Angiographic factors associated with haemorrhagic presentation of brain arteriovenous malformation in a Chinese paediatric population.

OBJECTIVE: To identify specific angiographic factors associated with haemorrhagic presentation of brain arteriovenous malformation in Chinese paediatric patients. DESIGN: Retrospective cross-sectional observational study. SETTING: Four locoregional tertiary neurosurgical centres in Hong Kong: Queen Elizabeth Hospital, Tuen Mun Hospital, Kwong Wah Hospital, and Pamela Youde Nethersole Eastern Hospital. PATIENTS: Patients aged 18 years or younger who underwent pretreatment digital subtraction angiography for brain arteriovenous malformation between 1 January 2005 and 31 July 2013 were included. Patients were divided into haemorrhagic and non-haemorrhagic groups based on the initial presentation. Pretreatment digital subtraction angiographies were independently reviewed by two experienced neuroradiologists. MAIN OUTCOME MEASURES: The following parameters were evaluated for their association with haemorrhagic presentation by univariate and multivariate analyses: nidus location, nidus size, nidus morphology (diffuse or compact); origin and number of arterial feeders; venous drainage; number of draining veins; presence of aneurysms, venous varices, and venous stenosis. RESULTS: A total of 67 children and adolescents (28 male, 39 female) with a mean age of 12 years were included. Of them, 52 (78%) presented with haemorrhage. Arteriovenous malformation size (P=0.004) and morphology (P=0.05) were found to be associated with haemorrhagic presentation by univariate analysis. Small arteriovenous malformation nidus size and diffuse nidal morphology were identified as independent risk factors for haemorrhage by multivariate analysis. CONCLUSION: Smaller arteriovenous malformation size and diffuse nidal morphology are angiographic factors independently associated with haemorrhagic presentation. Bleeding risk is important in determining the therapeutic approach (aggressive vs conservative) and timeframe, particularly in paediatric patients.

PIN1 inhibits apoptosis in hepatocellular carcinoma through modulation of the antiapoptotic function of survivin.

PIN1, a peptidyl-prolyl-isomerase, binds a specific motif comprising a phosphorylated serine or threonine preceding a proline (p-Ser/Thr-Pro) residue in proteins. Through cis-trans isomerization, it induces conformational changes and modulates functions of many proteins that are involved in cell cycle progression, cell proliferation, and oncogenesis. PIN1 is overexpressed in hepatocellular carcinomas (HCC) and contributes to hepatocarcinogenesis. We investigated the role of PIN1 and the significance of its interaction with the inhibitor of apoptosis protein survivin in evading apoptosis in HCC cells. Using cell line and xenograft models, we determined that PIN1 overexpression inhibits apoptosis through suppression of caspase-3 and caspase-9 activity. In addition, down-regulation of survivin in PIN1-overexpressing cells attenuated the antiapoptotic effect induced by PIN1, suggesting that the inhibition of apoptosis is mediated through PIN1-survivin interaction. Coimmunoprecipitation assays showed that PIN1 interacted with survivin via the phosphorylated Thr34-Pro35 motif and enhanced binding among survivin phosphorylated at Thr34, hepatitis B X-interacting protein (HBXIP), and pro-caspase-9. Taken together, these results suggest that the inhibition of apoptosis by PIN1 in HCC cells is mediated through modulation of the antiapoptotic function of survivin by increasing its binding to pro-caspase-9 via HBXIP. Such functional interaction between PIN1 and survivin may therefore play an important role in hepatocarcinogenesis and chemoresistance.