Abstract 2726: Tumor progression and treatment response characterization in a novel mouse model of colon cancer.

Abstract Background Pelvic magnetic resonance imaging (MRI) and whole-body positron emission tomography-computed tomography (PET-CT) play an important role at primary diagnostic work-up and in detecting recurrent disease in endometrial cancer (EC) patients, however the preclinical use of these imaging methods is currently limited. We demonstrate the feasibility and utility of MRI and dynamic 18F-fluorodeoxyglucose (FDG)-PET imaging for monitoring tumor progression and assessing chemotherapy response in an orthotopic organoid-based patient-derived xenograft (O-PDX) mouse model of EC. Methods 18 O-PDX mice (grade 3 endometrioid EC, stage IIIC1), selectively underwent weekly T2-weighted MRI (total scans = 32), diffusion-weighted MRI (DWI) (total scans = 9) and dynamic 18F-FDG-PET (total scans = 26) during tumor progression. MRI tumor volumes (vMRI), tumor apparent diffusion coefficient values (ADCmean) and metabolic tumor parameters from 18F-FDG-PET including maximum and mean standard uptake values (SUVmax/SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic rate of 18F-FDG (MRFDG) were calculated. Further, nine mice were included in a chemotherapy treatment study (treatment; n = 5, controls; n = 4) and tumor ADCmean-values were compared to changes in vMRI and cellular density from histology at endpoint. A Mann–Whitney test was used to evaluate differences between groups. Results Tumors with large tumor volumes (vMRI) had higher metabolic activity (MTV and TLG) in a clear linear relationship (r2 = 0.92 and 0.89, respectively). Non-invasive calculation of MRFDG from dynamic 18F-FDG-PET (mean MRFDG = 0.39 μmol/min) was feasible using an image-derived input function. Treated mice had higher tumor ADCmean (p = 0.03), lower vMRI (p = 0.03) and tumor cellular density (p = 0.02) than non-treated mice, all indicating treatment response. Conclusion Preclinical imaging mirroring clinical imaging methods in EC is highly feasible for monitoring tumor progression and treatment response in the present orthotopic organoid mouse model.

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Abstract B59: Magnetic resonance imaging monitoring of tumor promotion and tumor progression in mouse model of inflammation-promoted colon cancer

10.1158/1940-6207.prev-08-b59 ◽

2008 ◽

Author(s):

Matthew Young ◽

Lilia Ileva ◽

Lisa Riffle ◽

Marcelino Bernardo ◽

Yava Jones ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Colon Cancer ◽

Magnetic Resonance ◽

Mouse Model ◽

Tumor Progression ◽

Tumor Promotion ◽

Resonance Imaging

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Feasibility and Utility of MRI and Dynamic 18F-FDG-PET in An Orthotopic Organoid-Based Patient-Derived Mouse Model of Endometrial Cancer

10.21203/rs.3.rs-479819/v1 ◽

2021 ◽

Author(s):

Heidi Espedal ◽

Hege Fredriksen Berg ◽

Tina Fonnes ◽

Kristine Eldevik Fasmer ◽

Camilla Krakstad ◽

...

Keyword(s):

