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Avatar mice model

Max A Cayo, Sunil K Mallanna, Francesca Di Furio, Ran Jing, Lauren B Tolliver, Matthew Bures, Amanda Urick, Fallon K Noto, Evanthia E Pashos, Matthew D Greseth, Maciej Czarnecki, Paula Traktman, Wenli Yang, Edward E Morrisey, Markus Grompe, Daniel J Rader, Stephen A Duncan
Efforts to identify pharmaceuticals to treat heritable metabolic liver diseases have been hampered by the lack of models. However, cells with hepatocyte characteristics can be produced from induced pluripotent stem cells (iPSCs). Here, we have used hepatocyte-like cells generated from homozygous familial hypercholesterolemia (hoFH) iPSCs to identify drugs that can potentially be repurposed to lower serum LDL-C. We found that cardiac glycosides reduce the production of apolipoprotein B (apoB) from human hepatocytes in culture and the serum of avatar mice harboring humanized livers...
April 6, 2017: Cell Stem Cell
Alexandre Plessier, Ludivine Le Dret, Pascale Varlet, Kévin Beccaria, Joëlle Lacombe, Sébastien Mériaux, Françoise Geffroy, Laurence Fiette, Patricia Flamant, Fabrice Chrétien, Thomas Blauwblomme, Stéphanie Puget, Jacques Grill, Marie-Anne Debily, David Castel
Diffuse Instrinsic Pontine Glioma is the most aggressive form of High Grade Gliomas in children. The lack of biological material and the absence of relevant models have hampered the development of new therapeutics. Their extensive infiltration of the brainstem renders any surgical resection impossible and until recently biopsies were considered not informative enough and therefore not recommended. Thus, most models were derived from autopsy material. We aimed to develop relevant in vivo DIPG models that mimic this specific disease and its molecular diversity from tumor material obtained at diagnosis...
February 2, 2017: Oncotarget
Sebastian M Dieter, Klara M Giessler, Mark Kriegsmann, Taronish D Dubash, Lino Möhrmann, Erik R Schulz, Christine Siegl, Sarah Weber, Hendrik Strakerjahn, Ava Oberlack, Ulrike Heger, Jianpeng Gao, Eva-Maria Hartinger, Felix Oppel, Christopher M Hoffmann, Nati Ha, Benedikt Brors, Felix Lasitschka, Alexis Ulrich, Oliver Strobel, Manfred Schmidt, Christof von Kalle, Martin Schneider, Wilko Weichert, K Roland Ehrenberg, Hanno Glimm, Claudia R Ball
Patient-derived cancer xenografts (PDX) are widely used to identify and evaluate novel therapeutic targets, and to test therapeutic approaches in preclinical mouse avatar trials. Despite their widespread use, potential caveats of PDX models remain considerably underappreciated. Here, we demonstrate that EBV-associated B-lymphoproliferations frequently develop following xenotransplantation of human colorectal and pancreatic carcinomas in highly immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice (18/47 and 4/37 mice, respectively), and in derived cell cultures in vitro...
March 15, 2017: International Journal of Cancer. Journal International du Cancer
Yong Zhang, Makoto Toneri, Huaiyu Ma, Zhijian Yang, Michael Bouvet, Yusuke Goto, Naohiko Seki, Robert M Hoffman
There are two major types of mouse xenograft models of cancer: subcutaneous implantation and orthotopic implantation. Subcutaneous transplant models are widely used with both cancer cell lines and human-tumor specimens. Recently, subcutaneous models of patient tumors, termed patient-derived xenographs (PDX) have become highly popular and have acquired such names as "Avatar" and "Xenopatients." However, such s.c. models rarely metastasize and are therefore not patient-like. In contrast, orthotopic models have the capability to metastasize...
November 2016: Journal of Cellular Biochemistry
Amira A Zayed, Sumithra J Mandrekar, Paul Haluska
Innovation in oncology drug development has been hindered by lack of preclinical models that reliably predict clinical activity of novel therapies in cancer patients. Increasing desire for individualize treatment of patients with cancer has led to an increase in the use of patient-derived xenografts (PDX) engrafted into immune-compromised mice for preclinical modeling. Large numbers of tumor-specific PDX models have been established and proved to be powerful tools in pre-clinical testing. A subset of PDXs, referred to as Avatars, establish tumors in an orthotopic and treatment naïve fashion that may represent the most clinical relevant model of individual human cancers...
