- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
The KRAS signalling pathway is pivotal for pancreatic ductal adenocarcinoma (PDAC) development. After the failure of most conventional cytotoxic and targeted therapeutics tested so far, the combination of taxane nab-paclitaxel (Abraxane) with gemcitabine recently demonstrated promising improvements in the survival of PDAC patients. This study aimed to explore interactions of conventional paclitaxel and experimental taxane SB-T-1216 with the KRAS signalling pathway expression in in vivo and in vitro PDAC models in order to decipher potential predictive biomarkers or targets for future individualised therapy. Mouse PDAC PaCa-44 xenograft model was used for evaluation of changes in transcript and protein levels of the KRAS signalling pathway caused by administration of experimental taxane SB-T-1216 in vivo. Subsequently, KRAS wild-type (BxPc-3) and mutated (MiaPaCa-2 and PaCa-44) cell line models were treated with paclitaxel to verify dysregulation of the KRAS signalling pathway gene expression profile in vitro and investigate the role of KRAS mutation status. By comparing the gene expression profiles, this study observed for the first time that in vitro cell models differ in the basal transcriptional profile of the KRAS signalling pathway, but there were no differences between KRAS mutated and wild-type cells in sensitivity to taxanes. Generally, the taxane administration caused a downregulation of the KRAS signalling pathway both in vitro and in vivo, but this effect was not dependent on the KRAS mutation status. In conclusion, putative biomarkers for prediction of taxane activity or targets for stimulation of taxane anticancer effects were not discovered by the KRAS signalling pathway profiling in various PDAC models.
- MeSH
- albuminy farmakologie MeSH
- deoxycytidin analogy a deriváty farmakologie MeSH
- duktální karcinom pankreatu farmakoterapie genetika MeSH
- lidé MeSH
- myši nahé MeSH
- myši MeSH
- nádorové biomarkery genetika MeSH
- nádorové buněčné linie MeSH
- nádory slinivky břišní farmakoterapie genetika MeSH
- paclitaxel farmakologie MeSH
- přemostěné cyklické sloučeniny farmakologie MeSH
- proliferace buněk účinky léků genetika MeSH
- protokoly antitumorózní kombinované chemoterapie farmakologie MeSH
- protoonkogenní proteiny p21(ras) genetika MeSH
- signální transdukce účinky léků genetika MeSH
- taxoidy farmakologie MeSH
- transkriptom účinky léků genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
In our experiment, we deal with the phenomenon of radiation hormesis and improvements based on this phenomenon to different growing characteristics of the fast-growing, very feed-efficient, and with a high-yielding carcass hybrid of the Peking duck (Cherry Valley SM3 medium). In the first phase of the project, we exposed hatching duck eggs to low and middle doses of gamma radiation 60Co (0.06-2.00 Gy) before placing them into a setter in the hatchery. We then followed the standards of artificial incubation. The treatment of our chosen doses of gamma radiation has no significant influence on the history and results of hatching (from 85.5% to 92.6%); it was influenced only by the basic management and husbandry of the parent stock. From our observations we confirm that the Peking duck, despite genetic progress, retained its vitality and robustness. Its embryos are not damaged even with a dose of 2 Gy, which is over the deterministic effect of ionizing radiation for vertebrates. At the end of the fatting period a significant drop in plasma phosphorus levels was measured in the ducks; however, it was dependent on the radiation dose to which the hatching eggs were exposed (r = -0.965). A positive effect of radiation hormesis may be expected in the case of 1 Gy dose where the highest values of mean corpuscular hemoglobin, mean corpuscular hemoglobin, combined hemoglobin, and drake weight were measured. Lower and higher doses of ionizing radiation used did not display these effects.
- MeSH
- hormeze MeSH
- kachny fyziologie MeSH
- náhodné rozdělení MeSH
- ovum fyziologie účinky záření MeSH
- radioizotopy kobaltu aplikace a dávkování MeSH
- rozmnožování účinky záření MeSH
- vztah dávky záření a odpovědi MeSH
- záření gama * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: To provide a 3D dosimetric evaluation of a commercial portal dosimetry system using 2D/3D detectors under ideal conditions using VMAT. METHODS: A 2D ion chamber array, radiochromic film and gel dosimeter were utilised to provide a dosimetric evaluation of transit phantom and pre-treatment 'fluence' EPID back-projected dose distributions for a standard VMAT plan. In-house 2D and 3D gamma methods compared pass statistics relative to each dosimeter and TPS dose distributions. RESULTS: Fluence mode and transit EPID dose distributions back-projected onto phantom geometry produced 2D gamma pass rates in excess of 97% relative to other tested detectors and exported TPS dose planes when a 3%, 3 mm global gamma criterion was applied. Use of a gel dosimeter within a glass vial allowed comparison of measured 3D dose distributions versus EPID 3D dose and TPS calculated distributions. 3D gamma comparisons between modalities at 3%, 3 mm gave pass rates in excess of 92%. Use of fluence mode was indicative of transit results under ideal conditions with slightly reduced dose definition. CONCLUSIONS: 3D EPID back projected dose distributions were validated against detectors in both 2D and 3D. Cross validation of transit dose delivered to a patient is limited due to reasons of practicality and the tests presented are recommended as a guideline for 3D EPID dosimetry commissioning; allowing direct comparison between detector, TPS, fluence and transit modes. The results indicate achievable gamma scores for a complex VMAT plan in a homogenous phantom geometry and contributes to growing experience of 3D EPID dosimetry.
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
