實驗使用的奈米鍺是利用還原反應所製成，具水溶性及可發出藍綠色螢光。此奈米鍺表面覆蓋烯丙基胺物（allylamine），具有穩定的物理特性並且可以進一步修飾做生物上的應用。利用水溶性奈米鍺進行細胞測試，由MTT試驗、細胞群落分析以及PI拒染試驗，發現水溶性奈米鍺具有明顯的細胞毒性，而且不會使細胞週期停滯在特定階段，也不會造成細胞中DNA的裂解及caspase 3活性增加。利用細胞壞死抑制劑處理細胞則可以抑制奈米鍺所造成的細胞死亡，證實水溶性奈米鍺是造成細胞壞死現象。分析細胞中鈣離子濃度發現，處理奈米鍺會造成鈣離子濃度增加，共同處理細胞中鈣離子螯合劑可以抑制鈣離子增加並降低細胞壞死狀況。當細胞處理奈米鍺會使細胞內活性氧化物質增加，而共同處理抗氧化劑可以抑制奈米鍺所產生的細胞傷害。此外也發現奈米鍺會造成粒線體膜電位下降，共同處理粒線體通透性轉換抑制劑則可以抑制此現象。當細胞處理奈米鍺，鈣離子在12小時後會上升，細胞內活性氧化物在15小時後產生，而粒線體膜電位在21小時後下降，若分別利用鈣離子螯合劑、抗氧化劑及粒線體通透轉換抑制劑處理細胞以分析訊號產生上下游關係，可以推知，處理奈米鍺，首先造成細胞內鈣離子濃度上升，接著細胞內活性氧化物增加，導致粒線體膜電位下降，最後走向細胞壞死。

Water-soluble germanium nanoparticles (GeNP) are fabricated by reduction method which emits blue-green fluorescence. Surface of this GeNP is coated by allylamine that allows the particles to present in great physical stability and is suitable for bioconjugation. The cytotoxicity of GeNP was analyzed in this study. The fabricated water-soluble GeNP generated significant cytotoxicity was analyzed by MTT, chronogenic and propidium exclusion assay. Flow cytometric analysis revealed that GeNP did not cause the blockage of cell cycle progression and the appearance of sub-G1 fraction. Furthermore, neither DNA ladder nor caspase 3 activity was increased by GeNP treatment. Administration of necrosis inhibitor, necrostatin-1, attenuated the GeNP-induced cell damage. These results demonstrated that GeNP caused necrotic cell death in CHO K1 cells. The mechanism involved in the cell death was subsequently investigated. Intracellular calcium content was estimated after GeNP treatment. Elevation of the calcium content occurred 12 hours later and this effect was diminished by calcium cheletor, BAPTA-AM. Relative oxygen species (ROS) increased 15 hours after giving GeNP. Addition of N-acetylcysteine (NAC), an antioxidant, decreased the ROS level and cell damage. Reduction of mitochondrial membrane potential (MMP) was observed 21 hours after GeNP treatment. The reduction can be attenuated by the administration of cyclosporine A (CsA), an inhibitor of mitochondrial membrane transition pore. Using BAPTA-AM, NAC and CsA respectively to examine the relationship of the signaling factors, a pathway for the GeNP-induced necrotic cell death can be established. The water-soluble GeNP stimulates the release of intracellular calcium storage which leads to the elevation of ROS production. The ROS then causes the reduction of MMP and subsequently results in necrotic cell death.

Andreyev, A.Y., Kushnareva, Y.E. and Starkov, A.A. (2005) Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc), 70, 200-214.

Armen Avoyan, C.T., and John C. Hemminger. (1998) Chemistry of HNO3 on Ge(100). J. Phys. Chem. B, 102, 5069-5076.

Aso, H., Suzuki, F., Ebina, T. and Ishida, N. (1989) Antiviral activity of carboxyethylgermanium sesquioxide (Ge-132) in mice infected with influenza virus. J Biol Response Mod, 8, 180-189.

Badger, A.M., Mirabelli, C.K., Swift, B.A. and DiMartino, M.J. (1989) Inhibition of autoimmune disease and the generation of suppressor cells by spirogermanium: a biological profile similar to total lymphoid irradiation. Agents Actions, 27, 335-337.

