| Summary: | 碩士 === 國立臺灣大學 === 分子暨比較病理生物學研究所 === 107 === Feline injection site sarcomas (FISSs) are malignant entities of mesenchymal origin. The disease has been proven to be associated with a vaccine adjuvant, aluminum, which serves as a stimulus, continuously inducing exaggerated inflammatory and immunologic reactions. Chronic inflammation has been implicated in sarcomagenesis. Among various factors, the activation of the nuclear factor-kappa B (NF-κB) signaling pathway has been documented to promote genes associated with tumor progression, and to up-regulate the expression of tumor-promoting cytokines and survival genes in several human solid tumors. To understand the contribution of NF-κB in oncogenesis of FISS, we first detected activated NF-κB in paraffin-embedded specimens and showed that activated form of NF-κB was detected in 82% of FISS cases. To evaluate the role of activated NF-κB on the sarcomagenesis of FISS, three primary cells derived from FISS of three cats exhibiting similar immunohistochemical characteristics were also successfully established. Dose-dependent induction of apoptosis and inhibition of cell proliferation, cell migration, and clonogenicity in FISS primary cells treated with the NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), suggested that NF-κB might play an important role in the sarcomagenesis of FISS. The inhibition of NF-κB may be a new direction for developing therapeutic target for FISS.
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