scholarly journals ETMR-03. THE ROLE OF FOXR2 IN PEDIATRIC BRAIN CANCER

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii323-iii323
Author(s):  
Felix Schmitt-Hoffner ◽  
Sjoerd van Rijn ◽  
Jens-Martin Hübner ◽  
Sander Lambo ◽  
Monika Mauermann ◽  
...  
Keyword(s):  
Pediatric Brain Tumors ◽  
Tumor Formation ◽  
Human Neural Stem Cells ◽  
Chip Sequencing ◽  
Nsg Mice ◽  
Forkhead Box ◽  
Neuroectodermal Tumors ◽  
The Central Nervous System ◽  
Pediatric Brain

Abstract Forkhead Box R2 (FOXR2) is a transcription factor of the Forkhead Box family that has been correlated with tumorigenesis, aberrant cell growth or tumor progression. Expression of FOXR2 in pediatric brain tumors is, besides in subsets of medullo-, pineo- and glioblastoma, primarily present in CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2), a novel entity that we in 2016 identified from the former class of primitive neuroectodermal tumors of the central nervous system (CNS-PNET). Analyzing CNS-NB-FOXR2 tumors we found that FOXR2 mRNA is expressed in an anti-correlative manner compared to the proto-oncogenes MYC and MYCN. With immunoprecipitation analyses we show that FOXR2 binds to MYC and MYCN and is thereby stabilizing these proteins. These observations on the interaction and the anti-correlative manner suggest that FOXR2 and MYC(N) may drive tumor formation in a molecularly similar fashion. To investigate this further we stably expressed FOXR2, MYCN and MYC and a combination of FOXR2 with MYC(N) in human neural stem cells (hNSC) and injected these in the striatum of NSG mice. We could show that hNSC itself do not from a tumor, whereas the expression of FOXR2 and/or MYC(N) in hNSC results in tumorigenesis. Tumors expressing both, FOXR2 and MYC(N) were growing faster than tumors with FOXR2 alone. In addition, tumors are currently being analyzed by ChIP-sequencing for FOXR2, MYC, and MYCN, to better understand the mechanisms how FOXR2 drives tumor formation compared to its interaction partners MYC and MYCN.

scholarly journals PDTM-09. Yap1 FUNCTION IN SEX-BIASED MEDULLOBLASTOMA FORMATION AND ANTI-TUMOR IMMUNITY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi188-vi188
Author(s):  
Nourhan Abdelfattah ◽  
Sivaraman Natarajan ◽  
Yaohui Chen ◽  
Kin-Hoe Chow ◽  
Shu-hsia Chen ◽  
...  
Keyword(s):  
Cytotoxic T Cells ◽  
Therapeutic Benefit ◽  
Tumor Formation ◽  
Normal Brain ◽  
A Cell ◽  
Developing Mouse Brain ◽  
Pediatric Brain ◽  
Normal Brain Development ◽  
Extended Survival

Abstract Immunotherapies offer remarkable potential to provide robust therapeutic benefit. Patients suffering from medulloblastoma (MB), the most frequent pediatric brain malignancy, can especially benefit from this approach, minimizing the devastating side effects of aggressive radiation and chemotherapies that disrupt normal brain development. However, regulators of the immune landscape remain poorly understood and no effective immunotherapies exist yet for MB. Here, we describe a sex-dependent Yap1 function in fSmoM2;GFAPcre SHH-MB (SG) mouse model. We show that Yap1 is both a cell-autonomous regulator of MB stem-cells and a non-cell-autonomous regulator of immune infiltrates in SHH-MB. Yap1 deletion in SG mice results in increased neuronal differentiation, significantly extended survival, and enhanced infiltration of peripheral blood immune cells (including cytotoxic T-cells, neutrophils, and macrophages). Additionally, this rescue phenotype is observed in a sex-biased manner: 65% of Yap1f/f;fSmoM2;GFAPcre males are rescued in contrast to 35% of females. These observations implicate Yap1 as a mediator of sex-biased brain-tumor formation, either through direct modulation of MB cells and/or through indirectly mediating the MB immune landscape. We are currently testing the role of sex-specific differences in the developing mouse brain to elucidate context-dependent function of Yap1 in MB genesis and maintenance.

