Non-invasive dynamic monitoring initiation and growth of pancreatic tumor in the LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre (KPC) transgenic mouse model

Su Hu, Liang Pan, Junjie Shangguan, Matteo Figini, Aydin Eresen, Chong Sun, Bin Wang, Quanhong Ma, Chunhong Hu, Vahid Yaghmai, Yury Velichko, Jia Yang*, Zhuoli Zhang

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre (KPC) mouse is one of the most widely used transgenic models to evaluate tumor characteristics and to develop novel therapies for pancreatic ductal adenocarcinoma (PDAC). There is no report of the effective systemic evaluation of longitudinal KPC tumor imitation and growth. Therefore, we aimed to characterize the initiation and progression of pancreatic cancer in KPC mice using longitudinal multiparametric magnetic resonance imaging (MRI) approaches and overall survival. Ten KPC mice were used to develop spontaneous PDAC and monitored by MRI. Tumor growth was evaluated using weekly acquired MRI data. The relationship between diffusion-weighted MRI (DW-MRI) imaging biomarkers (apparent diffusion coefficient - ADC) and tumor fibrosis measurement by pathological methods was assessed by Pearson correlation coefficient. Six KPC mice developed spontaneously pancreatic tumors at the age of 20.0 ± 2.9 weeks with a relatively short life span (6.8 ± 1.8 weeks). The tumors could be detected by MRI with a minimum diameter of 3.88 ± 1.18 mm (range, 2.18–5.20 mm), showing a rapid growth curve according to both the longest diameter (1.63 ± 0.52 mm/week) and tumor volume (148.77 ± 80.87 mm 3 )/week. Pathological results confirmed that the tumors display histopathological features of human pancreatic cancer. A strong correlation between ADC values and fibrosis measurements was observed (R = −0.825, P =.043). Our results show that the initiation and progression of pancreatic tumor in KPC mice can be evaluated by longitudinally non-invasive dynamic MRI approaches. The findings will be the fundamental KPC background data for developing novel therapeutic approaches, in particular for evaluation of response to novel treatments.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalJournal of Immunological Methods
Volume465
DOIs
StatePublished - Feb 1 2019

Fingerprint

Transgenic Mice
Growth
Magnetic Resonance Imaging
Neoplasms
Pancreatic Neoplasms
Adenocarcinoma
Fibrosis
Diffusion Magnetic Resonance Imaging
Tumor Burden
Biomarkers
Survival
Therapeutics

Keywords

  • KPC mouse model
  • Magnetic resonance imaging
  • Pancreatic cancer
  • Tumorigenesis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Hu, Su ; Pan, Liang ; Shangguan, Junjie ; Figini, Matteo ; Eresen, Aydin ; Sun, Chong ; Wang, Bin ; Ma, Quanhong ; Hu, Chunhong ; Yaghmai, Vahid ; Velichko, Yury ; Yang, Jia ; Zhang, Zhuoli. / Non-invasive dynamic monitoring initiation and growth of pancreatic tumor in the LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre (KPC) transgenic mouse model In: Journal of Immunological Methods. 2019 ; Vol. 465. pp. 1-6.
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abstract = "The LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre (KPC) mouse is one of the most widely used transgenic models to evaluate tumor characteristics and to develop novel therapies for pancreatic ductal adenocarcinoma (PDAC). There is no report of the effective systemic evaluation of longitudinal KPC tumor imitation and growth. Therefore, we aimed to characterize the initiation and progression of pancreatic cancer in KPC mice using longitudinal multiparametric magnetic resonance imaging (MRI) approaches and overall survival. Ten KPC mice were used to develop spontaneous PDAC and monitored by MRI. Tumor growth was evaluated using weekly acquired MRI data. The relationship between diffusion-weighted MRI (DW-MRI) imaging biomarkers (apparent diffusion coefficient - ADC) and tumor fibrosis measurement by pathological methods was assessed by Pearson correlation coefficient. Six KPC mice developed spontaneously pancreatic tumors at the age of 20.0 ± 2.9 weeks with a relatively short life span (6.8 ± 1.8 weeks). The tumors could be detected by MRI with a minimum diameter of 3.88 ± 1.18 mm (range, 2.18–5.20 mm), showing a rapid growth curve according to both the longest diameter (1.63 ± 0.52 mm/week) and tumor volume (148.77 ± 80.87 mm 3 )/week. Pathological results confirmed that the tumors display histopathological features of human pancreatic cancer. A strong correlation between ADC values and fibrosis measurements was observed (R = −0.825, P =.043). Our results show that the initiation and progression of pancreatic tumor in KPC mice can be evaluated by longitudinally non-invasive dynamic MRI approaches. The findings will be the fundamental KPC background data for developing novel therapeutic approaches, in particular for evaluation of response to novel treatments.",
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Non-invasive dynamic monitoring initiation and growth of pancreatic tumor in the LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre (KPC) transgenic mouse model . / Hu, Su; Pan, Liang; Shangguan, Junjie; Figini, Matteo; Eresen, Aydin; Sun, Chong; Wang, Bin; Ma, Quanhong; Hu, Chunhong; Yaghmai, Vahid; Velichko, Yury; Yang, Jia; Zhang, Zhuoli.

In: Journal of Immunological Methods, Vol. 465, 01.02.2019, p. 1-6.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Non-invasive dynamic monitoring initiation and growth of pancreatic tumor in the LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre (KPC) transgenic mouse model

AU - Hu, Su

AU - Pan, Liang

AU - Shangguan, Junjie

AU - Figini, Matteo

AU - Eresen, Aydin

AU - Sun, Chong

AU - Wang, Bin

AU - Ma, Quanhong

AU - Hu, Chunhong

AU - Yaghmai, Vahid

AU - Velichko, Yury

AU - Yang, Jia

AU - Zhang, Zhuoli

PY - 2019/2/1

Y1 - 2019/2/1

N2 - The LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre (KPC) mouse is one of the most widely used transgenic models to evaluate tumor characteristics and to develop novel therapies for pancreatic ductal adenocarcinoma (PDAC). There is no report of the effective systemic evaluation of longitudinal KPC tumor imitation and growth. Therefore, we aimed to characterize the initiation and progression of pancreatic cancer in KPC mice using longitudinal multiparametric magnetic resonance imaging (MRI) approaches and overall survival. Ten KPC mice were used to develop spontaneous PDAC and monitored by MRI. Tumor growth was evaluated using weekly acquired MRI data. The relationship between diffusion-weighted MRI (DW-MRI) imaging biomarkers (apparent diffusion coefficient - ADC) and tumor fibrosis measurement by pathological methods was assessed by Pearson correlation coefficient. Six KPC mice developed spontaneously pancreatic tumors at the age of 20.0 ± 2.9 weeks with a relatively short life span (6.8 ± 1.8 weeks). The tumors could be detected by MRI with a minimum diameter of 3.88 ± 1.18 mm (range, 2.18–5.20 mm), showing a rapid growth curve according to both the longest diameter (1.63 ± 0.52 mm/week) and tumor volume (148.77 ± 80.87 mm 3 )/week. Pathological results confirmed that the tumors display histopathological features of human pancreatic cancer. A strong correlation between ADC values and fibrosis measurements was observed (R = −0.825, P =.043). Our results show that the initiation and progression of pancreatic tumor in KPC mice can be evaluated by longitudinally non-invasive dynamic MRI approaches. The findings will be the fundamental KPC background data for developing novel therapeutic approaches, in particular for evaluation of response to novel treatments.

AB - The LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre (KPC) mouse is one of the most widely used transgenic models to evaluate tumor characteristics and to develop novel therapies for pancreatic ductal adenocarcinoma (PDAC). There is no report of the effective systemic evaluation of longitudinal KPC tumor imitation and growth. Therefore, we aimed to characterize the initiation and progression of pancreatic cancer in KPC mice using longitudinal multiparametric magnetic resonance imaging (MRI) approaches and overall survival. Ten KPC mice were used to develop spontaneous PDAC and monitored by MRI. Tumor growth was evaluated using weekly acquired MRI data. The relationship between diffusion-weighted MRI (DW-MRI) imaging biomarkers (apparent diffusion coefficient - ADC) and tumor fibrosis measurement by pathological methods was assessed by Pearson correlation coefficient. Six KPC mice developed spontaneously pancreatic tumors at the age of 20.0 ± 2.9 weeks with a relatively short life span (6.8 ± 1.8 weeks). The tumors could be detected by MRI with a minimum diameter of 3.88 ± 1.18 mm (range, 2.18–5.20 mm), showing a rapid growth curve according to both the longest diameter (1.63 ± 0.52 mm/week) and tumor volume (148.77 ± 80.87 mm 3 )/week. Pathological results confirmed that the tumors display histopathological features of human pancreatic cancer. A strong correlation between ADC values and fibrosis measurements was observed (R = −0.825, P =.043). Our results show that the initiation and progression of pancreatic tumor in KPC mice can be evaluated by longitudinally non-invasive dynamic MRI approaches. The findings will be the fundamental KPC background data for developing novel therapeutic approaches, in particular for evaluation of response to novel treatments.

KW - KPC mouse model

KW - Magnetic resonance imaging

KW - Pancreatic cancer

KW - Tumorigenesis

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