• Journal of Radiation Protection and Research
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• v.28 no.3
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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.

• Journal of Life Science
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• v.25 no.9
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• pp.1051-1058
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• 2015

Citrus mutant fruits were induced by irradiation of citrus budsticks with 120 Gy of cobalt (⁶⁰CO) gamma irradiation. The citrus mutant inhibited the growth and induced apoptosis in various human cancer cells, including A549, HepG2, HCT116, MCF-7, and Hela. The results of a trypan blue exclusion assay showed that citrus mutant fruits exhibited excellent antiproliferation activity in various human cancer cells and low cytotoxicity in normal 16HBE140- and CHANG cells. In addition, the cell death induced by the citrus mutant fruits was associated with an increased population of cells in sub-G1 phase, and it caused DNA fragmentation in human lung adenocarcinoma A549 and hepatocellular carcinoma HepG2 cells. It also up-regulated the amount of cellular nitric oxide (NO^•) produced as a result of nitric oxide synthase (NOS) activation and suppressed the inhibitor of apoptosis protein (IAP) family in A549 and HepG2 cells. These findings indicate that the citrus mutant fruits activates the NO^•-mediated apoptotic pathway in A549 and HepG2 cells. It may merit further investigation as a potential chemotherapeutic and chemopreventive agent for the treatment of various types of cancer cells. The results provide important major new insights into the mechanisms of the anticancer activity of citrus mutant fruits.

• Progress in Medical Physics
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• v.29 no.1
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• pp.1-7
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• 2018

The $TomoTherapy^{(R)}$ beam-delivery method creates helical beam-junctioning patterns in the dose distribution within the target. In addition, the dose discrepancy results in the particular region where the resonance by pattern of dose delivery occurs owing to the change in the position and shape of internal organs with a patient's respiration during long treatment times. In this study, we evaluated the dose pattern of the longitudinal profile with the change in respiration. The superior-inferior motion signal of the programmable respiratory motion phantom was obtained using AbChes as a four-dimensional computed tomography (4DCT) original moving signal. We delineated virtual targets in the phantom and planned to deliver the prescription dose of 300 cGy using field widths of 1.0 cm, 2.5 cm, and 5.0 cm. An original moving signal was fitted to reflecting the beam delivery time of the $TomoTherapy^{(R)}$. The EBT3 film was inserted into the phantom movement cassette, and static, without the movement and with the original movement, was measured with signal changes of 2.0 s, 4.0 s, and 5.0 s periods, and 2.0 mm and 4.0 mm amplitudes. It was found that a dose fluctuation within ${\pm}4.0%$ occurred in all longitudinal profiles. Compared with the original movement, the region of the gamma index above 1 partially appeared within the target and the border of the target when the period and amplitude were changed. Gamma passing rates were 95.00% or more. However, cases for a 5.0 s period and 4.0 mm amplitude at a field width of 2.5 cm and for 2.0 s and 5.0 s periods at a field width of 5.0 cm have gamma passing rates of 92.73%, 90.31%, 90.31%, and 93.60%. $TomoTherapy^{(R)}$ shows a small difference in dose distribution according to the changes of period and amplitude of respiration. Therefore, to treat a variable respiratory motion region, a margin reflecting the degree of change of respiration signal is required.

• Journal of Korean Neurosurgical Society
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• v.50 no.4
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• pp.299-303
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• 2011

Objective : Brainstem metastases are rarely operable and generally unresponsive to conventional radiation therapy or chemotherapy. Recently, Gamma Knife Radiosurgery (GKRS) was used as feasible treatment option for brainstem metastasis. The present study evaluated our experience of brainstem metastasis which was treated with GKRS. Methods : Between November 1992 and June 2010, 32 patients (23 men and 9 women, mean age 56.1 years, range 39-73) were treated with GKRS for brainstem metastases. There were metastatic lesions in pons in 23, the midbrain in 6, and the medulla oblongata in 3 patients, respectively. The primary tumor site was lung in 21, breast in 3, kidney in 2 and other locations in 6 patients. The mean tumor volume was $1,517mm^3$ (range, 9-6,000), and the mean marginal dose was 15.9 Gy (range, 6-23). Magnetic Resonance Imaging (MRI) was obtained every 2-3 months following GKRS. Follow-up MRI was possible in 24 patients at a mean follow-up duration of 12.0 months (range, 1-45). Kaplan-Meier survival analysis was used to evaluate the prognostic factors. Results : Follow-up MRI showed tumor disappearance in 6, tumor shrinkage in 14, no change in tumor size in 1, and tumor growth in 3 patients, which translated into a local tumor control rate of 87.5% (21 of 24 tumors). The mean progression free survival was 12.2 months (range, 2-45) after GKRS. Nine patients were alive at the completion of the study, and the overall mean survival time after GKRS was 7.7 months (range, 1-22). One patient with metastatic melanoma experienced intratumoral hemorrhage during the follow-up period. Survival was found to be associated with score of more than 70 on Karnofsky performance status and low recursive partitioning analysis class (class 1 or 2), in terms of favorable prognostic factors. Conclusion : GKRS was found to be safe and effective for management of brainstem metastasis. The integral clinical status of patient seems to be important in determining the overall survival time.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6883-6888
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• 2013

Background: Platinum based concurrent chemo-radiation is the de-facto standard of care in the non-surgical management of locally-advanced head and neck cancer of squamous origin. Three-weekly single agent cisplatin at 100 $mg/m^2$ concurrent with radical radiotherapy has demonstrated consistent improvement in loco-regional control and survival. This improvement is however at the cost of considerable hematologic toxicity and poor overall compliance. The routine use of this regime is improbable in developing countries with limited resources. We therefore aimed to determine the safety and efficacy of an alternative regime of weekly cisplatin and concurrent radiotherapy in such patients. Materials and Methods: January-05 and April-12, 188 patients of locally-advanced head and neck cancer of squamous origin were treated with concurrent weekly-cisplatin at $35mg/m^2$ and conventional radiotherapy 60-66Gy/30-33 fractions/5days per week. Results: Overall, 95% patients received planned doses of RT while 74% completed within the stipulated overall treatment time of <50 days. Eighty-two percent received at-least 5 weekly cycles. Grade-III/IV mucositis was seen in 58%/9% respectively, which resulted in mean weight loss of 9.2% from a pre-treatment mean of 54.5 kg. Grade-III hematologic toxicity-0.5%; grade II nephrotoxicity-2.5% and grade III emesis-3% were also seen. Grade-III/IV subcutaneous toxicity-10%/1% and grade-III/IV xerostomia-10%/0% were observed. Complete responses at the primary site, regional nodes and overall disease were seen in 86%, 89% and 83% patients respectively. The median and 5-years disease-free survival were 26 months and 39.4% respectively, while the median and overall survival were 27 months and 41.8% respectively. Conclusions: Weekly-cisplatin at 35 $mg/m^2$ when delivered concurrently with conventional radical RT (at-least 66y/33 fractions) in locally-advanced head and neck cancer is well tolerated with minimal hematologic and neprologic toxicity and can be routinely delivered on an out-patient basis. It is an effective alternative to the standard 3-weekly cisplatin especially in the context of developing countries.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4121-4126
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• 2013

Objective: Low dose radiation may stimulate the growth and development of animals, increase life span, enhance fertility, and downgrade the incidence of tumor occurrence.The aim of this study was to investigate the antitumor effect and hormesis in an erythrocyte system induced by low-dose radiation. Methods: Kunming strain male mice were subcutaneously implanted with S180 sarcoma cells in the right inguen as an experimental in situ animal model. Six hours before implantation, the mice were given 75mGy whole body X-ray radiation. Tumor growth was observed 5 days later, and the tumor volume was calculated every other day. Fifteen days later, all mice were killed to measure the tumor weight, and to observe necrotic areas and tumor-infiltration-lymphoreticular cells (TILs). At the same time, erythrocyte immune function and the level of 2,3-diphosphoglyceric acid (2,3-DPG) were determined. Immunohistochemical staining was used to detect the expression of EPO and VEGFR of tumor tissues. Results: The mice pre-exposed to low dose radiation had a lower tumor formation rate than those without low dose radiation (P < 0.05). The tumor growth slowed down significantly in mice pre-exposed to low dose radiation; the average tumor weight in mice pre-exposed to low dose radiation was lighter too (P < 0.05). The tumor necrosis areas were larger and TILs were more in the radiation group than those of the group without radiation. The erythrocyte immune function, the level of 2,3-DPG in the low dose radiation group were higher than those of the group without radiation (P < 0.05). After irradiation the expression of EPO of tumor tissues in LDR group decreased with time. LDR-24h, LDR-48h and LDR-72h groups were all statistically significantly different from sham-irradiation group. The expression of VEGFR also decreased, and LDR-24h group was the lowest (P < 0.05). Conclusion: Low dose radiation could markedly increase the anti-tumor ability of the organism and improve the erythrocyte immune function and the ability of carrying $O_2$. Low-dose total body irradiation, within a certain period of time, can decrease the expression of hypoxia factor EPO and VEGFR, which may improve the situation of tumor hypoxia and radiosensitivity of tumor itself.

• Radiation Oncology Journal
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• v.7 no.1
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• pp.29-36
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• 1989

One hundred and ten patients with carcinoma of the nasopharynx were treated by radiation therapy in Department of Therapeutic Radiology, Seoul National University Hospital between 1979 and 1985. Among these, one hundred and five patients were treated with curative intent and 5 patients with palliative aim. Excluding 16 patients who did not receive a full course of radiation therapy, the remaining 89 patients were reviewed for this analysis. Minimum follow-up period of survivors was 36 months. Forty-three percent of the patients had T4 primary lesions and $72\%$ had stage IV disease. The histology was squamous cell carcinoma in $46\%$ of the patients. undifferentiated carcinoma in $49\%$, and lymphoepithelioma in $5\%$. Total radiation dose to the primary site averaged 6,500cCY for T1, T2 lesions and 7500cCY for T3, T4 lesions. Neck node were given boost treatment to a maximum 7,500cCY depending on the extent of disease. Early primary lesion (T1, T2) and neck nodes were successfully controlled in most cases when dose of greater than 6,500cCY was delievered. Forty two patients $(47\%)$ had recurred, 16 of whom $(38\%)$ed at the primary site and $24(57\%)$ developed distant metastases. Of these. 9 patients received re-irradiation with or without chemotherapy and local control was obtained in 2 patients$(22\%)$. Actuarial overall survival and disease-free survival rate was $42\%\;and\;38\%$ at 5 years. T-stage and histologic subtype were not correlated with survival. However, N-stage was related to survival significantly (p=0.043).

• Journal of Radiation Protection and Research
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• v.36 no.2
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• pp.86-92
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• 2011

This study used the optically stimulated luminescence dosimeters (OSLDs), recently, received the revaluation of usefulness in vivo dosimetry, and the diode detecters to measure the skin dose of patient with the rectal cancer. The measurements of dose delivered were compared with the planned dose from the treatment planning system (TPS). We evaluated the clinical application of OSDs in radiotherapy. We measured the calibration factor of OSLDs and used the percent depth dose to verified, also, we created the three point of surface by ten patients of rectal cancer to measured. The calibration factors of OSLD was 1.17 for 6 MV X-ray and 1.28 for 10 MV X-ray, demonstrating the energy dependency of X-ray beams. Comparison of surface dose measurement using the OSLDs and diode detectors with the planned dose from the TPS, The skin dose of patient was increased 1.16 ~ 2.83% for diode detectors, 1.36 ~ 2.17% for OSLDs. Especially, the difference between planned dose and the delivery dose was increased in the perineum, a skin of intense flexure region, and the OSLDs as a result of close spacing of measuring a variate showed a steady dose verification than the diode detecters. Therefore, on behalf of the ionization chamber and diode detecters, OSLDs could be applied clinically in the verification of radiation dose error and in vivo dosimety. The research on the dose verification of the rectal cancer in the around perineal, a surface of intense flexure region, suggest continue to be.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8911-8916
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• 2014

Background: The aim of the present study was to determine the predictive/prognostic value of the secreted protein, acidic and rich in cysteine (SPARC) in cases of unresectable, locally advanced, non-small cell lung cancer. Materials and Methods: The study included 84 patients with Stage IIIA-B non-small cell lung cancer, undergoing simultaneous chemoradiotherapy including radiotherapy at a dose of 66 Gy and weekly docataxel ($20mg/m^2$) and cisplatin ($20mg/m^2$). SPARC expression was studied in biopsy material by immunohistochemical methods and correlations with treatment responses or survival were evaluated. Results: Median overall survival was $16{\pm}2.73$ (11.55-20.46) months for low expression vs $7{\pm}1.79$ months (7.92-16.08) months for high expression (p=0.039), while median local control was $13{\pm}2.31$ (8.48-17.5) months for low expression vs $6{\pm}0.85$ (4.34-7.66) months for high expression (p=0.045) and median progression-free survival was $10{\pm}2.31$ (5.48-14.5) months for low expression vs $6{\pm}1.10$ (3.85-8.15) months for high expression (p=0.022). In both univariate and multivariate analyses, high SPARC expression was associated with significantly shorter overall survival (p=0.003, p=0.007, respectively), local control (p=0.008, p=0.036) and progression-free survival (p=0.004, p=0.029) when compared to low SPARC expression. No significant difference was detected between high and low SPARC expression groups regarding age, sex, T stage, N stage, histopathology and stage-related patient characteristics. Conclusions: High SPARC expression was identified as a poor prognostic factor in cases with locally advanced NSCLC treated with concurrent chemoradiotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5383-5387
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• 2014

Purpose: To investigate whether pretreatment serum carbohydrate antigen 19-9 (CA 19-9) levels are associated with pathological responses to preoperative chemoradiotherapy (CRT) in patients with rectal cancer. Materials and Methods: In total, 260 patients with locally advanced rectal cancer (cT3-4NanyM0) who underwent preoperative CRT and radical surgery were analyzed retrospectively. CRT consisted of 50.4 Gy pelvic radiotherapy and concurrent chemotherapy. Radical surgery was performed at a median of 7 weeks after CRT completion. Pathological CRT response criteria included downstaging (ypStage 0-I) and ypT0-1. A discrimination threshold of CA 19-9 level was determined using a receiver operating characteristics analysis. Results: The median CA 19-9 level was 8.0 (1.0-648.0) U/mL. Downstaging occurred in 94 (36.2%) patients and ypT0-1 in 50 (19.2%). The calculated optimal threshold CA 19-9 level was 10.2 U/mL for downstaging and 9.0 U/mL for ypT0-1. On multivariate analysis, CA 19-9 (${\leq}9.0U/mL$) was significantly associated with downstaging (odds ratio, 2.089; 95% confidence interval, 1.189-3.669; P=0.010) or ypT0-1 (OR, 2.207; 95%CI, 1.079-4.512; P=0.030), independent of clinical stage or carcinoembryonic antigen. Conclusions: This study firstly showed a significant association of pretreatment serum CA 19-9 levels with pathological CRT responses of rectal cancer. The CA 19-9 level is suggested to be valuable in predicting CRT responses of rectal cancer cases before treatment.