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90-day Repeated-dose Oral Toxicity Study of 20 kGy Irradiated Cold Water Extract Powder of Mistletoe (20 kGy 감마선으로 조사된 겨우살이 냉수 추출물의 90일 반복투여 독성평가)

  • Kim, Jin-Kyung;Jeon, Young-Eun;Yin, Xing Fu;Lee, Ju-Woon;Kang, Il-Jun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.5
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    • pp.704-711
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    • 2011
  • Traditionally, mistletoes have been used as immunostimulant for the management of certain diseases such as cancer with high profile immune depleting potentials. In order to examine the safety of the 20 kGy irradiated cold water extract powder of mistletoes, we performed a 90-day repeated-dose toxicity study with ICR mice. The mice were treated with daily doses of the 20 kGy irradiated cold water extract powder of mistletoes by gavage at 0, 20, 100, and 500 mg/kg/day for 90 consecutive days. We recorded clinical signs of toxicity, body weight, organ weights, histological changes in target organs, hematology, and clinical blood chemistry analysis data for all mice. There were no significant changes in body and organ weights during the experimental period. The hematological analysis and clinical blood chemistry data revealed no toxic effects from the 20 kGy irradiated cold water extract powder of mistletoes. Pathologically, neither gross abnormalities nor histopathological changes were observed between the control and treated mice of both sexes. Collectively, these data suggest that the 20 kGy irradiated cold water extract powder of mistletoes have a high margin of safety.

Panax ginseng total protein promotes proliferation and secretion of collagen in NIH/3T3 cells by activating extracellular signal-related kinase pathway

  • Chen, Xuenan;Wang, Manying;Xu, Xiaohao;Liu, Jianzeng;Mei, Bing;Fu, Pingping;Zhao, Daqing;Sun, Liwei
    • Journal of Ginseng Research
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    • v.41 no.3
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    • pp.411-418
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    • 2017
  • Background: Recently, protein from ginseng was studied and used for the treatment of several kinds of diseases. However, the effect of ginseng total protein (GTP) on proliferation and wound healing in fibroblast cells remains unclear. Methods: In this study, cell viability was analyzed using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Cell cycle distribution was analyzed by flow cytometer. The levels of transforming growth factor ${\beta}1$, vascular endothelial growth factor, and collagens were analyzed by enzyme-linked immunosorbent assay and immunofluorescence staining. The expressions of cyclin A, phosphorylation of extracellular signal-related kinase (p-ERK1/2), and ERK1/2 were analyzed by Western blotting. Results: Our results showed that GTP promoted cell proliferation and increased the percentage of cells in S phase through the upregulation of cyclin A in NIH/3T3 cells. We also found that GTP induced the secretion of type I collagen, and promoted the expression of other factors that regulate the synthesis of collagen such as transforming growth factor ${\beta}1$ and vascular endothelial growth factor. In addition, the phosphorylation of ERK1/2 at Thr202/Tyr204 was also increased by GTP. Conclusion: Our studies suggest that GTP promoted proliferation and secretion of collagen in NIH/3T3 cells by activating the ERK signal pathway, which shed light on a potential function of GTP in promoting wound healing.

Relative Abundance of a Vector of Scrub Typhus, Leptotrombidium sialkotense, in Southern Yunnan Province, China

  • Lv, Yan;Guo, Xian-Guo;Jin, Dao-Chao;Song, Wen-Yu;Fan, Rong;Zhao, Cheng-Fu;Zhang, Zhi-Wei;Mao, Ke-Yu;Zou, Yun-Ji;Yang, Zhi-Hua
    • Parasites, Hosts and Diseases
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    • v.58 no.2
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    • pp.153-159
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    • 2020
  • The chigger mite Leptotrombidium sialkotense is one of the 6 main vectors of scrub typhus in China. Before present study, L. sialkotense was found in some parts of Hunan province, China with a narrow geographical distribution. During field investigation 2016-2017, we found L. sialkotense in Jingha, southern Yunnan, China. Of 15 small mammal host species, L. sialkotense were collected from 6 species of the hosts. Rattus brunneusculus was a dominant host of L. sialkotense, from which 98.3% of the mites were collected. The chigger mite showed a relatively high infestation prevalence (PM =11.7%) and mean abundance (MA=0.5) in comparison with the rest 5 host species. These results reveal a certain host specificity of L. sialkotense to a rat R. brunneusculus. The mite L. sialkotense showed an aggregated distribution on the host (P<0.05). A positive correlation observed between L. sialkotense and the body length of hosts. There was a positive interspecific association between L. sialkotense and 2 other dominant vectors, L. deliense and L. scutellare.

