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1.
Int J Mol Sci ; 25(19)2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39409110

RESUMO

Triple-negative breast cancer (TNBC) is a challenging subtype of breast cancer characterized by the absence of estrogen and progesterone receptors and HER2 expression, leading to limited treatment options and a poorer prognosis. TNBC is particularly prevalent in premenopausal African-descent women and is associated with aggressive tumor behavior and higher metastatic potential. Tumor-associated macrophages (TAMs) are abundantly present within the TNBC microenvironment and play pivotal roles in promoting tumor growth, progression, and metastasis through various mechanisms, including immune suppression and enhancement of angiogenesis. This review provides an in-depth overview of TNBC, focusing on its epidemiology, its molecular characteristics, and the critical influence of TAMs. It discusses the pathological and molecular aspects that define TNBC's aggressive nature and reviews current and emerging therapeutic strategies aimed at targeting these dynamics. Special attention is given to the role of TAMs, exploring their potential as therapeutic targets due to their significant impact on tumor behavior and patient outcomes. This review aims to highlight the complexities of the TNBC landscape and to present the innovative approaches that are currently being pursued to improve therapeutic efficacy and patient survival.


Assuntos
Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Macrófagos Associados a Tumor , Humanos , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Feminino , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Animais
2.
Int J Mol Sci ; 25(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38892243

RESUMO

This research paper presents a novel approach to identifying biomarkers that can be used to prognosticate patients with triple-negative breast cancer (TNBC) eligible for neoadjuvant therapy. The study utilized survival and RNA sequencing data from a cohort of TNBC patients and identified 276 genes whose expression was related to survival in such patients. The gene expression data were then used to classify patients into two major groups based on the presence or absence of Wingless/Integrated-pathway (Wnt-pathway) and mesenchymal (Mes) markers (Wnt/Mes). Patients with a low expression of Wnt/Mes-related genes had a favorable outcome, with no deaths observed during follow-up, while patients with a high expression of Wnt/Mes genes had a higher mortality rate of 50% within 19 months. The identified gene list could be validated and potentially used to shape treatment options for TNBC patients eligible for neoadjuvant therapy providing valuable insights into the development of more effective treatments for TNBC. Our data also showed significant variation in gene expression profiles before and after chemotherapy, with most tumors switching to a more mesenchymal/stem cell-like profile. To verify this observation, we performed an in silico analysis to classify breast cancer tumors in Prediction Analysis of Microarray 50 (PAM50) molecular classes before treatment and after treatment using gene expression data. Our findings demonstrate that following drug intervention and metastasis, certain tumors undergo a transition to alternative subtypes, resulting in diminished therapeutic efficacy. This underscores the necessity for reevaluation of patients who have experienced relapse or metastasis post-chemotherapy, with a focus on molecular subtyping. Tailoring treatment strategies based on these refined subtypes is imperative to optimize therapeutic outcomes for affected individuals.


Assuntos
Biomarcadores Tumorais , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética , Neoplasia Residual/genética , Neoplasia Residual/tratamento farmacológico , Terapia Neoadjuvante/métodos , Prognóstico , Metástase Neoplásica , Pessoa de Meia-Idade , Perfilação da Expressão Gênica/métodos
3.
Folia Med Cracov ; 64(2): 51-62, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39324677

RESUMO

Glaucoma is a disease that leads to optic nerve damage and irreversible loss of the visual field. Gonioscopy-assisted transluminal trabeculotomy (GATT) is a minimally invasive glaucoma surgery technique, where the surgeon opens the trabecular network and Schlemm's canal to improve the outflow of the aqueous humor. This method has shown efficacy in reducing intraocular pressure in patients with primary and secondary glaucoma. GATT has gained popularity due to its minimally invasive nature, compatibility with cataract surgery and relatively low cost. Despite its advantages, the procedure can be associated with many complications such as hyphema, intraocular pressure spikes and corneal edema. In rare cases, it can lead to Descemet's membrane detachment or cystoid macular edema. The success of GATT procedure mostly depends on the surgeon's skill and experience, but also on the patient's risk factors, including age and preoperative intraocular pressure levels. Further studies are required to understand long outcomes and identify the patients, who may be at higher risk of complications.


