RESUMO
Since the second half of the 20th century, our knowledge about the biology of cancer has made extraordinary progress. Today, we understand cancer at the genomic and epigenomic levels, and we have identified the cell that starts neoplastic transformation and characterized the mechanisms for the invasion of other tissues. This knowledge has allowed novel drugs to be designed that act on specific molecular targets, the immune system to be trained and manipulated to increase its efficiency, and ever more effective therapeutic strategies to be developed. Nevertheless, we are still far from winning the war against cancer, and thus biomedical research in oncology must continue to be a global priority. Likewise, there is a need to reduce unequal access to medical services and improve prevention programs, especially in countries with a low human development index.
Assuntos
Pesquisa Biomédica/organização & administração , Oncologia/organização & administração , Neoplasias/fisiopatologia , Neoplasias/terapia , Antineoplásicos Imunológicos/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos/métodos , Epigênese Genética , Genômica , Acessibilidade aos Serviços de Saúde , Humanos , Invasividade Neoplásica/fisiopatologia , Neoplasias/epidemiologia , Neoplasias/genética , Células-Tronco Neoplásicas/fisiologiaRESUMO
The Coatomer protein complex subunit beta 2 (COPB2) is involved in the formation of the COPI coatomer protein complex and is responsible for the transport of vesicles between the Golgi apparatus and the endoplasmic reticulum. It plays an important role in maintaining the integrity of these cellular organelles, as well as in maintaining cell homeostasis. More importantly, COPB2 plays key roles in embryonic development and tumor progression. COPB2 is regarded as a vital oncogene in several cancer types and has been implicated in tumor cell proliferation, survival, invasion, and metastasis. Here, we summarize the current knowledge on the roles of COPB2 in cancer development and progression in the context of the hallmarks of cancer.
Assuntos
Proteína Coatomer/fisiologia , Neoplasias/etiologia , Animais , Apoptose/genética , Apoptose/fisiologia , Morte Celular Autofágica/fisiologia , Ciclo Celular/fisiologia , Proliferação de Células/genética , Sobrevivência Celular/genética , Proteína Coatomer/genética , Modelos Animais de Doenças , Progressão da Doença , Desenvolvimento Embrionário , Retículo Endoplasmático/fisiologia , Complexo de Golgi/fisiologia , Homeostase , Humanos , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/fisiopatologia , Metástase Neoplásica/genética , Metástase Neoplásica/fisiopatologia , Neoplasias/patologia , Vesículas Transportadoras/fisiologiaRESUMO
OBJECTIVE: To explore the role of ADMA in gastric cancer. METHODS: The specimens of 115 gastric cancer patients were analyzed by ELISA and survival analysis. Functional assays were used to assess the effects of ADMA on gastric cancer cells. Experiments were conducted to detect the signaling pathway induced by ADMA in GC. RESULTS: Gastric cancer patients with high ADMA levels had poor prognosis and low survival rate. Furthermore, high level of ADMA did not affect the proliferation while promoted the migration and invasion of gastric cancer cell. Moreover, ADMA enhanced the epithelial-mesenchymal transition (EMT). Importantly, ADMA positively regulated ß-catenin expression in GC and promoted GC migration and invasion via Wnt/ß-catenin pathway. CONCLUSIONS: ADMA regulates gastric cancer cell migration and invasion via Wnt/ß-catenin signaling pathway and which may be applied to clinical practice as a diagnostic and prognostic biomarker.
Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/patologia , Arginina/análogos & derivados , Transição Epitelial-Mesenquimal , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Via de Sinalização Wnt , Adenocarcinoma/mortalidade , Arginina/sangue , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/fisiopatologia , Prognóstico , Neoplasias Gástricas/mortalidade , Cicatrização/fisiologiaRESUMO
Abstract Introduction: Parotid carcinomas have varying histological types and diverse biologic behaviors. Establishing an adequate treatment plan and predicting recurrence is important. Objective: To analyze the risk factors associated with recurrence in our 5 year experience with 30 cases of primary parotid carcinoma undergoing surgery at a single institute. Methods: From January 2009 to December 2013, 30 patients with surgical treatment of parotid carcinoma were identified based on their medical records. Results: The 30 patients were comprised of 17 males and 13 females. Among 11 patients with T4 tumors, seven patients had recurrence. Among seven patients with cervical nodal metastasis, all patient except one had recurrence. Clinically late stages (stage III and IV) showed more common recurrence than early stage (stage I and II) lesions. Lymphovascular invasion was seen in 5 patients, and all patients had recurrence. Among 11 patients with extracapsular spread, 7 patients had recurrence. In 17 patients with high grade carcinomas, ten patients had recurrence. In 13 patients with low grade carcinomas, no patients experienced recurrence. Conclusion: T- and N-stage, clinical stage, lymphovascular invasion, extracapsular spread, and histopathologic grade correlate significantly with recurrence in parotid carcinoma.
