Cancer cells require glucose to support their rapid growth through a process known as aerobic glycolysis, or the Warburg effect. As in ovarian cancer cells, increased metabolic activity and glucose concentration has been linked to aggressiveness of cancer. However, it is unclear as to whether targeting the glycolytic pathway may kill the malignant cells and likely have broad therapeutic implications against ovarian cancer metastasis. In the present research, we found that EF24, a HIF-1a inhibitor, could significantly block glucose uptake, the rate of glycolysis, and lactate production compared with vehicle treatment in SKOV-3, A2780 and OVCAR-3 cells. These results might possibly contribute to the further observation that EF24 could inhibit ovarian cancer cell migration and invasion from wound healing and Transwell assays. Furthermore, as an important mediator of glucose metabolism, glucose transporter 1 (Glut1) was found to contribute to the function of EF24 in both energy metabolism and metastasis. To examine the effect of EF24 and the mediated role of Glut1 in vivo in a xenograph subcutaneous tumor model, intraperitoneal metastasis and lung metastasis model were introduced. Our results indicated that EF24 treatment could inhibit tumor growth, intraperitoneal metastasis and lung metastasis of SKOV-3 cells, and Glut1 is a possible mediator for the role of EF24. In conclusion, our results highlight that an anti-cancer reagent with an inhibiting effect on energy metabolism could inhibit metastasis, and EF24 is a possible candidate for anti-metastasis therapeutic applications for ovarian cancer. (Cancer Sci 2013; 104: 1690-1696

Our results indicate that HPV infection and subsequent transformation take place through complex regulatory patterns of gene expression in the host cells, part of which are regulated by the E6 protein.

Testes-specific protease 50 (TSP50) has threonine activity and has homology to serine proteases. TSP50 protein, which is encoded by a possible proto-oncogene, is overexpressed in cervical tumor tissues. Through overexpression experiments using both TSP50 and a TSP50 mutant (TSP50 T310A), it is clear that this protein may play an important role in carcinogenesis and progression of cervical tumor. However, the mechanism underlying how TSP50 modulates cancer cell growth is still unclear. To examine the difference in TSP50 expression in cervical carcinoma tissues and in paracarcinoma tissues, we detected TSP50 mRNA and protein in ten paired tissues from patients with cervical cancer. To determine whether TSP50's threonine protease activity is crucial for its effects on tumor formation, we generated a mutant version of TSP50 (T310A). Via overexpression and silencing experiments, we identified a role for TSP50 in cell proliferation and migration. Furthermore, we examined the signaling pathway of TNF-α-induced NFκB activation to explain the mechanism by which TSP50 participates in tumorigenesis. Similarly, we found that all these effects could be abolished by the TSP50 T310A mutation. Our results suggest that the threonine 310 residue within TSP50 helps modulate its role in cervical tumorigenesis and indicates that TSP50's role in tumorigenesis may be dependent on its interaction with TNF-α-induced NF-κB.

Due to the excellent infrared transparency, low phonon energy, and high rare‐earth solubility, germanate laser glass has attracted much attention in mid‐infrared fiber lasers for potential coherent laser radar systems, optical detection, remote sensing, and laser surgery. However, radiation‐induce darkening often occurs in fiber lasers that operate in radiation environment. Here, we report a useful strategy to improve the radiation resistance by adding multivalence Bi ions and discuss its radiation resistance mechanism. In order to study the effect of valence states on the radiation resistance of barium gallo‐germanate glass, we adjust the valence states of Bi ions by heat treatment, the potential mechanism of which is discussed in detail based on the absorption, photoluminescence (PL), and Raman spectra. The absorption, electron paramagnetic resonance, and photoluminescence spectra have proved the interconversion of Bi ions between low and high valence, which inhibits the formation of Ge‐related electron center (GEC) and non‐bridging oxygen hole center defects in the irradiation process. In addition, the Bi3+ content increased by heat treatment is beneficial to serve as electron‐trapping centers in γ‐ray irradiation, thus further reducing the formation of GEC. This study provides a simple method to achieve Bi valence regulation, so as to improve the radiation resistance.

A large quantity of M2-polarized tumor-associated macrophages (TAMs) is present in the tissue, ascitic fluid and peritoneum of ovarian cancer patients. A thorough understanding of the roles of M2-TAM in the development of ovarian cancer may provide new insight into the treatment of this disease. The rapid advancement of omics techniques presents a great challenge to biologists to extract meaningful biological information from vast pools of data. In the present study, using microarray method, we identified 996 genes in SKOV3 ovarian carcinoma cells that underwent expression level changes under the influence of TAMs. Subsequently, based on the protein-protein interactions network and the differentially expressed genes, a network showing the influence of TAMs on SKOV3 cells was constructed. The resulting network was analyzed with CFinder software and four modules were found; these modules were further analyzed using David software to perform functional annotations. It was found that module I was mainly related to tumorigenesis and cell cycle. Hence, 31 genes in module I were analyzed with Cytoscape software to generate a gene-function network, which revealed that four gene proteins (E2F1, RB1, CDK2 and CDK4) were functional. Based on literature review, we postulated that CDK2 and CDK4 were key players in the network. In the subsequent molecular experiments, western blot analysis and kinase activity detection demonstrated that TAMs can significantly boost the expression levels and activities of CDK2 and CDK4 in SKOV3 cells. With 3H-TdR incorporation and flow cytometry assay, the proliferation and cell cycle distribution of SKOV3 cells were detected in the absence or presence of CDK2 and CDK4 inhibitors and the results confirmed that the two kinases played a key role in TAM cells enhancing SKOV3 cell proliferation by promoting G0/G1 to S transition. In the present study, we identified the specific changes in the gene expression profile of SKOV3 cells under the influence of TAMs and explored a method for analyzing the gene expression profile data. The results may aid in the design of subsequent molecular experiments.