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Biomedical subjects

K Lapis

Publications and source records attributed to K Lapis.

At least 91 records · Page 5Linked to original sources
PubMed1990

Modulation of membrane phenotype, matrix adhesion and microinvasiveness of metastatic tumour cells by HUdR.

The effect of HUdR, proved to be anti-metastatic in vivo, was studied in vitro on cell proliferation, nucleoside uptake, membrane fluidity, expression of galactosylated glycans and proteoglycans in metastatic HM tumour cells. The observed increase in membrane fluidity and the suppression of nucleoside transport were early events of the HUdR action followed by decrease of galactosylated glycan and HSPG expression. However, these changes did not influence the proliferation capacity of the cells at the concentrations studied. As a consequence of the membrane alterations a reduced adhesiveness and spreading on extracellular matrix components was detected. In addition, the HUdR treated HM cells showed reduced capacity to invade fibroblast monolayers in vitro. Based on these observations, HUdR could be the prototype of new anti-metastatic agents acting at the level of tumour-host interaction.

Animals↗
PubMed1990

Fine structure of hepatocytes during the etiology of several common pathologies.

Hepatocytes respond to injury by a few basic pathological reactions that are reflected in cell death, different types of degeneration, regeneration, or tumorous transformation. At the ultrastructural level, alterations of cell organelles can be observed in different combinations as a result of the injury, depending on the etiological agent(s) or pathological conditions developed. Nuclear bodies, dilation and fragmentation of rough endoplasmic reticulum (rer), swelling of mitochondria, and an increased number of lysosomes occur during acute viral hepatitis. The core and surface components of the hepatitis B virus can be localized in the liver cells in chronic hepatitis and in carriers. Close contact of hepatocytic and lymphocytic cell membranes were observed in chronic active hepatitis. Hepatocytes surrounded by an increased amount of collagen fibers are characteristic of cirrhosis. Loosely arranged, fine fibrils or condensed forms of Mallory bodies are pathognomic for alcoholic injury. A wide spectrum of alterations are noted after drug treatment: the proliferation of smooth endoplasmic reticulum (ser) as an adaptive phenomenon, focal or complete necrosis of the cell, inflammation, and the like. The fine structural analysis of hepatocytic inclusions in storage diseases has a differential diagnostic value. The storage of copper and other elements can be measured by x-ray microanalysis. The study of the hepatocytic differentiation in liver tumors is highly important in establishing the diagnosis and in proving the hepatocytic origin of the tumor.

Humans↗
PubMed1990

Intrasellar hamartoma associated with pituitary adenoma.

The histological, ultrastructural and immunocytochemical features are reported of an intrasellar neuronal and lipomatous hamartoma associated with pituitary growth hormone (GH) cell adenoma and acromegaly. Electron microscopy demonstrated a close contact between neurons and adenomatous GH cells. By immunohistochemistry the adenoma cells revealed a positive staining for GH and prolactin. The neurons of hamartoma showed neurosecretory activity which might have induced the development of pituitary GH cell adenoma.

Acromegaly↗
PubMed1990

Ultrastructure of invasion in different tissue types by Lewis lung tumour variants.

Ultrastructural studies on the interactions of low and highly metastatic 3LL tumour lines with the basement membranes (BMs) of capillaries, veins, muscles, nerves and adipose tissue were performed by injecting tumour cells into the foot pad of mice. Haematogenous dissemination is the principle route of metastasis formation. Cells from the highly metastatic line were able to penetrate the blood vessels more efficiently than those from the low metastatic line. This difference was mainly due to a more pronounced diapedesis-like activity of the 3LL-HH cells, and partly to the altered intratumour vessel architecture in the highly metastatic tumour line. There was no difference between the two lines in the ultrastructure and frequency of invasion of nerves and adipose tissue BMs. However, in the highly metastatic line an extremely efficient penetration of muscle cell BM was observed. These results provide further evidence that the interaction of tumour cells with the BMs of different tissue types is one of the main determinants in local and distant dissemination.

