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Volume 27,Issue 7,2020 Table of Contents
2020, 27(7):715-724.
DOI: 10.3872/j.issn.1007-385X.2020.07.001
Abstract:
Chemokines are small secreted proteins produced by cancer and stromal cells. Chemokine receptors are also expressed on the surface of tumor cells and stromal cells. Chemokines bind to their homologous receptors to regulate tumor growth directly and indirectly, including direct regulation of tumor proliferation and metastasis by activating signal pathway, indirect regulation of tumor through acting on vascular endothelial cells and regulating immune response by coordinating the migration and localization of immune cells in tissues. Chemokines can be divided into four categories: CXC, CC, CX3C and C, among which CXC and CC are the most studied subtypes. In view of the fact that CXC chemokines and their receptors play a wide range of roles in malignant tumors and are closely related to the immune system, they are expected to become potential therapeutic targets, to improve tumor immune response by combining with immune checkpoint inhibitors to act in tumor microenvironment (TME). This paper reviews the research progress on chemokine/chemokine receptor axis of CXC subtypes, including the basic biological characteristics of tumor-promoting axis CXCR2/CXCLs, CXCR4/CXCL12 and tumor-suppressing axis CXCR3/CXCL9-11, their direct effect on tumor, indirect effect on TME, targeted therapy and prognostic significance of the receptors and ligands contained in these three axes.
Chemokines are small secreted proteins produced by cancer and stromal cells. Chemokine receptors are also expressed on the surface of tumor cells and stromal cells. Chemokines bind to their homologous receptors to regulate tumor growth directly and indirectly, including direct regulation of tumor proliferation and metastasis by activating signal pathway, indirect regulation of tumor through acting on vascular endothelial cells and regulating immune response by coordinating the migration and localization of immune cells in tissues. Chemokines can be divided into four categories: CXC, CC, CX3C and C, among which CXC and CC are the most studied subtypes. In view of the fact that CXC chemokines and their receptors play a wide range of roles in malignant tumors and are closely related to the immune system, they are expected to become potential therapeutic targets, to improve tumor immune response by combining with immune checkpoint inhibitors to act in tumor microenvironment (TME). This paper reviews the research progress on chemokine/chemokine receptor axis of CXC subtypes, including the basic biological characteristics of tumor-promoting axis CXCR2/CXCLs, CXCR4/CXCL12 and tumor-suppressing axis CXCR3/CXCL9-11, their direct effect on tumor, indirect effect on TME, targeted therapy and prognostic significance of the receptors and ligands contained in these three axes.
2020, 27(7):725-734.
DOI: 10.3872/j.issn.1007-385X.2020.07.002
Abstract:
Objective: To explore the regulatory effect of lncRNA maternal imprinting gene 3 (MEG3) on proliferation, migration,invasion and epithelial-mesenchymal transition (EMT) of cervical cancer cells via miR-9-5p/SOCS5 axis. Methods: A total of 20 pairs of cancer and para-cancerous tissue specimens resected from cervical cancer patients in Chongqing Hospital of Traditional Chinese Medicine from January 2017 to June 2019 were collected for this study. Using liposome transfection technology, pcDNA3.1-MEG3,si-MEG3, miR-9-5p mimics, miR-9-5p inhibitor and their control plasmids were transfected into cervical cancer HeLa and SiHa cells respectively to construct overexpression and silence cell model. qPCR was used to detect the expression levels of MEG3, miR-9-5p and SOCS5 in cervical cancer tissues and cell lines. CCK-8 method and Transwell chamber method were used to detect cell proliferation,migration and invasion ability. The expression levels of E-cadherin and vimentin in cells were detected by cellular immunofluorescence experiments. Target genes were predicted through the Online Bioinformatics TargetScan database. Dual luciferase reporter gene assay was used to verify the targeting relationship between miR-9-5p and MEG3, SOCS5, respectively. Results: Compared with para-cancerous tissues and cervical epithelial HcerEpic cells, the expressions of MEG3 and SOCS5 were significantly down-regulated and the expression of miR-9-5p was significantly up-regulated in cervical cancer tissues and cell lines (all P<0.01). TargetScan database analysis and Dual luciferase reporter gene assay confirmed the targeting relationship between miR-9-5p and MEG3 or SOCS5. MEG3 and SOCS5 significantly inhibited while miR-9-5p significantly promoted cell proliferation, migration and invasion ability (all P<0.01). MEG3 and SOCS5 promoted E-cadherin expression and inhibited vimentin expression, while miR-9-5p inhibited E-cadherin expression and promoted vimentin expression (P<0.05 or P<0.01). Conclusion: lncRNA MEG3 regulates proliferation,migration, invasion and EMT of cervical cancer cells via miR-9-5p/SOCS5 axis.
Objective: To explore the regulatory effect of lncRNA maternal imprinting gene 3 (MEG3) on proliferation, migration,invasion and epithelial-mesenchymal transition (EMT) of cervical cancer cells via miR-9-5p/SOCS5 axis. Methods: A total of 20 pairs of cancer and para-cancerous tissue specimens resected from cervical cancer patients in Chongqing Hospital of Traditional Chinese Medicine from January 2017 to June 2019 were collected for this study. Using liposome transfection technology, pcDNA3.1-MEG3,si-MEG3, miR-9-5p mimics, miR-9-5p inhibitor and their control plasmids were transfected into cervical cancer HeLa and SiHa cells respectively to construct overexpression and silence cell model. qPCR was used to detect the expression levels of MEG3, miR-9-5p and SOCS5 in cervical cancer tissues and cell lines. CCK-8 method and Transwell chamber method were used to detect cell proliferation,migration and invasion ability. The expression levels of E-cadherin and vimentin in cells were detected by cellular immunofluorescence experiments. Target genes were predicted through the Online Bioinformatics TargetScan database. Dual luciferase reporter gene assay was used to verify the targeting relationship between miR-9-5p and MEG3, SOCS5, respectively. Results: Compared with para-cancerous tissues and cervical epithelial HcerEpic cells, the expressions of MEG3 and SOCS5 were significantly down-regulated and the expression of miR-9-5p was significantly up-regulated in cervical cancer tissues and cell lines (all P<0.01). TargetScan database analysis and Dual luciferase reporter gene assay confirmed the targeting relationship between miR-9-5p and MEG3 or SOCS5. MEG3 and SOCS5 significantly inhibited while miR-9-5p significantly promoted cell proliferation, migration and invasion ability (all P<0.01). MEG3 and SOCS5 promoted E-cadherin expression and inhibited vimentin expression, while miR-9-5p inhibited E-cadherin expression and promoted vimentin expression (P<0.05 or P<0.01). Conclusion: lncRNA MEG3 regulates proliferation,migration, invasion and EMT of cervical cancer cells via miR-9-5p/SOCS5 axis.
2020, 27(7):735-741.
DOI: 10.3872/j.issn.1007-385X.2020.07.003
Abstract:
Objective: To investigate the molecular mechanism of miR-143-3p regulating the proliferation, migration and invasion of colon cancer RKO cells via targeting enhancer of zeste homolog 2 (EZH2). Methods: A total of 40 pairs of colon cancer tissues and corresponding para-cancerous tissues resected in the First Affiliated Hospital of Kunming Medical University from March 2015 to July 2017 were collected for this study. In addition, colon cancer cell lines (COLO320, RKO and CL-11) and normal intestinal mucosa NCM460 cells were also collected. qPCR was applied to detect the expression level of miR-143-3p in colon cancer tissues and cell lines. miR-143-3p mimics, miR-143-3p inhibitor, EZH2 siRNA and negative control plasmids were transfected into RKO cells,respectively. The effect of miR-143-3p/EZH2 axis on the proliferation, migration and invasion of RKO cells were detected by CCK-8 and Transwell assay, respectively.Western blotting was used to detect the expression level of EZH2 protein in RKO cells. The targeting relationship between miR-143-3p and EZH2 was verified by Dual luciferase reporter gene assay. Results: The expression level of miR-143-3p was downregulated in colon cancer tissues and cell lines (all P<0.01). Overexpression of miR-143-3p significantly inhibited the proliferation, migration and invasion of RKO cells (all P<0.01). Dual luciferase reporter gene assay confirmed that EZH2 was a target gene of miR-143-3p. Simultaneous knockdown of miR-143-3p and EZH2 attenuated the inhibition of EZH2 knockdown on the proliferation, migration and invasion of RKO cells. Conclusion: miR-143-3p suppresses the proliferation, migration and invasion of colon cancer cells via targetedly down-regulating EZH2.
Objective: To investigate the molecular mechanism of miR-143-3p regulating the proliferation, migration and invasion of colon cancer RKO cells via targeting enhancer of zeste homolog 2 (EZH2). Methods: A total of 40 pairs of colon cancer tissues and corresponding para-cancerous tissues resected in the First Affiliated Hospital of Kunming Medical University from March 2015 to July 2017 were collected for this study. In addition, colon cancer cell lines (COLO320, RKO and CL-11) and normal intestinal mucosa NCM460 cells were also collected. qPCR was applied to detect the expression level of miR-143-3p in colon cancer tissues and cell lines. miR-143-3p mimics, miR-143-3p inhibitor, EZH2 siRNA and negative control plasmids were transfected into RKO cells,respectively. The effect of miR-143-3p/EZH2 axis on the proliferation, migration and invasion of RKO cells were detected by CCK-8 and Transwell assay, respectively.Western blotting was used to detect the expression level of EZH2 protein in RKO cells. The targeting relationship between miR-143-3p and EZH2 was verified by Dual luciferase reporter gene assay. Results: The expression level of miR-143-3p was downregulated in colon cancer tissues and cell lines (all P<0.01). Overexpression of miR-143-3p significantly inhibited the proliferation, migration and invasion of RKO cells (all P<0.01). Dual luciferase reporter gene assay confirmed that EZH2 was a target gene of miR-143-3p. Simultaneous knockdown of miR-143-3p and EZH2 attenuated the inhibition of EZH2 knockdown on the proliferation, migration and invasion of RKO cells. Conclusion: miR-143-3p suppresses the proliferation, migration and invasion of colon cancer cells via targetedly down-regulating EZH2.
2020, 27(7):742-748.
DOI: 10.3872/j.issn.1007-385X.2020.07.004
Abstract:
Objective: To investigate the effect and mechanism of sevoflurane on the proliferation and invasion of colon cancer SW480 cells and the growth of transplanted tumor in nude mice by regulating the phosphorylation of PI3K. Methods: Colon cancer SW480 cells were treated with sevoflurane and randomly divided into control group, 0.5% sevoflurane group, 1.0% sevoflurane group and 2.0% sevoflurane group for subsequent experiments. The proliferation ability of SW480 cells was detected by Clone formation assay, mRNA expression levels of MDM2 and survivin in cells were detected by RT-PCR, invasion ability of cells was detected by Transwell assay, and protein expression levels of MDM2, survivin, VEGF, PI3K, p-PI3K, AKT and p-AKT were detected by Western blotting. PI3K activator 740Y-P was added for verification. SW480 cell transplanted tumor model was constructed on nude mice, and the tumor mass was weighed. The positive expression rates of MDM2 and VEGF in the transplanted tumor tissues were detected by Immunohistochemistry. Results: As compared with the control group and the low-dose group, the clone formation rate of SW480 cells and the number of invaded cells in the 1.0% and 2.0% sevoflurane groups were significantly decreased (all P<0.01), the mRNA and protein levels of MDM2 in the cells were significantly increased (all P<0.01), while the mRNA and protein levels of survivin were significantly decreased (all P<0.01); and the protein levels of VEGF, p-PI3K/PI3K and p-AKT/AKT were significantly decreased (all P<0.01). 740Y-P could reverse the effect of sevoflurane on the proliferation, invasion and expression of proteins associated with the PI3K/AKT signaling pathway in SW480 cells. The mass of transplanted tumor in 2.0% sevoflurane group was significantly decreased (P<0.01), and the positive MDM2 expression rate in tumor tissues was significantly increased (P<0.01), while the positive VEGF expression rate was significantly decreased (P<0.01). Conclusion: Sevoflurane inhibits the proliferation and invasion of colon cancer SW480 cells and the growth of xenografts in nude mice possibly by inhibiting PI3K phosphorylation.
Objective: To investigate the effect and mechanism of sevoflurane on the proliferation and invasion of colon cancer SW480 cells and the growth of transplanted tumor in nude mice by regulating the phosphorylation of PI3K. Methods: Colon cancer SW480 cells were treated with sevoflurane and randomly divided into control group, 0.5% sevoflurane group, 1.0% sevoflurane group and 2.0% sevoflurane group for subsequent experiments. The proliferation ability of SW480 cells was detected by Clone formation assay, mRNA expression levels of MDM2 and survivin in cells were detected by RT-PCR, invasion ability of cells was detected by Transwell assay, and protein expression levels of MDM2, survivin, VEGF, PI3K, p-PI3K, AKT and p-AKT were detected by Western blotting. PI3K activator 740Y-P was added for verification. SW480 cell transplanted tumor model was constructed on nude mice, and the tumor mass was weighed. The positive expression rates of MDM2 and VEGF in the transplanted tumor tissues were detected by Immunohistochemistry. Results: As compared with the control group and the low-dose group, the clone formation rate of SW480 cells and the number of invaded cells in the 1.0% and 2.0% sevoflurane groups were significantly decreased (all P<0.01), the mRNA and protein levels of MDM2 in the cells were significantly increased (all P<0.01), while the mRNA and protein levels of survivin were significantly decreased (all P<0.01); and the protein levels of VEGF, p-PI3K/PI3K and p-AKT/AKT were significantly decreased (all P<0.01). 740Y-P could reverse the effect of sevoflurane on the proliferation, invasion and expression of proteins associated with the PI3K/AKT signaling pathway in SW480 cells. The mass of transplanted tumor in 2.0% sevoflurane group was significantly decreased (P<0.01), and the positive MDM2 expression rate in tumor tissues was significantly increased (P<0.01), while the positive VEGF expression rate was significantly decreased (P<0.01). Conclusion: Sevoflurane inhibits the proliferation and invasion of colon cancer SW480 cells and the growth of xenografts in nude mice possibly by inhibiting PI3K phosphorylation.
2020, 27(7):749-756.
DOI: 10.3872/j.issn.1007-385X.2020.07.005
Abstract:
Objective: To explore the mechanism of TRIM21 regulating the proliferation of ovarian cancer cells and the resistance of PARP inhibitors by activating Wnt/β-catenin signaling pathway. Methods: Eight pairs of ovarian cancer tissues and cervical epithelial tissues that surgically removed at Yan'an People's Hospital from January 2018 to January 2019 were collected for this study. And the tissues were classified into resistant group and non-resistant group (4 case/group) according to whether the patients were resistant to PARP inhibitor (nilapanib). Ovarian cancer cell lines CAOV3, SKOV3, OVCAR3, ES-2, HO8910, A2780 and OV2008 were also collected for this study. qPCR and Western blotting (WB) were used to detect the expression levels of TRIM21 and β -catenin in the above mentioned tissues and cell lines. Cell lines with TRIM21 overexpression and knockdown were constructed. CCK-8 method was used to detect the proliferation activity of ovarian cancer cells in each group, TOP/FOP dual luciferase assay was used to detect the effect of TRIM21 on Wnt signaling pathway activation, qPCR and WB were used to detect the effect of TRIM21 on mRNA and protein levels of β-catenin, which was further verified by Wnt pathway inhibitor XAV-939. Results: The expression level of TRIM21 in ovarian cancer tissues was significantly higher than that in cervical epithelial tissues (P<0.01), and its expression was more higher in the drug-resistant tissues (P<0.01). TRIM21 expression was the highest in ES-2 cells but comparatively low in CAOV3 and A270 cells (all P<0.01). After TRIM21 knockdown, the expression of TRIM21 in ES-2 cells was significantly decreased, and the cell proliferation was significantly reduced (all P<0.01). After overexpressing TRIM21, the proliferative capacity of ovarian cancer CAOV3 cells was significantly increased (P<0.01), and the antitumor effect of nilaparib was inhibited; TRIM21 overexpression could regulate Wnt/β-catenin pathway activation, while β -catenin knockdown or Wnt/β-catenin inhibitor XAV-939 could significantly reverse the effect of TRIM21 in ovarian cancer. Conclusion: TRIM21 can enhance the proliferation of ovarian cancer cells via regulating Wnt/β-catenin pathway, it plays a certain role in the process of drug resistance of PARP inhibitor nilapani.
Objective: To explore the mechanism of TRIM21 regulating the proliferation of ovarian cancer cells and the resistance of PARP inhibitors by activating Wnt/β-catenin signaling pathway. Methods: Eight pairs of ovarian cancer tissues and cervical epithelial tissues that surgically removed at Yan'an People's Hospital from January 2018 to January 2019 were collected for this study. And the tissues were classified into resistant group and non-resistant group (4 case/group) according to whether the patients were resistant to PARP inhibitor (nilapanib). Ovarian cancer cell lines CAOV3, SKOV3, OVCAR3, ES-2, HO8910, A2780 and OV2008 were also collected for this study. qPCR and Western blotting (WB) were used to detect the expression levels of TRIM21 and β -catenin in the above mentioned tissues and cell lines. Cell lines with TRIM21 overexpression and knockdown were constructed. CCK-8 method was used to detect the proliferation activity of ovarian cancer cells in each group, TOP/FOP dual luciferase assay was used to detect the effect of TRIM21 on Wnt signaling pathway activation, qPCR and WB were used to detect the effect of TRIM21 on mRNA and protein levels of β-catenin, which was further verified by Wnt pathway inhibitor XAV-939. Results: The expression level of TRIM21 in ovarian cancer tissues was significantly higher than that in cervical epithelial tissues (P<0.01), and its expression was more higher in the drug-resistant tissues (P<0.01). TRIM21 expression was the highest in ES-2 cells but comparatively low in CAOV3 and A270 cells (all P<0.01). After TRIM21 knockdown, the expression of TRIM21 in ES-2 cells was significantly decreased, and the cell proliferation was significantly reduced (all P<0.01). After overexpressing TRIM21, the proliferative capacity of ovarian cancer CAOV3 cells was significantly increased (P<0.01), and the antitumor effect of nilaparib was inhibited; TRIM21 overexpression could regulate Wnt/β-catenin pathway activation, while β -catenin knockdown or Wnt/β-catenin inhibitor XAV-939 could significantly reverse the effect of TRIM21 in ovarian cancer. Conclusion: TRIM21 can enhance the proliferation of ovarian cancer cells via regulating Wnt/β-catenin pathway, it plays a certain role in the process of drug resistance of PARP inhibitor nilapani.
2020, 27(7):757-763.
DOI: 10.3872/j.issn.1007-385X.2020.07.006
Abstract:
Objective: To investigate the effects of CRISPR/Cas9 gene editing mediated PD-1 knockdown on the proliferation,phenotype, IFN-γ and IL-2 secretion of T cells in Cynomolgus monkeys. Methods: gRNA targeting PD-1 gene of Cynomolgus monkey was designed, and the corresponding plasmid was constructed and extracted. peripheral blood mononuclear cells (PBMCs) of Cynomolgus monkeys were isolated, and plasmid DNAs were added for transfection by using Lonza 4D electrorotometer. FACS analysis and fluorescence microscopy were used to detect transfection efficiency at 48 h after transfection. Genomic DNAof T cells was extracted for PCR amplification and T7E1 digestion identification. The proliferation of T cells was induced under the stimulation of human CD3 antibody and IL-2, and the cell growth curve was drawn. PI staining flow cytometry was used to detect cell cycle and the expression levels of CD4 and CD8, and ELISA was used to detect the secretion of IFN- γ and IL-2. Results: At 48 h after transfection, the cells with green fluorescent protein expression in experimental group were observed under fluorescence microscopy with a transfection efficiency of (21.6±3.2)%. T7E1 enzyme digestion results showed that the PCR product of genomic DNA of cells in experimental group showed 3 bands after digestion, including the target cleavage bands (243，197 bp). Compared with non-transfected cells, the cells in experimental group exhibited slow proliferation, delayed colony formation, with small volume and weak refraction; the number of T cells at G0/G1 phase of the experimental group was significantly increased (P<0.05), while the number of cells at G2/M phase was significantly reduced (P<0.05); and the secretion levels of IFN-γ and IL-2 in the cells of the experimental group increased significantly (both P<0.05). However, the difference in the expression levels of CD4 and CD8 was not statistically significant between the two groups (both P>0.05). Conclusion: PD-1 gene knockout can arrest T cells in Cynomolgus monkey at G0/G1 phase, thereby inhibiting its proliferation and increasing the secretion of IFN-γ and IL-2 in the meanwhile.
