RESUMO
Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects, namely antioxidant, anti-inflammatory and immunomodulatory effects, which involve inhibiting molecular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential and cytokine, protein and gene expression were investigated in head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified morphology and inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in the G2/M and S phases. A decrease in cell migration was also observed, and there was decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IFN-γ and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anticancer effects on tumor cells by regulating signaling pathways associated with head and neck cancer.
Assuntos
Alcaloides , Apoptose , Benzodioxóis , Neoplasias de Cabeça e Pescoço , Inflamação , Piperidinas , Alcamidas Poli-Insaturadas , Transdução de Sinais , Alcamidas Poli-Insaturadas/farmacologia , Benzodioxóis/farmacologia , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Alcaloides/farmacologia , Humanos , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/genética , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/genética , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Citocinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
Alternative splicing is the process of generating different mRNAs from the same primary transcript, which contributes to increase the transcriptome and proteome diversity. Abnormal splicing has been associated with the development of several diseases including cancer. Given that mutations and abnormal levels of the RIPK2 transcript and RIP-2 protein are frequent in tumors, and that RIP-2 modulates immune and inflammatory responses, we investigated alternative splicing events that result in partial deletions of the kinase domain at the N-terminus of RIP-2. We also investigated the structure and expression of the RIPK2 truncated variants and isoforms in different environments. In addition, we searched data throughout Supraprimates evolution that could support the biological importance of RIPK2 alternatively spliced products. We observed that human variants and isoforms were differentially regulated following temperature stress, and that the truncated transcript was more expressed than the long transcript in tumor samples. The inverse was found for the longer protein isoform. The truncated variant was also detected in chimpanzee, gorilla, hare, pika, mouse, rat, and tree shrew. The fact that the same variant has been preserved in mammals with divergence times up to 70 million years raises the hypothesis that it may have a functional significance.
Assuntos
Processamento Alternativo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor , Animais , Humanos , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Evolução Molecular , Isoformas de Proteínas/genética , Camundongos , Neoplasias/genética , RatosRESUMO
The complex evolution of genetic alterations in cancer that occurs in vivo is a selective process involving numerous factors and mechanisms. Chemotherapeutic agents that prevent the growth and spread of cancer cells induce selective pressure, leading to rapid artificial selection of resistant subclones. This rapid evolution is possible because antineoplastic drugs promote alterations in tumorcell metabolism, thus creating a bottleneck event. The few resistant cells that survive in this new environment obtain differential reproductive success that enables them to pass down the newly selected resistant gene pool. The present review aims to summarize key findings of tumor evolution, epithelialmesenchymal transition and resistance to cetuximab therapy in head and neck squamous cell carcinoma.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genéticaRESUMO
Metabolomics has proven to be an important omics approach to understand the molecular pathways underlying the tumour phenotype and to identify new clinically useful markers. The literature on cancer has illustrated the potential of this approach as a diagnostic and prognostic tool. The present study aimed to analyse the plasma metabolic profile of patients with oral squamous cell carcinoma (OSCC) and controls and to compare patients with metastatic and primary tumours at different stages and subsites using nuclear magnetic resonance and mass spectrometry. To our knowledge, this is the only report that compared patients at different stages and subsites and replicates collected in diverse institutions at different times using these methodologies. Our results showed a plasma metabolic OSCC profile suggestive of abnormal ketogenesis, lipogenesis and energy metabolism, which is already present in early phases but is more evident in advanced stages of the disease. Reduced levels of several metabolites were also associated with an unfavorable prognosis. The observed metabolomic alterations may contribute to inflammation, immune response inhibition and tumour growth, and may be explained by four nonexclusive views-differential synthesis, uptake, release, and degradation of metabolites. The interpretation that assimilates these views is the cross talk between neoplastic and normal cells in the tumour microenvironment or in more distant anatomical sites, connected by biofluids, signalling molecules and vesicles. Additional population samples to evaluate the details of these molecular processes may lead to the discovery of new biomarkers and novel strategies for OSCC prevention and treatment.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Biomarcadores Tumorais/metabolismo , Metabolômica/métodos , Espectroscopia de Ressonância Magnética , Microambiente TumoralRESUMO
Ilhéus virus (ILHV) is a neglected mosquito-borne flavivirus. ILHV infection may lead to Ilhéus fever, an emerging febrile disease like dengue fever with the potential to evolve into a severe neurological disease characterized by meningoencephalitis; no specific treatments are available for this disease. This study assessed the antiviral properties of caffeic acid, an abundant component of plant-based food products that is also compatible with the socioeconomic limitations associated with this neglected infectious disease. The in vitro activity of caffeic acid on ILHV replication was investigated in Vero and A549 cell lines using plaque assays, quantitative RT-PCR, and immunofluorescence assays. We observed that 500 µM caffeic acid was virucidal against ILHV. Molecular docking indicated that caffeic acid might interact with an allosteric binding site on the envelope protein.
Assuntos
Antivirais , Animais , Humanos , Simulação de Acoplamento Molecular , Células A549 , Sítio Alostérico , Antivirais/farmacologiaRESUMO
Cervical cancer is the fourth-most common type of cancer in the world that causes death in women. It is mainly caused by persistent infection by human papillomavirus (HPV) that triggers a chronic inflammatory process. Therefore, the use of anti-inflammatory drugs is a potential treatment option. The effects of piperine, an amino alkaloid derived from Piper nigrum, are poorly understood in cervical cancer inflammation, making it a target of research. This work aimed to investigate the antitumor effect of piperine on cervical cancer and to determine whether this effect is modulated by the cyclooxygenase 2 (PTGS2) pathway using in vitro model of cervical cancer (HeLa, SiHa, CaSki), and non-tumoral (HaCaT) cell lines. The results showed that piperine reduces in vitro parameters associated with neoplastic evolution such as proliferation, viability and migration by cell cycle arrest in the G1/G0 and G2/M phases, with subsequent induction of apoptosis. This action was modulated by downregulation of cyclooxygenase 2 (PTGS2) pathway, which in turn regulates the secretion of cytokines and the expression of mitogen-activated protein kinases (MAPKs), metalloproteinases (MMPs), and their antagonists (TIMPs). These findings indicate the phytotherapeutic potential of piperine as complementary treatment in cervical cancer.
RESUMO
Wheat flour is the main ingredient used in the preparation of bread. Factors such as low gluten content and the addition of nontraditional ingredients in baking affect the quality of wheat flour and may limit its use in baking. With the increasing trend of "clean label" products, it may be interesting to develop and use physical processes to improve the quality of wheat flour and avoid the use of chemical additives. High hydrostatic pressure, non-thermal plasma, ultrasound, ozonation, ultraviolet light, and pulsed light treatments are non-thermal emerging technologies (NTETs) that have been studied for this purpose. They were originally developed to inactivate microorganisms and enzymes in foods. Additionally, these technologies can be used at low temperatures to modify the most important component of wheat flour, i.e., gluten and its fractions, which are responsible for the rheological properties of wheat flour dough. Thus, this review focuses on the effects of these NTETs by considering the following factors: (1) the technological properties of gluten, (2) gluten-starch interactions, (3) possible effects of NTETs on minor components of flours, and (4) the quality of wheat flour and the resulting final products.