Berridge, M.J. (1995) Capacitative calcium entry. Biochem J, 312 ( Pt 1), 1-11.

Bianchi, L., Gerstbrein, B., Frokjaer-Jensen, C., Royal, D.C., Mukherjee, G., Royal, M.A., Xue, J., Schafer, W.R. and Driscoll, M. (2004) The neurotoxic MEC-4(d) DEG/ENaC sodium channel conducts calcium: implications for necrosis initiation. Nat Neurosci, 7, 1337-1344.

Cantoni, O., Guidarelli, A., Palomba, L. and Fiorani, M. (2005) U937 cell necrosis mediated by peroxynitrite is not caused by depletion of ATP and is prevented by arachidonate via an ATP-dependent mechanism. Mol Pharmacol, 67, 1399-1405.

Chiu, H.W., Kauzlarich, S.M. and Sutter, E. (2006) Thermal behavior and film formation from an organogermanium polymer/nanoparticle precursor. Langmuir, 22, 5455-5458.

Chiu, S.J., Hsu, T.S. and Chao, J.I. (2007) Expression of securin promotes colorectal cancer cell death via a p53-independent pathway after radiation. Chem Biol Interact, 170, 153-161.

Chiu, S.J., Lee, M.Y., Chen, H.W., Chou, W.G. and Lin, L.Y. (2002) Germanium oxide inhibits the transition from G2 to M phase of CHO cells. Chem Biol Interact, 141, 211-228.

Chiu, S.J., Lee, M.Y., Chou, W.G. and Lin, L.Y. (2003) Germanium oxide enhances the radiosensitivity of cells. Radiat Res, 159, 391-400.

Cho, Y., Shi, R., Borgens, R.B. and Ivanisevic, A. (2008) Functionalized mesoporous silica nanoparticle-based drug delivery system to rescue acrolein-mediated cell death. Nanomedicine (Lond), 3, 507-519.

Choi, M.R., Stanton-Maxey, K.J., Stanley, J.K., Levin, C.S., Bardhan, R., Akin, D., Badve, S., Sturgis, J., Robinson, J.P., Bashir, R., Halas, N.J. and Clare, S.E. (2007) A cellular Trojan Horse for delivery of therapeutic nanoparticles into tumors. Nano Lett, 7, 3759-3765.

Clarke, P.G. (1990) Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol (Berl), 181, 195-213.

Clarke, S.J., McStay, G.P. and Halestrap, A.P. (2002) Sanglifehrin A acts as a potent inhibitor of the mitochondrial permeability transition and reperfusion injury of the heart by binding to cyclophilin-D at a different site from cyclosporin A. J Biol Chem, 277, 34793-34799.

Danial, N.N. and Korsmeyer, S.J. (2004) Cell death: critical control points. Cell, 116, 205-219.

de Duve, C. (1983) Lysosomes revisited. Eur J Biochem, 137, 391-397.

Degterev, A., Hitomi, J., Germscheid, M., Ch'en, I.L., Korkina, O., Teng, X., Abbott, D., Cuny, G.D., Yuan, C., Wagner, G., Hedrick, S.M., Gerber, S.A., Lugovskoy, A. and Yuan, J. (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol, 4, 313-321.

Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N., Cuny, G.D., Mitchison, T.J., Moskowitz, M.A. and Yuan, J. (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol, 1, 112-119.
Dieter, P., Fitzke, E. and Duyster, J. (1993) BAPTA induces a decrease of intracellular free calcium and a translocation and inactivation of protein kinase C in macrophages. Biol Chem Hoppe Seyler, 374, 171-174.

Dozono, H., Ikeda, K. and Onishi, T. (1996) [Effectiveness of Ge-132 to relieve pain and smooth home care administration for the terminal cancer patient]. Gan To Kagaku Ryoho, 23 Suppl 3, 291-295.

Eaglesham, D.J. and Cerullo, M. (1990) Dislocation-free Stranski-Krastanow growth of Ge on Si(100). Phys Rev Lett, 64, 1943-1946.

Earnshaw, W.C., Martins, L.M. and Kaufmann, S.H. (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem, 68, 383-424.

Fatt, P. and Ginsborg, B.L. (1958) The ionic requirements for the production of action potentials in crustacean muscle fibres. J Physiol, 142, 516-543.

Festjens, N., Kalai, M., Smet, J., Meeus, A., Van Coster, R., Saelens, X. and Vandenabeele, P. (2006a) Butylated hydroxyanisole is more than a reactive oxygen species scavenger. Cell Death Differ, 13, 166-169.

Festjens, N., Vanden Berghe, T. and Vandenabeele, P. (2006b) Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta, 1757, 1371-1387.

Frohlich, E., Samberger, C., Kueznik, T., Absenger, M., Roblegg, E., Zimmer, A. and Pieber, T.R. (2009) Cytotoxicity of nanoparticles independent from oxidative stress. J Toxicol Sci, 34, 363-375.

Fukazawa, H., Ohashi, Y., Sekiyama, S., Hoshi, H., Abe, M., Takahashi, M. and Sato, T. (1994) Multidisciplinary treatment of head and neck cancer using BCG, OK-432, and GE-132 as biologic response modifiers. Head Neck, 16, 30-38.

Gagne, F., Marion, M. and Denizeau, F. (1990) Metal homeostasis and metallothionein induction in rainbow trout hepatocytes exposed to cadmium. Fundam Appl Toxicol, 14, 429-437.
Galis, Z.S., Asanuma, K., Godin, D. and Meng, X. (1998) N-acetyl-cysteine decreases the matrix-degrading capacity of macrophage-derived foam cells: new target for antioxidant therapy? Circulation, 97, 2445-2453.

Han, W., Li, L., Qiu, S., Lu, Q., Pan, Q., Gu, Y., Luo, J. and Hu, X. (2007) Shikonin circumvents cancer drug resistance by induction of a necroptotic death. Mol Cancer Ther, 6, 1641-1649.

Haworth, R.A. and Hunter, D.R. (1979) The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site. Arch Biochem Biophys, 195, 460-467.

Haworth, R.A. and Hunter, D.R. (2000) Control of the mitochondrial permeability transition pore by high-affinity ADP binding at the ADP/ATP translocase in permeabilized mitochondria. J Bioenerg Biomembr, 32, 91-96.

Hengartner, M.O. (2000) The biochemistry of apoptosis. Nature, 407, 770-776.

Hill, B.T., Whatley, S.A., Bellamy, A.S., Jenkins, L.Y. and Whelan, R.D. (1982) Cytotoxic effects and biological activity of 2-aza-8-germanspiro[4,5]-decane-2-propanamine-8,8-diethyl-N,N-dimethyl dichloride (NSC 192965; spirogermanium) in vitro. Cancer Res, 42, 2852-2856.

Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Valitutti, S., Bodmer, J.L., Schneider, P., Seed, B. and Tschopp, J. (2000) Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol, 1, 489-495.

Hsu, T.S., Yang, P.M., Tsai, J.S. and Lin, L.Y. (2009) Attenuation of cadmium-induced necrotic cell death by necrostatin-1: potential necrostatin-1 acting sites. Toxicol Appl Pharmacol, 235, 153-162.

Hu, K.W., Huang, C.C., Hwu, J.R., Su, W.C., Shieh, D.B. and Yeh, C.S. (2008) A new photothermal therapeutic agent: core-free nanostructured Au x Ag1-x dendrites. Chemistry, 14, 2956-2964.

Hu, Y., Churchill, H.O., Reilly, D.J., Xiang, J., Lieber, C.M. and Marcus, C.M. (2007) A Ge/Si heterostructure nanowire-based double quantum dot with integrated charge sensor. Nat Nanotechnol, 2, 622-625.

Hunter, D.R. and Haworth, R.A. (1979a) The Ca2+-induced membrane transition in mitochondria. I. The protective mechanisms. Arch Biochem Biophys, 195, 453-459.

Hunter, D.R. and Haworth, R.A. (1979b) The Ca2+-induced membrane transition in mitochondria. III. Transitional Ca2+ release. Arch Biochem Biophys, 195, 468-477.

Jamie H Warner, R.D.T. (2006) Synthesis of water-soluble photoluminescent germanium nanocrystals. nanotechnology, 17, 3745-3749.

Jin, Y., Kannan, S., Wu, M. and Zhao, J.X. (2007) Toxicity of luminescent silica nanoparticles to living cells. Chem Res Toxicol, 20, 1126-1133.

