Radiobiologic response of medulloblastoma cell lines: involvement of β-catenin?

Salaroli, Roberta; Tomaso, Tiziano Di; Ronchi, Alice; Ceccarelli, Claudio; Cammelli, S.; Cappellini, Alessandra; Martinelli, G.; Barbieri, Enza; Giangaspero, Felice; Cenacchi, Giovanna

doi:10.1007/s11060-008-9659-5

Cited by 17 publications

(28 citation statements)

References 47 publications

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“…D283MED and DAOY cells were harvested 8,16,24,29,40 and 48 h after the addition of LiCl and total protein extracts were prepared as previously described (29), using the following extraction buffer: 1% Triton, 10% glycerol, 50 mM Tris pH 7.4, 150 mM NaCl, 2 mM EDTA pH 8.0, 2 mM MgCl 2 , 50 mM sodium fluoride, 10 mM sodium pyrophosphate, 1 mM sodium orthovanadate and Complete EDTA-free (Roche Diagnostic; Indianapolis, IN) 2X.…”

Section: Methodsmentioning

confidence: 99%

“…Nuclear proteins were extracted 24, 29, 32, 40 and 48 h after the addition of LiCl, as previously described (29). Aliquots of nuclear pellets were stained with hematoxylineosin (HE) and observed under a light microscope (Carl Zeiss GmbH; Oberkochen, Germany) to verify the lack of cytoplasmic contamination.…”

Section: Methodsmentioning

confidence: 99%

“…Aliquots of nuclear pellets were stained with hematoxylineosin (HE) and observed under a light microscope (Carl Zeiss GmbH; Oberkochen, Germany) to verify the lack of cytoplasmic contamination. Western Blotting (WB) was performed as previously described (29), using the following primary antibodies at the respective dilutions in blocking solution: rabbit monoclonal anti-GSK-3ß (27C10, Cell Signaling Technology; Danvers, MA) 1:1000; rabbit polyclonal anti-phospho-GSK-3ß (Ser9, Cell Signaling Technology) 1:1000; goat polyclonal anti-ß-actin (I-19, Santa Cruz Biotechnology; Santa Cruz, CA) 1:1000; rabbit polyclonal anti-ß-catenin (H-102, Santa Cruz Biotechnology) 1:600; goat polyclonal anti-lamin B (C-20, Santa Cruz Biotechnology) 1:1000; mouse monoclonal anti-HSP90 (SPA-830, Stressgen Bioreagents; Ann Arbor, MI) 1:100. Primary antibodies were detected with horseradish peroxidase (HRP)-labelled secondary antibodies at the respective dilutions in blocking solution: anti-rabbit (NA934, GE Healthcare Europe GmbH; Freiburg, Germany) 1:10000; anti-goat (sc-2020, Santa Cruz Biotechnology) 1:1000.…”

Section: Methodsmentioning

confidence: 99%

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Lithium induces mortality in medulloblastoma cell lines

et al. 2010

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Abstract. Lithium is the main therapeutic agent for the treatment of bipolar disorders but nerve cells are not the sole target of this drug. Indeed, lithium has been reported to target numerous cell types and to affect cell proliferation, differentiation and death. Lithium targets a variety of enzymes among which there is GSK-3ß and a number of cell responses elicited by lithium are mediated by the Wnt pathway that is involved in medulloblastoma (MB) pathogenesis. We studied the in vitro effects of lithium on two different MB cell lines: D283MED and DAOY. High doses of lithium inhibited GSK3-ß, decreased cell proliferation and induced nonapoptotic cell death in both cell lines independently by intracellular levels of ß-catenin that is consistently high only in D283MED. At clinical doses, the anti-neoplastic effects were observed only in this cell line, highlighting the importance of a specific molecular background in determining the target therapy response. In conclusion, lithium could be a promising drug in MB, but an accurate molecular profile predictive of drug response still needs to be clarified.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Lithium induces mortality in medulloblastoma cell lines

et al. 2010

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“…In addition, even though McMillan et al 43 demonstrated in 1993 that medulloblastomas are very radiosensitive, invading cells seem to be relatively resistant. This has prompted a few research teams to investigate ways by which to predict and/or increase the radio-sensitivity of these tumours [44][45][46][47] . In general these studies have demonstrated (1) that different cell lines differ in their degree of radio-sensitivity [48][49][50] ; and (2) that cell radio-sensitivity can, in fact, be altered by a variety of external means 45,47 .…”

Section: Discussionmentioning

confidence: 99%

“…Salaroli et al 44 studied the gamma-radiation response of two MB cell lines, both from a cellular and molecular point of view, and discovered that a p53 wild-type cell line was more sensitive to ionizing radiation than a p53 mutated line. And Tsuboi et al 50 isolated two mutant clones from a single medulloblastoma, one radiosensitive (OS-3) and one resistant (OR-5), but also found that the administration of 5mM of caffeine generated greater cytotoxicity in the latter cells.…”

Section: Discussionmentioning

confidence: 99%

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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The pivotal role of irradiation‐induced apoptosis in the pathogenesis and therapy of medulloblastoma

Richard

2024

Cancer Reports

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BackgroundMedulloblastoma (MB) is a rare primitive neuroectodermal tumors originating from the cerebellum. MB is the most common malignant primary brain tumor of childhood. MB originates from neural precursor cells in distinctive regions of the rhombic lip, and their maturation occurs in the cerebellum or the brain stem during embryonal development. Also, apoptosis is a programmed cell death associated with numerous physiological as well as pathological regulations.Recent FindingsIrradiation (IR)‐induce apoptosis triggers cell death, with or without intervening mitosis within a few hours of IR and these share different morphologic alteration such as, loss of normal nuclear structure as well as degradation of DNA. Moreover, MB is strikingly sensitive to DNA‐damaging therapies and the role of apoptosis a key treatment modality. Furthermore, in MB, the apoptotic pathways are made up of several triggers, modulators, as well as effectors. Notably, IR‐induced apoptotic mechanisms in MB therapy are very complex and they either induce radiosensitivity or inhibit radioresistance leading to potential effective treatment strategies for MB.ConclusionThis review explicitly explores the pivotal roles of IR‐induced apoptosis in the pathogenesis and therapy of MB.

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Radiobiologic response of medulloblastoma cell lines: involvement of β-catenin?

Cited by 17 publications

References 47 publications

Lithium induces mortality in medulloblastoma cell lines

Lithium induces mortality in medulloblastoma cell lines

Effects of Surgical Excision and Radiation on Medulloblastoma Cell Invasiveness

The pivotal role of irradiation‐induced apoptosis in the pathogenesis and therapy of medulloblastoma

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