A 50% inhibition of NFP degradation was seen with AK295 at 10 μM and was almost completely inhibited at 25–50 μM. AK295 was slightly more potent than AK275. These studies suggest that these potent calpain inhibitors may be used therapeutically to provide neuroprotection in vivo in experimental central nervous system trauma and ischemia. J. Neurosci. Res. 51:218–222, 1998. © 1998 Wiley-Liss, Inc.     

Molecular characterization of human adenovirus type 8 (HAdV-8), including a novel genome type detected in Japan

Human adenovirus type 8 (HAdV-8) is a common agent of severe epidemic keratoconjunctivitis (EKC). Twenty-six strains were isolated from sporadic cases of EKC in the southern part of Japan between 1998 and 1999 and were identified as HAdV-8 by the neutralization method using type-specific antiserum against HAdV-8. A comparative analysis of different HAdV-8 genome types was performed using various molecular methods. Restriction enzyme analyses of genomic DNA were performed with BamHI, HindIII, PstI, SacI, SalI, and SmaI and identified 25 isolates as HAdV-8E and 1 isolate as HAdV-8J, a novel genome type. The genetic relatedness between HAdV-8J and the other genome types was calculated by pairwise comigrating restriction fragments. The new genome type was most genetically related to HAdV-8E. In a phylogram of both the hexon and fiber, HAdV-8J formed a monophyletic cluster with other genome types of HAdV-8. Although HAdV-8J was identified from a sporadic case of EKC, this strain may cause future outbreaks and thus warrants further monitoring.     

Regulation of Th1/Th17 cytokines and IDO gene expression by inhibition of calpain in PBMCs from MS patients

Multiple sclerosis (MS) pathology is marked by the massive infiltration of myelin-specific T cells into the central nervous system (CNS). During active disease, pro-inflammatory Th1/Th17 cells predominate over immunoregulatory Th2/Treg cells. Here, we show that calpain inhibition downregulates Th1/Th17 inflammatory cytokines and mRNA in MS patient peripheral blood mononuclear cells (PBMCs) activated with anti-CD3/28 or MBP. Interestingly, calpain inhibition elevated IDO gene expression in MS PBMCs, which was markedly decreased in calpain expressing cells. Functional assay showed that incubation of MS patient PBMCs with calpain inhibitor or recombinant IDO attenuates T cell proliferation. These results suggest that calpain inhibition may attenuate MS pathology and augment the efficacy of standard immunomodulatory agents used to treat this disease.     

A cutaneous adnexal neoplasm with features of adamantinoid trichoblastoma (lymphadenoma) in the benign component and lymphoepithelial-like carcinoma in the malignant component: a possible case of malignant transformation of a rare trichoblastoma variant

The authors describe a case of cutaneous adnexal tumor with a component reminiscent of adamantinoid trichoblastoma (lymphadenoma) that shows gradual transition to a high-grade carcinoma resembling lymphoepithelial-like carcinoma. The tumor was located above the upper lip of a 57-year-old woman and metastasized in regional lymph nodes. This seems to be the first documented report of malignant transformation of adamantinoid trichoblastoma. We discuss also other possibilities of histogenesis of this unique neoplasm.