※一部利用できない機能があります
| 1.
図書 |
図書
|
研究代表者:伏田幸夫
|
||||
| 2.
論文 |
論文
|
Nakanuma, Shinichi ; Miyashita, Tomoharu ; Hayashi, Hironori ; Tajima, Hidehiro ; Takamura, Hiroyuki ; Makino, Isamu ; Oyama, Katsunobu ; Nakagawara, Hisatoshi ; Fushida, Sachio ; Ohta, Tetsuo ; 中沼, 伸一 ; 宮下, 知治 ; 高村, 博之 ; 林, 泰寛 ; 田島, 秀浩 ; 牧野, 勇 ; 尾山, 勝信 ; 中川原, 寿俊 ; 伏田, 幸夫 ; 太田, 哲生
概要:
金沢大学附属病院肝胆膵・移植外科<br />Objectives: Continuous thrombocytopenia after liver transplant is associated with a less favorable
…
prognosis, but this pathogenesis remains unclear. We focused on the consumption of platelets in the allograft. We assessed platelet consumption in allografts, and evaluated the pathology of platelet aggregation in an allograft tissue and its involve-ment in clinical outcomes.Materials and Methods: We took biopsy specimens from 20 patients. To examine the localization of platelet aggregation, CD42b was assayed immuno-histochemically, and its level of expression correlated with clinical data and outcomes.Results: Platelet aggregation in zone 3 was 70%, compared with 30% in zone 1 and 50% in zone 2. Platelets were found mainly as extravasated platelet aggregates in local microenvironments. Patients were stratified according to the extent of extravasated platelet aggregates in zone 3 into extravasated platelet aggregate-negative and -positive groups. Graft weight/recipient body weight ratio with the extravasated platelet aggregate-positive group was significantly lower than that of the extravasated platelet aggregate-negative group. Platelet count after surgery was lower, while total bilirubin and prothrombin time/international normalized ratio were higher in the extravasated platelet aggregate-positive than they were in the extravasated platelet aggregate-negative group.Conclusions: Extravasated platelet aggregates in the zone 3 of allograft tissue cause the consumption of platelets and continuous thrombocytopenia after transplant, and may be the clinical marker for deterioration of graft function. Platelet activation and degranulation following the release by platelets of some negative regulators may be involved partially in liver damage.
続きを見る
|
||||
| 3.
論文 |
論文
|
Watanabe, Toshifumi ; Tajima, Hidehiro ; Hayashi, Hironori ; Nakagawara, Hisatoshi ; Ohnishi, Ichiro ; Takamura, Hiroyuki ; Ninomiya, Itasu ; Kitagawa, Hirohisa ; Fushida, Sachio ; Tani, Takashi ; Fujimura, Takashi ; Ohta, Tetsuo ; Wakayama, Tomohiko ; Iseki, Shoichi ; Harada, Shinichi ; 田島, 秀浩 ; 林, 泰寛 ; 中川原, 寿俊 ; 高村, 博之 ; 二宮, 致 ; 北川, 裕久 ; 伏田, 幸夫 ; 谷, 卓 ; 藤村, 隆 ; 太田, 哲生 ; 若山, 友彦 ; 井関, 尚一 ; 原田, 真市
概要:
金沢大学医薬保健研究域医学系<br />Histone acetylation and deacetylation have been thought to be related to gene expression, and there
…
are many reports indicating that histone deacetylase inhibitors (HDACis) exert antifibrogenic effects in several organs. In injured livers, hepatic stellate cells (HSCs) are activated in response to profibrogenic mediators and produce large amounts of extracellular matrix. In particular, transforming growth factor-β1 (TGF-β1) is considered as a key factor in accelerating hepatic fibrosis because it is released from activated HSCs and further stimulates them. The present study aimed to clarify whether sodium valproate (VPA) has suppressive effects on cultured human HSCs (LI90). We showed that treatment with VPA had no significantly suppressive effect on cell proliferation at a concentration of 1 mM, which corresponded approximately to the serum concentration obtained by the administration of a clinical dose. However, VPA prevented the morphological changes characteristic for activation and inhibited the expression of collagen type 1 α1 (COL1A1) and TGF-β1 in activated LI90 cells at the mRNA and protein levels. Our results support the hypothesis that VPA exerts antifibrogenic activity with little cytotoxicity at 1 mM, and HDACis are expected to be used in clinical practice for the treatment of fibrotic diseases.<br />Embargo Period 6 months
続きを見る
|
||||
| 4.
