| Chapter 1 Clinical studies of intracystic chemotherapy with interferon-a on craniopharyngiomasObjective To investigate the efficacy and safety of intracystic interferon(INFa)by Ommaya reservoir in the treatment of cystic craniopharyngioma and to provide new method for clinical treatment of cystic craniopharyngioma.Methods In accordance with the experimental inclusion criteria and exclusion criteria,116 patients participated in the clinical trial(Female/Male:65:51)from January 2014 to December 2017 in the People's Liberation Army Navy General Hospital.The average age of the patient was 42.32 ± 21.09 years.92 patients(79.31%,the experimental group)received intracystic interferon(INFa)by Ommaya reservoir in treatment of craniopharyngioma,and 24 patients(20.68%,the control group)refused to undergo this treatment and only accepted cystic fluid suction.All patients underwent insertion of Ommaya reservoir.After the leakage tests was performed in the experimental group,3,000,000 units of INF-a 2b were injected to tumor cysts,three times in a week.Every 12 times was a course of treatment.Neurological function,visual field,pituitary secretion,hypothalamic function and treatment side effects were regards as clinical indices.The patients underwent neuroimaging to analyze the tumor control ratio and progression-free survivalResults Follow-up duration is 3-29 months(average 14 months).The patients'progression-free survival(PFS)was 16.4(95%CI:15.8-17.8)months in the entire group.The PFS was 17.2(95%CI:15.8-19.6)months in the experimental group.The PFS was only 8.7(95%CI:6.7-10.7)months in the control group.There was a statistically significant difference between the two groups(p = 0.02).In the experimental group,the PFS was17.1(95%CI:15.1-19.2)months in the ACP group and 17.4(95%CI:15.3-19.5)months in the PCP group.There were no statistical differences between these groups(p= 0.0745).The PFS was 20.9(95%CI:17.9-23.9)months for patients under 20-years-old and 16.5(95%CI:15.0-18.0)months for patients older than 20-years-old in the experimental group.There were also no statistical differences between these groups(p= 0.0961).The N-CCSS?V-CCSS?P-CCSS?H-CCSS and E-CCSS were 0.878?2.19±0.794?1.23±0.597 and 2.01±0.457 respectively in the experimental group.After the intracystic interferon(INFa)by Ommaya reservoir,the N-CCSS?V-CCSS?P-CCSS?H-CCSS and E-CCSS were 1.58 ±0.64?2.41 ±0.72?2.64 ± 0.899?1.23 ± 0.597 and 1.77 ± 0.786.The craniopharyngioma control rate was of 75%in the treatment of cystic craniopharyngioma.The most common side effects was fever(n=80,86%),loss of appetite(n=83,90%)and weary(n=79,85%).Conclusion The results of this study indicate that the intracystic interferon(INFa)by Ommaya reservoir in the treatment of cystic craniopharyngioma can obtain ideal tumor control rates and acceptable incidence and incidence of side effects.Therefore,it can be used as an effective and safe treatment option for the craniopharyngioma patients.Meanwhile,the long-term efficacy still needs further study.Chapter 2 The vitro culture of craniopharyngioma tumor cells and the inhibition of interferon on the craniopharyngioma cellsObjective It was to explore the establishment of experimental models of craniopharyngiomas in vitro,and further verify the drug sensitivity of different concentrations of interferon on craniopharyngioma cells by CCK-8 test.Methods In this experiment,4 primary craniopharyngioma cells were cultured by trypsinization method.One craniopharyngioma cell was divided into three groups and each group was given the 2ml 10%serum cell culture medium containing 100U/ml,200U/ml and 300U/ml interferon,the control group was added 2ml 10%fetal bovine serum cell culture medium.The apoptosis of tumor cells at different times were observed.Results After 72 hours of the addition of interferon,the proliferation activity of craniopharyngioma cells began to diminish in all group.However,the proliferation activity of tumor cells in IFN-alpha group was lower than that in the control group,and the higher the drug concentration,the weaker the proliferation activity of tumor cells.Conclusion The interferon can inhibit the proliferation of craniopharyngioma cells and control the progress of tumor.The higher the concentration of interferon in culture fluid,the weaker the proliferation activity of craniopharyngiomas.Chapter3:Effect of interferon on Alpha Defensin in the craniopharyngioma cysticObjective It was to explore the influence of interferon on the inflammatory reaction process between craniopharyngioma and brain and to provide clinical basis for intracystic interferon in the treatment of craniopharyngioma.Methods Elisa method was used to determine the concentration of a-defensin of the cystic fluid in 20 cases undergoing intracystic interferon and 10 cases which didn't undergo this treatment before operation and in the first,the second,and the third month after operation.Result Before injection of interferon,the total concentration of a-defensin in cystic fluid was 204.94±10.69ug/L in the experimental group and a-defensinl,a-defensin2,and ?-defensin3 were 112.87±12.52ug/L?62.43±10.49ug/L and 29.45± 10.89ug/L in this group.In the experimental group,the total concentration of a-defensin was 29.75±3.75ug/L after the first month,and ?-defensin2,and a-defensin3 were 14.56±2.71ug/L?11.65±3.92ug/L and 3.54± 1.76ug/L.After the second month,the total concentration of a-defensin after interferon was 13.73±4.53ug/L in the experimental group,and ?-defensinl,a-defensin2,and?-defensin3 respectively were8.34±4.22ug/L?3.30±0.806ug/L and 2.07±0.577ug/L in this group.In the experimental group,the total concentration of a-defensin was 13.57±4.07ug/L after the third month,and ?-defensinl,?-defensin2,and ?-defensin3 respectively were 8.61 ±4.04ug/L?3.06±1.09ug/L and 2.19±0.588ug/L.After the first injection of interferon the cyst a-defensin content decreased significantly with statistical differences compared with that before operation(p=0.0051).Preoperatively,the total concentration of ?-defensin in cystic fluid was 210.04±10.81ug/L in the contal group and ?-defensinl,a-defensin2,and ?-defensin3 were 126.42 ±6.62 ug/L?63.72±6.20 ug/L?9.85 ±4.67 ug/L in this group.In the contral group,the total concentration of ?-defensin was 105.99±15.21ug/L after the first month,and a-defensin2;and ?-defensin3 were58.34±9.42ug/L?29.97± 14.92ug/L and 17.66±5.34ug/L.After the second month,the total concentration of a-defensin after interferon was 88.09±11.33ug/L in the contral group,and ?-defensinl,?-defensin2,and a-defensin3 respectively wer49.40±8.64 ug/L?24.77±10.35 ug/L and 13.91 ±5.25 ug/L in this group.In the contal group,the total concentration of ?-defensin was 90.56±11.03ug/Lafter the third month,and ?-defensinl,?-defensin2,and ?-defensin3 respectively were 51.60±7.56ug/L?26.30±8.86ug/L and 12.74±5.27ug/L.Compared with the experimental group,the statistical results showed that the concentration of a-defensins after intracystic interferon was significantly lower than that of patients treated without interferon.Conclusion Interferon therapy can obviously inhibit the secretion of a-defensins from tumor cells.This directly proves that interferon therapy can reduce the inflammatory reaction between the tumor and the surrounding brain tissue and reduce the invasion of the tumor to the surrounding structures.On the other hand,it indirectly proves the interferon can inhibition or kill the craniopharyngioma tumor cells.But the specific mechanism of action remains to be further studied. |
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