Corrosion Resistance of Modified Heat-Treated 16Cr-4Ni Steel for Geothermal Steam Turbine Blades

Immersion corrosion tests and electrochemical corrosion tests were carried out in the simulated geothermal water on a modified heat-treated material of 16Cr-4Ni steel, which is used for geothermal steam turbine blades. Incidentally, the purpose of the modified heat treatment is for reducing the susceptibility of stress corrosion cracking (SCC) of the steel in the geothermal fluids. For comparison, a conventional heat-treated material of the 16Cr-4Ni steel was also used in the corrosion tests. In the immersion corrosion tests up to 4,000 hours, the modified heat-treated material showed lower corrosion rates than those of the conventional heat-treated one in the test water. In the electrochemical corrosion tests, the modified heat-treated material exhibited noble and stable corrosion potential behavior. The XPS analysis results exhibited that the passive films formed on the materials were consisted mainly of Cr-oxides (CrOOH, CrO3) and Fe-oxides (FeO, Fe2O3). Furthermore, the composition ratio of Cr-oxides in the outermost surface of the passive film formed on the modified heat-treated material was higher than that on the conventional heat-treated one. It was suggested that the better corrosion resistance of the modified heat-treated 16Cr-4Ni steel was contributed to the formation of the passive film with higher compositions of Cr-oxides

Hepatocyte Growth Factor

Hepatocyte growth factor (HGF) exerts biological activity through the Met receptor tyrosine kinase. HGF plays essential roles in the embryonic development of the liver and placenta, and in the migration of myogenic precursor cells. In mature tissues, HGF plays roles in tissue protection and regeneration, including in the liver and kidney. HGF participates in invasion, metastasis, and drug resistance. Drug development targeting HGF-Met has been challenging. One focus has been the use of recombinant HGF as a biological drug and another has been the use of HGF-Met inhibitors for cancer treatment. Clinical trials using HGF or HGF-Met inhibitors are ongoing. © 2014 Elsevier Inc. All rights reserved.[Book Chapter

Lack of Demand and Investment Overseas

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肺高血圧症に対するトロンボキサン合成阻害作用をもった新規長期作用型プロスタサイクリンアゴニストの経口投与

BACKGROUND: Continuous administration of prostacyclin has improved the survival of patients with pulmonary arterial hypertension (PAH). However, this treatment has some problems, including its short duration of activity and difficult delivery. Therefore, we developed ONO-1301, an orally active, long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. METHODS AND RESULTS: We investigated whether oral administration of ONO-1301 can both prevent and reverse monocrotaline (MCT)-induced PAH in rats. Rats were randomly assigned to receive repeated oral administration of ONO-1301 twice daily beginning either 1 or 8 days after subcutaneous injection of MCT. A control group received oral saline, and a sham group received a subcutaneous injection of saline instead of MCT. MCT-treated controls developed significant pulmonary hypertension. Treatment with ONO-1301 from day 1 or 8 significantly attenuated the increases in right ventricular systolic pressure and the increase in medial wall thickness of pulmonary arterioles. Kaplan-Meier survival curves demonstrated that the effect of ONO-1301 was equivalent to that of an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor. A single oral dose of ONO-1301 increased plasma cAMP levels for up to 6h. Treatment with ONO-1301 significantly decreased urinary 11-dehydro-thromboxane B2 and increased the plasma hepatocyte growth factor concentration. CONCLUSIONS: Oral administration of ONO-1301 ameliorated PAH in rats, an effect that may occur through cAMP and hepatocyte growth factor.博士（医学）・乙1326号・平成26年3月17日日本循環器学会の許諾を得て登録（2014年6月6日付）ジャーナル公式サイト（日本循環器学会HP内）：https://www.j-circ.or.jp/journal/公開サイト（J-STAGE）：https://www.jstage.jst.go.jp/browse/circj

Hepatocyte growth factor and Met in drug discovery

Activation of the hepatocyte growth factor (HGF)-Met pathway evokes dynamic biological responses that support the morphogenesis, regeneration and survival of cells and tissues. A characterization of conditional Met knockout mice indicates that the HGF-Met pathway plays important roles in the regeneration, protection and homeostasis of cells such as hepatocytes, renal tubular cells and neurons. Preclinical studies in disease models have indicated that recombinant HGF protein and expression plasmid for HGF are biological drug candidates for the treatment of patients with diseases or injuries that involve impaired tissue function. The phase-I and phase-I/II clinical trials of the intrathecal administration of HGF protein for the treatment of patients with amyotrophic lateral sclerosis and spinal cord injury, respectively, are ongoing. Biological actions of HGF that promote the dynamic movement, morphogenesis and survival of cells also closely participate in invasion-metastasis and resistance to the molecular-targeted drugs in tumour cells. Different types of HGF-Met pathway inhibitors are now in clinical trials for treatment of malignant tumours. Basic research on HGF and Met has lead to drug discoveries in regenerative medicine and tumour biology. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved

Hepatocyte growth factor and Met in tumor biology and therapeutic approach with NK4

金沢大学がん研究所分子標的がん医療研究開発センターHepatocyte growth factor (HGF) and Met/HGF receptor tyrosine kinase play a role in the progression to invasive and metastatic cancers. A variety of cancer cells secrete molecules that enhance HGF expression in stromal fibroblasts, while fibroblast-derived HGF, in turn, is a potent stimulator of the invasion of cancer cells. In addition to the ligand-dependent activation, Met receptor activation is negatively regulated by cell-cell contact and Ser985 phosphorylation in the juxtamembrane of Met. The loss of intercellular junctions may facilitate an escape from the cell-cell contact-dependent suppression of Met-signaling. Significance of juxtamembrane mutations found in human cancers is assumed to be a loss-of-function in the negative regulation of Met. In attempts to block the malignant behavior of cancers, NK4 was isolated as a competitive antagonist against HGF-Met signaling. Independently on its HGF-antagonist action, NK4 inhibited angiogenesis induced by vascular endothelial cell growth factor and basic fibroblast growth factor, as well as HGF. In experimental models of distinct types of cancers, NK4 inhibited Met activation and this was associated with inhibition of tumor invasion and metastasis. NK4 inhibited tumor angiogenesis, thereby suppressing angiogenesis-dependent tumor growth. Cancer treatment with NK4 suppresses malignant tumors to be "static" in both tumor growth and spreading. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA

Hepatocyte growth factor twenty years on: Much more than a growth factor

金沢大学がん研究所Liver regeneration depends on the proliferation of mature hepatocytes. In the 1980s, the method for the cultivation of mature hepatocytes provided an opportunity for the discovery of hepatocyte growth factor (HGF) as a protein that is structurally and functionally different from other growth factors. In 1991, the scatter factor, tumor cytotoxic factor, and 3-D epithelial morphogen were identified as HGF, and Met tyrosine kinase was identified as the receptor for HGF. Thus, the connection of apparently unrelated research projects rapidly enriched the research on HGF in different fields. The HGF-Met pathway plays important roles in the embryonic development of the liver and the placenta, in the migration of myogenic precursor cells, and in epithelial morphogenesis. The use of tissue-specific knockout mice demonstrated that in mature tissues the HGF-Met pathway plays a critical role in tissue protection and regeneration, and in providing less susceptibility to chronic inflammation and fibrosis. In various injury and disease models, HGF promotes cell survival, regeneration of tissues, and suppresses and improves chronic inflammation and fibrosis. Drug development using HGF has been challenging, but extensive preclinical studies to address its therapeutic effects have provided significant results sufficient for the development of HGF as a biological drug in the regeneration-based therapy of diseases. Clinical trials using recombinant human HGF protein, or HGF genes, are in progress for the treatment of diseases. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd

High-speed atomic force microscopy combined with inverted optical microscopy for studying cellular events.

A hybrid atomic force microscopy (AFM)-optical fluorescence microscopy is a powerful tool for investigating cellular morphologies and events. However, the slow data acquisition rates of the conventional AFM unit of the hybrid system limit the visualization of structural changes during cellular events. Therefore, high-speed AFM units equipped with an optical/fluorescence detection device have been a long-standing wish. Here we describe the implementation of high-speed AFM coupled with an optical fluorescence microscope. This was accomplished by developing a tip-scanning system, instead of a sample-scanning system, which operates on an inverted optical microscope. This novel device enabled the acquisition of high-speed AFM images of morphological changes in individual cells. Using this instrument, we conducted structural studies of living HeLa and 3T3 fibroblast cell surfaces. The improved time resolution allowed us to image dynamic cellular events