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Mesothelioma: HELP
Articles by Guang-Hui Xiao
Based on 2 articles published since 2008
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Between 2008 and 2019, Guang-Hui Xiao wrote the following 2 articles about Mesothelioma.
 
+ Citations + Abstracts
1 Article Inhibition of mesothelioma cancer stem-like cells with adenovirus-mediated NK4 gene therapy. 2015

Deng, Xu-Bin / Xiao, Li / Wu, Yue / Jin, Fang / Mossman, Brooke / Testa, Joseph R / Xiao, Guang-Hui. ·Cancer Institute, Southern Medical University, Guangzhou, China. · Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA. · Department of Pathology, University of Vermont College of Medicine, Burlington, VT. ·Int J Cancer · Pubmed #25501304.

ABSTRACT: Malignant mesothelioma (MM) is a highly invasive and chemoresistant malignancy induced by asbestos fibers. NK4, a hepatocyte growth factor antagonist and angiogenesis inhibitor, consists of the N-terminal hairpin domain and four kringle domains of the α-chain of hepatocyte growth factor. The therapeutic potential of NK4 has been demonstrated in a variety of tumor types. However, the mechanisms by which NK4 inhibits tumor growth have not been well delineated. In this study, it is shown that the NK4 adenovirus (Ad-NK4) potently inhibits cell viability, invasiveness and tumorigenicity of human MM cells. Significantly, this study demonstrates for the first time that Ad-NK4 inhibits cancer stem-like cell (CSC) properties as assessed by spheroid formation assay, side population analysis and flow cytometric sorting of CD24 cells. In addition to inhibiting phosphorylation of Met and AKT, Ad-NK4 markedly suppressed the active form of β-catenin, a key mediator of both Wnt and AKT pathways. It is further demonstrated that expression of NK4 suppresses β-catenin nuclear localization and transcriptional activity. Intriguingly, the expression levels of Oct4 and Myc, two critical stem cell factors and downstream targets of β-catenin, were also diminished by Ad-NK4. Furthermore, the strong antitumor effect of NK4 was found to be linked to its ability to inhibit CSCs as revealed by immunohistochemical examination of tumor specimens from a mouse xenograft model of human MM. These findings suggest that NK4 acts as a CSC inhibitor by impeding Met/AKT/β-catenin signaling and holds promise for achieving durable therapeutic responses in MM by constraining the CSC component of these aggressive tumors.

2 Article Tumor suppressor alterations cooperate to drive aggressive mesotheliomas with enriched cancer stem cells via a p53-miR-34a-c-Met axis. 2014

Menges, Craig W / Kadariya, Yuwaraj / Altomare, Deborah / Talarchek, Jacqueline / Neumann-Domer, Erin / Wu, Yue / Xiao, Guang-Hui / Shapiro, Irina M / Kolev, Vihren N / Pachter, Jonathan A / Klein-Szanto, Andres J / Testa, Joseph R. ·Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111. · Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32827. · Cancer Research Institute, Southern Medical University, Guangdong Province, PR China. · Verastem Inc., Cambridge MA 02142. ·Cancer Res · Pubmed #24371224.

ABSTRACT: Malignant mesothelioma is a highly aggressive, asbestos-related cancer frequently marked by mutations of both NF2 and CDKN2A. We demonstrate that germline knockout of one allele of each of these genes causes accelerated onset and progression of asbestos-induced malignant mesothelioma compared with asbestos-exposed Nf2(+/-) or wild-type mice. Ascites from some Nf2(+/-);Cdkn2a(+/-) mice exhibited large tumor spheroids, and tail vein injections of malignant mesothelioma cells established from these mice, but not from Nf2(+/-) or wild-type mice, produced numerous tumors in the lung, suggesting increased metastatic potential of tumor cells from Nf2(+/-);Cdkn2a(+/-) mice. Intraperitoneal injections of malignant mesothelioma cells derived from Nf2(+/-);Cdkn2a(+/-) mice into severe combined immunodeficient mice produced tumors that penetrated the diaphragm and pleural cavity and harbored increased cancer stem cells (CSC). Malignant mesothelioma cells from Nf2(+/-);Cdkn2a(+/-) mice stained positively for CSC markers and formed CSC spheroids in vitro more efficiently than counterparts from wild-type mice. Moreover, tumor cells from Nf2(+/-);Cdkn2a(+/-) mice showed elevated c-Met expression/activation, which was partly dependent on p53-mediated regulation of miR-34a and required for tumor migration/invasiveness and maintenance of the CSC population. Collectively, these studies demonstrate in vivo that inactivation of Nf2 and Cdkn2a cooperate to drive the development of highly aggressive malignant mesotheliomas characterized by enhanced tumor spreading capability and the presence of a CSC population associated with p53/miR-34a-dependent activation of c-Met. These findings suggest that cooperativity between losses of Nf2 and Cdkn2a plays a fundamental role in driving the highly aggressive tumorigenic phenotype considered to be a hallmark of malignant mesothelioma.