scholarly journals In vivo models of brain tumors: roles of genetically engineered mouse models in understanding tumor biology and use in preclinical studies

2014 ◽  
Vol 71 (20) ◽  
pp. 4007-4026 ◽  
Author(s):  
Iva Simeonova ◽  
Emmanuelle Huillard
Keyword(s):  
Brain Tumors ◽  
Mouse Models ◽  
Tumor Biology ◽  
Genetically Engineered ◽  
Preclinical Studies ◽  
In Vivo Models ◽  
Genetically Engineered Mouse Models

Development of multi-drug loaded PEGylated nanodiamonds to inhibit tumor growth and metastasis in genetically engineered mouse models of pancreatic cancer

Nanoscale ◽  
2019 ◽  
Vol 11 (45) ◽  
pp. 22006-22018 ◽  
Author(s):  
Vijay Sagar Madamsetty ◽  
Krishnendu Pal ◽  
Sandeep Keshavan ◽  
Thomas R. Caulfield ◽  
Shamit Kumar Dutta ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Models ◽  
Genetically Engineered ◽  
Inhibit Tumor Growth ◽  
Schematic Representation ◽  
Genetically Engineered Mouse Models ◽  
Tumor Growth And Metastasis ◽  
Nano Formulation ◽  
Immune Competent Mouse

Schematic representation demonstrating the fabrication and in vivo evaluation of an immune-modulatory nano-formulation consisting of irinotecan and curcumin in immune-competent mouse models of pancreatic adenocarcinoma.

scholarly journals How Genetically Engineered Mouse Tumor Models Provide Insights Into Human Cancers

2011 ◽  
Vol 29 (16) ◽  
pp. 2273-2281 ◽  
Author(s):  
Katerina Politi ◽  
William Pao
Keyword(s):  
Mouse Models ◽  
Cancer Biology ◽  
Human Cancer ◽  
Genetically Engineered ◽  
Mouse Tumor ◽  
Tumor Models ◽  
Genetically Engineered Mouse Models ◽  
Human Cancers ◽  
Chemically Induced

Genetically engineered mouse models (GEMMs) of human cancer were first created nearly 30 years ago. These early transgenic models demonstrated that mouse cells could be transformed in vivo by expression of an oncogene. A new field emerged, dedicated to generating and using mouse models of human cancer to address a wide variety of questions in cancer biology. The aim of this review is to highlight the contributions of mouse models to the diagnosis and treatment of human cancers. Because of the breadth of the topic, we have selected representative examples of how GEMMs are clinically relevant rather than provided an exhaustive list of experiments. Today, as detailed here, sophisticated mouse models are being created to study many aspects of cancer biology, including but not limited to mechanisms of sensitivity and resistance to drug treatment, oncogene cooperation, early detection, and metastasis. Alternatives to GEMMs, such as chemically induced or spontaneous tumor models, are not discussed in this review.

scholarly journals Genetic Mutations of Pancreatic Cancer and Genetically Engineered Mouse Models

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 71
Author(s):  
Yuriko Saiki ◽  
Can Jiang ◽  
Masaki Ohmuraya ◽  
Toru Furukawa
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Models ◽  
Tumor Biology ◽  
Genetically Engineered ◽  
Lineage Tracing ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Tumors ◽  
Precursor Lesions ◽  
Genetically Engineered Mouse Models ◽  
Molecular Alterations

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, and the seventh leading cause of cancer-related deaths worldwide. An improved understanding of tumor biology and novel therapeutic discoveries are needed to improve overall survival. Recent multi-gene analysis approaches such as next-generation sequencing have provided useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic cancer and precursor lesions are characterized by specific molecular alterations. Genetically engineered mouse models (GEMMs) of PDAC are useful to understand the roles of altered genes. Most GEMMs are driven by oncogenic Kras, and can recapitulate the histological and molecular hallmarks of human PDAC and comparable precursor lesions. Advanced GEMMs permit the temporally and spatially controlled manipulation of multiple target genes using a dual-recombinase system or CRISPR/Cas9 gene editing. GEMMs that express fluorescent proteins allow cell lineage tracing to follow tumor growth and metastasis to understand the contribution of different cell types in cancer progression. GEMMs are widely used for therapeutic optimization. In this review, we summarize the main molecular alterations found in pancreatic neoplasms, developed GEMMs, and the contribution of GEMMs to the current understanding of PDAC pathobiology. Furthermore, we attempted to modify the categorization of altered driver genes according to the most updated findings.

