Glioblastomas belong to the most aggressive human cancers with short survival times. Due to the blood-brain barrier, they are mostly inaccessible to traditional chemotherapy. We have recently shown that doxorubicin bound to polysorbate-coated nanoparticles crossed the intact blood-brain barrier, thus reaching therapeutic concentrations in the brain. Here, we investigated the therapeutic potential of this formulation of doxorubicin in vivo using an animal model created by implantation of 101/8 glioblastoma tumor in rat brains. Groups of 5-8 glioblastoma-bearing rats (total n ؍ 151) were subjected to 3 cycles of 1.5-2.5 mg/kg body weight of doxorubicin in different formulations, including doxorubicin bound to polysorbate-coated nanoparticles. The animals were analyzed for survival (% median increase of survival time, Kaplan-Meier). Preliminary histology including immunocytochemistry (glial fibrillary acidic protein, ezrin, proliferation and apoptosis) was also performed. Rats treated with doxorubicin bound to polysorbate-coated nanoparticles had significantly higher survival times compared with all other groups. Over 20% of the animals in this group showed a long-term remission. Preliminary histology confirmed lower tumor sizes and lower values for proliferation and apoptosis in this group. All groups of animals treated with polysorbatecontaining formulations also had a slight inflammatory reaction to the tumor. There was no indication of neurotoxicity. Additionally, binding to nanoparticles may reduce the systemic toxicity of doxorubicin. This study showed that therapy with doxorubicin bound to nanoparticles offers a therapeutic potential for the treatment of human glioblastoma.
Whey protein concentrate (WPC 80) was hydrolyzed by Alcalase 2.4 L and Protamex to 5, 10, 15 and 20% degree of hydrolysis (DH). WPC 80 and its hydrolysates were analyzed, compared and used for measuring some functional properties. All hydrolysates were different from WPC 80 in protein, moisture and ash content. Free amino groups and protein solubility increased with increasing DH. The peptides produced by hydrolysis had smaller molecular sizes, and their average molecular weight decreased as the DH increased. Except hydrolysates generated by Alcalase 2.4 L at 5% DH, all others showed poor emulsifying and foaming properties compared with unhydrolyzed WPC 80. Gelation properties of WPC 80 and its hydrolysates were different. The global amino acid compositions did not differ significantly between the different hydrolysates, and they were very close among WPC 80 and its hydrolysates except for Methionine, Glycine, Histidine and Valine.
The AFP receptor (rAFP) was discovered in embryonal and tumor tissues with a high level of proliferation. The AFP‐binding protein (AFPbp) possibly containing the AFP‐receptor (rAFP) was isolated from human embryos and human breast cancer tissue using affinity chromatography on an AFP‐Sepharose column. The similarity of molecular weight, subunit composition, and immunological characteristics was shown for embryonal and tumor AFPbp using immunoblotting, gel‐filtration, and PAAG electrophoresis. Judging from Superose‐12 gel‐filtration data, the protein molecular weight made up to 320‐380 kDa. The presence of an IgG‐binding site was detected in embryonal and tumor AFPbp by Western blot analysis.
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