BACKGROUND/AIM: Although it has been accepted that the tandem repeat galectin-8 (Gal-8) is linked to angiogenesis, the underlying mechanisms in endothelial cells has remained poorly understood. In this study we aimed to investigate the effect of Gal-8 on selected biological processes linked to angiogenesis in in vitro and in vivo models. MATERIALS AND METHODS: In detail, we assessed how exogenously added human recombinant Gal-8 (with or without vascular endothelial growth factor - VEGF) affects selected steps involved in vessel formation in human umbilical vein endothelial cells (HUVECs) as well as using the chick chorioallantoic membrane (CAM) assay. Gene expression profiling of HUVECs was performed to extend the scope of our investigation. RESULTS: Our findings demonstrate that Gal-8 in combination with VEGF enhanced cell proliferation and migration, two cellular events linked to angiogenesis. However, Gal-8 alone did not exhibit any significant effects on cell proliferation or on cell migration. The molecular analysis revealed that Gal-8 in the presence of VEGF influenced cytokine-cytokine receptor interactions, HIF-1 and PI3K/AKT signaling pathways. Gal-8 alone also targeted cytokine-cytokine receptor interactions, but with a different expression profile as well as a modulated focal adhesion and TNF signaling. CONCLUSION: Gal-8 promotes a pro-angiogenic phenotype possibly in a synergistic manner with VEGF.

• MeSH
• chorioalantoická membrána krevní zásobení   účinky léků   metabolismus   MeSH
• endoteliální buňky pupečníkové žíly (lidské) cytologie   účinky léků   metabolismus   MeSH
• fyziologická neovaskularizace účinky léků   MeSH
• galektiny metabolismus   farmakologie   MeSH
• kuřecí embryo MeSH
• lidé MeSH
• pohyb buněk účinky léků   MeSH
• stanovení celkové genové exprese MeSH
• techniky in vitro MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive scar formation. In the present review paper, we define key signaling molecules (growth factors, cytokines, chemokines, and galectins) involved in the formation of the tumor microenvironment that decrease overall survival and increase drug resistance in cancer suffering patients. Additional attention will also be given to show whether targeted modulation of these regulators promote tissue regeneration and wound management. Whole-genome transcriptome profiling, in vitro and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X-C motif) ligand 1, galectin-1, and selected proteins of the extracellular matrix (e.g., fibronectin) do have similar regulation during wound healing and tumor growth. Published data demonstrate remarkable similarities between the tumor and wound microenvironments. Therefore, tailor made manipulation of cancer stroma can have important therapeutic consequences. Moreover, better understanding of cancer cell-stroma interaction can help to improve wound healing by supporting granulation tissue formation and process of reepithelization of extensive and chronic wounds as well as prevention of hypertrophic scars and formation of keloids.

• MeSH
• buněčné mikroprostředí MeSH
• cytokiny metabolismus   MeSH
• galektiny metabolismus   MeSH
• hojení ran MeSH
• imunitní systém cytologie   imunologie   metabolismus   MeSH
• keloid metabolismus   patologie   MeSH
• lidé MeSH
• mezibuněčné signální peptidy a proteiny metabolismus   MeSH
• nádorové kmenové buňky metabolismus   patologie   MeSH
• nádorové mikroprostředí * MeSH
• nádory imunologie   metabolismus   patologie   MeSH
• rány a poranění imunologie   metabolismus   patologie   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The formation of new blood vessels plays a crucial for the development and progression of pathophysiological changes associated with a variety of disorders, including carcinogenesis. Angiogenesis inhibitors (anti-angiogenics) are an important part of treatment for some types of cancer. Some natural products isolated from marine invertebrates have revealed antiangiogenic activities, which are diverse in structure and mechanisms of action. Many preclinical studies have generated new models for further modification and optimization of anti-angiogenic substances, and new information for mechanistic studies and new anti-cancer drug candidates for clinical practice. Moreover, in the last decade it has become apparent that galectins are important regulators of tumor angiogenesis, as well as microRNA. MicroRNAs have been validated to modulate endothelial cell migration or endothelial tube organization. In the present review we summarize the current knowledge regarding the role of marine-derived natural products, galectins and microRNAs in tumor angiogenesis.

• MeSH
• biologické přípravky farmakologie   MeSH
• galektiny účinky léků   MeSH
• inhibitory angiogeneze farmakologie   MeSH
• látky modulující angiogenezi farmakologie   MeSH
• lidé MeSH
• mikro RNA účinky léků   MeSH
• mořské toxiny farmakologie   MeSH
• nádory farmakoterapie   MeSH
• protinádorové látky farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Estrogen deprivation is considered responsible for many age-related processes, including poor wound healing. Guided by previous observations that estradiol accelerates re‑epithelialization through estrogen receptor (ER)‑β, in the present study, we examined whether selective ER agonists [4,4',4''-(4-propyl [1H] pyrazole-1,3,5-triyl)‑trisphenol (PPT), ER‑α agonist; 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), ER‑β agonist] affect the expression of basic proliferation and differentiation markers (Ki‑67, keratin‑10, ‑14 and ‑19, galectin‑1 and Sox‑2) of keratinocytes using HaCaT cells. In parallel, ovariectomized rats were treated daily with an ER modulator, and wound tissue was removed 21 days after wounding and routinely processed for basic histological analysis. Our results revealed that the HaCaT keratinocytes expressed both ER‑α and ‑β, and thus are well-suited for studying the effects of ER agonists on epidermal regeneration. The activation of ER‑α produced a protein expression pattern similar to that observed in the control culture, with a moderate expression of Ki‑67 being observed. However, the activation of ER‑β led to an increase in cell proliferation and keratin‑19 expression, as well as a decrease in galectin‑1 expression. Fittingly, in rat wounds treated with the ER‑β agonist (DPN), epidermal regeneration was accelerated. In the present study, we provide information on the mechanisms through which estrogens affect the expression patterns of selected markers, thus modulating keratinocyte proliferation and differentiation; in addition, we demonstrate that the pharmacological activation of ER-α and -β has a direct impact on wound healing.

• MeSH
• alfa receptor estrogenů agonisté   metabolismus   MeSH
• beta receptor estrogenů agonisté   metabolismus   MeSH
• buněčná diferenciace účinky léků   MeSH
• buněčné linie MeSH
• fenoly farmakologie   MeSH
• hojení ran účinky léků   MeSH
• keratinocyty cytologie   účinky léků   metabolismus   patologie   MeSH
• kůže účinky léků   metabolismus   patologie   MeSH
• lidé MeSH
• nitrily farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• pyrazoly farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Reactive oxygen species (ROS) are highly considered in the ethiopathogenesis of different pathological conditions because they may cause significant damage to cells and tissues. In this paper, we focused on potential antioxidant properties of two medical plants such as the Agrimonia eupatoria L. and Cynara cardunculus L. Both plants have previously been studied for their pharmacological activities, especially as hepatoprotective and hypoglycemic activities. It has been suggested, that their effects are related to the antioxidant properties of polyphenols, which are dominant compounds of the plants' extracts. In the present study HPLC-MS analysis of water infusion was performed allowing the identification of several phenolic constituents. Furthermore, antioxidant effects of the two extracts were compared showing higher effects for agrimony extract compared to artichoke. Thus, agrimony was selected for the in vivo study using the skin flap viability model. In conclusion, our results provide evidence that the A. eupatoria extract may be a valuable source of polyphenols to be studied for the future development of supplements useful in the prevention of diseases linked to oxidative stress.

• MeSH
• Agrimonia chemie   MeSH
• antioxidancia chemie   farmakologie   MeSH
• buněčné linie účinky léků   metabolismus   MeSH
• Cynara chemie   MeSH
• fenoly chemie   farmakologie   MeSH
• katalasa metabolismus   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• oxidační stres účinky léků   MeSH
• poškození DNA účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rostlinné extrakty chemie   farmakologie   MeSH
• superoxiddismutasa metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G2/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms.

• MeSH
• genistein chemie   farmakologie   terapeutické užití   MeSH
• Glycine max chemie   MeSH
• inhibitory angiogeneze chemie   farmakologie   terapeutické užití   MeSH
• isoflavony chemie   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• nádory prsu krevní zásobení   farmakoterapie   metabolismus   patologie   MeSH
• patologická angiogeneze farmakoterapie   metabolismus   patologie   MeSH
• prsy krevní zásobení   účinky léků   metabolismus   patologie   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Galektíny patria medzi endogénne lektíny – bielkoviny špecificky rozpoznávajúce cukorné motívy. Galektíny hrajú významné úlohy v procesoch bunkovej proliferácie, diferenciácie, migrácie a tvorby medzibunkovej hmoty. Navyše sú schopné prenášať bunkové signály a podieľať sa na medzibunkových interakciách. Podobne bolo dokázané, že galektíny zohrávajú dôležitú úlohu pri tvorbe mikroprostredia nádoru a/alebo hojacej sa rany. Táto práca poskytuje prehľad experimentálnych a klinických štúdií zaoberajúcich sa biologickými úlohami galektínov v tkanivovej reparácii a jej paralele k raste nádoru.

