The expression of p63 is associated with the differential stage in nasopharyngeal carcinoma and EBV infection

BACKGROUND: Nasopharyngeal carcinoma (NPC) is common among Southern Chinese and the main histology is the undifferentiated carcinoma associated with Epstein-Barr virus (EBV) infection. p63 is a recently proved member of the p53 family based on the structural similarity to p53, but its function in NPC is still unknown. This study was aimed to investigate the association between p63 and NPC. RESULTS: p63 was expressed in 100%(202/202) of nasopharyngeal carcinoma (NPC) tissues but not in 29 nasopharynx inflammation and 17 non-cancerous nasopharyngeal epidermises on a tissue microarray by immunohistostaining. Further investigation suggested that the p63 expression was associated with the differential stage of NPC: p63 strong staining in Keratinizing squamous cell carcinoma, differentiated non-keratinizing NPC and undifferentiated non-keratinizing NPC presented the percentage of 5/8 (62.5%), 43/48 (92.5%) and 50/50 (100%), respectively. A significant difference (p = 0.001) existed between the keratinizing and non-keratinizing groups. No pathogenic mutations were detected in p63 gene in 12 primary NPC tissues and matched peripheral blood lymphocytes (PBL). Half-life measurement study revealed distinct stability of p63 protein in the different cell lines, especially between the carcinoma cell lines with EBV infection and the non-cancerous cell lines. The results of immunoprecipitation suggested a direct interaction between Epstein-Barr virus nuclear antigen 5 (EBNA-5) and p63 protein in NPC, and this binding would increase the stability of p63. CONCLUSION: Our data suggested p63 might be used as an adjunct diagnostic marker of NPC and contributed a new way to understand the contribution of the EBV in the pathogenesis of NPC

CASOG: Conservative Actor-critic with SmOoth Gradient for Skill Learning in Robot-Assisted Intervention

Robot-assisted intervention has shown reduced radiation exposure to physicians and improved precision in clinical trials. However, existing vascular robotic systems follow master-slave control mode and entirely rely on manual commands. This paper proposes a novel offline reinforcement learning algorithm, Conservative Actor-critic with SmOoth Gradient (CASOG), to learn manipulation skills from human demonstrations on vascular robotic systems. The proposed algorithm conservatively estimates Q-function and smooths gradients of convolution layers to deal with distribution shift and overfitting issues. Furthermore, to focus on complex manipulations, transitions with larger temporal-difference error are sampled with higher probability. Comparative experiments in a pre-clinical environment demonstrate that CASOG can deliver guidewire to the target at a success rate of 94.00\% and mean backward steps of 14.07, performing closer to humans and better than prior offline reinforcement learning methods. These results indicate that the proposed algorithm is promising to improve the autonomy of vascular robotic systems.Comment: 13 pages, 5 figure, preprin

ApoG2, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces apoptosis and suppresses tumor growth in nasopharyngeal carcinoma xenografts

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in South China. It has been reported that overexpression of antiapoptotic Bcl-2 family proteins in NPC has caused the lack of long-term efficacy of conventional therapies. Apogossypolone (ApoG2), a novel small-molecule inhibitor of antiapoptotic Bcl-2 family proteins, has been discovered as the optimized derivative of gossypol. In this study, we found that in NPC cells, ApoG2 totally blocked the antiapoptotic function of Bcl-2 family proteins without affecting the expression levels of these proteins. ApoG2 selectively inhibited proliferation of 3 NPC cell lines (C666-1, CNE-1 and CNE-2) that highly expressed the antiapoptotic Bcl-2 proteins. This inhibitory activity was associated with release of cytochrome c, activation of caspase-9 and caspase-3 and apoptosis of sensitive NPC cells. However, ApoG2 had no obvious inhibitory effect on NPC cell line HONE-1, which expressed antiapoptotic Bcl-2 and Bcl-xL at a low level. We further found that ApoG2 effectively suppressed tumor growth of NPC xenografts in nude mice and enhanced the antitumor effect of CDDP (cisplatin) on NPC cells in vitro and in vivo . Immunohistochemical results showed that the expression of CD31 decreased after ApoG2 treatment, which suggested inhibition of angiogenesis in NPC xenografts. Our findings strongly suggest that ApoG2 may serve as a novel inhibitor of Bcl-2 family proteins and, by targeting these proteins, may become a promising drug for the treatment of NPC. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60986/1/23752_ftp.pd

Altered Brain Functional Hubs and Connectivity Underlie Persistent Somatoform Pain Disorder

This study investigated the degree of brain functional impairment in persistent somatoform pain disorder (PSPD) by examining changes in the patterns of brain functional hubs. Resting-state functional magnetic resonance imaging was performed in 21 PSPD patients with headache as the main symptom and 17 sex- and age-matched healthy controls. Degree centrality (DC) analysis as well as the connectivity among these hubs by functional connectivity (FC) analysis and Granger causality analysis (GCA) were performed to characterize abnormal brain networks in PSPD (Gaussian random field corrected: P < 0.001, Z > 3.09). The relationships between DC and connectivity and clinical parameters were also examined. DC values in the bilateral inferior occipital gyrus (IOG), bilateral calcarine fissure (CAL), and left paracentral lobule (PCL) and FC values of right IOG–left CAL, right IOG–right CAL, right IOG–left IOG, left CAL–right CAL, left CAL–left IOG, left CAL–left PCL, right CAL–left PCL, and left IOG–left PCL were lower in PSPD patients as compared to controls. A negative causal effect from the left CAL to the left paracentral lobule and a positive effect from the right CAL to the right IOG were observed in PSPD patients. Abnormal DC, FC, and signed-path coefficients in PSPD patients were negatively correlated with self-rating anxiety and depression scale scores. These results indicate that altered functional hubs and connectivity patterns in the somatosensory cortex may reflect emotional disturbance in PSPD patients