BackgroundMarkers of systemic inflammation are correlated with patient survival in various cancers. The prognostic value of neutrophil-to-lymphocyte ratio (NLR) was compared with that of platelet-to-lymphocyte ratio (PLR) in patients with glioblastoma. The association of NLR with neutrophil and T- cell infiltration was also explored.MethodsA total of 152 patients with glioblastoma were retrospectively analyzed. Clinical information was obtained from electronic medical records. Kaplan-Meier analysis and the Cox proportional hazards models were used to examine the survival function of pre-treatment NLR and PLR in these glioblastoma patients. Neutrophil and CD3+ T-cell infiltration was assessed by immunohistochemical staining of tissue microarray cores from glioblastomas.ResultsPre-treatment NLR levels were significantly correlated with overall survival (OS) in glioblastoma patients (multivariate hazard ratio =1.050; 95 % confidence interval, 1.003–1.100; P = 0.037). Despite the correlation between NLR and PLR (R = 0.509, P < 0.001), NLR was superior to PLR as a prognostic factor. High pre-treatment NLR (≥4 versus < 4) was significantly associated with high neutrophil infiltration and low CD3+ T-cell infiltration into tumors, and predicted poor OS (mean, 10.6 vs. 17.9 months, P < 0.001).ConclusionsPre-treatment NLR is of prognostic significance independent of MGMT status and is superior to PLR as a prognostic factor. Our results demonstrate a correlation between elevated peripheral blood NLR levels and increased tumor neutrophil infiltration/decreased CD3+ T-cell infiltration.

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The Hippo signaling pathway is a critical regulator of organ size control during development, and its deregulation is associated with cancers. Acting downstream of this pathway, Yes-associated protein (YAP) was implicated in tumorigenesis. The present study aimed to explore the expression patterns and clinical significance of YAP in human colorectal cancer (CRC). In addition, we investigated the relationship between YAP expression and Wnt/β-catenin pathway activation in CRC. A total of 139 cases of CRC tissues were investigated by immunohistochemistry for the expression of YAP, cyclin D1, and β-catenin. The association between YAP expression and clinicopathologic features was analyzed. Our results showed that YAP was overexpressed in 52.5 % (73/139) cases of CRC and predominantly presented in the nucleus. There was an excellent correlation between YAP expression and pTNM stage (p = 0.0024). YAP expression in CRC was significantly correlated with nodal status (p = 0.0034), tumor status (p = 0.0382), and cyclin D1 overexpression (p < 0.0001). Importantly, YAP expression was associated with short overall survival (p < 0.001). Furthermore, patients with YAP-positive and nuclear β-catenin-positive profiles had worse overall survival. Univariate and multivariate analyses revealed that YAP expression was an independent prognostic indicator of CRC (p = 0.0207). Our results indicated that YAP overexpression contributed to the tumorigenesis and played a pivotal role in the progression in CRC, and the interaction of YAP and Wnt/β-catenin pathways needs further exploration.

Connexins have long been believed to suppress tumour development during carcinogenesis by exerting gap junctional intercellular communication (GJIC). Although GJIC is abrogated in hepatocellular carcinoma (HCC), connexin32 (Cx32) protein tends to remain expressed in cytoplasm, but not in cell-cell contact areas; thus, it is incapable of forming gap junctions. Hypothesising that cytoplasmic Cx32 protein that has accumulated in HCC should have its proper functions, which are independent of GJIC, we established an inducible expression system of Cx32 in human HuH7 HCC cells, which were unable to support the formation of Cx32-mediated gap junctions, so that Cx32 protein could be overexpressed by doxycycline (Dox) withdrawal. Although the established clone HuH7 Tet-off Cx32 cells exhibited a 4-fold increase in Cx32 expression after Dox withdrawal, none of them were dyecoupled, and Cx32 protein was retained in the Golgi apparatus. However, the proliferation rate of the HuH7 Tet-off Cx32 cells was significantly higher in the Dox-free medium than in the Doxsupplemented one. Transwell assays also revealed that Dox withdrawal enhanced serum-stimulated motility and invasiveness into Matrigel of the HuH7 Tet-off Cx32 cells. Furthermore, when HuH7 Tet-off Cx32 cells were xenografted into the liver of SCID mice, only the mice to which no Dox was administered developed metastatic lesions, indicating that overexpression of cytoplasmic Cx32 protein induced metastasis of HuH7 cells. Our results suggest that, while Cx32-mediated GJIC suppresses the development of HCCs, cytoplasmic Cx32 protein exerts effects favourable for HCC progression, such as invasion and metastasis, once the cells have acquired a malignant phenotype. ' 2007 Wiley-Liss, Inc.

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• DKI is a new and important method. • DKI can provide additional information on microstructural architecture. • Histogram analysis of DKI may be more effective in glioma grading.

Sirtuin 5 (SIRT5), a mitochondrial class III NAD-dependent deacetylase, plays controversial roles in tumorigenesis and chemoresistance. Accordingly, its role in ovarian cancer development and drug resistance is not fully understood. Here, we demonstrate that SIRT5 is increased in ovarian cancer tissues compared to its expression in normal tissues and this predicts a poor response to chemotherapy. SIRT5 levels were also found to be higher in cisplatin-resistant SKOV-3 and CAOV-3 ovarian cancer cells than in cisplatin-sensitive A2780 cells. Furthermore, this protein was revealed to facilitate ovarian cancer cell growth and cisplatin-resistance in vitro . Mechanistically, we show that SIRT5 contributes to cisplatin resistance in ovarian cancer by suppressing cisplatin-induced DNA damage in a reactive oxygen species (ROS)-dependent manner via regulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway.