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Biomedical subjects

G N Tzanakakis

Publications and source records attributed to G N Tzanakakis.

12 recordsLinked to original sources
PubMed1992

In vivo selection of a highly metastatic cell line from a human pancreatic carcinoma in the nude mouse.

A cell line with high metastatic capacity to the liver was established by sequential passages of a human pancreatic cancer cell line through the nude mouse liver. A subline, L3.5, established after five passages of the fast-growing variant (FG) of the human pancreatic cancer COLO 357 through the nude mouse liver produced extensive hepatic metastases in 100% of experimental animals when injected into the spleen. The incidence of pulmonary metastases decreased from 43% for FG to 9% for L3.5. The L3.5 cell line showed aggressive growth with almost complete replacement of the hepatic parenchyma in one third of the mean time required for the development of macroscopic metastases of FG in the liver after splenic injections of tumor cells. This study indicates that the nude mouse provides a good model for in vivo selection of metastatic cells from human pancreatic cancer. The L3.5 cell line will be valuable in the study of human pancreatic cancer metastasis, particularly in the area of survival and growth of metastatic cells in the microenvironment of the liver.

Adenocarcinoma↗
PubMed1992

Light microscopy of dried saliva in the evaluation of xerostomia of the sicca syndrome. A preliminary report.

Dried, freshly produced saliva from 21 patients with xerostomia related to the sicca syndrome [15 with primary Sjögren's syndrome (pSS), 3 with rheumatoid arthritis (RA) and secondary Sjögren's syndrome (sSS), and 3 with Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE)] and 21 age and sex matched controls, was examined by light microscopy. A typical fern-like pattern was demonstrated by the crystallized mucus of the healthy individuals. In contrast, much thicker, shorter, irregular and densely arranged branches of crystallized mucus, sometimes giving a reindeer horn appearance, were observed in the patients' saliva. Given the lack of a reliable clinical measure for the objective evaluation of xerostomia, light salivary microscopy, simple and easy as it is, may fill this deficit, if its sensitivity and specificity are documented.

Aged↗
PubMed1991

Effects of antiplatelet agents alone or in combinations on platelet aggregation and on liver metastases from a human pancreatic adenocarcinoma in the nude mouse.

There is ample evidence to suggest that hematogenous metastasis may be related to the ability of tumor cells to promote aggregation of host platelets. Arachidonic acid metabolism in platelets and vessel walls may also contribute to the metastatic process. Several preliminary trials of platelet inhibitory agents have been performed. Ketoconazole (inhibitor of lipoxygenase and thromboxane synthetase), verapamil (calcium antagonist), forskolin (stimulator of platelet adenylate cyclase), and indomethacin (inhibitor of cyclooxygenase) were examined, alone and in combination, to investigate their effects on platelet aggregation and on hepatic metastases from human pancreatic tumor cells (RWP-2) in nude mice. The tumor cells were injected intrasplenically, and the animals were divided into control, single-drug and combination treatment groups. The agents were administered intraperitoneally 1 hr before and every 24 hr after the tumor cell injections for 6 days. Statistically significant differences were observed between the control and single-treatment groups on the reduction of liver tumor nodules (range P less than 0.001-0.032) and in the liver surface areas occupied by tumor (range P less than 0.001-0.013). Furthermore, when these agents were combined, similar reductions in liver tumor nodules were noted (range P less than 0.001-0.008), while even greater inhibitory effects were seen in the liver surface areas occupied by tumor (P less than 0.001) compared with the single-treatment groups. Also, the combination studies strongly inhibited RWP-2-induced platelet aggregation in human platelet-rich plasma.

Adenocarcinoma↗
PubMed1990

Inhibition of hepatic metastasis from a human pancreatic adenocarcinoma (RWP-2) in the nude mouse by prostacyclin, forskolin, and ketoconazole.

Metastasis is a multistep phenomenon in which platelets appear to play an important role. This study examined several compounds for their effects on experimental hepatic metastasis and on human pancreatic tumor cell-platelet interactions. Prostacyclin (PGI2) and forskolin (stimulators of platelet adenylate cyclase) and ketoconazole (inhibitor of lipoxygenese and thromboxane synthetase) were used in order to investigate their effects on hepatic metastases from a human pancreatic tumor cell (RWP-2) in the nude mouse. The tumor cells were injected intrasplenically and the animals were divided into control, prostacyclin (PGI2 200 micrograms), forskolin (150 micrograms), and ketoconazole (180 micrograms) groups. All three drugs were administered intraperitoneally 30 minutes before and 24 hours after the tumor cell injections. Statistically significant differences were observed between control and treated groups in tumor surface area (P less than 0.001), percentage of liver surface area occupied by tumor (P less than 0.001), and number of tumor colonies (P less than 0.004 for prostacyclin, P less than 0.005 for forskolin, and P less than 0.001 for ketoconazole). These agents also strongly inhibited RWP-2-induced platelet aggregation in human platelet-rich plasma.

Adenocarcinoma↗
PubMed1990

Epidermal growth factor stimulation and metastatic rate in human pancreatic carcinoma cell lines.

Pancreatic carcinoma is usually a fatal disease with most patients dying of metastases. We have developed several pancreatic carcinoma cell lines that have varying metastatic abilities in a splenic injection/liver metastasis model. Epidermal growth factor (EGF) is a mitogen to most cell types with increased levels of EGF receptor. The parent cell line (COLO-357) of the pancreatic carcinoma cell lines used in this study has been shown to have a high number of EGF receptors per cell. We studied the relationship between the mitogenic responsiveness to EGF and the metastatic rate of each of the cell lines. Three of the six cell lines were significantly stimulated by EGF as determined by an increase in cell number over the course of 4 days, and three of the cell lines were not. There was no correlation between metastatic rate and EGF responsiveness. Further work will be needed to determine if there is any relationship between growth factors and their receptors and tumor metastasis with these pancreatic cancer cell lines.

Animals↗
PubMed1990

Effects of prostacyclin on hepatic metastases from human pancreatic cancer in the nude mouse.

Human pancreatic cancer is an aggressive malignancy, with systemic metastases ultimately accounting for its grave prognosis. Arachidonic acid metabolites known to affect platelet function also interfere with tumor growth and metastases. We evaluated the effect of prostacyclin on the hepatic metastases of a human pancreatic cancer in a nude mouse model. The mean surface area of tumor on the liver was significantly reduced in all treatment groups. In the control group 485 mm2 of tumor was present on the liver surface. Animals treated with 200 micrograms of prostacyclin 0.5 hr prior to the injection of tumor cells had 21 mm2 of tumor present on the liver surface (P = 0.004). Similarly, 400 micrograms of prostacyclin caused a reduction of tumor surface area to 20 mm2 (P = 0.004). The maximal reduction of tumor surface area, 11 mm2, was observed when 200 micrograms of prostacyclin was given 0.5 hr prior to and 4.0 hr after the injection of tumor cells (P = 0.003). For the group given 200 micrograms of prostacyclin 4.0 hr after the injection of tumor, the surface area of tumor was 85 mm2 (P = 0.017). The number of tumor colonies on the liver surface was significantly reduced from 20 to 11 when 200 micrograms of prostacyclin was administered intraperitoneally 0.5 hr before and 4.0 hr after the injection of tumor cells (P = 0.047). These results indicate that prostacyclin has antimetastatic activity on hepatic metastases from a human pancreatic adenocarcinoma in the nude mouse.

Animals↗
PubMed1990

Primary extranodal non-Hodgkin's lymphoma of the extrahepatic biliary tract.

A case of extranodal non-Hodgkin's diffuse, mixed small and large cell lymphoma of the extrahepatic biliary tract with jaundice as the initial manifestation is reported in this paper. Obstructive jaundice is very rarely an early symptom in lymphoma. The pathogenesis of jaundice in this case was infiltration of the extrahepatic bile duct by lymphoma cells and fibrosis.

Aged↗
PubMed1989

Histopathological lesions produced by P. aeruginosa lipopolysaccharide in rats.

The lipopolysaccharide (LPS) of Pseudomonas aeruginosa is considered to be less toxic than the LPS from the Enterobacteriaceae family. The present study was undertaken to determine the time course of lesions produced in the lungs, spleen, liver, kidneys and bone marrow from 1 to 168 hours following a single (1.5mg) intravenous injection of P. aeruginosa LPS--1R (S-form), and its mutant strains, 557 (R-form) and 605 (more-R-form)--in rats. The lesions consisted of atelectasis, infiltration by polymorphonuclear leukocytes, intraalveolar hemorrhage and perivascular edema of the lung, hyperplasia of the white pulp of the spleen, necrosis of hepatic parenchyma, vacuolization of cells of the adrenal zone fasciculata, and hyperplasia of bone marrow. Immunoperoxidase stain for the R-form and the more-R forms of LPS of P. aeruginosa showed similar distribution kinetics within hepatocytes and Kupffer cells, while the S-form required 24 hours to become evident within hepatocytes. The data show that all 3 LPS preparations are toxic, distributed differently within hepatocytes, as demonstrated by immunoperoxidase stains, and exhibit different time courses and severity of lesions within the affected organs.

Adrenal Gland Diseases↗
PubMed1989

Inhibition of neoplastic growth by N-homocysteine thiolactonyl retinamido cobalamin.

Because of the importance of homocysteine thiolactone metabolism in the growth of normal tissues, and because of abnormal metabolism of homocysteine thiolactone in malignant cells, N-substituted derivatives of homocysteine thiolactone were synthesized and assayed for antineoplastic and anticarcinogenic activities. A single dose of 2.5 mg/kg of the synthetic derivative, N-homocysteine thiolactonyl retinamido cobalamin, injected directly into subcutaneous human pancreatic adenocarcinoma neoplasms in athymic mice, caused 50% inhibition of growth without evidence of toxicity. The findings suggest a novel approach to counteracting the growth of malignant neoplasms and support the hypothesis of a deficiency of an N-homocysteine thiolactonyl derivative in malignant cells.

Adenocarcinoma↗