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Volume 24,Issue 10,2017 Table of Contents
2017, 24(10):1045-1050.
DOI: 10.3872/j.issn.1007-385X.2017.10.001
Abstract:
Immunometabolism is a burgeoning field that aims toexplore the contribution of key metabolic path-ways to immune cell development, differentiation, and function. In recent years, a substantial number of important achievements have been made in this area. Here, we focus on the latest findings related to fatty acid metabolism and immune cell functions in tumor, providing a general framework for understanding how fatty acid metabolism fuels and regulates the immune responses. By giving specific examples, this review will illustrate how the metabolites changes infatty acid metabolic pathway precisely modulate the development, differentiation and functioning of im-mune cellsandexplore the metabolic regulation mechanisms of immune cells in tumor micro-environment, to pro-vide new methods and insights for studyingthe immunity mechanism in tumor.
Immunometabolism is a burgeoning field that aims toexplore the contribution of key metabolic path-ways to immune cell development, differentiation, and function. In recent years, a substantial number of important achievements have been made in this area. Here, we focus on the latest findings related to fatty acid metabolism and immune cell functions in tumor, providing a general framework for understanding how fatty acid metabolism fuels and regulates the immune responses. By giving specific examples, this review will illustrate how the metabolites changes infatty acid metabolic pathway precisely modulate the development, differentiation and functioning of im-mune cellsandexplore the metabolic regulation mechanisms of immune cells in tumor micro-environment, to pro-vide new methods and insights for studyingthe immunity mechanism in tumor.
2017, 24(10):1051-1057.
DOI: 10.3872/j.issn.1007-385X.2017.10.002
Abstract:
Objective：To detect the expression and methylation status of miR-6867 and its host gene RAPGEFL1 (rap guanine nucleotide exchange factor like 1) in human esophageal carcinoma cell lines and esophageal squamous cell carcinoma (ESCC) tissues, and to explore the role of miR-6867 and RAPGEFL1 in occurrence and development of ESCC. Methods： ：Tissue specimens were obtained from 87 ESCC patients treated in the Fourth Affiliated Hospi-tal of Hebei Medical University between January 2014 and January 2016. The expression of miR-6867 and RAPGE-FL1 gene in esophageal cancer cell lines and ESCC tissues as well as the corresponding noncancerous tissues were detected by real-time fluorescent quantitative PCR. The relationship of miR-6867 and RAPGEFL1 gene expression were analyzed. The methylation status of RAPGEFL1 in esophageal cancer cell lines and ESCC tissues and the cor-responding noncancerous tissues was detected by methylation specific PCR methods. Results： ：The relative expres-sion of miR-6867 in ESCC tissues was significantly lower than that in corresponding normal tissues (P<0.05), and its expression was closely correlated with lymph node metastasis and TNM staging (P<0.05). The relative expres-sion of RAPGEFL1 in ESCC tissues was significantly lower than that in corresponding normal tissues (P<0.05), and its expression was closely correlated with lymph node metastasis, pathological differentiation and TNM staging (P<0.05). The expression of miR-6867 and RAPGEFL1 was positively correlated in ESCC tissues (P<0.05). After 5-Aza-dC treatment, the relative expression of miR-6867 and RAPGEFL1 in four cell lines was increased, and the methylation status of RAPGEFL1 was significantly decreased. The methylation rate of RAPGEFL1 in ESCC tissues was significantly higher than that in corresponding normal tissues (P<0.05), which was closely correlated with lymph node metastasis, pathological differentiation and TNM staging (P<0.05). Conclusions： ：The occurrence and development of ESCC may be related to the abnormally decreased expression of miR-6867 and RAPGEFL1 and the high methylation status of RAPGEFL1; the expression of miR-6867 was consistent with RAPGEFL1 expression.Moreover, the methylation of RAPGEFL1 gene promoter might be one of the mechanisms underlying the silence of miR-6867 and RAPGEFL1.
Objective：To detect the expression and methylation status of miR-6867 and its host gene RAPGEFL1 (rap guanine nucleotide exchange factor like 1) in human esophageal carcinoma cell lines and esophageal squamous cell carcinoma (ESCC) tissues, and to explore the role of miR-6867 and RAPGEFL1 in occurrence and development of ESCC. Methods： ：Tissue specimens were obtained from 87 ESCC patients treated in the Fourth Affiliated Hospi-tal of Hebei Medical University between January 2014 and January 2016. The expression of miR-6867 and RAPGE-FL1 gene in esophageal cancer cell lines and ESCC tissues as well as the corresponding noncancerous tissues were detected by real-time fluorescent quantitative PCR. The relationship of miR-6867 and RAPGEFL1 gene expression were analyzed. The methylation status of RAPGEFL1 in esophageal cancer cell lines and ESCC tissues and the cor-responding noncancerous tissues was detected by methylation specific PCR methods. Results： ：The relative expres-sion of miR-6867 in ESCC tissues was significantly lower than that in corresponding normal tissues (P<0.05), and its expression was closely correlated with lymph node metastasis and TNM staging (P<0.05). The relative expres-sion of RAPGEFL1 in ESCC tissues was significantly lower than that in corresponding normal tissues (P<0.05), and its expression was closely correlated with lymph node metastasis, pathological differentiation and TNM staging (P<0.05). The expression of miR-6867 and RAPGEFL1 was positively correlated in ESCC tissues (P<0.05). After 5-Aza-dC treatment, the relative expression of miR-6867 and RAPGEFL1 in four cell lines was increased, and the methylation status of RAPGEFL1 was significantly decreased. The methylation rate of RAPGEFL1 in ESCC tissues was significantly higher than that in corresponding normal tissues (P<0.05), which was closely correlated with lymph node metastasis, pathological differentiation and TNM staging (P<0.05). Conclusions： ：The occurrence and development of ESCC may be related to the abnormally decreased expression of miR-6867 and RAPGEFL1 and the high methylation status of RAPGEFL1; the expression of miR-6867 was consistent with RAPGEFL1 expression.Moreover, the methylation of RAPGEFL1 gene promoter might be one of the mechanisms underlying the silence of miR-6867 and RAPGEFL1.
2017, 24(10):1058-1062.
DOI: 10.3872/j.issn.1007-385X.2017.10.003
Abstract:
Objective: To investigate the expression characteristics of adhesion molecules on human liver cancer microvascular endothelial cells (HLCMVECs) and its influence on adhesion and trans-endothelial migration of im-mune cells. Methods: HLCMVECs were isolated and cultured, and human liver sinusoid endothelial cells (LSECs) were used as control. The expression of adhesion molecules was evaluated by cell-based ELISA. Peripheral blood mononuclear cells (PBMCs) were labeled with BCECF (a fluorescent dye) and then co-cultured with HLCMVEC or LSEC; the adhesion to endothelial cells and trans-endothelial migration of PBMCs were observed by inverted fluo-rescence microscope and continuous spectrum luminoscope. In addition, the functional antibody against each adhe-sion molecule was respectively added to endothelial cells before co-culture, which could determine the contribution of each adhesion molecule to the adhesion and trans-endothelial migration of PBMC. Results: Compared to LSECs,HLCMVECs expressed low level of CD31, CD34 and intercellular adhesion molecule-3 (ICAM-3) (P<0.05) and an even lower level of intercellular adhesion molecule-1 (ICAM-1) and Vascular cell adhesion molecule-1 (VCAM-1)(P<0.01), but expressed significantly higher level of αvβ3 and αvβ5 (P<0.01). Compared with LSECs, the adhesion of PBMCs to HLVMVECs were significantly decreased; and under the inducement of chemo-tactic agent, trans-en-dothelial migration of PBMCs through HLVMVECs were also significantly decreased (adhesion: [205.5±46.0] vs [330.5±48.4]; migration: [49.0±10.6] vs [110.0±19.2]; all P<0.01). However, the adhesion and migration could be obviously blocked by antibodies against ICAM-3 (P<0.05), ICAM-1 and VCAM-1(P<0.01); Antibody against CD31 did not influence PBMC adhesion greatly but significantly reduced trans-endothelial migration (P<0.05).Conclusion: The distinct expression of adhesion molecules on HLCMVECs reduced the adhesion and trans-endo-thelial migration of PBMCs.
