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Feasibility and Efficacy of Adaptive Intensity Modulated Radiotherapy Planning according to Tumor Volume Change in Early Stage Non-small Cell Lung Cancer with Stereotactic Body Radiotherapy (폐암의 정위적체부방사선치료에서 육안적종양체적 변화에 따른 적응방사선치료의 효용성 및 가능성 연구)

  • Park, Jae Won;Kang, Min Kyu;Yea, Ji Woon
    • Progress in Medical Physics
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    • v.26 no.2
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    • pp.79-86
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    • 2015
  • The purpose of this study is to evaluate efficacy and feasibility of adaptive radiotherapy according to tumor volume change (TVC) in early stage non-small cell lung cancer (NSCLC) using stereotactic body radiotherapy (SBRT). Twenty-two lesions previously treated with SBRT were selected. SBRT was usually performed with a total dose of 48 Gy or 60 Gy in four fractions with an interval of three to four days between treatments. For evaluation of TVC, gross tumor volume (GTV) was contoured on each cone-beam computed tomography (CBCT) image used for image guidance. Intensity modulated radiotherapy (IMRT) planning was performed in the first CBCT (CBCT1) using a baseline plan. For ART planning (ART), re-optimization was performed at $2^{nd}$, $3^{rd}$, and $4^{th}$ CBCTs (CBCT2, CBCT3, and CBCT4) using the same angle and constraint used for the baseline plan. The ART plan was compared with the non-ART plan, which generated copying of the baseline plan to other CBCTs. Average GTV volume was 10.7 cc. Average TVC was -1.5%, 7.3%, and -25.1% in CBCT2, CBCT3, and CBCT4 and the TVC after CBCT3 was significant (p<0.05). However, the nine lesions were increased GTV in CBCT2. In the ART plan, $V_{20\;Gy}$, $D_{1500\;cc}$, and $D_{1000\;cc}$ of lung were significantly decreased (p<0.05), and $V_{30\;Gy}$ and $V_{32\;Gy}$ of the chest wall were also decreased (p<0.05). While D min of planning target volume (PTV) decreased by 8.3% in the non-ART plan of CBCT2 compared with the baseline plan in lesions with increased tumor size (p=0.021), PTV coverage was not compromised in the ART plan. Based on this result, use of the ART plan may improve target coverage and OAR saving. Thus ART using CBCT should be considered in early stage NSCLC with SBRT.

Superoxide Dismutase Gene Expression Induced by Lipopolysaccharide in Alveolar Macrophage of Rat (폐포대식세포에서 내독소 자극에 의한 Superoxide Dismutase 유전자발현의 조절 기전)

  • Park, Kye-Young;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Hyun, In-Gyu
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.4
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    • pp.522-534
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    • 1995
  • Background: In the pathogenesis of acute lung injury induced by lipopolysaccharide(LPS), oxygen radiclls are known to be involved in one part. Superoxide dismutase(SOD) protects oxygen radical-induced tissue damage by dismutating superoxide to hydrogen peroxide. In eukaryotic cells, two forms of SOD exist intracellularly as a cytosolic, dimeric copper/zinc-containing SOD(CuZnSOD) and a mitochondrial, tetrameric manganese-containing SOD(MnSOD). But there has been little information about SOD gene expression and its regulation in pulmonary alveolar macrophages(PAMs). The objective of this study is to evaluate the SOD gene expression induced by LPS and its regulation in PAMs of rat. Method: In Sprague-Dawley rats, PAMs obtained by broncholaveolar lavage were purified by adherence to plastic plate. To study the effect of LPS on the SOD gene expression of PAMs, they were stimulated with different doses of LPS($0.01{\mu}g/ml{\sim}10{\mu}g/ml$) and for different intervals(0, 2, 4, 8, 24hrs). Also for evaluating the level of SOD gene regulation actinomycin D(AD) or cycloheximide(CHX) were added respectively. To assess whether LPS altered SOD mRNA stability, the rate of mRNA decay was determined in control group and LPS-treated group. Total cellular RNA extraction by guanidinium thiocyanate/phenolfchlorofonn method and Northern blot analysis by using a $^{32}P$-labelled rat MnSOD and CuZnSOD cDNAs were performed. Results: The expression of mRNA in MnSOD increased dose-dependently, but not in CuZnSOD. MnSOD mRNA expression peaked at 8 hours after LPS treatment. Upregulation of MnSOD mRNA expression induced by LPS was suppressed by adding AD or CHX respectively. MnSOD mRNA stability was not altered by LPS. Conclusion: These findings show that PAMs of rat could be an important source of SOD in response to LPS, and suggest that their MnSOD mRNA expression may be regulated transcriptionally and require de novo protein synthesis without affecting mRNA stability.

