Mortality and morbidity of newborns with sepsis can be improved by early and accurate diagnosis and targeted therapy. To evaluate the early molecular events associated with inflammation and infection, we evaluated markers of endothelial activation and injury and circulating plasma miRNAs in preterm newborns with sepsis. The study group consisted of newborns with gestational age ≤ 32 weeks, with culture-positive early-onset neonatal sepsis (sepsis group, N = 8), and as a control group, we enrolled newborns without sepsis (control group, N = 12). Soluble markers of inflammation were measured using Luminex-based multiplex assay. Platelet-free plasma RNA was used to construct the library for miRNA sequencing analysis. Normalized counts were calculated and used to measure differential expression of individual detected miRNAs. We found a significant increase of interleukin 18 (IL-18) in the cord blood of the sepsis group (mean ± SEM, 104.7 ± 30.4 pg/ml vs 52.7 ± 5.6 pg/ml, P = 0.02). In peripheral blood of sepsis group patients, we found a significant increase of VEGF-A compared to controls (196.0 ± 70.5 pg/ml vs 59.6 ± 8.5 pg/ml, P = 0.02). In the cord blood plasma, eight miRNAs had significantly differential expression (P < 0.05), four miRNAs were up-regulated and four miRNAs down-regulated. In peripheral blood plasma, all nine miRNAs with significant differential expression were up-regulated. In conclusion, in early-onset neonatal sepsis, IL-18 and VEGF-A might be considered in diagnostic workup. Early-onset sepsis in preterm newborns is associated with significant changes in the circulating miRNA pattern.

• MeSH
• Biomarkers metabolism   MeSH
• Interleukin-18 MeSH
• Infant MeSH
• Humans MeSH
• MicroRNAs * genetics   MeSH
• Infant, Newborn MeSH
• Neonatal Sepsis * diagnosis   MeSH
• Sepsis * diagnosis   genetics   MeSH
• Vascular Endothelial Growth Factor A MeSH
• Inflammation MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Journal Article MeSH

Diabetická retinopatie (DR) je typickou mikrovaskulární komplikací diabetu 1. i 2. typu. Ve vyspělých zemích je nejčastější příčinou slepoty u osob v produktivním věku. Základní metabolickou odchylkou, která hraje nejdůležitější roli při jejím vzniku, je hyperglykemie. Hyperglykemie zvyšuje mitochondriální produkci reaktivních kyslíkových radikálů a oxidační stres, vede k hromadění pokročilých produktů glykace, tvorbě hexosaminu, akcentaci polyolové cesty a zvýšení osmoticky aktivního sorbitolu a také ke zvýšení proteinkinázy C. Závažnost vaskulární patologie je významně ovlivněna genetickou dispozicí jedince a je modifikována dalšími epigenetickými (včetně microRNA), metabolickými a hemodynamickými faktory, jako je dyslipidemie, hypertenze, inzulinová rezistence a další. Uvedené abnormity ovlivní nejprve funkci a později i morfologii celé řady cílových buněk, které zahrnují nejen vlastní buňky retiny (endotelové buňky, pericyty, neurony, mikroglie, makroglie, pigmentový epitel), ale také imunokompetentní buňky, které infiltrují do místa patologie z cévního řečiště (non-rezidentní buňky). Aktivované buňky pak vedou k produkci řady mediátorů s vazoaktivními a růstovými vlastnostmi, které dál zhoršují oxidační stres a subklinický zánět. Zdrojem těchto mediátorů mohou být i další tkáně, např. tuková tkáň, játra, CNS, střevo, kosterní sval a další. Výsledkem je komplex, zpočátku funkčních a později strukturálních změn, které se projeví v dysregulaci (a) krevního průtoku, (b) buněčného růstu – apoptóza, proliferace, hypertrofie, a vedou k (c) proliferaci vaziva, zmnožení extracelulární hmoty ztluštění bazálních membrán. Důsledkem je pak rozvoj morfologicky fixované orgánové patologie. Léčba a prevence DR se v současné době opírá (a) o režimovou a farmakologickou léčbu ovlivnitelných rizikových faktorů, to znamená snahu o normalizaci hladin glykemie, krevního tlaku a hladin lipidů, (b) aktivní screening DR a (c) specializovanou oftalmologickou léčbu, která zahrnuje laserovou fotokoagulaci, intravitreální aplikaci farmak a vitreoretinální chirurgické postupy. Poznání patofyziologických mechanizmů rozvoje DR dává naději na možnou kauzální léčbu a prevenci.

