This work presents results on the efficiency of newly designed zinc phthalocyanine-mediated photodynamic therapy of both tumoral and nontumoral cell models using the MTT assay. Further detailed examinations of mechanistic and cell biological effects were focused on the HELA cervical cancer cell model. Here, ROS production, changes in the mitochondrial membrane potential, the determination of genotoxicity, and protein changes determined by capillary chromatography and tandem mass spectrometry with ESI were analyzed. The results showed that, in vitro, 5 Jcm-2 ZnPc PDT caused a significant increase in reactive oxygen species. Still, except for superoxide dismutase, the levels of proteins involved in cell response to oxidative stress did not increase significantly. Furthermore, this therapy damaged mitochondrial membranes, which was proven by a more than 70% voltage-dependent channel protein 1 level decrease and by a 65% mitochondrial membrane potential change 24 h post-therapy. DNA impairment was assessed by an increased level of DNA fragmentation, which might be related to the decreased level of DDB1 (decrease in levels of more than 20% 24 h post-therapy), a protein responsible for maintaining genomic integrity and triggering the DNA repair pathways. Considering these results and the low effective concentration (LC50 = 30 nM), the therapy used is a potentially very promising antitumoral treatment.
- MeSH
- fotochemoterapie * metody MeSH
- fotosenzibilizující látky * farmakologie chemie MeSH
- HeLa buňky MeSH
- indoly * farmakologie chemie MeSH
- isoindoly * MeSH
- lidé MeSH
- membránový potenciál mitochondrií * účinky léků MeSH
- organokovové sloučeniny * farmakologie chemie MeSH
- oxidační stres účinky léků MeSH
- poškození DNA účinky léků MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- sloučeniny zinku * farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Herein, a series of new 1,1,2-trimethyl-1H-benzo[e]indole dyes was prepared via Knoevenagel condensation reaction between 1,1,2-trimethyl-1H-benzo[e]indole and benzaldehydes, and characterized using various spectroscopic methods. The obtained compounds showed cytotoxic properties in G361 melanoma cell line upon irradiation with 414 nm blue light at submicromolar doses. The mechanism of action of the most potent compound 15 was further investigated. The treatment induced substantial generation of reactive oxygen species, leading to DNA damage followed by cell death depending on the concentration of the photosensitizer compound and the irradiation intensity.
- MeSH
- antitumorózní látky * farmakologie chemická syntéza chemie MeSH
- barvicí látky farmakologie chemie chemická syntéza MeSH
- fotosenzibilizující látky farmakologie chemická syntéza chemie MeSH
- indoly * chemie farmakologie chemická syntéza MeSH
- léky antitumorózní - screeningové testy * MeSH
- lidé MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- poškození DNA účinky léků MeSH
- proliferace buněk účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- světlo MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The aim was to assess therapeutic outcomes and tolerance in patients with metastatic castration resistant prostate cancer (mCRPC) treated with androgen receptor targeted agents (ARTA) treatment at one oncological center in the Czech Republic. MATERIALS AND METHODS: Retrospective analysis of 64 patients with mCRPC treated with abiraterone (50 patients) and enzalutamide (14 patients) in the first line of this disease was conducted. Kaplan-Meier analysis was used to calculate progression free survival (PFS) and overall survival (OS). We performed a multivariate analysis of risk factors for treatment outcomes (PFS, OS) by Cox regression analysis. RESULTS: The median follow-up was 28.4 months. The median PFS was 15.4 months [95% confidence interval (CI): 12.3-18.5], median OS was 38.2 months (95% CI: 19.9-56.5). Regression analysis demonstrated a favorable prognostic effect on PFS in patients with reduction of PSA ≥ 50 %, in patients with early reduction of prostate-specific antigen (PSA) ≥ 50% within 3 months, in patients younger than 74 years and in overall performance status (PS) 0. Regression analysis demonstrated a favorable prognostic effect on OS in patients with reduction of PSA ≥ 50 %, in patients with early reduction of PSA ≥ 50 % within 3 months and in patients with overall PS 0. Adverse effects grade 3-4 were reported in 17 (27.9%) patients in abirateron arm and in 1 (7.1%) patient in enzalutamide arm. CONCLUSION: The analysis of patients with mCRPC treated with ARTA in the first line showed that ARTA represents an effective and safe therapy and contributes to longer survival.