Effects of exploration and molecular mechanism of CsV on eNOS and vascular endothelial functions

  • Zuo, Deyu;Jiang, Heng;Yi, Shixiong;Fu, Yang;Xie, Lei;Peng, Qifeng;Liu, Pei;Zhou, Jie;Li, Xunjia
    • Advances in nano research
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    • v.12 no.5
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    • pp.501-514
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    • 2022
  • This study aimed to investigate the effects and potential mechanisms of Chikusetsusaponin V (CsV) on endothelial nitric oxide synthase (eNOS) and vascular endothelial cell functions. Different concentrations of CsV were added to animal models, bovine aorta endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) cultured in vitro. qPCR, Western blotting (WB), and B ultrasound were performed to explore the effects of CsV on mouse endothelial cell functions, vascular stiffness and cellular eNOS mRNA, protein expression and NO release. Bioinformatics analysis, network pharmacology, molecular docking and protein mass spectrometry analysis were conducted to jointly predict the upstream transcription factors of eNOS. Furthermore, pulldown and ChIP and dual luciferase assays were employed for subsequent verification. At the presence or absence of CsV stimulation, either overexpression or knockdown of purine rich element binding protein A (PURA) was conducted, and PCR assay was employed to detect PURA and eNOS mRNA expressions, Western blot was used to detect PURA and eNOS protein expressions, cell NO release and serum NO levels. Tube formation experiment was conducted to detect the tube forming capability of HUVECs cells. The animal vasodilation function test detected the vasodilation functions. Ultrasonic detection was performed to determine the mouse aortic arch pulse wave velocity to identify aortic stiffness. CsV stimulus on bovine aortic cells revealed that CsV could upregulate eNOS protein levels in vascular endothelial cells in a concentration and time dependent manner. The expression levels of eNOS mRNA and phosphorylation sites Ser1177, Ser633 and Thr495 increased significantly after CsV stimulation. Meanwhile, CsV could also enhance the tube forming capability of HUVECs cells. Following the mice were gavaged using CsV, the eNOS protein level of mouse aortic endothelial cells was upregulated in a concentration- and time-dependent manner, and serum NO release and vasodilation ability were simultaneously elevated whereas arterial stiffness was alleviated. The pulldown, ChIP and dual luciferase assays demonstrated that PURA could bind to the eNOS promoter and facilitate the transcription of eNOS. Under the conditions of presence or absence of CsV stimulation, overexpression or knockdown of PURA indicated that the effect of CsV on vascular endothelial function and eNOS was weakened following PURA gene silence, whereas overexpression of PURA gene could enhance the effect of CsV upregulating eNOS expression. CsV could promote NO release from endothelial cells by upregulating the expression of PURA/eNOS pathway, improve endothelial cell functions, enhance vasodilation capability, and alleviate vessel stiffness. The present study plays a role in offering a theoretical basis for the development and application of CsV in vascular function improvement, and it also provides a more comprehensive understanding of the pharmacodynamics of CsV.

