New type of BACE1 siRNA delivery to cells.

Background: Small interfering RNA (siRNA) gene therapy is a new molecular approach in the search for an efficient therapy for Alzheimer disease (AD), based on the principle of RNA interference. Reducing BACE activity can have great therapeutic potential for the treatment of AD. In this study, receptor-mediated delivery was used to deliver opioid peptide-conjugated BACE 1 to INR-32 human neuroblastoma cells.

The study of t-PA, u-PA and PAI-1 genes polymorphisms in patients with abdominal aortic aneurysm.

The most important feature of abdominal aortic aneurysm (AAA) pathogenesis is an enzymatic degradation of elastic lamellae and extracellular matrix proteins particularly with participation of matrix metalloproteinases. Plasmin, which is responsible for the dissolution of fibrin in blood vessels, plays also a key role in the cascade for activation of the metalloproteinases. The purpose of this study was to evaluate the influence of selected polymorphisms in genes coding for tissue plasminogen activator (-7351 C/T polymorphism), urokinase-type plasminogen activator (1788 C/T polymorphism) and plasminogen activator inhibitor 1 (-675 4G/5G and -844 G/A polymorphism) on the susceptibility to AAA.

Association analysis of genetic polymorphisms of factor V, factor VII and fibrinogen β chain genes with human abdominal aortic aneurysm.

Increased activity of the coagulation system is associated with the increased risk of many arterial thrombotic diseases and atherosclerosis. The purpose of this study was to evaluate the influence of selected polymorphisms in genes coding for coagulation factor V (1691 G/A, the so-called Leiden mutation), factor VII (-323 0/10 bp insertion/deletion) and fibrinogen β chain (-455 G/A) on the risk of abdominal aortic aneurysm, a particular form of atherothrombosis. We conducted a case-control study of 153 Polish patients hospitalized due to abdominal aortic aneurysm (AAA) and compared the results to those obtained from matched healthy control subjects.

Coordinated increase of miRNA-155 and miRNA-196b expression correlates with the detection of the antigenomic strand of hepatitis C virus in peripheral blood mononuclear cells.

A tight relationship has been revealed between cellular microRNAs (miRNAs) and the course of hepatitis C virus (HCV) replication in human hepatoma cells. Although the detection of the antigenomic HCV RNA strand in peripheral blood mononuclear cells (PBMCs) has provided evidence for viral replication in PBMCs, no reports have shown how miRNAs are affected upon HCV RNA synthesis in PBMCs. The aim of the present study was to assess if and how the expression levels of miRNA-155 and miRNA-196b in PBMCs are related to HCV replication in PBMCs of chronic hepatitis C (CHC) patients.

[Influence of the thymidine phosphorylase (platelet-derived endothelial cell growth factor) on tumor angiogenesis. Catalytic activity of enzyme inhibitors].

Thymidine phosphorylase, also known as platelet-derived endothelial cell growth factor, is a potent angiogenic factor. Thymidine phosphorylase is overexpressed in various human tumors and plays an important role in angiogenesis. A novel inhibitor of thymidine phosphorylase (TP), 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI) is about 1000-fold more active than 6-amino-5-chlorouracil, one of the most potent TP inhibitors to 1999 year.

Manganese superoxide dismutase (MnSOD) gene (Ala-9Val, Ile58Thr) polymorphism in patients with age-related macular degeneration (AMD).

Background: Oxidative stress is involved in the pathogenesis of many chronic disorders including cancer, inflammation, and neurologic diseases. Reactive oxygen species (ROS) may play a major role in age-related macular degeneration (AMD). This study investigated the mRNA and protein profiles of manganese superoxide dismutase MnSOD in patients with AMD and healthy controls, while examining its genetic sequence polymorphism (Ala-9Val, Ile58Thr).

[The thymidine phosphorylase as the platelet-derived endothelial cell growth factor of endometrial cancer].

Objectives: The aim of the study was to assess the correlation between the activity of thymidine phosphorylase (TP) and the platelet derived-endothelial cell growth factor (PD-ECGF) expression in endometrial carcinoma.

Methods: The study group consisted of 40 tissue samples taken from patients with endometrial carcinoma, who underwent surgery in First Clinic of Gynecology and Oncologic Gynecology of Medical University in Lodz. The control tissue samples were taken from patients who were operated on for non-oncologic reason.

[Influence of the selected pyrimidine compounds on the activity of thymidine phosphorylase from normal and tumor endometrial cells].

Objectives: The aim of this study was to evaluate the influence of the selected pyrimidine compounds on the activity of thymidine phosphorylase (TP) of normal and tumor endometrial cells.

Materials And Methods: Influence of 28 chemical compounds on the TP activity in the cytosol of the endometrial cells was studied by the spectrophotometric method. The studied group comprised postmenopausal women with endometrial cancer: adenocarcinoma endometrialis (Adeno Ca E).

Mevalonate pathway modulation is associated with hepatitis C virus RNA presence in peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMC) constitute the main extrahepatic reservoir of hepatitis C virus (HCV). Lipid metabolism of host seems to play important role in HCV infection. The relationship between HCV presence in PBMC and the expression of mevalonate pathway has not been elucidated.

The positive correlation between gene expression of the two angiogenic factors: VEGF and BMP-2 in lung cancer patients.

Lung cancer is a particular challenge in oncology. More than 1 million new cases occur worldwide every year and despite many clinical trials and modern diagnostic techniques, long-term survival rate has only marginally improved. The aim of the current research is to explore new molecular prognostic factors and identify new targets for anticancer therapy.

Effect of oxidative stress on the expression of t-PA, u-PA, u-PAR, and PAI-1 in endothelial cells.

In this study we examined the effects of exogenous nitric oxide (sodium nitroprusside, SNP) and hydrogen peroxide (H2O2) on the expression level of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), urokinase-type plasminogen activator receptor (u-PAR), and plasminogen activator inhibitor type 1 (PAI-1) in human umbilical vein endothelial cells (HUVEC). The expression of selected genes involved in fibrynolysis under the influence of oxidative stress was analyzed at the levels of mRNA, protein, and promoter activity. The results of the conducted studies revealed that oxidative stress in endothelial cells causes a significant increase in PAI-1 and u-PAR expression and a moderate increase in t-PA and u-PA expression at all of the investigated levels.

[Role of lipid rafts in hepatitis C virus life cycle].

Although the mechanism of HCV RNA replication is still poorly characterized, we know that HCV active replication complex contains membrane structures. Biochemical analysis showed that these membrane structures were resistant to nonionic detergents at low temperature and contained caveolin-2, characteristic of lipid rafts. Further analysis suggested that lipid rafts protect HCV replication complex against degradation.

Cloning and expression of a new recombinant thrombolytic and anthithrombotic agent - a staphylokinase variant.

To develop a more potent antithrombin agent with thrombolytic and antiplatelet properties, a new staphylokinase (SAK) variant was constructed. The kringle 2 domain (K2) of tissue type-plasminogen activator (t-PA) containing a fibrin-specific binding site (i), the RGD sequence (Arg-Gly-Asp) for the prevention of platelet aggregation (ii) and the antithrombotic agent - hirulog (iii) was assembled to the C-terminal part of recombinant staphylokinase (r-SAK). cDNA for the hybrid protein SAK-RGD-K2-Hirul was cloned into Pichia pastoris pPIC9K yeast expression vector.

The cytosol activity of thymidine phosphorylase in endometrial cancer.

Background: Thymidine phosphorylase (TP) is identical with platelet-derived endothelial cell growth factor (PD-ECGF) which promotes angiogenesis. The aim of this study was to evaluate the cytosol activity of TP in tumor samples from patients with endometrial cancer.

Methods: The activity of TP was measured by the spectrophotometric method in the cytosol of endometrial tumor samples from 43 patients.

[Expression of bone morphogenetic proteins, matrix metalloproteinases and inhibitors of matrix metalloproteinases in lung cancers and their prognostic significance].

Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are one of the molecules that have become a topic of great interest among scientists studying lung cancers. There is a distinct tendency toward higher expression of selected MMP and TIMP in tumor lung tissue. Furthermore, there is a significant correlation between high expression of TIMP-1 or MMP-2 in lung cancer and shortened survival and between high expression of TIMP-1 or MMP-7 in lung cancer and higher stage of disease.

[Evaluation of bone mineral density in women with chronic liver diseases during perimenopausal period].

