Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with an extremely low median survival rate of 12-15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to the treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain-specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and miR-338-5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased cell proliferation, increased cell cycle arrest, and apoptosis in comparison to irradiation-only cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, and ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation, and cell cycle regulation. To our knowledge, this is the first study to describe the role of miR-338-5p in GBM and its potential to improve the sensitivity of GBM to radiation.

• Klíčová slova
• GBM, Glioblastoma multiforme, Radiation resistance, miRNA, miRNA338-5p,
• MeSH
• buněčné dělení účinky léků   účinky záření   MeSH
• glioblastom genetika   patologie   MeSH
• kontrolní body buněčného cyklu účinky léků   účinky záření   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny biosyntéza   genetika   MeSH
• mikro RNA genetika   MeSH
• monomerní proteiny vázající GTP biosyntéza   genetika   MeSH
• nádorové buněčné linie MeSH
• nádorové proteiny biosyntéza   genetika   MeSH
• nádory mozku genetika   patologie   MeSH
• neuropeptidy biosyntéza   genetika   MeSH
• poškození DNA genetika   MeSH
• protein Rheb MeSH
• proteinfosfatasa 2 biosyntéza   genetika   MeSH
• regulace genové exprese u nádorů genetika   MeSH
• RNA nádorová genetika   MeSH
• stanovení celkové genové exprese MeSH
• tolerance záření genetika   MeSH
• transportní proteiny biosyntéza   genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• membránové proteiny MeSH
• mikro RNA MeSH
• MIRN338 microRNA, human MeSH Prohlížeč
• monomerní proteiny vázající GTP MeSH
• nádorové proteiny MeSH
• NDFIP1 protein, human MeSH Prohlížeč
• neuropeptidy MeSH
• PPP2R5A protein, human MeSH Prohlížeč
• protein Rheb MeSH
• proteinfosfatasa 2 MeSH
• RHEB protein, human MeSH Prohlížeč
• RNA nádorová MeSH
• transportní proteiny MeSH

BACKGROUND: UV radiation from sunlight is a potent environmental risk factor in skin cancer pathogenesis. UVA is the major portion of UV light reaching the earth surface ( approximately 95%) and it is reported to lead to benign and malignant tumor formation. UVA-mediated cellular damage occurs primarily through the release of reactive oxygen species (ROS) and it is responsible for inflammation, immunosuppression, photoaging and photocarcinogenesis. OBJECTIVE: The aim of our study was to investigate the potency of silymarin, the polyphenol fraction from the seeds of Silybum marianum, to modulate UVA-induced oxidative damage to human keratinocytes. METHODS: Skin epidermal cell line HaCaT, extensively used for studying the influence of UV radiation, was chosen as an experimental model. Silymarin's effect on UVA-disrupted cell viability, proliferation, mitochondrial function, and intracellular ATP and GSH level was measured. Furthermore, silymarin's potency to reduce UVA-induced ROS generation, membrane lipid peroxidation, caspase-3 activation and DNA damage was monitored. RESULTS: Treatment of irradiated HaCaT (20 J/cm(2)) with silymarin (0.7-34 mg/l; 4h) resulted in concentration-dependent diminution of UVA-caused oxidative stress on all studied parameters. Silymarin application extensively reduced GSH depletion and ROS production as well as lipid peroxidation in irradiated cells. Formation of UVA-induced DNA single strand breaks and caspase-3 activity was also significantly decreased by silymarin. CONCLUSION: The results suggest that silymarin may be beneficial in the treatment of UVA-induced skin oxidative injury and inflammation. However, further studies especially whose using human systems are needed to determine efficacy of silymarin in vivo.

• MeSH
• antioxidancia chemie   farmakologie   toxicita   MeSH
• apoptóza účinky léků   účinky záření   MeSH
• buněčné dělení účinky léků   účinky záření   MeSH
• energetický metabolismus účinky léků   účinky záření   MeSH
• keratinocyty cytologie   účinky léků   metabolismus   MeSH
• lidé MeSH
• oxidační stres účinky léků   účinky záření   MeSH
• poškození DNA účinky léků   MeSH
• silymarin chemie   farmakologie   toxicita   MeSH
• transformované buněčné linie MeSH
• ultrafialové záření škodlivé účinky   MeSH
• viabilita buněk účinky léků   účinky záření   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• silymarin MeSH

The color of light (white, red, blue, and green) had a significant effect on the growth and reproductive processes (both in the nucleocytoplasmic and chloroplast compartment of the cells) in synchronous cultures of Scenedesmus obliquus. This effect decreased in the order red > white > blue > green. In the same order, the light phase of the cell cycle (time when first autospores started to be released) was prolonged. The length of dark phase (time when 100 % of daughters were allowed to release from mothers) was not influenced and was the same for all colors. Critical cell size for cell division in green light was shifted to a smaller size (compared with cells grown in other lights) and so was the size of released daughters. The nuclear cycle was slowed in blue and even in green light, contrary to cells grown in red and white light. At the beginning of the cell cycle, one-nucleus daughters possess approximately 10 nucleoids; during the cell cycle their number doubled in all variants before the division of nuclei. Both events were delayed in cultures grown more slowly most markedly in green light. Smaller daughters in the green variant possessed a lower number of nucleoids. Motile cells released in continuous green or blue lights but not in red one were rarely observed.

• MeSH
• buněčné dělení účinky záření   MeSH
• chloroplasty metabolismus   MeSH
• chronobiologické jevy fyziologie   MeSH
• fluorescenční mikroskopie MeSH
• fotobiologie metody   MeSH
• fotosyntéza účinky záření   MeSH
• Scenedesmus růst a vývoj   metabolismus   MeSH
• světlo * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Methods for determining the points of commitment for cell division are described for species of green algae dividing by multiple fission, both forming coenobia (Scenedesmus quadricauda) and releasing single daughter cells (Chlamydomonas eugametos, Scenedesmus armatus). The timing of commitment points was followed in detail in synchronous cultures of S. quadricauda grown under various light intensities, illumination regimes, and temperatures. The pre-commitment periods were rate limiting, while the post-commitment periods remained more or less constant under various light intensity. Temperature, on the other hand, affected both periods in a similar manner and they were prolonged with decreasing temperature.

• MeSH
• buněčné dělení * fyziologie   účinky záření   MeSH
• buněčný cyklus * MeSH
• Chlamydomonas cytologie   růst a vývoj   MeSH
• kultivační média MeSH
• Scenedesmus cytologie   růst a vývoj   MeSH
• světlo MeSH
• teplota MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kultivační média MeSH

This work studies biological effects of low-frequency electromagnetic fields. We have exposed three different bacterial strains-Escherichia coli, Leclercia adecarboxylata and Staphylococcus aureus to the magnetic field (t<30 min, B(m)=10 mT, f=50 Hz) in order to compare their viability (number of colony-forming units (CFU)). We have measured the dependence of CFU on time of exposure and on the value of the magnetic field induction B(m). Viability decreases with longer exposure time and/or higher induction B(m) for all strains, but the quantity of the effect is strain-dependent. The highest decrease of the viability and the biggest magnetic field effect was observed with E. coli. The smallest magnetic field effect appears for S. aureus. From the measurement of the growth dynamics we have concluded that the decrease of the CFU starts immediately after the magnetic field was switched on.

• MeSH
• buněčné dělení účinky záření   MeSH
• dávka záření MeSH
• druhová specificita MeSH
• elektřina MeSH
• elektromagnetická pole * MeSH
• Enterobacteriaceae cytologie   fyziologie   účinky záření   MeSH
• Escherichia coli cytologie   fyziologie   účinky záření   MeSH
• fyziologická adaptace účinky záření   MeSH
• Staphylococcus aureus cytologie   fyziologie   účinky záření   MeSH
• viabilita buněk MeSH
• vztah dávky záření a odpovědi MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Ionising radiation is used for the treatment of pituitary tumours as fractionated radiotherapy, where the total dose reaching the tumour area is in the range of 40-50 Gy, or during stereotactic radiosurgery, where the total dose reaching the tumour area during one session is in the range of 20-90 Gy. In this study, we investigated the effect of ionising radiation of (60)Co (dose rate of 3 Gy/min, similar to that used during gamma knife procedure) on the mode of cell death of the somatomammotroph pituitary cell line, GH3, an immortalized cell line derived from a rat pituitary adenoma. We found that the basic mechanism of cell death induced by irradiation of this GH3 cell line by gamma-rays was programmed cell death-apoptosis. Doses of 20-50 Gy were shown to inhibit proliferation in these cells. 24 hours after irradiation with a dose of 20 and 50 Gy, cells were shown to accumulate in the G(2)/M phase of cell cycle. This cell cycle arrest lasted for at least ten days. Apoptosis was detected 72 hours towards until the end of the study (10 days). However, a significant number of cells were still alive ten days following irradiation. We conclude that ionising radiation doses of 20 and 50 Gy induce pituitary GH3 cell apoptosis following cell cycle arrest in the G(2)/M phase.

• MeSH
• adenohypofýza metabolismus   patologie   účinky záření   MeSH
• apoptóza účinky záření   MeSH
• buněčné dělení účinky záření   MeSH
• buněčný cyklus účinky záření   MeSH
• krysa rodu Rattus MeSH
• nádorové buněčné linie MeSH
• prolaktin metabolismus   MeSH
• růstový hormon metabolismus   MeSH
• vztah dávky záření a odpovědi MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• prolaktin MeSH
• růstový hormon MeSH

Possible UVC-protective properties of CA, a plant phenolic compound with antioxidant activity, were investigated on human KF1 diploid fibroblast and A431 epidermoid carcinoma cell lines. Cell populations, untreated and treated by antioxidants (CA and alpha-tocopherol), were irradiated by UVC at the wavelength of 254 nm and their proliferation activity was determined by the MTT assay. The results show a strong protective effect of CA at both concentrations used (55.5 and 166.5 microM): a significant increase of proliferation activity after UVC irradiation was detected in both cell populations growing in the presence of CA in comparison with cells in DMEM only. The described protective effect of CA was more obvious in transformed cells than in normal diploid cells. This protective ability is probably based on the antioxidant and scavenging activities of CA, which seems to be more efficient than alpha-tocopherol in protection against the cytotoxic effect caused by UVC irradiation.

• MeSH
• buněčné dělení účinky léků   účinky záření   MeSH
• buněčné linie MeSH
• kůže cytologie   účinky léků   patologie   účinky záření   MeSH
• kyseliny kávové farmakologie   MeSH
• lidé MeSH
• nádorová transformace buněk účinky léků   patologie   účinky záření   MeSH
• ochranné látky farmakologie   MeSH
• ultrafialové záření * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• caffeic acid MeSH Prohlížeč
• kyseliny kávové MeSH
• ochranné látky MeSH

We studied the mechanism of the cytotoxic effects of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT; induction with 1 mM ALA for 4 h followed by a blue light dose of 18 J/cm(2)) on the human promyelocytic leukemia cell line HL60 using biochemical and electron microscopy methods. The disruption of mitochondrial membrane potential, deltapsi(m), was paralleled by a decrease in ATP level, unmasking of the mitochondrial antigen 7A6, release of cytochrome c into the cytoplasm, activation of caspases 9 and 3 and cleavage of poly(ADP-ribose) polymerase (PARP). This was followed by DNA fragmentation. These data suggest that ALA-PDT activates the mitochondrial apoptotic pathway. The level of endoplasmic reticulum Ca(2+)-binding chaperones ERp57 and ERp72 and of anti-apoptotic proteins Bcl-2 and Bcl-x(L) was decreased whereas that of Ca(2+)-binding protein calmodulin and the stress protein HSP60 was elevated following ALA-PDT. Inhibition of the initiator caspase 9, execution caspase 3 and Ca(2+)-dependent protease m-calpain, did not prevent DNA fragmentation. We conclude that, in our in vitro model, ALA-based photodynamic treatment initiates several signaling processes in HL60 cells that lead to rapidly progressing apoptosis, which is followed by slow necrosis. Two apoptotic processes proceed in parallel, one representing the mitochondrial pathway, the other involving disruption of calcium homeostasis and activation of the endoplasmic reticulum stress-mediated pathway.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• aminokyseliny neutrální farmakologie   MeSH
• apoptóza účinky léků   účinky záření   MeSH
• buněčné dělení účinky léků   účinky záření   MeSH
• endoplazmatické retikulum účinky léků   účinky záření   ultrastruktura   MeSH
• fotochemoterapie metody   MeSH
• fotosenzibilizující látky farmakologie   MeSH
• fyziologický stres chemicky indukované   metabolismus   patologie   MeSH
• HL-60 buňky účinky léků   fyziologie   účinky záření   ultrastruktura   MeSH
• lidé MeSH
• membránové potenciály účinky léků   účinky záření   MeSH
• mitochondrie účinky léků   fyziologie   účinky záření   MeSH
• nádorové proteiny metabolismus   MeSH
• regulace genové exprese účinky léků   účinky záření   MeSH
• viabilita buněk účinky léků   účinky záření   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 5-aminovaleric acid MeSH Prohlížeč
• adenosintrifosfát MeSH
• aminokyseliny neutrální MeSH
• fotosenzibilizující látky MeSH
• nádorové proteiny MeSH

Dialyzed leukocyte extract (DLE) (Immodin SEVAC, Czech Republic) was shown to enhance the recovery of the pools of hemopoietic stem cells (CFUs) and of granulocyte-macrophage hemopoietic progenitor cells (GM-CFC) in the bone marrow in vivo, as well as to increase the numbers of leukocytes and thrombocytes in the peripheral blood of mice exposed to a sublethal dose of gamma-rays, with an ensuing increase in the numbers of mice surviving the lethal radiation dose. In experiments performed in vitro, DLE or sera of mice administered with DLE were added to cultures of intact mouse bone marrow cells containing suboptimal concentrations of hemopoietic stimulatory cytokines, namely recombinant mouse interleukin-3 (rmIL-3) or recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF); under these experimental conditions, both DLE and sera of mice administered DLE were found to increase the counts of GM-CFC colonies in the cultures. It can be hypothesized on the basis of the findings obtained in vitro that the described co-stimulating activity (CoSA) of DLE may play a role also under in vivo conditions; the enhancement of the recovery of hemopoiesis suppressed by ionizing radiation may be due to a co-operation of the stimulatory effects of DLE with the action of cytokines endogenously produced in irradiated tissues.

• MeSH
• buněčné dělení účinky záření   MeSH
• faktory stimulující kolonie farmakologie   MeSH
• hematopoetické kmenové buňky fyziologie   účinky záření   MeSH
• hematopoéza účinky záření   MeSH
• leukocyty fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši inbrední CBA MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktory stimulující kolonie MeSH

Ninety-five squamocellular carcinomas of the uterine cervix, clinical Stages II and III, were treated by either four schedules combining 252-californium neutron-gamma-radiotherapy with different proportions of a neutron component (9, 6 and 3 Gy) or gamma-irradiation alone. Flow cytometric DNA profiles were obtainable in 72 cases before treatment and 56 cases were monitored for DNA content by flow cytometry (FCM) in weekly intervals by analysis of sequential microbiopsies for one month during and after radiotherapy. DNA aneuploidy was reduced from 40% (25/63) to 19% (9/47) one week within therapy in neutron-treated groups, but not after initial gamma-radiotherapy alone. Extinction of DNA aneuploid subpopulations occurred after neutron therapy in all remaining aneuploid tumors (9/9) during further monitoring, but only in 40% (2/5) of tumors after sole gamma-irradiation. In contrast, proliferation index by more than 50% was more often achieved in groups with a higher gamma-radiation component than after neutrons only. When all therapy-induced DNA flow cytometric events are taken together for evaluation of the effects of various radiotherapy schedules, it appears that the regimen with the maximal neutron dose may not be optimal for all tumors. It is hypothesized that the differences in the early flow cytometric DNA profiles may select the DNA aneuploid squamous cell uterine cervical carcinomas as candidates for combined neutron-brachytherapy, while highly proliferating DNA near-diploid tumors may profit more from treatment with a higher gamma-radiotherapy component. However, these early DNA flow cytometric findings need to be correlated with clinical course of the disease to validate this hypothesis, a process which will be completed at the end of the expected five-year clinical outcome in 2000.

• MeSH
• aneuploidie MeSH
• biopsie MeSH
• brachyterapie MeSH
• buněčné dělení účinky záření   MeSH
• DNA nádorová analýza   genetika   účinky záření   MeSH
• kalifornium terapeutické užití   MeSH
• lidé MeSH
• nádory děložního čípku genetika   radioterapie   MeSH
• neutrony terapeutické užití   MeSH
• průtoková cytometrie MeSH
• spinocelulární karcinom genetika   radioterapie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA nádorová MeSH
• kalifornium MeSH