scholarly journals MPC-09 THE OPTIMIZATION OF TREATMENTS FOR SO-CALLED PRIMITIVE NEUROECTODERMAL TUMORS WITH MOLECULAR ANALYSIS

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii23-ii24
Author(s):  
Mario Suzuki ◽  
Naohide Fujita ◽  
Ikuko Ogino ◽  
Junya Fujimura ◽  
Akihide Kondo
Keyword(s):  
Molecular Analysis ◽  
High Grade Glioma ◽  
Pediatric Brain Tumors ◽  
High Throughput Analysis ◽  
Institutional Review ◽  
Neuroectodermal Tumors ◽  
Molecular Information ◽  
Pediatric Brain ◽  
Informed Parental Consent

Abstract INTRODUCTION In the previous WHO classification of central nervous tumors, the supratentorial tumors comprise small round blue cells with aggressive clinical features had been defined as primitive neuroectodermal tumor (PNET). Recent molecular analysis revealed that they do not belong to a single entity, but they are re-classified as the tumors of other well-defined tumors and newly defined tumor species. These facts were reflected to the new classifications. While, there are few studies those showed the re-consideration of treatments for tumors diagnosed as so-called PNET. In this study, we propose the optimization of treatments for tumors diagnosed by the new classification to clarify which treatments were effective for the tumors those were diagnosed as PNET. MATERIALS AND METHODS The tumor samples diagnosed as so-called PNETs were analyzed. The molecular information was extracted from tumor specimens. We used high throughput analysis with microarray, FISH, and immunohistochemistry. They all had treated in our institution in last 6 years and their clinical courses were followed by medical records. Informed parental consent was obtained from their guardians and this study was approved by the institutional review board of Juntendo university. RESULTS Nine tumor samples were able to be analyzed and they are re-classified into high-grade glioma, neuroblastoma, sarcoma, embryonal tumors with multilayered rosettes, C19MC altered (ETMR). They resembled each other closely in morphology, and therefore, it was not able to be classified by histopathological findings. There was a case of pineoblastoma, whose molecular background suggested that the tumor was re-classified into neuroblastoma. In terms of treatments, we have succeeded in neuroblastoma cases so far, ETMRs were required multiple surgeries and radiations to maintain remissions. CONCLUSIONS Re-classification of diagnosis based on the molecular background is necessary to clarify the optimization of treatments for pediatric brain tumors, and the comprehensive methods is required. We present our methods for molecular diagnosis in clinical field and future plans.

scholarly journals Cerebrospinal fluid cytology of choroid plexus tumor: A report of two cases

CytoJournal ◽  
2019 ◽  
Vol 16 ◽  
pp. 9
Author(s):  
Manjari Kishore ◽  
Prajwala Gupta ◽  
Minakshi Bhardwaj
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Choroid Plexus Papilloma ◽  
Female Child ◽  
Pediatric Brain Tumors ◽  
Choroid Plexus Tumor ◽  
The Central Nervous System ◽  
Pediatric Brain ◽  
Plexus Papilloma ◽  
Fluid Cytology

Choroid plexus tumors (CPTs) are relatively uncommon tumors of the central nervous system, constituting approximately 5% of all pediatric brain tumors. Although squash cytology of CPT has been described in literature, shedding of tumor cells into cerebrospinal fluid (CSF) has rarely been described. We report two such cases of atypical choroid plexus papilloma in a 5-month-old male child and a 12-year-old female child, where characteristic cytomorphology of CPT was noted in the CSF.

Role of intraoperative ultrasound in resection of pediatric brain tumors

2010 ◽  
Vol 26 (9) ◽  
pp. 1189-1193 ◽  
Author(s):  
Mohamed Ahmed El Beltagy ◽  
Mohamed Aggag ◽  
Mohamed Kamal
Keyword(s):  
Brain Tumors ◽  
Intraoperative Ultrasound ◽  
Pediatric Brain Tumors ◽  
Pediatric Brain

Epigenetic mechanisms regulating neural development and pediatric brain tumor formation

2011 ◽  
Vol 8 (2) ◽  
pp. 119-132 ◽  
Author(s):  
Claudia M. C. Faria ◽  
James T. Rutka ◽  
Christian Smith ◽  
Paul Kongkham
Keyword(s):  
Brain Tumors ◽  
Neural Development ◽  
Treatment Strategies ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Tumor Formation ◽  
Cancer Epigenetics ◽  
Development And Differentiation ◽  
Altered Gene ◽  
Pediatric Brain

Pediatric brain tumors are the leading cause of cancer-related death in children, and among them, embryonal tumors represent the largest group with an associated poor prognosis and long-term morbidity for survivors. The field of cancer epigenetics has emerged recently as an important area of investigation and causation of a variety of neoplasms, and is defined as alterations in gene expression without changes in DNA sequence. The best studied epigenetic modifications are DNA methylation, histone modifications, and RNA-based mechanisms. These modifications play an important role in normal development and differentiation but their dysregulation can lead to altered gene function and cancer. In this review the authors describe the mechanisms of normal epigenetic regulation, how they interplay in neuroembryogenesis, and how these can cause brain tumors in children when dysregulated. The potential use of epigenetic markers to design more effective treatment strategies for children with malignant brain tumors is also discussed.

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy in pediatric brain tumors

2008 ◽  
Vol 8 (1) ◽  
pp. 121-132 ◽  
Author(s):  
Simon S Lo ◽  
Achilles J Fakiris ◽  
Ramzi Abdulrahman ◽  
Mark A Henderson ◽  
Eric L Chang ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Stereotactic Radiosurgery ◽  
Stereotactic Radiotherapy ◽  
Pediatric Brain Tumors ◽  
Fractionated Stereotactic Radiotherapy ◽  
Pediatric Brain

scholarly journals NCOG-39. PROGRESSION-FREE AND SURVIVAL RATE OF CHEMOTHERAPY IN PEDIATRICS WITH OPTIC PATHWAY GLIOMAS: A SYSTEMATIC REVIEW

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii137-ii137
Author(s):  
Vega Pangaribuan ◽  
Jemmy Kurniawan ◽  
Doni Widyandana
Keyword(s):  
Systematic Review ◽  
Progression Free Survival ◽  
Pediatric Brain Tumors ◽  
High Rate ◽  
Optic Pathway ◽  
Inclusion Criteria ◽  
Free Survival ◽  
Pediatric Brain ◽  
Optic Pathway Gliomas

Abstract BACKGROUND Optic pathway gliomas (OPG) are typically astrocytic neoplasms that represent 3-5% of all pediatric brain tumors. The prognosis of these tumors has often been poor. Total surgical resection of OPG is not amenable, thus the role of surgery remains limited. Chemotherapy can be considered as the main modality of treatment; it is also able to postpone the use of radiotherapy which may harm the brain growth in children. METHODS We conducted the PRISMA-guided systematic literature search from 6 electronic databases to identify studies reporting outcomes of chemotherapy in OPG patients. The inclusion criteria are literature reporting the survival outcomes of chemotherapy in OPG patients with minimum subjects of 10 patients and aged below 22 years old. RESULTS A total of 48 out of 557 studies were assessed for its full paper eligibility. Thus, we found 10 studies comprising of 451 patients that met the inclusion criteria for analysis. From 8 different regimens of chemotherapy that were reported, the most commonly used regimens are Carboplastin ± Vincristine. The 3-year, 5-year, and 10-year progression-free survival (PFS) rates were ranged from 23-70%, 34-73%, and 47.1% respectively. The 3-year, 5-year, and 10-year overall survival (OS) rate has a range of 91-95%, 70.1-97%, and 61.3%-62.3% respectively. In detail, we found that 1 study with Cisplatin with Etoposide regimens reported 0% of the 5-year PFS rate, therefore it was excluded from the analysis. There are 2 studies that reported a high rate of 5-year radiotherapy free survival with chemotherapy, ranging from 61-82%. CONCLUSION This systematic review showed that chemotherapy in patients with OPG leads to an unsatisfactory 5-year PFS rate (34-73%), however it is able to provide a high 5-year OS (91-95%). In the absence of good quality control for these studies, future prospective clinical trials with adjusted confounding factors are urgently needed.

Role of temozolomide in pediatric brain tumors

2006 ◽  
Vol 22 (7) ◽  
pp. 652-661 ◽  
Author(s):  
Giuseppe Barone ◽  
Palma Maurizi ◽  
Giampiero Tamburrini ◽  
Riccardo Riccardi
Keyword(s):  
Brain Tumors ◽  
Pediatric Brain Tumors ◽  
Pediatric Brain
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