Creation of porcine liver tumour using human hepatoma cell lines: Experimental study

Rai, Rajani; Flecknell, P. A.; Richardson, Christopher D.; Manas, D.

doi:10.4161/cbt.4.6.1707

Cited by 8 publications

(4 citation statements)

References 10 publications

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“…This success in macroscopic tumor formation is presumably the result of using a porcine SCID model. Meanwhile, no macroscopic tumor formation was observed in wild pig liver parenchyma following orthotopic transplantation of human HCC cell lines with immunosuppressive agents [7].…”

Section: Plos Onementioning

confidence: 96%

“…To overcome this limitation, studies have begun to focus on establishing large-animal xenograft models of human HCC. Accordingly, several methods have been proposed for the orthotopic transplantation of human HCC in pigs using immunosuppressive agents; however, the ensuing tumor engraftment has not yet been evaluated [7,8]. Further, the administration of immunosuppressive agents does not sufficiently allow for the effective engraftment of human HCC cell lines into the liver parenchyma of wild-type pigs.…”

Section: Introductionmentioning

confidence: 99%

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Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model

et al. 2021

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Hepatocellular carcinoma (HCC) is the fifth most common primary tumor and the third leading cause of cancer-related deaths worldwide. Rodent models of HCC have contributed to the advancement of studies investigating liver carcinogenesis, tumor-host interactions, and drug screening. However, their small size renders them unsuitable for surgical or clinical imaging studies, necessitating the development of larger-size HCC models. Here, we developed a xenograft model of human HCC in X-linked interleukin-2 receptor gamma chain gene (Il2rg)-targeted severe combined immunodeficient (SCID) pigs. HepG2 cell suspension in serum-free medium containing 50% membrane matrix was directly injected into the liver parenchyma of eight X-linked Il2rg-targeted SCID pigs (6.6–15.6 kg) via ultrasonography-guided percutaneous puncture. Tumor engraftment was evaluated weekly using ultrasonography, and cone-beam computed tomography was performed during arterial portography (CTAP) and hepatic arteriography (CTHA) to evaluate the hemodynamics of engrafted tumors. The engrafted tumors were histologically analyzed following necropsy and assessed for pathological similarities to human HCCs. Macroscopic tumor formation was observed in seven of the eight pigs (simple nodular tumors in three and multinodular tumors in four). Engrafted tumors were identified as low-echoic upon ultrasonography and as perfusion-defect nodules on the CTAP images. Meanwhile, CTHA showed that the tumors were hyperattenuating. Further, histopathological findings of the engrafted tumors were consistent with those of human HCC. In conclusion, the porcine model of human HCC, successfully generated herein, might help develop more effective therapeutic strategies for HCC.

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Section: Plos Onementioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model

et al. 2021

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“…Models similar to the anatomy and physiology of humans have been used. For the treatment of hepatic tumours with HIFU, pigs are a common model, and the development of human hepatocarcinomas in the pig has been attempted by using triple immunosuppression with results still inconclusive (Rai et al 2005). As a result, hepatic applications for HIFU are usually studied in a combination of models using VX2 tumours in rabbits to validate the therapy response (Prat et al 1995) and HIFU lesions performed on healthy pigs to validate the size of coagulation and the safety of the device (Vaezy et al 2001, Melodelima et al 2009.…”

Section: Introductionmentioning

confidence: 99%

Suitability of a tumour-mimicking material for the evaluation of high-intensity focused ultrasound ablation under magnetic resonance guidance

Pichardo¹,

Kivinen²,

Melodelima³

et al. 2013

Phys. Med. Biol.

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This study tests the suitability of a tumour-mimic for targeting magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU). An agarose-based tumour-mimic was injected as a warm solution that polymerized in tissue. Thermal characteristics and acoustic absorption of the mimic were observed within the values reported for tissues. The relaxation times at 3T were 1679 ± 15 ms for T1 and 41 ± 1 ms for T2. The mimic was clearly visible on in vivo images. With lower contrast the tumour-mimic was visible on T2-weighted images, where it was possible to detect the ablated tissue surrounding the mimic after sonications. HIFU sonications were performed to induce thermal ablation on and around the mimic using a Sonalleve system (Philips). MR thermometry maps were performed during HIFU. The average temperature when the sonication was done at the tumour-mimic was 67.6 ± 8.0 °C in vitro and 67.6 ± 5.0 °C in vivo. The average temperature for sonications at tissues was 68.4 ± 8.7 °C in vitro (liver) and 66.0 ± 2.6 °C in vivo (muscle), with no significant difference between tissue and tumour-mimic (p > 0.05). The tumour-mimic behaviour when using MR-guided HIFU was similar to tissues, showing that this mimic can be used as an alternative to tumour models for validating MR-guided HIFU devices targeting.

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“…Thus, because its size and physiology are more similar to humans, the porcine model is considered as an ideal animal model, especially for studying HIFU applied to the treatment of hepatic tumors (hepatocarcinomas and liver metastases of colorectal cancer). However, no liver tumor model has been established in the pig despite recent work on triple immunosuppression which did not succeed in developing human hepatocarcinomas in porcine liver (Rai et al 2005). Consequently, preclinical applications of high-intensity ultrasound are most often studied in healthy pig livers (ter Haar et al 1989, Makin et al 2005, Melodelima et al 2007, Sibille et al 1993, Vaezy et al 2001.…”

Section: Introductionmentioning

confidence: 99%

In vivopreclinical evaluation of the accuracy of toroidal-shaped HIFU treatments using a tumor-mimic model

et al. 2010

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The pig is an ideal animal model for preclinical evaluation of HIFU treatments, especially in the liver. However, there is no liver tumor model available for pigs. In this work, we propose to study an in vivo tumor-mimic model as a tool for evaluating if a sonographycally guided HIFU treatment, delivered by a toroidal-shaped device dedicated for the treatment of liver metastases, is correctly located in the liver. One centimeter tumor-mimics were created in liver tissues. These tumor-mimics were detectable on ultrasound imaging and on gross pathology. Two studies were carried out. First, an in vivo study of tolerance at mid-term (30 days, 10 pigs) revealed that tumor-mimics are suitable for studying HIFU treatments at a preclinical stage, since local and biological tolerances were excellent. The dimensions of the tumor-mimics were reproducible (diameter at day 0: 9.7 +/- 2.0 mm) and were the same as a function of time (p = 0.64). A second in vivo study was carried out in ten pigs. Tumor mimics were used as targets in liver tissues in order to determine if the HIFU treatment is correctly located in the liver. A procedure of extensive HIFU ablation using multiple HIFU lesions juxtaposed manually was then tested on eight tumor-mimics. In 88% of the cases (seven out of eight), tumor-mimics were treated with negative margins (>or=1 mm) in all directions. On average, negative margins measured 10.0 +/- 6.7 mm. These tumor-mimics constitute an excellent reference for studying in vivo the accuracy of HIFU therapy in the liver.

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Creation of porcine liver tumour using human hepatoma cell lines: Experimental study

Cited by 8 publications

References 10 publications

Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model

Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model

Suitability of a tumour-mimicking material for the evaluation of high-intensity focused ultrasound ablation under magnetic resonance guidance

In vivopreclinical evaluation of the accuracy of toroidal-shaped HIFU treatments using a tumor-mimic model

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