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A Study of the Additional Toxicity of Mixed Food Additives to Rat (혼합(混合)된 식품첨가물(食品添加物)이 흰쥐의 생리(生理)에 미치는 상승적(相乘的) 독성(毒性) 효과(效果)에 관(關)한 연구(硏究))

  • Chung, Ho-Kwon
    • Applied Biological Chemistry
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    • v.18 no.2
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    • pp.71-97
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    • 1975
  • To improve the food qualities in Korea, two hundred and fourtynine kinds of food additives have been allowed in food processing, of which one hundred and nineteen kinds could be used under the limitted conditions. Hence, in practical uses in food processing, many kinds of them are mixed at random within the permitted amounts for their special purposes. For last several years, many kinds of the food additives were prohibited because they have been proved to be toxic even with the single dose. Until recently a few studies on the toxicity in the mixture of food additives were reported, however, they were shown to be no severe additional effect on the animal. This study was performed to see if any elevation of chronic or subacute toxicity of food additives occur especially when they are mixed with each other, using three kinds of food additives (DHA, AF-2, BHT) most widely used as food preservatives, antiseptics and antioxidants. One hundred and fifty young male rats were taken and divided into ten feeding groups, one first control group (food additives blank), three second control groups (DHA 0.1%, AF-2 0.1%, BHT 0.5%), three mixture groups of low level (mixture of each 60% of two second control level) and three mixture groups of high level (mixture of each 90% of two second control level). As the methods of biological and clinical tests, the change of body weight (growth rate), daily intake of diets, organ to body weight ratio, histopathological findings of organs, hematological observation, liver and kidney function tests were checked three times during the periods of 24 weeks. The following results were obtained. 1. The low level group of DHA, AF-2 mixture and DHA, BHT mixture revealed a little retardation in growth rate than the first control group, however, they were similar to the second controls, while all the mixture groups of high level showed a more remarkable retardation than the first and second controls. 2. Average daily intake of the diets was the same in each group, showing a similar decreasing tendency (70-100g/kg of body weight) in accordance with the growth rate. It was observed that there are no differences in the taste and appetite in each group of rats. 3. Abnormal enlargements of kidney and lung were not seen in all the mixture groups compared with the controls, while a slight hepatomegaly was observed in all mixture groups of low level as in the second controls. Significant differences (almost 1% level) were observed between the high level groups and the first control group. 4. Histopathological effects of the food additives on lung, kidney and liver tissues were found in all mixture group of high level. The less frequencies of the same effects were also seen in the low level groups. 5. The esterified cholesterol to total cholesterol ratio in the mixture groups of high level showed a little lower values, and the activities of serum glutamate oxaloacetate transaminase and alkaline phosphatase decreased almost with significance of 5% level compared with the first control group. The serum A/G ratio in the mixture groups also decreased. The results demonstrated that the liver function was decreased in the mixture groups compared with the controls. 6. In all groups throughout the test period, kidney functions (concentration of protein and creatinine excreated per hour in urine and renal filtration rate) were shown almost as normal as the first control. 7. Average values of hematocrit, erythrocytes and leucocytes in the mixture groups were in the normal ranges as in the controls, which denotes that the production of blood cells in bone marrow were also normal in all groups. With the above results, it is concluded that when the food additives (DHA, AF-2, BHT) were given together to the rats in several combinations even in less amount, they showed more toxic signs than the single doses.

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Effects of Dietary Supplementation with Allium hookeri Root on Hepatic Enzyme Contents in Streptozotocin-induced Diabetic Rats (삼채 보충식이가 당뇨흰쥐 간의 항산화효소 함량에 미치는 영향)

  • Kim, Myung-Wha
    • Journal of the East Asian Society of Dietary Life
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    • v.27 no.4
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    • pp.399-407
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    • 2017
  • The purpose of this study was to examine the effect of Allium hookeri (AH) root on hepatic antioxidative enzyme contents in streptozotocin (STZ)-induced rats. Diabetes mellitus was induced in male Sprague-Dawley rats through injection of STZ dissolved in citrate buffer into tail veins at a dose of 45 mg/kg body weight. Sprague-Dawley rats were fed an AIN-93 recommended diet, and the experimental groups were fed a modified diet containing 5% and 10% of AH root powder for 4 weeks. The experimental groups were divided into four groups: a normal control (N-control), STZ-control, STZ-AH 5%, and STZ-AH 10% supplemented groups. The STZ-AH 5% group showed a significant increase in liver glycogen compared to the STZ-control group. Muscle glycogen and liver protein contents significantly increased in the AH-supplemented groups compared to the STZ-control group. The liver malondialdehyde content of the AH-supplemented group was significantly lower than that of the STZ-control group. Xanthine oxidase content was significantly reduced in all experimental groups. Glutathione-S-transferase content was significantly elevated in the AH-treated groups compared to the STZ-control group. Superoxide dismutase content was not significantly different among the experimental groups. Catalase content was significantly higher in the STZ-AH 10% group compared to the STZ-control group. These results show that supplementation with AH root may be useful for diabetic therapy and damage from oxidative stress.

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.

Principle and Recent Advances of Neuroactivation Study (신경 활성화 연구의 원리와 최근 동향)

  • Kang, Eun-Joo
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.2
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    • pp.172-180
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    • 2007
  • Among the nuclear medicine imaging methods available today, $H_2^{15}O-PET$ is most widely used by cognitive neuroscientists to examine regional brain function via the measurement of regional cerebral blood flow (rCBF). The short half-life of the radioactively labeled probe, $^{15}O$, often allows repeated measures from the same subjects in many different task conditions. $H_2^{15}O-$ PET, however, has technical limitations relative to other methods of functional neuroimaging, e.g., fMRI, including relatively poor time and spatial resolutions, and, frequently, insufficient statistical power for analysis of individual subjects. However, recent technical developments, such as the 3-D acquisition method provide relatively good image quality with a smaller radioactive dosage, which in turn results in more PET scans from each individual, thus providing sufficient statistical power for the analysis of individual subject's data. Furthermore, the noise free scanner environment $H_2^{15}O$ PET, along with discrete acquisition of data for each task condition, are important advantages of PET over other functional imaging methods regarding studying state-dependent changes in brain activity. This review presents both the limitations and advantages of $^{15}O-PET$, and outlines the design of efficient PET protocols, using examples of recent PET studies both in the normal healthy population, and in the clinical population.

Antioxidant Activity and Cytotoxicity of Different Taraxacum Species in Korea (국내 자생 민들레의 종류별 항산화성 및 세포독성 연구)

  • Chon, Sang-Uk
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.57 no.1
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    • pp.51-59
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    • 2012
  • Contents of phenolics and flavonoids, antioxidant activity and cytotoxicity were investigated in the methanol extracts of three different $Taraxacum$ species, $Taraxacum$ $coreanum$, $Taraxacum$ $mongolicum$, and $Taraxacum$ $officinale$. Total phenolics content at $1000mg\;kg^{-1}$ was more present in shoot parts than in roots, and was highest in $T.$ $mongolicum$ shoot and root extracts (76.8 and $40.0mg\;kg^{-1}$, respectively), followed by $T.$ $coreanum$ and $T.$ $officinale$ ($p$ < 0.05). Total flavonoid level had same tendency to total phenolics among $Taraxacum$ species, showing lower amounts ($6.5{\sim}36.4mg\;kg^{-1}$) than total phenolics. The antioxidant activity of the methanol extracts from all the species dose-dependently increased. DPPH free radical scavenging activity at $1,000mg\;kg^{-1}$ was highest in shoot and root extracts from $T.$ $mongolicum$ by 89.6 and 83.4%, respectively. According to MTT assay, cell viability of Calu-6 (human pulmonary carcinoma) was lowest in the $T.$ $mongolicum$ shoot and root extracts ($IC_{50}$ values=83.4 and $66.4mg\;kg^{-1}$, respectively), and followed by $T.$ $coreanum$ and $T.$ $officinale$ (lowest). Calu-6 was more sensitive to the extracts than SNU-601 (human gastric carcinoma). Antioxidative and anticancer activities in three different $Taraxacum$ species was more correlated with total phenolics content ($r^2$=0.0097 to 0.6213) than with total flavonoids level ($r^2$=0.0027 to 0.4627). The results showed total phenolics content and total flavonoids level were highly correlated with anticancer activity and antioxidant activity, and their content and activities were different depending on species.

