This model was generated by creating a double-transgenic Myc/Bcl-X L mouse strain shown to develop plasma cell tumors with an average onset of 135 days at 100% tumor penetrance. Johnson J. Their significant disadvantages, however, include a general lack of tumor context or microenvironment (partially improved by orthotopic models), and inability to determine the effects of immune systems on tumor growth. doi:10.1182/blood-2002-10-3182. Pubmed.ncbi.nlm.nih.gov The murine model provides a valuable and affordable means to understanding the potential and limitations of IUT prior to pre-clinical large animal studies and an eventual clinical application. 1978;4:329–35. GDL performed CT acquisitions, analysis and interpretation of the related results, and participated in drafting of the manuscript. Murine animal models have particular advantages for comparative study to evaluate the efficacy and safety of different treatment modalities because many mice can be treated at … Kavanagh KT, Hafer LJ, Kim DW, et al. 53. Results obtained from the models cannot precisely predict the clinical sensitivity, specificity, accuracy, positive and negative prediction values of the screened contrast agent candidate in actual medical use. 2003;63:8742–8. Murine models have been adopted as a significant and powerful tool in the study of cancer. Int J Cancer. During the same initial contrast enhanced period showing rim enhancement, most of the malignant xenografts (11/11 or 100 % of MDA-MB 231 xenografts; 11/12 or 91.7 % of MCF-7 xenografts) had angular/ill-defined margin, while none of the benign xenografts showed sign of angular/ill-defined margin. Fujiwara S, Imadome K, Takei M. Modeling EBV infection and pathogenesis in new-generation humanized mice. Often, it is acceptable and sufficient to access online databases to choose your knockout of interest, on a standard background strain, such as FVB/N, BALB/c, or C57BL/6. Correlation of whole-breast vascularity with ipsilateral breast cancers using contrast-enhanced MDCT. EBV-associated Hodgkin’s lymphomas developed in mice with activated T-cell environment, while non-Hodgkin’s lymphoma developed in T-cell depressed mice following infection with EBV (83). This study aimed to review the literature on murine models of CADS induction using acrylic intraoral devices simulating dentures. Particularly, use of separate strains of mice to generate inducible models allows avoidance of early gene expression (43, 44). Now known as the “3Rs,” these principles have been since adapted and … There were 20 MDF-7, 17 MDA-MD 231 and 36 benign xenografts. Science (1990) 247(4944):824–30. The human breast adenocarcinoma cell line, MCF-7 and MDA-MB 231, were obtained from the National Health Research Institute Cell Bank (Hsinchu, Taiwan) and cultured as recommended by the American Type Culture Collection (Manassas, Virginia, USA) with culture reagents obtained from Quantum Biotechnology (distributor of Life Technologies, Inc. and Invitrogen, Taichung, Taiwan) unless otherwise indicated. Tannenbaum J, Bennett BT. Murine models will remain the most appropriate tool for evaluating new therapeutic strategies for the treatment of various diseases. Andrique L, Poglio S, Prochazkova-Carlotti M, Kadin ME, Giese A, Idrissi Y, et al. doi:10.1073/pnas.0506654102, 61. Pui CH, Kane JR, Crist WM. The detection rate of increased blood flow in the tumor xenografts from color Doppler imaging was 17.6 % (3/17) for MCF-7 xenografts (Fig. 9c) and 10 % (1/10) for MDA-MB 231 xenografts. 2005;19:2008–10. Homozygous deletion of the upstream regulatory element of PU.1 results in downregulation of this protein within hematopoietic stem and progenitor cells and leukemia development in a mouse model of AML (25). J Cell Biochem. Frequent MED12 mutations in phyllodes tumours of the breast. Cancer Discov (2016). Krejsgaard T, Kopp K, Ralfkiaer E, Willumsgaard AE, Eriksen KW, Labuda T, et al. 39. Am J Roentgenol. A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression. J Clin Invest (2010) 120(7):2254–64. Rosenthal N, Brown S. The mouse ascending: perspectives for human-disease models. © 2021 BioMed Central Ltd unless otherwise stated. A final transgenic murine MM model, which also focuses on overexpression of MYC oncogene is the Myc/Bcl-X L model (Cheung et al., 2004). Immunohistological analysis of CD31 and VEGF (indications of neovascular development and facilitators for uncontrolled growth, invasion and metastasis of breast cancer [31–33]) in xenograft sections indicated the presence of the endogenous targeting contrasts. Receptor-targeted nanoparticles for in vivo imaging of breast cancer. Mice also share many physiologic characteristics with humans and, therefore, provide similar organ system biology for the study of cardiovascular, endocrine, immune diseases, and others. Overexpression of oncogenic Tax and HBZ viral proteins from HTLV-1 has elucidated mechanisms of leukemia development. https://doi.org/10.1186/s12929-016-0261-4, DOI: https://doi.org/10.1186/s12929-016-0261-4. Elenbaas B, Spirio L, Koerner F, et al. However, most of the contrast features achieved exceeding 85 % accuracy, sensitivity, specificity, positive predictive value and negative predictive value except for the contrast from neovascular blood flow detected by color Doppler US. The mouse is the foremost mammalian model for studying human disease and human health. Benign and malignant breast masses and axillary nodes: evaluation with echo-enhanced color power Doppler US. 1. murine - a rodent that is a member of the family Muridae. TEL/AML-1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia. The xenograft-type occurrence of those contrast features are summarized in Table 1. A specific inhibitor of Syk was used to cause tumor regression in vivo (80). doi:10.1016/j.jim.2014.02.011, 12. Mori S, Rempel RE, Chang JT, Yao G, Lagoo AS, Potti A, et al. Marchetti S, Schellens JH. Agdeppa ED, Spilker ME. Concerning hematopoiesis, in mice, lymphocytes are the predominant circulating white blood cell, whereas the neutrophil predominates in humans (3, 6, 7). Donnou S, Galand C, Touitou V, Sautès-Fridman C, Fabry Z, Fisson S. Murine models of B-cell lymphomas: promising tools for designing cancer therapies. The high incidence of leukemia and lymphoma in some mouse strains is further enhanced in immunocompromised mice—an experimental tool often used to model these diseases. doi:10.1038/nrd4539, Keywords: leukemia, lymphoma, mouse models, hematologic neoplasms, mouse genetic models, Citation: Kohnken R, Porcu P and Mishra A (2017) Overview of the Use of Murine Models in Leukemia and Lymphoma Research. Humanization of the entire murine Mapt gene provides a murine model of pathological human tau propagation Blood (2006) 107(12):4917–25. Development of murine models that model these issues as closely as possible requires insight in the structure/function relationship of murine airways. Oncologist. Ye D, Wolff N, Li L, Zhang S, Ilaria RL. Privacy The xenograft specimens for histological analysis were processed with conventional hematoxylin and eosin (H&E) staining for the visualization of general tissue morphology and mitotic figures under microscopic inspection. The reaction was stopped by rinsing the section with 0.01 M phosphate-buffered saline (PBS). [Murine Model Definition] - 大中华超市 Murine Model Definition Full Spectrum CBD Oil High strength CBD drops. Correspondence to Serial transfer in TCL-1 transgenic mice allows rapid progression of the disease and has been useful for preclinical studies (64). The sections were washed in 50 mM Tris–HCl, 0.05 % Tween, pH 7.6 for 2 min. Generating mouse models using CRISPR-Cas9-mediated genome editing. Phase “0” studies utilize miniscule doses of novel drugs in human subjects to collect data on pharmacodynamics and target specificity (90, 93). Inducible germline models, or knock-in systems, can be designed to activate mutations in specific tissues in response to drug or vector treatment (4, 18). 2001;220:795–802. Morphology of MCF-7 xenografts at time points post implantation. Blood (1996) 88(11):4252–8. 2004;233:830–49. Many of the genetic aberrations involved in the oncogenesis of AML have been characterized, with recurrent genetic abnormalities to include CEBPA mutations, RUNX1 mutations, and BCR-ABL1 gene translocations (24) (Table 2). Ultrasound Med Biol. 52. The xenografts were implanted subcutaneously into the flank region of nude mice (Foxn1 gene disruption; athymic; nu/nu) for eliminating interferences, such as the accumulation of agents in organs (liver, kidneys, bladder, intestine) responsible for their clearance (stronger contrast enhancement of organs hindering signal from xenograft and resulting in specificity reduction from hindered contrast enhanced indicating malignancy from xenografts’ signal in abdominal area, such as orthotopical breast xenograft), and the unwanted signal interferences from animal hair absorption or scattering [25, 26]. Am J Pathol. 2008;248:12–5. doi:10.1182/blood-2008-07-077982, 15. Malignant xenografts appeared morphologically taller than wide (axis parallel to skin) with angular/ill-defined margin under sonogram observations, revealed more evident rim enhancement, angular margin and washout pattern in the time-density curve from dynamic contrast enhance multi-detector computed tomography images, and had more visible cancer vascular markers (CD31 and VEGF) expression. Mak IW, Evaniew N, Ghert M. Lost in translation: animal models and clinical trials in cancer treatment. doi:10.1159/000356651, 34. A rapid photo-curing system based on poly(2-ethyl-2-oxazoline-co-2-allylamidopropyl-2-oxazoline) and its in vivo compatibility are presented. One final question, Is there a better way? Molecular Pathology of Hematolymphoid Diseases. Mettler FA, Upton AC, Kelsey CA, et al. Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma. Aside from these common background findings, each of these strains is predisposed to developing certain spontaneous tumors, with lymphoma often being most common (7). 100–71). (B) Conditional transgenics can be generated for tissue-specific expression under the control of a Cre recombinase. The carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) was found to induce both benign and malignant mammary lesions in rats [17]. doi:10.1016/j.ccr.2009.11.019, 68. Adv Hematol (2012) 2012:701704. doi:10.1155/2012/701704, 75. PubMed  Here, we describe a protocol for performing an IUT in the murine fetus through intravenous and intra-amniotic routes. The two xenografts were then characterized by in vivo imaging inspections (US, CT) to verify the presence of those endogenous morphological and non-targeting exogenous contrasts. However, while there are many advantages to these models, limitations remain. Leukemias and lymphomas are a group of highly heterogeneous hematologic malignancies that affect people of all ages and ethnicities. 2006;22:53–66. Therefore, while the mouse is a powerful tool, it must also be viewed as an independent contributor to the research conducted upon it and as one that deserves consideration. 2000;5:379–91. Wells PNT, Halliwell M, Skidmore R, et al. The benign implants showed a relatively milder maximal contrast enhancement (205 %) in a more extended period (exhibited as a plateau lasting from 60th to 180th minutes). 1. murine - of or relating to or transmitted by a member of the family Muridae (rats and mice); "a murine plague". Another important contribution of this work is that it clearly shows that human and murine cells can be quite different in their responses to factors such as diet, and we have to be careful when interpreting mouse studies of human conditions, Bissig said. Li S, Ilaria RL, Million RP, Daley GQ, Van Etten RA. doi:10.1242/dmm.000976, 10. Proc Natl Acad Sci U S A. Ultrasound Med Biol. Duque-Afonso J, Feng J, Scherer F, Lin CH, Wong SH, Wang Z, et al. C57BL/6J mice are resistant to audiogenic seizures, have a relatively low bone density, and develop age related hearing loss. One hundred twenty-nine mice are often used as donors of embryonic stem cells and are prone to pulmonary proteinosis and hypocollosity (7). doi:10.1111/j.1600-0609.2011.01626.x, 69. Murine models are very well described in the literature but human health low-risk alternatives are not. Curr Protoc Mouse Biol (2016) 6(1):39–66. Murine models of cancer include transplantable models, spontaneous and autochthonous models, human tumor xenografts, orthotopic models, models of metastasis and transgenic tumor models. Nat Rev Drug Discov (2015) 14(4):248–60. GEMM, humanized mice). Input-specific modulation of murine nucleus accumbens differentially regulates hedonic feeding ... and 12% fat by calories (4.00 kcal/g: Purina Lab Diet). Another key factor in their increased use is their relative simplicity compared with other immunocompetent models (e.g. Stat5 is indispensable for the maintenance of bcr/abl-positive leukaemia. PubMed  E mu-BRD2 transgenic mice develop B-cell lymphoma and leukemia. Poor engraftment by CLL cells into mice has limited the utility of xenograft models for this disease. Those contrast features of the xenograft model with high (exceeding 85 %) accuracy, sensitivity, specificity, positive predictive value and negative predictive value, surpassing the evaluation efficiency from 3 conventional imaging modalities (mammogram had 70.2 % accuracy, 67.8 % sensitivity, 75 % specificity and 85.7 % positive predictive value; US had 67.8 % accuracy, 83 % sensitivity, 34 % specificity and 73.5 % positive predictive value; MRI had 72.9 % accuracy, 94.4 % sensitivity, 26 % specificity and 73.6 % positive predictive value) for breast lesion screening [15]. Generation of murine models using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome editing is an emerging and powerful tool to study cancer. Leukemia (2016) 30(10):2064–73. For all of their advantages, there are also numerous limitations that must be considered when choosing the model and interpreting their findings. Blood (2004) 103(4):1475–84. Oncol. Springer Nature. It is clear that many of these conditions could confound individual studies, and therefore, the strain of mouse must be considered carefully. Br J Cancer (2007) 97(5):577–81. However, the field is quickly advancing and, may shortly, allow in vitro examination of hematopoietic systems and hematopoietic neoplasia. Mulloy JC. It may not be. J Exp Med (2010) 207(5):911–3. Benign breast lesions in an African population: A 25-year histopathological review of 1864 cases. Journal of Biomedical Science They also had angular/ill-defined margins (penetrating into adjacent derma layer structures) (Fig. 9a). doi:10.1006/scbi.2001.0423, 70. Randomly chosen 54 developed xenografts (10 MDA-MB 231, 17 MCF-7 and 27 benign xenogrsfts) were inspected by sonogram. CA Cancer J Clin (2016) 66(1):7–30. Decorin is a member of the family of small leucine-rich proteoglycans. Cancer Cell (2010) 17(1):28–40. The mixtures without cells were agitated vigorously to incorporate air bubbles before implantation. In examining the morphological features of the xenograft images under DCE-MDCT, the most visible features that could be used to indicate the malignancy of xenografts were the angular/ill-defined margin and rim enhancement. C57BL/6 are often utilized for mutagenesis studies and are overall the most commonly used strain in academic institutions (3). Lee EK, Joo EH, Song KA, Choi B, Kim M, Kim SH, et al. While murine models are frequently used for preclinical investigations of novel drug targets, success in these studies is often poorly predictive of success in the clinic.
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