Stem cells have the capability of self-renewal and can differentiate into different cell types that might be used in regenerative medicine. Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) currently lack effective treatments. Although stem cell therapy is still on the way from bench to bedside, we consider that it might provide new hope for patients suffering with neurodegenerative diseases. In this article, we will give an overview of recent studies on the potential therapeutic use of mesenchymal stem cells (MSCs), neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and perinatal stem cells to neurodegenerative disorders and we will describe their immunomodulatory mechanisms of action in specific therapeutic modalities.
PURPOSE: Fruit and vegetable intake is inversely correlated with cancer; thus, it is proposed that an extract of phytochemicals as present in whole fruits, vegetables, or grains may have anti-carcinogenic properties. Thus, the anti-tumour effects of fruit peel polyphenols (Flavin7) in the chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. METHODS: Lyophilized substance of Flavin7 (F7) was administered at two concentrations of 0.3 and 3 % through diet. The experiment was terminated 14 weeks after carcinogen administration, and mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. In addition, using an in vitro cytotoxicity assay, apoptosis and proliferation after F7 treatment in human breast adenocarcinoma (MCF-7) cells were performed. RESULTS: High-dose F7 suppressed tumour frequency by 58 % (P < 0.001), tumour incidence by 24 % (P < 0.05), and lengthened latency by 8 days (P > 0.05) in comparison with the control rats, whereas lower dose of F7 was less effective. Histopathological analysis of tumours showed significant decrease in the ratio of high-/low-grade carcinomas after high-dose F7 treatment. Immunohistochemical analysis of rat carcinoma cells in vivo found a significant increase in caspase-3 expression and significant decrease in Bcl-2, Ki67, and VEGFR-2 expression in the high-dose group. Both doses demonstrated significant positive effects on plasma lipid metabolism in rats. F7 significantly decreased survival of MCF-7 cells in vitro in MTT assay by dose- and time-dependent manner compared to control. F7 prevented cell cycle progression by significant enrichment in G1 cell populations. Incubation with F7 showed significant increase in the percentage of annexin V-/PI-positive MCF-7 cells and DNA fragmentation. CONCLUSIONS: Our results reveal a substantial tumour-suppressive effect of F7 in the breast cancer model. We propose that the effects of phytochemicals present in this fruit extract are responsible for observed potent anti-cancer activities.
- MeSH
- antigen Ki-67 genetika metabolismus MeSH
- antitumorózní látky fytogenní analýza farmakologie MeSH
- apoptóza účinky léků MeSH
- experimentální nádory mléčných žláz farmakoterapie MeSH
- flavonoidy analýza farmakologie MeSH
- fragmentace DNA účinky léků MeSH
- kaspasa 3 genetika metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- methylnitrosomočovina toxicita MeSH
- MFC-7 buňky MeSH
- modely nemocí na zvířatech MeSH
- ovoce chemie MeSH
- polyfenoly analýza farmakologie MeSH
- proliferace buněk účinky léků MeSH
- protein X asociovaný s bcl-2 genetika metabolismus MeSH
- receptor 2 pro vaskulární endoteliální růstový faktor genetika metabolismus MeSH
- stilbeny analýza farmakologie MeSH
- tyrosin analogy a deriváty metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: There has been considerable interest in both clinical and preclinical research about the role of phytochemicals in the reduction of risk for cancer in humans. The aim of this study was to determine the antineoplastic effects of Chlorella pyrenoidosa in experimental breast cancer in vivo and in vitro. METHODS: In this experiment, the antineoplastic effects of C. pyrenoidosa in the chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. Chlorella powder was administered through diet at concentrations of 0.3% and 3%. The experiment was terminated 14 wk after carcinogen administration. At autopsy, mammary tumors were removed and prepared for histopathological and immunohistochemical analysis. In vitro cytotoxicity assay, parameters of apoptosis, and proliferation after chlorella treatment in human breast adenocarcinoma (MCF-7) cells were carried out. RESULTS: Basic parameters of experimental carcinogenesis, mechanism of action (biomarkers of apoptosis, proliferation, and angiogenesis), chosen metabolic variables, and side effects after long-term chlorella treatment in animals were assessed. Chlorella at higher concentration suppressed tumor frequency by 61% (P < 0.02) and lengthened tumor latency by 12.5 d (P < 0.02) in comparison with the controls. Immunohistochemical analysis of rat tumor cells showed caspase-7 expression increase by 73.5% (P < 0.001) and vascular endothelial growth factor receptor-2 expression decrease by 19% (P = 0.07) after chlorella treatment. In a parallel in vitro study, chlorella significantly decreased survival of MCF-7 cells in a dose-dependent manner. In chlorella-treated MCF-7 cells, a significant increase in cells having sub-G0/G1 DNA content and significant increase of early apoptotic and late apoptotic/necrotic cells after annexin V/PI staining assay were found. Decreases in mitochondrial membrane potential and increasing reactive oxygen species generation were observed in the chlorella-treated MCF-7 cells. CONCLUSIONS: This study is the first report on the antineoplastic effects of C. pyrenoidosa in experimental breast cancer in vivo and in vitro.
