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1.
J Cell Mol Med ; 26(23): 5755-5766, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36403194

RESUMO

The role of protein members containing the WD40 repeat domain in many diseases, including cancer, is well documented. However, the role of WD repeat domain 48 (WDR48) in hepatocellular carcinoma (HCC) and its molecular basis remain to be further investigated. In the present study, we report that WDR48 is downregulated in clinical HCC samples and evaluate the relationship between its expression and clinical features of HCC. In vitro experiments showed that WDR48 positively regulated the proliferation, invasion and metastasis of HCC cells and in vivo experiments showed that downregulation of WDR48 significantly inhibited the tumorigenicity of HCC cells. Mechanistically, WDR48 binds to the proto-oncogene transcriptional regulator c-Myc and stabilizes c-Myc expression by mediating its deubiquitination, thereby enhancing cell proliferation and EMT signalling. Our study demonstrates the oncogenic role of WDR48 and suggests that WDR48 can be an important target in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Repetições WD40 , Neoplasias Hepáticas/genética , Carcinogênese/genética , Oncogenes
2.
Cell Prolif ; 55(9): e13273, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35748106

RESUMO

As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic ß-catenin destruction complex (GSK-3ß and Axin), promotes the ubiquitination degradation of ß-catenin, and inhibits its nuclear transfer, thus, decreasing c-Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.


Assuntos
Carcinoma Hepatocelular , Endodesoxirribonucleases/metabolismo , Neoplasias Hepáticas , beta Catenina/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Neoplasias Hepáticas/genética , Ubiquitina/metabolismo , Via de Sinalização Wnt
3.
Surg Radiol Anat ; 30(1): 77-81, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18074072

RESUMO

INTRODUCTION: Developments in the field of digitalized technique and three-dimensional (3D) reconstruction methods allowed a precise description of anatomy structures. With the development of computer reconstructive techniques, we could get more precise anatomic images. Digitized visible models of these structures can be as a useful tool in clinical training. The purpose of this study was to observe the anatomy of arteria circumflexa femoris lateralis (ACFL) flap and to discuss the methods in the visualization of anterolateral thigh (ATL) flap by digitalized technique. METHODS: Six adults volunteer underwent contrast-enhanced CT angiography of pelvic and lower limbs utilizing a 64-row multi-slice spiral CT after median cubital vein injection with Ultravist (3.5 ml/s). 2D images from these data in Dicom format were transformed into computer. Next two adult fresh cadaver specimens, one male and one female, were subject to radiographic CT scanning before and after perfused with lead oxide-gelatine mixture, whose collimation are 0.5 mm (120 kV, 110 mA, 512 x 512 matrix). Through Amira 3.1 (TGS) software, the 2D images in Dicom format were transformed into the 3D models of the entire region. The structures of arteria circumflexa femoris lateralis (ACFL) were observed and the digitized visible models of ALT flap were established through 3D computerized reconstructions methods from these data using Amira 3.1 software. Then merging volume rendering with surface rendered reconstruction from lead oxide-gelatine mixture perfusion database. RESULTS: The 3D reconstructed visible models established from these datasets perfectly displayed the characteristic of ACFL and ALT flap anatomy. CONCLUSION: The digitized models could offer the anatomy of ALT flap perfectly, and the reconstructed methods may be used in other flap reconstruction with 3D demonstration.


Assuntos
Coxa da Perna/diagnóstico por imagem , Adulto , Feminino , Humanos , Imageamento Tridimensional , Masculino , Radiografia , Coxa da Perna/anatomia & histologia , Coxa da Perna/irrigação sanguínea
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