Biomedical subjects

K Lapis

Publications and source records attributed to K Lapis.

At least 55 records · Page 3Linked to original sources

PubMed1993

Significance of cellular DNA content in human liver tumors.

The nuclear DNA content of 26 liver tumors (1 adenoma, 10 focal nodular hyperplasia and 15 hepatocellular carcinoma) was measured by flow cytometry (FCM) on formalin-fixed, paraffin-embedded tissues. All lesions developed in noncirrhotic liver and were negative for HBsAg. DNA aneuploidy was found in 1/10 FNH (one hypodiploid) and in 11/15 HCC (73%). Intratumoral heterogeneity was observed in three cases. In HCC the ploidy level showed no correlation with tumor size or histopathological grading. Results support the potential of FCM to measure DNA content in archival pathological specimens, and also that DNA content itself has no diagnostic value.

Adenoma↗

PubMed1992

[Prognostic value of cell proliferation markers in malignant tumor diseases].

Novel methods used in studying the proliferation activity and cell kinetics of malignant neoplasms such as: the in vivo and in vitro bromodeoxyuridine labeling, the flow cytometric DNS analysis, the immunohistochemical demonstration of the so called proliferation associated antigens and the counting of nucleolar organized regions are briefly introduced. The data obtainable by these methods are reviewed and critically discussed. The prognostic value of the obtained data and their utility in planning and monitoring of cancer patients' therapy are also discussed.

Antigens, Neoplasm↗

PubMed1992

Inhibition of two-step urinary bladder carcinogenesis by the somatostatin analogue RC-160.

Fisher 344 female rats were exposed for 4 weeks to the initiator carcinogen N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) 0.05% in the drinking water and thereafter to the promoter carcinogen mitomycin C (0.08 mg per animal per week) intravesically for 12 weeks. High incidence of urinary bladder transitional cell cancers was observed (17 in situ and 17 invasive carcinomas among 40 rats). When the somatostatin analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) was administered s.c. at the dose of 50 micrograms per animal per day during 6-week period of promotion with mitomycin C, the incidence of urinary bladder cancer was dramatically reduced. Only 1 in situ carcinoma was observed among 20 rats and only preblastomatous lesions (dysplasias and papillomas) occurred. This effect could indicate that RC-160 interferes with the process of promotion by induction of enhanced apoptosis (programmed cell death) of the dysplastic urothelial cells. RC-160 could be tried therapeutically for the hormonal prevention of malignant transformation of preneoplastic lesions in the urinary bladder.

Amino Acid Sequence↗

PubMed1992

Growth inhibition of estrogen independent MXT mouse mammary carcinomas in mice treated with an agonist or antagonist of LH-RH, an analog of somatostatin, or a combination.

Female BDF1 mice inoculated with MXT (3.2) estrogen independent mouse mammary carcinoma were treated for three weeks with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6]LH-RH, the antagonist SB-75, the somatostatin analog RC-160, or combinations. The lack of estrogen dependence of the tumor was proved by bilateral surgical ovariectomy, which had no effect. In two experiments, treatment with 25 micrograms/day doses of each analog alone resulted in a significant inhibition of tumor growth as shown by a 40-53% inhibition of tumor volumes, 38-43% decrease in tumor weights, and histological signs of tumor regression. However, the combination of SB-75 or [D-Trp6]LH-RH with somatostatin analog RC-160 caused greater reduction of tumor volume (68 and 61%) or tumor weights (59 and 56%), than single analogs, and histologically the occurrence of apoptosis and decrease in AgNOR numbers was more pronounced in the groups receiving combination therapy. Specific binding sites for [D-Trp6]LH-RH, EGF, and IGF-I were demonstrated in the tumor membranes. The binding capacity of LH-RH receptors was decreased by treatment with the analogs, the greatest down-regulation being caused by combination therapy. A significant decrease in EGF binding capacity was observed after treatment with the LH-RH analogs, alone or especially in combination with somatostatin analog RC-160. The combination of these analogs also caused a reduction in IGF-I receptors. The finding that LH-RH agonists and antagonists and somatostatin analogs inhibit the growth of estrogen independent mammary tumors, and that combinations are more effective than single analogs, might be of practical importance in human breast cancer therapy.

