ABSTRACT
Hepatocellular carcinoma (HCC) is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA) is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1 µM) and cAMP (1 mM), an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3β) and liver differentiation (E-cadherin, connexin 26 (Cx26), and Cx32). RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3β (inactive form) expression while the expression of Cx43, Tyr216-GSK-3β (active form) and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells.
Subject(s)
Animals , Rats , Carcinoma, Hepatocellular/pathology , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cyclic AMP/pharmacology , Liver Neoplasms/pathology , Tretinoin/pharmacology , Cell Line, Tumor , Carcinoma, Hepatocellular/metabolism , Drug Combinations , Enzyme-Linked Immunosorbent Assay , Immunoblotting , Liver Neoplasms/metabolism , Microscopy, Confocal , Mitotic Index , Polymerase Chain ReactionABSTRACT
Estimular a regeneração do nervo facial é ainda hoje um desafio. OBJETIVO: Estudar a possível influência neurotrófica do nucleotídeo cíclico adenosina monofosfato (AMPc) na regeneração do nervo facial de ratos Wistar. MÉTODO: Trinta e dois animais foram submetidos à transecção completa com sutura imediata do nervo facial direito, sendo divididos em expostos ou não expostos à aplicação tópica de AMPc, com análises comportamentais (movimentação de vibrissas e fechamento da rima palpebral) e histométrica (contagem de fibras mielinizadas) em dois períodos, 14 e 28 dias após a lesão. RESULTADO: Encontramos diferenças estatísticas (p<0,05) nas análises comportamental e histométrica no 14º dia, sugerindo uma precocidade na regeneração do nervo facial exposto ao AMPc. CONCLUSÃO: Nosso estudo constatou uma possível ação neurotrófica do AMPc na regeneração do nervo facial em ratos.
Promoting facial nerve regeneration is a significant challenge. AIM: To evaluate the possible neurotrophic influence of cyclic AMP on facial nerve regeneration of Wistar rats. METHOD: The right facial nerve of thirty-two animals were completely transected and immediately sutured, followed by exposure or not to topical cyclic AMP. Behavioral and histometric analyses were done at 14 and 28 days. RESULTS: Statistical differences (p<0.05) were found in the behavioral and histometric analyses on the 14th day, suggesting an early regenerative response of the facial nerve to cAMP exposure. CONCLUSION: This study demonstrates a possible neurotrophic effect of cAMP on facial nerve regeneration in rats.
Subject(s)
Animals , Humans , Male , Rats , Cyclic AMP/pharmacology , Facial Nerve Injuries/surgery , Facial Nerve/physiology , Nerve Regeneration/drug effects , Administration, Topical , Analysis of Variance , Facial Nerve/drug effects , Models, Animal , Nerve Growth Factors/physiology , Nerve Regeneration/physiology , Rats, Wistar , Suture TechniquesABSTRACT
No abstract available.
Subject(s)
Humans , Adenosine Triphosphate/pharmacology , Anions/metabolism , Bicarbonates/metabolism , Chlorides/metabolism , Cyclic AMP/pharmacology , Cystic Fibrosis Transmembrane Conductance Regulator/physiology , Electric Conductivity , Electrophysiology , Gluconates/pharmacology , Membrane Potentials/physiology , Membrane Potentials/drug effects , Potassium/pharmacology , Sweat Glands/metabolismSubject(s)
Humans , Animals , Nobel Prize , GTP-Binding Proteins/physiology , Signal Transduction , Cyclic AMP/pharmacologySubject(s)
Animals , Cholesterol/metabolism , Chromatography/methods , Chromatography, Gel , Cyclic AMP/pharmacology , Cycloheximide/pharmacology , Female , Fishes/physiology , Gonadotropins/pharmacology , Hydrolysis , Luteinizing Hormone/pharmacology , Mitochondria/analysis , Oocytes/analysis , Ovary/drug effects , Peptide Hydrolases , Pregnenolone/analysisABSTRACT
Se estudió la especifidad de la prueba de "CAMP reversa" para la identificación de Clostridium perfringens en relación a la posible existencia de reacciones cruzadas frente a estreptococos grupos A, C y G. Noventa y ocho cepas de Clostridium se enfrentaron a 10 cepas de S. agalactiae, 10 cepas de S. pyogenes, 2 cepas de Streptococcus grupo C y 1 del grupo G. Todas las cepas de S. agalactiae ensayadas permitieron poner de manifiesto una reacción de "CAMP reversa" positiva al enfrentarlas a cepas de C. perfringens. No se observaron reacciones cruzadas de C. perfringens frente a los Streptococcus de los grupos A, C y G probados. La prueba de "CAMP reversa" fue específica para todas las cepas de C. perfringens ensayadas