Publications (4)5.44 Total impact
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Article: Cyclin D1‐CDK4 complex, a possible critical factor for cell proliferation and prognosis in laryngeal squamous cell carcinomas
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ABSTRACT: Cyclin D1 and its catalytic partner CDK4 are known to play important roles in the G1/S checkpoint of the cell cycle. The complex formed by CDK4 and cyclin D1 has been strongly implicated in the control of cell proliferation and prognoses in human malignancies. We investigated the immunohistochemical expression of cyclin D1, CDK4 and proliferating cell nuclear antigen (PCNA) in 102 patients with laryngeal squamous cell carcinoma (LSCC). Cyclin D1 overexpression was observed in 59 cases (57.8%) of LSCC, and was significantly correlated with tumor site, tumor size, lymph node metastasis and advanced stage. CDK4 overexpression was observed in 48 cases (47.1%), and was significantly correlated with tumor size and advanced stage. Cyclin D1 and CDK4 expression was significantly associated with cell proliferation measured by PCNA (r = 0.812, p < 0.0001 and r = 0.725, p < 0.0001, respectively). The Kaplan–Meier analysis showed that cyclin D1 overexpression was significantly associated with disease-free survival and overall survival. CDK4 overexpression was significantly associated with overall survival. When cyclin D1 and CDK4 are combined, the patients with co-overexpression of cyclin D1-CDK4 revealed the poorest overall survival. Additionally, in early-stage (I-II) cases, co-overexpression of cyclin D1-CDK4 was also revealed to possess a significant prognostic role. By multivariate analysis, cyclin D1 overexpression, lymph node metastasis and advanced stage were independent prognostic factors for disease-free survival. Cyclin D1 overexpression, CDK4 overexpression, tumor grade, lymph node metastasis and advanced stage were independent prognostic factors for overall survival. These findings indicate that cyclin D1 and CDK4 overexpression and/or co-overexpression of these proteins may play a pivotal role in the biological behavior of LSCC and may provide a strong prognostic implication. © 2001 Wiley-Liss, Inc.International Journal of Cancer 07/2001; 95(4):209 - 215. · 5.44 Impact Factor -
Article: Purification, identification and phosphorylation of annexin I from rat liver mitochondria.
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ABSTRACT: Annexin was purified from rat liver mitochondria to an apparent homogeneity with a molecular weight of 35 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified mitochondrial annexin (AXmito) was identified as annexin I by an immunoblot analysis using anti-annexin I antibody. The inhibitory effect of AXmito I on porcine pancreatic phospholipase A2 activity was as potent as that of bovine lung annexin I. The presence of annexin I in mitochondria was confirmed by an electron-microscopic study. AXmito I was shown to be phosphorylated by intrinsic protein tyrosine kinases on its tyrosine residues. This annexin was also phosphorylated by protein kinase C.Acta Medica Okayama. -
Article: Expression and subcellular localization of multifunctional calmodulin-dependent protein kinases-I, -II and -IV are altered in rat hippocampal CA1 neurons after induction of long-term potentiation
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ABSTRACT: Long-term potentiation (LTP) is considered to be associated with an increase in expression as well as activity of Ca2+/calmodulin-dependent protein kinases (CaMKs). LTP-induced and control hippocampal slices were studied by immunohistochemical and electronmicroscopic analyses using anti-CaMK-I, -II and -IV antibodies. All three kinases were demonstrated to increase their expression in CA1 neurons. CaMK-I was shown to mainly localize in the cytoplasm of the control and LTP-induced neurons, and a significant increase of immunoreactivity was observed in the latter neurons. A part of CaMK-I was found to translocate to the nuclei of LTP-induced hippocampal CA1 neurons. Direct evidence of the translocation of CaMK-II from cytoplasm to nuclei in LTP was demonstrated by immuno-electronmicroscopy. A significant increase in expression of CaMK-IV in the nuclei was also observed. Our data suggest that all the three CaMKs were actively involved in nuclear Ca2+-signaling in LTP.Neuroscience Letters. -
Article: Implication of Malignancy and Prognosis of p27kip1, Cyclin E, and Cdk2 Expression in Epithelial Ovarian Tumors
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ABSTRACT: Objective. The aim of this study was to further evaluate whether the expression of p27kip1, cyclin E, and cdk2 is related to the malignancy of ovarian tumors and whether their expressions, alone or in combination, are associated with prognosis in epithelial ovarian carcinoma.Methods. Immunohistochemical analysis using anti-p27kip1, anti-cyclinE, and anti-cdk2 antibodies was carried out for 103 cases consisting of benign, borderline, and malignant ovarian tumors, and Western blot analysis and cdk2 activity assay were performed in 26 fresh ovarian tumor samples.Results. p27kip1 expression was reduced in ovarian carcinomas in contrast to benign and borderline tumors. The expression of cyclin E and cdk2 gradually increased from benign to borderline to malignant tumors. Kaplan–Meier survival analysis showed that patients with p27kip1 expression had a high overall survival rate. Patients with cyclin E overexpression had a low overall survival rate. When the combination of these proteins was analyzed, patients with the p27kip1 (−)/cyclin E (++)/cdk2 (++) phenotype were significantly associated with the poorest overall survival. In multivariate Cox regression analysis, the combined phenotype of p27kip1 (−)/cyclin E (++)/cdk2 (++) was independently related to poor prognosis.Conclusions. Our results suggest that loss of p27kip1 expression and overexpression of cyclin E or cdk2 were significantly associated with malignancy in ovarian tumors. p27kip1 and cyclin E proteins may be valuable prognostic factors for epithelial ovarian carcinoma patients. Furthermore, the combined evaluation of p27kip1/cyclin E/cdk2 may provide the most important prognostic implication.Gynecologic Oncology.
