Novel therapeutic approach is urgently required. CXC chemokine receptor2 (CXCR2) have been found to
be associated with tumorigenesis and metastasis in human malignancy. In the present Ibrutinib in vivo study, we investigated the suppressive effect of ICC growth by blockage of CXCR2. Material/Methods: Expression of CXCR2 in ICC is estimated by immunohistochemical staining using thirty three ICC specimens and investigated relevance with prognosis. The role of CXCR2 was estimated using human ICC cell lines, RBE and SSP25. CXCR2 siRNA and antagonist (SB225002) were used to block CXCR2. Proliferation assay, migration assay and invasion assay were performed to confirm the suppressive effect by blockage of CXCR2. Expression of CXC ligand (CXCL) that binds to CXCR2 were also investigated in human ICC CDK inhibitor samples and in supernatant of ICC cell lines. Subcutaneous SSP25 tumours established in athymic nude mice were administered SB225002.
Results: Prognosis of patients who had higher CXCR2 expression in ICC was significantly poor (p=0. 004). CXCR2 SiRNA significantly suppressed CXCR2 expression both RBE and SSP25. Cell proliferation, migration and invasion was significantly suppressed by both CXCR2 SiRNA and SB225002 compared with control group. SB225002 also suppressed growth of transplanted subcutaneous tumours (p=0. 02). By contrast, knockdown or addition of CXC ligand 8 (CXCL8) did not affect on ICC proliferation Molecular motor and migration, though CXCL8 expression was confirmed in human ICC samples and in supernatant of ICC cell lines. SB225002 suppressed growth of transplanted subcutaneous tumours (p=0. 02). Conclusions: Our results demonstrated that down regulation of CXCR2 markedly suppressed growth and metastasis of ICC. These results suggested that CXCR2 acts crucial role in the development of ICC and blockage of CXCR2 may represent a novel strategy for ICC. Disclosures: The following people have nothing to disclose: Tadamichi Hirano, Hideaki Sueoka,
Yugo Uda, Nobukazu Kuroda, Toshihiro Okada, Yasukane Asano, Yuuichi Kondou, Ikuo Nakamura, Shogo Tanaka, Seikan Hai, Yuji Iimuro, Jiro Fuji-moto Background and aims Mir-122 is highly expressed in hepatocytes, where it represents 70% of the total miRNAs. Mir-122 binding within Hepatitis C virus (HCV) RNA stimulates its replication, in vitro. A reduction of hepatic mir-122 expression has been suggested in patients with primary non-response (pNR) to PEG-IFN/ribavirin. IL28B CC genotype (rs12979860) is strongly associated with sustained virological response (SVR). The aim of the study was to investigate, in vivo, the relationships between hepatic and serum expression of mir-122, IL28B and response to PEG-IFN/ribavirin. Patients and Methods Pre-treatment liver biopsies and serums from 133 patients with CHC were included. Eighty three men and 50 women were included in the study.