A specifically radiolabeled somatostatin analog with strong antitumor activity induces apoptosis and accumulates in the cytosol and the nucleus of HT29 human colon carcinoma cells.

The new heptapeptide somatostatin analog TT-232 decreases proliferation of HT-29 human colon carcinoma cells in vitro by reducing mitotic and increasing apoptotic activity. We have synthesized and characterized a specifically tritium labeled 3H-Tyr3-TT-232 (30 Ci/mmol) to investigate the effect and the fate of this antitumor peptide on human colon tumor cells. 3H-labeled TT-232 could be detected on the cell surface, on cytoplasmic membranes and also in the nucleus of HT-29 cells, 1-6 h after the administration of 0.

The pathomorphology of a human xenotransplanted basaloid squamous cell carcinoma.

To elucidate some factors related to the malignant phenotype of an oral tumor with mixed cell population the question has been raised whether the biological behavior of the basaloid or the squamous cells show any difference in an immunosuppressed host organism. Basaloid squamous cell carcinoma (BSCC) surgically removed from sublingual location was xenotransplanted either subcutaneously or in the oral submucosa and the histology, ultrastructures, LDH isoenzyme pattern were investigated. The epithelial origin of the established tumor line (HTB-1) could be recognized according to the characteristic epithelial ultrastructures, while the type of the LDH isoenzymes proved its human origin.

Oral administration of a trace element preparation and zinc inhibit liver metastasis of 3LL-HH murine tumor cells.

A trace element preparation (TEP-Beres Drops Plus) was given to liver metastasizing 3LL-HH tumor bearing mice in the presence and after the removal of the primary spleen tumor. In both models when TEP was provided daily and orally in a dose range of 100-5,000 microgram/kg, the number of liver metastasis decreased at an end-point of day 14 and TEP also had inhibitory effect on the primary tumor. The antitumor action proved to be dependent on tumor burden.

A new method to localize acid phosphatase using the confocal laser-scanning microscope.

The aim of the study was to work out a technique for the detection of acid phosphatase enzyme activity by confocal laser-scanning microscope using the histochemical acid phosphatase detection method (after Barka and Anderson 1962, modified by Bowen and Lewis 1985) routinely used for light microscopy. The density and the distribution of enzyme reaction product is dependent on the incubation time, as shown by different confocal images or ELISA reader. The inhibition of the enzyme activity with metal ions shows the same profile known from the literature.

Pancreatic leiomyosarcoma. Case report with immunohistochemical and flow cytometric studies.

A leiomyosarcoma originating from the pancreas of a 57-year-old man is presented. A 6x5x4 cm tumour was located in the head region, and the patient underwent surgical palliation. Immunohistochemical studies excluded an epithelial origin; a myogenic origin was suggested by strong vimentin and smooth muscle actin positivity.

Establishment and characterization of a new transplantable pancreatic cancer xenograft (PZX-5) in immunosuppressed mice.

Conclusion: A new, stable, transplantable human pancreatic cancer xenograft (PZX-5) model has been established in CBA immunosuppressed mice.

Background: Numerous human pancreatic carcinomas have been successfully transplanted into athymic nude mice. However, artificially immunosuppressed animals have rarely been used as recipients.

Clinicopathologic aspects of 8 Kaposi's sarcomas among 1009 renal transplant patients.

In 8 of 1009 patients receiving renal grafts and consecutive immunosuppressive therapy during the last 20 years in Budapest, Hungary, Kaposi's sarcoma developed 6.5 months (average) after transplantation. Of 8 cutaneous cases of this disease, 5 also presented visceral manifestations.

Role of sinusoidal heparan sulfate proteoglycan in liver metastasis formation.

Previous studies have indicated that the predominant sites of tumor cell extravasation in the liver are the sinusoidal vessels, where tumor cells contact the sinusoidal endothelium and the subendothelial extracellular matrix containing the basic components of the basement membrane. We studied the role of sinusoidal extracellular matrix in metastatsis formation by 3LL-HH murine tumor cells selected for their preferential liver colonization. 3LL-HH tumor cells did not efficiently adhere to cryosections of the liver, but they recognized the sinusoids and vessel walls.

