Analysis of preoperative blood platelet parameters in terms of diversity of epithelial ovarian cancer.

Smouldering inflammation, thrombocytosis, and platelet hyper-reactivity are linked to malignancy. The relationships between preoperative diagnostic blood morphology parameters and cancer have been the focus of much interest, because some of these parameters are correlated with advanced cancer stages and poor patient survival rates. This study aimed to perform an observational, retrospective analysis of the intradiversity of blood platelet parameters in patients with different International Federation of Gynaecology and Obstetrics (FIGO) stages and different histological types of epithelial ovarian carcinomas (EOC), and also an analysis of the overall survival rate.

Evaluation of nitric oxide donors impact on cisplatin resistance in various ovarian cancer cell lines.

Ovarian cancer chemoresistance, both intrinsic and acquired, is the main obstacle in improving the outcome of anticancer therapies. Therefore the development of new treatment strategies, including the use of new compounds that can support the standard therapeutics is required. Among many candidates, nitric oxide (NO) donors, agents with multivalent targeted activities in cancer cells, are worth considering.

Secretion of cytokines and heat shock protein (HspA1A) by ovarian cancer cells depending on the tumor type and stage of disease.

Epithelial ovarian cancer is a heterogeneous disease comprising several tumor types that each have multiple histopathological features and different biological behaviors. Recent morphologic and molecular genetic studies have allowed for the categorization of various types of ovarian cancer into two groups: type I and type II. Type I tumors are low-grade and are genetically more stable, while type II tumors are high-grade and genetically unstable.

Heterogeneity of the Mac-1 expression on peripheral blood neutrophils in patients with different types of epithelial ovarian cancer.

The expression level of Mac-1 on the surface of neutrophils is an important indicator of neutrophil activation. Under pathological conditions, Mac-1 is believed a key adhesion molecule that facilitates cancer progression and mediates the adhesion of tumour cells to the endothelium of blood vessels. Our previous findings indicated that circulating peripheral blood neutrophils in patients with advanced epithelial ovarian cancer (EOC) expressed enhanced levels of Mac-1, which was functionally associated with an increased adhesive function of neutrophils.

Antitumoral Activity Of Nitric Oxide-Releasing Compounds.

Background: Despite significant improvements in the conventional anti-ovarian cancer therapies, tumor cell resistance to various cytostatic drugs remains a relevant problem. Therefore, the new cancer treatment strategies are being developed. Among many agents that have been studied for their potential anti-cancer activity, the most promising are the nitric oxide (NO) donors-syntethic compounds that release NO in vivo and/or in vitro.

Mycobacterium tuberculosis RecA is indispensable for inhibition of the mitogen-activated protein kinase-dependent bactericidal activity of THP-1-derived macrophages in vitro.

Our knowledge about the mechanisms utilized by Mycobacterium tuberculosis to survive inside macrophages is still incomplete. One of the mechanism that protects M. tuberculosis from the host's microbicidal products and allows bacteria to survive involves DNA repair systems such as the homologous recombination (HR) and nonhomologous end-joining (NHEJ) pathways.

Cholesterol oxidase binds TLR2 and modulates functional responses of human macrophages.

Cholesterol oxidase (ChoD) is considered to be an important virulence factor for Mycobacterium tuberculosis (Mtb), but its influence on macrophage activity is unknown. Here we used Nocardia erythropolis ChoD, which is very similar to the Mtb enzyme (70% identity at the amino-acid level), to evaluate the impact of bacterial ChoD on the activity of THP-1-derived macrophages in vitro. We found that ChoD decreased the surface expression of Toll-like receptor type 2 (TLR2) and complement receptor 3 (CR3) on these macrophages.

Nitric oxide donors reduce the invasion ability of ovarian cancer cells in vitro.

The most important factors involved in tumor metastasis and angiogenesis are metalloproteinases (MMPs), vascular endothelial growth factor, and multifunctional transforming growth factor β1. These factors are responsible for extracellular matrix degradation, induction of vascular permeability, and enhancement of tumor cells' invasion and metastasis. Elevated expression and secretion of the above-mentioned factors are correlated with the higher aggressiveness of tumors and low patient survival for example, patients with ovarian cancer.

Modulation of human neutrophil activity by adenosine modified with a carborane pharmacophore.

An impact of adenosine modification with electroneutral, lipophilic 1,12-dicarba-closo-dodecaborane or electronegative 7,8-dicarba-nido-undecaborane boron cluster at the 6-N, 2'-C and 2-C positions on human neutrophil oxidative burst, neutrophil adherence to fibronectin and protein kinase C activity was studied. Modification of adenosine with 1,12-dicarba-closo-dodecaborane, but not 7,8-dicarba-nido-undecaborane, changes the function of adenosine from an inactive to an active state in regulating neutrophil response to PMA stimulation by reducing neutrophils' reactivity through a mechanism involving the PKC signaling pathway. Our results show that exogenously administered adenosine derivatives can be useful in regulating the oxidative burst of neutrophils in the inflammatory process.

Either non-homologous ends joining or homologous recombination is required to repair double-strand breaks in the genome of macrophage-internalized Mycobacterium tuberculosis.

The intracellular pathogen Mycobacterium tuberculosis (Mtb) is constantly exposed to a multitude of hostile conditions and is confronted by a variety of potentially DNA-damaging assaults in vivo, primarily from host-generated antimicrobial toxic radicals. Exposure to reactive nitrogen species and/or reactive oxygen species causes different types of DNA damage, including oxidation, depurination, methylation and deamination, that can result in single- or double-strand breaks (DSBs). These breaks affect the integrity of the whole genome and, when left unrepaired, can lead to cell death.

Nitric oxide donors: spermine/NO and diethylenetriamine/NO induce ovarian cancer cell death and affect STAT3 and AKT signaling proteins.

The important features of cancer cells are uncontrolled growth and proliferation, as well as the ability to metastasis. These features depend mainly on the constant overexpression and activity of various cell signaling proteins, such as signal transducer and activator of transcription 3 (STAT3) and serine-threonine protein kinase AKT proteins. Nitric oxide (NO) has the potential of being anti-tumoral agent, however the exact character of anti-tumoral action of NO is still a matter of debate.

Cholesterol oxidase is indispensable in the pathogenesis of Mycobacterium tuberculosis.

Despite considerable research effort, the molecular mechanisms of Mycobacterium tuberculosis (Mtb) virulence remain unclear. Cholesterol oxidase (ChoD), an extracellular enzyme capable of converting cholesterol to its 3-keto-4-ene derivative, cholestenone, has been proposed to play a role in the virulence of Mtb. Here, we verified the hypothesis that ChoD is capable of modifying the bactericidal and pro-inflammatory activity of human macrophages.

The role of 3-ketosteroid 1(2)-dehydrogenase in the pathogenicity of Mycobacterium tuberculosis.

Background: A growing body of evidence suggests that Mycobacterium tuberculosis (Mtb) uses the host's cholesterol as a source of carbon and energy during infection. Strains defective in cholesterol transport or degradation exhibit attenuated growth in activated macrophages and diminished infectivity in animal models. The aim of this study was to evaluate intracellular replication of a cholesterol degradation-deficient Mtb mutant in human macrophages (MØ) in vitro and assess the functional responses of Mtb mutant-infected MØ.

Effect of adenosine modified with a boron cluster pharmacophore on reactive oxygen species production by human neutrophils.

Methods for the synthesis of adenosine/boron cluster conjugates are proposed and the potential of the obtained derivatives to modulate neutrophil activity, especially reactive oxygen species (ROS) production in vitro, is described. An efficient inhibition of ROS production in activated neutrophils by adenosine modified at the 2'-C and 6-N positions with a para-carborane cluster (C(2)B(10)H(11)) was discovered. The high affinity of the selected compounds for adenosine receptor A(2A) was established.

The interaction of HspA1A with TLR2 and TLR4 in the response of neutrophils induced by ovarian cancer cells in vitro.

Inducible heat shock protein (HspA1A) promotes tumor cell growth and survival. It also interacts with effector cells of the innate immune system and affects their activity. Recently, we showed that the direct contact of ovarian cancer cells, isolated from tumor specimens, with neutrophils intensified their biological functions.

JAK3, STAT3 and CD3-zeta signaling proteins status in regard to the lymphocytes function in patients with ovarian cancer.

Several groups of author have published that, in most cases of carcinoma, circulating lymphocytes are unable to carry out immune functions successfully. A molecular mechanism responsible for T lymphocytes defective reactivity in cancer patients is not completely defined. We evaluated whether the impaired function of peripheral blood lymphocytes (PBLs) from ovarian cancer patients could be associated with signaling elements such as JAK3, STAT3 and CD3-zeta chain.

Seasonal changes in activities of human neutrophils in vitro.

Objective And Design: We present a retrospective analysis of previously collected blood samples to determine whether the immune response of neutrophils depends on the season i.e., short versus long days, in which blood samples were collected.

Adenosine and 2'-deoxyadenosine modified with boron cluster pharmacophores as new classes of human blood platelet function modulators.

Novel types of adenosine and 2'-deoxyadenosine derivatives containing boron clusters at positions C2', N6, or C8 were synthesized. The effect of these modified compounds on platelet function was studied. Modification of adenosine at the C2' position with a para-carborane cluster (C(2)B(10)H(11)) results in efficient inhibition of platelet function, including aggregation, protein secretion, and P-selectin expression induced by thrombin or ADP.

Effect of nitric oxide donors on NADPH oxidase signaling pathway in human neutrophils in vitro.

The production of reactive oxygen species (ROS) in activated neutrophils is catalyzed by NADPH oxidase, a multiproteins complex. Various protein kinases including protein kinase C (PKC) and mitogen activated protein kinases (MAPKs) are involved in NADPH oxidase phosphorylation and activation. The main step in the NADPH oxidase activation is phosphorylation of its cytosolic protein p47(phox).

Application of intracellular alkaline phosphatase activity measurement in detection of neutrophil adherence in vitro.

We have proposed the use of the fluorimetric method with 4-methylumbelliferyl phosphate (4-MUP) specific substrate for the alkaline phosphatase determination in the neutrophil adhesion assay. We provide evidence that the endogenous neutrophil alkaline phosphatase (NAP) activity evaluation is reliable to quantify neutrophil adhesion at a wide range of cell numbers (10(4)-10(6)). The results obtained by fluorimetric NAP activity test correlate to the results of adherence evaluated using the MTT reduction assay.

Flow cytometric evaluation of human neutrophil apoptosis during nitric oxide generation in vitro: the role of exogenous antioxidants.

Among numerous inflammatory mediators a nitric oxide molecule is supposed to be important in the modulation of neutrophil survival in vivo and in vitro. The effect of exogenous supply of NO donors such as SNP, SIN-1, and GEA-3162 on the course of human neutrophil apoptosis and the role of extracellular antioxidants in this process was investigated. Isolated from peripheral blood, neutrophils were cultured in the presence or absence of NO donor compounds and antioxidants for 8, 12, and 20 hours.

Oxidative and adhesive responses of human neutrophils to nitrovasodilators in vitro: the role of protein kinases.

Background: Sodium nitroprusside (SNP) and molsidomine are used in the treatment of coronary heart disease. Since the neutrophils play a pathological role in ischaemic heart disease, it is important to understand the direct action of nitrovasodilators on their function.

Aim: We examined the effects of SNP and 3-morpholinosydnonimine (SIN-1, molsidomine metabolite) on the respiratory burst of human neutrophils and their adhesion in vitro .

Effects of uraemia and haemodialysis on neutrophil apoptosis and expression of apoptosis-related proteins.

Background: In haemodialysis (HD) patients, it is unclear whether increased apoptosis of neutrophils is due to uraemia or HD itself. The purpose of the current study was to assess the effect of uraemia and HD on the rate of apoptosis and apoptosis-related protein expression in whole blood neutrophils.

Methods: We employed a whole-blood micromethod to test spontaneous apoptosis and expression of apoptosis-regulating proteins in cultured neutrophils from uraemic patients (pre-HD), HD patients and healthy controls.

Effect of exogenous opioid peptides on TNF-alpha-induced human neutrophil apoptosis in vitro.

Polymorphonuclear leukocyte (neutrophil) apoptosis is an important mechanism regulating the life span and some functions of neutrophils at inflamed sites. Opioid peptides are present in the peripheral circulation and their concentrations rapidly increase as a result of stress and inflammation. The effect of opioid peptides such as met-enkephalin (M-ENK) and beta-endorphin (beta-END) on tumor necrosis factor (TNF)-alpha-induced apoptosis in human neutrophils in vitro was investigated.

Involvement of nitric oxide donor compounds in the bactericidal activity of human neutrophils in vitro.

The bactericidal activity of human neutrophils against extracellular and facultatively intracellular bacteria was studied in the presence of the nitric oxide (NO) donors sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), a molsidomine metabolite. SNP and molsidomine are drugs commonly used as nitrovasodilators in coronary heart disease. It is demonstrated here that the NO donor compounds themselves did not affect the viability and survival of the bacterial strains tested.