ABSTRACT
Comunidades complexas de bactérias, fungos e vírus prosperam em nossa pele. A composição dessas comunidades depende das características da pele, como concentração das glândulas sebáceas, teor de umidade e temperatura, bem como da genética do hospedeiro e fatores ambientais exógenos. Estudos metagenômicos recentes descobriram uma diversidade surpreendente dentro desses ecossistemas e promoveram uma nova visão dos organismos comensais durantes as diferentes fases da vida humana. Portanto nesta revisão de literatura buscamos compreender as interações micróbio-hospedeiro e descobrir os fatores que impulsionam a colonização microbiana nos ajudará a entender a patogênese das doenças de pele e a desenvolver novas terapêuticas pro-microbianas e antimicrobianas.
Complex communities of bacteria, fungi and viruses thrive on our skin. The composition of these communities depends on the characteristics of the skin, such as concentration of sebaceous glands, moisture and temperature content, as well as the host's genetics and exogenous environmental factors. Recent metagenomic studies have discovered a surprising diversity within these ecosystems and have promoted a new view of commensal organisms during the different stages of human life. Thus, this review explores microbe-host interactions and discovering the factors that drive microbial colonization will help us understand the pathogenesis of skin diseases and develop new promicrobial and antimicrobial therapies
ABSTRACT
A autofagia é uma via metabólica essencial para a manutenção da homeostase celular, e pode desempenhar diferentes papéis dentro do contexto fisiológico e patológico. Por este motivo tem sido foco de muitos estudos por ser um alvo terapêutico promissor, principalmente contra o câncer, onde atua de maneira ambígua, podendo suprimir ou promover o tumor de acordo com o contexto. Compreender a base molecular desse mecanismo é de interesse emergente para se alcançar terapias eficazes utilizando a modulação da autofagia. Neste trabalho, realizou-se uma revisão da literatura para abordar o papel da autofagia na biologia do câncer e como ela pode ser usada como estratégia terapêutica antitumoral através de sua ativação ou inibição no tratamento de vários tipos e estágios do câncer.
Autophagy is an essential metabolic pathway for the maintenance of cellular homeostasis and may play different roles within the physiological and pathological context. For this reason, it has been the focus of many studies because it is a promising therapeutic target, especially against cancer, in which plays a duo role, and it may suppress or promote the tumor according to the context. Understanding the molecular basis of this mechanism is an emerging interest to provide effective therapies using autophagy modulation. In this paper, we performed a literature review to address the role of autophagy in cancer biology and how it can be used as an antitumoral therapeutic strategy through its activation or inhibition to treat various types and stages of cancer.
ABSTRACT
Objective: GADD45A is a growth arrest-associated gene, directly involved in the maintenance of genomic stability. In fact, in the absence of this protein cells became sensitized to death by ultraviolet irradiation or cisplatin. However, this role with respect to cell damage triggered by Reactive Oxygen Species (ROS) is not well understood. Thus, in an attempt to evaluate its role in oxidative stress-induced apoptosis, we analyzed its expression after induction of ROS in human colon cell lines. Material and methods: Cell lines derived from human colon tumors (RKO-AS45-1 and HuTu-80) were treated with Menadione (MEN) and Hydrogen Peroxide (HP). Next, the expression of GADD45A was evaluated by semi-quantitative RT-PCR analysis. Results: The results indicated that expression of this gene was associated with resistance to apoptosis. Additionally, cells with high expression of GADD45A were resistant to treatment with oxidative stress-inducing compounds. Conclusion: In conclusion, we propose that the expression of the GADD45A gene can be used as a functional tool to predict cellular responses to antitumor treatments.
Subject(s)
Apoptosis , Colorectal Neoplasms , Hydrogen Peroxide , Oxidative Stress , Reactive Oxygen Species , Cell DeathABSTRACT
O melanoma cutâneo é a principal causa de morte por câncer de pele no Brasil, apresentando como principais fatores etiológicos e de predisposição a exposição à radiação UV e, as alterações genéticas e epigenéticas. Um modelo aceito para o processo tumorigênico do melanoma cutâneo é a transformação contínua dos melanócitos normais à displasia melanocítica, e por último ao melanoma maligno. ... Ao empregar a metodologia de busca de módulos funcionais descrita por SEGAL et al. (2003; 2004) identificamos alguns módulos funcionais que apresentaram mudança de estado de ativação com significância estatística (p0,05), segundo o grupo de melanoma: desenvolvimento da epiderme; atividade de peptidase; comunicação celular; adesão celular; receptor neuroativo ligante e assinatura metastática. Além disso, através da abordagem hipóteses baseadas em dados, identificamos milhares de pares de genes funcionalmente relacionados que apresentaram significativa quebra de correlação segundo o grupo de melanoma. Dentre estes destacamos aqueles presentes nos módulos funcionais desenvolvimento da epiderme (KLK7 x LAMA3; KLK7 x EVPL; KLK7 x BNC e KLK7 x SCEL); atividade de peptidase (KLK6 x KLK13); comunicação celular (COL3A1 x COL6A3); adesão celular (GPR56 x POSTN) e assinatura metastática (LUM x COL6A3 e IGFBP4 x IGF2). E finalmente, a partir das redes de relevância baseadas no processo de descamação da epiderme e no sistema IGF propusemos: 1) um mecanismo de transposição da camada basal ou de migração intra-epidérmica modulado, principalmente, por kalicreínas e por suas proteases-inibidoras; e 2) um mecanismo de sobrevivência e proliferação modulado por IGFBP-4 e por suas serina-proteases reguladoras (KLKs e MMPs).
Cutaneous melanoma is the leading cause of skin cancer death in occidental countries, having as major etiological and predisposing factors the exposion to UV radiation, and genetic and epigenetic susceptibility. The tumorigenesis of melanoma is explained by a continuous malignant transformation, from normal melanocytes to melanocytic displasia and melanoma. The underlying molecular events that explain malignant melanoma genesis have been only partially characterized, and only a small number of genes have been identified as playing key roles in melanoma initiation and progression. Among these, some cell cycle regulators, apoptotic, signal transduction, cell adhesion, and matrix digestion genes have been demonstrated to be deregulated in this neoplasm. In current project, we determined the gene expression profiling in primary and metastatic human melanoma disease. We improved the methodology developing by SEGAL et al. (2003; 2004) to stablish some functional maps which demonstrated significant alteration (p≤0,05) when primary and metastatic disease were compared: epidermis development; peptidase activity; cell communication; cell adhesion; neuroactive ligand receptor and metastatic signature. Furthermore, we determined according to relevance networks concept pair of genes functionally related that showed significant alteration in your correlations coefficients when primary and metastatic disease were compared. Among these we report those related to epidermis development - KLK7 (Kallikrein-7 precursor) x LAMA3 (Laminin, alpha 3); KLK7 x EVPL (Envoplakin); KLK7 x BNC (Basonuclin 1) and KLK7 x SCEL (Sciellin); peptidase activity - KLK6 (Kallikrein-6 precursor) x KLK13 (Kallikrein-13 precursor); cell communication - COL3A1 (Collagen, type III, alpha 1) x COL6A3 (Collagen, type VI, alpha 3cell adhesion - GPR56 (G protein-coupled receptor 56) x POSTN (Periostin precursor) and metastatic signature - LUM (Lumican precursor) x COL6A3 and IGFBP4 (Insulin-like growth factor-binding protein 4) x IGF2 (Insulin-like growth factor-2). And finally, we proposed two biological processes for melanoma progression that were based on epidermis desquamation and IGF system relevance networks (AU)