TRAIL-induced apoptosis and expression of death receptor TRAIL-R1 and TRAIL-R2 in bladder cancer cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a member of TNF superfamily able to induce programmed death in cancer cells with no toxicity against normal tissues. TRAIL mediate apoptosis follows binding to the two death receptors, TRAIL-R1 (DR4) and/or TRAIL-R2 (DR5). In this study we investigated the cytotoxic and apoptotic effect of TRAIL on bladder cancer cells and the expression of death receptor TRAIL-R1 and TRAIL-R2 on the surface of these cancer cells. Three human bladder transitional cancer cell (TCC) lines - SW780, 647V and T24 were tested for TRAIL sensitivity. The bladder cancer cells were incubated with human soluble recombinant TRAIL. Cytotoxicity was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-dimethyltetrazolium bromide) and LDH (lactate dyhydrogenase) assays. Apoptosis was detected by flow cytometry with annexin V-FITC/propidium iodide and by fluorescence microscopy with Hoechst 33342/annexin V-FITC/Ethidium Homodimer. The cell surface expression of TRAIL death receptors on bladder cancer were determined using flow cytometry with phycoerythrin-conjugated monoclonal anti-human TRAIL-R1 and TRAIL-R2. Our investigations confirmed that SW780 cells were sensitive to TRAIL, and two other bladder cancer cell lines, 647V and T24, were resistant to TRAIL induced apoptosis. We therefore examined the expression of TRAIL death receptors on bladder cancer cell surfaces. We showed decreased expression of TRAIL-R2 receptor in TRAIL-resistant bladder cancer cells and increased expression of this death receptor in TRAIL-sensitive SW780 cells. The expression of TRAILR1 receptor was similar in all bladder cancer cell lines. TRAIL is one of the promising candidates for cancer therapeutics. However, some cancer cells are resistant to TRAIL-mediated apoptosis. It is therefore important to overcome this resistance for the clinical use of TRAIL in cancer therapy. TRAIL death receptors are attractive therapeutic targets in cancer treatment. The cytotoxic agents capable of up-regulating the expression of TRAIL-R1 and TRAIL-R2 can sensitize cancer cells to TRAIL induced apoptosis

Potential applications of tenascin C for cancer diagnosis and therapy

Tenascyny są rodziną czterech wielodomenowych glikoprotein macierzy zewnątrzkomórkowej: tenascyna C, X, R i W. Pierwszym poznanym przedstawicielem tej rodziny była tenascyna C. Białko to spotykane jest również pod innymi nazwami, takimi jak antygen macierzy zewnątrzkomórkowej glejaka, myotendinous antigen, heksabrachion, glikoproteina J1220/200 czy neuronektyna. Tenascyna C jest heksamerem; każde ramię heksabrachionu zawiera: aminokońcową domenę oligomeryzacji, powtórzenia podobne do naskórkowego czynnika wzrostu, domeny typu fi bronektyny III oraz homologiczną do fi brynogenu domenę globularną. Wzór ekspresji tenascyny C zależy od fazy rozwoju organizmu, a ekspresja zmienia się znacząco w wielu różnych stanach patologicznych. W czasie embriogenezy tenascyna C jest obecna zwłaszcza w rozwijającym się ośrodkowym układzie nerwowym, w mezenchymie w miejscach przejścia mezenchymalno-epitelialnego, a także w rozwijających się tkankach łącznych. W dojrzałych tkankach ekspresja tenascyny C jest słabsza, natomiast jest indukowana podczas gojenia ran, regeneracji nerwów, inwolucji tkanek, a także w stanach patologicznych, takich jak choroby naczyniowe, nowotworzenie i przerzutowanie. Ekspresja tenascyny C zarówno podczas rozwoju organizmu, jak i w przebiegu choroby jest indukowana przez cytokiny pro- i przeciwzapalne, czynniki wzrostu, a także przez wolne rodniki tlenowe, hipoksję i stres mechaniczny. Udział tenascyny C w rozwoju nowotworów polega na: 1) bezpośredniej stymulacji komórek nowotworowych do proliferacji i migracji, 2) promocji angiogenezy przez wpływ na komórki endotelialne. Tenascyna C bierze udział nie tylko w rozwoju guza pierwotnego, ale także uczestniczy w procesie przerzutowania i w ucieczce spod nadzoru immunologicznego. Jest ona przedstawiana jako niekorzystny czynnik rokowniczy, między innymi w nowotworach piersi, nerek, pęcherza moczowego, wewnątrzwątrobowych dróg żółciowych, płuca, krtani i gardła dolnego oraz mózgu. Z kolei w raku szyjki macicy wysoka ekspresja koreluje z dobrą prognozą. Poza tym ekspresja tenascyny C może zostać wykorzystana do wykrywania wznowy nowotworów mózgu, a fragmenty tenascyny C — do wykrywania raka płuca. Tenascyna C może być nie tylko narzędziem diagnostycznym, badane jest również jej zastosowanie w obrazowaniu i leczeniu nowotworów. Nowe strategie bazują na przeciwciałach, oligonukleotydach antysensownych, rybozymach, aptamerach oraz w zastosowaniu interferencji RNA.Tenascins are a family of four multimeric extracellular matrix glycoproteins: tenascin C, X, R and W. The fi rst described member of the family was tenascin C. This protein is also known as glial mesenchymal extracellular matrix protein, myotendinous antigen, hexabrachion, cytotactin, J1220 200, neuronectin. Tenascin C is a hexamer; each arm of the hexabrachion comprises an amino-terminal assembly domain, epidermal growth factor-like repeats, fi bronectin type III domain and globular fi brinogen-homology domain. The tenascin C pattern of expression is variable depending on the developmental stage of the organism, and its expression changes dramatically under many diff erent pathological conditions. During embriogenesis, tenascin C is especially prevalent in the developing central nervous system, in mesenchyme in sites of mesenchymal-epithelial interactions, and in developing connective tissues. In normal adult tissues, tenascin C expression is less abundant, but it is induced during wound healing, nerve regeneration, tissue involution and in pathological conditions including vascular diseases, tumourigenesis, and metastases. Expression of tenascin C in both development and disease is induced by various pro- and anti-infl ammatory cytokines, growth factors, but also by reactive oxygen species, hypoxia, and by mechanical stress. The contribution of tenascin C to tumor development relies on two main actions: (1) its direct stimulation of the tumor cells by activation of their proliferation, invasion and migration capacities and (2) through its impact on endothelial cells by promotion of angiogenesis. Besides the role in primary tumor development, tenascin C participates in process of metastasis and in escape from tumor immunosurveillance. Tenascin C has been reported as an indicator of bad prognosis, in tumors of breast, kidney, bladder, intrahepatic bile ducts, lung, larynx, hypopharynx and brain. On the other hand in cervical cancer a high expression of tenascin C was correlated with good prognosis. In addition, tenascin C expression represents a predictive value for local recurrence of brain tumors, and tenascin C fragments for lung cancer. Tenascin C may be not only a diagnostic tool, and its application in tumors localization and treatment is also investigated. The new strategies are based on antibodies, antisense oligonucleotides, ribozymes, aptamers, and intervention with interference RNA

