RESUMEN
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents a promising anticancer agent, as it selectively induces apoptosis in transformed cells without altering the cellular machinery of healthy cells. Unfortunately, the presence of TRAIL resistance mechanisms in a variety of cancer types represents a major hurdle, thus limiting the use of TRAIL as a single agent. Accumulating studies have shown that TRAIL-mediated apoptosis can be facilitated in resistant tumors by combined treatment with antitumor agents, ranging from synthetic molecules to natural products. Among the latter, flavonoids, the most prevalent polyphenols in plants, have shown remarkable competence in improving TRAIL-driven apoptosis in resistant cell lines as well as tumor-bearing mice with minimal side effects. Here, we summarize the molecular mechanisms, such as the upregulation of death receptor (DR)4 and DR5 and downregulation of key anti-apoptotic proteins [e.g., cellular FLICE-inhibitory protein (c-FLIP), X-linked inhibitor of apoptosis protein (XIAP), survivin], underlying the TRAIL-sensitizing properties of different classes of flavonoids (e.g., flavones, flavonols, isoflavones, chalcones, prenylflavonoids). Finally, we discuss limitations, mainly related to bioavailability issues, and future perspectives regarding the clinical use of flavonoids as adjuvant agents in TRAIL-based therapies.
Asunto(s)
Antineoplásicos , Flavonoides , Neoplasias , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Línea Celular Tumoral , Flavonoides/farmacología , Flavonoides/uso terapéutico , Ligandos , Neoplasias/tratamiento farmacológico , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC), two of the main inflammatory bowel diseases (IBD), have been increasingly diagnosed in South America. Although IBD have been intensively studied in the last years, epidemiologic data in Brazil are scarce. OBJECTIVE: To study the clinical and epidemiologic profile of IBD patients treated in the Clinical Hospital of the Federal University of Uberlândia from 1999 to 2014. METHODS: We performed a retrospective study of the medical records of patients diagnosed with IBD, according to the international classification of diseases (ICD) - ICD K50 for CD and ICD K51 for UC - confirmed by endoscopic examination in the case of both diseases. We analyzed the following variables: age; sex; ethnicity; smoking habit; primary diagnosis; site of disease manifestation; main clinical manifestations; IBD-related complications; extraintestinal manifestations; and established drug and/or surgical treatment. RESULTS: We evaluated 183 IBD cases (91 UC and 92 CD cases). The estimated prevalence rate of UC was 15.06/100.000 inhabitants and of CD was 15.23/100.000. The CU and CD female to male incidence ratios were 1.7 and 1.8, respectively. The average age of patients diagnosed with UC was 39.4 years and of those diagnosed with CD was 31.1 years. White-skinned people were the most affected by UC (66.0%) and CD (69.0%). Few patients were submitted to surgical procedures as treatment alternative. CONCLUSION: The estimated prevalence of IBD in this population was low compared to that of populations of North America, but high compared to that of other regions considered to present low incidence, such as some Asian and Latin American countries.
Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Adulto , Brasil/epidemiología , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología , Femenino , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/epidemiología , Masculino , Estudios RetrospectivosRESUMEN
ABSTRACT BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC), two of the main inflammatory bowel diseases (IBD), have been increasingly diagnosed in South America. Although IBD have been intensively studied in the last years, epidemiologic data in Brazil are scarce. OBJECTIVE: To study the clinical and epidemiologic profile of IBD patients treated in the Clinical Hospital of the Federal University of Uberlândia from 1999 to 2014. METHODS: We performed a retrospective study of the medical records of patients diagnosed with IBD, according to the international classification of diseases (ICD) - ICD K50 for CD and ICD K51 for UC - confirmed by endoscopic examination in the case of both diseases. We analyzed the following variables: age; sex; ethnicity; smoking habit; primary diagnosis; site of disease manifestation; main clinical manifestations; IBD-related complications; extraintestinal manifestations; and established drug and/or surgical treatment. RESULTS: We evaluated 183 IBD cases (91 UC and 92 CD cases). The estimated prevalence rate of UC was 15.06/100.000 inhabitants and of CD was 15.23/100.000. The CU and CD female to male incidence ratios were 1.7 and 1.8, respectively. The average age of patients diagnosed with UC was 39.4 years and of those diagnosed with CD was 31.1 years. White-skinned people were the most affected by UC (66.0%) and CD (69.0%). Few patients were submitted to surgical procedures as treatment alternative. CONCLUSION: The estimated prevalence of IBD in this population was low compared to that of populations of North America, but high compared to that of other regions considered to present low incidence, such as some Asian and Latin American countries.
RESUMO CONTEXTO: A doença de Crohn (DC) e a retocolite ulcerativa (RCU), duas das principais doenças inflamatórias intestinais (DIIs), têm sido cada vez mais diagnosticadas na América do Sul. Embora a DII tenha sido intensamente estudada nos últimos anos, os dados epidemiológicos no Brasil são escassos. OBJETIVO: Estudar o perfil clínico e epidemiológico dos pacientes com DII atendidos no Hospital das Clínicas da Universidade Federal de Uberlândia de 1999 a 2014. MÉTODOS: Foi realizado um estudo retrospectivo dos prontuários de pacientes com diagnóstico de DII, de acordo com a classificação internacional de doenças (CID) - CID K50 para DC e CID K51 para RCU - confirmado por exame endoscópico para ambas as doenças. Analisamos as seguintes variáveis: idade; sexo; etnia; hábito tabágico; diagnóstico primário; local de manifestação da doença; principais manifestações clínicas; complicações relacionadas a DII; manifestações extraintestinais; tratamentos medicamentoso e/ou cirúrgico instituídos. RESULTADOS: Foram avaliados 183 casos de DII (91 casos de RCU e 92 casos de DC). A prevalência estimada de RCU foi de 15,06/100.000 habitantes e de DC foi de 15,23/100.000. As taxas de incidência entre pacientes do sexo feminino e masculino foram de 1,7 para RCU e 1,8 para DC. A idade média dos pacientes com diagnóstico de RCU foi de 39,4 anos e daqueles com DC foi de 31,1 anos. A raça branca foi o grupo étnico mais afetado por RCU (66,0%) e DC (69,0%). Poucos pacientes foram submetidos a procedimentos cirúrgicos como alternativas de tratamento. CONCLUSÃO: A prevalência estimada de DII nesta população foi baixa em comparação com populações da América do Norte, mas elevada em comparação com outras regiões consideradas de baixa incidência, como alguns países da Ásia e da América Latina.