• Title/Summary/Keyword: 획득

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Off Pump Total Arterial Myocardial Revascularization (동맥 도관만을 이용하여 체외심폐순환 없이 시행한 관상동맥우회술)

  • Youn Young Nam;Lee Kyo Joon;Lee Gy Jong;Joo Hyun Chul;Lim Sang Hyun;Kim Seung Ho;Kwak Young Lan;Yoo Kyung Jong
    • Journal of Chest Surgery
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    • v.38 no.5 s.250
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    • pp.349-356
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    • 2005
  • Background: Arterial conduits using in coronary artery bypass grafting (CABG) have been known a great long term patency rates, and improved short and long term clinical outcomes. It has been reported that Off pump CABG has better clinical results than CABG using cardiopulmonary bypass. To evaluate the advantage of arterial conduits over venous conduits and to avoid the adverse effects of cardiopulmonary bypass, we performed total arterial Off pump CABG. Material and Method: From January 2001 to October 2004, Off pump CABG using only arterial conduits was performed on 325 patients with a mean age of $59.3\pm11.9$ years ($36\~83$). Mean ejection fraction was $55.4\pm14.0\%\;(15\~86).$ Angiography showed left main disease or triple-vessel disease in $81.9\%$ of the patients. Indications of using arterial conduits was stenosis $\ge50\%$ of left anterior descending artery, stenosis $\ge80\%$ of branches of left circumflex artery, and stenosis $\ge90\%$ of right coronary artery and its branches. Multi-slice computed tomography was performed on 194 patients to evaluate the short term patency rates. Result: A total of 928 distal anastomoses were performed and the average anastomoses per a patient were $2.86\pm0.78$. There was 1 operative mortality. Postoperative complications were mediastinitis in 6 patients ($1.8\%$), renal failure in 4 patients ($1.2\%$), perioperative myocardial infarction in 3 patients ($0.9\%$), reoperation for bleeding in 3 patients ($0.9\%$). There was no postoperative stroke. Patency rate of arterial conduits was $99.3\%$ (581/585). There were 4 stenoses or competitive flows in 2 radial arteries and 2 right internal mammary arteries. Conclusion: Total arterial Off pump CABG appears to be safe, showing a low surgical mortality and morbidity and excellent short term patency rates of arterial conduits.

Comparison of Tc-99m-Tetrofosmin and Tc-99m-MIBI Scintimammography in Differential Diagnosis of Breast Mass (유방종양의 감별진단에서 Tc-99m-Tetrofosmin과 Tc-99m-MIBI 유방신티그라피의 비교)

  • Park, Jung-Mi;Choi, Joon-Young;Lee, Kyung-Han;Choi, Yong;Choe, Yearn-Seong;Kim, Sang-Eun;Kim, Byung-Tae;Nam, Seok-Jin;Yang, Jeong-Hyun
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.5
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    • pp.393-402
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    • 2000
  • Purpose: Tc-99m-MIBI (MIBI) and Tc-99m-Tetrofosmin (TF) are commonly used for scintimammog (SMM). We compared the diagnostic ability of SMM using Tc-99m-MIBI and Tc-99m-TF for the diagnosis of breast mass. Materials and Methods: The study subjects were comprised of 123 breast lesior 86 normal breasts of 114 patients who underwent SMM. Bilateral prone images and anterior supine images obtained at 5 minutes and 1 or 3 hours after intravenous injection of 740 MBq of either MIBI or TF. of tumors were not significantly different between the MIBI and TF groups. First, two observers read the SMM without clinical information (1st interpretation), then read again with information about location (2nd interpretation). Sensitivity and specificity of each radiopharmaceutical for the diagnosis of cancer were evaluated in terms of image acquisition time, tumor size, and location. Results: The SMM a good agreement between two observers for 1st and 2nd interpretation, except for TF SMM at 3 hr. first interpretation, the sensitivities at 5 min, 1 hr, and 3 hr were not significantly different between MIBI TF SMM (81.6%, 80.0%, 60.9% in MIBI vs. 88.9%, 80.6%, 42.9% in TF), although the sensitivities of images were significantly lower than 5 min images in both MIBI and TF SMM. The specificity of TF at was superior to that of MIBI (81.5%, 90.0%, 82.9% in MIBI vs. 96.7%, 100%, 90.0% in TF, p<0.01 MIBI TF at 5 min). For the second interpretation with information of mass location, the sensitivities at 3 hr were significantly lower than 5 min images (86.8%, 86.7%, 78.3% in MIBI vs. 88.9%, 93.5%, 57.1% between MIBI and TF SMM. However, there was no significant difference in the specificity (60.0%, 75.0% for MIBI vs. 86.7%, 100%, 100% for TF). MIBI and TF SMM showed lower sensitivities for the with less than 1 cm than tumors with more than 1 cm. However, the location of tumors did not sensitivity and specificity between MIBI and TF SMM. Conclusion: The ability for the differential of breast tumor is similar between MIBI and TF SMM, and delayed image is not necessary. TF may be than MIBI considering the specificity of SMM without clinical information and labeling convenience.

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In vitro Antioxidant and Anti-Inflammatory Activities of Ethanol Extract and Sequential Fractions of Flowers of Prunus persica in LPS-Stimulated RAW 264.7 Macrophages (복숭아꽃 에탄올 추출물과 분획물의 in vitro 항산화 효과 및 RAW 264.7 대식세포에서의 항염증 효과)

  • Kwak, Chung Shil;Choi, Hye-In
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.10
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    • pp.1439-1449
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    • 2015
  • Prunus persica Flos (PPF) were investigated for their antioxidant and anti-inflammatory activities to find a natural functional food resource preventing degenerative diseases associated with excessive oxidative stress and chronic inflammation. PPF was extracted using ethanol (EtOH) and then sequentially fractioned by hexane (Hx), dichloromethane (DM), ethyl acetate (EA), n-butanol (BtOH), and water (DW). Contents of total phenolics and flavonoids, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities were measured. Anti-inflammatory effects in terms of nitric oxide (NO), prostaglandin (PG) E2, and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$ production were also measured using LPS-treated RAW 264.7 macrophages. EtOH extract showed relatively high antioxidant activity with high total phenolic (78.1 mg tannic acid/g) and flavonoid contents (55.3 mg rutin/g). EA fraction contained the highest total phenolic and flavonoid contents (394.6 mg tannic acid/g, 253.7 mg rutin/g), followed by BtOH (128.3 mg tannic acid/g, 93.1 mg rutin/g). EA and BtOH fractions and EtOH extract showed higher DPPH radical and ABTS radical scavenging activities than the others (P<0.05). In LPS-treated RAW 264.7 macrophages, EtOH extract ($200{\mu}g/mL$) showed significantly reduced (P<0.05) NO, PGE2, and TNF-${\alpha}$ production levels to 38.5%, 32.3%, and 48.9% of the control, respectively, as well as reduced iNOS and COX-2 protein expression. DM fraction ($50{\mu}g/mL$) showed significantly reduced (P<0.05) NO, PGE2, IL-6, and TNF-${\alpha}$ production levels to 43.5%, 13.3%, 38.7%, and 41.3% of the control, respectively, and EA fraction ($50{\mu}g/mL$) showed significantly reduced NO, PGE2, IL-6, and TNF-${\alpha}$ production levels to 44.8%, 22.4%, 45.7%, and 62.0% of the control, respectively. Taken together, EtOH extract of PPF showed potent antioxidant and anti-inflammatory activities, and EA and BtOH fractions showed comparatively stronger antioxidant activities while DM and EA fractions showed stronger anti-inflammatory activities. It can be concluded that EtOH extract of PPF and its fractions are good candidates as natural resources for the development of anti-oxidative and anti-inflammatory functional food products.

Image Quality Evaluation of CsI:Tl and Gd2O2S Detectors in the Indirect-Conversion DR System (간접변환방식 DR장비에서 CsI:Tl과 Gd2O2S의 검출기 화질 평가)

  • Kong, Changgi;Choi, Namgil;Jung, Myoyoung;Song, Jongnam;Kim, Wook;Han, Jaebok
    • Journal of the Korean Society of Radiology
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    • v.11 no.1
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    • pp.27-35
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    • 2017
  • The purpose of this study was to investigate the features of CsI:Tl and $Gd_2O_2S$ detectors with an indirect conversion method using phantom in the DR (digital radiography) system by obtaining images of thick chest phantom, medium thickness thigh phantom, and thin hand phantom and by analyzing the SNR and CNR. As a result of measuring the SNR and CNR according to the thickness change of the subject, the SNR and CNR were higher in CsI:Tl detector than in $Gd_2O_2S$ detector when the medium thickness thigh phantom and thin hand phantom were scanned. However, when the thick chest phantom was used, for the SNR at 80~125 kVp and the CNR at 80~110 kVp in the $Gd_2O_2S$ detector, the values were higher than those of CsI:Tl detector. The SNR and CNR both increased as the tube voltage increased. The SNR and CNR of CsI:Tl detector in the medium thickness thigh phantom increased at 40~50 kVp and decreased as the tube voltage increased. The SNR and CNR of $Gd_2O_2S$ detector increased at 40~60 kVp and decreased as the tube voltage increased. The SNR and CNR of CsI:Tl detctor in the thin hand phantom decreased at the low tube voltage and increased as the tube voltage increased, but they decreased again at 100~110 kVp, while the SNR and CNR of $Gd_2O_2S$ detector were found to decrease as the tube voltage increased. The MTF of CsI:Tl detector was 6.02~90.90% higher than that of $Gd_2O_2S$ detector at 0.5~3 lp/mm. The DQE of CsI:Tl detector was 66.67~233.33% higher than that of $Gd_2O_2S$ detector. In conclusion, although the values of CsI:Tl detector were higher than those of $Gd_2O_2S$ detector in the comparison of MTF and DQE, the cheaper $Gd_2O_2S$ detector had higher SNR and CNR than the expensive CsI:Tl detector at a certain tube voltage range in the thick check phantom. At chest X-ray, if the $Gd_2O_2S$ detector is used rather than the CsI:Tl detector, chest images with excellent quality can be obtained, which will be useful for examination. Moreover, price/performance should be considered when determining the detector type from the viewpoint of the user.

Synthesis and Preliminary Evaluation of $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$ Guanine $([^{18}F]FHBG)$ in HSV1-tk Gene Transduced Hepatoma Cell (9-(4-$[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine $([^{18}F]FHBG)$의 합성과 헤르페스 단순 바이러스 티미딘 키나아제 이입 간암 세포주에서의 기초 연구)

  • Moon, Byung-Seok;Lee, Tae-Sup;Lee, Myoung-Keun;Lee, Kyo-Chul;An, Gwang-Il;Chun, Kwon-Soo;Awh, Ok-Doo;Chi, Dae-Yoon;Choi, Chang-Woon;Lim, Sang-Moo;Cheon, Gi-Jeong
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.4
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    • pp.218-227
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    • 2006
  • Purpose: The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine ($[^{18}F]FHBG$) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Materials and Methods: Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with $K[^{18}F]/K2.2.2.$ in acetonitrile using N2-monomethoxytrityl-9-14-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of $[^{18}F]FHBG$ were performed, and was analyzed correlation between $[^{18}F]FHBG$ uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model. Results: $[^{18}F]FHBG$ was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiothemical yield was about 20-25%) (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 $GBq/{\mu}\;mol$. Specific accumulation of $[^{18}F]FHBG$ was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked $[^{18}F]FHBG$ was retained inside of cells. The uptake of $[^{18}F]FHBG$ was showed a highly significant linear correlation ($R^2=0.995$) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. Conclusion: $[^{18}F]FHBG$ appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.

The Measurement of Sensitivity and Comparative Analysis of Simplified Quantitation Methods to Measure Dopamine Transporters Using [I-123]IPT Pharmacokinetic Computer Simulations ([I-123]IPT 약역학 컴퓨터시뮬레이션을 이용한 민감도 측정 및 간편화된 운반체 정량분석 방법들의 비교분석 연구)

  • Son, Hye-Kyung;Nha, Sang-Kyun;Lee, Hee-Kyung;Kim, Hee-Joung
    • The Korean Journal of Nuclear Medicine
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    • v.31 no.1
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    • pp.19-29
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    • 1997
  • Recently, [I-123]IPT SPECT has been used for early diagnosis of Parkinson's patients(PP) by imaging dopamine transporters. The dynamic time activity curves in basal ganglia(BG) and occipital cortex(OCC) without blood samples were obtained for 2 hours. These data were then used to measure dopamine transporters by operationally defined ratio methods of (BG-OCC)/OCC at 2 hrs, binding potential $R_v=k_3/k_4$ using graphic method or $R_A$= (ABBG-ABOCC)/ABOCC for 2 hrs, where ABBG represents accumulated binding activity in basal ganglia(${\int}^{120min}_0$ BG(t)dt) and ABOCC represents accumulated binding activity in occipital cortex(${\int}^{120min}_0$ OCC(t)dt). The purpose of this study was to examine the IPT pharmacokinetics and investigate the usefulness of simplified methods of (BG-OCC)/OCC, $R_A$, and $R_v$ which are often assumed that these values reflect the true values of $k_3/k_4$. The rate constants $K_1,\;k_2\;k_3$ and $k_4$ to be used for simulations were derived using [I-123]IPT SPECT and aterialized blood data with a standard three compartmental model. The sensitivities and time activity curves in BG and OCC were computed by changing $K_l$ and $k_3$(only BG) for every 5min over 2 hours. The values (BG-OCC)/OCC, $R_A$, and $R_v$ were then computed from the time activity curves and the linear regression analysis was used to measure the accuracies of these methods. The late constants $K_l,\;k_2\;k_3\;k_4$ at BG and OCC were $1.26{\pm}5.41%,\;0.044{\pm}19.58%,\;0.031{\pm}24.36%,\;0.008{\pm}22.78%$ and $1.36{\pm}4.76%,\;0.170{\pm}6.89%,\;0.007{\pm}23.89%,\;0.007{\pm}45.09%$, respectively. The Sensitivities for ((${\Delta}S/S$)/(${\Delta}k_3/k_3$)) and ((${\Delta}S/S$)/(${\Delta}K_l/K_l$)) at 30min and 120min were measured as (0.19, 0.50) and (0.61, 0,23), respectively. The correlation coefficients and slopes of ((BG-OCC)/OCC, $R_A$, and $R_v$) with $k_3/k_4$ were (0.98, 1.00, 0.99) and (1.76, 0.47, 1.25), respectively. These simulation results indicate that a late [I-123]IPT SPECT image may represent the distribution of the dopamine transporters. Good correlations were shown between (3G-OCC)/OCC, $R_A$ or $R_v$ and true $k_3/k_4$, although the slopes between them were not unity. Pharmacokinetic computer simulations may be a very useful technique in studying dopamine transporter systems.

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A Novel in Vitro Method for the Metabolism Studies of Radiotracers Using Mouse Liver S9 Fraction (생쥐 간 S9 분획을 이용한 방사성추적자 대사물질의 새로운 체외 측정방법)

  • Ryu, Eun-Kyoung;Choe, Yearn-Seong;Kim, Dong-Hyun;Lee, Sang-Yoon;Choi, Yong;Lee, Kyung-Han;Kim, Byung-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.4
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    • pp.325-329
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    • 2004
  • Purpose: Usefulness of mouse liver S9 fraction was evaluated for the measurement of the metabolites in the in vitro metabolism study of $^{18}F$-labeled radiotracers. Materials and Methods: Mouse liver S9 fraction was isolated at au early step in the course of microsome preparation. The in vitro metabolism studies were tarried out by incubating a mixture containing the radiotracer, S9 fraction and NADPH at $37^{\ciirc}C$, and an aliquot of the mixture was analyzed at the indicated time points by radio-TLC. Metabolic defluorination was further confirmed by the incubation with calcium phosphate, a bone mimic. Results: The radiotracer $[^{18}F]1$ underwent metabolic defluorination within 15 min, which was consistent with the results of the in vivo method and the in vitro method using microsome. Radiotracer $[^{18}F]2$ was metabolized to three metabolites including $4-[^{18}F]fluorobenzoic$ acid within 60 min. It is likely that the one of these metabolites at the origin of radio-TLC was identical with the one that obtained from the in vivo and in vitro (microsome) method. Compared with the in vitro method using microsome, the method using S9 fraction gave a similar pattern of the metabolites but with a different ratio, which can be explained by the presence of cytosol in the S9 fraction. Conclusion: These results suggest that the findings of the in vitro metabolism studies using S9 fraction can reflect the in vivo metabolism of novel radiotracers in the liver. Moreover, this method can be used as a tool to determine metabolic defluorination along with calcium phosphate absorption method.

Radioiodine Therapy of Liver Cancer Cell Following Tissue Specific Sodium Iodide Symporter Gene Transfer and Assessment of Therapeutic Efficacy with Optical Imaging (조직 특이 발현 Sodium Iodide Symporter 유전자 이입에 의한 방사성옥소 간암세포 치료와 광학영상을 이용한 치료효과 평가)

  • Jang, Byoung-Kuk;Lee, You-La;Lee, Yong-Jin;Ahn, Sohn-Joo;Ryu, Min-Jung;Yoon, Sun-Mi;Lee, Sang-Woo;Yoo, Jeong-Soo;Cho, Je-Yeol;Lee, Jae-Tae;Ahn, Byeong-Cheol
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.5
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    • pp.383-393
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    • 2008
  • Purpose: Cancer specific killing can be achieved by therapeutic gene activated by cancer specific promotor. Expression of sodium iodide symporter (NIS) gene causes transportation and concentration of iodide into the cell, therefore radioiodine treatment after NIS gene transfer to cancer cell could be a form of radionuclide gene therapy. luciferase (Luc) gene transfected cancer cell can be monitored by in vivo optical imaging after D-luciferin injection. Aims of the study are to make vector with both therapeutic NIS gene driven by AFP promoter and reporter Luc gene driven by CMV promoter, to perform hepatocellular carcinoma specific radiodiodine gene therapy by the vector, and assessment of the therapy effect by optical imaging using luciferase expression. Materials and Methods: A Vector with AFP promoter driven NIS gene and CMV promoter driven Luc gene (AFP-NIS-CMV-Luc) was constructed. Liver cancer cell (HepG2, Huh-7) and non liver cancer cell (HCT-15) were transfected with the vector using liposome. Expression of the NIS gene at mRNA level was elucidated by RT-PCR. Radioiodide uptake, perchlorate blockade, and washout tests were performed and bioluminescence also measured by luminometer in these cells. In vitro clonogenic assay with 1-131 was performed. In vivo nuclear imaging was obtained with gamma camera after 1-131 intraperitoneal injection. Results: A Vector with AFP-NIS-CMV-Luc was constructed and successfully transfected into HepG2, Huh-7 and HCT-15 cells. HepG2 and Huh-7 cells with AFP-NIS-CMV-Luc gene showed higher iodide uptake than non transfected cells and the higher iodide uptake was totally blocked by addition of perchlorate. HCT-15 cell did not showed any change of iodide uptake by the gene transfection. Transfected cells had higher light output than control cells. In vitro clonogenic assay, transfected HepG2 and Huh-7 cells showed lower colony count than non transfected HepG2 and Huh-7 cells, but transfected HCT-15 cell did not showed any difference than non transfected HCT-15 cell. Number of Huh-7 cells with AFP-NIS-CMV-Luc gene transfection was positively correlated with radioidine accumulation and luciferase activity. In vivo nuclear imaging with 1-131 was successful in AFP-NIS-CMV-Luc gene transfected Huh-7 cell xenograft on nude mouse. Conclusion: A Vector with AFP promoter driven NIS and CMV promoter driven Luc gene was constructed. Transfection of the vector showed liver cancer cell specific enhancement of 1-131 cytotoxicity by AFP promoter, and the effect of the radioiodine therapy can be successfully assessed by non-invasive luminescence measurement.

Analysis of the Causes of Subfrontal Recurrence in Medulloblastoma and Its Salvage Treatment (수모세포종의 방사선치료 후 전두엽하방 재발된 환자에서 원인 분석 및 구제 치료)

  • Cho Jae Ho;Koom Woong Sub;Lee Chang Geol;Kim Kyoung Ju;Shim Su Jung;Bak Jino;Jeong Kyoungkeun;Kim Tae_Gon;Kim Dong Seok;Choi oong-Uhn;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.22 no.3
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    • pp.165-176
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    • 2004
  • Purpose: Firstly, to analyze facto in terms of radiation treatment that might potentially cause subfrontal relapse in two patients who had been treated by craniospinal irradiation (CSI) for medulloblastoma, Secondly, to explore an effective salvage treatment for these relapses. Materials and Methods: Two patients who had high-risk disease (T3bMl, T3bM3) were treated with combined chemoradiotherapy CT-simulation based radiation-treatment planning (RTP) was peformed. One patient who experienced relapse at 16 months after CSI was treated with salvage surgery followed by a 30.6 Gy IMRT (intensity modulated radiotherapy). The other patient whose tumor relapsed at 12 months after CSI was treated by surgery alone for the recurrence. To investigate factors that might potentially cause subfrontal relapse, we evaluated thoroughly the charts and treatment planning process including portal films, and tried to find out a method to give help for placing blocks appropriately between subfrotal-cribrifrom plate region and both eyes. To salvage subfrontal relapse in a patient, re-irradiation was planned after subtotal tumor removal. We have decided to treat this patient with IMRT because of the proximity of critical normal tissues and large burden of re-irradiation. With seven beam directions, the prescribed mean dose to PTV was 30.6 Gy (1.8 Gy fraction) and the doses to the optic nerves and eyes were limited to 25 Gy and 10 Gy, respectively. Results: Review of radiotherapy Portals clearly indicated that the subfrontal-cribriform plate region was excluded from the therapy beam by eye blocks in both cases, resulting in cold spot within the target volume, When the whole brain was rendered in 3-D after organ drawing in each slice, it was easier to judge appropriateness of the blocks in port film. IMRT planning showed excellent dose distributions (Mean doses to PTV, right and left optic nerves, right and left eyes: 31.1 Gy, 14.7 Gy, 13.9 Gy, 6.9 Gy, and 5.5 Gy, respectively. Maximum dose to PTV: 36 Gy). The patient who received IMRT is still alive with no evidence of recurrence and any neurologic complications for 1 year. Conclusion: To prevent recurrence of medulloblastoma in subfrontal-cribriform plate region, we need to pay close attention to the placement of eye blocks during the treatment. Once subfrontal recurrence has happened, IMRT may be a good choice for re-irradiation as a salvage treatment to maximize the differences of dose distributions between the normal tissues and target volume.

A Phase I/II Trial of $DCVac/IR^{(R)}$ Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases (기존의 치료에 반응하지 않는 다발성 간전이 대장암 환자에서 방사선조사와 병합한 수지상세포 면역치료의 1, 2상 임상시험)

  • Choi, Young-Min;Lee, Hyung-Sik;Kwon, Hyuk-Chan;Han, Sang-Young;Choi, Jong-Cheol;Chung, Ju-Seop;Kim, Chang-Won;Kim, Dong-Won;Kang, Chi-Duk
    • Radiation Oncology Journal
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    • v.26 no.2
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    • pp.104-112
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    • 2008
  • Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.