Proteomic analysis of cerebrospinal fluid: toward the identification of biomarkers for gliomas.

Gliomas are the most common primary brain tumors in adults and, despite advances in the understandings of glioma pathogenesis in the genetic era, they are still ineradicable, justifying the need to develop more reliable diagnostic and prognostic biomarkers for this malignancy. Because changes in cerebrospinal fluid (CSF) are suggested to be capable of sensitively reflecting pathological processes, e.g., neoplastic conditions, in the central nervous system, CSF has been deemed a valuable source for potential biomarkers screening in this era of proteomics. This systematic review focused on the proteomic analysis of glioma CSF that has been published to date and identified a total of 19 differentially expressed proteins. Further functional and protein-protein interaction assessments were performed by using Protein Analysis Through Evolutionary Relationships (PANTHER) website and Ingenuity Pathway Analysis (IPA) software, which revealed several important protein networks (e.g., IL-6/STAT-3) and four novel focus proteins (IL-6, galanin (GAL), HSPA5, and WNT4) that might be involved in glioma pathogenesis. The concentrations of these focus proteins were subsequently determined by enzyme-linked immunosorbent assay (ELISA) in an independent set of CSF and tumor cyst fluid (CF) samples. Specifically, glioblastoma (GBM) CF had significantly lower GAL, HSPA5, and WNT4 levels than CSF from different grades of glioma. In contrast, IL-6 level was significantly higher in GBM CF when compared with CSF and, among different CSF groups, was highest in GBM CSF. Therefore, these candidate protein biomarkers, identified from both the literatures and in silico analysis, may have potentials in clinical diagnosis, prognosis evaluation, treatment response monitoring, and novel therapeutic targets identification for patients with glioma.

Serum GFAP autoantibody as an ELISA-detectable glioma marker.

Glioma is the most common primary brain tumor, yet the high cost of diagnostic imaging has made early detection of asymptomatic glioma a formidable challenge. Thus, the development of a convenient, sensitive, and cost-effective diagnostic strategy, such as enzyme-linked immunosorbent assay (ELISA) based on glioma-specific and World Health Organization (WHO) grade-specific autoantibody serum markers, is necessary. To this end, a comparative proteomic analysis based on two-dimensional western blotting was carried out with the sera of glioma patients and normal controls. Of the 11 novel glioma-expressed autoantibodies, the autoantibody against glial fibrillary acidic protein (GFAP) showed the highest differential expression. To investigate the potential clinical utility of the GFAP autoantibody as an early diagnostic marker for glioma, an ELISA-based assay was developed and validated with sera from glioma patients with WHO grades II (n = 19), III (n = 17), and IV (n = 24). The GFAP autoantibody level directly correlated with WHO grade and tumor volume. Sera from patients of non-glioma brain tumors, as well as non-brain tumors, showed much lower levels of GFAP autoantibody than those of the glioma patients, indicating that elevated GFAP autoantibody is specific to glioma patients. Analysis of the receiver operating characteristics curve suggested that the new ELISA has good distinguishing power and sensitivity for diagnosing glioma patients. This is the first ELISA assay developed for an autoantibody of a glioma antigen and may prove valuable for the clinical detection of glioma.

EGFR-mediated G1/S transition contributes to the multidrug resistance in breast cancer cells.

Despite the improvement of strategies against cancer therapy, the multidrug resistance (MDR)is the critical problem for successful cancer therapy. Recurrent cancers after initial treatment with chemotherapy are generally refractory to second treatments with these anticancer therapies. Therefore, it is necessary to elucidate the therapy-resistant mechanism for development of effective therapeutic modalities against tumors. Here we demonstrate a phase-specific chemotherapy resistance due to epidermal growth factor receptor (EGFR) in human breast cancer cells. Thymidine-induced G1-arrested cultures showed upregulated chemosensitivity, whereas S-phase arrested cells were more resistant to chemotherapeutic agents. Overexpression of EGFR promoted the MDR phenotypes in breast cancer cells via accelerating the G1/S phase transition, whereas depletion of EGFR exerted the opposite effects. Furthermore, CyclinD1, a protein related to cell cycle, was demonstrated to be involved in above EGFR-mediated effects since EGFR increased the expression of CyclinD1, and the specific RNA interference against CyclinD1 could primarily abolish the EGFR-induced MDR phenotypes. These data provide new insights into the mode by which MDR breast cancers evade cytoxic attacks from chemotherapeutic agents and also suggest a role for EGFR-CyclinD1 axis in this process.

Factors affecting prognosis of patients with intracranial anaplastic oligodendrogliomas: a single institutional review of 70 patients.

Anaplastic oligodendroglioma (AO) is an uncommon intracranial tumor and prognosis is poor. In this study, we assessed the factors affecting the prognosis of AO patients. Seventy AO patients were recruited from 2001 to 2006 in Shanghai Huashan Hospital of Fudan University; all were treated surgically. Kaplan-Meier survival analysis and Cox regression analysis were used to analyze the prognostic effects of 14 different factors, which were selected from clinical, radiological, pathological, and treatment variables. The results showed that chemotherapy, age, primary or secondary tumors, preoperative Karnofsky Performance Scale (KPS) scores, the presence of epilepsy at initial presentation, radiological contrast infusion, and neurological parameters all correlated with the prognosis of the patients. Furthermore, Cox multivariate analysis also showed that the age (P < 0.048), primary or secondary tumors (P < 0.010), and chemotherapy (P < 0.010) were significantly correlated with the prognosis of the patients. Age and chemotherapy correlated with the prognosis of AO. The patients younger than 50 years old and who received regular chemotherapy were likely to achieve a good outcome. Moreover, individualized treatment after molecular biological typing of AO may improve the prognosis of AO.