MSI i LOH w rozwoju i prognozowaniu przebiegu nowotworów wywodzących się z komórki pęcherzykowej tarczycy

Microsatellite instability (MSI) and loss of heterozygosity (LOH) represent molecular disorders acquired by the cell during neoplastic transformation. Both are associated with genetic instability. Functional silencing of tumour suppressor genes may be the consequence of genomic instability, particularly of the globally occurring LOH phenomenon. Numerous studies have confirmed the role of MSI/LOH at both the early and the late stages of thyroid tumourigenesis. This paper reviews the available study results on MSI/LOH significance and prevalence in thyroid neoplasms. Additionally, it summarises the knowledge regarding the practical usage of the study findings on MSI/LOH in aspects of cancer risk assessment as well as the development of prognostic markers for thyroid neoplasms. (Pol J Endocrinol 2012; 63 (2): 126–136)Niestabilność mikrosatelitarna (MSI) i utrata heterozygotyczności (LOH) to zaburzenia molekularne, które w znacznym stopniu wiążą się z nabywaniem przez komórkę nowotworową niestabilności genetycznej. Funkcjonalną konsekwencją niestabilności w genomie — a w szczególności globalnie występującego LOH — może być utrata funkcji genów supresorowych. Przeprowadzone liczne badania procesu nowotworzenia w gruczole tarczowym potwierdziły rolę MSI/LOH zarówno we wczesnych, jak i poźnych stadiach karcynogenezy. W pracy przedstawiono wyniki badań dotyczących znaczenia i częstości występowania MSI/LOH w procesie nowotworzenia w gruczole tarczowym. Artykuł jest także podsumowaniem stanu wiedzy na temat praktycznego wykorzystania rezultatów badań dotyczących MSI/LOH w ocenie ryzyka wystąpienia nowotworu i w opracowaniu markerów prognostycznych przebiegu choroby nowotworowej tarczycy. (Endokrynol Pol 2012; 63 (2): 126–136

Powłoki antybakteryjne jako obiecująca strategia profilaktyczna zakażeń implantów o etiologii Staphylococcus aureus

Technological progress in the development of various types of implants is one of the greatest achievements of contemporary surgery. Such devices can replace or restore the function of damaged tissues, significantly improving people’s quality of life and its longevity. Unfortunately, infections are the main reason for removing implants from patients who usually then need expensive and challenging treatment. Staphylococcus aureus is the most frequent pathogen detected in such complications. Therefore, prevention methods become more attractive. Antimicrobial coatings are the most important techniques to prevent implant infections. They give the biomaterials from which medical devices are obtained antiadhesive and antibacterial properties. In this paper, we review promising methods of creating such coatings. The majority of concepts are about covering implants with germicidal substances like antibiotics or silver nanoparticles. Interestingly, even changes in the surface topography may be necessary to prevent Staphylococcus aureus adhesion effectivelyPostęp technologiczny w tworzeniu różnego typu implantów jest jednym z największych osiągnięć współczesnej chirurgii. Takie urządzenia mogą zastąpić lub przywrócić funkcję uszkodzonych tkanek, co znacząco poprawia jakość i długość życia pacjentów. Niestety infekcje są głównym powodem usuwania implantów. Pacjenci wymagają też zazwyczaj trudnego i kosztownego leczenia. Gronkowiec złocisty jest najczęściej wykrywanym patogenem w tego typu powikłaniach. Powoduje to, że metody profilaktyczne zyskują na atrakcyjności. Najważniejszymi technikami umożliwiającymi zapobieganie infekcjom implantów są pokrycia przeciwdrobnoustrojowe. Dzięki nim biomateriały, z których otrzymywane są urządzenia medyczne mogą uzyskać właściwości antyadhezyjne i bakteriobójcze. W niniejszej pracy dokonujemy przeglądu obiecujących metod tworzenia takich pokryć. Większość koncepcji dotyczy pokrywania implantów substancjami bakteriobójczymi, takimi jak antybiotyki czy nanocząsteczki srebra. Co ciekawe, nawet zmiany w topografii powierzchni mogą być konieczne, aby skutecznie zapobiec adhezji gronkowca złocistego

Role of Beta-Carotene in Lung Cancer Primary Chemoprevention: A Systematic Review with Meta-Analysis and Meta-Regression

Lung cancer is one of the most common neoplasms globally, with about 2.2 million new cases and 1.8 million deaths annually. Although the most important factor in reducing lung cancer risk is lifestyle change, most patients favour the use of supplements, for example, rather than quitting smoking or following a healthy diet. To better understand the efficacy of such interventions, a systematic review was performed of data from randomized controlled trials concerning the influence of beta-carotene supplementation on lung cancer risk in subjects with no lung cancer before the intervention. The search corpus comprised a number of databases and eight studies involving 167,141 participants, published by November 2021. The findings indicate that beta-carotene supplementation was associated with an increased risk of lung cancer (RR = 1.16, 95% CI = 1.06–1.26). This effect was even more noticeable among smokers and asbestos workers (RR = 1.21, 95% CI = 1.08–1.35) and non-medics (RR = 1.18, 95% CI = 1.07–1.29). A meta-regression found no relationship between the beta-carotene supplementation dose and the size of the negative effect associated with lung cancer risk. Our findings indicate that beta-carotene supplementation has no effect on lung cancer risk. Moreover, when used as the primary chemoprevention, beta-carotene may, in fact, increase the risk of lung cancer

Serum Extracellular Vesicle-Derived miRNAs in Patients with Non-Small Cell Lung Cancer—Search for Non-Invasive Diagnostic Biomarkers

The aim of the study was a search for diagnostic and/or prognostic biomarkers in patients with non-small cell lung cancer (NSCLC) patients, based on circulating microRNAs (miRs: miR-23a, miR-361, miR-1228 and miR-let7i) in extracellular vesicles (EVs). Serum EVs were isolated from NSCLC patients (n = 31) and control subjects (n = 21). RNA was isolated from EVs and reverse transcription reaction was performed. Relative levels of miR-23a, miR-361, miR-1228 and miR-let7i were assessed in real-time qPCR using TaqMan probes. Analysis was based on the 2-ΔΔCT method. Statistically significant lower levels of miR-23a and miR-let7i were observed among NSCLC patients vs. control group: miR-23a, 0.054 vs. 0.107; miR-let7i, 0.193 vs. 0.369 (p = 0.003, p = 0.005, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential of each individual serum EV-derived miRNA with an area under the curve AUC = 0.744 for miR-23a (p = 0.0003), 0.733 for miR-let7i (p = 0.0007). The decreased level of miR-23a in patients correlated with metastasis to lymph nodes and with AJCC tumor staging system. The results demonstrate that miR-23a and miR-let7i may prove clinically useful as significant, non-invasive markers in NSCLC diagnosis. Additionally, changing profile level of miR-23a that correlates with cancer development may be considered as an NSCLC progression marker

Expression analysis of selected classes of circulating exosomal miRNAs in soccer players as an indicator of adaptation to physical activity

Recently studies have shown that, depending on the type of training and its duration, the expression levels of selected circulating myomiRNAs (c-miR-27a,b, c-miR-29a,b,c, c-miR-133a) differ and correlate with the physiological indicators of adaptation to physical activity. To analyse the expression of selected classes of miRNAs in soccer players during different periods of their training cycle. The study involved 22 soccer players aged 17-18 years. The multi-stage 20-m shuttle run test was used to estimate VO2 max among the soccer players. Samples serum were collected at baseline (time point I), after one week (time point II), and after 2 months of training (time point III). The analysis of the relative quantification (RQ) level of three exosomal myomiRNAs, c-miRNA-27b, c-miR-29a, and c-miR-133, was performed by quantitative polymerase chain reaction (qPCR) at three time points – before the training, after 1 week of training and after the completion of two months of competition season training. The expression analysis showed low expression levels (according to references) of all evaluated myomiRNAs before the training cycle. Analysis performed after a week of the training cycle and after completion of the entire training cycle showed elevated expression of all tested myomiRNAs. Statistical analysis revealed significant differences between the first and the second time point in soccer players for c-miR- 27b and c-miR-29a; between the first and the third time point for c-miR-27b and c-miR-29a; and between the second and the third time point for c-miR-27b. Statistical analysis showed a positive correlation between the levels of c-miR-29a and VO2 max. Two months of training affected the expression of c-miR-27b and miR‑29a in soccer players. The increased expression of c-miR-27b and c-miR-29 with training could indicate their probable role in the adaptation process that takes place in the muscular system. Possibly, the expression of c-miR-29a will be found to be involved in cardiorespiratory fitness in future research

CTLA-4 polymorphisms (+49 A/G and -318 C/T) are important genetic determinants of AITD susceptibility and predisposition to high levels of thyroid autoantibodies in Polish children - preliminary study

Autoimmune thyroid diseases (AITDs), including Hashimoto' s thyroiditis (HT) and Graves' disease (GD), are related to environmental and genetic factors. We analyzed the association of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene two polymorphisms (+49 A/G, -318 C/T) with HT and GD development in Polish children, and correlated both polymorphisms with the production of thyroid autoantibodies (TPOAb and TgAb). The study involved 49 AITD patients (age 10-19) with HT (n=25) or GD (n=24) and 69 healthy controls. SNP genotyping was performed using genomic DNA and TaqMan® probes. The obtained results indicated that CTLA-4 +49 GG genotype was significantly more frequent in both HT and GD patients, whereas the AA genotype was more common in controls. CTLA-4-318 CT genotype was significantly more frequent in AITD, and the CC genotype more often occurred in controls. Significantly higher median TPOAb and TgAb values were associated with G allele in HT, and with T allele in GD patients. Concluding, both studied polymorphisms seem to be important genetic determinants of the risk of HT and GD, and appear to be associated with a predisposition to high levels of TAbs and clinical AITD. The obtained results give more information on the distribution of the CTLA-4 polymorphism in Polish AITD children, and further support the proposal that the CTLA-4 gene plays an important role in a TAb production

Expression of STAT5, COX-2 and PIAS3 in correlation with NSCLC histhopathological features.

Signal transducers and activators of transcription (STATs), their inhibitors and cyclooxygenase-2 (COX-2) participate in transformations of many various types of cancers. The aim of the present study was to evaluate the relationship between STAT5A/B, COX-2, and PIAS3 mRNA expression and tumor staging, metastasis status, and histopathological subtype in 71 patients with confirmed non-small cell lung cancer (NSCLC) diagnosis. Total RNA was isolated from NSCLC tissue samples and the expression of the studied genes was assessed using TaqMan probes in real-time PCR assay. The expression levels of STAT5A, STAT5B, and COX-2 genes were increased in 69%, 79%, and 71% NSCLC samples respectively, while PIAS3 expression was decreased in the majority (69%) of the studied tissues. Statistically significant differences were observed between STAT5 isoforms (P = 0.0008), with higher expression of STAT5B. We found statistically significant positive correlation between STAT5B and COX-2 (rho = 0.045), and significant negative correlation between STAT5B and PIAS3 (rho = -0.049). The negative correlation between STAT5B and PIAS3 (rho = -0.43) was also observed in T2a+T2b tumor group. Additionally, STAT5B and COX-2 expression levels were significantly different between T1a+T1b and T2a+T2b tumors (P = 0.002 and P = 0.041, respectively), with higher expression of both genes in T2 tumor stage. PIAS3 expression was significantly lower in NSCC subtype as compared with SCC subtype (P = 0.017). Also, STAT5A and STAT5B immunoexpression was assessed, and the results indicated significantly higher protein levels in NSCLC patients as compared with controls (P = 0.048 and P = 0.034, respectively). High STAT5B immunoexpression was positively correlated with STAT5B gene expression in tumors (rho = 0.755). STAT5B protein level was also significantly higher in T2a+T2b tumors, reflecting high STAT5B gene expression in this group. There was no statistically significant association between mRNA and protein expression levels of the studied genes and patients' characteristics: age, gender, smoking. The obtained results highlight the importance of the genes STAT5B and COX-2 in lung cancer progression