Diabetic retinopathy (DR) develops in patients with both type 1 and type 2 diabetes and is the major cause of vision loss and blindness in the working population. The main risk factor of DR is hyperglycemia accompanied by enhanced mitochondrial production of reactive oxygen species and oxidative stress, formation of advanced glycation end products (AGE) and hexosamines, increase in polyol metabolism of glucose. The severity of vascular injury depends on the individual genetic background and is modified by other epigenetic, metabolic and haemodynamic factors, including hypertension, dyslipidemia and oxidative stress. In diabetes, damage to the retina occurs in the vasculature (endothelial cells and pericytes), neurons and glia, pigment epithelial cells and infiltrating immunocompetent cells: monocytes, granulocytes, lymfocytes. These activated cells change the production pattern of a number of mediators such as growth factors, proinflammatory cytokines, vasoactive molecules, coagulation factors and adhesion molecules resulting in increased blood flow, increased capillary permeability, proliferation of extracellular matrix and thickening of basal membranes, altered cell turnover (apoptosis, proliferation, hypertrophy), procoagulant and proaggregant pattern, and finally in angiogenesis and tissue remodelling. Brain, liver, adipose tissue, GUT, skeletal muscle and other tissues could be another source of mediators. Therapeutic approaches used for patients with or at risk for diabetic retinopathy include drug therapy to reduce modifiable risk factors, laser photocoagulation, intravitreous administration of anti-VEGF agents/steroids and intraocular surgery. Screening plays an important role in early detection and intervention to prevent the progression of diabetic retinopathy. Described insights into pathophysiological mechanisms responsible for DR, could help in the development of more targeted approach for prevention and treatment of diabetic retinopathy.

• Keywords
• aflibercept,
• MeSH
• Bevacizumab therapeutic use   MeSH
• Endothelium, Vascular MeSH
• Diabetic Retinopathy * etiology   drug therapy   physiopathology   MeSH
• Dyslipidemias complications   MeSH
• Hyperglycemia * complications   MeSH
• Hypertension complications   MeSH
• Intravitreal Injections MeSH
• Humans MeSH
• MicroRNAs MeSH
• Retinal Neurons MeSH
• Oxidative Stress MeSH
• Pericytes MeSH
• Ranibizumab therapeutic use   MeSH
• Receptors, Vascular Endothelial Growth Factor therapeutic use   MeSH
• Recombinant Fusion Proteins therapeutic use   MeSH
• Retinal Vessels physiopathology   MeSH
• Vascular Endothelial Growth Factors MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Východiska: Nejnovější poznatky ohledně podílu mikroRNA na nádorové angiogenezi a onkogenních účincích mikroRNA ukazují na jejich případnou roli v angiogenezi karcinomu prsu. Exozomy získané z nádoru jsou považovány za bohatý zdroj mikroRNA, které dokáží regulovat ostatní buňky v nádorovém mikroprostředí, vč. vaskulárních endoteliálních buněk. Tato studie analyzuje účinek chemoterapie tamoxifenem na expresi klíčové microRNA, miR-329, a upozorňuje na spojitost mezi touto mikroRNA a genem KDM1A, který se účastní dráhy vaskulárního endoteliálního růstového faktoru (VEGF). Materiál a metody: Byly zakoupeny buňky karcinomu prsu MCF-7 a kultivovány v kompletním živném médiu. K těmto buňkám byl přidán tamoxifen a pak byly z média extrahovány jejich exozomy. Z nich byly izolovány RNA a pomocí metody polymerázové řetězové reakce (polymerase chain reaction – PCR) v reálném čase byla zkoumána exprese genů miR-329, VEGF a KDM1A v exozomech. Výsledky: Výsledky této studie ukázaly, že při léčbě tamoxifenem se v exozomech získaných z buněk karcinomu prsu MCF-7 zvýšila exprese genů miR-329. Exprese genů KDM1A a VEGF v exozomech buněk ošetřených léčivem byla downregulovaná. Závěr: Výsledky tohoto experimentu ukázaly, že po přidání tamoxifenu k buňkám karcinomu prsu dochází vlivem zvýšení miR-329 ke snížení exprese VEGF a KDM1A. Tím se snižuje angiogeneze a uplatňují se tak protinádorové účinky tohoto léku.