Objective: To investigate the effects of CRISPR/Cas9 gene editing mediated PD-1 knockdown on the proliferation,phenotype, IFN-γ and IL-2 secretion of T cells in Cynomolgus monkeys. Methods: gRNA targeting PD-1 gene of Cynomolgus monkey was designed, and the corresponding plasmid was constructed and extracted. peripheral blood mononuclear cells (PBMCs) of Cynomolgus monkeys were isolated, and plasmid DNAs were added for transfection by using Lonza 4D electrorotometer. FACS analysis and fluorescence microscopy were used to detect transfection efficiency at 48 h after transfection. Genomic DNAof T cells was extracted for PCR amplification and T7E1 digestion identification. The proliferation of T cells was induced under the stimulation of human CD3 antibody and IL-2, and the cell growth curve was drawn. PI staining flow cytometry was used to detect cell cycle and the expression levels of CD4 and CD8, and ELISA was used to detect the secretion of IFN- γ and IL-2. Results: At 48 h after transfection, the cells with green fluorescent protein expression in experimental group were observed under fluorescence microscopy with a transfection efficiency of (21.6±3.2)%. T7E1 enzyme digestion results showed that the PCR product of genomic DNA of cells in experimental group showed 3 bands after digestion, including the target cleavage bands (243，197 bp). Compared with non-transfected cells, the cells in experimental group exhibited slow proliferation, delayed colony formation, with small volume and weak refraction; the number of T cells at G0/G1 phase of the experimental group was significantly increased (P<0.05), while the number of cells at G2/M phase was significantly reduced (P<0.05); and the secretion levels of IFN-γ and IL-2 in the cells of the experimental group increased significantly (both P<0.05). However, the difference in the expression levels of CD4 and CD8 was not statistically significant between the two groups (both P>0.05). Conclusion: PD-1 gene knockout can arrest T cells in Cynomolgus monkey at G0/G1 phase, thereby inhibiting its proliferation and increasing the secretion of IFN-γ and IL-2 in the meanwhile.
2020, 27(7):764-769.
DOI: 10.3872/j.issn.1007-385X.2020.07.007
Abstract:
Objective: To investigate the expression of lncRNA linc01503 in esophageal squamous cell carcinoma (ESCC) tissues and cell lines, as well as its effect on the proliferation, invasion and epithelial-mesenchymal transition (EMT) of ESCC cells. Methods: A total of 119 pairs of tumor tissues and corresponding para-cancerous tissues of ESCC patients were obtained from the Fourth Affiliated Hospital of Hebei Medical University between Jan. 2012 and Dec. 2014. The expression of linc01503 in ESCC tissues and cell lines (Kyse150, Kyse170, Eca109, TE1 and TE13) was detected by qPCR. The ESCC cells were transfected with pGPU6-shRNA-linc01503 or treated with TGF-β. The expressions of EMT related genes before and after transfection as well as linc01503 expression before and after TGF-β treatment were detected with qPCR. MTS and Transwell assay were performed to assess the effect of linc01503 on proliferation and invasion of ESCC cells. Results: The expression of linc01503 was significantly elevated in ESCC tissues and cell lines (all P<0.05). High expression of linc01503 was correlatedwith lymph node metastasis, depth of infiltration, TNM stage and the survival of ESCC patients (all P<0.05). Treatment with TGF-β promoted EMT of ESCC cells and induced a significant up-regulation of linc01503 expression. Knockdown of linc01503 significantly inhibited proliferation and invasion ability of ESCC cells; Meanwhile, the low expression of linc01503 increased the expression of E-cadherin but decreased the expressions of N-cadherin and vimentin (all P<0.05).Conclusion: lncRNA linc01503, as one of the downstream effect genes of TGF- β , promotes the proliferation, invasion and EMT process of ESCCcells.
Objective: To investigate the expression of lncRNA linc01503 in esophageal squamous cell carcinoma (ESCC) tissues and cell lines, as well as its effect on the proliferation, invasion and epithelial-mesenchymal transition (EMT) of ESCC cells. Methods: A total of 119 pairs of tumor tissues and corresponding para-cancerous tissues of ESCC patients were obtained from the Fourth Affiliated Hospital of Hebei Medical University between Jan. 2012 and Dec. 2014. The expression of linc01503 in ESCC tissues and cell lines (Kyse150, Kyse170, Eca109, TE1 and TE13) was detected by qPCR. The ESCC cells were transfected with pGPU6-shRNA-linc01503 or treated with TGF-β. The expressions of EMT related genes before and after transfection as well as linc01503 expression before and after TGF-β treatment were detected with qPCR. MTS and Transwell assay were performed to assess the effect of linc01503 on proliferation and invasion of ESCC cells. Results: The expression of linc01503 was significantly elevated in ESCC tissues and cell lines (all P<0.05). High expression of linc01503 was correlatedwith lymph node metastasis, depth of infiltration, TNM stage and the survival of ESCC patients (all P<0.05). Treatment with TGF-β promoted EMT of ESCC cells and induced a significant up-regulation of linc01503 expression. Knockdown of linc01503 significantly inhibited proliferation and invasion ability of ESCC cells; Meanwhile, the low expression of linc01503 increased the expression of E-cadherin but decreased the expressions of N-cadherin and vimentin (all P<0.05).Conclusion: lncRNA linc01503, as one of the downstream effect genes of TGF- β , promotes the proliferation, invasion and EMT process of ESCCcells.
2020, 27(7):770-775.