Endometrial Cancer ◽

Mouse Model ◽

Tumor Progression ◽

Treatment Response ◽

Fdg Pet ◽

Whole Body ◽

Pelvic Magnetic Resonance Imaging ◽

Imaging Methods ◽

Cellular Density ◽

Spearman Test

Abstract Background: Pelvic magnetic resonance imaging (MRI) and whole-body positron emission tomography-computed tomography (PET-CT) play an important role at primary diagnostic work-up and in detecting recurrent disease in endometrial cancer (EC) patients, however the preclinical use of these imaging methods is currently limited. We demonstrate the feasibility and utility of MRI and dynamic 18F-fluorodeoxyglucoce (FDG)-PET imaging for monitoring tumor progression and assessing chemotherapy response in an orthotopic organoid-based patient-derived xenograft (O-PDX) mouse model of EC.Methods: 19 O-PDX mice (grade 3 endometrioid EC, stage IIIC1), selectively underwent weekly T2-weighted MRI (total scans=32), diffusion-weighted MRI (DWI) (total scans=9) and dynamic 18F-FDG-PET (total scans=26) during tumor progression. MRI tumor volumes (vMRI), tumor apparent diffusion coefficient values (ADCmean) and metabolic tumor parameters from 18F-FDG-PET including maximum and mean standard uptake values (SUVmax/SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic rate of 18F-FDG (MRFDG) were calculated. Correlation between imaging parameters was assessed using a two-tailed Spearman test. Further, nine mice were included in a chemotherapy treatment study (treatment; n=5, controls; n=4) and tumor ADCmean-values were compared to changes in vMRI and cellular density from histology at endpoint. A Mann-Whitney test was used to evaluate differences between groups. Results: Tumors with large tumor volumes (vMRI) had significantly higher metabolic activity (MTV and TLG; r=0.93, p<0.0001). Non-invasive calculation of MRFDG from dynamic 18F-FDG-PET (mean MRFDG=0.39 mmol/min) was feasible using an image-derived input function. Treated mice had higher tumor ADCmean (p=0.03) and lower vMRI (p=0.03) and tumor cellular density (p=0.02) than non-treated mice, all indicating treatment response.Conclusion: Preclinical imaging mirroring clinical imaging methods in EC is highly feasible for monitoring tumor progression and treatment response in the present orthotopic organoid mouse model.

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CtIP suppresses primary microRNA maturation and promotes metastasis of colon cancer cells in a xenograft mouse model

Journal of Biological Chemistry ◽

10.1016/j.jbc.2021.100707 ◽

2021 ◽

pp. 100707

Author(s):

Jianping Ren ◽

Yan Wu ◽

Ya Wang ◽

Yuqin Zhao ◽

Youhang Li ◽

...

Keyword(s):

Colon Cancer ◽

Mouse Model ◽

Cancer Cells ◽

Colon Cancer Cells ◽

Xenograft Mouse Model

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Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington’s Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31

Neurotherapeutics ◽

10.1007/s13311-021-01023-8 ◽

2021 ◽

Author(s):

Danielle A. Simmons ◽

Brian D. Mills ◽

Robert R. Butler III ◽

Jason Kuan ◽

Tyne L. M. McHugh ◽

...

Keyword(s):

Mouse Model ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Treatment Response ◽

Diffusion Tensor ◽

Disease Onset ◽

Therapeutic Effects ◽

Plasma Cytokine ◽

Cytokine Levels ◽

Pharmacodynamic Biomarkers

AbstractHuntington’s disease (HD) is caused by an expansion of the CAG repeat in the huntingtin gene leading to preferential neurodegeneration of the striatum. Disease-modifying treatments are not yet available to HD patients and their development would be facilitated by translatable pharmacodynamic biomarkers. Multi-modal magnetic resonance imaging (MRI) and plasma cytokines have been suggested as disease onset/progression biomarkers, but their ability to detect treatment efficacy is understudied. This study used the R6/2 mouse model of HD to assess if structural neuroimaging and biofluid assays can detect treatment response using as a prototype the small molecule p75NTR ligand LM11A-31, shown previously to reduce HD phenotypes in these mice. LM11A-31 alleviated volume reductions in multiple brain regions, including striatum, of vehicle-treated R6/2 mice relative to wild-types (WTs), as assessed with in vivo MRI. LM11A-31 also normalized changes in diffusion tensor imaging (DTI) metrics and diminished increases in certain plasma cytokine levels, including tumor necrosis factor-alpha and interleukin-6, in R6/2 mice. Finally, R6/2-vehicle mice had increased urinary levels of the p75NTR extracellular domain (ecd), a cleavage product released with pro-apoptotic ligand binding that detects the progression of other neurodegenerative diseases; LM11A-31 reduced this increase. These results are the first to show that urinary p75NTR-ecd levels are elevated in an HD mouse model and can be used to detect therapeutic effects. These data also indicate that multi-modal MRI and plasma cytokine levels may be effective pharmacodynamic biomarkers and that using combinations of these markers would be a viable and powerful option for clinical trials.

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