Studies on the Applications of PSL, TL and ESR Methods for the Detection of Dried Fruits and Mushrooms (PSL, TL 및 ESR 분석에 의한 건조과일류 및 버섯류에 대한 검지 특성 연구)

  • Kim, Kyu-Heon;Son, Jin-Hyok;Kang, Yoon-Jung;Park, Hye-Young;Hwang, Cho-Rong;Kim, Jae-I;Lee, Kang-Bong;Jo, Tae-Yong;Eom, Mi-Ok;Park, Sue-Nie;Seong, Rack Seon;Jang, Young-Mi;Lee, Jae-Hwang;Park, Yong-Chjun;Lee, Hwa-Jung;Lee, Sang-Jae;Han, Sang-Bae
    • Journal of Radiation Industry
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    • v.7 no.1
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    • pp.7-14
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    • 2013
  • In this study, we investigated the applicability of the photostimulated luminescence (PSL), thermoluminescence (TL) and electron spin resonance (ESR) methods for various foods. The analysed samples consist of 11 items including dried fruits (6 items) and mushrooms (5 items). To compare between non-irradiated and irradiated food, all samples were irradiated with $^{60}Co$ gamma-ray source. In PSL study, the photon counts of all the unirradiated sample were identified negative (lower than 700). The photon counts irradiated (1, 5, 10 kGy) dried date-palm, dried jujube and mushrooms (Auricularia auricula, Phellinus linteus and Sarcodon aspratus) showed positive (higher than 5,000) and the results for the other samples were negative or intermediate (>700 and >5,000). In TL analysis most of items can be applicable to detect irradiated foods because of showing TL ratio above 0.1. The glow curves by TL method were estimated in the range of $150{\sim}250^{\circ}C$ in irradiated samples. In ESR measurements, the intensity of ESR signal (single-line) increased as the dose of irradiation increased. In particular, the specific ESR signals of irradiation-induced radical were detected in dried papaya, dried date-palm, dried banana, dried pineapple and S. aspratus. According to the results, PSL, TL and ESR methods were successfully applied to detect the irradiated foods. It is concluded that PSL, TL and ESR methods are suitable for detection of irradiated samples and a combined method is recommendable for enhancing the reliability of detection results.

Anti-inflammatory effects of Cudrania tricuspidata twig sawdust fermented with Ganoderma lucidum mycelium (영지버섯균 발효 꾸지뽕나무 가지 톱밥 추출물의 항염증 활성)

  • Park, Se-Eun;Kim, Myung Kon;Kim, Seung
    • Journal of Mushroom
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    • v.19 no.3
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    • pp.225-233
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    • 2021
  • In this study, we evaluated the anti-inflammatory effect of extract from Cudrania tricuspidata twig sawdust fermented with Ganoderma lucidum mycelium. Fermented Cudrania tricuspidata twig sawdust extracted with 70% ethanol and elucidated the potential signaling pathway in lipopolysaccharide (LPS)-induced RAW264.7 cells. Fermented Cudrania tricuspidata twig sawdust inhibits LPS-stimulated nitric oxide (NO) production without affecting cell viability in a dose-dependent manner and production of LPS-induced pro-inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and prostaglandin2 (PGE2). Fermented Cudrania tricuspidata twig sawdust also suppressed the expression of the pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 cells. Moreover, Fermented Cudrania tricuspidata twig sawdust significantly attenuated LPS-induced IkappaB (IκB) degradation and suppressed nuclear factor kappa B (NF-κB) nuclear translocation. These results suggest that fermented Cudrania tricuspidata twig sawdust may have great potential for the development of anti-inflammatory agent.