Assuntos
Farinha , Triticum , Triticum/química , Glutens , PãoRESUMO
The objective of the present study was to evaluate the action of the crude hydroalcoholic extract of Piper cubeba fruits and isolated lignans (cubebin, dihydrocubebin, ethylcubebin, hinokinin and methylcubebin) on head and neck cancer cells. We evaluated the influence of the Piper cubeba extract and isolated lignans (10, 50 e 100 µg/mL) for 4, 24, 48 and 72 h, in the larynx (Hep-2) and oral (SCC-25) squamous cell carcinoma cells and normal fibroblasts, on morphology, cell proliferation and migration, cytotoxicity, genotoxicity and gene and protein expression (PTGS2, PTGER3, PTGER4, MMP2, MMP9). The results showed that the P. cubeba extract and different lignans do not alter the cellular morphology, but decrease cell proliferation and migration, have low cytotoxic and genotoxic effects, probably due to the alteration of the expression of genes and proteins involved with inflammatory process. From these data, we can conclude that the lignans cubebin and methylcubebin had a greater effect on head and neck cancer cells in the antiproliferative, antimigratory and genotoxic action, and could be the target of the development of new therapies including possible new drugs as a therapeutic resource for the treatment of head and neck cancer due to its immense range of biological properties.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Lignanas/isolamento & purificação , Lignanas/farmacologia , Fitoterapia , Piper/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Células Cultivadas , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias de Cabeça e Pescoço/genética , Humanos , Lignanas/química , Lignanas/uso terapêutico , Terapia de Alvo Molecular , Extratos Vegetais/uso terapêutico , Fatores de TempoRESUMO
Mammary tumours (MT) are one of the most prevalent malignancies in female dogs and women. Currently, molecular analyzes have shown that each tumour type presents its own genetic signature. In this context, liquid biopsy allows a comprehensive genetic characterisation of the tumour, enabling early diagnosis and personalised treatment of patients. In women, deleterious mutations inherited in BRCA2 gene are associated with an increased risk of breast cancer, resistance to therapies and worse prognosis. In female dogs, there are many divergent data on the involvement of BRCA2 gene with mammary carcinogenesis and what its pathogenic potential is. Therefore, the objective was to identify BRCA2 gene variants in 20 plasma DNA samples, from 10 newly diagnosed dogs with mammary cancer (RD), five control (CTR) and five mastectomized patients. Eleven single nucleotide polymorphisms (SNPs) were detected, most of them in the exon 11 and two indels (deletion/insertion) in the BRCA2 gene. However, there was no statistically significant difference in the SNPs/indels detected between the groups. In addition, only one SNP (p.T1425P) and one deletion (p.L2307del) were considered deleterious using in silico computational models. Interestingly, most common variants were present in the plasma of all groups, except for the Ile2614Thr, Ile2614Val, Thr1425Pro and p.L2307del variants. Thus, we observed that SNPs are common in the BRCA2 gene of female dogs with MT, with a similar condition identified in women with breast cancer. Liquid biopsy approach in dogs with MT is useful for genetic and therapeutic proposals.
Assuntos
Neoplasias da Mama , Doenças do Cão , Genes BRCA2 , Neoplasias Mamárias Animais , Animais , Neoplasias da Mama/veterinária , Doenças do Cão/diagnóstico , Doenças do Cão/genética , Cães , Feminino , Predisposição Genética para Doença , Biópsia Líquida/veterinária , Neoplasias Mamárias Animais/diagnóstico , Neoplasias Mamárias Animais/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Chronic inflammation provides a favorable microenvironment for tumorigenesis, which opens opportunities for targeting cancer development and progression. Piplartine (PL) is a biologically active alkaloid from long peppers that exhibits anti-inflammatory and antitumor activity. In the present study, we investigated the physical and chemical interactions of PL with anti-inflammatory compounds and their effects on cell proliferation and migration and on the gene expression of inflammatory mediators. Molecular docking data and physicochemical analysis suggested that PL shows potential interactions with a peptide of annexin A1 (ANXA1), an endogenous anti-inflammatory mediator with therapeutic potential in cancer. Treatment of neoplastic cells with PL alone or with annexin A1 mimic peptide reduced cell proliferation and viability and modulated the expression of MCP-1 chemokine, IL-8 cytokine and genes involved in inflammatory processes. The results also suggested an inhibitory effect of PL on tubulin expression. In addition, PL apparently had no influence on cell migration and invasion at the concentration tested. Considering the role of inflammation in the context of promoting tumor initiation, the present study shows the potential of piplartine as a therapeutic immunomodulator for cancer prevention and progression.
