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Pharmacological Inhibition of MTORC2 Reduces Migration and Metastasis in Melanoma
Abstract: Despite recent advances in therapy, liver metastasis from melanoma is still associated with poor prognosis. Although targeting the mTOR signaling pathway exerts potent anti-tumor activity, little is known about specific mTORC2 inhibition regarding liver metastasis. Using the novel mTORC2 specific inhibitor JR-AB2-011, we show significantly reduced migration and invasion capacity by impaired activation of MMP2 in melanoma cells. In addition, blockade of mTORC2 induces cell death by non-apoptotic pathways and reduces tumor cell proliferation rate dose-dependently. Furthermore, a significant reduction of liver metastasis was detected in a syngeneic murine metastasis model upon therapy with JR-AB2-011 as determined by in vivo imaging and necropsy. Hence, our study for the first time highlights the impact of the pharmacological blockade of mTORC2 as a potent novel anti-cancer approach for liver metastasis from melanoma
Molecular Diagnostics
The 2e of Molecular Diagnostics, the only book dealing with diagnosis on a molecular level, discusses current molecular biological techniques used to identify the underlying molecular defects in inherited disease. The book delves further into the principle and brief description of the technique, followed by examples from the authors' own expertise. Contributors to the 2e are well-known experts in their field, and derive from a variety of disciplines, to ensure breadth and depth of coverage. Molecular Diagnostics, 2e , is a needed resource for graduate students, researchers, physicians and practicing scientists in molecular genetics and professionals from similar backgrounds working in diagno...
Inhibition of MTORC2/RICTOR Impairs Melanoma Hepatic Metastasis
Abstract: Mammalian target of rapamycin complex 2 (mTORC2) with its pivotal component rapamycin-insensitive companion of mTOR (RICTOR) is the major regulator of AKT phosphorylation and is increasingly implicated in tumor growth and progression. In cutaneous melanoma, an extremely aggressive and highly metastatic disease, RICTOR overexpression is involved in tumor development and invasiveness. Therefore, we investigated the impact of RICTOR inhibition in melanoma cells in vitro and in vivo with special emphasis on hepatic metastasis. Moreover, our study focused on the interaction of tumor cells and hepatic stellate cells (HSC) which play a crucial role in the hepatic microenvironment. In sili...
Liver Myofibroblasts
Myofibroblasts (MFB) are found in most tissues of the body. They have the matrix-producing functions of fibroblasts and contractile properties that are known from smooth muscle cells. Fundamental work of the last decades has shed remarkable light on their origin, biological functions and role in disease. During hepatic injury, they fulfill manifold functions in connective tissue remodeling and wound healing, but overshooting activity of MFB on the other side induces fibrosis and cirrhosis. The present e-book "Liver myofibroblasts" contains 9 articles providing comprehensive information on "hot topics" of MFB. In our opening editorial we provide a short overview of the origin of MFB and their relevance in extracellular matrix formation which is the hallmark of hepatic fibrosis. Thereafter, leading experts in the field share their current perspectives on special topics of (i) MFB in development and disease, ii) their role in hepatic fibrogenesis, and (iii) promising therapies and targets that are suitable to interfere with hepatic fibrosis.
Family Talk
Through everyday talk, individuals forge the ties that can make a family. Family members use language to manage a household, create and maintain relationships, and negotiate and reinforce values and beliefs. The studies gathered in Family Talk are based on a unique research project in which four dual-income American families recorded everything they said for a week. Family Talk extends our understanding of family discourse and of how family members construct, negotiate, and enact their identities as individuals and as families. The volume also contributes to the discourse analysis of naturally-occurring interaction and makes significant contributions to theories of framing in interaction. Fa...
Four-and-a-half LIM-domain Protein 2 (FHL2) Induces Neuropeptide Y (NPY) Inmacrophages in Visceral Adipose Tissue and Promotes Diet-induced Obesity
Abstract: Obesity is characterized by the expansion of the adipose tissue, usually accompanied by inflammation, with a prominent role of macrophages infiltrating the visceral adipose tissue (VAT). This chronic inflammation is a major driver of obesity-associated comorbidities. Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of various biological functions and the maintenance of the homeostasis of different tissues. In this study, we aimed to gain new insights into the expression and functional role of FHL2 in VAT in diet-induced obesity. We found enhanced FHL2 expression in the VAT of mice with Western-type diet (WTD)-induce...
Cell Motility in Cancer Invasion and Metastasis
Cancer Morbidity and mortality result from invasive and metastatic spread. Currently, no therapies are aimed at the underlying mechanisms that enable this progression due to only nascent recognition of the distinct biology which occurs only during tumor dissemination. Recent advances have highlighted the central role of cell motility during the dynamic and transient process of tumor invasion and metastasis. This book includes state-of-the-art updates by international leaders in these studies. Chapters first present the novel model systems that enable new investigations and insights. Chapters then describe in depth the key processes and molecules that may be therapeutically targeted. Finally, the role of cell motility and its signals is explored in a number of key tumor types. This compilation should be useful to researchers in basic and translational oncology as well as those developing novel agents to prevent tumor invasion and metastasis.
The Encyclopedia of Hepatitis and Other Liver Diseases
Hepatitis is an inflammation of the liver brought on by viral infections, autoimmune diseases, alcohol abuse, exposure to toxins, or other causes.