Establishment of Test Conditions and Interlaboratory Comparison Study of Neuro-2a Assay for Saxitoxin Detection (Saxitoxin 검출을 위한 Neuro-2a 시험법 조건 확립 및 실험실 간 변동성 비교 연구)

  • Youngjin Kim;Jooree Seo;Jun Kim;Jeong-In Park;Jong Hee Kim;Hyun Park;Young-Seok Han;Youn-Jung Kim
    • Journal of Marine Life Science
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    • v.9 no.1
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    • pp.9-21
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    • 2024
  • Paralytic shellfish poisoning (PSP) including Saxitoxin (STX) is caused by harmful algae, and poisoning occurs when the contaminated seafood is consumed. The mouse bioassay (MBA), a standard test method for detecting PSP, is being sanctioned in many countries due to its low detection limit and the animal concerns. An alternative to the MBA is the Neuro-2a cell-based assay. This study aimed to establish various test conditions for Neuro-2a assay, including cell density, culture conditions, and STX treatment conditions, to suit the domestic laboratory environment. As a result, the initial cell density was set to 40,000 cells/well and the incubation time to 24 hours. Additionally, the concentration of Ouabain and Veratridine (O/V) was set to 500/50 μM, at which most cells died. In this study, we identified eight concentrations of STX, ranging from 368 to 47,056 fg/μl, which produced an S-shaped dose-response curve when treated with O/V. Through inter-laboratory variability comparison of the Neuro-2a assay, we established five Quality Control Criteria to verify the appropriateness of the experiments and six Data Criteria (Top and Bottom OD, EC50, EC20, Hill slop, and R2 of graph) to determine the reliability of the experimental data. The Neuro-2a assay conducted under the established conditions showed an EC50 value of approximately 1,800~3,500 fg/μl. The intra- & inter-lab variability comparison results showed that the coefficients of variation (CVs) for the Quality Control and Data values ranged from 1.98% to 29.15%, confirming the reproducibility of the experiments. This study presented Quality Control Criteria and Data Criteria to assess the appropriateness of the experiments and confirmed the excellent repeatability and reproducibility of the Neuro-2a assay. To apply the Neuro-2a assay as an alternative method for detecting PSP in domestic seafood, it is essential to establish a toxin extraction method from seafood and toxin quantification methods, and perform correlation analysis with MBA and instrumental analysis methods.

Efficacy of Interferon-Gamma Treatment in Bronchial Asthma (기관지천식에서 Interferon-Gamma 치료의 효과)

  • Kim, Kwan-Hyoung;Kim, Seok-Chan;Kim, Young-Kyoon;Kwon, Soon-Seog;Kim, Chi-Hong;Moon, Hwa-Sik;Song, Jung-Sup;Park, Sung-Hak;Lee, Choong-Eon;Byun, Kwang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.822-835
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    • 1997
  • Background : There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-$\gamma$) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN-$\gamma$ might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo effect of IFN-$\gamma$ in bronchial asthma we tried a clinical study. Methods : Fifty bronchial asthmatics(serum IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anion(${O_2}^-$) generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine $PC_{20}$ in addition to the above parameters were also compared before and after IFN-$\gamma$ treatment. IFN-$\gamma$ was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks. Results : The ${O_2}^-$ generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects($8.23{\pm}0.94$ vs $5.00{\pm}0.68\;nmol/1{\times}10^6$ cells, P<0.05), and significantly decreased after IFN-$\gamma$ treatment compared to initial values($3.69{\pm}0.88$ vs $8.61{\pm}1.53\;nmol/1{\times}10^6$ cells, P<0.05). CD23 expression of peripheral B-cells in bronchial asthmatics was higher than normal subjects($47.47{\pm}2.96%$, vs $31.62{\pm}1.92%$, P<0.05), but showed no significant change after IFN-$\gamma$ treatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects($191.04{\pm}23.3\;U/ml$ vs $162.85{\pm}4.85\;U/ml$), and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN-$\gamma$ treatment. However the means of serum sCD23 levels were not different before and after IFN-$\gamma$ treatment. The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects($22.48{\pm}6.81%$ vs $18.90{\pm}2.43%$), and slightly increased after IFN-$\gamma$ treatment($27.90{\pm}2.56%$). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN-$\gamma$ treatment. And the levels of serum IgE were significantly decreased after IFN-$\gamma$ treatment compared to initial values ($658.67{\pm}120.84\;IU/ml$ vs $1394.32{\pm}314.42\;IU/ml$, P<0.05). Ten(83.3%) of 12 patients showed an improving pattern in bronchial hyperresponsiveness after IFN-$\gamma$ treatment, and the means of histamine $PC_{20}$ were significantly increased after IFN-$\gamma$ treatment compared to initial values ($1.22{\pm}0.29mg/ml$ vs $0.69{\pm}0.17mg/ml$, P<0.05). Conclusion : Our results suggest that IFN-$\gamma$ may be useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN-$\gamma$ may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.

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Combined Modality Treatment in Nasopharyngeal Carcinoma (비인강암의 병합요법)

  • Yun, Sang-Mo;Kim, Jae-Cheol;Park, In-Kyu
    • Radiation Oncology Journal
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    • v.19 no.2
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    • pp.100-106
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    • 2001
  • Purpose : We performed a retrospective analysis to compare short term results of induction chemotherapy-radiotherapy versus concurrent chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Materials and Methods : From Oct. 1989 to May 1998, 62 patients with locally advanced nasopharyngeal carcinoma were treated with induction chemotherapy followed by radiotherapy (induction group) or concurrent chemo-radiotherapy (concurrent group). Induction chemotherapy was done for 50 patients, and concurrent chemotherapy for 12 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Stage distribution showed $32\%$ with IIB, $32\%$ with III, and $38\%$ with IV in induction group, and $50\%,\;33.3\%,\;and\;16.7\%$ in concurrent group, respectively. Chemotherapy regimen was CF (cisplatin and 5-FU) in both groups, and drug delivery method also same. Cisplatin $100\;mg/m^2$ was intravenously infused on day 1, and 5-FU $1,000\;mg/m^2$ on day $2\~6$. This was repeated at 3 weeks interval. At the end of radiotherapy, total cycles of chemotherapy were $1\~3$ (median 2) in both groups. Conventionally fractionated radiotherapy with daily fraction size $1.8\~2.0\;Gy$ and 5 fractions/week was done. Total dose was $69.4\~86\;Gy$(median 73.4 Gy) for induction group, and $69.4\~75.4\;Gy$ (median 70.8 Gy) for concurrent group. Follow-up time was $9\~116$ months (median 40.5 months) for induction group, $14\~29$ months (median 21 months) for concurrent group, respectively. Results : Overall 2 year survival rate (2YSR) for all patients was $78.7\%$. According to treatment modality, 2YSR were $77\%$ for induction group, $87\%$ for concurrent group (p>0.05). 2 year disease-free survival rate were $56\%$ and $81\%\;(p>0.05)$, respectively. Complete response to treatment were $75.5\%$ for induction group and $91.7\%$ for concurrent group, but there was no statistical difference. The incidence of grade $3\~4$ hematologic toxicity during radiotherapy was not differ between two groups, but grade 2 leukopenia was more frequent in concurrent group $(18\%\;vs\;66.7\%)$Grade $3\~4$ mucositis was more frequent in concurrent group $(4.0\%\;vs\;33.3\%)$. Overall incidence of grade $3\~4$ acute toxicity during radiotherapy was more frequent in concurrent group $(6.0\%\;vs\;41.7\%,\;p=0.005)$. Conclusion : Concurrent chemo-radiotherapy showed a trend of improvement in short-term survival and in treatment response when compared with induction chemotherapy-radiotherapy in locally advanced nasopharyngeal carcinoma. More controlled randomized trial are needed.

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