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Aim: To investigate the association and prognostic value of ANKZF1 gene for survival in colorectal cancer, the mechanism of ANKZF1 level alteration and correlated signaling pathways ANKZF1 is involved. Patients & methods: The Cancer Genome Atlas COREAD dataset was analyzed by bioinformatical investigation. Results: High ANKZF1 expression is associated with poor overall survival (hazard ratio [HR]: 2.094; 95% CI: 1.188-3.689; p = 0.011) and recurrence-free survival (HR: 1.762; 95% CI: 1.021-3.042; p = 0.042) in colon cancer. Bioinformatical analysis showed ANKZF1 was upregulated by amplification and exon expression. ANKZF1 was associated with angiogenesis and cancer signaling pathways. Conclusion: High ANKZF1 is an independent factor of poor survival (overall survival and recurrence-free survival) in colon cancer by taking part in angiogenesis and some cancer signaling pathways. [ABSTRACT FROM AUTHOR]

To identify invasion-associated genes in extranodal natural killer (NK)/T-cell lymphoma, we performed microarray analysis on seven tumor samples and two control pools (composed of normal NK cells and T cells, tonsil and spleen) using Affymetrix GeneChip. Compared with all control pools, 59 uniquely expressed genes were discovered in the tumor samples. Overexpressed genes related to proteolysis, cell motility and chemotaxis, including CTSL, uPAR, TIMP-1, CXCL9, CXCL11 and DEFB1, were identified. Comparing the gene expression profiles of five upper aerodigestive tract (UAT) cases with two non-UAT cases, we found some overexpressed genes in non-UAT cases related to proteolysis and cell adhesion function, including matrix metalloproteinase 9 (MMP-9). Immunohistochemistry detection was performed on 34 paraffin sections to evaluate the expression of selected genes. A correlation of urokinase-type plasminogen activator receptor (uPAR) expression with MMP-9 expression was revealed. Analysis of prognosis demonstrated that expressions of MMP-2 and MMP-9 were closely correlated with a poor prognosis. These invasion-associated genes may become targets for diagnostic and therapeutic procedures. [ABSTRACT FROM AUTHOR]

The surface marker PROM1 is considered one of the most important marker of tumor-initiating cells, and its high expression is believed to be an adverse prognostic factor in gliomas, medulloblastoma and in other malignancies. The aims of our research were to explore the expression profile of the PROM1 in non-small cell lung cancer (NSCLC) and to assess its possible role as a prognostic factor. The protein expression profiles were determined via immunohistochemical staining assay. The clinical prognostic values of protein expression were investigated with univariate and multivariate survival analysis. The quantitative variable PROM1 expression was dichotomized according to the best cutoff value obtained by the receiver operating characteristics (ROC) analysis. The protein level of PROM1 of NSCLC was higher compared with normal tissues, and the survival analysis demonstrated the positive membrane expression and combination of membrane/cytoplasm groups of PROM1 had worse prognosis than those negative expression groups. Also, multivariate Cox regression analysis showed membrane expression of PROM1 and lymph node invasion were the independent prognostic factors. The expression of PROM1 was significantly higher than normal tissue, and high levels of PROM1 membrane expression and combination of membrane/cytoplasm expression were associated with adverse prognosis.

Background/aims: The aim of this study was to investigate the association of human epidermal growth factor receptor 2 (HER2) expression with clinicopathological characteristics of resectable gastric cancer patients., Methodology: A total of 394 stage I-III surgical gastric cancer patients who were detected of immunohistochemical (IHC) HER2 expression postoperatively were included in this retrospective study. Association of IHC HER2 over-expression (3+) rate with clinicopathological characteristics was tested by univariate and multivariate analyses., Results: IHC HER2 over-expression rate was 5.1% (95% CI 3.1%-7.7%). By univariate analyses, none of the clinicopathological characteristics was associated with the IHC HER2 over-expression compared to negative expression (0/1+) (p>0.05), with the exception of a higher rate (12.2%) of IHC HER2 (3+) in moderate differentiation subset (p=0.02). However, the multivariate analyses didn’t selected any characteristic as an independent risk factor of IHC HER2 over-expression or the combination of IHC HER2 (2/3+)., Conclusions: IHC HER2 over-expression rate is relatively low among stage I-III gastric cancer patients, and might be generally not associated with clinicopathological characteristics.

A network tubular system is an important structure in the body and organ of metazoa. The lumen of tube is fundamental units in the structure, which serve to transport material, divide the organ into different functional compartments and separate the organ from the environment. The defects of lumen formation will lead to abnormalities of the organ morphogenesis and disorder of the function. Zebrafish (Danio rerio)is an important model for development research. Meanwhile easy observation of tubular organ, the relevant mutants, and transgene linages make zebrafish to become an excellent model to study the formation of lumen in the tubular organs, including the blood vessels, neural tube, gut, exocrine pancreas, and pronephric duct, which undergo the typical morphogenesis of lumen that is involved in the organs' development. The process of lumen formation is mainly consisted of induction of extracellular signals, polarization of epithelial cell, directional transportation in the polar cells, the aggregation and transportation of fluid in the lumen, and the reconstruction of cytoskeleton in polar cells and controlled by the precise and complicated molecular networks during embryonic development. This review will summarize our current knowledge on lumen morphogenesis in four kinds of typical tubular organs during zebrafish embryonic development and the related molecular mechanisms as well as to supply helpful reference to the future studies.

During zebrafish gastrulation, large cellular rearrangements create the formation of the three germ layers, ectoderm, mesoderm, and endoderm. This process includes three types of conserved morphogenetic movement: epiboly, involution, and convergent extension. Specially, the anterior movement of prechordal plate progenitors is essential for the location and differentiation of mesendoderm progenitors, and the pechordal plate progenitors'coherent migration is thought to be a good model to study the mechanism of cell movement in vivo. Gastrulation migration is known to be controlled by many signaling pathways such as Wnt/planar cell polarity signaling; however, the underlying molecular mechanism for cellular behavior remains unknown. At present, it is generally agree that cell adhesion and cytoskeletal rearrangement are critical factors during zebrafish gastrulation cell migration. In addition, the role of extraembryonic tissue (yolk syncytial layer) during gastrulation is concerned increasingly. Here, we described the essential factors for controlling cellular behaviors and highlighted the major issues and questions that require further investigation during zebra fish gastrular cell migration in order to provide a complete map containing all the factors for regulating gastrulation cell migration and their interactions on a cellular level.

Background/aims: To evaluate the correlation between the expression of stem cell makers and prognosis in colorectal cancer., Methodology: Eligible studies evaluating the correlation between stem cell makers and prognosis were selected based on the references in PubMed, Embase and Cochrane libraries. Outcome measures included overall survival, relevant pathological parameters. Meta-analyses were performed by RevMan 5.0., Results: Seventeen eligible articles involving 3098 patients were included. Meta-analysis showed CD44 expression is not significant difference of 5-year overall survival rate (OR=0.69, p=0.22) and relevant clinical parameters, such as histological grade (OR=1.98, p=0.06), dukes grade (OR=0.77, p=0.43) and metastasis (OR=1.03, p=0.89). Likewise, there is no correlation between CD44v6 and dukes stage (OR=0.56, p=0.23), metastasis (OR= 2.81, p=0.33), except for histological grade (OR=0.48, p=0.02). However, CD44v6 positive cells (OR=0.36, p=0.02) were significantly associated with poor overall survival., Conclusions: Based on current retrospective evidence, a stem cell maker, CD44 cannot become a prognostic marker in colorectal cancer. In contrast, CD44v6, an isoform of CD44 plays a significant role to predict clinic outcome.

Objective: To study the expression and clinical significance of AKT2, phosphorylated AKT2 (p-AKT2) in non-small cell lung cancer (NSCLC)., Methods: The tumor tissues were obtained from 137 cases of NSCLC, the expressions of AKT2 and p-AKT2 in the tissues were measured by immunohistochemistry. The statistic analysis was carried on to study the correlation of AKT2, p-AKT2 expression to the type of lung cancer, TNM stage, pathological grading. Survival analysis was also studied., Results: The positive rates of AKT2 in lung adenocarcinoma and squamous carcinoma were 60.5% and 54.1% respectively (P > 0.05). While the positive rates of p-AKT2 in lung adenocarcinoma and squamous carcinoma were 68.4% and 47.5% (P < 0.05). The expressions of AKT2 and p-AKT2 were not correlated with age, gender, TNM stage and cell differentiation degree. Further more, survival analysis revealed that 5-year survival rate and median survival time for the patients with positive expression of p-AKT2 were significantly poorer than those with negative expression (20% vs 56%, (28.464 +/- 2.235) months vs (39.214 +/- 3.075) months, P < 0.053, while there were no significant differences with regard to AKT2 expression., Conclusion: The positive expression of p-AKT2 in lung adenocarcinoma was higher than that in lung squamous carcinomas. p-AKT2 may be a prognostic factor for non-small cell lung cancer.

Objective: To study the co-expression and prognostic significance of hnRNP B1 and CD44 in non-small cell lung cancers (NSCLC)., Methods: The co-expressions of CD44 and hnRNP B1 in the tissues from 88 cases of NSCLC were measured by immunohistochemistry. The relationship between the expressions and the prognosis of NSCLC was analysed., Results: The NSCLC had a high expression of hnRNP B1 (68.18%) and CD44 (52.27%). The cells had the longest average life [(59.607 +/- 4.092) months] in the conditions of high expressed hnRNP B1 and low expressed CD44, and shortest average life [(21.357 +/- 3.545) months] in the conditions of low expressed hnRNP B1 and high expressed CD44., Conclusion: Combined detection of hnRNP B1 and CD44 can help forecast the prognosis of NSCLC.

Objective: To study the expression of CD133, CD34 and CD44 in lung cancer, and distribution of cell subpopulations that generated by combination of different markers., Methods: By collecting 10 normal lung tissues and 40 lung cancer fresh samples that were diagnosed pathologically, preparing single cell suspension, and labelling cells with CD133, CD34, CD44, CD117, CD43, CD45 and LIN(CD2, CD3, CD31, CD64) monoclone antibodies, we analyzed the distribution of the above-mentioned antibodies in lung cancer cells on FCM. By double-parameters plots, we analyzed the naive cell subpopulations that were generated through combination of positive and negative antigen expression., Results: In lung cancer parenchymal-cells (LIN- CD45-) expressed CD133, CD34 and CD44 dim positive and, expressed CD117 and CD43 negative. The mann-Whitney rank test results shows that there was no significant difference for the expression of CD133, CD34, CD44 between lung cancer and normal lung tissue, and CD44+, CD133- CD34-, CD133+ CD44+, CD133+ CD44-, CD133+ CD34+, CD133- CD34+ and CD133- CD44+ expressed differently (P < 0.05) between lung adenocarcinoma and lung squamous cell carcinoma. The cluster analysis results suggest that they are classified to 4 subsets., Conclusion: CD133, CD34, CD44 could be the marker of lung cancer naive cells, which could contribute to study lung cancer cell development.

The transcription factor NF-kappaB plays an important role in both physiological and pathological events in the central nervous system. Nevertheless, the mechanisms of NF-kappaB-mediated regulation of gene expression, and the signaling molecules participating in the NF-kappaB pathway in the central nervous system are, to date, poorly understood. To identify such molecules, we conducted a yeast two-hybrid screen of a human brain cDNA library using NIK as bait. As a result, we identified a novel NIK and IKK(beta) binding protein designated NIBP that is mainly expressed in brain, muscle, heart, and kidney. Interestingly, low levels of expression were detected in immune tissues such as spleen, thymus, and peripheral blood leukocytes, where NF-kappaB is known to modulate immune function. We demonstrated by immunohistochemistry that NIBP expression in the brain is localized to neurons. NIBP physically interacts with NIK, IKK(beta), but not IKK(alpha) or IKK(gamma). NIBP overexpression potentiates tumor necrosis factor-alpha-induced NF-kappaB activation through increased phosphorylation of the IKK complex and its downstream I(kappa)B(alpha) and p65 substrates. Finally, knockdown of NIBP expression by small interfering RNA reduces tumor necrosis factor-alpha-induced NF-kappaB activation, prevents nerve growth factor-induced neuronal differentiation, and decreases Bcl-xL gene expression in PC12 cells. Our data demonstrate that NIBP, by interacting with NIK and IKK(beta), is a new enhancer of the cytokine-induced NF-(kappa)B signaling pathway. Because of its neuronal expression, we propose that NIBP may be a potential target for modulating the NF-(kappa)B signaling cascade in neuronal pathologies dependent upon abnormal activation of this pathway.

NF-kappaB-inducing kinase (NIK) has been implicated as an essential component of NF-kappaB activation. However, the regulatory mechanism of NIK signaling remains elusive. We have identified a novel NIK interacting protein, TNAP (for TRAFs and NIK-associated protein). In mammalian cells, TNAP physically interacts with NIK, TRAF2, and TRAF3 but not IKK1 or IKK2. TNAP specifically inhibits NF-kappaB activation induced by tumor necrosis factor (TNF)-alpha, TNF receptor 1, TRADD, RIP, TRAF2, and NIK but does not affect IKK1- and IKK2-mediated NF-kappaB activation. Knockdown of TNAP by lentiviral-mediated small interference RNA potentiates TNF-alpha-induced NF-kappaB activation. TNAP suppresses NIK kinase activity and subsequently reduces p100 processing, p65 phosphorylation, and IkappaBalpha degradation. These data suggest that TNAP is a repressor of NIK activity and regulates both the classical and alternative NF-kappaB signaling pathways.