Expression of CD44v3 protein in human endothelial cells in vitro and in tumoral microvessels in vivo.

The most universal angiogenic cytokines (VEGF, bFGF, HGF) are all heparin-binding proteins, the function of which is dependent on cell surface heparan sulfate proteoglycans (HSPG). Several proteoglycans have been demonstrated in endothelial cells, but only glypican-1 from the cell surface HSPG subfamily was documented at protein level. Here, we show that CD44v3 is expressed in human immortalized endothelial cells [anchorage-dependent human umbilical vein endothelial cells (HUVEC) and anchorage-independent Kaposi sarcoma (KS-Imm)] at mRNA and protein level, but is absent from the primary culture of human brain microvascular endothelial cells.

Molecular identification, localization and function of platelet-type 12-lipoxygenase in human melanoma progression, under experimental and clinical conditions.

As previous studies suggested the expression of a 12-LOX enzyme in murine and human melanoma cell lines, the primary aim of this project was to genetically identify the 12-LOX enzyme (platelet-, leukocyte- or epithelial form). By using reverse transcriptase-polymerase chain reaction, sequencing and various immunological techniques we have demonstrated conclusively the expression of the platelet-type 12-LOX in human melanoma cells of different origin, in their transplanted xenografts and in fresh human skin tumors. Furthermore, we found that p12-LOX is able to provide a survival signal for melanoma cells since inhibition of the enzyme by general LOX or selective 12-LOX inhibitors induced apoptosis in vitro.

[Report of the National Oncology Research and Developement Consortium, 2003].

Consorcial projects focused on 5 cancer types, breast-, colorectal-, head and neck- and pediatric cancers, and malignant melanoma. Breast cancer studies revealed unique splicing mechanisms concerning BRCA1. In sporadic breast cancers the involvement of DNA-repair genes was proved to be dependent on the histological type.

[Molecular mechanism of tumor progression. From Krompecher to the DNA microarray].

Rate limiting steps of the metastatic cascade are proliferation-independent cellular events integrated into the common sequence of tumor cell-extracellular matrix interactions (adhesion, degradation, migration). The two common dissemination forms, lymphatic and hematogenous, are highly similar in respect of the individual steps, but fundamentally different in respect of tissue specificity. Although the scheme of the metastatic cascade is well known for some time, its tumor type-specific molecular characteristics are poorly understood.

Loss of vascular adhesion protein-1 expression in intratumoral microvessels of human skin melanoma.

Intratumoral vessels are different both structurally and phenotypically, and this may have clinical significance. In this study we analysed the expression of an adhesion molecule--vascular adhesion protein-1 (VAP-1)--in melanoma-associated blood vessels in 28 primary skin melanoma cases using immunocytochemistry and immunoelectron microscopy. We have found that VAP-1 protein expression is significantly decreased in intratumoral vessels compared with peritumoral ones; this difference was independent of the tumour thickness.

A WT1 expressing metastatic human Kaposi sarcoma xenograft model.

We have established a non-metastatic and a metastatic human Kaposi sarcoma (KS) xenograft model in SCID mice by injecting KS-Imm cells subcutaneously and intrasplenically, respectively. KS-Imm cells expressed endothelial markers, CD34 and vWF in vivo. Furthermore, we have shown that these cells express all the splice variants of the WT1 gene and WT1wt protein in vitro and in vivo detected by nested PCR and immunohistochemistry.

Accuracy of the determination of S100B protein expression in malignant melanoma using polyclonal or monoclonal antibodies.

Aims: To compare the routinely used polyclonal anti-S100 and a mouse monoclonal anti-S100B antibody for their accuracy in the detection of the S100B expression profile (pattern and intensity) in a series of 67 primary (n = 37) and lymph node metastatic (n = 30) melanoma tissues. S100B is the lineage marker of malignant melanoma. Antibodies routinely used for melanoma diagnosis are not necessarily specific for this protein.

T-cell activation marker expression on tumor-infiltrating lymphocytes as prognostic factor in cutaneous malignant melanoma.

The central role of T cells in antitumor immunity is well established. However, tumor progression, often seen in the presence of substantial lymphocytic infiltration, suggests that these T cells are not capable of mounting an effective immune response to control tumor growth. Evidence has accumulated that T lymphocytes infiltrating human neoplasms are functionally defective, incompletely activated, or anergic.

The effect of leukocyte interleukin injection (Multikine) treatment on the peritumoral and intratumoral subpopulation of mononuclear cells and on tumor epithelia: a possible new approach to augmenting sensitivity to radiation therapy and chemotherapy in oral cancer--a multicenter phase I/II clinical Trial.

Objectives/hypothesis: The main objective of this study was to investigate the effect of the administration of a novel immunoadjuvant, leukocyte interleukin injection, as part of an immuno-augmenting treatment regimen on the peritumoral and intratumoral subpopulations of the tumor infiltrating mononuclear cells and on the epithelial and stromal components, when administered to patients with advanced primary oral squamous cell carcinoma classified as T2-3N0-2M0, as compared with disease-matched control patients (not treated with leukocyte interleukin injection).

Study Design: Multicenter Phase I/II clinical trial. Fifty-four patients from four clinical centers were included in the dose-escalating study (27 in each group [leukocyte interleukin injection-treated and control groups]).

Low-dose irradiation and short-exposure suboptimal-dose paclitaxel adversely modulate metastatic potential of squamous carcinoma cells.

Background And Purpose: Low-dose irradiation and suboptimal drug concentrations may induce unexpected biological responses. Paclitaxel (PTX) is a widely used drug, which has a range of antitumoral effects and which is also regarded as a radiation sensitizer. In this study, it was tested how "suboptimal" short exposure to PTX modifies the biological effects of low-dose irradiation on human epithelial carcinoma cell lines.

Adhesion dynamics and cytoskeletal structure of gliding human fibrosarcoma cells: a hypothetical model of cell migration.

During motility of fibroblast type cells on planar surfaces, adhesions are formed at the anterior of the protruding lamella, which remain stationary relative to the substrate and undergo a maturation process as the cell passes over them. Through these adhesions force is exerted, the orientation of which is parallel to the direction of the movement. Here we show that, during gliding-type motility of human tumor cells, characterized by a semicircular shape, adhesions were found at the outer rim of the cells, along the semicircle.

Trace elements improve survival of DTIC-treated mice with overt liver metastases of Lewis lung carcinoma.

Trace elements have been previously shown to have specific antimetastatic effects in a mouse 3LLHH liver metastasis model. Here we have analyzed the effect on the survival of animals with liver metastases. Trace elements administered per os at 500-5000 mg/kg/day did not affect the survival of animals with liver metastases.

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.

Behavioural changes in rats treated with a neurotoxic dose regimen of dextrorotatory amphetamine derivatives.

Repeated administration of amphetamine derivatives is reported to induce neurotoxicity in rat brain. Methamphetamine (MA) impairs the function of both the dopaminergic and serotonergic systems, 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) affects primarily the latter system. The neurochemical deficits induced by these amphetamines have been described in detail, but relatively few data have been reported regarding the behavioural consequences of the neurotoxic treatment.

Heterogenous S-100B protein expression patterns in malignant melanoma and association with serum protein levels.

Objective: Serum S-100B is a reliable tumor marker of malignant melanoma, but efficient use is restricted to patients with metastatic disease. Therefore, the aim of our study was to assess serum S-100B levels at different stages of malignant melanoma and to compare these levels with the expression of the S-100B phenotype in primary tumors and lymph node metastases.

Methods: Fifty-nine patients were included in this study; serum S-100B protein was measured using an immunoluminometric assay while the expression pattern in the primary tumor was determined by immunohistochemistry using an anti-S-100B monoclonal antibody.

[Laboratory markers of melanoma progression].

Extracellular tumour markers may have potential role in the follow-up of patients with malignant melanoma, in therapy monitoring and in prediction of prognosis. In our article circulating tumour markers in melanoma (melanoma inhibitory activity, lipid bound sialic acid, neuron specific enolase, TA90 immune complex, S-100B protein, 5-S-cysteinyldopa, tyrosinase, cytokines, metalloproteinases, LDH) were reviewed. Among laboratory melanoma markers the S-100B protein is the most investigated.

[Molecular diagnostics of malignant melanoma: molecular staging, minimal residual disease].

Nucleic acid based molecular techniques have been introduced into the diagnosis of malignant melanoma similarly to other cancers. They were applied for refinement of staging and to detect minimal residual disease. There are several good melanocyte-specific genetic markers such as tyrosinase, gp100, Melan-A/MART-1 and MIA.

Molecular pathology of tumor metastasis III. Target array and combinatorial therapies.

Therapy of tumor progression and the metastatic disease is the biggest challenge of clinical oncology. Discovery of the diverse molecular pathways behind this complex disease outlined an approach to better treatment strategies. The development of combined cytotoxic treatment protocols has produced promising results but no breakthrough in the clinical management of metastatic disease.

Follow-up of minimal residual disease in acute childhood lymphoblastic leukemia by WT1 gene expression in the peripheral blood: the Hungarian experience.

The aim of the study was to investigate if monitoring WT1 gene expression in the peripheral blood is an appropriate approach to monitor the progression of childhood acute lymphoblastic leukemia (ALL). Forty-six patients have been enrolled into this study (24 ALL and 22 control, nonleukemic cases). The peripheral blood was tested for WT1 gene expression using a sensitive nested RT-PCR technique.

[Report on the first year of the activity of the National Oncological RD Consortium].

The project focuses on cancer types with outstanding publich health importance (breast-, colorectalhead and neck cancers and childhood tumors). Epidemiological studies revealed significant regional differences in the mobidity/mortality of these cancer types in Hungary. Molecular epidemiological studies revealed characteristic BRCA1 mutation patterns of familiar breast cancer and DNA repair enzyme polymorphism in head and neck cancer.

Basic HGF-like peptides inhibit generation of liver metastases in murine and human tumor models.

Purpose: We have postulated that the peptide domain(s) of the heparin-binding cytokine(s) might have biological activity, which theoretically could be exploited for modulation of the biological behavior of cancer cells.

Materials And Methods: We used HGF as a model heparin-binding cytokine and synthesized two HGF beta-chain domains, HHRGK (HGP1) and RYRNKH (HGP2), as well as four variants. As target cells, we used three cancer cell lines (HT25 human colonic, HT168-M1/9 human melanoma and 3LL-HH murine lung carcinoma) all characterized by strong liver metastatic potentials.

Molecular pathology of tumor metastasis. II. Molecular staging and differential diagnosis.

Molecular Pathology of Tumor Metastasis With the development of non-invasive methods, diagnosis of metastasis from various solid malignancies has become a routine task for diagnostic pathology. However, the differential diagnosis between primary and metastatic cancers and the precise identification of various metastatic cancer types requires the coordinated use of various morphological (light- and electron microscopic-), immunological and molecular techniques. The detection of the lymphatic spread of the primary tumor may now based on the sentinel lymph node technology while the identification of the hematogenous progression may be based on the analysis of the peripheral blood and the bone marrow.

Role for beta3 integrins in human melanoma growth and survival.

The role of alphaIIbbeta3 integrin in regulating platelet function is well appreciated, whereas its role in tumor progression and metastasis is not. The purpose of our study was to determine a functional relevance to expression of alphaIIbbeta3 integrin in cells derived from human solid tumors. A study of human melanoma biopsies (n = 24) showed that alphaIIbbeta3 expression increased with tumor thickness, which is indicative of metastatic propensity.

Vascularization of cutaneous melanoma involves vessel co-option and has clinical significance.

This study was undertaken to determine the role and the fate of the peritumoural vascular plexus during the vascularization of human malignant melanoma (hMM) and in an appropriate murine melanoma model system. The prognostic significance of the vascularity of different tumour areas was also evaluated. Despite morphometry revealing several-fold higher microvessel densities (MVDs) in the peritumoural tissue than at the centre of the tumour, the development of visceral metastases of hMM was exclusively correlated with the MVD of the tumour centre.

Role of elastin-matrix interactions in tumor progression.

Data from the literature now indicate that cancer cells can specifically interact with the unique extracellular matrix protein, elastin. The interaction is mediated by two elastin-binding proteins (EBP), S-gal/EBP (organized into the elasin receptor/elastonectin complex) and galectin-3, components of two laminin receptors. Studies revealed that the expression of both EBPs is closely associated to the invasive/metastatic potential of various cancer types.