MEDULLOBLASTOMA IN CHILDREN 0–3 YEARS OLD: Forty Years' Experience in Slovenia

Kopač, Štefan; Jereb, Berta

doi:10.1080/08880010490263344

Cited by 3 publications

(2 citation statements)

References 11 publications

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“…Radiotherapy remains the single most effective treatment for various cancers, including medulloblastoma. However, after successful surgical resection followed by craniospinal radiation, it has been well documented that this treatment module induces medulloblastoma recurrence [2], [6], [33], [34]. Although radiation decreases the proliferation rate of cancer cells, several in vitro studies have demonstrated that sublethal doses of radiation resulted in increased invasiveness of cancer cells [15], [35]–[38].…”

Section: Discussionmentioning

confidence: 99%

Suppression of uPAR Retards Radiation-Induced Invasion and Migration Mediated by Integrin β1/FAK Signaling in Medulloblastoma

et al. 2010

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BackgroundDespite effective radiotherapy for the initial stages of cancer, several studies have reported the recurrence of various cancers, including medulloblastoma. Here, we attempt to capitalize on the radiation-induced aggressive behavior of medulloblastoma cells by comparing the extracellular protease activity and the expression pattern of molecules, known to be involved in cell adhesion, migration and invasion, between non-irradiated and irradiated cells.Methodology/Principal FindingsWe identified an increase in invasion and migration of irradiated compared to non-irradiated medulloblastoma cells. RT-PCR analysis confirmed increased expression of uPA, uPAR, focal adhesion kinase (FAK), N-Cadherin and integrin subunits (e.g., α3, α5 and β1) in irradiated cells. Furthermore, we noticed a ∼2-fold increase in tyrosine phosphorylation of FAK in irradiated cells. Immunoprecipitation studies confirmed increased interaction of integrin β1 and FAK in irradiated cells. In addition, our results show that overexpression of uPAR in cancer cells can mimic radiation-induced activation of FAK signaling. Moreover, by inhibiting FAK phosphorylation, we were able to reduce the radiation-induced invasiveness of the cancer cells. In this vein, we studied the effect of siRNA-mediated knockdown of uPAR on cell migration and adhesion in irradiated and non-irradiated medulloblastoma cells. Downregulation of uPAR reduced the radiation-induced adhesion, migration and invasion of the irradiated cells, primarily by inhibiting phosphorylation of FAK, Paxillin and Rac-1/Cdc42. As observed from the immunoprecipitation studies, uPAR knockdown reduced interaction among the focal adhesion molecules, such as FAK, Paxillin and p130Cas, which are known to play key roles in cancer metastasis. Pretreatment with uPAR shRNA expressing construct reduced uPAR and phospho FAK expression levels in pre-established medulloblastoma in nude mice.Conclusion/SignificanceTaken together, our results show that radiation enhances uPAR-mediated FAK signaling and by targeting uPAR we can inhibit radiation-activated cell adhesion and migration both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Suppression of uPAR Retards Radiation-Induced Invasion and Migration Mediated by Integrin β1/FAK Signaling in Medulloblastoma

et al. 2010

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“…El tratamiento de los meduloblastomas consiste en la resección quirúrgica seguido por radioterapia craneoespinal que trae consigo efectos colaterales significativos tales como déficit cognitivo y psicosocial mayor, disminución en la puntuación de coeficiente de intelectual y deficiencias endocrinológicas como hipotiroidismo e insuficiencia de la hormona del crecimiento [5][6][7][8]15 . Por ello, se ha comenzado a implementar la quimioterapia en altas dosis acompañada de la utilización de células madre como terapia de rescate en niños con un pronóstico completamente desfavorable [6][7][8]15 . Los estudios de seguimiento radioló-gico están elaborados para identificar recaídas tempranas, por lo que las terapias secundarias mejorarían de manera significativa el tratamiento.…”

Section: Tratamientounclassified

Meduloblastoma bilateral: reporte de caso y revisión de la literatura

et al. 2019

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Effects of Surgical Excision and Radiation on Medulloblastoma Cell Invasiveness

Ranger¹,

McDonald²,

Maestro

2009

Can. j. neurol. sci.

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In children, brain cancers can be particularly devastating; and medulloblastoma (MB), a primitive tumour of neuroectodermal origin, is among the most common. Rare in adults [1][2][3][4][5] , these tumours generally account for between 20 and 40% of paediatric intracranial malignancies worldwide [6][7][8][9][10][11][12] , and have an incidence of approximately 1-7 per million, depending upon the population studied and how medulloblastoma and the base populations are defined 11,[13][14][15][16] . They are especially common among preschoolers 17,18 , even among infants who are less than 18 months-of-age 19,20 . Outcomes in paediatric medulloblastoma patients, relative to those with most other childhood malignancies, tend to be poor, with five-year survival rates in ABSTRACT: Objectives: Surgical resection and adjuvant radiation are mainstays of medulloblastoma (MB) patient management. We utilized a novel 3-dimensional assay to identify how (a) radiation, (b) excision of the primary tumour aggregate, and (c) both treatments combined influence MB cell invasiveness. Methods: Five MB cell lines (UW228-1, 2 and 3; Daoy, and Madsen) were implanted onto a 3-dimensional, type I collagen gel assay to assess tumour invasion distance over five days, in response to (1) needle-assisted excision of the central cell aggregate; (2) pre-exposure to single-dose and fractionated dose irradiation in doses from 6-25 and 8-24 Gy, respectively; and (3) excision plus either single-dose or fractionated radiation. Results: Within hours, individual MB cells detached from the surface of the cell aggregates and invaded the collagen matrix, to distances up to 1200 µm and at rates up to 300 µm daily. The UW228-1 cell line was less invasive than the other cell lines and was dropped from further analysis. In the four remaining lines, a dosedependent decline in tumour invasiveness was identified, both for single-dose and fractionated radiation, which achieved statistically decreased invasion distances at higher doses, especially of fractionated irradiation. Excision of the central tumour aggregate tended towards exerting a late effect on cell invasion, but exerted no significant influence on the radio-sensitivity of residual cells. Conclusions: Both single-dose and fractionated dose irradiation appear to inhibit MB cell invasiveness in a dose-dependent manner, whereas excision of the central cell aggregate exerts no effect on residual invading cells. RÉSUMÉ: Effets de l'excision chirurgicale et de l'irradiation sur le caractère envahissant du médulloblastome.Objectifs : La résection chirurgicale et la radiothérapie sont le traitement de base du médulloblastome (MB). Nous avons utilisé une nouvelle méthode d'analyse tridimensionnelle pour identifier comment l'irradiation, l'excision de la tumeur primaire et les deux traitements combinés influencent le caractère envahissant des cellules du MB. Méthodes : Cinq lignées cellulaires de MB (UW228-1, 2, 3, Daoy et Madsen) ont été implantées dans un gel de collagène de type I tridimensionnel pour évaluer la...

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MEDULLOBLASTOMA IN CHILDREN 0–3 YEARS OLD: Forty Years' Experience in Slovenia

Cited by 3 publications

References 11 publications

Suppression of uPAR Retards Radiation-Induced Invasion and Migration Mediated by Integrin β1/FAK Signaling in Medulloblastoma

Suppression of uPAR Retards Radiation-Induced Invasion and Migration Mediated by Integrin β1/FAK Signaling in Medulloblastoma

Meduloblastoma bilateral: reporte de caso y revisión de la literatura

Effects of Surgical Excision and Radiation on Medulloblastoma Cell Invasiveness

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