Supplementary Table S2 from NAD<sup>+</sup> Metabolic Enzyme Inhibitor as Radiosensitizer for Malignant Meningioma and its Modulation of P53 Expression
Yifan LvYuxuan DengJie FengJinqiu LiuMingxu YangZhuonan PuShaodong ZhangZhen WuNan JiDeric M. ParkShuyu Hao
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<p>Supplementary Table S2</p>Keywords:
Radiosensitizer
In article number 1801806, Xing-Jie Liang, Jianfeng Liu, and co-workers develop a gold nanoparticles (GNPs) system with acid-triggered aggregation as a radiosensitizer. With a sensitizer enhancement ratio (SER) value of 1.730 (vs. single GNPs of 1.16), this GNPs system improves sensitivity of MCF-7 cells and MCF-7 tumor xenograft to ionizing radiation. This work provides a strategy for fabricating radiosensitizer by in situ acid-triggered nano-aggregates formation.
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Ionizing irradiation is a well-established therapeutic modality for cancer. Photodynamic therapy (PDT), especially with 5-ALA and Photofrin, is highly effective in some tumor types. Chemical modifiers, so-called radiosensitizers, are used in order to increase the efficacy of radiotherapy. Most of the known and routinely used radiosensitizers are not tumor selective, so that the normal tissue reaction toxicity is also increased. In the present study we investigated whether a porphyrin derivative that is currently used as a tumor-photosensitizing agent in photodynamic therapy (PDT) may also act as a tumor-specific radiosensitizer.For our investigation we used Balb/c mice implanted with Lewis sarcoma and irradiated with 3 Gy combined with injection of 5-ALA or Photofrin at various concentrations before irradiation.5-ALA had no effect as a radiosensitizer at any of the concentrations examined. Photofrin at a concentration of 5 mg/kg proved to be a chemical modifier of ionizing radiation, delaying tumor growth and reducing the overall tumor volume by about 50% after six days.Photofrin has marked efficacy as a radiosensitizer and can be used in the future as a selective tumor radiosensitizer.
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Lewis lung carcinoma
Verteporfin
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e13546 Background: A key research objective in radiation oncology is to identify agents that can improve chemoradiotherapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiotherapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiotherapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer as a model disease. Methods: The physical characteristics and drug release profile of Genexol-PM were characterized. Genexol-PM’s efficacy as a radiosensitizer was evaluated in vitro using NSCLC cell lines and in vivousing mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared to that of after Taxol administration. Results: Genexol-PM have a size of 23.91 ± 0.41 nm and surface charge of -8.1 ± 3.1 mV. It releases paclitaxel in a controlled release profile. In vitro evaluation of Genexol-PM as a radiosensitizer showed it is an excellent radiosensitizer and is more effective than Taxol, its small molecule counterpart at the half maximal inhibitory concentration (IC50). In vivostudy of Genexol-PM as a radiosensitizer demonstrated that it is more effective as a radiosensitizer than Taxol. We also found that Genexol-PM leads to lower paclitaxel exposure to normal lung and liver tissue than Taxol at 6 hours post administration. Conclusions: We have demonstrated that Genexol-PM is more effective than Taxol as a radiosensitizer in the preclinical setting and holds high potential for clinical translation. Our data support the clinical evaluation of Genexol-PM in chemoradiotherapy for NSCLC.
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Chemoradiotherapy
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Radiosensitizer as a promising novel anti-tumor medicine has synergetic effects with radiotherapy, and can enhance the kill rate of tumor cells and radiotherapy effect. In recent years, due to the new theory and technology, the researches of radiosensitizer extend to different fields, from the traditional DNA target sensitizer to new radiosensitizer including nano-particles. Consequently, radiosensitizer combined with radiotherapy will become a new and effective treatment strategy for esophageal carcinoma to enhance the therapeutic effect of esophageal carcinoma.
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Esophageal neoplasms; Radiotherapy; Radiation-sensitizing agents
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Limited effective intervention for advanced hepatocellular carcinoma (HCC) is available. This study aimed to investigate the potential clinical utility of apatinib, a highly selective inhibitor of the vascular endothelial growth factor receptor-2 (VEGFR2) tyrosine kinase, as a radiosensitizer in the treatment of HCC.Four human HCC cell lines SMMC-7721, MHCC-97H, HCCLM3 and Hep-3B were treated with apatinib, irradiation or combination treatment. Colony formation assay, flow cytometry and nuclear γ-H2AX foci immunofluorescence staining were performed to evaluate the efficacy of combination treatment. RNA sequencing was conducted to explore the potential mechanism. The impact of combination treatment on tumor growth was assessed by xenograft mice models.Colony formation assay revealed that apatinib enhanced the radiosensitivity of HCC cell lines. Apatinib suppressed repair of radiation-induced DNA double-strand breaks. Flow cytometry analysis showed that apatinib increased radiation-induced apoptosis. Apatinib radiosensitized HCC via suppression of radiation-induced PI3K/AKT pathway. Moreover, an in vivo study indicated apatinib combined with irradiation significantly decreased xenograft tumor growth.Our results indicate that apatinib has therapeutic potential as a radiosensitizer in HCC, and PI3K/AKT signaling pathway plays a critical role in mediating radiosensitization of apatinib.
Apatinib
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Niacin
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We recently developed Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas (KORTUC) as a strategy to increase intratumoral oxygen concentrations and degrade antioxidant enzymes such as peroxidase and catalase. We then developed KORTUC II, which uses sodium hyaluronate containing hydrogen peroxide as a radiosensitizer. KORTUC II requires twice-weekly administration to sustain its effects, but decreasing the frequency of radiosensitizer injections to once-weekly would reduce the burden on the patients and the physicians. The goal of this study was thus to develop a new formulation of KORTUC (New KORTUC) that only requires once-weekly administration. We performed experimental studies using a mouse tumor model and biodegradable hydrogel. C3H/He mice were allocated to control, KORTUC, or hydrogel groups. At 72 h after injection, each tumor was irradiated with a 6 MeV electron beam to a total dose of 30 Gy. During a 62-day observation period, changes in tumor volume and survival rates were assessed in each group. Tumor growth rate was slowest in the hydrogel groups. These data suggest that hydrogel could represent a useful adjunct as a long-acting radiosensitizer in place of sodium hyaluronate. New KORTUC, which contains hydrogen peroxide and hydrogel, exerted a radiosensitizing effect that persisted beyond 72 h following injection of the agent. Use of this new formulation allows radiosensitizer injections to be performed once-weekly with good effect.
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Sodium hyaluronate
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Rumex
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The present study performed in 92 tumor-bearing mice showed that a compound of traditional Chinese medicine with hydrogen peroxide which was injected directly into the tumors could in some extent sensitive the hypoxic cells of S180 solid tumor to radiate. For example, both the tumor regression rate within 40 days of radiation and hydrogen peroxide compound group were significantly greater than those of radiation alone group. The increasing rate of tumor diameter in 10 days was 77.1%, 47.0% and -10.1% in group control, radiation alone and radiosensitizer alone, radiation and hydrogen peroxide compound respectively. Some of the problems about the intratumoral injection of radiosensitizer were discussed.
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