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Volume 28,Issue 4,2021 Table of Contents
2021, 28(4):317-324.
DOI: 10.3872/j.issn.1007-385X.2021.04.001
Abstract:
In the past, surgery and chemotherapy were the main treatment strategies for malignant melanoma, but companied with poor prognosis. With the development of high-throughput gene sequencing technology and the deepening understanding of tumor molecular mechanisms, it has been found that tumor heterogeneity and the diversity of tumor microenvironment affect tumor formation,drug resistance and treatment selection, leading to different responses and benefits of melanoma patients to the same treatment. The emerge and progression of targeted therapy and immunotherapy have significantly increased the survival rates of patients with metastatic melanoma, promoting the individualization and precision of melanoma treatment and making precise treatment a research hotspot as well as a trend. This review mainly summarizes the research progress of systemic individualized treatment of advanced melanoma based on precise subtyping and molecular level, and to get a more comprehensive view of the survival status of melanoma patients in the era of precision medicine, as well as the prospect and necessity of developing various targeted therapy, immunotherapy or combination therapy.
In the past, surgery and chemotherapy were the main treatment strategies for malignant melanoma, but companied with poor prognosis. With the development of high-throughput gene sequencing technology and the deepening understanding of tumor molecular mechanisms, it has been found that tumor heterogeneity and the diversity of tumor microenvironment affect tumor formation,drug resistance and treatment selection, leading to different responses and benefits of melanoma patients to the same treatment. The emerge and progression of targeted therapy and immunotherapy have significantly increased the survival rates of patients with metastatic melanoma, promoting the individualization and precision of melanoma treatment and making precise treatment a research hotspot as well as a trend. This review mainly summarizes the research progress of systemic individualized treatment of advanced melanoma based on precise subtyping and molecular level, and to get a more comprehensive view of the survival status of melanoma patients in the era of precision medicine, as well as the prospect and necessity of developing various targeted therapy, immunotherapy or combination therapy.
2021, 28(4):325-331.
DOI: 10.3872/j.issn.1007-385X.2021.04.002
Abstract:
Objective: To explore the effect of exosome-derived miR-181a on angiogenesis and tumor progression in gliomas.Methods: 83 cases of glioma tissues and 13 cases of peritumoral tissues resected in the Second Affiliated Hospital of Hainan Medical University from August 2017 to December 2019, glioma cells U87, A172, U251, LN229, U373 and microglial cell line HM, were selected to detect the expression of miR-181a in tumor tissues and cells by qPCR method. Glioma U373 cells with miR-181a overexpression or knockdown were constructed, and exosomes were isolated and identified. The effects of exsome-derived miR-181a on angiogenesis of HUVEC cells were investigated by tubule formation and chicken chorioallantoic membrane assay in vitro. Nude mice bearing U373 cell transplanted xenograft was constructed to observe the effect of exsome-derived miR-181a on angiogenesis and tumor growth in vivo. Results: The expression of miR-181a in glioma tissues and cells was significantly higher than that in normal tissues and normal glial HM cells (all P<0.01). The exsome-derived miR-181a could significantly promote the tubule formation of HUVEC cells (P<0.01) and the angiogenesis of chicken chorioallantoic membrane (all P<0.01). In vivo experiments showed that the growth of xenografts was promoted (P<0.05) and the amount of angiogenesis in the tumor tissues was increased in the nude mice after being transfused with exsome-derived miR-181a (P<0.01). Conclusion: miR-181a plays an important role in promoting angiogenesis of gliomas and may be a potential target for diagnosis and treatment of gliomas.
Objective: To explore the effect of exosome-derived miR-181a on angiogenesis and tumor progression in gliomas.Methods: 83 cases of glioma tissues and 13 cases of peritumoral tissues resected in the Second Affiliated Hospital of Hainan Medical University from August 2017 to December 2019, glioma cells U87, A172, U251, LN229, U373 and microglial cell line HM, were selected to detect the expression of miR-181a in tumor tissues and cells by qPCR method. Glioma U373 cells with miR-181a overexpression or knockdown were constructed, and exosomes were isolated and identified. The effects of exsome-derived miR-181a on angiogenesis of HUVEC cells were investigated by tubule formation and chicken chorioallantoic membrane assay in vitro. Nude mice bearing U373 cell transplanted xenograft was constructed to observe the effect of exsome-derived miR-181a on angiogenesis and tumor growth in vivo. Results: The expression of miR-181a in glioma tissues and cells was significantly higher than that in normal tissues and normal glial HM cells (all P<0.01). The exsome-derived miR-181a could significantly promote the tubule formation of HUVEC cells (P<0.01) and the angiogenesis of chicken chorioallantoic membrane (all P<0.01). In vivo experiments showed that the growth of xenografts was promoted (P<0.05) and the amount of angiogenesis in the tumor tissues was increased in the nude mice after being transfused with exsome-derived miR-181a (P<0.01). Conclusion: miR-181a plays an important role in promoting angiogenesis of gliomas and may be a potential target for diagnosis and treatment of gliomas.
2021, 28(4):332-338.
DOI: 10.3872/j.issn.1007-385X.2021.04.003
Abstract:
Objective: To explore the effects of miR-21 targeting PDCD4 (programmed cell death factor 4) on proliferation and migration of non-small cell lung cancer (NSCLC) A549 cells and the possible mechanism. Methods: The miR-21 mimics, miR-21 inhibitors and miR-NC plasmids were transfected into A549 cells in logarithmic growth phase by liposome transfection technology. Forty-eight hours after transfection, the transfection efficiency was observed under a fluorescence microscope, and the mRNA expression levels of miR-21 and PDCD4 in A549 cells were detected by qPCR. Dual luciferase reporter gene experiment was used to detect the targeting relationship between miR-21 and PDCD4, MTT method was used to detect cell proliferation, Transwell chamber method was used to detect cell migration ability,and ELISA was used to detect the content of TNF-α in each group of cell culture fluids. WB was used to detect the protein expression levels of PDCD4, NF-κB p65 and p-NF-κB p65 in cells. Results: The A549 cell line with miR-21 over-expression or knockdown was successfully constructed. Dual luciferase reporter gene assay confirmed that miR-21 targetedly inhibited PDCD4 expression. Over-expression of miR-21 could significantly inhibit the mRNA expression of PDCD4 in A549 cells (P<0.01), promote cell proliferation and migration (P<0.05 or P<0.01), increase the secretion level of TNF-α (P<0.01), down-regulate the expression of PDCD4 protein (P<0.01), and up-regulate p-NF-κB p65 protein level (P<0.05). The effect of silencing miR-21 on cells was opposite to the effect of miR-21 over-expression.Conclusion: Over-expression of miR-21 can promote the proliferation and migration ability of A549 cells, which may be related to its targeted inhibition of PDCD4 and activating the NF-κB/TNF-α pathway.
Objective: To explore the effects of miR-21 targeting PDCD4 (programmed cell death factor 4) on proliferation and migration of non-small cell lung cancer (NSCLC) A549 cells and the possible mechanism. Methods: The miR-21 mimics, miR-21 inhibitors and miR-NC plasmids were transfected into A549 cells in logarithmic growth phase by liposome transfection technology. Forty-eight hours after transfection, the transfection efficiency was observed under a fluorescence microscope, and the mRNA expression levels of miR-21 and PDCD4 in A549 cells were detected by qPCR. Dual luciferase reporter gene experiment was used to detect the targeting relationship between miR-21 and PDCD4, MTT method was used to detect cell proliferation, Transwell chamber method was used to detect cell migration ability,and ELISA was used to detect the content of TNF-α in each group of cell culture fluids. WB was used to detect the protein expression levels of PDCD4, NF-κB p65 and p-NF-κB p65 in cells. Results: The A549 cell line with miR-21 over-expression or knockdown was successfully constructed. Dual luciferase reporter gene assay confirmed that miR-21 targetedly inhibited PDCD4 expression. Over-expression of miR-21 could significantly inhibit the mRNA expression of PDCD4 in A549 cells (P<0.01), promote cell proliferation and migration (P<0.05 or P<0.01), increase the secretion level of TNF-α (P<0.01), down-regulate the expression of PDCD4 protein (P<0.01), and up-regulate p-NF-κB p65 protein level (P<0.05). The effect of silencing miR-21 on cells was opposite to the effect of miR-21 over-expression.Conclusion: Over-expression of miR-21 can promote the proliferation and migration ability of A549 cells, which may be related to its targeted inhibition of PDCD4 and activating the NF-κB/TNF-α pathway.
2021, 28(4):339-345.
DOI: 10.3872/j.issn.1007-385X.2021.04.004
Abstract:
Objective: To explore the application value of human IL-15 transgenic NCG mice (NCG-hIL-15 mice) in preclinical evaluation of chimeric antigen receptor modified NK (CAR-NK) cell therapy for tumor treatment. Methods: qPCR and WB were performed to detect the expression of human IL-15 in the bone marrow and main organs (spleen, liver, lung, kidney and pancreas) of transgenic mice. After being transfused with human PBMC-derived NK (PB-NK) cells, the NCG-hIL-15 mice and control NCG mice were continuously monitored for the in vivo amplification of NK cells and the changes in body weight and survival time. Flow cytometry was used to detect the differential expressions of activated receptors and inhibitory receptors in amplified NK cells. WB was used to detect the expressions of perforin and granzyme-B. NCG-hIL-15 mice or NCG mice bearing MIAPaca-2 cell transplanted tumor were treated with anti-MUC1-CAR-NK cell reinfusion; then, the CAR-NK cell survival in different groups of mice was detected by Flow cytometry, and the survival time of tumor bearing mice was recorded and tumor growth was detected by in vivo imaging. Results:The results indicated that PB-NK cells could proliferate stably within 10 weeks in NCG-hIL-15 mice without obvious graft versus host diseases (GVHD) during the observation period. The in vivo-expanded human NK cells maintained the original expression patterns of various surface molecules, including KARs and KIRs. Compared with the NK cells in NCG mice, the NK cells in NCG-hIL-15 mice contained significantly higher amounts of granzyme-B and perforin (all P<0.05). CAR-NK cells showed significantly increased survival rate and stronger tumor-inhibitory effect in NCG-hIL-15 mice as compared with those in control NCG mice, resulting in significantly prolonged survival in NCG-hIL-15 mice (all P<0.01). Conclusion: NCG-hIL-15 mouse model has potential application value in preclinical trial and biological evaluation of NK cell-based immunotherapy.
Objective: To explore the application value of human IL-15 transgenic NCG mice (NCG-hIL-15 mice) in preclinical evaluation of chimeric antigen receptor modified NK (CAR-NK) cell therapy for tumor treatment. Methods: qPCR and WB were performed to detect the expression of human IL-15 in the bone marrow and main organs (spleen, liver, lung, kidney and pancreas) of transgenic mice. After being transfused with human PBMC-derived NK (PB-NK) cells, the NCG-hIL-15 mice and control NCG mice were continuously monitored for the in vivo amplification of NK cells and the changes in body weight and survival time. Flow cytometry was used to detect the differential expressions of activated receptors and inhibitory receptors in amplified NK cells. WB was used to detect the expressions of perforin and granzyme-B. NCG-hIL-15 mice or NCG mice bearing MIAPaca-2 cell transplanted tumor were treated with anti-MUC1-CAR-NK cell reinfusion; then, the CAR-NK cell survival in different groups of mice was detected by Flow cytometry, and the survival time of tumor bearing mice was recorded and tumor growth was detected by in vivo imaging. Results:The results indicated that PB-NK cells could proliferate stably within 10 weeks in NCG-hIL-15 mice without obvious graft versus host diseases (GVHD) during the observation period. The in vivo-expanded human NK cells maintained the original expression patterns of various surface molecules, including KARs and KIRs. Compared with the NK cells in NCG mice, the NK cells in NCG-hIL-15 mice contained significantly higher amounts of granzyme-B and perforin (all P<0.05). CAR-NK cells showed significantly increased survival rate and stronger tumor-inhibitory effect in NCG-hIL-15 mice as compared with those in control NCG mice, resulting in significantly prolonged survival in NCG-hIL-15 mice (all P<0.01). Conclusion: NCG-hIL-15 mouse model has potential application value in preclinical trial and biological evaluation of NK cell-based immunotherapy.
2021, 28(4):346-352.
DOI: 10.3872/j.issn.1007-385X.2021.04.005
Abstract:
Objective: To investigate the effects of miR-361-5p on the oxaliplatin (OXA) resistance of gastric cancer SGC-7901 cells and its mechanism. Methods: The expression of miR-361-5p in gastric cancer cells (MKN-45, MGC80-3 and SGC-7901) and drugresistant SGC-7901/OXA cells was detected by qPCR. The SGC-7901/OXA cells were transfected with miR-361-5p mimics/inhibitor or sh-CCND1 by using Liposome transfection technology. Then, cell proliferation, apoptosis and cell cycle of SGC-7901/OXA cells were measured by CCK-8 assay and Flow cytometry, respectively. The targeting relationship between miR-361-5p and CCND1 was examined by Dual luciferase report gene assay. The expression level of CCND1 in SGC-7901/OXA cells was detected by WB.Results: miR-361-5p was down-regulated in multiple gastric cancer cells and SGC-7901/OXA cells (P<0.05 or P<0.01). Over-expression of miR-361-5p significantly promoted the apoptosis, induced G0/G1 cell cycle arrest and inhibited cell proliferation of SGC-7901/OXA cells (P<0.05 or P<0.01). Dual luciferase reporter gene results verified that miR-361-5p targeted CCND1 and negatively regulated its expression (P<0.01). Further experiments showed that targeted down-regulation of CCND1 induced apoptosis and G0/G1 cell cycle arrest and inhibited CCND1 expression and proliferation of SGC-7901/OXA cells (P<0.05 or P<0.01). Over-expression of miR-361-5p targetedly down-regulated CCND1 and further promoted cell apoptosis, induced G0/G1 cell cycle arrest and inhibited cell proliferation of SGC-7901/OXA cells (P<0.05 or P<0.01). Conclusion: miR-361-5p over-expression can reverse the resistance of SGC-7901/OXA cells to OXA, and the mechanism may be related to its targeted down-regulation of CCND1 expression.
Objective: To investigate the effects of miR-361-5p on the oxaliplatin (OXA) resistance of gastric cancer SGC-7901 cells and its mechanism. Methods: The expression of miR-361-5p in gastric cancer cells (MKN-45, MGC80-3 and SGC-7901) and drugresistant SGC-7901/OXA cells was detected by qPCR. The SGC-7901/OXA cells were transfected with miR-361-5p mimics/inhibitor or sh-CCND1 by using Liposome transfection technology. Then, cell proliferation, apoptosis and cell cycle of SGC-7901/OXA cells were measured by CCK-8 assay and Flow cytometry, respectively. The targeting relationship between miR-361-5p and CCND1 was examined by Dual luciferase report gene assay. The expression level of CCND1 in SGC-7901/OXA cells was detected by WB.Results: miR-361-5p was down-regulated in multiple gastric cancer cells and SGC-7901/OXA cells (P<0.05 or P<0.01). Over-expression of miR-361-5p significantly promoted the apoptosis, induced G0/G1 cell cycle arrest and inhibited cell proliferation of SGC-7901/OXA cells (P<0.05 or P<0.01). Dual luciferase reporter gene results verified that miR-361-5p targeted CCND1 and negatively regulated its expression (P<0.01). Further experiments showed that targeted down-regulation of CCND1 induced apoptosis and G0/G1 cell cycle arrest and inhibited CCND1 expression and proliferation of SGC-7901/OXA cells (P<0.05 or P<0.01). Over-expression of miR-361-5p targetedly down-regulated CCND1 and further promoted cell apoptosis, induced G0/G1 cell cycle arrest and inhibited cell proliferation of SGC-7901/OXA cells (P<0.05 or P<0.01). Conclusion: miR-361-5p over-expression can reverse the resistance of SGC-7901/OXA cells to OXA, and the mechanism may be related to its targeted down-regulation of CCND1 expression.
2021, 28(4):353-358.
DOI: 10.3872/j.issn.1007-385X.2021.04.006
Abstract:
Objective: To investigate the effect of breast cancer susceptibility gene 1 (BRCA1) on the proliferation, migration and invasion of non-small cell lung cancer (NSCLC) H1650 cells through Wnt/β-catenin pathway. Methods: WB and qPCR were used to detect the mRNA and protein expressions of BRCA1 in NSCLC A549, H1299, H1650 cells and normal lung epithelial BEAS-2B cell. A stable BRCA1 over-expression cell line (LV-BRCA1) was constructed in H1650 cells, and blank control group (NC), negative control group (LV-BRCA1-NC), experimental group (LV-BRCA1) and inhibitor group (LV-BRCA1+XAV-939) were set up. The proliferative activity of cells in each group was detected by MTT assay, the migration ability of cells was detected by scratch test, the invasive ability of cells was detected by Transwell method, and the protein expression levels of BRCA1, cyclin D1, β-catenin, c-Myc and Cox2 were detected by WB. Results: The mRNA and protein expression levels of BRCA1 in NSCLC cells were significantly higher than those in BEAS-2B cells (all P<0.01). Up-regulation of BRCA1 expression in H1650 cells could significantly enhance cell proliferation, migration and invasion (P<0.05 or P<0.01), and increase the protein expressions of cyclin D1, β -catenin, c-Myc, Cox2 and c-Jun (P<0.05 or P<0.01). β-catenin inhibitor XAV-939 significantly down-regulated the proliferation, migration and invasion ability of H1650 cells overexpressing BRCA1, and decreased the protein expressions of cyclin D1, β -catenin, c-Myc, Cox2 and c-Jun (P<0.05 or P<0.01).Conclusion: BRCA1 can promote the proliferation, migration and invasion of NSCLC H1650 cells by activating Wnt/β-catenin pathway,and it is expected to be a potential diagnostic biomarker and treatment target for NSCLC.
Objective: To investigate the effect of breast cancer susceptibility gene 1 (BRCA1) on the proliferation, migration and invasion of non-small cell lung cancer (NSCLC) H1650 cells through Wnt/β-catenin pathway. Methods: WB and qPCR were used to detect the mRNA and protein expressions of BRCA1 in NSCLC A549, H1299, H1650 cells and normal lung epithelial BEAS-2B cell. A stable BRCA1 over-expression cell line (LV-BRCA1) was constructed in H1650 cells, and blank control group (NC), negative control group (LV-BRCA1-NC), experimental group (LV-BRCA1) and inhibitor group (LV-BRCA1+XAV-939) were set up. The proliferative activity of cells in each group was detected by MTT assay, the migration ability of cells was detected by scratch test, the invasive ability of cells was detected by Transwell method, and the protein expression levels of BRCA1, cyclin D1, β-catenin, c-Myc and Cox2 were detected by WB. Results: The mRNA and protein expression levels of BRCA1 in NSCLC cells were significantly higher than those in BEAS-2B cells (all P<0.01). Up-regulation of BRCA1 expression in H1650 cells could significantly enhance cell proliferation, migration and invasion (P<0.05 or P<0.01), and increase the protein expressions of cyclin D1, β -catenin, c-Myc, Cox2 and c-Jun (P<0.05 or P<0.01). β-catenin inhibitor XAV-939 significantly down-regulated the proliferation, migration and invasion ability of H1650 cells overexpressing BRCA1, and decreased the protein expressions of cyclin D1, β -catenin, c-Myc, Cox2 and c-Jun (P<0.05 or P<0.01).Conclusion: BRCA1 can promote the proliferation, migration and invasion of NSCLC H1650 cells by activating Wnt/β-catenin pathway,and it is expected to be a potential diagnostic biomarker and treatment target for NSCLC.
2021, 28(4):359-364.
DOI: 10.3872/j.issn.1007-385X.2021.04.007
Abstract:
Objective: To construct and purify the recombinant bispecific antibody (BsAb) targeting PD-1 and CD19 and evaluate its activity.Methods: With pCAR1 plasmid as the vector, the eukaryotic expression vector of anti-PD-1/CD19 BsAb was constructed by molecular cloning technology, and then transfected into mammalian cell line CHO-S by PEI reagent for transiently expressing antibody. The BsAb was purified by Affinity chromatography and then identified by SDS-PAGE and WB. The blocking activity of BsAb on PD-1/PD-L1 in vitro was detected by Luciferase reporter gene assay. The activity of antibody (BsAb)-dependent cell (PBMC)-mediated cytotoxicity (ADCC) in vitro was evaluated by lactate dehydrogenase (LDH) cytotoxicity assay. Results: The double plasmid eukaryotic expression vector pCAR1-19X3 was successfully constructed, and anti-PD-1/CD19BsAb was successfully expressed in CHO-S cells, named pCAR1-19X3-TY. pCAR1-19X3-TY could effectively block the binding of PD-1 to its ligand PD-L1 in vitro, and the EC50 based on the dose-response curve was 0.306 μg/ml.ADCC results showed that pCAR1-19X3-TY could mediate the cytotoxicity of PBMC against Raji cells, and the curve showed a linear upwardtrend; when the effect/target ratio was 50∶1, the target cell lysis rate of pCAR1-19X3-TY was (38.9±0.3)%, which was not significantly different from that of the positive treatment group (46.7±4.9)% (P>0.05), but significantly higher than that of the negative control group (1.2±0.1)% (P<0.05). Conclusion: The recombinant anti-PD-1/CD19 BsAb can effectively block the binding of PD-1 and PD-L1 and activate PBMC mediated cytotoxicity against Raji cells. pCAR1-19X3-TY has the potential application value in the treatment of B-cell malignant tumor.
Objective: To construct and purify the recombinant bispecific antibody (BsAb) targeting PD-1 and CD19 and evaluate its activity.Methods: With pCAR1 plasmid as the vector, the eukaryotic expression vector of anti-PD-1/CD19 BsAb was constructed by molecular cloning technology, and then transfected into mammalian cell line CHO-S by PEI reagent for transiently expressing antibody. The BsAb was purified by Affinity chromatography and then identified by SDS-PAGE and WB. The blocking activity of BsAb on PD-1/PD-L1 in vitro was detected by Luciferase reporter gene assay. The activity of antibody (BsAb)-dependent cell (PBMC)-mediated cytotoxicity (ADCC) in vitro was evaluated by lactate dehydrogenase (LDH) cytotoxicity assay. Results: The double plasmid eukaryotic expression vector pCAR1-19X3 was successfully constructed, and anti-PD-1/CD19BsAb was successfully expressed in CHO-S cells, named pCAR1-19X3-TY. pCAR1-19X3-TY could effectively block the binding of PD-1 to its ligand PD-L1 in vitro, and the EC50 based on the dose-response curve was 0.306 μg/ml.ADCC results showed that pCAR1-19X3-TY could mediate the cytotoxicity of PBMC against Raji cells, and the curve showed a linear upwardtrend; when the effect/target ratio was 50∶1, the target cell lysis rate of pCAR1-19X3-TY was (38.9±0.3)%, which was not significantly different from that of the positive treatment group (46.7±4.9)% (P>0.05), but significantly higher than that of the negative control group (1.2±0.1)% (P<0.05). Conclusion: The recombinant anti-PD-1/CD19 BsAb can effectively block the binding of PD-1 and PD-L1 and activate PBMC mediated cytotoxicity against Raji cells. pCAR1-19X3-TY has the potential application value in the treatment of B-cell malignant tumor.
2021, 28(4):365-369.
DOI: 10.3872/j.issn.1007-385X.2021.04.008
Abstract:
Objective: To investigate the lung cancer-associated driver gene mutations in peripheral blood of patients with advanced non-small cell lung cancer (NSCLC) in Yunnan area, and to explore their association with clinical pathological features. Methods:Peripheral blood of 304 patients with stage Ⅳ NSCLC were collected from Molecular Diagnostic Center of Yunnan Cancer Hospital during January 2019 to December 2019. Next generation sequencing (NGS) technique was used to detect the mutation of NSCLC related driver genes, chi-square test was used to analyze the relationship between the major mutant genes and the clinicopathological features of patients, and Logistic regression was used to analyze the independent risk factors. Results: In the peripheral blood of 304 patients with stage Ⅳ NSCLC, there were 120 (39.47%) cases with EGFR mutations, 12 (3.95%) cases with ALK fusion, 36 (11.84%)case with other mutations such as KRAS, BRAF and RET. The main EGFR mutations were 19del and L858R (69.17%). The mutation rate of EGFR was higher in female, young, non-smoking, non-chemotherapy and lung adenocarcinoma patients (49.26% vs 31.55%,45.39% vs 33.56%, 45.92% vs 27.78%, 45.07% vs 26.37%, 42.39% vs 10.71%, all P<0.05). Multivariate analysis showed that female,no history of chemotherapy and lung adenocarcinoma were independent risk factors for EGFR mutations (all P<0.05). Conclusion:Using NGS technology to detect the driver genes in peripheral blood of patients with advanced NSCLC in Yunnan area showed that the mutation rate of EGFR was higher in women and lung adenocarcinoma patients without chemotherapy history.
Objective: To investigate the lung cancer-associated driver gene mutations in peripheral blood of patients with advanced non-small cell lung cancer (NSCLC) in Yunnan area, and to explore their association with clinical pathological features. Methods:Peripheral blood of 304 patients with stage Ⅳ NSCLC were collected from Molecular Diagnostic Center of Yunnan Cancer Hospital during January 2019 to December 2019. Next generation sequencing (NGS) technique was used to detect the mutation of NSCLC related driver genes, chi-square test was used to analyze the relationship between the major mutant genes and the clinicopathological features of patients, and Logistic regression was used to analyze the independent risk factors. Results: In the peripheral blood of 304 patients with stage Ⅳ NSCLC, there were 120 (39.47%) cases with EGFR mutations, 12 (3.95%) cases with ALK fusion, 36 (11.84%)case with other mutations such as KRAS, BRAF and RET. The main EGFR mutations were 19del and L858R (69.17%). The mutation rate of EGFR was higher in female, young, non-smoking, non-chemotherapy and lung adenocarcinoma patients (49.26% vs 31.55%,45.39% vs 33.56%, 45.92% vs 27.78%, 45.07% vs 26.37%, 42.39% vs 10.71%, all P<0.05). Multivariate analysis showed that female,no history of chemotherapy and lung adenocarcinoma were independent risk factors for EGFR mutations (all P<0.05). Conclusion:Using NGS technology to detect the driver genes in peripheral blood of patients with advanced NSCLC in Yunnan area showed that the mutation rate of EGFR was higher in women and lung adenocarcinoma patients without chemotherapy history.
2021, 28(4):370-377.
DOI: 10.3872/j.issn.1007-385X.2021.04.009
Abstract:
Objective: To investigate the effect of circular RNA FBXO11 (circFBXO11) regulating the miR-376a-3p/SNRPB (small nuclear ribonucleoprotein polypeptides B gene) axis on the proliferation and apoptosis of gastric cancer SNU-1 cells. Methods: Cancer and para-cancerous tissue samples from 30 patients with gastric cancer who underwent surgical resection were surgically resected in the Department of Oncosurgery, the Affiliated Hospital of North China University of Science and Technology from January 2018 to January 2019 were collected. The positive expression rate of SNRPB protein in gastric cancer tissues was detected by Immunohistochemical staining. The expression levels of circFBXO11, miR-376a-3p and SNRPB mRNA in gastric cancer tissues, gastric cancer cell lines (SNU-1, AGS and HS-746T) and gastric mucosal cell line GES1 were detected by qPCR. Dual luciferase reporter gene assay was used to determine the relationship between circFBXO11 and miR-376a-3p as well as between miR-376a-3p and SNRPB. The si-NC,si-circFBXO11, miR-NC, miR-376a-3p, si-SNRPB, si-circFBXO11+anti-miR-NC, si-circFBXO11+anti-miR-376a-3p, si-circFBXO11+pcDNA-NC, si-circFBXO11+pcDNA-SNRPB were transfected into gastric cancer SNU-1 cells, respectively. CCK-8 assay, Flow cytometry and WB assay were used to detect cell proliferation activity, apoptosis rate and protein expressions of SNRPB, cyclin D1 and C-caspase-3, respectively. Results: Compared with para-cancerous tissues, the expression level of circFBXO11 and the positive rate of SNRPB protein in gastric cancer tissues were significantly increased (all P<0.01), while the expression of miR-376a-3p was significantly decreased (P<0.01). Compared with GES1 cells, the expressions of circFBXO11 and SNRPB were significantly increased, while the expression of miR-376a-3p was significantly decreased (all P<0.01) in gastric cancer cells. circFBXO11 negatively regulated miR-376a-3p expression, and miR-376a-3p negatively regulated SNRPB expression. After inhibiting the expression of circFBXO11 or over-expressing miR-376a-3p or suppressing the expression of SNRPB, the proliferation viability of SNU-1 cells was decreased, and the apoptosis rate was increased (P<0.01). Either inhibiting miR-376a-3p or over-expressing SNRPB could partially reverse the effect of circFBXO11 suppression on proliferation and apoptosis of SNU-1 cells (all P<0.01). Conclusion:circFBXO11 is highly expressed in gastric cancer tissues. Inhibiting circFBXO11 inhibits the proliferation and induces apoptosis of gastric cancer cells, and the mechanism is related to the regulation of miR-376A-3p/SNRPB pathway.
Objective: To investigate the effect of circular RNA FBXO11 (circFBXO11) regulating the miR-376a-3p/SNRPB (small nuclear ribonucleoprotein polypeptides B gene) axis on the proliferation and apoptosis of gastric cancer SNU-1 cells. Methods: Cancer and para-cancerous tissue samples from 30 patients with gastric cancer who underwent surgical resection were surgically resected in the Department of Oncosurgery, the Affiliated Hospital of North China University of Science and Technology from January 2018 to January 2019 were collected. The positive expression rate of SNRPB protein in gastric cancer tissues was detected by Immunohistochemical staining. The expression levels of circFBXO11, miR-376a-3p and SNRPB mRNA in gastric cancer tissues, gastric cancer cell lines (SNU-1, AGS and HS-746T) and gastric mucosal cell line GES1 were detected by qPCR. Dual luciferase reporter gene assay was used to determine the relationship between circFBXO11 and miR-376a-3p as well as between miR-376a-3p and SNRPB. The si-NC,si-circFBXO11, miR-NC, miR-376a-3p, si-SNRPB, si-circFBXO11+anti-miR-NC, si-circFBXO11+anti-miR-376a-3p, si-circFBXO11+pcDNA-NC, si-circFBXO11+pcDNA-SNRPB were transfected into gastric cancer SNU-1 cells, respectively. CCK-8 assay, Flow cytometry and WB assay were used to detect cell proliferation activity, apoptosis rate and protein expressions of SNRPB, cyclin D1 and C-caspase-3, respectively. Results: Compared with para-cancerous tissues, the expression level of circFBXO11 and the positive rate of SNRPB protein in gastric cancer tissues were significantly increased (all P<0.01), while the expression of miR-376a-3p was significantly decreased (P<0.01). Compared with GES1 cells, the expressions of circFBXO11 and SNRPB were significantly increased, while the expression of miR-376a-3p was significantly decreased (all P<0.01) in gastric cancer cells. circFBXO11 negatively regulated miR-376a-3p expression, and miR-376a-3p negatively regulated SNRPB expression. After inhibiting the expression of circFBXO11 or over-expressing miR-376a-3p or suppressing the expression of SNRPB, the proliferation viability of SNU-1 cells was decreased, and the apoptosis rate was increased (P<0.01). Either inhibiting miR-376a-3p or over-expressing SNRPB could partially reverse the effect of circFBXO11 suppression on proliferation and apoptosis of SNU-1 cells (all P<0.01). Conclusion:circFBXO11 is highly expressed in gastric cancer tissues. Inhibiting circFBXO11 inhibits the proliferation and induces apoptosis of gastric cancer cells, and the mechanism is related to the regulation of miR-376A-3p/SNRPB pathway.
2021, 28(4):378-383.
