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Statkiewicz M.,Center of Oncology of Poland | Maryan N.,Medical Center for Postgraduate Education | Lipiec A.,Center of Oncology of Poland | Grecka E.,National Research Institute of Mother and Child | And 5 more authors.
Prostate | Year: 2014

BACKGROUND The increased activity of the Sonic Hedgehog (SHH) pathway has been demonstrated in many types of cancer including prostate cancer (PCa). It has been shown that SHH pathway is involved in tumor angiogenesis and in regulation of metabolism of cancer stem cells. The increased activity of the SHH pathway is responsible for generation and maintenance of the multidrug resistance in cancer cells. A key role in the development of this insensitivity to cytotoxic drugs play ATP-binding cassette (ABC) transporters. METHODS SHH encoding plasmid was stably transfected into PCa cell lines DU145 and LNCaP. The expression of SHH was silenced by shRNA and the level of SHH was tested by quantitative (q)PCR and western blot methods. The effect of SHH overexpression in cells after treatment with paclitaxel was measured by MTT assay, crystal violet assay and flow cytometry. The level of 44 ABC transporters was estimated by qPCR. RESULTS Expression of exogenous SHH protein in DU145 and LNCaP cell lines enhanced their resistance to paclitaxel along with increased expression of ABC transporters transcripts. Paclitaxel treatment further enhanced the expression of increased ABC transporters transcripts in cells overexpressing SHH. CONCLUSIONS Overexpression of SHH enhances PCa cell lines resistance to paclitaxel. Higher level of SHH leads to increase in ABC transporters expression in a manner dependent on paclitaxel. © 2014 Wiley Periodicals, Inc. Source

Mohangoo A.D.,Applied Scientific Research | Buitendijk S.E.,Applied Scientific Research | Szamotulska K.,National Research Institute of Mother and Child | Chalmers J.,NHS National Services Scotland | And 5 more authors.
PLoS ONE | Year: 2011

Background: The first European Perinatal Health Report showed wide variability between European countries in fetal (2.6-9.1‰) and neonatal (1.6-5.7‰) mortality rates in 2004. We investigated gestational age patterns of fetal and neonatal mortality to improve our understanding of the differences between countries with low and high mortality. Methodology/Principal Findings: Data on 29 countries/regions participating in the Euro-Peristat project were analyzed. Most European countries had no limits for the registration of live births, but substantial variations in limits for registration of stillbirths before 28 weeks of gestation existed. Country rankings changed markedly after excluding deaths most likely to be affected by registration differences (22-23 weeks for neonatal mortality and 22-27 weeks for fetal mortality). Countries with high fetal mortality ≥28 weeks had on average higher proportions of fetal deaths at and near term (≥37 weeks), while proportions of fetal deaths at earlier gestational ages (28-31 and 32-36 weeks) were higher in low fetal mortality countries. Countries with high neonatal mortality rates ≥24 weeks, all new member states of the European Union, had high gestational age-specific neonatal mortality rates for all gestational-age subgroups; they also had high fetal mortality, as well as high early and late neonatal mortality. In contrast, other countries with similar levels of neonatal mortality had varying levels of fetal mortality, and among these countries early and late neonatal mortality were negatively correlated. Conclusions: For valid European comparisons, all countries should register births and deaths from at least 22 weeks of gestation and should be able to distinguish late terminations of pregnancy from stillbirths. After excluding deaths most likely to be influenced by existing registration differences, important variations in both levels and patterns of fetal and neonatal mortality rates were found. These disparities raise questions for future research about the effectiveness of medical policies and care in European countries. © 2011 Mohangoo et al. Source

Dokoupil K.,Ludwig Maximilians University of Munich | Gokmen-Ozel H.,Hacettepe University | Lammardo A.M.,University of Milan | MacDonald A.,The Childrens Hospital | And 5 more authors.
Molecular Genetics and Metabolism | Year: 2012

