The expandion in application of novel treatment through the liver specific siginaling pathway for the intractable and advanced hepatocellular carcinoma
Project/Area Number |
21390378
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | Osaka University |
Principal Investigator |
NAGANO Hiroaki 大阪大学, 医学系・研究科, 准教授 (10294050)
|
Co-Investigator(Kenkyū-buntansha) |
MARUBASHI Sigeru 大阪大学, 医学系・研究科, 助教 (20362725)
KOBAYASHI Shougo 大阪大学, 医学系・研究科, 助教 (30452436)
TAKEMASA Ichiro 大阪大学, 医学系・研究科, 助教 (50379252)
武田 裕 大阪大学, 医学系研究科, 助教 (90397696)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2010: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2009: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
|
Keywords | 肝細胞癌 / 難治性進行癌 / 門脈内腫瘍栓 / インターフェロン / 化学療法 / インターフェロン受容体 / 血管新生 / トランスクリプトーム解析 / 進行癌 / 抗腫瘍効果 / apoptosis / 5FU |
Research Abstract |
SUMMARY OF RESEARCH RESULTS (1) The mechanism of the antitumor effect through the IFN-IFNAR signaling The anti-tumor effect of IFN/ 5-FU combined therapy was significantly correlated with the strength of IFNAR expression, in the HCC cells in-vitro. This was also proved in the experiment of the IFNAR gene transfection model. In this mechanism, the upragulation of the p-STATS and Bcl-xl expression were most significantly correlated with anti-tumor effect, among the several signal transductional factors. (2) Anti tumor effect through TRAIL/ TRAIL receptor and Fas/ FasL Among peripheral blood cells, NK cells were found to exert the cytotoxic effects on human hepatoma cells. In addition, the involvement of CTL system in the anti tumor effect was examined and confirmed in terms of the relationship of apoptosis in this study. (3) The Gene Expression Profiling Using the clinical samples treated by IFN-αand 5-FU, the gene expression profiling would be suggested to be useful for the prediction of the treatment efficacy. In addition, the 2 candidates of predictive factors for anti-tumor effect of IFN-αand 5-FU was identified by Gene Expression Profiling with unresponsive HCC cell lines.
|
Report
(4 results)
Research Products
(65 results)
-
[Journal Article] Increases in p53 expression induce CTGF synthesis by mouse and human hepatocytes and result in liver fibrosis in mice2011
Author(s)
Kodama T, Takehara T, Hikita H, Shimizu S, Shigekawa M, Tsunematsu H, Li W, Miyagi T, Hosui A, Tatsumi T, Ishida H, Kanto T, Hiramatsu N, Kubota S, Takigawa M, Tomimaru Y, Tomokuni A, Nagano H, Doki Y, Mori M, Hayashi N
-
Journal Title
J Clin Invest
Volume: 121(8)
Pages: 3343-3356
Related Report
Peer Reviewed
-
[Journal Article] miR-146a suppresses the sensitivity to interferon-<alpha> in hepatocellular carcinoma cells2011
Author(s)
Tomokuni, A, Eguchi H ; Tomimaru Y, Wada H, Kawamoto K, Kobayashi S, Marubashi S, Tanemura M, Nagano H, Mori M, Doki Y
-
Journal Title
BBRC 2011
Volume: 414(4)
Pages: 675-68
Related Report
Peer Reviewed
-
-
-
[Journal Article] Long-term outcome of combined subcutaneous interferon-τand intra-arterial 5-fluorouracil treatment for advanced hepatocellular carcinoma with major portal vein thrombosis2011
Author(s)
Nagano H, Wada H, Kobayashi S, Marubashi S, Eguchi H, Tanemura M, Tomimaru Y, Osuga K, Umeshita K, Doki Y, Mori M
-
Journal Title
Oncology 2011
Volume: 80(1-2)
Pages: 63-69
Related Report
Peer Reviewed
-
[Journal Article] Prognosis of hepatocellular carcinoma with biliary tumor thrombi following liver surgery2011
Author(s)
Noda T, Nagano H, Tomimaru Y, Murakami M, Wada H, Kobayashi S, Marubashi S, Eguchi H, Takeda Y, Tanemura M, Umeshita K, Kim T, Wakasa K, Doki Y, Mori M
-
Journal Title
Surgery
Volume: 149(3)
Pages: 371-377
Related Report
Peer Reviewed
-
[Journal Article] Tyrosine kinase inhibitor PTK/ ZK enhances the anti-tumor effects of interferon-α/ 5-fluorouracil therapy for hepatocellular carcinoma cells2011
Author(s)
Murakami M, Kobayashi S, Marubashi S, Tomimaru Y, Noda T, Wada H, Eguchi S, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M, Nagano H
-
Journal Title
Ann Surg Oncol
Volume: 18(2)
Pages: 589-596
Related Report
Peer Reviewed
-
-
-
-
-
[Journal Article] MicroRNA-21 induces resistance to the anti-tumor effect of interferon-α/ 5-fluorouracil in hepatocellular carcinoma cells2010
Author(s)
Tomimaru Y, Eguchi H, Nagano H, Wada H, Tomokuni A, Kobayashi S, Marubashi S, Tanemura M, Takeda Y, Umeshita K, Doki Y, Mori M
-
Journal Title
Br J Cancer
Volume: 103(10)
Pages: 1617-1626
Related Report
Peer Reviewed
-
[Journal Article] Gd-EOB-DTPA-enhanced magnetic resonance images of hepatocellular carcinoma : correlation with histological grading and portal blood flow2010
Author(s)
