Local immunotherapy with interleukin - 2 delivered from biodegradable polymer microspheres combined with interstitial chemotherapy: a novel treatment for experimental malignant glioma.

OBJECTIVE:Local delivery of carmustine(BCNU)from biodegradablepolymers prolongs survival against experi-mental brain tumors.Moreover,paracrine administration of interleukin-2(IL-2)has been shown to elicit apotent antitumor immune response and to improve survival in animal brain tumor models.We report the use of anovel polymeric microsphere delivery vehicle to release IL-2.We demonstrate both in vitro release of cytokinefrom the microspheres and histological evidence of the inflammatory response elicited by IL-2 released from themicrospheres in the rat brain.Thees microspheres are used to deliver IL-2,and biodegradable polymer wafers

In vitro Study of Interstitial Combination Chemotherapy in the Treatment of Glioma

Objective： To investigate the inhibitory effects of combination chemotherapy of Carboplatin （CBP）, Teniposide （Vm-26）, Methasquin （MTX）, and Nimodipine （NIM） on glioma, and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods： MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells, and to compare the sen- sitivity of glioma cells to administration of CBP, Vm-26, MTX, and NIM with that of the administration of CBP＋NIM, Vm-26＋NIM, MTX＋NIM, CBP＋Vm-26＋MTX, or CBP＋Vm-26＋MTX＋NIM, respectively. Results： The inhibition rate of CBP＋Vm-26＋MTX＋NIM combination administration against glioma cells was 96.64%, higher than that of CBP＋NIM （69.03%）, Vm-26＋NIM （71.53%）, MTX＋NIM （52.75%）, CBP＋Vm-26＋MTX （78.59%） （P〈0.01）, and the dosage of CBP, Vm-26, and MTX was declined to 1/10- 1/100 that of respective use of CBP, Vm-26, and MTX. Conclusion： The curative effect of combination administration of CBP, Vm-26, MTX, and NIM was much better than that of respective administration, suggesting a higher inhibition rate and a lower dosage use.

BCNU/PLGA microspheres:a promising strategy for the treatment of gliomas in mice

Objective：To investigate the effects of BCNU/PLGA microspheres on tumor growth,apoptosis and chemotherapy resistance in a C57BL/6 mice orthotopic brain glioma model using GL261 cell line.Methods：BCNU/PLGA sustained-release microspheres were prepared by the water-in-oil-in-water emulsion technique.GL261 cells were intracranially injected into C57BL/6 mouse by using the stereotactic technology.A total of 60 tumor-bearing mice were randomly and equally divided into three groups：untreated control,PLGA treated,BCNU/PLGA treated.Magnetic resonance imaging （MRI） was taken to evaluate tumor volume.BCNU/PLGA sustained-release wafers were implanted in the treatment group two weeks after inoculation.Survival time and quality were observed.Specimens were harvested,and immunohistochemical staining was used to check the expression of Bax,Bcl-2,and O6-methylguanine-DNA methyltransferase （MGMT）.Statistical methods was used for analysis of relevant data.Results：BCNU/PLGA sustained-release wafers were fabricated and implanted successfully.There is statistical difference of survival time between the BCNU/PLGA treated group and control groups （P＜0.05）.MRIscan showed inhibitory effect of BCNU/PLGA on tumor growth.Compared to the group A and B,BCNU/PLGA decreased the expression of apoptosis related gene Bcl-2 （P＜0.05）,but did not elevate the expression level of Bax （P＞0.05）,with the ratio of Bax/Bcl-2 increased.For MGMT protein expression,no statistically significant change was found in treated group （P＞0.05）.Conclusions：Local implantation of BCNU/PLGA microspheres improved the survival quality and time of GL261 glioma-bearing mice significandy,inhibited the tumor proliferation,induced more cell apoptosis,and did not increase the chemotherapy resistance.