Amino Acid Sequence↗

PubMed1992

Modification of DENA-induced hepatocarcinogenesis by CCl4 cirrhosis. Comparison of the marker enzyme patterns.

The modifying action of chronic liver injury on the process of hepatocarcinogenesis was investigated. To induce cirrhosis or fibrosis F344 rats received CCl4 alone or in combination with phenobarbital, either before (model 1) or after (model 2) the application of initiator, diethylnitrosamine (DENA). In these models, morphology, tumor incidence as well as polysubstrate monooxygenase system, gamma-glutamyltransferase (GGT) and glucose-6-phosphatase (G-6-Pase) were studied. The data presented show that in model 1 the tumor incidence was much lower than in rats treated with DENA alone. This reduction appeared to be associated with the decrease in cytochrome P450 content occurring in model 1 after DENA administration. Promotion of the hepatocarcinogenic process was observed when CCl4 injury followed the application of DENA (model 2). Comparison of marker enzymes in cirrhotic livers and in tumors either with or without cirrhosis indicated that changes in cytochrome P450 and G-6-Pase were rather the results of parenchymal damage, while GGT was elevated only in tumorous livers. In tumorous livers none of the xenobiotic metabolizing activities decreased as much as the cytochrome P450 content of the same samples. Thus conceivably the cytochrome P450 operates more rapidly in tumors than in normal livers.

Animals↗

PubMed1992

Development and characterization of a sex-dependent metastatic preputial gland adenocarcinoma in human tumor-bearing immunosuppressed F344 rats.

Newborn F344 rats were treated with polyclonal rabbit anti-thymocyte serum, which caused partial immunosuppression for a limited period. These rats were injected s.c. with cells from human tumor cell lines (two melanomas and a B lymphoma). Within 46 days after the tumor regression a renal carcinosarcoma, resembling Wilms' tumor, developed in each animal, however in male rats an adenocarcinoma of the preputial gland arised. Chromosome analysis and transplantation experiments proved the rat origin of the new tumors. In the present study we describe the biological and morphological characteristics of the adenocarcinoma of the preputial gland (ACPG). Their invasive properties were demonstrated in the lung colony assay, after intra-arterial injection and in the spleen-liver model. ACPG showed unique metastatic phenotype: dependence on the sex of the host.

Adenocarcinoma↗

PubMed1992

Ultrastructure of normal and hepatitis virus infected human and chimpanzee liver: similarities and differences.

Ultrastructure of liver biopsy specimens obtained from normal and hepatitis B (HBV) and hepatitis C virus (HCV) infected livers of patients and chimpanzees were compared. Nuclear alterations (glycogen particles, nuclear bodies, "vermicellar bodies", etc.), intracytoplasmic crystalloid inclusions were observed before and after the HBV and HCV infections both in human and chimpanzee hepatocytes, however, some of them were more common during the viral infection. Extreme endoplasmic reticulum dilatation characterized the human, while the presence of membranous cytoplasmic inclusions the hepatocytes of chimpanzees during HCV infection. Interferon-associated membrane alterations were noted during acute or chronic hepatitis, however, in slightly different forms in humans and chimpanzees. Data suggest to be precautions in the interpretation of the ultrastructural alteration observed in different species even to be so closely related as humans and chimpanzees especially during infection with hepatotropic viruses.

Animals↗

PubMed1992

Differential expression of proteoglycans on the surface of human melanoma cells characterized by altered experimental metastatic potential.

Heparan sulphate (HS) and chondroitin sulphate (CS) proteoglycans (PGs) frequently have opposite biologic functions in cell-matrix adhesion as well as in the regulation of cell proliferation. Data revealed that sulphated glycosaminoglycans (sGAGs) (sugar chains of PGs) are differently expressed in tumor cells characterized by different metastatic potential; the more metastatic cells contain a higher HS/CS ratio. As the proliferative capacity of tumor cells is also frequently altered in parallel with their metastatic potential, it was not clear whether observed PG alterations reflect changes in cell proliferation or metastatic potential. The cell-associated PG expression and sGAG biosynthesis was studied in tumor cells of human melanoma lines characterized by different experimental metastatic potential to the mouse liver but similar in vitro/in vivo proliferation rates. Using antibodies against PGs we found different expression of PG epitopes in melanoma lines, except from the melanoma antigen. Unlike the low CSPG (melCSPG) metastatic melanoma cells, the cell line with high metastatic capacity contained a higher proportion of positive cells for surface-HSPG without the coexpression of certain cartilage-type CSPG epitopes (recognized by MAb HSFPG 529) as well as by an increased pericellular HS/CS ratio due to intracellular accumulation/retention of CS. Immunocytochemistry of adherent cells revealed HSPGs at substrate-attached membrane areas only in cases of highly metastatic melanoma cells. These data further support our view that the absolute or relative dominance of HSPGs over CSPGs at the cell surface of metastatic tumor cells can be considered a marker of a more metastatic phenotype.

Cell Membrane↗

PubMed1991

Effect of combination treatment with analogs of luteinizing hormone-releasing hormone (LH-RH) or somatostatin and 5-fluorouracil on pancreatic cancer in hamsters.

Ductal pancreatic cancers were induced with N-nitrosobis(2-oxopropyl)amine (BOP) in female Syrian golden hamsters. The animals were then treated for 2 months with 5-fluorouracil (5-FU) and with sustained delivery systems of the LH-RH agonist D-Trp-6-LH-RH antagonist (Ac-D-Nal(2)'-D-Phe(4Cl)2-D-Pal(3)3-D-Cit6,D-Ala10)LH- RH(SB-75) and somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), and with some combinations thereof. In the first experiment, the treatment with D-Trp-6-LH-RH plus 5-FU resulted in 52% inhibition of tumorous pancreas weight, a smaller number of tumor nodules on histology, a marked increase of programmed cell death (apoptosis) and a reduced number of AgNOR (argyrophilic nucleolar organizer region) in tumor cells, as compared with controls. The inhibitory effects of this combination were greater than those obtained with 5-FU and D-Trp-6-LH-RH treatment alone. In the 2nd experiment, a 76% inhibition of tumorous pancreas weight, a significant decrease in the number of tumor nodules, an increased amount of stroma, enhanced apoptosis and decreased AgNORs were observed after therapy with somatostatin analog RC-160 plus 5-FU. Most of these tumor inhibition parameters were superior to those in the group treated with 5-FU alone, and in some cases slightly better than those treated with RC-160 alone. Both LH-RH antagonist SB-75 and somatostatin analog RC-160 caused a significant inhibition of tumors, and their combination had the strongest tumor inhibitory effect, with the best survival of animals, the lowest tumorous pancreas weight and the highest apoptosis index among groups. Our results suggest that the combinations of LH-RH analogs with somatostatin analogs or of either type of analog with 5-FU may be superior to single agents in the therapy of pancreatic cancer.

Animals↗

PubMed1991

Localization of receptors for luteinizing hormone-releasing hormone in pancreatic and mammary cancer cells.

Previous work showed that hamster and human pancreatic tumors but not normal pancreata exhibit low-affinity cell-membrane receptors for luteinizing hormone-releasing hormone (LHRH). Although the regression of experimental pancreatic cancers induced by treatment with LHRH agonists or antagonists could be explained in part by the creation of sex-steroid deficiency, direct effects mediated by LHRH receptors might also play a role. Here, we demonstrate that pancreatic tumor cells do exhibit high-affinity binding sites for LHRH, but only in their nuclei; low-affinity sites are associated with the cell membranes. These binding sites appear to be LHRH receptors since electron microscopic immunohistochemical studies show that an antibody to the LHRH receptor reacted with sites in the nucleus of pancreatic tumor cells. Immunoreactive sites in the nucleus also were found in a restricted set of normal hamster pituitary cells thought to be luteinizing hormone-secreting cells and in MXT mouse mammary tumor cells. Such nuclear receptors may be involved in the transmission of the direct action of LHRH analogues on the tumor cells, resulting in the enhancement of programmed cell death.

Animals↗

PubMed1991

[Hepato-lobectomy for carcinoid tumor of the hepatic duct].