Kogita S, Imai Y, Okada M, Kim T, Onishi H, Takamura M, Fukuda K, Igura T, Sawai Y, Morimoto O, Hori M, Nagano H, Wakasa K, Hayashi N, Murakami T
-
Journal Title
Eur Radiol
Volume: 20(10)
Pages: 2405-2413
Related Report
Peer Reviewed
-
[Journal Article] Exploration of Potential Genomic Portraits Associated with Intrahepatic Recurrence in Human Hepatocellular Carcinoma2010
Author(s)
Kittaka N, , Seno S, Takeda Y, Kobayashi S, Marubashi S, Dono K, Umeshita K, Nagano H, Matsuda H, Monden M, Mori M, Doki Y
-
Journal Title
Ann Surg Oncol
Volume: 17(12)
Pages: 3145-3154
Related Report
Peer Reviewed
-
-
[Journal Article] Effects of preceding interferon therapy on outcome after surgery for hepatitis C virus-related hepatocellular carcinoma2010
Author(s)
Tomimaru Y, Nagano H, Eguchi H, Kobayashi S, Marubashi S, Wada H, Tanemura M, Umeshita K, Hiramatsu H, Takehara T, Doki Y, Mori M
-
Journal Title
J of Surg Oncol
Volume: 102
Pages: 308-314
Related Report
Peer Reviewed
-
[Journal Article] Insulin-Like Growth Factor-Binding Protein 7 Alters the Sensitivity to Interferon-Based Anticancer Therapy in Hepatocellular Carcinoma Cells2010
Author(s)
Tomimaru Y, Eguchi H, Wada H, Noda H, Murakami M, Kobayashi S, Marubashi S, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M, Nagano H
-
Journal Title
B J Cancer
Volume: 102(10)
Pages: 1483-1490
Related Report
Peer Reviewed
-
[Journal Article] The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma2010
Author(s)
Shimizu S, Takehara T, Hikita H, Kodama T, Miyagi T, Hosui A, Tatsumi T, Ishida H, Noda T, Nagano H, Doki Y, Mori M, Hayashi N
-
Journal Title
J Hepatol
Volume: 52(5)
Pages: 698-704
Related Report
Peer Reviewed
-
[Journal Article] Hepatocellular carcinoma : hepatocyte-selective enhancement at gadoxetic acid-enhanced MRImaging-correlation with expression of sinusoidal and canalicular transporters and bile accumulation2010
Author(s)
Tsuboyama T, Onishi H, Kim T, Akita H, Hori M, Tatsumi M, Nakamoto A, Nagano H, Matsuura N, Wakasa K, Tomoda K
-
Journal Title
Radiology
Volume: 255(3)
Pages: 824-833
Related Report
Peer Reviewed
-
[Journal Article] Isolated Metastasis to the Gall Bladder from Hepatocellular Carcinoma2010
Author(s)
Murakami M, Kobayashi S, Marubashi S, Eguchi S, Takeda Y, Tanemura M, Wada H, Umeshita K, , Wakasa K, Doki Y, Mori M, Nagano H
-
Journal Title
Hepatology Research
Volume: 40(8)
Pages: 793-798
Related Report
Peer Reviewed
-
[Journal Article] Effects of preoperative transcatheter arterial chemoembolization for resectable hepatocellular carcinoma : Implication of circulating cancer cells by detection of alpha-fetoprotein mRNA2010
Author(s)
Murakami M, Nagano H, Kobayashi S, Nakamura M, Marubashi S, Eguchi H, Takeda Y, Tanemura M, Sugita Y, Umeshita K, Monden M, Doki Y, Mori M
-
Journal Title
Experimental and Therapeutic Medicine
Volume: 1
Pages: 485-491
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
[Journal Article] Molecular prediction of early recurrence after resection of hepatocellular carcinoma2009
Author(s)
Yoshioka S, Takemasa I, Nagano H, Kittaka N, Noda T, Wada H, Kobayashi S, Marubashi S, Takeda Y, Umeshita K, Dono K, Matsubara K, Matsubara N, Monden M
-
Journal Title
EJ Cancer
Volume: 45(5)
Pages: 881-889
Related Report
Peer Reviewed
-
[Journal Article] Activation of Wnt/ beta-catenin signalling pathway induces chemoresistance to interferon-alpha/ 5-fluorouracil combination therapy for hepatocellular carcinoma2009
Author(s)
Noda T, Nagano H, Takemasa I, Yoshioka S, Murakami M, Wada H, Kobayashi S, Marubashi S, Takeda Y, Dono K, Umeshita K, Matsuura N, Matsubara K, Doki Y, Mori M, Monden M
-
Journal Title
Br J Cancer
Volume: 100(10)
Pages: 1647-1658
Related Report
Peer Reviewed
-
[Journal Article] A safe protocol of intermittent hilar vascular clamping for hepatic resection in cirrhosis2009
Author(s)
Nagano H, Miyamoto A, Kishimoto S, Takeda Y, Marubashi S, Kobayashi S, Tomimaru Y, Noda T, Umeshita K, Dono K, SakonM, Monden M
-
Journal Title
Hepatogastroenterol
Volume: 88(9)
Pages: 1123-1130
Related Report
Peer Reviewed
-
[Journal Article] Combination of interferon-alpha and 5-fluorouracil inhibits endothelial cell growth through regulation of angiogenic factors released by tumor cells2009
Author(s)
Wada H, Nagano H, Yamamoto H, Noda T, Murakami M, Kobayashi S, Marubashi S, Eguchi H, Takeda Y, Tanemura M, Umeshita K, Doki Y and Mori M
-
Journal Title
BMC Cancer
Volume: 9
Pages: 361-372
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] 肝癌に対する外科治療2011
Author(s)
永野浩昭、土岐祐一郎、森正樹
Organizer
第28回日本医学会総会
Place of Presentation
(東京)[シンポジウム]
Year and Date
2011-04-08
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-