Survival and capability of cancer cells to form metastases fundamentally depend on interactions with their microenvironment. Secondary tumors originating from prostate carcinomas affect remodeling of bone tissue and can induce both osteolytic and osteocondensing lesions. However, particular molecular mechanisms responsible for selective homing and activity of cancer cells in bone microenvironment have not been clarified yet. Growth/differentiation factor-15 (GDF-15), a distant member of the TGF-beta protein family, has recently been associated with many human cancers, including prostate. We show that both pure GDF-15 and the GDF-15-containing growth medium of 1,25(OH)(2)-vitamin D(3)-treated prostate adenocarcinoma LNCaP cells suppress formation of mature osteoclasts differentiated from RAW264.7 macrophages and bone-marrow precursors by M-CSF/RANKL in a dose-dependent manner. GDF-15 inhibits expression of c-Fos and activity of NFkappaB by delayed degradation of IkappaB. Moreover, GDF-15 inhibits expression of carbonic anhydrase II and cathepsin K, key osteoclast enzymes, and induces changes in SMAD and p38 signaling. The lack of functional osteoclasts can contribute to accumulation of bone matrix by reduction of bone resorption. These results unveil new role of GDF-15 in modulation of osteoclast differentiation and possibly in therapy of bone metastases.

• MeSH
• buněčná diferenciace účinky léků   MeSH
• buněčné linie MeSH
• časové faktory MeSH
• faktor stimulující kolonie makrofágů farmakologie   MeSH
• femur cytologie   MeSH
• inbrední kmeny myší MeSH
• izoenzymy metabolismus   MeSH
• kalcitriol farmakologie   MeSH
• karboanhydrasa II antagonisté a inhibitory   MeSH
• kathepsin K antagonisté a inhibitory   genetika   MeSH
• kultivační média speciální farmakologie   MeSH
• kyselá fosfatasa metabolismus   MeSH
• lidé MeSH
• ligand RANK farmakologie   MeSH
• makrofágy cytologie   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory prostaty metabolismus   MeSH
• NF-kappa B antagonisté a inhibitory   MeSH
• osteoklasty metabolismus   účinky léků   MeSH
• protoonkogenní proteiny c-fos antagonisté a inhibitory   MeSH
• růstový diferenciační faktor 15 farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

During mouse preimplantation embryo development, the classically described second cell-fate decision involves the specification and segregation, in blastocyst inner cell mass (ICM), of primitive endoderm (PrE) from pluripotent epiblast (EPI). The active role of fibroblast growth factor (Fgf) signalling during PrE differentiation, particularly in the context of Erk1/2 pathway activation, is well described. However, we report that p38 family mitogen-activated protein kinases (namely p38α/Mapk14 and p38β/Mapk11; referred to as p38-Mapk14/11) also participate in PrE formation. Specifically, functional p38-Mapk14/11 are required, during early-blastocyst maturation, to assist uncommitted ICM cells, expressing both EPI and earlier PrE markers, to fully commit to PrE differentiation. Moreover, functional activation of p38-Mapk14/11 is, as reported for Erk1/2, under the control of Fgf-receptor signalling, plus active Tak1 kinase (involved in non-canonical bone morphogenetic protein (Bmp)-receptor-mediated PrE differentiation). However, we demonstrate that the critical window of p38-Mapk14/11 activation precedes the E3.75 timepoint (defined by the initiation of the classical 'salt and pepper' expression pattern of mutually exclusive EPI and PrE markers), whereas appropriate lineage maturation is still achievable when Erk1/2 activity (via Mek1/2 inhibition) is limited to a period after E3.75. We propose that active p38-Mapk14/11 act as enablers, and Erk1/2 as drivers, of PrE differentiation during ICM lineage specification and segregation.

