• Title/Summary/Keyword: 간 독성

Search Result 750, Processing Time 0.038 seconds

Inhibitory effects of heavy metals on CYP1A expression in eel hepatocyte cultures (뱀장어 배양 간세포에서의 Cytochrome P4501A (CYP1A) 유전자 발현에 대한 중금속들의 억제효과)

  • Kwon, Hyuk-Chu;Maeng, Joon-Ho;Choi, Seong-Hee
    • Journal of fish pathology
    • /
    • v.23 no.2
    • /
    • pp.245-254
    • /
    • 2010
  • Effects of heavy metal ions on the gene expression of cytochrome P4501A (CYP1A) were examined in cultured eel hepatocytes. When the expression of CYP1A mRNA was measured by RT-PCR after incubation of eel hepatocytes with benzo[$\alpha$]pyrene (B[$\alpha$]P) at concentrations of 10-8~10-5 M, the CYP1A expression increased with B[$\alpha$]P treatment in a dose dependent manner, showing significant increase at concentrations more than 10-7 M. When the eel hepatocyte was treated with cadmium (10-6 and 10-5 M), the expression of CYP1A was inhibited and especially at higher concentration (10-5 M). The inhibition of CYP1A expression by cadmium was also observed in cells treated with B[$\alpha$]P. In another study, effects of heavy metal ions on the expression of CYP1A were examined in cultured hepatocytes isolated from eel which was treated previously with B[$\alpha$]P in vivo. Hepatocytes isolated from the liver of eel taken at 48 hours after injection of B[$\alpha$]P (10 mg/kg) were cultured for 2 days with cadmium, copper, lead or zinc (10-6 and 10-5 M). The expression of CYP1A was found to be suppressed by the metal ions compared with the control in which CYP1A was induced with previous treatment of B[$\alpha$]P in vivo. The present results may provide an important basic information for studying the effects of heavy metal ions on CYP1A expression in other species of fish and studying toxicological mechanisms of heavy metal ions in aquatic livings.

A Study on the Cd Accumulation and Tolerance of Pisolithus Tinctorius in Vitro (배양기내(培養器內)에서 모래밭버섯균(菌)의 Cd 축적(蓄積)과 내성(耐性)에 관(關)한 연구(硏究))

  • Han, Sim Hee;Lee, Kyung Joon;Hyun, Jung Oh
    • Journal of Korean Society of Forest Science
    • /
    • v.90 no.1
    • /
    • pp.83-89
    • /
    • 2001
  • This study was conducted to test the Cd accumulation and Cd-tolerance of Pisotithus tinctorius(Pt). Pt was isolated from Pinus thunbergii forest in Muan, Chonnam Province in 1997. Pt was cultured on MMN medium supplemented with $CdSO_4{\cdot}5H_2O$ at the final concentration of 0, 0.2, 0.5, 2, and $10{\mu}g/m{\ell}$ for 40 days. Growth rate and tolerance index of the fungus were measured every week, while Cd concentration, superoxide dismutase(SOD), and glutathione reductase(GR) of the fungus were analyzed at the end of the culturing, Pt showed growth reduction in vitro at $2{\mu}g/m{\ell}$ Cd in the medium and almost stopped growth at $10{\mu}g/m{\ell}$ Cd. Tolerance index of Pt decreased with increasing Cd concentration. Cd concentration of Pt was the highest at $10{\mu}g/m{\ell}$ Cd. Activities of SOD did not show significant difference between Cd concentrations, but GR of Pt increased at $0.5{\mu}g/m{\ell}$ Cd, and decreased at $2{\mu}g/m{\ell}$ Cd. Consequently Pt could be called Cd accumulator with a tolerance mechanism to Cd. Their tolerance to Cd were expressed through the higher production of antioxidants such as GR. Pt may be used for revegetation and decontamination of soil polluted by heavy metals.

  • PDF

Development of A Material Flow Model for Predicting Nano-TiO2 Particles Removal Efficiency in a WWTP (하수처리장 내 나노 TiO2 입자 제거효율 예측을 위한 물질흐름모델 개발)

  • Ban, Min Jeong;Lee, Dong Hoon;Shin, Sangwook;Lee, Byung-Tae;Hwang, Yu Sik;Kim, Keugtae;Kang, Joo-Hyon
    • Journal of Wetlands Research
    • /
    • v.24 no.4
    • /
    • pp.345-353
    • /
    • 2022
  • A wastewater treatment plant (WWTP) is a major gateway for the engineered nano-particles (ENPs) entering the water bodies. However existing studies have reported that many WWTPs exceed the No Observed Effective Concentration (NOEC) for ENPs in the effluent and thus they need to be designed or operated to more effectively control ENPs. Understanding and predicting ENPs behaviors in the unit and \the whole process of a WWTP should be the key first step to develop strategies for controlling ENPs using a WWTP. This study aims to provide a modeling tool for predicting behaviors and removal efficiencies of ENPs in a WWTP associated with process characteristics and major operating conditions. In the developed model, four unit processes for water treatment (primary clarifier, bioreactor, secondary clarifier, and tertiary treatment unit) were considered. Additionally the model simulates the sludge treatment system as a single process that integrates multiple unit processes including thickeners, digesters, and dewatering units. The simulated ENP was nano-sized TiO2, (nano-TiO2) assuming that its behavior in a WWTP is dominated by the attachment with suspendid solids (SS), while dissolution and transformation are insignificant. The attachment mechanism of nano-TiO2 to SS was incorporated into the model equations using the apparent solid-liquid partition coefficient (Kd) under the equilibrium assumption between solid and liquid phase, and a steady state condition of nano-TiO2 was assumed. Furthermore, an MS Excel-based user interface was developed to provide user-friendly environment for the nano-TiO2 removal efficiency calculations. Using the developed model, a preliminary simulation was conducted to examine how the solid retention time (SRT), a major operating variable affects the removal efficiency of nano-TiO2 particles in a WWTP.

Safety and Efficacy of Gemcitabine Based Chemotherapy in Elderly Patients with Advanced Pancreatic Cancer - Safety of Gemcitabine in Elderly (진행성 췌장암을 가진 노인환자에서 Gemcitabine 항암화학요법의 안정성과 효과 - 노인에서 Gemcitabine의 안정성 -)

  • You Ie Choi;Dong Uk Kim;Jae Hoon Cheong;Bong Eun Lee;Gwang Ha Kim;Geun Am Song
    • Journal of Digestive Cancer Research
    • /
    • v.1 no.1
    • /
    • pp.36-42
    • /
    • 2013
  • Background/Aims: Gemcitabine is regarded as a reference regimen for advanced pancreatic cancer and shows relatively safe toxicity profiles compared with other cytotoxic agents. However, many oncologists are appeared to be still reluctant to treat elderly pancreatic cancer patients with cytotoxic chemotherapy because of predicted low response rate and potential adverse events. Methods: All patients who were received gemcitabine based chemotherapy between 2007 and 2010 were identified and clinical, laboratory, radiographic data were retrospectively reviewed. Patients were divided into two groups based on their ages: less than 65, and equal or more than 65 years old. Gemcitabine, at a dose of 1,000 mg per square meter of body surface area, was administered by intravenously over 30 minutes weekly for 3 weeks followed by 1 week rest, alone or along with other chemotherapeutic agents including cisplatin, capecitabine and erlotinib. Results: A total of 61 patients were identified and all patients were not eligible to receive operation because of advanced stage at diagnosis. Twenty three patients (37.7%) were equal or more than 65 year of age. Mean age was 56 years old and 71 years old in each group. Laboratory data including CA 19-9 were not significantly different. More gemcitabine monotherapy was delivered (56.5% vs. 26.3%, p=0.029) and less second or third line therapy was adminis- tered (17.4% vs. 50.0%, p=0.014) in elderly group. Cholangitis occurred and stent placement were performed similarly in both groups. Conclusion: Gemcitabine based chemotherapy can be administered safely to elderly pancreatic cancer patients and comparable response rate and progression free survival can be expected as young patients.

  • PDF

Effects of a Herb Drug Extracts on Mitigation of Reproductive Toxicity after a Continuous Dose of Dioxin in Mice (생약재제가 Dioxin의 연속투여 후 생식독성의 완화에 미치는 영향 관한 연구)

  • 김상근;김민수
    • Korean Journal of Animal Reproduction
    • /
    • v.24 no.3
    • /
    • pp.241-248
    • /
    • 2000
  • In this study, we examined the number and motility of sperms, and also observed the changes in testes weight, and histological changes of several organs after 5 days of a continuous administration of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) of per oral administration of a herb drug extracts, which were administerated altermate days, to elucidate the effects of the a herb drug extracts on reproductive toxicity of dioxin. 1. The sperm numbers of dioxin-administered groups were 90.7$\pm$3.6~l18.5$\pm$3.6$\times$10/suup 6/$m\ell$ and 67.3$\pm$4.1~88.2$\pm$3.3$\times$10$^{6}$ $m\ell$ for 10~20 $\mu\textrm{g}$/kg and 30~40 $\mu\textrm{g}$/kg dosages of dioxin-administerated groups, respectively. Each dioxin-administered group showed prominently lower value than that of control group's which was 119.3$\pm$3.4~120.2$\pm$4.7 $\times$ 10$^{6.}$$m\ell$. 2. The sperm motility of each dioxin-administered group's also showed lower value than that of control group's which was 93.6$\pm$3.8~94.9$\pm$3.4%. The sperm motility of each dioxin-administerated group were 77.0$\pm$4.7~89.5$\pm$3.6% and 66.5$\pm$3.3 ~79.9$\pm$3.8% for 10~20 $\mu\textrm{g}$/kg and 30~40 $\mu\textrm{g}$/kg dosages of dioxin-administerated groups, respectively. 3. The sperm numbers of each group, which was administered a herb drug extracts, were 77.4$\pm$3.2~90.9$\pm$3.4$\times$10$^{6}$ $m\ell$, 78.0$\pm$3.3~105.0$\pm$4.2$\times$10$^{6}$ $m\ell$, 76.2$\pm$2.8~84.4$\pm$3.5$\times$10$^{6}$ $m\ell$ and 75.4$\pm$3.3~80.2$\pm$3.3$\times$10$^{6}$ $m\ell$ for extracts of green leaf, red ginseng, Kugija and Oume-administered groups respectively. And the sperm motility of each group were 63.4$\pm$3.8~77.0$\pm$4.0%, 65.5$\pm$4.1~87.4$\pm$3.8%, 64.3$\pm$4.2~69.8$\pm$4.2%, 66.3$\pm$3.9~66.0$\pm$4.0% for extracts of green leaf, red ginseng, Kugija and Oume extracts-administered groups, respectively. 4. The number and motility of sperm of control group were 119.3$\pm$3.4~120.2$\pm$4.7$\times$10$^{6}$ $m\ell$ and 93.0$\pm$3.5~96.1$\pm$3.5%, respectively. Red ginseng extracts- administered group seemed to be recovered than my other groups, and the green leaf extracts-administered group was shown to be the next. The Kugija and Oume extracts-administered groups didn't show to be recovered much. 5. Most a herb drug extracts-administered group except the red ginseng-administered group displayed prominently lower values of testes weights than that of control group's which was 0.15$\pm$0.01~0.16$\pm$0.01g. The red ginseng extracts-administered group seemed to be recovered conspicuously. 6. After 5 days of a continuous administration of 30 $\mu\textrm{g}$/kg dosage of dioxin followed by 3 weeks of per oral administration of green leaf, red ginseng, Kugija, or Oume extracts, histological findings showed that the liver, spleen, and testis of most a herb drug extracts-administered groups were damaged severely. By the way, the testes of red ginseng extracts-administered group seemed to recover compared to the other group's.ompared to the other group's.

  • PDF

Characteristics and Sensory Optimization of Taro (Colocasia esculenta) under Different Aging Conditions for Food Application of Black Taro (흑토란의 식품재료화를 위한 숙성 조건에 따른 토란의 특성 및 관능 최적화)

  • Jeon, Yu-Ho;Lee, Ji-Won;Son, Yang-Ju;Hwang, In-Kyeong
    • Korean Journal of Food Science and Technology
    • /
    • v.48 no.2
    • /
    • pp.133-141
    • /
    • 2016
  • The physicochemical properties, antioxidant capacities, and sensory optimization of taro (Colocasia esculenta) under different aging conditions were investigated to develop black taro. Black taro was processed in three steps (steaming: $95{\pm}3^{\circ}C$ for 1 h; aging: 85, 90, $95^{\circ}C$ for 20, 40, and 60 h; drying: $60^{\circ}C$ for 24 h) and ground into a powder for all experiments. Black taro showed an increased crude fiber content and browning index compared to raw taro. Calcium oxalate contents, reducing sugar contents, moisture contents, and lightness values were decreased during the processing of taro. Improvements in total polyphenol content and antioxidant activity (DPPH, ABTS, FRAP) were observed in the black taro samples aged at higher temperature. Response surface methodology was used for sensory optimization, and the optimum aging conditions with the highest acceptance values were found to be $88.73^{\circ}C$ for 39.50 h for taste, and $88.82^{\circ}C$ for 42.60 h for overall acceptance.

Changes of Polyamine Metabolism and Delayed Neuronal Degeneration of Hippocampus after Transient Cerebral Ischemia in Mongolian Gerbils (뇌허혈 손상에 있어서 Polyamine 대사의 변동이 해마신경세포의 지연성괴사에 미치는 효과에 관한 연구)

  • Shin, Kyung-Ho;Shin, Hwa-Jung;Lee, Young-Jae;Kim, Hyung-Gun;Choi, Sang-Hyun;Chun, Yeon-Sook;Chun, Boe-Gwun
    • The Korean Journal of Pharmacology
    • /
    • v.32 no.3
    • /
    • pp.323-334
    • /
    • 1996
  • Male Mongolian gerbils $(60{\sim}80g)$ were given DL-difluoromethylornithine (DFMO; 250mg/kg, ip) and methylglyoxal bis(guanylhydrazone) (MGBG; 50 mg/k, ip), respectively, 1 h prior to transient (7 min) occlusion of bilateral common carotid arteries (OBC7) and a daily dose of one of them for 6 days after recirculation, and the polyamine contents, activities of ornithine and S-adenosylmethionine decarboxylases (ODC and SAM-DC), and light microscopic findings of the hippocampus were evaluated. The hippocampal putrescine (PT) levels of the control gerbils treated with saline (STGr), markedly increased after OBC7, showing a peak level at 24 h after recirculation. The peak PT level was reduced in DFMO treated gerbils (DTCr) and in MGBG treated gerbils (MTGr). And 7 days after recirculation, the PT level of DTGr was decreased to about 75% of the PT level in the sham operated group (nonTGr) and to about 55% of the STGr level, respectively. The hippocampal spermidine (SD) level of STGr tended to decline, showing the lowest value at 8 h after recirculation. But the spermidine (SD) level of DTGr was somewhat higher at 8 h after OBC7 than those of STGr and MTGr The hippocampal spermine (SM) levels of all the experimental groups were little changed for 7 days after OBC. OBC7 markedly increased the hippocampal ODC activity. reaching a maximum (about 3 times higher than preischemic level) at 8 h and rapidly recovered to the control value by 24 h in STGr gerbils, and the OBC7-induced increase of ODC activity was significantly attenuated by DFMO or MGBG treatment. Whereas OBC7 induced a rapid decrease of the hippocampal SAMDC activity follwed by gradual recovery to the preischemic level, and the decrease of the SAMDC activity was slightly attenuated by DFMO or MGBG treatment. 7 Days after OBC7 the histological finding of the hippocampal complex stained with cresyl violet showed an extensive delayed neuronal damage in the CA1 region and to a lesser extent, in the dentate gyrus, sparing the CA3 region. And the neuronal death was aggevated by DFMO but significantly attenuated by MGBG. The immunochemical reactivity of hippocampus to anti-GFAP antibody was significantly increased in the CA1 region and to a lesser extent, in the dentate gyrus 7 days after OBC7, but was little changed in the CA3. And the increase of the anti-GFAP immunoreactivity was moderately enhanced by DFMO and significantly suppressed by MGBG. These results suggest that the polyamine metabolism may play a modulatory role in the ischemic brain damage.

  • PDF

The Effect of Soil Acidification on the Distribution of Nutrients and Heavy metals in Forest Ecosystem near Ulsan Industrial Estate (울산(蔚山) 공단주변(工團周邊) 산림토양(山林土壤)의 산성화(酸性化)가 산림생태계(山林生態系)의 양료(養料)와 중금속(重金屬) 분포(分布)에 미치는 영향(影響))

  • Lee, Seung Woo;Lee, Soo Wook
    • Journal of Korean Society of Forest Science
    • /
    • v.84 no.3
    • /
    • pp.286-298
    • /
    • 1995
  • This study was carried out to investigate the effect of forest soil acidification on the distribution of exchangeable cations($Ca^{2+}$, $Mg^{2+}$, $Al^{3+}$) and heavy metals(Cu, Zn, Mn, Pb, Cd) in soil, and to understand the relation of the soil chemical properties and the distribution of nutrients and hear metals in fine root and foliage. The results through survey on the long - term change of soil pH and the contents of nutrient and heavy metal in soil, fine root and foliage by 2 sites near Ulsan - Onsan industrial estate and 2 sites in limited development district are summarized as follows : 1. The average forest soil pH(A horizon) in Ulsan had been proceeded down to 3.73 in deciduous forest and 3.86 in coniferous forest in 1994 from 4.45 and 4.78 in 1987, respectively, which indicated serious soil acidification. As comparing soil pH among sites, Dongcheon coniferous forest(pH 4.57) in limited development district showed the highest values and Dangwol deciduous forest(pH 3.19) near Onsan industrial estate showed the lowest values in 1994. 2. Contents of exchangeable calcium in forest soils of limited development district where showed much higher soil pH than industrial estate were 3.5 times more in deciduous forest soil and 11 times more in coniferous forest soil than in industrial estate, and contents of exchangeable magnesium were also 4.5 and 5 times more in limited development district than in industrial estate, respectively. However contents of exchangeable aluminium which had been supposed more in forest soil of industrial estate were more in limited development district. 3. Contents of calcium and magnesium in fine root of deciduous trees(A hirsuta. Q. acutissima) were 3.6 and 1.7 times more in limited development district than in industrial estate, respectively, and those of coniferous trees(P. rigida, P. thunbergii) were 4.6 and 1.5 times more in Limited development district than in industrial estate, respectively. Also contents of calcium and magnesium in foliage of deciduous trees were 1.1 and 2.2 times more in limited development district than in industrial estate, respectively, and those of coniferous trees were 1.8 and 3.3 times more in limited development district, respectively. And contents of aluminium in fine root and foliage were nearly as same as in soil. 4. Ca/Al molar ratios in soil and fine root, which could be related with the dgree of soil acidification and Al toxicity on trees, were Less than 1 in all sites except Dongcheon, suggesting that the soil and fine root in the sites have high sensitivity to soil acidification and the decrease in nutrient uptake and root enlargement. The Ca/Al molar ratios in soil and fine root in coniferous forest were highly correlated with the soil pH one another. 5. Contents of Cu, Zn and Pb in soil, fine root and foliage were more in industrial estate than in limited development district in both deciduous and coniferous forests, however, oppositely contents of Mn and Cd in soil were more in limited development district than in industrial estate.

