• Journal of Chest Surgery
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• v.34 no.6
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• pp.447-453
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• 2001

Background: Although pulmonary resection is the standard approach for the management of pulmonary metastases from soft tissue sarcoma, most of them are unresectable and chemotherapy remains the only option. The effectiveness of the cytotoxic drugs may be limited by the toxicities that occur before the therapeutic dose is reached. The regional administration of doxorubicin using pulmonary arterial perfusion in a rodent model can produce 10 to 25 times higher concentrations in the lung than systemic administration with minimal systemic toxicities. However, it is unclear whether a high concentration of doxorubicin has beneficial effects for killing cancer cells. Material and Method: We studied this to evaluate the dose-dependent cytotoxic and apoptotic effects of doxorubicin on methylcholanthrene-induced rat fibrosarcoma(MCA) cells. This study examined the cytotoxicity and apoptosis-related gene expressions(Fas, FasL, Bax, caspase 1, caspase 2, caspase 8, Bcl-2, Bcl-xL, Bcl-xS) in MCA cells after 24 hours exposure to various concentrations of doxorubicin such as 1, 5, 10, 50, and 100 $\mu$M. Result: Dose-dependent cytotoxicity was observed after 24 hours exposure to doxorubicin. However, peak apoptosis after 24 hours exposure was observed at 5 $\mu$M of doxorubicin. Above 5 $\mu$M, apoptotic activity was decreased with dose-increment. All mRNA levels of apoptosis-related genes after 24 hours exposure were up-regulated above the control level at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment except caspase 8, which showed higher levels than the control level at 5 $\mu$M. Apoptosis-related protein levels were highest at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment. However, Bax and Bcl-xL proteins steadily showed higher levels than the control throughout the different concentrations of doxorubicin. Conclusion: These results suggest that apoptosis is the main cytotoxic mechanism in low concentrations of doxorubicin in MCA cells and apoptosis-related genes, such as Bax, caspase 8, and Bcl-xL, are involved. At high concentrations, doxorubicin still can kill MCA cells, even when apoptosis is inhibited, and have its propriety for achieving much cytotoxicity against MCA cells.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.67-76
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• 2006

Purpose: Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Materials and Methods: Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGF-treated groups. Rats were topically applied with rhEGF (15 or $30{\mu}g/oral$ cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. Results: rhEGF-treated groups (15 or $30{\mu}g/oral$) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous or ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. Conclusion: These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.128-139
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• 1998

Background: It is well known that various cytokines and growth factors secreted mainly from alveolar macrophages do the key role in the pathogenesis of IPF. But recently it has been known that structural cells like fibroblast can also release cytokines. So the phenotypic changes in fibroblasts of IPF may do a role in continuous progression of fibrosis. The aim of this study is to find out whether there is a change in the biologic properties of the lung fibroblasts of IPF. Subjects and Method: The study was done on 13 patients with IPF diagnosed by open or thoracoscopic lung biopsy and 7 control patients who underwent resectional surgery for lung cancer. Lung fibroblast cell lines (FB) were established by explant culture technique from the biopsy or resected specimen Result: Basal proliferation of the fibroblast of IPF(IFB) measured by BrdU uptake tended to be highter than control fibroblast(NFB) (0.212 0.107 vs $0.319{\pm}0.143$, p=0.0922), also there was no significant difference in proliferation after the stimulation with PDGF or 10% serum. On the contrary, the degree of inhibition in proliferation by PGE2 was significantly lower($33.0{\pm}13.1%$) in IFB than control($46.7{\pm}10.0%$, p=0.0429). The IFB secreted significantly higher amount of MCP-l($l574{\pm}1283$ pg/ml) spontaneously than NFB($243{\pm}100$ pg/ml) and also after the stimulation with TGF-$\beta$($3.23{\pm}1.31$ ng/ml vs $0.552{\pm}0.236$ ng/ml, p=0.0012). Similarly IL-8 and IL-6 seretion of IFB was significantly higher than NFB at basal state and with TGF-$beta$ stimulation. But after the maximal stimulation with IL-1,8, no significant difference in cytokine secretion was found between IFB and NFB. Conclusion : Above data suggest that the fibroblasts of IPF were phenotypically changed and these change may do a role in the pathogenesis of IPF.