Prevalence of overweight and obesity in preschool children from Rzeszow region

WSTĘP. Celem pracy było określenie częstości występowania nadwagi i otyłości u dzieci w wieku przedszkolnym z regionu rzeszowskiego. MATERIAŁ I METODY. Zważono i zmierzono 576 dzieci przedszkolnych z regionu rzeszowskiego, w tym 302 dziewczęta i 274 chłopców w wieku 4,82 roku ± 1,10 odchylenia standardowego (SD, standard deviation). Na podstawie uzyskanych pomiarów obliczono ich wskaźnik masy ciała (BMI, body mass index). Nadwagę i otyłość określono na podstawie kryteriów IOTF. WYNIKI. Nadwagę stwierdzono u 9,1% dziewcząt i 9,9% chłopców. Otyłość stwierdzono u 7,2% dziewcząt i 8,4% chłopców. Nadwaga występowała znamiennie częściej u chłopców 3-letnich, podczas gdy w tej samej grupie wiekowej otyłość statystycznie częściej stwierdzono u dziewcząt. W grupie badanych 5- i 6-letnich chłopców stwierdzono znamiennie częstsze występowanie otyłości niż w badanej grupie dziewcząt w tym wieku. WNIOSKI. Nadwaga i otyłość u dzieci w wieku przedszkolnym stanowią duży problem zdrowia publicznego. Wyniki badań autorów niniejszej pracy wskazują na konieczność pilnego podjęcia działań profilaktycznych i leczniczych otyłości u dzieci przedszkolnych.INTRODUCTION. The aim of the study was to assess the prevalence of overweight and obesity in preschool children from Rzeszow region. MATERIAL AND METHODS. Weight and height were measured in 576 preschool children (302 girls and 274 boys) in the mean age 4.82 years ± 1.10 SD from Rzeszow region, and their body mass index (BMI) was calculated. Overweight and obesity were diagnosed according to the International Obesity Task Force criteria. RESULTS. Overweight was present in 9.1% of girls and 9.9% of boys. The prevalence of obesity was 7.2% and 8.4%s respectively. Three years old boys were significantly more overweight than the girls in the same age. However obesity was significantly more prevalent in 3 years old girls than boys and in 5-6 years old boys than girls. CONCLUSIONS. Overweight and obesity in preschool children are an emerging problem of the public health. The study results indicate that obesity prevention and treatment should be focused already at the preschool children

Cardiac amyloidosis: a review

Cardiac amyloidosis is a type of amyloidosis in which one of the affected organs is the heart. The disease is characterized by the formation of protein aggregates between the cells of the organ, namely amyloid, which disables its function. The following types of amyloidosis can be distinguished: systemic senile amyloidosis (wild-type ATTR), light chain amyloidosis (AL) and hereditary transthyretin-related amyloidosis. The symptoms include, e.g., systolic dysfunction or arrhythmia. The treatment is focused on the therapy with melphalan and, additionally, stem cells transplant and chemotherapy with dexamethasone or cyclophosphamide. In the advanced stage of the disease, a heart transplant is necessary. The diagnosis is made on the basis of laboratory testing, electrocardiogram changes, and echocardiography

Carbamazepine - hematologic effects of the use

Carbamazepine is an antiepileptic drug which exhibits a number of side effects, namely including a headache, abdominal pain, increased blood pressure, but also hematologic disorders. Thrombocytopenia, hypogammaglobulinemia, leukopenia, neutropenia, agranulocytosis, aplastic anemia, pure red cell aplasia, leukemia or eosinophilia with DRESS syndrome belong to the latter. There is a low incidence of carbamazepine pharmacotherapy related symptoms and their exact mechanisms of action are still unknown

Metallo-Beta-Lactamases: NDM

New Delhi, an enzyme belonging to the Metallo-beta-lactamases and Carbapenemases group, is most commonly found in Klebsiella pneumoniae and Escherichia coli. It determines these bacteria resistance to the majority of known antibiotics. NDM-1 was discovered in 2008 in a man treated in New Delhi for E. coli infection. Since the first appearance, 17 subtypes of this enzyme have been discovered. Its occurrence has been reported in Europe (Great Britain, France, Belgium - where even a national alert has been issued) as well as in the United States and in Africa. Most cases of New Delhi enzyme bacterial infections are reported in India or in people who have traveled to this country. There is no treatment method described so far. Therapy is based on antibiotic susceptibility test results. Colistin shows the highest effectiveness against NDM. There are also tests suggesting that Isomargololone and Nimbolide may be effective in most cases of NDM infection

Chalcones and Dihydrochalcones Augment TRAIL-Mediated Apoptosis in Prostate Cancer Cells

Chalcones and dihydrochalcones exhibit chemopreventive and antitumor activity. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a natural endogenous anticancer agent. We examined the cytotoxic and apoptotic effect of chalcones and dihydrochalcones on TRAIL-mediated apoptosis in LNCaP prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was detected using annexin V-FITC by flow cytometry and fluorescence microscopy. The ΔΨm was evaluated using DePsipher staining by fluorescence microscopy. Our study showed that two tested chalcones (chalcone and 2’,6’dihydroxy-4’-methoxychalcone) and three dihydrochalcones (2’,6’-dihydroxy-4’4-dimethoxydihydrochalcone, 2’,6’-dihydroxy-4’-methoxydihydro- chalcone,  and 2’,4’,6’-trihydroxydihydrochalcone, called phloretin) markedly augmented TRAIL-induced apoptosis and cytotoxicity in LNCaP cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer

Report on the implementation of WorkPackage 2 "Analyses of legal, ethical, human, technical and social factors of ICT and e-learning development and intercultural competences state in every partner country" in the framework of the IRNet project

This article, prepared by an international team of researchers from different scientific areas, connected with ICT, e-learning, pedagogy, and other related disciplines, focuses on the objectives and some results of the international project IRNet. In particular, the article describes research tools, methods, and a procedure of the WP2, that is, analyses of legal, ethical, human, technical, and social factors of ICT and e-learning development, and the state of intercultural competences in partner countries: objectives, tasks, deliverables, and implementation of research trips. Researchers from Poland, the Netherlands, Spain, Slovakia, Portugal, Czech Republic, Australia, Ukraine, and Russia analyzed the results of WP2 in the context of the next stages and Work packages of IRNet project – International Research Network

Report on the implementation of WP3 "Analyses and evaluation of the ICT level, e-learning and intercultural development in every participating country" in the framework of the IRNet project

This article, prepared by an international team of authors – researchers from different scientific areas, connected with ICT, e-learning, pedagogy, and other related disciplines – focuses on the objectives and some results of the IRNet international project. In particular, this article describes the research tools, methods and some procedures of the WP3 “Analyses and Evaluation of the ICT Level, E-learning and Intercultural Development in Every Participating Country”: Objectives, Tasks, Deliverables, and implementation of research trips. Except that, the article presents more important events, such as (video)conferences, seminars, workshops, an e-round table debate; among these events are ICTE2014, DLCC2014, “New Educational Strategies in Modern Information Space,” “Hightech information educational environment,” during which some more important results of the project research were presented. The list of publications includes 32 papers and a manuscript with WP3 results. Researchers from Poland, Russia, Ukraine, the Netherlands, Spain, Slovakia, Portugal, Czech Republic and Australia analysed the results of WP3 in the context of the next stages and Work packages of IRNet project – International Research Network