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Pharmacokinetics of ofloxacin in Patients with Multidrug-Resistant Tuberculosis (다제내성결핵 환자에서 ofloxacin의 약동학적 분석)

  • Park, Seung-Kyu;Yoon, Young-Ran;Lee, Woo-Chul;Jun, Hyung-Min;Shon, Ji-Hong;Kim, Kyoung-Ah;Park, Ji-Young;Shin, Jae-Gook
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.2
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    • pp.128-136
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    • 2002
  • Background: There are few studies that have reported on the pharmacokinetic(PK) disposition of fluoroquinolones in patients with multi-drug resistant tuberculosis(MDR-Tb), even though fluoroquinolones are frequently co-prescribed to those patients. In this study, the PK disposition of ofloxacin, a fluoroquinolone, was evaluated in patients with MD R -Tb. Methods: Twenty patients with MDR-Tb were given 2nd line Tb drugs including ofloxacin (300mg twice a day), prothionamide, cycloserine, para-aminosalicylic acid, kanamycin, and streptomycin. The patients were grouped according to their body mass index(BMI) as an index of emaciation (group A : 18.5$\leq$BMI <23, group B : BMI < 18.5). Blood samples were serially drawn and urine samples were collected upto 24 hours after the last dose of those drugs at steady state (over 1 month). The ofloxacin concentrations were determined using HPLC (High Performance Liquid Chromatography). Results: The AUC of ofloxacin in group B was greater than that in group A ($31.4{\pm}8.9{\mu}g/ml{\cdot}h$ vs. $24.1{\pm}6.2{\mu}g/ml{\cdot}h$)(Check the symbols), (p<0.05). The total clearance(Cl/F) of ofloxacin was $0.16{\pm}0.03$ L/h/kg in group A, and $0.14{\pm}0.03$ L/h/kg in group B. The half-lives of ofloxacin in two groups were similar (group A : $5.3{\pm}0.8$ hours, group B : $5.7{\pm}0.9$ hours). In addition, the other PK parameters in two groups were also similar. Conclusions: The pharmacokinetics of ofloxacin in patients with MDR-Tb appears to be comparable with those of normal subjects, and the extent of emaciation appears to have an influence on the pharmacokinetics of ofloxaicn in chronic debilitated MDR-Tb patients.

GnRH Antagonist Versus Agonist Flare-up Protocol in Ovarian Stimulation of Poor Responder Patients (저 반응군의 체외수정시술을 위한 과배란유도에 있어 GnRH Antagonist 요법과 GnRH Agonist Flare Up 요법의 효용성에 관한 연구)

  • Ahn, Young-Sun;Yeun, Myung-Jin;Cho, Yun-Jin;Kim, Min-Ji;Kang, Inn-Soo;Koong, Mi-Kyoung;Kim, Jin-Yeong;Yang, Kwang-Moon;Park, Chan-Woo;Kim, Hye-Ok;Cha, Sun-Hwa;Song, In-Ok
    • Clinical and Experimental Reproductive Medicine
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    • v.34 no.2
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    • pp.125-131
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    • 2007
  • Objective: The aim of this study was to compare GnRH antagonist and agonist flare-up treatment in the management of poor responder patients. Methods: One hundred forty-four patients from Jan. 1, 2002 to Aug. 31, 2005 undergoing IVF/ICSI treatment who responded poorly to the previous cycle (No. of oocyte retrieved$\leq$5) and had high early follicular phase follicle stimulating hormone (FSH>12 mIU/ml were selected. Seventy-five patients received agonist flare-up protocol and 71 patients received antagonist protocol. We analyzed the number of oocytes retrieved, number of good embryos (GI, GI-1), total dose of hMG administered, implantation rate, cycle cancellation rate, pregnancy rate, live birth rate. Results: The cancellation rate was high in antagonist protocol (53.5% vs. 30.1%). The number of oocyte retrieved, the number of good embyos were high in agonist flare-up group. There was no statistical difference between GnRH agonist flare up protocol and GnRH antagonist protocol in implantation rate (14.5%, 10.1%), clinical pregnancy rate per transfer (29.4%, 21.2%) and live birth rate per transfer (21.6%, 18.2%). Although the result was not statistically significant, GnRH agonist flare up group showed a nearly doubled pregnancy rate and live birth rate per initial cycle than GnRH antagonist group. Conclusions: The agonist flare-up protocol appears to be slightly more effective than the GnRH antagonist protocol in implantation rate, pregnancy rate, live birth rate but shows statistically no significance. Agonist flare-up protocol improved the ovarian response in poor responders. However, based of the result of the study, we can expect improved ovarian response in poor responders by GnRH agonist flare up protocol.

The Effect of Ginseng Saponins on the Biosynthesis of Prostaglandins (인삼 Saponin이 Prostaglandin 대사에 미치는 영향)

  • Park C.W.;Lee S.H.
    • Proceedings of the Ginseng society Conference
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    • 1988.08a
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    • pp.77-80
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    • 1988
  • The effects of ginseng saponins and some phenolic acids on the in vitro biosynthesis of prostaglandins was examined in order to identify the role of some ginseng components on the regulaion of arachidonic acid metabolism. The productions of prostaglandin $E_2(PGE_2).$ prostaglandin $F_2{\alpha}(PGF_2{\alpha}).$ thromboxane $B_2(TxB_2)$ and 6-keto-prostaglandin $F_1{\alpha}(6-keto-PGF_1{\alpha})$ from $[^3H]-arachidonic$ acid were evaluated with rabbit kidney microsome. human platelet homogenate and bovine aortic microsome. The amounts of the total cyclooxy-genase products from arachidonic acid did't show significant changes in the presence of ginseng saponins. Panaxadiol. panaxatriol and all of the ginsenosides used in these experiments reduced the formation of $TxB_2.$ while increased the $6-keto-PGF_1{\alpha}$ production dose dependently. Ginseng saponins did't inhibit the ADP($10{\mu}M$) induced platelet aggregation. but sodium arachidonate (0.5 mM) induced platelet aggregation. but sodium arachidonate (0.5 mM) induced platelet aggregation was signiticantly inhibited. These findings suggest that ginseng saponins seem to playa role in the regulation of the arachidonate metabolism. probably by affecting the divergent biosynthetic pathway of prostaglandins from endoperoxide.

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Allium tuberosum Reverses PCSK9-Mediated LDLR Degradation by Inhibition of HNF1α (부추 추출물의 PCSK9 억제를 통한 LDL 콜레스테롤 저감 효능)

  • Choi, Hyo-Kyoung;Kim, Hyo Jin;Hwang, Jin-Taek;Chung, Min-Yu
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1278-1285
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    • 2017
  • Accumulation of excess low density lipoprotein (LDL) cholesterol in the blood can initiate and accelerate atherosclerosis. Statins mediate the transactivation of proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn limits their cholesterol-lowering effects via LDL receptor (LDLR) degradation. The objective of this study was to investigate whether or not Allium tuberosum (AT) regulates LDLR and PCSK9. Mice were fed a low fat control diet (LD) or Western diet (WD) supplemented with AT (1%, w/w). AT significantly attenuated total and LDL cholesterol levels in mice fed WD (P<0.05). AT also significantly inhibited hepatic PCSK9 gene expression (P<0.05) while AT maintained hepatic LDLR gene expression. To further investigate AT-mediated PCSK9 regulation, HepG2 cells were treated with 10% delipidated serum (DLPS) in the presence or absence of AT. Non-toxic level of AT dose-dependently increased the LDLR protein level, and AT at $400{\mu}g/mL$ markedly inhibited PCSK9 protein expression. Similarly, AT significantly increased LDLR gene expression, whereas it significantly down-regulated PCSK9 gene expression. AT-mediated reduction of PCSK9 gene expression is likely due to decreased hepatic nuclear factor $1{\alpha}$ ($HNF1{\alpha}$) expression, but not SREBP2 in HepG2 cells under lipid-depleted conditions. AT-mediated PCSK9 inhibition contributed to LDLR protein stabilization via protection against LDLR lysosomal degradation in HepG2 cells under lipid-depleted conditions. Further investigation is warranted to determine the active components of AT and whether or not these components are effective in reducing hypercholesterolemia.

Effect of Exercise on Blood Concentrations of Ethanol, Lactate and Glucose in Men Showing Facial Flush after Ethanol Ingestion (음주후(飮酒後) 얼굴 붉어지는 사람에 있어서 운동(運動)이 혈중(血中) 에타놀, 유산(乳酸) 및 포도당(葡萄糖) 농도(濃度)에 미치는 효과(效果))

  • Cho, Young-Ho;Kim, Hyeong-Jin;Lee, Won-Jung;Choo, Young-Eun
    • The Korean Journal of Physiology
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    • v.20 no.1
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    • pp.65-77
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    • 1986
  • To elucidate the effect of exercise on blood concentrations of ethanol, lactate and glucose in men who show facial flush after ethanol ingestion, 59 healthy male college students were studied. After 6 or more hours of fasting, the subjects were administered 3 ml of 25% ethanol solution(Soju) per liter of total body water. For control experiment Soju was replaced with the same dose of water. Exercise performed was vertical jumping on a rebounder for 3 min immediately after drinking. The subjects were classified into 6 groups: water ingestion(W), flushed (F) and non-flushed (N) groups after ethanol ingestion, water ingestion and exercise(WE), flushed(FE) and non-flushed (NE) groups after ethanol ingestion and exercise. Blood ethanol concentration in the exercise groups(NE, FE) was lower until 60 min after drinking than that in the non-exercise groups(N,F). Factor k representing the rate of ethanol absorption was markedly lower in the exercise groups than in the non-exercise groups. The flushed groups(F,FE) showed higher blood ethanol level than the non-flushed groups (N,NE) from 30 to 120 min after drinking. Blood lactate concentration in WE group was elevated immediately after exercise and returned to the resting level at 60 min after exercise. Ethanol increased blood lactate level from 30 to 120 min after ethanol drinking, Exercise after ethanol ingestion produced a sharp increase and then drop in blood lactate level which was stilled significantly higher than the resting level all the way through 120 min. Blood glucose concentration was decreased at 15 min after exercise. Ethanol-administered groups except F group showed a steady decrease in blood glucose level from 30 through 120 min. Heart rate was elevated by ethanol only in the flushed groups. Heart rate in F group was significantly increased at 4 min after ethanol and was maintained at high level until 120 min. In WE and NE groups, heart rate was significantly increased immediately after exercise and returned to the resting level at 60 min. The FE group, however, showed a consistently elevated heart rate throughout the 120-min experimental period. Taken together, the exercise alone produced a delayed ethanol absorption, a prompt increase in heart rate and blood lactate level and a decrease in blood glucose level early in the recovery period from exercise. After ethanol administration, blood lactate was elevated and blood glucose was lowered from 30 to 120 min. Flushed subjects showed rapid increase in heart rate after ethanol drinking and higher blood ethanol level than non-flushed ones from 30 to 120 min after drinking.

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Effect of Ethane 1,2-Dimethane Sulfonate(EDS) on the Apoptosis in the Rat Epididymis (흰쥐 부정소에서의 세포자연사에 미치는 Ethane 1,2-Dimethane Sulfonate(EDS)의 효과)

  • Son, Hyeok-Jun;Lee, Sung-Ho
    • Development and Reproduction
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    • v.10 no.3
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    • pp.203-209
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    • 2006
  • Ethane 1,2-Dimethane sulfonate(EDS), a toxin which specifically kills Leydig cells(LC), has been widely used to prepare the reversible testosterone(T) depletion rat model. Previous studies including our own clearly demonstrated that the dramatic weight loss of the T-dependent accessory sex organs such as epididymis and seminal vesicle in this 'LC knock-out' rats. These weight loss could be derived from massive and abrupt death of the cells via apoptotic process. The present study was performed to test the effect of EDS administration on the expression of some apoptotic genes in the rat epididymis. Adult male Sprague-Dawley rats($300{\sim}350$ g B.W.) were injected with single dose of EDS(75 mg/kg, i.p.) and sacrificed on Weeks 0, 1, 2, 3, 4, 5, 6 and 7. Tissue weights and the numbers of the epididymal sperm were measured. The transcriptional activities of the bcl-2, bax, Fas and Fas ligand(Fas-L) were evaluated by semi-quantitative RT-PCR. As expected, the weights and the sperm counts of epididymis declined progressively after the EDS treatment during Week 1 and 2. These decrements were discontinued with a gradual return towards normal during Weeks $5{\sim}7$, although the maximal recoveries of the epididymal weights(71%) and sperm count(38%) were subnormal on Week 7. The initial level of bcl-2 transcripts persisted to Week 6 then elevated significantly on Week 7. The level of bax transcripts significantly decreased on Week 6, and no remarkable change was found in the rest of the experimental period. The transcripts for the Fas in epididymis elevated during Weeks $1{\sim}2$, returned to normal on Week 3, and the level persisted to the Week 7. Similarly, the level of Fas-L transcripts elevated during Weeks $1{\sim}3$ and returned to normal after Week 4. Our results demonstrated the transient T depletion by EDS administration could induce the changes in expression of the apoptotic genes in rat epididymis. The activation of Fas and Fas-L in the epididymis of EDS-treated rats might be responsible for the initial apototic process and consequently the tissue damage and the sperm loss. Future studies will attempt to determine the precise molecular mechanism(s) of apoptosis in the rat epididymis.

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Effects of Postoperative Radiotherapy on Distribution of Bone Metastases in Breast Cancer (유방암환자에서 수술 후 방사선치료가 골전이 분포에 미치는 영향)

  • Kim, Bo-Kyoung;Ha, Sung-Whan
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.211-215
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    • 2001
  • Purpose : This study was done to evaluate the efficacy of low-dose radiation in reduction of thoracic vertebral metastases in patients with breast cancer. Materials and Methods : 109 patients who were treated for bone metastasis from breast cancer from June, 1988 to June, 1998 in the Department of Therapeutic Radiology, Seoul National University were included. Of the 109 patients, 40 patients had been previously treated by postoperative radiotherapy and 69 had not. Postoperative radiotherapy had been given using Co-60 teletherapy device in 30 patients or 6 MV linear accelerator in 10. Thoracic spines from 1 to 10 were usually irradiated except in 1 patient and cervical vertebrae 6 and/or 7 were partially included in ,: patients. A total of 50.4 Gy was given with 1.8 Gy fraction. Metastatic bone diseases were scored in 11 regions, i. e., skull, conical spine, thoracic spine from 1 to 4, from 5 to 8, 9 and 10, 11 and 12, lumbar spine, pelvis, femur, ribs and others. Results : In no postoperative parasternal irradiation group, lumbar vertebrae were the most common metastatic sites $(55.1\%)$ followed by pelvis $(44.9\%)$, ribs $(40.6\%)$, thoracic vertebrae 11 and 12 $(37.7\%)$, thoracic vertebrae between 5 and 8 $(36.2\%)$, thoracic vertebrae 9 and 10 $(34.8\%)$, and thoracic vertebrae between 1 and 4 $(26.1\%)$. In postoperative parasternal irradiation group, lumbar vertebrae and pelvis were also the most common sites of metastases ($55.0\%$, respectively) followed by ribs $(37.5\%)$, and thoracic vertebrae 11 and 12 $(32.5\%)$. But significant less metastases were seen at thoracic vertebrae from 1 to 10. Conclusion : We can find that the were significantly less bony metastases at thoracic vertebrae which had been previously irradiated postoperatively.

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Induction Chemotherapy Followed by Radiotherapy for Stage IV Hypopharyngeal Cancer (4기 병기 하인두암에서 선행 항암화학요법후 방사선치료)

  • Kang Ki Mun;Chai Gyu Young;Kim Jin Pyeong;Lee Won Seop
    • Radiation Oncology Journal
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    • v.22 no.4
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    • pp.247-253
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    • 2004
  • Purpose: Hypopharyngeal cancer is diagnosed at the advanced stage in most cases, which the prognosis known to be poor. Thus, the efficacy of induction chemotherapy followed by radiotherapy, with regards to the response and survival rate for stage IV hypopharyngeal cancer patients, was examined. Materials and Methods: From July 1998 to February 2000, 18 cases were diagnosedas AJCC stage IV hypopharyngeal cancer without distant metastasis. These patients were treated with induction chemotherapy followed by radiotherapy, and the results retrospectively analyzed. The regimen of the induction chemotherapy was the 5-FU and cisplatincombination, at 3-week intervals for, 2 cycles. The total radiation dose for the primary lesion and metastatic lymph nodes was $68.4\~72.0$Gy (median: 70.2 Gy). Results: The: The median follow up period was 28 months, ranging from 7 to 99 months. The 3-year overall survival and disease-free survival rate were 41.7 and $31.1\%$, respectively. In 6 cases ($33.3\%$), conservation of the larynx for over 3 years was possible. After the induction chemotherapy there were 16 partial responses ($88.8\%$), 1 complete response and 1 with no response ($5.6\%$ each), therefore, 17 of the 18 cases ($94.6\%$) showed responses. After the completion of the induction chemotherapy and radiotherapy, a complete response was noted in 13 cases ($72.2\%$), a partial response in 5 ($27.8\%$), with an overall response rate of $100\%$. In the analysis of the prognostic factors influencing the survival rate, the 3-year and disease-free survival rates for the complete and partial response groups were 43.1, and $20.0\%$, and 39.6, and $20.0\%$, respectively (p=0.0003, p=0.002). Only the final response after treatment completion was statistically significant. Conclusion: For stage IV hypopharyngeal cancer, induction chemotherapy followed by radiotherapy was an effective treatment, with no severe side effects.