Cancer is a complex, multifactorial disease that modern medicine ultimately aims to overcome. Downstream of tyrosine kinase 2 (DOK2) is a well-known tumor suppressor gene, and a member of the downstream protein DOK family of tyrosine kinases. Through a search of original literature indexed in PubMed and other databases, the present review aims to extricate the mechanisms by which DOK2 acts on cancer, thereby identifying more reliable and effective therapeutic targets to promote enhanced methods of cancer prevention and treatment. The review focuses on the role of DOK2 in multiple tumor types in the lungs, intestines, liver, and breast. Additionally, we discuss the potential mechanisms of action of DOK2 and the downstream consequences via the Ras/MPAK/ERK or PI3K/AKT/mTOR signaling pathways.
Hypersensitive pain response is observed in patients with Parkinson's disease (PD). However, the signal pathways leading to hyperalgesia still need to be clarified. Chronic oxidative stress is one of the hallmarks of PD pathophysiology. Since the midbrain periaqueductal gray (PAG) is an important component of the descending inhibitory pathway controlling on central pain transmission, we examined the role NADPH oxidase (NOX) of the PAG in regulating exaggerated pain evoked by PD. PD was induced by central microinjection of 6-hydroxydopamine to lesion the left medial forebrain bundle of rats. Then, Western Blot analysis and ELISA were used to determine NOXs and products of oxidative stress (i.e., 8-isoprostaglandin F2alpha and 8-hydroxy-2'-deoxyguanosine). Pain responses to mechanical and thermal stimulation were further examined in control rats and PD rats. In results, among the NOXs, protein expression of NOX4 in the PAG of PD rats was significantly upregulated, thereby the products of oxidative stress were increased. Blocking NOX4 pathway in the PAG attenuated mechanical and thermal pain responses in PD rats and this was accompanied with decreasing production of oxidative stress. In addition, inhibition of NOX4 largely restored the impaired GABA within the PAG. Stimulation of GABA receptors in the PAG of PD rats also blunted pain responses. In conclusions, NOX4 activation of oxidative stress in the PAG of PD rats is likely to impair the descending inhibitory GABAergic pathways in regulating pain transmission and thereby plays a role in the development of pain hypersensitivity in PD. Inhibition of NOX4 has beneficial effects on the exaggerated pain evoked by PD.
- MeSH
- bolest farmakoterapie etiologie metabolismus patologie MeSH
- fasciculus telencephali medialis účinky léků metabolismus MeSH
- GABA metabolismus MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- NADPH-oxidasa 4 antagonisté a inhibitory MeSH
- Parkinsonova nemoc enzymologie metabolismus patologie MeSH
- potkani Sprague-Dawley MeSH
- práh bolesti účinky léků fyziologie MeSH
- pyrazolony farmakologie MeSH
- pyridony farmakologie MeSH
- signální transdukce účinky léků MeSH
- substantia grisea centralis účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
To investigate the effect of vanadyl trehalose (VT) on oxidative stress and reduced glutathione/glutathione-S-transferase (GSH/GSTs) pathway gene expression in mouse gastrointestinal tract, as well as the protective effects of vitamin C (VC) and reduced glutathione (GSH). Thirty male Kunming mice were randomly divided into five groups: control group (group A), VT group (group B), VC + VT group (group C), GSH + VT group (group D) and VC + GSH + VT group (group E). The content of reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) activity and the expressions of glutamate-cysteine ligase catalytic subunit (GCLC), glutathione synthetase (GSS), regulated through glutathione reductase (GSR) and glutathione-S-transferase pi (GSTpi) in stomach and duodenum in vanadyl trehalose treated group were lower than those in group A (P<0.05). The C, D, E group can significantly improve the above indicators, but those only in the stomach in E group reached the level of the control group. Vanadyl trehalose (VT) was able to cause oxidative stress damage to the gastrointestinal tract of mice, which affects GSH content and GSH-Px activity and interferes with the normal expression of GSH/GSTs pathway. Exogenous vitamin C, reduced glutathione and the combination of the two could play a specific role in antioxidant protection and reduce the toxicity of vanadyl trehalose.
- MeSH
- antioxidancia farmakologie MeSH
- biomimetika MeSH
- glutathion metabolismus MeSH
- glutathionperoxidasa metabolismus MeSH
- glutathionreduktasa metabolismus MeSH
- glutathiontransferasa metabolismus MeSH
- hypoglykemika farmakologie MeSH
- inzulin farmakologie MeSH
- kyselina askorbová farmakologie MeSH
- myši MeSH
- oxidační stres MeSH
- trehalosa farmakologie MeSH
- vanadáty farmakologie MeSH
- žaludek účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND PURPOSE: MRA is widely accepted as a noninvasive diagnostic tool for the detection of intracranial aneurysms, but detection is still a challenging task with rather low detection rates. Our aim was to examine the performance of a computer-aided diagnosis algorithm for detecting intracranial aneurysms on MRA in a clinical setting. MATERIALS AND METHODS: Aneurysm detectability was evaluated retrospectively in 48 subjects with and without computer-aided diagnosis by 6 readers using a clinical 3D viewing system. Aneurysms ranged from 1.1 to 6.0 mm (mean = 3.12 mm, median = 2.50 mm). We conducted a multireader, multicase, double-crossover design, free-response, observer-performance study on sets of images from different MRA scanners by using DSA as the reference standard. Jackknife alternative free-response operating characteristic curve analysis with the figure of merit was used. RESULTS: For all readers combined, the mean figure of merit improved from 0.655 to 0.759, indicating a change in the figure of merit attributable to computer-aided diagnosis of 0.10 (95% CI, 0.03-0.18), which was statistically significant (F(1,47) = 7.00, P = .011). Five of the 6 radiologists had improved performance with computer-aided diagnosis, primarily due to increased sensitivity. CONCLUSIONS: In conditions similar to clinical practice, using computer-aided diagnosis significantly improved radiologists' detection of intracranial DSA-confirmed aneurysms of ≤6 mm.
- MeSH
- algoritmy * MeSH
- diagnóza počítačová metody MeSH
- intrakraniální aneurysma radiografie MeSH
- lidé MeSH
- magnetická rezonanční angiografie metody MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
