The ABCG2 transporter is a key molecular determinant of the efficacy of sonodynamic therapy with Photofrin in glioma stem-like cells

Xu, Zhongye; Wang, Kai; Li, Xiaoqing; Chen, Song; Deng, Jinmu; Yuan, Chao; Wang, Zhigang

doi:10.1016/j.ultras.2012.06.005

Cited by 61 publications

(39 citation statements)

References 29 publications

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“…GSCs express the ATP-binding cassette (ABC) transporter channels at an increased rate compared to differentiated tumor cells, adding to the known challenges in drug delivery presented by the BBB and irregular tumor vasculature [26,70]. ABC channels actively and expeditiously transport molecules, including TMZ, both at the BBB and the cellular level to allow some cells to completely elude therapy and promote recurrence [52,71].…”

Section: Molecular Mechanisms Of Glioma Stem Cell Resistance To Chmentioning

confidence: 99%

The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence

Auffinger

Spencer

Pytel

et al. 2015

Expert Review of Neurotherapeutics

235

184

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Glioma stem cells (GSCs) constitute a slow-dividing, small population within a heterogeneous glioblastoma. They are able to self-renew, recapitulate a whole tumor, and differentiate into other specific GBM subpopulations. Therefore, they have been held responsible for malignant relapse after primary standard therapy and the poor prognosis of recurrent GBM. The failure of current therapies to eliminate specific GSC subpopulations has been considered a major factor contributing to the inevitable recurrence in GBM patients following treatment. Here, we discuss the molecular mechanisms of chemoresistance of GSCs and the reasons why complete eradication of GSCs is so difficult to achieve. We will also describe the targeted therapies currently available towards GSCs and possible mechanisms to overcome such chemoresistance and avoid therapeutic relapse.

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Section: Molecular Mechanisms Of Glioma Stem Cell Resistance To Chmentioning

confidence: 99%

The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence

Auffinger

Spencer

Pytel

et al. 2015

Expert Review of Neurotherapeutics

235

184

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“…21 Xu and colleagues reported that SDT with Photofrin was less effective in killing GSL cells due to the overexpression of ABCG2 in the GSL cells, resulting in a high efflux of Photofrin to the outside of the cells. 25,26 We have previously demonstrated that U251…”

Section: Optimum Dose Of 5-ala For Enabling the Antitumor Activity Inmentioning

confidence: 99%

Enhancement of antitumor activity by using 5-ALA–mediated sonodynamic therapy to induce apoptosis in malignant gliomas: significance of high-intensity focused ultrasound on 5-ALA-SDT in a mouse glioma model

Suehiro¹,

Ohnishi

Yamashita³

et al. 2018

Journal of Neurosurgery

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ABBREVIATIONS DCFH-DA = dichlorodihydrofluorescein diacetate; DPBS = Dulbecco phosphate-buffered saline; FBS = fetal bovine serum; FUS = focused ultrasound; GSL = glioma stemlike; HIFU = high-intensity focused ultrasound; IP = intraperitoneal; NSC = neural stem cell; PDT = photodynamic therapy; PFA = paraformaldehyde; PpIX = protoporphyrin IX; ROS = reactive oxygen species; SDT = sonodynamic therapy; TBS = Tris-buffered saline; US = ultrasound; 5-ALA = 5-aminolevulinic acid; 5-ALA-SDT = 5-ALA-mediated SDT. OBJECTIVE High invasiveness of malignant gliomas frequently causes early local recurrence of the tumor, resulting in extremely poor outcome. To control such recurrence, novel therapies targeted toward infiltrating glioma cells around the tumor border are required. Here, the authors investigated the antitumor activity of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of 5-ALA-mediated SDT (5-ALA-SDT). METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251 SUBMITTEDOct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry and TUNEL staining. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined by analysis of the effect of pretreatment with the radical scavenger edaravone. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated. RESULTS The 5-ALA-SDT inhibited cell growth and changed cell morphology, inducing cell shrinkage, vacuolization, and swelling. Flow cytometric analysis and TUNEL staining indicated that 5-ALA-SDT induced apoptotic cell death in all gliomas. The 5-ALA-SDT generated significantly higher ROS than in the control group, and inhibition of ROS generation by edaravone completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. The proliferative activity of the entire tumor was markedly decreased. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact. CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field, whereas the surrounding brain tissue remained normal, resulting in longer survival of the HIFU-treated mice compared with that of untreated mice. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-...

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“…The over-expression of BCRP in glioma stem-like cells (GSC) isolated from U251 glioma cells can result in e®lux of Photofrin, which can be reversed by a pretreatment of GSC with a speci¯c BCRP inhibitor fumitremorgin C (FTC). 47 The DNA damage reversal mechanisms may have important functions in Photofrin PDT resistance through the activation of alkylation repair homologue 2 by tumor protein TP53 in glioma cells. 48 The PS selectivity of BCRP was still unclear at that time.…”

Section: Bcrp and Ps Uptakementioning

confidence: 99%

Photodynamic therapy of cancer — Challenges of multidrug resistance

Huang

Hsu

et al. 2015

J. Innov. Opt. Health Sci.

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can lead to the generation of cytotoxic reactive oxygen species (ROS) and consequently destroy cancer. Similar to many other anticancer therapies, PDT is also subject to intrinsic cancer resistance mediated by multidrug resistance (MDR) mechanisms. This paper will review the recent progress in understanding the interaction between MDR transporters and PS uptake. The strategies that can be used in a clinical setting to overcome or bypass MDR will also be discussed.

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The ABCG2 transporter is a key molecular determinant of the efficacy of sonodynamic therapy with Photofrin in glioma stem-like cells

Cited by 61 publications

References 29 publications

The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence

The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence

Enhancement of antitumor activity by using 5-ALA–mediated sonodynamic therapy to induce apoptosis in malignant gliomas: significance of high-intensity focused ultrasound on 5-ALA-SDT in a mouse glioma model

Photodynamic therapy of cancer — Challenges of multidrug resistance

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