• The Journal of Korean Society for Radiation Therapy
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• v.28 no.1
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• pp.7-16
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• 2016

Purpose : This study aimed to compare and evaluate between the efficiency of two respective devices, 3D-bolus and step-bolus when the devices were used for the treatment of patients whose chest walls were required to undergo the electron beam therapy after the surgical procedure of modified radical mastectomy, MRM. Materials and Methods : The treatment plan of reverse hockey stick method, using the photon beam and electron beam, had been set for six breast cancer patients and these 6 breast cancer patients were selected to be the subjects for this study. The prescribed dose of electron beam for anterior chest wall was set to be 180 cGy per treatment and both the 3D-bolus, produced using 3D printer(CubeX, 3D systems, USA) and the self-made conventional step-bolus were used respectively. The surface dose under 3D-bolus and step-bolus was measured at 5 measurement spots of iso-center, lateral, medial, superior and inferior point, using GAFCHROMIC EBT3 film (International specialty products, USA) and the measured value of dose at 5 spots was compared and analyzed. Also the respective treatment plan was devised, considering the adoption of 3D-bolus and stepbolus and the separate treatment results were compared to each other. Results : The average surface dose was 179.17 cGy when the device of 3D-bolus was adopted and 172.02 cGy when step-bolus was adopted. The average error rate against the prescribed dose of 180 cGy was -(minus) 0.47% when the device of 3D-bolus was adopted and it was -(minus) 4.43% when step-bolus was adopted. It was turned out that the maximum error rate at the point of iso-center was 2.69%, in case of 3D-bolus adoption and it was 5,54% in case of step-bolus adoption. The maximum discrepancy in terms of treatment accuracy was revealed to be about 6% when step-bolus was adopted and to be about 3% when 3D-bolus was adopted. The difference in average target dose on chest wall between 3D-bolus treatment plan and step-bolus treatment plan was shown to be insignificant as the difference was only 0.3%. However, to mention the average prescribed dose for the part of lung and heart, that of 3D-bolus was decreased by 11% for lung and by 8% for heart, compared to that of step-bolus. Conclusion : It was confirmed through this research that the dose uniformity could be improved better through the device of 3D-bolus than through the device of step-bolus, as the device of 3D-bolus, produced in consideration of the contact condition of skin surface of chest wall, could be attached to patients' skin more nicely and the thickness of chest wall can be guaranteed more accurately by the device of 3D-bolus. It is considered that 3D-bolus device can be highly appreciated clinically because 3D-bolus reduces the dose on the adjacent organs and make the normal tissues protected, while that gives no reduction of dose on chest wall.

• Radiation Oncology Journal
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• v.18 no.3
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• pp.194-199
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• 2000

Purpose : Then determining the lower margin of post-operative pelvic radiation therapy field according to the traditional method (recommended by Gunderson), the organs located in the low pelvic cavity and the perineum are vulnerable to unnecessary radiation. This study evaluated the effect of individualized determination of the lower margin at 2 cm to 3 cm below the anastomotic site on the failure patterns. Materials and Methods . Authors included ぉ patients with modified Astler-Coiler (MAC) stages from B2 through C3, who received low anterior resection and post-operative pelvic radiation therapy from Sept. 1994 to May 1998 at Samsung Medical Center, Sungkyunkwan University. The numbers of male and female patients were 44 and 44, and the median age was 57 years (range: 32-81 years). Three field technique (posterior-anterior and bilateral portals) by 6, 10, 15 MV X-rays was used to deliver 4,500 cGy to the whole pelvis followed by Sn cGy's small field boost to the tumor bed over 5.5 weeks. Sixteen patients received radiation therapy by traditional field margin determination, and the lower margin was set either at the low margin of the obturator foramen or at 2 cm to 3 cm below the anastomotic site, whichever is lower. In 72 patients, the lower margin was set at 2 cm to 3 cm below the anastomotic site, irrespectively of the obturator foramen, by which the reduction of radiation volume was possible in 55 patients ($76\%$). Authors evaluated and compared survival, local control, and disease-free survival rates of these two groups. Results : The median follow-up period was 27 months (range : 7-58 months). MAC stages B2 in 32($36\%$), B3 in 2 ($2\%$), Cl in 2 ($2\%$), C2 in 50 ($57\%$), and C3 in 2 ($2\%$) Patients, respectively. The entire patients' overall survival rates at 2 and 4 years were $94\%$ and $68\%$, respectively, and disease-free survival rates at 2 and 4 years were $86\%$ and $58\%$, respectively. The first failure sites were local only in 4, distant only in 14, and combined local and distant in 1 patient, respectively. There was no significant difference with respect to local control and disease-free survival rates ( p=0.42, p=0.68) between two groups of different lower margin determination policies. Conclusion : The new concept in the individualized determination of the lower margin depending on the anastomotic site has led to the equivalent local control and disease-free survival rates, and is expected to contribute to the reduction of unnecessary radiation-related morbidity by reduction of radiation volume, compared with the traditional method of lower margin determination.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

