RESUMO
BACKGROUND: Loeys-Dietz syndrome (LDS) is a congenital multisystem disorder affecting the cardiovascular and musculoskeletal system. Limited data have reported neurodevelopmental (ND) issues in LDS. AIMS: To determine the extent of ND issues in patients with LDS. METHODS: A prospective study was performed of LDS patients or their caregivers. The study included data collected via an online survey of age-specific questions. Standard statistical methods were used for baseline and demographic characteristics, as well as group comparisons. OUTCOMES: Data were obtained from 67 patients with LDS (54% female). Median age was 14.9 years. Gene mutations included TGFBR1 (39%), TGFBR2 (40%), SMAD3 (7%), and unknown (14%). Motor delays (30%, 18/61) and hypotonia (63%, 37/60) occurred frequently. Physical (62%, 39/62), occupational (41%, 23/56), and speech therapies (34%, 20/58) were common. Feeding issues were common (41%, 23/56). TGFBR1 mutations were more frequent among those with motor delays and feeding issues. CONCLUSIONS: Patients with LDS and/or their caregivers report at least one ND problem in most cases, and many require therapies. These data suggest ND disorders should be considered to be part of the phenotype.
Assuntos
Transtornos do Desenvolvimento da Linguagem/terapia , Síndrome de Loeys-Dietz , Destreza Motora , Transtornos do Neurodesenvolvimento , Modalidades de Fisioterapia/estatística & dados numéricos , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Adolescente , Criança , Desenvolvimento Infantil , Comportamento Alimentar/fisiologia , Feminino , Humanos , Síndrome de Loeys-Dietz/epidemiologia , Síndrome de Loeys-Dietz/fisiopatologia , Síndrome de Loeys-Dietz/psicologia , Masculino , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/terapia , Estudos Prospectivos , Fonoterapia/estatística & dados numéricos , Estados UnidosRESUMO
In multicellular organisms, communication between individual cells is essential for the regulation and coordination of complex cellular processes such as growth, differentiation, migration and apoptosis. The plethora of signal transduction networks mediating these biological processes is regulated in part by polypeptide growth factors that can generate signals by activating cell surface receptors either in paracrine or autocrine manner. The primary mediators of such physiological cell responses are receptor tyrosine kinases (RTKs) that couple ligand binding to downstream signalling cascades and gene transcription. Investigations over the past 18 years have revealed that RTKs are not only key regulators of normal cellular processes but are also critically involved in the development and progression of human cancers. Therefore, signalling pathways controlled by tyrosine kinases offer unique opportunities for pharmaco logical intervention. The aim of this review is to give a broad overview of RTK signalling involved in tumorigenesis and the possibility of target-selective intervention for anti-cancer therapy.
Assuntos
Neoplasias/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , Animais , Humanos , Fosforilação , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Receptores de Fatores de Crescimento/metabolismoRESUMO
The recent completion of the human genome sequence has raised great hopes for the discovery of new breast cancer therapies based on newly-discovered genes linked to breast cancer development and progression. Here we describe breast cancer therapies that have emerged from gene-based scientific efforts over the past 20 years and that are now approved for clinical testing or treatment.
