Animal models of human colorectal cancer: Current status, uses and limitations

Mittal, Vijay K.; Bhullar, Jasneet Singh; Jayant, Kumar

doi:10.3748/wjg.v21.i41.11854

Cited by 43 publications

(59 citation statements)

References 31 publications

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“…This technique is not only applicable to genetically and chemically induced CRC models, but also to CRC orthotopic models such as surgical transplantation models, enema models, microinjection models, and transanal low dose electrocoagulation models. 7 Additionally, given the clarity of the colon wall images obtained, this technique may prove useful in mouse models of colitis and inflammatory bowel disease. 34,35 …”

Section: Discussionmentioning

confidence: 99%

“…5 Due to the limitations of xenograft studies, the in vivo murine models of CRC have been optimized for a variety of mechanistic and drug-development studies in the last decade. 6–8 Among the in vivo mouse models, the inducible model type is less invasive than orthotopic models 7 and able to closely recapitulate the macroenvironment of CRC, including growth and metabolism. 8,9 In addition to inducible CRC models, genetic manipulation or the use of genetically susceptible mouse models have become ideal tools for CRC research.…”

Section: Introductionmentioning

confidence: 99%

“…These data enabled quantification of relative vascularity via calculations using percent agent (PA, obtained from 3D reconstructions), and relative blood volume and perfusion (obtained from 2D sagittal images), providing multiple advantages over previous CRC evaluation techniques. 7,21,22 This approach included the opportunity to acquire tumor load data at multiple stages of colon cancer progression. This straightforward, reproducible, and noninvasive method provides an in vivo and real-time assessment of tumor burden in any type of murine CRC model.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of murine colorectal cancer by micro-ultrasound using three dimensional reconstruction and non-linear contrast imaging

Freeling

Rezvani

2016

Molecular Therapy - Methods & Clinical Development

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The relatively low success rates of current colorectal cancer (CRC) therapies have led investigators to search for more specific treatments. Vertebrate models of colorectal cancer are essential tools for the verification of new therapeutic avenues such as gene therapy. The evaluation of colorectal cancer in mouse models has been limited due to the lack of an accurate quantitative and longitudinal noninvasive method. This work introduces a method of three-dimensional micro-ultrasound reconstruction and microbubble administration for the comprehensive and longitudinal evaluation of CRC progression. This approach enabled quantification of both tumor volume and relative vascularity using a well-established inducible murine model of colon carcinogenesis. This inducible model recapitulated the adenocarcinoma sequence that occurs in human CRC allowing systematic in situ evaluation of the ultrasound technique. The administration of intravenous microbubbles facilitated enhancement of colon vascular contrast and quantification of relative vascularity of the mid and distal colon of the mouse in three dimensions. In addition, two-dimensional imaging in the sagittal orientation of the colon using Non-Linear Contrast Mode enabled calculation of relative blood volume and perfusion as the microbubbles entered the colon microvasculature. Quantitative results provided by the outlined protocol represent a noninvasive tool that can more accurately define CRC development and progression. This ultrasound technique will allow the practical and economical longitudinal study of murine CRC in both basic and preclinical studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Assessment of murine colorectal cancer by micro-ultrasound using three dimensional reconstruction and non-linear contrast imaging

Freeling

Rezvani

2016

Molecular Therapy - Methods & Clinical Development

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“…The xenograft model allows the detection of cancer stem cells, but lacks the direct relation with local invasion and metastases. Despite its limitations, it is still amply used nowadays, especially in therapeutic studies …”

Section: What Type Of Crc Models Exist?mentioning

confidence: 99%

The role of mouse models in colorectal cancer research—The need and the importance of the orthotopic models

Oliveira

Abrantes

Tralhão

et al. 2020

Anim Models and Exp Med

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Colorectal cancer is a worldwide health burden, with high incidence and mortality, especially in the advanced stages of the disease. Preclinical models are very important and valuable to discover and validate early and specific biomarkers as well as new therapeutic targets. In order to accomplish that, the animal models must replicate the clinical evolution of the disease in all of its phases. In this article, we review the existent mouse models, with their strengths and weaknesses in the replication of human cancer disease progression, with major focus on orthotopic models. K E Y W O R D Scolorectal cancer, mouse model, orthotopic model

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“…15 However, human xenograft models have shown better results than murine allograft models in drug development. 32 Therefore, we investigated the antitumor effect of FA-M-β-CyD in mice xenografted with KB cells (FR-α (+)). As shown in Figure 8A and B, a single, intravenous dose of FA-M-β-CyD showed a potent inhibitory effect on tumor growth in BALB/c nu/nu mice xenografted with KB cells (FR-α (+)) compared to M-β-CyD.…”

Section: In Vivo Antitumor Activity Of Fa-m-β-cydmentioning

confidence: 99%

Induction of mitophagy-mediated antitumor activity with folate-appended methyl-β-cyclodextrin

Kameyama¹,

Motoyama²,

Tanaka³

et al. 2017

IJN

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Mitophagy is the specific autophagic elimination system of mitochondria, which regulates cellular survival via the removal of damaged mitochondria. Recently, we revealed that folate-appended methyl-β-cyclodextrin (FA-M-β-CyD) provides selective antitumor activity in folate receptor-α (FR-α)-expressing cells by the induction of autophagy. In this study, to gain insight into the detailed mechanism of this antitumor activity, we focused on the induction of mitophagy by the treatment of FR-α-expressing tumor cells with FA-M-β-CyD. In contrast to methyl-β-cyclodextrin, FA-M-β-CyD entered KB cells, human epithelial cells from a fatal cervical carcinoma (FR-α (+)) through FR-α-mediated endocytosis. The transmembrane potential of isolated mitochondria after treatment with FA-M-β-CyD was significantly elevated. In addition, FA-M-β-CyD lowered adenosine triphosphate (ATP) production and promoted reactive oxygen species production in KB cells (FR-α (+)). Importantly, FA-M-β-CyD enhanced light chain 3 (LC3) conversion (LC3-I to LC3-II) in KB cells (FR-α (+)) and induced PTEN-induced putative kinase 1 (PINK1) protein expression, which is involved in the induction of mitophagy. Furthermore, FA-M-β-CyD had potent antitumor activity in BALB/c nu/nu mice xenografted with KB cells (FR-α (+)) without any significant side effects. Taken together, these findings demonstrate that the autophagic cell death elicited by FA-M-β-CyD could be associated with mitophagy induced by an impaired mitochondrial function.

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Animal models of human colorectal cancer: Current status, uses and limitations

Cited by 43 publications

References 31 publications

Assessment of murine colorectal cancer by micro-ultrasound using three dimensional reconstruction and non-linear contrast imaging

Assessment of murine colorectal cancer by micro-ultrasound using three dimensional reconstruction and non-linear contrast imaging

The role of mouse models in colorectal cancer research—The need and the importance of the orthotopic models

Induction of mitophagy-mediated antitumor activity with folate-appended methyl-β-cyclodextrin

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Animal models of human colorectal cancer: Current status, uses and limitations

Cited by 43 publications

References 31 publications

Assessment of murine colorectal cancer by micro-ultrasound using three dimensional reconstruction and non-linear contrast imaging

Assessment of murine colorectal cancer by micro-ultrasound using three dimensional reconstruction and non-linear contrast imaging

The role of mouse models in colorectal cancer research—The need and the importance of the orthotopic models

Induction of mitophagy-mediated antitumor activity with folate-appended methyl-&beta;-cyclodextrin

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Induction of mitophagy-mediated antitumor activity with folate-appended methyl-β-cyclodextrin