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        The Current Status of Adenovirus-based Cancer Gene Therapy

        Toshiro Shirakawa 한국분자세포생물학회 2008 Molecules and cells Vol.25 No.4

        Adenoviruses are the most commonly used gene-delivery vectors due to the efficiency of their in vivo gene transfer. Since 1993, about 300 protocols using an adenoviral vector have been performed, although they have yet to be proven effective in clinical trials. The adenovirus-based vector has been continuously improved by modification of the adenoviral genome and capsid, and novel adenovirus- delivery systems, such as the carrier-cell delivery system, have been recently proposed. Adenovirus-based cancer gene therapy is fast becoming one component of a multi-modality treatment approach to advanced cancer, along with surgery, radiotherapy, and chemotherapy

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        Possible Role of Sonic Hedgehog and Epithelial-Mesenchymal Transition in Renal Cell Cancer Progression

        Hosny M. Behnsawy,Katsumi Shigemura,Fatma Y. Meligy,Fukashi Yamamichi,Masuo Yamashita,Wen-Chin Haung,Xiangyan Li,Hideaki Miyake,Kazushi Tanaka,Masato Kawabata,Toshiro Shirakawa,Masato Fujisawa 대한비뇨의학회 2013 Investigative and Clinical Urology Vol.54 No.8

        Purpose: Sonic hedgehog (Shh) signaling and epithelial-mesenchymal transition (EMT) are both known to relate to cancer progression. The purpose of this study was to investigate the role of Shh signaling and EMT in renal cell carcinoma (RCC). Materials and Methods: Cell proliferation was assayed in RCC cell lines in the presence or absence of a Shh signaling stimulator, recombinant Shh (r-Shh) protein, or a Shh signaling inhibitor, cyclopamine. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to study the expression of EMT markers (E-cadherin, N-cadherin, and vimentin) and osteonectin. The expression of Ki-67, Gli-1, osteonectin, and EMT markers in nephrectomy specimens from RCC patients was also measured by immunohistochemical (IHC) staining. Results: RCC cells showed enhanced cell proliferation by r-Shh protein, whereas cell proliferation was suppressed by the addition of cyclopamine in RenCa cells. Real-time RT-PCR showed that r-Shh suppressed the expression of E-cadherin and that this suppression was partly blocked by cyclopamine alone in RenCa cells. In the IHC results, osteonectin significantly correlated with vein sinus invasion (p=0.0218), and the expression of vimentin significantly correlated with lymphatic invasion (p=0.0392). Conclusions: Shh signaling and EMT play roles in RCC progression, and the Shh signaling inhibitor cyclopamine might be a possible molecular targeted therapeutic strategy for RCC.

      • Augmentation of natural cytotoxicity by chronic low-dose ionizing radiation in murine natural killer cells primed by IL-2

        Sonn, Chung Hee,Choi, Jong Rip,Kim, Tae-Jin,Yu, Young-Bin,Kim, Kwanghee,Shin, Suk Chul,Park, Gil-Hong,Shirakawa, Toshiro,Kim, Hee Sun,Lee, Kyung-Mi Oxford University Press 2012 Journal of radiation research Vol.53 No.6

        <P>The possible beneficial effects of chronic low-dose irradiation (LDR) and its mechanism of action in a variety of pathophysiological processes such as cancer are a subject of intense investigation. While animal studies involving long-term exposure to LDR have yielded encouraging results, the influence of LDR at the cellular level has been less well defined. We reasoned that since natural killer (NK) cells constitute an early responder to exogenous stress, NK cells may reveal sentinel alterations in function upon exposure to LDR. When purified NK cells received LDR at 4.2 mGy/h for a total of 0.2 Gy <I>in vitro</I>, no significant difference in cell viability was observed. Likewise, no functional changes were detected in LDR-exposed NK cells, demonstrating that LDR alone was insufficient to generate changes at the cellular level. Nonetheless, significant augmentation of cytotoxic, but not proliferative, function was detected when NK cells were stimulated with low-dose IL-2 prior to irradiation. This enhancement of NK cytotoxicity was not due to alterations in NK-activating receptors, NK1.1, NKG2D, CD69 and 2B4, or changes in the rate of early or late apoptosis. Therefore, LDR, in the presence of suboptimal cytokine levels, can facilitate anti-tumor cytotoxicity of NK cells without influencing cellular proliferation or apoptosis. Whether these results translate to <I>in vivo</I> consequences remains to be seen; however, our data provide initial evidence that exposure to LDR can lead to subtle immune-enhancing effects on NK cells and may explain, in part, the functional basis underlying, diverse beneficial effects seen in the animals chronically exposed to LDR.</P>

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