Background: Recent developments regarding the contribution of microRNAs to tumor angiogenesis and the oncogenic effects of microRNAs point to their potential role in breast cancer angiogenesis. Tumor-derived exosomes are considered a rich source of microRNAs that can regulate the function of other cells in the tumor microenvironment, including vascular endothelial cells. This study analyzes the effect of tamoxifen chemotherapy on the expression of a key microRNA, miR-329, and introduces a regulatory link between this microRNA and the KDM1A gene associated with the vascular endothelial growth factor (VEGF) messaging pathway. Materials and methods: MCF-7 breast cancer cells were purchased and cultured in a complete culture medium. These cells were treated with tamoxifen and then their exosomes were extracted from the culture medium. The RNAs of the exosomes were isolated and the expression of miR-329, VEGF, and KDM1A genes in the exosomes was investigated using the real-time polymerase chain reaction (PCR) method. Results: The results of this study showed that tamoxifen treatment increased the expression of miR-329 in exosomes derived from MCF-7 cancer cells. The expression of KDM1A and VEGF genes in drug-treated cell exosomes is downregulated. Conclusion: The results of this experiment demonstrated that the treatment of breast cancer cells with tamoxifen reduces the expression of VEGF and KDM1A by increasing miR-329. The treatment therefore reduces angiogenesis, and thus its anti-tumor effects are applied.

• Keywords
• KDM1A,
• MeSH
• Exosome Multienzyme Ribonuclease Complex drug effects   MeSH
• Humans MeSH
• MicroRNAs analysis   genetics   MeSH
• Biomarkers, Tumor analysis   MeSH
• Cell Line, Tumor pathology   MeSH
• Breast Neoplasms * genetics   MeSH
• Neovascularization, Pathologic * etiology   pathology   MeSH
• Tamoxifen therapeutic use   MeSH
• Vascular Endothelial Growth Factor A analysis   genetics   MeSH
• Research MeSH
• Check Tag
• Humans MeSH
• Publication type
• Clinical Study MeSH

The aim of the study was to examine the effect of previous pregnancies and classical cardiovascular risk factors on vascular endothelial function in a group of 264 young and middle-aged women 3 to 11 years postpartum. We examined microvascular functions by peripheral arterial tonometry and EndoPAT 2000 device with respect to a history of gestational hypertension, preeclampsia, fetal growth restriction, the severity of the disease with regard to the degree of clinical signs and delivery date. Besides, we compared Reactive Hyperemia Index (RHI) values and the prevalence of vascular endothelial dysfunction among the groups of women with normal and abnormal values of BMI, waist circumference, systolic and diastolic blood pressures, heart rate, total serum cholesterol levels, serum high-density lipoprotein cholesterol levels, serum low-density lipoprotein cholesterol levels, serum triglycerides levels, serum lipoprotein A levels, serum C-reactive protein levels, serum uric acid levels, and plasma homocysteine levels. Furthermore, we determined the effect of total number of pregnancies and total parity per woman, infertility and blood pressure treatment, presence of trombophilic gene mutations, current smoking of cigarettes, and current hormonal contraceptive use on the vascular endothelial function. We also examined the association between the vascular endothelial function and postpartum whole peripheral blood expression of microRNAs involved in pathogenesis of cardiovascular/cerebrovascular diseases (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p). A proportion of overweight women (17.94% and 20.59%) and women with central obesity (18.64% and 21.19%) had significantly lower RHI values at 10.0% false positive rate (FPR) both before and after adjustment of the data for the age of patients. At 10.0% FPR, a proportion of women with vascular endothelial dysfunction (RHI ≤ 1.67) was identified to have up-regulated expression profile of miR-1-3p (11.76%), miR-23a-3p (17.65%), and miR-499a-5p (18.82%) in whole peripheral blood. RHI values also negatively correlated with expression of miR-1-3p, miR-23a-3p, and miR-499a-5p in whole peripheral blood. Otherwise, no significant impact of other studied factors on vascular endothelial function was found. We suppose that screening of these particular microRNAs associated with vascular endothelial dysfunction may help to stratify a highly risky group of young and middle-aged women that would benefit from early implementation of primary prevention strategies. Nevertheless, it is obvious, that vascular endothelial dysfunction is just one out of multiple cardiovascular risk factors which has only a partial impact on abnormal expression of cardiovascular and cerebrovascular disease associated microRNAs in whole peripheral blood of young and middle-aged women.

