Ductular reaction correlates with fibrogenesis but does not contribute to liver regeneration in experimental fibrosis models.

Background And Aims: Ductular reaction is a standard component of fibrotic liver tissue but its function is largely unknown. It is supposed to interact with the matrix producing myofibroblasts and compensate the declining regenerative capacity of hepatocytes. The relationship between the extent of fibrosis-ductular reaction, proliferative activity of hepatocytes and ductular reaction were studied sequentially in experimental hepatic fibrosis models.

Imatinib accelerates progenitor cell-mediated liver regeneration in choline-deficient ethionine-supplemented diet-fed mice.

Severe chronic hepatic injury can induce complex reparative processes. Ductular reaction and the appearance of small hepatocytes are standard components of this response, which is thought to have both adverse (e.g.

Human liver regeneration in advanced cirrhosis is organized by the portal tree.

Background & Aims: In advanced cirrhosis new hepatocytic nodules are generated by budding of ductules in areas of parenchymal extinction. However, the vascular alterations in the areas of parenchymal extinction, the blood supply and the structure of the new hepatocytic nodules have not been analyzed in detail.

Methods: Explanted human cirrhotic livers of three different etiologies and two experimental rat models of cirrhosis were thoroughly examined.

Mechanisms of vascularization in murine models of primary and metastatic tumor growth.

Directed capillary ingrowth has long been considered synonymous with tumor vascularization. However, the vasculature of primary tumors and metastases is not necessarily formed by endothelial cell sprouting; instead, malignant tumors can acquire blood vessels via alternative vascularization mechanisms, such as intussusceptive microvascular growth, vessel co-option, and glomeruloid angiogenesis. Importantly, in response to anti-angiogenic therapies, malignant tumors can switch from one vascularization mechanism to another.

EZH2 is a sensitive marker of malignancy in salivary gland tumors.

Background: The immunohistochemical detection of Enhancer of zeste homologue 2 (EZH2) proved to be a useful tool to recognize the malignant nature of tumors in a wide variety of neoplasms. The histological diagnostics of salivary gland tumors is a challenging task, and a reliable marker of malignancy would be extremely helpful.

Methods: EZH2 expression was investigated in 54 malignant and 40 benign salivary gland tumors of various histological types by standard immunohistochemistry.

Quantitative morphometric and immunohistochemical analysis and their correlates in cirrhosis--A study on explant livers.

Background: Reproducible structural analysis was made on cirrhotic human liver samples in order to reveal potential connections between morphological and laboratory parameters.

Material And Methods: Large histological samples were taken from segment VII of 56 cirrhotic livers removed in connection with liver transplantation. Picro Sirius red and immunohistochemically (smooth muscle actin [SMA], cytokeratin 7 [CK7], Ki-67) stained sections were digitalized and morphometric evaluation was performed.

Alterations in hepatic lobar function in regenerating rat liver.

Background: Ligation of a branch of the portal vein redirects portal blood to nonligated lobes resulting in lobar hypertrophy. Although the effect of portal vein ligation on liver volume is well documented, the parallel alterations in liver function are still the subject of controversy. Our aim was to assess the time-dependent reactions of regional hepatic function to portal vein ligation by selective biliary drainage.

Rapamycin can restore the negative regulatory function of transforming growth factor beta 1 in high grade lymphomas.

TGF-β1 (transforming growth factor beta 1) is a negative regulator of lymphocytes, inhibiting proliferation and switching on the apoptotic program in normal lymphoid cells. Lymphoma cells often lose their sensitivity to proapoptotic/anti-proliferative regulators such as TGF-β1. Rapamycin can influence both mTOR (mammalian target of rapamycin) and TGF-β signaling, and through these pathways it is able to enhance TGF-β induced anti-proliferative and apoptotic responses.

The presence of human papillomavirus 16 in neural structures and vascular endothelial cells.

Human papillomavirus (HPV) is known as a strictly epitheliotropic pathogen. Our results raised the possibility that HPV 16 is present in neural cells and in the vascular endothelium. By in situ hybridization, we have detected HPV 16 E6 ORF sequence in small blood vessels and peripheral nerves adjacent to oral and cervical cancers.

Prognostic significance of high-risk HPV status in advanced cervical cancers and pelvic lymph nodes.

Objective: In this study, we investigated the presence of high-risk (HR) HPV types most prevalent in the Hungarian population in surgically removed cervical cancers and pelvic lymph nodes. The aim of our work was to determine the prognostic significance of HPV status in the lymph nodes draining the tumor.

Methods: Primary tumor specimens from 150 patients and 900 lymph node samples (six per case) were studied.

Immunohistochemical analysis of cytokeratin 7 expression in resting and proliferating biliary structures of rat liver.

Cytokeratins are the largest subfamily of intermediate filament proteins and include more than 20 different gene products, which are expressed in an epithelial tissue-specific manner. We studied by immunohistochemistry and confocal microscopy the distribution of cytokeratin subtypes in the biliary system of adult rat liver. A cytokeratin (CK)19+/7- cholangiocyte population was observed in the smaller branches of the biliary tree including the canals of Hering.

Development of the vasculature in "pushing-type" liver metastases of an experimental colorectal cancer.

A mechanism for stroma formation (development of vasculature and supportive connective tissue) is suggested in an experimental "pushing-type" colorectal carcinoma liver metastasis model. The key element is the appearance of smooth muscle actin (SMA)-positive cells and the sinusoidal lakes at the border of the metastases. These lakes are the consequence of the disappearance ('stepping back' of hepatocytes from the border zone, resulting in the fusion of partially capillarized sinusoids.

2-acetylaminofluorene dose-dependent differentiation of rat oval cells into hepatocytes: confocal and electron microscopic studies.

The 2-acetylaminofluorene (AAF)/partial hepatectomy (PH) model is one of the most extensively studied experimental systems for oval cell proliferation and differentiation. We have previously described the oval cells as forming ductular structures surrounded by basement membrane, representing extensions of the canals of Hering. Herein we analyze the differentiation of oval cells into hepatocytes after varying degrees of liver damage induced by AAF.

Organ-specificity of the extravasation process: an ultrastructural study.

Unlabelled: The process of extravasation of the high metastatic Lewis lung carcinoma line was examined in different organs. Four of the five organs (liver, lungs, brain and adrenals) represent the most frequent metastatic sites in humans. In the case of each organ 150-350 tumor cells were analysed.

Role of the basement membrane in tumor cell dormancy and cytotoxic resistance.

Objectives And Methods: Tumor dormancy and resistance to cytotoxic agents are key limiting events in the treatment of malignant diseases. To determine whether both are influenced by the extracellular milieu in which tumors reside, HT1080 human fibrosarcoma, MCF-7 breast carcinoma and OSCORT osteosarcoma cell proliferation, viability, apoptosis and cytoreductive-treatment-induced death were investigated in the presence or absence of extracellular matrix (ECM).

Results: ECM-adherent, but not plastic-adherent HT1080 cells formed a multicellular network accompanied by reduced proliferation and lowered DNA synthetic capacity.

Origin and structural evolution of the early proliferating oval cells in rat liver.

We have analyzed the histological changes in rat liver after 2-acetylaminofluorene (AAF) administration. The data demonstrate that AAF-induced oval cells were preferentially generated by proliferation of the terminal biliary ductules that we suggest constitute the primary hepatic stem cell niche. The oval cells formed ductular structures, representing an extension of the canals of Hering.

A specifically radiolabeled somatostatin analog with strong antitumor activity induces apoptosis and accumulates in the cytosol and the nucleus of HT29 human colon carcinoma cells.

The new heptapeptide somatostatin analog TT-232 decreases proliferation of HT-29 human colon carcinoma cells in vitro by reducing mitotic and increasing apoptotic activity. We have synthesized and characterized a specifically tritium labeled 3H-Tyr3-TT-232 (30 Ci/mmol) to investigate the effect and the fate of this antitumor peptide on human colon tumor cells. 3H-labeled TT-232 could be detected on the cell surface, on cytoplasmic membranes and also in the nucleus of HT-29 cells, 1-6 h after the administration of 0.

A new method to localize acid phosphatase using the confocal laser-scanning microscope.

The aim of the study was to work out a technique for the detection of acid phosphatase enzyme activity by confocal laser-scanning microscope using the histochemical acid phosphatase detection method (after Barka and Anderson 1962, modified by Bowen and Lewis 1985) routinely used for light microscopy. The density and the distribution of enzyme reaction product is dependent on the incubation time, as shown by different confocal images or ELISA reader. The inhibition of the enzyme activity with metal ions shows the same profile known from the literature.

Current concepts of tumor-induced angiogenesis.

Tumor induced angiogenesis is responsible for the nutrition of the growing tumor and can also increase the probability of hematogenous tumor dissemination. Data obtained from morphological analysis of tumor angiogenesis can contribute to the development of new anti-angiogenic therapies. Based on in vitro and in vivo observations several models of angiogenesis were introduced, explaining the mechanism of lumen formation and the timing of basement membrane depositon.