DOI: 10.3872/j.issn.1007-385X.2020.07.008
Abstract:
Objective: To investigate the efficacy and safety of apatinib monotherapy in the treatment for patients with advanced colorectal cancer (CRC) who failed standard regimen. Methods: The required sample size in this prospective study was calculated with the PASS 15 software. A total of 52 patients with advanced colorectal cancer who failed standard regimen from July 2017 to August 2018 were included in this study. The patientswere given apatinib monotherapy with an initial dosage of 750mg or 500 mg. The objective remission rate (ORR) and disease control rate (DCR) were evaluated; the patients were followed up and progression-free survival (PFS) and overall survival (OS) were evaluated, and adverse events during treatment were recorded. The primary endpoint of this study was PFS, and secondary endpoints were ORR, DCR, OS and safety. Result: Of the 52 patients included, 45 patients, all of whom were late stage CRC patients with at least two systematic chemotherapeutic treatments, were available for efficacy evaluation. Treatment efficacy evaluation showed complete response of 0 case, partial response of 5 cases, stable disease of 30 cases and progression disease of 10 cases; the ORR was 11.11%, and the DCR was 77.78%. The prognosis data indicated that the median PFS of the 45 CRC patients was 3.95 months (95% CI=3.16-4.74), and the median OS was 10.3 months (95% CI=5.70-14.90). In terms of adverse events evaluation, the adverse reactions with grade 3 or above were hand-foot syndrome (6 cases, 13.33%), hypertension (5 cases, 11.11%), proteinuria (3 cases, 6.67%), diarrhea (3 cases, 6.67%), fatigue (2 cases, 4.44%) and bleeding (1 case, 2.22%). Conclusion: Apatinib monotherapy for patients with advanced colorectal cancer, who failed the standard regimens, has potential clinical benefits, and the overall toxicity profile is manageable.
Objective: To investigate the efficacy and safety of apatinib monotherapy in the treatment for patients with advanced colorectal cancer (CRC) who failed standard regimen. Methods: The required sample size in this prospective study was calculated with the PASS 15 software. A total of 52 patients with advanced colorectal cancer who failed standard regimen from July 2017 to August 2018 were included in this study. The patientswere given apatinib monotherapy with an initial dosage of 750mg or 500 mg. The objective remission rate (ORR) and disease control rate (DCR) were evaluated; the patients were followed up and progression-free survival (PFS) and overall survival (OS) were evaluated, and adverse events during treatment were recorded. The primary endpoint of this study was PFS, and secondary endpoints were ORR, DCR, OS and safety. Result: Of the 52 patients included, 45 patients, all of whom were late stage CRC patients with at least two systematic chemotherapeutic treatments, were available for efficacy evaluation. Treatment efficacy evaluation showed complete response of 0 case, partial response of 5 cases, stable disease of 30 cases and progression disease of 10 cases; the ORR was 11.11%, and the DCR was 77.78%. The prognosis data indicated that the median PFS of the 45 CRC patients was 3.95 months (95% CI=3.16-4.74), and the median OS was 10.3 months (95% CI=5.70-14.90). In terms of adverse events evaluation, the adverse reactions with grade 3 or above were hand-foot syndrome (6 cases, 13.33%), hypertension (5 cases, 11.11%), proteinuria (3 cases, 6.67%), diarrhea (3 cases, 6.67%), fatigue (2 cases, 4.44%) and bleeding (1 case, 2.22%). Conclusion: Apatinib monotherapy for patients with advanced colorectal cancer, who failed the standard regimens, has potential clinical benefits, and the overall toxicity profile is manageable.
2020, 27(7):776-780.
DOI: 10.3872/j.issn.1007-385X.2020.07.009
Abstract:
Objective: To explore the effects of triptolide on immune function and tumor cell proliferation in patients with cervical cancer. Methods: Sixty-two patients with cervical cancer admitted in the Department of Obstetrics and Gynecology of the Second Affiliated Hospital of Hebei North College between July 2015 and April 2018 were randomly divided into the control group (n=31) and the observation group (n=31). All patients received routine treatment after laparoscopy, while those in the observation group received additional triptolide. The treatment efficacy, serum immune cells, inflammatory factors and the levels of cyclinD1, estrogen receptor α (ERα ) were observed and compared between the two groups. Results: The total remission rate of the patients in the observation group was 87.10%, significantly higher than 61.29% in the control group (P<0.05). After treatment, the levels of CD3+ and CD4+ T lymphocytes and CD4+/CD8+ T lymphocytes in the two groups increased significantly, with more obvious increase in the observation group than that in the control group (P<0.01). The levels of CD8+ and programmed cell death-ligand 1 (PD-L1) T lymphocytes in the two groups decreased significantly after treatment, with a more obvious decrease in observation group than that in control group (P<0.01). After treatment, the levels of interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) in the two groups decreased,and those in the observation group were significantly lower than those in the control group (P<0.05). After treatment, the positive expression rate of cyclinD1 decreased and the positive expression rate of ER α increased in both groups (all P<0.05), with no significant difference between the two groups (all P>0.05). Conclusion: On the basis of routine surgical treatment, triptolide can effectively improve the immune function, reduce the inflammatory response, inhibit the proliferation of tumor cells and regulate the expression of cancer-related factors in patients with cervical cancer, which has a certain therapeutic effect on cervical cancer.
Objective: To explore the effects of triptolide on immune function and tumor cell proliferation in patients with cervical cancer. Methods: Sixty-two patients with cervical cancer admitted in the Department of Obstetrics and Gynecology of the Second Affiliated Hospital of Hebei North College between July 2015 and April 2018 were randomly divided into the control group (n=31) and the observation group (n=31). All patients received routine treatment after laparoscopy, while those in the observation group received additional triptolide. The treatment efficacy, serum immune cells, inflammatory factors and the levels of cyclinD1, estrogen receptor α (ERα ) were observed and compared between the two groups. Results: The total remission rate of the patients in the observation group was 87.10%, significantly higher than 61.29% in the control group (P<0.05). After treatment, the levels of CD3+ and CD4+ T lymphocytes and CD4+/CD8+ T lymphocytes in the two groups increased significantly, with more obvious increase in the observation group than that in the control group (P<0.01). The levels of CD8+ and programmed cell death-ligand 1 (PD-L1) T lymphocytes in the two groups decreased significantly after treatment, with a more obvious decrease in observation group than that in control group (P<0.01). After treatment, the levels of interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) in the two groups decreased,and those in the observation group were significantly lower than those in the control group (P<0.05). After treatment, the positive expression rate of cyclinD1 decreased and the positive expression rate of ER α increased in both groups (all P<0.05), with no significant difference between the two groups (all P>0.05). Conclusion: On the basis of routine surgical treatment, triptolide can effectively improve the immune function, reduce the inflammatory response, inhibit the proliferation of tumor cells and regulate the expression of cancer-related factors in patients with cervical cancer, which has a certain therapeutic effect on cervical cancer.
10 Identification and characteristic analysis of enhancer-miRNA regulatory pairs in hepatic carcinoma
2020, 27(7):781-786.
