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991.
992.
Sajni Josson Yasuhiro Matsuoka Murali Gururajan Takeo Nomura Wen-Chin Huang Xiaojian Yang Jin-tai Lin Roger Bridgman Chia-Yi Chu Peter A. Johnstone Majd Zayzafoon Peizhen Hu Haiyen Zhau Dror Berel Andre Rogatko Leland W. K. Chung 《PloS one》2013,8(7)
Background
Bone metastasis is the most lethal form of several cancers. The β2-microglobulin (β2-M)/hemochromatosis (HFE) complex plays an important role in cancer development and bone metastasis. We demonstrated previously that overexpression of β2-M in prostate, breast, lung and renal cancer leads to increased bone metastasis in mouse models. Therefore, we hypothesized that β2-M is a rational target to treat prostate cancer bone metastasis.Results
In this study, we demonstrate the role of β2-M and its binding partner, HFE, in modulating radiation sensitivity and chemo-sensitivity of prostate cancer. By genetic deletion of β2-M or HFE or using an anti-β2-M antibody (Ab), we demonstrate that prostate cancer cells are sensitive to radiation in vitro and in vivo. Inhibition of β2-M or HFE sensitized prostate cancer cells to radiation by increasing iron and reactive oxygen species and decreasing DNA repair and stress response proteins. Using xenograft mouse model, we demonstrate that anti-β2-M Ab sensitizes prostate cancer cells to radiation treatment. Additionally, anti-β2-M Ab was able to prevent tumor growth in an immunocompetent spontaneous prostate cancer mouse model. Since bone metastasis is lethal, we used a bone xenograft model to test the ability of anti-β2-M Ab and radiation to block tumor growth in the bone. Combination treatment significantly prevented tumor growth in the bone xenograft model by inhibiting β2-M and inducing iron overload. In addition to radiation sensitive effects, inhibition of β2-M sensitized prostate cancer cells to chemotherapeutic agents.Conclusion
Since prostate cancer bone metastatic patients have high β2-M in the tumor tissue and in the secreted form, targeting β2-M with anti-β2-M Ab is a promising therapeutic agent. Additionally, inhibition of β2-M sensitizes cancer cells to clinically used therapies such as radiation by inducing iron overload and decreasing DNA repair enzymes. 相似文献993.
994.
While informative, protein amounts and physical protein associations do not provide a full picture of protein function. This Commentary highlights the potential of structural and stability proteomic technologies to derive new insights in biology and medicine. The ultimate goal of proteomics is to provide a holistic view of the biological processes that explain phenotypes. To this end, proteomics approaches have been frequently used to map protein expression in multiple experimental conditions and to identify protein–protein interactions. While informative to a certain extent, protein amounts and physical protein associations do not provide a full picture of protein function. Here, we highlight the novel insights that are made possible in biology and medicine by structural and stability proteomic technologies. 相似文献
995.
Lipid nanopores can form a stable, ion channel-like conduction pathway in cell membrane 总被引:2,自引:0,他引:2
Andrei G. Pakhomov Angela M. Bowman Franck M. Andre Karl H. Schoenbach 《Biochemical and biophysical research communications》2009,385(2):181-186
Cell permeabilization by electric pulses (EPs), or electroporation, has been well established as a tool to indiscriminately increase membrane flows of water solutes down the concentration and voltage gradients. However, we found that EPs of nanosecond duration (nsEPs) trigger formation of voltage-sensitive and inward-rectifying membrane pores. NsEP-treated cells remain mostly impermeable to propidium, suggesting that the maximum pore size is ∼1 nm. The ion-channel-like properties of nsEP-opened nanopores vanish if they break into larger, propidium-permeable “conventional” pores. However, nanopores can be stable for many minutes and significantly impact cell electrolyte and water balance. Multiple nsEPs cause fast cell swelling and blebbing, whereas opening of larger pores with digitonin abolishes swelling and causes blebs to implode. The lipid nature of nsEP-opened nanopores is confirmed by fast externalization of phosphatidylserine residues. Nanopores constitute a previously unexplored ion transport pathway that supplements classic ion channels but is distinctly different from them. 相似文献
996.
997.
Andre Durudas Jeffrey M. Milush Hui-Ling Chen Jessica C. Engram Guido Silvestri Donald L. Sodora 《Journal of virology》2009,83(23):12229-12240
998.
999.
Andre F Steinert Benedikt Proffen Manuela Kunz Christian Hendrich Steven C Ghivizzani Ulrich Nöth Axel Rethwilm Jochen Eulert Christopher H Evans 《Arthritis research & therapy》2009,11(5):R148-15
Introduction
The present study compares bone morphogenetic protein (BMP)-4 and BMP-2 gene transfer as agents of chondrogenesis and hypertrophy in human primary mesenchymal stem cells (MSCs) maintained as pellet cultures. 相似文献1000.