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OBJECTIVE: To investigate the protective effect of cimetidine (CMTD) on rats irradiated with 60Co γ-rays at low dose rate.METHODS: Sixty male SD rats were randomly divided into normal group, model group, positive drug group, CMTD groups.The mice were irradiated with 60Co γ rays and an absorbed dose was 0.3 Gy, and the dose rate was 3.228 mGy•h-1. Twenty-four hours after irradiation, white blood cells, bone marrow DNA content, bone marrow polynuclear erythrocyte micronucleus rate (fMNPCE), sperm motility and sex hormones were detected. RESULTS When the cumulative absorbed dose was 0.3 Gy, the peripheral blood cells and bone marrow DNA content decreased significantly, fMNPCE increased significantly, and the sperm motility, follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels reduced while the level of estradiol increased. Cimetidine not only could effectively increase the number of white blood cells, bone marrow DNA content, the level of FSH and LH but also reduce fMNPCE and the level of estradiol. CONCLUSION: CMTD could reduce the DNA damage which caused by 0.3 Gy cumulative irradiation, regulate sex hormone disturbance, and effectively improve hematopoietic function and reproductive function of irradiated rats.All RESULTS: shows that CMTD might be a good radioprotector.
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Objective To investigate the protective effects of cimetidine on rats with low dose rate (LDR) 60Co γ-ray cumulative irradiation. Methods Sixty male SD rats (6-8 weeks old) were randomized into 6 groups (10 each): normal control group, model group, positive control group (89.0 mg/kg lentinan), low-dose cimetidine group (23.3 mg/kg cimetidine), medium-dose cimetidine group (70.0 mg/kg cimetidine), and high-dose cimetidine group (210.0 mg/kg cimetidine). Except for rats in normal control group, the rest rats were irradiated with 60Coγ-ray to a cumulative dose of 0.5 Gy with a dose rate of 3.228 mGy/ h. Twenty-four hours after the last irradiation, peripheral blood cells, bone marrow DNA content, frequencies of micronucleated polychromatic erythrocytes (fMNPCE), bone marrow nucleated cells, sperm count, testis HE, sex hormones, superoxide dismutase (SOD), glutathione (GPx), catalase (CAT) activity, and malondialdehyde (MDA) content were measured. Results Compared with normal control group, in model group, WBC, lymphocyte and granulocyte content, bone marrow DNA content and the number of nucleated cells significantly decreased (P<0.05), but fMNPCE increased significantly (P<0.01). In addition, sperm count, testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels significantly reduced (P<0.05 or P<0.01), estradiol (E2) levels significantly increased (P<0.05), SOD, GPx and CAT activities significantly decreased (P<0.05 or P<0.01), and MDA levels significantly increased (P<0.01). Rat models were established successfully. Compared with model group, in positive control group, the bone marrow DNA content and T content significantly increased (P<0.05), antioxidant enzyme activity of SOD, GPx and CAT significantly increased (P<0.05 or P<0.01), while the contents of fMNPCE, MDA and E2 significantly reduced (P<0.05 or P<0.01). In the cimetidine-treated groups, the blood lymphocyte number and bone marrow DNA content significantly increased (P<0.01), the activity of antioxidant enzymes SOD, CAT, GPx, T, FSH and LH increased, and the content of fMNPCE, E2 and MDA decreased, the damage of testicular tissue structure decreased (P<0.05), and the number of sperm increased, but there has no statistic significance. Conclusion Cimetidine, as a potential radiation protection drugs, could effectively improve the rat injury with low-dose-rate 60Coγ-ray cumulative irradiation.
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OBJECTIVE： To study the effects of cimetidine on low dose rate irradiation-induced liver cell apoptosis in Beagle dogs. METHODS： Healthy male Beagle dogs were randomly divided into normal control group， model control group， positive drug group （lentinan， 21.33 mg/kg） and cimetidine low-dose， medium-dose and high-dose groups （5.33， 10.67， 21.33 mg/kg）， with 4 Beagle dogs each. Except for normal control group， other groups were given 60Co-γ accumulative irradiation （dosage rate： 0.040 8 mGy/min） for 23 d； the medication groups were given relevant medicine orally before irradiation， once a day. Twenty-four hours after stopping irradiation， TUNEL method was used to detect the apoptosis of liver cells in Beagle dogs. The percentage of apoptotic cells was calculated. The expression level of apoptosis-related proteins （Bax， Bcl-2， Caspase-3， p53） in liver tissue was detected by immunohistochemistry. RESULTS： Compared with normal control group， apoptotic cells and Bax， Caspase-3， p53 positive cells were increased significantly in liver tissue of Beagle dogs in model control group； the percentage of apoptotic cells， protein expression levels of Bax， Caspase-3 and p53 were increased significantly； Bcl-2 positive cells were decreased significantly， and its protein expression level was decreased significantly （P＜0.05 or P＜0.01）. Compared with model control group， above positive cells of liver tissue in Beagle dogs were changed to different extents in medication groups； the percentage of apoptotic cells and protein expression levels of p53 in medication groups， protein expression levels of Bax in positive drug group， cimetidine low-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were decreased significantly； protein expression levels of Bcl-2 were increased significantly in cimetidine groups. The percentage of apoptotic cells in cimetidine medium-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were all lower than positive control group. Protein expression level of p53 in cimetidine low-dose group was significantly higher than positive drug group （P＜0.05 or P＜0.01）. CONCLUSIONS： Cimetidine can inhibit the low dose rate irradiation-induced apoptosis of liver cells in Beagle dogs， and certainly protect liver cells against irradiation. The mechanism of it may be associated with up-regulating the protein expression of Bcl-2 and down-regulating the protein expression of Bax， Caspase-3 and p53 in liver cells.
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Objective To investigate the biological effects of 125I seeds and 60Co γ-rays on the non-small cell lung cancer cells A549 and the normal bronchial epithelium cells BEAS-2B.Methods A549 and BEAS-2B cells were irradiated with 125I seeds and 60Co γ-rays.The survival fraction was detected by colony formation assay.The cell cycle and cell apoptotic ratio were detected by flow cytometry.The expression of cell apoptotic related proteins was examined by western blot.Results After irradiation with different doses,the survival of A549 cells irradiated with 125I seeds was lower than that irradiated with γ-rays (t =6.06,9.42,4.90,P ＜0.05).After irradiation with 4 Gy of 125I seeds and 60Co γ-rays,the G1 phase percentages of A549 cells were 70.67％ ± 1.49％ and 59.59％ ± 0.71％ (t =10.77,P ＜ 0.05),and the apoptotic ratios of A549 cells were 18.09％ ±0.73％ and 9.81％ ±0.16％ (t =19.40,P＜ 0.05),respectively.125I seeds irradiation remarkably up-regulated the expressions of Bax and cleaved Caspase-3 proteins,down-regulated the expression of Bcl-2 proteins compared with 60Co γ-rays irradiation on A549 cells.However,the apoptotic ratio and the expressions of apoptosis-related proteins in BEAS-2B cells had little difference between two types of radiation.Conclusions The anti-proliferative effect of 125I seeds irradiation on A549 cell is more remarkably than that of 60Co γ-rays.The imbalance of Bcl-2/Bax ratio and the eventually activation of Caspase-3 proteins may play an important role in the anti-proliferative effect induced by the continuous low dose radiation of 125I-seeds.
