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1.
Exp Cell Res ; 430(1): 113715, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37429373

RESUMO

In cancer, cell migration contributes to the spread of tumor cells resulting in metastasis. Heterogeneity in the migration capacity can produce individual cells with heightened capacity leading to invasion and metastasis. Our hypothesis is that cell migration characteristics can divide asymmetrically in mitosis, allowing a subset of cells to have a larger contribution to invasion and metastasis. Therefore, our aim is to elucidate whether sister cells have different migratory capacity and analyze if this difference is defined by mitosis. Through time-lapse videos, we analyzed migration speed, directionality, maximum displacement of each trajectory, and velocity as well as cell area and polarity and then compared the values between mother-daughter cells and between sister cells of three tumor cell lines (A172, MCF7, SCC25) and two normal cell lines (MRC5 and CHO·K1 cells). We observed that daughter cells had a different migratory phenotype compared to their mothers, and one single mitosis is enough for the sisters behave like nonrelated cells. However, mitosis did not influence cell area and polarity dynamics. These findings indicates that migration performance is not heritable, and that asymmetric cell division might have an important impact on cancer invasion and metastasis, by producing cells with different migratory capacity.


Assuntos
Mitose , Células-Tronco , Movimento Celular , Divisão Celular Assimétrica , Linhagem Celular Tumoral
2.
J Oral Pathol Med ; 52(9): 877-884, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37549991

RESUMO

BACKGROUND: Considering that microRNAs (miRNAs), extracellular vesicles and particles (EVPs) and the amyloid precursor protein (APP) processing have been shown to be altered in oral squamous cells carcinoma (OSCC), it is possible that miRNAs that target APP processing pathways in EVPs are impacted in tumor cells. Our aim was to evaluate miRNAs that target APP itself or disintegrin and metalloproteinase domain 10 (ADAM10), which generate a trophic compound, sAPPα, in EVPs derived from OSCC cell lines, an aggressive and non-invasive, compared to normal keratinocytes. METHODS: We used two OSCC cell lines, an aggressive human oral squamous cell carcinoma cell line (SCC09) and a less aggressive cell line (CAL27) compared with a keratinocyte lineage (HaCaT). Cells were maintained in cell media, from which we isolated EVPs. EVPs were evaluated regarding their size and concentration using Nanotracking Analysis. We measured the levels of miRNAs which had as potential downstream target APP or ADAM10, specifically miR-20a-5p, miR-103a-3p, miR-424-5p, miR-92b-3p, miR-31-5p, and miR-93-5. RESULTS: There were no differences on size distributions and concentration of isolated EVPs. OSCC cell lines-derived EVPs miR-20a-5p, miR-92b-3p, and miR-93-5p were upregulated in comparison to HaCaT-derived EVPs; while miR-31-5p was reduced in EVPs obtained from CAL27 cells. CONCLUSION: Our results indicate changes in miRNAs that target APP machinery processing in EVPs derived from OSCC cell lines of different aggressiveness, which may be involved with abnormal miRNA expression in OSCC tissue and/or releasing tumor suppressor miRNA.


Assuntos
Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Humanos , MicroRNAs/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Neoplasias Bucais/patologia , Neoplasias de Cabeça e Pescoço/genética , Células Epiteliais/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética
3.
Phytother Res ; 37(11): 5354-5365, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37583121

RESUMO

We evaluated the impact of an Achyrocline satureioides inflorescence infusion on the clinical outcomes of viral respiratory infections, including those caused by SARS-CoV-2, in a monocentric, randomized, open-label, placebo-controlled clinical trial. Patients with symptoms of viral respiratory infection, including suspected cases of COVID-19, were included and assigned to receive either A. satureioides (n = 57) or Malus domestica (n = 67) infusions twice a day for 14 days. All participants were included before the RT-PCR results, performed using a nasopharyngeal swab. The patients were further divided into subgroups according to real-time polymerase chain reaction results: SARS-CoV-2-positive and SARS-CoV-2-negative subgroups for statistical analyses. We assessed clinical outcomes, such as the latency to resolution of cough, dyspnea, fever, sore throat, chest pain, smell and taste dysfunctions, diarrhea, nausea, abdominal pain, and loss of appetite; hospitalization; and mortality with questionnaires and medical records. The subjects that received early A. satureioides infusion showed a significant reduction in the average number of days with respiratory and neurological symptoms compared with the control group (M. domestica infusion). We conclude that A. satureioides is a safe agent and, in combination with standard care, improves viral respiratory infection symptoms, especially those related to COVID-19.


Assuntos
Achyrocline , COVID-19 , Humanos , SARS-CoV-2 , Projetos de Pesquisa , Terapia Combinada , Resultado do Tratamento
4.
Lasers Med Sci ; 37(9): 3571-3581, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36125659

RESUMO

The aim of the present study was to analyze for the first time the effect of photobiomodulation therapy (PBMT) using defocused high-power laser (DHPL) in myoblast cell line C2C12 viability and migration and compare them with low-power laser therapy. Cells were divided into 9 groups: Sham irradiation 10% fetal bovine serum (FBS); Sham irradiation 5%FBS; low-power laser 0.1 W; DHPL 810 1 W; DHPL 810 2 W; DHPL 980 1 W; DHPL 980 2 W; DHPL dual 1 W; DHPL dual 2 W. To simulate stress conditions, all groups exposed to irradiation were maintained in DMEM 5% FBS. The impact of therapies on cell viability was assessed through sulforhodamine B assay and on cells migration through scratch assays and time-lapse. Myoblast viability was not modified by PBMT protocols. All PBMT protocols were able to accelerate the scratch closure after 6 and 18 h of the first irradiation (p < 0.001). Also, an increase in migration speed, with a more pronounced effect of DHPL laser using dual-wavelength protocol with 2 W was observed (p < 0.001). In conclusion, the diverse PBMT protocols used in this study accelerated the C2C12 myoblasts migration, with 2-W dual-wavelength outstanding as the most effective protocol tested. Benefits from treating muscle injuries with PBMT appear to be related to its capacity to induce cell migration without notable impact on cell viability.


Assuntos
Terapia com Luz de Baixa Intensidade , Mioblastos , Mioblastos/efeitos da radiação , Terapia com Luz de Baixa Intensidade/métodos , Sobrevivência Celular/efeitos da radiação , Movimento Celular , Lasers
5.
J Oral Pathol Med ; 50(5): 470-477, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33340378

RESUMO

BACKGROUND: Imidazolium salts (IS), ionic derivatives of neutral imidazoles, have properties that can be adjusted by structural modifications to their cations and anions, which makes this particular class of compounds a promising option for developing biologically active compounds. The anti-tumor effects of the IS 1-n-butyl-3-methylimidazolium chloride (C4 MImCl), 1-n-decyl-3-methylimidazolium chloride (C10 MImCl), 1-n-hexadecyl-3-methylimidazolium chloride (C16 MImCl), 1-n-hexadecyl-2,3-dimethylimidazolium chloride (C16 M2 ImCl), 1-n-octadecyl-3-methylimidazolium chloride (C18 MImCl), 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16 MImMeS), and 1-n-hexadecyl-2,3- dimethylimidazolium methanesulfonate (C16 M2 ImMeS) on oral squamous cell carcinoma (OSCC) have been studied here. METHODS: Oral squamous cell carcinoma cells (CAL27) were incubated with increasing IS doses and then submitted to proliferation (2D), cell death (2D) and spheroid assay (3D). RESULTS: The IS anti-tumor effect was dependent on both its N-alkyl chain length and anion, whereby C16 MImCl proved to be more effective in combination for inhibiting cell proliferation and cell-cell adhesion, outperforming the methylated C16 M2 ImCl derivative and, most importantly, the gold standard-cisplatin. In addition, C16 MImCl had little effect on keratinocytes and more pronounced effects on more aggressive tumor cells. It also exhibited similar effects on inducing cell death when compared to Cisplatin. This compound spread to a greater area of the tumor sphere and produced an enhanced number of apoptotic and necrotic cells in the tumor cell line, demonstrating only a small rise in the healthy cells. CONCLUSION: These data indicate that the effect of C16 MlmCl on OSCC is promising, as it is selective for cancer cells.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Neoplasias Bucais/tratamento farmacológico , Sais , Carcinoma de Células Escamosas de Cabeça e Pescoço
6.
Environ Res ; 200: 111432, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34062204

