Giant cell fibroblastoma is a rare locally aggressive tumor of subcutaneous mesenchymal tissue, occurring mostly on the trunk in young individuals with maximal incidence in the first decade of life. Local recurrences of giant cell fibroblastoma are common if marginally excised, however, distant metastases do not occur. Giant cell fibroblastoma was labelled as a juvenile variant of dermatofibrosarcoma protuberans (DFSP) due to quite frequent combination of both lesions, morphological similarities, identical immunoprofile, and shared gene fusion t(17;22) COL1A1-PDGFB. In this paper, we report a case of a young man with a slowly growing subcutaneous tumor in the groin. The tumor was excised and histological examination identified a mesenchymal tumor with variable cellularity, presence of multinucleated giant cells and pleomorphic spindle cells, which lined pseudovascular or angiectoid spaces. The CD34 immunohistochemistry showed strong positivity in all of these cells, whereas ERG was positive only in endothelial cells in true vessels. These findings led to a suspicion on giant cell fibroblastoma. Because of its borderline malignant behaviour and positive surgical margins, the lesion was subsequently reexcised. The molecular analysis identified the transcription product of gene fusion COL1A1-PDGFB and thus, final diagnosis was confirmed. The article includes review of the literature and brief historical overview of giant cell fibroblastoma concept as an unique entity.
- Klíčová slova
- dermatofibrosarcoma protuberans, fibroblastoma, giant cell, juvenile,
- MeSH
- dermatofibrosarkom * genetika patologie MeSH
- endoteliální buňky patologie MeSH
- lidé MeSH
- nádory kůže * patologie MeSH
- obrovské buňky patologie MeSH
- protoonkogenní proteiny c-sis genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- přehledy MeSH
- Názvy látek
- protoonkogenní proteiny c-sis MeSH
The increased proliferation and migration of airway smooth muscle cells (ASMCs) is a key process in the formation of airway remodeling in asthma. In this study, we focused on the expression of mircoRNA-18a (miR-18a) in airway remodeling in bronchial asthma and its related mechanisms. ASMCs are induced by platelet-derived growth factor BB (PDGF-BB) for in vitro airway remodeling. The expression of miR-18a in sputum of asthmatic patients and healthy volunteers was detected by qRT-PCR. The expression of miR-18a was over-expressed or interfered with in PDGF-BB-treated ASMCs. Cell proliferation, apoptosis and migration were detected by MTT, flow cytometry and Transwell, respectively; the expression of contractile phenotype marker proteins (SM-22?, ?-SM-actin, calponin) and key molecules of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway (PI3K, p-PI3K, AKT and p-AKT) in ASMCs were detected by Western blot. The expression of miR-18a was down-regulated in the sputum and PDGF-BB-treated ASMCs of asthma patients. PDGF-BB could promote the proliferation and migration of ASMCs and inhibit their apoptosis; it could also promote the phenotypic transformation of ASMCs and activate the PI3K/AKT pathway. MiR-18a could inhibit the proliferation, migration ability and phenotypic transformation of ASMCs induced by PDGF-BB to a certain extent and alleviate the effect of PDGF-BB in supressing apoptosis, while miR-18a could inhibit the activation of the PI3K/AKT pathway. MiR-18a inhibits PDGF-BB-induced proliferation, migration and phenotypic conversion of ASMCs by inhibiting the PI3K/AKT pathway, thus attenuating airway remodeling in asthma.
- MeSH
- becaplermin metabolismus MeSH
- bronchiální astma metabolismus MeSH
- dospělí MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA metabolismus MeSH
- mladiství MeSH
- mladý dospělý MeSH
- myocyty hladké svaloviny fyziologie MeSH
- protoonkogenní proteiny c-akt metabolismus MeSH
- remodelace dýchacích cest * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- signální transdukce MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- becaplermin MeSH
- mikro RNA MeSH
- MIRN18A microRNA, human MeSH Prohlížeč
- protoonkogenní proteiny c-akt MeSH
Platelet concentrates and especially their further product platelet lysate, are widely used as a replacement for cell culturing. Platelets contain a broad spectrum of growth factors and bioactive molecules that affect cellular fate. However, the cellular response to individual components of the human platelet concentrate is still unclear. The aim of this study was to observe cellular behavior according to the individual components of platelet concentrates. The bioactive molecule content was determined. The cells were supplemented with a medium containing 8% (v/v) of platelet proteins in plasma, pure platelet proteins in deionized water, and pure plasma. The results showed a higher concentration of fibrinogen, albumin, insulin growth factor I (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF), in the groups containing plasma. On the other hand, chemokine RANTES and platelet-derived growth factor bb (PDGF-bb), were higher in the groups containing platelet proteins. The groups containing both plasma and plasma proteins showed the most pronounced proliferation and viability of mesenchymal stem cells and fibroblasts. The platelet proteins alone were not sufficient to provide optimal cell growth and viability. A synergic effect of platelet proteins and plasma was observed. The data indicated the importance of plasma in platelet lysate for cell growth.
