DJ-1 is activated in medulloblastoma and is associated with cell proliferation and differentiation.

BACKGROUND: DJ-1 is a key regulator in human tumorigenesis, including brain malignancies. The mechanisms by which DJ-1 contributes to the pathogenesis of medulloblastoma (MB) remain unclear, and its impact on the prognosis for patients with MB has not been identified. The aim of this study was to determine whether the DJ-1 protein is associated with tumorigenesis of MBs, and whether DJ-1 is a valuable factor for predicting the prognosis of patients with MB. METHODS: We collected 66 pairs of MB and adjacent normal cerebellum samples. Expression of DJ-1, Ser 473-phosphorylated-Akt (p-Akt), PTEN, and Ki-67 (MIB-1) was detected by immunohistochemical staining, and the correlation of these immunostaining results with the clinicopathological features of patients with MB was determined. RESULTS: High DJ-1 expression (48.5%, 32/66) in tumor cells of MBs was significantly associated with the classic MB variant (P = 0.003), high proliferative activity (P = 0.002) and undifferentiated tumor (P = 0.001), whereas high p-Akt expression (56.1%, 37/66) was associated with tumor metastasis stage (P = 0.007), undifferentiated tumor (P = 0.007), and high-risk tumor (P = 0.002). High DJ-1 expression also correlated with high p-Akt expression and high MIB-1 index. However, only high levels of DJ-1(P = 0.009) and high MIB-1 index (P = 0.001) were strong independent prognostic factors associated with worse overall survival. CONCLUSIONS: Although the validity of the preliminary data in this study needs to be confirmed by a larger number of cases, our study indicates that DJ-1, PTEN, and p-Akt might play important roles in cell proliferation and differentiation of MBs. The evaluation of expression of DJ-1 and related proteins might be useful for predicting the prognosis of patients with MB.

Midazolam inhibits the proliferation of human head and neck squamous carcinoma cells by downregulating p300 expression.

The objective of this study was to investigate the mechanism of midazolam in inhibiting the proliferation of hypopharyngeal squamous carcinoma cells. Cultured FaDu cancer cells were treated with different concentrations of midazolam. MTT and BrdU incorporation assays were then used to evaluate cancer cell proliferation. The mRNA and protein levels of p300, a key factor involved in the tumorigenesis of numerous cancers, were measured with RT-PCR and Western blotting, respectively. Midazolam inhibited the expression of p300 and the proliferation of FaDu cells. Additionally, knockdown of p300 resulted in increased expression of p21 and p27 and decreased expression of p-Rb while inhibiting the proliferation of FaDu cells. Midazolam inhibits the proliferation of human head and neck squamous carcinoma cells by downregulating p300. Midazolam may be useful for the treatment of hypopharyngeal squamous cancers.