BACKGROUND:The YKL-40 coding chitinase 3-like 1 gene is 1 of the most overexpressed genes in human glioblastomas. The objectives of this study were to explore YKL-40 protein expression status and World Health Organization (WHO) pathologic grades of primary human astrocytoma and to investigate the role of YKL-40 in the proliferation of both established and primary astrocytoma cells in vitro. METHODS: WHO grade 1, 2, 3, and 4 primary astrocytomas (210 patients) were evaluated for YKL-40 protein expression status in immunohistochemical analyses. In addition, after transfection with a plasmid that contained YKL-40 small-interfering RNA (siRNA), cell proliferation and the cell cycle were measured with a cell-viability assay and flow cytometry. Expression levels of phosphorylated, total mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) were detected by Western blot analysis. RESULTS: The percentage of positive cells and the staining intensity differed significantly between different pathologic tumor grades (P < .001). The YKL-40 immunoreactivity score increased markedly with increased pathologic grade (F ¼ 18.89; P < .001). In the in vitro experiment, the cell cycle was arrested in G 1 phase. An inhibitor of the p38 MAPK, SB203580, could partially abrogate the cell proliferation inhibition effect by siRNA treatment. The expression levels of phosphorylated extracellular signal-regulated kinase 1/2 and phosphorylated AKT were notably decreased in siRNA-transfected U87 cells. In contrast, the expression levels of phosphorylated p38 and phosphorylated c-jun N-terminal kinase 1 and 2 increased significantly (P < .01). CONCLUSIONS: YKL-40 expression status correlated well with the pathologic grade of primary astrocytomas. The current results also indicted that YKL-40 plays a pivotal role in glioma cell proliferation through activation of the MAPK and AKT pathways. YKL-40 may be an attractive target for glioma therapy. Cancer 2010;116:2688-97.

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Recent studies indicate that centrally released arginine vasopressin (AVP) facilitates brain water permeability in normal and pathological conditions. The effects of central administration of arginine vasopressin (AVP) receptor antagonists on vasogenic brain edema were studied in rats. V1 or V2 receptor antagonists were stereotactically injected into the lateral ventricle 10 min prior to or 1 h after cold brain injury. The injury resulted in significant increases in the mean water content of the lesion and the contralateral hemispheres by 1.15 and 0.38%, respectively. Twenty-four hours after injury, the brain water and sodium contents, the brain swelling, and plasma osmolality were measured. V1 receptor antagonist of 50 ng significantly decreased the brain water and sodium contents and the brain swelling in the adjacent cortex of the lesion without changes in serum osmolality. On the other hand, 5 ng of V1 receptor antagonist and V2 receptor antagonist had no effect on edema. The V1 receptor of AVP is thought to act predominantly on water permeability of the brain. Peptide therapy may become an additional tool for brain edema treatment.