RESUMO
Thoracic aortic aneurysms (TAAs) are permanent pathological dilatations of the thoracic aorta, which can lead to life-threatening complications, such as aortic dissection and rupture. TAAs frequently occur in a syndromic form in individuals with an underlying genetic predisposition, such as Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). Increasing evidence supports an important role for transforming growth factor-ß (TGF-ß) and the renin-angiotensin system (RAS) in TAA pathology. Eventually, most patients with syndromic TAAs require surgical intervention, as the ability of present medical treatment to attenuate aneurysm growth is limited. Therefore, more effective medical treatment options are urgently needed. Numerous clinical trials investigated the therapeutic potential of angiotensin receptor blockers (ARBs) and ß-blockers in patients suffering from syndromic TAAs. This review highlights the contribution of TGF-ß signaling, RAS, and impaired mechanosensing abilities of aortic VSMCs in TAA formation. Furthermore, it critically discusses the most recent clinical evidence regarding the possible therapeutic benefit of ARBs and ß-blockers in syndromic TAA patients and provides future research perspectives and therapeutic implications.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Aneurisma da Aorta Torácica/tratamento farmacológico , Aneurisma da Aorta Torácica/patologia , Sistema Renina-Angiotensina/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas de Receptores de Angiotensina/farmacologia , Animais , Aneurisma da Aorta Torácica/genética , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Transdução de Sinais/fisiologia , Síndrome , Fator de Crescimento Transformador beta/efeitos dos fármacosRESUMO
In this work, a novel magnetic resonance (MR)-compatible microwave antenna was designed and validated in a small animal superficial hyperthermia applicator. The antenna operates at 2.45 GHz and matching is made robust against production and setup inaccuracies. To validate our theoretical concept, a prototype of the applicator was manufactured and tested for its properties concerning input reflection, sensitivity for setup inaccuracies, environment temperature stability and MR-compatibility. The experiments show that the applicator indeed fulfils the requirements for MR-guided hyperthermia investigation in small animals: it creates a small heating focus (<1 cm3), has a stable and reliable performance (S11< -15 dB) for all working conditions and is MR-compatible.
Assuntos
Hipertermia Induzida/métodos , Imageamento por Ressonância Magnética/métodos , Animais , CamundongosRESUMO
PURPOSE: Hyperbaric oxygen therapy (HBOT) is used in the treatment of radiation-induced tissue injury but its effect on (residual) tumor tissue is indistinct and therefore investigated in this study. PROCEDURES: Orthotopic FaDu tumors were established in mice, and the response of the (irradiated) tumors to HBOT was monitored by bioluminescence imaging. Near infrared fluorescence imaging using AngioSense750 and Hypoxisense680 was applied to detect tumor vascular permeability and hypoxia. RESULTS: HBOT treatment resulted in accelerated growth of non-irradiated tumors, but mouse survival was improved. Tumor vascular leakiness and hypoxia were enhanced after HBOT, whereas histological characteristics, epithelial-to-mesenchymal transition markers, and metastatic incidence were not influenced. CONCLUSIONS: Squamous cell carcinoma responds to HBOT with respect to tumor growth, vascular permeability, and hypoxia, which may have implications for its use in cancer patients. The ability to longitudinally analyze tumor characteristics highlights the versatility and potential of optical imaging methods in oncological research.
Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Oxigenoterapia Hiperbárica , Imagem Óptica/métodos , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Oxigênio/uso terapêuticoRESUMO
A side effect of radiation therapy in the head and neck region is injury to surrounding healthy tissues such as irreversible impaired function of the salivary glands. Hyperbaric oxygen therapy (HBOT) is clinically used to treat radiation-induced damage but its mechanism of action is largely unknown. In this study, we investigated the molecular pathways that are affected by HBOT in mouse salivary glands two weeks after radiation therapy by microarray analysis. Interestingly, HBOT led to significant attenuation of the radiation-induced expression of a set of genes and upstream regulators that are involved in processes such as fibrosis and tissue regeneration. Our data suggest that the TGFß-pathway, which is involved in radiation-induced fibrosis and chronic loss of function after radiation therapy, is affected by HBOT. On the longer term, HBOT reduced the expression of the fibrosis-associated factor α-smooth muscle actin in irradiated salivary glands. This study highlights the potential of HBOT to inhibit the TGFß-pathway in irradiated salivary glands and to restrain consequential radiation induced tissue injury.