Background: In eukaryotic cells, nucleolar processing of preribosomal RNAs (prerRNAs) is assisted by a large number of small nucleolar RNAs (snoRNAs) that function in the 2 H -O-methylation or the pseudouridylation of rRNAs. Most snoRNAs so far characterized are encoded and processed from introns of premRNAs.

Therapeutic Level IV.

No abstract

Hip dysplasia is the most common cause of secondary osteoarthritis (OA). To prevent the early onset of secondary OA, Nishio's transposition osteotomy, Steel's triple osteotomy, Eppright's dial osteotomy, Wagner's spherical acetabular osteotomy, Tagawa's rotational acetabular osteotomy (RAO), and Ganz' periacetabular osteotomy (PAO) have been proposed. PAO and RAO are now commonly used in surgical treatment of symptomatic acetabular dysplasia in Europe, North America, and Asia. The aim of this paper is to present the followings: the patient selection criteria for RAO; the surgical technique of RAO; the long-term outcome of RAO; and the future perspectives.

Blood levels of acute-phase protein α1-acid glycoprotein (AGP, orosmucoid) increase in patients with cancer. Although AGP is produced from hepatocytes following stimulation by immune cell–derived cytokines under conditions of inflammation and tumorigenesis, the functions of AGP in tumorigenesis and tumor progression remain unknown. In the present study, we revealed that AGP contributes directly to tumor development by induction of programmed death ligand 1 (PD-L1) expression and IL6 production in macrophages. Stimulation of AGP induced PD-L1 expression in both human monocyte–derived macrophages through STAT1 activation, whereas AGP had no direct effect on PD-L1 expression in tumor cells. AGP also induced IL6 production from macrophages, which stimulated proliferation in tumor cells by IL6R-mediated activation of STAT3. Furthermore, administration of AGP to AGP KO mice phenocopied effects of tumor-associated macrophages (TAM) on tumor progression. AGP decreased IFNγ secretion from T cells and enhanced STAT3 activation in subcutaneous tumor tissues. In addition, AGP regulated PD-L1 expression and IL6 production in macrophages by binding with CD14, a coreceptor for Toll-like receptor 4 (TLR4), and inducing TLR4 signaling. These results provide the first evidence that AGP is directly involved in tumorigenesis by interacting with TAMs and that AGP might be a target molecule for anticancer therapy. Significance: AGP-mediated suppression of antitumor immunity contributes to tumor progression by inducing PD-L1 expression and IL6 production in TAMs.