ABSTRACT
Cuidados paliativos são um conjunto de procedimentos ofertados ao paciente por uma equipe multidisciplinar com objetivo de garantir bem-estar, autonomia,conforto e alívio de sintomas decorrentes de doença ou tratamento quando a cura é impossibilitada. O câncer representa uma das doenças que possuem chances de evoluir o paciente ao estágio terminal, momento em que cuidados paliativos são indicados e necessários. Dentro da equipe responsável, o cirurgião-dentista atua na prevenção, diagnóstico e tratamento de lesões expressas no sistema estomatognático que se manifestam estimuladas pelo câncer ou pelos tratamentos utilizados. O objetivo desta pesquisa é destacar a função do odontólogo dentro da equipe multidisciplinar paliativista para pacientes oncológicos. Trata-se de uma revisão bibliográfica sistemáticada literatura. Foram feitas buscas nas plataformas Biblioteca Virtual em Saúde (BVS) e Scientific Electronic Library Online (SciELO) e após aplicação dos critérios de inclusão e exclusão foram selecionados 14 artigos. A literatura evidencia que alterações orais estão relacionadas com o curso da neoplasia ou seu tratamento; as lesões mais descritas foram: mucosite, xerostomia, candidíase, cárie, periodontite e osteorradionecrose. Isso faz com que o paciente sofra limitações em realizar atividades básicas, alterando negativamente a sua qualidade de vida. A complexidade da manifestação oral pode interromper o tratamento antineoplásico. As medidas de enfrentamento mais empregadas para a saúde bucal do paciente oncológico são a laserterapia, bochechos com clorexidina 0,12%, instrução de higiene oral, uso de anti-inflamatórios, analgésicos e antifúngicos. A atuação do odontólogo na equipe multidisciplinar oncológica paliativista é indispensável para o controle das manifestações orais.
Palliative care comprises a set of procedures offered by a multidisciplinary team to patients who cannot be cured, aiming to restore and ensure well-being, autonomy, independence, comfort and relief from symptoms resulting from illness or treatments. Cancer commonly leads the patient to the terminal stage, and at this stage palliative care is indicated and necessary. Composing the multidisciplinary team, the dentist works in the prevention, diagnosis and treatment of injuries that arise in the stomatognathic system, which manifest themselves due to cancer or its treatments. The objective of this research was to highlight the work of the dentist in the multidisciplinary team of palliative care for cancer patients. This is a systematic bibliographic review of the literature, with an integrative character. Study searches were performed in the Virtual Health Library (VHL) and Scientific Electronic Library Online (SciELO). After applying the inclusion and exclusion criteria, 14 articles were selected. Results showed that oral alterations are completely related to the development of the neoplasm or its treatment; the most described lesions were: mucositis, xerostomia, candidiasis, osteoradionecrosis, radiation caries and periodontitis. These injuries make the patient suffer limitations to perform basic activities, such as eating or communicating, negatively altering their quality of life. The complexity of the oral manifestation can determine the interruption of the anticancer treatment. The most used coping measures for the oral healthof cancer patients are: low- potency laser therapy, mouthwash with 0.12% chlorhexidine, instructionin oral hygiene and use of anti-inflammatory, analgesic and antifungal drugs. The role of dentists in the multidisciplinary palliative oncology team is essential for the control of oral lesions.
Los cuidados paliativos son un conjunto de procedimientos ofrecidos al paciente por un equipo multidisciplinar con el objetivo de garantizar el bienestar, la autonomía, el confort y el alivio de los síntomas derivados de la enfermedad o del tratamiento cuando la curación es imposible. El cáncer representa una de las enfermedades que tienen posibilidades de evolucionar al paciente hasta la fase terminal, momento en el que los cuidados paliativos son indicados y necesarios. Dentro del equipo responsable, el cirujano dentista actúa en la prevención, diagnóstico y tratamiento de las lesiones expresadas en el sistema estomatognático que se manifiestan estimuladas por el cáncer o por los tratamientos utilizados. El objetivo de esta investigación es destacar la función del odontólogo dentro del equipo paliativo multidisciplinar para pacientes oncológicos. Se trata de una revisión bibliográfica sistemática. Se realizaron búsquedas en las plataformas Virtual Health Library (BVS) y Scientific Electronic Library Online (SciELO) y tras aplicar los criterios de inclusión y exclusión, se seleccionaron 14 artículos. La literatura muestra que las alteraciones orales están relacionadas con el curso del cáncer o su tratamiento; las lesiones más comúnmente descritas fueron: mucositis, xerostomía, candidiasis, caries, periodontitis y osteorradionecrosis. Esto hace que el paciente sufra limitaciones para realizar actividades básicas, alterando negativamente su calidad de vida. La complejidad de la manifestación oral puede interrumpir el tratamiento antineoplásico. Las medidas de afrontamiento más utilizadas para la salud bucodental de los pacientes con cáncer son la terapia láser, los enjuagues bucales con clorhexidina al 0,12%, las instrucciones de higiene bucodental y el uso de fármacos antiinflamatorios, analgésicos y antifúngicos. La actuación del odontólogo en el equipo multidisciplinar de oncología paliativa es fundamental para el control de las manifestaciones orales.
Subject(s)
Palliative Care , Dentists , Medical Oncology/instrumentation , Patient Care Team/organization & administration , Radiotherapy/instrumentation , Stomatitis/complications , Stomatitis/diagnosis , Stomatognathic System , Mouth Neoplasms/diagnosis , Mouth Neoplasms/drug therapy , Mouth Neoplasms/radiotherapy , Oral Medicine/instrumentation , Drug Therapy/instrumentationABSTRACT
La evidencia científica presente en la literatura indica que el cannabis puede ser utilizado con fines terapéuticos para tratar distintas afecciones odontológicas. Dado el acceso sencillo a la cavidad bucal, las distintas formulaciones de cannabis pueden aplicarse de forma tópica. La aplicación local de dosis bajas de cannabis ha demostrado alta efectividad para tratar distintas afecciones bucales, constituyendo un tratamiento seguro con baja probabilidad de generar repercusiones sistémicas indeseadas. En la actualidad, está siendo incorporado a materiales convencionales de uso e higiene odontológica con la finalidad de aprovechar sus efectos terapéuticos. El cannabis tiene múltiples usos en odontología: como componen-te de enjuagues bucales y soluciones para la desinfección de conductos radiculares, en tratamientos de trastornos de ansiedad bucal, como complemento en terapias oncológicas, como analgésico para atenuar el dolor inflamatorio y el neuropático, como miorrelajante y condroprotector para tratar trastornos de articulación témporomandibular (ATM) y bruxismo, como osteomodulador para el tratamiento de patologías que comprometen la integridad ósea, como la enfermedad periodontal y la osteoporosis, y para la cicatrización ósea asociada a fracturas, extracciones dentarias e implantes, y como inmunomodulador con potencial terapéutico para tratar patologías autoinmunes como las enfermedades reumáticas. El trata-miento local con cannabis es efectivo, bien tolerado por el paciente y con pocos efectos adversos. Por lo tanto, se puede concluir que el cannabis aporta un enorme abanico de posibilidades terapéuticas para tratar distintas afecciones odontológicas, aunque aún se requiere mayor cantidad de estudios científicos que avalen su utilización en cada situación fisiopatológica particular (AU)
The scientific evidence present in the literature indicates that cannabis can be used for therapeutic purposes to treat different dental conditions. Given the easy access to the oral cavity, the different cannabis formulations can be applied topically. The local application of low doses of cannabis has shown high effectiveness in treating different oral conditions, constituting a safe treatment with a low probability of generating unwanted systemic repercussions. It is currently being incorporated into conventional materials for dental use and hygiene in order to take advantage of its therapeutic effects. Cannabis has multiple uses in dentistry: as a component of mouthwashes and solutions for disinfecting root canals, in the treatment of oral anxiety disorders, as a complement in oncological therapies, as an analgesic to reduce inflammatory and neuropathic pain, as a muscle relaxant and chondroprotective to treat temporomandibular joint disorders and bruxism, as an osteomodulator for the treatment of pathologies that compromise bone integrity, such as periodontal disease and osteoporosis, and or bone healing associated with fractures, dental extractions and implants, and as immunomodulator with therapeutic potential to treat autoimmune pathologies such as rheumatic diseases. Local treatment with cannabis is effective, well tolerated by the patient and with few adverse effects. Local treatment with cannabis is effective, well tolerated by the patient and with few adverse effects. Therefore, it can be concluded that cannabis provides an enormous range of therapeutic possibilities to treat different dental conditions, although more scientific studies are still required to support its use in each particular pathophysiological situation (AU)
Subject(s)
Humans , Dronabinol/therapeutic use , Cannabinoids/therapeutic use , Receptors, Cannabinoid/therapeutic use , Oral Hygiene/instrumentation , Periodontal Diseases/drug therapy , Pulpitis/drug therapy , Trigeminal Neuralgia/drug therapy , Bone Diseases/drug therapy , Facial Pain/drug therapy , Bruxism/drug therapy , Mouth Neoplasms/drug therapy , Rheumatic Diseases/drug therapy , Administration, Oral , Dental Anxiety/drug therapy , Mouth Diseases/drug therapyABSTRACT
Abstract: FITOPROT, which contains curcuminoids and Bidens pilosa L. extract, is an innovative mucoadhesive formulation indicated for the topical treatment of chemoradiotherapy-induced oral mucositis (OM) in patients with advanced and visible oral squamous cell carcinoma. The formulation is used as a mouthwash directly on tumor tissue of patients with advanced neoplasms, without triggering cancer cell proliferation or tumor invasiveness. Thus, the aim of this study was to evaluate the biological effects of FITOPROT on an oral squamous cell carcinoma cell line (SCC-4). The viability of SCC-4 cells was assessed after exposure to FITOPROT using MTT reduction assay. The effects of the mucoadhesive formulation on cell cycle progression and cell death parameters were evaluated using flow cytometry. In addition, the inflammatory profile of the tumor cells was evaluated using the cytometric bead array (CBA) assay. FITOPROT promoted a concentration-dependent decrease in cell viability and cell cycle arrest at the G2/M phase (p < 0.05). Mitochondrial membrane potential was also altered after exposure to the formulation (p < 0.05), in parallel with a reduction in VEGF and IL-8 production (p = 0.01 and p = 0.05, respectively). In summary, the results indicate that FITOPROT reduces SCC-4 cell viability, promotes cell cycle arrest, modulates mitochondrial membrane potential, and exhibits antiangiogenic and anti-inflammatory properties, thus indicating its potential for topical use in patients with OM and visible tumors in the mouth.