Authors performed successful right hepatolobectomy in a 13-year-old girl because of a carcinoid tumor of the right hepatic duct, resulting in obstructive jaundice. The patient remains well 2 years after surgical treatment, complaint- and symptom free. This is the first hepatolobectomy in the Hungarian--and the second one in the world literature performed for carcinoid of the extrahepatic bile ducts.

Adolescent↗

PubMed1991

Histological changes in Dunning prostate tumors and testes of rats treated with LH-RH antagonist SB-75.

Rats bearing Dunning R-3327 hormone-dependent prostate tumors were treated with LH-RH antagonist SB-75 in the form of microcapsules for sustained delivery administered every 3 weeks and which released 24, 48, 72 micrograms/day respectively. The effects were compared with those of microcapsules of the agonist D-Trp-6-LH-RH releasing 25 micrograms/day. Both types of LH-RH analogs significantly inhibited tumor growth over a period of treatment lasting 8 weeks. The effect of SB-75 was dose-dependent. The total inhibition of spermatogenesis, as well as atrophic signs in the prostate and seminal vesicles, demonstrated a marked suppression of the pituitary-gonadal system by these analogs. The histological signs of tumor regression were analyzed. The vascular content of tumors did not change after the treatments, but an increased amount of connective tissue was found in the treated tumors, especially after administration of SB-75. Both the agonist and the antagonist caused a moderate decrease of the number of mitotic cells and a marked increase of apoptosis in the tumors. The apoptotic index, i.e. the percentage of tumorous glands showing signs of apoptosis, reached 40-50% in treated groups, compared to only 15% in controls. An apoptotic index of 60% was noted in a separate group of rats treated with 200 micrograms SB-75/animal/day for 3 days. The signs of enhanced apoptosis disappeared 1 week after the short-term treatment. The induction of apoptosis by LH-RH analogs seemed to be of greater importance in tumor growth inhibition than their antimitotic effect. These results extend our previous observations on the efficacy of LH-RH antagonists in inhibition of various cancers. This histopathologic evaluation clearly supports our contention that modern antagonists of LH-RH, free of edematogenic effects, inhibit the growth of Dunning prostate tumors. Because of the immediate inhibitory effects, the use of LH-RH antagonists might lead to an improvement in the clinical response in patients with prostate cancer.

Animals↗

PubMed1991

Cytometric analysis of DNA replication inhibited by emetine and cyclosporin A.

DNA staining methods based on aspecific interactions with dye molecules have been replaced by an immunofluorescent approach to measure DNA replication. Biotin-11-dUTP was incorporated into permeable thymocytes isolated after emetine or cyclosporin A treatment of mice. Active sites of DNA replication were amplified based on biotin-avidin interaction and verified under fluorescent microscope. Cytometry of fluorescent images allow the direct measurement of replicating DNA without aspecific detection of total cellular DNA. Cytometric analysis of replication revealed that emetine acts at the early S phase, while cyclosporin A blocks in vivo DNA synthesis at mid S phase.

Animals↗

PubMed1991

Interaction between elastin and tumor cell lines with different metastatic potential; in vitro and in vivo studies.

Interactions between the extracellular matrix macromolecules and tumor cells are critical in the process of metastasis formation. We show here that elastins (both mature insoluble elastin and a 75-kDa soluble peptide: K-elastin) adhere rapidly to two cell lines with high metastatic capacities: a metastatic lung carcinoma cell line (3LL-HM) and a human amelanotic melanoma cell line (A-2058); by contrast the low-metastatic Lewis lung carcinoma cell line variant as well as a rhabdomyosarcoma cell line with a low metastatic potential bind to elastins to a much lower extent. 3H-labelled K-elastin was used in order to study elastin--3LL-HM interaction. It was found to be saturable (2 ng 3H-labelled K-elastin/10(6) cells), with one class of high-affinity binding sites having Kd equal to 1.3 nM and 16,000 sites/cell. The binding of K-elastin to 3LL-HM cells at its receptor triggered several cell responses; (a) increase of intracellular Ca2+ concentration; (b) induction of 3LL-HM chemotaxis toward the K-elastin gradient; (c) stimulation of the adherence of mature insoluble elastin. In contrast to non-transformed cells such as fibroblasts and smooth muscle cells, the adhesion kinetics of insoluble elastin to 3LL-HM did not exhibit a lag period; the rapid binding of insoluble elastin to the tumor cells was followed by its slow detachment from the cells, which lasted for 6 h. 3LL-HM cells but not human skin fibroblasts were shown to secrete elastinolytic activity inhibitable by metal-chelating agents. In vivo studies were performed in order to evaluate the influence of K-elastin binding to 3LL-HM cells on their ability to form lung colonies in mice. It was shown that pretreatment of 10(4) 3LL-HM cells with 10 microM K-elastin and the simultaneous i.v. injection into mice of 750 micrograms K-elastin together with the highly metastatic cells was able to reduce the number of lung colonies by more than 70% after 12 days.