Effects of particle size and loading rate on the tensile failure of asphalt specimens based on a direct tensile test and particle flow code simulation

  • Q. Wang;D.C. Wang;J.W. Fu;Vahab Sarfarazi;Hadi Haeri;C.L. Guo;L.J. Sun;Mohammad Fatehi Marji
    • Structural Engineering and Mechanics
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    • v.86 no.5
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    • pp.607-619
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    • 2023
  • This study, it was tried to evaluate the asphalt behavior under tensile loading conditions through indirect Brazilian and direct tensile tests, experimentally and numerically. This paper is important from two points of view. The first one, a new test method was developed for the determination of the direct tensile strength of asphalt and its difference was obtained from the indirect test method. The second one, the effects of particle size and loading rate have been cleared on the tensile fracture mechanism. The experimental direct tensile strength of the asphalt specimens was measured in the laboratory using the compression-to-tensile load converting (CTLC) device. Some special types of asphalt specimens were prepared in the form of slabs with a central hole. The CTLC device is then equipped with this specimen and placed in the universal testing machine. Then, the direct tensile strength of asphalt specimens with different sizes of ingredients can be measured at different loading rates in the laboratory. The particle flow code (PFC) was used to numerically simulate the direct tensile strength test of asphalt samples. This numerical modeling technique is based on the versatile discrete element method (DEM). Three different particle diameters were chosen and were tested under three different loading rates. The results show that when the loading rate was 0.016 mm/sec, two tensile cracks were initiated from the left and right of the hole and propagated perpendicular to the loading axis till coalescence to the model boundary. When the loading rate was 0.032 mm/sec, two tensile cracks were initiated from the left and right of the hole and propagated perpendicular to the loading axis. The branching occurs in these cracks. This shows that the crack propagation is under quasi-static conditions. When the loading rate was 0.064 mm/sec, mixed tensile and shear cracks were initiated below the loading walls and branching occurred in these cracks. This shows that the crack propagation is under dynamic conditions. The loading rate increases and the tensile strength increases. Because all defects mobilized under a low loading rate and this led to decreasing the tensile strength. The experimental results for the direct tensile strengths of asphalt specimens of different ingredients were in good accordance with their corresponding results approximated by DEM software.

Effects of stocking density on the homeostasis of uric acid and related liver and kidney functions in ducks

  • Peiyi Lin;Sui Liufu;Jinhui Wang;Zhanpeng Hou;Yu Liang;Haiyue Wang;Bingxin Li;Nan Cao;Wenjun Liu;Yunmao Huang;Yunbo Tian;Danning Xu;Xiujin Li;Xinliang Fu
    • Animal Bioscience
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    • v.37 no.5
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    • pp.952-961
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    • 2024
  • Objective: Stocking density (SD) is an important issue in the poultry industry, which is related to the production performance, intestinal health and immune status. In the present study, the effects of SD on the metabolism and homeostasis of uric acid as well as the related functions of the liver and kidney in ducks were examined. Methods: A total of 360 healthy 56-day-old Shan-ma ducks were randomly divided into the low stocking density (n = 60, density = 5 birds/m2), medium stocking density (n = 120, density = 10 birds/m2) and high stocking density groups (HSD; n = 180, density = 15 birds/m2). Samples were collected in the 3rd, 6th, and 9th weeks of the experiment for analysis. Results: The serum levels of uric acid, lipopolysaccharide and inflammatory cytokines (interleukin-1β [IL-1β], IL-8, and tumor necrosis factor-α [TNF-α]) were increased significantly in the HSD group. Serious histopathological lesions could be seen in both the livers and kidneys in the HSD group in the 9th week. The mRNA expression levels of inflammatory cytokines (IL-8 and TNF-α) and related pathway components (toll-like receptor 4, myeloid differentiation primary response gene 88, and nuclear factor-κB) were increased significantly in both the livers and kidneys in the HSD group. The mRNA expression levels of enzymes (adenosine deaminase, xanthine oxidase, phosphoribosyl pyrophosphate amidotransferase, and phosphoribosyl pyrophosphate synthetase 1) related to the synthesis of uric acid increased significantly in the livers in the HSD group. However, the mRNA expression level of solute carrier family 2 member 9, which plays an important role in the excretion of uric acid by the kidney, was decreased significantly in the kidneys in the HSD group. Conclusion: These results indicated that a higher SD could cause tissue inflammatory lesions in the liver and kidney and subsequently affect the metabolism and homeostasis of uric acid, and is helpful for guiding decisions related to the breeding and production of ducks.

Retrospective Study on the Therapeutic Effects of an Etoposide, Adriamycin, Cisplatin-II (EAPII) versus an Etoposide, Leucovorin, 5-Furorouracil (ELF) Combination Chemotheraphy in Unresectable Gastric Cancer (절제 불가능한 진행성 위암 환자에서 Etoposide, Adriamycin 및 Cisplatin-II (EAP-II)와 Etoposide, Leucovorin 및 5-Furorouracil (ELF) 복합 화학요법의 치료효과에 대한 후향적 연구)

  • Moon Hee-Seok;Kang Yoon-Sae;Kim Yeon-Soo;Park Ki-Oh;Lee Eum-Seok;Sung Jae-Kyu;Lee Byong-Seok;Noh Seung-Moo;Song Kyu-Sang;Cho June-Sick;Shin Kyung-Sook;Jeong Hyun-Yong
    • Journal of Gastric Cancer
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    • v.3 no.3
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    • pp.122-127
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    • 2003
  • Purpose: The incidence rate and the mortality rate of gastric cancer have decreased in developed countries over the last several decades. On the other hand, they remain high in far eastern countries such as Korea, Japan, China and in many developing countries. The cure of patients with gastric carcinomas can be achieved mostly through complete surgical resection, but most gastric cancer patients are in advanced stages when diagnosed and have poor prognoses. therefore, the development of an effective systemic therapy is essential for far advanced gastric cancer patients. Until recently, the most commonly used combination chemotherapy was based on 5-flurouracil or cisplatin, but the results were not satisfactory, so recently etoposide, adriamycin and cisplatin (EAP-II) combination chemotherapy was introduced in patients with advanced gastric cancer. Early studies showed a high response rate and the ability to convert unresectable cases to resectable ones, but later studies couldn't duplicate the result. the purpose of this study was to evaluate the relative efficacy & toxicity of EAP-II chemotherapy and ELF chemotherapy which is based on 5-flurouracil. Materials and Methods: Between July 1992 and July 2002, sixty-five patients with inoperable advanced gastric cancer were enrolled for this study. Thirty-seven patient received EAP-II chemotherapy:etoposide (20 mg/$m^{2}$ IV for $1\∼5 days$), adriamycin (20 mg/$m^{2}$ IV for $1\∼5 days$) and cisplatin (20 mg/$m^{2}$ IV for $1\∼5 days$) and Twenty-eight patients receieved ELF chemotherapy : etoposide (100 mg/$m^{2}$ IV for $1\∼3 days$), leucovorin (20 mg/$m^{2}$ IV for $1\∼5 days$) and 5-FU (500 mg/$m^{2}$ IV for $1\∼5 days$). Each treatment schedule for each group was repeated every four weeks: EAP-II means 3.4 cycles per patient..ELF means 4.1 cycles per patient Results: Total respones rates were $5.4\%$ in the ELF group and $3.6\%$ in the EAP group (P-value>0.05). The median times to progression were 144 days in the ELF group and 92 days in the EAP-II group (P-value<0.05), and themedian overall survival times were 189 days in the ELF group and 139 days in the EAP-II group (P-value>0.05). The difference in the survival curves for the two regimens was not statistically significant. Non-hematologic toxicitis & hematologic toxicitis were more frequently observed for the EAP-II regimen. Anemia: $27.6\%$ in ELF vs $54\%$ in EAP-II; Leukopenia: $8.5\%$ in ELF vs $19\%$ in EAP-II; nausea & vomiting: $45.9\%$ in ELF vs $67.8\%$ in EAP-II. Conclusion: EAP-II regimen is not superior to ELF regimen in the tratment of inoperable advanced gastric cancer (J Korean Gastric Cancer Assoc 2003;3:122-127)

