Three-Dimensional Cell Growth Confers Radioresistance by Chromatin Density Modification

Storch, Katja; Eke, Iris; Borgmann, Kerstin; Krause, Mechthild; Richter, Christian; Becker, Kerstin; Schröck, Evelin; Cordes, Nils

doi:10.1158/0008-5472.can-09-3848

Cited by 164 publications

(181 citation statements)

References 50 publications

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“…This approach reflects the 3D morphology of tumour cells and pathophysiological gradients (oxygen, metabolites, pH), which may influence their intrinsic radiosensitivity. 70,71 CIERT compared with EBRT alone led to a pronounced enhancement of spheroid control probability in the SAS cells as a model. However, SAS and FaDu were already controlled after RIT treatment alone in spheroids as well as 2D cultures.…”

Section: 65mentioning

confidence: 96%

Improving external beam radiotherapy by combination with internal irradiation

Dietrich¹,

Koi²,

Zöphel³

et al. 2015

BJR

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The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

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Section: 65mentioning

confidence: 96%

Improving external beam radiotherapy by combination with internal irradiation

Dietrich¹,

Koi²,

Zöphel³

et al. 2015

BJR

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“…For the apoptosis analysis, the cells were treated at the indicated time points (8 or 24 h) and fixed with 80% ethanol for at least 24 h as previously published (25). Typical apoptotic nuclear shape was analyzed using Vectashield/DAPI mounting medium.…”

Section: Antibodiesmentioning

confidence: 99%

“…Total protein extracts from 2D cell cultures were isolated as previously described (25). Therefore, the cells were lysed using modified RIPA buffer [50 mM Tris-HCl (Carl Roth, Karlsruhe, Germany, (pH, 7.4)], 1% Nonidet-P40 (Sigma-Aldrich, Taufkirchen, Germany), 0.25% sodium deoxycholate (Applichem), 150 mM NaCl (VWR International, Darmstadt, Germany), 1 mM ethylenediaminetetraacetic acid (Merck), complete protease inhibitor cocktail (Roche, Mannheim, Germany), 1 mM NaVO 4 (Applichem), 2 mM NaF (Applichem).…”

Section: Antibodiesmentioning

confidence: 99%

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Cytotoxic and radiosensitizing effects of FAK targeting in human glioblastoma cells in vitro

2015

Self Cite

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Abstract. Glioblastoma multiforme (GBM) is a highly aggressive and extremely lethal cancer and novel molecular therapies are required for optimized multimodal therapy regimes. While focal adhesion kinase (FAK) is regarded as a therapeutic target, its radiosensitizing potential remains to be elucidated in glioblastoma. Thus, FAK was inhibited using the pharmaco logical inhibitor TAE226 and cytotoxicity and radiosensitization of glioblastoma cells were investigated in vitro. Monolayer and suspension cell cultures of a panel of glioblastoma cell lines (A172, LN229, U87MG, U138MG, U343MG, DD-HT7607, and DD-T4) were treated with increasing TAE226 concentrations (0-10 µM) alone or in combination with X-rays (0-6 Gy). Subsequently, clonogenic cell survival, expression and the phosphorylation of FAK downstream signaling, apoptosis and autophagy were analyzed. Efficient FAK inhibition by TAE226 mediated significant cytotoxicity and reduced sphere formation in a dose-and time-dependent manner. Two out of seven glioblastoma cell lines showed radiosensitization. Apoptotic induction by TAE226 was cell line-dependent. The results demonstrated that pharmacological FAK inhibitor TAE226 efficiently reduced clonogenicity and sphere formation in glioblastoma cells without generally modifying their radiosensitivity. However, future studies are necessary to define the potential of FAK inhibition by TAE226 or other pharmacological inhibitors in combination with radiochemotherapy.

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“…A number of studies have been done to reveal the effects of 2D versus 3D cell culture on differentiation, [21][22][23][24][25] drug metabolism, [26][27][28][29][30] gene expression and protein synthesis, [31][32][33][34][35] general cell function, [36][37][38][39][40] increase of in vivo relevance, 31,[41][42][43] morphology, [44][45][46][47] proliferation, 26,[48][49][50][51] response to stimuli, 41,[52][53][54] viability, 36,[55][56][57] and migration. [58][59][60][61] Adding the third dimension to cellular environment provides them with more in vivo-like morphology, behaviors, and intercellular interactions for understanding cytology in more physiological conditions.…”

Section: Introductionmentioning

confidence: 99%

Electrotaxis of lung cancer cells in ordered three-dimensional scaffolds

et al. 2012

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In this paper, we report a new method to incorporate 3D scaffold with electrotaxis measurement in the microfluidic device. The electrotactic response of lung cancer cells in the 3D foam scaffolds which resemble the in vivo pulmonary alveoli may give more insight on cellular behaviors in vivo. The 3D scaffold consists of ordered arrays of uniform spherical pores in gelatin. We found that cell morphology in the 3D scaffold was different from that in 2D substrate. Next, we applied a direct current electric field (EF) of 338 mV/mm through the scaffold for the study of cells' migration within. We measured the migration directedness and speed of different lung cancer cell lines, CL1-0, CL1-5, and A549, and compared with those examined in 2D gelatin-coated and bare substrates. The migration direction is the same for all conditions but there are clear differences in cell morphology, directedness, and migration speed under EF. Our results demonstrate cell migration under EF is different in 2D and 3D environments and possibly due to different cell morphology and/or substrate

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Three-Dimensional Cell Growth Confers Radioresistance by Chromatin Density Modification

Cited by 164 publications

References 50 publications

Improving external beam radiotherapy by combination with internal irradiation

Improving external beam radiotherapy by combination with internal irradiation

Cytotoxic and radiosensitizing effects of FAK targeting in human glioblastoma cells in vitro

Electrotaxis of lung cancer cells in ordered three-dimensional scaffolds

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