  • PDF

Comparison of the Result of Radiation Alone and Radiation with Daily Low Dose Cisplatin in Management of Locally Advanced Cervical Cancer (국소적으로 진행된 자궁경부암에서 방사선 단독치료와 방사선 및 저용량 Cisplatin 항암화학요법 병용치료의 비교)

  • Kim Hun Jung;Kim Woo Chul;Lee Mee Jo;Kim Chul Su;Song Eun Seop;Loh John J K.
    • Radiation Oncology Journal
    • /
    • v.22 no.3
    • /
    • pp.200-207
    • /
    • 2004
  • Purpose: An analysis was to compare the results of radiation alone with those of radiation with dally low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. Materials and Methods: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was peformed. Thirty one patients received radiation alone and 28 patients received dally low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900$\~$l,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000$\~$3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4$\%$) and 8 (13.6$\%$) stages IIB and stage IIIB, respectively. Results: The overall 5 year survival rate was 65.65$\%$ and according to treatment modality were 56.75$\%$ and 73.42$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39$\%$ and 63.34$\%$ in the radiation alone and chemoradiatoin groups, respectively (p=0.053), The 5 year locoregional control rates were 52.34$\%$ and 73.58$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29$\%$ and 81.46$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.477), Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia $\geq$grade) occurred in 3.2$\%$and 28.5$\%$ of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. Conclusion: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates In locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.

Optimum Radiotherapy Schedule for Uterine Cervical Cancer based-on the Detailed Information of Dose Fractionation and Radiotherapy Technique (처방선량 및 치료기법별 치료성적 분석 결과에 기반한 자궁경부암 환자의 최적 방사선치료 스케줄)

  • Cho, Jae-Ho;Kim, Hyun-Chang;Suh, Chang-Ok;Lee, Chang-Geol;Keum, Ki-Chang;Cho, Nam-Hoon;Lee, Ik-Jae;Shim, Su-Jung;Suh, Yang-Kwon;Seong, Jinsil;Kim, Gwi-Eon
    • Radiation Oncology Journal
    • /
    • v.23 no.3
    • /
    • pp.143-156
    • /
    • 2005
  • Background: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. Materials and Methods: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of $23.4\~59.4$ Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-IBT) was also peformed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of $14.4\~43.2$ Gy (Median 36.0) of EBRT in 495 patients, while In the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor ($\alpha/\beta$=10) and late-responding tissues ($\alpha/\beta$=3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED $Gy_3$ and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED $Gy_3$ and rectal complications and between V-BED $Gy_3$ and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED $Gy_{10}$, and the treatment duration. Results: The overall complication rate for RTOG Grades $1\~4$ toxicities was $33.1\%$. The 5-year actuarial pelvic control rate for ail 743 patients was $83\%$. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to 121.9 $Gy_{10}$ (median 93.0) for tumors and from 93.6 to 187.3 $Gy_3$ (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED $Gy_3$) and bladder Point BED (V-BED $Gy_3$) were 118.7 $Gy_3$ (range $48.8\~265.2$) and 126.1 $Gy_3$ (range: $54.9\~267.5$), respectively. MD-BED $Gy_3$ showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED $Gy_3$ had a very strong association (p=<0.0001), and was more predictive of rectal complications than A-BED $Gy_3$. B-BED $Gy_3$ also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. Conclusion: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences In tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very Important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered.