• Publikační typ
• abstrakt z konference MeSH

The stem cell marker nestin (NES) is found in dividing cells of developing and regenerating tissues. Upon terminal differentiation, NES expression is diminished but may be re-expressed following injury or in cancer. Surprisingly, we recently confirmed NES as a tumour-specific marker for mature CD138(+) 38(+) plasma cells (PC) in multiple myeloma (MM). The present study analysed NES expression throughout the spectrum of MM developmental stages, starting with individuals with no haematological malignancy, through monoclonal gammopathy of undetermined significance (MGUS) and MM to plasma cell leukaemia (PCL) and MM cell lines. NES was analysed in bone marrow PC of 163 MM, four PCL and nine MGUS patients, 10 individuals with no haematological malignancy and 6 myeloma cell lines (OPM-2, RPMI-8226, MOLP-8, U-266, EJM, NCI-H929) by flow cytometry and/or real-time polymerase chain reaction or immunochemistry. We observed a tendency of increased NES expression in parallel with disease progression. NES was evaluated as a reliable marker for accurate discrimination between MM patients and the control group. High NES levels were strongly associated with the presence of 1q21 gain. For the first time, NES was demonstrated to predict worse response to conventional therapy/novel agents. These results suggest that NES might become a useful clinical parameter with an important role in MM pathogenesis.

• MeSH
• dospělí MeSH
• imunofenotypizace MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• mnohočetný myelom diagnóza   imunologie   metabolismus   patologie   MeSH
• monoklonální gamapatie nejasného významu metabolismus   MeSH
• nádorové biomarkery biosyntéza   genetika   MeSH
• nádorové buňky kultivované MeSH
• nádorové proteiny biosyntéza   genetika   MeSH
• nestin biosyntéza   genetika   MeSH
• plazmocelulární leukemie metabolismus   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• recidiva MeSH
• RNA nádorová genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Nestin is considered to be a characteristic marker of multipotent proliferative precursors found in some embryonic and fetal tissues. Its expression might be a suitable diagnostic and prognostic indicator of malignancy and a potential marker of cancer stem cells in solid tumors. Unexpectedly, nestin protein was detected in mature CD138(+)CD38(+) plasma cells of multiple myeloma patients and statistical analysis confirmed significant differences between myeloma patients and control group without hematological malignancy. Our results represent the first evidence of nestin expression in multiple myeloma. Further studies are required to elucidate the role of this protein in multiple myeloma.

• MeSH
• dospělí MeSH
• imunofenotypizace MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorové kmenové buňky metabolismus   MeSH
• pilotní projekty MeSH
• plazmatické buňky metabolismus   MeSH
• prognóza MeSH
• proteiny intermediálních filament metabolismus   MeSH
• proteiny nervové tkáně metabolismus   MeSH
• průtoková cytometrie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• western blotting MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

The existence of an adult PSC that may be used in the treatment of diabetes is still a matter of scientific debate as conclusive evidence of such a stem cell in the adult pancreas has not yet been presented. The main reason why putative PSC has not yet been identified is the lack of specific markers that may be used to isolate and purify them. In order to increase the list of potential PSC markers we have focused on the human pancreatic cells that express cell surface receptor CXCR4, a marker of stem cells derived from different adult tissues. Here we report that CXCR4-positive pancreatic cells express markers of pancreatic endocrine progenitors (neurogenin-3, nestin) and markers of pluripotent stem cells (Oct-4, Nanog, ABCG2, CD133, CD117). Upon in vitro differentiation, these cells form ILCC and produce key islet hormones including insulin. Based on our results, we assume that CXCR4 marks pancreatic endocrine progenitors and in combination with other cell surface markers may be used in the attempt to identify and isolate PSC.

