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Background: Cyclin A is a cell-cycle regulatory gene and its overexpression promotes tumor cell growth. Y-Box-binding protein 1 (YB1) is a transcription/translation factor involved in tumor growth, invasion, and drug resistance. We investigated whether an association exists between protein products of these genes in epithelial ovarian cancer (EOC) specimens and clinicopathological parameters, patient response and EOC sensitivity to platinum-based first-line chemotherapy., Patients and Methods: Cyclin A and YB1 expression were analyzed by immunohistochemistry in 54 human primary EOC tissues. Immunolabeling of both proteins was graded according to their staining intensity (scale 0-3) and the proportion of immunostained cancer cells (scale 0-4) to obtain a staining index (SI; value=0-12)., Results: Significantly higher cyclin A immunostaining (SI≥4) in EOC specimens was discovered in patients with advanced (International Federation of Gynaecology and Obstetrics (FIGO) III and IV, p=0.003), poorly differentiated (G3, p<0.001) tumors, and tumors of those with residual disease>1 cm (p=0.001). YB1 immunostaining was significantly higher in EOCs from patients with suboptimal debulking (p=0.025). Over-expression of cyclin A (SI≥9) in EOCs was significantly linked with poorer patient response (p=0.001) and higher resistance of tumors to platinum-based first-line chemotherapy (p=0.007), while immunolabeling of YB1 in EOCs was not significantly associated with either of these variables (p>0.05). Cyclin A expression was significantly and positively correlated with that of YB1 (R=0.588, p<0.001)., Conclusion: Increased cyclin A expression in EOC is related to a more aggressive tumor behavior and predicts the response of patients to first-line platinum-based chemotherapy., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Disruption of the G1/S check point leads to uncontrolled cell growth, resulting in the development of cancers., Materials and Methods: Cell cycle regulatory molecules were investigated in 33 surgically resected hepatocellular carcinoma (HCC) samples from 30 patients by Western blotting., Results: Enhanced expressions of cyclin E and cyclin A were detected at frequencies of 18/33 and 26/33 in HCCs, respectively, as compared with their neighboring noncancerous tissues. The enhanced expression of cyclin E, but not that of cyclin A, correlated with hyperphosphorylation of pRb and high frequency of Ki-67-positive cells. Thus, the HCCs with enhanced cyclin E expression probably contain a relatively large number of proliferating cancer cells., Conclusions: The degree of cyclin E expression can be used as a prognostic parameter of HCC. In addition, cyclin E may become a molecular target in the treatment of HCCs.

In this paper, we present evidence that Ginsenoside-Rs3 (G-Rs3), a new diol-type ginseng saponin isolated from the roots of Panax ginseng C.A. Meyer, efficiently arrests the cell cycle at the G1/S boundary at lower doses, 0.1-5 microM, but induces apoptosis at higher doses, 10-25 microM, the effects of which were associated with selectively elevating protein levels of p53 and p21WAF1 in SK-HEP-1 cells. The cell growth suppressive and apoptosis inducing effects were confirmed by MTT assays together with flow cytometric analyses, morphological changes and DNA fragmentation. Immunoblotting showed that G-Rs3 significantly elevated protein levels of p53 and p21WAF1 prior to inducing apoptosis, while it did not elevate those of cyclin E, cyclin A, p27Kip1, and PCNA. Immune complex kinase assays showed that G-Rs3 downregulated the activities of both cyclins E- and A-associated kinases. Collectively, we suggest that G-Rs3 selectively elevates protein levels of p53 and p21WAF1 and hence downregulates the activities of the cyclin-dependent kinases, resulting in cell cycle arrest at the G1/S boundary. We also propose that apoptosis induced by G-Rs3 is related to the elevations of p53 and p21WAF1 in the cells.