• MeSH
• Endothelium, Vascular physiopathology   MeSH
• Adult MeSH
• Epigenesis, Genetic * MeSH
• Cardiovascular Diseases blood   genetics   MeSH
• Pregnancy Complications blood   genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Logistic Models MeSH
• MicroRNAs genetics   metabolism   MeSH
• Young Adult MeSH
• Obesity genetics   physiopathology   MeSH
• Risk Factors MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

MiR-126 has been shown to suppress malignant mesothelioma (MM) by targeting cancer-related genes without inducing toxicity or histopathological changes. Exosomes provide the opportunity to deliver therapeutic cargo to cancer stroma. Here, a tumour stromal model composed of endothelial cells (HUVECs), fibroblasts (IMR-90 cells), non-malignant mesothelial cells (Met-5A cells) and MM cells (H28 and MM-B1 cells) was used. The cells were treated with exosomes from HUVECs carrying endogenous (exo-HUVEC) and enriched miR-126 (exo-HUVECmiR-126), and the uptake/turnover of exosomes; miR-126 distribution within the stroma; and effect of miR-126 on cell signalling, angiogenesis and cell proliferation were evaluated. Based on the sensitivity of MM cells to exo-HUVEC miR-126 treatment, miR-126 was distributed differently across stromal cells. The reduced miR-126 content in fibroblasts in favour of endothelial cells reduced angiogenesis and suppressed cell growth in an miR-126-sensitive environment. Conversely, the accumulation of miR-126 in fibroblasts and the reduced level of miR-126 in endothelial cells induced tube formation in an miR-126-resistant environment via VEGF/EGFL7 upregulation and IRS1-mediated cell proliferation. These findings suggest that transfer of miR-126 via HUVEC-derived exosomes represents a novel strategy to inhibit angiogenesis and cell growth in MM.

• MeSH
• EGF Family of Proteins metabolism   MeSH
• Exosomes metabolism   MeSH
• Fibroblasts metabolism   MeSH
• Carcinogenesis metabolism   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Cell Communication physiology   MeSH
• Mesothelioma metabolism   MeSH
• MicroRNAs metabolism   MeSH
• Lung Neoplasms metabolism   MeSH
• Calcium-Binding Proteins metabolism   MeSH
• Signal Transduction physiology   MeSH
• Vascular Endothelial Growth Factor A metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Východiska: Nejnovější výzkumy týkající se podílu microRNA (miRNA) na nádorové angiogenezi a onkogenních účinků miRNA ukazují na jejich potenciální roli při angiogenezi karcinomu prsu. Exozomy získané z nádoru jsou považovány za bohatý zdroj miRNA, které regulují funkce ostatních buněk v nádorovém mikroprostředí, vč. endoteliálních buněk cév. Tato studie analyzuje účinek chemoterapie tamoxifenem na expresi klíčové miRNA, miR-573, která se účastní angiogeneze v exozomech nádoru a působí jako regulační spojka mezi miRNA a genem CD146, který je součástí dráhy vaskulárního endoteliálního růstového faktoru (vascular endothelial growth factor – VEGF). Materiál a metody: Byly zakoupeny buňky karcinomu prsu MCF-7 a kultivovány v kompletním médiu. Tyto buňky byly ošetřeny tamoxifenem a z média byly následně exrahovány jejich exozomy. Byla izolována RNA exozomů a pomocí metody polymerázové řetězové reakce (PCR) v reálném čase byla vyhodnocena exprese genů miR-573, VEGF a CD146 v exozomech. Výsledky: Výsledky této studie ukázaly, že ošeření buněk tamoxifenem zvýšilo expresi miR-573 v exozomech získaných z nádorových buněk MCF-7. Exprese genů CD146 a VEGF v exozomech buněk ošetřených léčivem měla klesající tendenci. Závěr: Výsledky tohoto pokusu prokázaly, že ošetření nádorových buněk tamoxifenem snižuje expresi genů VEGF and CD146 zvýšením miR-573. Dochází tedy k omezení angiogeneze a tím k protinádorovému působení léčiva.

Background: Recent developments regarding the contribution of microRNAs (miRNAs) to tumor angiogenesis and the oncogenic effects of miRNAs point to their potential role in breast cancer angiogenesis. Tumor-derived exosomes are considered a rich source of miRNAs that can regulate the function of other cells in the tumor microenvironment, including vascular endothelial cells. This study analyzes the effect of tamoxifen chemotherapy on the expression of a key miRNA, miR-573, involved in the angiogenesis of the tumor exosomes and introduces a regulatory link between this miRNA and the CD146 gene associated with the vascular endothelial growth factor (VEGF) messaging pathway. Materials and methods: MCF-7 breast cancer cells were purchased and cultured in a complete culture medium. These cells were treated with tamoxifen and then their exosomes were extracted from the culture medium. The RNAs of the exosomes were isolated and the expression of miR-573, VEGF, and CD146 genes in the exosomes was investigated using the real-time polymerase chain reaction (PCR) method. Results: The results of this study showed that tamoxifen treatment increased the expression of miR-573 in exosomes derived from MCF-7 cancer cells. The expression of CD146 and VEGF genes in drug-treated cell exosomes had a downward pattern. Conclusion: The results of this experiment demonstrated that the treatment of breast cancer cells with tamoxifen reduces the expression of VEGF and CD146 by increasing miR-573. Thus, angiogenesis is reduced and, therefore, its anti-tumor effects are applied.

• Keywords
• miR-573,
• MeSH
• Exosome Multienzyme Ribonuclease Complex therapeutic use   drug effects   MeSH
• Humans MeSH
• MCF-7 Cells pathology   MeSH
• MicroRNAs analysis   genetics   drug effects   MeSH
• Tumor Cells, Cultured drug effects   MeSH
• Breast Neoplasms * drug therapy   genetics   pathology   MeSH
• Neovascularization, Pathologic etiology   genetics   prevention & control   MeSH
• Tamoxifen * analysis   administration & dosage   pharmacology   therapeutic use   MeSH
• Vascular Endothelial Growth Factors genetics   drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Clinical Study MeSH
• Research Support, Non-U.S. Gov't MeSH

Renální karcinom patří mezi časté nádory uropoetického traktu s postupně narůstající incidencí i prevalencí. Úkolem urologa je toto onemocnění včas diagnostikovat a dle rozsahu tumorózního postižení rozhodnout o způsobu terapie a navržení podoby a frekvence dalšího sledování. V tomto nám pomáhají nejrůznější prognostické faktory a prognostické modely, které umožní stratifikaci rizika a navržení nejoptimálnější terapie. Tento přehledový článek přináší souhrn nejdůležitějších prognostických faktorů pro karcinom ledviny se zaměřením na prognostické biomarkery.

Renal cell carcinoma is a very common tumour with slightly increasing both incidence and prevalence. Our role is in early detection of the disease and selecting the most optimal treatment option and surveillance after therapy. There are several prognostic factors and prognostic models that allow risk stratification. These tools provide information for treatment planning and patient counselling. The review summarizes the most commonly used prognostic factors of renal cell carcinoma with a focus on prognostic biomarkers.

• MeSH
• Carcinoma, Renal Cell * diagnosis   classification   MeSH
• Humans MeSH
• MicroRNAs MeSH
• Biomarkers, Tumor MeSH
• Prognosis MeSH
• Neoplasm Staging MeSH
• Vascular Endothelial Growth Factor A MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

PURPOSE: TACE induces variable systemic effects by producing factors that promote inflammation, oncogenesis, and angiogenesis. Here we compare concentrations of microRNAs (miR-21, miR-210 and miR-34a) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) patients undergoing TACE with degradable (DSM) and nondegradable (DEB) particles and potential use of these biomarker changes for prediction of patient outcomes. MATERIALS AND METHODS: Overall, 52 patients with HCC treated with DSM TACE (24 patients) and DEB TACE (28 patients) were included in this prospective study. Concentrations of studied biomarkers were measured from blood plasma preprocedurally, immediately (< 90 min) postprocedurally, and 24-h after TACE. Levels were compared between DSM and DEB TACE and correlated with treatment response six and 12 months after the first TACE. RESULTS: Both DSM and DEB TACE elevated plasma levels of miR-21, miR-34a, and miR-210 at 24 h post-procedure compared to baseline levels (FC 1.25-4.0). MiR-34a elevation immediately after TACE was significantly associated with nonprogressive disease compared to those with progressive disease at both six months (FCa: p = 0.014) and 12 months (FCa: p = 0.029) post-TACE. No significant biomarker changes were found between the embolization particle groups. However, VEGF levels showed a decrease only in the DSM TACE group (FC24: p = < 0.001). CONCLUSION: Embolization particle type did not significantly impact miRNA or VEGF changes post-TACE. However, miR-34a elevation immediately after the procedure predicts better patient outcome and may prove useful as a biomarkers for the monitoring of clinical outcomes. LEVEL OF EVIDENCE: Level 3 Prospective cohort study.

• MeSH
• Biomarkers blood   MeSH
• Chemoembolization, Therapeutic * methods   MeSH
• Carcinoma, Hepatocellular * therapy   blood   genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• MicroRNAs * blood   MeSH
• Biomarkers, Tumor * blood   MeSH
• Liver Neoplasms * therapy   genetics   blood   MeSH
• Prospective Studies MeSH
• Aged MeSH
• Vascular Endothelial Growth Factor A * blood   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Pulmonary hypertension is a complex and heterogeneous condition with five main subtypes (groups). This review focuses on pulmonary hypertension caused by chronic hypoxia (hypoxic pulmonary hypertension, HPH, group 3). It is based mainly on our own experimental work, especially our collaboration with the group of Professor Herget, whose fifth anniversary of death we commemorate. We have found that oxidation and degradation of the extracellular matrix (ECM) in vitro, in either the presence or the absence of pro-inflammatory cells, activate vascular smooth muscle cell (VSMC) proliferation. Significant changes in the ECM of pulmonary arteries also occurred in vivo in hypoxic rats, namely a decrease in collagen VI and an increase in matrix metalloproteinase 9 (MMP-9) in the tunica media, which may also contribute to the growth activation of VSMCs. The proliferation of VSMCs was also enhanced in their co-culture with macrophages, most likely due to the paracrine production of growth factors in these cells. However, hypoxia itself has a dual effect: on the one hand, it can activate VSMC proliferation and hyperplasia, but on the other hand, it can also induce VSMC hypertrophy and increased expression of contractile markers in these cells. The influence of hypoxia-inducible factors, microRNAs and galectin-3 in the initiation and development of HPH, and the role of cell types other than VSMCs (endothelial cells, adventitial fibroblasts) are also discussed. Keywords: Vasoconstriction, Remodeling, Oxidation, Degradation, Extracellular matrix, Collagen, Proteolytic enzymes, Metalloproteinases, Macrophages, Mast cells, Smooth muscle cells, Endothelial cells, Fibroblasts, Mesenchymal stem cells, Hypoxia-inducible factor, microRNA, Galectins, Hyperplasia, Hypertrophy, Therapy of hypoxic pulmonary hypertension.