DOI: 10.3872/j.issn.1007-385X.2020.07.010
Abstract:
Objective: To explore the regulatory relationship between enhancer and miRNA and the characteristics of the enhancers that regulate miRNA in hepatic carcinoma and normal hepatic tissues, and to screen the differentially expressed miRNAs regulated by enhancers as well as their association with the treatment targets in liver cancer. Methods: Based on the TCGA and FANTOM5 databases, Co-expression and 3D genomic analysis were performed on 417 samples of enhancers and miRNAs in liver cancer and normal liver tissues. The difference in signal value of the enhancer that regulates miRNA was analyzed by ChIP-seq data of histone modification and transcription factor in liver cancer and normal liver tissues in ENCODE database. The differentially expressed miRNAs regulated by enhancers were screened out, and the correlation analysis was performed on the patient's survival and treatment targets. Results: 93 and 40 pairs of enhancer-miRNA were identified in liver cancer and normal liver tissues, respectively. ChIP-seq data comparison analysis found that the signal of H3K27ac, H3K4me1 and sH3K4me3 histone modification in the region of enhancers regulating miRNA was significantly higher than that in the region of enhancers not regulating miRNA (|rho|>0.3, P<0.05). Moreover,the enrichment of multiple transcription factors in liver cancer-related enhancers was significantly lower than that in normal liver tissue-realted enhancers (|rho|>0.3, P<0.05). Differential expression analysis of enhancer-regulated miRNAs identified 6 miRNAs related to the survival of liver cancer patients (hsa-miR-4664, hsa-miR-5003,hsa-miR-1915,hsa-miR-3619,hsa-miR-4745, hsa-miR-6728),and found that these miRNAs were significantly associated with 87 genes for targeted therapy and 8 tumor immune checkpoint genes (|rho|>0.1, FDR<0.05). Conclusion: The enhancer-miRNA regulatory pairs and the characteristics of the enhancer that regulates miRNA were successfully identified in liver cancer. The miRNAs regulated by enhancers and related to the therapeutic targets and survival of patients with liver cancer were also screened out. It provides a valuable preliminary basis for future in-depth basic and clinical research in hepatic carcinoma.
Objective: To explore the regulatory relationship between enhancer and miRNA and the characteristics of the enhancers that regulate miRNA in hepatic carcinoma and normal hepatic tissues, and to screen the differentially expressed miRNAs regulated by enhancers as well as their association with the treatment targets in liver cancer. Methods: Based on the TCGA and FANTOM5 databases, Co-expression and 3D genomic analysis were performed on 417 samples of enhancers and miRNAs in liver cancer and normal liver tissues. The difference in signal value of the enhancer that regulates miRNA was analyzed by ChIP-seq data of histone modification and transcription factor in liver cancer and normal liver tissues in ENCODE database. The differentially expressed miRNAs regulated by enhancers were screened out, and the correlation analysis was performed on the patient's survival and treatment targets. Results: 93 and 40 pairs of enhancer-miRNA were identified in liver cancer and normal liver tissues, respectively. ChIP-seq data comparison analysis found that the signal of H3K27ac, H3K4me1 and sH3K4me3 histone modification in the region of enhancers regulating miRNA was significantly higher than that in the region of enhancers not regulating miRNA (|rho|>0.3, P<0.05). Moreover,the enrichment of multiple transcription factors in liver cancer-related enhancers was significantly lower than that in normal liver tissue-realted enhancers (|rho|>0.3, P<0.05). Differential expression analysis of enhancer-regulated miRNAs identified 6 miRNAs related to the survival of liver cancer patients (hsa-miR-4664, hsa-miR-5003,hsa-miR-1915,hsa-miR-3619,hsa-miR-4745, hsa-miR-6728),and found that these miRNAs were significantly associated with 87 genes for targeted therapy and 8 tumor immune checkpoint genes (|rho|>0.1, FDR<0.05). Conclusion: The enhancer-miRNA regulatory pairs and the characteristics of the enhancer that regulates miRNA were successfully identified in liver cancer. The miRNAs regulated by enhancers and related to the therapeutic targets and survival of patients with liver cancer were also screened out. It provides a valuable preliminary basis for future in-depth basic and clinical research in hepatic carcinoma.
2020, 27(7):787-793.
DOI: 10.3872/j.issn.1007-385X.2020.07.011
Abstract:
Objective: To explore the key genes and molecular mechanisms of liver metastasis in colorectal cancer (CRC), and to provide potential targets and biomarkers for the treatment of CRC with liver metastasis. Methods: Based on the bioinformatics method,the gene data sets of CRC liver metastasis were downloaded from the GEO database to screen the differentially expressed genes (DEGs); the GO and KEGG enrichment analyses of DEGs were performed by using DAVID online tool, and the protein-protein interaction (PPI) network was constructed to screen out the key genes, and subsequently the prognosis was analyzed. Results: A total of 321 DEGs were selected from 183 CRC specimens and 39 liver metastasis specimens, including 153 up-regulated genes and 168 downregulated genes. The results of enrichment analysis of GO and KEGG showed that the functions of DEGs were mainly related to protein activation cascade, inflammatory response, extracellular matrix, platelet degranulation, complement and coagulation cascade reaction etc. 8 key CRC genes (ALB, APOB, FGA, F2,APOA1, SERPINC1, FGG andAHSG) were screened by PPI network. Survival analysis showed that patients with high expressions of SERPINC1 and FGG had poor prognosis (all P<0.05). Conclusion: The biological functions and signaling pathways of DEGs are related to the occurrence and development of liver metastasis. The 8 key genes may be the potential therapeutic targets of CRC liver metastasis, and SERPINC1 and FGG may be new prognostic markers.
Objective: To explore the key genes and molecular mechanisms of liver metastasis in colorectal cancer (CRC), and to provide potential targets and biomarkers for the treatment of CRC with liver metastasis. Methods: Based on the bioinformatics method,the gene data sets of CRC liver metastasis were downloaded from the GEO database to screen the differentially expressed genes (DEGs); the GO and KEGG enrichment analyses of DEGs were performed by using DAVID online tool, and the protein-protein interaction (PPI) network was constructed to screen out the key genes, and subsequently the prognosis was analyzed. Results: A total of 321 DEGs were selected from 183 CRC specimens and 39 liver metastasis specimens, including 153 up-regulated genes and 168 downregulated genes. The results of enrichment analysis of GO and KEGG showed that the functions of DEGs were mainly related to protein activation cascade, inflammatory response, extracellular matrix, platelet degranulation, complement and coagulation cascade reaction etc. 8 key CRC genes (ALB, APOB, FGA, F2,APOA1, SERPINC1, FGG andAHSG) were screened by PPI network. Survival analysis showed that patients with high expressions of SERPINC1 and FGG had poor prognosis (all P<0.05). Conclusion: The biological functions and signaling pathways of DEGs are related to the occurrence and development of liver metastasis. The 8 key genes may be the potential therapeutic targets of CRC liver metastasis, and SERPINC1 and FGG may be new prognostic markers.
2020, 27(7):794-800.
