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Pathological angiogenesis plays an essential role in tumor aggressiveness and leads to unfavorable prognosis. The aim of this study is to detect the potential role of Retinoblastoma binding protein 2 (RBP2) in the tumor angiogenesis of non-small cell lung cancer (NSCLC). Immunohistochemical staining was used to detect the expression of RBP2, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and CD34. Two pairs of siRNA sequences and pcDNA3-HA-RBP2 were used to down-regulate and up-regulate RBP2 expression in H1975 and SK-MES-1 cells. An endothelial cell tube formation assay, VEGF enzyme-linked immunosorbent assay, real-time PCR and western blotting were performed to detect the potential mechanisms mediated by RBP2 in tumor angiogenesis. Of the 102 stage I NSCLC specimens analyzed, high RBP2 protein expression is closely associated with tumor size (P = 0.030), high HIF-1α expression (P = 0.028), high VEGF expression (P = 0.048), increased tumor angiogenesis (P = 0.033) and poor prognosis (P = 0.037); high MVD was associated with high HIF-1α expression (P = 0.034), high VEGF expression (P = 0.001) and poor prognosis (P = 0.040). Multivariate analysis indicated that RBP2 had an independent influence on the survival of patients with stage I NSCLC (P = 0.044). By modulating the expression of RBP2, our findings suggested that RBP2 protein depletion decreased HUVECs tube formation by down-regulating VEGF in a conditioned medium. RBP2 stimulated the up-regulation of VEGF, which was dependent on HIF-1α, and activated the HIF-1α via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Moreover, VEGF increased the activation of Akt regulated by RBP2. The RBP2 protein may stimulate HIF-1α expression via the activation of the PI3K/Akt signaling pathway under normoxia and then stimulate VEGF expression. These findings indicate that RBP2 may play a critical role in tumor angiogenesis and serve as an attractive therapeutic target against tumor aggressiveness for early-stage NSCLC patients.

The study was designed to detect the expression level of thimet oligopeptidase (THOP1) protein in non-small cell lung cancer (NSCLC) and investigate its correlation with clinicopathologic features and prognosis. Immunohistochemical staining was used to determine the expression of THOP1 protein in 120 NSCLC specimens and 53 distant normal lung tissues. Quantitative real-time PCR and western blotting were employed to measure the expression of THOP1 in 16 pairs of primary NSCLC and corresponding normal tissues. Analysis of immunohistochemical staining suggested low THOP1 expression was found in 71 (59.2%) of the 120 NSCLC specimens and significantly correlated with positive lymph node metastasis (P = 0.048). However, low THOP1 expression was found in 22 (41.5%) of the 53 normal lung tissues. Chi-square test suggested that the expression of THOP1 was significantly higher in the normal lung tissues than that in the NSCLC specimens (P = 0.032). Real-Time PCR and western blotting showed that NSCLC specimens had decreased THOP1 mRNA and protein expression compared to corresponding normal tissues. Univariate analysis demonstrated that low THOP1 expression significantly predicted decreased 5-year disease-free survival (P = 0.038) and overall survival (P = 0.017). In addition, positive lymph node metastasis (P = 0.025) and advanced TNM stage (P = 0.009) significantly predicted decreased 5-year overall survival. However, multivariate Cox regression analysis showed that only low THOP1 expression retained its significance as an independent prognostic factor for unfavorable 5-year disease-free survival (P = 0.046) and overall survival (P = 0.021). THOP1 may have clinical potentials to be employed as a promising biomarker to identify individuals with better prognosis and a novel antitumor agent for therapy of patients with NSCLC.

In this paper, we introduce a new subclass of p-harmonic functions and investigate the univalence and sense-preserving, extreme points, distortion bounds, convex combination, neighborhoods of mappings belonging to the subclass. Relevant connections of the results presented here with the results of previous research are briefly indicated. Finally, we also prove new properties of the Hadamard product of these classes.

There are many articles in the literature dealing with the first-order and the second-order differential subordination and superordination problems for analytic functions in the unit disk, but only a few articles are dealing with the above problems in the third-order case (see, e.g., Antonino and Miller (2011) and Ponnusamy et al. (1992)). The concept of the third-order differential subordination in the unit disk was introduced by Antonino and Miller in (2011). Let Ω be a set in the complex plane C. Also let p be analytic in the unit disk U=z:z∈C and z<1 and suppose that ψ:C4×U→C. In this paper, we investigate the problem of determining properties of functions p(z) that satisfy the following third-order differential superordination: Ω⊂ψpz,zp′z,z2p′′z,z3p′′′z;z:z∈U. As applications, we derive some third-order differential subordination and superordination results for meromorphically multivalent functions, which are defined by a family of convolution operators involving the Liu-Srivastava operator. The results are obtained by considering suitable classes of admissible functions.

There are many articles in the literature dealing with the first-order and the second-order differential subordination and differential superordination problems for analytic functions in the unit disk, but there are only a few articles dealing with the third-order differential subordination problems. The concept of third-order differential subordination in the unit disk was introduced by Antonino and Miller, and studied recently by Tang and Deniz. Let Ω be a set in the complex plane C, let p(z) be analytic in the unit disk U={z:z∈Cand|z|<1}, and let ψ:C4×U→C. In this paper, we investigate the problem of determining properties of functions p(z) that satisfy the following third-order differential superordination: Ω⊂ψ(p(z),zp′(z),z2p′′(z),z3p′′′(z);z):z∈U.As applications, we derive some third-order differential superordination results for analytic functions in U, which are associated with a family of generalized Bessel functions. The results are obtained by considering suitable classes of admissible functions. New third-order differential sandwich-type results are also obtained.

Li Yu, Ya-Ping Zhang, Chung-I Wu and colleagues report the de novo genome of the black snub-nosed monkey Rhinopithecus bieti and the genomic sequences of four other Rhinopithecus species, including three high-altitude and two lowland species. The species- and population-level genomic analyses as well as the transcriptomic analysis and functional assays find adaptive signatures associated with adaptation to high altitude. The snub-nosed monkey genus Rhinopithecus includes five closely related species distributed across altitudinal gradients from 800 to 4,500 m. Rhinopithecus bieti , Rhinopithecus roxellana , and Rhinopithecus strykeri inhabit high-altitude habitats, whereas Rhinopithecus brelichi and Rhinopithecus avunculus inhabit lowland regions. We report the de novo whole-genome sequence of R. bieti and genomic sequences for the four other species. Eight shared substitutions were found in six genes related to lung function, DNA repair, and angiogenesis in the high-altitude snub-nosed monkeys. Functional assays showed that the high-altitude variant of CDT1 (Ala537Val) renders cells more resistant to UV irradiation, and the high-altitude variants of RNASE4 (Asn89Lys and Thr128Ile) confer enhanced ability to induce endothelial tube formation in vitro . Genomic scans in the R. bieti and R. roxellana populations identified signatures of selection between and within populations at genes involved in functions relevant to high-altitude adaptation. These results provide valuable insights into the adaptation to high altitude in the snub-nosed monkeys.

Background The purposes of the present study were to detect the expression of metastasis-associated protein 1 (MTA1) in patients with esophageal squamous cell cancer (ESCC), and to evaluate the relevance of MTA1 protein expression to the tumor progression, angiogenesis, and prognosis. Methods Both MTA1 protein and intratumoral microvessels were examined by immunohistochemical staining in 131 ESCC patients who successfully underwent subtotal esophagectomy and esophagogastric anastomosis at Qilu Hospital between Jan 2004 and Dec 2005. Intratumoral microvessel density (MVD) was recorded by counting CD-34 positive immunostained endothelial cells. All statistical analyses were performed with SPSS 13.0 statistical software. Results High expression of MTA1 protein was detected in 57 cases and significantly correlated with tumor invasion depth ( P  = 0.041), lymph node metastasis ( P  = 0.021), pathologic stage ( P  = 0.003), and MVD ( P  = 0.044). Survival analysis showed that patients with MTA1 protein high expression had significantly poor overall 5-year survival ( P  = 0.002), and the factor found on multivariate analysis to significantly affect overall survival was only pathologic stage ( P  = 0.040). Further stratified survival analysis split by pathologic stage demonstrated that MTA1 protein high expression significantly predicted unfavorable prognosis among patients with pathologic stage II disease ( P  = 0.006). Conclusions High expression of the MTA1 protein is common in ESCC, and is closely associated with tumor progression, increased tumor angiogenesis, and poor survival. These findings indicate that MTA1 protein has clinical potentials as a useful indicator of progressive phenotype, a promising prognostic predictor to identify patients with poor prognosis, and a potential novel therapeutic target of antiangiogenesis for patients with ESCC.

Background The purpose of the present study was to investigate the expression of metastasis-associated protein 1 (MTA1) and its relationship to the disease-free interval after resection of pathologic N0 (pN0) esophageal squamous cell cancer (ESCC). Methods The subjects were 90 patients who successfully underwent complete resection of pN0 ESCC between May 2001 and May 2003. Immunohistochemical staining for MTA1 protein was performed using the avidin–biotin peroxidase complex method. Log-rank test was performed to compare the disease-free interval, and Cox regression multivariate analysis was performed to judge independent prognostic factors. Results Metastasis-associated protein 1 overexpression was detected in 40 esophageal cancer tissues. Disease-free interval was significantly associated with MTA1 protein overexpression ( p  = 0.015). The overall 5-year survival rate was 45.6%, the 5-year survival rate of patients with MTA1 protein overexpression was significantly lower than that of those without overexpression (25.0 versus 62.0%; p  < 0.001). The results of multivariate analysis confirmed that T status and MTA1 protein overexpression were independent prognostic factors. Conclusions Metastasis-associated protein 1 overexpression was detected in pN0 ESCC and was significantly correlated with shorter disease-free interval. T status and MTA1 protein overexpression were both independent prognostic factors. These findings suggested MTA1 might be a predictor of relapsing phenotype and a prognostic factor in esophageal cancer.

In this paper, we introduce and investigate two new subclasses H σ μ ( λ , φ ) and M σ γ ( λ , μ , φ ) of Ma-Minda bi-univalent functions defined by using subordination in the open unit disk D = { z ∈ C : | z | < 1 } . For functions belonging to these new subclasses, we obtain estimates for the initial coefficients | a 2 | and | a 3 | . The results presented in this paper would generalize those in related works of several earlier authors. MSC: 30C45, 30C80.

There are many articles in the literature dealing with differential subordination problems for analytic functions in the unit disk, and only a few articles deal with the above problems in the upper half-plane. In this paper, we aim to derive several differential subordination results for analytic functions in the upper half-plane by investigating certain suitable classes of admissible functions. Some useful consequences of our main results are also pointed out.