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most widespread malignancies. One of the alternative therapeutic methods appears to be photodynamic therapy (PDT). MATERIALS AND METHODS: This study investigated the efficiency of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin zinc (ZnTPPS4) and chloro-aluminum phthalocyanine disulfonate (ClAlPcS2) with two commercial photosensitive compounds 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP) and tetramethylthionine chloride (methylene blue, MB) in PDT for CRC in vitro. In addition to the study of the photodynamic effect on the viability of the colorectal carcinoma cell line HT29, cellular uptake, ROS production, and DNA damage were investigated. RESULTS: All photosensitizers showed good accumulation within HT29 cells, high efficiency in killing the cells, and a concentration-dependent increase in the production of ROS. CONCLUSION: PDT using ZnTPPS4 and ClAlPcS2 may be effective in the treatment of CRC, achieving a similar photocytotoxic effect at much lower concentrations compared to MB.
- MeSH
- adenokarcinom * farmakoterapie metabolismus patologie MeSH
- buňky HT-29 MeSH
- fotochemoterapie * metody MeSH
- fotosenzibilizující látky * farmakologie MeSH
- indoly * farmakologie MeSH
- kolorektální nádory * farmakoterapie patologie metabolismus MeSH
- lidé MeSH
- metaloporfyriny * farmakologie MeSH
- organokovové sloučeniny * farmakologie MeSH
- poškození DNA účinky léků MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Triclosan and Triclocarban, preservatives widely used in cosmetics and other consumer products, underwent evaluation using a battery of new-approach methodologies in vitro (NAMs). Specifically, the Microplate Ames Test (MPFTM Test, Xenometrix, Allschwil, Switzerland) was employed to assess mutagenicity, the Comet assay in vitro on the HaCat cell line and the Mammalian Chromosome Aberration Test were utilized to evaluate genotoxicity, and the XenoScreen® YES/YAS assay was applied to investigate endocrine disruption. The chemicals did not exhibit any positive responses for mutagenicity. However, the mammalian chromosome aberration test identified both chemicals as being positive for genotoxicity at 10 μg/mL. In the Comet assay, the percentage of DNA in the tail significantly increased in a concentration-dependent manner (at 5 and 10 μg/mL for Triclosan, at 2.5, 5, and 10 μg/mL for Triclocarban). The positive response depended on the increasing concentration and the duration of exposure. Triclosan, but not Triclocarban in any of the endocrine assays performed, indicated a potential for endocrine activity in the anti-estrogenic and anti-androgenic assays. The positive in vitro results detected were obtained for concentrations relevant to final products. The alarming findings obtained with the use of new-approach methodologies (NAMs) justify the current precautionary regulatory approach, limiting the use of these preservatives.
- Publikační typ
- časopisecké články MeSH
Animal testing has been prohibited for the safety assessment of cosmetic ingredients or finished products. Thus, alternative non-animal methods, followed by confirmatory clinical studies on human volunteers, should be used as the sole legally acceptable approach within the EU. The safety assessment of cosmetic products requires the involvement of multiple scientific disciplines, including analytical chemistry and biomedicine, as well as in chemico, in vitro and in silico toxicology. Recent data suggest that fragrance components may exert multiple adverse biological effects, e.g. cytotoxicity, skin sensitisation, (photo)genotoxicity, mutagenicity, reprotoxicity and endocrine disruption. Therefore, a pilot study was conducted with selected samples of fragrance-based products, such as deodorant, eau de toilette and eau de parfum, with the aim of integrating results from a number of alternative non-animal methods suitable for the detection of the following toxicological endpoints: cytotoxicity (with 3T3 Balb/c fibroblasts); skin sensitisation potential (in chemico method, DPRA); skin sensitisation potential (LuSens in vitro method, based on human keratinocytes); genotoxicity potential (in vitro Comet assay with 3T3 Balb/c cells); and endocrine disruption (in vitro YES/YAS assay). The presence of twenty-four specific known allergens in the products was determined by using GC-MS/MS. The strategies for estimation of the NOAEL of a mixture of allergens, which were proposed by the Scientific Committee on Consumer Products in their 'Opinion on Tea tree oil' document and by the Norwegian Food Safety Authority in their 'Risk Profile of Tea tree oil' report, were used as models for the NOAEL estimation of the mixtures of allergens that were identified in the individual samples tested in this study.
- MeSH
- alergeny toxicita analýza MeSH
- kosmetické přípravky * toxicita MeSH
- lidé MeSH
- parfém * analýza MeSH
- pilotní projekty MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- tandemová hmotnostní spektrometrie MeSH
- tea tree oil * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Precise control over the ultrasound field parameters experienced by biological samples during sonication experiments in vitro may be quite challenging. The main goal of this work was to outline an approach to construction of sonication test cells that would minimize the interaction between the test cells and ultrasound. METHODS: Optimal dimensions of the test cell were determined through measurements conducted in a water sonication tank using 3D-printed test objects. The offset of local acoustic intensity variability inside the sonication test cell was set to value of ±50% of the reference value (i.e., local acoustic intensity measured at last axial maximum in the free-field condition). The cytotoxicity of several materials used for 3D printing was determined using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. RESULTS: The sonication test cells were 3D printed from polylactic acid material, which was not toxic to the cells. Silicone membrane HT-6240, which was used to construct the bottom of the test cell, was found to reduce ultrasound energy minimally. Final ultrasound profiles inside the sonication test cells indicated the desired variability of local acoustic intensity. The cell viability in our sonication test cell was comparable to that of commercial culture plates with bottoms constructed with silicone membrane. CONCLUSION: An approach to construction of sonication test cells minimizing the interaction of the test cell and ultrasound has been outlined.
Ultraviolet (UV) radiation is a non-ionizing radiation, which has a cytotoxic potential, and it is therefore necessary to protect against it. Human skin is exposed to the longer-wavelength components of UV radiation (UVA and UVB) from the sun. In the present paper, we focused on the study of eight organic UV-absorbing compounds: astragalin, beta-carotene, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, hyperoside, 3-(4-methylbenzylidene)camphor, pachypodol, and trans-urocanic acid, as possible protectives of skin cells against UVA and UVB radiation. Their protective effects on skin cell viability, ROS production, mitochondrial membrane potential, liposomal permeability, and DNA integrity were investigated. Only some of the compounds studied, such as trans-urocanic acid and hyperoside, had a significant effect on the examined hallmarks of UV-induced cell damage. This was also confirmed by an atomic force microscopy study of morphological changes in HaCaT cells or a study conducted on a 3D skin model. In conclusion, hyperoside was found to be a very effective UV-protective compound, especially against UVA radiation. Commonly used sunscreen compounds such as 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, and 3-(4-methylbenzylidene)camphor turned out to be only physical UV filters, and pachypodol with a relatively high absorption in the UVA region was shown to be more phototoxic than photoprotective.
- MeSH
- kůže metabolismus MeSH
- kyselina urokanová * farmakologie MeSH
- lidé MeSH
- přípravky chránící proti slunci farmakologie MeSH
- ultrafialové záření * škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Photodynamic therapy is an alternative treatment mainly for cancer but also for bacterial infections. This treatment dates back to 1900 when a German medical school graduate Oscar Raab found a photodynamic effect while doing research for his doctoral dissertation with Professor Hermann von Tappeiner. Unexpectedly, Raab revealed that the toxicity of acridine on paramecium depends on the intensity of light in his laboratory. Photodynamic therapy is therefore based on the administration of a photosensitizer with subsequent light irradiation within the absorption maxima of this substance followed by reactive oxygen species formation and finally cell death. Although this treatment is not a novelty, there is an endeavor for various modifications to the therapy. For example, selectivity and efficiency of the photosensitizer, as well as irradiation with various types of light sources are still being modified to improve final results of the photodynamic therapy. The main aim of this review is to summarize anticancer and antibacterial modifications, namely various compounds, approaches, and techniques, to enhance the effectiveness of photodynamic therapy.
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- buněčná smrt MeSH
- fotochemoterapie * metody MeSH
- fotosenzibilizující látky farmakologie terapeutické užití MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Východiska: Zhodnocení léčebných výsledků a toxicity u pacientů s metastaticky kastračně rezistentním karcinomem prostaty (metastatic castration-resistant prostate carcinoma – mCRPC) léčených enzalutamidem nebo abirateronem po předchozí terapii docetaxelem. Pacienti a metody: Retrospektivní analýza 66 pacientů s mCRPC léčených enzalutamidem (55 pacientů) a abirateronem (11 pacientů) po předchozí terapii docetaxelem. Medián sledování pacientů byl 31,2 měsíce. Enzalutamid byl u pacientů aplikován v jedné denní perorální dávce 160 mg (4 tbl ? 40 mg). Abirateron byl u pacientů aplikován v jedné denní perorální dávce 1 000 mg (2 tbl ? 500 mg). Přežití bez známek progrese (progression-free survival – PFS) a celkové přežití (overall survival – OS) bylo vypočteno pomocí Kaplanovy-Meierovy analýzy. Vliv vybraných faktorů na OS byl zhodnocen pomocí regresní analýzy. Výsledky: Progrese byla zjištěna u 55 pacientů (83 %), medián PFS u nemocných léčených po podání chemoterapie činil 12,1 měsíce (95% CI 7,7–16,4). Celkem zemřelo 43 pacientů (65 %), medián OS u nemocných léčených po podání chemoterapie činil 21,9 měsíce (95% CI 12,2–31,7). V regresní analýze jsme prokázali statisticky prognosticky příznivý významný vliv na OS u pacientů s poklesem prostatického specifického antigenu (PSA) ≥ 50 %, u pacientů s časným poklesem PSA ≥ 50 % v průběhu 3 měsíců od zahájení léčby preparáty cílenými na androgenní receptory (androgen-receptor targeted agents (ARTA), u pacientů bez viscerálního metastatického postižení, u pacientů předléčených jedním režimem chemoterapie a u nemocných bez vzniku anemie v průběhu léčby ARTA. Neprokázali jsme vliv hodnot Gleasonova skóre, věku ani délky předchozí androgen-deprivační terapie na OS. Toxicita stupně 3–4 byla popsána u 45,5 % léčených enzalutamidem a u 36,3 % pacientů léčených abirateronem. Závěr: Naše analýza prokázala účinnost léčby enzalutamidem a abirateronem u pacientů s mCRPC po předchozí terapii docetaxelem.
Background: The evaluation of treatment outcomes and toxicity in patients with metastatic castration-resistant prostate cancer (mCRPC) treated by enzalutamide or abiraterone after previous docetaxel. Patients and methods: We analyzed 66 patients with mCRPC treated by enzalutamide (55 patients) or abiraterone (11 patients) after previous therapy with docetaxel. The median follow-up was 31.2 months. Enzalutamide and abiraterone were administered in daily doses of 160 mg and 1,000 mg per day, respectively. The progression free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier analysis. The prognostic influence of the factors on OS was evaluated by regression analysis. Results: The progression was observed in 55 (83%) patients, and mPFS was 12.1 (95% CI 7.7–16.4) months. In total, 43 patients died, and he median OS was 21.9 (95% CI 12.2–31.7) months. In the regression analysis, we observed statistical favorable influence of the following factors on OS: PSA decrease ≥ 50%, in patients with early decrease of prostatic specific antigen (PSA) ≥ 50% in 3 months after initiation of enzalutamide or abiraterone treatment, in patients with visceral metastatic sites, in patients treated with only one regimen of previous chemotherapy and in those without anemia. We observed the toxicity grades 3–4 in 45.5% and 36.3% patients treated with enzalutamide and abiraterone, respectively. Conclusion: Our analysis demonstrated efficacy and good tolerance in patients with mCRPC treated with enzalutamide and abiraterone after previous docetaxel therapy.
- Klíčová slova
- enzalutamid,
- MeSH
- abirateron farmakologie terapeutické užití MeSH
- analýza přežití MeSH
- antagonisté androgenů farmakologie klasifikace terapeutické užití MeSH
- cílená molekulární terapie MeSH
- docetaxel farmakologie terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty rezistentní na kastraci * diagnóza farmakoterapie sekundární MeSH
- prostatický specifický antigen analýza MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