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Postoperative Adjuvant Chemoradiotherapy in Rectal Cancer (직장암의 근치적 수술 후 보조 화학방사선요법)

  • Chang, Sei-Kyung;Kim, Jong-Woo;Oh, Do-Yeun;Chong, So-Young;Shin, Hyun-Soo
    • Radiation Oncology Journal
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    • v.24 no.3
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    • pp.157-163
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    • 2006
  • [ $\underline{Purpose}$ ]: To evaluate the role of postoperative adjuvant chemoradiotherapy in rectal cancer, we retrospectively analyzed the treatment outcome of patients with rectal cancer taken curative surgical resection and postoperative adjuvant chemoradiotherapy. $\underline{Materials\;and\;Methods}$: A total 46 patients with AJCC stage II and III carcinoma of rectum were treated with curative surgical resection and postoperative adjuvant chemoradiotherapy. T3 and T4 stage were 38 and 8 patients, respectively. N0, N1, and N2 stage were 12, 16, 18 patients, respectively. Forty patients received bolus infusions of 5-fluorouracil ($500\;mg/m^2/day$) with leucovorin ($20\;mg/m^2/day$), every 4 weeks interval for 6 cycles. Oral Uracil/Tegafur on a daily basis for $6{\sim}12$ months was given in 6 patients. Radiotherapy with 45 Gy was delivered to the surgical bed and regional pelvic lymph node area, followed by $5.4{\sim}9\;Gy$ boost to the surgical bed. The follow up period ranged from 8 to 75 months with a median 35 months. $\underline{Results}$: Treatment failure occurred in 17 patients (37%). Locoregional failure occurred in 4 patients (8.7%) and distant failure in 16 patients (34.8%). There was no local failure only. Five year actuarial overall survival (OS) was 51.5% and relapse free survival (RFS) was 58.7%. The OS and RFS were 100%, 100% in stage N0 patients, 53.7%, 47.6% in N1 patients, and 0%, 41.2% in N2 patients (p=0.012, p=0.009). The RFS was 55%, 78.5%, and 31.2% in upper, middle, and lower rectal cancer patients, respectively (p=0.006). Multivariate analysis showed that N stage (p=0.012) was significant prognostic factor for OS and that N stage (p=0.001) and location of tumor (p=0.006) were for RFS. Bowel complications requiring surgery occurred in 3 patients. $\underline{Conclusion}$: Postoperative adjuvant chemoradiotherapy was an effective modality for locoregional control of rectal cancer. But further investigations for reducing the distant failure rate are necessary because distant failure rate is still high.

Treatment Results in Anal Cancer : Non-operative Treatment Versus Operative Treatment (항문암의 치료성적 : 비수술적방법과 수술적방법의 결과 비교)

