Response of xenografts of human malignant gliomas and squamous cell carcinomas to fractionated irradiation

Baumann, Michaël; DuBois, Willem; Pu, Anthony T.; Freeman, Jill; Suit, Herman D.

doi:10.1016/0360-3016(92)90653-y

Cited by 54 publications

(24 citation statements)

References 18 publications

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“…Already with doses of 5 × 3.5 Gy (17.5 Gy total dose) we observed a significant tumour growth delay compared to the non-irradiated controls. This corroborates earlier findings showing exceptional in vivo radiation sensitivity of this glioblastoma cell line but is in contrast to the clinical experience of high radiation resistance in glioblastoma tumours [32-34]. …”

Section: Discussionsupporting

confidence: 91%

Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice

et al. 2012

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BackgroundErufosine is a promising anticancer drug that increases the efficacy of radiotherapy in glioblastoma cell lines in vitro. Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.MethodsIn the present study we aimed to evaluate the effects of a combined treatment with radiotherapy and Erufosine on growth and local control of T98G subcutaneous glioblastoma xenograft-tumours in NMRI nu/nu mice.ResultsWe show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice. Moreover, short-term treatment with 5 intraperitoneal Erufosine injections caused a transient decrease in the growth of T98G tumours without radiotherapy. Furthermore, an increased radiation-induced growth delay of T98G xenograft tumours was observed when fractionated irradiation was combined with short-term Erufosine-treatment. However, no beneficial drug effects on fractionated radiotherapy in terms of local tumour control were observed.ConclusionsWe conclude that short-term treatment with Erufosine is not sufficient to significantly improve local control in combination with radiotherapy in T98G glioblastoma xenograft tumours. Further studies are needed to evaluate efficacy of extended drug treatment schedules.

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Section: Discussionsupporting

confidence: 91%

Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice

et al. 2012

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“…Lactate production, due to the high glycolytic rates in cancer cells, enhances intracellular acidosis, which in turn leads to apoptosis. Previous works [37, 38] have also demonstrated that glioma cells could rapidly discharge lactate into the nearby microenvironment through monocarboxylate transporters. Thus, the lactate down-regulation observed in this work might be associated with the anti-apoptotic ability of glioma cells.…”

Section: Discussionmentioning

confidence: 99%

Malignancy-associated metabolic profiling of human glioma cell lines using 1H NMR spectroscopy

Shao

Huang

et al. 2014

Mol Cancer

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BackgroundAmbiguity in malignant transformation of glioma has made prognostic diagnosis very challenging. Tumor malignant transformation is closely correlated with specific alterations of the metabolic profile. Exploration of the underlying metabolic alterations in glioma cells of different malignant degree is therefore vital to develop metabolic biomarkers for prognosis monitoring.MethodsWe conducted 1H nuclear magnetic resonance (NMR)-based metabolic analysis on cell lines (CHG5, SHG44, U87, U118, U251) developed from gliomas of different malignant grades (WHO II and WHO IV). Several methods were applied to analyze the 1H-NMR spectral data of polar extracts of cell lines and to identify characteristic metabolites, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), fuzzy c-means clustering (FCM) analysis and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). The expression analyses of glial fibrillary acidic protein (GFAP) and matrix metal proteinases (MMP-9) were used to assess malignant behaviors of cell lines. GeneGo pathway analysis was used to associate characteristic metabolites with malignant behavior protein markers GFAP and MMP-9.ResultsStable and distinct metabolic profiles of the five cell lines were obtained. The metabolic profiles of the low malignancy grade group (CHG5, SHG44) were clearly distinguished from those of the high malignancy grade group (U87, U118, U251). Seventeen characteristic metabolites were identified that could distinguish the metabolic profiles of the two groups, nine of which were mapped to processes related to GFAP and MMP-9. Furthermore, the results from both quantitative comparison and metabolic correlation analysis indicated that the significantly altered metabolites were primarily involved in perturbation of metabolic pathways of tricarboxylic acid (TCA) cycle anaplerotic flux, amino acid metabolism, anti-oxidant mechanism and choline metabolism, which could be correlated with the changes in the glioma cells’ malignant behaviors.ConclusionsOur results reveal the metabolic heterogeneity of glioma cell lines with different degrees of malignancy. The obtained metabolic profiles and characteristic metabolites are closely associated with the malignant features of glioma cells, which may lay the basis for both determining the molecular mechanisms underlying glioma malignant transformation and exploiting non-invasive biomarkers for prognosis monitoring.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-197) contains supplementary material, which is available to authorized users.

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“…observations that (i) growth delay reflects radiation-induced cell kill, and (ii) growth delay correlates with local tumor control after irradiation (42).…”

Section: Discussionmentioning

confidence: 99%

Preclinical Assessment of Efficacy of Radiation Dose Painting Based on Intratumoral FDG-PET Uptake

Trani

Yaromina

Dubois

et al. 2015

Clinical Cancer Research

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Response of xenografts of human malignant gliomas and squamous cell carcinomas to fractionated irradiation

Cited by 54 publications

References 18 publications

Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice

Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice

Malignancy-associated metabolic profiling of human glioma cell lines using 1H NMR spectroscopy

Preclinical Assessment of Efficacy of Radiation Dose Painting Based on Intratumoral FDG-PET Uptake

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