• MeSH
• blastocysta fyziologie   MeSH
• buněčná diferenciace MeSH
• embryonální vývoj * MeSH
• endoderm embryologie   MeSH
• fibroblastové růstové faktory metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 11 metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 14 metabolismus   MeSH
• myši MeSH
• signální transdukce MeSH
• zárodečné listy fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

This study was focused on characterizing the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) into corneal-like cells. Mouse MSCs were isolated from the bone marrow, grown in cell culture for 3 weeks, and purified using a magnetic activated cell sorter. Purified MSCs were cultured with an extract prepared from excised corneas and in the presence or absence of insulin-like growth factor-I (IGF-I). Analysis by quantitative real-time polymerase chain reaction showed that the expression of corneal specific markers, such as cytokeratin 12 (K12), keratocan, and lumican, was already induced after a 3-day cultivation and gradually increased during the 10-day incubation of MSCs with the extract. The presence of IGF-I significantly increased differentiation. Immunofluorescence analysis of differentiated MSCs showed positive results for the K12 protein. The morphology of the differentiated cells and the expression of cell surface markers CD45, CD11b, CD73, CD44, and CD105 were comparable in the control and differentiated MSCs. Proliferative activity was even higher in differentiated cells than in untreated MSCs. Both untreated and differentiated MSCs inhibited the production of interleukin-2 and interferon-γ in spleen cells stimulated with Concanavalin A. The results thus show that MSCs cultured in the presence of corneal extract and IGF-I efficiently differentiate into corneal-like cells. The differentiated cells possess characteristics of corneal epithelial cells and keratocytes, while at the same time maintaining MSC properties.

• MeSH
• biologické markery metabolismus   MeSH
• buněčná diferenciace účinky léků   genetika   MeSH
• imunosupresivní léčba MeSH
• insulinu podobný růstový faktor I farmakologie   MeSH
• mezenchymální kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• myši inbrední BALB C MeSH
• proliferace buněk účinky léků   genetika   MeSH
• regulace genové exprese účinky léků   MeSH
• rohovka cytologie   MeSH
• tvar buňky účinky léků   genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

AIM: Obstructive uropathies (OU) in childhood constitute one of the major causes of chronic renal insufficiency. Transforming growth factor-β1 (TGF-β1) is considered to be the major fibrogenic growth factor. The aim of the present study was to investigate urinary TGF-β1 levels in children with obstructive and non-obstructive uropathies (NOU). METHODS: This study involved 19 children with OU, 11 children with non-obstructive hydronephrosis and 21 healthy children. Urinary TGF-β1, proteinuria, microalbuminuria and urinary α1-microglobulin were measured, and renal function was assessed. The results were statistically analyzed. RESULTS: Mean urinary TGF-β1 concentrations in patients with OU were significantly higher than those with NOU (4.14 ± 0.67 creatinine vs 1.80 ± 0.24 pg/mmol creatinine, P < 0.05) and healthy controls (1.66 ± 0.28 pg/mmol creatinine, P < 0.05). Positive correlations of urinary TGF-β1 concentrations with proteinuria (r = 0.87, P < 0.0001) and urinary α1-microglobulin (r = 0.82, P = 0.0002) were found in patients with OU. CONCLUSION: Children with OU have higher urinary TGF-β1 than children with NOU. Urinary TGF-β1 may be a useful non-invasive tool for the differential diagnosis between OU and NOU in children. A positive correlation of TGF-β1 with markers of renal tissue damage in patients with OU was found.

• MeSH
• albuminurie etiologie   moč   MeSH
• alfa-globuliny moč   MeSH
• analýza rozptylu MeSH
• biologické markery moč   MeSH
• chronická renální insuficience diagnóza   etiologie   patofyziologie   moč   MeSH
• hodnoty glomerulární filtrace MeSH
• hydronefróza etiologie   moč   MeSH
• kojenec MeSH
• kreatinin moč   MeSH
• ledviny patofyziologie   MeSH
• lidé MeSH
• obstrukce močové trubice komplikace   diagnóza   patofyziologie   moč   MeSH
• obstrukce močovodu komplikace   diagnóza   patofyziologie   moč   MeSH
• prediktivní hodnota testů MeSH
• předškolní dítě MeSH
• průřezové studie MeSH
• studie případů a kontrol MeSH
• transformující růstový faktor beta1 moč   MeSH
• upregulace MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