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Objective To investigate the biological effect of 125I seeds continuous low dose rate (CLDR) irradiation and 60Co γ-ray high dose rate (HDR) irradiation on H1299 cell line of non-small cell lung cancer (NSCLC). Methods H1299 cells in exponential growth were separately irradiated with 125I seeds CLDR irradiation and 60Co γ-ray HDR irradiation. The cell survival fraction was inspected with clone formation experiment, the cell cycle and apoptosis rate was determined with flow cytometry, and the expressions of Bax and Bcl-2 proteins were measured by Western blot method. Results With the irradiation dose increasing, the anti-proliferation effect of 125I seeds CLDR irradiation on H1299 cells became more remarkable than that of 60Coγ-ray HDR irradiation. When the irradiation dose reached 4 Gy, the G2/M phase percentage and the apoptotic ratio of H1299 cells in 125I seeds CLDR irradiation group were 21.77±0.31%and 13.79±0.50% respectively, which were only 18.85±0.99% and 8.79±0.22% respectively in 60Co γ-ray HDR irradiation group, the difference was statistically significant (P<0.05). In 125I seeds CLDR irradiation group the expression of Bax protein was remarkably up-regulated, while the expression of Bcl-2 protein was down-regulated. Conclusion The inhibition effect of 125I seeds CLDR internal irradiation on the proliferation of H1299 cells is more obvious than that of 60Co γ-ray HDR irradiation. In 125I seeds CLDR irradiation group, the imbalance of Bcl-2/Bax ratio may play an important role in achieving the antitumor effect.
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Objective To determine the biological effectiveness of 125I radioactive seeds with continuous low dose rate radiation on the human esophageal cancer cell line KYSE150 in vitro and explore the underlying cellular mechanisms.Methods The cells were divided into three cell groups:control group,single dose radiation group (SDR) and 125I radioactive seeds with continuous low dose rate radiation group (125 I-CLDR).The KYSE150 cells were exposed to radiation of X-ray at a high dose rate of 1.052 Gy/min or 125I radioactive seeds at a low dose rate of 2.77 cGy/h.The responses of KYSE150 cells to two modes of irradiation were evaluated by the colony-forming assay,cell apoptosis as well as cell cycle analysis.Furthermore,the expression levels of γ-H2AX and Bax were detected by Western blot.Results KYSE150 cells were more radiosensitive to 125I-CLDR than SDR.The relative biological effectiveness (RBE) for 125I-CLDR related to SDR was 1.56.Compared with SDR,125I-CLDR yielded more proportions of the early and late apoptosis rate (t =4.07,11.08,P ＜0.05) as well as cells at G2/M phase (t =11.25,P ＜0.05).Moreover,γ-H2AX and Bax expression levels in 125I-CLDR significantly increased compared with SDR.Conclusions Compared with the high dose rate X-ray radiation,the continuous low dose rate radiation of 125I radioactive seeds had stronger inhibition effect on KYSE150 esophageal cancer cells by impairing clonogenic capacity,inducing apoptosis and G2/M cell cycle arrest,and increasing radiosensitivity.
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Objective To investigate the effect of cetuximab (C225) on the radiosensitivity of colorectal cancer cells CL187 and underlying mechanism.Methods Cell survival was detected by colony forming assay.The levels of apoptosis and cell cycle distribution were determined by flow cytometer.The mitotic ratio was measured by Wright' s-Giemsa mixed coloring method.The protein levels of Bax and Bcl2 were detected by Western blot.Results The sensitizing enhancement ratio of C225 was approximately 1.4.C225 treatment and 125I seed radiation induced G1 cell cycle arrest individually.C225 increased the radiation-induced apoptosis (t =6.6,P ＜ 0.05) and cellular Bax/Bcl-2 ratio (t =9.4,P ＜ 0.05),but did not increase radiation-induced G1 arrest.In addition,there was no difference in mitotic index among different groups.Conclusions C225 sensitizes CL187 to 125I seed irradiation,which might be related with increase of radiation-induced apoptosis.
