Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling

Purpose: We aimed to investigate the effects of adiponectin on liver cancer growth and metastasis and explore the underlying mechanisms. Experimental Design: An orthotopic liver tumor nude mice model with distant metastatic potential was applied. Either Ad-adiponectin (1 × 10 8; treatment group) or Ad-luciferase (control group) was injected via portal vein after tumor implantation. Tumor growth and metastasis were monitored by Xenogen In vivo Imaging System. Hepatic stellate cell activation by α-smooth muscle actin staining, microvessel density by CD34 staining, macrophage infiltration in tumor tissue, and cell signaling leading to invasion, migration [Rho kinase (ROCK), IFN-inducible protein 10 (IP10), and matrix metalloproteinase 9], and angiogenesis [vascular endothelial growth factor (VEGF) and angiopoietin 1] were also compared. Tumor-nontumor margin was examined under electron microscopy. Direct effects of adiponectin on liver cancer cells and endothelial cells were further investigated by a series of functional studies. Results: Tumor growth was significantly inhibited by adiponectin treatment, accompanied by a lower incidence of lung metastasis. Hepatic stellate cell activation and macrophage infiltration in the liver tumors were suppressed by adiponectin treatment, along with decreased microvessel density. The treatment group had less Ki-67-positive tumor cells and downregulated protein expression of ROCK1, proline-rich tyrosine kinase 2, and VEGF. Tumor vascular endothelial cell damage was found in the treatment group under electron microscopy. In vitro functional study showed that adiponectin not only downregulated the ROCK/IP10/VEGF signaling pathway but also inhibited the formation of lamellipodia, which contribute to cell migration. Conclusion: Adiponectin treatment significantly inhibited liver tumor growth and metastasis by suppression of tumor angiogenesis and downregulation of the ROCK/IP10/matrix metalloproteinase 9 pathway. ©2010 AACR.postprin

Suppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on homeoprotein Six1

We previously demonstrated that the overexpression of homeoprotein Six1 in hepatocellular carcinoma (HCC) patients is associated with venous infiltration, advanced pathologic tumor metastasis (pTNM) stage and poor overall survival rate (Ng et al. Br J Cancer 2006;95:1050-5). In this study, short hairpin RNA (shRNA) interference approach was used to suppress the expression of Six1 in a metastatic HCC cell line MHCC97L. Stable transfectant MHCC97L-shSix1 carrying Six1-specific shRNA plasmid was established to downregulate Six1 expression to about 40% when compared with MHCC97L-Control. In vitro functional assays demonstrated that the growth rate and proliferation ability of MHCC97L-shSix1 cells were markedly decreased. Moreover, significant decrease of cell motility and invasiveness were observed in MHCC97L-shSix1 cells. Data from in vivo xenograft tumorigenesis model demonstrated that the size of tumor in MHCC97L-shSix1 group was dramatically reduced. Experimental and spontaneous metastasis models indicated that targeting Six1 suppression noticeably reduced the pulmonary metastasis in MHCC97L-shSix1 group. To identify Six1-regulated targets, cDNA microarray was employed to compare the expression profiles of MHCC97L-Control and MHCC97L-shSix1 cells. Twenty-eight downregulated and 24 upregulated genes with known functions were identified in MHCC97L-shSix1. The functions of these target genes are involved in diverse biological activities. Our data suggest that Six1 may be involved in regulation of proliferation and invasiveness of HCC; thus targeting suppression of Six1 is a viable option for treating HCC patients. © 2009 UICC.postprin

Frequent CEO Turnover and Firm Performance: The Resilience Effect of Workforce Diversity

© 2020, Springer Nature B.V. CEO turnover (or succession) is a critical event in an organization that influences organizational processes and performance. The objective of this study is to investigate whether workforce diversity (i.e., age, gender, and education-level diversity) might have a resilience effect on firm performance under the frequency of CEO turnover. Based on a sample of 409 Korean firms from 2010 to 2015, our results show that firms with more frequent CEO turnover have a lower firm performance. However, firms with more gender and education-level diversity could buffer the disruptive effect of frequent CEO turnover on firm performance to offer a benefit to the organization. Our theory and findings suggest that effectively managing diverse workforce can be a resilience factor in an uncertain organizational environment because diverse workforce has complementary skills and behaviors that can cope better with uncertainty and signals social inclusion of an organization, thus fostering a long-term exchange relationship. These findings contribute to the literature on CEO turnover (or succession) and diversity

Attenuation of hepatic I/R injury on small liver remnant by FTY720 markedly suppressed liver tumor growth and metastasis

link_to_OA_fulltextThe 10th Annual Congress of the International Liver Transplantation Society, Kyoto, Japan, 9-12 June 2004. In Liver Transplantation, 2004, v. 10 n. 6, p. C75, abstract no. 29

FTY720 selectively induced human hepatoma cell line apoptosis via Akt dephosphorylation

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Attenuation of hepatic I/R injury on small liver remnant by FTY720 markedly suppressed liver tumor growth and metastasis

link_to_OA_fulltextThe 10th Annual Congress of the International Liver Transplantation Society, Kyoto, Japan, 9-12 June 2004. In Liver Transplantation, 2004, v. 10 n. 6, p. C75, abstract no. 29

Hepatic I/R injury on small liver remnant promotes liver tumor growth and metastasis - activation of cell invasion and migration pathways

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FTY720 attenuates small-for-size liver graft injury - the significance of activation of cell survival signaling pathway

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Rescue of small-for-size fatty liver grafts injury by FTY720 plus adiponectin combination therapy

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