論文 |
論文
|
Nakanuma, Shinichi ; Tajima, Hidehiro ; Okamoto, Koichi ; Hayashi, Hironori ; Nakagawara, Hisatoshi ; Onishi, Ichiro ; Takamura, Hiroyuki ; Kitagawa, Hirohisa ; Fushida, Sachio ; Tani, Takashi ; Fujimura, Takashi ; Kayahara, Masato ; Ohta, Tetsuo ; Wakayama, Tomohiko ; Iseki, Shoichi ; Harada, Shinichi ; 中村, 信一 ; 田島, 秀浩 ; 岡本, 浩一 ; 林, 泰寛 ; 中川原, 寿俊 ; 高村, 博之 ; 北川, 裕久 ; 伏田, 幸夫 ; 谷, 卓 ; 藤村, 隆 ; 萱原, 正都 ; 太田, 哲生 ; 若山, 友彦 ; 井関, 尚一 ; 原田, 真市
概要:
金沢大学医薬保健研究域医学系<br />In primary malignant liver tumors, trypsinogen-immunoreactivity was present in 70% of intrahepatic c
…
holangiocarcinoma (ICC) specimens, but absent in hepato-cellular carcinoma (HCC) specimens. We suggest the secretion of trypsinogen to be a key difference in biological behavior between ICC and HCC cells. The purpose of this study was to investigate the secretion of tumor-derived trypsin and the expression of its specific receptor, protease-activated receptor-2 (PAR-2), in ICC using cell lines and surgical specimens. The expression of trypsinogen-1 mRNA was observed in three of four ICC cell lines, but none of three HCC cell lines. Western blot analysis detected trypsinogen-1 in serum-free conditioned medium from one of the ICC cell lines positive for the mRNA. Gelatin zymography revealed a gelatinolytic activity for trypsin, the activated form of trypsinogen, in the same conditioned medium. PAR-2 mRNA and protein were observed in ICC cell lines. The proliferative activity of ICC cells was increased by concentrations of trypsin as low as 10 nM, and peaked at 100 nM. The effect of trypsin was suppressed by a serine protease inhibitor, gabexate mesilate. PAR-2 expression was detected in 64% of ICC surgical specimens immunohistochemically. In addition, stroma fibroblasts expressed PAR-2 in 52% of ICC specimens. These results suggest that trypsinogen-1 contributes to the growth of ICC cells and also tumor-associated fibroblasts.<br />Embargo Period 6 months
続きを見る
|
||||
| 5.
