Precision cut tissue slices of the liver as morphological tool for investigation of apoptosis.

Background: Apoptosis, programmed cell death, is involved in a broad range of pathological processes. Dysregulation of apoptosis plays a key role in the pathogenesis of hepatitis, toxic liver disease and also liver tumor development. For the study of apoptosis in liver diseases, different in vivo models and different in vitro approaches have been developed.

Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade--results of an explorative CGH meta-analysis.

All available comparative genomic hybridisation (CGH) analyses (n=31, until 12/2003) of human hepatocellular carcinomas (HCCs; n=785) and premalignant dysplastic nodules (DNs; n=30) were compiled and correlated with clinical and histological parameters. The most prominent amplifications of genomic material were present in 1q (57.1%), 8q (46.

Characterization of metaplastic and heterotopic epithelia in the human gastrointestinal tract by the expression pattern of acyl-CoA synthetase 5.

Metaplastic and heterotopic epithelia are frequently found in the human intestine. The recently cloned human acyl-CoA synthetase 5 (ACS5) is a key enzyme in providing cytosolic acyl-CoA thioesters. The aim of the study was to identify and to locate the expression of ACS5 in the gastric body and the small intestine with metaplasia or heterotopia by different methods.

Mixed hepatoblastoma in an adult.

We report a case in an elderly adult of a highly malignant liver tumor with blastoid features that resembled hepatoblastoma. A liver tumor with a diameter of 23 cm was removed in a 78-year-old woman. The tumor showed highly differentiated epithelial hepatocellular and poorly differentiated epithelial and mesenchymal components.

Liver-specific expression of interferon gamma following adenoviral gene transfer controls hepatitis B virus replication in mice.

Interferons control viral replication and the growth of some malignant tumors. Since systemic application may cause severe adverse effects, tissue-specific expression is an attractive alternative. Liver-directed interferon gene therapy offers promising applications such as chronic viral hepatitis B or C or hepatocellular carcinoma and thus needs testing in vivo in suitable animal models.

Acute hepatitis induced by an Aloe vera preparation: a case report.

Aim: Aloe vera, plant extracts of Aloe barbadensis miller, is widely used in phytomedicine. The first case of acute hepatitis due to this compound was described.

Methods: Description of a clinical case.

Pancreatic metastasis from gastric carcinoma: a case report.

Background: The pancreas is a rare but occasionally favored target for metastasis. Metastatic lesions in the pancreas have been described for various primary cancers, such as carcinomas of the lung, the breast, renal cell carcinoma and sarcomas.

Case Presentation: We report the case of a 60-year old female with a mass in the pancreatic head four years after partial gastrectomy for gastric adenocarcinoma.

Factors of transforming growth factor beta signalling are co-regulated in human hepatocellular carcinoma.

Transforming growth factor beta (TGFbeta) is a central mitoinhibitory factor for epithelial cells, and alterations of TGFbeta signalling have been demonstrated in many different human cancers. We have analysed human hepatocellular carcinomas (HCCs) for potential pro-tumourigenic alterations in regard to expression of Smad4 and mutations and expression changes of the pro-oncogenic transcriptional co-repressors Ski and SnoN, as well as mRNA levels of matrix metalloproteinase-2 (MMP2), which is transcriptionally regulated by TGFbeta. Smad4 mRNA was detected in all HCCs; while, using immunohistology, loss of Smad4 expression was found in 10% of HCCs.

Molecular profiling of human hepatocellular carcinoma defines mutually exclusive interferon regulation and insulin-like growth factor II overexpression.

Molecular subtyping of human hepatocellular carcinoma (HCC) with potential mechanistic and therapeutic impact has not been achieved thus far. We have analyzed the mRNA expression patterns of 43 different human HCC samples and 3 HCC cell lines in comparison with normal adult liver using high-density cDNA microarrays. Two main groups of HCC, designated group A (65%) and group B (35%), were distinguished based on clustering of the most highly varying genes.

Acute liver failure in a renal transplant patient caused by adenoviral hepatitis superimposed on a fibrosing cholestatic hepatitis B.

We report the first case of fulminant liver failure due to necrotizing adenovirus hepatitis superimposed on a fibrosing cholestatic hepatitis B in an immunosuppressed patient after renal transplantation. Diagnosis was made in vivo by liver biopsy and confirmed at autopsy.

Oxidative damage is increased in human liver tissue adjacent to hepatocellular carcinoma.

Accumulation of genetic alterations in hepatocarcinogenesis is closely associated with chronic inflammatory liver disease. 8-oxo-2'-deoxyguanosine (8-oxo-dG), the major promutagenic DNA adduct caused by reactive oxygen species (ROS), leads to G:C --> T:A transversions. These lesions can be enzymatically repaired mainly by human MutT homolog 1 (hMTH1), human 8-oxo-guanine DNA glycosylase (hOGG1) and human MutY homolog (hMYH).

Autocrine inhibition of chemotherapy response in human liver tumor cells by insulin-like growth factor-II.

Insulin-like Growth Factor (IGF)-II is frequently overexpressed in experimental and human hepatocellular carcinomas (HCCs) and has been correlated with increased tumor growth. We have analyzed, whether IGF-II affects chemotherapy response and apoptosis in human liver tumor cells. Three liver tumor cell lines highly expressed IGF-II and supported their growth in an autocrine manner by secreting excessive amounts of IGF-II.

Cyclooxygenase-2 inhibitors suppress the growth of human hepatocellular carcinoma implants in nude mice.

Cyclooxygenase (COX)-2 is expressed in hepatocellular carcinomas (HCCs) and HCC cell lines. COX-2 inhibition strongly suppresses growth of HCC cells in vitro by inducing apoptosis and reducing proliferation. Here, we evaluate the in vivo effects and mechanism of COX-2 inhibition of human HCC cell line derived xenotransplanted tumors in nude mice.

Beta-catenin accumulation in the progression of human hepatocarcinogenesis correlates with loss of E-cadherin and accumulation of p53, but not with expression of conventional WNT-1 target genes.

Beta-catenin integrates intracellular WNT signalling and the intercellular E-cadherin-catenin adhesion system. To date, little is known about the role of beta-catenin activation and nuclear accumulation in hepatocarcinogenesis. This study has analysed beta-catenin expression patterns in human dysplastic nodules (DNs), as well as in hepatocellular carcinomas (HCCs) in comparison with proliferation, expression of WNT-1 target genes, E-cadherin, and p53.

Modulation of MUC1 and blood group antigen expression in gastric adenocarcinoma cells by cytokines.

Immunohistological studies demonstrated that MUC1 expression in gastric cancer is associated with a poor prognosis. As a mediator of cell-cell interactions, MUC1 may also be involved in metastasis. However, these aspects are of relevance since cytokine levels are locally increased as a consequence of peritumorous inflammatory response and coexisting chronic gastritis.

[Evaluation of her-2/neu amplification/overexpression in OSCC with fluorescence in situ hybridization (FISH) and immunohistochemistry].

Introduction: The human epidermal growth factor receptor ( her-2/ neu) protooncogene encodes a membrane tyrosine kinase with homology to the epidermal growth factor receptor (EGFR). Amplification and protein overexpression have been identified in various solid tumors and a significant association with poor clinical outcome was reported. This investigation was performed to assess the frequency of her-2/ neu overexpression and to compare these results with clinical outcome in OSCC.

Congenital absence of the portal vein with splenomegaly and hypersplenism in a young woman.

Congenital absence of portal vein (CAPV) with a systemic shunt of enteric blood is a rare malformation. Twenty-seven cases have been reported to date; with the exception of 4 patients all cases had either liver anomalies or cardiac anomalies. CAPV is usually diagnosed before the age of 18 (25/27 cases).

Overexpression of human Dickkopf-1, an antagonist of wingless/WNT signaling, in human hepatoblastomas and Wilms' tumors.

Hepatoblastomas (HBs) represent the most frequent malignant liver tumors of childhood; yet little is known about the molecular pathogenesis and the alterations in expression patterns of these tumors. We used a suppression subtractive hybridization approach to identify new candidate genes that may play a role in HB tumorigenesis. cDNA species derived from corresponding liver and fetal liver were subtracted from HB cDNAs, and a series of interesting candidates were isolated that were differentially expressed.

Helicobacter pylori genotyping in gastric adenocarcinoma and MALT lymphoma by multiplex PCR analyses of paraffin wax embedded tissues.

Background: Gastric infection with Helicobacter pylori is the major cause of chronic active gastritis and is associated with the pathogenesis of peptic ulcer and gastric carcinoma. Gastric mucosal damage involves both host and H pylori dependent factors, such as the presence of the cag pathogenicity island and allelic variations of the vacA and iceA genes.

Aims: To evaluate the association of these virulence factors with the development of gastric malignancies, a retrospective study was performed on archived tissue routinely obtained for diagnostic histopathology.

Minilaparoscopy in the diagnosis of cirrhosis: superiority in patients with Child-Pugh A and macronodular disease.

Background And Study Aims: The diagnosis of cirrhosis has prognostic and therapeutic implications, but early forms are difficult to diagnose. Laparoscopy with histology has been reported to be superior to histology alone, but is often considered to be too invasive. This study aimed to assess whether minilaparoscopy offers similarly high sensitivity coupled with only minor invasiveness.

Impairment of TGF-beta signaling in T cells increases susceptibility to experimental autoimmune hepatitis in mice.

In autoimmune hepatitis, strong TGF-beta1 expression is found in the inflamed liver. TGF-beta overexpression may be part of a regulatory immune response attempting to suppress autoreactive T cells. To test this hypothesis, we determined whether impairment of TGF-beta signaling in T cells leads to increased susceptibility to experimental autoimmune hepatitis (EAH).

Proapoptotic and antiproliferative potential of selective cyclooxygenase-2 inhibitors in human liver tumor cells.

Recent studies have shown increased levels of cyclooxygenase-2 (COX-2) in a variety of human malignancies, including hepatocellular carcinoma (HCC), but so far it is unknown whether COX-2 contributes to the malignant growth and whether inhibition of COX-2 function modifies the malignant potential of liver tumors. COX-1 and COX-2 expression was determined in 4 liver tumor cell lines (Hep 3B, HuH-7, Hep G2, Sk-hep1) by Northern hybridization and Western immunoblot. The functional effects of the nonselective inhibitor sulindac sulfide and the COX-2 selective inhibitors SC-58635 and meloxicam were examined by 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT)-assays and BrdU uptake, morphology, and TUNEL analysis of apoptosis.