• MeSH
• Hypoxia * metabolism   MeSH
• Humans MeSH
• Myocytes, Smooth Muscle * metabolism   pathology   MeSH
• Hypertension, Pulmonary * metabolism   pathology   MeSH
• Cell Proliferation MeSH
• Muscle, Smooth, Vascular * metabolism   pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Východiska: Duktální adenokarcinom pankreatu je vysoce agresivní onemocnění s celkovým 5letým přežitím nepřesahujícím 5 %. V ČR má incidence tohoto nádoru vzestupný trend, dle posledních statistik již patříme celosvětově na první místo ve výskytu této malignity. Pro toto onemocnění je typická pozdní diagnostika vzhledem k asymptomatickému průběhu nemoci v časném stadiu. Cíl: Cílem tohoto článku je podat přehled o nejvýznamnějších faktorech, které dle současných znalostí u adenokarcinomu pankreatu mají prognostický a prediktivní potenciál. Práce popisuje jednak tradiční prognostické faktory, jako je resekabilita nádoru, jeho rozsah a lokalizace, aplikace adjuvantní chemoterapie, mikroskopicky pozitivní resekční okraj, přítomnost metastáz v lymfatických uzlinách, histologický grading, vaskulární a perineurální invaze. Dále uvádí celou řadu různých biologických markerů, které by mohly přispět k včasné detekci nádoru, lepší prognóze a k optimalizaci léčby, např. hENT1 (human equilibrative nucleoside transporter-1), SPARC (secreted protein acidic and rich in cystein), AGR2, Bcl-2, VEGF, Ki-67, COX-2 a další. Zmíněny jsou rovněž genové alterace a význam mikroRNA. Závěr: I přes velké úsilí, které bylo věnováno výzkumu biologických markerů, zatím jediný klinicky akceptovaný a v klinice používaný zůstává nádorový marker CA 19-9. Jeho využití je především u pacientů s již diagnostikovaným adenokarcinomem pankreatu. Velká pozornost je v poslední době zaměřena na další potenciální biomarkery, jejich zavedení do klinické praxe bude ale ještě vyžadovat další výzkum.

Background: Pancreatic ductal adenocarcinoma is a highly aggressive disease with 5-year overall survival not exceeding 5%. In the Czech Republic, the incidence of this tumor has been increasing; according to recent statistics, the Czech Republic is already number one worldwide in the occurrence of this malignancy. Delayed diagnosis due to asymptomatic course of the disease in the early stages is characteristic for this disease. Aim: The objective of this article is to give an overview of the most important factors, which according to current knowledge of pancreatic adenocarcinoma have a prognostic and predictive potential. This work describes both traditional prognostic factors, such as tumor resectability, its extent and localization, application of adjuvant chemotherapy, microscopically positive resection margin, presence of metastases in lymph nodes, histological grade, vascular and perineural invasion. Further, the paper lists a number of different biological markers that could contribute to early detection of cancer, better prognosis and optimization of treatment, for example hENT1 (human equilibrative nucleoside transporter-1), SPARC (secreted protein acidic and rich in cysteine), AGR2, Bcl-2, VEGF, Ki-67, COX-2 and more. Also, genetic mutations and significance of microRNA are discussed. Conclusion: Despite great efforts that have been devoted to the research of biological markers, so far the only clinically accepted and used marker is CA 19-9. Its use is primarily in patients already diagnosed with adenocarcinoma of the pancreas. A lot of attention has recently been focused on other potential biomarkers, their application in clinical practice would however still require further research.

• Keywords
• hENT1, SPARC, BCL2, S100A4, AGR2,
• MeSH
• CA-19-9 Antigen blood   MeSH
• Ki-67 Antigen blood   MeSH
• Cyclooxygenase 2 blood   MeSH
• Carcinoma, Pancreatic Ductal * genetics   blood   MeSH
• Equilibrative Nucleoside Transporter 1 blood   MeSH
• Humans MeSH
• MicroRNAs genetics   MeSH
• Biomarkers, Tumor * genetics   blood   metabolism   MeSH
• Pancreatic Neoplasms * genetics   blood   MeSH
• Osteonectin blood   MeSH
• Prognosis MeSH
• S100 Proteins blood   MeSH
• Proto-Oncogene Proteins c-bcl-2 blood   MeSH
• Proto-Oncogene Proteins p21(ras) blood   MeSH
• Vascular Endothelial Growth Factors blood   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH