Pattern of multiple human papillomavirus infection and type competition: An analysis in healthy Chinese women aged 18-45 years.

To assess the pattern of multiple human papillomavirus infection to predict the type replacement postvaccination. A total of 7372 women aged 18-45y from a phase III trial of an Escherichia coli-produced HPV-16/18 vaccine were analyzed at enrollment visit before vaccination. Hierarchical multilevel logistic regression was used to evaluate HPV vaccine type and nonvaccine-type interactions with age as a covariate. Binary logistic regression was construed to compare multiple infections with single infections to explore the impact of multiple-type infections on the risk of cervical disease. Multiple HPV infections were observed in 25.2% of HPV-positive women and multiple infections were higher than expected by chance. Statistically significant negative associations were observed between HPV16 and 52, HPV18 and HPV51/52/58, HPV31 and HPV39/51/52/53/54/58, HPV33 and HPV52/58, HPV58 and HPV52, HPV6 and HPV 39/51/52/53/54/56/58. Multiple HPV infections increased the risk of CIN2+ and HSIL+, with the ORs of 2.27(95%CI: 1.41, 3.64) and 2.26 (95%CI: 1.29, 3.95) for multiple oncogenic HPV infection separately. However, no significant evidence for the type-type interactions on risk of CIN2+ or HSIL+. There is possibility of type replacement between several pairs of vaccine and nonvaccine HPV type. Multiple HPV infection increased the risk of cervical disease, but coinfection HPV types seem to follow independent disease processes. Continued post-vaccination surveillance for HPV 51/52/58 types and HPV 39/51 types separately was essential after the first and second generation of HPV vaccination implementation in China.

L22 ribosomal protein is involved in dynamin-related protein 1-mediated gastric carcinoma progression.

Mitochondrial fission depends on dynamin-related protein 1 (Drp1) guanosine triphosphatase activity. Although there is some association between Drp1 and gastric cancer, the detailed mechanism remains largely unknown. In this study, the elevation of Drp1 was observed in human gastric carcinoma specimens including gastric mixed adenocarcinoma tissues, gastric intestinal-type adenocarcinoma tissues, and human gastric cancer cells compared to normal control, but not in diffuse gastric adenocarcinoma tissues. Gastric cancer patients with high Drp1 harbored advanced pathological stages and poor progression-free survival probability compared to those with low Drp1. Mdivi-1-mediated inactivation of Drp1 robustly inhibited cell viability and tumor growth but conversely induced cell apoptotic events in vitro and in vivo. Based on the Encyclopedia of RNA Interactomes Starbase, L22 ribosomal protein (RPL22) was recognized as the potential downstream oncogene of Drp1. Clinically, the significant correlation of Drp1 and RPL22 was also verified. Mechanistically, Drp1 inactivation did not affect the accumulation of RPL22 in gastric carcinoma. However, the intracellular distribution of RPL22 had an endonuclear location in Drp1-inactivated tumors. Of note, Drp1 inactivation notably reduced the expression of cytoplasmic RPL22 and increased its nuclear level in gastric cancer cells. Collectively, Drp1 had high levels in human gastric carcinoma specimens and could serve as a potential diagnostic and prognostic biomarker in gastric carcinoma. The Drp1 inactivation-mediated anti-proliferative and pro-apoptosis effects on gastric cancer were possibly associated with nuclear import of RPL22. This knowledge may provide new therapeutic tools for treating gastric carcinoma via targeting mitochondria-related ribosome pathway.

Immunosuppressive receptor LILRB1 acts as a potential regulator in hepatocellular carcinoma by integrating with SHP1.

BACKGROUND: Immunosuppressive receptor LILRB1 regulates tumors progression by transducing immune inhibitory signals via intracellular immunoreceptor tyrosine-based inhibitory motifs. However, its role in Hepatocellular Carcinoma (HCC) remains vague. OBJECTIVE: This study is aimed to disclose the association between LILRB1 and HCC. METHODS: Immunoblotting and qRT-PCR were employed to evaluate the level of LILRB1 in hepatocarcinoma cells. LILRB1-positive cells in tissue array were measured using immunohistochemistry staining. The relation among LILRB1, SHP1 and SHP2 and survival rates were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) and Oncomine database. RESULTS: LILRB1 was robustly reduced in hepatocarcinoma cells compared to normal cells. Clinically, LILRB1 was significantly higher in 49 of 75 (65%) paired paracarcinoma tissues than that in paired HCC samples. 48 of 75 (64%) HCC subjects in tissue microarray showed low level of LILRB1, compared to 25 of 75 (33%) in paired-adjacent tissues. Oncomine database and GEPIA analysis confirmed that LILRB1 was lower in HCC than normal tissues. Additionally, lowLILRB1 had a significant association with clinicopathological characteristics and Disease Free Survival, but no association with Overall Survival in HCC patients. Mechanismly, positive correlation between LILRB1 and SHP1, but not SHP2 was observed in HCC. CONCLUSIONS: LILRB1 possibly plays an antitumor effect in hepatocarcinoma cells by integrating SHP1, providing evidence that LILRB1 might be involved in the pathologic progression of HCC.