Animal PET for Thioacetamide-Induced Rat Cholangiocarcinoma: A Novel and Reliable Platform

Yeh, Chun‐Nan; Lin, Kun‐Ju; Hsiao, Ing‐Tsung; Yen, Tzu‐Chen; Chen, Tsung-Wen; Jan, Yi-Yin; Chung, Y.; Lin, Chung-Fu; Chen, Miin-Fu

doi:10.1007/s11307-008-0141-8

Cited by 23 publications

(32 citation statements)

References 31 publications

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“…These inflammatory macrophages express WNT7B ligand in line with what has been described in other contexts (9)(10)(11). In xenografts of human CC cells, a transgenic murine line that develops CC (12), and also a well-validated, chemically induced rat model of CC (13)(14)(15)(16)(17) that reflects the progression of CC in humans, we find that depletion of macrophages or inhibition of the canonical WNT pathway results in reduced tumor burden. This strategy offers, for the first time to our knowledge, a small molecule approach to the treatment of CC in vivo.…”

Section: Introductionsupporting

confidence: 85%

WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited

Boulter¹,

Guest²,

Kendall³

et al. 2015

J. Clin. Invest.

233

242

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Section: Introductionsupporting

confidence: 85%

WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited

Boulter¹,

Guest²,

Kendall³

et al. 2015

J. Clin. Invest.

233

242

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“…CCA-xenograft mouse model in conjunction with PET-CT is widely applied in research on targeted drug therapy in cancers. PET-CT was also shown to be successfully applied in thioacetamide (TAA)-induced CCA rat model for detection and monitoring the progression of CCA (Laverman et al, 2007;Yeh et al, 2008). The present study was the first study which applied PET-CT as a tool (for detection and monitoring the progression of cancer) for investigation of anti-CCA activity of a candidate medicinal plant in OV/DMNinduced CCA hamster model.…”

Section: Discussionmentioning

confidence: 83%

Anticancer Activity of Atractylodes lancea (Thunb.) DC in a Hamster Model and Application of PET-CT for Early Detection and Monitoring Progression of Cholangiocarcinoma

Plengsuriyakarn¹,

Matsuda²,

Karbwang³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…SUVs were used to quantify tracer uptake according to the following formula:The SUVmax and SUVmean are maximal and mean SUV, respectively, within the voxels of interest (VOIs). Tumor counts and FDG uptake values were obtained in all animals (Yeh et al, 2008). …”

Section: Methodsmentioning

confidence: 99%

Synergistic anti-proliferative effect of mTOR inhibitor (rad001) plus gemcitabine on cholangiocarcinoma by decreasing choline kinase activity

Lin

Wang

et al. 2018

Disease Models &Amp; Mechanisms

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Although gemcitabine plus cisplatin is the gold standard chemotherapy regimen for advanced cholangiocarcinoma, the response rate has been disappointing. This study aims to investigate a novel therapeutic regimen [gemcitabine plus everolimus (rad001), an mTOR inhibitor] for cholangiocarcinoma. Gemcitabine, oxaliplatin, cetuximab and rad001 in various combinations were first evaluated in vitro using six cholangiocarcinoma cell lines. In vivo therapeutic efficacies of gemcitabine and rad001 alone and their combination were further evaluated using a xenograft mouse model and a chemically induced orthotopic cholangiocarcinoma rat model. In the in vitro study, gemcitabine plus rad001 exerted a synergistic therapeutic effect on the cholangiocarcinoma cells, irrespective of the KRAS mutation status. In the xenograft study, gemcitabine plus rad001 showed the best therapeutic effect on tumor volume change, and was associated with increased caspase-3 expression, decreased eIF4E expression, as well as overexpression of both death receptor- and mitochondrial apoptotic pathway-related genes. In a chemically induced cholangiocarcinoma-afflicted rat model, the gemcitabine plus rad001 treatment suppressed tumor glycolysis as measured by 18F-fludeoxyglucose micro-positron emission tomography. Also, increased intratumoral free choline, decreased glycerophosphocholine and nearly undetectable phosphocholine levels were demonstrated by proton nuclear magnetic resonance, supported by results of decreased choline kinase expression in western blotting. We concluded that gemcitabine plus rad001 has a synergistic antiproliferative effect on cholangiocarcinoma, irrespective of the KRAS mutation status. The antitumor effect is associated with activation of both death receptor and mitochondrial pathways, as well as the downregulation of choline kinase activity, resulting in a characteristic change in choline metabolism.

show abstract

Animal PET for Thioacetamide-Induced Rat Cholangiocarcinoma: A Novel and Reliable Platform

Abstract: We conclude that animal PET in the setting of the TAA rat model seems to be feasible for the detection of CCA. Future translational studies are needed to confirm and expand our findings.

Cited by 23 publications

References 31 publications

WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited

WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited

Anticancer Activity of Atractylodes lancea (Thunb.) DC in a Hamster Model and Application of PET-CT for Early Detection and Monitoring Progression of Cholangiocarcinoma

Synergistic anti-proliferative effect of mTOR inhibitor (rad001) plus gemcitabine on cholangiocarcinoma by decreasing choline kinase activity

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