September 2015: Chinese Clinical Oncology
K Lodhia, M Becker, X Hou, K Kalli, M Harrell, K Wilcoxen, E Swisher, S Weroha, P Halsuka
Ovarian cancer is the most lethal gynecologic malignancy. Current standard of care post surgical cytoreduction is combination platinum/taxane chemotherapy, with initial response varying widely; subsets of carcinomas demonstrate resistance or sensitivity from the onset. The underlying cause of this response heterogeneity remains unknown. Patient-derived xenografts (PDX) serve as useful in vivo models to study molecular response markers and test the efficacy of targeted therapies. Our group has demonstrated a high engraftment rate (>70%) of ovarian cancer PDXs (Avatars) by injecting treatment naïve patient tumor directly into the peritoneal cavity of immunocompromised mice, in an effort to better mimic the anatomic context by which ovarian cancer naturally develops...
March 2015: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Maria Veronica Russo, Alice Faversani, Stefano Gatti, Dario Ricca, Alessandro Del Gobbo, Stefano Ferrero, Alessandro Palleschi, Valentina Vaira, Silvano Bosari
INTRODUCTION: Lung cancer remains the leading cause of tumor-related deaths, despite advances in the understanding of the disease pathogenesis and in its clinical treatment. It is crucial to develop novel technologies to discover disease biomarkers and predict individual therapy response. MATERIALS AND METHODS: We established 48 patients-derived tumor xenografts (PDTXs) implanted in the subrenal capsule of immunodeficient mice using thin, precision-cut tumor tissue slices, derived from five patients affected by non-small cell lung cancer...
2015: Frontiers in Oncology
Anders W Ohman, Noor Hasan, Daniela M Dinulescu
The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects...
2014: Frontiers in Oncology
Opal Lin-Tsai, John A Taylor, Peter E Clark, Rosalyn M Adam, Xue-Ru Wu, David J DeGraff
PURPOSE OF REVIEW: High-risk, nonmuscle invasive bladder cancer (HR-NMIBC) represents a costly and difficult-to-treat disease, the molecular pathogenesis of which has a limited understanding. Most preclinical models for the study of bladder cancer are more appropriate for the study of advanced disease. However, recent key advances in preclinical animal models places us at an opportune position to better understand HR-NMIBC. RECENT FINDINGS: Discoveries in the basic sciences allow us to better understand tumor biology when building models of bladder cancer...
September 2014: Current Opinion in Urology
Markus von Schaewen, Alexander Ploss
The study of interactions between hepatitis C virus (HCV) with its mammalian host, along with the development of more effective therapeutics and vaccines has been delayed by the lack of a suitable small animal model. HCV readily infects only humans and chimpanzees, which poses logistic, economic and ethical challenges with analyzing HCV infection in vivo. Progress has been made in understanding the determinants that dictate HCV's narrow host range providing a blueprint for constructing a mouse model with inheritable susceptibility to HCV infection...
April 2014: Antiviral Research
Javier A Menendez, Tomás Alarcón, Bruna Corominas-Faja, Elisabet Cuyàs, Eugeni López-Bonet, Angel G Martin, Luciano Vellon
In the science-fiction thriller film Minority Report, a specialized police department called "PreCrime" apprehends criminals identified in advance based on foreknowledge provided by 3 genetically altered humans called "PreCogs". We propose that Yamanaka stem cell technology can be similarly used to (epi)genetically reprogram tumor cells obtained directly from cancer patients and create self-evolving personalized translational platforms to foresee the evolutionary trajectory of individual tumors. This strategy yields a large stem cell population and captures the cancer genome of an affected individual, i...
2014: Cell Cycle
Prerna Malaney, Santo V Nicosia, Vrushank Davé
Over the last few decades, study of cancer in mouse models has gained popularity. Sophisticated genetic manipulation technologies and commercialization of these murine systems have made it possible to generate mice to study human disease. Given the large socio-economic burden of cancer, both on academic research and the health care industry, there is a need for in vivo animal cancer models that can provide a rationale that is translatable to the clinic. Such a bench-to-bedside transition will facilitate a long term robust strategy that is economically feasible and clinically effective to manage cancer...
March 1, 2014: Cancer Letters
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