| Objective:To screen the optimized fractionated irradiation schedules by comparing the dose-response relationship of different fractionated irradiation schedules with total dose of40Gy to60Gy in subclinical tumor of breast cancer.To provide the experimental basis in clinical to develop radiotherapy after breast-conserving surgery.Materials and Methods:Balb/c-nude mice bearing human breast cancer xenograft were assigned randomly into control group, fractionated irradiation schedules group. The fractionated schedules were200cGy×5/w,300cGy×5/w,160cGy×2×5/w and400cGyx3/w with total dose40Gy and60Gy, respectively. Measurement indexes were tumor-forming rate, short-term tumor control rate, long-term tumor control rate, Tumor recurrence time and maximum diameter of the bottom of solid. The observation lasted24weeks.Results:With the total dose of40Gy, the tumor formation rate of control group was25%(number of inoculated cells is1.5×105).At the end of treatment, the short-term tumor control rate of all treatment groups was100%(tumor formation rate0/4). At the end of observation, the long-term tumor control rate of all treatment groups reduced to0(tumor formation rate4/4) except160cGy×2×5/w fractionated schedule group.The recurrence time of200cGyx5/w fractionated schedule group was63d. The maximum diameter of the bottom of solid of300cGy×5/w and400cGy×3/w fractionated schedule groups were0.65cm and0.7cm, respectively, which indicated that the growth of tumor recurrence of hypofraction groups was slower than conventional schedule and control groups.The results suggested that160cGy×2×5/w was the optimized fractionated schedule,300cGy×5/w and400cGyx3/w took second place,200cGyx5/w was the most unsatisfactory for subclincal breast tumor with low density.With the total dose of60Gy, the tumor formation rate of control group was100%(number of inoculated cells is3.1×105). The short-term and long-term tumor control rate of200cGy×5/w fractionated schedule group was0(tumor formation rate8/8) and0(tumor formation rate8/8),respectively; The short-term and long-term tumor control rate of160cGyx2x5/w fractionated schedule group was50%(tumor formation rate4/8) and25%(tumor formation rate6/8),respectively; The short-term and long-term tumor control rate of400cGyx3/w fractionated schedule group was28.6%(tumor formation rate5/7) and28.6%(tumor formation rate5/7),respectively; The short-term and long-term tumor control rate of300cGyx5/w fractionated schedule group was50%(tumor formation rate4/8) and50%(tumor formation rate4/8),respectively.The result above showed:With the60Gy total dose and100%tumor formation rate of control group,the curative effect of all groups had improved by varying degrees except conventional radiotherapy group. Short-term curative effect of300cGyx5/w fractionated schedule group and160cGyx2x5/w fractionated schedule group was the best with the50%tumor control rate. Long-term curative effect of300cGyx5/w fractionated schedule group was the best with the50%tumor control rate,which suggested that300cGy×5/w is the optimized fractionated schedule.Conclusion:With the different number of inoculated cells,different total dose for tumor control was required. In term of long-term control rate,300cGyx5/w is the best fractionated schedule and200cGyx5/w is the worst fractionated schedule under the100%tumor formation rate. Propose:To measure the radiation response characteristics of MCF-7cell line by evaluate the radiobiology parameters of MCF-7cells in vitro.To provide experimental basis at the cellular level for investigating the mechanisms of different dose-response relationship among the schedules.Methods and materials:Clonogenic assay was used to evaluate the parameters of cell survival curve of MCF-7cell line (from the radiobiology laboratory of Cancer Hospital (Institute), Peking Union Medical College, Chinese Academy of Medical Sciences)(The irradiation dose points were0,1,2,4,6,8,10Gy). Cell survival curve was fitted with the linear-quadratic and multi-target/singel-hit model;living cells count assay was used to drawing MCF-7cell growth curve to calculate the doubling time(number of inoculated cells is1.5×105/bottle; the measure time points were0,1,2,3,4,5,6d;3parallel samples were operated at each time point);comet assay was used to determine half-time of repairment to irradiation with5Gy single dose,T1/2(time points were0,15,30,45,60,120min)Result:When fitted with L-Q model,a was0.307Gy-1and β was0.028Gy-2.When fitted with multi-target/single-hit model,Do was1.588Gy,Dq was1.186Gy and SF2was0.505,respectively. The cell doubling time of MCF-7cell was27.6h.The T1/2was17.6min.Conclusion:SF2of MCF-7was0.505. MCF-7cell line was moderately radiosensitive. Propose:To determine the characteristics of the biological effects of different pathological types of subclinical tumor and optimize the fraction schedule by comparing the difference of dose-response relationship of subclinical tumor of nude mice xenograft between different Pathological type(the current and prior periods).Methods and materials:Experimental materials, including materials of breast cancer during current period and malignant glioblastoma during prior period/was used to analysis the comparison of the radiobiology parameters and dose-response relationship with the same condition and endpoint.Result:In term of the total dose of40Gy,400cGy×3/w fraction schedule received same short-term control rate(100%)in the different subclinical tumor(breast caner and malignant glioblastoma).The other schedules showed a better short-term control rate in subclinical tumor of breast caner than malignant glioblastoma. All fraction schedules received certain long-term control rate except conventional fraction schedule(the long-term control rate of160cGy×2/d×5/w group was0, the growth of400cGy×3/w and300cGy×5/w groups was delayed) in subclinical tumor of breast caner and no long-term control rate in subclinical tumor of malignant glioblastoma. The result suggested that the number of inoculated cells was the key factors affect the short and long term control rate. In term of the total dose of60Gy, all fraction schedules received better short-term control rate except conventional fraction schedule in subclinical tumor of breast caner than malignant glioblastoma.160cGy×2/d×5/w group received same long-term control rate in subclinical tumor of breast caner with malignant glioblastoma.Hypofraction schedules(400cGy×3/w and300cGy×5/w groups) received better long-term control rate in subclinical tumor of breast caner than malignant glioblastoma(long-term control rate wasO-12.5%).In addition,300cGy×5/w produced a best long-term curative effect.The result suggested that intrinsic sensitivity of cell is an important factor to fraction sensitivity of tumor.The radiobiology parameter of MCF-7and BT325were as follows:α=0.307Gy-1,β=0.028Gy-2,α/β=10.96Gy and a=0.360Gy-1, β=0.057Gy-2, α/β=6.32Gy,respectively. Conclusion:The total dose of40Gy could receive certain control rate only when the tumor formation rate is low. As tumor rate is high, it would be difficult to achieve the desired control. Hypofractionated irradiation could produce a better control rate for subclinical tumor of breast, but in contrast it produce a poor effect for subclinical tumor of malignant glioma with the total dose of60Gy and100%tumor formation rate. |
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