[Non-specific immunotherapy inhibits angiogenesis - results of the monitoring of serum levels of vascular endothelial growth factor and matrix metalloproteinase 8 in patients with malignant melanoma receiving adjuvant high-dose interferon therapy]. / Nespecifická imunoterapie inhibuje angiogenezi - výsledky monitorování sérových hladin vaskulárního endotelového rustového faktoru a matrixmetaloproteinázy 8 v prubehu adjuvantní lécby vysokodávkovaným interferonem u pacientu s maligním melanomem.

OBJECTIVE: Interestingly, evidence is currently emerging that the activation of angiogenesis leads to immunomodulatory/immunosuppressive effects both at the local and systemic levels. These are very complex and interconnected processes. In this study, our aim was to establish interferon alpha-2b as an anti-angiogenic agent and show the complexity of angiogenesis and immunomodulation through the serum levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 8 (MMP-8) in high-risk resected malignant melanoma before and after adjuvant therapy with high-dose interferon alpha-2b (HDI). Clinical outcomes of patients were also evaluated. MATERIAL AND METHODS: We prospectively measured the serum levels of VEGF and MMP-8 by ELISA in 29 patients with high-risk resected malignant melanoma receiving adjuvant HDI. Blood samples were collected before and within one week after the treatment. RESULTS: To see the results clearly, we divided our patients into two groups. The first group of patients whose VEGF serum level decreased after HDI (66%) showed long-term complete remission. The mean VEGF serum level in these patients decreased from 779.4 pg/ml to 446.2 pg/ml. This downward trend in VEGF was statistically significant. The second group of patients who did not show a decrease in VEGF serum level after HDI (34%) had no clinical benefit from the treatment. The mean VEGF serum levels in group 2 patients were 408 pg/ml before the treatment and 500 pg/ml after HDI. Results for MMP-8 were ambivalent. CONCLUSIONS: Non-specific immunotherapy with interferons reduces angiogenesis. Our results are in line with the current view of the interconnection and complexity of angiogenesis and immunomodulation/immunosuppression. Non-specific immunotherapy with interferons disrupts the immunosup-pressive effect of the angiogenesis on the development of immune response against tumours and supports anti-tumour response in both direct and indirect way. The interference of HDI with the activation of angiogenesis and tumour progression could explain good clinical outcomes of patients with a decrease in serum VEGF. The outcomes of MMP-8 are inconclusive, its role remain unclear, and MMP-8 does not seem to function as a tumour suppressor.

Determination of angiogenic factors in serum by protein array in patients with renal cell carcinoma.

Using the protein array method we determined the serum levels of a number of angiogenic factors. We identified serum levels of angiogenin, PDGF and MCP-1 (CCL2 chemokine) in serum of 32 patients with RCC, and 14 healthy volunteers by means of antibody array analysis. The patients were divided into three groups according to their disease stages (I+II, III, and IV). We found significant differences between the controls and patients with RCC both pre-operatively and post-operatively in angiogenin, PDGF and MCP-1 serum levels. The increase in angiogenin, PDGF and MCP-1 lasted in patients with RCC stages I-III even without metastases eight weeks post-operatively. The patients with stage IV RCC showed disturbed production of PDGF and MCP-1. Protein array analysis is a powerful tool for the identification of large numbers of trace proteins. Multiplex antibody array is able to provide data more precisely reflecting the nature of pathological processes.

Pathological complete response after primary chemotherapy in a mother and daughter with hereditary breast carcinoma: two case reports.

The prognosis of patients with BRCA1-related breast carcinomas is inferior to the patients without BRCA1 mutation, but most of these tumors have a so-called triple negative phenotype characterized by increased chemosensitivity. Information regarding the chemosensitivity of BRCA1-related breast carcinomas is limited. We present a case of a mother and daughter with hereditary breast carcinoma treated with primary chemotherapy using the dose-dense combination of doxorubicin and cyclophosphamide and sequential weekly paclitaxel administration. Pathological complete response was observed in both patients. Subsequent genetic analysis revealed the same BRCA1 mutation with exon 5-14 deletion in both women. The present experience as well as other reports indicate increased sensitivity of BRCA1-related breast carcinoma to primary chemotherapy.

