AimThe role of Sirtuin 1 (SIRT 1) in carcinogenesis is controversial. This study was to explore the association between the SIRT1 expression and the clinical characteristics, the responsiveness to chemotherapy and prognosis in Non-small cell lung cancer (NSCLC).MethodsWe enrolled 295 patients with inoperable advanced stage of NSCLC, namely, stage III (A+B) and IV NSCLC. All patients had received platinum-based chemotherapy after diagnosis and the chemotherapy response were evaluated. All patients were followed up for overall survival (OS) and progression free survival (PFS). In vitro, H292 cells were tranfected with SIRT1 small interfering RNA (siRNA). The cell biological behaviors and chemosensitivity to cisplatin treatment were studied. The in vivo tumorgenesis and metastasis assays were performed in nude mice.ResultsWe found that the SIRT1 expressions were significantly associated with the tumor stage, tumor size and differentiation status. Patients with high SIRT 1 expressions had a significantly higher chance to be resistant to chemotherapy than those with low SIRT 1 expression. Patients with high expression of SIRT1 had significantly shorter OS and DFS than those with low expression. Cox analyses confirmed that the SIRT 1 expression was a strong predictor for a poor OS and PFS in NSCLC patients underwent Platinum-based chemotherapy. In vitro studies revealed that the reduced expression SIRT 1 by siRNA technique significantly inhibited cell proliferation, migration and invasion. More importantly, SIRT1 si-RNA significantly enhanced the chemosensitivity of H292 cells to cisplatin treatment. The in vivo tumorgenesis and metastasis assays showed that SIRT1 knockdown dramatically reduced the tumor volume and the metastatic ability in nude mice.ConclusionCollectively, our data suggest that the SIRT1 expression may be a molecular marker associated with the NSLCLC clinical features, treatment responsiveness and prognosis of advanced NSCLC.

Experimental and epidemiological studies suggest that serum levels of trace elements may be associated with breast cancer risk. We compared serum levels of 15 trace elements between breast cancer patients and normal controls from Shandong, China, for the first time to assess whether serum levels of trace elements were associated with breast cancer risk. Eighty-eight breast cancer patients and 84 healthy controls were enrolled in the study. A Spectraspan V direct current plasma atomic emission spectrometer was used to determine the serum levels of 15 trace elements including Zn, Mn, Al, Cd, Fe, Mg, Ca, Pb, Cu, Se, Ni, Ti, Co, Li, and Cr. Breast cancer patients had significantly higher serum levels of Cd (p = 0.000), Mg (p = 0.001), Cu (p = 0.000), Co (p = 0.006), and Li (p = 0.003) and borderline higher Cr (p = 0.052), while significantly lower Mn (p = 0.000), Al (p = 0.000), Fe (p = 0.000), and Ti (p = 0.000) compared to their matched controls. However, there were no significant differences in serum levels of Zn (p = 0.824), Ca (p = 0.711), Pb (p = 0.274), Se (p = 0.236), and Ni (p = 0.185) between the two groups. Our study showed a possible association between serum levels of trace elements and breast cancer risk in eastern China, though it warrants further investigations to confirm the association. If confirmed, modulation of trace elements may help reduce breast cancer risk.

In this work we propose a spatial point process (SPP) approach to improve the detection accuracy of clustered microcalcifications (MCs) in mammogram images. The conventional approach to MC detection has been to first detect the individual MCs in an image independently, which are subsequently grouped into clusters. Our proposed approach aims to exploit the spatial distribution among the different MCs in a mammogram image (i.e., MCs tend to appear in small clusters) directly during the detection process. We model the MCs by a marked point process (MPP) in which spatially neighboring MCs interact with each other. The MCs are then simultaneously detected through maximum a posteriori (MAP) estimation of the model parameters associated with the MPP process. The proposed approach was evaluated with a dataset of 141 clinical mammograms from 66 cases, and the results show that it could yield improved detection performance compared to a recently proposed SVM detector. In particular, the proposed approach achieved a sensitivity of about 90% with the FP rate at around 0.5 clusters per image, compared to about 83% for the SVM; the performance of the proposed approach was also demonstrated to be more stable over different composition of the test images.

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Nedd4-2 is an archetypal HECT ubiquitin E3 ligase that disposes target proteins for degradation. Because of the proven roles of Nedd4-2 in degradation of membrane proteins, such as epithelial Na ؉ channel, we examined the effect of Nedd4-2 on the apical Ca 2؉ channel TRPV6, which is involved in transcellular Ca 2؉ transport in the intestine using the Xenopus laevis oocyte system. We demonstrated that a significant amount of Nedd4-2 protein was distributed to the absorptive epithelial cells in ileum, cecum, and colon along with TRPV6. When coexpressed in oocytes, Nedd4-2 and, to a lesser extent, Nedd4 down-regulated the protein abundance and Ca 2؉ influx of TRPV6 and TRPV5, respectively. TRPV6 ubiquitination was increased, and its stability was decreased by Nedd4-2. The Nedd4-2 inhibitory effects on TRPV6 were partially blocked by proteasome inhibitor MG132 but not by the lysosome inhibitor chloroquine. The rate of TRPV6 internalization was not significantly altered by Nedd4-2. The HECT domain was essential to the inhibitory effect of Nedd4-2 on TRPV6 and to their association. The WW1 and WW2 domains interacted with TRPV6 terminal regions, and a disruption of the interactions by D204H and D376H mutations in the WW1 and WW2 domains increased TRPV6 ubiquitination and degradation. Thus, WW1 and WW2 may serve as a molecular switch to limit the ubiquitination of TRPV6 by the HECT domain. In conclusion, Nedd4-2 may regulate TRPV6 protein abundance in intestinal epithelia by controlling TRPV6 ubiquitination.

Investigations of the nitridoborates of lanthanides (Ln) have progressed significantly during the last few years. New compounds have been synthesized and characterized and are presented here together with some of their properties. Currently two distinct methods serve for the preparation of nitridoborate compounds; either hexagonal boron nitride undergoes a fragmentation through the reaction with LnN, or dinitridoborate ions are converted into other nitridoborate ions. Lanthanide nitridoborates contain molecular anions such as [BN]n-, [BN2]3-, [B2N4]8-, [B3N6]9-, and [BN3]6- which may occur in combinations with other nitridoborates or with additional nitride ions. In crystal structures of lanthanide nitridoborates these anions are arranged in layers and are surrounded by metal atoms in a characteristic fashion. Terminal N atoms are capped by metal atoms forming a square-pyramid, and B atoms prefer a trigonal-prismatic environment of metal atoms. Nitridoborates form saltlike as well as metal-rich compounds and have the potential to show a lot of what are considered to be important solid-state properties, thus they have a good chance to establish their position within the group of relevant materials.

Prostate cancer (PCa) is the second most common cancer in men. The Gleason score (GS) and biomarkers play important roles in the diagnosis and treatment of patients with PCa. The purpose of this study was to investigate the relationship between the apparent diffusion coefficient (ADC) and the molecular markers Ki-67, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in PCa. Thirty-nine patients with 39 lesions, who had been diagnosed with PCa, were enrolled in this study. All patients underwent diffusion-weighted magnetic resonance imaging (DW-MRI) (b = 800 s/mm ). The expression of Ki-67, HIF-1α and VEGF was assessed by immunohistochemistry. Statistical analysis was applied to analyze the association between ADC and prostate-specific antigen (PSA), GS and the expression of Ki-67, HIF-1α and VEGF. The group differences in ADC among different grades of Ki-67, HIF-1α and VEGF were also analyzed. The mean ± standard deviation of ADC was (0.76 ± 0.27) × 10 mm /s. ADC correlated negatively with PSA and GS (p < 0.05). The Ki-67 staining index (SI), HIF-1α expression and VEGF expression in PCa were correlated inversely with ADC, controlling for age (r = -0.332, p < 0.05; r = -0.662, p < 0.0005; and r = -0.714, p < 0.0005, respectively). ADC showed a significant difference among different grades of Ki-67 (F = 9.164, p = 0.005), HIF-1α (F = 40.333, p < 0.0005) and VEGF (F = 22.048, p < 0.0005). In conclusion, ADC was correlated with PSA, GS, and Ki-67, HIF-1α and VEGF expression in patients with PCa. ADC may be used to evaluate tumor proliferation, hypoxia and angiogenesis in PCa.

Use of additional cases from a reference library that have similar image features can improve the classification accuracy of a CADx classifier on a query case. It can even outperform retraining the classifier with all the cases from the entire reference library. This implies that cases with similar image features are more relevant in defining the local decision boundary of the CADx classifier around the query.