Unlabelled: Osteoporosis is the most frequently occurring metabolic diseases of bones, observed especially in women after menopause. The goal of the paper was a comparison of bone mineral density (BMD) of health women with that in perimenopausal patients with chronic liver diseases. The study was performed in 47 patients with chronic liver diseases, aged: 37-56 years.

[Regulation of gene expression by nitric oxide].

During the past over 20 years, nitric oxide has become a subject of intensive research in molecular biology and other fields of science. Conducted studies discover its important role both in physiological and pathophysiological processes. A significant feature of nitric oxide is its participation in the regulation of gene expression.

A new recombinant thrombolytic and antithrombotic agent with higher fibrin affinity - a staphylokinase variant. An in-vivo study.

The recombinant protein SAK-RGD-K2-Hir is characterized by its fibrin-specific properties of plasminogen activation combined with antithrombin and antiplatelet activities. It was previously shown in our in-vitro studies to be a more potent and faster-acting thrombolytic agent compared with standard r-SAK. In order to document the effects of the thrombolytic potential of SAK-RGD-K2-Hir we examined this protein in an electrically induced carotid artery thrombosis model and stasis-induced venous model in rats.

[The influence of nitric oxide on the regulation of plasminogen activator inhibitor type 1 and tissue-type plasminogen activator expression].

Nitric oxide produced in various human tissues by nitric oxide synthase is involved in the regulation of many physiological processes. Mechanism of its action is diverse. The most important physiological activity of nitric oxide is guanylate cyclase activation and an increase of cGMP synthesis.

Evaluation of P53 and BAX gene expression and induction of apoptosis and necrosis by the cis-Pt(II) complex of 3-aminoflavone in comparison with cis-diamminedichloroplatinum(II) (cis-DDP) in human lymphocytes.

Currently cis-diamminedichloroplatinum(II) (cis-DDP) is one of the most commonly applied compounds in chemotherapy of many types of cancer. However, a drawback is that its effectiveness presents with many side effects. Therefore, human normal lymphocytes were chosen as a model system to study cis-bis(3-aminoflavone)dichloroplatinum(II) (the cis-Pt(II) complex of 3-aminoflavone) in comparison with cis-DDP.

Exposure to polychlorinated naphthalenes affects GABA-metabolizing enzymes in rat brain.

There is substantial evidence that polychlorinated naphthalenes (PCNs) are widespread global environmental pollutants, which accumulate in biota. The aim of our study was to characterize the effect of prolonged PCNs exposure on γ-aminobutyric acid (GABA) metabolism in rat brain regions with a high amount of GABAergic neurons (cerebellum, brain stem and basal ganglia). PCNs mixture was administered intragastrically for 7, 14 and 21 days in a dose 10mg/kg of body weight daily, and next the activity of glutamate decarboxylase (GAD), GABA-aminotransferase (GABA-T), succinic semialdehyde dehydrogenase (SDH) and succinate dehydrogenase (SSA-DH) was assayed.

[Significance of MDM2 protein in the cell cycle].

The basis of oncogenesis underlies the modification of the control of the cell cycle, which leads to disturb balance between proliferation and apoptosis. The MDM2 protein suppresses the ability of p53 to activate genes responsible for repairing or apoptosis, but also promotes p53 degradation by ubiquitination. MDM2 inhibits tumor suppressor property of pRb, by releasing E2F1, which stimulates DNA synthesis in S-phase.

Enhanced P53 and BAX gene expression and apoptosis in A549 cells by cis-Pt(II) complex of 3-aminoflavone in comparison with cis-DDP.

Lung cancer remains one of the most common causes of cancer-related death worldwide. Approximately 80% is histologically non-small cell lung carcinoma (NSCLC) and in about 70% of patients it is an unresectable type. Clinical studies indicated that application of platinum derivatives caused good results and combinations of platinum with other agents could improve median survivals.

Atypical molecular background of glioblastoma and meningioma developed in a patient with Li-Fraumeni syndrome.

We observed three neoplasms with completely different histologies: malignant fibrous histiocytoma (MFH), atypical meningioma (AM), and glioblastoma (GB), developing in a patient with Li-Fraumeni syndrome. By using a combined molecular approach we performed molecular characterization of all three tumours. Data obtained showed an interesting molecular background of the AM and GB.