Biomedical subjects

K Lapis

Publications and source records attributed to K Lapis.

At least 73 records · Page 4Linked to original sources

PubMed1991

Liver damaging effect of suramin in normal and carbon-tetrachloride treated rats.

Male Fischer 344 (F344) rats were treated with phenobarbital + carbon tetrachloride (CCl4) for 16 weeks to induce liver cirrhosis. Another group of rats received 50 mg/kg iv suramin once a week for 16 weeks. The third group of rats was treated with both phenobarbital + CCl4 and suramin. After 16 weeks of suramin treatment, a massive periportal infiltration composed of macrophages, many of them containing glycosaminoglycans in their cytoplasm, mast cells, and other inflammatory cells were observed. This lesion was added to the liver cirrhosis caused by CCl4 in the group treated with suramin and CCl4. The changes in glycosaminoglycan metabolism caused by suramin did not influence the CCl4 cirrhosis. Since suramin has been reported to be a prototype of a new generation of antitumor compounds, we suggest caution in the use of chronic suramin treatment, especially in patients with livers which are already damaged.

Animals↗

PubMed1991

Flow cytometric analysis of DNA content in focal nodular hyperplasia and hepatocellular carcinoma.

DNA index of twenty-three surgically removed, formalin-fixed and paraffin-embedded liver specimens (10 focal nodular hyperplasias--FNH, and 13 hepatocellular carcinomas--HCC) were studied by flow cytometry. Diploid value appeared in 9/10 FNH (one was hypodiploid), while 10/13 HCC (77%) had DNA aneuploidy (one hypo- and 9 hyperdiploid). The presence of normal DNA content in 3 HCCs suggests that DNA aneuploidy only cannot indicate the malignant transformation of a benign lesion (e.g. FNH).

Adolescent↗

PubMed1991

Hepatocellular carcinoma in Fanconi's anemia treated with androgen and corticosteroid.

The case of an 11-year-old boy is reported who was known to have Fanconi's anemia for 3 years and was treated with androgens, corticosteroids and transfusions. Two weeks before his death he was readmitted because of aplastic crisis with septicemia and marked abnormalities in liver function and died of hemorrhagic bronchopneumonia. At autopsy peliosis and multiple hepatic tumors were found which histologically proved to be well-differentiated hepatocellular carcinoma. This case contributes to the previous observations that non-metastasizing hepatic neoplasms and peliosis can develop in patients with androgen- and corticosteroid-treated Fanconi's anemia.

Adrenal Cortex Hormones↗

PubMed1991

Connective tissue content of fibrolamellar carcinoma and other human liver tumors.

The connective tissue content of four different human liver tumors (Fibrolamellar carcinoma, FLC; hepatocellular carcinoma, HCC; focal nodular hyerplasia, FNH and hepatocellular adenoma, HCA) was investigated by computer aided morphometry. A significantly higher connective tissue content was found in FNH and FLC as compared to HCA and HCC. The distribution of the connective tissue was homogeneous in the cases of FNH, HCA and HCC, while a highly unhomogeneous distribution was observed in FLC cases.

Adolescent↗

PubMed1991

Connective tissue content of fibrolamellar carcinoma and other human liver tumors.

The connective tissue content of four different human liver tumors (Fibrolamellar carcinoma, FLC; hepatocellular carcinoma, HCC; focal nodular hyperplasia, FNH and hepatocellular adenoma, HCA) was investigated by computer aided morphometry. A significantly higher connective tissue content was found in FNH and FLC as compared to HCA and HCC. The distribution of the connective tissue was homogeneous in the cases of FNH, HCA and HCC, while a highly unhomogeneous distribution was observed in FLC cases.

Adolescent↗

PubMed1991

Immunocytochemical demonstration of tissue transglutaminase indicative of programmed cell death (apoptosis) in hormone sensitive mammary tumours.

Tissue transglutaminase (TG) positive tumour cells in MXT mouse mammary cancer were localized by immunohistochemistry. The number of TG-positive tumour cells increased after treatment with analogs of luteinizing hormone-releasing hormone (LH-RH) and somatostatin, which inhibit tumour growth by the enhancement of apoptosis (programmed cell death). TG positivity has been previously reported to be closely linked with apoptosis. In this study, the increase in the number of TG positive tumour cells after hormonal treatment was well correlated with the augmented apoptotic index, i.e. the ratio of tumourous glandular structures which contained tumour cells showing the signs of programmed cell death. TG-positive tumour cells are, therefore, believed to be undergoing programmed cell death.

Amino Acid Sequence↗

PubMed1991

Immunohistochemical detection of transforming growth factor-beta 1 in fibrotic liver diseases.