Assuntos
Anexina A1/genética , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Piper/química , Piperidonas/farmacologia , Alcaloides/química , Alcaloides/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinogênese/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quimiocina CCL2/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias/patologia , Piperidonas/química , Microambiente Tumoral/efeitos dos fármacosRESUMO
Deregulation of VEGFA (Vascular Endothelial Growth Factor A) and NFE2L2 (Nuclear Factor (Erythroid-derived 2)-Like 2), involved in angiogenesis and oxidative stress, can lead to thyroid cancer progression. MiR-17-5p and miR-612 are possible regulators of these genes and may promote thyroid disorders. In order to evaluate the involvement of VEGFA, NFE2L2, hsa-miR-17-5p, and hsa-miR-612 in thyroid pathology, we examined tissue samples from colloid goiter, papillary thyroid cancer (PTC), and a normal thyroid. We found higher levels of VEGFA and NFE2L2 transcripts and the VEGFA protein in goiter and PTC samples than in normal tissue. In the goiter, miR-612 and miR-17-5p levels were lower than those in PTC. Tumors, despite showing lower VEGFA mRNA expression, presented higher VEGFA protein levels compared to goiter tissue. In addition, NRF2 (Nuclear Related Transcription Factor 2) protein levels in tumors were higher than those in goiter and normal tissues. Inhibition of miR-17-5p resulted in reduced NFE2L2 expression. Overall, both transcript and protein levels of NFE2L2 and VEGFA were elevated in PTC and colloid goiter. Hsa-miR-612 showed differential expression in PTC and colloid goiter, while hsa-miR-17-5p showed differential expression only in colloid goiter, suggesting that hsa-miR-17-5p may be a positive regulator of NFE2L2 expression in PTC.
Assuntos
Biomarcadores Tumorais/metabolismo , Bócio Nodular/patologia , MicroRNAs/genética , Fator 2 Relacionado a NF-E2/metabolismo , Câncer Papilífero da Tireoide/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Bócio Nodular/genética , Bócio Nodular/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/genética , Prognóstico , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Over the past years, it has become evident that cancer initiation and progression depends on several components of the tumor microenvironment, including inflammatory and immune cells, fibroblasts, endothelial cells, adipocytes, and extracellular matrix. These components of the tumor microenvironment and the neoplastic cells interact with each other providing pro and antitumor signals. The tumor-stroma communication occurs directly between cells or via a variety of molecules secreted, such as growth factors, cytokines, chemokines and microRNAs. This secretome, which derives not only from tumor cells but also from cancer-associated stromal cells, is an important source of key regulators of the tumorigenic process. Their screening and characterization could provide useful biomarkers to improve cancer diagnosis, prognosis, and monitoring of treatment responses.
RESUMO
Docking process is one of the most significant activities for the analysis of protein-protein or protein-ligand complexes. These tools have become of unique importance when allocated in web services, collaborating scientifically with several areas of knowledge in an interdisciplinary way. Among the several web services dedicated to carrying out molecular docking simulations, we selected the DockThor web service. To illustrate the application of DockThor to protein-ligand docking simulations, we analyzed the docking of a ligand against the structure of epidermal growth factor receptor, an essential molecular marker in cancer research.
