Periostin Promotes Colorectal Tumorigenesis through Integrin-FAK-Src Pathway-Mediated YAP/TAZ Activation

肠道炎症与结直肠癌的发生发展密切相关，溃疡性肠炎（Ulcerative colitis）和克罗恩病(Crohn’s disease)患者发展为结直肠癌的风险明显高于正常人群。因此，研究炎症条件下结直肠癌的发生发展机制有望为预防和治疗肠炎相关结直肠癌提供重要的理论依据。细胞外基质蛋白Periostin与多种疾病的发生发展密切相关。大量的研究表明细胞外基质蛋白Periostin能够影响组织再生、炎症、纤维化以及肿瘤的发生发展。2020年1月21日，我校生命科学学院欧阳高亮教授课题组首次阐明了Periostin蛋白在炎症相关肿瘤发生发展中的功能及其作用机制，并可能为肠炎相关肠癌的治疗提供新的靶点。我校生命科学学院博士生马汉栋为该论文的第一作者，欧阳高亮教授和我校医学院刘迎福副教授为该论文的共同通讯作者。Periostin is a multifunctional extracellular matrix protein involved in various inflammatory diseases and tumor metastasis; however, evidence regarding whether and how periostin actively contributes to inflammation-associated tumorigenesis remains elusive. Here, we demonstrate that periostin deficiency significantly inhibits the occurrence of colorectal cancer in azoxymethane/dextran sulfate sodium-treated mice and in ApcMin/+ mice. Moreover, periostin deficiency attenuates the severity of colitis and reduces the proliferation of tumor cells. Mechanistically, stromal fibroblast-derived periostin activates FAK-Src kinases through integrin-mediated outside-in signaling, which results in the activation of YAP/TAZ and, subsequently, IL-6 expression in tumor cells. Conversely, IL-6 induces periostin expression in fibroblasts by activating STAT3, which ultimately facilitates colorectal tumor development. These findings provide the evidence that periostin promotes colorectal tumorigenesis, and identify periostin- and IL-6-mediated tumor-stroma interaction as a promising target for treating colitis-associated colorectal cancer.We thank Prof. Bin Zhao for providing pCMV5-FLAG-YAP WT and pCMV5-FLAG-YAP 5SA plasmids. We thank Prof. Yongyou Zhang for providing technical support. This work was supported by grants from the National Natural Science Foundation of China (81572598, 81772616, and 81972748), the Natural Science Foundation of Fujian Province of China (2019J02002), and the Health-Education Joint Research Program of Fujian Province (WKJ2016-2-16). 该研究工作获得了国家自然科学基金、福建省自然科学基金等资助

Novel Silicone-Coated 125I Seeds for the Treatment of Extrahepatic Cholangiocarcinoma.

125I seeds coated with titanium are considered a safe and effective interstitial brachytherapy for tumors, while the cost of 125I seeds is a major problem for the patients implanting lots of seeds. The aim of this paper was to develop a novel silicone coating for 125I seeds with a lower cost. In order to show the radionuclide utilization ratio, the silicone was coated onto the seeds using the electro-spinning method and the radioactivity was evaluated, then the anti-tumor efficacy of silicone 125I seeds was compared with titanium 125I seeds. The seeds were divided into four groups: A (control), B (pure silicone), C (silicone 125I), D (titanium 125I) at 2 Gy or 4 Gy. Their anti-tumour activity and mechanism were assessed in vitro and in vivo using a human extrahepatic cholangiocarcinoma cell line FRH-0201 and tumor-bearing BALB/c nude mice. The silicone 125I seeds showed higher radioactivity; the rate of cell apoptosis in vitro and the histopathology in vivo demonstrated that the silicone 125I seeds shared similar anti-tumor efficacy with the titanium 125I seeds for the treatment of extrahepatic cholangiocarcinoma, while they have a much lower cost

Effects of Appendectomy on the Onset and Course of Ulcerative Colitis in Chinese Patients

Background. Previous epidemiological studies have suggested that appendectomy may be a protective factor against the development of ulcerative colitis (UC). However, the results of these studies were inconsistent, with rare studies in Chinese populations. Aim. This study examined the associations between appendectomy performed before UC diagnosis and the occurrence and clinical course of UC in Chinese patients. Methods. A case control study was conducted to compare the rate of appendectomy between UC patients and controls matched for age and sex at two Chinese hospitals. Clinical course of UC was compared between UC patients who underwent appendectomies before UC diagnosis and who did not. Results. 402 UC patients and 402 controls were included. The percentage of appendectomy performed before UC diagnosis in UC patients did not differ significantly from controls (2.74% vs 3.98%, P=0.442). Subgroup analysis on the basis of localization of UC patients did not find significant difference from controls. The extent of disease involvement in UC patients who underwent appendectomy was smaller than patients who did not (P=0.009). Appendectomy was found to be significantly related to the location of the disease independent of smoking status in multivariate analysis (P<0.001). Appendectomy did not influence severity of disease and need for immunosuppressive treatment or colectomy. Conclusion. We did not find a significant negative association between appendectomy and the UC occurrence in Chinese patients. Appendectomy performed before UC diagnosis may reduce the extent of UC involvement

Evaluation of the in vitro anti-tumour effects of ¹²⁵I seeds.

<p>(a) and (b)apoptotic progression in FRH-0201 cell lines in response to the titanium ¹²⁵I seeds and silicone ¹²⁵I seeds treatment for 2Gy and 4Gy; (c) cell FACS distributions (%) of apoptotic cells in different groups. Quadrant Q1,Q2,Q3 and Q4 reflect necrosis, late apoptosis, alive and early apoptosis, respectively.Total apoptosis includes late apoptosis plus early apoptosis. There was not significance between titanium ¹²⁵I seeds and silicone ¹²⁵I seeds groups. * P <0.05 means 4Gy compared with the 2 Gy groups respectively.</p

The radioactivity comparison of s-¹²⁵I seeds and t-¹²⁵I seeds.

<p>The radioactivity of s-¹²⁵I is higher than t-¹²⁵I obviously.</p

The radioactivity and radionuclide utilization ratio comparison of s-¹²⁵I Seeds and t-¹²⁵I Seeds.

<p>The radioactivity and radionuclide utilization ratio comparison of s-¹²⁵I Seeds and t-¹²⁵I Seeds.</p

HE staining.

<p>The tumor histopathology for all ¹²⁵I seeds and pure silicone groups after treatment. Tissue necrosis and ischemia were most frequently observed in the control and pure silicone groups, the silicone and titanium ¹²⁵I groups showed very few necrotic or apoptotic cells were observed in the tumors.</p