Łódź, Poland
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Motzer R.J.,Sloan Kettering Cancer Center | Escudier B.,Institute Gustave Roussy | Tomczak P.,University Medyczny | Hutson T.E.,Sammons Cancer Center | And 10 more authors.
The Lancet Oncology | Year: 2013

Background: In a phase 3 trial comparing the efficacy and safety of axitinib versus sorafenib as second-line treatment for metastatic renal cell carcinoma, patients given axitinib had a longer progression-free survival (PFS). Here, we report overall survival and updated efficacy, quality of life, and safety results. Methods: Eligible patients had clear cell metastatic renal cell carcinoma, progressive disease after one approved systemic treatment, and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1. 723 patients were stratified by ECOG PS and previous treatment and randomly allocated (1:1) to receive axitinib (5 mg twice daily; n=361) or sorafenib (400 mg twice daily; n=362). The primary endpoint was PFS assessed by a masked, independent radiology review committee. We assessed patient-reported outcomes using validated questionnaires. Baseline characteristics and development of hypertension on treatment were studied as prognostic factors. Efficacy was assessed in the intention-to-treat population, and safety was assessed in patients who received at least one dose of the study drug. This ongoing trial is registered on ClinicalTrials.gov, number NCT00678392. Findings: Median overall survival was 20·1 months (95% CI 16·7-23·4) with axitinib and 19·2 months (17·5-22·3) with sorafenib (hazard ratio [HR] 0·969, 95% CI 0·800-1·174; one-sided p=0·3744). Median investigator-assessed PFS was 8·3 months (95% CI 6·7-9·2) with axitinib and 5·7 months (4·7-6·5) with sorafenib (HR 0·656, 95% CI 0·552-0·779; one-sided p<0·0001). Patient-reported outcomes scores were similar in the treatment groups at baseline, were maintained during treatment, but decreased at end-of-treatment. Common grade 3 or higher treatment-related adverse events were hypertension (60 [17%]), diarrhoea (40 [11%]), and fatigue (37 [10%]) in 359 axitinib-treated patients and hand-foot syndrome (61 [17%]), hypertension (43 [12%]), and diarrhoea (27 [8%]) in 355 sorafenib-treated patients. In a post-hoc 12-week landmark analysis, median overall survival was longer in patients with a diastolic blood pressure of 90 mm Hg or greater than in those with a diastolic blood pressure of less than 90 mm Hg: 20·7 months (95% CI 18·4-24·6) versus 12·9 months (10·1-20·4) in the axitinib group (p=0·0116), and 20·2 months (17·1-32·0) versus 14·8 months (12·0-17·7) in the sorafenib group (one-sided p=0·0020). Interpretation: Although overall survival, a secondary endpoint for the study, did not differ between the two groups, investigator-assessed PFS remained longer in the axitinib group compared with the sorafenib group. These results establish axitinib as a second-line treatment option for patients with metastatic renal cell carcinoma. Funding: Pfizer Inc. © 2013 Elsevier Ltd.


Nowinska K.,Katedra i Zaklad Histologii i Embriologii | Dziegiel P.,University Medyczny
Postepy Higieny i Medycyny Doswiadczalnej | Year: 2010

The MCM (minichromosome maintenance protein) protein family was identified for the first time in budding yeast, Saccharomyces cerevisiae. The subgroup consists of MCM proteins 2-9, that possess the characteristic ATPase domain (MCM box). There are also MCM1 and MCM10, which are important in DNA replication, but they do not possess the specific MCM box. The main function of MCM proteins is cooperation with other factors in molecular mechanisms that form the replication fork and in regulation of DNA synthesis. MCM proteins form a ring-shaped complex, which is activated when other factors are bound. MCM 2-7 complex is one of the pre-replication factors. Association of MCM 2-7 complex is a crucial moment initiating the replication fork. MCM proteins play a role in maintaining genome integrity and prevent re-replication once per cell cycle. Proliferating cells have high levels of MCM, whereas they are not detected in quiescent, differentiated or senescent cells. They are also potential useful markers of cell proliferation. Recent studies suggested that MCMs are good markers of proliferation activity degree, because they are highly expressed in a variety of tumors. The aim of this work is to summarize current knowledge about the role of MCM proteins in DNA replication and potential diagnostic markers of proliferating cancer cells.


The introduction of sonographic imaging has revolutionized the diagnostics of thyroid pathologies. Nowadays, thyroid ultrasound examination has become an essential part of routine thyroid gland evaluation. Although one of the greatest advantages of this examination lies in its simplicity, it requires a solid theoretical background, as well as a lot of experience for the examiner to become fluent in adequate interpretation of its results. The aim of this summary is to present a review of the most important aspects of both the technique and interpretation of thyroid ultrasound pictures with regard to the most common difficulties a thyroid sonographer may come across in everyday practice.


This article reviews the most important aspects of antibiotic treatment failure in respiratory tract infection which may occur with empirical as well as under target antibiotic therapy. Potential risk factors leading or predisposing to treatment failure exist in hospital acquired infections which cover polymicrobial aetiology with high multidrug resistance bacteria, changed conditions of pharmacokinetic and pharmacodynamic (PK/PD) parameters of antibiotics, bioavailability, drug interactions and inactivation. Microbial determinants of treatment failure includes bacterial physiology in laboratory cultures and inside the host, inadequqte drug choice, lack of knowledge of PK/PD parameters with insufficient antibiotic level in target tissue. Differences between microbial in vitro tests and clinical outcome can be caused by varied CFU concentration, growing phase, nutritional, pH and redox conditions. Many factors of treatment failure are focused on bacterial biofilm structure and phenomenon of small-colony variants (SCVs) which both display reduced susceptibility to antimicrobial agents protected by matrix feature, enhanced production of PIA and by slow multiplication of biofilm forming cells.


Ropacka-Lesiak M.,University Medyczny | Breaborowicz G.,University Medyczny
Ginekologia Polska | Year: 2012

Intrauterine growth restriction (IUGR) is defined as fetal growth below the expected genetic potential. The paper presents the principles of fetal surveillance in pregnancy complicated by IUGR in accordance with the guidelines of the Fetal Medicine Foundation (FMF). Fetal surveillance includes integrated monitoring by analyzing Doppler blood flow in selected vessels, fetal heart rate, biophysical profile and amniotic fluid volume. The aim of the integrated fetal monitoring is to prolong the pregnancy, to minimize the consequences of prematurity and prevent a potentially lethal damage. The paper presents the symptoms preceding the intrauterine demise and proposes methods of determining the date of delivery according to the guidelines of FMF. © Polskie Towarzystwo Ginekologiczne.


Proper metabolism of folates has a crucial role for body homeostasis. Folate metabolism regulates changing of aminoacids (homocysteine and methionine), purine and pyrimidine synthesis and DNA methylation. These whole biochemical processes have significant influence on hematopoietic, cardiovascular and nervous system functions. The disturbances of folatecycle could result in chronic hypertension, coronary artery disease, higher risk of heart infarction, could promote cancers development, and psychic and neurodegenerative diseases. No less important is the connection with complications appearing in pregnant woman (recurrent miscarriages, preeclampsia, fetus hypotrophy, intrauterine death, preterm placenta ablation, preterm delivery) and fetus defects (Down syndrome, spina bifida, encephalomeningocele, myelomeningocele). The complex process of folate metabolism requires adequate activity of many enzymes and presence of co-enzymes. A key enzymein folate metabolism is methylenetetrahydrofolate reductase (MTHFR - methylenetetrahydrofolate reductase), and 677C>T polymorphism of MTHFR gene is connected with lower enzymatic activity. In several researches it was indicated that 677C>T MTHFR polymorphism is an independent factor influencing homocysteine concentration in serum, and also folate concentration in serum and red blood cells. Nevertheless, it was also observed the correlation of 677C>T MTHFR polymorphism with Down syndrome, and neural tube defects appearance in fetus. In European populations frequency of mutated 677TT genotype ranges from a few to several percent. Women carriers of 677TT or 677CT MTHFR genotypes are exposed on folate metabolism disturbances and on the consequences of incorrect folate process during pregnancy. Nowadays in this group of women folic acid supplementation is widely recommended. In the light of modern knowledge the attention was also focused on the importance of metafolin administration that omitted pathways of folic acid transformation after administration, and in pregnant women certainly is valuable complement of supplementation in this respect.


Proper folate supplementation is required in order to ensure proper folate concentration in the organism, and consequently to prevent the development of numerous complications in general population and pregnant women. Metafolin (stable calcium salt of L-5-methyltetrahydrofolate acid, L-5-MTHF) is the most active form of reduced folate circulating in plasma, which directly enters the metabolic process of folate. After administration metafolin shows optimum absorption, comparable or higher bioavailability as well as physiological activity when compared to folic acid. Metafolin supplementation is effective in decreasing plasma homocysteine, as well as increasing folate in plasma and erythrocytes, in pregnant and breastfeeding women or those who wish to conceive. In addition, metafolin administration omits the multistage process of reduction before entering the folate cell cycle, as well as a possible deficiency of activity of enzymes participating in the reduction of folate process in the intestine epithelium (DHFR and MTHFR enzymes). So far, no potential adverse and toxic effects of metafolin management have been reported. The published findings require confirmation in larger groups of patients and an additional analysis of the presence of particular genotypes of 677C>T polymorphism of the MTHFR gene. Analysis of the recent literature reposts suggests that metafolin could be an effective and safe alternative to folic acid supplementation and could effectively prevent complications in pregnancy and series birth defects in fetuses and newborns. © Polskie Towarzystwo Ginekologiczne.


The β isoform of glycogen synthase kinase 3 enzyme (GSK3β), which is found at particularly high concentrations in the central nervous system, is crucial for its proper development and functioning. The role of GSK3β in the pathogenesis of affective disorders, schizophrenia and Alzheimer's disease, as well as its involvement in other neurological disorders and neurogenesis, is discussed. A hypothesis is proposed that inhibitory phosphorylation of GSK3β induced by non-selective cyclooxygenase (COX) inhibitors mediates the non-selective COX inhibitors' Alzheimer's disease and Parkinson's disease risk-lowering effects. Throughout the review special attention is paid to the therapeutic potential of GSK3β inhibitors. Supplementary information on GSK3β cellular activity regulation, the place of GSK3β in the Wnt signalling pathway, the link between GSK3β and memory, neuroplasticity and circadian rhythms is provided.


Ropacka-Lesiak M.,University Medyczny | Bretaowicz G.H.,University Medyczny
Ginekologia Polska | Year: 2014

The paper presents current views and recommendations for pregnancy complicated by TTTS. The symptoms that should attract our attention during the first-trimester ultrasound, i.e. CRL asymmetry, NT >95th percentile, or 20% or more of the NT difference between the fetuses, absent or reversed A wave in DV, and TV regurgitation, are discussed and presented. Similarly, symptoms that should attract our attention in the second trimester, such as amniotic fluid volume imbalance, asymmetry in the size of the urinary bladders, abdominal circumferences discordance, inter-twin membrane folding, membranous attachment of the donor's umbilical cord, different placental echogenicity, and abnormal Doppler measurements, are listed. © Polskie Towarzystwo Ginekologiczne.


The market of dietary supplements develops extremely fast in the whole world, also in Poland. A great popularity is ascribed to preparations aiding slimming diet. The application of dietary supplements aimed at reducing body's weight is a result of trends connected with the popularity of a healthy lifestyle and the care about one's appearance. Dietary supplements produced on the basis of natural products frequently contain significant amounts of mineral compounds, including microelements indispensable for man (in strictly specified amounts), among others: nickel and chromium. The subject of the study was 16 chosen dietary supplements aiding slimming in which the levels of chromium and nickel were determined. The samples were mineralized "dry" at the temperature of 480 degrees C. The ashes were dissolved in 15%-aqueous solution of HCl (Suprapur, Merck). The levels of the investigated elements were determined in Pye Unicam SP192 Atomic Absorption Spectrometer: nickel - by the extraction method from the organic phase, chromium - directly from a mineralised substance. Determined levels of nickel ranged from 0.11 microg/g in Nivelazione-"kapsulki na noc" supplement to 3.35 microg/g in Teavera preparation, and of chromium from 0.12 microg/g (Adipobon mono) to 22.93 microg/g (Chitobon-preparation with the addition of chromium). The levels of nickel and chromium in the studied supplements were different and depended on the preparation content. The capsules of some preparations, e.g., those with the addition of organic chromium contained levels of chromium exceeding AI dose for this element.

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