To evaluate the oncologic prognostic value of fibroblast growth factor receptor (FGFR) and to assess the safety and efficacy of its inhibitors in patients with urothelial bladder carcinoma. A literature search using PubMed, Scopus, and Cochrane Library was conducted on June 2020 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The pooled recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS) were calculated using a fixed or random effects model in patients with nonmuscle invasive bladder cancer (NMIBC). Overall, 62 studies comprising 9,229 patients were eligible and included in this systematic review and meta-analysis. Both FGFR3 mutation and protein overexpression were significantly associated with RFS, PFS, CSS, and overall survival. FGFR3 mutation was associated with worse RFS and better PFS (pooled hazard ratio: 1.30; 95% confidence interval: 1.08-1.57, and pooled hazard ratio: 0.62; 95% confidence interval: 0.42-0.92, respectively) in patients with NMIBC. In 11 studies reporting on the response to FGFR inhibitors, complete response rates, disease control rates, and overall response rate of 0% to 8%, 59.3% to 64.2%, and 40% were reported for dovitinib, infigratinib, and erdafitinib, respectively. Based on this study, FGFR3 mutation is a statistically significant prognostic factor for RFS in NMIBC. FGFR inhibitors have measurable benefit in patients with advanced and metastatic urothelial carcinoma. However, the results of ongoing RCTs and future well-designed studies are awaited to capture the differential biologic and clinical behavior of tumors harboring FGFR while helping to identify those who are most likely to benefit from FGFR inhibitors.

• MeSH
• karcinom z přechodných buněk farmakoterapie   MeSH
• lidé MeSH
• nádory močového měchýře farmakoterapie   MeSH
• prognóza MeSH
• receptory fibroblastových růstových faktorů antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

• MeSH
• dospělí MeSH
• epidermální růstový faktor analýza   krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory štítné žlázy diagnóza   MeSH
• radioizotopy jodu terapeutické užití   MeSH
• senioři MeSH
• thyreoglobulin krev   MeSH
• thyroxin krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

• MeSH
• cvičení fyziologie   MeSH
• růst fyziologie   MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• rehabilitační a fyzikální medicína
• fyziologie
• rehabilitační a fyzikální medicína

We examined the effect of epidermal growth factor (EGF) treatment in mice that received bone marrow transplantation (BMT) after 11 Gy whole-body irradiation. C57Bl/6 mice were divided into three treatment groups: 0 Gy; 11 Gy ((60)Co, single dose, 0.51 Gy/min) with BMT (5 × 10(6) bone marrow cells isolated from green fluorescent protein syngeneic mice, 3-4 h postirradiation); and 11 Gy with BMT and EGF (2 mg/kg applied subcutaneously 1, 3 and 5 days postirradiation). Survival data were collected. Bone marrow, peripheral blood count and cytokines, gastrointestine and liver parameters and migration of green fluorescent protein-positive cells were evaluated at 63 days postirradiation. Epidermal growth factor increased survival of irradiated animals that received BMT from 10.7 to 85.7% at 180 days postirradiation. In the BMT group, we found changes in differential bone marrow and blood count, plasma cytokine levels, gastrointestinal tissues and liver at 63 days postirradiation. These alterations were completely or in some parameters at least partially restored by epidermal growth factor. These findings indicate that epidermal growth factor, administered 1, 3 and 5 days postirradiation in combination with bone marrow transplantation, significantly improves long-term prognosis.

• MeSH
• apoptóza účinky léků   účinky záření   MeSH
• bezpečnost MeSH
• časové faktory MeSH
• celotělové ozáření škodlivé účinky   MeSH
• cytokiny krev   MeSH
• epidermální růstové faktory farmakologie   MeSH
• kostní dřeň účinky léků   imunologie   účinky záření   MeSH
• mitóza účinky léků   účinky záření   MeSH
• myši MeSH
• počet buněk MeSH
• radiační poranění krev   farmakoterapie   patologie   terapie   MeSH
• slezina účinky léků   patologie   účinky záření   MeSH
• střeva účinky léků   patologie   účinky záření   MeSH
• transplantace kostní dřeně * MeSH
• velikost orgánu účinky léků   účinky záření   MeSH
• vztah dávky záření a odpovědi MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• chronická lymfatická leukemie farmakoterapie   krev   MeSH
• cyklofosfamid aplikace a dávkování   farmakologie   MeSH
• fibroblastový růstový faktor 2 krev   MeSH
• finanční podpora výzkumu jako téma MeSH
• inhibitory angiogeneze MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   farmakologie   MeSH
• patologická angiogeneze farmakoterapie   MeSH
• prediktivní hodnota testů MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• vaskulární endoteliální růstový faktor B krev   MeSH
• vidarabin analogy a deriváty   aplikace a dávkování   farmakologie   MeSH
• Check Tag
• lidé MeSH

• MeSH
• buněčná diferenciace MeSH
• gestační stáří MeSH
• somatomediny MeSH
• vývoj plodu MeSH