Systematic profiling identifies PDLIM2 as a novel prognostic predictor for oesophageal squamous cell carcinoma (ESCC).

Till now, no appropriate biomarkers for high-risk population screening and prognosis prediction have been identified for patients with oesophageal squamous cell carcinoma (ESCC). In this study, by the combined use of data from the Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA)-oesophageal carcinoma (ESCA), we aimed to screen dysregulated genes with prognostic value in ESCC and the genetic and epigenetic alterations underlying the dysregulation. About 222 genes that had at least fourfold change in ESCC compared with adjacent normal tissues were identified using the microarray data in GDS3838. Among these genes, only PDLIM2 was associated with nodal invasion and overall survival (OS) at the same time. The high PDLIM2 expression group had significantly longer OS and its expression was independently associated with better OS (HR: 0.64, 95% CI: 0.43-0.95, P = 0.03), after adjustment for gender and pathologic stages. The expression of its exon 7/8/9/10 had the highest AUC value (0.724) and better prognostic value (HR: 0.43, 95% CI: 0.22-0.83, P = 0.01) than total PDLIM2 expression. PDLIM2 DNA copy deletion was common in ESCC and was associated with decreased gene expression. The methylation status of two CpG sites (cg23696886 and cg20449614) in the proximal promoter region of PDLIM2 showed a moderate negative correlation with the gene expression in PDLIM2 copy neutral/amplification group. In conclusion, we infer that PDLIM2 expression might be a novel prognostic indicator for ESCC patients. Its exon 7/8/9/10 expression had the best prognostic value. Its down-regulation might be associated with gene-level copy deletion and promoter hypermethylation.

An analysis of risk factors for clinically relevant pancreatic fistulas after laparoscopic pancreaticoduodenectomy.

This study aimed to explore the risk factors of clinically relevant pancreatic fistulas (PF) after laparoscopic pancreaticoduodenectomy (LPD). The clinical data of 80 patients who underwent pancreaticoduodenectomy in our hospital were retrospectively analyzed. The potential risk factors for PF after LPD were determined using univariate and multivariate logistic regression analyses. Results from the univariate analyses showed that the pancreatic duct diameter (P < .001), pancreatic texture (P < .001), abdominal infection (P = .002), and reoperation (P < .001) were associated with clinically relevant PF. Results from the multivariate logistic regression analysis showed that the pancreatic duct diameter (P = .002) and pancreatic texture (P = .016) were significant risk factors for clinically relevant PF. Based on this study, the pancreatic duct diameter and pancreatic texture are independent risk factors for clinically relevant PF after LPD.

Fangchinoline exerts anticancer effects on colorectal cancer by inducing autophagy via regulation AMPK/mTOR/ULK1 pathway.

Autophagy has become a promising target for cancer therapy. Fangchinoline (Fan) has been shown to exert anticancer effects in some types of cancers. However, the anticancer effects on colorectal cancer (CRC) and the underlying mechanisms have never been elucidated. More specifically, regulation of autophagy in CRC by Fan has never been reported before. In the present study, Fan was found to induce apoptosis and autophagic flux in the CRC cell lines HT29 and HCT116, which was reflected by the enhanced levels of LC3-II protein and p62 degradation, and the increased formation of autophagosomes and puncta formation by LC3-II. Meanwhile, combination with the early-stage autophagy inhibitor 3-methyladenine (3-MA) but not the late-stage autophagy inhibitor chloroquine (CQ) further increased Fan-induced cell death, which suggested the cytoprotective function of autophagy induced by Fan in both HT29 and HCT116 cells. Moreover, Fan treatment demonstrated a dose- and time-dependently increase in the phosphorylation of AMPK and decrease in the phosphorylation of mammalian target of rapamycin (mTOR) and ULK1, leading to the activation of the AMPK/mTOR/ULK1 signaling pathway. Furthermore, in the HT29 xenograft model, Fan inhibited tumor growth in vivo. These results indicate that Fan inhibited CRC cell growth both in vitro and in vivo and revealed a new molecular mechanism involved in the anticancer effect of Fan on CRC, suggesting that Fan is a potent autophagy inducer and might be a promising anticancer agent.

Fabrication of a novel whole tissue-engineered intervertebral disc for intervertebral disc regeneration in the porcine lumbar spine.

Tissue-engineered intervertebral discs (IVDs) have been proposed as a useful therapeutic strategy for the treatment of intervertebral disc degeneration (IDD). However, most studies have focused on fabrication and assessment of tissue-engineered IVDs in small animal models and the mechanical properties of the scaffolds are far below those of native human IVDs. The aim of this study was to produce a novel tissue-engineered IVD for IDD regeneration in the porcine lumbar spine. Firstly, a novel whole tissue-engineered IVD scaffold was fabricated using chitosan hydrogel to simulate the central nucleus pulposus (NP) structure, surrounded with a poly(butylene succinate-co-terephthalate) (PBST) fiber film for inner annulus fibrosus (IAF). And, a poly(ether ether ketone) (PEEK) ring was used to stimulate the outer annulus fibrosus (OAF). Then, the scaffolds were seeded with IVD cells and the cell-scaffold hybrids were transplanted into the porcine damaged spine and harvested at 4 and 8 weeks. In vitro cell experiments showed that IVD cells distributed and grew well in the scaffolds including porous hydrogel and PBST fibers. After implantation into pigs, radiographic and MRI images indicated that the tissue-engineered IVD construct could preserve the disc height in the case of discectomy as the normal disc height and maintain a large extracellular matrix and water content in the NP. Combined with the histological and gene expression results, it was concluded that the tissue-engineered IVD had similar morphological and histological structure to the natural IVD. Moreover, after implantation for 8 weeks, the tissue-engineered IVD showed a good compressive stress and elastic moduli, approaching those of natural porcine IVD. Therefore, the prepared tissue-engineered IVD construct had similar morphological and biofunctional properties to the native tissue. Also, the tissue-engineered IVD construct with excellent biocompatibility and mechanical properties provides a promising candidate for human IDD regeneration.

Effects of 1,25(OH)2D3 regulating ERK pathway on the biological behaviors of esophageal squamous cell carcinoma cells / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨1,25-二羟维生素D3 [1,25(OH)2D3]对食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）细胞增殖、迁移和细胞周期的影响及其相关机制。方法：用不同浓度1,25(OH)2D3处理ESCC细胞TE-11、KYSE30、TE-1和KYSE510后，用CCK-8法检测细胞的增殖能力。再用浓度分别是0、0.1、0.15、0.2 μmol/L的1,25(OH)2D3处理TE-11和KYSE30细胞，划痕愈合实验、流式细胞术分别检测细胞的迁移能力和细胞周期分布情况，WB法检测细胞中cyclin D1、P27、ERK和p-ERK蛋白的表达水平。结果：1,25(OH)2D3显著抑制TE-11和KYSE30细胞的增殖能力，其抑制程度呈时间依赖性和浓度依赖性。0.1和0.2 μmol/L的1,25(OH)2D3处理48 h后，与空白对照组比较，TE-11和KYSE30细胞的迁移能力均显著降低（P<0.05或P<0.01），处于G0/G1期细胞显著增加（P<0.05或P<0.01），细胞中cyclin D1和p-ERK蛋白水平显著下调、P27蛋白水平明显上调（P<0.05或P<0.01）而ERK蛋白的表达无明显变化。结论：1,25(OH)2D3显著抑制ESCC细胞的增殖和迁移能力并阻滞细胞周期进程，其可能通过调控ERK信号通路而发挥作用。