Terlipressin has been used extensively in the management of certain complications associated with end-stage liver diseases (ESLDs). In our pilot study, terlipressin treatment showed beneficial effects on liver function in patients with decompensated cirrhosis, however whether it plays a role in liver ischemia-reperfusion injury (IRI) remains unknown. Using a mouse nonlethal hepatic IR model, we found terlipressin administration significantly ameliorated IR-induced liver apoptosis, necrosis and inflammation. Furthermore, despite its known effect on visceral vasoconstriction, hemodynamic evaluation of murine hepatic tissue after IR revealed no change of overall hepatic blood flow after terlipressin treatment. Further studies identified the upregulation of vasopressin receptor 1 (V1R) expression on hepatocytes upon IR. In isolated hepatocyte hypoxia/reoxygenation model, the active component of terlipressin, lysine vasopressin, conferred hepatocytes resistant to oxidative stress-induced apoptosis. Mechanistic studies revealed the V1R engagement activated the Wnt/β-catenin/FoxO3a/AKT pathway, which subsequently circumvented the proapoptotic events, thus ameliorated hepatocyte apoptosis. Furthermore, genetic knockdown of V1R expression in hepatocyte cell lines or blockade of this signaling pathway abrogated such protective effect. Conclusion: These data highlight the functional importance of the hepatocyte V1R/Wnt/β-catenin/FoxO3a/AKT pathway in protecting liver from oxidative stress-induced injury.
The ERCC1 enzyme in the nucleotide excision repair (NER) pathway plays a vital role in DNA repair. Numerous epidemiological studies have evaluated the association between ERCC1 polymorphisms and the risk of colorectal cancer (CRC), with conflicting results. To evaluate the potential associations, we conducted a meta-analysis. Eligible studies were identified by searching electronic databases. The odds ratio (OR) and 95% confidence interval (CI) were applied to assess the associations between ERCC1 polymorphisms and CRC risk. The meta-analysis results revealed significant associations between ERCC1 rs3212986 and rs2298881 polymorphisms and CRC risk (rs3212986 GG vs CC: OR = 1.66, 95% CI = 1.13-2.44; CG vs CC: OR = 1.12, 95% CI = 0.82-1.55; the dominant model: OR = 1.21, 95% CI = 0.86-1.71; the recessive model: OR = 1.59, 95% CI = 1.09-2.31; rs2298881 CC vs. AA: OR = 2.04, 95% CI = 1.29-3.23; AC vs. AA: OR = 1.19, 95% CI = 0.91-1.56; the dominant model: OR = 1.33, 95% CI = 1.04-1.72; the recessive model: OR = 1.91, 95% CI = 1.22-3.00). However, no association with CRC risk was identified for ERCC1 polymorphisms rs11615 and rs2276466. In conclusion, these findings identified no association between rs11615 and rs2276466 polymorphisms and CRC susceptibility, but the data indicate that ERCC1 rs3212986 and rs2298881 polymorphisms may increase susceptibility to CRC. Large and well-designed studies are needed to further validate our findings.
Long noncoding RNAs (lncRNAs) are nonprotein coding transcripts longer than 200 nucleotides. Aberrant expression of lncRNAs has been found to be associated with hepatocellular carcinoma, one of the most malignant tumors. In this paper, we give a systematic and comprehensive review of existing literature about the involvement of lncRNAs in hepatocellular carcinoma. To date, evidence suggests that a number of lncRNAs, including HEIH, H19, HOTAIR, MALAT1, and PVT1, may regulate the transcription of target genes by recruiting histone-modifying complexes. Under certain circumstances, lncRNAs form RNA-dsDNA triplexes. Certain lncRNAs, such as HULC, HOTAIR, H19, HOTTIP and PTENP1, exhibit their biological roles by associating with microRNAs (miRNAs). In addition, by complementary base pairing with mRNAs or forming complexes with RNA binding proteins (RBPs), lncRNA-ATB, MALAT1 and PCNA-AS1 may mediate mRNA stability and splicing. In conclusion, interactions with DNA, RNA and proteins appears to be involved in lncRNAs' participation in tumorigenesis and developmental processes related to hepatocellular carcinoma.
Open Life Sci. 2016; 11: 110-115 invasion and metastases. These characteristics are results of genetic deregulation. Accumulation of genetic mutations results in increasingly aggressive phenotypes [5]. E-cadherin in Breast Cancer Structure and Functions of E-CadherinThe CDH1 gene is located on human chromosome 16q22.1 and encodes for the E-cadherin protein [6]. The E-cadherin glycoprotein is composed of three major structural domains: a single transmembrane domain, connected with a cytoplasmic domain, and an extracellular domain comprising five tandemly repeated domains called EC1-EC5, which are exclusive to cadherins [7]. The extracellular domain of E-cadherin is essential for cell to cell adhesion, as well as for the correct folding and homo/hetero dimerisation of the proteins. The cytoplasmic domain of E-cadherin interacts with the catenins (α-, β-, γ-and p120 catenin) anchored to the actin cytoskeleton, establishing cadherin-catenin complexes [8]. Conformation of E-cadherin is only stable upon Ca 2+ binding to its highly conserved, negatively charged extracellular motifs [9]. Its stabilization at the cell membrane and accurate function occur by association to cytoplasmic p120-catenin [10]. E-cadherin forms adherens junction with its binding partner β-catenin and actin filaments. This complex is critical to inhibit individual epithelial cell motility and to provide homeostatic tissue architecture [11,12] (Figure 1). Signaling Pathways Regulated by E-CadherinIn addition to its role in cell to cell adhesion, E-cadherin is involved in a number of signaling pathways in carcinogenesis [13]. For the Wnt/β-catenin pathway, free β-catenins may accumulate in the cytoplasm attributed Abstract: Breast cancer is the most prevalent cancer in women worldwide. Numerous studies have suggested that the E-cadherin adhesion system is dysregulated in cancer cells. These impaired functions of E-cadherin contribute to releasing cancer cells from the primary lesion to cell dedifferentiation. Some studies have shown that polymorphism may affect E-cadherin expression, and then play a role in susceptibility to breast cancer. However, the results remained controversial. In this short review, we summarize the functions of E-cadherin and the signaling pathways it regulates, and assess the association between CDH1 polymorphisms and breast cancer susceptibility. This study suggests that genetic variation in CDH1 and -160C/A polymorphism may have an association with breast cancer risk. The assessment of CDH1 polymorphisms may be used for the identification of patients suitable for anti-CDH1 therapy.
Overall response rate, stable disease, and progressive disease, as well as 1-year survival rate in patients who received GEM + CIS, were superior to those treated with GEM alone. Combination chemotherapy with GEM and CIS may offer greater benefits in the treatment of pancreatic cancer than that of GEM alone although the combination group had higher hematological toxicities.
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