DOI: 10.3872/j.issn.1007-385X.2021.04.010
Abstract:
基因表达异常是肿瘤发生发展的重要原因之一，其可导致肿瘤细胞恶性增殖、抵抗凋亡、浸润甚至转移，基因及其编码蛋白的研究有助于加深对肿瘤发生发展的分子机制的认识以及相关基因诊断和治疗的开展。近年来研究显示，干扰素诱导的穿膜蛋白（interferon-induced transmembrane protein，IFITM）家族异常表达与肿瘤的发生发展有关，其中 IFITM1、IFITM2 和IFITM3已被证实在胃癌、乳腺癌、肺癌和肝癌等多种实体肿瘤中高表达，通过调控细胞周期和凋亡相关蛋白的水平，促进肿瘤细胞增殖并抑制凋亡；通过上调基质金属蛋白酶的表达和活性，加速上皮间质转化进程，促进肿瘤细胞的侵袭和转移。IFITM高表达也与患者预后不良显著相关。本综述将围绕IFITM1、IFITM2和IFITM3讨论IFITM在肿瘤发生发展中的作用，阐述其调控机制及在肿瘤诊断和预后预测等方面的临床价值，为寻找新的肿瘤诊断标志物和治疗靶点提供帮助。
基因表达异常是肿瘤发生发展的重要原因之一，其可导致肿瘤细胞恶性增殖、抵抗凋亡、浸润甚至转移，基因及其编码蛋白的研究有助于加深对肿瘤发生发展的分子机制的认识以及相关基因诊断和治疗的开展。近年来研究显示，干扰素诱导的穿膜蛋白（interferon-induced transmembrane protein，IFITM）家族异常表达与肿瘤的发生发展有关，其中 IFITM1、IFITM2 和IFITM3已被证实在胃癌、乳腺癌、肺癌和肝癌等多种实体肿瘤中高表达，通过调控细胞周期和凋亡相关蛋白的水平，促进肿瘤细胞增殖并抑制凋亡；通过上调基质金属蛋白酶的表达和活性，加速上皮间质转化进程，促进肿瘤细胞的侵袭和转移。IFITM高表达也与患者预后不良显著相关。本综述将围绕IFITM1、IFITM2和IFITM3讨论IFITM在肿瘤发生发展中的作用，阐述其调控机制及在肿瘤诊断和预后预测等方面的临床价值，为寻找新的肿瘤诊断标志物和治疗靶点提供帮助。
2021, 28(4):384-391.
DOI: 10.3872/j.issn.1007-385X.2021.04.011
Abstract:
研发生物标志物以准确预测或评估抗PD-1/PD-L1治疗的疗效具有重要意义。T细胞、B细胞、巨噬细胞、DC、中性粒细胞、NK细胞和髓源性抑制细胞等肿瘤相关免疫细胞通过多种途径影响肿瘤免疫治疗的疗效。近年来的研究发现，有些免疫细胞可以作为预测指标，在治疗前预判肿瘤患者能否对抗PD-1/PD-L1治疗产生应答；有些免疫细胞可以作为疗效评估指标，在治疗早期判断患者从长期治疗中获益的可能性。本文主要就上述肿瘤相关免疫细胞对于肿瘤免疫治疗的影响以及预测作用进行综述。
研发生物标志物以准确预测或评估抗PD-1/PD-L1治疗的疗效具有重要意义。T细胞、B细胞、巨噬细胞、DC、中性粒细胞、NK细胞和髓源性抑制细胞等肿瘤相关免疫细胞通过多种途径影响肿瘤免疫治疗的疗效。近年来的研究发现，有些免疫细胞可以作为预测指标，在治疗前预判肿瘤患者能否对抗PD-1/PD-L1治疗产生应答；有些免疫细胞可以作为疗效评估指标，在治疗早期判断患者从长期治疗中获益的可能性。本文主要就上述肿瘤相关免疫细胞对于肿瘤免疫治疗的影响以及预测作用进行综述。
2021, 28(4):392-397.
DOI: 10.3872/j.issn.1007-385X.2021.04.012
Abstract:
近年来，免疫疗法尤其是单克隆抗体靶向药物越来越多地应用于肺癌的临床治疗，但仍有很多局限性。嵌合抗原受体基因修饰T淋巴细（chimeric antigen receptor gene modified-T lymphocytes，CAR-T）疗法对于部分B细胞淋巴瘤和白血病的疗效显著，也为实体瘤的疫治疗开辟了新途径。肺癌CAR-T疗法的热门靶点包括间皮素（MSLN）、黏蛋白突变体（TnMUC1）、表皮生长因子受体（EGFR）、人皮生长因子受体2（HER2）、受体酪氨酸激酶样孤儿受体1（ROR1）和δ样配体3（DLL3）等，但相关临床研究均处于早期探索阶段。所面的主要障碍包括脱靶毒性、肿瘤免疫抑制微环境和CAR-T细胞体内效能不足等。通过基因编辑改进CAR结构、设计多靶点CAR或组合应用多点CAR-T细胞、精细调控CAR-T细胞体内动态分布、改进给药方式或联合其他免疫治疗等策略可能有助于解决这些问题。
近年来，免疫疗法尤其是单克隆抗体靶向药物越来越多地应用于肺癌的临床治疗，但仍有很多局限性。嵌合抗原受体基因修饰T淋巴细（chimeric antigen receptor gene modified-T lymphocytes，CAR-T）疗法对于部分B细胞淋巴瘤和白血病的疗效显著，也为实体瘤的疫治疗开辟了新途径。肺癌CAR-T疗法的热门靶点包括间皮素（MSLN）、黏蛋白突变体（TnMUC1）、表皮生长因子受体（EGFR）、人皮生长因子受体2（HER2）、受体酪氨酸激酶样孤儿受体1（ROR1）和δ样配体3（DLL3）等，但相关临床研究均处于早期探索阶段。所面的主要障碍包括脱靶毒性、肿瘤免疫抑制微环境和CAR-T细胞体内效能不足等。通过基因编辑改进CAR结构、设计多靶点CAR或组合应用多点CAR-T细胞、精细调控CAR-T细胞体内动态分布、改进给药方式或联合其他免疫治疗等策略可能有助于解决这些问题。
2021, 28(4):398-404.
DOI: 10.3872/j.issn.1007-385X.2021.04.013
Abstract:
宫颈癌是妇科最常见的恶性肿瘤之一，严重威胁女性的生命健康。然而，目前尚未确定用于诊断和治疗宫颈癌的有效手段。长链非编码RNA（long non-coding RNA, lncRNA）是长度大于200个核苷酸且无蛋白质编码功能的RNA分子，近年来越来越多的研究发现，lncRNA可能是细胞多种生物学过程的关键调节剂。多种lncRNA在宫颈癌组织和细胞中表达异常，参与多条信号通路的调控，影响宫颈癌细胞的增殖、凋亡、迁移和侵袭等过程，在宫颈癌的发生发展中起抑制肿瘤或促进肿瘤的重要作用。本文在简要介绍lncRNA结构与功能的基础上，着重对近年来宫颈癌中异常表达的lncRNA和lncRNA基因中单核苷酸多态性与宫颈癌的关系、分子调节机制以及潜在的临床应用等研究进展进行综述。
宫颈癌是妇科最常见的恶性肿瘤之一，严重威胁女性的生命健康。然而，目前尚未确定用于诊断和治疗宫颈癌的有效手段。长链非编码RNA（long non-coding RNA, lncRNA）是长度大于200个核苷酸且无蛋白质编码功能的RNA分子，近年来越来越多的研究发现，lncRNA可能是细胞多种生物学过程的关键调节剂。多种lncRNA在宫颈癌组织和细胞中表达异常，参与多条信号通路的调控，影响宫颈癌细胞的增殖、凋亡、迁移和侵袭等过程，在宫颈癌的发生发展中起抑制肿瘤或促进肿瘤的重要作用。本文在简要介绍lncRNA结构与功能的基础上，着重对近年来宫颈癌中异常表达的lncRNA和lncRNA基因中单核苷酸多态性与宫颈癌的关系、分子调节机制以及潜在的临床应用等研究进展进行综述。
2021, 28(4):405-409.
DOI: 10.3872/j.issn.1007-385X.2021.04.014
Abstract:
非小细胞肺癌（non-small cell lung cancer，NSCLC）是最常见的恶性肿瘤之一。早期发现和干预可以大大延长NSCLC患者的生存期。近年来液体活检在肿瘤的诊断中发展迅速，其中血小板RNA（platelet RNA）作为新型生物标志物得到广泛关注。血小板RNA是与肿瘤发生相互作用而形成的一种特殊血小板，由于血小板无细胞核，因此血小板中的RNA都来自巨核细胞或血小板吸收的RNA。多项研究表明，血小板RNA在健康人和NSCLC患者体内存在差异表达，其内具有不同的RNA而形成肿瘤特异的RNA谱。血小板RNA在止血、免疫和炎症以及肿瘤的生长和转移中起重要作用，尤其是对于NSCLC的诊断、分期、治疗以及提高患者的生存率等方面具有一定的指导意义。本文综述血小板RNA的生物来源及其在NSCLC中作用的研究进展。
非小细胞肺癌（non-small cell lung cancer，NSCLC）是最常见的恶性肿瘤之一。早期发现和干预可以大大延长NSCLC患者的生存期。近年来液体活检在肿瘤的诊断中发展迅速，其中血小板RNA（platelet RNA）作为新型生物标志物得到广泛关注。血小板RNA是与肿瘤发生相互作用而形成的一种特殊血小板，由于血小板无细胞核，因此血小板中的RNA都来自巨核细胞或血小板吸收的RNA。多项研究表明，血小板RNA在健康人和NSCLC患者体内存在差异表达，其内具有不同的RNA而形成肿瘤特异的RNA谱。血小板RNA在止血、免疫和炎症以及肿瘤的生长和转移中起重要作用，尤其是对于NSCLC的诊断、分期、治疗以及提高患者的生存率等方面具有一定的指导意义。本文综述血小板RNA的生物来源及其在NSCLC中作用的研究进展。
2021, 28(4):410-415.
DOI: 10.3872/j.issn.1007-385X.2021.04.015
Abstract:
随着肿瘤发病率的上升及患者生存期的改善，胃癌合并多原发癌（multiple primary cancer, MPC）的病例逐渐增多。胃癌患者发生第二肿瘤的相对风险较一般人群要高，特别是发生消化系统其他器官肿瘤的风险显著升高。在胃癌患者的治疗和随访中应高度警惕同时性结直肠癌、食管癌以及异时性肺癌。高龄、男性、嗜好烟酒、有肿瘤家族史以及曾接受过放化疗的患者是重点关注人群。具有共同高危因素或遗传因素的多个肿瘤在治疗上也具有相似策略，如免疫检查点抑制剂用于错配修复缺陷的多个肿瘤。建立规范的高危人群MPC筛查和随访体系，有利于及早发现胃癌MPC。
随着肿瘤发病率的上升及患者生存期的改善，胃癌合并多原发癌（multiple primary cancer, MPC）的病例逐渐增多。胃癌患者发生第二肿瘤的相对风险较一般人群要高，特别是发生消化系统其他器官肿瘤的风险显著升高。在胃癌患者的治疗和随访中应高度警惕同时性结直肠癌、食管癌以及异时性肺癌。高龄、男性、嗜好烟酒、有肿瘤家族史以及曾接受过放化疗的患者是重点关注人群。具有共同高危因素或遗传因素的多个肿瘤在治疗上也具有相似策略，如免疫检查点抑制剂用于错配修复缺陷的多个肿瘤。建立规范的高危人群MPC筛查和随访体系，有利于及早发现胃癌MPC。
2021, 28(4):416-418.
DOI: 10.3872/j.issn.1007-385X.2021.04.016
Abstract:
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.