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Hoffmann O., Priller J., Prozorovski T., Schulze-Topphoff U., Baeva N., Lunemann J.D., Aktas O., Mahrhofer C., Stricker S., Zipp F., et al. TRAIL limits excessive host immune responses in bacterial meningitis. J Clin Invest 117 (2007) 2004-2013
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Rus V., Nguyen V., Puliaev R., Puliaeva I., Zernetkina V., Luzina I., Papadimitriou J.C., and Via C.S. T cell TRAIL promotes murine lupus by sustaining effector CD4 Th cell numbers and by inhibiting CD8 CTL activity. J Immunol 178 (2007) 3962-3972
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The authors generated TRAIL-receptor deficient mice and subsequently initiated skin tumors. The number, rate of development, and malignant transformation rate of benign papilloma did not differ between TRAIL-R-/- mice compared to TRAIL-R+/- and TRAIL-R+/+ mice. However TRAIL-R-/- mice developed earlier and significant more lymph node metastases, suggesting a protective role for the TRAIL-R in mice.
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Grosse-Wilde A., Voloshanenko O., Bailey S.L., Longton G.M., Schaefer U., Csernok A.I., Schutz G., Greiner E.F., Kemp C.J., and Walczak H. TRAIL-R deficiency in mice enhances lymph node metastasis without affecting primary tumor development. J Clin Invest 118 (2008) 100-110. The authors generated TRAIL-receptor deficient mice and subsequently initiated skin tumors. The number, rate of development, and malignant transformation rate of benign papilloma did not differ between TRAIL-R-/- mice compared to TRAIL-R+/- and TRAIL-R+/+ mice. However TRAIL-R-/- mice developed earlier and significant more lymph node metastases, suggesting a protective role for the TRAIL-R in mice.
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In this paper, the authors inoculated SCID mice with human pancreatic cancer cells overexpressing Bcl-XL, thereby inhibiting TRAIL-induced apoptosis. Upon rhTRAIL treatment a 5.8-fold increase in the tumor volume and a significant increase in the number of liver metastases were found compared to saline-treated mice.
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Trauzold A., Siegmund D., Schniewind B., Sipos B., Egberts J., Zorenkov D., Emme D., Roder C., Kalthoff H., and Wajant H. TRAIL promotes metastasis of human pancreatic ductal adenocarcinoma. Oncogene 25 (2006) 7434-7439. In this paper, the authors inoculated SCID mice with human pancreatic cancer cells overexpressing Bcl-XL, thereby inhibiting TRAIL-induced apoptosis. Upon rhTRAIL treatment a 5.8-fold increase in the tumor volume and a significant increase in the number of liver metastases were found compared to saline-treated mice.
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Belyanskaya L.L., Ziogas A., Hopkins-Donaldson S., Kurtz S., Simon H.U., Stahel R., and Zangemeister-Wittke U. TRAIL-induced survival and proliferation of SCLC cells is mediated by ERK and dependent on TRAIL-R2/DR5 expression in the absence of caspase-8. Lung Cancer 60 (2008) 355-365
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Marini P., Denzinger S., Schiller D., Kauder S., Welz S., Humphreys R., Daniel P.T., Jendrossek V., Budach W., and Belka C. Combined treatment of colorectal tumours with agonistic TRAIL receptor antibodies HGS-ETR1 and HGS-ETR2 and radiotherapy: enhanced effects in vitro and dose-dependent growth delay in vivo. Oncogene 25 (2006) 5145-5154
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S to the death-inducing signaling complex and contributes to TRAIL resistance in human glioma. Cancer Res 67 (2007) 9482-9489. The authors show that high levels of the antiapoptotic protein FLIP alone are not sufficient enough to inhibit apoptosis. HSP90α is needed to serve as chaperone protein by recruiting FLIP to the DISC and inhibiting apoptosis in human glioma cells.
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