The breast cancer affects women with high mortality and morbidity worldwide. The risk is highest in the most developed world but also is markedly rising in the developing countries. It is well documented that melatonin has a significant anti-tumor activities demonstrated on various cancer types in a plethora of preclinical studies. In breast cancer, melatonin is capable to disrupt estrogen-dependent cell signaling, resulting in a reduction of estrogen-stimulated cells, moreover, it's obvious neuro-immunomodulatory effect in organism was described. Several prospective studies have demonstrated the inverse correlation between melatonin metabolites and the risk of breast cancer. This correlation was confirmed by observational studies that found lower melatonin levels in breast cancer patients. Moreover, clinical studies have showed that circadian disruption of melatonin synthesis, specifically night shift work, is linked to increased breast cancer risk. In this regard, proper light/dark exposure with more selective use of light at night along with oral supplementation of melatonin may have benefits for high-risk women. The results of current preclinical studies, the mechanism of action, and clinical efficacy of melatonin in breast cancer are reviewed in this paper. Melatonin alone or in combined administration seems to be appropriate drug for the treatment of early stages of breast cancer with documented low toxicity over a wide range of doses. These and other issues are also discussed.
- MeSH
- lidé MeSH
- melatonin aplikace a dávkování metabolismus farmakologie MeSH
- nádory prsu farmakoterapie metabolismus MeSH
- prospektivní studie MeSH
- signální transdukce účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by the neurotransmitter acetylcholine, leads to paradoxical vasoconstriction as it binds to smooth muscle cell M3 receptors. Thus, inhibition of coronary artery vasospasm will improve clinical outcomes. Inhibition of insulin regulated aminopeptidase has been shown to improve vessel function, thus we tested the hypothesis that HFI419, an inhibitor of insulin regulated aminopeptidase, could reduce blood vessel constriction to acetylcholine. The abdominal aorta was excised from New Zealand white rabbits (n=15) and incubated with 3mM Hcy to induce vascular dysfunction in vitro for 1h. HFI419 was added 5min prior to assessment of vascular function by cumulative doses of acetylcholine. In some rings, vasoconstriction to acetylcholine was observed in aortic rings after pre-incubation with 3mM homocysteine. Incubation with HFI419 inhibited the vasoconstrictive response to acetylcholine, thus improving, but not normalizing, vascular function (11.5±8.9% relaxation vs 79.2±37% constriction, p<0.05). Similarly, in another group with mild vasoconstriction, HFI419 inhibited this effect (34.9±4.6% relaxation vs 11.1±5.2%, constriction, p<0.05). HFI419 had no effect on control aorta or aorta with mild aortic dysfunction. The present study shows that HFI419 prevents acetylcholine mediated vasoconstriction in dysfunctional blood vessels. HFI419 had no effect on normal vasodilation. Our results indicate a therapeutic potential of HFI419 in reducing coronary artery vasospasm.
- MeSH
- acetylcholin toxicita MeSH
- aorta abdominalis účinky léků enzymologie MeSH
- cévní endotel účinky léků enzymologie MeSH
- cystinylaminopeptidasa antagonisté a inhibitory metabolismus MeSH
- inhibitory enzymů farmakologie MeSH
- králíci MeSH
- orgánové kultury - kultivační techniky MeSH
- vazokonstrikce účinky léků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication of type 2 diabetes mellitus (T2DM). Several lines of evidence implicate the endothelin (ET) system in the pathophysiology of DN. The aim of the present study was to analyze if genetic polymorphisms of the ET-1 (EDN1) gene affect susceptibility to DN in Caucasians with T2DM. MATERIALS AND METHODS: The study population consisted of 651 Caucasian subjects with T2DM of more than 10 years' duration: 276 patients with DN (cases) and 375 patients without evidence of DN (controls). Polymorphisms in ET-1 (EDN1) gene, rs5370, rs1476046, and rs3087459, were studied. RESULTS: Genotype distributions of the studied polymorphisms showed no significant difference between cases and controls. CONCLUSIONS: We provide evidence that the rs5370, rs1476046, and rs3087459 polymorphisms of EDN1 gene are not risk factors for DN in Caucasians with T2DM.
- MeSH
- běloši genetika MeSH
- diabetes mellitus 2. typu etnologie genetika patofyziologie MeSH
- diabetické nefropatie etnologie genetika patofyziologie MeSH
- dospělí MeSH
- endotelin-1 genetika MeSH
- genetická predispozice k nemoci epidemiologie MeSH
- hodnocení rizik MeSH
- lidé středního věku MeSH
- lidé MeSH
- polymorfismus genetický * MeSH
- průřezové studie MeSH
- referenční hodnoty MeSH
- retrospektivní studie MeSH
- senzitivita a specificita MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The formation of new blood vessels plays a crucial for the development and progression of pathophysiological changes associated with a variety of disorders, including carcinogenesis. Angiogenesis inhibitors (anti-angiogenics) are an important part of treatment for some types of cancer. Some natural products isolated from marine invertebrates have revealed antiangiogenic activities, which are diverse in structure and mechanisms of action. Many preclinical studies have generated new models for further modification and optimization of anti-angiogenic substances, and new information for mechanistic studies and new anti-cancer drug candidates for clinical practice. Moreover, in the last decade it has become apparent that galectins are important regulators of tumor angiogenesis, as well as microRNA. MicroRNAs have been validated to modulate endothelial cell migration or endothelial tube organization. In the present review we summarize the current knowledge regarding the role of marine-derived natural products, galectins and microRNAs in tumor angiogenesis.
- MeSH
- antitumorózní látky farmakologie MeSH
- biologické přípravky farmakologie MeSH
- galektiny účinky léků MeSH
- inhibitory angiogeneze farmakologie MeSH
- látky modulující angiogenezi farmakologie MeSH
- lidé MeSH
- mikro RNA účinky léků MeSH
- mořské toxiny farmakologie MeSH
- nádory farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