• The Korean Journal of Nuclear Medicine Technology
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• v.22 no.1
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• pp.90-97
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• 2018

Purpose The lung segment ratio which is obtained through quantitative analyses of lung perfusion scan images is calculated to evaluate the lung function pre and post surgery. In this Study, the planar image production methods by using Q-Metrix (GE Healthcare, USA) program capable of not only quantitative analysis but also computation of the segment ratio after having performed SPECT/CT are comparatively evaluated. Materials and Methods Lung perfusion scan and SPECT/CT were performed on 50 lung cancer patients prior to surgery who visited our hospital from May 1, 2015 to September 13, 2016 by using Discovery 670(GE Healthcare, USA) equipment. AP(Anterior Posterior)method that uses planar image divided the frontal and rear images into three rectangular portions by means of ROI tool while PO(Posterior Oblique)method computed the segment ratio by dividing the right lobe into three parts and the left lobe into two parts on the oblique image. Segment ratio was computed by setting the ROI and VOI in the CT image by using Q-Metrix program and statistically analysis was performed with SPSS Ver. 23. Results Regarding the correlation concordance rate of Q-Metrix and AP methods, RUL(Right upper lobe), RML(Right middle lobe) and RLL(Right lower lobe) were 0.224, 0.035 and 0.447. LUL(Left upper lobe) and LLL(Left lower lobe) were found to be 0.643 and 0.456, respectively. In the PO method, the right lobe were 0.663, 0.623 and 0.702, respectively, while the left lobe were 0.754 and 0.823. When comparison was made by using the Paired sample T-test, Right lobe were $11.6{\pm}4.5$, $26.9{\pm}6.2$ and $17.8{\pm}4.2$, respectively in the AP method. Left lobe were $28.4{\pm}4.8$ and $15.4{\pm}5.6$. The right lobe of PO had values of $17.4{\pm}5.0$, $10.5{\pm}3.6$ and $27.3{\pm}6.0$, while the left lobe had values of $21.6{\pm}4.8$ and $23.1{\pm}6.6$, thereby having statistically significant difference in comparison to the Q-Metrix method for each of the lobes (P<0.05). However, there was no statistically significant difference in Right middle lobe (P>0.05). Conclusion The AP method showed low concordance rate in correlation with the Q-Metrix method. However, PO method displayed high concordance rate overall. although AP method had significant differences in all lobes, there was no significant difference in Right middle lobe of PO method. Therefore, at the time of production of lung perfusion scan results, utilization of Q-Metrix method of SPECT/CT would be useful in computation of accurate resultant values. Moreover, it is deemed possible to expect obtain more practical sectional computation result values by using PO method at the time of planar image acquisition.

• The Korean Journal of Nuclear Medicine
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• v.39 no.4
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• pp.252-256
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• 2005

Purpose: Thyroglobulin (Tg) is a valuable and sensitive tool as a marker for diagnosis and follow-up for several thyroid disorders, especially, in the follow-up of patients with differentiated thyroid cancer (DTC). Often, clinical decisions rely entirely on the serum Tg concentration. But the Tg assay is one of the most challenging laboratory measurements to perform accurately owing to antithyroglobulin antibody (Anti-Tg). In this study, we have compared the degree of Anti-Tg effects on the measurement of Tg between availale Tg measuring kits. Materials and Methods: Measurement of Tg levels for standard Tg solution was performed with two different kits commercially available (A/B kits) using immunoradiometric assay technique either with absence or presence of three different concentrations of Anti-Tg. Measurement of Tg for patient's serum was also performed with the same kits. Patient's serum samples were prepared with mixtures of a serum containing high Tg levels and a serum containg high Anti-Tg concentrations. Results: In the measurements of standard Tg solution, presence of Anti-Tg resulted in falsely lower Tg level by both A and B kits. Degree of Tg underestimation by h kit was more prominent than B kit. The degree of underestimation by B kit was trivial therefore clinically insignificant, but statistically significant. Addition of Anti-Tg to patient serum resulted in falsely lower Tg levels with only A kit. Conclusion: Tg level could be underestimated in the presence of anti-Tg. Anti-Tg effect on Tg measurement was variable according to assay kit used. Therefore, accuracy test must be performed for individual Tg-assay kit.

• Journal of the Korean Society of Radiology
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• v.4 no.4
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• pp.17-24
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• 2010

Hemoptysis which is comparatively common symptom in respiratory disease patients is a clinical symptom which has high risk of death in spite of many curative means. Bronchial tube embolization is a very useful medical procedure when hemoptysis does not stop for treatment of internal medicine or surgery and in addition to the purpose of instant hemostasis, for patients for whom surgical operation is impossible or for the purpose of gaining time to improve the state of the patient before surgical operation. In relation to this, this study is to know of the usefulness of bronchial tube artery embolization. The objects were 60 persons for whom bronchial tube artery embolizations are conducted because of large hemoptysis occurred from March 2007 to December 2009 in J hospital. They had large hemoptysis of 400ml or more per day and 200ml or more at a time or though the quantity of hemoptysis was less than 400ml they did not respond to the treatment of internal medicine for 10 days or longer. The average age was 60.5 years and cause diseases were tuberculosis, bronchiectasis, and pneumonia and lung cancer. Embolus parts were Rt bronchial artery 19 examples, Lt bronchial artery, both bronchial artery, Rt Intercostobronchial artery, and they were the case where embolization for many blood vessels were simultaneously carried out. As embolus materials, PVA (conteour) and microcoil were used. In 76.6% of 60 persons of patients hemorrhage stopped with the lapse of time after the procedure and in 4 examples (6.6) re-embolization was carried out due to re-bleeding after the procedure. Bronchial tube artery embolization has high early success rate and effectively controls hemoptysis in the treatment of hemoptysis and is an effective emergency remedy for hemorrhage due to large hemoptysis and will be a good medical procedure which reduces death rate. In addition, primarily if it is conducted together with the treatment of internal medicine it will be, as an effective curative means for hemorrhage due to large hemoptysis, a good mediate radial rays medical procedure which reduces death rate.

• The Korean Journal of Nuclear Medicine
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• v.39 no.4
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• pp.231-238
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• 2005

Purpose: We investigated prospectively whether the interpretation considering the patterns of FDG uptake and the findings of unenhanced CT for attenuation correction can improve the diagnostic accuracy for assessing malignant lymph node (LN) and N stage in non-small cell lung cancor (NSCLC) using CT-corrected FDG-PET (PET/CT). Materials & Methods: Subjects were 91 NSCLC patients (M/F 62/29, age: $60{\pm}9$ yr) who underwent PET/CT before in dissection. We evaluated the maximum SUV (maxSUV), patterns of FDG uptake, short axis diameter, and calcification of LN showing abnormally increased FDG uptake. Then we investigated criteria improving the diagnostic accuracy and correlated results with postoperative pathology. In step 1, in was classified as benign or malignant based on maxSUV only. In step 2, LN was regarded as benign if it had lower maxSUV than the cut-off value of step 1 or it had calcification irrespective of its maxSUV. In step 3, LN regarded as malignant in step 2 was classified as benign if they had indiscrete margin of FDG uptake. Results: Among 432 LN groups surgically resected (28 malignant, 404 benign), 71 showed abnormally increased FDG uptake. We determined the cut-off as maxSUV=3.5 using ROC curve analysis. The sensitivity, specificity, and accuracy for assessing malignant LN were 64.3%, 86.9%, 85.4% in step 1, 64.3%, 95.0%, 93.1% in step 2, and 57.1%, 98.0%, 95.4% in step3, respectively. The accuracy for assessing N stage was 64.8% in step 1, 80.2% in step 2, and 85.7% in step 3. Conclusion: interpreting PET/CT, consideration of calcification and shape of the FDG uptake margin along with maxSUV can improve the diagnostic accuracy for assessing malignant involvement and N stage of hilar and mediastinal LNs in NSCLC.