1.Research advances in the role of gastrointestinal microbe in pancreatic cancer
Chinese Journal of Hepatobiliary Surgery 2022;28(3):237-240
In recent years, there have been increasing studies on the role of microorganisms in pancreatic cancer which show that bacteria and fungi are closely associated with pancreatic cancer. In the past, the pancreas has usually been considered as a sterile organ. Recent studies, however, show that microbiome exists in the pancreas. Bacteria can migrate from the intestine to the pancreas. Changing the composition of the microbiome may have positive effects on treatment of pancreatic cancer. This article reviews the relationship between gastrointestinal microbiome and pancreatic cancer.
2.Research progress of gastric schwannoma
Changsheng PU ; Jianfei CHEN ; Yuanhu TIAN ; Jun CAI ; Tiantian WU ; Zhilei CHENG ; Xiaopeng SUO ; Wenzai SHI ; Xianjia WU ; Keming ZHANG
International Journal of Surgery 2020;47(4):284-288
Gastric schwannoma is a tumor originating from mesenchymal tissue. The clinical incidence is relatively rare, accounting for 6.3% of all gastric stromal tumors. The tumor is more likely to occur in the body of the stomach and usually originates from the gastric submucosal nerve. Most gastric schwannomas do not have any clinical symptoms. Imaging examination can play a diagnostic role, but the diagnosis still requires pathological examination, especially S-100 protein which is the gold standard for the diagnosis of gastric schwannomas. Gastric schwannoma usually needs to be distinguished from gastrointestinal stromal tumors and gastrointestinal autonomic nerve tumors. In terms of treatment, complete surgical resection is the first choice.
3.Construction of EZH2 gene site-directed knock-in Hut78 cells by CRISPR/Cas9 system
Zhuolin LU ; Xianjia XIONG ; Yundan WU ; Hui ZHOU ; Jun JIA ; Shuanglin WANG ; Lili WU ; Yijie LIU ; Yang QIAO ; Bing YANG ; Xiujuan ZHAO ; Qingsong WANG ; Chunyong HAN ; Ling ZHANG ; Yan SUN
Tianjin Medical Journal 2017;45(5):449-453
Objective To construct the Hut78 cell line with EZH2 gene knocked into by CRISPR/Cas9 system. Methods The EZH2 expression vector pMD-18T-EZH2 with homologous arm and the sgRNA expression vector pSpCas9 (BB)-2A-Puro-sgRNA, which could cut the double stranded genomic DNA, were constructed, and the two vectors were co-transfected into Hut78 cells. Then the expression of EZH2 mRNA was detected by qPCR, and the expressions of EZH2 and H3K27me3 proteins were detected by Western blot assay. Results The pMD-18T-EZH2 and pSpCas9(BB)-2A-Puro-sgRNA recombinant vectors were confirmed by DNA sequencing. When Hut78 cells were transfected with the two recombinant plasmid, qPCR results showed that the expression of EZH2 mRNA was significantly increased, and Western blot analysis showed that the expressions of EZH2 and H3K27me3 proteins were significantly increased. Conclusion EZH2 gene is successfully knocked into Hut78 cells by CRISPR/Cas9 system.
4.Application of real-time virtual sonography surgical navigation combined with indocyanine green fluorescence imaging technology during anatomical liver resection
Changsheng PU ; Tiantian WU ; Wenzai SHI ; Xiaopeng SUO ; Xianjia WU ; Qiang WANG ; Jun LIU ; Keming ZHANG
Chinese Journal of Hepatobiliary Surgery 2023;29(5):333-338
Objective:To analyze the clinical effect of real-time virtual sonography (RVS) surgical navigation combined with indocyanine green fluorescence imaging technology in the anatomical liver segmentectomy for hepatocellular carcinoma (HCC).Methods:The clinical data of 35 patients who underwent anatomical liver segmentectomy using RVS surgical navigation combined with indocyanine green fluorescence imaging technology in the Department of Hepatobiliary Surgery of Peking University International Hospital from January 2020 to January 2022 were retrospectively analyzed. There were 22 males and 13 females, aged (60.0±10.0) years. RVS is real-time virtual sonography, which fuses real-time intraoperative ultrasound images with corresponding preoperative CT or MRI images to guide the surgical plane. Methods of operation, time of operation, intraoperative blood loss, operative margin, hospital stay and postoperative complications were analyzed. Postoperative complications were graded by Clavien-Dindo system. The 1-year overall survival and tumor-free survival rates of patients were followed up by outpatient or telephone review.Results:Anatomical liver segmentectomy was performed on 36 patients, including 1 patient (2.9%) of segment Ⅱ, 1 patient (2.9%) of segment Ⅲ, 5 patients (14.3%) of segment Ⅳ, 6 patients (17.1%) of segment Ⅴ, 10 patients (28.6%) of segment Ⅵ, 7 patients (20.0%) of segment Ⅶ, 4 patients (11.4%) of segment Ⅷ, and 1 patient (2.9%) of segments Ⅴ+ Ⅷ. The operation time of 35 patients was (310.2±81.6) min, with an intraoperative blood loss of [ M( Q1, Q3)] 390.0(250.0, 500.0) ml. The hospital stay was (11.6±2.1) d. There was no postoperative death. Postoperative complications occurred in 3 cases (8.6%), of which 2 cases (5.7%) were ascites, Clavien-Dindo grade Ⅰ; Postoperative hemorrhage occurred in 1 case (2.9%), Clavien-Dindo grade Ⅱ. HCC was confirmed by pathology in all cases, and the operative margins were negative. The median follow-up time was 14 months (12 to 20 months). The 1-year overall survival rate after surgery was 100.0%(35/35), three patients (8.6%) had tumor recurrence, and the 1-year tumor-free survival rate was 91.4% (32/35). Conclusion:RVS surgical navigation combined with indocyanine green fluorescence imaging technology could be feasible in anatomical segmental hepatectomy for HCC.
5.Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics.
Jian GAO ; Zhigui WU ; Mingxia ZHAO ; Rui ZHANG ; Manru LI ; Dongdong SUN ; Haibo CHENG ; Xianjia QI ; Yuxian SHEN ; Qiang XU ; Hongqi CHEN ; Dijun CHEN ; Yang SUN
Acta Pharmaceutica Sinica B 2022;12(1):149-166
Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.