Ruthenium complexes have emerged as part of new approaches to cancer therapy and have showed extremely promising results in the development of novel metal anticancer drugs. This study demonstrates that aquation is a crucial activation step for anticancer action of ruthenium(II) polypyridyl complexes to trigger cancer cell apoptosis. The results could provide useful information for fine-tuning the rational design of next-generation metal medicines. More information can be found in the Full Paper by Tianfeng Chen et al. on page 310 in Issue 2, 2016 (DOI: 10.1002/asia.201501048).
Background: Claudins (CLDNs) are a family of closely related transmembrane proteins that have been linked to oncogenic transformation and metastasis across a range of cancers, suggesting that they may be valuable diagnostic and/or prognostic biomarkers that can be used to evaluate patient outcomes. However, CLDN expression patterns associated with colorectal cancer (CRC) remain to be defined. Methods: The mRNA levels of 21 different CLDN family genes were assessed across 20 tumor types using the Oncomine database. Correlations between these genes and patient clinical outcomes, immune cell infiltration, clinicopathological staging, lymph node metastasis, and mutational status were analyzed using the GEPIA, UALCAN, Human Protein Atlas, Tumor Immune Estimation Resource, STRING, Genenetwork, cBioportal, and DAVID databases in an effort to clarify the potential functional roles of different CLDN protein in CRC. Molecular docking analyses were used to probe potential interactions between CLDN4 and TGFβ1. Levels of CLDN4 and CLDN11 mRNA expression in clinical CRC patient samples and in the HT29 and HCT116 cell lines were assessed via qPCR. CLDN4 expression levels in these 2 cell lines were additionally assessed following TGFβ1 inhibitor treatment. Results: These analyses revealed that COAD and READ tissues exhibited the upregulation of CLDN1, CLDN2, CLDN3, CLDN4, CLDN7, and CLDN12 as well as the downregulation of CLDN5 and CLDN11 relative to control tissues. Higher CLDN11 and CLDN14 expression as well as lower CLDN23 mRNA levels were associated with poorer overall survival (OS) outcomes. Moreover, CLDN2 and CLDN3 or CLDN11 mRNA levels were significantly associated with lymph node metastatic progression in COAD or READ lower in COAD and READ tissues. A positive correlation between the expression of CLDN11 and predicted macrophage, dendritic cell, and CD4+ T cell infiltration was identified in CRC, with CLDN12 expression further being positively correlated with CD4+ T cell infiltration whereas a negative correlation was observed between such infiltration and the expression of CLDN3 and CLDN15. A positive correlation between CLDN1, CLDN16, and neutrophil infiltration was additionally detected, whereas neutrophil levels were negatively correlated with the expression of CLDN3 and CLDN15. Molecular docking suggested that CLDN4 was able to directly bind via hydrogen bond with TGFβ1. Relative to paracancerous tissues, clinical CRC tumor tissue samples exhibited CLDN4 and CLDN11 upregulation and downregulation, respectively. LY364947 was able to suppress the expression of CLDN4 in both the HT29 and HCT116 cell lines. Conclusion: Together, these results suggest that the expression of different CLDN family genes is closely associated with CRC tumor clinicopathological staging and immune cell infiltration. Moreover, CLDN4 expression is closely associated with TGFβ1 in CRC, suggesting that it and other CLDN family members may represent viable targets for antitumor therapeutic intervention.
The relationship between matrix metalloproteinase (MMP) polymorphisms and bladder cancer risk has become a hot topic and was studied extensively in recent years, but the results are still controversial. In order to estimate the relationship of MMP polymorphisms and the risk of bladder cancer, we performed this meta-analysis. We conducted a comprehensive search of databases; PubMed, Web of Science, Embase, Chinese Biomedical Literature Database (CBM, Chinese) and Wanfang Database (Chinese) were searched for all case-control studies which mainly study the relationship between MMP-1-1607 1G/2G, MMP-2-1306 C/T, and MMP-9-1562 C/T polymorphisms and the susceptibility of bladder cancer. The association between the MMP polymorphisms and bladder cancer risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). At last, totally five literatures with 1,141 cases and 1,069 controls were contained in the meta-analysis. Among these articles, four articles with 1,103 cases and 1,053 controls were about MMP-1-1607 1G/2G polymorphism and three studies with 839 cases and 775 controls for MMP-2-1306 C/T polymorphism and MMP-9-1562 C/T polymorphism. With regard to MMP-1-1607 1G/2G polymorphism, significant association was found with bladder cancer susceptibility only under recessive model (2G2G vs. 1G2G/1G1G: OR = 1.44, 95% CI = 1.05-1.97, P = 0.022), and as to the MMP-2-1306 C/T polymorphism, significant association was found with bladder cancer susceptibility only under homozygote model (TT vs. CC: OR = 2.10, 95% CI = 1.38-3.10, P = 0), but no associations was found between MMP-9-1562 C/T polymorphism and bladder cancer susceptibility. The results suggest that the MMP-2-1306 C/T and MMP-9-1562 C/T polymorphisms are significantly associated with bladder cancer susceptibility, and no associations were found between MMP-9-1562 C/T polymorphism and bladder cancer susceptibility.
Chamaejasmine is one of the major bioactive components of Stellera chamaejasme L, which is a Chinese traditional herbal medicine that has been used widely in the treatment of cancer. The aim of this study is to investigate the potential effect of chamaejasmine on cervical cancer cells and elucidate the underlying mechanisms of action. We first examined the antitumor activity of chamaejasmine both in vitro and in vivo. In the following experiments with HeLa cells, cell apoptosis and ultrastructure changes were assessed by flow cytometry and transmission electron microscopy, respectively. The effects of chamaejasmine on reactive oxygen species production and mitochondrial membrane potential (Δψm) were examined using 2',7'-dichlorohydrofluorescein and rhodamine-123 staining. The mRNA and protein levels of apoptosis-related proteins were detected by real-time PCR and western blot. The activity of caspases 3, 8, and 9 was measured using the corresponding assay kit. The effect of chamaejasmine on the phosphoinositide 3-kinase (PI3K)/Akt pathway was evaluated by luciferase assay and western blot, and further confirmed in Akt overexpressing HeLa cells. We found that chamaejasmine has potent antitumor effects on cervical cancer cell lines both in vitro and in vivo. Mechanistic studies showed that chamaejasmine could induce apoptosis in HeLa cells, and this apoptosis-inducing effect may be mediated through the suppression of PI3K/Akt signaling cascades. These findings not only indicate the therapeutic potential of chamaejasmine for cervical cancer, but provide valuable insight into its mechanism of action.
This article studies meromorphic functions that share three values CM.By using the group of functions,we prove a uniqueness theorem,which generalizes the results of G.Brosch,H.Ueda,etc.
Objective
To observe the effect of lncRNA DIGIT on vascular endothelial cell tube formation.
Methods
Human microvascular endothelial cells (HMEC-1) were cultured in vitro. The changes of tubes/nucleus ratio were observed by microscope. The expression of mRNA and protein was detected by real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) and Western blotting. The DIGIT expression in human microvascular endothelial HMEC-1 cells was silenced by DIGIT transfection with shRNAs targeting. The effects of DIGIT silencing on cell vitality (Typan Blue Staining Cell Viability Assay Kit), migration ability (Trans-Well method), apoptosis [Annexin V-fluoresceine isothiocyanate (FITC) apoptosis detection method] and tube formation ability (microscope mapping method) were observed. The effects of DIGIT silencing on cell viability, migration, apoptosis and tube formation were then assessed.
Results
HMEC-1 cells were cultured for 24 h. The ratio of tubes/nucleus was increased with the time prolonged. The mRNA levels of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), CD144, and endothelial nitric oxide synthase (eNOS) were all significantly up-regulated (F=11.813, 10.336, 13.201, 10.125, P<0.01), and all these four angiogenesis-associated proteins accumulated with the prolonged time. Cell viability (80.29±4.68)% vs. (62.50±4.78)%, migration capacity (99.65±3.07)% vs. (37.53±2.78)%, and tubes/nucleus ratio (0.691±0.060) vs. (0.192±0.020) were all significantly reduced in sh-DIGIT group when compared with sh-NC group (F=20.386, 33.573, 13.471, P< 0.01). DIGIT silencing down-regulated the levels of B cell lymphoma/leukemia-2 (bcl-2), VEGF, VEGFR2, CD144 and eNOS, up-regulated bcl-2 associated X protein (bax), and activated cysteinyl aspartate-specific protease (Caspase)-3 and Caspase-9 expression.
Conclusion
LncRNA DIGIT plays an important role in promoting growth, migration and tubule formation in endothelial cells, and DIGIT may be effective molecular targets for the treatment of atherosclerosis.
Key words:
Divergent to GSC; Atherosclerosis; Vascular endothelial cell; Long non-coding RNA
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