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Long B.,Cancer Research Institute of Chongqing | Tan B.,Cancer Research Institute of Chongqing | Zhou X.,Cancer Research Institute of Chongqing | Fan C.,Cancer Research Institute of Chongqing | And 2 more authors.
Chinese Journal of Clinical Oncology | Year: 2012

Objective: To observe the effect of combined radiotherapy and chemotherapy on advanced nasopharyngeal carcinoma (NPC) patients with two modalities. Methods: A total of 144 patients with local advanced NPC were randomly divided into two: synchronal and sequential therapy groups. In the former group, the patients were treated with external beam radiation (EBR) plus concurrent chemotherapy with thymidine phosphorylase. In the latter group, the patients received induction chemotherapy and radical radiotherapy plus three courses of adjuvant chemotherapy. Three-dimensional conformal radiotherapy and cisplatin-paclitaxel combination chemotherapy were performed. No difference in the means of radiotherapy and chemotherapy was found between the two groups. Results: All patients were followed up for at least 2 years. The local control rate and distant metastasis rate in the synchronal therapy group were 81.2% and 9.7%, respectively, whereas those in the sequential therapy group were 76.3% and 19.4%, respectively. For 2 year survivors, the tumor-free survival rates in the synchronal and sequential therapy groups were 76.4% and 66.7%, respectively. Conclusion: The preliminary results of EBR plus concurrent chemotherapy for local advanced NPC showed that the multimodality treatment could improve the local control rate and reduce distant metastasis rates. Compared with sequential therapy, multimodal therapy mainly increased mucositis incidence and severity. Generally, patients could tolerate the active treatment without increased side effects.

Xu Z.-Y.,Chongqing Medical University | Wang K.,General Hospital of Daqing Oil Field | Li X.-Q.,Chongqing Medical University | Li X.-Q.,Cancer Research Institute of Chongqing | And 4 more authors.
Ultrasonics | Year: 2013

We aimed to investigate the role of the ABCG2 transporter in the efficacy of sonodynamic therapy (SDT) with Photofrin in the glioma stem-like cells (GSCs) isolated and cultured from U251 glioma cells. Immunocytochemistry and flow cytometry analyses showed that ABCG2 was overexpressed in GSCs, and the percentage of ABCG2-positive GSCs was approximately 100%. The effect of ABCG2 on Photofrin extrusion in the absence or presence of a specific inhibitor of ABCG2 (fumitremorgin C; FTC) was investigated by determining the intracellular concentration of Photofrin in GSCs incubated with 20 μg/ml Photofrin. Extrusion of Photofrin by ABCG2 was inhibited by 10 μM FTC, which significantly increased the intracellular Photofrin concentration (p < 0.05) from 0.32 ± 0.11 μg/10 6 cells to 0.89 ± 0.13 μg/10 6 cells. MTT and TUNEL assays showed that the antitumor effect of SDT (incubation of GSCs with 20 μg/ml Photofrin for 6 h in the dark and ultrasonic activation at 1.0 MHz and 0.5 W/cm 2 for 2 min) was significantly improved by FTC pretreatment (p < 0.05). Moreover, incubation of GSCs with FTC significantly increased the relative production of ROS in response to SDT. The overexpression of ABCG2 in GSCs results in efflux of Photofrin, indicating that the antitumor effect of SDT with Photofrin may be reduced in GSCs overexpressing ABCG2. However, since FTC improves the efficacy of SDT in GSCs by inhibiting ABCG2-mediated efflux of Photofrin, FTC may be useful in SDT treatment of ABCG2-expressing cancer cells. © 2012 Elsevier B.V. All rights reserved.

Xu Z.-Y.,Chongqing Medical University | Li X.-Q.,Chongqing Medical University | Li X.-Q.,Cancer Research Institute of Chongqing | Chen S.,Chongqing Medical University | And 3 more authors.
Technology in Cancer Research and Treatment | Year: 2012

Despite remarkable progress in diagnosis and treatment, malignant glioma, a highly lethal cancer of the central nervous system, remains incurable. Although glioma stem-like cells (GSCs) represent a relatively small fraction of the cells in malignant glioma, they can proliferate and self renew extensively, being crucial for tumor recurrence. Cancer treatment by sonodynamic therapy (SDT) chiefly depends on antitumor effects of reactive oxygen species (ROS) generated from a sonosensitizer activated by ultrasound. Although SDT effectively kills glioma cells, its efficiency against GSCs is not established. We attempted to compare the susceptibility of GSCs to SDT, using Photofrin, a porphyrin-derivative photosensitizer, with that of glioma cells. Cell viability and apoptosis assays showed that SDT damaged both GSCs and U251 glioma cells, but GSCs were significantly less susceptible to SDT (p < 0.01). To elucidate the mechanism of the antitumor effects of SDT, we evaluated intracellular ROS production and Photofrin uptake: ROS production and Photofrin content were significantly lower (p < 0.01) in GSCs than in U251 glioma cells. Thus, cellular differences in sonosensitizer uptake and ROS production influence the antitumor effects of SDT. Furthermore, the resistance of GSCs may be caused by decreased sonosensitizer uptake due to ABCG2 overexpression. © Adenine Press (2012).

Xu Z.-Y.,Chongqing Medical University | Li X.-Q.,Cancer Research Institute of Chongqing | Chen W.-F.,Chongqing Medical University | Cheng Y.,Chongqing Medical University | Wang Z.-G.,Chongqing Medical University
Chinese Journal of Medical Imaging Technology | Year: 2013

Objective: To explore the inhibition role of ATP-binding cassette transporter G2 (ABCG2) on the lethal effect of sonodynamic therapy (SDT) on glioma stem cells (GSCs). Methods: GSCs were isolated and cultured from glioma cells in the suspend culture medium. The expression of ABCG2 on GSCs was analyzed by flow cytometry and immunocytochemical assay. The exocytosis of ABCG2 on Photofrin were studied by ABCG2 specific inhibitor fumitremorgin C (FTC). The reactive oxygen species (ROS) production, cell viability as well as cell apoptosis were measured to assess the effect of FTC on SDT. Results: GSCs were successfully isolated and cultured, on which ABCG2 was overexpressed demonstrated by flow cytometry and immunocytochemical assay. FTC could effectively inhibit the Photofrin excetion caused by ABCG2. FTC increased ROS production through inhibition of Photofrin excetion, which lead to the enhancement effect on SDT-induced cell viability reduction and apoptosis increase. Conclusion: The overexpression of ABCG2 in GSCs results in efflux of Photofrin. ABCG2 specific inhibitor can improve the lethal effect of SDT on GSCs. Copyright © 2013 by the Press of Chinese Journal of Medical Imaging Technology.

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