Regulation of Differentiation, Proliferation and Drug-Induced Apoptosis in HT58 Lymphoma Cells.

Recently, it has been suggested, that differentiated cells are more resistant to the apoptotic effect of DNA damaging agents possibly due to the decreased activity of "damage detecting/apoptosis triggering" mechanism. Previously, we have shown, that PMA pretreatment reduced etoposide-(ETO) but enhanced staurosporine- (STA) -induced apoptosis in HT58 cells. Data presented here show that the HT58 human, "mature" B-lymphoma cells exposed to PMA secrete more IgM into the supernatant indicating commitment of cells to perform differentiated function.

Search for prognostic factors in head and neck cancer.

Fifteen patients with head and neck carcinoma were treated with irradiation (14-70 Gy telecobalt). Apoptotic and mitotic index, DNA index, ratio of cells in S phase, p53 protein overexpression in untreated tumours as well as the changes of these parameters after the first 2 Gy irradiation except proliferative kinetics parameters were examined in order to determine the prognostic value of these factors. The data show that inducibility of apoptosis is very low in head and neck carcinomas which correlate with the unfavourable prognosis.

Proteoglycan gene expression in rat liver after partial hepatectomy.

Liver regeneration is regulated by several factors. Among these extracellular matrix plays a crucial role in the restoration of normal structure. Proteoglycans are major components of extracellular matrix and they are able to bind growth factors implicated in liver growth.

The antitumor effect of Tiazofurin (TR) consists of anti-proliferative and anti-invasive elements.

We have studied the effects of the antimetabolite, Tiazofurin (TR-2-beta-D-furanosylthiazole-4-carboxamide), on the metastatization of HT168-M1 human melanoma cell line compared to 3LL-HH murine lung carcinoma. TR pretreatment of 3LL-HH cells, in a dose range 15-60 microM, caused inhibition of cell proliferation as well as adhesion to the EHS-matrix. TR inhibited the entry of adherent tumor cells to the S phase and accumulation in G1, however in non-adherent cells TR completely inhibited the entry of tumor cells to G2 phase.

Multiple use of a signal transduction pathway in tumor cell invasion.

Recent reports have indicated that a poorly characterized signaling pathway involving 12-lipoxygenase and PKC is involved in several steps of the metastatic cascade such as tumor cell adhesion to matrix, lysosomal enzyme release and migration. We investigated here the upstream elements of this signalling pathway looking for receptors which it might be coupled to. We described tumor cell alpha IIb beta 3-like integrin and the AMF receptor, gp78, as two transmembrane receptors which utilize the 12-lipoxygenase/PKC signaling.

Apoptosis in Untreated and Hormone-Treated Prostate Cancer of Various Histological Types.

A total of 102 (66 untreated and 36 hormone-treated) prostate cancers were examined histologically in order to determine their histological grade and the percentage of apoptotic tumor cells. The less differentiated the tumors were, the higher the spontaneous apoptotic activity was. Hormone therapy increased the apoptotic index in the prostate cancers.

Differential Expression of Markers in Extensive and Restricted Langerhans Cell Histiocytosis (LCH).

Langerhans cell histiocytosis (LCH) represents a poorly defined pathologic entity characterized by diverse clinical appearence and falling into two major categories namely a restricted and an extensive disease. Since the outcome and the course of the disease is variable, we postulated that this might be reflected by the phenotype of the Langerhans cells. We have selected 11 adult restricted cases and 10 extensive childhood cases and compared the phenotype of LCH cells by immunohistochemistry on paraffin sections.

Intracerebral Human Lymphoma - An Experimental Model.

Primary central nervous system lymphomas are rather rare, however, their frequency seems to be increasing in both high risk and immunocompetent patients with very poor prognosis. Here we describe a model intracerebrally xenotransplating human non Hodgkin lymphoma cells of B cell origin (HT 58). This offers a unique possibility to study the theraputic response, especially on systemic treatment.