Kada, T., Mochizuki, H. and Miyao, K. (1984) Antimutagenic effects of germanium oxide on Trp-P-2-induced frameshift mutations in Salmonella typhimurium TA98 and TA1538. Mutat Res, 125, 145-151.

Kaneko, T., Saeki, K., Lee, T. and Mizuno, N. (1996) Improved retrograde axonal transport and subsequent visualization of tetramethylrhodamine (TMR) -dextran amine by means of an acidic injection vehicle and antibodies against TMR. J Neurosci Methods, 65, 157-165.

Kim, J.S., He, L. and Lemasters, J.J. (2003) Mitochondrial permeability transition: a common pathway to necrosis and apoptosis. Biochem Biophys Res Commun, 304, 463-470.

Kirui, D.K., Rey, D.A. and Batt, C.A. (2010) Gold hybrid nanoparticles for targeted phototherapy and cancer imaging. Nanotechnology, 21, 105.

Kong, X. (1993) [Organic germanium: its toxic effect and function in medical care]. Zhonghua Yi Xue Za Zhi, 73, 454-456.

Kumano, N., Ishikawa, T., Koinumaru, S., Kikumoto, T., Suzuki, S., Nakai, Y. and Konno, K. (1985) Antitumor effect of the organogermanium compound Ge-132 on the Lewis lung carcinoma (3LL) in C57BL/6 (B6) mice. Tohoku J Exp Med, 146, 97-104.

Leist, M., Single, B., Castoldi, A.F., Kuhnle, S. and Nicotera, P. (1997) Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med, 185, 1481-1486.

Leonard, G.a. (1997) Mutagenicity, carcinogenicity and teratogenicity of germanium compounds. Murat Res, 387, 141-146.

Levine, B. and Yuan, J. (2005) Autophagy in cell death: an innocent convict? J Clin Invest, 115, 2679-2688.

Li, P., Allen, H., Banerjee, S., Franklin, S., Herzog, L., Johnston, C., McDowell, J., Paskind, M., Rodman, L., Salfeld, J. and et al. (1995) Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell, 80, 401-411.

Lin, M.H., Hsu, T.S., Yang, P.M., Tsai, M.Y., Perng, T.P. and Lin, L.Y. (2009) Comparison of organic and inorganic germanium compounds in cellular radiosensitivity and preparation of germanium nanoparticles as a radiosensitizer. Int J Radiat Biol, 85, 214-226.

Liu, X., Van Vleet, T. and Schnellmann, R.G. (2004) The role of calpain in oncotic cell death. Annu Rev Pharmacol Toxicol, 44, 349-370.

Maiuri, M.C., Zalckvar, E., Kimchi, A. and Kroemer, G. (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol, 8, 741-752.

Majno, G. and Joris, I. (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol, 146, 3-15.

Marzo, I., Brenner, C., Zamzami, N., Jurgensmeier, J. M., Susin, S. A., Vieira, H. L., Prevost, M. C., Xie, Z., Matsuyama, S., Reed, J. C., and Kroemer, G. (1998) Bax and adenine nucleotide translocator cooperate in the mitocondrial control of apoptosis. Science, 281, 2027-2031.

Matsumuro, K., Izumo, S., Higuchi, I., Ronquillo, A.T., Takahashi, K. and Osame, M. (1993) Experimental germanium dioxide-induced neuropathy in rats. Acta Neuropathol, 86, 547-553.

McConkey, D.J. (1998) Biochemical determinants of apoptosis and necrosis. Toxicol Lett, 99, 157-168.

McConkey, D.J. and Orrenius, S. (1996) The role of calcium in the regulation of apoptosis. J Leukoc Biol, 59, 775-783.

Medintz, I.L., Trammell, S.A., Mattoussi, H. and Mauro, J.M. (2004) Reversible modulation of quantum dot photoluminescence using a protein- bound photochromic fluorescence resonance energy transfer acceptor. J Am Chem Soc, 126, 30-31.

Mirabelli, C.K., Badger, A.M., Sung, C.P., Hillegass, L., Sung, C.M., Johnson, R.K., Picker, D., Schwartz, D., Dorman, J. and Martellucci, S. (1989) Pharmacological activities of spirogermanium and other structurally related azaspiranes: effects on tumor cell and macrophage functions. Anticancer Drug Des, 3, 231-242.