Resumo: Introdução: Os carcinomas da parótida têm diferentes tipos histológicos e comportamentos biológicos diversos. O estabelecimento de um plano de tratamento adequado e a previsão de recorrência são muito importantes. Objetivo: Analisar os fatores de risco associados à recorrência em nossa experiência de cinco anos com 30 casos de carcinoma parotídeo primário submetidos a cirurgia em uma única instituição. Método: De janeiro de 2009 a dezembro de 2013, 30 pacientes com tratamento cirúrgico de carcinoma parotídeo foram identificados com base nos prontuários. Resultados: Entre os 30 pacientes, 17 eram homens e 13, mulheres. Dos 11 pacientes com tumores T4, sete apresentaram recorrência. Entre sete pacientes com metástase em linfonodo cervical, todos, exceto um, apresentaram recorrência. Lesões em estágios clínicos tardios (III e IV) apresentaram recorrência mais comumente do que as dos estágios iniciais (I e II). A invasão linfovascular foi observada em cinco pacientes e todos os cinco apresentaram recorrência. Entre 11 pacientes com disseminação extracapsular, sete apresentaram recorrência. Dos 17 pacientes com carcinomas de alto grau, dez apresentaram recorrência. Em 13 pacientes com carcinomas de baixo grau, nenhum apresentou recorrência. Conclusão: Estágios T e N, estágio clínico, invasão linfovascular, disseminação extracapsular e grau histopatológico correlacionam-se de maneira significante com recorrência do carcinoma de parótida.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Neoplasias Parotídeas/mortalidade , Neoplasias Parotídeas/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Complicações Pós-Operatórias , Recidiva , Neoplasias Parotídeas/cirurgia , Taxa de Sobrevida , Estudos Retrospectivos , Fatores de Risco , Seguimentos , Paralisia Facial/complicações , Gradação de Tumores , Margens de Excisão , Invasividade Neoplásica/fisiopatologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de NeoplasiasRESUMO
Mathematical modelling approaches have become increasingly abundant in cancer research. Tumour infiltration extent and its spatial organization depend both on the tumour type and stage and on the bio-physicochemical characteristics of the microenvironment. This sets a complex scenario that often requires a multidisciplinary and individually adjusted approach. The ultimate goal of this work is to present an experimental/numerical combined method for the development of a three-dimensional mathematical model with the ability to reproduce the growth and infiltration patterns of a given avascular microtumour in response to different microenvironmental conditions. The model is based on a diffusion-convection reaction equation that considers logistic proliferation, volumetric growth, a rim of proliferative cells at the tumour surface, and invasion with diffusive and convective components. The parameter values of the model were fitted to experimental results while radial velocity and diffusion coefficients were made spatially variable in a case-specific way through the introduction of a shape function and a diffusion-limited-aggregation (DLA)-derived fractal matrix, respectively, according to the infiltration pattern observed. The in vitro model consists of multicellular tumour spheroids (MTSs) of an epithelial mammary tumour cell line (LM3) immersed in a collagen I gel matrix with a standard culture medium ("naive" matrix) or a conditioned medium from adipocytes or preadipocytes ("conditioned" matrix). It was experimentally determined that both adipocyte and preadipocyte conditioned media had the ability to change the MTS infiltration pattern from collective and laminar to an individual and atomized one. Numerical simulations were able to adequately reproduce qualitatively and quantitatively both kinds of infiltration patterns, which were determined by area quantification, analysis of fractal dimensions and lacunarity, and Bland-Altman analysis. These results suggest that the combined approach presented here could be established as a new framework with interesting potential applications at both the basic and clinical levels in the oncology area.
Assuntos
Modelos Biológicos , Invasividade Neoplásica/patologia , Invasividade Neoplásica/fisiopatologia , Microambiente Tumoral/fisiologia , Células 3T3-L1 , Adipócitos/citologia , Animais , Linhagem Celular Tumoral , Meios de Cultivo Condicionados , Feminino , Imageamento Tridimensional , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/fisiopatologia , Camundongos , Inoculação de Neoplasia , Esferoides Celulares/patologia , Esferoides Celulares/fisiologiaRESUMO
INTRODUCTION: Parotid carcinomas have varying histological types and diverse biologic behaviors. Establishing an adequate treatment plan and predicting recurrence is important. OBJECTIVE: To analyze the risk factors associated with recurrence in our 5 year experience with 30 cases of primary parotid carcinoma undergoing surgery at a single institute. METHODS: From January 2009 to December 2013, 30 patients with surgical treatment of parotid carcinoma were identified based on their medical records. RESULTS: The 30 patients were comprised of 17 males and 13 females. Among 11 patients with T4 tumors, seven patients had recurrence. Among seven patients with cervical nodal metastasis, all patient except one had recurrence. Clinically late stages (stage III and IV) showed more common recurrence than early stage (stage I and II) lesions. Lymphovascular invasion was seen in 5 patients, and all patients had recurrence. Among 11 patients with extracapsular spread, 7 patients had recurrence. In 17 patients with high grade carcinomas, ten patients had recurrence. In 13 patients with low grade carcinomas, no patients experienced recurrence. CONCLUSION: T- and N-stage, clinical stage, lymphovascular invasion, extracapsular spread, and histopathologic grade correlate significantly with recurrence in parotid carcinoma.
Assuntos
Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Neoplasias Parotídeas/mortalidade , Neoplasias Parotídeas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Paralisia Facial/complicações , Feminino , Seguimentos , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica/fisiopatologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasias Parotídeas/cirurgia , Complicações Pós-Operatórias , Recidiva , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto JovemRESUMO
Ovarian cancer (OC) is the fifth cancer death cause in women worldwide. The malignant nature of this disease stems from its unique dissemination pattern. Epithelial-to-mesenchymal transition (EMT) has been reported in OC and downregulation of Epithelial cadherin (E-cadherin) is a hallmark of this process. However, findings on the relationship between E-cadherin levels and OC progression, dissemination and aggressiveness are controversial. In this study, the evaluation of E-cadherin expression in an OC tissue microarray revealed its prognostic value to discriminate between advanced- and early-stage tumors, as well as serous tumors from other histologies. Moreover, E-cadherin, Neural cadherin (N-cadherin), cytokeratins and vimentin expression was assessed in TOV-112, SKOV-3, OAW-42 and OV-90 OC cell lines grown in monolayers and under anchorage-independent conditions to mimic ovarian tumor cell dissemination, and results were associated with cell aggressiveness. According to these EMT-related markers, cell lines were classified as mesenchymal (M; TOV-112), intermediate mesenchymal (IM; SKOV-3), intermediate epithelial (IE; OAW-42) and epithelial (E; OV-90). M- and IM-cells depicted the highest migration capacity when grown in monolayers, and aggregates derived from M- and IM-cell lines showed lower cell death, higher adhesion to extracellular matrices and higher invasion capacity than E- and IE-aggregates. The analysis of E-cadherin, N-cadherin, cytokeratin 19 and vimentin mRNA levels in 20 advanced-stage high-grade serous human OC ascites showed an IM phenotype in all cases, characterized by higher proportions of N- to E-cadherin and vimentin to cytokeratin 19. In particular, higher E-cadherin mRNA levels were associated with cancer antigen 125 levels more than 500 U/mL and platinum-free intervals less than 6 months. Altogether, E-cadherin expression levels were found relevant for the assessment of OC progression and aggressiveness.