• MeSH
• buněčná diferenciace MeSH
• C-peptid metabolismus   MeSH
• dospělí MeSH
• fluorescenční protilátková technika MeSH
• glukagon metabolismus   MeSH
• inzulin metabolismus   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• pankreas * cytologie   MeSH
• proteiny intermediálních filament metabolismus   MeSH
• proteiny nervové tkáně metabolismus   MeSH
• receptor leukemického inhibičního faktoru - alfa-podjednotka metabolismus   MeSH
• receptory CXCR4 genetika   metabolismus   MeSH
• regulace genové exprese MeSH
• senioři MeSH
• separace buněk * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• práce podpořená grantem MeSH

Plasma cell leukaemia (PCL) is a rare and very aggressive plasma cell disorder. Preventing a dismal outcome of PCL requires early diagnosis with appropriate analytical tools. Therefore, the investigation of 33 patients with primary and secondary PCL was done when the quantity of circulating plasma cells (PCs) using flow cytometry (FC) and morphology assessment was evaluated. The phenotypic profile of the PCs was also analysed to determine if there is an association with clinical outcomes and to evaluate the prognostic value of analysed markers. Our results revealed that FC is an excellent method for identifying circulating PCs as a significantly higher number was identified by FC than by morphology (26·7% vs. 13·5%, P = 0·02). None of secondary PCL cases expressed CD19 or CD20. A low level of expression with similar positivity of CD27, CD28, CD81 and CD117 was found in both PCL groups. A decrease of CD44 expression was detected only in secondary PCL. Expression of CD56 was present in more than half of PCL cases as well as cytoplasmic nestin. A decreased level of platelets, Eastern Cooperative Oncology Group score of 2-3 and lack of CD20+ PC were associated with a higher risk of death. FC could be incorporated in PCL diagnostics not only to determine the number of circulating PCs, but also to assess their phenotype profile and this information should be useful in patients' diagnosis and possible prognosis.

• MeSH
• antigeny nádorové analýza   MeSH
• buňky kostní dřeně chemie   MeSH
• časná detekce nádoru MeSH
• CD antigeny analýza   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• falešně negativní reakce MeSH
• imunofenotypizace MeSH
• Kaplanův-Meierův odhad MeSH
• kostní dřeň patologie   MeSH
• krevní obraz * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové cirkulující buňky * MeSH
• plazmatické buňky * chemie   ultrastruktura   MeSH
• plazmocelulární leukemie krev   mortalita   MeSH
• průtoková cytometrie metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Nitro-oleic acid (NO2-OA), pluripotent cell-signaling mediator, was recently described as a modulator of the signal transducer and activator of transcription 3 (STAT3) activity. In our study, we discovered new aspects of NO2-OA involvement in the regulation of stem cell pluripotency and differentiation. Murine embryonic stem cells (mESC) or mESC-derived embryoid bodies (EBs) were exposed to NO2-OA or oleic acid (OA) for selected time periods. Our results showed that NO2-OA but not OA caused the loss of pluripotency of mESC cultivated in leukemia inhibitory factor (LIF) rich medium via the decrease of pluripotency markers (NANOG, sex-determining region Y-box 1 transcription factor (SOX2), and octamer-binding transcription factor 4 (OCT4)). The effects of NO2-OA on mESC correlated with reduced phosphorylation of STAT3. Subsequent differentiation led to an increase of the ectodermal marker orthodenticle homolog 2 (Otx2). Similarly, treatment of mESC-derived EBs by NO2-OA resulted in the up-regulation of both neural markers Nestin and β-Tubulin class III (Tubb3). Interestingly, the expression of cardiac-specific genes and beating of EBs were significantly decreased. In conclusion, NO2-OA is able to modulate pluripotency of mESC via the regulation of STAT3 phosphorylation. Further, it attenuates cardiac differentiation on the one hand, and on the other hand, it directs mESC into neural fate.

• MeSH
• biologické markery metabolismus   MeSH
• buněčná diferenciace * účinky léků   MeSH
• dusíkaté sloučeniny farmakologie   MeSH
• embryoidní tělíska účinky léků   metabolismus   MeSH
• kardiomyocyty účinky léků   metabolismus   MeSH
• kyseliny olejové farmakologie   MeSH
• myší embryonální kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• myši MeSH
• neurony cytologie   účinky léků   metabolismus   MeSH
• organogeneze účinky léků   MeSH
• pluripotentní kmenové buňky účinky léků   metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• transkripční faktor STAT3 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH