Chitosan-coated magnetic graphene oxide for targeted delivery of doxorubicin as a nanomedicine approach to treat glioblastoma.

In this study, magnetic graphene oxide (mGO) was first prepared and modified with chitosan to prepare chitosan-coated mGO (mGOC). Gastrin-releasing peptide (GRP)-conjugated mGOC (mGOCG) was then prepared from mGOC. The chemo drug doxorubicin (DOX) was adsorbed to mGOCG surface for dual active/magnetic targeted drug delivery. The DOX loading to mGOCG is 1.71 mg/mg, and drug release is pH-sensitive to facilitate drug delivery in endosomes. In vitro studies confirmed enhanced mGOCG endocytosis by U87 glioblastoma cells, with which enhanced cytotoxicity towards cancer cells could be achieved. This could be revealed from the drastically reduced half-maximal inhibitory concentration of mGOCG/DOX compared with DOX and mGOC/DOX. Furthermore, mGOCG/DOX can be localized under the influence of a magnetic field (MF) to exert this cytotoxic effect. An orthotopic brain tumor model by implanting U87 cells in the intracranial area of BALB/c nude mice was used to study the in vivo anti-tumor efficacy by intravenous injection of different samples and followed with bioluminescence imaging. The tumor size in the mGOCG/DOX + MF group demonstrated the best potency to suppress tumor growth and prolong animal survival time compared with mGOCG/DOX, mGOC/DOX, or DOX groups, indicating this new dual-targeting delivery system for DOX can effectively treat glioblastoma.

Detection of autoantibodies against Rabphilin-3A-like protein as a potential biomarker in patient's sera of colorectal cancer.

BACKGROUND: Rabphilin-3A-like (RPH3AL) protein functions in the regulation of hormone exocytosis, and mutations in the RPHA3L gene have been associated with tumorigenesis in colorectal cancer (CRC). We evaluated the potential use of anti-RPH3AL autoantibodies as a marker for CRC detection. METHODS: Sera from 84 patients with CRC and 63 healthy controls were analysed for the presence of RPH3AL autoantibodies with a Western blotting assay. RESULTS: The frequencies of RPH3AL autoantibodies in the early stage, advanced stage and all CRC patients were 64.7%, 78.0% and 72.6%, respectively. These values are significantly higher than the frequency of RPH3AL autoantibodies in healthy controls (15.9%, P<0.001). Although the presence of RPH3AL autoantibodies did not correlate with clinical parameters, RPH3AL autoantibodies were found in 69.4% (34/49) of CRC patients who were negative for carcinoembryonic antigen. The value of the area under the receiver operating characteristic curve of RPH3AL autoantibody was 0.84, which suggests that screening for these autoantibodies could potentially be used for CRC diagnosis. CONCLUSION: Circulating RPH3AL autoantibodies are prevalent in patients with CRC, and detection of these autoantibodies might provide a novel non-invasive approach for CRC diagnosis.

Identification of SEC61ß and its autoantibody as biomarkers for colorectal cancer.

BACKGROUND: To identify novel serological biomarkers for human colorectal cancer (CRC), we analyzed CRC tissues using gel-assisted digestion and isobaric tags with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS). By comparing pairs of tumor tissues and matched normal tissues, we discovered the SEC61ß with expression changes 3.3-fold and a marginal statistical significance (p=0.052) previously. METHODS: SEC61ß expression in CRC tissues was further analyzed by western blotting and immunohistochemistry. We next assessed the putative diagnostic value of the SEC61ß autoantibody as a serum marker. RESULTS: Using western blotting analysis, SEC61ß expression was increased 1.9-fold in tumor tissues. Immunohistochemical analysis of 64 CRC specimens showed that SEC61ß was positively detected in 64% of the tumors, but weakly or not detected in >80% of the adjacent nontumor epithelial cells. Western blot analysis with plasma samples showed that the sensitivity and specificity of the SEC61ß autoantibody from patients with CRC were 79% and 75%, respectively. Importantly, the results of the SEC61ß autoantibody for early detection of colorectal cancer revealed a higher sensitivity of 77% than the carcinoembryonic antigen (CEA) assay. CONCLUSIONS: Measurement of SEC61ß autoantibody levels may provide an alternative detection indicator for CRC, particularly among early-stage patients.

Quantitative detection of survivin in malignant pleural effusion for the diagnosis and prognosis of lung cancer.

In the present study, pleural effusions are the first time to be used as the specimens for detection of survivin expression in lung cancer patients. We demonstrated that by quantifying survivin expression with enzyme-linked immunosorbent assay (ELISA) in the 80 effusion samples exhibited a diagnostic power of 85% and 75% in sensitivity and specificity, respectively. A multivariate analysis with the Cox regression model revealed that both high survivin expression and cancer cells of stage IV were the indicators for poor prognosis of lung cancer. In conclusion, quantitative assay of survivin in pleural effusion could be useful both in diagnosis and prognosis for lung cancer.