二宮尊徳の「分度」思想再考

In view of the "sharing extension" thought of NinomiyaSontoku, by deeply defining and database analyzing of the "sharing extension" , as well as the elementarily research of some relative practice, this paper aims on analyzing the real essence of the "sharing extension" . As the parallel accumulation method of public interest and saving, the "sharing extension" combines the morality and economy skillfully and thus demonstrates the main thought of NinomiyaSontoku, the harmonious unification of the above two. By giving priority to the harmonious happy life of the farmers, during the practice of morality devotion, NinomiyaSontoku successfully dealt with the problem of the desolation of countries in that period. With the skillful and peaceful "sharing extension" method which aims to strengthen the nation and sarisfy the people, he gained the compromise of the lairds of decreasing their financial interests and bleeds from farmers and consequently helped the farmers to reduce the tax burden and develop their production without any bloody conflicts. Therefore, the authou does not think NinomiyaSontoku as a \u27Paid Thinker\u27 and his thoughts should be discussed again

二宮尊徳の思想ー大原幽学との比較を中心にしてー

This article makes a comparative analysis of the thoughts of later farmer thinkers Ninomiya Sontoku and Ohara Yugaku, which both emphasized a philosophy of obeying social status system during the Age of Edo. Ohara Yugaku adhered to his idea of harmony between man and nature. in which exceedingly emphasized the feudal status system from the standpoints of warriors and political point of view, and consequently, his thinking could not surmount the limitation of the warrior ethics of feudalism. Meanwhile, Ninomiya Sontoku tried to distinguish the human laws from the natural laws, and regarded subjective initiative of human beings based on follwing the natural laws, in which demonstrated his strong concern over the farmers\u27 interests from a practical point. Also, Ninomiya Sontoku advocated the coordinated development of both morality and economy, which was characterized by stressing social public welfare and social coordination. In comparison, Ninomiya Sontoku\u27s thought conformed to the historical trend and built up positive practical significance

Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway

<p>Abstract</p> <p>Background</p> <p>Trop2 is a cell-surface glycoprotein overexpressed by a variety of epithelial carcinomas with reported low to restricted expression in normal tissues. Expression of Trop2 has been associated with increased tumor aggressiveness, metastasis and decreased patient survival, but the signaling mechanisms mediated by Trop2 are still unknown. Here, we studied the effects murine Trop2 (mTrop2) exerted on tumor cellular functions and some of the signaling mechanisms activated by this oncogene.</p> <p>Results</p> <p>mTrop2 expression significantly increased tumor cell proliferation at low serum concentration, migration, foci formation and anchorage-independent growth. These <it>in vitro </it>characteristics translated to increased tumor growth in both subcutaneous and orthotopic pancreatic cancer murine models and also led to increased liver metastasis. mTrop2 expression also increased the levels of phosphorylated ERK1/2 mediating cell cycle progression by increasing the levels of cyclin D1 and cyclin E as well as downregulating p27. The activation of ERK was also observed in human pancreatic ductal epithelial cells and colorectal adenocarcinoma cells overexpressing human Trop2.</p> <p>Conclusions</p> <p>These findings demonstrate some of the pathogenic effects mediated by mTrop2 expression on cancer cells and the importance of targeting this cell surface glycoprotein. This study also provides the first indication of a molecular signaling pathway activated by Trop2 which has important implications for cancer cell growth and survival.</p

Mesothelin confers pancreatic cancer cell resistance to TNF-α-induced apoptosis through Akt/PI3K/NF-κB activation and IL-6/Mcl-1 overexpression

<p>Abstract</p> <p>Background</p> <p>Previous studies showed that mesothelin (MSLN) plays important roles in survival of pancreatic cancer (PC) cells under anchorage dependent/independent conditions as well as resistance to chemotherapy. The recent success of intratumorally-injected adeno-encoded, chemo/radiation-inducible-promoter driven hTNF-α, (TNFerade) + gemcitabine in pre-clinical models of PC have renewed interest in use of TNF-α as a therapeutic component. To help find additional factors which might affect the therapy, we examined the resistance of MSLN-overexpressing pancreatic cancer cell lines to TNF-α-induced growth inhibition/apoptosis.</p> <p>Methods</p> <p>Stable MSLN overexpressing MIA PaCa-2 cells (MIA-MSLN), stable MSLN-silenced AsPC-1 cells (AsPC-shMSLN) and other pancreatic cells (MIA-PaCa2, Panc 28, Capan-1, BxPC3, PL 45, Hs 766T, AsPC-1, Capan-2, Panc 48) were used. NF-κB activation was examined by western blots and luciferase reporter assay. TNF-α induced growth inhibition/apoptosis was measured by MTT, TUNEL assay and caspase activation. IL-6 was measured using luminex based assay.</p> <p>Results</p> <p>Compared to low endogenous MSLN-expressing MIA PaCa-2 and Panc 28 cells, high endogenous MSLN-expressing Capan-1, BxPC3, PL 45, Hs 766T, AsPC-1, Capan-2, Panc 48 cells were resistant to TNF-α induced growth inhibition. Stable MSLN overexpressing MIA-PaCa2 cells (MIA-MSLN) were resistant to TNF-α-induced apoptosis while stable MSLN-silenced AsPC1 cells (AsPC-shMSLN) were sensitive. Interestingly, TNF-α-treated MIA-MSLN cells showed increased cell cycle progression and cyclin A induction, both of which were reversed by caspase inhibition. We further found that MIA-MSLN cells showed increased expression of anti-apoptotic Bcl-XL and Mcl-1; deactivated (p-Ser⁷⁵) BAD, and activated (p-Ser⁷⁰) Bcl-2. Constitutively activated NF-κB and Akt were evident in MIA-MSLN cells that could be suppressed by MSLN siRNA with a resultant increase in sensitivity of TNF-α induced apoptosis. Blocking NF-κB using IKK inhibitor wedelolactone also increased sensitivity to TNF-α-mediated cytotoxicity with concomitant decrease in Mcl-1. Blocking Akt using PI3K inhibitor also had a likewise effect presumably affecting cell cycle. MIA-MSLN cells produced increased IL-6 and were increased furthermore by TNF-α treatment. SiRNA-silencing of IL-6 increased TNF-α sensitivity of MIA-MSLN cells.</p> <p>Conclusions</p> <p>Our study delineates a MSLN-Akt-NF-κB-IL-6-Mcl-1 survival axis that may be operative in PC cells, and might help cancer cells' survival in the highly inflammatory milieu evident in PC. Further, for the success of TNFerade + gemcitabine to be successful, we feel the simultaneous inhibition of components of this axis is also essential.</p

Cyclophilin A enhances cell proliferation and tumor growth of liver fluke-associated cholangiocarcinoma

<p>Abstract</p> <p>Background</p> <p>Cyclophilin A (CypA) expression is associated with malignant phenotypes in many cancers. However, the role and mechanisms of CypA in liver fluke-associated cholangiocarcinoma (CCA) are not presently known. In this study, we investigated the expression of CypA in CCA tumor tissues and CCA cell lines as well as regulation mechanisms of CypA in tumor growth using CCA cell lines.</p> <p>Methods</p> <p>CypA expression was determined by real time RT-PCR, Western blot or immunohistochemistry. CypA silence or overexpression in CCA cells was achieved using gene delivery techniques. Cell proliferation was assessed using MTS assay or Ki-67 staining. The effect of silencing CypA on CCA tumor growth was determined in nude mice. The effect of CypA knockdown on ERK1/2 activation was assessed by Western blot.</p> <p>Results</p> <p>CypA was upregulated in 68% of CCA tumor tissues. Silencing CypA significantly suppressed cell proliferation in several CCA cell lines. Likewise, inhibition of CypA peptidyl-prolyl cis-trans isomerase (PPIase) activity using cyclosporin A (CsA) decreased cell proliferation. In contrast, overexpression of CypA resulted in 30% to 35% increases in proliferation of CCA cell lines. Interestingly, neither silence nor overexpression of CypA affected cell proliferation of a non-tumor human cholangiocyte cell line, MMNK1. Suppression of CypA expression attenuated ERK1/2 activity in CCA M139 cells by using both transient and stable knockdown methods. In the <it>in vivo </it>study, there was a 43% reduction in weight of tumors derived from CypA-silenced CCA cell lines compared with control vector CCA tumors in mice; these tumors with stable CypA silencing showed a reduced cell proliferation.</p> <p>Conclusions</p> <p>CypA is upregulated in majority of CCA patients' tissues and confers a significant growth advantage in CCA cells. Suppression of CypA expression decreases proliferation of CCA cell lines <it>in vitro </it>and reduces tumor growth in the nude mouse model. Inhibition of CypA activity also reduces CCA cell proliferation. The ERK1/2 pathway may be involved in the CypA-mediated CCA cell proliferation. Thus, CypA may represent an important new therapeutic target for liver fluke-associated CCA.</p

Neutralization of hemmorrhagic activity of Crotalus basiliscus venom fraction CB10 by indigo snake serum

Abstract not availabl