RESUMO

The occurrence of neurotoxicity caused by xenobiotics such as pesticides (dichlorodiphenyltrichloroethane, organophosphates, pyrethroids, etc.) or metals (mercury, lead, aluminum, arsenic, etc.) is a growing concern around the world, particularly in vulnerable populations with difficulties on both detection and symptoms treatment, due to low economic status, remote access, poor infrastructure, and low educational level, among others features. Despite the numerous molecular markers and questionnaires/clinical evaluations, studying neurotoxicity and its effects on cognition in these populations faces problems with samples collection and processing, and information accuracy. Assessing cognitive changes caused by neurotoxicity, especially those that are subtle in the initial stages, is fundamentally challenging. Finding accurate, non-invasive, and low-cost strategies to detect the first signals of brain injury has the potential to support an accelerated development of the research with these populations. Saliva emerges as an ideal pool of biomarkers (with interleukins and neural damage-related proteins, among others) and potential alternative diagnostic fluid to molecularly investigate neurotoxicity. As a source of numerous neurological biomarkers, saliva has several advantages compared to blood, such as easier storage, requires less manipulation, and the procedure is cheaper, safer and well accepted by patients compared with drawing blood. Regarding cognitive dysfunction, neuropsychological batteries represent, with their friendly interface, a feasible and accurate method to evaluate the eventual cognitive deficits associated with neurotoxicity in people from diverse cultural and educational backgrounds. The association of these two tools, saliva and neuropsychological batteries, to cover the molecular and cognitive aspects of neurotoxicity in vulnerable populations, could potentially increase the prevalence of early intervention and successful treatment.


Assuntos
Poluentes Ambientais , Biomarcadores , Cognição , Poluentes Ambientais/toxicidade , Humanos , Saliva , Populações Vulneráveis
7.
J Clin Periodontol ; 48(7): 880-885, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33899251

RESUMO

AIMS: SARS-CoV-2 RNA has been recovered from different sites in the human body, including the mouth. The present study aimed to investigate the presence of SARS-CoV-2 RNA in the dental biofilm of symptomatic patients who tested positive in nasopharyngeal and oropharyngeal (NASO/ORO) samples. MATERIALS & METHODS: An observational clinical study of individuals with flu-like symptoms was conducted between July and September 2020. Dental biofilm (BIO) samples were collected and analysed using real-time quantitative polymerase chain reaction (RT-qPCR) to determine the virus's presence. RESULTS: Seventy participants (40 ± 9.8 years of age, 71.4% female) tested positive for SARS-CoV-2 RNA in NASO/ORO samples and were included in the study. Among them, 13 tested positive in BIO samples (18.6%; 95% CI: [9.5, 27.7]). The median and interquartile range of cycle quantification (Cq) for NASO/ORO and BIO samples were 15.9 [6.9] and 35.9 [4.0] (p = .001), respectively. BIO-positive participants showed a higher virus load in NASO/ORO samples (p = .012) than those testing negative (Cq = 20.4 [6.1]). CONCLUSIONS: Dental biofilms from symptomatic COVID-19 patients harbour SARS-CoV-2 RNA and might be a potential reservoir with an essential role in COVID-19 transmission.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , Biofilmes , Feminino , Humanos , Masculino , RNA Viral , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral
8.
Phytother Res ; 34(3): 568-582, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31752046

RESUMO

Flavonoids have been proposed as potential chemotherapeutic agents because they are toxic against cancer cells but not harmful to healthy cells. This systematic review analyzed flavonoid effectiveness in human cancer chemotherapy. Overall, 22 phase II and 1 phase III clinical trials (PubMed, Scopus, and Web of Science) that used flavonoids as a single agent or combined with other therapeutics against hematopoietic/lymphoid or solid cancer published by January 2019 were selected for analysis. Flavopiridol was the most commonly used flavonoid (at a dose of 50-mg/m2 IV) for all tumor types. Aside from the relatively low rate of complete response (CR) or partial response (PR) with any administration protocol, flavonoids showed higher positive outcomes for hematopoietic and lymphoid tissues (140 patients with CR and 88 with PR among 615 patients in 11 trials) than for solid tumors (4 patients with CR and 21 with PR among 525 patients in 12 trials). However, because of the high variety in administration schedule, more studies are needed to further understand how flavonoids can promote positive outcomes for cancer patients.


