• Tuberculosis and Respiratory Diseases
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• 제66권3호
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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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• 제62권6호
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• pp.523-530
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• 2007

Background: A ThinPrep$^{(R)}$ Processor was developed to overcome the limitations of conventional cytology and is widely used to diagnose various cancers. This study compared the diagnostic efficacy of conventional cytology for lung cancer with that of the ThinPrep$^{(R)}$ cytology using the bronchial washing fluid. Methods: The bronchial washing fluid of 790 patients from Jan. 2002 to Dec. 2006, who were suspected of gaving a lung malignancy, was evaluated. Both ThinPrep$^{(R)}$ and conventional cytology were performed for all specimens. Result: Four hundred forty-six men and 344 women were enrolled in this study, and 197 of them were diagnosed with cancer from either a bronchoscopic biopsy or a percutaneous needle aspiration biopsy. ThinPrep$^{(R)}$ cytology showed a sensitivity, specificity, positive predictive value, negative predictive value and false negative error rate of 71.1%, 98.0%, 92.1%, 91.1%, 8.9%, respectively. The conventional cytology showed sensitivity, specificity, positive predictive value, nagative predictive value and false negative error rate of 57.9%, 98.0%, 90.5%, 87.5%, 12.5%, respectively. For central lesions, the sensitivity of conventional cytology and ThinPrep$^{(R)}$ were 70.1% and 82.8%, respectively. Conclusion: ThinPrep$^{(R)}$ cytology showed a higher sensitivity and lower false negative error rate than conventional cytology. This result was unaffected by the histological classification of lung cancer. Therefore, ThinPrep$^{(R)}$ cytology appears to be a useful method for increasing the detection rate of lung cancer in bronchial washing cytology test.

• Progress in Medical Physics
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• 제24권3호
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• pp.154-161
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• 2013

This study assessed compared photon and proton treatment techniques, such as intensity modulated radiation therapy (IMRT), uniform scanning proton therapy (USPT), and intensity modulated proton therapy (IMPT), for a total of 10 prostate cancers. All treatment plans delivered 70 Gy to 95% of the planned target volume in 28 fractions. IMRT plans had 7 fields for the step and shoot technique, while USPT and IMPT plans employed two equally weighted, parallel-opposed lateral fields to deliver the prescribed dose to the planned target. Inverse planning was then incorporated to optimize IMPT. The homogeneity index (HI) and conformity index (CI) for the target and the normal tissue complication probability (NTCP) for organ at risk (OAR) were calculated. Although the mean HI and CI for target were not significantly different for each treatment techniques, the NTCP of the rectum was 2.233, 3.326, and 1.707 for IMRT, USPT, and IMPT, respectively. The NTCP of the bladder was 0.008, 0.003, and 0.002 respectively. The NTCP values at the rectum and bladder were significantly lower using IMPT. Our study shows that using proton therapy, particularly IMPT, to treat prostate cancer could be beneficial compared to 7-field IMRT with similar target coverage. Given these results, radiotherapy using protons, particularly optimized IMPT, is a worthwhile treatment option for prostate cancer.

• The Korean Journal of Nuclear Medicine
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• 제36권2호
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• pp.121-132
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• 2002

Purpose : Taxol(Paclitaxel), an antineoplastic agent, has been used in the treatment of ovarian and breast cancers. The determination of optimal Taxol concentrations in human serum was required for enhancing therapeutic effect and maintaining the appropriate Taxol level in blood. This study was aimed to synthesizeradiolabeled Taxol derivatives as radiotracer in competitive radioimmunoassay for monitoring Taxol concentrations in blood and to determine the usefulness of its derivatives. Materials and Methods : Hemisucdcinyltaxol(HT) was synthesized by esterification of Taxol with succinic anhydride. Tyraminehemisuccinyltaxol(THT) was synthesized by coupling of HT with tyramine using isobutylchlormate as coupling agent and purified by HPLC. By using chloramine-T($5.25mg/ml,\;10{\mu}{\ell}$) as oxidant agent, THT($4mg/ml,\;30{\mu}{\ell}$) was labeled wity $^{125}I\;(37MBq,\;1mCi)$. To estimate the stability of purified THT, $^{125}I-iodotyraminehemisuccinyltaxol(^125}ITHT)$ was dissolved in 80% acetonitrile aqueous solution, and the solution was incubated at $4^{\circ}C\;and\;37^{\circ}C$ for 7 days. At various time intervals, the stability of THT and $^{125}ITHT$ was monitored. The titer of Taxol monoclonal antibody, 3G5A7, was determined by competitive radioimmunoassay using $^{125}ITHT$ as a labeled antigen. A standard dose-response curve was demonstated by Taxol competitive radioimmunoassay. Resulls : HT and THT were synthesized with 79.9% and 19.5% yield, respectively. The labeling yield of $^{125}ITHT$ was 93%. After 7 days, the chemical purity of THT was 96.5% at $4^{\circ}C$, and 97.5% at $37^{\circ}C$. After 3 days, $^{125}ITHT$ was stable with 94.7% at $4^{\circ}C$ and 93.4% at $37^{\circ}C$. After 7 days, fadiochemical purity was diminished to 88.1% at $37^{\circ}C$. The titer of Taxol monoclonal antibody, 3G5A7, was determined to 1:256. A standard dose-response curve demonstated good collinearity ($R^2=0.971$) as Taxol concentration-dependent manner. Conclusion : Competitive radioimmunoassay using $^{125}I-iodotyraminehemisuccinytaxol$ as radiotracer could be used to monitor for concentration of Taxol in the human serum.

• Journal of Yeungnam Medical Science
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• 제17권1호
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• pp.39-48
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• 2000

Background: There arc two theories in the development of colon cancer. One is the adenoma-carcinoma sequence theory and the other is the de novo cancer theory. Western countries believe in the adenoma-carcinoma sequence theory, however there are many recent reports from, Japan about cancers developing from small adenomas. Methods: The present study analyzed 408 polyps from 508 cases that were taken by colonoscopic polypectomy at the Department of internal Medicine, Yeungnam University Hospital. Results: The percentage of patients who had a polyp was 41.3% (210 cases out of 526 cases), and the peak incidence was noted in patients in their 50s and 60s, There was no difference between the sexes, but we noted significant increase in the incidence of polyps in patients over the age of thirty. We found 395 polyps below 1cm and 13 polyps above 1cm. Among 408 polyps, 5 cases were cancerous polyps and 3 cases showed polyp size of less than 1cm each. The first case was a polyp of 0.4cm in size with elevated mucosa at the ascending colon. The second was 0.5cm in size with round elevation and hyperemic mucosa in the rectum. The third was 0.6cm in size with tubular elevation at the hepatic flexure. Conclusions: Colon polyp is a common disease in Koreans, Even small polyps can have cancer tissue, which should be removed if discovered during colonoscopy. We believe that not all colon cancer originates in the manner described by the adenoma-carcinoma sequence theory. However further studies with a larger sample population arc needed to determine the exact role of colon polyps in the development of colon cancer.

• Journal of the Korean Applied Science and Technology
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• 제29권1호
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• pp.71-80
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• 2012

