Bioluminescence Imaging of Angiogenesis in a Murine Orthotopic Pancreatic Cancer Model

Angst, Eliane; Chen, Monica; Mojadidi, Michelle; Hines, Oscar J.; Reber, Howard A.; Eibl, Guido

doi:10.1007/s11307-010-0310-4

Cited by 17 publications

(14 citation statements)

References 26 publications

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“…Angiogenesis inhibitor drugs, such as sorafenib and bevacizumab, have opened a wide range of clinical applications for VEGF-based strategies in the liver [31]. BLI of angiogenesis represents an attractive tool to monitor progression of a disease and evaluate efficacy of a therapy [13, 32-34]. …”

Section: Discussionmentioning

confidence: 99%

Expression of VEGFR-2 during Liver Regeneration after Partial Hepatectomy in a Bioluminescence Mouse Model

et al. 2017

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Background: Liver regeneration requires the formation of new blood vessels. Endothelial cell proliferation is stimulated by vascular endothelial growth factor (VEGF) and its receptor tyrosine kinase VEGFR-2. The aim of this study was to investigate VEGFR-2 expression in vivo during liver regeneration after partial hepatectomy (PHx). Methods: Transgenic VEGFR-2-luc mice were used in which the luciferase reporter gene was under control of the VEGFR-2 promoter. Following 2/3 PHx, the mice underwent in vivo bioluminescence imaging until the 14th postoperative day. Additionally, liver tissue was analyzed by immunohistochemistry, in vitro luminescence assays, and quantitative RT-PCR. Results: In vivo bioluminescence imaging showed a significant increase in VEGFR-2 promoter activity after PHx. Maximum signal was recorded on the 3rd day; 8 days postoperatively the signal intensity decreased significantly. On the 14th day, bioluminescence signal reached almost baseline levels. Immunohistochemistry, quantitative RT-PCR, and in vitro luminescence confirmed a significant increase on the 3rd day following resection. The mRNA expression of VEGFR-2 was significantly higher on day 3 than preoperatively as well as on day 8. Conclusion: In vivo bioluminescence imaging with transgenic VEGFR-2-luc mice is feasible and provides a convenient model for noninvasively studying VEGFR-2 expression during liver regeneration. This may facilitate further experiments with modulation of angiogenesis by different substances.

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Section: Discussionmentioning

confidence: 99%

Expression of VEGFR-2 during Liver Regeneration after Partial Hepatectomy in a Bioluminescence Mouse Model

et al. 2017

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“…In that model, tumors are grown subcutaneously in donor mice, then a 1 mm 3 piece is transplanted into a small pocket in the pancreas tail of a recipient mouse. [6][7][8]17 Primary tumor growth may be monitored using bioluminescence imaging using donor tumors derived from luciferase-tagged tumor cells. In contrast to the orthotopic model described here, transplantation models require additional time (up to 1 month) and additional mice for generation of donor tumors.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9] In contrast to in vitro cell-based assays of pancreatic cancer cell behavior and subcutaneous in vivo models of pancreatic cancer, orthotopic models allow investigation of tumor cell interactions with the pancreatic microenvironment. The kinetics of disease progression are highly reproducible in orthotopic models and occur over a short time frame (weeks), which makes them well suited to pre-clinical testing of novel therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Bioluminescent Orthotopic Model of Pancreatic Cancer Progression

Chai

Kim-Fuchs

Angst

et al. 2013

JoVE

Self Cite

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Pancreatic cancer has an extremely poor five-year survival rate of 4-6%. New therapeutic options are critically needed and depend on improved understanding of pancreatic cancer biology. To better understand the interaction of cancer cells with the pancreatic microenvironment, we demonstrate an orthotopic model of pancreatic cancer that permits non-invasive monitoring of cancer progression. Luciferase-tagged pancreatic cancer cells are resuspended in Matrigel and delivered into the pancreatic tail during laparotomy. Matrigel solidifies at body temperature to prevent leakage of cancer cells during injection. Primary tumor growth and metastasis to distant organs are monitored following injection of the luciferase substrate luciferin, using in vivo imaging of bioluminescence emission from the cancer cells. In vivo imaging also may be used to track primary tumor recurrence after resection. This orthotopic model is suited to both syngeneic and xenograft models and may be used in pre-clinical trials to investigate the impact of novel anti-cancer therapeutics on the growth of the primary pancreatic tumor and metastasis. Video LinkThe video component of this article can be found at

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“…Bioluminescence imaging (BLI), especially, demonstrates the most desirable combination of high sensitivity and easy handling (5) and is suitable for acquire signal deep in tissue (6). It has been widely used for monitoring different cancer biological processes [angiogenesis (7,8), infinite proliferation and meta stasis (9,10), multidrug resistance (11,12)] and assessing the efficacy of different therapeutic modalities (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Real-time bioluminescence and tomographic imaging of gastric cancer in a novel orthotopic mouse model

Liu

Yao

et al. 2012

Oncol Rep

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Abstract. Gastric cancer is the second leading cause of cancer mortality worldwide. Understanding the multistep process of carcinogenesis of gastric cancer is pivotal to develop novel therapeutic strategies. Molecular imaging in preclinical cancer models bridges the gap of laboratory-based experiment and clinical translation. To this end, the human gastric cancer cell line SGC-7901 was established to stably express luciferase and GFP by lentiviral transduction (SGC7901-Luc-GFP). Preclinical models were developed by orthotopic transplantation of SGC-7901-Luc-GFP into the sub-serosal layer of the stomach of immunocompromised mice. Tumor progression and therapeutic responses were dynamically tracked by bioluminescence imaging (BLI). Bioluminescence tomography (BLT) was used to monitor stereoscopic morphological and signal changes during tumor progression. Good correlation between cell number and bio luminescence/ fluorescence intensity was observed (R 2 =0.9983/r 2 =0.9974) in vitro. Tumor progression and therapeutic response could be successfully followed directly by BLI. Importantly, BLT provided a more accurate spatial location and tomographic quantification of the internal lesion. In conclusion, our novel bioluminescence-based preclinical gastric cancer models enable superior, noninvasive monitoring gastric cancer progression and their drug responses. The BLT technique in particular, may have great potential for future oncological studies.

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Bioluminescence Imaging of Angiogenesis in a Murine Orthotopic Pancreatic Cancer Model

Cited by 17 publications

References 26 publications

Expression of VEGFR-2 during Liver Regeneration after Partial Hepatectomy in a Bioluminescence Mouse Model

Expression of VEGFR-2 during Liver Regeneration after Partial Hepatectomy in a Bioluminescence Mouse Model

Bioluminescent Orthotopic Model of Pancreatic Cancer Progression

Real-time bioluminescence and tomographic imaging of gastric cancer in a novel orthotopic mouse model

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