Background and aims: To gather exploratory data on the costs and reimbursement of special dietary foods used in the management of phenylketonuria (PKU) from ten international specialist PKU centers. Methods: Experts from each center provided data on retail costs of the three most frequently used phenylalanine-free protein substitutes and low-protein foods at their center; reimbursement of protein substitutes and low-protein foods; and state monetary benefits provided to PKU patients. Results: The mean annual cost of protein substitutes across 4 age groups (2. y, 8. y, 15. y and adults) ranged from €4273 to €21,590 per patient. The cost of low-protein products also differed; the mean cost of low-protein bread varied from €0.04 to €1.60 per 100. kcal. All protein substitutes were either fully reimbursed or covered by health insurance. However, reimbursement for low-protein products varied and state benefits differed between centers. Conclusions: The variation in the cost and reimbursement of diet therapy and the level of additional state benefits for PKU patients demonstrates the large difference in expenditure on and access to PKU dietary products. This highlights the inequality between healthcare systems and access to special dietary products for people with PKU, ultimately leading to patients in some countries receiving better care than others. © 2011 Elsevier Inc. Source

Zeitlin J.,French Institute of Health and Medical Research | Zeitlin J.,University Pierre and Marie Curie | Szamotulska K.,National Research Institute of Mother and Child | Drewniak N.,French Institute of Health and Medical Research | And 11 more authors.
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2013

Objective To investigate time trends in preterm birth in Europe by multiplicity, gestational age, and onset of delivery. Design Analysis of aggregate data from routine sources. Setting Nineteen European countries. Population Live births in 1996, 2000, 2004, and 2008. Methods Annual risk ratios of preterm birth in each country were estimated with year as a continuous variable for all births and by subgroup using log-binomial regression models. Main outcome measures Overall preterm birth rate and rate by multiplicity, gestational age group, and spontaneous versus non-spontaneous (induced or prelabour caesarean section) onset of labour. Results Preterm birth rates rose in most countries, but the magnitude of these increases varied. Rises in the multiple birth rate as well as in the preterm birth rate for multiple births contributed to increases in the overall preterm birth rate. About half of countries experienced no change or decreases in the rates of singleton preterm birth. Where preterm birth rates rose, increases were no more prominent at 35-36 weeks of gestation than at 32-34 weeks of gestation. Variable trends were observed for spontaneous and non-spontaneous preterm births in the 13 countries with mode of onset data; increases were not solely attributed to non-spontaneous preterm births. Conclusions There was a wide variation in preterm birth trends in European countries. Many countries maintained or reduced rates of singleton preterm birth over the past 15 years, challenging a widespread belief that rising rates are the norm. Understanding these cross-country differences could inform strategies for the prevention of preterm birth. © 2013 The Authors. BJOG: An International Journal of Obstetrics & Gynaecology published by John Wiley and Sons on behalf of the Royal College of Obstetricians and Gynaecologists. Source

Jedrzejowska M.,Polish Academy of Sciences | Gos M.,National Research Institute of Mother and Child | Zimowski J.G.,Institute of Psychiatry and Neurology | Kostera-Pruszczyk A.,Medical University of Warsaw | And 2 more authors.
Neuromuscular Disorders | Year: 2014

The aim of our study was to identify point mutations in a group of 606 patients diagnosed for spinal muscular atrophy with excluded biallelic loss of the SMN1 gene. Point missense mutations or small deletions in the SMN1 gene were ultimately identified in 18 patients. Six patients were found to have small deletions, the c.429_435del mutation in 3 cases, the c.431delC mutation in 2 and c.722delC in one. Those mutations, not described previously, were characteristic of patients presenting a severe phenotype. The most frequent missense mutation - p.Thr274Ile, was identified in 9 patients presenting a rather mild phenotype. Three other missense mutations, i.e. p.Ser230Leu, p.Ala111Gly and p.Pro244Leu, were identified in a further 3 SMA3 patients. Mutation p.Pro244Leu, not described so far, was identified in a patient with a mild form of SMA and more distal distribution of muscle weakness. Our results suggest a specific point mutation spectrum in the Polish population. The existence of small deletions not identified thus far could suggest a possible founder effect. In patients with preserved one SMN1 allele without common exon 7 deletion, presenting a mild form of SMA, a special consideration should be given to the p.Thr274Ile mutation. © 2014 Elsevier B.V. Source

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