Glycosylation and Glycoproteins in Thyroid Cancer: A Potential Role for Diagnostics

Rozdział książki Updates in the Understanding and Management of Thyroid Cancer Edited by Thomas J. Fahe

Identification of vertebral deformities in the Polish population by morphometric X-ray absorptiometry - results of the EPOLOS study

Introduction: The aim of the study was the determination of the prevalence of asymptomatic vertebral deformities in healthy persons of the Polish population, based on morphometric X-ray absorptiometry (MXA), and comparison of the results with data from literature, obtained by other techniques. Material and methods: The study involved 829 persons, including 520 women and 309 men, aged 18-79 years, untreated for osteoporosis before. The Th4 to L4 vertebrae were examined. Lateral scans of the thoracic-lumbar spine were made by an Expert-XL densitometer. Sixpoint digitization was used to calculate the anterior (Ha), central (Hc), and posterior (Hp) height of the Th4-L4 vertebral bodies. The vertebrae were defined as having prevalent deformities when at least one ratio value (Ha/Hp, Hc/Hp, Hp/Hp up, or Hp/Hp low) fell 3 SDs below or even more than the reference mean of that ratio at any vertebral level. Results: The analysis was performed on 9629 vertebrae, of which 167 (1.75%), evaluated as deformed and considered as fractures, were observed in 113 patients (13.63 % of the examined patients). In 81 persons (74% of the patients with fractures; 9.7% of the studied population), single fractures were demonstrated, while in 28 persons, multiple deformities prevailed. Fractures occurred in 108 women (20.7% of the examined women) and 42 men (13.5% of the examined men). The highest incidence of deformities was observed in women over 55 years of age. First-degree deformities dominated. Deformities of the Th8 and Th6 vertebrae were most frequently observed. Conclusions: 1. Using MXA, it was found that in the Polish population deformities of vertebrae are common, as was demonstrated in X-ray morphometric studies in the European Vertebral Observation Study (EVOS). 2. Densitometric morphometry, as a non-invasive technique, may become a useful tool in the diagnostics of vertebral fractures.Wstęp: Celem badania było określenie częstości występowania bezobjawowych zniekształceń trzonów kręgowych u zdrowych osób populacji polskiej przy wykorzystaniu morfometrii densytometrycznej (MXA) i porównanie wyników z danymi z piśmiennictwa uzyskanymi innymi technikami. Materiał i metody: Badaniu poddano 829 osób, w tym 520 kobiet i 309 mężczyzn w wieku 18-79 lat, dotąd nieleczonych z powodu osteoporozy. Uwidoczniono kręgi od Th4 do L4. Boczne skany kręgosłupa piersiowo-lędźwiowego wykonano aparatem Expert-XL. Oznaczono sześć punktów w celu wyznaczenia przedniej (Ha), środkowej (Hc) i tylnej (Hp) wysokości trzonów kręgowych Th4-L4. Kręg uznawano za zniekształcony, jeśli którakolwiek z wartości Ha/Hp, Hc/Hp lub Hp/Hp kręgu następnego lub Hp/Hp kręgu poprzedniego była niższa niż 3 odchylenia standardowego od średniej wartości referencyjnej. Wyniki: Analizie poddano 9629 kręgów. Jako zniekształcone, uznane za złamane oceniono 167 kręgów, występowały one u 113 pacjentów (13,63% badanych osób). U 81 osób (74% osób ze złamaniami; 9,7% populacji badanej) wykazano pojedyncze złamanie, a u 28 osób występowały mnogie deformacje. Złamania występowały u 108 kobiet (20,7%) i 42 mężczyzn (13,5%). Dominowały zniekształcenia pierwszego stopnia. Największa częstość deformacji występowała w grupie kobiet po 55. roku życia. Dominowały zniekształcenia pierwszego stopnia. Najczęściej obserwowano deformacje kręgu Th8 i Th6. Wnioski: 1. Stosując metodę MXA, potwierdzono częste występowanie deformacji trzonów kręgowych w populacji polskiej. Dane te są zbliżone do wyników uzyskanych w badaniach morfometrii rentgenowskiej w badaniach EVOS. 2. Morfometria densytometryczna jako badanie nieinwazyjne może stać się przydatnym narzędziem w diagnostyce złamań trzonów kręgowych

Fluvastatin increases tyrosinase synthesis induced by UVB irradiation of B16F10 melanoma cells.

