• The Journal of Korean Society for Radiation Therapy
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• v.31 no.1
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• pp.43-49
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• 2019

Purpose : We apply the Layered Rescanning PBS designed to complement the Pencil Beam Scanning(PBS), which is vulnerable to moving organs with the Moving Phantom, and compare the homogeneity with the single scan PBS. Methods and materials: Matrix X (IBA, Belgium) and Moving Phantom (standard imaging, USA) were used. A dose of 200 cGy was measured in the AP direction on a hypothetical tumor $10{\times}10{\times}5cm$. The plan type was planned as 4 kinds of sinlge scan PBS, rescan number 4, 8, 12 times. Were measured three times for each types. During the measurement, the respiratory cycle of the Moving Phantom was generally set to 4 seconds per cycle, and the movement radius in the S-I direction was set to 2 cm. In addition, beam on time was measured. Results : The mean values of $D_{max}$ in the PTV were $246.47{\pm}18.8cGy$, $223.43{\pm}8.92cGy$, and $222.47{\pm}7.7cGy$, $213.9{\pm}6.11cGy$ and the mean values of $D_{min}$ were $165.53{\pm}4.32cGy$, $173.13{\pm}11.94cGy$, $184.13{\pm}8.04cGy$, $182.67{\pm}4.38cGy$ and the mean values of $D_{mean}$ $192.77{\pm}6.98cGy$, $196.7{\pm}4.01cGy$, $198.17{\pm}4.96cGy$, $195.77{\pm}3.15cGy$ respectively. As the number of rescanning increased, the Homogeneity Index converged to 1. The beam on time was measured as 2:15, 3:15, 4:30, 5:37 on average. In the measurement process, in the low dose layer of the MU, the problem was found that it was not rescanned as many times as the set number of rescan. Conclusions : In the treatment of tumors with long-term movements, the application of layered rescanning PBS showed a more uniform dose distribution than single scan PBS. And as the number of rescan increase, the distribution of homogeneity is uniform. Compared with single scan plan and 12 rescan plan, HI value was improved by 0.32. Further studies are expected to be applicable to patients who can not be treated with respiratory synchronous radiation therapy.

• The Korean Journal of Nuclear Medicine Technology
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• v.19 no.2
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• pp.63-67
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• 2015

Purpose Among various causes that influence image quality degradation, various methods for decrease in Artifact occurred by respiration of patients are being used. Among them, this study intended to evaluate CTAC Shift correction method and additional scan compare to the Scan(Q static scan) using respiratory gated system. Materials and Methods This study was conducted on 10 patients, and used PET-CT Discovery 710 (GE Healthcare, MI, USA) and Varian's RPM system. 5.18 Mbq per kg of $^{18}F$-FDG was injected on patients, asked them to take a rest for 1 hour in the bed, and conducted test after urination. Images were visualized through Q static scan, CTAC Shift correction method, Additional scan based on the Whole body scan(WBS) with Artifact. Decrease in Artifact was compared in each image, conducted Gross Evalution, and measured changes of SUVmax. Results For image obtained through the CTAC Shift correction method through WBS with Artifact, 12~56%, Q static scan image showed 17~54% of change rate and Additional Scan showed -27~46% of change rate. In Blind Test, the CTAC Shift correction image showed the highest point with 4 points, Q static scan image showed 3.5 points, and Additional scan image showed 3.4 points. The standardized WBS scan through Oneway ANOVA and three types of Scan method showed significant difference(p<0.05), and did not show significant difference between the three Scan methods(p>0.05). However, the three Scan methods showed significant difference in Blind test. Conclusion Additional scan and Q static scan require more time than the CTAC Shift correction method, there is concern about excessive exposure to patients by CT rescan and Q static scan is difficult to apply on patients with inconsistent respiration or irregular respiration cycle due to pain. For CTAC Shift correction method, limited correction is possible and the range is limited as well. It is considered as a useful method of improving diagnostic value when hospitals use the system appropriately and develop various advantageous factors of each method.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.776-784
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• 1997

Background : Various combinations of treatment modalities have been reported in stage III non-small cell lung cancer (NSCLC). however, the standard treatment modality has not established yet. Recently, the efficacy of concurrent chemotherapy and radiation therapy has been reported in locally advanced lung cancer. We evaluate the response rate, toxicity, and survival of concurrent chemotherapy with etoposide and cisplatin(EP) and radiation therapy for unresectable stage III NSCLC. Method : Between October 1995 and December 1996, 32 patients with histologically proven unresectable stage III NSCLC without malignant pleural effusion were entered into this study. Twenty-nine patients were eligible for the response, survival, and toxicity analysis. Induction was two cycles of chemotherapy with etoposide and cisplatin plus concurrent chest RT to 4500cGy. Resection was attempted if the clinical response offered surgical resectability. Boost radiation therapy upto 5940cGy and one cycle of EP were performed if the disease were stable or responsive but still unresectable. Results : Of 29 eligible patients, 22(75.9%) showed partial response(PR). The progression free interval was 6.3months(range 1.1 to 19.5months). Surgical resection was performed in one patient. The median survival was 12.1months and one-year survival rate was 50.6%. The major toxicity was leukopenia($\geq$ grade 3, 46%). Thrombocytopenia over grade 3 was found in 11%. Radiation pneumonitis occurred in 13 patients(46%). Conclusion : Concurrent chemotherapy(EP) plus radiotherapy was effective and tolerable in the treatment of unresectable stage III NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.485-496
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• 2002

Background : Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful in the chemoprevention of colon cancers. Continuous NSAID use results in a 40% to 50% reduction in the relative risk of colorectal cancer. The precise mechanism by which NSAIDs prevent and/or cause the regression of colorectal tumors is not known. Some investigators have reported that certain NSAIDs induce apoptosis and alter the expression of the cell cycle regulatory genes in some carcinoma cells when administered at a relatively high concentration. However, the possibility of NSAIDs application as chemopreventive agents in lung cancers remains to be elucidated. To address this question, the human lung cancer cell line NCI-H1299 was used to investigate whether or not NSAIDs might induce the apoptotic death of NCI-H1299 cells. Methods : A viability test was carried out using a MTT assay. Apoptosis was measured by flow cytometric analysis and unclear staining(DAPI). The talytic activity of the caspase family was measured by the fluirigenic cleavage of biosubstrates. To define the mechanical basis of apoptosis, western blot was performed to analyze the expression of the death substrates(PARP and ICAD). Results : NaSaL significantly decreased the viability of the NCI-H1299 cells, which was revealed as apoptosis characterized by an increase in the $subG_0/G_1$ population and unclear fragmentation. The catalytic activity of caspase-3 protease began to increase after 24 Hr and reached a peak 30 Hr after treatment with 10 mM NaSaL. In contrast, caspase-6, 8, and 9 proteases did not have a significantly altered enzymatic activity. Consistent with activation of caspase-3 protease, NaSaL induced the cleavage of the protease biosubstrate. Conclusion : NaSaL induces the apoptotic death of NCI-H1299 human lung cancer cells via the activation of caspase-3 protease.

• Progress in Medical Physics
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• v.18 no.1
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• pp.27-34
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• 2007

Respiration sating radiotherapy technique developed In consideration of the movement of body surface and Internal organs during respiration, is categorized into the method of analyzing the respiratory volume for data processing and that of keeping track of fiducial landmark or dermatologic markers based on radiography. However, since these methods require high-priced equipments for treatment and are used for the specific radiotherapy. Therefore, we should develop new essential method whilst ruling out the possible problems. This study alms to obtain body surface motion by using the couch based computer-controlled motion phantom (CBMP) and US sensor, and to develop respiration gating techniques that can adjust patients' beds by using opposite values of the data obtained. The CBMP made to measure body surface motion is composed of a BS II microprocessor, sensor, host computer and stopping motor etc. And the program to control and operate It was developed. After the CBMP was adjusted by entering random movement data, and the phantom movements were acquired using the sensors, the two data were compared and analyzed. And then, after the movements by respiration were acquired by using a rabbit, the real-time respiration gating techniques were drawn by operating the phantom with the opposite values of the data. The result of analysing the acquisition-correction delay time for the data value shows that the data value coincided within 1% and that the acquistition-correction delay time was obtained real-time $(2.34{\times}10^{-4}sec)$. And the movement was the maximum movement was 6 mm In Z direction, In which the respiratory cycle was 2.9 seconds. This study successfully confirms the clinical application possibility of respiration gating techniques by using a CBWP and sensor.

• Tuberculosis and Respiratory Diseases
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• v.53 no.4
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• pp.369-378
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• 2002

Background : The effects of chemotherapy on pulmonary function are mainly a reduced diffusion capacity and a restrictive ventilatory impairment. Exercise can expose cardiovascular and pulmonary abnormalities not evident at rest. Exercise related cardiopulmonary function is important in patients with malignant disease as a determinant of quality of life. We performed this study to evaluate the changes of body composition and cadiopulmonary exercise perfoemance of patients with locally advanced, non-small cell, lung cancer (NSCLC) before and after chemotherapy. Methods : We evaluated resting pulmonary function, body composition, physiologic performance status, and cardiopulmonary exercise function in 11 patients with locally advanced NSCLC, at diagnosis and prior to the fourth cycle of chemotherapy. Results : After chemotherapy, 4 patients (36.4%) showed partial response and 7 (63.4%) had stable disease. After chemotherapy, diffusion capacity of the lung for carbon monoxide was reduced ($89.7{\pm}34.1%$, vs. $71.9{\pm}20.5%$) but not significantly. There were no significant changes in body composition or the state of physiologic performance after chemotherapy. There was a significant impairment of cardiopulmonary exercise tolerance in patients with NSCLC, evidenced by a reduction of maximal oxygen uptake ($VO_2$max, ml/kg/min, $17.9{\pm}2.6$ : $12.6{\pm}6.1$, <0.05) and $O_2$pulse ($O_2$ pulse, ml/beat, $7.0{\pm}1.7$, $5.2{\pm}2.1$, <0.05). Conclusion : Systemic chemotherapy resulted in a loss of cardiopulmonary exercise function in patients with locally advanced NSCLC within the short-term period, but not a physiologic change of body composition within the same period.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.473-479
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• 2005

Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.178-185
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• 2009

Background: Epigallocatechin-3-gallate (EGCG) is the major catechin in green tea, and has shown antiproliferative, antiangiogenic, antimetastatic and cell cycle pertubation activity in various tumor models. Hypoxia can be induced because angiogenesis is insufficient for highly proliferating cancer. Hypoxia-inducible factor-1$\alpha$ (HIF-1$\alpha$) and its downstream target, vascular endothelial growth factor (VEGF), are important for angiogenesis, tumor growth and metastasis. The aim of this study was to determine how hypoxia could cause changes in the cellular phenomena and microenvironment in a non-small cell culture system and to examine the effects of EGCG on a HIF-1$\alpha$ and VEGF in A549 cell line. Methods: A549 cells, a non-small cell lung cancer cell line, were cultured with DMEM and 10% fetal bovine serum. A decrease in oxygen tension was induced using a hypoxia microchamber and a $CO_2-N_2$ gas mixture. Gas analysis and a MTT assay were performed. The A549 cells were treated with EGCG (0, 12.5, 25, 50 ${\mu}mol/L$), and then examined by real-time-PCR analysis of HIF-1$\alpha$, VEGF, and $\beta$-actin mRNA. Results: Hypoxia reduced the proliferation of A549 cells from normoxic conditions. EGCG inhibited HIF-1$\alpha$ transcription in A549 cells in a dose-dependent manner. Compared to HIF-1$\alpha$, VEGF was not inhibited by EGCG. Conclusion: HIF-1$\alpha$ can be inhibited by EGCG. This suggests that targeting HIF-1$\alpha$ with a EGCG treatment may have therapeutic potential in non-small cell lung cancers.