Assuntos
Glaucoma , Gonioscopia , Pressão Intraocular , Trabeculectomia , Humanos , Trabeculectomia/métodos , Trabeculectomia/efeitos adversos , Glaucoma/cirurgia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
4.
Folia Med Cracov ; 64(2): 77-86, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39324680

RESUMO

The present study sought to investigate the effects of chronic prenatal alcohol exposure (PAE) on nociceptive responses to mechanical and thermal stimuli in rats. The Von Frey and Hot Plate tests were employed to assess the nociceptive responses of 10 control rats and 7 experimental rats whose mothers had been administered ethanol from day 5 to day 20 of gestation. In healthy animals, a decrease in pain sensitivity was observed between days 28 and 70, which was not observed in the experimental group. The findings also indicated that rats with PAE exhibited diminished sensitivity to nociceptive stimuli during the early postnatal period, as evidenced by a higher threshold response to mechanical stimuli at day 28 than in the control group. However, those observations did not apply to thermal stimuli. It appears that this may be a result of distinctiveness in neural pain pathways for particular stimuli at the receptor or ion channel level, while a disruption in the equilibrium between the sympathetic and parasympathetic nervous systems may be a contributing factor. The results of this study highlight a critical aspect of the harmful systemic effects of alcohol, while also underscoring the need for further research to elucidate the underlying mechanisms, including the role of the hypothalamic-pituitary-adrenal axis and the serotonergic system in modulating pain responses in individuals prenatally exposed to alcohol.


Assuntos
Etanol , Efeitos Tardios da Exposição Pré-Natal , Animais , Gravidez , Feminino , Ratos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Etanol/efeitos adversos , Limiar da Dor , Medição da Dor , Nociceptividade/fisiologia , Nociceptividade/efeitos dos fármacos , Ratos Wistar , Modelos Animais de Doenças
5.
Molecules ; 28(24)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38138511

RESUMO

Defatted seed residues after the extraction of rose oil have their potential not fully described in the existing literature. The aim of this study was to determine and characterize the components important for the human body that are found in Rosa rugosa defatted seeds, including dietary fibers, proteins, selected minerals, polyphenols and antioxidant activity. Rosa rugosa seeds defatted with CO2 in supercritical conditions are a rich source of dietary fibers (approx. 65%) and proteins (15%); their macronutrients include the following: Ca (175.9), Mg (83.9), K (199.2) and Na (3.5 mg/100 g). They also contain polyphenols, including flavanols (0.9%) and total ellagic acid (0.5%), and they exhibit antioxidant activity (143.8 µM TAEC/g). Tellimagrandin I and II and rugosin A were found in the extracts, and ellagitannins with a yet-indeterminate structure were also present. The seeds also contained ellagitannin derivatives-galloyl-HHDP-glucose and bis-HHDP-glucose-at the same time, and they are characterized by a low-fat content-0.4%. The energy value of defatted rose seeds is about half the energy value of popular seeds used in the food industry. The findings of the present study suggest that defatted rosehip seeds, the by-product of rosehip processing, could be an important source of bioactive components like dietary fibers, flavanols, ellagitannins and mineral compounds. Therefore, defatted rose seeds are very promising and require further research, because they can potentially be used as a natural source of chemopreventive agents.


Assuntos
Antioxidantes , Rosa , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Rosa/química , Taninos Hidrolisáveis , Polifenóis/química , Minerais , Fibras na Dieta , Glucose
6.
Folia Med Cracov ; 62(3): 51-61, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36309831

RESUMO

Colorectal cancer (CRC) is the third most common malignancy worldwide and the second most deadly cancer. Scientists have projected that by 2040, the prevalence will reach up to 3.2 million new cases annually due to population aging, disadvantageous diet transformations, and elevated exposure to risk factors. In the past decades, the five-year survival rate in colorectal cancer has significantly increased to 65% due to the development of an early endoscopic diagnosis and new chemotherapeutic approaches. Fluoropyrimidines, such as 5-fluorouracil or capecitabine, are commonly used to treat CRC. One of the most fundamental mechanisms of 5-FU is based on the inhibition of thymidylate synthase. This action is responsible for the therapeutic, but also toxic, effects of the drug. In this short review, we discuss the possible effects of vitamin D activity on colorectal cancer cells in relation to fluoropyrimidines. PubMed, Embase, and Web of Science databases were searched up to January 2022 for studies on vitamin D and 5-fluorouracil interaction mechanisms. Original studies, case reports, and review articles were included. Vitamin D or its analogs target multiple biochemical pathways and modulate numerous pathophysiological mechanisms in the course of colon cancer, including those related to the pharmacological sites of fluoropyrimidines. However, the available data concerning vitamin D-fluoropyrimidine pharmacological interactions are limited, especially regarding patients suffering from colon cancer and being treated with fluoropyrimidines.s.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Vitamina D/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Fluoruracila/efeitos adversos , Capecitabina/efeitos adversos , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/tratamento farmacológico
7.
Int Arch Occup Environ Health ; 94(3): 487-494, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33156392

