Virové bradavice jsou celosvětově časté onemocnění způsobené lidským papilomavirem, který má řadu genotypů. Mnoho z těchto virů je komenzálních a u imunokompetentních hostitelů nevyvolávají žádné projevy. Za vhodných podmínek některé způsobují klinické změny na kůži nebo na sliznicích v anogenitální či orofaryngeální oblasti. U dětí se nejčastěji setkáváme s verruca vulgaris, verruca plantaris a verruca plana. Řada těchto projevů samovolně vymizí, problémem jsou perzistentní či úporně recidivující bradavice. Léčbou se snažíme nejen zlikvidovat viditelné změny za minimalizace bolesti a bez jizvení, ale také o prevenci recidivy ať již v místě původní bradavice nebo kdekoli jinde na těle.
Viral warts are a common disease worldwide caused by the human papillomavirus, which has a number of genotypes. Many of these viruses are commensal and do not cause any symptoms in immunocompetent hosts. Under appropriate conditions, however, some cause clinical changes on the skin or mucous membranes in the anogenital or oropharyngeal part. Verruca vulgaris, verruca plantaris and verruca plana are most often encountered in children. Many of these manifestations disappear on their own, the problem is persistent or stubbornly recurring warts. With the treatment, we try not only to eliminate visible changes while minimizing pain and without scarring, but also to prevent recurrence, whether at the site of the original wart or anywhere else on the body.
- MeSH
- Warts * drug therapy therapy MeSH
- Child * MeSH
- Fluorouracil pharmacology therapeutic use MeSH
- Papillomavirus Infections transmission therapy MeSH
- Keratinocytes pathology MeSH
- Cryotherapy methods MeSH
- Salicylic Acid therapeutic use MeSH
- Trichloroacetic Acid therapeutic use MeSH
- Lasers MeSH
- Humans MeSH
- Podophyllin pharmacology therapeutic use MeSH
- Check Tag
- Child * MeSH
- Humans MeSH
- Keywords
- imiquimod,
- MeSH
- Imidazoles therapeutic use MeSH
- Condylomata Acuminata * drug therapy therapy MeSH
- Trichloroacetic Acid therapeutic use MeSH
- Humans MeSH
- Podophyllotoxin therapeutic use MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Review MeSH
Conventional chemotherapy is mostly effective in the treatment of rapidly-dividing differentiated tumor cells but has limited application toward eliminating cancer stem cell (CSC) population. The presence of a very small number of CSCs may contribute to the development of therapeutic resistance, metastases, and relapse. Thus, treatment failure by developing novel anticancer drugs capable of effective targeting of CSCs is at present a major challenge for research focused on chemotherapy of cancer. Here, we show that Os(II) complex 2 [Os(η6-pcym)(bphen)(dca)]PF6 (pcym = p-cymene, bphen = bathophenanthroline, and dca = dichloroacetate), is capable of efficient and selective killing CSCs in heterogeneous populations of human breast cancer cells MCF-7 and SKBR-3. Notably, its remarkable submicromolar potency to kill CSCs is considerably higher than that of its Ru analog, [Ru(η6-pcym)(bphen)(dca)]PF6 (complex 1) and salinomycin, one of the most selective CSC-targeting compounds hitherto identified. Furthermore, Os(II) complex 2 reduces the formation, size, and viability of three-dimensional mammospheres which more closely reflect the tumor microenvironment than cells in traditional two-dimensional cultures. The antiproliferation studies and propidium iodide staining using flow cytometry suggest that Os(II) complex 2 induces human breast cancer stem cell death predominantly by necroptosis, a programmed form of necrosis. The results of this study demonstrate the promise of Os(II) complex 2 in treating human breast tumors. They also represent the foundation for further preclinical and clinical studies and applications of Os(II) complex 2 to comply with the emergent need for human breast CSCs-specific chemotherapeutics capable to treat chemotherapy-resistant and relapsed human breast tumors.
- MeSH
- Apoptosis drug effects MeSH
- Chloroacetates pharmacology MeSH
- Cymenes pharmacology MeSH
- Phenanthrolines pharmacology MeSH
- Coordination Complexes pharmacology MeSH
- Humans MeSH
- Neoplasm Recurrence, Local pathology MeSH
- Cell Line, Tumor MeSH
- Neoplastic Stem Cells drug effects metabolism MeSH
- Tumor Microenvironment drug effects MeSH
- Breast Neoplasms drug therapy pathology MeSH
- Necroptosis drug effects MeSH
- Necrosis metabolism MeSH
- Organoplatinum Compounds pharmacology MeSH
- Osmium pharmacology MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents pharmacology MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
We report on the preparation and thorough characterization of cytotoxic half-sandwich complexes [Ru(η⁶-pcym)(bphen)(dca)]PF₆ (Ru-dca) and [Os(η⁶-pcym)(bphen)(dca)]PF₆ (Os-dca) containing dichloroacetate(1-) (dca) as the releasable O-donor ligand bearing its own cytotoxicity; pcym = 1-methyl-4-(propan-2-yl)benzene (p-cymene), bphen = 4,7-diphenyl-1,10-phenanthroline (bathophenanthroline). Complexes Ru-dca and Os-dca hydrolyzed in the water-containing media, which led to the dca ligand release (supported by ¹H NMR and electrospray ionization mass spectra). Mass spectrometry studies revealed that complexes Ru-dca and Os-dca do not interact covalently with the model proteins cytochrome c and lysozyme. Both complexes exhibited slightly higher in vitro cytotoxicity (IC50 = 3.5 μM for Ru-dca, and 2.6 μM for Os-dca) against the A2780 human ovarian carcinoma cells than cisplatin (IC50 = 5.9 μM), while their toxicity on the healthy human hepatocytes was found to be IC50 = 19.1 μM for Ru-dca and IC50 = 19.7 μM for Os-dca. Despite comparable cytotoxicity of complexes Ru-dca and Os-dca, both the complexes modified the cell cycle, mitochondrial membrane potential, and mitochondrial cytochrome c release by a different way, as revealed by flow cytometry experiments. The obtained results point out the different mechanisms of action between the complexes.
- MeSH
- Phenanthrolines chemistry pharmacology MeSH
- Coordination Complexes chemistry pharmacology MeSH
- Dichloroacetic Acid chemistry pharmacology MeSH
- Humans MeSH
- Ligands MeSH
- Ovarian Neoplasms drug therapy MeSH
- Osmium chemistry MeSH
- Cell Proliferation drug effects MeSH
- Ruthenium chemistry MeSH
- Drug Liberation MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The Warburg effect states that the main source of energy for cancer cells is not aerobic respiration, but glycolysis-even in normoxia. The shift from one to the other is governed by mutually counteracting enzymes: pyruvate dehydrogenase and pyruvate dehydrogenase kinase (PDK). Anaerobic metabolism of cancer cells promotes cell proliferation, local tissue immunosuppression, resistance to hypoxic conditions, and metastatic processes. By switching glucose back to oxidative metabolism, these effects might be reversed. This can be achieved using PDK inhibitors, such as dichloroacetate. Patients suffering from ischemic conditions might benefit from this effect. On the other hand, the β-blockers (adrenergic β-antagonists) often used in these patients appear to improve cancer-specific survival, and nonselective β-blockers have been shown to promote glucose oxidation. Might there be a link?
- MeSH
- Adrenergic beta-Antagonists pharmacology MeSH
- Glucose metabolism MeSH
- Glycolysis MeSH
- Ischemia drug therapy metabolism MeSH
- Dichloroacetic Acid pharmacology MeSH
- Humans MeSH
- Neoplasms drug therapy metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Exposure to β-N-methylamino-l-alanine (BMAA) might be linked to the incidence of amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease. Analytical chemistry plays a crucial role in determining human BMAA exposure and the associated health risk, but the performance of various analytical methods currently employed is rarely compared. A CYANOCOST initiated workshop was organized aimed at training scientists in BMAA analysis, creating mutual understanding and paving the way towards interlaboratory comparison exercises. During this workshop, we tested different methods (extraction followed by derivatization and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis, or directly followed by LC-MS/MS analysis) for trueness and intermediate precision. We adapted three workup methods for the underivatized analysis of animal, brain and cyanobacterial samples. Based on recovery of the internal standard D₃BMAA, the underivatized methods were accurate (mean recovery 80%) and precise (mean relative standard deviation 10%), except for the cyanobacterium Leptolyngbya. However, total BMAA concentrations in the positive controls (cycad seeds) showed higher variation (relative standard deviation 21%-32%), implying that D₃BMAA was not a good indicator for the release of BMAA from bound forms. Significant losses occurred during workup for the derivatized method, resulting in low recovery (<10%). Most BMAA was found in a trichloroacetic acid soluble, bound form and we recommend including this fraction during analysis.
- MeSH
- Amino Acids, Diamino analysis metabolism MeSH
- Chromatography, Liquid methods MeSH
- Daphnia MeSH
- Trichloroacetic Acid chemistry MeSH
- Brain metabolism MeSH
- Neurotoxins analysis metabolism MeSH
- Reproducibility of Results MeSH
- Cyanobacteria metabolism MeSH
- Tandem Mass Spectrometry methods MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
x
- MeSH
- Acrolein analogs & derivatives pharmacology adverse effects MeSH
- Chemical Warfare Agents * pharmacology adverse effects MeSH
- Chloroacetates chemistry adverse effects MeSH
- Irritants * history adverse effects MeSH
- Phosgene analogs & derivatives pharmacology adverse effects MeSH
- Humans MeSH
- Bromine Compounds chemistry adverse effects MeSH
- Tear Gases chemistry adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Coherence-controlled holographic microscopy (CCHM) in low-coherence mode possesses a pronounced coherence gate effect. This offers an option to investigate the details of cellular events leading to cell death caused by cytopathic turbid emulsions. CCHM capacity was first assessed in model situations that showed clear images obtained with low coherence of illumination but not with high coherence of illumination. Then, the form of death of human cancer cells induced by treatment with biologically active phospholipids (BAPs) preparation was investigated. The observed overall retraction of cell colony was apparently caused by the release of cell-to-substratum contacts. This was followed by the accumulation of granules decorating the nuclear membrane. Then, the occurrence of nuclear membrane indentations signaled the start of damage to the integrity of the cell nucleus. In the final stage, cells shrunk and disintegrated. This indicated that BAPs cause cell death by necrosis and not apoptosis. An intriguing option of checking the fate of cancer cells caused by the anticipated cooperative effect after adding another tested substance sodium dichloroacetate to turbid emulsion is discussed on grounds of pilot experiments. Such observations should reveal the impact and mechanism of action of the interacting drugs on cell behavior and fate that would otherwise remain hidden in turbid milieu.
- MeSH
- Cell Death physiology MeSH
- Cytological Techniques methods MeSH
- Phospholipids MeSH
- Holography methods MeSH
- Dichloroacetic Acid MeSH
- Humans MeSH
- Microscopy methods MeSH
- Cell Line, Tumor MeSH
- Neoplasms physiopathology MeSH
- Necrosis MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Dichloroacetate (DCA) is beneficial in cancer therapy because it induces apoptosis and decreases cancer growth in vitro and in vivo without affecting non-cancer cells. DCA stimulates the activity of the enzyme pyruvate dehydrogenase by inhibiting pyruvate dehydrogenase kinase. Consequently, DCA promotes oxidative phosphorylation after glycolysis. Therefore, DCA produces changes in energy metabolism that could affect the mitochondrial network and mitophagy. This investigation determined the effects of DCA treatment on mitophagy in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were cultured and distributed into 3 groups: control, NH4Cl and chloroquine. Each group was treated with DCA at 0, 5, 30 and 60 mM for 16 h. Samples were analyzed for cell viability, mtDNA copy number, mitochondrial network morphology and expression of key proteins involved in mitochondrial dynamics, such as LC3b, FIS1, OPA1, PARKIN and PINK1. In all groups, DCA caused a decrease in cell viability, an induction of autophagy in a dose-dependent manner and a decrease in Tim23, FIS1 and PARKIN protein expression, leading to profound morphological changes in the mitochondrial network resulting in shorter and more fragmented filaments. However, TFAM protein levels remained unchanged. Similarly, the mitochondrial copy number was not significantly different among the treatment groups. In conclusion, DCA induces mitophagy and remodeling of the mitochondrial network. In this remodeling, DCA induces a decrease in the expression of key proteins involved in protein degradation and mitochondrial dynamics but does not significantly affect the mtDNA density. Blocking late phase autophagy increases the effects of DCA, suggesting that autophagy protects the cell, at least partially, against DCA.
- MeSH
- Autophagy drug effects MeSH
- Chloroquine pharmacology MeSH
- Dichloroacetic Acid pharmacology MeSH
- Humans MeSH
- DNA, Mitochondrial drug effects MeSH
- Mitochondrial Proteins metabolism MeSH
- Mitophagy drug effects MeSH
- Cell Line, Tumor MeSH
- Neuroblastoma genetics metabolism pathology MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- DNA Copy Number Variations MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
