PMID- 29658349
OWN - NLM
STAT- MEDLINE
DCOM- 20190603
LR  - 20190603
IS  - 2169-141X (Electronic)
IS  - 2169-1401 (Linking)
VI  - 46
IP  - sup2
DP  - 2018
TI  - Biodegradable hybrid-structured nanofibrous membrane supported chemoprotective 
      gene therapy enhances chemotherapy tolerance and efficacy in malignant glioma 
      rats.
PG  - 515-526
LID - 10.1080/21691401.2018.1460374 [doi]
AB  - Chemotherapy is ineffective for treating malignant glioma (MG) because of the low 
      therapeutic levels of pharmaceuticals in tumour tissues and the well-known tumour 
      resistance. The resistance to alkylators is modulated by the DNA repair protein 
      O(6)-alkylguanine-DNA alkyltransferase (AGT). O(6)-benzylguanine (O(6)-BG) can 
      irreversibly inactivate AGT by competing with O(6)-methylguanine and has been 
      confirmed to increase the therapeutic activity of alkylators. We developed 
      hybrid-structured poly[(d,l)-lactide-co-glycolide] nanofibrous membranes (HSNMs) 
      that enable the sequential and sustained release of O(6)-BG and two alkylators 
      (carmustine and temozolomide [TMZ]). HSNMs were surgically instilled into the 
      cerebral cavity of pathogen-free rats and F98 glioma-bearing rats. The release 
      behaviours of loaded drugs were quantified by using high-performance liquid 
      chromatography. The treatment results were compared with the rats treated with 
      intraperitoneal injection of O(6)-BG combined with surgical implantation of 
      carmustine wafer and oral TMZ. The HSNMs revealed a sequential drug release 
      behaviour with the elution of high drug concentrations of O(6)-BG in the early 
      phase, followed by high levels of two alkylators. All drug concentrations 
      remained high for over 14 weeks. Tumour growth was slower and the mean survival 
      time was significantly prolonged in the HSNM-treated group. Biodegradable HSNMs 
      can enhance therapeutic efficacy and prevent toxic systemic effects.
FAU - Liu, Shih-Jung
AU  - Liu SJ
AUID- ORCID: 0000-0003-2083-4865
AD  - a Department of Mechanical Engineering , Chang Gung University , Tao-Yuan , 
      Taiwan, ROC.
AD  - b Department of Orthopedic Surgery , Chang Gung Memorial Hospital , Tao-Yuan , 
      Taiwan, ROC.
FAU - Yang, Tao-Chieh
AU  - Yang TC
AUID- ORCID: 0000-0003-4523-2422
AD  - c Department of Neurosurgery , Asia University Hospital , Taichung , Taiwan, ROC.
FAU - Yang, Shun-Tai
AU  - Yang ST
AD  - d Division of Neurosurgery, Department of Surgery , Shuang Ho Hospital, Taipei 
      Medical University , Taipei , Taiwan, ROC.
AD  - e Department of Surgery, School of Medicine, College of Medicine , Taipei Medical 
      University , Taipei , Taiwan, ROC.
FAU - Chen, Ying-Chun
AU  - Chen YC
AD  - a Department of Mechanical Engineering , Chang Gung University , Tao-Yuan , 
      Taiwan, ROC.
FAU - Tseng, Yuan-Yun
AU  - Tseng YY
AUID- ORCID: 0000-0003-4968-3298
AD  - d Division of Neurosurgery, Department of Surgery , Shuang Ho Hospital, Taipei 
      Medical University , Taipei , Taiwan, ROC.
AD  - e Department of Surgery, School of Medicine, College of Medicine , Taipei Medical 
      University , Taipei , Taiwan, ROC.
LA  - eng
PT  - Journal Article
DEP - 20180416
PL  - England
TA  - Artif Cells Nanomed Biotechnol
JT  - Artificial cells, nanomedicine, and biotechnology
JID - 101594777
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Drug Carriers)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/adverse effects/chemistry/*pharmacology
MH  - Brain Neoplasms/drug therapy/genetics/*pathology/*therapy
MH  - Drug Carriers/chemistry/metabolism
MH  - Drug Liberation
MH  - *Genetic Therapy
MH  - Glioma/drug therapy/genetics/*pathology/*therapy
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Nanofibers/*chemistry
MH  - Rats
MH  - Survival Analysis
MH  - Tumor Burden/drug effects
OTO - NOTNLM
OT  - -benzylguanine (-BG)
OT  - Nanofibrous membrane
OT  - alkylguanine-DNA alkyltransferase (AGT)
OT  - chemo-resistance
OT  - malignant glioma
OT  - poly[(d,l)-lactide-co-glycolide] (PLGA)
EDAT- 2018/04/17 06:00
MHDA- 2019/06/04 06:00
CRDT- 2018/04/17 06:00
PHST- 2018/04/17 06:00 [pubmed]
PHST- 2019/06/04 06:00 [medline]
PHST- 2018/04/17 06:00 [entrez]
AID - 10.1080/21691401.2018.1460374 [doi]
PST - ppublish
SO  - Artif Cells Nanomed Biotechnol. 2018;46(sup2):515-526. doi: 
      10.1080/21691401.2018.1460374. Epub 2018 Apr 16.