DOI: 10.3872/j.issn.1007-385X.2020.07.012
Abstract:
Objective: To explore the expression and regulation mechanism of Dickkopf-1 (DKK1) in head and neck squamous cell carcinoma (HNSCC) tissues. Methods: Based on the TCGA database, the relationship of DKK1 expression in HNSCC tissues and its methylation site with patients’prognosis was analyzed. GO and KEGG gene enrichment method were used to analyze the signaling pathways of DKK1 enrichment. STRING was used to analyze the interaction between DKK1 protein and other proteins. TargetScan was used to analyze the miRNAs that regulate the expression of DKK1, and the transcription factors of DKK1 were analyzed with the TRRUST website. Results: DKK1 gene was highly expressed in HNSCC tissues (P<0.01), and its expression level was significantly correlated with the HPV status, age, pathological grade, and clinical stage of patients (all P<0.05); the prognosis of HNSCC patients with high DKK1 expression was poorer than those with low DKK1 expression (P<0.01). There were 19 methylation sites in DKK1, 12 of which were significantly different between cancer tissues and normal tissues (P<0.05), and 11 sites were significantly related to the prognosis of HNSCC (P<0.05). In addition, miRNA, circRNA, lincRNA and transcription factors, etc. also participated in the regulation of DKK1. A total of 5 DKK1-related PPI networks that may involve in the occurrence, development, invasion and metastasis of HNSCC were obtained. Conclusion: DKK1 is highly expressed in HNSCC tissues and is a risk factor for poor prognosis of HNSCC patients. DKK1 plays an important role in the pathogenesis of HNSCC and is expected to become a potential target for HNSCC treatment.
Objective: To explore the expression and regulation mechanism of Dickkopf-1 (DKK1) in head and neck squamous cell carcinoma (HNSCC) tissues. Methods: Based on the TCGA database, the relationship of DKK1 expression in HNSCC tissues and its methylation site with patients’prognosis was analyzed. GO and KEGG gene enrichment method were used to analyze the signaling pathways of DKK1 enrichment. STRING was used to analyze the interaction between DKK1 protein and other proteins. TargetScan was used to analyze the miRNAs that regulate the expression of DKK1, and the transcription factors of DKK1 were analyzed with the TRRUST website. Results: DKK1 gene was highly expressed in HNSCC tissues (P<0.01), and its expression level was significantly correlated with the HPV status, age, pathological grade, and clinical stage of patients (all P<0.05); the prognosis of HNSCC patients with high DKK1 expression was poorer than those with low DKK1 expression (P<0.01). There were 19 methylation sites in DKK1, 12 of which were significantly different between cancer tissues and normal tissues (P<0.05), and 11 sites were significantly related to the prognosis of HNSCC (P<0.05). In addition, miRNA, circRNA, lincRNA and transcription factors, etc. also participated in the regulation of DKK1. A total of 5 DKK1-related PPI networks that may involve in the occurrence, development, invasion and metastasis of HNSCC were obtained. Conclusion: DKK1 is highly expressed in HNSCC tissues and is a risk factor for poor prognosis of HNSCC patients. DKK1 plays an important role in the pathogenesis of HNSCC and is expected to become a potential target for HNSCC treatment.
2020, 27(7):801-806.
DOI: 10.3872/j.issn.1007-385X.2020.07.013
Abstract:
Objective: To explore the pathogenosis and prognostic markers for non-smoking female lung cancer patients with bioinformatics analysis and functional prediction of potential lung cancer associated genes in female non-smokers. Methods: Data for nonsmoking female patients with lung cancer were downloaded from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were identified using GEO2R. DAVID online data base was used to perform gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG), and STRING online software was used to perform protein-protein interaction (PPI) analysis; then the plug-in (M-CODE) was used to screen the key DEGs; finally, GEPIA and Kaplan-Meier plotter were used to perform function prediction and prognosis analysis of key DEGs. Results: A total of 160 DEGs were screened, including 54 up-regulated and 106 down-regulated genes; GO enrichment analysis showed that these DEGs were mainly related to neovascularization, single cell adhesion, positive regulation of GTPase activity and signal transduction (all P<0.05). KEGG pathway analysis revealed that DEGs were mainly involved in cell adhesion molecules (CAMs), leukocyte transendothelial migration, tight junction and endocytosis (all P<0.05);PPI network analysis revealed 8 key DEGs, including TIE1, PECAM1, CLDN5, VEGFD, ICAM2, ESAM, EMCN and ROBO4.Conclusion: TIE1, CLDN5, ICAM2, ESAM, VEGFD and ROBO4 may be the research targets of the pathogenesis of non-smoking female lung cancer patients. PECAM1 and EMCN may be the new bio-markers to predict the progression and prognosis of nonsmoking female lung cancer patients.
Objective: To explore the pathogenosis and prognostic markers for non-smoking female lung cancer patients with bioinformatics analysis and functional prediction of potential lung cancer associated genes in female non-smokers. Methods: Data for nonsmoking female patients with lung cancer were downloaded from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were identified using GEO2R. DAVID online data base was used to perform gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG), and STRING online software was used to perform protein-protein interaction (PPI) analysis; then the plug-in (M-CODE) was used to screen the key DEGs; finally, GEPIA and Kaplan-Meier plotter were used to perform function prediction and prognosis analysis of key DEGs. Results: A total of 160 DEGs were screened, including 54 up-regulated and 106 down-regulated genes; GO enrichment analysis showed that these DEGs were mainly related to neovascularization, single cell adhesion, positive regulation of GTPase activity and signal transduction (all P<0.05). KEGG pathway analysis revealed that DEGs were mainly involved in cell adhesion molecules (CAMs), leukocyte transendothelial migration, tight junction and endocytosis (all P<0.05);PPI network analysis revealed 8 key DEGs, including TIE1, PECAM1, CLDN5, VEGFD, ICAM2, ESAM, EMCN and ROBO4.Conclusion: TIE1, CLDN5, ICAM2, ESAM, VEGFD and ROBO4 may be the research targets of the pathogenesis of non-smoking female lung cancer patients. PECAM1 and EMCN may be the new bio-markers to predict the progression and prognosis of nonsmoking female lung cancer patients.
2020, 27(7):807-812.
DOI: 10.3872/j.issn.1007-385X.2020.07.014
Abstract:
卵巢癌是女性常见的恶性肿瘤之一，其中以上皮性卵巢癌最多见，发病率及病死率均居高不下，对女性生命造成严重威胁。化疗是重要的治疗手段之一，但多药耐药（multidrug resistance，MDR）是卵巢癌复发和难治的主要原因。卵巢癌MDR的发生和发展是多因素参与的极其复杂的过程，其机制尚不十分明确，探明卵巢癌MDR发生的分子机制，有利于寻找敏感的治疗分子靶标，从而提高卵巢癌的治疗效果。本文就影响卵巢癌细胞内药物外排、细胞凋亡及自噬、细胞信号转导通路以及卵巢癌干细胞、卵巢癌的肿瘤异质性和非编码RNA等耐药因素的分子机制作一综述。
卵巢癌是女性常见的恶性肿瘤之一，其中以上皮性卵巢癌最多见，发病率及病死率均居高不下，对女性生命造成严重威胁。化疗是重要的治疗手段之一，但多药耐药（multidrug resistance，MDR）是卵巢癌复发和难治的主要原因。卵巢癌MDR的发生和发展是多因素参与的极其复杂的过程，其机制尚不十分明确，探明卵巢癌MDR发生的分子机制，有利于寻找敏感的治疗分子靶标，从而提高卵巢癌的治疗效果。本文就影响卵巢癌细胞内药物外排、细胞凋亡及自噬、细胞信号转导通路以及卵巢癌干细胞、卵巢癌的肿瘤异质性和非编码RNA等耐药因素的分子机制作一综述。
2020, 27(7):813-819.
