Expression of c-MET Protein in Various Subtypes of Hepatocellular Adenoma Compared to Hepatocellular Carcinoma and Non-Neoplastic Liver in Human Tissue.

Hepatocellular adenoma (HA) is a benign neoplasm of the liver, whose aetiopathogenesis is little known. Newest research allowed dividing all cases into three types based on molecular characteristics: inflammatory HA, HA with HNF1A mutation, ß-catenin-mutated HA. The clinical significance of HA is chiefly due to the possibility of malignant transformation into hepatocellular carcinoma (HCC). The aim of the present study was to immunohistochemically assess the expression pattern and level of c-MET protein in hepatocellular adenoma (taking into account its status of Wnt/ß-catenin pathway functioning) and intertwining the results into a wider pattern of expression in non-neoplastic liver and hepatocellular carcinoma of various histological grades. It was found that expression of c-MET in poorly-differentiated HCC was significantly higher than in non-neoplastic liver and well- to moderately-differentiated HCC. The expression in HA was variable and differed between molecular subtypes of this neoplasm: inflammatory and HNF1A mutation-associated type are characterized by overexpression of c-MET to an extent comparable with poorly-differentiated HCC, whereas Wnt/ß-catenin dysfunction-associated type lacks overexpression, and the amount of c-MET protein accumulated in its cells is similar to the levels in non-neoplastic tissue and well- to moderately-differentiated HCC. These findings suggest that c-MET overexpression in HA is not an early event in hepatocarcinogenesis, but constitutes a divergent molecular pathway leading to neoplastic change compared to overexpression observed in the late stages of tumour progression.

Comparison of Subtypes of Hepatocellular Adenoma to Hepatocellular Carcinoma and Non-Neoplastic Liver Tissue in Terms of PTEN Expression.

PTEN is a tumour suppressor gene whose loss of function has been found to be present in a variety of neoplasms, both benign and malignant. In hepatocellular carcinoma (HCC), loss of PTEN is associated with poorly differentiated cancer, advanced clinical stage and tendency to recur. The extent and meaning of PTEN loss in hepatocellular adenoma (HA), one of the precursor lesions for HCC, has not yet been analysed. The aim of the present study was to evaluate the possible loss of PTEN expression in HA in the wider context of hepatocarcinogenesis. Immunohistochemical analysis of PTEN expression was performed in non-neoplastic liver tissue, HAs and HCCs. It has been found that the loss of PTEN was markedly present in poorly differentiated HCC, whereas well to moderately differentiated HCC showed similar levels of PTEN expression to nonneoplastic liver. HAs presented as a heterogeneous group, with loss of PTEN observed in the inflammatory and HNF1A-mutated subtype and relatively intact PTEN expression in HA with nuclear ß-catenin overexpression. This suggests that the loss of PTEN might occur both in HA and HCC, constituting different outcomes of the same molecular lesion in the various contexts of malignant or benign neoplasms.

Axillary vein spasm during cardiac implantable electronic device implantation.

BACKGROUND: The technique of axillary vein (AV) or subclavian vein (SV) puncture has become an important alternative to cephalic vein (CV) cutdown as an approach allowing cardiac lead introduction into the venous system during cardiac implantable electronic device (CIED) implantation procedures. Irrespective of the technique used, the injury associated with lead insertion may induce a reflex venous spasm that can even cause total venous obstruction. In order to assess the incidence of AV spasm during AV puncture, we analysed a total of 735 (382 in females and 353 in males; mean age 75 ± 11 years) de novo CIED implantation procedures involving transvenous lead insertion conducted between January 2014 and December 2015. MATERIALS AND METHODS: In 337 patients the leads were introduced via AV puncture only, in 66 patients AV puncture was used in combination with CV cutdown, together yielding a total of 403 procedures (55% of all de novo CIED implantation procedures; mean patient age 72 ± 14 years), out of which we observed 12 cases (mean patient age 57 ± 25 years) of AV spasm (3%). RESULTS: We evaluated only the procedures with unambiguous fluoroscopy images recorded during AV puncture: complete blockage of contrast medium flow through the AV, with preserved flow through the CV or collateral vessels, followed by eventually resumed flow of contrast via the AV. The contrast-enhanced movements of AV walls showed the spasm propagating both proximally and distally along the vessel, while the subsequent vessel wall relaxation occurred along the entire spasm-affected venous segment simultaneously. CONCLUSIONS: An AV spasm induced by AV puncture during CIED implantation is a rare phenomenon; however, if severe, it may significantly affect the course of the procedure.

Inflammation increases oxidative DNA damage repair and stimulates preneoplastic changes in colons of newborn rats.

Oxidative DNA damage may be a risk factor for development of various pathologies, including malignancy. We studied inflammation triggered modulation of repair activity in the intestines of three weeks old rats injected i.p. with E.coli or S. typhimurium lipopolysaccharides (LPS) at doses of 1, 5 or 10 mg/kg. Subsequent formation in these animals of colonic preneoplastic lesions, aberrant crypt foci (ACF) was also investigated. Five days after LPS administration no differences were observed in repair rate of 1,N(6)-ethenoadenine (εA), 3,N(4)-ethenocytosine (εC) and 8-oxoguanine (8-oxoG) in intestines of these rats, as measured by the nicking assay. However a significant increase in all three repair activities was found within one and two months after S. typhimurium LPS treatment. E. coli LPS significantly increased only the 8-oxoG repair. S. typhimurium LPS stimulated mRNA transcription of pro-inflammatory proteins, lipooxygenase-12 and cyclooxygenase-2, as well as some DNA repair enzymes like AP-endonuclease (Ape1) and εC-glycosylase (Tdg). mRNA level of DNA glycosylases excising εA (MPG) and 8-oxoG (OGG1) was also increased by LPS treatment, but only at the highest dose. Transcription of all enzymes increased for up to 30 days after LPS, and subsequently decreased to the level observed before treatment, with the exception of APE1, which remained elevated even two months after LPS administration. Thus, the repair efficiency of εA, εC and 8-oxoG depends on the availability of APE1, which increases OGG1 and TDG turnover on damaged DNA, and presumably stimulates MPG. One and two months after administration of E. coli or S. typhimurium LPS, the number of aberrant crypt foci in rat colons increased in a dose and time dependent manner. Thus, inflammation stimulates the repair capacity for εA, εC and 8-oxoG, but simultaneously triggers the appearance of preneoplastic changes in the colons. This may be due to increased oxidative stress and imbalance in DNA repair.

CD55, CD59, factor H and factor H-like 1 gene expression analysis in tumors of the ovary and corpus uteri origin.

The expression level of complement regulators in ovarian and corpus uteri tumors was not fully established so far. In current manuscript we performed gene expression analysis by the real-time PCR approach to investigate both membrane bound - CD55 and CD59 and fluid phase - factor H and factor H-like 1 complement regulators. We found increased CD55 expression in corpus uteri tumors when compared to control tissues, whereas in ovarian cancer CD55 expression was lower than in control sections. Additionally we found CD59 expression to be more prominent in ovarian cancer than in corpus uteri tumor samples. We observed also the strong positive correlation between the level of expression of the whole group of regulators, which was particularly significant between the expression of factor H and factor H- like 1. In conclusion we present novel results which implicates different role of particular complement inhibitors in the regulation of the complement system in two cancer types examined. Strong positive correlation between examined proteins implicates similar pattern of the regulation which should be taken into consideration with regards to the possible immunotherapy applied as adjuvant therapeutic approach in these two indications. The inhibition of complement regulation may serve as a strategy to potentiate the efficacy of such treatment.