• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7285-7290
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• 2015

Background: Although radiotherapy is one of the most effective strategies in the treatment of cancers, it is associated with short and long term side effects on normal tissues. Zataria multiflora Boiss (Laminacea) (ZM) has several biological properties such as antioxidant and anti-inflammation activities.Here we investigated cell killing effects of a hydroalcoholic Zataria multiflora extract on cell death induced by ionizing radiation in a human glioblastoma cell line (A172) and human non-malignant fibroblasts (HFFF2) in vitro. Materials and Methods: A172 and HFFF2 cells were treated with a hydroalcoholic extract of dried aerial parts of Zataria multiflora at different concentrations (25, 50, 100, 150 and $200{\mu}g/ml$) and then exposed to ionizing radiation (IR). Cell proliferation and DNA fragmentation were evaluated. Thymol content in the extract was analyzed and quantified by HPLC methods. Results: A172 cell proliferation was significantly inhibited by ZM. The percentage cell survival was $91.8{\pm}8.57$ for cells treated with $200{\mu}g/ml$ of ZM extract alone while it was $76.0{\pm}4.27$ and $66.2{\pm}8.42$ for cells treated with ZM and exposed to IR at doses of 3Gy and 6Gy, respectively. Radiation-induced apoptosis in A172 cells was significantly increased following treatment with ZM at doses of $200{\mu}g/ml$. ZM extract did not exhibit any enhanced cell killing effects and apoptosis caused by IR on HFFF2 cells. Conclusions: These data show selective radiosensitization effects of ZM in A172 cells apparently due to increased radiation-induced apoptosis.

• Radiation Oncology Journal
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• 제23권2호
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• pp.116-122
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• 2005

목적: 히스톤탈아세틸화효소 억제제는 그 자체의 항암효과뿐만 아니라 방사선 감작제로서의 효과가 점차분명해져가고 있다. 최근 Class I 특이적인 히스톤탈아세틸화효소 억제제의 개발로 계층 특이적인(Class specific) 연구가 가능해짐에 따라, 본 연구에서는 서로 다른 히스톤탈아세틸화효소억제제의 방사선감작효과를 비교함과 동시에 p53 발현도의 차이가 히스톤탈아세틸화효소억제제의 방사선 감수성에 미치는 영향을 알아보고자 하였다. 대상 및 방법: 이를 위해 p53 발현도가 매우 낮은 HeLa 세포에 p53의 핵 외 수송을 억제하여 세포질 내 분해를 차단하는 Leptomycin B를 처리하여 p53의 발현도를 현저하게 높인 후, Trichostatin와 SK7041의 방사선 민감도를 비교 관찰하였다. 결과: 세포생존곡선, SER 및 SF2를 비교 분석 시, p53의 발현이 높은 Leptomycin B 처리군에서 Trichostatin A가 Class I HDAC만을 억제하는 SK7041에 비해 유의하게 높은 방사선 감작효과를 나타내었다. 이는 p53이 Class I 특이적 억제제인 SK7041과 Class I과 II를 모두 억제하는 TSA의 방사선감작효과에 미치는 영향의 차이에 기전적으로 관여함을 시사한다. 결론: Leptomycln B에 의해 유도된 p53의 발현증가는 Class I과 Class I과 II를 모두 억제하는 TSA의 방사선 감작효과를 증강시킨다.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2010년도 심포지엄 및 추계학술발표회
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• pp.313-314
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• 2010

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2002년도 제9회 학술 발표회 프로그램과 논문초록
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• pp.52-52
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• 2002

It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline and wortmannin. Human colorecta1 cancer RKO.C cells and RKO-ATM cells (RKO cells overexpressing ATM) were used in the present study. (omitted)

• Journal of Radiation Protection and Research
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• 제28권3호
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• pp.233-237
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• 2003

It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline and wortmannin. Human colorectal cancer RKO.C cells and RKO-ATM cells (RKO cells overexpressing ATM) were used in the present study. The clonogenic cell survival in vitro indicated that RKO-ATM cells were markdely radioresistant than RKO.C cells. Treatment with 3 mM of caffeine significantly increased the radiosensitivity of cells, particulary the RKO-ATM cells, so that the radiosensitivity of RKO.C cells and RKO-ATM cells were almost similar. The radiation induced G2/M arrest in RKO-ATM cells was noticeably longer than that in RKO.C cells and caffeine treatment significantly reduced the length of the radiation induced G2/M arrest in both RKO.C and RKO-ATM cells. Pentoxifylline and wortmannin were also less effective than caffeine to radiosensitize RKO.C or RKO-ATM cells. However, wortmannin was more effective than caffeine against human lung adenocarcinoma A549 cells indicating the efficacy of ATM inhibitor to increase radiosensitivity is cell line dependent. For in vivo study, RKO.C cells were injected s.c. into the hind-leg of BALB/C-nuslc nude mice, and allowed to grow to 130mm3 tumor. The mice were i.p. injected with caffeine solution or saline and the tumors irradiated with 10 Gy of X-rays. The radiation induced growth delay was markedly increased by 1-2 mg/g of caffeine. It was concluded that caffeine increases radiosensitivity of tumor cells by inhibiting ATM kinase function, thereby inhibiting DNA repair, that occurs during the G2/M arrest after radiation.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1617-1623
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• 2016

Cisplatin-based concurrent chemoradiation plays an undisputed key role as definitive treatment in unresectable patients with locally advanced squamous cell carcinoma head and neck or as an organ preservation strategy. Treatment with 100 mg/m2 3-weekly cisplatin is considered the standard of care but is often associated with several adverse events. The optimum drug schedule of administration remains to be defined and presently, there is insufficient data limiting conclusions about the relative tolerability of one regimen over the other. This review addresses regarding the optimal dose schedule of cisplatin focusing mainly on three-weekly and weekly dose of cisplatin based concurrent chemoradiotherapy in locally advanced head and neck cancer with an emphasis on mucositis, dermatitis, systemic toxicity, compliance, and treatment interruptions. To derive a definitive conclusion, large prospective randomized trials are needed directly comparing standard 3-weekly cisplatin ($100mg/m^2$) with weekly schedule ($30-40mg/m^2$) of concurrent cisplatin based chemoradiotherapy in locally advanced squamous cell carcinoma head and neck.

• Radiation Oncology Journal
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• 제35권2호
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• pp.129-136
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• 2017

Purpose: The concentration of capecitabine peaks at 1-2 hours after administration. We therefore assumed that proper timing of capecitabine administration and radiotherapy would maximize radiosensitization and influence survival among patients with locally advanced rectal cancer. Materials and Methods: We retrospectively reviewed 223 patients with locally advanced rectal cancer who underwent preoperative chemoradiation, followed by surgery from January 2002 to May 2006. All patients underwent pelvic radiotherapy (50 Gy/25 fractions) and received capecitabine twice daily at 12-hour intervals ($1,650mg/m^2/day$). Patients were divided into two groups according to the time interval between capecitabine intake and radiotherapy. Patients who took capecitabine 1 hour before radiotherapy were classified as Group A (n = 109); all others were classified as Group B (n = 114). Results: The median follow-up period was 72 months (range, 7 to 149 months). Although Group A had a significantly higher rate of good responses (44% vs. 25%; p = 0.005), the 5-year local recurrence-free survival rates of 93% in Group A and 97% in Group B did not differ significantly (p = 0.519). The 5-year disease-free survival and overall survival rates were also comparable between the groups. Conclusions: Despite the better pathological response in Group A, the time interval between capecitabine and radiotherapy administration did not have a significant effect on survivals. Further evaluations are needed to clarify the interaction of these treatment modalities.

• Asian Pacific Journal of Cancer Prevention
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• 제17권9호
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• pp.4367-4375
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• 2016

The objective of the present study was to evaluate the anticancer and radio-sensitizing efficacy of a Withania somnifera extract/Gadolinium III oxide nanocomposite (WSGNC) in mice. WSGNC was injected to solid Ehrlich carcinoma-bearing mice via i.p. (227 mg/kg body weight) 3 times/week during 3 weeks. Irradiation was performed by whole body fractionated exposure to 6Gy, applied in 3 doses of 2 Gy/week over 3 weeks. Biochemical analyses as well as DNA fragmentation were performed. Treatment of solid Ehrlich carcinoma bearing mice with WSGNC combined with ${\gamma}$-radiation led to a significant decrease in the tumor size and weight associated with a significant decrease in mitochondrial enzyme activities, GSH content and SOD activity as well as a significant increase in caspase-3 activity, MDA concentration and DNA fragmentation in cancer tissues. Combined treatment of WSGNC and low dose of ${\gamma}$-radiation showed great amelioration in lipid peroxidation and antioxidant status (GSH content and SOD activity) in liver tissues in animals bearing tumors. It is concluded that WSGNC can be considered as a radio-sensitizer and anticancer modulator, suggesting a possible role in reducing the radiation exposure dose during radiotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.795-799
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• 2013

Ku70/80 heterodimer is a central element in the nonhomologous end joining (NHEJ) DNA repair pathway, Ku80 playing a key role in regulating the multiple functions of Ku proteins. It has been found that the Ku80 protein located at telomeres is a major contributor to radiosensitivity in some telomerase positive human cancer cells. However, in ALT human osteosarcoma cells, the precise function in radiosensitivity and telomere maintenance is still unknown. The aim of this study was to investigate the effects of Ku80 depletion in the U2OS ALT cell line cell line. Suppression of Ku80 expression was performed using a vector-based shRNA and stable Ku80 knockdown in cells was verified by Western blotting. U2OS cells treated with shRNA-Ku80 showed lower radiobiological parameters (D0, Dq and SF2) in clonogenic assays. Furthermore, shRNA-Ku80 vector transfected cells displayed shortening of the telomere length and showed less expression of TRF2 protein. These results demonstrated that down-regulation of Ku80 can sensitize ALT cells U2OS to radiation, and this radiosensitization is related to telomere length shortening.

• Radiation Oncology Journal
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• 제10권1호
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• pp.27-34
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• 1992

CIS-PLATINUM (DDP)을 제 3기, 제 4기 두경부종양환자에게 방사선 민감제로 사용한 임상연구 결과를 보고한다. 1984년부터 1987년까지 DDP 20 $mg/M^2$/day를 4일간 방사선 치료와 동시에 투여 하였으며 DDP는 3주 간격으로 반복투여 되었다. 치료는 종양세포 감소시기, 근치시기및 보조 치료 시기로 나누어 시행되었다. 본 논문에서 59명 환자의 치료결과및 합병증에 대하여 보고한다. 근치시기동안27명이 방사선치료45Gy 후 근치적 수술을 시행한 제I치료군으로, 29명이 근치적 방사선치료 65Gy를 시행한 제II치료군으로 분류되고 3명의 환자는 근치시기의 치료를 끝내지 못하였다. 종양세포 감소시기의 치료로 완전관해 $47.5\%$, 부분관해 $47.5\%$로 전체 반응률 $95\%$를 보였다. 근치시기 치료후 전체적으로는 $84\%$(47/56)의 완전 관해를 보였고, 제I치료군에서는 $96\%$(26/27), 제 II치료군에서는 $72\%$(21/29)가 완전 관해를 보였다. 제I치료군에서 원발병소의 $67\%$에서, 임파절 병변의 $70\%$에서 병리소견상 종양이 관찰되지 않았다. 근치시기치료후 완전관해 환자중 $34\%$에서 재발하였으며 재발까지의 평균시간은 8개월이었다. 전체 56명 환자의 4년 무병생존율은 $59\%$였고 근치시기에 완전관해를 보인 환자중 $51\%$(24/47)가 31개월의 평균 추적관찰기간(범위 : $10\~51$개월)동안 무병생존하였다. 제I치료군과 제II치료군사이에 전체생존율, 무병생존율에 있어서 유의한 차이는 보이지 않았다. 종양세포감소시기에 완전관해및 부분관해를 보인 환자들 사이에 생존율에서는 차이가 없었으며 가장 중요한 예후인자는 근치시기 치료로 완전관해 되었는지 여부이었다. 전체대상 환자의 합병증은 일반적인 치료시에 비하여 심하지 않았으며 치료에 잘 적응하였다. 본 연구에서 DDP가 비교적 적은 합병증을 동반한 의미있는 방사선 민감제임을 확인하였으며 치료효과를 증대시키기 위하여 DDP와 방사선치료의 적절한 투여 계획을 결정하는 전향적 연구가 필요하다고 생각한다.