  • Chie Eui Kyu;Ha Sung Whan;Park Jae-Gahb;Bang Yung-Jue;Heo Dae Seog;Kim Noe Kyeong
    • Radiation Oncology Journal
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    • v.20 no.1
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    • pp.62-67
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    • 2002
  • Purpose : This study was undertaken to analyze the efficacy and sphincter preservation rate of platinum based neoadjuvant chemotherapy Plus radiotherapy versus abdominoperineal resection and Postoperative radiotherapy for anal cancer. Materials and Methods : Data of forty-two patients with anal cancer were retrospectively analyzed. Among thirty-eight patients with epidermoid histology, four patients received radiotherapy, and nineteen patients received abdominoperineal resection and adjuvant radiotherapy with or without chemotherapy $(APR+RT{\pm}CT)$, and fifteen patients received neoadjuvant chemotherapy and radiotherapy (CRT). The CRT regimen was composed of three cycles of 5-fluorouracil $(1,000\;mg/m^2\;bolus\;on\;D1\~5)$ and cisplatin $(60\;mg/m^2\;bolus\;on\;D1)$ followed by 50.4 Gy to the tumor bed and regional lymphatics over 5.5 weeks. Both inguinal lymphatics were treated with an identical dose schedule. Residual disease was treated with an additional three cycles of identical adjuvant chemotherapy. An identical dose schedule was used for post-operative radiotherapy. Median follow-up period was eighty-five months. Results : Overall five-year survival rates were $80.3\%$, 88.9 and $79.4\%$ for entire patients, $APR+RT{\pm}CT$ group, and the CRT group, respectively. No significant difference was found between the two groups (p=0.49). Anus preservation rate for the CRT group was $86.7\%$. Age (0=0.0164) and performance status (p=0.0007) were found to be significant prognostic factors by univariate analysis. Age (p=0.0426), performance status (p=0.0008), and inguinal lymph node metastasis (e=0.0093) were statistically significant prognostic factors by multivariate analysis. No case of RTOG grade 3 complication or higher was reported. Conclusion : This and other recent studies have shown that combined chemotherapy plus radiotherapy for anal cancer results in a high rate of anal sphincter preservation as well as local control and survival. Furthermore, neoadjuvant use of chemotherapy with a cisplatin based regimen rather than a concurrent regimen may lead to a decrease in complications.

Postoperative Radiotherapy for Locally Advanced Gastric Cancer (국소적으로 진행된 위암의 수술후 방사선 치료성적)

  • Lee Myung Za;Chun Ha Chung;Kim Insoon;Chung Tejune
    • Radiation Oncology Journal
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    • v.15 no.2
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    • pp.113-119
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    • 1997
  • Purpose : Radical gastrectomy is main treatment of gastric cancer. But the result is not satisfactory with surgery alone. Most of pattern of failure remain locoregional recurrence. To improve 5 year survival postoperative chemotherapy with or without radiotherapy has been used. We analyzed patients with stage III and IV stomach cancer who had radical operation and received postoperative radiation therapy combined with or without chemotherapy retrospectively. Material and Method : From March 1985 to June 1993, 68 patients treated with curative resection and received postoperative adiuvant radiotherapy with 36Gy or more were evaluated. Median age was 60 years(range 28-66 yrs) . Patients were followed from 3 to 133 months with median follow up of 48 months. Thirty seven patients had non signet ring adenocarcinoma, 29 signet ring cell, 2 other cell. Patients with stage IIIA, IIIB, IV disease were 19, 25 and 24 respectively Chemotherapy was given to all patients except two. Results : Five-year overall survival and disease-free survival rate were 36.6% and 33.6%, respectively. Prognostic factor affecting survival were assessed. High ratio of jnvolved/dissected Iymph node, signet ring histology showed Poor Prognosis with statistical significance. Presence of residual tumor after surgery, stageIV. split course of radiation therapy, age, number of involved Iymph node, number of Iymph node dissection and grade of tumor affected survival without statistical significance, Type of chemotherapy did not affect survival. Recurrence was documented in 34 patients. High recurrence was seen in omentum and peritoneum with 23.5%, and remnant stomach, anastomosis site, A-loop and I-loop had also high recurrence with 13.2%. In field locoregional recurrence was 20.7% and total distant metastases were 39.7%. Total intraabdominal failure was 47.1% and extraabdominal failure was 13.2%. Treatment toxicity was considered to be acceptable. 22.1% of patients had grade 3 and only 1 patient had grade 4 leukopenia. Six Patients(8.8%) had weigh loss more than 10%. Conclusion : Treatment toxicity was acceptable with combined treatment with chemotherapy and radiotherapy. Locoregional recurrence was relatively low compared to distant failure with addition of irradiation. Peritoneal and omental seeding was high Five-rear surival was increased with combined modality. Radiation may eradicate minimal residual disease and improve survival, To evaluate role of radiation Prospective randomized study employing chemotherapy alone and chemotherapy plus radiation is necessary. Futhermore to reduce intraabdominal failure, role of intraabdominal chemotherapy in addition to combined chemotherapy plus radiation has to be explored.

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