Assuntos
Antineoplásicos/administração & dosagem , Flavonoides/administração & dosagem , Neoplasias/tratamento farmacológico , Piperidinas/administração & dosagem , Polifenóis/administração & dosagem , Ensaios Clínicos como Assunto , Humanos
9.
Biol Cell ; 110(10): 225-236, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30157294

RESUMO

BACKGROUND INFORMATION: Cell migration requires the coordinated activation of structural and signalling molecules, such as the RhoGTPase Rac1. It is known that the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex assembly, which generates reactive oxygen species (ROS) at the cell membrane, also relies on Rac1 activation, indicating a possible effect of ROS during cell migration. In this study, we evaluated the effect of NADPH-oxidase-derived ROS on the migration process. RESULTS: Using time-lapse videos of CHO.K1 cells plated on fibronectin (2 µg/ml) or collagen (5 µg/cm2 ), we observed that depletion of ROS by N-acetyl-cysteine (NAC, 10 mM), an unspecific antioxidant, or diphenyliodonium (DPI, 10 µM), a NADPH-oxidase inhibitor, induced a ∼50% decrease in migration speed and severely impacted migration directionality. Then, we analysed the effects of NADPH oxidase on three migratory events: protrusion rate, adhesion process and signalling pathways related to cell migration. DPI induced an increase of ∼3 protrusion/cell, which were 2× faster but had a ∼50% retraction when compared with control. By pull-down assay, we observed no changes on Rac1 activation, indicating that ROS-mediated effects were related to downstream molecules, such as adhesion-related molecules. A reduction of the adhesion marker FAK-Y397 levels in cells treated with NAC and DPI was observed. In order to analyse adhesion dynamics, CHO.K1 cells transfected with paxillin-GFP analysed with total internal reflectance fluorescence (TIRF) indicated that DPI (5 µM) induced larger adhesions when compared with control. CONCLUSION: These results indicate that the local generation of NADPH-oxidase-derived ROS can modulate cell migration due to changes on adhesion dynamics and signalling. SIGNIFICANCE: This study highlights the physiological requirement of ROS for cell migration and the potential use of these molecules as targets to modulate the cell migration process at different diseases.


Assuntos
Adesão Celular , Movimento Celular , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Compostos de Bifenilo , Células CHO , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Cricetulus , Oniocompostos , Transdução de Sinais/efeitos dos fármacos
10.
Ann Plast Surg ; 83(1): 99-103, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31194709

RESUMO

Peracetic acid (PAA) has been used to sterilize biomaterial scaffolds and allografts before their implantation. Although the antimicrobial effectiveness of PAA is widely known, there are no studies investigating its cytotoxicity on keratinocytes. This study aimed to investigate the cytotoxicity of PAA concentrations on keratinocytes by growing HaCaT cells in culture medium. Different concentrations of PAA (control-untreated, 0.01, 0.1, 1, 10, 100, 200, 400, 800, 1200, 1600, and 2000 ppm) were added to the culture wells and allowed to be in direct contact with cells for up to 24 hours. Cytotoxicity was quantitatively and qualitatively determined by cell viability assay and analysis of morphological changes. Statistical analysis was performed with 1-way analysis of variance and Tukey test at 5% significance. Cells treated with 0.01 and 0.1 ppm followed the same morphological pattern of untreated cells, whereas cells treated with 1.0 ppm presented about 20% of floating cells and dark cytoplasmic granules. More than 50% of the cells treated with 10 and 100 ppm were destroyed, whereas the attached ones showed unclear and interrupted cell membranes. Concentrations of 1 ppm or greater had less than 64.4% of viable cells compared with the control group. This study concluded that exposure of keratinocytes to concentrations of 1 ppm or greater of PAA resulted in strong cytotoxic effects.


Assuntos
Anti-Infecciosos/efeitos adversos , Queratinócitos/efeitos dos fármacos , Ácido Peracético/efeitos adversos , Próteses e Implantes , Esterilização/métodos , Análise de Variância , Anti-Infecciosos/farmacologia , Estudos de Casos e Controles , Morte Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Ácido Peracético/farmacologia , Infecções Relacionadas à Prótese/prevenção & controle , Valores de Referência , Medição de Risco
11.
J Prosthet Dent ; 121(6): 966.e1-966.e6, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31078286

RESUMO

STATEMENT OF PROBLEM: Soaking dentures in vinegar or hydrogen peroxide does not seem to remove the microorganisms involved with prosthetic stomatitis efficiently. A mixture of these 2 substances may be effective, but studies are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the antimicrobial effect and cytotoxic activity of vinegar-hydrogen peroxide mixtures against Candida albicans and Staphylococcus aureus. MATERIAL AND METHODS: For antimicrobial tests, planktonic cells and biofilms of C. albicans and S. aureus cultured on acrylic resin disks were exposed to 0.5% sodium hypochlorite; 0.2% peracetic acid; vinegar-hydrogen peroxide mixtures at concentration ratios 1:1, 1:3, and 3:1; vinegar-water mixtures at concentration ratios 1:1, 1:3, and 3:1; and hydrogen peroxide-water mixtures at concentration ratios 1:1, 1:3, and 3:1. Antimicrobial activity was evaluated by counting viable colony-forming units after disinfection. For cytotoxicity tests, the 1:1 vinegar-hydrogen peroxide mixture was serially diluted (10-1 to 10-4) and allowed to be in direct contact with HaCaT keratinocytes for 24 hours. Cytotoxicity was quantitatively and qualitatively determined by counting the number of viable cells and analyzing morphological cell changes. RESULTS: All vinegar-hydrogen peroxide mixtures, sodium hypochlorite, and peracetic acid efficiently eliminated C. albicans and S. aureus (P<.05), whereas vinegar and hydrogen peroxide solutions used separately were not as efficient as the experimental mixtures. The 10-3 and 10-4 dilutions of vinegar-hydrogen peroxide solutions were considered noncytotoxic, whereas dilutions below 10-2 were strongly cytotoxic, comparable with the 10-2 dilution of 0.2% peracetic acid. CONCLUSIONS: The vinegar-hydrogen peroxide mixture effectively eliminated C. albicans and S. aureus from acrylic resin. Dilutions equal or below 10-2 of this mixture presented strong cytotoxic effects.


Assuntos
Anti-Infecciosos , Desinfecção , Ácido Acético , Biofilmes , Candida albicans , Dentaduras , Peróxido de Hidrogênio , Staphylococcus aureus
12.
J Oral Pathol Med ; 47(5): 460-467, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28940738

RESUMO

Oral Squamous Cell Carcinoma (OSCC) presents a tumor microenvironment rich in inflammatory cells. Depending on the stimulus, macrophages can polarize in M1 or M2 profile, where M1 acts as proinflammatory and antitumor, and M2 is anti-inflammatory and shows protumor activity. Several studies have shown that macrophages are important to the prognosis of patients with different types of cancer. Our aim was to conduct a systematic review to evaluate the role of macrophages in the prognosis of OSCC patients. A search in the Pubmed, Scopus, and ISI Web of Knowledge database was performed, and it was included only studies that evaluated the importance of macrophages in the prognosis of OSCC patients. From initial 286 articles, 14 fully attended the inclusion criteria. In the majority of the articles, it was evaluated only CD68, a panmacrophage marker, or CD163, a M2 marker. Only one article evaluated the M1 marker, CD11c. Besides, 5 articles analyzed the presence of macrophages in different areas of the tumor. Higher concentrations of CD68 and CD163 were associated with worse survival. In conclusion, macrophages are important to OSCC patients' prognosis; however, it is necessary to address in which tumor region the presence of polarized macrophage is more important to the outcome.


Assuntos
Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/mortalidade , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Macrófagos/imunologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores Tumorais/metabolismo , Bases de Dados Bibliográficas , Intervalo Livre de Doença , Feminino , Humanos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores de Superfície Celular/metabolismo , Adulto Jovem
13.
J Oral Pathol Med ; 47(3): 246-252, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29292531

RESUMO

BACKGROUND: Focal adhesion kinase (FAK) phosphorylation contributes to the regulation of growth factors that promote cellular adhesion, mobility, and survival, being a key factor in tumor development. The objective of this study was to evaluate the immunohistochemical expression patterns of FAK and its phosphorylated forms, FAK Tyr-576 and FAK Tyr-925, in head and neck squamous cell carcinoma and non-neoplastic adjacent epithelial tissue (AE). METHODS: The percentage of immunohistochemistry stained cells and its correlation with clinicopathological variables and prognosis were determined using samples from 54 patients. RESULTS: FAK, FAK Tyr-576, and FAK Tyr-925 overexpression was observed in tumor zones and AE. FAK Tyr-576 immunostaining showed a relationship with tumor clinicopathological parameters. Moreover, positive immunostaining of FAK Tyr-576 in AEsue was associated with patients prognoses. CONCLUSIONS: Increased expression of FAK Tyr-576 could enable identification of tumors with a more aggressive behavior and epithelial alterations before the appearance of clinical or histological manifestations.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Epitélio/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico
14.
Phytother Res ; 31(9): 1433-1440, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28782139

RESUMO

Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti-proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell-cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC. Curcumin (2 µM) decreased cell proliferation in cell lines with mesenchymal characteristics, while cell death was detected only at 50 µM. We observed that highly migratory cells showed a decrease on migration speed and directionality when treated with 2 or 5 µM of curcumin (50% and 40%, respectively, p < 0.05). Using spheroids, we observed that curcumin dose dependently decreased cell-cell adhesion, especially on tumor-derived spheroids. Also, in a xenograft model with patient-derived OSCC cells, the administration of curcumin decreased tumor growth and aggressiveness when compared with untreated tumors, indicating the potential antitumor effect in oral cancer. These results suggest that lower doses of curcumin can influence several steps involved in tumorigenesis, including migration properties, suggesting a possible use in cancer therapy. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Curcuma/química , Curcumina/farmacologia , Neoplasias Bucais/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Carcinogênese , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Bucais/patologia , Células NIH 3T3 , Esferoides Celulares/efeitos dos fármacos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Wound Repair Regen ; 24(6): 981-993, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27684945

RESUMO

Oxidative stress aggravates several long-term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan-induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post-wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b+ and Ly6G+ cells) and reduced levels of KC, TNF-α, IL-1ß, and IL-12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG+ /CD206- macrophages whereas CD206+ /MIG- macrophages were decreased. Cytokines IL-12p40, TNF-α, IL-1ß, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia.


Assuntos
Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/patologia , Inflamação/patologia , Estresse Oxidativo/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/patologia , Administração Oral , Animais , Glicemia/metabolismo , Catalase/metabolismo , Subunidade p40 da Interleucina-12/metabolismo , Camundongos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
17.
Acta Odontol Scand ; 72(5): 386-91, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24125038

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effects of X radiation on the distribution of filamentous actin (F-actin) in the mouse exorbital lacrimal gland. MATERIALS AND METHODS: Mice were divided into groups that received no radiation (n = 6) or one single exposure of 36 mGy of X radiation (n = 12). The animals were sacrificed after 4, 8 or 24 h. The lacrimal glands were stained with Hematoxylin/Eosin or Rhodamine-phalloidin and the filamentous actin arrangement was analyzed by confocal microscopy. RESULTS: After 4 h of X-ray exposure there was an apparent increase in acini area and a decrease in the cortical F-actin content in secretory cells. This effect decreased gradually over time, returning to values close to the control after 24 h. CONCLUSION: This study shows that a 36 mGy diagnostic X-ray dose affected reversibly the mouse exorbital lacrimal gland, suggesting that radiation used in diagnosis may induce changes on cell morphology due to actin remodeling.


Assuntos
Citoesqueleto de Actina/efeitos da radiação , Aparelho Lacrimal/efeitos da radiação , Animais , Aparelho Lacrimal/metabolismo , Masculino , Camundongos , Doses de Radiação , Raios X
18.
Cancers (Basel) ; 16(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38275880

RESUMO

Head and neck squamous cell carcinoma (HNSCC) exhibits considerable variability in patient outcome. It has been reported that SOX2 plays a role in proliferation, tumor growth, drug resistance, and metastasis in a variety of cancer types. Additionally, SOX9 has been implicated in immune tolerance and treatment failures. SOX2 and SOX9 induce treatment failure by a molecular mechanism that has not yet been elucidated. This study explores the inverse association of SOX2/SOX9 and their distinct expression in tumors, influencing the tumor microenvironment and radiotherapy responses. Through public RNA sequencing data, human biopsy samples, and knockdown cellular models, we explored the effects of inverted SOX2 and SOX9 expression. We found that patients expressing SOX2LowSOX9High showed decreased survival compared to SOX2HighSOX9Low. A survival analysis of patients stratified by radiotherapy and human papillomavirus brings additional clinical relevance. We identified a gene set signature comprising newly discovered candidate genes resulting from inverted SOX2/SOX9 expression. Moreover, the TGF-ß pathway emerges as a significant predicted contributor to the overexpression of these candidate genes. In vitro findings reveal that silencing SOX2 enhances tumor radioresistance, while SOX9 silencing enhances radiosensitivity. These discoveries lay the groundwork for further studies on the therapeutic potential of transcription factors in optimizing HNSCC treatment.

19.
Sci Rep ; 14(1): 15421, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965297

RESUMO

Aedes aegypti and Aedes albopictus are the main vectors of arboviruses such as Dengue, Chikungunya and Zika, causing a major impact on global economic and public health. The main way to prevent these diseases is vector control, which is carried out through physical and biological methods, in addition to environmental management. Although chemical insecticides are the most effective strategy, they present some problems such as vector resistance and ecotoxicity. Recent research highlights the potential of the imidazolium salt "1-methyl-3-octadecylimidazolium chloride" (C18MImCl) as an innovative and environmentally friendly solution against Ae. aegypti. Despite its promising larvicidal activity, the mode of action of C18MImCl in mosquito cells and tissues remains unknown. This study aimed to investigate its impacts on Ae. aegypti larvae and three cell lines of Ae. aegypti and Ae. albopictus, comparing the cellular effects with those on human cells. Cell viability assays and histopathological analyses of treated larvae were conducted. Results revealed the imidazolium salt's high selectivity (> 254) for mosquito cells over human cells. After salt ingestion, the mechanism of larval death involves toxic effects on midgut cells. This research marks the first description of an imidazolium salt's action on mosquito cells and midgut tissues, showcasing its potential for the development of a selective and sustainable strategy for vector control.


Assuntos
Aedes , Imidazóis , Inseticidas , Larva , Aedes/efeitos dos fármacos , Animais , Larva/efeitos dos fármacos , Imidazóis/toxicidade , Imidazóis/farmacologia , Inseticidas/toxicidade , Inseticidas/farmacologia , Humanos , Mosquitos Vetores/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Controle de Mosquitos/métodos
20.
Photodiagnosis Photodyn Ther ; 41: 103238, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36509404

RESUMO

Oral cancer represents an important health problem, as it is the sixth most common type of cancer in the world and is associated with high rates of morbidity and mortality. The treatment considered the gold standard for this type of tumor is surgical resection with negative margins, with a distance of at least 5 mm from the tumor. This procedure is strongly associated with local control and disease-specific survival, however, in many cases, large amounts of healthy tissue are removed, resulting in surgical defects, compromising various functions and directly affecting the individual's quality of life. From this perspective, this systematic review aimed to evaluate the use of autofluorescence and fluorescent probes as potential adjuvant techniques to facilitate the delineation of surgical margins for oral cancers. A comprehensive search was performed in Pubmed, Scopus, Web of Science, LIVIVO, Embase, ProQuest Open Access Dissertations & Theses, Open Access Theses and Dissertations, and DART Europe databases, where 1948 articles were found. After the different stages of critical evaluation, 15 articles were selected, eligible for the inclusion criteria. Of these, 7 articles used autofluorescence, 7 used fluorescent probes and 1 article used both methods. As for autofluorescence, the most used device was the VELScope, and indocyanine green was the most used probe. Compared to histopathology, autofluorescence did not obtain significant and/or superiors results. In contrast to fluorescent probes that, most articles showed a good performance of margins during surgical resection, making them a promising alternative. However, it is still necessary to carry out the analysis of more articles, with more significant samples and sensitivity and specificity data to qualify the results.


Assuntos
Carcinoma , Neoplasias Bucais , Fotoquimioterapia , Humanos , Corantes Fluorescentes , Qualidade de Vida , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Neoplasias Bucais/cirurgia
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