Establishment of experimental glioma models at the intrinsic brainstem region of the rats

Sho, Atsuko; Kondo, Shinji; Kamitani, Hideki; Otake, Minoru; Watanabe, Takashi

doi:10.1179/016164106x115080

Cited by 16 publications

(10 citation statements)

References 24 publications

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“…Subsequent to the injection, the needle remained in place for 10 min to avoid a backflow of cells. The needle was then slowly withdrawn from the burr hole, which was closed with bone wax, then the skin was sutured (14,15). …”

Section: Methodsmentioning

confidence: 99%

Differences between brainstem gliomas in juvenile and adult rats

et al. 2013

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Clinical studies have shown that gliomas of the brainstem behave differently in children and adults. The aim of the present study was to compare and analyze the differences between these gliomas in juvenile and adult rats with regard to tumor growth, survival, pathology and magnetic resonance imaging (MRI). A total of 25 juvenile and 25 adult Wistar rats were divided into groups A (15 juvenile rats), B (10 juvenile rats), C (15 adult rats) and D (10 adult rats). The rats of groups A and C (experimental) were injected with glioma cells, while groups B and D (control) were injected with a physiological saline solution. Rat neurological signs, survival time, tumor size, hematoxylin and eosin (HE) staining and immunohistochemical staining for MMP-2, MMP-9 and β-catenin were compared. The survival time of group A was 19.47±2.232 days, whereas that of group C was 21.47±2.232 days (P<0.05). The tumor sizes were 4.55 and 4.62 mm (P>0.05) in groups A and C, respectively. HE and immunohistochemical staining revealed no differences between the groups. The results suggest that the growth patterns and invasiveness of brainstem gliomas may vary in children compared with adults due to the varied biological behaviors of the tumor cells.

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Section: Methodsmentioning

confidence: 99%

Differences between brainstem gliomas in juvenile and adult rats

et al. 2013

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“…Others have also questioned the subcutaneous inoculation method. Tumor biology in subcutaneous models remained questionable and unreliable, and orthotopic models are now the standard (17)(18)(19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Establishment of reproducible osteosarcoma rat model using orthotopic implantation technique

Sun²,

Fan³

et al. 2009

Oncol Rep

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Abstract. In experimental musculoskeletal oncology, there remains a need for animal models that can be used to assess the efficacy of new and innovative treatment methodologies for bone tumors. Rat plays a very important role in the bone field especially in the evaluation of metabolic bone diseases. The objective of this study was to develop a rat osteosarcoma model for evaluation of new surgical and molecular methods of treatment for extremity sarcoma. One hundred male SD rats weighing 125.45±8.19 g were divided into 5 groups and anesthetized intraperitoneally with 10% chloral hydrate. Orthotopic implantation models of rat osteosarcoma were performed by injecting directly into the SD rat femur with a needle for inoculation with SD tumor cells. In the first step of the experiment, 2x10 5 to 1x10 6 UMR106 cells in 50 μl were injected intraosseously into median or distal part of the femoral shaft and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from ultrasound with findings from necropsia and determining time of survival. In the third stage, the orthotopically implanted tumors and lung nodules were resected entirely, sectioned, and then counter stained with hematoxylin and eosin for histopathologic evaluation. The tumor take rate was 100% for implants with 8x10 5 tumor cells or more, which was much less than the amount required for subcutaneous implantation, with a high lung metastasis rate of 93.0%. Ultrasound and necropsia findings matched closely (r=0.942; p<0.01), which demonstrated that Doppler ultrasonography is a convenient and reliable technique for measuring cancer at any stage. Tumor growth curve showed that orthotopically implanted tumors expanded vigorously with time-lapse, especially in the first 3 weeks. The median time of survival was 38 days and surgical mortality was 0%. The UMR106 cell line has strong carcinogenic capability and high lung metastasis frequency. The present rat osteosarcoma model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. It may be a useful tool in the investigation of antiangiogenic and anticancer therapeutics. Ultrasound was found to be a highly accurate tool for tumor diagnosis, localization and measure-ment and may be recommended for monitoring tumor growth in this model.

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“…The first animal models developed for DIPG specifically involved the intracranial injection of rat glioma cell lines, F98, 9L, or C6 into the brainstem of neonatal ( 23 , 24 ) or adult ( 25 – 27 ) rats leading to the generation of brainstem glioma (BSG). All of these allogenic orthotopic models utilized a stereotactic approach for implantation of the tumor cells into specific coordinates of the rat brain, targeting the pons.…”

Section: Transplantation-based Rodent Modelsmentioning

confidence: 99%

Pre-Clinical Models of Diffuse Intrinsic Pontine Glioma

2015

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Diffuse intrinsic pontine glioma (DIPG) is a rare and incurable brain tumor that arises in the brainstem of children predominantly between the ages of 6 and 8. Its intricate morphology and involvement of normal pons tissue precludes surgical resection, and the standard of care today remains fractionated radiation alone. In the past 30 years, there have been no significant advances made in the treatment of DIPG. This is largely because we lack good models of DIPG and therefore have little biological basis for treatment. In recent years, however, due to increased biopsy and acquisition of autopsy specimens, research is beginning to unravel the genetic and epigenetic drivers of DIPG. Insight gleaned from these studies has led to improvements in approaches to both model these tumors in the lab and to potentially treat them in the clinic. This review will detail the initial strides toward modeling DIPG in animals, which included allograft and xenograft rodent models using non-DIPG glioma cells. Important advances in the field came with the development of in vitro cell and in vivo xenograft models derived directly from autopsy material of DIPG patients or from human embryonic stem cells. Finally, we will summarize the progress made in the development of genetically engineered mouse models of DIPG. Cooperation of studies incorporating all of these modeling systems to both investigate the unique mechanisms of gliomagenesis in the brainstem and to test potential novel therapeutic agents in a preclinical setting will result in improvement in treatments for DIPG patients.

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Establishment of experimental glioma models at the intrinsic brainstem region of the rats

Abstract: Because in our model the cannula is permanently implanted, additional inocula can be delivered. Here we detail our rat brainstem glioma model and discuss its usefulness for the investigation of these tumor in humans.

Cited by 16 publications

References 24 publications

Differences between brainstem gliomas in juvenile and adult rats

Differences between brainstem gliomas in juvenile and adult rats

Establishment of reproducible osteosarcoma rat model using orthotopic implantation technique

Pre-Clinical Models of Diffuse Intrinsic Pontine Glioma

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