ATP binding cassette (ABC) transporters related to multidrug resistance (MDR) actively efflux various xenobio-tics from the cells across the cell membrane and decrease a drugs efficiency. Lung cancer is the leading cause of death among all types of cancer in the Czech Republic, and its incidence is still rising. Ciglitazone, rosiglitazone and troglitazone belonging to PPARγ agonist family (formerly used in diabetes mellitus treatment) were selected to investigate their capability to influence expression of ABC transporters on lung cancer cells. Therefore, the effect of PPARγ of agonists on transcription of following ABC transporters was investigated: multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP). We have investigated if these PPARγ agonists are substrates of ABC transporters using HL60 and HL60 derived cell lines (HL60-MDR1, HL60-MRP1, PLB-BCRP) by cytotoxicity test WST-1. We have mapped the changes in mRNA expression level of those transporters in A549 and HEK293 cells after PPARγ agonists treatment using quantitative reverse transcription real-time PCR (qRT-PCR). All three PPARγ agonists serve as substrates to at least one ABC transporter under study. PPARγ activation correlates with up-regulation of PTEN which may modulate the expression of ABC transporters through PI3K/ Akt signaling pathway. We have shown that rosiglitazone and troglitazone inhibit mRNA expression of MDR1 transporter in both cell lines whereas the expression of MRP1 in HEK293 cell was up-regulated after rosiglitazone treatment and the expression of MDR1 was upregulated after ciglitazone treatment.
- MeSH
- ABC transportéry biosyntéza MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory plic metabolismus patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- thiazolidindiony farmakologie MeSH
- transkriptom MeSH
- western blotting MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABC transportéry MeSH
- thiazolidindiony MeSH
The aim of this study is to evaluate the biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma, with emphasis on smoking, protein p16(INK4a) (p16) expression, and human papillomavirus (HPV) status.The study sample consisted of 48 patients with OSCC and 44 patients with OPSCC. Half of the patients were nonsmokers and the other half were gender-, age- and tumor localization-matched smokers. p16 expression was detected in 17/48 (35 %) OSCCs and in 36/44 (82 %) OPSCCs and HPV DNA was present in 7/48 (15 %) OSCCs and in 35/44 (80 %) OPSCCs. The sensitivity and specificity of p16 expression for HPV DNA presence were 0.74 and 0.88, respectively. The OPSCCs were more frequently basaloid (p < 0.001) while the OSCCs were more frequently conventional (p < 0.000001). The OSCCs were more likely to recur locally and to be the cause of death (p = 0.009 in both parameters).The HPV-positive tumors were more frequently localized in oropharynx, were basaloid SCCs and were p16- and HPV-positive (p < 0.000001 in all 4 parameters). The HPV-negative tumors were more frequently localized in oral cavity (p < 0.000001), more frequently asociated with local, regional and locoregional recurence (p = 0.011, p = 0.019 and p = 0.030, respectively) and with tumor-related death (p = 0.003). There was no significant difference with regard to smoking history (p > 0.05). The survival of patients with HPV-positive tumors was significantly longer (median 112 months; 95% CI 54 - 112 months) than that of patients with HPV-negative tumors (median 17 months; 95% CI 12 - 39 months) (p < 0.001). The HPV status of OSCC/OPSCC is an important biological and prognostic parameter and should be examined in all cases, using PCR or immunohistochemical detection of surrogate marker p16. Smoking itself does not seem to be an important prognostic factor.
- MeSH
- DNA virů MeSH
- dospělí MeSH
- imunoenzymatické techniky MeSH
- infekce papilomavirem metabolismus mortalita virologie MeSH
- inhibitor p16 cyklin-dependentní kinasy metabolismus MeSH
- kouření škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru metabolismus mortalita virologie MeSH
- míra přežití MeSH
- nádory orofaryngu metabolismus mortalita virologie MeSH
- nádory úst metabolismus mortalita virologie MeSH
- Papillomaviridae genetika izolace a purifikace MeSH
- polymerázová řetězová reakce MeSH
- prognóza MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom metabolismus mortalita virologie MeSH
- staging nádorů MeSH
- studie případů a kontrol 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
- Názvy látek
- DNA virů MeSH
- inhibitor p16 cyklin-dependentní kinasy MeSH
Head and neck squamous cell carcinomas develop predominantly in individuals over 40 years of age and more frequently in males. The strongest risk factors for this disease are long-term abuse of tobacco products and alcohol. Recently, several reports of increasing incidence of head and neck cancer in atypical population groups of females or young adults have been published, often in patients with no history of smoking or alcohol abuse. It seems highly probable that at least in a part of these cases, human papillomavirus (HPV) played an important etiological role. Some of the HPV types were proved to cause certain anogenital carcinomas, particularly cervical carcinoma. It seems that in some cases these very HPV types are also involved in head and neck carcinogenesis. Published data on the prevalence of HPV infection in head and neck squamous cell carcinomas vary in different studies. However, it is generally understood that the infection is more commonly present in carcinomas of the oropharynx and palatine tonsils than in oral cavity carcinomas. The hypothesis of sexual transmission of oncogenic HPV types has yet to be confirmed. It is not clear whether current HPV vaccines could possibly decrease the incidence of head and neck squamous carcinomas.
Sexual differences in the total content of ribosomal RNA, established by cytophotometric measurements in neurones from selected brain regions, were studied in rats of the Wistar strain. In females of reproductive age, cyclic changes of RNA were synchronized with their oestrous cycle, the values being higher in the oestrous phase than in dioestrus. These changes were observed in pyramidal cells of the hippocampus and of the frontal cortex, in cells of anterior thalamus, of ventromedial and lateral hypothalamus and of tuberculi olfactorii. However, cycling cells were not disclosed in septum and thalamus posterior. A dependence upon the actual level of ovarial hormones was found in ventromedial hypothalamic cells only. In general, the RNA values in males of the same age corresponded to values of dioestrous females. The differences between newborn and 7-day-old pups were not marked enough and did not allow to define the critical period responsible for initiation of this sexual difference. In senescent rats, this difference persisted. During the stable phase of long-lasting dioestrus, the total RNA content in cells of the frontal cortex, hippocampus and hypothalamus was higher in females than in males of the same age which may suggest a faster reduction of this substance in aged males. The prolonged influence of oestrogens in the oestrous phase of the climacteric period (preceding the permanent dioestrus) decreased the RNA values in hippocampal and hypothalamic neurones even below the level established during the permanent dioestrus (and thus reached male values). On the contrary, in frontal cortical neurones, the female values remained higher in the permanent dioestrus as well as during long-lasting oestrus. A discussion concerns the possible participation of genetic determination and of the actual state of ovarial hormones in the manifestation of sexual differences in brain cells of the rat.
- MeSH
- hypofyzektomie MeSH
- krysa rodu Rattus MeSH
- mozek cytologie metabolismus MeSH
- novorozená zvířata růst a vývoj metabolismus MeSH
- ovarektomie MeSH
- pohlavní dimorfismus * MeSH
- potkani Wistar MeSH
- RNA ribozomální metabolismus MeSH
- stárnutí metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- RNA ribozomální MeSH
Some recent studies on dyslexia have suggested a selective abnormality in the magnocellular visual pathway. To verify this hypothesis, we investigated motion-onset visual evoked potentials (VEPs) (predominantly testing the magnocellular system) as well as pattern-reversal VEPs (presumably testing the parvocellular system) in 20 dyslexics and 16 controls (both groups with a mean age of 10.0 years). Although the latencies and amplitudes of the main positive peak of pattern-reversal VEPs did not differ between the dyslexic and control group, the motion specific negative peak of motion-onset VEPs was significantly delayed (p < 0.001) in dyslexics. Our results confirm a selective magnocellular pathway disorder in dyslexics and indicate that the motion-onset VEPs might serve as an objective method for early diagnosis of dyslexia.
- MeSH
- dítě MeSH
- dyslexie patologie patofyziologie MeSH
- lidé MeSH
- světelná stimulace MeSH
- vidění monokulární fyziologie MeSH
- vnímání pohybu fyziologie MeSH
- zrakové dráhy patologie patofyziologie MeSH
- zrakové evokované potenciály fyziologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
Bilateral lesions of the dorsal part of the septal area were produced in the brain of female rats of Wistar and Long-Evans stocks. The cytogram of their vaginal smears was evaluated repeatedly from the 30th day after surgery and permanent impairment of their oestrous cycle was found. In comparison with intact control females, oestrous phases were detected more frequently whereas dioestrous phases were observed less frequently. The proportions between the individual periods of the oestrous phase (i.e. pro-oestrus, oestrus and metoestrus) were equal in both septal and intact animals. No difference was found between the rat stocks used. Similarly, the previous life history of the rats which had been housed either in a socially impoverished environment (i.e. single cages) or in large communities (colonies) exerted no influence upon the postoperative impairment of the oestrous cycle.
- MeSH
- bydlení zvířat MeSH
- estrus fyziologie MeSH
- krysa rodu Rattus MeSH
- mateřské chování fyziologie MeSH
- nucleus ventromedialis hypothalami fyziologie MeSH
- ovarium fyziologie MeSH
- potkani Wistar MeSH
- RNA analýza MeSH
- septální jádra fyziologie chirurgie MeSH
- sexuální chování zvířat fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- RNA MeSH
The relationship between milk fat concentration and the growth of rat pups from birth to the 20th day was investigated. A total of 36 first-time-lactating Wistar rats and 366 pups from litters of 8-12 were used. The concentration of milk fat was determined by the crematocrit method, on the 2nd, 5th, 10th, 15th, 20th and 25th day of lactation. A wide range of milk fat concentration with a great variability in each individual dam was observed during lactation. To correlate milk fat and pup's growth, the mean value of the milk fat of the individual mothers was calculated for the first 10 days from the values of the 2nd, 5th and 10th day of lactation, and for the second 10 days from the values of the 10th, 15th and 20th days. The results show that pups fed higher fat milk in the first 10 days of life grew faster than pups fed lower fat milk. A significant positive correlation (P < 0.001) was found between the fat concentration of milk and the weight gains of pups in the first 10 days, but not in the older groups. It indicates that the fat concentration of milk is important for the growth of pups mainly in the early postnatal period of life.
- MeSH
- dietní tuky analýza farmakologie MeSH
- kojená zvířata růst a vývoj MeSH
- krysa rodu Rattus MeSH
- mléčné bílkoviny analýza farmakologie MeSH
- mléko * chemie MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dietní tuky MeSH
- mléčné bílkoviny MeSH
Dorsal lesions of the septum influenced the maternal behaviour of Wistar and Long-Evans females, as well as of their hybrids, in a different way. The phenomenon of infanticide appeared in Wistar females only, whereas mothering was not impaired in others. However, the mouse-killing activity was not enhanced in Wistar females displaying infanticide. On the contrary, they exhibited xenoparental behaviour. If these females had grown up in a species-typical environment, characterized by enriched social stimulation during their critical developmental period, no impairment of maternal behaviour following dorsal septal lesions occurred. The ablation of the whole septum caused a break-down of maternal behaviour with the appearance of infanticide in all females regardless of their stock origin and their individual life history. The specific role of the septum in the control of maternal behaviour is discussed.
- MeSH
- agrese fyziologie MeSH
- chování zvířat fyziologie MeSH
- inbrední kmeny potkanů MeSH
- krysa rodu Rattus MeSH
- mateřské chování fyziologie MeSH
- myši MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- septum pellucidum fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- arterioskleróza krev patologie MeSH
- cholesterol krev MeSH
- dietní tuky nenasycené aplikace a dávkování farmakologie MeSH
- králíci MeSH
- peroxidace lipidů MeSH
- rybí oleje aplikace a dávkování farmakologie MeSH
- triglyceridy krev MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cholesterol MeSH
- dietní tuky nenasycené MeSH
- rybí oleje MeSH
- triglyceridy MeSH
The RNA content of the ventromedial hypothalamus (VMH) and lateral hypothalamic area (LHA) neurons, and the epididymal, retroperitoneal, and liver fat content of 150-day-old male rats submitted to neonatal undernutrition, were investigated. The neonatal undernutrition was carried out by two different ways. First, by reducing the litters to two pups per nest from birth to weaning. The pups from normal litters (eight pups/nest) served as controls. Secondly, by separating half of the pups (four pups) from normal litters for 8 h daily during the first 5 postnatal days. The remaining nonseparated pups served as their controls. The data show that both groups of early undernourished pups had a significantly increased RNA content in the VMH neurons (RNA content in the LHA neurons was unchanged) and a significantly decreased epididymal, retroperitoneal, and liver fat content in comparison with their controls. The results indicate that early undernutrition leads to a permanent increase in the functional activity of VMH and alteration in fat metabolism in rats.
- MeSH
- area hypothalamica lateralis patofyziologie MeSH
- krysa rodu Rattus MeSH
- mapování mozku MeSH
- mobilizace lipidů fyziologie MeSH
- neurony fyziologie MeSH
- nucleus ventromedialis hypothalami patofyziologie MeSH
- potkani Wistar MeSH
- protein-energetická malnutrice patofyziologie MeSH
- RNA metabolismus MeSH
- složení těla fyziologie MeSH
- sympatický nervový systém patofyziologie MeSH
- tělesná hmotnost fyziologie MeSH
- tuková tkáň inervace metabolismus MeSH
- velikost vrhu fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- RNA MeSH