Assuntos
Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Software , Navegador , Bases de Dados Genéticas , Desenho de Fármacos , Humanos , Ligantes , Ligação Proteica , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteínas/químicaRESUMO
As exodontias são os procedimentos cirúrgicos mais realizados nas graduações de Odontologia. Embora sejam preconizadas técnicas seguras e simples, esse tipo de procedimento não deixa de ser invasivo, sendo passível de acidentes e complicações que dificultam o sucesso do tratamento e até mesmo colocam a saúde do paciente em risco. Essa pesquisa propõe avaliar a frequência de acidentes cirúrgicos transoperatórios em 232 exodontias realizadas no curso de graduação em Odontologia da Faculdade de Ciências Biomédicas de Cacoal, entre julho e outubro de 2015, assim como relacioná los com as características individuais dos elementos extraídos e com a complexidade do caso. Em 71 exodontias realizadas houve a incidência de acidentes transoperatórios. Ocorreram 23 fraturas de coroa, 21 fraturas de raiz, 19 lacerações do tecido gengival, 7 fraturas do osso alveolar, 2 escoriações em pele na comissura labial e 1 luxação do dente vizinho. Esses acidentes prevaleceram principalmente em elementos com raízes longas, finas ou curvas ou com destruição coronária. A maioria dos acidentes já estava prevista pelos operadores, sendo estas facilmente controladas no ato cirúrgico, sem gerar maiores complicações aos pacientes. Concluiu-se que um bom planejamento cirúrgico é fundamental na prevenção e/ou controle dos acidentes transoperatórios... (AU)
The extractions are the most performed procedures in Dentistry graduation course. Although safe and simple techniques are recommended, this procedure does not cease to be invasive and may be subject to accidents and complications that hinder the success of treatment and even put the patient's health at risk. This survey aimed to evaluate the frequency of transoperative surgical accidents in 232 extractions performed in the Dentistry graduation course at the Faculty of Biomedical Sciences of Cacoal, between July and October of 2015, and relate them to the characteristics of the extracted element and the complexity of the case. 71 extractions had transoperative acidentes. There were 23 crown fractures, 21 root fractures, 19 lacerations of the gum tissue, 7 fractures of the alveolar bone, 2 excoriation on the skin in labial commissure and one dislocation of the next tooth. These accidents predominate mainly in elements with long, thin or curved roots or with coronary destruction. Most of the accidents were already predicted by the operators, being these easily controlled in the surgical act, without generating greater complications to the patients. It was also concluded that a good surgical planning is essential in the prevention and / or control of transoperative accidents... (AU)
Assuntos
Humanos , Masculino , Feminino , Procedimentos Cirúrgicos Operatórios , Cirurgia Bucal , Prevenção de Acidentes , Complicações Intraoperatórias , Pacientes , Acidentes , Incidência , Odontologia , Luxações Articulares , Fraturas ÓsseasRESUMO
BACKGROUND: Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteria for the diagnosis of nodal status remain limited. In the present study, we aimed to characterize the proteomic profile of lymph node metastasis from HNSCC patients. METHODS: In the present study, we used one- and two-dimensional electrophoresis and mass spectrometry analysis to characterize the proteomic profile of lymph node metastasis from HNSCC. RESULTS: Comparison of metastatic and non-metastatic lymph nodes showed 52 differentially expressed proteins associated with neoplastic development and progression. The results reinforced the idea that tumors from different anatomical subsites have dissimilar behaviors, which may be influenced by micro-environmental factor including the lymphatic network. The expression pattern of heat shock proteins and glycolytic enzymes also suggested an effect of the lymph node environment in controlling tumor growth or in metabolic reprogramming of the metastatic cell. Our study, for the first time, provided direct evidence of annexin A1 overexpression in lymph node metastasis of head and neck cancer, adding information that may be useful for diagnosing aggressive disease. CONCLUSIONS: In brief, this study contributed to our understanding of the metastatic phenotype of HNSCC and provided potential targets for diagnostic in this group of carcinomas.
Assuntos
Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Proteômica , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/genética , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
The total amount of scientific literature has grown rapidly in recent years. Specifically, there are several million citations in the field of cancer. This makes it difficult, if not impossible, to manually retrieve relevant information on the mechanisms that govern tumor behavior or the neoplastic process. Furthermore, cancer is a complex disease or, more accurately, a set of diseases. The heterogeneity that permeates many tumors is particularly evident in head and neck (HN) cancer, one of the most common types of cancer worldwide. In this study, we present HNdb, a free database that aims to provide a unified and comprehensive resource of information on genes and proteins involved in HN squamous cell carcinoma, covering data on genomics, transcriptomics, proteomics, literature citations and also cross-references of external databases. Different literature searches of MEDLINE abstracts were performed using specific Medical Subject Headings (MeSH terms) for oral, oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinomas. A curated gene-to-publication assignment yielded a total of 1370 genes related to HN cancer. The diversity of results allowed identifying novel and mostly unexplored gene associations, revealing,for example, that processes linked to response to steroid hormone stimulus are significantly enriched in genes related to HN carcinomas. Thus, our database expands the possibilities for gene networks investigation, providing potential hypothesis to be tested. Database URL:http://www.gencapo.famerp.br/hndb.
