Publications (3)4.17 Total impact
Article: PTK787/ZK222584 Combined with Interferon Alpha and 5-Fluorouracil Synergistically Inhibits VEGF Signaling Pathway in Hepatocellular Carcinoma.[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus remains poor. We previously reported the beneficial effects of interferon alpha (IFN) and 5-fluorouracil (5-FU) combination therapy for these patients. We showed that the mechanism of therapy was regulation of vascular endothelial growth factor (VEGF). Here, we combined IFN/5-FU therapy with the VEGF receptor-selective inhibitor PTK787/ZK222584 (PTK/ZK) and examined the antitumor effects and the mechanism of action. METHODS: We studied two HCC cell lines, PLC/PRF/5 and HuH7, and a human umbilical vein endothelial cell line, HUVEC. We studied the effects of IFN/5-FU with or without PTK/ZK in growth inhibition assays, immunohistochemistry, Western blot analysis, and immunocytochemistry. RESULTS: In a HuH7 xenograft model, the combination of PTK/ZK and IFN/5-FU significantly inhibited proliferation, induced apoptosis, decreased microvessel density, reduced the number of tumor cells that expressed VEGF receptor 2 (VEGFR-2), and repressed the phosphorylation of Akt in vivo. In HCC cells and HUVECs in vitro, IFN/5-FU plus PTK/ZK repressed the expression of VEGFR-2 and repressed the phosphorylation of VEGFR, Akt, Erk, and p38MAPK. CONCLUSIONS: VEGF signaling inhibition enhanced the antitumor effects of IFN/5-FU therapy on HCC cells and endothelial cells via Erk, Akt, and p38MAPK pathways.Annals of Surgical Oncology 03/2013; · 4.17 Impact Factor
Article: [A case of complete response to interferon-α and S-1 combination therapy for multiple pulmonary recurrences of hepatocellular carcinoma after hepatic resection].[show abstract] [hide abstract]
ABSTRACT: A 77-year-old man was diagnosed as hepatocellular carcinoma, and was referred to our hospital. After he was treated by transcatheter chemoembolization, he underwent a left hepatic lobectomy of the liver and cholecystectomy. Serum AFP and PIVKA-II remarkably elevated 7 months after surgery, and CT scan revealed multiple metastatic nodules in bilateral lungs. The nodules were diagnosed as lung metastasis of HCC. Because the lesions grew larger, S-1/IFN was administered. Diagnostic imaging and tumor markers showed a marked improvement after 4 courses of S-1/IFN therapy, and he is still alive with good condition without recurrence and progression of tumors.Gan to kagaku ryoho. Cancer & chemotherapy 11/2011; 38(12):2487-9.
Article: [A case of curative resected hilar bile duct cancer with hepatic artery and portal vein reconstructions].[show abstract] [hide abstract]
ABSTRACT: The indication for surgical resection due to hilar bile duct cancer (BDC) with vessel reconstructions is still controversial. We report herein a successfully resected case due to hilar BDC with hepatic artery (HA) and portal vein (PV) reconstructions using autograft from a resected liver. A 57-year-old woman was diagnosed as hilar BDC, and computed tomography showed a tumor invaded left and common hepatic duct, right and left HA, and left main branch of PV. Because the extrahepatic area of right HA was free from the tumor, we performed left hepatectomy and caudate lobectomy with HA and PV reconstructions. We used auto left hepatic vein graft from the resected liver for PV reconstruction, because there was no appropriate size vein graft, e.g. inferior mesenteric vein. The patient is alive without any evidence of recurrence for 8 months after the surgery.Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(12):2720-2.