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Biomedical subjects

K Lapis

Publications and source records attributed to K Lapis.

At least 361 records · Page 20Linked to original sources

Pathology of primary liver cancer.

After a brief survey of the factors that play a role in the etiopathogenesis of human hepatocellular carcinomas, a detailed description is given of the macroscopic and microscopic features of human liver cancers as well as their association with cirrhosis. The ultrastructural features of liver cancers of various degrees of differentiation are described. The mode of spread, metastasis formation of primary liver cancers, and most frequent causes of death of liver cancer patients are reviewed.

Bile Duct Neoplasms↗

Histology and ultrastructural aspects of virus-induced primary liver cancer and transplantable hepatomas of viral origin in chickens.

The macroscopic, light microscopic and electron microscopic features and biological properties of MC-29 virus-induced hepatocellular carcinomas in chickens are described. The tumors developed in noncirrhotic livers within a very short time and formed metastases. Virus production was also evidenced in the tumors. There were also indications of virus production in the transplantable tumors. The tumors grew equally well after sc, ip, or im inoculation. In about 25% of the tumor-bearing animals, tumorous nodules developed in the liver. It could not be established whether they were metastases or primary liver cancers induced by viruses released from the transplantable tumors.

Animals↗

Biochemical behavior of MC-29 virus-induced transplantable chicken hepatoma.

Studies were performed to test the applicability of the molecular correlation concept developed in chemically induced transplantable rat hepatomas to virally induced transplantable hepatoma in chicken. In a comparison of the activities of carbohydrate, purine, and pyrimidine key enzymes in rat and chicken hepatomas, similar patterns were observed in rodent and avian tumors. These results show that the enzymatic imbalance elucidated in chemically induced rat hepatomas is applicable to the virus-induced hepatoma in chicken, independent of the nature of the carcinogenic agent and the species.

Animals↗

Chromatin alterations and gene function disorder in MC-29 virus-derived hepatoma.

The disorder of gene expression in hepatomas was studied by following certain metabolic alterations (enzyme stimulation, nucleic acid labeling) after glucocorticoid treatment and analyzing the site of action of glucocorticoids. Compared to normal liver, the MC-29 virus-derived transplantable hepatoma (VTH) responded abnormally to glucocorticoids, which failed to stimulate the activity of certain enzymes (glucose-6-phosphatase, aryl hydrocarbon hydroxylase) or to inhibit DNA synthesis. Since the binding capacity of the cytosol steroid receptor was the same in liver and VTH but the interaction between the steroid receptor and DNA was reduced in VTH, it was concluded that structural alterations of chromatin nonhistones--including processed steroid receptor--may be responsible for the lack of physiological responses to steroids in VTH. Furthermore, the increased proportion or repetitive sequences in VTH DNA may be a feature of the disorder of gene regulation in malignant cells.

Animals↗

Comparative study of tumor-specific transplantation antigens of MC-29 chicken hepatoma and Rous sarcoma virus-induced sarcomas in mice.

Immunization of CBAT6T6 mice with MC-29 hepatoma antigen did not change the take of Rous sarcoma virus, Schmidt-Ruppin strain [RSV(SR)] mouse tumors after sc transplantation. Immunization with MC-29 hepatoma antigen only slightly increased the average survival time of the mice and significantly decreased tumor growth only at the minimal lethal dose level. Immunization of mice with MC-29 hepatoma antigen and immunization with chicken Rous sarcoma gave similar results; both elicited much less transplantation resistance than immunization with irradiated RSV(SR) mouse tumor cells. The data indicate that there are common tumor-specific transplantation antigens of MC-29 hepatoma and Rouse sarcoma, but further in vitro experiments are needed to prove this.

Animals↗

Occurrence of tubuloreticular inclusions in acute viral hepatitis.

Light and electron microscopy were used to study the liver needle-biopsy material of 20 patients with acute viral hepatitis. According to clinical and serologic data, 5 cases proved to be acute viral hepatitis type A, 13 were type B, and 2 were type non-A/non-B. In 2 of the hepatitis type A, in 6 of the hepatitis type B, and in one of the type non-A/non-B cases, tubuloreticular inclusions (TRI) were found in the endoplasmic reticulum of the sinusoidal endothelial cells of the liver. These data support the possible presumption that the inclusions represent a characteristic reaction of the endoplasmic reticulum to different influences, as for example to viral infection, rather than to the virus itself.

Biopsy, Needle↗

Intracytoplasmic crystalline inclusions in the hepatocytes of humans and chimpanzees.

Intracytoplasmic crystalline inclusions (CCIs) were observed in liver biopsy specimens taken from three patients and three chimpanzees. CCIs are rare in human hepatocytes and have never been described in chimpanzees. All three human cases were connected with alcoholic liver disease; no viral infection was noted. The histologies of the two liver biopsy specimens obtained from healthy chimpanzees were normal, but hepatitis B virus (HBV) infection was demonstrated in the third case by immunohistochemistry and radioimmunoassay. In the last biopsy specimen a large accumulation of HBV core particles was present in the nuclei and among the filaments of CCIs of the hepatocytes. This finding suggests that crystallizations of viral proteins may form intracytoplasmic inclusions in hepatocytes, whereas in other cases toxic effects (alcohol) or normal conditions (storage) may lead to the formation of similar structures.

Animals↗

Alterations in nucleoside monophosphate concentrations in 3LL tumours after combined treatment with tiazofurin and 5-hexyl-2'-deoxyuridine.

The IMP and GMP concentrations were compared after treatment with tiazofurin alone and in combination with 5-hexyl-2'-deoxyuridine (HUdR) in 3LL-HH adenocarcinoma in vivo. The elevation in IMP/GMP ratio, indicating guanylate depletion and increase of inosine-5'-monophosphate concentration, showed a dose dependence and was the highest at the 7th hour after treatment with tiazofurin. HUdR application alone caused only a modest change in the nucleotide concentration of LL-HH tumour. However, the rise of IMP but not the reduction of guanylate concentration induced by tiazofurin was remarkably mitigated by HUdR treatment, without affecting the antitumour potency of tiazofurin. Thus HUdR showed modifying activity on some of the tiazofurin-induced changes in nucleotide metabolism which appeared not to be associated with the antiproliferative activity of tiazofurin. It follows that reduced GMP concentration and not the elevation of IMP/GMP ratio could predict therapeutic responses to tiazofurin.

Animals↗

Role of the modified (glycosaminoglycan producing) perisinusoidal fibroblasts in the CCl4-induced fibrosis of the rat liver.

Development and regression of liver fibrosis and cirrhosis induced by CCl4 in male F-344 rats were strictly followed during and after an 8-week treatment. The relative amount of collagen was measured by morphometry and the number of glycosaminoglycan (GAG) containing fat storing cells was counted at each time point. The expression of proteoglycan genes (decorin, versican and BPG-5 HSPG) was studied in parallel with the development of cirrhosis. Collagen content of the liver as well as the number of GAG-containing mesenchymal (fat storing) cells increased in parallel until two weeks after the cessation of CCl4 treatment. Later, both the collagen content and the number of GAG-containing cells decreased in parallel and significantly. Proteoglycan gene expression in the nonparenchymal fraction of liver cells indicated an active proteoglycan synthesis in the course of the development of cirrhosis. It is concluded that modified Ito (fat storing) cells synthesize proteoglycans and play an important role in the formation of connective tissue fibers in liver fibrosis.

Animals↗

Flow cytometric analysis of proteoglycan expression on murine tumor cells with different metastatic capacity.

Proteoglycan epitopes recognized by poly- or monoclonal antibodies were studied at the cell surface of 3LL murine tumor cell lines with different metastatic capacity. A decreased expression of heparan sulphate and chondroitin sulphate core protein epitopes was observed in the highly metastatic variant HM compared to the low metastatic counterpart LM. Interestingly, the biochemical analysis demonstrated an increased glycosaminoglycan-especially heparan sulphate-production in highly metastatic HM cells. A similar decrease in heparan sulphate proteoglycan core epitope expression was observed in the highly metastatic B16F10 cell line compared to its low metastatic variant F1. The under-representation of proteoglycan core protein epitopes at the cell surface of highly metastatic murine tumor cell lines could be interpreted by the increased glycosylation, or by the loss of those particular epitopes.

Animals↗

Effect of interferon-alpha (IFN alpha) on various human tumor xenografts.

The growth of some human tumor xenografts (3 out of 8, melanoma, non-Hodgkin's lymphoma, squamous cell carcinoma) was successfully--but moderately and temporarily--inhibited, when interferon-alpha (EGIS, Hungary) was given for 10 days. The route of administration (intratumoral or intraperitoneal) was usually not a decisive factor. An attempt to potentiate IFNa action with Zymozan or Cyclophosphamide did not succeed.

Animals↗

Transplantable human non-Hodgkin lymphoma line in artificially immunesuppressed mice.

Diffuse non-Hodgkin lymphoma of B-cell origin has been established as a serially transplantable xenograft line in artificially immunesuppressed mice. The take rate and growth rate increased with repeated passages compared to the first transplant generation. However the xenografted tumor preserved many of its characteristics, including morphology, cell surface markers and DNA index. Chromosome analysis proved the human origin of tumors grown in mice and revealed translocation 8,14. Cyclophosphamide, Methotrexate and Vincristine produced substantial inhibition of tumor growth, while Dianhydrogalactitol and Adriamycin were less effective. Human alpha interferon also produced a delay in tumor growth.

Animals↗