scholarly journals Genetically Engineered Mouse Models of Liver Tumorigenesis Reveal a Wide Histological Spectrum of Neoplastic and Non-Neoplastic Liver Lesions

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2265
Author(s):  
Katja Steiger ◽  
Nina Gross ◽  
Sebastian A. Widholz ◽  
Roland Rad ◽  
Wilko Weichert ◽  
...  
Keyword(s):  
Mouse Models ◽  
Liver Tumors ◽  
Genetically Engineered ◽  
Liver Lesions ◽  
Genetically Engineered Mouse Models ◽  
Chemically Induced ◽  
Wide Range ◽  
Correct Application ◽  
Huge Variety

Genetically engineered mouse models (GEMM) are an elegant tool to study liver carcinogenesis in vivo. Newly designed mouse models need detailed (histopathological) phenotyping when described for the first time to avoid misinterpretation and misconclusions. Many chemically induced models for hepatocarcinogenesis comprise a huge variety of histologically benign and malignant neoplastic, as well as non-neoplastic, lesions. Such comprehensive categorization data for GEMM are still missing. In this study, 874 microscopically categorized liver lesions from 369 macroscopically detected liver “tumors” from five different GEMM for liver tumorigenesis were included. The histologic spectrum of diagnosis included a wide range of both benign and malignant neoplastic (approx. 82%) and non-neoplastic (approx. 18%) lesions including hyperplasia, reactive bile duct changes or oval cell proliferations with huge variations among the various models and genetic backgrounds. Our study therefore critically demonstrates that models of liver tumorigenesis can harbor a huge variety of histopathologically distinct diagnosis and, depending on the genotype, notable variations are expectable. These findings are extremely important to warrant the correct application of GEMM in liver cancer research and clearly emphasize the role of basic histopathology as still being a crucial tool in modern biomedical research.

scholarly journals A pipeline for rapidly generating genetically engineered mouse models of pancreatic cancer using in vivo CRISPRCas9 mediated somatic recombination

2018 ◽  
Author(s):  
Noboru Ideno ◽  
Hiroshi Yamaguchi ◽  
Takashi Okumara ◽  
Jonathon Huang ◽  
Mitchel J. Brun ◽  
...  
Keyword(s):  
Mouse Models ◽  
Mouse Strain ◽  
Gene Editing ◽  
High Efficiency ◽  
Intraepithelial Neoplasia ◽  
Genetically Engineered ◽  
Ductal Adenocarcinoma ◽  
Specific Expression ◽  
Genetically Engineered Mouse Models

ABSTRACTGenetically engineered mouse models (GEMMs) that recapitulate the major genetic drivers in pancreatic ductal adenocarcinoma (PDAC) have provided unprecedented insights into the pathogenesis of this lethal neoplasm. Nonetheless, generating an autochthonous model is an expensive, time consuming and labor intensive process, particularly when tissue specific expression or deletion of compound alleles are involved. In addition, many of the current PDAC GEMMs cause embryonic, pancreas-wide activation or loss of driver alleles, neither of which reflects the cognate human disease scenario. The advent of CRISPR/Cas9 based gene editing can potentially circumvent many of the aforementioned shortcomings of conventional breeding schema, but ensuring the efficiency of gene editing in vivo remains a challenge. Here we have developed a pipeline for generating PDAC GEMMs of complex genotypes with high efficiency using a single “workhorse” mouse strain expressing Cas9 in the adult pancreas under a p48 promoter. Using adeno-associated virus (AAV) mediated delivery of multiplexed guide RNAs (sgRNAs) to the adult murine pancreas of p48-Cre; LSL-Cas9 mice, we confirm our ability to express an oncogenic KrasG12D allele through homology-directed repair (HDR), in conjunction with CRISPR-induced disruption of cooperating alleles (Trp53, Lkb1 and Arid1A). The resulting GEMMs demonstrate a spectrum of precursor lesions (pancreatic intraepithelial neoplasia [PanIN] or Intraductal papillary mucinous neoplasm [IPMN] with eventual progression to PDAC. Next generation sequencing of the resulting murine PDAC confirms HDR of oncogenic KrasG12D allele at the endogenous locus, and insertion deletion (“indel”) and frameshift mutations of targeted tumor suppressor alleles. By using a single “workhorse” mouse strain and optimal AAV serotype for in vivo gene editing with combination of driver alleles, we have created a facile autochthonous platform for interrogation of the PDAC genome.

A novel method of intracranial injection via the postglenoid foramen for brain tumor mouse models

2012 ◽  
Vol 116 (3) ◽  
pp. 630-635 ◽  
Author(s):  
Kenichiro Iwami ◽  
Hiroyuki Momota ◽  
Atsushi Natsume ◽  
Sayano Kinjo ◽  
Tetsuya Nagatani ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Human Brain ◽  
Mouse Models ◽  
Adult Mouse ◽  
Surgical Techniques ◽  
Genetically Engineered ◽  
Percutaneous Injection ◽  
Genetically Engineered Mouse Models ◽  
Human Brain Tumors ◽  
Intracranial Injection

Object Mouse models have been widely used in developing therapies for human brain tumors. However, surgical techniques such as bone drilling and skin suturing to create brain tumors in adult mice are still complicated. The aim of this study was to establish a simple and accurate method for intracranial injection of cells or other materials into mice. Methods The authors performed micro CT scans and skull dissection to assess the anatomical characteristics of the mouse postglenoid foramen. They then used xenograft and genetically engineered mouse models to evaluate a novel technique of percutaneous intracranial injection via the postglenoid foramen. They injected green fluorescent protein–labeled U87MG cells or virus-producing cells into adult mouse brains via the postglenoid foramen and identified the location of the created tumors by using bioluminescence imaging and histological analysis. Results The postglenoid foramen was found to be a well-conserved anatomical structure that allows percutaneous injection into the cerebrum, cerebellum, brainstem, and basal cistern in mice. The mean (± SD) time for the postglenoid foramen injection technique was 88 ± 15 seconds. The incidence of in-target tumor formation in the xenograft model ranged from 80% to 100%, depending on the target site. High-grade gliomas were successfully developed by postglenoid foramen injection in the adult genetically engineered mouse using virus-mediated platelet-derived growth factor B gene transfer. There were no procedure-related complications. Conclusions The postglenoid foramen can be used as a needle entry site into the brain of the adult mouse. Postglenoid foramen injection is a less invasive, safe, precise, and rapid method of implanting cells into the adult mouse brain. This method can be applied to both orthotopic xenograft and genetically engineered mouse models and may have further applications in mice for the development of therapies for human brain tumors.

Deciphering the RAS/ERK pathway in vivo

2017 ◽  
Vol 45 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Coralie Dorard ◽  
Georg Vucak ◽  
Manuela Baccarini
Keyword(s):  
Mouse Models ◽  
Short Review ◽  
Genetically Engineered ◽  
Tissue Homeostasis ◽  
Pharmacological Intervention ◽  
Erk Pathway ◽  
Erk Activation ◽  
Genetically Engineered Mouse Models ◽  
Mutational Activation

The RAS/ERK pathway has been intensely studied for about three decades, not least because of its role in human pathologies. ERK activation is observed in the majority of human cancers; in about one-third of them, it is driven by mutational activation of pathway components. The pathway is arguably one of the best targets for molecule-based pharmacological intervention, and several small-molecule inhibitors are in clinical use. Genetically engineered mouse models have greatly contributed to our understanding of signaling pathways in development, tissue homeostasis, and disease. In the specific case of the RAS/ERK pathway, they have revealed unique biological roles of structurally and functionally similar proteins, new kinase-independent effectors, and unsuspected relationships with other cascades. This short review summarizes the contribution of mouse models to our current understanding of the pathway.

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