Adipose Tissue↗
PubMed1990

Galactosylated glycan expression and macrophage sensitivity of Lewis lung tumor cells with different metastatic phenotype.

Biochemical and cytochemical analysis of Lewis lung tumor variants revealed that the low metastatic cells contained more galactose/N-acetylgalactosamine residues in a high-molecular-mass (15-20 kDa) mixed N- and O-glycan fraction than the highly metastatic ones. It was also found that the highly metastatic variant was less sensitive to macrophage cytotoxicity in vitro. The cytotoxicity against the low metastatic target cells was inhibited by asialofetuin (10-20 microM), and, to a small degree--and at much higher concentration--by lactose, while galactose and other monosaccharides were ineffective. We suppose that complex galactosylated tumor cell membrane glycans could play a role in the antitumoral cytotoxicity of macrophages.

Animals↗
PubMed1990

Selective restoration of immunosuppressive effect of cytotoxic agents by thymopoietin fragments.

Swiss male mice were immunosuppressed by cyclophosphamide, cisplatinum, vincristine and methotrexate. The ability of the thymopoietin (TP) fragments TP-3, TP-4 and TP-5 to restore antibody production and phagocytosis was studied. Impaired antibody production after vincristine treatment was partially or totally restored by TP-3, TP-4 or TP-5. Only TP-3 or TP-5 interfered with the antibody-production-damaging effect of cisplatinum. The same effect of methotrexate could not be influenced by any of the TP fragments. The phagocytic capacity of peritoneal macrophages was reduced by vincristine, methotrexate and cyclophosphamide treatment. In this respect, TP-3 protected the function of macrophages against vincristine and cyclophosphamide treatment. TP-4 was active in the case of damage caused by vincristine and methotrexate, and TP-5 interfered with the phagocytosis-inhibiting effect of methotrexate. Each TP fragment seems to have a specific target orientation within the immune system. This also means that the proper TP fragment should always be chosen for combination therapy with various types of cytotoxic drugs.

Animals↗
PubMed1990

Methylcellulose prevents the regression of carbon tetrachloride-induced liver fibrosis and cirrhosis in rats.

Male F344 rats were treated with carbon tetrachloride (CCl4; 0.3 ml/kg per os, 3 times a week) for 2 mo. At the end of the CCl4 administration out of the 65 animals 30 received methylcellulose (MCL; 3.85 ml/kg, 5% solution, per os, 3 times a week) for 6 wk. Thirty-five rats did not receive any further treatment. The fibrotic change caused by CCl4 reached its maximum 2 wk after the end of the treatment. After this, the severity of the fibrotic change regressed spontaneously. This regression was not observable in the liver of rats that received MCL. The fact that MCL is used as a solvent for drugs and as a food additive underlines the importance of the effect of this compound on chronic liver injury.

Animals↗
PubMed1990

Effectiveness of tiazofurin (NSC 286193) in treating disseminated tumor cells and micrometastases in mice.

The authors studied the metastasis-inhibiting effect of various dosages of tiazofurin in mice inoculated with a low (LLT) and a highly (LLT-HH) metastatic variant of the Lewis lung carcinoma. The tumor cells were inoculated intravenously (lung colony assay), intramuscularly (muscle-lung metastasis model), and intrasplenically (spleen-liver metastasis model), respectively. In the lung colony assay the tiazofurin proved to be curative. In the muscle-lung and the spleen-liver model the tiazofurin treatment, started after the removal of the parent tumor, drastically decreased the number of metastases in both model systems and brought about a significant prolongation of the survival time in the spleen-liver model. Authors suggest that tiazofurin as one of the most promising candidates for metastasis prevention and inhibition in human beings, too.

Animals↗
PubMed1990

Experimental metastasis inhibition by pretreatment of the host.

In an experimental murine metastasis model host pretreatment protocol (HPP) was tested to abrogate lung colonization of tumor cells. The stimulation of the host defense by lentinan or TP4, and the PGI2 administration was effective in the case of the immunosensitive low metastatic tumor. The modulation of the host cells and/or the extracellular matrix by the glycosaminoglycan biosynthesis blocking agent KL-103--but not by the degradation inhibitor suramin--inhibited the lung colonization of the highly metastatic immunoresistant tumor variant. In combination with the cytotoxic antiproliferative agents these non-toxic drugs could be useful in new protocols to prevent tumor dissemination.