Subject(s)
Humans , Mouth Neoplasms/drug therapy , Carcinoma, Squamous Cell/drug therapy , Bidens , Cell Line , Apoptosis , Diarylheptanoids , Cell ProliferationABSTRACT
O estudo buscou investigar se o tempo máximo de demora (60 dias) para o início do tratamento dos pacientes com câncer de boca a partir do diagnóstico, previsto na Lei Federal nº 12.732/2012, foi alcançado no Brasil no período de 2013-2019 e descrever a tendência do número de casos que iniciaram o tratamento no tempo máximo. Realizou-se um estudo de séries temporais utilizando dados dos tratamentos (N = 37.417) do Painel-Oncologia, disponível no Departamento de Informática do SUS (DATASUS), segundo região de residência dos pacientes. Para análise da tendência executou-se a regressão de Prais-Winsten. Nos anos 2018 e 2019 foram observados percentuais mais elevados para os tratamentos em até 60 dias, sendo mais acentuado no intervalo de até 30 dias. Em 2019, 61,5% dos tratamentos iniciaram em até 60 dias, com maiores proporções nas regiões Sul (71,3%), Sudeste (60,1%) e Centro-oeste (59,1%). A tendência temporal da categoria 0-60 dias foi crescente na Região Norte, com variação percentual anual (VPA) de 15,7% e estacionária nas demais regiões e para o Brasil. A tendência do tempo de 0-30 dias foi crescente apenas para as regiões Norte e Nordeste, com VPA de 29,75% e 20,56%, respectivamente. Conclui-se que a partir de 2018 houve um maior número de casos que iniciaram o tratamento do câncer de boca no tempo de demora, conforme previsto na Lei nº 12.732/2012 (até 60 dias), com diferenças regionais e tendência estacionária na maioria das regiões e no Brasil. O alcance parcial da meta, o predomínio da tendência estacionária e as desigualdades regionais indicam a necessidade de continuar monitorando o tempo de demora para o início do tratamento do câncer no país e intensificar esforços para garantir o cuidado em saúde.
The study aimed to investigate whether the maximum delay (60 days) for initiating oral cancer treatment following diagnosis, as provided in Federal Law n. 12,732/2012, was achieved in Brazil from 2013 to 2019 and to describe the trend in the number of cases that initiated treatment within this timeframe. A time series was performed with treatment data (N = 37,417) from the Oncology Dashboard of the Brazilian Health Informatics Department (DATASUS) database, according to the patient's region of residence. Analysis of trend used Prais-Winsten regression. In 2018 and 2019, we observed higher percentages of treatments within 60 days, and especially within 30 days. In 2019, 61.5% of treatments began within 60 days, with the highest proportions in the South (71.3%), Southeast (60.1%), and Central-west (59.1%) regions of Brazil. The time trend for the category from 0-60 days was upward in the North of Brazil, with 15.7% annual percent change (APC), and was stationary in the other four major geographic regions of Brazil. The time trend for 0-30 days was only upward in the North and Northeast, with APCs of 29.75% and 20.56%, respectively. In conclusion, since 2018 there were more cases that initiated oral cancer treatment within the stipulated timeframe, as provided in Law n. 12,732/2012 (up to 60 days), with regional differences and a stationary trend in most regions and in Brazil as a whole. Partial achievement of the target, the predominance of a stationary trend, and regional inequalities indicate the need to continue monitoring time-to-treatment for oral cancer in Brazil and to intensify efforts to guarantee timely healthcare.
El estudio tuvo como meta investigar si el tiempo máximo de demora (60 días) para el inicio del tratamiento de los pacientes con cáncer de boca, a partir del diagnóstico previsto en la Ley Federal nº 12.732/2012, se alcanzó en Brasil durante el período 2013-2019, y describir la tendencia del número de casos que comenzaron el tratamiento en el tiempo máximo. Se realizó un estudio de series temporales utilizando datos de los tratamientos (N = 37.417) del Panel-oncología, disponible en Departamento de Informática del Sistema Único de Salud (DATASUS), según la región de residencia de los pacientes. Para el análisis de la tendencia se realizó la regresión de Prais-Winsten. En los años 2018 y 2019 se observaron porcentajes más elevados para los tratamientos en hasta 60 días, siendo más acentuado en el intervalo de hasta 30 días. En 2019, un 61,5% de los tratamientos comenzaron en hasta 60 días, con mayores proporciones en las regiones Sur (71,3%), Sudeste (60,1%) y Centro-oeste (59,1%). La tendencia temporal de la categoría 0-60 días fue creciente en la Región Norte, con variación porcentaje anual (VPA) de un 15,7% y estacionaria en las demás regiones y en Brasil. La tendencia del tiempo de 0-30 días fue creciente solamente para las regiones Norte y Nordeste, con VPA de 29,75% y 20,56%, respectivamente. Se concluye que a partir de 2018 hubo un mayor número de casos que comenzaron el tratamiento de cáncer de boca durante el tiempo de demora, conforme lo previsto en la Ley nº 12.732/2012 (hasta 60 días), con diferencias regionales y tendencia estacionaria en la mayoría de las regiones y en Brasil. El alcance parcial de la meta, el predominio de la tendencia estacionaria y las desigualdades regionales indican la necesidad de continuar supervisando el tiempo de demora para el inicio del tratamiento de cáncer en el país e intensificar esfuerzos para garantizar el cuidado en salud.
Subject(s)
Humans , Mouth Neoplasms/drug therapy , Delivery of Health Care , Time Factors , BrazilABSTRACT
Introduction: Oral cavity cancer is considered a public health problem worldwide. Malnutrition is prevalent in this population, increasing morbidity and mortality. Supplementation with eicosapentaenoic acid has been proposed to reverse protein catabolism and modulate inflammatory processes. Objective:Assess the effect of supplement with eicosapentaenoic acid in the weight and lean mass of patients with oral cavity cancer. Method: Clinical trial conducted with patients in oncologic pretreatment. The patients were randomized to receive nutritional supplement with eicosapentaenoic acid (2 g/day) or placebo. Nutritional parameters (weight, height, body composition and food intake) were assessed at baseline (T0) and after 4 weeks of supplementation (T1). The paired t-test or Wilcoxon test were used in intragroup comparisons. Associations between categorical variables were verified using the χ² or Fisher Exact test. Logistic regression was applied to identify the chance of weight loss. Differences were considered significant at p <0.05. Results:It was not observed significant difference on nutritional parameters between the groups after intervention. However, considering each group at the beginning and at the end of the study, it was observed that patients in the control group presented significant weight loss (T0: 57.2 kg x T1: 56.4 kg), reduction in the body mass index (T0: 22.6 kg/m2x T1: 22.0 kg/m2), fat mass (T0: 17.3 kg x T1: 15.3 kg) and arm circumference (T0: 27.4 cm xT1: 26.8 cm). Those who received supplement with eicosapentaenoic acid had 80% less chance of losing weight (95% CI: 0.045-0.860; OR: 0.19). Conclusion: This trial yielded data suggesting that patients with oral cavity cancer can benefit from eicosapentaenoic acid-containing nutritional supplement in oncologic pretreatment.
Introdução: O câncer de cavidade oral é considerado um problema de saúde pública no mundo. A desnutrição é prevalente nessa população, aumentando a morbimortalidade. A suplementação com ácido eicosapentaenoico tem sido proposta para reverter o catabolismo proteico e modular processos inflamatórios. Objetivo: Avaliar o efeito do suplemento nutricional enriquecido com ácido eicosapentaenoico no peso corporal e massa magra de pacientes com câncer de cavidade oral. Método: Ensaio clínico realizado com pacientes em pré-tratamento oncológico. Os pacientes foram randomizados para receber suplemento nutricional com ácido eicosapentaenoico (2 g/dia) ou placebo. Os parâmetros nutricionais (peso, estatura, composição corporal e ingestão alimentar) foram avaliados no início (T0) e após quatro semanas de suplementação (T1). O teste-t pareado ou de Wilcoxon foram usados nas comparações intragrupos. As associações entre as variáveis categóricas foram verificadas por meio do teste do χ² ou Exato de Fisher. A regressão logística foi aplicada para identificar a chance de perder peso. As diferenças foram consideradas significativas quando p<0,05. Resultados: Não foi observada diferença significativa nos parâmetros nutricionais entre os grupos após a intervenção. No entanto, considerando cada grupo no início e no final do estudo, observou-se que os pacientes do grupo controle apresentaram perda de peso significativa (T0: 57,2 kg x T1: 56,4 kg), redução no índice de massa corporal (T0: 22,6 kg/m2x T1: 22,0 kg/m2), massa gorda (T0: 17,3 kg x T1: 15,3 kg) e circunferência do braço (T0: 27,4 cm xT1: 26,8 cm). Aqueles que receberam suplemento com ácido eicosapentaenoico tiveram 80% menos chance de perder peso (95% IC: 0,045-0,860; OR: 0,19). Conclusão: Este estudo produziu dados que sugerem que pacientes com câncer de cavidade oral podem se beneficiar com o uso de suplemento nutricional contendo ácido eicosapentaenoico no pré-tratamento oncológico.
Introducción: El cáncer de la cavidad oral se considera un problema de salud pública en todo el mundo. La desnutrición prevalece en esta población, lo que aumenta la morbilidad y la mortalidad. Cuando la desnutrición se asocia con la anorexia, el aumento del gasto energético y la inflamación se denomina caquexia. Se ha propuesto la suplementación con ácido eicosapentaenoico para revertir el catabolismo proteico y modular los procesos inflamatorios. Objetivo: Evaluar el efecto de un suplemento nutricional enriquecido con ácido eicosapentaenoico sobre el peso corporal y la masa magra de pacientes con cáncer de cavidad oral. Método: Ensayo clínico realizado con pacientes sometidos a tratamiento previo al cáncer. Los pacientes fueron asignados al azar para recibir un suplemento nutricional con ácido eicosapentaenoico (2 g/día) o placebo. Los parámetros nutricionales (peso, altura, composición corporal e ingesta alimentaria) se evaluaron al inicio del estudio (T0) y después de 4 semanas de suplementación (T1). En las comparaciones intragrupo se utilizó la prueba t pareada o de Wilcoxon. Las asociaciones entre variables categóricas se verificaron mediante la prueba de la χ² o la prueba exacta de Fisher. Se aplicó regresión logística para identificar la posibilidad de perder peso. Las diferencias se consideraron significativas en p<0,05. Resultados: No hubo diferencias significativas en los parámetros nutricionales entre los grupos después de la intervención. Sin embargo, considerando cada grupo al principio y al final del estudio, se observó que los pacientes en el grupo de control tenían una pérdida de peso significativa (T0: 57,2 kg x T1: 56,4 kg), reducción en el índice de masa corporal (T0: 22,6 kg/m2x T1: 22,0 kg/m2), masa grasa (T0: 17,3 kg x T1: 15,3 kg) y circunferencia del brazo (T0: 27,4 cm x T1: 26,8 cm). Aquellos que fueron suplementados con ácido eicosapentaenoico tenían 80% menos probabilidades de perder peso (95% IC: 0,045-0,860; OR: 0,19). Conclusión: Este estudio produjo datos que sugieren que los pacientes con cáncer de la cavidad oral pueden beneficiarse del uso de un suplemento nutricional que contenga ácido eicosapentaenoico en el tratamiento previo al cáncer.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Mouth Neoplasms/drug therapy , Eicosapentaenoic Acid/administration & dosage , Dietary Supplements , Body Composition/drug effects , Nutritional StatusABSTRACT
OBJECTIVE@#To investigate the effects of salinomycin on the proliferation and apoptosis of oral squamous carcinoma cells and to further understand the mechanisms of these effects.@*METHODS@#The human oral squamous carcinoma cell line CAL-27 was cultured in different concentrations of salinomycin and cisplatin. After co-culture with 0, 1, 2, 4, 8, 16 and 32 μmol/L salinomycin or 0, 1.25, 2.5, 5, 10, 20, 40 and 80 μmol/L cisplatin for 24 hours and 48 hours, the proliferation of oral squamous carcinoma cells were detected by cell counting kit-8(CCK-8) assay. After being exposed to 0, 2, 4, 8 μmol/L salinomycin and 0, 5, 10, 20 μmol/L cisplatin for 48 hours, the cell cycle of oral squamous carcinoma cells was detected by flow cytometry assay, and Western blot analysis was performed to analyze the expressions of cysteine-containing aspartate-specific proteases-3(Caspase-3), cysteine-containing aspartate-specific proteases-9(Caspase-9), poly ADP-ribose polymerase (PARP), protein kinase B (Akt) and phosphorylated protein kinase B (p-Akt) protein in oral squamous carcinoma cells.@*RESULTS@#Both salinomycin and cisplatin significantly inhibited the proliferation of oral squamous cell carcinoma CAL-27 cells in a time- and dose-dependent manner. However, compared with the first-line chemotherapeutic drug cisplatin, salinomycin showed stronger anti-proliferation activity in oral squamous carcinoma cells than cisp-latin (P < 0.001). After being exposed to 8 μmol/L salinomycin, CAL-27 cells exhibited markedly higher proportion in quiescent/ first gap phases (40.40%±1.99% vs. 64.46%±0.90%, P < 0.05), and had a significantly lower proportion in synthesis phases and second gap / mitosis phases (24.32%±2.30% vs. 18.73%±0.61%, P < 0.05; 35.01%±1.24% vs. 16.54%±1.31%, P < 0.05) compared with the dimethyl sulfoxide control group; moreover cisplatin didn't show cell-cycle specific effect on CAL-27. Western blot proved that salinomycin could up-regulate the expressions of Caspase-3 and Caspase-9 protein in oral squamous cell carcinoma CAL-27 cells (P < 0.05). At the same time, the levels of PARP, Akt and p-Akt protein were down-regulated (P < 0.05).@*CONCLUSION@#Compared with cisplatin, salinomycin has a better inhibitory effect on the proliferation of oral squamous carcinoma cells and blocks the cell cycle process at the quiescent / first gap phase. At the same time, salinomycin could trigger apoptosis of oral squamous carcinoma cells and the mechanism is associated with the Akt/p-Akt signaling pathway.
Subject(s)
Humans , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Carcinoma, Squamous Cell/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Mouth Neoplasms/drug therapy , PyransABSTRACT
Objectives: A systematic review was conducted to evaluate effectiveness and safety of beta carotenes for the treatment of oral leukoplakia regarding clinical resolution and prevention of malignant transformation. Material and Methods: The systematic search was conducted in three electronic databases and the study's selection was performed according to pre-set eligibility criteria. Four studies evaluating the efficacy of beta carotenes in oral leukoplakia compared to placebo were included in the review; three of which were assigned for quantitative analysis. Data were extracted, tabulated, quality assessed and statistically analyzed. Results: The meta-analysis revealed that when comparing clinical resolution the beta carotene group favored was favored compared to placebo, with statistically significant difference. However, a meta-analysis comparing beta carotene and placebo groups regarding malignant transformation as a primary outcome failed to show any significant benefit. Furthermore, results showed evidence of beta carotene safety. Conclusion: the overall quality of evidence about efficacy of beta carotene in oral leukoplakia treatment was not high. However, given the obvious safety of this agent, data suggests it could have a promising effect in clinical improvement of oral leukoplakia lesions. However, no evidence supporting its benefits in reducing risk of malignant transformation in these lesions was found. Therefore, further long term, well designed randomized clinical trials are highly recommended.
Objetivos: Se realizó una revisión sistemática para evaluar la efectividad y la seguridad de los betacarotenos para el tratamiento de la leucoplasia oral en relación con la resolución clínica y la prevención de la transformación maligna. Material y Métodos: la búsqueda sistemática se realizó en tres bases de datos electrónicas y la selección del estudio se realizó de acuerdo con los criterios de elegibilidad preestablecidos. En la revisión se incluyeron cuatro estudios que evaluaban la eficacia de los betacarotenos en la leucoplasia oral en comparación con el placebo; tres de los cuales fueron asignados para el análisis cuantitativo. Los datos fueron extraídos, tabulados, su calidad evaluada y analizados estadísticamente. Resultados: El metanálisis reveló que al comparar la resolución clínica, el grupo de betacaroteno fue favorecido en comparación con el placebo, con una diferencia estadísticamente significativa. Sin embargo, un metaanálisis que comparó los grupos de betacaroteno y placebo con respecto a la transformación maligna como resultado primario no mostró ningún beneficio significativo. Además, los resultados mostraron evidencia de seguridad de betacaroteno. Conclusión: La calidad general de la evidencia sobre la eficacia del betacaroteno en el tratamiento de la leucoplasia oral no es alta. Sin embargo, dada la obvia seguridad de este agente, los datos sugieren que podría tener un efecto prometedor en la mejora clínica de las lesiones de leucoplasia oral. Sin embargo, no se encontraron pruebas que respalden sus beneficios en la reducción del riesgo de transformación maligna en estas lesiones. Por lo tanto, se recomiendan ensayos clínicos aleatorios bien diseñados a largo plazo.
Subject(s)
Humans , Leukoplakia, Oral/drug therapy , Carotenoids/therapeutic use , beta Carotene/therapeutic use , Precancerous Conditions , Mouth Neoplasms/drug therapyABSTRACT
ABSTRACT Objective: To evaluate the effect of red propolis and L-lysine on angiogenesis and tumor growth in a new model of hamster cheek pouch inoculated with Walker 256 tumor cells. Methods: The study consisted of two experiments with four groups each (total: 57 hamsters). In the experiment 1, the animals were inoculated with Walker tumor cells, followed by administration of test substances (red propolis 200mg/5mL/kg or L-lysine 150mg/kg) or control substances (gum arabic 5mL/kg or water 5mL/kg) for 10 days. The animals in the experiment 2 received red propolis, L-lysine, gum arabic or water at the same doses, for 33 days prior to inoculation of Walker tumor cells, followed by 10 days of treatment with the same substances. Based on single-plane images, angiogenesis was quantified (mean vascular area), in percentage, and tumor area (mm2) and perimeter (mm). Results: In the experiment 1, compared to animals receiving water, the mean vascular area expressed in percentage was significantly smaller in animal treated with propolis (p<0.05) and L-lysine (p<0.001). Conclusion: Both red propolis and L-lysine inhibited tumor angiogenesis in the new hamster cheek pouch model when administered after tumor inoculation.
RESUMO Objetivo: Avaliar o efeito da própolis vermelha e da L-lisina na angiogênese e no crescimento tumoral em novo modelo de bolsa jugal de hamster inoculada com células de tumor de Walker 256. Métodos: O estudo consistiu em dois experimentos com quatro grupos cada (total: 57 hamsters). No experimento 1, os animais foram inoculados com células de tumor de Walker, tendo em seguida administradas as substâncias teste (própolis vermelha 200mg/5mL/kg ou L-lisina 150mg/kg) ou controle (goma arábica 5mL/kg ou água 5mL/kg) por 10 dias. Os animais do experimento 2 receberam própolis vermelha, L-lisina, goma arábica ou água nas mesmas doses, por 33 dias antes do inóculo das células de tumor de Walker, seguido por 10 dias de tratamento com as mesmas substâncias. Baseado em imagens em plano único, foram quantificados a angiogênese (área vascular média), em termos percentuais, e a área (mm2) e o perímetro (mm) do tumor. Resultados: Comparada aos animais que receberam água, a área vascular média, expressa em percentagem, foi significativamente menor nos animais tratados com própolis (p<0,05) e com L-lisina (p<0,001). Conclusão: Tanto a própolis vermelha quanto a L-lisina inibiram a angiogênese no novo modelo de bolsa jugal de hamsters, quando administradas após a inoculação do tumor.
Subject(s)
Propolis/therapeutic use , Angiogenesis Inhibitors/therapeutic use , Lysine/therapeutic use , Neovascularization, Pathologic/drug therapy , Mouth Neoplasms/chemically induced , Mouth Neoplasms/blood supply , Mouth Neoplasms/drug therapy , Carcinoma 256, Walker/blood supply , Weight Gain , Cheek , Cricetinae , Mesocricetus , Treatment Outcome , Models, Animal , AntioxidantsABSTRACT
OBJECTIVES: This retrospective study performed a comprehensive analysis of the usage of intra-arterial chemotherapy (iaCh) for locally recurrent UICC stage IV oral squamous cell carcinoma (OSCC) over two decades at the Department of Cranio-Maxillofacial and Oral Surgery at the University Hospital Vienna to assess the utility of its future use. METHODS: Between 1994 and 2014, iaCh was indicated in 48 OSCC cases. In these, the two most frequent iaCh schemes, cisplatin/5-fluorouracil (Cis/5-FU) and methotrexate/bleomycin (MTX/Bleo), were chosen for further analysis. The effect on survival of two distinct intra-arterial protocols and their covariates were analyzed with the Kaplan-Meier method as well as univariate and multivariate Cox proportional hazard regression models. RESULTS: The mean follow-up period was 29.91 months. The two intra-arterial chemotherapy groups did not differ significantly in sample size, demographic data or therapeutic covariates. The Cis/5-FU iaCh regimen was associated with significantly better overall survival (median OS 2.6 years vs. 1.3 years; p=0.002) and had a beneficial effect on survival (HR=3.62, p=0.015). Side effects occurred at a frequency similar to that described in the literature for intravenous chemotherapy (ivCh). CONCLUSIONS: These results suggest a preference for administering Cis/5-FU for iaCh. Nevertheless, due to economic considerations in healthcare expenditures, there is no future for iaCh in the treatment of head and neck carcinomas because ivCh is known to be equivalent.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Mouth Neoplasms/drug therapy , Carcinoma, Squamous Cell/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Infusions, Intra-Arterial , Methotrexate/administration & dosage , Retrospective Studies , Cisplatin/administration & dosage , Treatment Outcome , Kaplan-Meier Estimate , Fluorouracil/administration & dosage , Neoplasm Recurrence, Local , Neoplasm StagingABSTRACT