論文 |
論文
|
Okamoto, Koichi ; Tajima, Hidehiro ; Nakanuma, Shinichi ; Sakai, Seisho ; Makino, Isamu ; Kinoshita, Jun ; Hayashi, Hironori ; Nakamura, Keishi ; Oyama, Katsunobu ; Nakagawara, Hisatoshi ; Fujita, Hideto ; Takamura, Hiroyuki ; Ninomiya, Itasu ; Kitagawa, Hirohisa ; Fushida, Sachio ; Fujimura, Takashi ; Harada, Shinichi ; Wakayama, Tomohiko ; Iseki, Shoichi ; Ohta, Tetsuo ; 岡本, 浩一 ; 田島, 秀浩 ; 中村, 信一 ; 牧野, 勇 ; 木下, 淳 ; 林, 泰寛 ; 中村, 慶史 ; 尾山, 勝信 ; 中川原, 寿俊 ; 藤田, 秀人 ; 高村, 博之 ; 二宮, 致 ; 北川, 裕久 ; 伏田, 幸夫 ; 藤村, 隆 ; 原田, 真市 ; 若山, 友彦 ; 井関, 尚一 ; 太田, 哲生
概要:
金沢大学医薬保健研究域医学系<br />We previously reported that hepatic stellate cells (HSCs) activated by angiotensin II (AngII) facili
…
tate stromal fibrosis and tumor progression in intrahepatic cholangiocarcinoma (ICC). AngII has been known as a growth factor which can promote epithelial-to-mesenchymal transition (EMT) in renal epithelial cells, alveolar epithelial cells and peritoneal mesothelial cells. However, in the past, the relationship between AngII and stromal cell-derived factor-1 (SDF-1) in the microenvironment around cancer and the role of AngII on EMT of cancer cells has not been reported in detail. SDF-1 and its specific receptor, CXCR4, are now receiving attention as a mechanism of cell progression and metastasis. In this study, we examined whether activated HSCs promote tumor fibrogenesis, tumor progression and distant metastasis by mediating EMT via the AngII/AngII type 1 receptor (AT-1) and the SDF-1/CXCR4 axis. Two human ICC cell lines and a human HSC line, LI-90, express CXCR4. Significantly higher concentration of SDF-1αwas released into the supernatant of LI-90 cells to which AngII had been added. SDF-1α increased the proliferative activity of HSCs and enhanced the activation of HSCs as a growth factor. Furthermore, addition of SDF-1α and AngII enhanced the increase of the migratory capability and vimentin expression, reduced E-cadherin expression, and translocated the expression of β-catenin into the nucleus and cytoplasm in ICC cells. Co-culture with HSCs also enhanced the migratory capability of ICC cells. These findings suggest that SDF-1α, released from activated HSCs and AngII, play important roles in cancer progression, tumor fibrogenesis, and migration in autocrine and paracrine fashion by mediating EMT. Our mechanistic findings may provide pivotal insights into the molecular mechanism of the AngII and SDF-1α-initiated signaling pathway that regulates fibrogenesis in cancerous stroma, tumor progression and metastasis of tumor cells expressing AT-1 and CXCR4.<br />Embargo Period 6 months
続きを見る
|
||||
| 6.
その他 |
その他
|
伏田, 幸夫 ; Fushida, Sachio
概要:
取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1050号, 学位授与年月日：平成4年3月25日,学位授与年：1992
|
||||
| 7.
論文 |
論文
|
伏田, 幸夫
|
||||
| 8.
論文 |
論文
|
伏田, 幸夫
|
||||
| 9.
論文 |
論文
|
伏田, 幸夫
|
||||
| 10.
論文 |
論文
|
太田, 哲生 ; 荒川, 元 ; 二上, 文夫 ; 伏田, 幸夫 ; 北川, 裕久 ; 萱原, 正都 ; 永川, 宅和 ; 宮崎, 逸夫 ; 沼田, 雅行 ; 大熊, 勝治
概要:
最近, 抗癌剤による癌細胞の死滅にはアポトーシスという能動的な死のプログラムが関与していることがわかってきた. したがって, 膵癌細胞にアポトーシスを誘導し消滅させることができる薬物があれば, それは理想的な抗癌剤となる可能性がある. しか
…
しながら, 現在のところ膵癌にアポトーシスを誘導するような有効な抗癌剤がないのが実状である. 最近, われわれは液胞型プロトンポンプの特異的インヒビターであるbafilomycin A1が膵癌細胞に対して効率よくアポトーシスを誘導することを突き止めた. 今後, このbafilomycin A1を用いたプロトンポンプインヒビター療法が膵癌に対する新しい治療戦略の1つとして確立されることを期待したい. アポトーシスという概念は, 約20年前に病理学者であるKerr1)によって提唱されたものであり, ネクローシスと区別される細胞死であることで最近注目を集めている. アポトーシスを起こした細胞では,細胞のサイズの減少,クロマチンの凝縮のような形態学的特徴のほか,DNAの断片化といった生化学的変化がみられ,生体内にあっては比較的すみやかに排除されることが知られている.
続きを見る
|