Animals↗
PubMed1990

Alterations of glycosaminoglycans in human liver and kidney tumors.

Glycosaminoglycans were investigated in surgically removed human liver and kidney tumours by applying biochemical methods. Four liver adenoma, 6 focal nodular hyperplasia and 9 primary hepatocellular carcinoma samples were compared with normal liver from autopsy cases and also with liver tissue adjacent to PHC. The studies on kidney included 14 renal cell carcinoma and 4 wilms' tumour samples. Three findings emerged from the quantitative and qualitative characterization of the tumours with epithelial origin. 1) The rise in the amount of total GAG was not limited to the malignant lesion. Similar increase was observed in benign liver tumours and also in the tissue adjacent to liver or kidney malignant tumours. 2) The dominant type of the GAG subclasses varies with the histology of the tumours. In benign liver tumours dermatan sulfate, in PHC and renal cell carcinoma chondroitin sulfate, but in Wilms' tumour hyaluronate was the prominent GAG subclass. 3) In all tumour-affected tissues dermatan and chondroitin sulfates had lower degree of sulfation. However, in the histologically different tumours various disaccharides showed reduced level of sulfation. The GAG alteration in renal cell carcinoma was compared with the prognostic factors of each individual case. This analysis showed a good correlation between HS/CS ratio and the prognostic factors of the kidney tumour cases.

Chromatography, High Pressure Liquid↗
PubMed1990

Glycosaminoglycans as novel target in antitumor therapy.

Considering the importance of intercellular contacts in the metastasis of malignant tumours drug action on glycosaminoglycan production as one of the underlying mechanisms in metastasis was investigated. 5-hexyl-2-deoxyuridine/HUdR/was shown to inhibit the conversion of glucosamine to UDP-sugars. Consequently various glycoconjugates were affected, especially the synthesis of heparan sulfate was reduced. It is noteworthy that HUdR inhibited the synthesis of glycosaminoglycans in tumour cells with high metastatic capacity. The biological consequence of the alterations in glycosaminoglycan production was studied on measuring HUdR action on cell surface markers, microinvasion and tumour metastasis in experimental systems. It was concluded that HUdR has remarkable antimetastatic activity which by all probability is due to the inhibition of heparane sulfate synthesis.

Animals↗
PubMed1990

[Fibrolamellar liver carcinoma].

Four fibrolamellar liver carcinomas were surgically removed and were postoperatively examined. Three patients are alive roughly three years from surgery, and there are no signs of imminent recurrence, while the fourth case was diagnosed only two months back. The carcinomas had developed in non-cirrhotic livers which also produced negative responses to serological tests for hepatitis B. In flow cytometry, DNA indices were indicative of diploidy in two cases and aneuploidy in the other two. The highest DNA index value was recorded from the smallest tumour which could be assigned to the category of "minute HCC". No correlation was found to exist either between age, sex, and DNA index. Positive CEA reaction was immunohistochemically recorded from few tumour cells, whereas negative AFP responses were exhibited by all four tumours. Appearance of AAT in tumour cells was detected in three cases. High degree of differentiation, similarity between tumour and liver cells, and oncocytoid nature of cells were revealed by optical light and electron microscopy. This high degree of differentiation was additionally confirmed by two factors: glucose-6-phosphatase activity was preserved in all four tumours, adenosinetriphosphatase activity was histochemically detectable from certain points of the tumour cell membrane. Gamma-glutamyl-transpeptidase activity, too, was very strongly pronounced in all tumour cells, which, however, cannot be interpreted as a sign of differentiation. Membrane-bordered "dense-core" granules were visible in few tumour cells in two cases. Intensive granular serotonin reactions were immunohistochemically recorded from the majority of tumour cells in the same cases. Our histochemical and ultrastructural parameters have produced clear-cut evidence to the hepatocyte nature of FLC cells. Yet, the presence of secretory granules and positive serotonin reaction might possibly support the assumption that the FLC originates from those pluripotent cells of the liver which may develop in two directions, depending on the individual case, to become either hepatocytes or neurosecretory cells.

Adolescent↗
PubMed1990

Interactions of exogenous heparan sulfate with tumor cells of different metastatic phenotype.

Heparan sulfate (HS) enhanced the growth of the highly metastatic (HM) 3LL cell line, but not that of the low metastatic (LM) counterpart, in a dose-dependent way. Heparin, chondroitin sulfate, hyaluronate did not produce this effect. At 4 degrees C both cell lines exhibited high affinity binding sites (Kd 10(-8) M) for exogenous HS. Unlike LM cells, the HM ones lost half of the surface-bound HS during the 24-hour incubation at 37 degrees C. HM cells in the exponential growth phase took up the bound HS at lower rate than the LM counterparts. Both cell lines fragmented the exogenous HS intracellularly, but only the HM cells were able to degrade it at the cell surface. The HM cells contained much more heparin-binding proteins--especially in the cell membrane and nuclear fraction--than the LM ones. These results clearly demonstrate that the interactions of tumor cells with exogenous HS are influenced by the invasive phenotype. We suggest also that there could be a correlation between the surface degradation, the slow uptake and the growth-promoting effect of the exogenous HS.

Animals↗
PubMed1990

[The effect of D-penicillamine on experimental liver cirrhosis induced by CCl4].

Authors examined the effect of D-penicillamin (Pw) on liver cirrhosis induced by chronic CCl4 and phenobarbital (Pb) treatment in Fischer 344 rats. Morphometric analysis of quantity of connective tissue fibres did not show decrease on the effect of Pe treatment. Quantity of hydroxiproline, which is one of the parameters of coll ahen decrease, did not change significantly on effect of drug, but only compared to CCl4 and Pb treated control. Quantity of glycosaminoglycan showed increase following Pe treatment. Lymphocyte stimulation by Con-A was different in CCl4 and Pb and Pe treated groups, respectively. According to our examinations in case of liver fibrosis cirrhosis induced by CCL4-PB treatment in rats the Pe treatment proved to be unsuccessful. It seems that Pe is effective only in forms of cirrhosis accompanied by significant copper accumulation, by decrease of toxic effects of copper.

Animals↗
PubMed1990

Modulation of glycoconjugate biosynthesis by 5-hexyl-2'-deoxyuridine in highly metastatic Lewis lung carcinoma cells.

The mechanism of action of 5-hexyl-2-'deoxyuridine (HUdR), a compound with antitumor activity, has been investigated in the HM cell lines derived from the highly metastatic variant of Lewis lung carcinoma (3LL-HH). It was shown that this pyrimidine analog did not inhibit the biosynthesis of nucleotides but modified the biosynthesis of glycoconjugates. The incorporation of [14C]-glucosamine into cytoplasmic glycoconjugates [glycosaminoglycan (GAG), glycolipid (GL), glycoprotein (GP), neutral polysaccharide (NP)] decreased to a similar level. The [14C]-glucosamine derived radioactivity was reduced to about 60-70% of the untreated controls in the presence of 15 micrograms/ml HUdR, which caused no inhibition of cell proliferation. These results might be explained by the reduced conversion of glucosamine into uridine-5'-diphospho-hexosamine. As more reduction was observed in the glucosamine labeling of glycoconjugates in nuclei and extracellular compartment, it may be conceivable that the intracellular transport of certain glycoconjugates (GAG, GP) is also affected by HUdR. In the extracellular compartment the reduced level of GAG labeling was the most apparent change. However, at a higher concentration of HUdR (75 micrograms/ml) there was a higher radioactivity in the combined GL + GP fraction. Using [35S]-labeling, the GAG fractions also showed a decreased radioactivity but only at the concentration of 75 micrograms/ml HUdR.

Antimetabolites, Antineoplastic↗