RESUMO
This review summarizes recently published data on the mechanisms of tumor cell interaction with the tumor microenvironment. Tumor stroma influences the processes of hepatocarcinogenesis, epithelial-to-mesenchymal transition, invasion, and metastasis. The tumor microenvironment includes both cellular and noncellular components. Main cellular components of hepatocellular carcinoma (HCC) stroma are tumor-associated fibroblasts, hepatic stellate cells, immune cells, and endothelial cells that produce extracellular components of tumor microenvironment such as extracellular matrix, various proteins, proteolytic enzymes, growth factors, and cytokines. The noncellular components of the stroma modulate signaling pathways in tumor cells and stimulate invasion and metastasis. The tumor microenvironment composition and organization can serve as prognostic factors in HCC pathogenesis. Current approaches in HCC targeted therapy are aimed at creating efficient strategies for interrupting tumor interactions with the stroma. Recent data on the composition and role of the microenvironment in HCC pathogenesis, as well as new developments in antitumor drug design are discussed.
Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Microambiente Tumoral/fisiologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Citocinas/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/metabolismo , Humanos , Leucócitos/citologia , Leucócitos/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismoRESUMO
Tumor progression is a complex process that also involves the restructuring of the actin cytoskeleton and the weakening of intercellular adhesive contacts due to the tumor cells that pass through the epithelial-mesenchymal transition (EMT). AIM: Тo identify correlations between clinical features, risk of progression and/or recurrence of human colon adenocarcinomas (CAC), and EMT-related tumor markers. MATERIAL AND METHODS: Descending colon and sigmoid colon adenocarcinoma samples were examined immunohistochemically. Formalin-fixed paraffin-embedded tissue sections were incubated with antigen-specific antibodies, then secondary antibodies labeled with fluorochromes, and the fluorescence intensity of microscopy images was analyzed. RESULTS: The cells of a tumor compared to those of intact colon tissue showed a weak staining of E-cadherin in the cell-cell contact areas. The reduced membrane staining and nuclear localization of ß-catenin were detected in moderately (G2) and poorly (G3) differentiated tumors. There were substantially decreased ß-actin levels in almost all tumor samples and increased γ-actin ones, mainly in the samples belonging to stage IV disease. CONCLUSION: A correlation was found between stage, tumor differentiation grade, risk for relapse or progression of disease, and the impaired expression of different EMT markers: total or partial loss of E-cadherin expression, ß-catenin reorganization in cell-cell contacts, and a change in the ratio of cytoplasmic actin isoforms in the late stages of CAC development. We believe that these molecular markers may have a prognostic potential.
Assuntos
Adenocarcinoma/genética , Caderinas/genética , Carcinogênese/genética , Neoplasias do Colo/genética , beta Catenina/genética , Actinas/genética , Adenocarcinoma/patologia , Caveolina 1/genética , Neoplasias do Colo/patologia , Citoplasma , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Proteínas de Membrana/genética , Estadiamento de Neoplasias , Isoformas de Proteínas/genéticaRESUMO
Experimental studies of the mussels hydrolysate (MIGI-K) have shown that this preparation can enhance the radioresistance and general resistance of the organism. The mechanisms of its action are related mainly with its influence on the components of the biochemical back-ground of the resistance and with its antioxidative activity. Some properties of this preparation, for example, absence of toxicity and harmful side effects, made it possible as an adaptogene and as a remedy, increasing radionuclides excretion.
Assuntos
Aditivos Alimentares/uso terapêutico , Centrais Elétricas , Hidrolisados de Proteína/uso terapêutico , Lesões por Radiação/reabilitação , Protetores contra Radiação/uso terapêutico , Liberação Nociva de Radioativos , Animais , Bivalves , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Megacariócitos/efeitos dos fármacos , Megacariócitos/efeitos da radiação , Camundongos , Lesões por Radiação/sangue , UcrâniaRESUMO
Acid mussel hydrolisate MIGI-K LP is a food product, and a medical and prophylactic preparation containing a full set of irreplaceable amino acids (with the exception of thriptophane), essential fatty acids, macro- and microelements. MIGI-K LP can be used as a foot additive which improves the taste and increases the food qualities of the product, and as a medical preparation against some diseases.
Assuntos
Bivalves/metabolismo , Aditivos Alimentares/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Hidrolisados de Proteína/isolamento & purificação , Protetores contra Radiação/isolamento & purificação , Frutos do Mar , Adolescente , Adulto , Idoso , Aminoácidos/análise , Animais , Criança , Pré-Escolar , Ácidos Graxos/análise , Gastroenteropatias/dietoterapia , Hepatite B/dietoterapia , Hepatite C/dietoterapia , Humanos , Lactente , Pessoa de Meia-Idade , Controle de Qualidade , Oligoelementos/análiseRESUMO
The physico-chemical properties of preparation MIGI-K from mussels are given. Some characteristics of melanoidin fractions of MIGI-K are presented, their similarity to standard melanoidin is revealed. The given data on biological activity of the preparation permit to consider MIGI-K as immunomodulator.