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( Junko Tsuboki ),( Kiyomi Takaishi ),( Fumiko Ito ),( Ritsuo Honda ),( Hironori Tashiro ),( Hidetaka Katabuchi ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-
Objective: In epithelial ovarian cancer (EOC), M2-polarized macrophage (Mø), a component of the cancer microenvironment in ascitic fluid as well as primary tumor, is thought to play an important role in cell- proliferation via paracrine activation of the STAT3 pathway. Onionin A (ONA), a natural compound purified from onions, biologically inhibits M2 polarization, and molecularly inactivates STAT3 signaling of Mø and tumor cells. Here we elucidated the indirect and direct anti-cancer effects of ONA via the STAT3 pathway. Methods: The indirect effects of ONA on EOC cells were analyzed under the co-culture system with human monocyte- derived Mø using BrdU ELISA assay. The direct effects of ONA alone and combinations with anti-cancer drugs (PTX, CBDCA, or CDDP) on proliferation and STAT3 activation of the human EOC cell lines (SKOV3, RMG1, or ES2) were evaluated using WST assay and western blot analysis. Results: M2Mø in the co-culture system enhanced proliferation of EOC cells, whereas ONA significantly reduced the enhancement of the cell-proliferation by inhibition of M2-polarization. In addition, ONA directly inhibited STAT3-activation and proliferation of EOC cells (P value < 0.01-0.05). Moreover, the suppressive effects against EOC cell proliferation were significantly increased by the combination of ONA with anti-cancer drugs (P value < 0.01-0.05). Conclusions: ONA exhibited direct anti-cancer effects in EOC as well as indirect effects by suppression of M2-polarization in co-culture system. It was suggested that the combination of ONA and anti-cancer drugs presents a new therapeutic strategy for treatment of EOC.
A New Cancer Cell Detection Method Using an Infectivity-enhanced Adenoviral Vector
Uchino, Junji,Takayama, Koichi,Nakagaki, Noriaki,Shuo, Wang,Hisasue, Junko,Nakatom, Keita,Ohta, Keiichi,Hirano, Ryosuke,Tashiro, Naoki,Miiru, Izumi,Fujita, Masaki,Watanabe, Kentaro,Nakanishi, Yoichi Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11
Cytological examination is widely used as a diagnostic tool because of the ease of collecting cells from the involved area. However, the diagnostic yield of cytological examination is unsatisfactory; the reasons include sampling error, poorly prepared samples, small numbers of malignant cells, and low grades of cellular atypia. In this study, we focused on the high infectivity of adenovirus towards epithelial cells and applied the luciferase-expressing adenoviral vector to a new cancer cell detection tool. In addition, adenoviral infectivity was enhanced by modifying viral fiber proteins. The sensitivity of the diagnostic tool was tested using the NCI-H1299 lung cancer cell line, and validated in body fluid samples from cancer patients with a variety of etiology. Results showed that the adenovirus efficiently transfected NCI-H1299 with high sensitivity. Only 10 cancer cells were sufficient for detection of luciferase signals. In body fluid samples, the adenovirus confirmed the diagnosis for malignant and benign cancer, but not in non-epithelial cell derived samples. This study provides proof-of-concept for a more reliable and sensitive diagnostic tool for epithelium-derived cancer.