title: BCNU/PLGA microspheres: a promising strategy for the treatment of gliomas in mice.
abstract: 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 O(6)-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). MRI scan 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 significantly, inhibited the tumor proliferation, induced more cell apoptosis, and did not increase the chemotherapy resistance.
authors.affiliation: Fudan University Huashan Hospital, Dept. of Neurosurgery, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science,Shanghai Medical College-Fudan University, Shanghai 200040, China.
authors.forename: Tongming
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Fudan University Huashan Hospital, Dept. of Neurosurgery, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science,Shanghai Medical College-Fudan University, Shanghai 200040, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Fudan University Huashan Hospital, Dept. of Neurosurgery, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science,Shanghai Medical College-Fudan University, Shanghai 200040, China.
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Fudan University Huashan Hospital, Dept. of Neurosurgery, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science,Shanghai Medical College-Fudan University, Shanghai 200040, China.
authors.forename: Luping
authors.initials: L
authors.lastname: Chen
authors.affiliation: Fudan University Huashan Hospital, Dept. of Neurosurgery, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science,Shanghai Medical College-Fudan University, Shanghai 200040, China.
authors.forename: Huasong
authors.initials: H
authors.lastname: Gao
authors.affiliation: Fudan University Huashan Hospital, Dept. of Neurosurgery, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science,Shanghai Medical College-Fudan University, Shanghai 200040, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhu
keywords: BCNU/PLGA microspheres; apoptosis; glioma; interstitial chemotherapy