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N V Engel'gardt

Publications and source records attributed to N V Engel'gardt.

17 recordsLinked to original sources

[Expression of tissue-specific genes with progression of mouse hepatocellular carcinoma].

Expression of hepatocyte-specific genes in slow- and fast-growing hepatocellular mouse carcinomas was studied. The fast-growing poorly differentiated passaged hepatocarcinoma (fHC) originated from the well-differentiated slow-growing variant (sHC). In contrast to the parental hepatocarcinoma, in fHC the expression of the hepatocyte nuclear factor 4 (HNF4), in fHC a key factor responsible for hepatocyte differentiation, and several HNF-4-responsive genes, such as those for transferrin, transthyretin, hepatocyte nuclear factor 1 (HNF1), and serum albumin, was significantly suppressed. The expression of exogenous HNF4 in the fHC cell culture partially restored the expression of hepatocyte marker genes and the appearance of epithelial cell islands in the culture. The described system may serve as a convenient model for further analysis of mechanisms underlying hepatocarcinogenesis and liver tumor progression.

Animals↗

[Mouse hepatoblastoma: comparative aspects].

The structure of 12 spontaneous hepatoblastomas found in old (average age 26.5 months) male mice is described. There were considerable strain differences in their incidence: 0.5% (1/194), 0.5% (1/194) and 5% (10/198) in strain C57B1, CBA and F1 (CBA X C57B1), respectively. This proves the importance of genetic factor the role of which in the development of human hepatoblastoma is not established so far. Mouse hepatoblastoma develops almost invariably within or adjacent to liver cell tumours (adenoma or carcinoma). There was a correlation between the incidence of liver cell tumours within a given strain treated with different doses of carcinogen but such correlation was absent in mice of different strains. Histologically and ultrastructurally, mouse hepatoblastoma corresponds to the anaplastic variant of human hepatoblastoma. As distinct from human tumour, mouse hepatoblastoma does not contain alpha-fetoprotein. One tumour was transplanted to the syngeneic host and passed 30 transplant generations retaining the structure of a primary tumour with areas of osteoid tissue and foci of squamous cell metaplasia. Mouse hepatoblastoma may be induced by carcinogens. Likewise, according to the literature, risk of hepatoblastoma is higher in children whose mothers were exposed to the potential carcinogens before or during the pregnancy.

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[Atypical alpha fetoprotein-synthesizing cells in the regenerating mouse liver].

Ultrastructural localization of alpha-fetoprotein (AFP) was studied with the use of the indirect immunoperoxidase technique in the regenerating liver of three strains of mice after CCl4 poisoning. Upon the use of monoclonal and monospecific antibodies AFP synthesis was revealed in part of mature hepatocytes and in smaller cells. No analogues of small cells were found in the normal liver. It is noted that there is structural similarity of atypical AFP-synthesizing cells to precursor cells of hepatocytes during chemical hepatocancerogenesis in rats. Approaches to identification of atypical cells are discussed.

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[Synthesis and localization of alpha fetoprotein in liver regeneration in mice].

Typical mature hepatocytes constituting not over several per cent of the total amount of preserved hepatocytes served as the principal site of the alpha-fetoprotein (AFP) localization in the liver of mice regenerating after the CCl4 poisoning or partial hepatectomy. Morphologically they failed to differ from the principal mass of hepatocytes and retained an antigen of the bile capillaries on the surface. A change id to the dynamics of the AFP level in the animal serum. Apparently in regeneration of the mouse liver the principal AFP production was realized by mature hepatocytes.

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Immunohistochemical study of alpha-fetoprotein and serum albumin in the early postnatal period in mice.

The localization of the embryo-specific protein alpha-fetoprotein (alpha-FP) and serum albumin in the organs of mice in the first three weeks of life was studied. Using a reaction of immunofluorescence, alpha-FP was detected in the cytoplasm of the hepatocytes. During the first three days of life it was contained in the overwhelming majority of the hepatocytes, but in different concentrations. Then the fluorescence intensity and number of cells containing alpha-FP decreased sharply, and by the seventh to 12th day such cells remained chiefly close to the central veins. In a simultaneous determination of alpha-FP and albumin in the liver, cells containing only alpha-FP, alpha-FP and albumin, and only albumin were detected. With increasing age of the animals, the number of the latter cells increased. On slices of other organs, alpha-FP, albumin, and transferrin were present in the same structures of gamma-globulin.

Alpha-Globulins↗

[Rapid progression of passaged mouse hepatocarcinoma associated with the loss of cell polarity].

Two transplantable differentiated mouse hepatocarcinomas were obtained in B6 D2 F1 mice from primary tumors induced by initiation (NDEA)-promotion (phenobarbital) protocol. Both HC were slowly growing with time from passage to passage of 5-7 months (s-HC). A fast-growing variant with time between passages of 2-3 weeks appeared in one mouse on the third passage (f-HC). The three HC strains constantly retained their phenotype. The s-HCs were characterized by prominent cell polarity according to organization of the cytoskeleton and distribution of domain-specific membrane-associated markers. Cell polarity was completely destroyed in the fast-growing variant. Cell adhesion in the latter tumor was very low. An in vitro growing strain of f-HC was easily obtained enabling experimental study of regulation of progression in HCs.

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[New differentiation markers of mouse liver epithelial cell lines].

We describe two new markers of mouse liver epithelial cells detected by monoclonal antibodies. Immunomorphological localization of antigens was performed using light and electron microscopy. Antigen G7 is a marker of cholangiocytes and oval cells. Antigen A6 is present in cholangiocytes and oval cells; moreover, it is expressed in normal liver in single hepatocytes adjacent to the portal vein, in preneoplastic liver, in newly formed hepatocytes, and in certain hepatocarcinomas. Thus, antigen A6 is a marker of cholangiocytes, oval cells and of certain stages of hepatocyte differentiation. We also detected phenotypic heterogeneity of Gehring cells in terms of antigen A6 content. We have formulated problem of the relationship between A6-negative Gehring cells and liver stem cells. Both marker antigens are species-specific but are not specific for the liver. Antigen A6 is simultaneously a differentiation marker of cells belonging to the erythroid series. It is expressed in erythroblasts of fetal liver and is absent in erythroblasts of the yolk sac and erythrocytes. The relationship between antigen A6 and blood group antigens is discussed.

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[Common antigens of oval cells and cholangiocytes in the mouse. Their detection by using monoclonal antibodies].

Monoclonal antibodies (MAb) were produced against antigens (Ag) of oval cells isolated from the preneoplastic murine liver. To suppress the immune response to major antigens common with hepatocytes, the principle of anti-idiotype immunization was employed. Characteristics of three MAb reacting selectively with the foci of oval cell proliferation are described. MAb A6 and G7 detected two different antigens (Ag A6 and Ag G7, respectively) common for oval cells and cholangiocytes. Ag A6 was also found in normal parenchyma (in membranes of single hepatocytes adjacent to portal veins), in the preneoplastic liver (in hepatocytes formed de novo) and in some hepatoma cells. Ag G7 was not detected in hepatocytes. MAb E5 stained the matrix in the areas adjacent to oval cells and large bile ducts. All the three Ag were widely distributed in normal tissues of mice. The significance of the detected Ag as markers of murine liver epithelial cell lines and stages of their differentiation is discussed as well as the possible relationship between Ag A6 and Ag of human blood groups.

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