To compare the effects of Ivor-Lewis esophagectomy and McKeown esophagectomy on perioperative anxiety and depression in patients with esophageal cancer. Sixty-three patients with stage I-III middle and lower esophageal carcinoma from June 2021 to December 2022 were randomly divided into observation group (n = 32) treated with laparoscopic Ivor-Lewis esophagectomy and control group (n = 31) treated with laparoscopic McKeown esophagectomy. Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) were measured on the second day of admission and the fifth day after surgery to assess the presence of depression and anxiety. The preoperative and postoperative clinical data of both groups were compared, and multivariate analysis was used to identify risk factors associated with depression and anxiety in patients with esophageal cancer. There was no significant difference in SDS and SAS standard scores between the observation group and the control group ( P > 0.05). The postoperative SDS and SAS scores in the control group were significantly higher than those before and after operation in the observation group ( P < 0.01). According to univariate analysis, patients with TNM stage III, tumor diameter greater than 3 cm, postoperative complications, radical McKeown esophagectomy, and C-reactive protein levels above 10 mg/L had a higher incidence of depression and anxiety ( P < 0.05). Multivariate logistic analysis showed that TNM stage III (depression: OR 1.683, 95 CI 1.429–1.861; Anxiety: OR 1.739, 95 CI 1.516–1.902), postoperative complications (depression: OR 2.345, 95 CI 1.435–3.891; Anxiety: OR 1.872, 95 CI 1.372–3.471), surgical approach (depression: OR 1.609, 95 CI 1.502–3.193; Anxiety: OR 1.658, 95 CI 1.469–2.059), and C-reactive protein (depression: OR 2.260, 95 CI 1.157–4.059; Anxiety: OR 0.373, 95 CI 0.253–0.976) were all independent factors for depression and anxiety in patients after esophageal cancer surgery ( P < 0.05). The Ivor-Lewis esophagectomy has the advantages of fewer complications and low inflammatory response, which can help alleviate anxiety and depression and improve patients’ quality of life and prognosis.

目的:研究EMR2在肝外胆管细胞癌(extrahepatic cholangiocarcinoma,EHCC)中的表达及临床意义、生物学功能及机制.方法:采用免疫组化(immunohistochemistry,IHC)实验检测EMR2在EHCC组织及癌旁组织中的表达情况,并分析EMR2表达与EHCC患者临床病理特征之间的关系.利用Kaplan-Meier方法、COX比例风险模型分析EMR2表达在EHCC患者预后中的作用以及对EHCC患者预后造成危险的因素.通过qRT-PCR和Western blot实验测定EMR2在EHCC细胞系(QBC939、SK-CHA-1、KMBC)和正常胆管上皮细胞HIBEpic中mRNA及蛋白的相对表达水平,检验细胞敲低和过表达的效率.Western blot实验检测EMR2在上皮间质转化(epithelial-mesenchymal transformation,EMT)中的表达变化.细胞侵袭、增殖、迁移能力分别用Transwell侵袭实验、CCK-8实验、细胞划痕及Tranwell迁移实验检测.结果:IHC结果显示,EMR2在癌旁组织中阳性表达率低于EHCC组织,EMR2的表达与EHCC分化程度有关.Kaplan-Meier生存曲线显示:EMR2的表达与EHCC患者的预后有相关性,EMR2表达和EHCC分化程度是影响EHCC患者预后的独立危险因素.通过qRT-PCR和Western blot实验确定了以EMR2高表达细胞株QBC 939和低表达细胞株KMBC作为后续实验对象,并且验证了转染效率.EMR2在EHCC细胞中的表达与细胞增殖、迁移、侵袭能力和N-cadherin、Vimentin蛋白水平成正比,与E-cadherin蛋白水平成反比.结论:EMR2表达与EHCC分化程度、预后有相关性,EMR2表达和分化程度是独立影响EHCC预后的因素.EMR2高表达能够促使EHCC细胞的增殖、侵袭、迁移能力增加,其机制可能与EMT有关.

BackgroundThis study aims to investigate the effects of ω-3, ω-6 polyunsaturated fatty acids (PUFAs), and their middle metabolites prostaglandin (PGE)2 and PGE3 on proliferation, invasion, and angiogenesis formation of gastric cancer cells and to explore associated mechanism.MethodsRT-PCR and ELISA were used to detect the expression of cyclooxygenase (COX)-1 and COX-2 in gastric cancer cell lines. The effect of ω-3, ω-6, PGE2, and PGE3 on the proliferation, invasion, and angiogenesis of gastric cancer cells were measured by cell proliferation, invasion, and angiogenesis assay in vitro. COX-2 small interfering RNA (siRNA) was transfected into gastric cancer cells, and the expression of COX-2 protein was detected by Western blot. COX-2 gene silencing influencing proliferation, invasion, and angiogenesis potential of gastric cancer cells was detected by WST-1, transwell chamber, and angiogenesis assay, respectively.ResultsCOX-2 was only expressed in MKN74 and MKN45 cells. In gastric cancer cell lines with positive COX-2 expression, ω-6 and PGE2 could significantly enhance the proliferation, invasion, and angiogenesis of gastric cancer cells, and after transfection with COX-2 siRNA, the effects of ω-6 and PGE2 on enhancing the proliferation, invasion, and angiogenesis of gastric cancer cells were significantly attenuated; ω-3 and PEG3 could inhibit the proliferation, invasion, and angiogenesis of gastric cancer cells. In gastric cancer cell lines with negative COX-2 expression, ω-6 and PGE2 had no significant effect on the proliferation, invasion, and angiogenesis of gastric cancer; ω-3 and PGE3 could significantly inhibit the proliferation, invasion, and angiogenesis of gastric cancer.Conclusionω-6 PUFAs reinforce the metastatic potential of gastric cancer cells via COX-2/PGE2; ω-3 PUFAs inhibit the metastatic potential of gastric cancer via COX-1/PGE3 signaling axis.

Objective To investigate the effect and its mechanism of the downregulation of protein arginine methyltransferase 6（PRMT6）gene on the proliferation of gastric cancer BGC823 cell.Methods The protein expression of PRMT6 was detected by immunohistochemical staining（IHC）in tumor and paracancer tissues of 30 patients with gastric cancer.Western blot was used to detect the expression levels of PRMT6 in normal gastric mucosa cells and various gastric cancer cell lines.After siRNA interfered with PRMT6 expression in gastric cancer cells, the transfection effect was verified by Western blot and qRT-PCR.MTT assay and colony cloning assay were used to detect the proliferation of gastric cancer cells.Western blot and qRT-PCR were used to detect the effect of downregulated PRMT6 expression on the expression of downstream cell cycle-related genes CDKN1 A,CDKN1 B,CDKN1 C and CCND1.Results Immunohistochemical results showed that the expression level of PRMT6 in gastric cancer tissues was significantly higher than that in adjacent tissues, and the difference was statistically significant（P＜0.01）.Western blot results showed that PRMT6 expression level was higher in gastric cancer cell lines BGC823.SiRNA significantly reduced the expression of PRMT6 protein and mRNA in cells.MTT and colony cloning results showed that the downregulation of PRMT6 expression significantly inhibited the proliferation of gastric cancer cells.After knockdown PRMT6 expression, qRT-PCR results showed that there was no significant difference in mRNA expression levels of CDKN1 A,CDKN1 B and CDKN1 C compared with the control group.Western blot and qRT-PCR results showed that the expression level of CCND1 downstream gene was decreased.Conclusion PRMT6 is highly expressed in gastric cancer tissues and can promote the proliferation of gastric cancer cells, which may be related to the regulation of CCND1 expression.

BACKGROUND:Protein arginine methyltransferase 6 (PRMT6) is a type I arginine methyltransferase that asymmetrically dimethylates histone H3 arginine 2 (H3R2me2a). However, the biological roles and underlying molecular mechanisms of PRMT6 in colorectal cancer (CRC) remain unclear.METHODS:PRMT6 expression in CRC tissue was examined using immunohistochemistry. The effect of PRMT6 on CRC cells was investigated in vitro and in vivo. Mass spectrometry, co-immunoprecipitation and GST pulldown assays were performed to identify interaction partners of PRMT6. RNA-seq, chromatin immunoprecipitation, Western blot and qRT-PCR assays were used to investigate the mechanism of PRMT6 in gene regulation.RESULTS:PRMT6 is significantly upregulated in CRC tissues and facilitates cell proliferation of CRC cells in vitro and in vivo. Through RNA-seq analysis, CDKN2B (p15INK4b) and CCNG1 were identified as new transcriptional targets of PRMT6. PRMT6-dependent H3R2me2a mark was predominantly deposited at the promoters of CDKN2B and CCNG1 in CRC cells. Furthermore, PRMT5 was firstly characterized as an interaction partner of PRMT6. Notably, H3R2me2a coincides with PRMT5-mediated H4R3me2s and H3R8me2s marks at the promoters of CDKN2B and CCNG1 genes, thus leading to transcriptional repression of these genes.CONCLUSIONS:PRMT6 functionally associates with PRMT5 to promote CRC progression through epigenetically repressing the expression of CDKN2B and CCNG1. These insights raise the possibility that combinational intervention of PRMT6 and PRMT5 may be a promising strategy for CRC therapy.

Gastric cancer (GC) remains a major public health problem. Ursolic acid (UA) is reported to be effective in inhibiting GC; however, its low solubility and poor biocompatibility have greatly hindered its clinical application. Herein, an innovative reactive oxygen species (ROS)-sensitive UA dimeric prodrug is developed by coupling two UA molecules via a ROS-cleavable linkage, which can self-assemble into stable nanoparticles in the presence of surfactant. This new UA-based delivery system comprises the following major components: (I) dimeric prodrug inner core that can achieve high drug-loading (55%, w/w) and undergo rapid and selective conversion into intact drug molecules in response to ROS; (II) a polyethylene glycol (PEG) shell to improve colloid stability and extend blood circulation, and (III) surface-modified internalizing RGD (iRGD) to increase tumor targeting. Enhancement of the antitumor effect of this delivery system was demonstrated against GC tumors in vitro and in vivo. This novel approach offers the potential for clinical applications of UA.

Abstract Background: The aim of this study was to investigate the co-operative role of CXCR4/ CXCL12 axis and IL-1Ra in metastatic processes mechanism by interactions between colorectal cancer cells and stromal cells in their microenvironment. Methods: Expression of IL-1a, CXCL12 and CXCR4 mRNA and proteins were determined by RT-PCR and Western blot. The effect of secreted level of CXCL12 by IL-1Ra on fibroblasts was measured by ELISA. CXCL12 regulate metastatic potential of colorectal cancer was evaluated by proliferation, invasion and angiogenesis assays, respectively, in which invasion and angiogenesis assays used an in vitro system consisting of co-cultured colorectal cells and stromal cells. Results: IL-1a was expressed in high liver metastatic colorectal cancer cell lines (HT-29 and WiDr). The colorectal cancer cell-derived IL-1a and rIL-1a significantly promoted CXCL12 expression by fibroblasts, and this enhancing effect can be significantly inhibited by IL-1Ra (P<0.01). CXCL12 not only enhanced the migration and proliferation of human umbilical vein endothelial cells (HUVECs), but also significantly enhanced angiogenesis (P<0.01). Furthermore, the high liver-metastatic colorectal cancer cell line (HT-29), which secretes IL-1a, significantly enhanced angiogenesis compared to the low liver-metastatic cell line (CaCo-2), which does not produce IL-1a (P<0.01). On the contrary, IL-1Ra can significantly inhibit migration, proliferation and angiogenesis (P<0.01). Conclusion: Autocrine IL-1a and paracrine CXCL12 co-enhances the metastatic potential of colorectal cancer cells; IL-1Ra can inhibit the metastatic potential of colorectal cancer cells via decrease IL-1a/CXCR4/CXCL12 signaling pathways.