Multifaceted p21 in carcinogenesis, stemness of tumor and tumor therapy.

Cancer cells possess metabolic properties that are different from those of benign cells. p21, encoded by CDKN1A gene, also named p21Cip1/WAF1, was first identified as a cyclin-dependent kinase regulator that suppresses cell cycle G1/S phase and retinoblastoma protein phosphorylation. CDKN1A (p21) acts as the downstream target gene of TP53 (p53), and its expression is induced by wild-type p53 and it is not associated with mutant p53. p21 has been characterized as a vital regulator that involves multiple cell functions, including G1/S cell cycle progression, cell growth, DNA damage, and cell stemness. In 1994, p21 was found as a tumor suppressor in brain, lung and colon cancer by targeting p53 and was associated with tumorigenesis and metastasis. Notably, p21 plays a significant role in tumor development through p53-dependent and p53-independent pathways. In addition, expression of p21 is closely related to the resting state or terminal differentiation of cells. p21 is also associated with cancer stem cells and acts as a biomarker for such cells. In cancer therapy, given the importance of p21 in regulating the G1/S and G2 check points, it is not surprising that p21 is implicated in response to many cancer treatments and p21 promotes the effect of oncolytic virotherapy.

GOLPH2-regulated oncolytic adenovirus, GD55, exerts strong killing effect on human prostate cancer stem-like cells in vitro and in vivo.

GOLPH2 (also called GP73) is a Golgi glycoprotein, which has been identified as a novel tumor marker upregulated in various cancers, including prostate cancer (PCa). GD55 is a novel GOLPH2-regulated oncolytic adenovirus that exhibits a strong killing effect on hepatoma cells. Here, we investigate the antitumor effect of GD55 on prostate cancer stem cell (CSC)-like cells in vitro and in vivo. Prostate CSC-like sphere cells were acquired and enriched by culturing DU145, LNCap or P3 prostate cancer cells in suspension. The prostate CSC-like sphere cells were capable of self-renewal, differentiation and quiescence, displaying tumorigenic feature and chemo-resistance to 5-FU, doxorubicin and DDP. Treatment with GD55 (1, 5, 10 MOI) dose-dependently suppressed the viability of DU145 sphere cells, which was a more pronounced compared to its cytotoxic action on the parental DU145 cells. In a mouse xenograft prostate CSC-like model, intratumoral injection of GD55 markedly suppressed the growth rate of xenograft tumors and induced higher levels of cell death and necrosis within the tumor tissues. Our results demonstrate that GD55 infection exerts strong anticancer effects on prostate CSC-like cells in vitro and in vivo, and has a potential to be used in the clinical therapy of PCa.

Lateral closing wedge osteotomy and modified cross pinning with external tension band fixation in the treatment of cubitus varus deformity in childrenLateral closing wedge osteotomy and modified cross pinning with external tension band fixation in the treatment of cubitus varus deformity in children / 中国骨伤

<p><b>OBJECTIVE</b>To explore the therapeutic effects of distal humeral lateral closing wedge osteotomy followed by modified pinning combined with external tension band fixation in the treatment of cubitus varus deformity in children.</p><p><b>METHODS</b>Total 26 adult patients with cubitus varus deformity were treated by operation from March 2011 to June 2015, 15 patients were boys and the other 11 patients were girls, ranging in age from 4 to 13 years, with an average of 7.8 years. The cubitus varus angel ranged from 11 degrees to 24 degrees, with a mean(17.50±6.73) degrees, 3 patients complicated more than 10 degrees constriction of flexion. Lateral closing wedge osteotomy retaining the medial 3 to 4 mm intact cortex by lateral elbow approach was applied in these 26 patients. The wedge defect were closed and fixed by crossing pinning. The lateral column compression was achieved with external tension band(the crossing pins were bended laterally and the pin ends were hooked mutually). The pre-operative, post-oparetive and contralateral carrying angles were compared and Laupattarakasem criteria was used to evaluate the results at follow-up.</p><p><b>RESULTS</b>All the patients got bony union 2 months after operation and there was no infection or nerve palsy. The average follow-up period was 18.8 months (ranged, 13 to 29 months). The carrying angle was restored to(11.50±3.17) degrees(ranged, 8 to 14 degrees). According to the Laupattarakasem evaluation criteria, 14 patients got an excellent result, 13 good and 1 fair.</p><p><b>CONCLUSIONS</b>Normal carrying angle and elbow flexion could be restored by lateral closing wedge osteotomy, and stable fixation could be achieved with crossing pinning and external tension band, which is available for early mobilization.</p>