RESUMO

PURPOSE: Nail technicians (NTs) are exposed to a low-level mixture of volatile organic solvents (VOCs), yet the health hazards related to such exposure are unknown. This study thus aimed to compare the blood plasma levels of selected biomarkers related to liver status and lipid profile among occupationally exposed NTs and unexposed controls. Associations between out-of-normal-range levels of such biomarkers and occupational exposure to VOCs mixture have also been investigated. METHODS: The study enrolled 145 female NTs and 152 unexposed controls. Biochemical analyses were performed using spectrophotometric assays and obtained data were analyzed using general linear model and Poisson regression modelling adjusted to multiple confounders. RESULTS: Compared to controls, NTs presented significantly increased plasma activities of ALT (2.04 ± 0.63 ln-U/l vs. 1.25 ± 0.71 ln-U/l; p < 0.0001) and AST (2.73 ± 0.25 ln-U/l vs. 2.08 ± 0.95 ln-U/l; p < 0.0001), and significantly increased plasma levels of TG (4.38 ± 0.53 ln-mg/dl vs. 4.21 ± 0.42 ln-mg/dl; p < 0.05) and TC/HDL ratio (1.18 ± 0.36 vs. 1.02 ± 0.27; p < 0.0005). Plasma levels of HDL were significantly lower among NTs (4.02 ± 0.29 ln-mg/dl vs. 4.21 ± 0.26 ln-mg/dl; p < 0.0001). Moreover, NTs were found to present significantly increased risk of occurrence of clinically relevant plasma HDL levels below 3.91 ln-mg/dl (i.e., 50 mg/dl; RR = 1.58, 95% CI 1.07-2.32, p < 0.05), as well as increased risk of clinically relevant TC/HDL ratio above the normal range limit of 3.5 (RR = 1.68, 95% CI 1.19-2.35, p < 0.005), as compared to unexposed controls. CONCLUSION: Nail technicians are subject to adverse changes in selected plasma biomarkers related to liver functions, some of which may be of clinical relevance.


Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Indústria da Beleza , Exposição Ocupacional/efeitos adversos , Compostos Orgânicos Voláteis/efeitos adversos , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Colesterol/sangue , Feminino , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Fígado , Pessoa de Meia-Idade , Unhas , Triglicerídeos/sangue , Adulto Jovem
8.
Molecules ; 26(2)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440790

RESUMO

Zeolite Y is one of the earliest known and most widely used synthetic zeolites. Many experimental investigations verify the valuable ion exchange capability of this zeolite. In this study, we assessed the effects of ion exchange on its vibrational spectra. We applied classical lattice dynamics methods for IR and Raman intensity calculations. Computed spectra of optimized zeolite Y structures with different cations were compared with experimental data. The spectra obtained in this study are in agreement with previous experimental and computational studies on zeolites from the faujasite group.


Assuntos
Zeolitas/química , Troca Iônica , Íons/química , Modelos Moleculares , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman
9.
Psychol Res ; 84(6): 1507-1516, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30864001

RESUMO

We performed a registered replication of the Oberman and Ramachandran (Soc Neurosci 3(3-4):348-355, 2008) study on the 'kiki/bouba' effect in autism spectrum conditions (ASC). The aim of the study was to test the robustness of the diminished crossmodal correspondences effect in autism, but also to verify whether this effect is not an artifact of differences in intelligence. We tested a Polish-speaking sample of 21 participants with ADOS-confirmed autism spectrum conditions (mean age 15.90) and 21 age- (mean age 15.86), sex- and IQ-matched neurotypical control participants. Procedure closely followed the replicated study. Participants' task was to match five pairs of unfamiliar words and shapes. Matching words and shapes had similar supramodal characteristics that allowed the match. We report partial replication of the diminished 'kiki/bouba' effect in individuals with ASC compared to the neurotypical control group. However, we found that nonverbal intelligence also significantly contributed to task performance, but only in participants with autism, suggesting a compensatory role of intelligence. Finally, the effect of autism severity (measured by ADOS classification) was significant-crossmodal correspondences were weaker in individuals with autism, compared to those with autism spectrum diagnosis.


Assuntos
Percepção Auditiva , Transtorno do Espectro Autista/psicologia , Percepção Espacial , Adolescente , Transtorno do Espectro Autista/diagnóstico , Estudos de Casos e Controles , Feminino , Humanos , Inteligência , Masculino , Desempenho Psicomotor
10.
Psychol Res ; 84(1): 245-258, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29464316

RESUMO

The aim of the study was not only to demonstrate whether eye-movement-based task decoding was possible but also to investigate whether eye-movement patterns can be used to identify cognitive processes behind the tasks. We compared eye-movement patterns elicited under different task conditions, with tasks differing systematically with regard to the types of cognitive processes involved in solving them. We used four tasks, differing along two dimensions: spatial (global vs. local) processing (Navon, Cognit Psychol, 9(3):353-383 1977) and semantic (deep vs. shallow) processing (Craik and Lockhart, J Verbal Learn Verbal Behav, 11(6):671-684 1972). We used eye-movement patterns obtained from two time periods: fixation cross preceding the target stimulus and the target stimulus. We found significant effects of both spatial and semantic processing, but in case of the latter, the effect might be an artefact of insufficient task control. We found above chance task classification accuracy for both time periods: 51.4% for the period of stimulus presentation and 34.8% for the period of fixation cross presentation. Therefore, we show that task can be to some extent decoded from the preparatory eye-movements before the stimulus is displayed. This suggests that anticipatory eye-movements reflect the visual scanning strategy employed for the task at hand. Finally, this study also demonstrates that decoding is possible even from very scant eye-movement data similar to Coco and Keller, J Vis 14(3):11-11 (2014). This means that task decoding is not limited to tasks that naturally take longer to perform and yield multi-second eye-movement recordings.


Assuntos
Cognição/fisiologia , Movimentos Oculares/fisiologia , Aprendizagem/fisiologia , Comportamento Espacial/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Int J Mol Sci ; 22(1)2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374571

RESUMO

In various diseases, there is an increased production of the free radicals needed to carry out certain physiological processes but their excessive amounts can cause oxidative stress and cell damage. Enzymes play a major role in the transformations associated with free radicals. One of them is nitric oxide synthase (NOS), which catalyzes the formation of nitric oxide (NO). This enzyme exists in three forms (NOS1, NOS2, NOS3), each encoded by a different gene. The following work presents the most important information on the NOS isoforms and their role in the human body, including NO synthesis in various tissues and cells, intercellular signaling and activities supporting the immune system and regulating blood vessel functions. The role of NOS in pathological conditions such as obesity, diabetes and heart disease is considered. Attention is also paid to the influence of the polymorphisms of these genes, encoding particular isoforms, on the development of these pathologies and the role of NOS inhibitors in the treatment of patients.


Assuntos
Suscetibilidade a Doenças , Inibidores Enzimáticos/farmacologia , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Polimorfismo Genético , Animais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Ativação Enzimática , Inibidores Enzimáticos/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Resistência à Insulina , Isoenzimas , Terapia de Alvo Molecular , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/química , Obesidade/etiologia , Obesidade/metabolismo , Estresse Oxidativo , Polimorfismo de Nucleotídeo Único , Relação Estrutura-Atividade
12.
Int J Mol Sci ; 21(14)2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32679799

RESUMO

Proteins, as a major component of organisms, are considered the preferred biomaterials for drug delivery vehicles. Hemoglobin (Hb) has been recently rediscovered as a potential drug carrier, but its use for biomedical applications still lacks extensive investigation. To further explore the possibility of utilizing Hb as a potential tumor targeting drug carrier, we examined and compared the biodistribution of Hb in healthy and lung tumor-bearing mice, using for the first time 89Zr labelled Hb in a positron emission tomography (PET) measurement. Hb displays a very high conjugation yield in its fast and selective reaction with the maleimide-deferoxamine (DFO) bifunctional chelator. The high-resolution X-ray structure of the Hb-DFO complex demonstrated that cysteine ß93 is the sole attachment moiety to the αß-protomer of Hb. The Hb-DFO complex shows quantitative uptake of 89Zr in solution as determined by radiochromatography. Injection of 0.03 mg of Hb-DFO-89Zr complex in healthy mice indicates very high radioactivity in liver, followed by spleen and lungs, whereas a threefold increased dosage results in intensification of PET signal in kidneys and decreased signal in liver and spleen. No difference in biodistribution pattern is observed between naïve and tumor-bearing mice. Interestingly, the liver Hb uptake did not decrease upon clodronate-mediated macrophage depletion, indicating that other immune cells contribute to Hb clearance. This finding is of particular interest for rapidly developing clinical immunology and projects aiming to target, label or specifically deliver agents to immune cells.


Assuntos
Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos , Hemoglobinas/farmacocinética , Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Animais , Linhagem Celular Tumoral , Complexos de Coordenação/química , Complexos de Coordenação/farmacocinética , Desferroxamina/análogos & derivados , Desferroxamina/farmacocinética , Portadores de Fármacos/química , Feminino , Hemoglobinas/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos/química , Radioisótopos/farmacocinética , Distribuição Tecidual , Zircônio/química , Zircônio/farmacocinética
13.
Sensors (Basel) ; 19(10)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126117

RESUMO

Existing research has shown that human eye-movement data conveys rich information about underlying mental processes, and that the latter may be inferred from the former. However, most related studies rely on spatial information about which different areas of visual stimuli were looked at, without considering the order in which this occurred. Although powerful algorithms for making pairwise comparisons between eye-movement sequences (scanpaths) exist, the problem is how to compare two groups of scanpaths, e.g., those registered with vs. without an experimental manipulation in place, rather than individual scanpaths. Here, we propose that the problem might be solved by projecting a scanpath similarity matrix, obtained via a pairwise comparison algorithm, to a lower-dimensional space (the comparison and dimensionality-reduction techniques we use are ScanMatch and t-SNE). The resulting distributions of low-dimensional vectors representing individual scanpaths can be statistically compared. To assess if the differences result from temporal scanpath features, we propose to statistically compare the cross-validated accuracies of two classifiers predicting group membership: (1) based exclusively on spatial metrics; (2) based additionally on the obtained scanpath representation vectors. To illustrate, we compare autistic vs. typically-developing individuals looking at human faces during a lab experiment and find significant differences in temporal scanpath features.


Assuntos
Algoritmos , Movimentos Oculares/fisiologia , Adolescente , Adulto , Transtorno do Espectro Autista/patologia , Criança , Face/fisiologia , Feminino , Humanos , Masculino , Método de Monte Carlo , Estimulação Luminosa , Adulto Jovem
14.
BMC Cancer ; 17(1): 728, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29115935

RESUMO

BACKGROUND: MicroRNAs may act as oncogenes or tumour suppressor genes, which make these small molecules potential diagnostic/prognostic factors and targets for anticancer therapies. Several common oncogenic microRNAs have been found for canine mammary cancer and human breast cancer. On account of this, large-scale profiling of microRNA expression in canine mammary cancer seems to be important for both dogs and humans. METHODS: Expression profiles of 317 microRNAs in 146 canine mammary tumours of different histological type, malignancy grade and clinical history (presence/absence of metastases) and in 25 control samples were evaluated. The profiling was performed using microarrays. Significance Analysis of Microarrays test was applied in the analysis of microarray data (both unsupervised and supervised data analyses were performed). Validation of the obtained results was performed using real-time qPCR. Subsequently, predicted targets for the microRNAs were searched for in miRBase. RESULTS: Results of the unsupervised analysis indicate that the primary factor separating the samples is the metastasis status. Predicted targets for microRNAs differentially expressed in the metastatic vs. non-metastatic group are mostly engaged in cell cycle regulation, cell differentiation and DNA-damage repair. On the other hand, the supervised analysis reveals clusters of differentially expressed microRNAs unique for the tumour type, malignancy grade and metastasis factor. CONCLUSIONS: The most significant difference in microRNA expression was observed between the metastatic and non-metastatic group, which suggests a more important role of microRNAs in the metastasis process than in the malignant transformation. Moreover, the differentially expressed microRNAs constitute potential metastasis markers. However, validation of cfa-miR-144, cfa-miR-32 and cfa-miR-374a levels in blood samples did not follow changes observed in the non-metastatic and metastatic tumours.


