Molecular Proteomic Characterization of a Pediatric Medulloblastoma Xenograft

Tsangaris, George T.; Dimas, Konstantinos; Malamou, Angeliki; Katsafadou, Angeliki I.; Papathanasiou, Chrissa; Stravopodis, Dimitrios J.; Vorgias, Constantinos E.; Gazouli, Maria; Anagnostopoulos, Athanasios K.

doi:10.21873/cgp.20037

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…Peritoneal and hepatic injection techniques could be considered to develop a metastatic neuroblastoma model in future studies as evidenced by the liver and peritoneal tumor growth identified early in model creation. Lastly, while we characterized the tumors by histologic staining, more rigorous methods for tumor characterization, such as proteomics, could be pursued as some studies have shown that the xenograft proteome do not necessarily mimic the native tumor proteome (16). Future studies could explore the proteomic differences of xenograft tumors from different sources and how this may influence tumor behavior in a xenograft model.…”

Section: Discussionmentioning

confidence: 99%

Development of a Simple and Reproducible Cell-derived Orthotopic Xenograft Murine Model for Neuroblastoma

DOYLE,

HASSAN,

SUTTER

et al. 2024

In Vivo

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Background/Aim: Neuroblastoma is a common childhood cancer with poor survival for children with highrisk disease, and ongoing research to improve outcomes is needed. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are reliable models for oncologic research; however, they are resource-intensive, expensive, and require significant expertise to develop and maintain. We developed an orthotopic xenograft murine model of neuroblastoma that utilizes cryopreserved banks of human neuroblastoma cell lines, requires minimal equipment, and is easily reproducible. Materials and Methods: The neuroblastoma cell line NB1643 was obtained from the Children's Oncology Group (COG) Childhood Cancer Repository. Nod-SCID-gamma (NSG) mice underwent orthotopic injection of 2x10 6 NB1643 cells suspended in 10 μl of collagen hydrogel directly into the adrenal gland via an open retroperitoneal surgical approach. Mice were monitored by ultrasound and in vivo imaging system (IVIS) until the tumor reached the volume of the ipsilateral kidney. Tumor identity was confirmed by necropsy and histologic analysis. Results: A total of 55 mice underwent surgery. Eight died due to anesthetic or surgical complications. 39/47 (78%) survivors grew primary adrenal tumors. Average anesthesia time was 30 min. Ultrasound and IVIS successfully characterized tumor growth in all mice. Average time to target tumor size was 5 weeks (range=3-9). Gross pathologic and histologic analysis confirmed adrenal tumors consistent with neuroblastoma in all mice with adrenal masses. Conclusion: A cell-derived orthotopic xenograft murine model can be successfully used to create an in vivo model of neuroblastoma. This model can be utilized in environments where PDX or GEMM models are not feasible.

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Section: Discussionmentioning

confidence: 99%

Development of a Simple and Reproducible Cell-derived Orthotopic Xenograft Murine Model for Neuroblastoma

DOYLE,

HASSAN,

SUTTER

et al. 2024

In Vivo

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“…In medulloblastoma, the most common CNS tumor in children, patient-derived samples have been successfully xenografted into the flanks of nude mice and could be serially passaged in vivo 140 , 141 . These studies have allowed for the study of medulloblastoma tumor biology and molecular characterization, leading to a greater understanding of the disease 141 , 142 . PDX and PDOX mouse models now exist for all four major molecular groups of medulloblastoma 19 .…”

Section: Xenograft Models In Central Nervous System Malignanciesmentioning

confidence: 99%

Xenograft models for pediatric cancer therapies

McNerney¹,

Teachey²

2021

Fac Rev

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The prognosis for childhood cancer has improved considerably over the past 50 years. This improvement is attributed to well-designed clinical trials which have incorporated chemotherapy, surgery, and radiation. With an increased understanding of cancer biology and genetics, we have entered an era of precision medicine and immunotherapy that provides potential for improved cure rates. However, preclinical evaluation of these therapies is more nuanced, requiring more robust animal models. Evaluation of targeted treatments requires molecularly defined xenograft models that can capture the diversity within pediatric cancer. The development of novel immunotherapies ideally involves the use of animal models that can accurately recapitulate the human immune response. In this review, we provide an overview of xenograft models for childhood cancers, review successful examples of novel therapies translated from xenograft models to the clinic, and describe the modern tools of xenograft biobanks and humanized xenograft models for the study of immunotherapies.

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“…population, pre-operative diagnosis may be challenging since radiological features may differ from pediatric cases, for example in terms of lower contrast enhancement (9). Standard treatments for children are usually based on the multimodal combination of surgery plus adjuvant craniospinal radiotherapy with or without chemotherapy (10,11).…”

mentioning

confidence: 99%

Salvage Re-irradiation Options in Adult Medulloblastoma: A Case Report and Review of the Literature

Cuccia

Mortellaro²,

Ognibene³

et al. 2020

In Vivo

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Background/Aim: Medulloblastoma is a rare tumor of adult age, while it occurs more frequently in children. Given the rarity, there is a lack of evidence for the treatment of recurrent disease. Few data are available about salvage reirradiation collecting very heterogeneous series. Case Report: A 51-year-old male presented with headache, nausea, double vision, and gait disorders. A contrast-enhanced brain-MRI showed the presence of multifocal medulloblastoma. After surgery, adjuvant craniospinal radiotherapy was performed, chemotherapy was stopped due to toxicity. After 27 months, a new MRI and a Methionine-PET revealed a late pontocerebellar relapse; multidisciplinary board decided for a SBRT treatment. The second course of RT was well tolerated and 14 months later, the patient is alive in good general conditions, with no evidence of disease. Conclusion: Our experience supports the use of salvage stereotactic radiotherapy as a safe and effective treatment option. Medulloblastoma is one of the most common central nervous system tumors of childhood (1), while it has an extremely lower incidence in the adult age, particularly in >40 years patients (2). Furthermore, in older patients it may occur with unusual presentations, like multifocal disease, of which only six cases are described in the literature (3-8). Due to its rarity in the older 1283 This article is freely accessible online.

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Molecular Proteomic Characterization of a Pediatric Medulloblastoma Xenograft

Abstract: Abstract. Background

Cited by 5 publications

References 17 publications

Development of a Simple and Reproducible Cell-derived Orthotopic Xenograft Murine Model for Neuroblastoma

Development of a Simple and Reproducible Cell-derived Orthotopic Xenograft Murine Model for Neuroblastoma

Xenograft models for pediatric cancer therapies

Salvage Re-irradiation Options in Adult Medulloblastoma: A Case Report and Review of the Literature

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