Muzio, M., Stockwell, B.R., Stennicke, H.R., Salvesen, G.S. and Dixit, V.M. (1998) An induced proximity model for caspase-8 activation. J Biol Chem, 273, 2926-2930.

Nicolli, A., Basso, E., Petronilli, V., Wenger, R.M. and Bernardi, P. (1996) Interactions of cyclophilin with the mitochondrial inner membrane and regulation of the permeability transition pore, and cyclosporin A-sensitive channel. J Biol Chem, 271, 2185-2192.

Nishimura, Y. and Lemasters, J.J. (2001) Glycine blocks opening of a death channel in cultured hepatic sinusoidal endothelial cells during chemical hypoxia. Cell Death Differ, 8, 850-858.

Nordberg, J. and Arner, E.S. (2001) Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med, 31, 1287-1312.

Novik, Y., Ryan, L.M., Haller, D.G.,Asbury, R., Dutcher, J.P. and Schutt, A. . (1999) Phase II protocol for the evaluation of new treatments in patient with advanced gastric carcinoma: results of ECOG 5282. Med Oncol, 16, 261-266.

Ohgoh, M., Shimizu, H., Ogura, H. and Nishizawa, Y. (2000) Astroglial trophic support and neuronal cell death: influence of cellular energy level on type of cell death induced by mitochondrial toxin in cultured rat cortical neurons. J Neurochem, 75, 925-933.

Orren, D.K., Petersen, L.N. and Bohr, V.A. (1995) A UV-responsive G2 checkpoint in rodent cells. Mol Cell Biol, 15, 3722-3730.

Pan, Y., Neuss, S., Leifert, A., Fischler, M., Wen, F., Simon, U., Schmid, G., Brandau, W. and Jahnen-Dechent, W. (2007) Size-dependent cytotoxicity of gold nanoparticles. Small, 3, 1941-1949.

Park, E.J., Yi, J., Kim, Y., Choi, K. and Park, K. (2010) Silver nanoparticles induce cytotoxicity by a Trojan-horse type mechanism. Toxicol In Vitro, 24, 872-878.

Ravagnan, L., Roumier, T. and Kroemer, G. (2002) Mitochondria, the killer organelles and their weapons. J Cell Physiol, 192, 131-137.

Rawlings, N.D. and Barrett, A.J. (1999) MEROPS: the peptidase database. Nucleic Acids Res, 27, 325-331.

Richter, C. and Schlegel, J. (1993) Mitochondrial calcium release induced by prooxidants. Toxicol Lett, 67, 119-127.

Santra, S., Zhang, P., Wang, K., Tapec, R. and Tan, W. (2001) Conjugation of biomolecules with luminophore-doped silica nanoparticles for photostable biomarkers. Anal Chem, 73, 4988-4993.

Saris, N.E. and Carafoli, E. (2005) A historical review of cellular calcium handling, with emphasis on mitochondria. Biochemistry (Mosc), 70, 187-194.

Shen, H.M., Dong, S.Y. and Ong, C.N. (2001) Critical role of calcium overloading in cadmium-induced apoptosis in mouse thymocytes. Toxicol Appl Pharmacol, 171, 12-19.

Singh, A.K., Kumar, V. and Kawazoe, Y. (2005) Design of a vary thin direct-band-gap semiconductor nanotube of germanium with metal encapsulation. Physical Review, 71, 75312.

Stallings, R.L., Crawford, B.D., Tobey, R.A., Tesmer, J. and Hildebrand, C.E. (1986) 5-Azacytidine-induced conversion to cadmium resistance correlates with early S phase replication of inactive metallothionein genes in synchronized CHO cells. Somat Cell Mol Genet, 12, 423-432.

Takeuchi, A., Yoshizawa, N., Oshima, S., Kubota, T., Oshikawa, Y., Akashi, Y., Oda, T., Niwa, H., Imazeki, N., Seno, A. and et al. (1992) Nephrotoxicity of germanium compounds: report of a case and review of the literature. Nephron, 60, 436-442.