- MeSH
- annexin A5 metabolismus MeSH
- antitumorózní látky fytogenní farmakologie terapeutické užití MeSH
- apoptóza MeSH
- Chlorella * MeSH
- dieta MeSH
- fytoterapie * MeSH
- kaspasa 7 metabolismus MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- MFC-7 buňky MeSH
- mikrořasy MeSH
- nádory prsu farmakoterapie metabolismus MeSH
- potkani Sprague-Dawley MeSH
- proliferace buněk MeSH
- reaktivní formy kyslíku metabolismus MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Our previous results indicated significant tumor-suppressive effects of different statins in rat mammary carcinogenesis. The purpose of this experiment was to examine the chemopreventive effects of Pitavastatin alone and in combination with the pineal hormone melatonin in the model of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female Sprague-Dawley rats. Pitavastatin was administered dietary (10mg/kg) and melatonin in an aqueous solution (20μg/ml). Chemoprevention began 7 days prior to carcinogen administration and subsequently continued for 15 weeks until autopsy. At autopsy, mammary tumors were removed and prepared for histopathological and immunohistochemical analysis. Compared to controls, Pitavastatin alone reduced average tumor volume by 58% and lengthened latency by 8 days; on the other hand, the drug increased tumor frequency by 23%. Combined administration of Pitavastatin with melatonin decreased tumor frequency by 23%, tumor volume by 44% and lengthened tumor latency by 5.5 days compared to control animals. The analysis of carcinoma cells showed significant increase in caspase-3 expression in both treated groups and a tendency of increased caspase-7 expression after Pitavastatin treatment alone. Significant expression decrease of Ki67 was found in carcinoma cells from both treated groups. Compared to control carcinoma cells, Pitavastatin alone increased VEGF expression by 41%, however melatonin totally reversed its undesirable effect. Pitavastatin combined with melatonin significantly increased femur compact bone thickness in animals. Pitavastatin alone decreased plasma triglycerides and total cholesterol levels, however it significantly increased levels of glucose. In summary, our results show a partial antineoplastic effect of Pitavastatin combined with melatonin in the rat mammary gland carcinoma model.
- MeSH
- antitumorózní látky terapeutické užití MeSH
- chinoliny terapeutické užití MeSH
- experimentální nádory mléčných žláz farmakoterapie MeSH
- krysa rodu rattus MeSH
- melatonin terapeutické užití MeSH
- nádory mléčné žlázy u zvířat farmakoterapie MeSH
- nádory prsu farmakoterapie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- chemoprofylaxe metody MeSH
- hodnotící studie jako téma MeSH
- karcinogeneze * genetika chemicky indukované patologie účinky léků MeSH
- lidé MeSH
- nádory prsu prevence a kontrola MeSH
- potkani Sprague-Dawley MeSH
- statiny * aplikace a dávkování terapeutické užití MeSH
- statistika jako téma MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
Východiská: Statíny (inhibítory 3-hydroxy-3-metylglutaryl koenzým A reduktázy) predstavujú látky s dobre dokumentovanými terapeutickými a preventívnymi účinkami u kardiovaskulárnych ochorení. V predklinických štúdiách statíny preukázali tumor-supresívne účinky u viacerých typov neoplázií vrátane rakoviny prsníka. Materiál a metódy: V tejto štúdii sme hodnotili antineoplastický účinok simvastatínu v chemoprevencii N-metyl-N-nitrozoureou – indukovanej mamárnej karcinogenézy u samíc potkanov. Farmakum bolo aplikované v potrave vo dvoch koncentráciách – 18 mg/kg (SIMVA 18) a 180 mg/kg (SIMVA 180). Výsledky: Po dlhodobej aplikácii simvastatínu sme na konci pokusu vyhodnotili základné parametre experimentálnej karcinogenézy. Simvastatín v skupine SIMVA 180 signifikantne znížil frekvenciu nádorov o 80,5 % a incidenciu nádorov o 58,5 % v porovnaní s kontrolou. Simvastatín v tej istej skupine zvierat nesignifikantne znížil priemerný objem nádorov o 23,5 % a nesignifikantne predĺžil latenciu o 14,5 dňa v porovnaní s kontrolnými zvieratami. U simvastatínu podávaného v nižšej dávke sme nepozorovali antineoplastické účinky. Simvastatín v oboch liečených skupinách signifikantne znížil sérové hladiny triacylglycerolov a VLDL-cholesterolu v porovnaní s kontrolnými zvieratami. V porovnaní s kontrolami sme v skupinách SIMVA 18 a SIMVA 180 pozorovali signifikantný nárast príjmu potravy u zvierat. Signifikantné zmeny prírastku telesnej hmotnosti medzi skupinami so simvastatínom a kontrolnou skupinou neboli zistené. Záver: Táto štúdia je prvou zmienkou o simvastatíne použitom v experimentálnej mamárnej karcinogenéze in vivo.