Vinca alkaloids produced from Catharanthus roseus are one of the most important natural product drugs in treatments of human cancers. These anticancer drugs are derived from coupling of the two monomeric indole alkaloids, catharanthine and vindoline. In order to investigate vindoline biosynthesis, tabersonine-$CD_3$ 1a is synthesized to use as a deuterium labeled precursor, which is distinguished clearly from the natural counterpart. We show that these deuterium labeled tabersonine 1a are successfully incorporated into the vindoline biosynthetic pathway to yield three deuterated vindoline intermediates. 16-Hydroxytabersonine-$CD_3$ (m/z 356) 2a, 16-Methoxytabersonine-$CD_3$ (m/z 370) 3a, 16-Methoxy-2,3-dihydro-3-hydroxytabersonine-$CD_3$ (m/z 388) 4a are produced from the cell suspension culture measured by UPLC/MS at 5 and 13 days after feeding tabersonine. The conversion rates from 1a to 2a and 2a to 3a are fast, whereas that from 3a to 4a is much slower. This indicates that the rate determining step among the first three vindoline biosynthesis is the last step. As a result of the slow conversion rate from 3a to 4a, the accumulation level of 16-Methoxytabersonine-$CD_3$ 3a is significantly increased up to 13 days. The accumulation ratio among 2a, 3a and 4a is 1, 2 and 0.1 at 5 days. However, the peaks of desacetoxyvindoline-$CD_3$ 5a, deacetylvindoline-$CD_3$ 6a and vindoline-$CD_3$ 7a are not found from the cell extracts even after 13 days of incubation which may indicate no presence of their corresponding enzymes.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.909-913
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• 2013

Purpose: The liver is the organ to which colorectal carcinomas (CRCs) most commonly metastasize, and surgical resection has been established as the most effective and potentially curative treatment for CRC with liver metastasis (LM). Therefore, surveillance of LM is vital for improvement of prognosis of CRC patients. In this study, we aimed to explore the potential value of carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), and marker enzymes in indicating LM with CRC. Methods: Three groups of eligible patients with metastatic cancers were retrospectively included: CRC patients with LM (CRC-LM) or without LM (CRC-NLM), and non-CRC patients with LM (NCRC-LM). All metastatic lesions were identified by CT or MRI. Data on characteristics of the patients, the primary site, the locations of metastasis, CA 19-9, CEA, and biochemical parameters were collected for analysis. Results: A total of 493 patients were retrospectively included. More alcohol consumption was found in CRC-LM than CRC-NLM. Some biochemical enzymes were found to be significantly higher in groups with LM than without (CRC-LM or NCRC-LM v.s CRC-NLM). Both CEA and CA 19-9 were much higher in CRC-LM than CRC-NLM or NCRC-LM. For CRC patients, CA 19-9, ${\gamma}$-glutamyl transpeptidase, CEA and alcohol consumption were identified as independent factors associated with LM. Conclusion: Our analysis suggested the CA 19-9 might be a potential valuable indicator for LM of CRC in the clinic.

• Investigative Magnetic Resonance Imaging
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• 제18권1호
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• pp.34-42
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• 2014

Purpose : To evaluate the correlation of lesion-to-normal ratio (LNR) of signal intensity from double inversion recovery MR imaging and total choline-containing compound (tCho) resonance from single voxel MR spectroscopy in breast cancers. Materials and Methods: Between August 2008 and December 2009, 28 patients who were diagnosed as breast cancer and had undergone both double inversion recovery (DIR) MR imaging and MR spectroscopy (MRS) were included in this study. The signal intensities of the lesion (L) and ipsilateral normal breast tissue (N) were measured in region of interest of each breast cancer in DIR and contrast enhance MR image (CE-T1WI) to calculate the LNR value for each technique. MRS was performed using single-voxel MR spectroscopy. The height, width and area of tCho resonance were compared with each LNR of DIR and CE-T1WI. We used Pearson's correlation coefficient(r) for correlation analysis and the significance level was p=0.05. Results: There was no statistically significant correlation between LNR of CE-T1WI and height (r=-0.322, p=0.094), width (r=-0.233, p=0.232) and area (r=-0.309, p=0.109) of MRS tCho. There was no statistically significant correlation between LNR of DIR and height (r=0.067, p=0.735), width (r=-0.287, p=0.139) and area (r=0.012, p=0.953) of MRS tCho, either. The Pearson's correlation coefficient was 0.186 between LNRs of CET1WI and DIR (p=0.344). Conclusion: There was no statistically significant correlation between LNR of DIR and relative amount of tCho resonance of MRS.