Tao, S.H. and Bolger, P.M. (1997) Hazard assessment of germanium supplements. Regul Toxicol Pharmacol, 25, 211-219.

Tartaglia, L.A., Ayres, T.M., Wong, G.H. and Goeddel, D.V. (1993) A novel domain within the 55 kd TNF receptor signals cell death. Cell, 74, 845-853.

Thornberry, N.A. (1998) Caspases: key mediators of apoptosis. Chem Biol, 5, R97-103.

Unakar, N.J., Tsui, J. and Johnson, M. (1997) Effect of pretreatment of germanium-132 on Na(+)-K(+)-ATPase and galactose cataracts. Curr Eye Res, 16, 832-837.

Van der Spoel, J.I., Stricker, B.H., Schipper, M.E., de Bruijn, W., de Smet, P.A. and Esseveld, M.R. (1991) [Toxic damage of kidney, liver and muscle attributed to the administration of germanium-lactate-citrate]. Ned Tijdschr Geneeskd, 135, 1134-1137.

Vanwinkle, B.A., de Mesy Bentley, K.L., Malecki, J.M., Gunter, K.K., Evans, I.M., Elder, A., Finkelstein, J.N., Oberdorster, G. and Gunter, T.E. (2009) Nanoparticle (NP) uptake by type I alveolar epithelial cells and their oxidant stress response. Nanotoxicology, 3, 307-318.

Verkhratsky, A. (2007) Calcium and cell death. Subcell Biochem, 45, 465-480.
Waring, P. (2005) Redox active calcium ion channels and cell death. Arch Biochem Biophys, 434, 33-42.

Watson, A.J., Askew, J.N. and Benson, R.S. (1995) Poly(adenosine diphosphate ribose) polymerase inhibition prevents necrosis induced by H2O2 but not apoptosis. Gastroenterology, 109, 472-482.

Woodgate, A., MacGibbon, G., Walton, M., and Dragunow, M. (1999) The toxicity of 6-hydroxydopamine on PC12 and P19 cells. Brain Res. Mol. Brain Res., 69, 84-92.

Wu, C.M., Matsuoka, T., Takemitsu, M., Goto, Y. and Nonaka, I. (1992) An experimental model of mitochondrial myopathy: germanium-induced myopathy and coenzyme Q10 administration. Muscle Nerve, 15, 1258-1264.

Xie, P., Hu, Y., Fang, Y., Huang, J. and Lieber, C.M. (2009) Diameter-dependent dopant location in silicon and germanium nanowires. Proc Natl Acad Sci U S A, 106, 15254-15258.

Yamashima, T. (2004) Ca2+-dependent proteases in ischemic neuronal death: a conserved 'calpain-cathepsin cascade' from nematodes to primates. Cell Calcium, 36, 285-293.

Yang, H., Wu, Q., Tang, M., Kong, L. and Lu, Z. (2009) Cell membrane injury induced by silica nanoparticles in mouse macrophage. J Biomed Nanotechnol, 5, 528-535.

Yang, P.M., Chen, H.C., Tsai, J.S. and Lin, L.Y. (2007) Cadmium induces Ca2+-dependent necrotic cell death through calpain-triggered mitochondrial depolarization and reactive oxygen species-mediated inhibition of nuclear factor-kappaB activity. Chem Res Toxicol, 20, 406-415.

Yang, S.J. and Rafla, S. (1983) Effect of spirogermanium on V79 Chinese hamster cells. Am J Clin Oncol, 6, 331-337.

Yen, H.J., Hsu, S.H. and Tsai, C.L. (2009) Cytotoxicity and immunological response of gold and silver nanoparticles of different sizes. Small, 5, 1553-1561.

Yu, D.H., Lu, Q., Xie, J., Fang, C. and Chen, H.Z. (2010) Peptide-conjugated biodegradable nanoparticles as a carrier to target paclitaxel to tumor neovasculature. Biomaterials, 31, 2278-2292.

Yu, S.W., Wang, H., Poitras, M.F., Coombs, C., Bowers, W.J., Federoff, H.J., Poirier, G.G., Dawson, T.M. and Dawson, V.L. (2002) Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science, 297, 259-263.

Zong, W.X. and Thompson, C.B. (2006) Necrotic death as a cell fate. Genes Dev, 20, 1-15.