Assuntos
Doenças do Cão/genética , Perfilação da Expressão Gênica/veterinária , Neoplasias Mamárias Animais/genética , MicroRNAs/genética , Animais , Cães , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias Mamárias Animais/patologia , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos/veterinária
15.
Molecules ; 22(2)2017 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-28208720

RESUMO

Feline injection-site sarcomas are malignant skin tumours with a high local recurrence rate, ranging from 14% to 28%. The treatment of feline injection-site sarcomas includes radical surgery, radiotherapy and/or chemotherapy. In our previous study it has been demonstrated that doxorubicin conjugated to glutathione-stabilized gold nanoparticles (Au-GSH-Dox) has higher cytotoxic effects than free doxorubicin for feline fibrosarcoma cell lines with high glycoprotein P activity (FFS1, FFS3). The aim of the present study was to assess the effectiveness of intratumoural injection of Au-GSH-Dox on the growth of tumours from the FFS1 and FFS3 cell lines on chick embryo chorioallantoic membrane. This model has been utilized both in human and veterinary medicine for preclinical oncological studies. The influence of intratumoural injections of Au-GSH-Dox, glutathione-stabilized gold nanoparticles and doxorubicin alone on the Ki-67 proliferation marker was also checked. We demonstrated that the volume ratio of tumours from the FFS1 and FFS3 cell lines was significantly (p < 0.01) decreased after a single intratumoural injection of Au-GSH-Dox, which confirms the positive results of in vitro studies and indicates that Au-GSH-Dox may be a potent new therapeutic agent for feline injection-site sarcomas.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Membrana Corioalantoide/patologia , Doxorrubicina/administração & dosagem , Glutationa , Ouro , Nanopartículas Metálicas , Sarcoma/patologia , Animais , Biomarcadores , Gatos , Linhagem Celular Tumoral , Embrião de Galinha , Modelos Animais de Doenças , Glutationa/química , Ouro/química , Injeções Intralesionais , Nanopartículas Metálicas/química , Sarcoma/tratamento farmacológico , Sarcoma/metabolismo , Carga Tumoral/efeitos dos fármacos
16.
Cogn Process ; 18(3): 335-342, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28364341

RESUMO

By allocating less attention to predictable events we are able to focus on novel, unpredictable and unexpected events that require more extensive processing. This strategy should result in improved performance by optimizing the use of brain's limited resources. Participants' task was to look at two types of stimuli presented simultaneously at the opposite sides of a computer screen: "static" stimuli, i.e. emotionally neutral photographs; and "dynamic" stimuli, i.e. video clips presenting a moving dot. The dot moved along a predictable, semi-predictable or random trajectory. This was followed by a memory test of the static stimuli. Participants spent more time looking at the dynamic stimuli when its trajectory was less predictable. Additionally, participants who readily adjusted their dwell time allocation to the dot trajectory performed better in the memory test, as demonstrated by a positive correlation between memory test sensitivity and the rate of eye movement patterns adjustment to stimulus predictability. This suggests that people adjust gaze duration to stimulus predictability and that doing so optimizes attentional resource allocation and improves performance. However, study design did not allow to distinguish between spatial and temporal predictability, so it is impossible to estimate the impact of each type of predictability specifically.


Assuntos
Atenção/fisiologia , Memória , Percepção Visual/fisiologia , Adulto , Emoções , Medições dos Movimentos Oculares , Movimentos Oculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção de Movimento/fisiologia , Adulto Jovem
17.
Mediators Inflamm ; 2016: 5230219, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27212807

RESUMO

Recent studies indicate the critical role of tumour associated macrophages, tumour associated neutrophils, dendritic cells, T lymphocytes, and natural killer cells in tumourigenesis. These cells can have a significant impact on the tumour microenvironment via their production of cytokines and chemokines. Additionally, products secreted from all these cells have defined specific roles in regulating tumour cell proliferation, angiogenesis, and metastasis. They act in a protumour capacity in vivo as evidenced by the recent studies indicating that macrophages, T cells, and neutrophils may be manipulated to exhibit cytotoxic activity against tumours. Therefore therapy targeting these cells may be promising, or they may constitute drug or anticancer particles delivery systems to the tumours. Herein, we discussed all these possibilities that may be used in cancer treatment.


Assuntos
Neoplasias/terapia , Animais , Humanos , Macrófagos/metabolismo , Macrófagos/fisiologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neutrófilos/metabolismo , Neutrófilos/fisiologia , Linfócitos T/metabolismo , Linfócitos T/fisiologia , Microambiente Tumoral/imunologia
18.
Chemistry ; 21(50): 18109-21, 2015 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-26531227

RESUMO

Migrastatin and isomigrastatin analogues have been synthesised in order to contribute to structure-activity studies on tumour cell migration inhibitors. These include macrocycles varying in ring size, functionality and alkene stereochemistry, as well as glucuronides. The synthesis work included application of the Saegusa-Ito reaction for regio- and stereoselective unsaturated macroketone formation, diastereoselective Brown allylation to generate 9-methylmigrastatin analogues and chelation-induced anomerisation to vary glucuronide configuration. Compounds were tested in vitro against both breast and pancreatic cancer cell lines and inhibition of tumour cell migration was observed in both wound-healing (scratch) and Boyden chamber assays. One unsaturated macroketone showed low affinity for a range of secondary drug targets, indicating it is at low risk of displaying adverse side effects.


Assuntos
Alcenos/química , Movimento Celular/efeitos dos fármacos , Glucuronídeos/química , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacologia , Macrolídeos/química , Macrolídeos/farmacologia , Neoplasias Pancreáticas/química , Piperidonas/química , Piperidonas/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Relação Estrutura-Atividade
19.
Chemistry ; 21(50): 17993, 2015 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-26537992

RESUMO

Invited for the cover of this issue are Paul V. Murphy and co-workers at the National University of Ireland Galway (NUI Galway) and Warsaw University. The image depicts MGSTA-6 giving a stop signal to tumour cells that are on the move. Read the full text of the article at 10.1002/chem.201502861.


Assuntos
Movimento Celular/efeitos dos fármacos , Compostos Macrocíclicos/química , Macrolídeos/síntese química , Macrolídeos/farmacologia , Piperidonas/síntese química , Piperidonas/farmacologia , Linhagem Celular Tumoral , Humanos , Macrolídeos/química , Estrutura Molecular , Piperidonas/química , Relação Estrutura-Atividade
20.
BMC Cancer ; 15: 657, 2015 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-26446998

RESUMO

BACKGROUND: Since targeting oxidative stress markers has been recently recognized as a novel therapeutic target in cancer, it is interesting to investigate whether genetic susceptibility may modify oxidative stress response in cancer. The aim of this study was to elucidate whether genetic polymorphism in the antioxidant enzymes is associated with lipid peroxidation in breast cancer. METHODS: We conducted a study among Polish women, including 136 breast cancer cases and 183 healthy controls. The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium - an antioxidant trace element involved in cancer. Genotyping was performed using the Real Time PCR. Lipid peroxidation was expressed as plasma concentration of thiobarbituric acid reactive substances (TBARS) and measured with the spectrofluorometric method. Glutathione peroxidase activity was spectrophotometrically determined in erythrocytes (GPx1) and plasma (GPx3) by the use of Paglia and Valentine method. Spectrophotometric methods were employed to measure activity of cytosolic superoxide dismutase (SOD1) in erythrocytes (Beauchamp and Fridovich method) and ceruloplasmin (Cp) in plasma (Sunderman and Nomoto method). Plasma selenium concentration was determined using graphite furnace atomic absorption spectrophotometry. RESULTS: Breast cancer risk was significantly associated with GPX1 rs1050450 (Pro198Leu) polymorphism, showing a protective effect of variant (Leu) allele. As compared to the control subjects, lipid peroxidation and GPx1 activity were significantly higher in the breast cancer cases, whereas ceruloplasmin activity was decreased. After genotype stratification, both GPx1 activity and TBARS concentration were the highest in GPX1 Pro/Pro homozygotes affected by breast cancer. At the same time, there was a significant correlation between the level of lipid peroxidation and GPx1 activity among the cancer subjects possessing GPX1 Pro/Pro genotype (r = 0.3043; p = 0.0089), whereas such a correlation was completely absent in the cases carrying at least one GPX1 Leu allele as well as in the controls (regardless of GPX1 genotype). CONCLUSIONS: GPX1 polymorphism may be an important factor modifying oxidative stress response in breast cancer subjects. Further studies are needed to elucidate its potential clinical significance.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos , Polimorfismo de Nucleotídeo Único , Adulto , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Ativação Enzimática , Feminino , Genes BRCA1 , Humanos , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Estadiamento de Neoplasias , Estresse Oxidativo , Fatores de Risco , Selenoproteínas/genética , Selenoproteínas/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico , Glutationa Peroxidase GPX1
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