- Publikační typ
- abstrakt z konference MeSH
Atranorin (ATR) is a secondary metabolite of lichens. While previous studies investigated the effects of this substance predominantly in an in vitro environment, in our study we investigated the basic physicochemical properties, the binding affinity to human serum albumin (HSA), basic pharmacokinetics, and, mainly, on the systematic effects of ATR in vivo. Sporadic studies describe its effects during, predominantly, cancer. This project is original in terms of testing the efficacy of ATR on a healthy organism, where we can possibly attribute negative effects directly to ATR and not to the disease. For the experiment, 24 Sprague Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided into four groups. The first group (n = 6) included healthy males as control intact rats (♂INT) and the second group (n = 6) included healthy females as control intact rats (♀INT). Groups three and four (♂ATR/n = 6 and ♀ATR/n = 6) consisted of animals with daily administered ATR (10mg/kg body weight) in an ethanol-water solution per os for a one-month period. Our results demonstrate that ATR binds to HSA near the binding site TRP214 and acts on a systemic level. ATR caused mild anemia during the treatment. However, based on the levels of hepatic enzymes in the blood (ALT, ALP, or bilirubin levels), thiobarbituric acid reactive substances (TBARS), or liver histology, no impact on liver was recorded. Significantly increased creatinine and lactate dehydrogenase levels together with increased defecation activity during behavioral testing may indicate the anabolic effect of ATR in skeletal muscles. Interestingly, ATR changed some forms of behavior. ATR at a dose of 10 mg/kg body weight is non-toxic and, therefore, could be used in further research.
- Publikační typ
- časopisecké články MeSH
Objev indukované pluripotence v roce 2006 umožnil revoluční způsob získávaní autologních terapeuticky aplikovatelných buněk, a mož‐ nost modelovat jakékoliv onemocnění v in vitro podmínkách. Možnost vrátit libovolnou, finálně diferencovanou buňku „v čase“ zpátky do stádia pluripotence je zajímavé i pro oblast onkologického výzkumu. Tato technologie umožnila studium procesů spojených s roz‐ vojem nádorového fenotypu buňky a taky s přechodem nádorové buňky do stádia s nižší mírou diferenciace. Reprogramování buněk do indukovaných pluripotentních kmenových buněk také pomáhá mnohem lépe studovat raritní populaci buněk, přítomných v nádo‐ rech – tzv. nádorové kmenové buňky. Indukovaná pluripotence některých typů nádorových buněk, spojená s jejich následnou řízenou diferenciací by se zároveň mohla stát jednou z možných terapeutických aplikací v onkologii.
Discovery of technology of induced pluripotency that allows the generation of autologous therapeutically applicable cells and generati‐ on of in vitro cell models for diseases with limited (or highly invasive) access to tested cells has also opened new horizons in the field of oncology research. The unique ability to reprogram the cancer cell into pluripotency with subsequent directed differentiation into cell with no malignant phenotype should be considered as a challenge in the field of new oncotherapy development. Although still conside‐ red to be realistic only on the level of experimental approach, the recent progress in the field of induced pluripotency gives the hope that dedifferentiation‐based therapies connected with the erase of malignant phenotype of original cancer cell will be more realistic in near future. By then, the most important role of induced pluripotency in oncology remains in the field of regenerative therapy as a source of autologous cells for regeneration of tissues or organs damaged by tumor growth or aggressive therapy
Pankreatický duktální adenokarcinom (PDAC) představuje jeden z nejagresivnějších typů lidských malignit. V současnosti je toto zhoubné onemocnění čtvrtou nejčastější příčinou úmrtí na rakovinu. Pětileté přežití pacientů s duktálním adenokarcinomem je méně než 8 %. Nové in vitro a in vivo modely jsou proto nutně potřebné pro vývoj nových terapií. S vlastní technologií pro derivaci nových, unikátních 3D nádorových buněčných linií izolovaných z lidských nádorů a ve spolupráci s Ústavem živočišné fyziologie a genetiky AV ČR v Liběchově představujeme plán vývoje velkého zvířecího modelu pro modelování lidského PDAC. S využitím tohoto modelu a nejmodernějších laboratorních technik provedeme profilovací analýzy (detekce a fenotypování cirkulujících rakovinných buněk, izolace a sekvenování cirkulující DNA, metabolomické profilování a analýzu onkoproteinů, a detekce cytokinů pomocí multiplexních protilátkových čipů za účelem nalezení biomarkerů nádoru pankreatu. Nově vyvinutý model zároveň poskytneme pro potřeby výzkumu spolupracujícím vědeckým pracovištím a farmaceutickým společnostem.
Pancreatic ductal adenocarcinoma represents one of the most aggressive type of human malignancy. Currently, this malignancy is the fourth most frequent cause of dead. 5-year survival of patients with ductal adenocarcinoma is less than 8 %. New in vitro and in vivo models are therefore desperately needed for new therapy development. With our own technology for derivation of new, unique 3D cancer cell lines from human tumors and in collaboration with Institute of Animal Physiology and Genetics, AS CR, in Libechov, we present here the plan for the development of large xenograft animal model (pig) bearing human pancreatic tumor. With the use of this model and state -of -the -art lab.techniques, we will perform multiple profiling analyses (circulating cancer cell detection and phenotyping, circulating DNA isolation and sequencing, metabolomic profiling and cancer -related proteins and cytokines detection with multiplex antibody array chips in order to find the hallmarks of pancreatic tumor.
Melanoma-bearing Libechov minipig (MeLiM) represents a large animal model for melanoma research. This model shows a high incidence of complete spontaneous regression of melanoma - a phenomenon uncommon in humans. Here, we present the first metabolomic characterisation of the MeLiM model comparing animals with progressing and spontaneously regressing melanomas. Plasma samples of 19 minipigs with progression and 27 minipigs with evidence of regression were analysed by a targeted metabolomic assay based on mass spectrometry detection. Differences in plasma metabolomics patterns were investigated by univariate and multivariate statistical analyses. Overall, 185 metabolites were quantified in each plasma sample. Significantly altered metabolomic profile was found, and 42 features were differentially regulated in plasma. Besides, the machine learning approach was used to create a predictive model utilising Arg/Orn and Arg/ADMA ratios to discriminate minipigs with progressive disease development from minipigs with regression evidence. Our results suggest that progression of melanoma in the MeLiM model is associated with alteration of arginine, glycerophospholipid and acylcarnitines metabolism. Moreover, this study provides targeted metabolomics characterisation of an animal model of melanoma with progression and spontaneous regression of tumours.
- MeSH
- metabolomika metody MeSH
- miniaturní prasata MeSH
- modely nemocí na zvířatech MeSH
- prasata MeSH
- progrese nemoci MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
