• Radiation Oncology Journal
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• v.28 no.2
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• pp.64-70
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• 2010

Purpose: The aim of the present study was to retrospectively evaluate the incidence of hypothyroidism in locally advanced head and neck cancer patients who received radiotherapy (RT) either with or without neck dissection. Materials and Methods: From January 2000 to December 2005, 115 patients with locally advanced head and neck cancer and who received definitive RT or postoperative RT including standard anterior low-neck field were recruited to be part of this study. Nineteen patients had undergone ipsilateral neck dissection, whereas, 18 patients underwent bilateral neck dissection, and 78 patients were received RT alone. Patients' ages ranged from 28 to 85 years (median, 59 years) and there were a total of 73 male and 42 female patients. The primary tumor sites were the oral cavity, oropharynx, hypopharynx, larynx, and other sites in 18, 40, 28, 22 and 7 patients, respectively. Radiation dose to the thyroid gland ranged from 44 Gy to 66 Gy with a median dose of 50 Gy. Follow-up time ranged from 2 to 91 months, with a median of 29 months. Results: The 1- and 3- year incidence of hypothyroidism was 28.7% (33 patients) and 33.0% (38 patients), respectively. The median time to detection of hypothyroidism was 8.5 months (range, 0 to 36 months). A univariate analysis revealed that neck node dissection was a risk factor for hypothyroidism (p=0.037). However, no factor was statistically significant from the results of a multivariate analysis. Conclusion: Patients treated for advanced head and neck cancer with radiotherapy with or without neck dissection will develop hypothyroidism. It is important to check the thyroid function periodically in these patientsespecially with the risk factor of neck node dissection.

• Journal of Oral Medicine and Pain
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• v.30 no.3
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• pp.287-300
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• 2005

Squamous cell carcinoma (SCC) in head and neck show a variability in the response to chemotherapy, even when it present with similar histological tumor type, grade, and clinical stage. The purpose of present study it to identify predictive bio-marker for the sensitivity or resistance to conventional chemotherapeutic agents, 5-fluorouracil (5-FU) and Cisplatin Oral cancer cell lines were used in present study. MTT assay was performed to evaluate the sensitivity and/or resistance to 5-FU and Cisplatin. And RT-PCR was carried out for evaluation of the mRNA expressions of various genes associated with mutation, inflammation (COX pathway), cell cycle, senescence and extracellular matrix (ECM). The molecules which are correlated with the sensitivity to 5-FU are XPA, XPC, OGG, APEX, COX-2, PPAR, Cyclin E, Cyclin B1, CDC2, hTERT, hTR, TIMP-3, TIMP-4 and HSP47. And the molecules are correlated with the sensitivity to Cisplatin are COX-1, iNOS, eNOS, PCNA, collagen 1 and MMP-9. Taken together, when choosing the appropriate chemotherpeutic agents for patients, considering the molecules which are correlated or reversely correlated is helpful to choose the resonable agents for cancer patients.

• The Journal of the Korea Contents Association
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• v.9 no.3
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• pp.278-287
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• 2009

The study find out developmental factors of the liver diseases in 29,531 subject of the healthy adults who diagnosed by using ultrasound at healthcare centers located at 6 cities around the nation. The results are as follows. Based on the result of the study, the liver diseases diagnosed by using ultrasound revealed to show 43.1％ of prevalence, and the occurrence was significantly higher in male(23.3％) than in female (19.8％)(p<0.001). The disease revealed to show highest prevalence rate in regionally, Dae-jeon was found to record the highest prevalence by showing 49.6％ (p<0.001). The order of liver disease prevalence was the highest in Dae-jeon(49.6%),which was followed by Seoul(48.2%), Busan(42.9%), Incheon(36.2%), Daegu(36.2%), Kangju(32.1%)(p<0.001). The order of hepatic disease prevalence was the highest in fatty liver (69.7％), which was followed by intrahepatic cysts (13.2％), intrahepatic calcification (9.6％), intrahepatic hemangioma (4.5％), intrahepatic tumor (1.4％), diffuse liver disease (1.0％),and liver cirrhosis (0.5％) (p<0.001). The liver disease revealed to show highest prevalence rate in 40s and regionally, disease was found to record the highest prevalence from 30s to 50s (p<0.001). The distribution of the liver diseases by sex revealed to show the higher occurrence of the fatty liver and the diffuse liver diseases in male, but the intrahepatic cysts, intrahepatic calcification and intrahepatic tumors were highly distributed in female. In the regional evaluation, the fatty liver was most often found in Busan, and intrahepatic cysts, intrahepatic hemangioma, intrahepatic calcification and intrahepatic tumors were highly found in Dae-jeon and Seoul revealed to show higher occurrence of diffuse liver disease than other regions (p<0.001). The multiple regression analysis for the related factors which affect the prevalence of the liver diseases resulted to show the higher prevalence by age. sex,

• Radiation Oncology Journal
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• v.19 no.2
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• pp.181-189
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• 2001

Purpose : Changes in the balance between MMP and TIMP can have a profound effect on the composition in the extracellular matrix (ECM) and affect various cellular functions including adhesion, migration, differentiation of cells, and fibrosis and invasion and metastasis of cancer cells. Radiation therapy is a popular treatment modality for benign and malignant tumor, but the study for radiation effect on MMP and TIMP is scarce. In the current study, we have examined the expression of TIMP in fibrosis-prone (C57BL/6) mice after radiation. Methods and Materials : Adult female mice of $10\~12$ weeks were used. The whole body were irradiated using a Varian CL-4/100 with 2 and 10 Gy. Immunohistochemical staining was peformed according to Avidin Biotin complex method and evaluated by observing high power field. For TIMP-1, TIMP-2 antibodies, reactivity was assessed in the parenchymal cell and in the stromal cell. The scale of staining was assessed by combining the quantitative and qualiative intensity of staining. Results : TIMP-1 immunoreactivity did not change in lung. But, in liver, TIMP-1 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell. in kidney, TIMP-1 immunoreactivity was localized in cytoplasm of some tubular cell. Temporal variations were not seen. Dose-response relationship was not seen except kidney. TIMP-2 immunoreactivity in lung was a score (++) at 0 Gy and elevated to a score (+++) at 2 Gy. TIMP-2 immunoreactivity was a score (++) in liver at 0 Gy. TIMP-2 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell as same as patterns of TIMP-1 immunoreactivity. The TIMP-2 immunoreactivity in liver was elevated to (+++) at 2 Gy. Immunoreactivity to TIMP-2 in kidney was a score (+++) at 0 Gy and was not changed at 10 Gy. The score of TIMP-2 immunoreactivity was reduced to (++) at 2 Gy. TIMP-2 immunoreactivity was confined to tubules in kidney. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIMP-2 immunoreactivity was not seen. Conclusions : Differences between intensity of expression of TIMP-1 and TIMP-2 in each organ was present. Expression of TIMP was localized to specific cell in each organ. Irradiation increased TIMP-1 immunoreactivity in the liver and the kidney. Irradiation increased TIMP-2 immunoreactivity in the lung. But, in the liver and the kidney, TIMP-2 expression to radiation was irregular. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIHP-2 immunoreactivity was not seen. In the future, we expect that the study of immunohistochemical staining of longer period of postirradiation and quantitative analysis using western blotting and northern blotting could define the role of TIMP in the radiation induced tissue fibrosis.

• Radiation Oncology Journal
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• v.25 no.2
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• pp.118-124
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• 2007

[ $\underline{Purpose}$ ]: This study was to evaluate the survival and pattern of failure after radiation therapy of sino-nasal cancer using partial attenuation filer and wedged beams and to help radiotherapy planning of sino-nasal cancer. $\underline{Materials\;and\;Methods}$: Between February 1992 and March 2003, 17 patients with sino-nasal cancers underwent radiation therapy using partial attenuation filter at Dongsan Medical Center, Keimyung university. There were 9 male and 8 female patients. Patients' age ranged from 40 to 75 years (median 59 years). There were 10 patients of maxillary sinus cancer, 7 patiens of nasal cancer. The histologic type was squamous cell carcinoma in 11, adenoid cystic carcinoma in 4 and olfactory neuroblastoma in 2. The distribution of clinical stage by the AJCC system was 3 for stage II, 7 for III and 6 for IV. The five patients were treated with radiation alone and 12 patients were treated with surgery and postoperative radiation therapy. The range of total radiation dose delivered to the primary tumor was from 44 to 76 Gy (median 60 Gy). The follow-up period ranged from 3 to 173 months with median of 78 months. $\underline{Results}$: The overall 2 year survival rate and disease free survival rate was 76.4%. The 5 year and 10 year survival rate were 76.4% and 45.6% and the 5 year and 10 year disease free survival rate was 70.6%. The 5 year disease free survival rate by treatment modality was 91.6% for postoperative radiation group and 20% for radiation alone group, statistical significance was found by treatment modality (p=0.006). There were no differences in survival by pathology and stage. There were local failure in 5 patients (29%) but no distant failure and no severe complication required surgical intervention. $\underline{Conclusion}$: Radiation therapy of sino-nasal cancer using partial attenuation filter was safe and effective. Combined modality with conservative surgery and radiation therapy was more advisable to achieve loco-regional control in sino-nasal cancer. Also we considered high precision radiation therapy with dose escalation and development of multi-modality treatment to improve local control and survival rate in advanced sino-nasal cancer.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.33-42
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• 2007