Pathomorphological Characteristics and Pathogenesis of Viral Hepatitis.

Viral hepatitis (VH) is an inflammatory reaction of the liver to hepatotropic viruses. Acute VH can be classified according to the virus and type of necrosis. Chronic hepatitis (CH) might be active, persistent or lobular based on previous classification.

Visceral Aluminum Deposition In Chronic Renal Insufficiency. (Light Microscopy and X-ray Microanalysis).

Aluminum is a common element in our environment, but has been proved to be toxic, mainly in chronic renal insufficiency. Most cases of ALU intoxication occur during hemodialysis due to treatment of aluminum-containing drugs. In the present case, we describe visceral manifestations of aluminum deposition in a middle aged, multidialysed, male patient.

Marker Enzymes of Rat Chemical Hepatocarcinogenesis in Human Liver Tumors.

Reduced glucose-6-phosphatase, increased GGT activity and reduction of cytochrome P-450 content are considered to be markers of chemical hepatocarcinogenesis in rats. The significance of these changes were studied in certain human liver lesions; adenoma, focal nodular hyperplasia and hepatocellular carcinoma all developed in non-cirrhotic livers. Enzymes showed normal values in 4 out of 5 adenomas, in 2/13 FNH and in 4/18 HCC samples.

Tyrphostin induces non-apoptotic programmed cell death in colon tumor cells.

The programmed cell death inducing effect of the EGF receptor tyrosine kinase inhibitor alpha-cyano-3,4-dihydroxycinnamthioamide (AG213) was investigated in vitro on HT-29 human colon tumor. AG213 at concentrations between 45 to 450 microM blocks the proliferation of HT-29 cells. Morphological findings suggest that the selective tyrosine kinase inhibitor AG213 induces Clarke III type (non-lysosomal vesiculate cytoplasmic) programmed cell death; unlike ATP analog non-selective tyrosine kinase inhibitors like Genistein which were found to induce apoptosis.

Immunomorphological characterization and effects of 12-(S)-HETE on a dynamic intracellular pool of the alpha IIb beta 3-integrin in melanoma cells.

In metastatic B16a murine melanoma cells, alpha IIb beta 3 integrin was shown to be one of the key adhesion molecules responsible for matrix adhesion and spreading. Upon stimulation, alpha IIb beta 3 can be upregulated at the cell surface due to translocation of the receptor to the plasma membrane from an intracellular pool. Here we have characterized this integrin pool as a tubulovesicular structure (TVS) corresponding to endosomes.

Sex-dependent liver metastasis of human melanoma lines in SCID mice.

The liver metastasis formation of two human melanoma cell lines were compared in male and female SCID mice. The intrasplenic injection of both tumour lines resulted in a significantly higher number of liver metastases in male than in female mice; the incidence and weight of spleen tumours, as well as the incidence of metastases were similar. Both melanoma cell lines bound fluorescent oestradiol, progesterone and testosterone conjugates, and proved to be positive for oestrogen receptor-related protein by immunocytochemistry.

Role of Proteoglycans in Tumor Progression.

Data is now starting to accumulate on the differential expression of PGs in tumor cells of various invasive/metastatic potential. This is not so surprising if one considers the key functions that PGs play in the regulation of cell proliferation, adhesion and motility. However, characterization of PG expression in individual tumor types still awaits further detailed studies.

Modification of Acute and Chronic Liver Damage by Thiazolidine Compounds.

As high sulfhydril levels were shown to reduce the action of agents causing tissueinjury, increasing glutathion concentrations may have cytoprotective potential. In this study the hepatoprotective effects of several derivatives of 4carboxy5,5dimethyl thiazolidine, a modulator of glutathion metabolism were studied in rat liver damaged with CCl4. It was found that 4(S) carboxy 5,5dimethyl2 (5'nitro2furyl) thiazolidine (dimethylthiazolidinenitrofuran: DTNF) had the most significant hepatoprotective action; therefore it was subjected to detailed investigation in various models for acute and chronic liver injury.