沉默前列腺特异性膜抗原促进前列腺癌LNCAP细胞上皮-间质转化及迁移、侵袭的研究

目的 利用RNAi技术沉默LNCAP细胞中前列腺特异性膜抗原（PSMA）表达并检测表达情况,检测沉默PSMA后LNCAP细胞迁移及侵袭等生物学行为的变化情况,以及LNCAP细胞中上皮-间质转化标志蛋白的变化情况。方法 培养LNCAP细胞,分为si-PSMA组,阴性对照（negative control siRNA）组,抑制剂LY294002组和LY294002+si-PSMA组,采用qRT-PCR和Western blot技术检测沉默PSMA后LNCAP细胞中PSMA的mRNA和蛋白表达情况,通过Transwell小室穿透实验检测LNCAP细胞迁移及侵袭能力改变,通过Western blot蛋白印迹法检测E-cadherin、β-cadherin、vimentin,snail等细胞上皮-间质转化标志蛋白的表达情况以及p-Akt(ser473)蛋白表达情况。结果 与阴性对照组相比,si-PSMA组PSMA的mRNA和蛋白表达水平都明显降低（P<0.05）,Transwell结果显示迁移及侵袭细胞增多（P<0.01）,LY294002组细胞迁移及侵袭下调（P<0.05）,...     

滑膜肉瘤相关发病机制的研究进展

滑膜肉瘤（synovial sarcoma, SS）是源于关节、滑膜及腱鞘滑膜的软组织恶性肿瘤,因其在关节周围的经典表现而得名。滑膜肉瘤可发生在身体任何部位,但以四肢近关节处多见。95%的SS以t（X;18）（p11.2-q11.2）染色体易位为特点,形成融合基因SYT-SSX,从而通过Wnt/β-catenin、PcG和ERK等信号通路促进SS细胞发生。另外,TGF-β1、Smad、Snail和Slug通过EMT途径也参与SS的发生发展。除此之外SS的发病还涉及有许多因子改变,如Twist1、Bmi1等。近年来研究表明上述因素均和SS的发病机制有关。本文将对这些因素在SS发生发展方面的作用作一概述。     

Cancer metastasis: issues and challenges

Metastasis is the major cause of treatment failure in cancer patients and of cancer-related deaths. This editorial discusses how cancer metastasis may be better perceived and controlled. Based on big-data analyses, a collection of 150 important pro-metastatic genes was studied. Using The Cancer Genome Atlas datasets to re-analyze the effect of some previously reported metastatic genes—e.g., JAM2, PPARGC1A, SIK2, and TRAF6—on overall survival of patients with renal and liver cancers, we found that these genes are actually protective factors for patients with cancer. The role of epithelial–mesenchymal transition (EMT) in single-cell metastasis has been well-documented. However, in metastasis caused by cancer cell clusters, EMT may not be necessary. A novel role of epithelial marker E-cadherin, as a sensitizer for chemoresistant prostate cancer cells by inhibiting Notch signaling, has been found. This editorial also discusses the obstacles for developing anti-metastatic drugs, including the lack of high-throughput technologies for identifying metastasis inhibitors, less application of animal models in the pre-clinical evaluation of the leading compounds,and the need for adjustments in clinical trial design to better reflect the anti-metastatic efficacy of new drugs.We are confident that by developing more effective high-throughput technologies to identify metastasis inhibitors,we can better predict, prevent, and treat cancer metastasis.     

Association of PD-L1 and ZEB-1 expression patterns with clinicopathological characteristics and prognosis in oral squamous cell carcinoma

Programmed cell death-1 (PD-1) and its ligand programmed cell death 1 ligand 1 (PD-L1) are immune checkpoint inhibitors that play an important role in the host immune avoidance mechanism of tumors. The relationship between PD-L1 expression and malignancy has been reported in various types of cancer, such as lung and gastric cancer. In addition, epithelial-mesenchymal transition (EMT) of cancer cells is deeply involved in the invasion and metastasis of cancer. It has been reported that zinc finger E-box binding homeobox 1 (ZEB-1), an EMT inducer, contributes to metastasis in pancreatic and colon cancer. The present study aimed to investigate the relationship between the expression patterns of two markers, PD-L1 and ZEB-1, and clinicopathological characteristics and prognosis of oral squamous cell carcinoma (OSCC). Biopsy or surgical excision specimens from 169 patients with OSCC were used in the present study. Immunohistochemical staining with monoclonal anti-PD-L1 antibody and anti-ZEB-1 antibody was conducted. Cases with >1% tumor cells positive for PD-L1 and those with >10% tumor cells positive for ZEB-1 were considered positive, respectively. The findings revealed that individual expression of PD-L1 and ZEB-1 in OSCC was not associated with tumor size, degree of differentiation or Yamamoto-Kohama invasion pattern classification. However, co-expression of PD-L1 and ZEB-1 was associated with higher cervical lymph node metastasis and a lower survival rate. In conclusion, the results of the present study indicated that co-expression of PD-L1 and ZEB-1 could serve as a potential marker for the prognosis of patients with OSCC.