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Little is known about the mechanisms underlying hepatocellular carcinoma (HCC). Some studies have focused on the role of HCV viral proteins in hepatocyte transformation. In this work we have compiled and analysed current articles regarding the impact of polymorphisms in the HCV core gene and protein on the development of HCC. An exhaustive search for full-text articles until November 2016 in PubMed database was performed using the MeSH keywords: 'hepatitis C', 'polymorphisms', 'core', 'hepatocellular cancer' and 'hepatocarcinogenesis'. Nineteen full-text articles published between 2000 and 2016 were considered. Different articles associate not only the HCC development with polymorphisms at residues 70 and 91 in the core protein, but more with mortality and treatment response. Also, different polymorphisms were found in core and other viral proteins related to HCC development. Eleven articles reported that HCC development is significantly associated with Gln/His70, four associated it with Leu91 and two more associated it with both markers together. Additional studies are necessary, including those in different types of populations worldwide, to validate the possibility of the usability and influence in chronically HCV-infected patients as well as to observe their interaction with other risk factors or prognosis and genetic markers of the host. [ABSTRACT FROM AUTHOR]

Objective: To study the relationship between the release of inflammatory cytokines and mobilization of zinc into liver, and the expression of metallothionein and Zip14 transporter after an abdominal surgery in rats. Materials: Thirty-five male Wistar rats were subjected to experimental surgical stress, then the subgroups of five animals were killed at 3, 6, 9, 12, 16, 20 and 24 h. Matched groups without surgery were used as controls. Methods: Zinc levels were determined by AAS, intracellular zinc by zinquin and dithizone staining. Hepatic metallothionein was assayed by a Cd-saturation method, and IL-1β, IL-6, and TNF-β by immunoassays. Zip14 expression was analyzed by real-time RT-PCR, and protein level by immunohistochemistry and Western blot. Results: Experimental surgery produced a hypozincemia, and the increase of hepatic zinc also produced the release of IL-1β, IL-6 in serum, and the increase of hepatic MT. Histochemistry showed a decrease of free zinc at 3-6 h, but an increase at 9 h (zinquin); meanwhile, total intracellular zinc increased after 9 h (dithizone). RNAm and protein levels of Zip14 were elevated between 6 and 20 h after surgery. Conclusion: Biochemical changes described in this work could be part of the APR, and directed to respond to the damage produced during surgical trauma. [ABSTRACT FROM AUTHOR]

Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumour progression and metastases. Altered expression of glycosidic antigens has been reported in cervical cancer. In cervix premalignant lesions, an increased expression of sialic acid has been reported. In the present study we determined the expression profiles of the glycosidic antigens Tn, sialyl Tn (sTn), Lewis a (Le), sialyl Lewis a (sLe), Lewis x (Le) and sialyl Lewis x (sLe) in cervical scrapes with cytological diagnoses of normal, low-grade squamous intraepithelial lesions (LGSIL) and high-grade squamous intraepithelial lesions (HGSIL). Cervical scrapings were collected to detect tumour antigens expressions by flow cytometry using monoclonal antibodies. Cytometry analysis of Tn, sTn, Le and Le did not reveal differences at the expression level among groups. The number of positive cells to sLe antigen increased in the HGSIL group with respect to the normal group ( p = 0.0495). The number of positive cells to sLe antigen in the samples increased with respect to the grade of squamous intraepithelial lesion (SIL) ( p < 0.001, Mann-Whitney U test). The intensity of expression of this antigen increased in the HGSIL samples with respect to normal samples ( p < 0.0068). sLe antigen could be a candidate to be used as biomarker for the early diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

The level of β-galactoside α2,6sialyltransferase I (ST6Gal I) mRNA, encoded by the gene siat1, is increased in malignant tissues. Expression is regulated by different promoters - P1, P2 and P3 - generating three mRNA isoforms H, X and YZ. In cervical cancer tissue the mRNA isoform H, which results from P1 promoter activity, is increased. To study the regulation of P1 promoter, different constructs from P1 promoter were evaluated by luciferase assays in cervical and hepatic cell lines. Deletion of a fragment of 1048 bp (−89 to +24 bp) increased 5- and 3-fold the promoter activity in C33A and HepG2 cell lines, respectively. The minimal region with promoter activity was a 37 bp fragment in C33A cells. The activity of this region does not require the presence of an initiator sequence. In HepG2 cells the minimal promoter activity was detected in the 66 bp fragment. Sp1 (−32) mutation increased the promoter activity only in HepG2 cells. HNF1 mutation decreased promoter activity in HepG2 cell line but not in C33A cells. We identified a large region that plays a negative regulation role. The regulation of promoter activity is cell type specific. Our study provides new insights into the complex transcriptional regulation of siat1 gene. [ABSTRACT FROM AUTHOR]