Assuntos
Carcinoma de Células Escamosas/genética , Bases de Dados Genéticas , Bases de Dados de Proteínas , Genes Neoplásicos , Neoplasias de Cabeça e Pescoço/genética , Bandeamento Cromossômico , Redes Reguladoras de Genes , Humanos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Human kallikrein-related peptidases (KLKs) are a subgroup of serine proteases that participate in proteolytic pathways and control protein levels in normal physiology as well as in several pathological conditions. Their complex network of stimulatory and inhibitory interactions may induce inflammatory and immune responses and contribute to the neoplastic phenotype through the regulation of several cellular processes, such as proliferation, survival, migration, and invasion. This family of proteases, which includes one of the most useful cancer biomarkers, kallikrein-related peptidase 3 or PSA, also has a protective effect against cancer promoting apoptosis or counteracting angiogenesis and cell proliferation. Therefore, they represent attractive therapeutic targets and may have important applications in clinical oncology. Despite being intensively studied, many gaps in our knowledge on several molecular aspects of KLK functions still exist. This review aims to summarize recent data on their involvement in different processes related to health and disease, in particular those directly or indirectly linked to the neoplastic process.
Assuntos
Calicreínas/metabolismo , Neoplasias/metabolismo , Doenças Neurodegenerativas/metabolismo , Animais , Humanos , Calicreínas/química , Calicreínas/genética , Neoplasias/enzimologia , Doenças Neurodegenerativas/enzimologia , ProteóliseRESUMO
Epithelial tissues are specialized to protect underlying tissues from environmental influences such as physical and chemical agents, infection by invasive microorganisms as well as water and heat loss. They are grouped into simple, transitional and stratified epithelia, which line the cavities and surfaces of structures throughout the body, and also form glands, separate compartments, regulate the exchange of molecules and act as sensory organs. Stratified epithelia such as the epidermis and the gingival and hard palate mucosa are in constant renewal, with cells proliferating in the lower layers, while the intermediate stratum and outermost layers undergo a tissue-specific process of differentiation to form a protective cornified barrier. This review focuses on a subclass of structural proteins, the small proline-rich proteins (SPRRs), which constitute cornified cell envelope precursors. Several studies have suggested that the SPRRs are related to increased epithelial proliferation and to malignant processes. Hence, we also review the literature for more extensive and in-depth profile of these proteins in cancer and other diseases. The understanding of SPRR functions has advanced in recent years, but many important questions about their role in pathophysiological processes remain unanswered, which stimulate new studies and approaches.
Assuntos
Proteínas Ricas em Prolina do Estrato Córneo/metabolismo , Células Epiteliais/metabolismo , Epitélio/metabolismo , Diferenciação Celular , Humanos , Queratinócitos/metabolismo , Neoplasias/patologia , Domínios Proteicos Ricos em Prolina , Cicatrização/fisiologiaRESUMO
The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread. In this study, we used one- and two-dimensional gel electrophoresis, mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas. Using a refinement for classifying oral carcinomas in regard to prognosis, we analyzed small but lymph node metastasis-positive versus large, lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination. Specific protein patterns favoring metastasis were observed in the "more-aggressive" group defined by the present study. This group displayed upregulation of proteins involved in migration, adhesion, angiogenesis, cell cycle regulation, anti-apoptosis and epithelial to mesenchymal transition, whereas the "less-aggressive" group was engaged in keratinocyte differentiation, epidermis development, inflammation and immune response. Besides the identification of several proteins not yet described as deregulated in oral carcinomas, the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Cofilina 1/metabolismo , Neoplasias Bucais/metabolismo , Proteômica , Idoso , Carcinoma de Células Escamosas/patologia , Cofilina 1/genética , Eletroforese em Gel Bidimensional , Eletroforese em Gel de Poliacrilamida , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Invasividade NeoplásicaRESUMO
Proteomic approach has allowed large-scale studies of protein expression in different tissues and body fluids in discrete conditions and/or time points. Recent advances of methodologies in this field have opened new opportunities to obtain relevant information on normal and abnormal processes occurring in the human body. In the current report, the main proteomics techniques and their application to human disease study are reviewed.