These results collectively indicate that combined treatment of TMZ can sensitize GBM cells to blockade of autocrine VEGF signaling through specific down-regulation of NRP-1, which provide a rationale for further evaluation and a potential clinical trial of combinatorial therapy of TMZ and SU1498 or other VEGF inhibitors for intractable brain tumors.
In the present study, dual-modified liposomes (At-Lp) was designed by attaching two receptorspecific peptides, Angiopep and tLyP-1, which specifically targeting low-density lipoprotein receptor (LRP) for brain tumor targeting and neuropilin-1 receptor (NRP-1) for tumor penetration, respectively.
This study provides insights into the mechanism by which the NRP/B modulates Nrf2-dependent NQO1 induction in cellular protection against ROS in brain tumors.
NRP/B mutations (13 mutations in the Kelch domains, two in the intervening sequence (IVS) domain and two in the BTB domain) were detected in brain tumor cell lines (A-172, CCF-STTG1, SK-N-SH and U87-MG) and in primary human malignant GBM tissues (eight samples).
Since our previous studies demonstrated that NRP/B is expressed in primary hippocampal neurons but not in primary astrocytes, we have characterized NRP/B mRNA and protein expression in various brain cell lines and in human brain tumors.