Statins are widely used to lower plasma concentrations of lipids, e.g. cholesterol. One of the main effects of statin treatment is inhibition of hydroxymethyl glutaryl-coenzyme A reductase. The role of fluvastatin, a frequently used statin, was examined in potential modulation of tyrosinase (key enzyme of melanogenesis) synthesis. Levels of tyrosinase mRNA induced by UVB irradiation of B16F10 melanoma cell line were measured by real time PCR. Fluvastatin increases tyrosinase mRNA production induced by UVB irradiation in B16F10 melanoma cell line. Fluvastatin treatment may potentially influence melanin synthesis and protection against UV irradiation

Metallothionein 2A genetic polymorphisms and risk of ductal breast cancer

Metallothioneins (MTs) are a family of metal binding proteins that play an important role in cellular processes such as proliferation and apoptosis. Metallothionein 2A is the most expressed MT isoform in the breast cells. A number of studies have demonstrated increased MT2A expression in various human tumors, including breast cancer. We carried out an association study to examine whether MT2A gene polymorphisms are associated with risk of breast cancer. Information on lifestyle risk factors was collected via a self-administered questionnaire. Genotyping was conducted using polymerase chain reaction–restriction fragment length polymorphism technique. Three single nucleotide polymorphisms (SNP) rs28366003, rs1610216 and rs10636 were genotyped in 534 breast cancer cases and 556 population controls. One SNP in MT2A (rs28366003) showed a positive association with breast cancer. Compared with homozygous common allele carriers, heterozygous for the G variant [odds ratio (OR) = 1.92, 95 % confidence interval (CI):1.28–2.81, p trend <0.01; the OR assuming a dominant model 1.93 (95 % CI: 1.29–2.89, p dominant <0.02) after adjustment for age, family history, smoking status, BMI, menarche, parity, menopausal status and use of contraceptive and menopausal hormones] had a significantly increased risk of breast cancer in Polish population, as well as women with haplotypes, including variant allele of rs28366003 SNP (OR = 1.58, CI: 0.41–6.33, p global = 0.03). Our data suggest that the rs28366003 SNP in MT2A is associated with risk of breast cancer in Polish population.This work was supported, in part, by the statutory fund for the Department of Cytobiochemistry, University of Łód

Antibiofilm and antimicrobial-enhancing activity of Chelidonium majus and Corydalis cheilanthifolia extracts against multidrug-resistant Helicobacter pylori

Helicobacter pylori is a Gram-negative bacterium that colonizes the stomach of about 60% of people worldwide. The search for new drugs with activity against H. pylori is now a hotspot in the effective and safe control of this bacterium. Therefore, the aim of this research was to determine the antibacterial activity of extracts from selected plants of the Papaveraceae family against planktonic and biofilm forms of the multidrug-resistant clinical strain of H. pylori using a broad spectrum of analytical in vitro methods. It was revealed that among the tested extracts, those obtained from Corydalis cheilanthifolia and Chelidonium majus were the most active, with minimal inhibitory concentrations (MICs) of 64 µg/mL and 128 µg/mL, respectively. High concentrations of both extracts showed cytotoxicity against cell lines of human hepatic origin. Therefore, we attempted to lower their MICs through the use of a synergistic combination with synthetic antimicrobials as well as by applying cellulose as a drug carrier. Using checkerboard assays, we determined that both extracts presented synergistic interactions with amoxicillin (AMX) and 3-bromopyruvate (3-BP) (FICI = 0.5) and additive relationships with sertraline (SER) (FICI = 0.75). The antibiofilm activity of extracts and their combinations with AMX, 3-BP, or SER, was analyzed by two methods, i.e., the microcapillary overgrowth under flow conditions (the Bioflux system) and assessment of the viability of lawn biofilms after exposure to drugs released from bacterial cellulose (BC) carriers. Using both methods, we observed a several-fold decrease in the level of H. pylori biofilm, indicating the ability of the tested compounds to eradicate the microbial biofilm. The obtained results indicate that application of plant-derived extracts from the Papaveraceae family combined with synthetic antimicrobials, absorbed into organic BC carrier, may be considered a promising way of fighting biofilm-forming H. pylori

Topoisomerase IIβ Binding Protein 1 c.*229C>T (rs115160714) Gene Polymorphism and Endometrial Cancer Risk

TopBP1 (topoisomerase IIβ binding protein 1) protein is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. In this study we investigated whether alterations in the TopBP1 gene can influence the risk of endometrial cancer. We examined the association between five single nucleotide polymorphisms (rs185903567, rs116645643, rs115160714, rs116195487, and rs112843513) located in the 3′UTR region of the TopBP1 gene and endometrial cancer risk as well as allele-specific gene expression. One hundred twenty-one endometrial cancer patients were genotyped for these SNPs. Allele-specific TopBP1 mRNA and protein expressions were determined by real time PCR and western blotting methods, respectively. Only one SNP (rs115160714) showed an association with endometrial cancer. Compared to homozygous common allele carriers, heterozygous for the T variant had significantly increased risk of endometrial cancer [adjusted odds ratio (OR) = 5.59, 95 % confidence interval (CI): 1.96–15.91, p = 0.0003]. Mean TopBP1 mRNA and protein expression were higher in the individuals with the CT genotype. There was a significant association between the rs115160714 and tumor grade and FIGO classification. Most carriers of minor allele had a high grade tumors (G3) classified as FIGO III/IV. The results of our study raise a possibility that a genetic variation of TopBP1 may be implicated in the etiology of endometrial cancer

The spring constant calibration of the piezoresistive cantilever based biosensor

Piezoresistive microcantilevers are widely applied to measurements of low forces, masses and viscosity [1]. After surface functionalization they might be used as a biochemical sensors being capable of the intermolecular force investigation. The problem is that such sensors change its mechanical properties in the environment they operate. Therefore there is a need for a high accuracy technique being capable of measuring of mechanical properties of functionalized cantilevers operating in the target environment. We suppose that such conditions meet the analysis of thermomechanical oscillation noise. In this paper the analysis of two types of cantilevers, that might be used in bioelectrochemical measurements, was performed. We determined the cantilever deflection and force sensitivity. The spring constant was measured by three different methods: the Cleveland methods [2] and the thermomechanical noise analysis. The obtained results indicate that analysis of thermomechanical excitation noise is the simplest and the most reliable method for spring constant calibration of piezoresistive cantilever based sensors

Association between the c.*229C>T polymorphism of the topoisomerase IIb binding protein 1 (TopBP1) gene and breast cancer

Topoisomerase IIb binding protein 1 (TopBP1) is involved in cell survival, DNA replication, DNA damage repair and cell cycle checkpoint control. The biological function of TopBP1 and its close relation with BRCA1 prompted us to investigate whether alterations in the TopBP1 gene can influence the risk of breast cancer. The aim of this study was to examine the association between five polymorphisms (rs185903567, rs116645643, rs115160714, rs116195487, and rs112843513) located in the 30UTR region of the TopBP1 gene and breast cancer risk as well as allele-specific gene expression. Five hundred thirty-four breast cancer patients and 556 population controls were genotyped for these SNPs. Allele-specific Top- BP1 mRNA and protein expressions were determined by using real time PCR and western blotting methods, respectively. Only one SNP (rs115160714) showed an association with breast cancer. Compared to homozygous common allele carriers, heterozygous and homozygous for the T variant had significantly increased risk of breast cancer (adjusted odds ratio = 3.81, 95 % confidence interval: 1.63–8.34, p = 0.001). Mean TopBP1 mRNA and protein expression were higher in the individuals with the CT or TT genotype. There was a significant association between the rs115160714 and tumor grade and stage. Most carriers of minor allele had a high grade (G3) tumors classified as T2-T4N1M0. Our study raises a possibility that a genetic variation of TopBP1 may be implicated in the etiology of breast cancer

Thermophysical properties of IoNanofluids composed of 1-ethyl-3- methylimidazolium thiocyanate and carboxyl-functionalized long multi-walled carbon nanotubes

The concept of IoNanofluids (INFs) as the stable dispersions of nanoparticles in ionic liquids was proposed in 2009 by Nieto de Castro’s group. INFs characterize exciting properties such as improved thermal conductivity, non-volatility, and non-flammability. This work is a continuation of our studies on the morphology and physicochemistry of carbon-based nanomaterials a ecting thermal conductivity, viscosity, and density of INFs. We focus on the characterization of dispersions composed of long carboxylic group-functionalized multi-walled carbon nanotubes and 1-ethyl-3-methylimidazolium thiocyanate. The thermal conductivity of INFs was measured using KD2 Pro Thermal Properties Analyzer (Decagon Devices Inc., Pullman, WA, USA). The viscosity was investigated using rotary viscometer LV DV-II+Pro (Brookfield Engineering, Middleboro, MA, USA). The density of INFs was measured using a vibrating tube densimeter Anton Paar DMA 5000 (Graz, Austria). The maximum thermal conductivity enhancement of 22% was observed for INF composed of 1 wt% long carboxylic group-functionalized multi-walled carbon nanotubes