Galectins are representatives of endogenous lectins – molecules specifically recognizing distinct sugar motifs. They play an important role in the processes of cell proliferation, differentiation, migration and extracellular matrix formation. Furthermore, galectins are able to transfer cellular signals and to participate in intercellular interaction. It has been proven that galectins play an important role in the formation of tumor and/or wound healing microenvironment. This review contains an overview of experimental and clinical studies dealing with biological roles of galectins in tissue repair and in its parallel – the tumor growth.

• MeSH
• exprese genu fyziologie   MeSH
• galektin 1 fyziologie   metabolismus   MeSH
• galektin 3 fyziologie   metabolismus   MeSH
• galektiny * fyziologie   klasifikace   metabolismus   MeSH
• hojení ran fyziologie   MeSH
• lidé MeSH
• modely u zvířat MeSH
• nádory patofyziologie   MeSH
• tkáně fyziologie   metabolismus   MeSH
• výzkum MeSH
• zánět patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND/AIM: Stromal cells in the tumor microenvironment are primarily considered as sources of promalignant factors. The objective of our study was to define the effect of extracellular matrix (ECM) produced by normal dermal or cancer-associated fibroblasts exposed to adhesion/growth-regulatory lectin galectin-1 on human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: Fibroblasts were cultured for 10 days with lectin, followed by removing cellular constituents after an osmotic shock. Freshly-isolated HUVECs were placed on the ECM. In parallel, HUVECs were seeded on untreated and gelatin-coated surfaces as controls. A positive control for growth of HUVECs culture using medium supplemented with vascular endothelial growth factor completed the test panel. Cells were kept in contact to the substratum for two days and then processed for immunocytochemistry. RESULTS: HUVECs seeded on fibroblast-generated ECM presented a comparatively high degree of proliferation. Furthermore, contact to substratum produced by tumor-associated fibroblasts led to generation of a meshwork especially rich in fibronectin. CONCLUSION: Galectin-1 is apparently capable to trigger ECM production favorable for growth of HUVECs, prompting further work on characterizing structural features of the ECM and in situ correlation of lectin presence, ECM constitution and neoangiogenesis.

• MeSH
• endoteliální buňky pupečníkové žíly (lidské) fyziologie   MeSH
• extracelulární matrix metabolismus   MeSH
• fibroblasty fyziologie   MeSH
• galektin 1 farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• nádorové mikroprostředí * MeSH
• proliferace buněk účinky léků   MeSH
• vaskulární endoteliální růstový faktor A farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

Non-small cell lung cancer has one of the highest mortality rates among cancer-suffering patients. It is well known that the unwanted psychotropic effects of cannabinoids (CBs) are mediated via the CB1 receptor (R), and selective targeting of the CB2R would thus avoid side effects in cancer treatment. Therefore, the aim of our study was to evaluate the effect of selective CB2R agonist, JWH-133, on A549 cells (non-small lung cancer) and human umbilical vein endothelial cells (HUVECs). Cytotoxicity assay and DNA fragmentation assay were employed to evaluate the influence of JWH-133 (3-(1,1-dimethylbutyl)- 1-deoxy-Δ8-tetrahydrocannabinol) on investigated cancer cells. In addition, migration assay and gelatinase zymography were performed in HUVECs to asses JWH-133 anti-angiogenic activity. Our study showed that JWH-133 exerted cytotoxic effect only at the highest concentration used (10-4 mol/l), while inhibition of colony formation was also detected at the non-toxic concentrations (10-5–10-8 mol/l). JWH-133 was also found to be able to induce weak DNA fragmentation in A549 cells. Furthermore, JWH-133 at non-toxic concentrations inhibited some steps in the process of angiogenesis. It significantly inhibited endothelial cell migration after 17 h of incubation at concentrations of 10-4–10-6 mol/l. In addition, JWH-133 inhibited MMP-2 secretion as assessed by gelatinase zymography. The present study demonstrates the in vitro anti-proliferative and anti-angiogenic potential of CB2R agonist, JWH-133, in nonsmall lung cancer cells and HUVECs. Our results generate a rationale for further in vivo efficacy studies with this compound in preclinical cancer models.

• MeSH
• buněčné kultury MeSH
• časové faktory MeSH
• endoteliální buňky pupečníkové žíly (lidské) účinky léků   MeSH
• fragmentace DNA MeSH
• hojení ran MeSH
• kanabinoidy farmakologie   metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory plic farmakoterapie   MeSH
• nemalobuněčný karcinom plic farmakoterapie   MeSH
• patologická angiogeneze MeSH
• pohyb buněk MeSH
• proliferace buněk MeSH
• receptor kanabinoidní CB2 agonisté   metabolismus   MeSH
• viabilita buněk MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH