• Radiation Oncology Journal
• /
• v.13 no.4
• /
• pp.377-383
• /
• 1995

Purpose : To obtain the optimal treatement method in patients with endometrial carcinoma(clinical stage FIGO I, II) by comparative analysis between preoperative radiotherapy (pre-op RT) and postoperative radiotherapy (post-op RT). Material and Methods : A retrospective review of 62 endometrial carcinoma patients referred to the Yonsei Cancer Center for radiotherapy between 1985 and 1991 was undertaken. Of 62 patients, 19 patients(Stagel : 12 patients. Stagell;7 patients) received pre-op RT before TAH(Total Abdominal Hysterectomy) and BSO (Bilateral Salphingoophorectomy) (Group 1) and 43 patients(Stage 1;32 patients, Stage 2; 11 patients) received post-op RT after TAH and BSO (Group 2). Pre-op irradiation was given 4-6 weeks prior to surgery and post-op RT administered on 4-5 weeks following surgery. All patients except 1 patient(Group 2: ICR alone) received external irradiation. Seventy percent(13/19) of pre-op RT group and 54 percent(23/42) of post-op RT group received external pelvic irradiation and intracavitary radiation therapy(ICR). External radiation dose was 39.6-55 Gy(median 45 Gy) in 5-6. 5weeks through opposed AP/PA fields or 4-field box technique treating daily, five days per week, 180 cGy per fraction. ICR doses were prescribed to point A(20-39.6 Gy, median 39 Gy) in Group 1 and 0.5cm depth from vaginal surface (18-30 Gy,median 21 Gy) in Group 2. Results : The overall 5 year survival rate was $95{\%}$. No survival difference between pre-op and post-op RT group.($89.3{\%}$ vs $97.7{\%}$, p>0.1) There was no survival difference by stage, grade and histology between two groups. The survival rate was not affected by presence of residual tumor of surgical specimen after pre-op RT in Group 1 (p>0.1), but affected by presence of lymph node metastasis in post-op RT group(P<0.5). The complication rate of pre-op RT group was higher than post-op RT. ($16{\%}$ vs $5{\%}$) Conclusion : Post-op radiotherapy offers the advantages of accurate surgical-pathological staging and low complication rate.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
• /
• v.29 no.1
• /
• pp.87-103
• /
• 1999

Purpose: This study was undertaken to quantitatively estimate the degree of the damage and recovery of the irradiated rat condylar cartilage using the Image Analyzer. Materials and Methods: Experimental animals were 16 male rats of the Sprague-Dawley strain at the age of 20 day irradiated with the dose of 10 Gy in their head and neck region. Four rats were sacrificed at the each of the following time intervals - 1, 4, 7 and 14 days, respectively. The same number of control group animals were sacrificed at the each age of 21. 24, 27 and 34 days, respectively. The specimens were stained with 0.5％ toluidine blue and examined with light microscope. The condylar cartilage was divided into 4 zones; fibrous zone, proliferating zone, upper hypertrophic zone, and lower hypertrophic zone. And then, the proliferating zone was subdivided into 2 layers - upper and lower layer, and upper and lower hypertrophic zone were subdivided into three layers, respectively - upper, middle and lower layer. With the aid of Image Analyzer, morphometric analysis was performed. The thickness, the numerical density of cells, the cell area density, the extracellular matrix area density, the mean area of single cell, the mean area of extracellular matrix per single cell were measured and analysed. Results: In the experimental group, the thickness of the fibrous zone was slightly increased and that of the proliferating zone and the upper and the lower hypertrophic zone was markedly decreased. With time, the thickness of the fibrous zone was gradually increased and that of the proliferating zone and the upper and the lower hypertrophic zone was steadily in the decreased state. The numerical density of cells of the proliferating zone was increased on post-irradiated 1 day, but decreased after post-irradiated 4 day, and that of the upper hypertrophic zone was decreased. The numerical density of cells of the lower hypertrophic zone was decreased in the early stage and then was decreased or not significantly different from that of the control group with time. In the experimental group, the cell area density of the fibrous zone and the proliferating zone was decreased in the early stage and then gradually increased or not significantly different from that of the control group with time. The cell area density of the upper and the lower hypertrophic zone was varied with time. The extracellular matrix area density value were totally opposite to the cell area density values: The mean area of single cell of the fibrous zone and the proliferating zone was .decreased on post-irradiated 1 day, and increased after post-irradiated 4 day. The mean area of single cell of the upper hypertrophic zone was varied with each layer and time. In the experimental group, the mean area of extracellular matrix per single cell of the fibrous zone was not significantly different with control group, and that of the proliferating zone was decreased on post-irradiated 1 day, and increased after post-irradiated 4 day. The mean area of extracellular matrix per single cell of the lower hypertrophic zone was increased in the early stage. and that of upper hypertrophic zone was varied with each layer and time. Conclusion: The condylar cartilages of rats were affected by irradiation, but the changes were vaned with each layer and time. By morphometric analysis. the changes of the cells of the condylar cartilage of irradiated rat could be calculated quantitatively.

• Radiation Oncology Journal
• /
• v.19 no.2
• /
• pp.153-162
• /
• 2001

Purpose : The mechanical insights of death of cancer cells by ionizing radiation are not of yet clearly defined. Recent evidences have demonstrated that radiation therapy may induce cell death via activation of signaling pathway for apoptosis in target cells. This study is designed whether ionizing radiation may activate the signaling cascades of apoptosis including caspase family cysteine pretenses, $Bcl_2/Bax$, cytochrome c and Fas/Fas-L in target cells. Materials and Methods : HL-60 cells were irradiated in vitro with 6 MV X-ray at dose ranges from 2 Gy to 32 Gy. The cell viability was tested by M assay and the extent of apoptosis was determined using agarose gel electrophoresis. The activities of caspase proteases were measured by proteolytic cleavages of substrates. Western blot analysis was used to monitor PARP, Caspase-3, Cytochrome-c, Bcl-2, Bax, Fas and Fas-L. Results : Ionizing radiation decreases the viability of HL-60 cells in a time and dose dependent manner. Ionizing radiation-induced death in HL-60 cells is an apoptotic death which is revealed as characteristic ladder-pattern fragmentation of genomic DNA over 16 Gy at 4 hours. ionizing radiation induces the activation of caspase-2, 3, 6, 8 and 9 of HL-60 cells in a time-dependent manner. The activation of caspase-3 pretense is also evidenced by the digestion of poly (ADP-ribose) polymerase and procaspase 3 with 16Gy ionizing irradiation. Anti-apoptotic Bcl2 expression is decreased but apoptotic Bax expression is increased with mitochondrial cytochrome c release in a time- dependent manner. In addiiton, expression of Fas and Fas-L is also increased in a time dependent manner. Conclusion : These data suggest that ionizing radiation-induced apoptosis is mediated by the activation of various signaling pathways including caspase family cysteine proteases, $Bcl_2/Bax$, Fas and Fas-L in a time and dose dependent manner.

• Radiation Oncology Journal
• /
• v.27 no.1
• /
• pp.35-41
• /
• 2009

Purpose: This study was designed to determine the optimum radiotherapy technique for internal mammary node (IMN) irradiation after breast-conserving surgery. Materials and Methods: We selected ten cases of early stage partial mastectomy for plan comparison. Five of the patients were treated to the right-side breast and the rest of the patients were treated to the left-side breast. For each case, four different treatment plans were made to irradiate the entire breast, IMNs and supraclavicular lymph nodes (SCLs). The four planning techniques include a standard tangential field (STF), wide tangential field (WTF), partially wide tangential field (PWT) and a photon-electron mixed field (PEM). We prescribed a dose of 50.4 Gy to the SCL field at a 3 cm depth and isocenter of the breast field. Results: The dose distribution showed clear characteristics depending on the technique used. All of the techniques covered the breast tissue well. IMN coverage was also good, except for the STF, which was not intended to cover IMNs. For the cases of the left-side breasts, the volume of the heart that received more than 30 Gy was larger (in order) for the WTF, PWT, PEM and STF. For radiation pneumonitis normal tissue complication probability (NTCP), the PWT showed the best results followed by the STF. Conclusion: Despite the variety of patient body shapes, the PWT technique showed the best results for coverage of IMNs and for reducing the lung and heart dose.

• The Korean Journal of Nuclear Medicine
• /
• v.35 no.2
• /
• pp.83-88
• /
• 2001

Purpose: The purpose of this study was to ascertain whether radiation adaptive response could be induced by high dose I-131 therapy in patients with differentiated thyroid cancer. Materials and Methods: Lymphocytes from 21 patients (7 males, 14 females, mean age $55{\pm}12$ years) were collected before and after administration of 5,550 MBq (150 mCi) I-131. They were exposed to a challenge dose of 1 Gy gamma rays using a Cs-137 cell irradiator. The number of ring-form (R) and dicentric (D) chromosomes was counted under the light microscope, and used to calculate the frequency of chromosomal aberration. Ydr, which was defined as the sum of R and D divided by the total number of counted lymphocytes. Results: Ydr in patients before I-131 therapy ($0.09{\pm}0.01$) was not different from that of controls ($0.08{\pm}0.01$). Ydr was significantly increased to $0.13{\pm}0.02$ (p<0.0001) after I-131 therapy. Increase of Ydr after the challenge irradiation of 1 Gy was significantly lower in patients after I-131 therapy than before I-131 therapy ($0.17{\pm}0.03\;vs\;0.21{\pm}0.02$, p<0.0001). Cycloheximide (CHM), an inhibitor of protein synthesis, abolished this effect. Ydr after CHM ($0.20{\pm}0.01$) was significantly higher than Ydr after I-131 therapy ($0.17{\pm}0.03$, p<0.0001), but was not different from Ydr before I-131 therapy ($0.21{\pm}0.02$).Conclusion: High dose I-131 therapy induces an adaptive response in peripheral lymphocytes of patients with well-differentiated thyroid cancer, which is associated with protein synthesis.

• Radiation Oncology Journal
• /
• v.5 no.2
• /
• pp.97-104
• /
• 1987

From January 1970 through December 1984, 15 patients with sinonasal Non-Hodgkin's lymphoma combined to the head and neck were treated by external irradiation.13 patients were stage It and 2 were stage IIE by Ann Arbor Classification. However, when using TNM system, 7 were locally advanced T3, T4 lesions. All patients had follow up from 3.7 to 16 years with the median follow-up of 8.5 years. The overall actuarial 5-year survival rates were $25\%,\;28\%$ for IE and $0\%$ for IIE. Total tumor dose varied from 40 to 68 Gy. $100\%$ complete response with a total tumor dose of more than 55 Gy and $73\%$ complete response with less than 55Gy. When the disease was staged using the TNM (AJC) system, the five-year disease free survival for T1 and T2 patients was $50\%$ as compared with $14\%$ for T3 and T4. Failure rate by stage was $33\%(2/6)$ for T1 and T2, $86\%(6/7)$ for T3 and T4, and $100\%$(2/2) for IIE. The results suggest that 1. Higher CR could be obtained with a total tuner dose of more than 55 Gy. 2. Use of TNM staging system is as important as Ann arbor in management of sinonasal NHL. 3. The addition of combination chemotherapy should be considered for T3, T4 and IIE the sinonasal Non-Hodgkin's lymphoma although the disease is limited to head and neck.

• Radiation Oncology Journal
• /
• v.23 no.4
• /
• pp.236-242
• /
• 2005

Purpose: To evaluate the role of surgical clips and scars in determining electron boost field for early stage breast cancer undergoing conserving surgery and postoperative radiotherapy and to provide an optimal method in drawing the boost field. Materials and Methods: Twenty patients who had $4{\sim}7$ surgical clips in the excision cavity were selected for this study. The depth informations were obtained to determine electron energy by measuring the distance from the skin to chest wall (SCD) and to the clip implanted in the most posterior area of tumor bed. Three different electron fields were outlined on a simulation film. The radiological tumor bed was determined by connecting all the clips implanted during surgery Clinical field (CF) was drawn by adding 3 cm margin around surgical scar. Surgical field (SF) was drawn by adding 2 cm margin around surgical clips and an Ideal field (IF) was outlined by adding 2 cm margin around both scar and clips. These fields were digitized into our planning system to measure the area of each separate field. The areas of the three different electron boost fields were compared. Finally, surgical clips were contoured on axial CT images and dose volume histogram was plotted to investigate 3-dimensional coverage of the clips. Results : The average depth difference between SCD and the maximal clip location was $0.7{\pm}0.55cm$. Greater difference of 5 mm or more was seen in 12 patients. The average shift between the borders of scar and clips were 1.7 1.2, 1.2, and 0.9 cm in superior, inferior, medial, and lateral directions, respectively. The area of the CF was larger than SF and IF in 6y20 patients. In 15/20 patients, the area difference between SF and if was less than 5%. One to three clips were seen outside the CF in 15/20 patients. In addition, dosimetrically inadequate coverage of clips (less than 80% of prescribed dose) were observed in 17/20 patients when CF was used as the boost field. Conclusion: The electron field determined from clinical scar underestimates the tumor bed in superior-inferior direction significantly and thereby underdosing the tissue at risk. The electron field obtained from surgical clips alone dose not cover the entire scar properly As a consequence, our technique, which combines the surgical clips and clinical scars in determining electron boost field, was proved to be effective in minimizing the geographical miss as well as normal tissue complications.

• Radiation Oncology Journal
• /
• v.26 no.2
• /
• pp.96-103
• /
• 2008

Purpose: To conduct a nationwide academic hospital patterns of the practice status and principles of radiotherapy for prostate cancer. The survey will help develop the framework of a database of Korean in Patterns of Case Study. Materials and Methods: A questionnaire about radiation treatment status and principles was sent to radiation oncologists in charge of prostate cancer treatment at thirteen academic hospitals in Korea. The data was analyzed to find treatment principles among the radiation oncologists when treating prostate cancer. Results: The number of patients with prostate cancer and treated with radiation ranged from 60 to 150 per academic hospital in Seoul City and 10 to 15 outside of Seoul City in 2006. The primary diagnostic methods of prostate cancer included the ultrasound guided biopsy on 6 to 12 prostate sites(mean=9), followed by magnetic resonance imaging and a whole body bone scan. Internal and external immobilizations were used in 61.5% and 76.9%, respectively, with diverse radiation targets. Whole pelvis radiation therapy(dose ranging from 45.0 to 50.4 Gy) was performed in 76.9%, followed by the irradiation of seminal vesicles($54.0{\sim}73.8$ Gy) in 92.3%. The definitive radiotherapy doses were increased as a function of risk group, but the range of radiation doses was wide(60.0 to 78.5 Gy). Intensity modulated radiation therapy using doses greater than 70 Gy, were performed in 53.8% of academic hospitals. In addition, the simultaneous intra-factional boost(SIB) technique was used in three hospitals; however, the target volume and radiation dose were diverse. Radiation therapy to biochemical recurrence after a radical prostatectomy was performed in 84.6%; however, the radiation dose was variable and the radiation field ranged from whole pelvis to prostate bed. Conclusion: The results of this study suggest that a nationwide Korean Patterns of Care Study is necessary for the recommendation of radiation therapy guidelines of prostate cancer.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2007.11a
• /
• pp.79-92
• /
• 2007

Oxidative stress have known to be a risk factor for the degenerative processes and closely related to a lot of diseases. It is well established that antioxidants are good in protection and therapeutic means against oxidative damage. There is increasing interest in natural antioxidants and many natural antioxidants have been found and utilized as the possible protection for various diseases and skin aging. We have screened natural antioxidant agents for cosmeceuticals, nutraceuticals, and drugs as therapeutic and preventive means against oxidative stress, and have developed a number of novel antioxidants from various natural sources. A novel melanin synthesis inhibitor, Melanocin A, isolated from the metabolite of a fungal strain Eupenicillium shearii F80695 inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with $IC_{50}$ value of 9.0 nM and MIC value of $0.9\;{\mu}M$, respectively. Melanocin A also exhibited potent antioxidant activity by scavenging of DPPH and superoxide anion radicals. UV was found to increase the level of hydrogen peroxides and other reactive oxygen species (ROS) in skin tissues. This increase in ROS may not only alter the structure and function of many genes and proteins directly but may also modulate their expressions through signal transduction pathways and, ultimately, lead to skin damage. We investigated the effect of Melanocin A on UV-induced premature skin aging. Firstly, the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT in vitro was investigated. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated UV-induced skin changes in hairless mice in vivo by Melanocin A. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. These results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging. Terrein is a bioactive fungal metabolite isolated from Penicillium species. Terrein has a relatively simple structure and can be easily synthesized. However, the biologic effects of terrein are comparatively unknown. We found for the first time that terrein potently inhibit melanin production in melanocytes and has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 mM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrain treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrain reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.

• The Journal of Korean Society for Radiation Therapy
• /
• v.28 no.1
• /
• pp.35-46
• /
• 2016

Purpose : BoS(Base of Skull) Frame, the fixation tool which is used for the proton of brain cancer increases the lateral penumbra by increasing the airgap (the distance between patient and beam jet), due to the collision of the beam of the posterior oblique direction. Thus, we manufactured the fixation tool per se for improving the limits of BoS frame, and we'd like to evaluate the utility of the manufactured fixation tool throughout this study. Materials and Methods : We've selected the 3 patients of brain cancer who have received the proton therapy from our hospital, and also selected the 6 beam angles; for this, we've selected the beam angle of the posterior oblique direction. We' ve measured the planned BoS frame and the distance of Snout for each beam which are planned for the treatment of the patient using the BoS frame. After this, we've proceeded with the set-up that is above the location which was recommended by the manufacturer of the BoS frame, at the same beam angle of the same patient, by using our in-house Bos frame fixation tool. The set-up was above 21 cm toward the superior direction, compared to the situation when the BoS frame was only used with the basic couch. After that, we've stacked the snout to the BoS frame as much as possible, and measured the distance of snout. We've also measured the airgap, based on the gap of that snout distance; and we've proceeded the normalization based on each dose (100% of each dose), after that, we've conducted the comparative analysis of lateral penumbra. Moreover, we've established the treatment plan according to the changed airgap which has been transformed to the Raystation 5.0 proton therapy planning system, and we've conducted the comparative analysis of DVH(Dose Volume Histogram). Results : When comparing the result before using the in-house Bos frame fixation tool which was manufactured for each beam angle with the result after using the fixation tool, we could figure out that airgap than when not used in accordance with the use of the in-house Bos frame fixation tool was reduced by 5.4 cm ~ 15.4 cm, respectively angle. The reduced snout distance means the airgap. Lateral Penumbra could reduce left, right, 0.1 cm ~ 0.4 cm by an angle in accordance with decreasing the airgap while using each beam angle in-house Bos frame fixation tool. Due to the reduced lateral penumbra, Lt.eyeball, Lt.lens, Lt. hippocampus, Lt. cochlea, Rt. eyeball, Rt. lens, Rt. cochlea, Rt. hippocampus, stem that can be seen that the dose is decreased by 0 CGE ~ 4.4 CGE. Conclusion : It was possible to reduced the airgap by using our in-house Bos frame fixation tool for the proton therapy; as a result, it was possible to figure out that the lateral penumbra reduced. Moreover, it was also possible to check through the comparative analysis of the treatment plan that when we reduce the lateral penumbra, the reduction of the unnecessary irradiation for the normal tissues. Therefore, Using the posterior oblique the Brain cancer proton therapy should be preceded by decreasing the airgap, by using our in-house Bos frame fixation tool; also, the continuous efforts for reducing the airgap as much as possible for the proton therapy of other area will be necessary as well.