Experimental models of brainstem tumors: development of a neonatal rat model

Jallo, George I.; Penno, Margaret B.; Sukay, Lindsey; Liu, Ja Yun; Tyler, Betty; Lee, James; Carson, Benjamin S.; Guarnieri, Michael

doi:10.1007/s00381-004-1100-6

Cited by 25 publications

(13 citation statements)

References 9 publications

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“…In summary, our results, along with those from other groups, demonstrate the feasibility of using an orthotopic brainstem model for pre-clinical therapeutic testing in mice [22–26]. The development of a panel of tumorigenic cell sources from DIPG patients, for use in a brainstem xenograft context, will further advance this approach for identifying effective therapeutics for treating pediatric patients afflicted with this cancer.…”

Section: Discussionsupporting

confidence: 62%

An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing

et al. 2012

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The prognosis for diffuse infiltrating pontine gliomas (DIPG) remains extremely poor, with the majority of patients surviving less than 2 years. Here, we have adapted standard xenograft techniques to study glioma growth in the mouse brainstem, and have utilized the mouse model for studying a relevant therapeutic for treating DIPGs. bioluminescence imaging monitoring revealed a progressive increase in signal following the injection of either of two tumor cell types into the brainstem. Mice with orthotopic GS2 tumors, and receiving a single 100 mg/kg dose of temozolomide showed a lengthy period of decreased tumor luminescence, with substantially increased survival relative to untreated mice (P<0.001). A small molecule inhibitor that targets cdk4/6 was used to test AM-38 brainstem xenograft response to treatment. Drug treatment resulted in delayed tumor growth, and significantly extended survival. Our results demonstrate the feasibility of using an orthotopic brainstem tumor model in athymic mice, and for application to testing therapeutic agents in treating DIPG.

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Section: Discussionsupporting

confidence: 62%

An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing

et al. 2012

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“…Many studies indicate that the C6 glioma model best mimics the cell biological stages of early glioma progression in human. Jallo et al have recently reported an experimental brainstem tumor model in neonatal rat pups and adult rats using 9L and F98 tumor cell suspensions [24,25]. In the present study, we modified the model by changing the coordinates from 1.4 mm right and 1.0 mm anterior to lambda to 0.5 mm right and 1 mm posterior to lambda in order to ensure that the lesion would be mainly in pons.…”

Section: Discussionmentioning

confidence: 99%

Brainstem glioma progression in juvenile and adult rats

Liu

Kashyap

et al. 2008

JNS

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Objective Brainstem gliomas are common in children and have the worst prognosis of any brain tumor in children. On the other hand, brainstem gliomas are rare in adult, and clinical studies have suggested different biological behavior between young and adult. The present study was designed to develop an orthotropic C6 brainstem glioma model in young and adult rats, and to investigate the tumor biological behavior in the two age groups. Methods C6 glioma cells were stereotactically implanted into the pons of young or adult male rats. Neurological presentation and survival time were recorded. Tumor proliferation and apoptosis in brainstem gliomas of young and adult rats were determined by immunohistochemical staining of Ki-67 and TUNEL assay, respectively. Results Striking difference were found between young and adult brainstem glioma in the onset of neurological signs, duration of symptoms, survival time, tumor growth pattern, as well as tumor proliferation and apoptosis. Relatively focal tumors were observed in adult rats harboring brainstem glioma, while diffusive tumors were found in young rats. Furthermore, brainstem gliomas in adult rats were less proliferative and had more apoptosis than those in young rats. Conclusion The present study demonstrated that C6 brainstem glioma model in young and adult rats closely imitates human brainstem glioma in neurological findings and histopathology. Our findings suggest that the different growth pattern and invasiveness of brainstem glioma between children and adult could be due to the different host cellular environments between the two age groups, hence, warrant further investigation of the different host-response between childhood and adult brainstem glioma in human.

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“…4). 56,57,65,123 Wu et al 122 demonstrated that carboplatin could be locally delivered to neoplastic cells in a rat brainstem tumor model with mini-osmotic pumps, which resulted in a prolongation of survival. Moreover, Lonser et al 71 documented the safety of locally infused Gd-bound albumin via stereotactically implanted cannulas into large areas of the primate midbrain and pons, followed by other reports showing the safety of CED of chemotherapeutic agents, such as gemcitabine and carboplatin, infused into the primate brainstem, although dose-dependent toxicity has been found with carboplatin.…”

Section: New Therapeutic Perspective Strategiesmentioning

confidence: 99%

Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies

Frazier¹,

Lee²,

Thomale

et al. 2009

PED

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128

107

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Diffuse intrinsic pontine gliomas constitute ~ 60–75% of tumors found within the pediatric brainstem. These malignant lesions present with rapidly progressive symptoms such as cranial nerve, long tract, or cerebellar dysfunctions. Magnetic resonance imaging is usually sufficient to establish the diagnosis and obviates the need for surgical biopsy in most cases. The prognosis of the disease is dismal, and the median survival is < 12 months. Resection is not a viable option. Standard therapy involves radiotherapy, which produces transient neurological improvement with a progression-free survival benefit, but provides no improvement in overall survival. Clinical trials have been conducted to assess the efficacy of chemotherapeutic and biological agents in the treatment of diffuse pontine gliomas. In this review, the authors discuss recent studies in which systemic therapy was administered prior to, concomitantly with, or after radiotherapy. For future perspective, the discussion includes a rationale for stereotactic biopsies as well as possible therapeutic options of local chemotherapy in these lesions.

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Experimental models of brainstem tumors: development of a neonatal rat model

Abstract: Our results demonstrate that neonatal rat models for brainstem tumors can be prepared using known injection coordinates and orthotopic cell lines. Decreasing rates of maternal removal during the course of the work suggests that the method involves a learning curve.

Cited by 25 publications

References 9 publications

An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing

An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing

Brainstem glioma progression in juvenile and adult rats

Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies

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