DOI: 10.3872/j.issn.1007-385X.2020.07.015
Abstract:
嵌合抗原受体基因修饰T细胞（chimeric antigen receptor gene modified T lymphocyte, CAR-T cell）治疗血液肿瘤显示了良好的效果，也为治疗食管癌、胃癌、肝细胞癌、胆管癌、胰腺癌和结直肠癌等消化系统肿瘤提供了新选择。消化系统不同部位肿瘤的细胞特征和肿瘤微环境存在差异，故靶向抗原的选择和CAR-T细胞的设计也相应地有所不同。CAR-T细胞治疗与其他免疫治疗联合使用也取得了一定的进展，但主要体现在细胞实验和小鼠体内实验。目前存在的脱靶效应、细胞因子释放综合征等副作用严重阻碍了CAR-T细胞的研究进展，限制了其在实体瘤中的应用。本文就近年来CAR-T细胞治疗消化系统肿瘤的研究进展作一阐述。
嵌合抗原受体基因修饰T细胞（chimeric antigen receptor gene modified T lymphocyte, CAR-T cell）治疗血液肿瘤显示了良好的效果，也为治疗食管癌、胃癌、肝细胞癌、胆管癌、胰腺癌和结直肠癌等消化系统肿瘤提供了新选择。消化系统不同部位肿瘤的细胞特征和肿瘤微环境存在差异，故靶向抗原的选择和CAR-T细胞的设计也相应地有所不同。CAR-T细胞治疗与其他免疫治疗联合使用也取得了一定的进展，但主要体现在细胞实验和小鼠体内实验。目前存在的脱靶效应、细胞因子释放综合征等副作用严重阻碍了CAR-T细胞的研究进展，限制了其在实体瘤中的应用。本文就近年来CAR-T细胞治疗消化系统肿瘤的研究进展作一阐述。
2020, 27(7):820-824.
DOI: 10.3872/j.issn.1007-385X.2020.07.016
Abstract:
胃癌（gastric carcinoma，GC）是最常见的消化系统恶性肿瘤之一，其病因及发病机制等都尚未明了，诊断、治疗及预后仍然面临着严峻的问题。微小RNA（microRNA，miRNA）作为一类重要的基因表达调节剂，能够与其相对应的靶基因相结合，从而影响基因表达，以此在GC发生发展中发挥重要的作用。miR-30 家族中5 个高度保守且成熟的成员——miR-30a、miR-30b、miR-30c、miR-30d 和miR-30e 位于不同的染色体或邻近位点，这些miRNA在5'末端附近有一个共同序列，3'末端附近具有不同的补偿序列。通过靶向各自相对应的基因影响着GC细胞的增殖、转移、侵袭和对化学药物的耐药性。miR-30 家族在GC中发挥着重要的抑癌作用。本文就近年来miR-30 家族中5 个成员在GC发生发展中作用的研究进展作一综述。
胃癌（gastric carcinoma，GC）是最常见的消化系统恶性肿瘤之一，其病因及发病机制等都尚未明了，诊断、治疗及预后仍然面临着严峻的问题。微小RNA（microRNA，miRNA）作为一类重要的基因表达调节剂，能够与其相对应的靶基因相结合，从而影响基因表达，以此在GC发生发展中发挥重要的作用。miR-30 家族中5 个高度保守且成熟的成员——miR-30a、miR-30b、miR-30c、miR-30d 和miR-30e 位于不同的染色体或邻近位点，这些miRNA在5'末端附近有一个共同序列，3'末端附近具有不同的补偿序列。通过靶向各自相对应的基因影响着GC细胞的增殖、转移、侵袭和对化学药物的耐药性。miR-30 家族在GC中发挥着重要的抑癌作用。本文就近年来miR-30 家族中5 个成员在GC发生发展中作用的研究进展作一综述。
2020, 27(7):825-829.
DOI: 10.3872/j.issn.1007-385X.2020.07.017
Abstract:
中国胃癌的发病率和病死率均居高不下，传统的手术和化疗等治疗手段对于晚期胃癌的疗效较差。针对HER-2 阳性胃癌的分子靶向治疗取得了一定成功，但由于胃癌患者中HER-2 阳性率极低，因此获益患者数量有限。胃癌的血管生成及其相关通路对胃癌的转移、复发起到了重要的促进作用。针对其关键分子的抗血管生成靶向治疗为提高晚期胃癌疗效提供了新的思路。目前抗血管生成靶向药物包括酪氨酸激酶抑制剂（tyrosine-kinase inhibitor，TKI）、单克隆抗体以及重组人血管内皮抑制素等几类，尽管一些TKI的疗效尚不尽如人意，但阿帕替尼和雷莫芦单抗等一系列临床研究表明，抗血管靶向治疗是改善晚期胃癌治疗新的希望。未来可通过二代测序技术探索新的分子靶点，并联合放疗、化疗和免疫治疗以及更为精准的个体化治疗进一步改善晚期胃癌抗血管靶向治疗的疗效。
中国胃癌的发病率和病死率均居高不下，传统的手术和化疗等治疗手段对于晚期胃癌的疗效较差。针对HER-2 阳性胃癌的分子靶向治疗取得了一定成功，但由于胃癌患者中HER-2 阳性率极低，因此获益患者数量有限。胃癌的血管生成及其相关通路对胃癌的转移、复发起到了重要的促进作用。针对其关键分子的抗血管生成靶向治疗为提高晚期胃癌疗效提供了新的思路。目前抗血管生成靶向药物包括酪氨酸激酶抑制剂（tyrosine-kinase inhibitor，TKI）、单克隆抗体以及重组人血管内皮抑制素等几类，尽管一些TKI的疗效尚不尽如人意，但阿帕替尼和雷莫芦单抗等一系列临床研究表明，抗血管靶向治疗是改善晚期胃癌治疗新的希望。未来可通过二代测序技术探索新的分子靶点，并联合放疗、化疗和免疫治疗以及更为精准的个体化治疗进一步改善晚期胃癌抗血管靶向治疗的疗效。
2020, 27(7):830-831.
DOI: 10.3872/j.issn.1007-385X.2020.07.018
Abstract:
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- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
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- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.