Transforming growth factor-beta 1 was localized by means of immunohistochemical reaction in liver biopsy specimens taken from patients having different chronic liver diseases with extending fibrosis. Two polyclonal antibodies that were produced in rabbits were directed against the amino terminal of transforming growth factor-beta 1. Staining by anti-CC(1-30) was primarily extracellular and located in the portal and periportal fibrotic areas of all seven cases with chronic active hepatitis. No staining was noted in the four chronic persistent cases studied. A strong reaction was seen with the antibody in nine of the ten cirrhotic samples, whereas it was negative in one inactive cirrhosis case and in all five cases with normal liver histological findings. No positive staining could be detected by the anti-LC(1-30) in any of the liver tissues. Detection of transforming growth factor-beta 1 in active liver diseases at the site of fibrosis suggests that transforming growth factor-beta 1 might have a role in the process and progression of fibrosis during the development of the disease.

Antibodies↗

PubMed1991

The relief of biliary obstruction in experimental rats by diverting the hepatic lymph into the duodenum.

Twelve days after their common bile ducts had been ligated rats were icteric and their hepatic lymph nodes and lymph ducts were two or three times their normal size. Cannulation of the hepatic lymph ducts of these rats yielded bile-stained lymph which flowed at nine times its normal rate. As the lymph flowed, so the concentration of bilirubin in the blood declined; after 5 days the rats were no longer jaundiced, and by day 11 there were normal amounts of bilirubin in the blood. In another series it proved possible on seven occasions to insert the free end of the hepatic lymph cannula into the duodenum at the time that the bile was obstructed. Five of these animals showed no increase in serum bilirubin and remained in good condition until the experiments were terminated up to 61 days later. It seems that the effects of biliary obstruction can be mitigated by shunting the hepatic lymph into the intestine.

Animals↗

PubMed1991

Liver-metastatic human colon carcinoma in immunosuppressed mice.

An experimental liver metastasis model using the HT-29 human colon carcinoma cell line is described. The tumor xenograft in immunosuppressed mice preserved the histological type as well as the human and gastrointestinal markers (HLA-I, CEA). This model seems to be suitable for the development of new therapeutic protocols as well as for the study of metastasizing of a frequent human tumor type.

Animals↗

PubMed1990

Investigations on the antitumor effect and mutagenicity of alpha-MSH fragments containing melphalan.

alpha-MSH fragments containing melphalan were tested in vivo on L1210 leukemia and on human amelanotic melanoma xenograft in mice and in vitro on human amelanotic melanoma cell lines. The compounds exhibit significant antitumor activity, but no selectivity in targeting of melanoma can be achieved. There is a difference between melphalan and the melphalyl-peptide in their action on protein synthesis. The peptide derivatives also are less mutagenic than melphalan, according to the SCE assay, furnishing further evidence for the positive effect of natural carrier molecules.

Amino Acid Sequence↗

PubMed1990

Modification of the inhibitory effects of CCl4 on phospholipid and protein biosynthesis by prostacyclin.

CCl4 induced cellular injury and its modification by prostacyclin (PGI2) was studied in cultured rat hepatocytes. Biosynthesis of both intracellular and serum proteins and that of phospholipids decreased upon CCl4 treatments (IC50 7.0, 2.5 and 3.2 mM, respectively). After 1 hr exposure of the cells to CCl4, the reductions in the biosynthesis increased further with time. PGI2 treatments (10(-5)-10(-9) M) of the hepatocytes subsequent to CCl4 poisoning resulted in partial recovery from the cell injury evaluated at the fifth hour of the experiment. Optimal effects of PGI2 were found at a concentration of 10(-7)-10(-8) M, while higher and lower concentrations offered less protection. Upon the addition of CCl4 a higher catabolic rate of PIP2 and an increased formation of inositol phosphates were observed. This alteration was shown to precede the defects in the labelling of the major phospholipid components. Furthermore, these changes were circumvented in the presence of PGI2. Thus, PIP2 metabolism appears to be a critical process in the mechanism of this type of cellular injury and its protection by PGI2.

Animals↗

PubMed1990

Selection and characterization of human melanoma lines with different liver-colonizing capacity.

Two human melanoma lines with low (HT168) and high (HT168-MI) liver metastatic capacity in immunosuppressed mice were selected in vivo from the A2058 cell line. After i.v. injection of the 2 tumor lines there was no significant difference either in the number of lung colonies or in the frequency and tissue distribution of extrapulmonary tumor deposits. These findings suggest that the selection in the spleen-liver system did not result in an overall increase in the metastatic potential of the melanoma cells, but rather that it represented an organ-preferential selection. The HT168-MI cells did not acquire an increased growth rate in vitro or in vivo, suggesting that other phenotypic alterations are responsible for the enhanced metastatic capacity. The 2 tumor lines were characterized by similar expression of HLA-A,B,C, transferrin receptor and melanoma-associated proteoglycan antigen. HT168 contained more NGF receptor, while HLA-DR appeared only on HT168-MI cells. This human metastasis model could be useful in studying the mechanisms of liver metastasis formation, as well as in revealing possible new targets of antimetastatic therapy.

Animals↗

PubMed1990

[The hepatitis C virus--principal causative agent in non-A, non-B hepatitis].

The diagnosis of non-A, non-B (NANB) hepatitis was based on the exclusion of hepatitis A and B infection and other known causes of hepatitis, such as other viruses, alcohol and toxic effects. More recently, an RNA has been isolated from a NANB-infected chimpanzee serum and with its aid a polypeptide antigen was produced by molecular biological methods. Antibodies to this antigen--as part of the infectious agent, called hepatitis C virus (HCV)--were detected in the sera of infected patients. Studies with this antigen/antibody system proved, the HCV is responsible for the majority of posttransfusion and sporadic NANB hepatitis cases worldwide. The antibody appears late, in the serum up to 6 months after the infection. The occurrence of the infection is high among hemophiliacs and drug abusers. Anti-HCV antibody was detected also in certain liver disease with "unknown etiology" (chronic active hepatitis, primary biliary cirrhosis). This newly developed test provides the possibility to prove HCV infection in different groups of patients by detecting an antibody to a component of HCV.

Hepacivirus↗

PubMed1990

5-Hexyl-2'-deoxyuridine blocks the cytotoxic effects of 5-fluorodeoxyuridine or deoxyadenosine in leukemia L1210 cells in culture.

Antitumor agents which block the de novo synthesis of nucleotides can be circumvented by the presence of salvage pathways for the reutilization of nucleobases and nucleosides. Studies have been carried out which show that 5-hexyl-2'-deoxyuridine (HdUrd) effectively blocks the cytotoxic effects of deoxyadenosine and fluorodeoxyuridine in L1210 cells. Although HdUrd (500 microM) had essentially no effect on the growth of L1210 cells in culture, the total uptake of [14C]cytidine into these cells was inhibited 99% by this concentration of HdUrd. The inhibitory effects of fluorodeoxyuridine (FdUrd) and deoxyadenosine could be completely prevented by the presence of HdUrd (200 microM). The growth inhibitory effects of fluorouracil were not prevented by HdUrd. Dipyridamole prevented the inhibition of L1210 cell growth by FdUrd but not by deoxyadenosine or fluorouracil. 5-Isopropyl-, 5-pentyl-, and 5-octyldeoxyuridine were not effective in preventing the cytotoxic effects of deoxyadenosine. The data suggest that HdUrd might be useful in blocking the salvage of nucleosides, thereby potentiating the effects of inhibitors of de novo nucleotide synthesis.

Animals↗

PubMed1990

Regression of nitrosamine-induced pancreatic cancers in hamsters treated with luteinizing hormone-releasing hormone antagonists or agonists.

Groups of 15 female Syrian golden hamsters with N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancers were treated for 2 mo with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) antagonist [Ac-D-Nal(2)1-D-Phe(4Cl)2-D-Pal(3)3,D-Cit6,D-Ala10] LH-RH (SB-75) releasing 8 micrograms/day or with the microcapsules of the LH-RH agonist D-tryptophan-6-luteinizing hormone-releasing hormone (D-Trp-6-LH-RH) releasing 8 micrograms/day or 25 micrograms/day. Chronic treatment with SB-75 resulted in 70% inhibition of pancreatic tumor weight; D-Trp-6-LH-RH in doses of 8 micrograms/day and 25 micrograms/day produced 66% and 62% inhibition, respectively. The number of animals with pancreatic tumors was reduced by about 50% in each treated group. Tumorous ascites were found in seven control hamsters and in one hamster in each group treated with D-Trp-6-LH-RH but not in the group given SB-75. Reduction in serum luteinizing hormone levels and ovarian as well as uterine weights indicated that an inhibition of the pituitary-gonadal axis occurred during chronic SB-75 and D-Trp-6-LH-RH treatment. Membrane receptor assays showed a significant decrease of the concentration of binding sites for LH-RH in tumor cells after SB-75 or D-Trp-6-LH-RH treatment. Insulin-like growth factor I receptors, but not epidermal growth factor receptors, were down-regulated by D-Trp-6-LH-RH. SB-75 did not influence the concentration or the binding capacity of insulin-like growth factor I and epidermal growth factor receptors in the tumor cells. The inhibitory effect of chronic treatment with SB-75 and D-Trp-6-LH-RH on tumor growth was mediated by enhanced apoptosis (programmed cell death) induced by the change in hormonal environment. Apoptosis was also produced in hamsters with N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancers by acute treatment (3 to 6 days) with high doses of D-Trp-6-LH-RH or SB-75. In view of its potency and an immediate powerful inhibitory effect, the LH-RH antagonist SB-75 might be considered as a possible new hormonal agent for the treatment of exocrine pancreatic cancer.

Animals↗

PubMed1990

Inhibitory effects of analogs of luteinizing hormone-releasing hormone and somatostatin on pancreatic cancers in hamsters. Events that accompany tumor regression.

Syrian golden hamsters bearing N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinomas were treated for 2 months with the delayed delivery systems of the agonist D-Trp-6-LH-RH (microcapsules releasing 25 micrograms/day for 30 days), the somatostatin analog RC-160 (the microcapsules liberating 48.2 micrograms/day for 30 days), or with the combination of these two analogues. The increase in the dose of RC-160 was possible in view of the lack of toxicity of this analog. This higher dose of RC-160 exerted a greater suppressive effect on pancreatic cancers than the regimens previously used (5-25 micrograms/day). RC-160, D-Trp-6-LH-RH, and their combination reduced the number of pancreatic carcinomas and significantly inhibited tumor growth as compared with the controls. The combination had the strongest tumor-inhibitory effect and reduced tumor weight by 85% as compared with controls. Both the light and electron microscopic analysis of the tumors showed that the inhibitory effect was due to the enhancement of apoptosis (programmed cell death) of tumor cells. Insulin-like growth factor (IGF-I) receptors were detected immunohistochemically in the untreated tumors and their number decreased after the treatment with the analogues. Binding of D-Trp-6-LH-RH and RC-160 to tumor cells was shown immunohistochemically and receptors to these analogues and IGF-I were also determined biochemically by radioligand titration. Treatment with D-Trp-6-LH-RH and RC-160 decreased the binding capacity of receptors for D-Trp-6-LH-RH and IGF-I, producing down-regulation of these receptors. This suggests that pancreatic tumor cells with receptors to these peptides are sensitive to the treatment. This work reinforces the view that the combination of high doses of somatostatin analog RC-160 with LH-RH agonists or antagonists should be considered for the development of a new hormonal therapy for ductal pancreatic cancers.

Amino Acid Sequence↗

PubMed1990

Altered glycosaminoglycan composition in reactive and neoplastic human liver.

We have investigated the glycosaminoglycan composition of normal human liver, focal nodular hyperplasia, hepatic adenoma, and hepatocellular carcinoma. Uronic acid increased about 4 fold in the benign and reactive lesions, and greater than 7 fold in the carcinoma. Whereas in focal nodular hyperplasia and adenoma dermatan sulfate was the predominant glycosaminoglycan, in hepatocellular carcinoma chondroitin sulfate was the predominant species; it increased 24 fold over normal liver and 3-5 fold over all the other tissues. HPLC analysis of chondroitinase ABC or AC digests showed a 58 fold increase in Delta-Di-OS disaccharides in hepatocellular carcinoma, indicating significant undersulfation of chondroitin sulfate. Surprisingly, the normal-appearing liver surrounding the carcinoma showed glycosaminoglycan changes similar to adenoma and nodular hyperplasia. These results thus indicate that specific glycosaminoglycan changes occur in hepatocellular carcinoma, and suggest for the first time that proteoglycan metabolism is also altered in the non-cirrhotic, hepatic parenchyma adjacent to liver carcinoma.

Adenoma↗

PubMed1990

Growth inhibition of mouse MXT mammary tumor by the luteinizing hormone-releasing hormone antagonist SB-75.

Female BDF1 mice bearing MXT mammary adenocarcinomas were treated for 3 weeks with the luteinizing hormone-releasing hormone (LH-RH) antagonist [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]-LH-RH (SB-75), with the agonist D-Trp6-LH-RH, with tamoxifen (5 micrograms per animal per day subcutaneously), with the combination of D-Trp6-LH-RH and tamoxifen, or by surgical ovariectomy. SB-75 and D-Trp6-LH-RH were administered in the form of microcapsules releasing 25 micrograms/day. The reduction in tumor weights after treatment with SB-75, D-Trp6-LH-RH, D-Trp6-LH-RH plus tamoxifen, or ovariectomy was 84%, 64%, 33%, and 67%, respectively. Tamoxifen alone was ineffective. Histologically, the regressive changes in the treated tumors were characteristic of apoptosis (programmed cell death). In view of its potency and its immediate inhibitory effect, the LH-RH antagonist SB-75 should be considered as a possible new hormonal agent for the treatment of breast cancer.

Adenocarcinoma↗