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2.
Crit Rev Oncol Hematol ; 185: 103965, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36931616

RESUMO

Cachexia is a life-threatening disorder affecting an estimated 50-80% of cancer patients. The loss of skeletal muscle mass in patients with cachexia is associated with an increased risk of anticancer treatment toxicity, surgical complications and reduced response. Despite international guidelines, the identification and management of cancer cachexia remains a significant unmet need owing in part to the lack of routine screening for malnutrition and suboptimal integration of nutrition and metabolic care into clinical oncology practice. In June 2020, Sharing Progress in Cancer Care (SPCC) convened a multidisciplinary task force of medical experts and patient advocates to examine the barriers preventing the timely recognition of cancer cachexia, and provide practical recommendations to improve clinical care. This position paper summarises the key points and highlights available resources to support the integration of structured nutrition care pathways.


Assuntos
Desnutrição , Neoplasias , Sarcopenia , Humanos , Caquexia/diagnóstico , Caquexia/etiologia , Caquexia/terapia , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Sarcopenia/terapia , Desnutrição/diagnóstico , Desnutrição/etiologia , Desnutrição/terapia , Neoplasias/complicações , Neoplasias/terapia , Estado Nutricional
3.
Aging Cell ; 16(1): 52-60, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27618784

RESUMO

Studies of the mTOR pathway have prompted speculation that diminished mTOR complex-1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long-lived mutant mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in this article, mice deficient in the pregnancy-associated protein-A (PAPPA-KO). The ways in which lower mTOR signals slow aging and age-related diseases are, however, not well characterized. Here, we show that Snell, GHKRO, and PAPPA-KO mice express high levels of two proteins involved in DNA repair, O-6-methylguanine-DNA methyltransferase (MGMT) and N-myc downstream-regulated gene 1 (NDRG1). Furthermore, we report that lowering mTOR enhances MGMT and NDRG1 protein expression via post-transcriptional mechanisms. We show that the CCR4-NOT complex, a post-transcriptional regulator of gene expression, is downstream of the mTORC1 pathway and may be responsible for the upregulation of MGMT and NDRG1 in all three varieties of long-lived mice. Our data thus suggest a novel link between DNA repair and mTOR signaling via post-transcriptional regulation involving specific alteration in the CCR4-NOT complex, whose modulation could control multiple aspects of the aging process.


Assuntos
Proteínas de Ciclo Celular/genética , Dano ao DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Nanismo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Longevidade , Proteína Plasmática A Associada à Gravidez/deficiência , Receptores da Somatotropina/deficiência , Serina-Treonina Quinases TOR/metabolismo , Proteínas Supressoras de Tumor/genética , Animais , Proteínas de Ciclo Celular/metabolismo , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Regulação para Baixo/efeitos dos fármacos , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Knockout , Modelos Biológicos , Proteína Plasmática A Associada à Gravidez/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CCR4/metabolismo , Receptores da Somatotropina/metabolismo , Sirolimo/farmacologia , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
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