Browsing by Author "Chen, Chi-Long"

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cIAP-2 Expression Increases in Elderly Patients with Squamous Cell Carcinoma of the Head and Neck
(2017-03-01)
Chen, Chi-Long
;
Chiang, Chun-Yi
;
Liao, Kuang-Wen
;
Ho, Shu-Yi
;
Chang, Yi-Fang
Background: Evidence indicates apoptosis deregulation is associated with aging. We correlated expression of cIAP-2, a member of the inhibitor of apoptosis protein family, with survival and age in patients with resected squamous cell carcinoma of head and neck (SCCHN). Methods: Immunohistochemical (IHC) staining for cIAP-2 and other markers were performed using tissue microarrays from 103 resected SCCHN patients. Expression was grouped according to IHC scores (0 -3) and statistical association with clinicalepathological factors was determined. Results: High expression of cIAP-2 was found to be increased in patients aged 60 or greater. High expression of cIAP-2 and an age >= 60 were significantly associated with worse survival in univariate analysis, but only an age >= 60, and not cIAP-2 expression, was prognostic in multivariate analysis. Conclusion: High expression of cIAP-2 was found more frequently in elderly SCCHN patients but was not independently associated with survival after adjusting other clinicalepathologic factors. Copyright (C) 2017, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC.
Targeting the XIAP/caspase-7 complex selectively kills caspase-3-deficient malignancies
(2013-09-01)
Lin, Yuan-Feng
;
Lai, Tsung-Ching
;
Chang, Chih-Kang
;
Chen, Chi-Long
;
Huang, Ming-Shyan
Caspase-3 downregulation (CASP3/DR) in tumors frequently confers resistance to cancer therapy and is significantly correlated with a poor prognosis in cancer patients. Because CASP3/DR cancer cells rely heavily on the activity of caspase-7 (CASP7) to initiate apoptosis, inhibition of activated CASP7 (p19/p12-CASP7) by X-linked inhibitor of apoptosis protein (XIAP) is a potential mechanism by which apoptosis is prevented in those cancer cells. Here, we identify the pocket surrounding the Cys(246) residue of p19/p12-CASP7 as a target for the development of a protein-protein interaction (PPI) inhibitor of the XIAP:p19/p12-CASP7 complex. Interrupting this PPI directly triggered CASP7-dependent apoptotic signaling that bypassed the activation of the apical caspases and selectively killed CASP3/DR malignancies in vitro and in vivo without adverse side effects in nontumor cells. Importantly, CASP3/DR combined with p19/p12-CASP7 accumulation correlated with the aggressive evolution of clinical malignancies and a poor prognosis in cancer patients. Moreover, targeting of this PPI effectively killed cancer cells with multidrug resistance due to microRNA let-7a-1-mediated CASP3/DR and resensitized cancer cells to chemotherapy-induced apoptosis. These findings not only provide an opportunity to treat CASP3/DR malignancies by targeting the XIAP:p19/p12-CASP7 complex, but also elucidate the molecular mechanism underlying CASP3/DR in cancers.