• Bulletin of the Korean Chemical Society
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• v.35 no.12
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• pp.3623-3626
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• 2014

Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates the expression of over 200 genes of antioxidant and phase II drug-metabolizing enzymes, and is highly expressed in non-small cell lung cancer (NSCLC). Nine derivatives of 4-(2-cyclohexylethoxy)aniline were designed. Our previous study demonstrated that IM3829 increases radiosensitivity of several lung cancer cells in vitro and in vivo. Here, biological effects of IM3829 derivatives (2a-2i) were evaluated. Compound 2g derivative effectively inhibits mRNA and protein expression of Nrf2 and HO-1. In addition, we observed over two fold enhancement in IR-induced cell death, from $2.90{\pm}0.22$ to $6.02{\pm}0.87$, in H1299 cancer cell-line. Among the nine derivatives, compound 2g derivative exhibited the highest enhancement of radiosensitizing effect via inhibition of Nrf2 activity.

• Radiation Oncology Journal
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• v.36 no.4
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• pp.265-275
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• 2018

Cancer is a complex multifaceted illness that affects different patients in discrete ways. For a number of cancers the use of chemotherapy has become standard practice. Chemotherapy is a use of cytostatic drugs to cure cancer. Cytostatic agents not only affect cancer cells but also affect the growth of normal cells; leading to side effects. Because of this, radiotherapy gained importance in treating cancer. Slaughtering of cancerous cells by radiotherapy depends on the radiosensitivity of the tumor cells. Efforts to improve the therapeutic ratio have resulted in the development of compounds that increase the radiosensitivity of tumor cells or protect the normal cells from the effects of radiation. Amifostine is the only chemical radioprotector approved by the US Food and Drug Administration (FDA), but due to its side effect and toxicity, use of this compound was also failed. Hence the use of herbal radioprotectors bearing pharmacological properties is concentrated due to their low toxicity and efficacy. Notably, in silico methods can expedite drug discovery process, to lessen the compounds with unfavorable pharmacological properties at an early stage of drug development. Hence a detailed perspective of these properties, in accordance with their prediction and measurement, are pivotal for a successful identification of radioprotectors by drug discovery process.

• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.151-155
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• 1998

Background and Objectives: Numerous studies were conducted to develop radiosensitizers to increase antitumor effect and decrease systemic toxicity of ionizing radiation. In current study, the authors tested the synergistic effect of mutant $TNF-{\alpha}(M_3S)$ with radiation therapy on heterotransplanted hypoparyngeal squamous cell carcinoma. Materials and Method: SNU-1041 cell line was heterotransplanted to nude mice. When the tumors grew up to $70mm^3$ or more, the animals were randomly placed into 4 groups(n=10/group). Group I : 0.1ml of normal saline injected intraperitoneally once a day for 5 days. Group II : 10ug of $TNF-{\alpha}$ injected intraperitoneally once a day for 5 days. Group III : a single radiation dose of 10 Gy per animal delivered. Group IV : single radiation dose of 10 Gy was delivered 1 hour after intraperitoneal injection of $TNF-{\alpha}$ 10 ug. Results: Four weeks after treatment, group IV showed the least tumor growth during the 4 weeks follow up and the relative tumor growth rate(RTG) of each groups after 4 weeks were 31, 5.8, 10, and 3.2 respectively(p<0.05). Conclusion: These study suggests that pretreatment with $TNF-{\alpha}$ can significantly enhance the effects of radiation therapy and further studies may be needed for clinical trials of combination treatment of $TNF-{\alpha}$ and radiation.

• Progress in Medical Physics
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• v.33 no.4
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• pp.114-120
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• 2022

Purpose: Particle beam therapy is advantageous over photon therapy. However, adequately delivering therapeutic doses to tumors near critical organs is difficult. Nanoparticle-aided radiation therapy can be used to alleviate this problem, wherein nanoparticles can passively accumulate at higher concentrations in the tumor tissue compared to the surrounding normal tissue. In this study, we investigate the dose enhancement effect due to gold nanoparticle (GNP) when Carbon-12, He-4, and proton beams are irradiated on GNP. Methods: First, monoenergetic Carbon-12 and He-4 ion beams of energy of 283.33 MeV/u and 150 MeV/u, respectively, and a proton beam of energy of 150 MeV were irradiated on a water phantom of dimensions 30 cm×30 cm×30 cm. Subsequently, the secondary-particle information generated near the Bragg peak was recorded in a phase-space (phsp) file. Second, the obtained phsp file was scaled down to a nanometer scale to irradiate GNP of diameter 50 nm located at the center of a 4 ㎛×4 ㎛×4 ㎛ water phantom. The dose enhancement ratio (DER) was calculated in intervals of 1 nm from the GNP surface. Results: The DER of GNP computed at 1 nm from the GNP surface was 4.70, 4.86, and 4.89 for Carbon-12, He-4, and proton beams, respectively; the DER decreased rapidly with increasing distance from the GNP surface. Conclusions: The results indicated that GNP can be used as radiosensitizers in particle beam therapy. Furthermore, the dose enhancement effect of the GNP absorbed by tumor cells can aid in delivering higher therapeutic doses.