Adult↗

PubMed1991

Inhibitory and promoting effects of carbon tetrachloride-induced liver cirrhosis on the diethylnitrosamine hepatocarcinogenesis in rats.

The modifying effect of the experimentally induced liver cirrhosis on the diethylnitrosamine (DENA)-hepatocarcino-genesis was investigated in male Fischer 344 rats. Cirrhosis was produced by either repeated intragastric doses of CCl4 for 3 months or by simultaneous administration of CCl4 and phenobarbital (PB) in drinking water for 6 weeks. The hepatocarcinogenic regimen consisted of multiple ip. administrations of DENA (10 mg/kg b.w. per dose, up to a total dose of 200 mg/kg b.w.). All the animals were killed 8 months after starting the experiment. The chronic CCl4-post-treatment exerted a strong promoting effect, while the established cirrhosis completely prevented the formation of hepatocellular carcinomas.

Animals↗

PubMed1991

Morphological studies on the effect of L-leucine methyl ester on mouse peritoneal macrophages in vitro.

Mouse peritoneal macrophages (MO) were treated in culture with 5 mM L-leucine methyl ester (L-Leu-OMe), for 5, 10, 20, 40, and 60 min. The treatment resulted in rapid vacuolisation of the cytoplasm due to the dilatation and disruption of lysosomes. Autophagy caused by lysosomal enzymes destroyed most of the cytoplasmic organelles by 40 minutes after L-Leu-OMe treatment, but the cell membrane and nucleus were in many MOs resistant to the damage. 60 min after L-Leu-OMe treatment most of the MOs were killed. It is supposed that the disruption of the lysosomes is caused by formaldehyde produced by the hydrolysis of L-Leu-OMe.

Animals↗

PubMed1991

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

The effect of D-penicillamine (Pe) on liver fibrosis-cirrhosis induced by chronic CCl4 and phenobarbital (Pb) administration in Fischer 344 male rats was studied. Morphometric analysis did not reveal a decrease in the amount of connective tissue fibers after Pe-treatment. Compared to the CCl4 and Pb-treated control groups, Pe had no significant effect on the concentrations of hydroxyproline, a parameter of collagen degradation, either; however, it increased the glycosaminoglycan concentrations. Lymphocyte stimulation by Con-A in the Pe-treated groups did not differ from that of the CCl4 and Pb-treated ones. According to our studies, Pe-treatment was ineffective in rats with liver fibrosis-cirrhosis induced by CCl4 and Pb administration. It seems that Pe can be effective only in the cirrhosis types accompanied by a considerable copper accumulation due to suppression of the toxic effects of copper.

Animals↗

PubMed1991

Alkaline phosphatase activity in human and rat liver tumors.

Enzyme activity measurements of alkaline phosphatase in surgically removed human liver tumors showed elevated level of the enzyme in 6 focal nodular hyperplasias, reduction in 8 primary hepatocellular carcinomas, and no change in the 4 adenoma samples. The activity represented liver type of alkaline phosphatase nearly in all cases because it could be inhibited by L-homoarginine more extensively than by L- phenylalanine. Studies on polyacrylamide gel electrophoresis indicated the presence of a variant type isoenzyme only in one focal nodular hyperplasia and in two hepatocellular carcinomas, one of which showed a fibrolamellar structure whereas the other was associated to cirrhosis. The importance of the elevated amount of connective tissue in the tumor, resulting in an isoenzyme shift of alkaline phosphatase, received substantial support upon comparing chemically induced rat liver tumors with and without cirrhosis.

Alkaline Phosphatase↗