- Klíčová slova
- fibroblasts, mesenchymal stem cells, plasma, platelets,
- MeSH
- albuminy MeSH
- becaplermin metabolismus MeSH
- buněčné kultury metody MeSH
- chemokiny metabolismus MeSH
- fibrinogen metabolismus MeSH
- fibroblastový růstový faktor 7 MeSH
- fibroblasty metabolismus MeSH
- hepatocytární růstový faktor MeSH
- insulinu podobný růstový faktor I MeSH
- krevní plazma chemie MeSH
- kultivační média chemie MeSH
- lidé MeSH
- mezenchymální kmenové buňky metabolismus MeSH
- plazma bohatá na destičky metabolismus MeSH
- proliferace buněk účinky léků MeSH
- protoonkogenní proteiny c-sis metabolismus MeSH
- trombocyty chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- albuminy MeSH
- becaplermin MeSH
- chemokiny MeSH
- fibrinogen MeSH
- fibroblastový růstový faktor 7 MeSH
- hepatocytární růstový faktor MeSH
- insulinu podobný růstový faktor I MeSH
- kultivační média MeSH
- protoonkogenní proteiny c-sis MeSH
Epidermal growth factor receptor (EGFR) gene amplification and the overexpression of EGFR are described as common features of glioblastoma multiforme (GBM). Nevertheless, we previously reported the loss of EGFR gene copy in a GBM specimen from a patient with an unusually favorable course of the disease, and the HGG-02 cell line with this aberration was successfully derived from this tumor. Here, we present a detailed analysis of changes in gene expression and cell signaling in the HGG-02 cell line; the GM7 reference cell line with a standard EGFR gene copy number derived from a very aggressive GBM was used as a control. We confirmed the downregulation of EGFR expression and signaling in HGG-02 cells using different methods (RTK analysis, gene profiling and RT-PCR). Other changes that may have contributed to the non-aggressive phenotype of the primary tumor were identified, including the downregulated phosphorylation of the Axl and Trk receptors, as well as increased activity of JNK and p38 kinases. Notably, differences in PDGF signaling were detected in both of these cell lines; HGG-02 cells preferentially expressed and signaled through PDGFRα, and PDGFRβ was strongly overexpressed and phosphorylated in the GM7 reference cell line. Using expression profiling of cancer-related genes, we revealed the specific profile of HGG-02 cells that included upregulated tumor-suppressors as well as downregulated genes associated with the extracellular matrix. This study represents the first comprehensive analysis of gene expression and cell signaling in glioblastoma cells with lower EGFR gene dosage. As indicated by our results, the TAM receptors, Trk receptors and PDGFRs need to be investigated further since their regulation appears to be important for glioblastoma biological features as well as the clinical course of the disease.
- MeSH
- delece genu * MeSH
- destičkový růstový faktor metabolismus MeSH
- erbB receptory genetika MeSH
- fosforylace MeSH
- genová dávka * MeSH
- glioblastom genetika MeSH
- JNK mitogenem aktivované proteinkinasy biosyntéza MeSH
- lidé MeSH
- mitogenem aktivované proteinkinasy p38 biosyntéza MeSH
- nádorové buněčné linie MeSH
- nádory mozku genetika MeSH
- protoonkogenní proteiny c-sis metabolismus MeSH
- protoonkogenní proteiny metabolismus MeSH
- receptor trkA metabolismus MeSH
- signální transdukce genetika MeSH
- stanovení celkové genové exprese MeSH
- tyrosinkinasové receptory metabolismus MeSH
- tyrozinkinasový receptor AXL MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- AXL protein, human MeSH Prohlížeč
- destičkový růstový faktor MeSH
- epidermal growth factor receptor VIII MeSH Prohlížeč
- erbB receptory MeSH
- JNK mitogenem aktivované proteinkinasy MeSH
- mitogenem aktivované proteinkinasy p38 MeSH
- platelet-derived growth factor A MeSH Prohlížeč
- protoonkogenní proteiny c-sis MeSH
- protoonkogenní proteiny MeSH
- receptor trkA MeSH
- tyrosinkinasové receptory MeSH
- tyrozinkinasový receptor AXL MeSH
High-molecular-weight DNAs from 5 bladder carcinomas were used in transfection of mouse NIH3T3 cells. The manifestation of heterologous oncogene(s) expression in NIH3T3 cells was morphological transformation very often accompanied by changes in growth characteristics of recipient cells. In DNA samples from secondary NIH3T3 transformants human c-Ha-ras and c-sis sequences were identified. In some secondary transformants these sequences were expressed. On the basis of change of the growth characteristics of some secondary transformants we could expect the integration and expression of another human gene(s) for growth factor or growth factor receptor or even activation of mouse genes. We did not manage to identify any Alu sequences in some secondary transformants carrying human c-Ha-ras sequences. On the other hand, it has not been revealed yet that BamHI DNA fragments carrying c-Ha-ras gene contained any Alu sequence. So, the identification of Alu sequences does not have to be the first step in investigation of DNA samples from NIH3T3 transformants.
- MeSH
- buněčné linie MeSH
- destičkový růstový faktor genetika MeSH
- DNA nádorová genetika izolace a purifikace MeSH
- geny ras * MeSH
- hybridizace nukleových kyselin MeSH
- lidé MeSH
- myši MeSH
- nádorová transformace buněk * MeSH
- nádory močového měchýře genetika MeSH
- protoonkogenní proteiny c-sis MeSH
- protoonkogenní proteiny genetika MeSH
- protoonkogeny * MeSH
- Southernův blotting MeSH
- transfekce * MeSH
- tyrosinkinasy genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- destičkový růstový faktor MeSH
- DNA nádorová MeSH
- protoonkogenní proteiny c-sis MeSH
- protoonkogenní proteiny MeSH
- tyrosinkinasy MeSH