BackgroundPrevious work has shown reduced expression levels of let-7 in lung tumors. But little is known about the expression or mechanisms of let-7a in prostate cancer. In this study, we used in vitro and in vivo approaches to investigate whether E2F2 and CCND2 are direct targets of let-7a, and if let-7a acts as a tumor suppressor in prostate cancer by down-regulating E2F2 and CCND2.Methodology/PrincipalFindings Real-time RT-PCR demonstrated that decreased levels of let-7a are present in resected prostate cancer samples and prostate cancer cell lines. Cellular proliferation was inhibited in PC3 cells and LNCaP cells after transfection with let-7a. Cell cycle analysis showed that let-7a induced cell cycle arrest at the G1/S phase. A dual-luciferase reporter assay demonstrated that the 3′UTR of E2F2 and CCND2 were directly bound to let-7a and western blotting analysis further indicated that let-7a down-regulated the expression of E2F2 and CCND2. Our xenograft models of prostate cancer confirmed the capability of let-7a to inhibit prostate tumor development in vivo.Conclusions/SignificanceThese findings help to unravel the anti-proliferative mechanisms of let-7a in prostate cancer. Let-7a may also be novel therapeutic candidate for prostate cancer given its ability to induce cell-cycle arrest and inhibit cell growth, especially in hormone-refractory prostate cancer.
Near-infrared fluorescence (NIRF) imaging is an attractive modality for early cancer detection with high sensitivity and multi-detection capability. Due to convenient modification by conjugating with moieties of interests, NIRF probes are ideal candidates for cancer targeted imaging. Additionally, the combinatory application of NIRF imaging and other imaging modalities that can delineate anatomical structures extends fluorometric determination of biomedical information. Moreover, nanoparticles loaded with NIRF dyes and anticancer agents contribute to the synergistic management of cancer, which integrates the advantage of imaging and therapeutic functions to achieve the ultimate goal of simultaneous diagnosis and treatment. Appropriate probe design with targeting moieties can retain the original properties of NIRF and pharmacokinetics. In recent years, great efforts have been made to develop new NIRF probes with better photostability and strong fluorescence emission, leading to the discovery of numerous novel NIRF probes with fine photophysical properties. Some of these probes exhibit tumoricidal activities upon light radiation, which holds great promise in photothermal therapy, photodynamic therapy, and photoimmunotherapy. This review aims to provide a timely and concise update on emerging NIRF dyes and multifunctional agents. Their potential uses as agents for cancer specific imaging, lymph node mapping, and therapeutics are included. Recent advances of NIRF dyes in clinical use are also summarized.
Aim: CD147 and MMPs have been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological significance of CD147, MMP-1, MMP-2 and MMP-9 expression in human prostate cancer (PCa) and to evaluate their involvement in the progression of PCa. Methods: CD147, MMP-1, MMP-2 and MMP-9 expression was assessed in paraffin-embedded specimens collected from 62 cases of PCa and 15 cases of benign prostatic hyperplasia (BPH) by immunohistochemistry. Spearman’s correlation was applied to determine possible relationships between CD147, MMP-1, MMP-2 and MMP-9 expression and PCa. The association of CD147 and MMP-2 protein expression with the clinicopathological characteristics and the prognosis of PCa was subsequently assessed. Results: CD147was expressed in 51/62 (82.3%) PCa patients and in 2/15 (13.3%) BPH cases. MMP-1, MMP-2 and MMP-9 expression was significantly higher in PCa tissue than in BPH tissue. Using Spearman analysis, a significant positive correlation between CD147 and MMP-1, MMP-2 and MMP-9 expression was found (p <0.05). CD147 and MMP-2 expression was correlated with TMN grade and Gleason score. Patients with concurrent expression of CD147+ and MMP-2+ had the lowest survival (p <0.01). Conclusion: The results suggest that concurrent expression of CD147 and MMP may be an important characteristic of PCa which may help in the prediction of PCa progression.
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