• Tuberculosis and Respiratory Diseases
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• v.48 no.3
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• pp.347-356
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• 2000

Background : Patients with obstructive sleep apnea syndrome are known to have high long-term mortality compared to healthy subjects because of their cardiovascular dysfunction. The observation of hemodynamic changes by obstructive apneas is helpful when attempting to understand the pathophysiological mechanism of the development of cardiovascular dysfunction in those patients. Therefore, we studied the changes in cardiovascular function with an animal model and tried to obtain the basic data for an ideal experimental model (this phrase is unclear), a requirement for a more advanced study. Methods : Sixteen anesthetized dogs with ${\alpha}$-chloralose delete were divided into two groups : 8 dogs of room air breathing group and 8 dogs of oxygen breathing group. We measured $PaO_2$, $PaCO_2$, heart rate, cardiac output, mean femoral artery pressure, and mean pulmonary artery pressure at specified times during the apnea-breathing cycle before endotracheal tube occlusion (baseline), 25 seconds after endotracheal tube occlusion (apneic period), 10 seconds (early phase of postapneic period, EPA) and 25 seconds (late phase of postapneic period, LPA) after spontaneous breathing. Results : In room air breathing group, the heart rate significantly decreased during the apneic period compared to that at baseline (P<0.01) and increased at EPA and LPA compared to that during the apneic period (P<0.01). But, the heart rate showed no significant changes during apneic and postapneic periods in the oxygen breathing group. Cardiac output tended to decrease during apneic period compared to that at baseline, but was statistically significant. Cardiac output significantly decreased at LP A compared to at baseline (P<0.01). Mean femoral artery pressure was significantly decreased at during apneic period compared to that at baseline (P<0.05). Conclusion : Through this experiment, we were partially able to understand the changes of cardiovascular function indirectly, but delete new experimental animal model displaying physiological mechanism close to natural sleep should be established, and the advanced study in the changes of cardiovascular function and their causes should be continued.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.36-43
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• 1999

Background : Tumor growth is the net result of intrinsic proliferation and escape from active cell death. bcl-2 is a member of a new category of oncogenes that is not involved in influencing cell proliferation but is involved in regulating cell death(apoptosis). Based on this information, it seems to be reasonable to expect that there may be clinical prognostic significance of bcl-2 expression in non-small cell lung cancer. But its prognostic significance is not established. Methods: To investigate the role of bcl-2 in lung cancer, we performed immunohistochemical stain of bcl-2 on 57 biopsy specimens from resected primary non-small cell lung cancer. Thereafter, flow cytometric cell cycle analysis was done. And we analyzed the correlation between bcl-2 expression, clinical parameters, S-, $G_1$-phase fraction and survival. Results: bcl-2 were detected in 43.8% of total 57 patients(according to histology, squamous cancer 47%, adenocarcinoma 32%, according to TNM stage, I 28.6%, II 52.3%, III 45.5%. both differences were insignificant). By using the flow cytometric analysis, mean S-phase fraction of bcl-2(+) and (-) group were 14.1($\pm7.8$)%, 24.7($\pm10.5$)% (p<0.005), mean $G_1$-phase fraction of bcl-2(+) and bcl-2(-) group were 75.5($\pm10.8$)%, 65.5($\pm11.4$)%(p<0.05). 2yr, 3yr and 5yr survival and median survival time of bcl-2(+) group were 65%, 54%, 41%, 53 months, and those of bcl-2(-) group were 71%, 52%, 46%, 37 months. (p>0.05, Kaplan-Meier, log rank) Conclusion: bcl-2 was detected in 43.8% of primary non-small cell lung cancer. The S-phase fraction of bcl-2(+) group was less than bcl-2(-) group, and G1-phase fraction of bcl-2(+) group was more than bcl-2(-) group. But, expression of bcl-2 could not be a prognostic factor.