Introduction: Burkitt's lymphoma is an aggressive form of B cell lymphoma generally diagnosed in children and young adults. This tumor has three variants: African (endemic), American (sporadic), and immunodeficiency-associated. Objective: present a case of Burkitt's lymphoma that manifested as a tumor mass in the upper right maxillary region of a patient with AIDS treated at Professor Edgar Santos University Hospital in Salvador, Bahia, Brazil. Clinical case: a male 20-year-old HIV-positive patient was referred from another hospital with a possible odontogenic infection that persisted after drainage and antibiotic therapy. The patient presented a tumor growth in the upper right gingival mucosa. After biopsy, histopathological findings were suggestive of Burkitt's lymphoma. An immunohistochemical panel was positive for CD20 and Bcl6 and negative for CD3, Bcl2, and terminal deoxynucleotidyl transferase antibodies. The Ki67 expression level was 80 percent. The final diagnosis was immunodeficiency-associated Burkitt's lymphoma. The patient was successfully treated with cytoreductive chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), followed by high-dose methotrexate, cyclophosphamide, doxorubicin and vincristine, alternating with high-dose cytarabine, ifosfamide and etoposide. No signs of recurrence have been noted during the follow-up period. Conclusions: Burkitt's lymphoma is an aggressive neoplasia with a rapidly progressing clinical course. Therefore, differential diagnosis from other benign oral diseases is of great importance(AU)
Introducción: el linfoma de Burkitt es una forma agresiva de linfoma de células B generalmente diagnosticado en niños y adultos jóvenes. El tumor tiene tres variantes: africana (endémica), americana (esporádica) y asociada con la inmunodeficiencia. Objetivo: presentar un caso de linfoma de Burkitt que se manifestó como una masa tumoral en la región maxilar superior derecha en un paciente con SIDA tratado en el Hospital Universitario Profesor Edgard Santos en Salvador, Bahia, Brasil. Caso clínico: un hombre VIH-positivo de 20 años de edad fue remitido de otro hospital con una posible infección odontogénica que persistió después del drenaje y tratamiento antibiótico. El paciente presentaba un abultamiento tumoral en la mucosa gingival superior derecha. Después de la biopsia, los resultados histopatológicos sugirieron la presencia de linfoma de Burkitt. Un panel inmunohistoquímico fue positivo para CD20 y Bcl6, y negativo para CD3, Bcl2 y para anticuerpos contra la desoxinucleotidil transferasa terminal. El nivel de expresión del Ki67 fue de 80 por ciento. El diagnóstico final fue linfoma de Burkitt asociado a la inmunodeficiencia. El paciente fue tratado con éxito con quimioterapia citorreductiva (ciclofosfamida, doxorrubicina, vincristina y prednisona), seguida de ciclofosfamida, doxorrubicina, vincristina y metotrexato en altas dosis, alternando con ifosfamida, etopósido y citarabina en altas dosis. No se observaron señales de recurrencia durante el período de seguimiento. Conclusiones: el linfoma de Burkitt es una neoplasia agresiva con rápida evolución clínica. Por lo tanto, el diagnóstico diferencial de otras enfermedades bucales benignas es de gran importancia(AU)
Subject(s)
Humans , Male , Adult , Burkitt Lymphoma/diagnosis , Lymphoma, AIDS-Related/drug therapy , Mouth Neoplasms/drug therapyABSTRACT
Abstract: The aim of this study was to evaluate the health-related quality of life (QOL) of patients with squamous cell carcinoma (SCC) according to tumor location. The sample consisted of 27 patients with primary SCC in the oral cavity (n = 15), pharynx (n = 7), and larynx (n = 5) who were undergoing cancer treatment at the Cancer Hospital of Londrina, regardless of age, sex, clinical stage, and type of antineoplastic treatment. Health-related QOL was evaluated using the 30-item Cancer-Quality of Life Questionnaire (QLQ-C30), the 35-item Head and Neck Cancer-Quality of Life Questionnaire (QLQ-HN35), and the University of Washington Quality of Life Questionnaire (UW-QOL). These questionnaires were administered individually to each patient before ambulatory care. Sociodemographic data (age and sex) and clinical data (T stage, tumor location, and type of antineoplastic treatment) were collected from the patients' medical records. Scores were compared according to tumor location using the chi-squared test and one-way analysis of variance (p < 0.05). No score differed significantly according to tumor location. It can be concluded that the health-related QOL of patients with SCC was not influenced by tumor location.
Subject(s)
Humans , Male , Female , Aged , Quality of Life , Mouth Neoplasms/pathology , Mouth Neoplasms/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/drug therapy , Pharyngeal Neoplasms/pathology , Pharyngeal Neoplasms/drug therapy , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/drug therapy , Sex Factors , Cross-Sectional Studies , Surveys and Questionnaires , Analysis of Variance , Age Factors , Middle Aged , Neoplasm Staging , Antineoplastic Agents/therapeutic useABSTRACT
Introdução: a quimioterapia é um tratamento anticâncer fundamentado na utilização de fármacos que induzem a morte das células neoplásicas. A literatura descreve que lesões bucais podem surgir em consequência do tratamento quimioterápico. Objetivo: identificar as manifestações bucais em pacientes submetidos à quimioterapia atendidos no serviço de referencia em oncologia da região sul do estado do Ceará-Brasil. Métodos: o presente estudo, do tipo transversal descritivo, avaliou 73 pacientes acometidos por algum tipo de neoplasia maligna e em tratamento quimioterápico no período de janeiro de 2013 a dezembro de 2014. Os dados clinico-patológicos como idade, gênero, diagnóstico da neoplasia maligna, tipos de tratamentos anticâncer, esquema medicamentoso quimioterápico, entre outros, foram obtidos a partir dos prontuários médicos. Foram ainda realizados exames intrabucais em todos os indivíduos desse estudo por um único examinador especialista em Estomatologia. Resultados: dos 73 pacientes 29 (39,7 porcento) eram do gênero masculino e 44 (60,3 porcento) do gênero feminino, com idade média de 57,7 anos, sendo 37 (50,7 porcento) dos pacientes fumantes. A mama foi o local mais prevalente de acometimento do câncer (35,6 porcento). Os fármacos mais utilizados na terapia quimioterápica foram a aredia em 23,3 porcento dos casos (n= 17) e o paclitaxel em 17,8 porcento (n= 13). Em relação às manifestações bucais, dos 73 pacientes do estudo, 44 (60,2 porcento) apresentaram algum tipo de desconforto bucal. A maioria dos pacientes, 77,3 porcento (n= 34), foram diagnosticados com xerostomia e em 22,7 porcento (n= 10) foram observados mucosite. Conclusão: as manifestações bucais encontradas em pacientes em tratamento quimioterápico foram a xerostomia e a mucosite, sendo a xerostomia a condição patológica bucal mais prevalente(AU)
Introducción: la quimioterapia es un tratamiento basado en el uso de fármacos anticancerígenos que inducen la muerte de las células cancerosas. La literatura describe lesiones bucales pueden surgir como resultado de la quimioterapia. Objetivo: identificar las manifestaciones bucales en pacientes sometidos a quimioterapia atendidos en el servicio de referencia en oncología en Estado del Ceará-Brasil. Métodos: se evaluaron 73 pacientes afectados por algún tipo de malignidad tratada con quimioterapia a partir de enero de 2013 hasta el mes de diciembre del 2014. Los datos clínicos y patológicos (edad, sexo, diagnóstico de malignidad, tipos de tratamientos con fármacos de quimioterapia contra el cáncer, entre otros), se obtuvieron de los registros médicos. También se realizaron exámenes bucales en todos los sujetos de este estudio por el experto en estomatología. Resultados: de los 73 pacientes 29 (39,7 por ciento) eran hombres y 44 (60,3 por ciento) mujeres, con una edad media de 57,7 años, y 37 (50,7 por ciento) eran fumadores. La mayor prevalencia del cáncer se observó en la mama (35,6 por ciento). Los fármacos más frecuentemente utilizados en el tratamiento de quimioterapia fueron aredia en 23,3 por ciento de los casos (n= 17) y paclitaxel en el 17,8 por ciento (n= 13). En relación con las enfermedades bucales, de los 73 pacientes estudiados, 44 (60,2 por ciento) tenían algún tipo de malestar bucal. La mayoría de los pacientes (77,3 por ciento; n= 34) fueron diagnosticados con xerostomía y 22,7 por ciento (n= 10) con mucositis. Conclusión: las lesiones bucales que se encontraron en los pacientes sometidos a quimioterapia fueron a xerostomía y mucositis. La xerostomía fue la condición patológica bucal más frecuente(AU)
Introduction: chemotherapy is a treatment based on the use of anticancer drugs that induce the death of cancer cells. The literature describes oral lesions may arise as a result of chemotherapy. Objective: to identify the oral manifestations in patients undergoing chemotherapy treated at the reference service in oncology southern state of Ceará - Brazil. Methods: we evaluated 73 patients affected by some type of malignancy and chemotherapy from January of 2013 to December of 2014. The clinical and pathological data such as age, gender, diagnosis of malignancy, types of treatments anticancer chemotherapeutic drug treatment, among others,were obtained from medical records. Were also carried out oral examinations in all subjects of this study by the same examiner specialist in stomatology. Results: of the 73 patients 29 (39.7 percent) were male and 44 (60.3 percent) females with a mean age of 57.7 years, and 37 (50.7 percent) of smokers. Regarding malignancy, the mama was the most prevalent location (35.6 %). The drugs most frequently used in chemotherapy treatment were aredia in 23.3 percent of cases (n= 17) and paclitaxel in 17.8 percent (n= 13). In the oral manifestations, of the 73 patients studied, 44 (60.2 percent) had some type of oral discomfort. Most patients, 77.3 percent (n= 34) were diagnosed with xerostomia and 22.7 percent (n= 10) were observed mucositis. Conclusion: oral lesions found in patients undergoing chemotherapy were xerostomia and mucositis. Xerostomia being the most prevalent oral pathological condition(AU)