[Inflammatory reaction and its importance in the course of tumour process]. / Zánetlivá reakce a její význam v prubehu nádorového procesu.

This article gives basic information about the formation and the course of the inflammatory reaction, which is the important adaptation mechanism of the organism on the various external and internal injurants. The main attention is fixated on the role of the immune system in the course of the inflammatory reaction. It deals with the presence and the sense of the inflammatory reaction in the tumour environment in more detail. It gives the short information about the mechanisms of the antitumour defence. The influence ofthe inflammatory reaction on the genesis, the course and the progression of the tumour disease is discussed in the third chapter.

[Monitoring of anti-tumour cell-mediated response in patients with renal cell carcinoma, disturbance of T cell proliferation]. / Sledování protinádorové bunecné imunitní odezvy u nemocných s renálním karcinomem, porucha proliferace T-lymfocytu.

INTRODUCTION: When checking tumour growth, a number of observations indicate that the immune system plays a significant role in patients with renal cell carcinoma (,,RCC"). Infiltration by lymphocytes (tumour infiltrating lymphocytes, "TILs") is more prevalent in RCC than any other tumours. T lymphocytes are the dominant population of TIL cells. Views concerning the role ofT lymphocytic subpopulations, B lymphocytes and NK cells in an anti-tumour response are not established. AIM: The aim is to determine the phenotype and activation of lymphocytic cells and to compare their representation in tumour stroma (TIL), peripheral blood (PBL) and renal vein blood in patients with RCC. PATIENTS AND METHODS: The samples of peripheral blood taken from the cubital and renal veins and tumour stroma cells were obtained from 60 patients in the course of their surgeries carried out due to primary RCC. TILs were isolated from mechanically disintegrated tumour tissue. Immunophenotype multiparametric analysis of PBL and TILs was carried out. Their surface and activation characteristics were determined by means of flow cytometer. RESULTS: CD3+ T lymphocytes (70.4%) were the main population of TILs. The number of CD3+/CD8+ T lymphocytes was significantly higher in TILs, 39.7% (p < 0.01), while CD4+ T lymphocytes were the majority population in peripheral blood, 41.35% (p < 0.001). The representation of CD3+/69+ T lymphocytes was significantly higher in TILs, 32.05%, compared to PBL (p < 0.001). On the contrary, the numbers of CD3+/CD25+, CD8+/57+ and CD4+/RA+ (naive CD4+ T lymphocytes) were higher in PBL (p < 0.001). The differences in representation of (CD3+/16+ 56+) NK cells and CD3+/DR+ T cells in TILs and PBL were not significant. CONCLUSION: The above-mentioned results prove that the characteristics and intensity of anti-tumour responses are different in compared compartments (tumour/PBL). CD3+/CD8+ T lymphocytes are the dominant lymphocytic population of TILs. The knowledge of phenotype and functions ofeffector cells, which are responsible for anti-tumour response, are the basic precondition for understanding the anti-tumour immune response and the cause of its failure.

Campylobacter sepsis with multiple organ failure in IgG subclass deficiency.

Some patients with immunodeficiency develop clinical features of autoimmune disorders. A previously asymptomatic antibody deficiency can underlie the development of autoimmune diseases and a severe course of infection, with a risk of sepsis; such cases are known in selective IgA deficiency. On the other hand, little information is available on selective IgG subclass deficiencies. An unexpectedly severe course of Campylobacter infection in a 19-year-old woman with a previously undiagnosed complex immune disorder, including selective IgG1 immunodeficiency, Hashimoto's autoimmune thyroiditis with hypothyroidism combined with Addison's disease presumably due to autoimmune adrenalitis, autoimmunity and allergy is described. The pathophysiological mechanisms of autoimmunity in latent humoral defects are discussed.

[Late complications of chronic respiratory infections in patients with common variable immunodeficiency]. / Pozdní komplikace chronických zánetu respiracního traktu u nemocných s beznou variabilní imunodeficiencí.

Common variable immunodeficiency (CVID) is the most frequent serious humoral deficiency manifested in adulthood in the form of acute and chronic respiratory infections which in most patients lead to respiratory failure. Retrospective analysis of 28 CVID patients was made. Mean age at time of diagnosis was 38.6 +/- 18.6 years. The time which elapsed from the first symptoms to determining the diagnosis was three times as long as that indicated in other studies, i.e., 14.1 +/- 10.2 years. Twenty-three patients (82.1%) had respiratory complications. Chronic obstructive pulmonary diseases, n=16 (57.1%), and bronchiectasis, n=10 (35.7%), were the most frequent types of lung damage. In addition, two patients (7.1%) displayed evidence of interstitial lung process. Morbidity associated with CVID can be reduced by early diagnosis and adequate dosage of immunoglobulins to minimise the occurrence and progression of lung damage.

[Tumor angiogenesis]. / Nádorová angiogeneze.

Angiogenesis have shown a major role in tumor growth and metastasis formation. For tumor growth beyond the size 1-2 mm3, angiogenesis must be started to form vascular supply of tumor cells. Angiogenesis is a complex process, involving degradation of the basement membrane of preexisting vessel, proliferation of endothelial cells towards the angiogenetic stimulus, maturation of endothelial cells with formation of luminized capillary, and finally formation of a functional vessel, surrounded by basement membrane and pericytes. Angiogenesis is regulated by numerous angiogenic and anti-angiogenic factors. Hypoxia is a significant stimulus for angiogenesis. For many cancers the extent of vascularisation is a negative prognostic indicator signifying aggressive disease and increased potential for metastasis.

[Latex allergy--report on two cases]. / Alergie na latex--dva kazuistické prípady.

In the last few years latex allergy has been increasingly recognised as a potential medical problem because of the increase in frequency and potential severity of latex-mediated reactions. Latex allergy is an IgE-mediated hypersensitivity response to natural rubber latex protein with a variety of clinical signs ranging from contact urticaria, angioedema, asthma, and anaphylaxis. Also IV. type of immunology response can participate in it. In highest risk for latex allergy are patients with spina bifida, but health care workers, latex industry workers, patients with multiple surgical procedures and others who wear gloves are also at risk. Patients with history of atopy belong to the high risk group. Diagnosis is done by positive in vitro tests (EAST, CAP-FEIA, immunoblott etc.) and skin prick test. Allergen avoidance and substitution and the use of latex-safe devices including synthetic gloves are essential for the affected patient.

Genetic defects in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is the most frequent clinically manifested primary immunodeficiency. According to clinical and laboratory findings, CVID is a heterogeneous group of diseases. Recently, the defects of molecules regulating activation and terminal differentiation of B lymphocytes have been described in some patients with CVID. In this study, we show the overview of deficiencies of inducible costimulator, transmembrane activator and calcium-modulator and cytophilin ligand interactor, CD19 molecules, their genetic basis, pathogenesis and clinical manifestations.

Similarity of hydrophobic properties of alpha-fetoprotein and albumin.

Human alpha-fetoprotein (AFP) and serum albumin (HSA) were studied by hydrophobic interaction chromatography. A close resemblance was observed both in the native state and after various perturbations (pH, salt and alcohol) indicating a significant similarity in their molecular structures. Both proteins displayed similar hydrophobic properties which apparently were different from those of other globular proteins. In agreement with the domain structure proposed by Brown (1976), our results indicated that surface nonpolar side chains of both the native HSA and AFP produced large hydrophobic areas located solely in crevices.