Background: Heme oxygenase-1 (HO-1) is known to modulates the cellular functions, including cell proliferation and apoptosis. It is known that a high level of HO-1 expression is found in many tumors, and HO-1 plays an important role in rapid tumor growth on account of its antioxidant and antiapoptotic effects. Cisplatin is a widely used anti-cancer agent for the treatment of lung cancer. However, the development of resistance to cisplatin is a major obstacle to its use in clinical treatment. We previously demonstrated that inhibiting HO-1 expression through the transcriptional activation of Nrf2 induces apoptosis in A549 cells. The aim of this study was to determine of the inhibiting HO-1 enhance the chemosensitivity of A549 cells to cisplatin. Materials and Methods: The human lung cancer cell line, A549, was treated cisplatin, and the cell viability was measured by a MTT assay. The change in HO-1, Nrf2, and MAPK expression after the cisplatin treatment was examined by Western blotting. HO-1 inhibition was suppressed by ZnPP, which is a specific pharmacologic inhibitor of HO activity, and small interfering RNA (siRNA). Flow cytometry analysis and Western blot were performed in to determine the level of apoptosis. The level of hydrogen peroxide ($H_2O_2$) generation was monitored fluoimetrically using 2',7'-dichlorofluorescein diacetate. Results: The A549 cells showed more resistance to the cisplatin treatment than the other cell lines examined, whereas cisplatin increased the expression of HO-1 and Nrf2, as well as the phosphorylation of MAPK in a time-dependent fashion. Inhibitors of the MAPK pathway blocked the induction of HO-1 and Nrf2 by the cisplatin treatment in A549 cells. In addition, the cisplatin-treated A549 cells transfected with dither the HO-1 small interfering RNA (siRNA) or ZnPP, specific HO-1 inhibitor, showed in a more significantly decrease in viability than the cisplatin-only-treated group. The combination treatment of ZnPP and cisplatin caused in a marked increase in the ROS generation and a decrease in the HO-1 expression. Conclusion: Cisplatin increases the expression of HO-1, probably through the MAPK-Nrf2 pathway, and the inhibition of HO-1 enhances the chemosensitivity of A549 cells to cisplatin.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.155-163
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• 2004

Purpose : To confirm the reproducibility of in vivo transmission dosimetry system and the accuracy of the a1gorithms for the estimation of transmission dose in head and neck radiation therapy patients. Materials and Methods : From September 5 to 18, 2001, transmission dose measurements were peformed when radiotherapy was given to brain or head and neck cancer patients. The data of 35 patients who were treated more than three times and whose central axis of the beam was not blocked were analyzed in this study. To confirm the reproducibility of this system, transmission dose was measured before dally treatment and then repetitively every hour during the treatment time, with a field size of 10$\times$10 cm$^{2}$ and a delivery of 100 MU. The accuracy of the transmission dose calculation algorithms was confirmed by comparing estimated dose with measured dose. To accurately estimate transmission dose, tissue inhomogeneity correction was done. Results : The measurement variations during a day were within $\pm$0.5$\%$ and the dally variations in the checked period were within $\pm$ 1.0$\%$, which were acceptable for system reproducibility. The mean errors between estimated and measured doses were within $\pm$5.0$\%$ in Patients treated to the brain, $\pm$2.5$\%$ in head, and $\pm$ 5.0%$\%$in neck. Conclusion : The results of this study confirmed the reproducibility of our system and its usefulness and accuracy for dally treatment. We also found that tissue inhomogeneity correction was necessary for the accurate estimation of transmission dose in patients treated to the head and neck.

• Journal of Life Science
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• v.25 no.6
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• pp.693-702
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• 2015

Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE’s anti-angiogenic properties, this study’s authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE’s anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.

• The Korean Journal of Nuclear Medicine Technology
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• v.22 no.1
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• pp.35-42
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• 2018

Purpose Standardized uptake value(SUV) has been widely used as a quantitative metric of uptake in PET/CT for diagnosis of malignant tumors and evaluation of tumor therapy response. However, the SUV depends on various factor including PET/CT scanner specifications and reconstruction parameter. The purpose of this study is to validate a EQ PET to evaluate SUV across different PET/CT systems. Materials and Methods First, NEMA IEC body phantom data were used to calculate the EQ filter for OSEM3D with PSF and TOF reconstruction from three different PET/CT systems in order to obtain EARL compliant recovery coefficients of each spheres. The Biograph true point 40 PET/CT images were reconstructed with a OSEM3D+PSF reconstruction, images of the Biograph mCT 40 and Biograph mCT 64 PET/CT scanners were reconstructed with a OSEM3D+PSF, OSEM3D+TOF, OSEM3D+PSF+TOF. Post reconstructions, the proprietary EQ filter was applied to the reconstruction data. Recovery coefficient can be estimated by ratio of measured to true activity concentration for spheres of different volume and coefficient variability(CV) value of RC for each sphere was compared. For clinical study, we compared SUVmax applying different reconstruction algorithms in FDG PET images of 61 patients with lung cancer using Biograph mCT 40 PET/CT scanner. Results For the phantom studied, the mean values of CV for OSEM3D, OSEM3D+PSF, OSEM3D+TOF and OSEM3D+PSF+TOF reconstructions were 0.05, 0.04, 0.04 and 0.03 respectively for RC. Application of the proprietary EQ filter, the mean values of CV for OSEM3D, OSEM3D+PSF, OSEM3D+TOF and OSEM3D+PSF+TOF reconstructions were 0.04, 0.03, 0.03 and 0.02 respectively for RC. Clinical study, there were no statistical significance of the difference applying EQ PET on SUVmax of 61 patients FDG PET image. (p=1.000) Conclusion This study indicates that CV values of RC in phantom were decreased after applying EQ PET for different PET/CT system and The EQ PET reduced reconstruction dependent variation in SUVs for 61 lung cancer patients, Therefore, EQ PET will be expected to provide accurate quantification when the patient is scanned on different PET/CT system.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.129-135
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• 1999

Purpose : This study evaluated early bowel complications in cervix cancer patients, following external radiotherapy (ERT and high dose rate intracavitary radiation (HDR ICR). Factors affecting the risk of developing early bowel complications and its incidence are analyzed and discussed Materials and Methods : The study is the retrospective review of 66 patients who received radiotherapy at Chungbuk National University Hospital from April 1994 to December 1998. The patients underwent 41.4 or 50.4 Gy ERT according to FIGO stage and tumor size, then A point dose was boosted to 71.4 or 74.4 Gy using a remotely controlled afterloading Buchler HDR ICR. The EORTC/RTOG morbidity criteria were used to grade early bowel complications, which are valid from day 1, the commencement of therapy, through day 90. The actuarial incidence, severity of complications were investigated and clinical pretreatment factors relevant to complications were found through univariate (Wilcoxon) and multivariate (Cox proportional hazard model) analysis. Results : Of the 66 patients, 30 patients (46$\%$) developed early bowel complications; 25 patients (38$\%$) with grade 1 or 2, 4 patients (0$\%$) with grade 3 and 1 patient (2$\%$) with grade 4. The complications usually began to occur 3 weeks after the commencement of radiotherapy. The actuarial incidence of early bowel complications was 41$\%$ at 10 weeks. The early bowel complications were associated significantly with an old age and a history of previous abdomino-pelvic surgery. All three patients who had a protracted overall treatment time (about 2 weeks) due to severe bowel complication, suffered from pelvic recurrences. Conclusion : Forty six percent of patients experienced early bowel complications, most of which were grade 1 or 2 and relieved spontaneously or by medication. The patients with an old age or a previous surgery have a high probability of early complications and they may be less compliant with planned radiotherapy. So more careful precaution is necessary for these patients.