Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most prevalent malignancies that seriously threaten people’s health worldwide.DEAD-box helicase 51(DDX51)is a member of the DEAD-box(DDX)RNA helicase family,and drives or inhibits tumor progression in multiple cancer types.AIM To determine whether DDX51 affects the biological behavior of ESCC.METHODS The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry(IHC)analyses and quantitative PCR(qPCR).We knocked down DDX51 in ESCC cell lines by using a small interfering RNA(siRNA)transfection.The proliferation,apoptosis,and mobility of DDX51 siRNAtransfected cells were detected.The effect of DDX51 on the phosphoinositide 3-kinase(PI3K)/AKT pathway was investigated by western blot analysis.A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.RESULTS DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC.Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis.Moreover,DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates.Investigations into the underlying mechanisms suggested that DDX51 knock down induced inactivation of the PI3K/AKT pathway,including decreased phosphorylation levels of phosphate and tensin homolog,PI3K,AKT,and mammalian target of rapamycin.Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development.Finally,we injected DDX51 siRNA-transfected TE-1 cells into an animal model,which resulted in slower tumor growth.CONCLUSION Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway;thus,DDX51 might be a therapeutic target for ESCC.     

骨填充网袋椎体成形术与经皮椎体后凸成形术治疗Kümmell病的疗效比较

目的比较骨填充网袋椎体成形术（Vesselplasty）与经皮椎体后凸成形术（percutaneous kyphoplasty，PKP）治疗 Kümmell 病的临床疗效。方法2015 年 1 月—2018 年 12 月收治 63 例 Kümmell 病患者，其中 28 例采用 Vesselplasty 治疗（Vesselplasty 组），35 例采用 PKP 治疗（PKP 组）。两组患者性别、年龄、病程、骨密度 T 值、骨折节段及术前疼痛视觉模拟评分（VAS）、Oswestry 功能障碍指数（ODI）、伤椎前缘高度、后凸 Cobb 角等一般资料比较，差异均无统计学意义（P>0.05），具有可比性。记录两组手术时间、术中透视时间、骨水泥注射量、骨水泥渗漏率、骨水泥弥散面积率和随访期间并发症发生情况，以及术前、术后 1 d、末次随访时 VAS 评分、ODI、伤椎前缘高度、后凸 Cobb 角。 结果两组患者均获随访，随访时间 12～36 个月，平均 24.2 个月。Vesselplasty 组手术时间、术中透视时间、骨水泥注射量、骨水泥弥散面积率均明显小于 PKP 组（P<0.05）。Vesselplasty 组骨水泥渗漏率（7.14%）明显低于 PKP 组（34.29%）（χ²=5.153，P=0.023）。两组患者术后 1 d 及末次随访时 VAS 评分、ODI、伤椎前缘高度、后凸 Cobb 角均较术前显著改善（P<0.05），术后两组间比较差异均无统计学意义（P>0.05）。随访期间两组均未见术椎再塌陷，Vesselplasty 组邻椎骨折发生率（7.14%）与 PKP 组（14.29%）比较，差异无统计学意义（χ²=0.243，P=0.622）。 结论Vesselplasty 和 PKP 治疗 Kümmell 病疗效相似，均能有效缓解患者疼痛症状，改善生活质量，部分恢复伤椎高度，矫正椎体后凸。但前者具有手术时间短、术中透视时间少、骨水泥渗漏少等优势。     

带蒂大网膜瓣在乳腺癌术后乳房再造中的应用研究

目的探讨带蒂大网膜瓣在乳腺癌术后乳房再造中的临床应用。方法2013 年 5 月—2017 年 10 月，对 205 例乳腺癌患者行改良根治术联合带蒂大网膜瓣移植再造乳房。患者均为女性；年龄 26～58 岁，平均 34.9 岁。左侧 127 例、右侧 78 例；肿瘤直径 2～5 cm，平均 2.9 cm。乳腺癌分期：Ⅰ期 120 例，Ⅱ期 85 例。病理诊断：浸润性导管癌 126 例，浸润性小叶癌 79 例。病程 10～92 d，平均 38.5 d。肿物切除后遗留缺损范围为 9 cm×6 cm～18 cm×12 cm。带蒂大网膜瓣切取范围为 18 cm×10 cm～22 cm×16 cm。结果根据术中观察的组织特点，将大网膜分为 4 种类型，稀薄型（42 例，20.5%）、中间型（133 例，64.9%）、肥厚型（24 例，11.7%）、缺如型（6 例，2.9%）。术后带蒂大网膜瓣均成活，切口Ⅰ期愈合。患者均获随访，随访时间 6～74 个月，平均 24.5 个月；其中 83 例随访达 5 年以上。再造乳房外形可、弹性好，无挛缩变形。供区仅遗留线性瘢痕，腹部功能无影响。随访期间无乳腺癌复发。结论带蒂大网膜瓣切取安全可靠、质地优良，是乳腺癌术后乳房再造的理想方法之一。     

The role of FKBP51 in the prognosis of ulcerative colitis-associated colorectal cancer

PurposeUlcerative colitis (UC) carries a high risk of developing colorectal cancer (CRC). FK506-binding protein 51 (FKBP51) is a key regulator of glucocorticoid resistance and inflammatory tumor microenvironment. This study aimed to investigate the role of FKBP51 in UC-CRC prognosis.Materials and methodsThe FKBP51 expression was measured by immunohistochemistry, qRT-PCR and western blot in control and tumor-containing tissues from UC-CRC patients. H&E staining was used to analyze the inflammatory status of each sample. The relationship between FKBP51 expression and UC-CRC prognosis was assessed by Kaplan–Meier curves and Mann-Whitney U test, and receiver-operating characteristic curves were generated to clarify the role of FKBP51 in predicting survival period and recurrence of UC-CRC patients.ResultsThe FKBP51 expression was significantly (p ​< ​0.01) increased by 36.3% in tumor-containing tissues compared to control tissues in UC-CRC patients. Nuclear enrichment of FKBP51 in tumor-containing tissues was significantly (p ​< ​0.001) increased by 78.5%. The UC-CRC patients with higher levels of FKBP51 expression ratio between tumor-containing tissues and control tissues had shorter survival periods, but greater neutrophil invasion and neutrophils to lymphocytes ratio (NLR) in peripheral blood. Moreover, the FKBP51 expression ratio was more helpful in predicting the survival periods and recurrence in the UC-CRC patients than the NLR in peripheral blood.ConclusionsThe FKBP51 expression ratio between tumor-containing tissue and control tissue may be an important biomarker of inflammatory tumor microenvironment and more helpful for the UC-CRC prognosis.     

Targeting autophagy in colorectal cancer: An update on pharmacological small-molecule compounds

Autophagy, an evolutionarily highly conserved cellular degradation process, plays the Janus role (either cytoprotective or death-promoting) in colorectal cancer, so the targeting of several key autophagic pathways with small-molecule compounds may be a new therapeutic strategy. In this review, we discuss autophagy-associated cell death pathways and key cytoprotective autophagy pathways in colorectal cancer. Moreover, we summarize a series of small-molecule compounds that have the potential to modulate autophagy-associated cell death or cytoprotective autophagy for therapeutic purposes. Taken together, these findings demonstrate the Janus role of autophagy in colorectal cancer, and shed new light on the exploitation of a growing number of small-molecule compounds to target autophagy in future cancer drug discovery.