1.Molecular basis and precision medicine for interactions of genetic and environmental risk factors in esophageal cancer
Lidong WANG ; Xin SONG ; Xueke ZHAO ; Minjie WU ; Fuyou ZHOU
Chinese Journal of Clinical Oncology 2016;43(12):515-520
Esophageal cancer is a unique malignant disease in China. A fundamental difference exists between the Chinese population and the western population on esophageal cancer in terms of epidemiology, histogenesis, and carcinogenic risk factors. Therefore, ap-plying the western academic achievements to Chinese is difficult. Thus, Chinese scientists have the responsibility to conquer esopha-geal cancer in China. This article reviews the progress of esophageal cancer focused on the molecular mechanism for interactions of ge-netic and environmental risk factors and human esophageal multistage carcinogenesis.
2.Involvement of p38-p53 signal pathway in neuroprotective effects of DGMI on SH-SY5 Y cells damaged by oxygen-glucose deprivation
Xueke LI ; Qiu LIU ; Zhiliang XU ; Jun ZHOU ; Liang CAO ; Gang DING ; Zhenzhong WANG ; Wei XIAO
Chinese Pharmacological Bulletin 2016;32(12):1699-1704
Aim To investigate the protective effects of Diterpene Ginkgolides Meglumine Injection(DGMI)on SY5 Y cells damaged by oxygen-glucose deprivation and its functional mechanisms.Methods After 4 h of OGD,the cells were treated with 25 mg·L-1 drugs for 1 h.Subsequently,cell viabilities were measured by cell counting kit-8(CCK-8 kit)and cell apoptosis was measured by flow cytometric analysis.Furthermore, the mitochondrial membrane potential was detected by rhodamine123 staining.The levels of phospho-p38, phospho-p53,Bcl-2,Bax and cleaved caspase-9/3 were evaluated by western blot.Results DGMI signif-icantly increased the cell viabilities of SY5 Y cells dam-aged by OGD,and reduced OGD-elicited dissipation of mitochondrial membrane potential and cell apoptosis. Furthermore,DGMI also reduced p-p38,p-p53,Bax/Bcl-2 ratio,cleaved caspase-9 and cleaved caspase-3. Conclusion DGMI shows good neuroprotective effects on SY5 Y cells after oxygen-glucose deprivation.The underlying mechanisms may be associated with the sup-pression of p38/p53/Bcl-2 /caspase-9/caspase-3 sig-naling pathway.
4.Effects of nocturnal nutritional support on nutritional status and liver function in patients with hepatitis B cirrhosis
Mingyu ZHOU ; Hong LI ; Xueke ZHAO ; Dagang YANG
Chinese Journal of Primary Medicine and Pharmacy 2020;27(12):1413-1417
Objective:To observe the effect of nocturnal nutritional support on the improvement of nutritional status and liver function in patients with hepatitis B cirrhosis.Methods:A total of 60 patients with hepatitis B cirrhosis who were treated at the Affiliated Hospital of Guizhou Medical University from April 2011 to August 2018 were selected, and they were divided into nutritional intervention group and control group according to the random digital table method, with 30 cases in each group.The two groups were given basic medical treatment, and the nutritional intervention group was given basic treatment plus 30g of complex functional nutrients, once per night, for 12 weeks.The changes of liver function and nutritional status of the two groups were observed every 4 weeks, and the occurrence of complications was recorded.Results:Before intervention, the ALB, PA, TBIL, body mass index, triceps cutaneous fold thickness and grip strength had no statistically significant differences between the two groups(all P>0.05). After 12 weeks of intervention, the albumin [(32.61±1.78) g/L], pre-albumin [(116.65±11.92) g/L], total bilirubin [(36.6±5.86)μmol/L], body mass index [(22.23±2.92) kg/m 2], skinfold [(17.34±1.31) mm], the grip strength [(23.36±2.44)kg] in the intervention group were superior to the control group[(30.38±1.58)g/L, (101.22±7.76)g/L, (47.75±4.83)μmol/L, (21.07±2.11)kg/m 2, (16.07±1.40)mm, (20.01±2.70)kg], the differences were statistically significant between the two groups( t=4.946, 5.105, 5.881, 2.407, 2.272, 3.805, all P<0.05). The incidence of the complications in the intervention group was 10%(3/30), which in the control group was 33%(10/30), the difference was statistically significant between the two groups(χ 2=4.381, P=0.033). Conclusion:Providing nutritional support at night can improve the nutritional status of patients with hepatitis B cirrhosis, promote the repair of liver function, and reduce the incidence of complications.
5.Application of aptamers in the detection of key inflammatory cytokines
Huimin NIU ; Xueke LIU ; Xi ZHOU ; Shengxing ZHANG
Chinese Journal of Laboratory Medicine 2023;46(6):641-647
Pro-inflammatory cytokines selectively induce specific signals to regulate host responses. Since the immunological imbalance caused by abnormal release of cytokines is involved in the development of many diseases, cytokine-specific detections are of great clinical significance for disease diagnosis and efficacy monitoring. Aptamers are single-stranded nucleic acid sequences which can bind to the target with high selectivity and affinity. It has attracted much attention in the development of novel aptamers-based methods for the detection of specific biomarkers of inflammatory diseases. This paper reviewed recent advances in electrochemical and optical aptasensors for the detection of tumor necrosis factor-α, interleukin-6, transforming growth factor-β, interferon-γ and interleukin-8. The findings offered valuable insights into the clinical application potential and challenges of nucleic acid aptamers in the detection of key inflammatory cytokines, providing a meaningful reference for the development of aptamer-based cytokines sensitive detection point-of-care testing equipment and novel diagnostic strategies for inflammatory disorders.
6.Dihydroartemisinin promotes radiotherapy sensitivity of nasopharyngeal carcinoma CNE-2Z cells by activating chloride channels
Shiqing LIU ; Congran ZHOU ; Xinwei TANG ; Hanfen ZHOU ; XueKe LI ; Xi-Uying HOU ; Haifeng YANG ; Linyan ZHU
Chinese Journal of Pathophysiology 2024;40(2):255-264
AIM:To investigate the role of ClC-3 chloride channel in the promotion of radio sensitization of na-sopharyngeal carcinoma CNE-2Z cells by dihydroartemisinin(DHA).METHODS:MTT was used to detect the inhibito-ry effect of DHA on the viability of CNE-2Z cells and normal nasopharyngeal epithelial NP69-SV40T cells,the radio sensi-tization effect of DHA on CNE-2Z cells was detected by cloning assay,the expression of ClC-3 protein was detected by Western blot,the expression of ClC-3 protein was down-regulated by siRNA technology,and the chlorine current of cells was recorded by whole cell patch-clamp technology.RESULTS:(1)Compared with NP69-SV40T cells,DHA selective-ly inhibited the proliferation of CNE-2Z cells,with IC10 values of(13.020±4.831)μmol/L and(5.244±1.050)μmol/L,respectively(P<0.01).(2)The results of clonal formation experiments showed that DHA had a radio sensitizing effect on CNE-2Z cells,with a radio sensitization ratio of 1.9.(3)DHA could activate the chlorine channel of CNE-2Z cells and produce an outward chlorine current,but had no effect on the chlorine channel of NP69-SV40T cells.(4)DHA promoted the expression of ClC-3 chloric channel protein in CNE-2Z cells(P<0.01).(5)Chlorine channel blocker NPPB could in-hibit the radio sensitizing effect of DHA on CNE-2Z cells by 1.84 times,and also inhibited the chlorine current activated by DHA.(6)the down-regulation of CNE-2Z ClC-3 protein could inhibit the radio sensitization effect of DHA on CNE-2Z cells by 4.19 times,and the activation of chlorine current by DHA on CNE-2Z cells was no longer produced.CONCLU-SION:DHA has a radio sensitizing effect on nasopharyngeal carcinoma CNE-2Z cells,which is likely to be related to the activation of ClC-3 chloride channel.
7.Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors
Lidong WANG ; Liuyu LI ; Xin SONG ; Xueke ZHAO ; Fuyou ZHOU ; Ruihua XU ; Zhicai LIU ; Aili LI ; Jilin LI ; Xianzeng WANG ; Liguo ZHANG ; Fangheng ZHU ; Xuemin LI ; Weixing ZHAO ; Guizhou GUO ; Wenjun GAO ; Xiumin LI ; Lixin WAN ; Jianwei KU ; Quanxiao XU ; Fuguo ZHU ; Aifang JI ; Huixiang LI ; Jingli REN ; Shengli ZHOU ; Peinan CHEN ; Qide BAO ; Shegan GAO ; Haijun YANG ; Jinchang WEI ; Weimin MAO ; Zhanqiang HAN ; Zhiwei CHANG ; Yingfa ZHOU ; Xuena HAN ; Wenli HAN ; Lingling LEI ; Zongmin FAN ; Ran WANG ; Yuanze YANG ; Jiajia JI ; Yao CHEN ; Zhiqiang LI ; Jingfeng HU ; Lin SUN ; Yajie CHEN ; Helin BAI ; Duo YOU
Chinese Journal of Internal Medicine 2022;61(9):1023-1030
Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.
8.Glycolysis reprogramming in cancer-associated fibroblasts promotes the growth of oral cancer through the lncRNA H19/miR-675-5p/PFKFB3 signaling pathway.
Jin YANG ; Xueke SHI ; Miao YANG ; Jingjing LUO ; Qinghong GAO ; Xiangjian WANG ; Yang WU ; Yuan TIAN ; Fanglong WU ; Hongmei ZHOU
International Journal of Oral Science 2021;13(1):12-12
As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.
Cancer-Associated Fibroblasts/metabolism*
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Carcinoma, Squamous Cell/genetics*
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Cell Line, Tumor
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Cell Proliferation
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Gene Expression Regulation, Neoplastic
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Glycolysis
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Head and Neck Neoplasms
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Humans
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MicroRNAs/metabolism*
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Mouth Neoplasms/genetics*
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Phosphofructokinase-2/genetics*
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RNA, Long Noncoding/genetics*
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Signal Transduction
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Tumor Microenvironment