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We previously determined that AKR/J mice housed in a low-dose-rate (LDR) (137Cs, 0.7 mGy/h, 2.1 Gy) gamma-irradiation facility developed less spontaneous thymic lymphoma and survived longer than those receiving sham or high-dose-rate (HDR) (137Cs, 0.8 Gy/min, 4.5 Gy) radiation. Interestingly, histopathological analysis showed a mild lymphomagenesis in the thymus of LDR-irradiated mice. Therefore, in this study, we investigated whether LDR irradiation could trigger the expression of thymic genes involved in the DNA repair process of AKR/J mice. The enrichment analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways showed immune response, nucleosome organization, and the peroxisome proliferator-activated receptors signaling pathway in LDR-irradiated mice. Our microarray analysis and quantitative polymerase chain reaction data demonstrated that mRNA levels of Lig4 and RRM2 were specifically elevated in AKR/J mice at 130 days after the start of LDR irradiation. Furthermore, transcriptional levels of H2AX and ATM, proteins known to recruit DNA repair factors, were also shown to be upregulated. These data suggest that LDR irradiation could trigger specific induction of DNA repair-associated genes in an attempt to repair damaged DNA during tumor progression, which in turn contributed to the decreased incidence of lymphoma and increased survival. Overall, we identified specific DNA repair genes in LDR-irradiated AKR/J mice.
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Animals , Female , Mice , DNA Repair/radiation effects , Dose-Response Relationship, Radiation , Gene Expression Regulation/radiation effects , Gene Regulatory Networks/radiation effects , Lymphoma/etiology , Mice, Inbred AKR , Oligonucleotide Array Sequence Analysis , Radiation, Ionizing , Reverse Transcriptase Polymerase Chain Reaction , Thymus Gland/radiation effects , Thymus Neoplasms/etiologyABSTRACT
Purpose: We are reporting results of a randomized study with the aim to compare the results of low-dose rate (LDR) versus high-dose rate (HDR) brachytherapy in locally advanced carcinoma cervix patients. Material and methods: Sixty cases of carcinoma of uterine cervix in Stage IIB-IIIB (FIGO) were included from a period of January 2002 to March 2003 and were randomized into HDR brachytherapy (6 Gy/fraction for 4 sessions) or LDR brachytherapy (27 Gy/single session) arm after completion of external beam radiotherapy (50 Gy/25#/5 weeks). Results: In HDR arm, 16/30 (53.33%) patients experienced complete response. In LDR arm, complete response was experienced by 13/30 (43.33%) of patients. Locoregional control in HDR group was 54.54%, 57.14% and 71.42% at 6, 9 and 12 months, respectively. Locoregional control in LDR group at 6, 9 and 12 months was 45%, 63.63% and 42.85%, respectively. Conclusion: The results of our study indicate that LDR and HDR groups are similar in locoregional control in the management of carcinoma uterine cervix. HDR brachytherapy can safely substitute LDR brachytherapy applications.
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Objective To investigate the radiosensitivity enhancement on CL187 cancer cell lines after continous low-dose-rate irradiation of 125I seeds blocked by EGFR antibody.Methods There were control group,the irradiation or plus EGFR antibody group,with 3 samples in each group.Clongenic assay was used to detect the survival of cells.The cell cycle distribution and apoptosis were analyzed by flow cytometry.Results The survival fraction of CL187 cells were lower after blocked by EGFR antibody at the same dose irradiation.The SER were 1.34,1.59 and 1.98 when the antibody concentration were 2,5 and 10 nmol/L,respectively.The irradiation plus antibody led to more apoptosis(39.86%±4.38%)of CL187 cells than the irradiation (21.57%±2.97%)plused antibody(12.49%±1.59%)worked alone.Comparison of the low dose rate irradiation related to G2/M cell cycle arrest(46.41%±4.48%),More G1 cell cycle arrest(84.51%±3.42%)walked together along with the EGFR antibody.Conclusions EGFR antibody could enhance the cell radiosensitivity after continuous low-dose-rate.irradiation.The cell cycle redistribution and apoptosis might be the main mechanism of the radiosensitivity enhancement.
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PURPOSE: The incidence of adenocarcinoma of the uterine cervix is low. Traditionally, Low Dose R ate (LDR) brachytherapy has been used as a standard modality in the treatment for patients with carcinoma of the uterine cervix. The PURPOSE of this report is to evaluate the effects of the High dose rate (HL)R) brachytherapy in the patients with adenocarcinoma of the uterine cervix compared with the LDR. MATERIALS AND METHODS: From January 1971 to December 1992, 106 patients of adenocarcinoma of uterine cervix were treated with radiation therapy in the Department of Radiation Oncology, Yonsei University with curative intent. LDR brachytherapy was carried out on 35 patients and 7 1 patients w -re treated with HDR brachytherapy. In LDR Group, 8 patients were in stage I, 18 in stage II and 9 in st;ge III. External radiation therapy was delivered with 10 MV X-ray, daily 2 Gy fractionation, total dose 40-46 Gy (median 43 Gy), And LDR Radium intracavitary irradiation was performed with Henschke applicator, 22-59 Gy to point A (median 43 Gy). In HDR Group, there were 16 patients in stage I, 38 in stag 0.05). There was no statistical difference in terms of the 5-year overall survival rate between HDR Group and LDR Group in a denocarcinoma of the uterine cervix. There was 1 1% of late complication rates in LDR Group and 27% in HDR Group. There were no prognostic factors compared HDR with LDR group. The incidence of the late complication rate in HDR Group stage II, III was higher than that in LDR Group ( 16.7% vs. 31.6% in stage II, 11. 1% vs. 35.3% in stage III, p>0.05). Although the incidence of radiation induced late complication rate was higher in HDR Group stage II and III patients than that in the LDR Group, statistical significance was not detected and within acceptable level. CONCLUSION: There was no difference in terms of 5-year survival rate and failure pattern in the patients with adenocarcinoma of the uterine cervix treated with HDR and LDR brachytherapy. Even late complication rates were higher in the HDR group it was an acceptable range. This retrospective study suggests that HDR brachytherapy seems to replace the LDR brachytherapy in the adenocarcinoma of the uterine cervix. However, further studies will be required to refine the dose rate effects.
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Female , Humans , Adenocarcinoma , Brachytherapy , Cervix Uteri , Incidence , Radiation Oncology , Radium , Retrospective Studies , Survival RateABSTRACT
Brachytherapy has been proved to be an effective method for the purpose of increasing radiation dose to the tumor and reducing the dose to the surrounding normal tissue. In head and neck cancer, the rationale of brachytherapy is as follows; Firstly, early small lesion is radiocurative and the major cause of failure is local recurrene. Seondly, it can diminish evidently the dose to the normal tissue especially masseteric muscle and salivary gland. Thirdly, the anatomy of head and neck is suitable to various technique of brachytherapy. On background of accumulated experience of LDR iridium brachytherapy of head and neck cancer for the last 15 years, the author reviewed the history of radioisotope therapy, the characteristics of radionuclides,and some important things in the method, clinical technique and treatment planning. The author analyzed the clinical result of 185 cases of head and neck cancer treated in the Korea Cancer Center Hospital. Finally the fu ture prospect of brachytherapy of head and neck cancer is discussed.
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Brachytherapy , Head and Neck Neoplasms , Head , Iridium , Korea , Neck , Radiotherapy , Salivary GlandsABSTRACT
PURPOSE: This is a retrospective study to compare the palliation rates, survival rates and complications of low dose rate and high dose rate endobronchial brachytherapy in the management of malignant airway obstruction. METHODS AND MATERIALS: Forty three consecutive patients with malignant airway compromise from primary or metastatic lung tumors were treated with low dose rate(LDR) endobronchial Iridium-192 insertion (21 patients) between October 1988 and June 1992, and high dose rate(HDR) endobronchial brachytherapy(22 patients) between August 1992 and April 1994 with palliative aim. Flexible fiberoptic bronchoscopy under fluoroscopic control was utilized in all 91 provedures. Twenty seven LDR provedures delivereda dose of 5-7.5 Gy to a 1.0 cm radius respectively. RESULTS: Subjective and objective responses to treatments were evaluated on follow-up examinations by clinical examination, chest x-rays and CT scan of the chest had been demonstrated on 8 LDR patients and 10 HDR patients. CONCLUSION: The technique of LDR and HDR endobronchial brachytherapy is simple and well tolerated procedure with minimal morbidity. It provides excellent palliation by keeping airway patent in these short life-spanned patients.