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Background: FAM83H was originally reported to be essential for dental enamel formation. However, FAM83H has recently been implicated in tumorigenesis and tumor progression. Analysis of a publicly available gene expression database revealed a significant correlation between FAM83H and Nectin1 mRNA expression and bladder urothelial carcinoma (BUC). Therefore, we investigated the association between FAM83H and Nectin1 expression levels and the survival and recurrence of BUC in BUC patients using a tissue microarray.Methods: We performed immunohistochemical staining of FAM83H and Nectin1 in 165 human BUC tissue sections, and analyzed the prognostic significance of FAM83H and Nectin1 expression.Results: Both FAM83H and Nectin1 were mainly expressed in the cytoplasm, and their expression was significantly associated. FAM83H expression was significantly correlated with higher histologic grade, higher T stage, higher TNM stage, and recurrence. Nectin1 expression was significantly associated with higher histologic grade and recurrence. Univariate analysis showed FAM83H expression and Nectin1 expression were significantly associated with worse overall survival (OS) and shorter relapse-free survival (RFS) of BUC patients. In multivariate analysis, levels of FAM83H and Nectin1 were independent indicators of shorter survival of BUC patients.Conclusions: Our results suggest that FAM83H and Nectin1 are important in the progression of BUC, and that expression patterns of these two proteins can be used as prognostic indicators of survival in BUC patients. [ABSTRACT FROM AUTHOR]

Recently, the roles of SIRT1 and deleted in breast cancer 1 (DBC1) in human cancer have been extensively studied and it has been demonstrated that they are involved in many human carcinomas. However, their clinical significance for soft-tissue sarcomas has not been examined. In this study, we evaluated the expression and prognostic significance of the expression of SIRT1, DBC1, P53, β-catenin, cyclin D1, and KI67 in 104 cases of soft-tissue sarcomas. RESULTS: Immunohistochemical expression of SIRT1, DBC1, P53, β-catenin, and cyclin D1 were seen in 71%, 74%, 53%, 48%, and 73% of sarcomas, respectively. The expression of SIRT1, DBC1, P53, β-catenin, and cyclin D1 were significantly correlated with advanced clinicopathological parameters such as higher clinical stage, higher histological grade, increased mitotic counts, and distant metastasis. The expression of SIRT1, DBC1, P53, β-catenin, cyclin D1, and KI67 were significantly correlated with each other and positive expression of all of these predicted shorter overall survival and event-free survival by univariate analysis. Multivariate analysis revealed the expression of SIRT1 as an independent prognostic indicator for overall survival and event-free survival of sarcoma patients. In conclusion, this study demonstrates that SIRT1- and DBC1-related pathways may be involved in the progression of soft-tissue sarcomas and can be used as clinically significant prognostic indicators for sarcoma patients. Moreover, the SIRT1- and DBC1-related pathways could be new therapeutic targets for the treatment of sarcomas. [ABSTRACT FROM AUTHOR]

Summary: Recently, it has been reported that SIRT1 and DBC1 may be involved in the development of tumors and predict poor survival in some cancers. However, their exact role is not clear. Therefore, we investigated the expression status and clinical significance of DBC1 and SIRT1 expression in breast carcinomas. We evaluated the immunohistochemical expression of DBC1, SIRT1, and p53 using a 3-mm core from 122 patients with breast cancer for tissue microarray. Positive expression of DBC1 and SIRT1 were seen in 71% and 67% of patients, respectively. In the patients with breast cancer, overall, expression of DBC1 and SIRT1 was significantly associated with distant metastatic relapse and shorter relapse-free survival and overall survival by univariate analysis. Tumor stage and DBC1 and SIRT1 expression were also independent prognostic factors by multivariate analysis. Among the patients who had received chemotherapy, DBC1 and SIRT1 expression was significantly associated with distant metastatic relapse and shorter survival by univariate analysis. DBC1 expression was also associated with distant metastatic relapse and shorter survival in patients who had received endocrine therapy, according to univariate and multivariate analysis. In conclusion, this study shows that expression of DBC1 and SIRT1 is a significant prognostic indicator for breast carcinoma patients. [ABSTRACT FROM AUTHOR]

Survivin, an apoptosis inhibitor, is highly expressed in a majority of human cancers and is required during embryonic development. Our present studies show that survivin is also expressed in normal gastric mucosa of adult humans and rats. In both human and rat gastric mucosa, survivin is expressed predominantly in the nuclei of mucosal surface epithelial cells. In rats, survivin is also detected in the nuclei of some neck cells, whereas in the humans, survivin is expressed in both nuclei and cytoplasm of chief and parietal cells. Furthermore, survivin is expressed at higher levels in the nuclei of cultured gastric mucosal epithelial cells than in gastric microvascular endothelial cells, which supports the expression pattern in intact tissues. Based on these expression studies, and the known role of survivin as an anti-apoptosis protein, survivin may play a role in maintaining gastric mucosal integrity and regulating cell renewal in the gastric mucosa. [Copyright &y& Elsevier]

Deleted in breast cancer 1 (DBC1/CCAR2) is a protein of interest because of its diverse roles in tumorigenesis and its possible role as an androgen receptor (AR) co-activator. However, there are limited studies on the role of DBC1 in osteosarcoma. Therefore, we investigated the role of DBC1 and AR and their relationship in osteosarcoma. Immunohistochemical expression of DBC1 and AR was significantly associated with higher clinical stage and higher histologic grade, and predicted shorter survival. Especially, DBC1 expression was an independent prognostic indicator of overall survival (p = 0.005) and relapse-free survival (p = 0.004) by multivariate analysis. In osteosarcoma cell lines, U2OS and SaOS2, the knock down of DBC1 and AR with siRNA significantly reduced cellular proliferation and inhibited proliferation-related signaling. In addition, the knock down of DBC1 and AR decreased the invasion activity and inhibited invasion-related signaling of osteosarcoma cells. Interestingly, DBC1 affects the stabilization of AR protein via a mechanism involving the ubiquitination of AR. Proteosome-mediated degradation and poly-ubiquitination of AR were increased with the knock-down of DBC1. In conclusion, this study has shown that DBC1 is involved in the stabilization of AR protein and DBC1-AR pathways might be involved in the progression of osteosarcoma. [ABSTRACT FROM AUTHOR]

Abstract: Sulforaphane (SFN) is an indirect antioxidant that protects animal tissues from chemical or biological insults by stimulating the expression of several NF-E2-related factor-2 (Nrf2)-regulated phase 2 enzymes. Treatment of RINm5F insulinoma cells with SFN increases Nrf2 nuclear translocation and expression of phase 2 enzymes. In this study, we investigated whether the activation of Nrf2 by SFN treatment or ectopic overexpression of Nrf2 inhibited cytokine-induced β-cell damage. Treatment of RIN cells with IL-1β and IFN-γ induced β-cell damage through a NF-κB-dependent signaling pathway. Activation of Nrf2 by treatment with SFN and induction of Nrf2 overexpression by transfection with Nrf2 prevented cytokine toxicity. The mechanism by which Nrf2 activation inhibited NF-κB-dependent cell death signals appeared to involve the reduction of oxidative stress, as demonstrated by the inhibition of cytokine-induced H2O2 production. The protective effect of SFN was further demonstrated by the restoration of normal insulin secreting responses to glucose in cytokine-treated rat pancreatic islets. Furthermore, pretreatment with SFN blocked the development of type 1 diabetes in streptozotocin-treated mice. [Copyright &y& Elsevier]

Abstract: Cortactin is an F-actin binding protein involved in cell migration and tumor metastasis. Recent reports suggest that silent mating-type information regulation 2 homologue 1 (sirtuin1; SIRT1) enhances the function of cortactin and promotes cell migration. We investigated SIRT1 and cortactin expression in 144 invasive non-small cell lung cancers (NSCLC) and 19 adenocarcinomas in situ (AIS) by immunohistochemistry and evaluated their clinicopathological significance in NSCLC. Positive SIRT1 and cortactin expression was observed in 67% (96 of 144) and 58% (84 of 144) of patients with invasive NSCLC, respectively. SIRT1 and cortactin expression was significantly associated with unfavorable clinicopathological factors, including high pathological T stage, lymph node metastasis, and advanced tumor invasion (AIS vs. invasive adenocarcinoma). Cortactin was significantly associated with high pathological T stage and lymph node metastasis in SIRT1-positive tumors. Cytoplasmic SIRT1 was significantly associated with high pathological T stage and large tumor size compared to that of nuclear SIRT1. Large tumor size, high pathological T stage, lymph node metastasis, and cytoplasmic SIRT1 expression were significantly associated with shorter overall survival in a univariate analysis. Our findings suggest that SIRT1 and cortactin may play a role in the progression of NSCLC and may cooperate during tumor progression in NSCLC. [Copyright &y& Elsevier]