BACKGROUND: Recent developments regarding the contribution of microRNAs (miRNAs) to tumor angiogenesis and the oncogenic effects of miRNAs point to their potential role in breast cancer angiogenesis. Tumor-derived exosomes are considered a rich source of miRNAs that can regulate the function of other cells in the tumor microenvironment, including vascular endothelial cells. This study analyzes the effect of tamoxifen chemotherapy on the expression of a key miRNA, miR-573, involved in the angiogenesis of the tumor exosomes and introduces a regulatory link between this miRNA and the CD146 gene associated with the vascular endothelial growth factor (VEGF) messaging pathway. MATERIALS AND METHODS: MCF-7 breast cancer cells were purchased and cultured in a complete culture medium. These cells were treated with tamoxifen and then their exosomes were extracted from the culture medium. The RNAs of the exosomes were isolated and the expression of miR-573, VEGF, and CD146 genes in the exosomes was investigated using the real-time polymerase chain reaction (PCR) method. RESULTS: The results of this study showed that tamoxifen treatment increased the expression of miR-573 in exosomes derived from MCF-7 cancer cells. The expression of CD146 and VEGF genes in drug-treated cell exosomes had a downward pattern. CONCLUSION: The results of this experiment demonstrated that the treatment of breast cancer cells with tamoxifen reduces the expression of VEGF and CD146 by increasing miR-573. Thus, angiogenesis is reduced and, therefore, its anti-tumor effects are applied.
- Klíčová slova
- breast cancer, exosome, miR-573, tamoxifen, tumor angiogenesis,
- MeSH
- antigen CD146 genetika MeSH
- endoteliální buňky metabolismus patologie MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí MeSH
- nádory prsu * farmakoterapie genetika patologie MeSH
- tamoxifen farmakologie terapeutické užití MeSH
- vaskulární endoteliální růstový faktor A genetika metabolismus terapeutické užití MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigen CD146 MeSH
- mikro RNA * MeSH
- MIRN573 microRNA, human MeSH Prohlížeč
- tamoxifen MeSH
- vaskulární endoteliální růstový faktor A MeSH
BACKGROUND: Vascular endothelial growth factor (VEGF) is not only a potent angiogenic factor but it also promotes axonal outgrowth and proliferation of Schwann cells. The aim of the present study was to quantitatively assess reinnervation of musculocutaneous nerve (MCN) stumps using motor and primary sensory neurons after plasmid phVEGF transfection and end-to-end (ETE) or end-to-side (ETS) neurorrhaphy. The distal stump of rat transected MCN, was transfected with plasmid phVEGF, plasmid alone or treated with vehiculum and reinnervated following ETE or ETS neurorrhaphy for 2 months. The number of motor and dorsal root ganglia neurons reinnervating the MCN stump was estimated following their retrograde labeling with Fluoro-Ruby and Fluoro-Emerald. Reinnervation of the MCN stumps was assessed based on density, diameter and myelin sheath thickness of regenerated axons, grooming test and the wet weight index of the biceps brachii muscles. RESULTS: Immunohistochemical detection under the same conditions revealed increased VEGF in the Schwann cells of the MCN stumps transfected with the plasmid phVEGF, as opposed to control stumps transfected with only the plasmid or treated with vehiculum. The MCN stumps transfected with the plasmid phVEGF were reinnervated by moderately higher numbers of motor and sensory neurons after ETE neurorrhaphy compared with control stumps. However, morphometric quality of myelinated axons, grooming test and the wet weight index were significantly better in the MCN plasmid phVEGF transfected stumps. The ETS neurorrhaphy of the MCN plasmid phVEGF transfected stumps in comparison with control stumps resulted in significant elevation of motor and sensory neurons that reinnervated the MCN. Especially noteworthy was the increased numbers of neurons that sent out collateral sprouts into the MCN stumps. Similarly to ETE neurorrhaphy, phVEGF transfection resulted in significantly higher morphometric quality of myelinated axons, behavioral test and the wet weight index of the biceps brachii muscles. CONCLUSION: Our results showed that plasmid phVEGF transfection of MCN stumps could induce an increase in VEGF protein in Schwann cells, which resulted in higher quality axon reinnervation after both ETE and ETS neurorrhaphy. This was also associated with a better wet weight biceps brachii muscle index and functional tests than in control rats.
- MeSH
- dextrany MeSH
- fluoresceiny MeSH
- genetická terapie metody MeSH
- krysa rodu Rattus MeSH
- mícha patologie MeSH
- modely nemocí na zvířatech MeSH
- nemoci periferního nervového systému patologie terapie MeSH
- nervová vlákna myelinizovaná patologie MeSH
- nervus musculocutaneus metabolismus patologie fyziologie MeSH
- neurologické vyšetření MeSH
- neurony metabolismus patologie MeSH
- potkani Wistar MeSH
- přední končetina patofyziologie MeSH
- regenerace nervu genetika fyziologie MeSH
- rhodaminy MeSH
- vaskulární endoteliální růstový faktor A biosyntéza metabolismus terapeutické užití MeSH
- velikost orgánu fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dextrany MeSH
- fluoresceiny MeSH
- fluoro-emerald MeSH Prohlížeč
- Fluoro-Ruby MeSH Prohlížeč
- rhodaminy MeSH
- vaskulární endoteliální růstový faktor A MeSH
AIM: To evaluate the effect difference of ranibizumab and sodium pegaptanib in the ablation treatment of the retinal pigment epithelium (RPE) in age-related macular degeneration MATERIAL AND METHODS: Retrospective analysis of data of patients with age-related macular degeneration treated by means of anti-VEGF therapy at the Department of Ophthalmology, School of Medicine, Palacky University, Olomouc, Czech Republic, E.U. during the period May 2009 - October 2010. For the analysis were used data from patients with follow-up period longer than 6 months and present serous RPE ablation caused by occult choroidal neovascularization (CNV), verified by optic coherence tomography (OCT) and fluoresceine angiography (FAG). STUDY GROUP: Ranibizumab was used as treatment during the period in 37 eyes of 37 patients (average age 73.2 years; right eye (RE) in 20 cases, left eye (LE) in 17 cases. Sodium pegaptanib was applied in 17 eyes of 17 patients (average age 72.4 years; RE in 10 cases and LE in 7 cases), The follow-up period in the ranibizumab group was 8.51 (SD 3.32) months, and in the pegaptanib group 9.94 (SD 5.50) months. RESULTS: In the ranibizumab group decreased the average RPE ablation base from 2865 microm (SD 810 microm) to 2270 microm (SD 1265 microm) and the prominence of the ablation from 334 microm (SD 160) to 238 microm (SD 178 microm). In patients treated by pegaptanib, decreased the average basis from 3245 microm (SD 930 microm) to 2159 microm (SD 1185 microm), and the prominence of the ablation from 354 microm (SD 173 microm) to 208 microm (SD 107 microm). The statistical significance test did not prove significant differences (level of significance p = 0.05) in the change either of the base or the prominence of the RPE ablation in any group of patients (prominence p = 0.09, base p = 0.21; Mann-Whitney test). In three patients (8.1%) treated by ranibizumab, the RPE rupture occurred. No RPE rupture was recorded in patients treated by sodium pegaptanib. CONCLUSION: Although no statistically significant difference in the efficacy of both drugs in the treatment of the RPE ablation was found, in patients treated by sodium pegaptanib, there is evident tendency of higher efficacy in decrease of the RPE ablation prominence, and lower incidence of RPE rupture. The study is limited by small number of patients and short follow-up period.
- MeSH
- aptamery nukleotidové terapeutické užití MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- lidé MeSH
- makulární degenerace farmakoterapie patologie MeSH
- optická koherentní tomografie MeSH
- ranibizumab MeSH
- retinální pigmentový epitel patologie MeSH
- senioři MeSH
- vaskulární endoteliální růstový faktor A terapeutické užití MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- aptamery nukleotidové MeSH
- humanizované monoklonální protilátky MeSH
- pegaptanib MeSH Prohlížeč
- ranibizumab MeSH
- vaskulární endoteliální růstový faktor A MeSH
VEGF, vascular endothelial growth factor, is a substance firstly described in 1983 as a tumor-secreted protein which causes the development of ascitic fluid in case of abdominal tumors. Its influence on angiogenesis was ascertained by many studies. The strongest stimulus for its production is hypoxia, which leads to higher secretion of VEGF and new angiogenesis of so affected tissue. The neurogenic effect was firstly mentioned in 1999. Its protective and proliferative influence both on CNS and peripheral nerves is now widely accepted. It was demonstrated that VEGF has more wide ranging effect than previously thought.
- MeSH
- fyziologická neovaskularizace fyziologie MeSH
- lidé MeSH
- nervový systém - fyziologické jevy MeSH
- signální transdukce MeSH
- vaskulární endoteliální růstový faktor A farmakologie fyziologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- vaskulární endoteliální růstový faktor A MeSH
