Longitudinal Assessment of Colonic Tumor Fate in Mice by Computed Tomography and Optical Colonoscopy

Durkee, Ben Y.; Shinki, Kazuhiko; Newton, Michael A.; Iverson, Caitlin E.; Weichert, Jamey P.; Dove, William F.; Halberg, Richard B.

doi:10.1016/j.acra.2009.07.023

Cited by 13 publications

(10 citation statements)

References 24 publications

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“…Our group has developed a long-lived mouse model with a germline truncating mutation in the mouse homolog of APC that forms adenomatous colonic polyps which can be monitored by serial colonoscopies (14,15). We previously showed that 24 to 87% of intestinal tumors in this model progress to adenocarcinoma, and 3% develop nodal metastases.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

Olson

Hadac

Sievers

et al. 2014

Cancer Prevention Research

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Colorectal cancer (CRC) often arises from adenomatous colonic polyps. Polyps can grow and progress to cancer, but may also remain static in size, regress, or resolve. Predicting which progress and which remain benign is difficult. We developed a novel long-lived murine model of CRC with tumors that can be followed by colonoscopy. Our aim was to assess whether these tumors have similar growth patterns and histologic fates to human colorectal polyps to identify features to aid in risk-stratification of colonic tumors. Long-lived ApcMin/+ mice were treated with dextran sodium sulfate to promote colonic tumorigenesis. Tumor growth patterns were characterized by serial colonoscopy with biopsies obtained for immunohistochemistry and gene expression profiling. Tumors grew, remained static, regressed, or resolved over time with different relative frequencies. Newly developed tumors demonstrated higher rates of growth and resolution than more established tumors that tended to remain static in size. Colonic tumors were hyperplastic lesions (3%), adenomas (73%), intramucosal carcinomas (20%), or adenocarcinomas (3%). Interestingly, the level of β-catenin was higher in adenomas that became intratumoral carcinomas as compared to those that failed to progress. In addition, differentially expressed genes between adenomas and intramucosal carcinomas were identified. This novel murine model of intestinal tumorigenesis develops colonic tumors that can be monitored by serial colonoscopy, mirror growth patterns seen in human colorectal polyps, and progress to CRC. Further characterization of cellular and molecular features are needed to determine which features can be used to risk-stratify polyps for progression to CRC and potentially guide prevention strategies.

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Section: Introductionmentioning

confidence: 99%

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

Olson

Hadac

Sievers

et al. 2014

Cancer Prevention Research

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“…There are advantages offered by colonoscopy, however. Compared to mCT colonography, colonoscopy is faster (an average of 5 minutes versus 20 minutes), requiring less time under anesthesia for experimental animals (Durkee et al, 2009). The equipment and set-up for colonoscopy are also less expensive than mCT, both in terms of actual hardware required as well as the dedicated space needed for a CT scanner.…”

Section: Micro-computed Tomography Colonographymentioning

confidence: 99%

“…Good quality mCT scans had a mean standard deviation in tumor volume measurements of 8%, meaning that changes in tumor volume of >16% are detectable with a 95% confidence interval. Thus, colon tumors can be reliably identified and followed over time by mCT in order to determine if they grow, regress, or remain static either spontaneously or in response to therapy (Durkee et al, 2009). This imaging platform is very powerful when testing therapeutic interventions.…”

Section: Micro-computed Tomography Colonographymentioning

confidence: 99%

“…Currently utilized methods include computed tomography (CT), magnetic resonance imaging (MRI), and direct visualization with colonoscopy. The ability to serially assess changes in the large intestine allows more detailed information about diseases to be gathered with a smaller cohort of experimental animals (Durkee et al, 2009). This chapter will discuss the use of colonoscopy in rodent models of IBD and CRC.…”

Section: Models Of Inflammatory Bowel Disease Geneticmentioning

confidence: 99%

“…With colonoscopy, diseases such as colitis or colon neoplasm can be studied at multiple time points in the same mouse, allowing the mouse to serve as its own control, thereby eliminating variation owing to genetic and environmental effects. In addition, being able to serially study the same mouse greatly reduces the number of mice needed in order to design an adequately powered study (Becker et al, 2005(Becker et al, , 2006Durkee et al, 2009;Hensley et al, 2009). Colonoscopy in mice is a relatively simple and cost-effective procedure that is well-tolerated by experimental animals.…”

Section: Strengthsmentioning

confidence: 99%

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Experimental Small Animal Colonoscopy

Olson¹,

Halberg²

2011

Colonoscopy

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Fisetin and 5‐fluorouracil: Effective combination for PIK3CA‐mutant colorectal cancer

Khan

Jajeh

Eberhardt

et al. 2019

Intl Journal of Cancer

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The normal colon epithelium is transformed into its neoplastic counterpart through a series of genetic alterations in driver genes including activating mutations in PIK3CA. Treatment often involves surgery followed by 5-fluorouracil (5-FU) based therapy, which has limited efficiency and serious side effects. We sought to determine whether fisetin, a dietary flavonoid, alone or in combination with 5-FU affected tumorigenesis in the mammalian intestine. We first determined the effect of fisetin, 5-FU or their combination on PIK3CA-mutant and PIK3CA wild-type colon cancer cells by assessing cell viability, colony formation, apoptosis and effects on PI3K/AKT/mTOR signaling. Treatment of PIK3CA-mutant cells with fisetin and 5-FU reduced the expression of PI3K, phosphorylation of AKT, mTOR, its target proteins, constituents of mTOR signaling complex and this treatment increased the phosphorylation of AMPKα. We then determined whether fisetin and 5-FU together or singly affected tumorigenesis in Apc Min/+ mice that also express constitutively active PI3K in the distal small intestine and colon. Tumor incidence was markedly lower in fisetin-treated FC 1 3K 1 Apc Min/+ mice that also express constitutively active PI3K in distal small intestine and colon, as compared to control animals, indicating that fisetin is a strong preventive agent. In addition, the combination of fisetin and 5-FU also reduced the total number of intestinal tumors. Fisetin could be used as a preventive agent plus an adjuvant with 5-FU for the treatment of PIK3CA-mutant colorectal cancer.

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Longitudinal Assessment of Colonic Tumor Fate in Mice by Computed Tomography and Optical Colonoscopy

Abstract: Rationale and Objectives-The purpose of this study was to evaluate the relative merits of microCT colonography (mCTC) and optical colonoscopy (OC) for longitudinal studies of colonic tumors in mice. Materials and Methods-Colonic

Cited by 13 publications

References 24 publications

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

Experimental Small Animal Colonoscopy

Fisetin and 5‐fluorouracil: Effective combination for PIK3CA‐mutant colorectal cancer

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