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Biomedical subjects

L Kopper

Publications and source records attributed to L Kopper.

At least 73 records · Page 4Linked to original sources

Potentiation of the antitumor action of 5-fluorouracil with 5-ethyl-2'-deoxyuridine in human colorectal tumor xenografts.

The tumor growth inhibitory effect of 5-ethyl-2'-deoxyuridine ( EUdR ) in combination with 5-fluorouracil (5-FU) has been studied on four human colorectal xenograft lines. In all lines the EUdR pretreatment potentiated the effect of 5-FU presumably due to the increased incorporation of 5-FU into RNA via elevated intracellular thymidine concentration and decreased rate of 5-FU catabolism.

Adenocarcinoma, Mucinous↗

Transmission and scanning-electronmicroscopy of experimental liver metastases derived from intrasplenically growing primary tumor.

Liver metastasis formation from intrasplenically growing Lewis lung tumor was studied with transmission and scanning electron microscopy. Tumor cells arrested in the sinusoids formed desmosome-like junctions with endothelial cells and crossed the endothelial lining at intercellular gaps and by transcellular diapedesis. The metastatic foci had no newly formed vessels, and the stroma was provided by non-parenchymatous liver cells. Morphology suggested different outcome for tumor cell-host cell interactions at different stages of tumor growth. The host cell activity to destroy tumor cells was present only at the early stage but disappeared later, when the tumor cells were ready to phagocyte normal cells. The reason for this could be the immunosuppressive effect of the primary tumor. Results emphasize the importance to study metastasis formation in primary tumor-bearing hosts.

Animals↗

Increased metastatic capacity of Lewis lung tumor cells by in vivo selection procedure.

Lewis lung tumor cells from liver metastases originally obtained from an intrasplenic tumor, and lung metastases obtained from an intramuscular transplant, were repeatedly passaged in the corresponding transplantation sites (spleen, intramuscular). Cells from liver metastases injected into the spleen gained an increased metastatic capacity. The same phenomenon was observed with lung metastatic cells injected intramuscularly, but to a lesser degree. In all passages metastases occurred only in the organs receiving the venous blood from the primary site. The enhanced metastasis formation may be a result of a selection of tumor cells resistant to host cytotoxic cells and/or of selection of tumor cells 'seeding' successfully in target organs.

Animals↗

Experimental model for liver metastasis formation using Lewis lung tumor.

A new experimental model is introduced for liver metastases using intrasplenically injected Lewis lung tumor cells. The appearance of liver metastases was studied in the presence and after the removal of primary tumor. The tumorous foci in the liver proved to be natural metastases and increased in number blocking the activity of the Kupffer cells by carragheenan. This model provides a useful tool to study different aspects of liver metastases.

Animals↗

HBsAg-like structures in immunosuppressed mice inoculated with human hepatitis B virus.

Thymectomised and irradiated DBA/2 mice were injected intraperitoneally with human serum containing high titer of HBsAg, and were positive for HBsAg. Through the entire experiment neither degenerative and inflammatory lesions nor hepatitis B virus antigens could be detected in the liver of these animals by histomorphology and immunofluorescence, respectively. The sera of all these mice were negative for HBsAg by radioimmunoassay. By electron microscopy, however, increasing amounts of filaments and round particles measuring 20-22 nm in diameter could be observed in the endoplasmic reticulum of the mouse hepatocytes from the 8th day following injection. From the 90th day after inoculation the number of the filaments increased in an extreme degree. After fixation with KMnO4 and EDTA preferential staining, the filaments proved to be highly electrondense. According to the authors the filaments observed in mouse livers are lipoproteins produced by the hepatocytes in response to HBV inoculation. The appearance of the filaments is HBsAg-like, though their immunological characteristics become modified.

Animals↗

Electronmicroscopical detection of iota-carrageenan as its ruthenium red complex.

Specific detection of iota-Carrageenan (i-CAR) at the ultrastructural level has been obtained by coupling with ruthenium red (RR) - an electron microscopic stain. The i-CAR-RR complex showed electron density on carbon layers. Peritoneal macrophages were treated with the complex and after 3 h it caused the same morphological changes in macrophages as iota-Carrageenan alone. On the surfaces of macrophages, fine filamentous electron dense material - the i-CAR-RR complex - was detected.

Animals↗

Growth of human colorectal tumor xenografts in immunosuppressed mice reconstituted with normal cells.

The growth of human colorectal tumor xenograft lines was studied in immunosuppressed mice after reconstitution with sensitized and nonsensitized macrophages, thymocytes and splenocytes obtained from normal mice. Intravenously injected macrophages caused temporary inhibition of tumor growth. This effect needed intact cells and was independent from the presence of the spleen. The weight of spleen increased in normal mice sensitized with xenograft tumor, and the sensitized splenocytes injected into tumor-bearing immunosuppressed mice caused substantial tumor-growth delay.

Animals↗

Ultrastructure of human colorectal tumour xenografts maintained serially in immunosuppressed mice.

Five colorectal human tumour xenograft lines maintained by serial transplantation in immunosuppressed mice were studied by light and electron microscopy. Three had adenomatous while two had a mixed (adenomatous and mucinous) structure in the surgical specimens. After xenotransplantation in the mixed tumours the mucinous areas became dominant. Beside this there were no striking differences in the fine structure of the primarily implanted tumour compared with serially transplanted ones or between the different passages. The cells in adenomatous tumours formed acini with well-developed junctional complexes while the mucinous areas of mixed tumours were composed of single or loosely attached cells. In the former ones the cells had irregular microvilli on the apical surface and were separated from the stroma by a continuous basal lamina missing. The partially preserved functional activity was indicated by small vesicles in adenomatous, and mucin-droplets in mucinous tumours, showing intimate relationship with the rough endoplasmic reticulum and well-developed Golgi region. Some cells had features characteristic of both adenomatous and mucinous tumours. The ultrastructure of the studied tumours called attention to the possibility that malignant transformation may occur at different levels of cell differentiation.

Adenocarcinoma↗

Effect of macrophages on the growth of syn- and xenogeneic tumors.

Human colorectal tumors transplanted in immune-suppressed mice (xenogeneic system) and metastasizing Lewis lung carcinoma (syngeneic system) were used to study the effect of macrophages on tumor progression. Carrageenan modifying the structure of macrophage cell coat and damaging the membrane of lysosomes led to severe disturbances in macrophage functions. The inhibition of macrophage activity by Carrageenan produced an enhancement in tumor take in both systems. In another set of experiments peritoneal macrophages were injected into tumor-bearing mice. In both systems the non-stimulated macrophages given i.v., produced a delay in tumor growth. These results indicated that the activity of macrophages influences markedly the tumor progression--even in hosts with damaged T cell population.

Animals↗

Effect of a new bifunctional nitrosoureido derivative on human colorectal tumor xenografts.

The tumor inhibiting effect of a newly developed bifunctional nitrosoureido derivative (GYKI-13324) was studied on human colorectal tumor xenograft lines. Given orally in single or multiple daily doses, GYKI-13324 produced long-term or total regression of adenomatous, but only marginal growth delay of mucinous tumors. GYKI-13324, with slightly lower toxicity than that of BCNU, seems to be a candidate in the clinical management of colorectal tumors.

Animals↗

Effect of combined surgical and chemotherapeutic treatment of Lewis lung carcinoma.

The effect of combined surgical and chemotherapeutic treatment on Lewis lung carcinoma was studied. The i.m. implanted primary tumor was removed on the 10th day after transplantation, and the survival of mice was registered. Cyclophosphamide proved to be the most effective among the drugs studied (Cyclophosphamide, 5-FU, DBD, CCNU, Adriamycin, Vincristin, Hexyldeoxyuridine). Using different schedules (pre- and/or post-operative treatment) the pre- and post-operative drug administration was the most advantageous. Combined therapy showed always better effect than monotherapy.

Animals↗

Chemotherapeutic sensitivity of human colorectal tumor xenografts.

Studies were made of the therapeutic response of six human colorectal tumor lines serially transplanted in immunosuppressed mice. The tumors with adenomatous structure showed greater sensitivity against different cytotoxic agents than the gelatinous ones. Among the drugs, 5-FU, BCNU and MeCCNU proved to be the most effective, producing not only temporary but long-term regressions. BCNU had its maximal effect at a single, oral administration. 5-FU sensitive and insensitive lines showed an equal uptake and incorporation of radiolabeled 5-FU. Both the take rate and the growth of nontreated and treated tumors in the same host revealed the influence of host-defence mechanisms on tumor progression.

Animals↗

New type bifunctional nitrosoureido derivatives with cytostatic activity.

Several bifunctional nitrosoureido sugar alcohol derivatives were synthesized at the Institute for Drug Research in Budapest. For detailed studies two D,L-threitol derivatives have been selected (GYKI 13 324, GYKI 13 485). These compounds were less toxic and more effective than BCNU, the calculated therapeutic index values in a broad scale of transplantable, induced and heterotransplanted tumours were found to be more advantageous than with the referent compound. Both GYKI 13 324 and GYKI 13 485 exert their curative effect when given orally even in leukaemia types of tumours. Their effect on the blood picture of rats is moderate and of short duration.

Animals↗

Cytochemical study of peritoneal macrophages in carrageenan-treated immunosuppressed mice.

In our examinations the cytochemical characters of the peritoneal macrophages of immunosuppressed mice (Is-PM) were studied. It was stated that the acid phosphatase activity of their lysosomal system decreased in comparison to control cells (N-PM). In Is-PM cells the polyanion content of the cell-coat and the expression of their ConA receptors decreased, while the glycos- and galactosaminoglycan (GAG) content showed a decrease on the surface of every cell of the population. On the first day following carrageenan treatment, acid phosphatase activity of the cells was very low, the GAG content and the conA receptors of the cell-coat disappeared. The characteristic lysosomal alterations could still be observed on the 6th day after treatment. On the basis of our observations treatment with carrageenan impaired not only the lysosomal system of macrophages, but the cell surface too. These cytochemical changes may explain the dramatic decrease in macrophage function observed in carrageenan treatment.

Acid Phosphatase↗