β-arrestins 1 and 2 are multifunctional adaptor proteins originally discovered for their role in desensitizing seven-transmembrane receptor signaling via the heterotrimeric guanine nucleotide binding proteins. Recently identified roles of β-arrestins include regulation of cancer cell chemotaxis and proliferation. Herein we report that β-arrestin1 expression regulates breast tumor colonization in nude mice and cancer cell viability during hypoxia. β-arrestin1 robustly interacts with nuclear hypoxia-induced factor 1α (HIF-1α) that is stabilized during hypoxia and potentiates HIF-1-dependent transcription of the angiogenic factor VEGF-A. Increased expression of β-arrestin1 in human breast cancer (infiltrating ductal carcinoma or IDC and metastatic IDC) correlates with increased levels of VEGF-A. While the anti-angiogenic drug thalidomide inhibits HIF-1-dependent VEGF transcription in breast carcinoma cells, it does not prevent HIF-1α stabilization, but leads to aberrant localization of HIF-1α to the perinuclear compartments and surprisingly stimulates nuclear export of β-arrestin1. Additionally, imatinib mesylate that inhibits release of VEGF induces nuclear export of β-arrestin1-HIF-1α complexes. Our findings suggest that β-arrestin1 regulates nuclear signaling during hypoxia to promote survival of breast cancer cells via VEGF signaling and that drugs that induce its translocation from the nucleus to the cytoplasm could be useful in anti-angiogenic and breast cancer therapies.

This systematic review indicated that the clinical efficacy of Er:YAG laser was similar to SRP 3 months postoperatively. The clinical benefits of Er:YAG laser as adjuvant to SRP was still lacking. Since Er:YAG laser has certain advantages, it could be expected to be a novel short-term alternative choice for chronic periodontitis.

BackgroundThe clinicopathological significance of cyclin D1 overexpression and prognosis of oral squamous cell carcinoma has not been fully quantified. We performed a comprehensive meta-analysis for evaluation of cyclin D1 overexpression in oral squamous cell carcinoma to determine the strength of this association.MethodsUsing both medical subheadings and free terms, we searched PubMed, Embase and the Institute for Scientific Information Web of Science for all eligible studies published before Nov. 2013. We retrieved 1674 citations, determining that 15 met the selection criteria. We used the odds ratio (OR) and hazard ratio (HR) as the common measures of association to quantitatively determine the correlation between cyclin D1 overexpression and outcomes of oral cancer. We performed a meta-analysis and heterogeneity, sensitivity, and subgroup analyses to clarify and validate the pooled results.ResultsThe pooled results provided compelling evidence that cyclin D1 overexpression was significantly correlated with increased tumor size (OR = 1.617, 95% confidence interval [CI] = 1.046–2.498, p = 0.031), lymphoid node metastasis (OR = 2.035, 95% CI = 1.572–2.635, p<0.001), tumor differentiation (OR = 1.976, 95% CI = 1.363–2.866, p<0.001), and advancement of clinical stages (OR = 1.516, 95% CI = 1.140–2.015, p = 0.004), and adversely influenced overall survival of OSCC patients (HR = 1.897, 95% CI = 1.577–2.282, p<0.001). The strength of association varied in different oral cavity subsites.ConclusionOur findings indicated that cyclin D1 expression correlates with detrimental clinicopathological outcome and poor prognosis in oral squamous cell carcinoma. Our results may be useful in the management of oral cancer.