Assuntos
Caderinas/metabolismo , Neoplasias Ovarianas/metabolismo , Antígenos CD , Ascite/metabolismo , Ascite/patologia , Biomarcadores Tumorais/metabolismo , Antígeno Ca-125/sangue , Adesão Celular/fisiologia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Sobrevivência Celular/fisiologia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/sangue , Invasividade Neoplásica/patologia , Invasividade Neoplásica/fisiopatologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , RNA Mensageiro/metabolismoRESUMO
An increased risk of developing breast cancer has been associated with high levels of dietary fat intake. Linoleic acid (LA) is an essential fatty acid and the major ω-6 polyunsaturated fatty acid in occidental diets, which is able to induce inappropriate inflammatory responses that contribute to several chronic diseases including cancer. In breast cancer cells, LA induces migration. However, the signal transduction pathways that mediate migration and whether LA induces invasion in MDA-MB-231 breast cancer cells have not been studied in detail. We demonstrate here that LA induces Akt2 activation, invasion, an increase in NFκB-DNA binding activity, miR34a upregulation and miR9 downregulation in MDA-MB-231 cells. Moreover, Akt2 activation requires EGFR and PI3K activity, whereas migration and invasion are dependent on FFAR4, EGFR and PI3K/Akt activity. Our findings demonstrate, for the first time, that LA induces migration and invasion through an EGFR-/PI3K-/Akt-dependent pathway in MDA-MB-231 breast cancer cells.
Assuntos
Neoplasias da Mama/metabolismo , Movimento Celular/efeitos dos fármacos , Ácido Linoleico/farmacologia , Invasividade Neoplásica/fisiopatologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy and is successfully treated by surgery and radiation. However, some patients have recurrent tumours and in these cases, few treatments options are available. Cancer stem cells (CSC) have been observed and isolated from different solid tumours based on the expression of stem cell markers. These cells are associated with tumour initiation, progression as well as treatment resistance. In this study, the expression of stem cell markers CD44, Bmi1, Oct4 and Nanog was evaluated in non-neoplastic salivary tissue and in MEC. METHODS: Twenty-eight samples of MEC and their corresponding non-neoplastic salivary tissue were examined by immunohistochemistry and the stem cell markers expression was correlated with histological and clinical parameters. RESULTS: CD44 was expressed in the membrane of serous and mucous acini as well as in the ductal cells in normal gland tissue. Bmi1, Oct4 and Nanog were mainly expressed in ductal structures. In MEC, CD44 and Bmi1 showed strong expression in all types of neoplastic cells and both markers revealed intense expression in tumour invasive front. Oct4 and Nanog protein expression was associated with desmoplasia and perineural invasion. Only Oct4 positive tumours were associated with dissociative growth pattern and committed margins. CONCLUSION: The stem cell markers CD44, Bmi1, Oct4 and Nanog are frequently expressed in MEC in relation to normal salivary gland and Oct4 and Nanog expression may contribute to aggressiveness and worst prognosis in MEC patients.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Proteína Homeobox Nanog/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Adolescente , Adulto , Idoso , Carcinoma Mucoepidermoide/patologia , Criança , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/fisiopatologia , Células-Tronco Neoplásicas , Complexo Repressor Polycomb 1/metabolismo , Neoplasias das Glândulas Salivares/patologia , Adulto JovemRESUMO
OBJECTIVE: To analyze the flow of retrobulbar vessels in retinoblastoma by color Doppler imaging. METHODS: A prospective study of monocular retinoblastoma treated by enucleation between 2010 and 2014. The examination comprised fundoscopy, magnetic resonance imaging, ultrasonography and color Doppler imaging. The peak blood velocities in the central retinal artery and central retinal vein of tumor-containing eyes (tuCRAv and tuCRVv, respectively) were assessed. The velocities were compared with those for normal eyes (nlCRAv and nlCRVv) and correlated with clinical and pathological findings. Tumor dimensions in the pathological sections were compared with those in magnetic resonance imaging and ultrasonography and were correlated with tuCRAv and tuCRVv. In tumor-containing eyes, the resistivity index in the central retinal artery and the pulse index in the central retinal vein were studied in relation to all variables. RESULTS: Eighteen patients were included. Comparisons between tuCRAv and nlCRAv and between tuCRVv and nlCRVv revealed higher velocities in tumor-containing eyes (p <0.001 for both), with a greater effect in the central retinal artery than in the central retinal vein (p =0.024). Magnetic resonance imaging and ultrasonography measurements were as reliable as pathology assessments (p =0.675 and p =0.375, respectively). A positive relationship was found between tuCRAv and the tumor volume (p =0.027). The pulse index in the central retinal vein was lower in male patients (p =0.017) and in eyes with optic nerve invasion (p =0.0088). CONCLUSIONS: TuCRAv and tuCRVv are higher in tumor-containing eyes than in normal eyes. Magnetic resonance imaging and ultrasonography measurements are reliable. The tumor volume is correlated with a higher tuCRAv and a reduced pulse in the central retinal vein is correlated with male sex and optic nerve invasion.