Backgrounds: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have proven therapeutic and preventive effects on cardiovascular diseases. Preclinical evidence demonstrates tumor-suppressive effects of statins in several human neoplasias, including breast cancer. Materials and Methods: In this study, antineoplastic effects of simvastatin in chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. The drug was dietary administered at two concentrations – 18 mg/kg (SIMVA 18) and 180 mg/kg (SIMVA 180). Results: Basic parameters of experimental carcinogenesis after long-term simvastatin treatment in animals were assessed. In the SIMVA 180 group, simvastatin significantly suppressed tumour frequency by 80.5% and tumour incidence by 58.5% in comparison to the controls. Higher dose simvastatin non-significantly decreased the mean tumor volume by 23.5%, as well as non-significantly lengthened the latency period by 14.5 days compared to the control animals. Simvastatin, administered at a lower dose did not change parameters of mammary carcinogenesis in comparison to the control group. Simvastatin in both treated groups significantly decreased serum levels of triacylglycerols and VLDL-cholesterol in comparison to the control animals. Compared to the controls, a significant increase in food intake by the animals was recorded in the SIMVA 18 and SIMVA 180 groups. No significant differences in the final body weight gain between the simvastatin-administered and the control group were found. Conclusion: This study represents the first report of simvastatin use in experimental mammary carcinogenesis in vivo.
- MeSH
- antitumorózní látky terapeutické užití MeSH
- experimentální nádory mléčných žláz farmakoterapie chemicky indukované prevence a kontrola MeSH
- financování organizované MeSH
- krysa rodu rattus MeSH
- potkani Sprague-Dawley MeSH
- simvastatin terapeutické užití MeSH
- statiny terapeutické užití MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
Nová generácia inhibítorov aromatázy predstavuje v súčasnosti prvú voľbu v endokrinnej liečbe pokročilého karcinómu prsníka u postmenopauzálnych pacientiek. Tieto farmaká sú rovnako účinné aj v adjuvantnej a neoadjuvantnej liečbe, výsledky niekoľkých prebiehajúcich štúdií môžu poukázať na ich úlohu v chemoprevencii rakoviny prsníka. Okrem toho sú potrebné dlhodobejšie štúdie, ktoré by dôsledne objasnili nežiaduce účinky inhibítorov aromatázy na ľudský organizmus. Účinnosť a bezpečnosť samostatne aplikovaných inhibítorov aromatázy u premenopauzálnych pacientiek s rakovinou prsníka je neznáma, v tejto oblasti bude potrebný ďalší výskum. Kombinované podávanie agonistov hormónu uvoľňujúceho luteinizačný hormón s inhibítormi aromatázy rozširuje využitie endokrinnej liečby rakoviny prsníka u premenopauzálnych žien či už s metastatickou alebo včasnou formou ochorenia. Výsledky našich štúdií chemoprevencie mamárnej karcinogenézy u samíc potkanov poukázali na potenciálnu výhodnosť aplikácie inhibítorov aromatázy – anastrozolu a letrozolu u premenopauzálnych žien postihnutých rakovinou prsníka.
The new generation of aromatase inhibitors has become the first choice of endocrine treatment of advanced breast cancer in postmenopausal patients. These compounds are also very effective as adjuvant and neoadjuvant treatment; results of several ongoing trials might elucidate their role in chemoprevention of breast cancer. Further studies with longer follow-up are required to provide a thorough evaluation of their safety profile. The effectiveness and safety of aromatase inhibitors as monotherapy in premenopausal breast cancer patients is unknown; this is an area for future research. Combined use of luteinising hormone releasing hormone agonists and aromatase inhibitors extends the use of endocrine therapy in premenopausal women with a metastatic or an early stage breast cancer. Our results of chemoprevention of mammary carcinogenesis in female rats have indicated potentially favourable effects of aromatase inhibitors – anastrozole and letrozole – in premenopausal women affected by breast cancer.
- MeSH
- estrogeny sekrece MeSH
- inhibitory aromatasy farmakologie terapeutické užití MeSH
- kombinovaná farmakoterapie metody MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- nádory prsu farmakoterapie MeSH
- postmenopauza metabolismus účinky léků MeSH
- premenopauza metabolismus účinky léků MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- antropologie fyzická MeSH
- dítě MeSH
- lidé MeSH
- pohlavní dimorfismus genetika MeSH
- pohlavní orgány růst a vývoj MeSH
- puberta genetika MeSH
- Romové MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