Subject(s)
Humans , Male , Female , Middle Aged , Oral Manifestations , Stomatitis/drug therapy , Xerostomia/pathology , Mouth Neoplasms/drug therapy , Epidemiology, Descriptive , Cross-Sectional Studies , Diagnosis, Oral/methodsABSTRACT
Introduction: in the last decade, with all the advanced medical research in the treatments for cancer, there is a constant debate for the best possible treatment for oral squamous cell carcinomas. Radiotherapy with surgery has they compared with the addition of chemotherapy for control of the disease or survival of the patient. Objective: to compare the effectiveness of radiotherapy with combined chemotherapy and radiotherapy for the control of oral squamous cell carcinomas. Methods: it was a systematic review with meta-analysis. Randomized trials in all phases were search with specific inclusion criteria through electronic database, hand searching and contacting experts in the field. After exclusion, criteria and the use of critical review checklist, three trials they selected for analysis. Three randomized trials representing 508 patients they identified. Some trials they analyzed in Review manager software 5.0®. The fix effect model they chosen for the statistical analysis, assuming that any observed variation in the score was an error of the specific article, with a confidence of 95 percent (CI 1.132.77). The I2 presents percent of heterogeneity of 0 percent, indicating that there is no clinically significant change in the results of the studies included. Result: evidenced the significance of 0.44 (higher than 0.05) in the chi square test indicating that the results are homogeneous or clinically similar. The Forest plot is located in the experimental group (chemotherapy and radiotherapy), establishing the clinical recommendation of use(AU) Conclusion: the usage of chemotherapy treatment in combination of radiotherapy regimen they recommended as for its promising results. Not also, the overall survival has improved, survival and distant metastasis free rates improve
Introducción: en la última década se ha avanzado en tratamientos para el cáncer; sin embargo, se mantiene un debate constante para determinar el mejor tratamiento para los carcinomas orales de células escamosas. El tratamiento combinado de radioterapia y cirugía fue comparado con la quimioterapia para el control de la enfermedad o la supervivencia de la paciente. Objetivo: comparar la efectividad de la radioterapia con la radioterapia y quimioterapia combinadas para el control de los carcinomas de células escamosas orales. Métodos: se realizó una revisión sistemática con metaanálisis. Se buscaron ensayos aleatorios en todas las fases a través de bases de datos, búsquedas manuales y el contacto con expertos. Después de evaluar los criterios de selección y el uso de lista de revisión crítica, se seleccionaron tres ensayos para el análisis identificando tres ensayos aleatorios que incluyendo 508 pacientes. Se analizaron con el software Review manager 5.0®. Para el análisis estadístico se eligió el modelo de efecto fijo, con una confianza de 95 por ciento (IC 1,13-2,77). El I2 presenta el porcentaje de la heterogeneidad de 0 por ciento, lo cual indica que no existe una variación clínicamente significativa en los resultados de los estudios incorporados. Resultado: se evidencia una significación de 0,44 (superior a 0,05) en la prueba de chi cuadrado, esto indica que los resultados son homogéneos o clínicamente similares. La medida de resumen del Forest Plot se sitúa en el grupo experimental (quimioterapia y radioterapia), el establecimiento de la recomendación clínica de uso. Conclusión: el uso de un tratamiento de quimioterapia en combinación con radioterapia es recomendable. La supervivencia en general ha mejorado y las tasas libres de metástasis también mejoran(AU)
Subject(s)
Humans , Mouth Neoplasms/drug therapy , Carcinoma, Squamous Cell/therapy , Meta-Analysis as Topic , Databases, Bibliographic/statistics & numerical data , Combined Modality Therapy/methodsSubject(s)
Humans , Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Facial Neoplasms/drug therapy , Mouth Neoplasms/drug therapy , Chemotherapy, Adjuvant , Carcinoma, Squamous Cell/pathology , Facial Neoplasms/pathology , Mouth Neoplasms/pathology , Neoplasm Recurrence, Local , Neoplasm Staging , Palliative CareABSTRACT
Objetivos: O objetivo deste estudo foi o de identificar compostos seletivamente tóxicos ao carcinoma espinocelular de boca in vitro por meio do reposicionamento de fármacos. Material e Métodos: Por meio de um escaneamento baseado na viabilidade celular de 1.280 fármacos, nós selecionamos três princípios ativos (luteolin, metixene hydrochloride e nitazoxanide) letais às células de câncer de boca SCC-25 e pouco tóxicos às células de queratinócitos cutâneos imortalizados HaCaT. Os fármacos candidatos foram investigados quanto à sua dose- e tempo-resposta bem como comparados e combinados à agentes quimioterápicos padrão por meio do ensaio por colorimetria com brometo de tiazolil azul de tetrazolio (MTT). O impacto dos fármacos na motilidade do SCC-25 e do HaCaT foi verificado pelo ensaio de migração celular e seus mecanismos de ação também foram explorados por meio da verificação dos níveis das proteínas fosforiladas pelo western blotting. Todos os experimentos foram realizados em triplicata e, pelo menos, três vezes independentes. O teste t de student foi utilizado para confrontar as variáveis e nível de significância de 5% foi estabelecido para todos os testes. Resultados: O flavonoide natural luteolin exerceu citotoxicidade potente contra as células de câncer de boca in vitro, apresentando baixa toxicidade ao HaCaT e alta eficiência quando comparado a quimioterápicos como a cisplatina e o AG1478. Do ponto de vista molecular, a luteolin ativou a via de sinalização do dano do DNA e, combinada com um inibidor do Chk, apresentou efeitos potencializados. Além disso, nós demonstramos que a nitazoxanide e o metixene hydrochloride são capazes de destruir células SCC-25 porém não as HaCaT de maneira proporcional à dose e ao tempo de tratamento. As combinações entre os três fármacos hit e com a cisplatina ou o AG1478 potencializaram seus efeitos contra as células malignas. Conclusões: O presente estudo traz a luteolin, o metixene hydrochloride e a nitazoxanide como...
Objectives: Here we aimed at identifying and reposition approved drugs that could be selectively toxic towards oral squamous cell carcinoma cells. Materials and Methods: Through a cell-based drug screening of 1,280 chemical molecules, we selected 3 compounds (luteolin, metixene hydrochloride, and nitazoxanide) lethal to oral cancer SCC-25 cells, while sparing immortalized keratinocyte HaCaT cells. The drugs were then further challenged for their time- and dose-responses, as well as their comparison and combination to standard chemotherapeutic agents by colorimetric assay 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan, Thiazolyl blue formazan (MTT). The impact on SCC-25 and HaCaT motility as well as the mode of action of the drugs was then further explored by scratching assay and western blotting, respectively. All the experiments were performed in triplicated and, at least, three independent times. Students t test was performed to verify the differences among the variables and the level of significance was set at 5%. Results: The natural flavonoid luteolin was a potent cytotoxic agent against oral cancer cells in vitro, presenting low toxicity against HaCaT cells and high efficiency as compared to standard-of-care, such as cisplatin and AG1478. From a molecular standpoint, luteolin coopted the DNA-damage pathway and could be efficiently combined with Chk pharmacological inhibitor. Moreover, we demonstrated that nitazoxanide and metixene hydrochloride kill the SCC-25 but not the HaCaT cells in a dose- and time-dependent. The combinations among the three drugs hit and with cisplatin and AG1478 improved their effect against the malignant cells. Conclusions: Luteolin, metixene hydrochloride, and nitazoxanide emerge as strong cytotoxic and/or adjuvant therapy in oral cancer, as these compounds present higher efficiency and lower toxicity against oral cancer cells in vitro than conventional chemotherapeutic agents.
Subject(s)
Humans , Male , Middle Aged , Aged , Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Drug Repositioning , Luteolin/therapeutic use , Mouth Neoplasms/drug therapy , Thiazoles/therapeutic use , Thioxanthenes/therapeutic use , Antineoplastic Agents/pharmacology , Blotting, Western , Feasibility Studies , Luteolin/pharmacology , Reproducibility of Results , Cell Survival , Thiazoles/pharmacology , Thioxanthenes/pharmacologyABSTRACT
A ativação do receptor beta 2 adrenérgico (β2-AR), pelos mediadores químicos do estresse, pode induzir efeitos estimuladores ou inibidores na migração e invasão celular, dependendo do tipo de tumor maligno. A importância deste receptor na evolução do câncer de boca não está totalmente esclarecida. O objetivo deste estudo foi verificar a expressão do β2-AR em linhagens de carcinomas espinocelular de boca (SCC-9 e SCC-25), e investigar o papel da ativação deste receptor pela norepinefrina e de seu bloqueio por um antagonista na migração e invasão destas células neoplásicas. As células SCC-9 e SCC-25 foram investigadas quanto à expressão gênica e proteica do β2-AR, respectivamente, pelo RT-qPCR e pelo Western blot. A migração e a invasão celular foram analisadas pelo ensaio de cicatrização de feridas e pelo sistema de câmeras de invasão Transwell, respectivamente. Diferentes concentrações (0,1; 1 e 10μM) de norepinefrina foram utilizadas para estimular e 1μM de propranolol foi empregado para bloquear os receptores beta adrenérgicos nas células neoplásicas. As diferenças das médias obtidas nos experimentos de invasão e migração de SCC-9 e SCC-25 e da expressão proteica do β2-AR, foram comparadas pelo teste t de Student com nível de significância de 5%. Os resultados mostraram que a expressão gênica e proteica do β2-AR foi verificada em ambas as linhagens de câncer de boca. A concentração de 10μM de norepinefrina inibiu, significativamente (p≤0,05), a migração e invasão celular de SCC-9 e SCC-25, sendo este efeito mais acentuado nas células SCC-25. Além disso, houve uma redução significativa (p≤0,05) do efeito da norepinefrina na migração celular quando os β2-AR foram inibidos pelo propranolol. Adicionalmente, o bloqueio dos β-ARs pelo propranolol reverteu parcialmente o efeito da norepinefrina na capacidade invasiva de SCC-9 e SCC-25. Estes resultados comprovam que a norepinefrina, via ativação do β2-AR, reduziu a migração e a invasão das...
The activation of beta 2 adrenergic receptor (β2-AR), by chemical mediators of stress, can induce stimulatory or inhibitory effects on cell migration and invasion, depending on the type of malignancy. The importance of this receptor in the oral cancer outcome is not fully understood. The aim of this study was to verify β2- AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of activation of this receptor by norepinephrine and its blockade by an antagonist in migration and invasion of these neoplastic cells. SCC-9 and SCC-25 cells were investigated for gene and protein expression of β2-AR, respectively, by RT-qPCR and Western blot. The cell migration and invasion were analyzed by wound healing assay and Transwell invasion camera system, respectively. Different concentrations (0.1, 1 and 10μM) of norepinephrine were used to stimulate and 1μM propranolol was used to block the beta adrenergic receptors on cancer cells. Differences in mean values of the invasion and migration assays of SCC-9 and SCC-25 and β2-AR protein expression were compared by the Student t test with 5% significance level. The results showed that β2-AR gene and protein expression was verified in both oral cancer cell lines. The concentration of 10μM of norepinephrine inhibited significantly (p≤0.05), cell migration and invasion of SCC-9 and SCC-25, being the most pronounced effect in SCC-25 cells. Furthermore, there was a significant reduction (p≤0.05) of norepinephrine effect on cell migration when the β2-AR was inhibited by propranolol. In addition, blockade of β-ARs by propranolol partially reversed the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25. These results show that norepinephrine via β2-AR activation, reduced the migration and invasion of oral squamous cell carcinoma cells and, therefore, the use of beta-adrenergic receptors agonists could become an adjuvant therapeutic target in the treatment of this malignancy.
Subject(s)
Humans , Male , Adult , Aged , Adrenergic alpha-Agonists/pharmacology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/drug therapy , Mouth Neoplasms/pathology , Mouth Neoplasms/drug therapy , Norepinephrine/pharmacology , Adrenergic alpha-Agonists/therapeutic use , Blotting, Western , Gene Expression , Cell Movement , Norepinephrine/therapeutic use , Real-Time Polymerase Chain Reaction , /analysisABSTRACT
O objetivo deste estudo foi o de identificar compostos seletivamente tóxicos ao carcinoma espinocelular de boca in vitro por meio do reposicionamento de fármacos. Material e Métodos: Por meio de um escaneamento baseado na viabilidade celular de 1.280 fármacos, nós selecionamos três princípios ativos (luteolin, metixene hydrochloride e nitazoxanide) letais às células de câncer de boca SCC-25 e pouco tóxicos às células de queratinócitos cutâneos imortalizados HaCaT. Os fármacos candidatos foram investigados quanto à sua dose- e tempo-resposta bem como comparados e combinados à agentes quimioterápicos padrão por meio do ensaio por colorimetria com brometo de tiazolil azul de tetrazolio (MTT). O impacto dos fármacos na motilidade do SCC-25 e do HaCaT foi verificado pelo ensaio de migração celular e seus mecanismos de ação também foram explorados por meio da verificação dos níveis das proteínas fosforiladas pelo western blotting. Todos os experimentos foram realizados em triplicata e, pelo menos, três vezes independentes. O teste t de student foi utilizado para confrontar as variáveis e nível de significância de 5% foi estabelecido para todos os testes. Resultados: O flavonoide natural luteolin exerceu citotoxicidade potente contra as células de câncer de boca in vitro, apresentando baixa toxicidade ao HaCaT e alta eficiência quando comparado a quimioterápicos como a cisplatina e o AG1478. Do ponto de vista molecular, a luteolin ativou a via de sinalização do dano do DNA e, combinada com um inibidor do Chk, apresentou efeitos potencializados. Além disso, nós demonstramos que a nitazoxanide e o metixene hydrochloride são capazes de destruir células SCC-25 porém não as HaCaT de maneira proporcional à dose e ao tempo de tratamento. As combinações entre os três fármacos hit e com a cisplatina ou o AG1478 potencializaram seus efeitos contra as células malignas. Conclusões: O presente estudo traz a luteolin, o metixene hydrochloride e a nitazoxanide como...
Here we aimed at identifying and reposition approved drugs that could be selectively toxic towards oral squamous cell carcinoma cells. Materials and Methods: Through a cell-based drug screening of 1,280 chemical molecules, we selected 3 compounds (luteolin, metixene hydrochloride, and nitazoxanide) lethal to oral cancer SCC-25 cells, while sparing immortalized keratinocyte HaCaT cells. The drugs were then further challenged for their time- and dose-responses, as well as their comparison and combination to standard chemotherapeutic agents by colorimetric assay 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan, Thiazolyl blue formazan (MTT). The impact on SCC-25 and HaCaT motility as well as the mode of action of the drugs was then further explored by scratching assay and western blotting, respectively. All the experiments were performed in triplicated and, at least, three independent times. Students t test was performed to verify the differences among the variables and the level of significance was set at 5%. Results: The natural flavonoid luteolin was a potent cytotoxic agent against oral cancer cells in vitro, presenting low toxicity against HaCaT cells and high efficiency as compared to standard-of-care, such as cisplatin and AG1478. From a molecular standpoint, luteolin coopted the DNA-damage pathway and could be efficiently combined with Chk pharmacological inhibitor. Moreover, we demonstrated that nitazoxanide and metixene hydrochloride kill the SCC-25 but not the HaCaT cells in a dose- and time-dependent. The combinations among the three drugs hit and with cisplatin and AG1478 improved their effect against the malignant cells. Conclusions: Luteolin, metixene hydrochloride, and nitazoxanide emerge as strong cytotoxic and/or adjuvant therapy in oral cancer, as these compounds present higher efficiency and lower toxicity against oral cancer cells in vitro than conventional chemotherapeutic agents...
Subject(s)
Humans , Male , Middle Aged , Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Drug Repositioning , Luteolin/therapeutic use , Mouth Neoplasms/drug therapy , Thiazoles/therapeutic use , Thioxanthenes/therapeutic use , Antineoplastic Agents/pharmacology , Blotting, Western , Feasibility Studies , Luteolin/pharmacology , Reproducibility of Results , Cell Survival , Thiazoles/pharmacology , Thioxanthenes/pharmacologyABSTRACT
A ativação do receptor beta 2 adrenérgico (β2-AR), pelos mediadores químicos do estresse, pode induzir efeitos estimuladores ou inibidores na migração e invasão celular, dependendo do tipo de tumor maligno. A importância deste receptor na evolução do câncer de boca não está totalmente esclarecida. O objetivo deste estudo foi verificar a expressão do β2-AR em linhagens de carcinomas espinocelular de boca (SCC-9 e SCC-25), e investigar o papel da ativação deste receptor pela norepinefrina e de seu bloqueio por um antagonista na migração e invasão destas células neoplásicas. As células SCC-9 e SCC-25 foram investigadas quanto à expressão gênica e proteica do β2-AR, respectivamente, pelo RT-qPCR e pelo Western blot. A migração e a invasão celular foram analisadas pelo ensaio de cicatrização de feridas e pelo sistema de câmeras de invasão Transwell, respectivamente. Diferentes concentrações (0,1; 1 e 10μM) de norepinefrina foram utilizadas para estimular e 1μM de propranolol foi empregado para bloquear os receptores beta adrenérgicos nas células neoplásicas. As diferenças das médias obtidas nos experimentos de invasão e migração de SCC-9 e SCC-25 e da expressão proteica do β2-AR, foram comparadas pelo teste t de Student com nível de significância de 5%. Os resultados mostraram que a expressão gênica e proteica do β2-AR foi verificada em ambas as linhagens de câncer de boca. A concentração de 10μM de norepinefrina inibiu, significativamente (p≤0,05), a migração e invasão celular de SCC-9 e SCC-25, sendo este efeito mais acentuado nas células SCC-25. Além disso, houve uma redução significativa (p≤0,05) do efeito da norepinefrina na migração celular quando os β2-AR foram inibidos pelo propranolol. Adicionalmente, o bloqueio dos β-ARs pelo propranolol reverteu parcialmente o efeito da norepinefrina na capacidade invasiva de SCC-9 e SCC-25. Estes resultados comprovam que a norepinefrina, via ativação do β2-AR, reduziu a migração e a invasão das...
The activation of beta 2 adrenergic receptor (β2-AR), by chemical mediators of stress, can induce stimulatory or inhibitory effects on cell migration and invasion, depending on the type of malignancy. The importance of this receptor in the oral cancer outcome is not fully understood. The aim of this study was to verify β2- AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of activation of this receptor by norepinephrine and its blockade by an antagonist in migration and invasion of these neoplastic cells. SCC-9 and SCC-25 cells were investigated for gene and protein expression of β2-AR, respectively, by RT-qPCR and Western blot. The cell migration and invasion were analyzed by wound healing assay and Transwell invasion camera system, respectively. Different concentrations (0.1, 1 and 10μM) of norepinephrine were used to stimulate and 1μM propranolol was used to block the beta adrenergic receptors on cancer cells. Differences in mean values of the invasion and migration assays of SCC-9 and SCC-25 and β2-AR protein expression were compared by the Student t test with 5% significance level. The results showed that β2-AR gene and protein expression was verified in both oral cancer cell lines. The concentration of 10μM of norepinephrine inhibited significantly (p≤0.05), cell migration and invasion of SCC-9 and SCC-25, being the most pronounced effect in SCC-25 cells. Furthermore, there was a significant reduction (p≤0.05) of norepinephrine effect on cell migration when the β2-AR was inhibited by propranolol. In addition, blockade of β-ARs by propranolol partially reversed the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25. These results show that norepinephrine via β2-AR activation, reduced the migration and invasion of oral squamous cell carcinoma cells and, therefore, the use of beta-adrenergic receptors agonists could become an adjuvant therapeutic target in the treatment of this malignancy...
Subject(s)
Humans , Male , Adult , Aged , Adrenergic alpha-Agonists/pharmacology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/drug therapy , Mouth Neoplasms/pathology , Mouth Neoplasms/drug therapy , Norepinephrine/pharmacology , Adrenergic alpha-Agonists/therapeutic use , Blotting, Western , Gene Expression , Cell Movement , Norepinephrine/therapeutic use , Real-Time Polymerase Chain Reaction , /analysisABSTRACT
The present study aimed to evaluate the influence of the following irrigating solutions on the microhardness of root canal dentin: 2% sodium hypochlorite (2NaOCl), 5% sodium hypochlorite (5NaOCl), super-oxidized water (400 ppm Sterilox - Sx) and 17% EDTA (E). Eighty roots from bovine incisors were randomly divided into 8 groups (n=10): 2NaOCl, 5NaOCl, Sx, and 2NaOCl + E, 5NaOCl + E, Sx + E (associated with E as final irrigant for 5 min), E solely and distilled water (dH2O) as the negative control. Root canal preparation was performed by hand instruments, using one of the irrigation protocols for 30 min. Then, 5 mm of the cervical root third were cut out from each sample and subjected to the Vickers microhardness test, at two points, one at approximately 500-1000 µm from the root canal lumen (distance 1), and the other at approximately 500-1000 µm from the external root surface (distance 2). Data were analyzed by Wilcoxon and Kruskal-Wallis tests at 5% significance level. Microhardness values at distance 1 were significantly lower than those at distance 2 for all groups, except 5NaOCl and 5NaOCl + E groups (p>0.05). EDTA showed the lowest microhardness values. However, no statistically significant difference was detected among groups at distance 1 and EDTA was significantly different only from Sx at distance 2. In conclusion, all tested solutions showed lower microhardness at the most superficial root canal dentin layer compared to the one found near the external root surface, except 5NaOCl and 5NaOCl + E; EDTA promoted lower microhardness values in comparison to Sterilox at this site.
O presente estudo teve como objetivo avaliar a influência das seguintes soluções irrigadoras na microdureza da dentina do canal radicular: hipoclorito de sódio a 2% (NaOCl2), hipoclorito de sódio a 5% (NaOCl5), água superoxidada (Sterilox(r) 400 ppm - Sx) e EDTA a 17% (E). Oitenta raízes de incisivos bovinos foram divididas aleatoriamente em 8 grupos (n=10): NaOCl2, NaOCl5, Sx e NaOCl2 + E, NaOCl5 + E, Sx + E (associados ao E como irrigante final por 5 min), E isolado e água destilada (H2Od), como controle negativo. O preparo dos canais radiculares foi realizado com instrumentos manuais, usando um dos protocolos de irrigação por 30 min. A seguir, 5 mm do terço cervical de cada amostra foram cortados perpendicularmente e submetidos ao teste de microdureza de Vickers, em dois pontos, um aproximadamente 500-1000 µm da luz do canal radicular (distância 1), e o outro aproximadamente 500-1000 µm da superfície externa da raiz (distância 2). Os dados foram analisados pelos testes de Wilcoxon e Kruskal-Wallis com um nível de significância de 5%. Os valores de microdureza na distância 1 foram significativamente menores do que na distância 2 para todos os grupos, exceto NaOCl5 e NaOCl5 +E (p>0,05). O EDTA mostrou os menores valores de microdureza. No entanto, não foi detectada diferença estatisticamente significativa entre os grupos na distância 1 e o EDTA foi significativamente diferente apenas do Sx na distância 2. Pode-se concluir que todas as soluções testadas mostraram menor microdureza na camada de dentina mais superficial do canal radicular em comparação aos valores encontrados próximo à superfície radicular externa, exceto NaOCl5 e NaOCl5 + E; o EDTA promoveu menor microdureza em comparação ao Sterilox(r) neste ponto.