• The Journal of Korean Society for Radiation Therapy
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• 제18권1호
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• pp.35-41
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• 2006

Purpose: A various find of radiotherapy treatment plans have been made to determine appropriate doses for breasts, chest walls and loco-regional lymphatics in the radiotherapy of breast cancers. The aim of this study was to evaluate the optimum radiotherapy plan technique method by analyzing dose distributions qualitatively and quantitatively. Materials and Methods: To evaluate the optimum breast cancer radiotherapy plan technique, the traditional method(two dimensional method) and computed tomography image are adopted to get breast volume, and they are compared with the three-dimensional conformal radiography (3DCRT) and the intensity modulated radiotherapy (IMRT). For this, the regions of interest (ROI) such as breasts, chest walls, loco-regional lymphatics and lungs were marked on the humanoid phantom, and the computed tomography(Volume, Siemens, USA) was conducted. Using the computed tomography image obtained, radiotherapy treatment plans (XiO 5.2.1, FOCUS, USA) were made and compared with the traditional methods by applying 3DCRT and IMRT. The comparison and analysis were made by analyzing and conducting radiation dose distribution and dose-volume histogram (DVH) based upon radiotherapy techniques (2D, 3DCRT, IMRT) and point doses for the regions of interest. Again, treatment efficiency was evaluated based upon time-labor. Results: It was found that the case of using 3DCRT plan techniques by getting breast volume is more useful than the traditional methods in terms of tumor delineation, beam direction and confirmation of field boundary. Conclusion: It was possible to present the optimum radiotherapy plan techniques through qualitative and quantitative analyses based upon radiotherapy plan techniques in case of breast cancer radiotherapy. However, further studies are required for the problems with patient setup reproducibility arising from the difficulties of planning target volume (PVT) and breast immobilization in case of three-dimensional radiotherapy planning.

• Radiation Oncology Journal
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• 제17권2호
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• pp.141-145
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• 1999

Purpose : Granisetron is a potent, the most selective 5-HT3 receptor antagonist and is reported to b effective in treatment of radiation-induced emesis. The antiemetic efficacy and safety of oral granisteron was evaluated in patients with receiving highly emetogenic treatment by conventional fractionated irradiation. Materials and Methods : Patients with various cancers who were being treated with irradiation were accrued into the present study. The intensity of nausea was evaluated on first 24 hours and on day-7 by patients according to the degree of interference with normal daily life as followings; a) none; b) present but no interference with normal daily life (mild): c) interference with normal daily life (moderate): and d) bedridden because of nausea (severe). Non or mild state was considered to indicate successful treatment. The efficacy of antiemetic treatment was graded as follows; a) complete response; no vomiting, no worse than mild nausea and receive no rescue antiemetic therapy over the 24h period, b) major response; either one episode of vomiting or moderate/severe nausea or had received rescue medication over 24h period, or any combination of these, c) minor response; two to four episodes of vomiting over the 24h period, regardless of nausea and rescue medication, d) failure; more than four medication. The score of the most symptom was recorded and the total score over 24 hours was summarized. The complete or major response was considered to indicate successful treatment. Results : A total of 10 patients were enrolled into this study, and all were assessable for efficacy analysis. Total nausea control was achieved in 90$\%$ (9/10:none=60$\%$ plus mild=30$\%$) of total patients after 7 days. The control of vomiting by granisteron was noted in seven patients (70$\%$) of complete response and three (30$\%$) of major response with a hundred-percent successful treatment over 7 days. The minor response or treatment failure were not observed. No significant adverse events or toxicities from granisetron were recorded in patient receiving granisetron. Conclusion : We concluded that granisetron is a highly effective antiemetic agent in controlling radiotherapy-induced nausea or vomiting with a minimal toxicity profile.