Pathogenic and targetable genetic alterations in 70 urachal adenocarcinomas.

Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy.

Circulating syndecan-1 is associated with chemotherapy-resistance in castration-resistant prostate cancer.

Objectives: Docetaxel chemotherapy is a standard treatment for castration-resistant prostate cancer (CRPC). Rapidly expanding treatment options for CRPC provide reasonable alternatives for those who are resistant to docetaxel. Therefore, prediction of docetaxel resistance has become of great clinical importance.

Soluble syndecan-1 (SDC1) serum level as an independent pre-operative predictor of cancer-specific survival in prostate cancer.

Background: PSA-screening detects many cases of clinically non-aggressive prostate cancer (PC) leading to significant overtreatment. Therefore, pre-operatively available prognostic biomarkers are needed to help therapy decisions. Syndecan-1 (SDC1) is a promising prognostic tissue marker in several cancers including PC but serum levels of shedded SDC1-ectodomain (sSDC1) have not been assessed in PC.

Differential inhibition of single and cluster type tumor cell migration.

For the control of tumor metastasis it is important to identify chemical compounds with antimigratory potency. Agents acting against single cell and cluster type migration are necessary for successful antimetastatic therapy. In the present study, the migration of HT-1080 fibrosarcoma cells and OSCORT osteosarcoma cells was compared in a Boyden chamber and in an extracellular matrix (ECM)-based three-dimensional cell culture (3-DCC) model system.

Development of arterial blood supply in experimental liver metastases.

In this study, we present a mechanism for the development of arterial blood supply in experimental liver metastases. To analyze the arterialization process of experimental liver metastases, we elucidated a few key questions regarding the blood supply of hepatic lobules in mice. The microvasculature of the mouse liver is characterized by numerous arterioportal anastomoses and arterial terminations at the base of the lobules.

Novel therapeutic approaches in the treatment of advanced pancreatic carcinoma.

Pancreatic cancer is still a malignant disease of grim prognosis despite all therapeutic efforts. Because clinical symptoms in the early stage are usually absent or aspecific, it is frequently discovered at advanced or metastatic stage, only around 15-20% of tumors are resectable. In the majority of patients only the chemotherapy offers a prolongation of life, but even the first-line chemotherapeutic agent, the gemcitabine has a modest survival benefit, and objective tumor response is rarely achieved.

Thioacetamide-induced hepatic fibrosis in transforming growth factor beta-1 transgenic mice.

Objective: Transforming growth factor beta-1 (TGF-beta 1) is thought to be one of the most important factors affecting the development of fibrotic processes in the liver.

Aim: To discover whether endogenously higher TGF-beta 1 production influences the progression and reversibility of liver fibrosis in mice.

Method: We compared thioacetamide-induced liver fibrosis between wild-type and transgenic mice overexpressing active TGF-beta 1 in the liver.

A novel concept of glomeruloid body formation in experimental cerebral metastases.

Glomeruloid bodies (GBs), tumor-associated vascular structures with a superficial resemblance to renal glomeruli, are important histopathological features of glioblastoma multiforme, but have also been described in other types of tumors and in cerebral metastases. The purpose of this study was to elucidate the pathogenesis of these lesions in an appropriate murine model of experimental brain metastases. To do so, we injected cells from 5 different tumor lines into the internal carotid artery of mice and investigated the development, composition, and fate of GBs growing within tumor nodules.

Expression of CD44v3 splice variant is associated with the visceral metastatic phenotype of human melanoma.

We analyzed the immunohistochemical expression of the metastasis-associated protein, CD44v3, in 46 primary human malignant melanomas (MMs). This is the first time that the v3 splice variant of CD44 was found to be expressed in human melanomas (15 of 46), ranging from 3% to 35% of the cell population in the positive tumors. The expression of CD44v3 was observed in tumors thicker than 1.

Interdigitation index - a parameter for differentiating between young and older skin specimens.

