Cellular binding partners of the human papillomavirus E6 protein

The high-risk strains of human papillomavirus (HR-HPV) are known to be causative agents of cervical cancer and have recently also been implicated in cancers of the oropharynx. E6 is a potent oncogene of HR-HPVs, and its role in the progression to malignancy has been and continues to be explored. E6 is known to interact with and subsequently inactivate numerous cellular proteins pivotal in the mediation of apoptosis, transcription of tumor suppressor genes, maintenance of epithelial organization, and control of cell proliferation. Binding of E6 to these proteins cumulatively contributes to the oncogenic potential of HPV. This paper provides an overview of these cellular protein partners of HR-E6, the motifs known to mediate oncoprotein binding, and the agents that have the potential to interfere with E6 expression and activity and thus prevent the subsequent progression to oncogenesis

Inflammatory bowel diseases: principles of nutritional therapy Doenças inflamatórias intestinais: princípios da terapia nutricional

Inflammatory Bowel Diseases - ulcerative colitis and Crohn's disease- are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Total parenteral nutrition has been used to correct and to prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission in adults and promoting growth in children. Due to its low complication rate and lower costs, enteral nutrition should be preferred over total parenteral nutrition whenever possible. Both present equal effectiveness in primary therapy for remission of active Crohn's disease. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted, especially in patients presumed to need total parenteral nutrition. Recent research has focused on the use of nutrients as primary treatment agents. Immunonutrition is an important therapeutic alternative in the management of inflammatory bowel diseases, modulating the inflammation and changing the eicosanoid synthesis profile. However, beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these and other nutrients (glutamine, short-chain fatty acids, antioxidants) still need further evaluation through prospective and randomized trials.<br>As doenças inflamatórias intestinais - retocolite ulcerativa inespecífica e doença de Crohn - são afecções inflamatórias gastrointestinais crônicas de causa ainda desconhecida. Caracterizam-se por diarréia crônica, malabsorção, síndrome do intestino curto, disfunção da barreira mucosa e processo inflamatório intestinal, fatores que determinam deficiências nutricionais e funcionais que ressaltam a importância da terapia nutricional em seu tratamento. As diversas formas de terapia nutricional visam corrigir os distúrbios nutricionais e modular à resposta inflamatória, podendo, desta forma, influir na atividade da doença. A nutrição parenteral total tem sido usada para corrigir os distúrbios nutricionais e proporcionar repouso intestinal na doença ativa. Seu uso deve ser reservado a pacientes que não podem tolerar a nutrição enteral. A nutrição enteral é efetiva em induzir remissão clínica da doença em adultos e promover crescimento em crianças. Devido à baixa incidência de complicações e menor custo, a nutrição enteral deve ser opção preferencial à nutrição parenteral total quando possível. Ambas apresentam igual efetividade na terapia primária na remissão da Doença de Crohn ativa. Embora a terapia nutricional possa melhorar a evolução de muitos pacientes, é necessária uma seleção criteriosa devido a seus custos e complicações, especialmente naqueles que requerem nutrição parenteral total. Recentes pesquisas têm se dedicado ao uso de nutrientes como agentes terapêuticos primários. A imunonutrição com ácidos graxos ômega-3 se constitui numa importante alternativa terapêutica no manuseio das doenças inflamatórias intestinais, modulando o processo inflamatório e modificando o perfil de produção de eicosanóides. Entretanto, a real eficácia deste e outros nutrientes (glutamina, ácidos graxos de cadeia curta) ainda necessitam de novas avaliações por estudos prospectivos, controlados e randomizados