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Re: MicroRNA-449a Acts as a Tumor Suppressor in Human Bladder Cancer Through the Regulation of Pocket Proteins
Urological Survey
Uro-Science Re: MicroRNA-449a Acts as a Tumor Suppressor in Human Bladder Cancer Through the Regulation of Pocket Proteins H. Chen, Y. W. Lin, Y. Q. Mao, J. Wu, Y. F. Liu, X. Y. Zheng and L. P. Xie Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China Cancer Lett 2012; 320: 40 – 47.
Frequent downregulation of microRNA-449a (miR-449a) was detected in 14 human bladder cancer tissues. The restoration of miR-449a inhibited cell growth and induced G1-phase arrest in T24 and 5637 human bladder cancer cells. CDK6 and CDC25a were downregulated after miR-449a treatment, resulting in the functional accumulation of the pocket proteins Rb and p130. The growth of T24 tumor xenografts was suppressed by exogenous miR-449a, and the nuclear proliferation antigen Ki-67 was downregulated in miR-449a-treated tumors. These results suggest a tumor-suppressive role for miR-449a in human bladder cancer. Editorial Comment: In this study the authors successfully inhibited tumor growth in vivo using liposome encapsulated miR-449a, with suppressed cell proliferation observed in treated tumors. These results indicate a potential application of miR-449a in clinical use. The key challenge for clinical application of small RNA is the delivery. Although liposomes were used to deliver RNA into cells and tissue, there are disadvantages to this process, such as the large doses required for efficacy, repeated treatments, nonspecific tissue targeting and possible toxicity. In the last decade novel delivery methods have been developed to increase the efficacy and target specificity, and RNA modification is also being studied to increase RNA stability and decrease its immunogenicity. All of these efforts may contribute to a promising future for the clinical application of microRNA. Anthony Atala, M.D.
Re: An Epirubicin-Conjugated Nanocarrier with MRI Function to Overcome Lethal Multidrug-Resistant Bladder Cancer H. W. Yang, M. Y. Hua, H. L. Liu, R. Y. Tsai, S. T. Pang, P. H. Hsu, H. J. Tang, T. C. Yen and C. K. Chuang Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, Chang Gung University, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China Biomaterials 2012; 33: 3919 –3930.
Multidrug resistance (MDR) presents a major obstacle to curing cancer. Chemotherapy failure can occur through both cell membrane drug resistance (CMDR) and nuclear drug resistance (NDR), and anticancer effectiveness of chemotherapeutic agents is especially reduced by their nuclear export. Here we report an exciting magnetically-targeted nanomedicine formed by conjugation of epirubicin (EPI) to non-toxic and high-magnetization nanocarrier (HMNC). Strikingly, HMNC-EPI overcomes both CMDR and NDR in human bladder cancer cell models, without using P-glycoprotein (P-gp) and nuclear pore inhibitors. Besides, the half-life of drug is prolonged ⬃1.8-fold (from 45 h to 81 h) at 37°C, 0022-5347/13/1891-0385/0 THE JOURNAL OF UROLOGY® © 2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2012.09.105 Vol. 189, 385-388, January 2013 Printed in U.S.A.
www.jurology.com
385
Uro-Science Re: MicroRNA-449a Acts as a Tumor Suppressor in Human Bladder Cancer Through the Regulation of Pocket Proteins H. Chen, Y. W. Lin, Y. Q. Mao, J. Wu, Y. F. Liu, X. Y. Zheng and L. P. Xie Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China Cancer Lett 2012; 320: 40 – 47.
Frequent downregulation of microRNA-449a (miR-449a) was detected in 14 human bladder cancer tissues. The restoration of miR-449a inhibited cell growth and induced G1-phase arrest in T24 and 5637 human bladder cancer cells. CDK6 and CDC25a were downregulated after miR-449a treatment, resulting in the functional accumulation of the pocket proteins Rb and p130. The growth of T24 tumor xenografts was suppressed by exogenous miR-449a, and the nuclear proliferation antigen Ki-67 was downregulated in miR-449a-treated tumors. These results suggest a tumor-suppressive role for miR-449a in human bladder cancer. Editorial Comment: In this study the authors successfully inhibited tumor growth in vivo using liposome encapsulated miR-449a, with suppressed cell proliferation observed in treated tumors. These results indicate a potential application of miR-449a in clinical use. The key challenge for clinical application of small RNA is the delivery. Although liposomes were used to deliver RNA into cells and tissue, there are disadvantages to this process, such as the large doses required for efficacy, repeated treatments, nonspecific tissue targeting and possible toxicity. In the last decade novel delivery methods have been developed to increase the efficacy and target specificity, and RNA modification is also being studied to increase RNA stability and decrease its immunogenicity. All of these efforts may contribute to a promising future for the clinical application of microRNA. Anthony Atala, M.D.
Re: An Epirubicin-Conjugated Nanocarrier with MRI Function to Overcome Lethal Multidrug-Resistant Bladder Cancer H. W. Yang, M. Y. Hua, H. L. Liu, R. Y. Tsai, S. T. Pang, P. H. Hsu, H. J. Tang, T. C. Yen and C. K. Chuang Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, Chang Gung University, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China Biomaterials 2012; 33: 3919 –3930.
Multidrug resistance (MDR) presents a major obstacle to curing cancer. Chemotherapy failure can occur through both cell membrane drug resistance (CMDR) and nuclear drug resistance (NDR), and anticancer effectiveness of chemotherapeutic agents is especially reduced by their nuclear export. Here we report an exciting magnetically-targeted nanomedicine formed by conjugation of epirubicin (EPI) to non-toxic and high-magnetization nanocarrier (HMNC). Strikingly, HMNC-EPI overcomes both CMDR and NDR in human bladder cancer cell models, without using P-glycoprotein (P-gp) and nuclear pore inhibitors. Besides, the half-life of drug is prolonged ⬃1.8-fold (from 45 h to 81 h) at 37°C, 0022-5347/13/1891-0385/0 THE JOURNAL OF UROLOGY® © 2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2012.09.105 Vol. 189, 385-388, January 2013 Printed in U.S.A.
www.jurology.com
385