BACKGROUND/AIMS: Quantitative morphometry developed rapidly during the last decade due to advances is computers and software. We wish to establish a simple baseline for the morphometric differences due to intrinsic ageing between young and old cohorts: the interdigitation index. It is an expression of the shape of the border between the epidermis and dermis.

Apoptosis in various organs of preterm infants: histopathologic study of lung, kidney, liver, and brain of ventilated infants.

Apoptosis, the well-characterized form of active programmed cell death, is a physiologic phenomenon in embryonal and fetal life in developing organs. Severe hypoxia, which occurs in most preterm infants, also leads to cell death, which may be necrotic or apoptotic. The aim of our study was to examine the incidence of apoptosis in various organs (such as lung, kidney, and brain) of preterm infants who suffered from clinically proven respiratory distress causing infantile respiratory distress syndrome (IRDS), cardiac failure, and periventricular leukomalacia (PVL).

Reconstitution of liver mass via cellular hypertrophy in the rat.

The liver has an extremely effective regenerative capacity. When 70% of a rat liver is removed by surgery, the liver mass regrows in 7 to 10 days by the compensatory hyperplasia of the remnant part. In case of damage to the surviving hepatocytes, the facultative stem-cell compartment is activated and the liver regenerates by means of oval-cell proliferation/differentiation.

Syndecan-1-dependent homotypic cell adhesion in HT58 lymphoma cells.

Objectives: Many cellular functions are controlled by cell-cell and cell-matrix interactions. It has recently been found that syndecans, transmembrane heparan sulphate (HS) proteoglycans, can act as receptors or co-receptors and modulate cell adhesion. Our aim was to study the role of syndecan-1 in the aggregation of human lymphoma cells, and to investigate its effect on cell survival.

Flow cytometric evidence of apoptosis in human pancreatic cancer xenografts treated with Sandostatin (octreotide).

Background: The antiproliferative effect of octreotide (Sandostatin) is partly attributed to induction of apoptosis in the given tumors. In this work, apoptosis was assessed in human pancreatic carcinoma xenografts after a 4-week high-dose Sandostatin treatment.

Materials And Methods: Subcutaneously growing human pancreatic cancer xenografts (PZX-5) in immunosuppressed mice were treated with 500 micrograms/kgb.

Effect of heparin and liver heparan sulphate on interaction of HepG2-derived transcription factors and their cis-acting elements: altered potential of hepatocellular carcinoma heparan sulphate.

Proteoglycan assembly in malignant tumours is subject to profound changes. The significance of these alterations is not well understood; especially, their role in nuclear regulation is a topic for debate. The capacity of heparin and liver carcinoma heparan sulphate (HS) to alter DNA-transcription factor interactions has been studied to provide further evidence concerning the regulatory potential of glycosaminoglycan (GAG) in the nucleus.

Studies on hepatic gene expression in different liver regenerative models.

We have investigated the expression of several growth-related genes in the liver after partial hepatectomy in three experimental models: normal, Dexamethasone-pretreated, and hypophysectomized rats. Dexamethasone and hypophysectomy resulted in a delay in the peak of cell replication in 6 and 18 h, respectively, when compared to the normal animals. TGFalpha mRNA expression was shifted together with the DNA synthesis, but the expression of c-myc, c-fos, c-jun, HGF, TGFbeta1, IL1beta did not delay.

Epidermal growth factor receptor, somatostatin and bcl-2 in human pancreatic tumor xenografts. An immunohistochemical study.

Xenografted human pancreatic tumors (5 ductal adenocarcinomas, 1 leiomyosarcoma, altogether 26 samples) were investigated about their immunohistochemical expression of epidermal growth factor receptor (EGFR), somatostatin (SS) and bcl-2 protein. The expression of the EGFR varied from tumor to tumor. One originally negative carcinoma became immunoreactive during passagings, one tumor has lost its early positive expression, and in 3 cancer lines a phenotypically constant pattern was seen.

Expression and function of the high affinity alphaIIbbeta3 integrin in murine melanoma cells.

In resting platelets integrin alphaIIbbeta3 is constitutively expressed in an inactive state and it does not recognize soluble proteins. Platelet activation results in a conformational change of the low-affinity alphaIIbbeta3 to a high-affinity state which then recognizes plasma fibrinogen. The ectopic expression of alphaIIbbeta3 integrin in rodent and human cells derived from solid tumors is well documented, although little is known about its affinity state in these tumor cells.

Establishment and long-term xenografting of human pancreatic carcinomas in immunosuppressed mice: changes and stability in morphology, DNA ploidy and proliferation activity.

The prognosis of pancreatic carcinoma is grave, therefore the experimental model systems remain major tools for testing new treatment modalities. We have developed human pancreatic cancer lines growing in immunosuppressed mice and characterized them by morphological and flow-cytometric studies. Immunosuppression has been achieved in young (4-week-old) CBA/CA mice by thymectomy, whole-body irradiation and bone marrow reconstruction.

Human and experimental hepatocarcinogenesis.

Human liver cancer is increasing worldwide, including in Hungary. The detection of liver tumors in premalignant or early malignant states is essential for successful treatment. MC-29 virus-induced chicken hepatoma and rodent, fish and monkey models for chemical hepatocarcinogenesis were studied and compared to humans.

Experimental and human liver fibrogenesis.

In this work, we provide an overview of our results obtained by studying the role of transforming growth factor beta1 and proteoglycans in liver fibrogenesis. It has been found that transforming growth factor beta1 is one of the most important stimulators of extracellular matrix synthesis in the liver. In chronic liver injury, desmin-positive non-parenchymal liver cells expressed transforming growth factor beta1.

Putative role of dihydropyrimidine dehydrogenase in the toxic side effect of 5-fluorouracil in colorectal cancer patients.

Dihydropyrimidine dehydrogenase (DPD) is the first and rate limiting enzyme in the catabolism of 5-fluorouracil (5-FU). It has been reported from various laboratories that the plasma concentration of 5-FU was influenced by DPD activities in various normal human organs (e.g.

Expression of transforming growth factor-alpha in hepatoblastoma.

Background: Transforming growth factor-alpha (TGF-alpha) is a potent stimulator of cell proliferation in the liver and in liver tumors; however, its significance and association with hepatocyte proliferation remains unclear.

Methods: Expression of TGF-alpha and proliferation markers, such as proliferating cell nuclear antigen (PCNA) and cyclin A, were studied and correlated with each other in samples of tumor and surrounding liver tissue taken from nine patients with hepatoblastoma. An avidin-biotin-peroxidase immunohistochemical method was used for detection of TGF-alpha, PCNA, and cyclin A, and in situ hybridization was used to detect TGF-alpha mRNA.

Flow cytometric studies on the relationship between DNA content and clinicopathologic features of pancreatic cancers.

The purpose of this study was to determine DNA (DI) and proliferation indices (PI) in 26 pancreatic and 10 ampulla of Vater carcinomas by flow cytometry using paraffin embedded tissue samples. Furthermore, we analysed the relationship between these parameters and the traditionally used prognostic parameters (type, stage and grade) of the tumor. Out of the 26 pancreas carcinomas 15 proved to be DNA diploid and 11 DNA aneuploid, while among the 10 ampulla of Vater tumors 7 DNA diploids and 3 DNA aneuploids were found.

Inhibition of DNA topoisomerase I activity by heparan sulfate and modulation by basic fibroblast growth factor.

Eukaryotic DNA topoisomerase I catalyzes changes in the superhelical state of duplex DNA by transiently breaking single strands thereby allowing relaxation of both positively and negatively supercoiled DNA. Topoisomerase I is a nuclear enzyme localized at active sites of transcription, and abnormal levels of the enzyme have been observed in a variety of neoplasms. Because the enzyme binds heparin and, given the presence of heparan sulfate within the nuclei of mammalian cells, we sought to investigate the interaction between topoisomerase I and sulfated glycosaminoglycans isolated from normal and neoplastic human liver.