Objective: To investigate the expression characteristics of adhesion molecules on human liver cancer microvascular endothelial cells (HLCMVECs) and its influence on adhesion and trans-endothelial migration of im-mune cells. Methods: HLCMVECs were isolated and cultured, and human liver sinusoid endothelial cells (LSECs) were used as control. The expression of adhesion molecules was evaluated by cell-based ELISA. Peripheral blood mononuclear cells (PBMCs) were labeled with BCECF (a fluorescent dye) and then co-cultured with HLCMVEC or LSEC; the adhesion to endothelial cells and trans-endothelial migration of PBMCs were observed by inverted fluo-rescence microscope and continuous spectrum luminoscope. In addition, the functional antibody against each adhe-sion molecule was respectively added to endothelial cells before co-culture, which could determine the contribution of each adhesion molecule to the adhesion and trans-endothelial migration of PBMC. Results: Compared to LSECs,HLCMVECs expressed low level of CD31, CD34 and intercellular adhesion molecule-3 (ICAM-3) (P<0.05) and an even lower level of intercellular adhesion molecule-1 (ICAM-1) and Vascular cell adhesion molecule-1 (VCAM-1)(P<0.01), but expressed significantly higher level of αvβ3 and αvβ5 (P<0.01). Compared with LSECs, the adhesion of PBMCs to HLVMVECs were significantly decreased; and under the inducement of chemo-tactic agent, trans-en-dothelial migration of PBMCs through HLVMVECs were also significantly decreased (adhesion: [205.5±46.0] vs [330.5±48.4]; migration: [49.0±10.6] vs [110.0±19.2]; all P<0.01). However, the adhesion and migration could be obviously blocked by antibodies against ICAM-3 (P<0.05), ICAM-1 and VCAM-1(P<0.01); Antibody against CD31 did not influence PBMC adhesion greatly but significantly reduced trans-endothelial migration (P<0.05).Conclusion: The distinct expression of adhesion molecules on HLCMVECs reduced the adhesion and trans-endo-thelial migration of PBMCs.
2017, 24(10):1063-1069.
DOI: 10.3872/j.issn.1007-385X.2017.10.004
Abstract:
Objective: To observe the inhibitory effect of target silencing pim-3 on mouse melanoma B16 cell line. Methods: Pim-3-shRNA vector and pim-3 over-expressing vector (pim-3-MIGR1) were respectively transfect-ed into B16 melanoma cells by liposome, and the changes in mRNA and protein expression of pim-3 was measured by qPCR and Western blotting assay, respectively; the apoptosis of B16 cells was detected by AnnexinV/PI staining and TUNEL staining; the expressions of apoptosis-related factors, such as p-Bad, Bcl-2, Bcl-xl, Bax, caspase-3,were evaluated by qPCR and Western blotting; MTT assay was applied to confirm the proliferation of B16 cells;Flow cytometry was used to detect cell cycle; RTCAxCELLigence system was performed to confirm cell migration;and Transwell assay was applied to examine cell invasion. Results: pim-3-shRNAsignificantly reduced while pim-3-MIGR1 significantly enhanced pim-3 expression in B16 cells at both mRNA and protein levels (all P<0.05). Pim-3-shRNA also effectively induced the apoptosis of B16 cells; however, co-transfection with pim-3-MIGR1 obviously reversed the apoptosis induced by Pim-3 silencing (P<0.05). Further studies found pim-3-shRNAsignificantly down-regulated the expressions of apoptosis-related molecules (p-Bad, Bcl-2 and Bcl-xl), but remarkably up-regulated Bax expression, and finally resulted in increased caspase-3 activity (all P<0.05). The proliferation and migration of B16 cells were significantly inhibited by pim-3 silencing (all P<0.05); however, there was no obvious change in cell cy-cle. Conclusion: Pim-3-specific gene silencing effectively promoted the apoptosis and inhibited both the prolifera-tion and migration of B16 cells, suggesting that pim-3 may serve as a potential effective gene therapy target for mel-anoma.
Objective: To observe the inhibitory effect of target silencing pim-3 on mouse melanoma B16 cell line. Methods: Pim-3-shRNA vector and pim-3 over-expressing vector (pim-3-MIGR1) were respectively transfect-ed into B16 melanoma cells by liposome, and the changes in mRNA and protein expression of pim-3 was measured by qPCR and Western blotting assay, respectively; the apoptosis of B16 cells was detected by AnnexinV/PI staining and TUNEL staining; the expressions of apoptosis-related factors, such as p-Bad, Bcl-2, Bcl-xl, Bax, caspase-3,were evaluated by qPCR and Western blotting; MTT assay was applied to confirm the proliferation of B16 cells;Flow cytometry was used to detect cell cycle; RTCAxCELLigence system was performed to confirm cell migration;and Transwell assay was applied to examine cell invasion. Results: pim-3-shRNAsignificantly reduced while pim-3-MIGR1 significantly enhanced pim-3 expression in B16 cells at both mRNA and protein levels (all P<0.05). Pim-3-shRNA also effectively induced the apoptosis of B16 cells; however, co-transfection with pim-3-MIGR1 obviously reversed the apoptosis induced by Pim-3 silencing (P<0.05). Further studies found pim-3-shRNAsignificantly down-regulated the expressions of apoptosis-related molecules (p-Bad, Bcl-2 and Bcl-xl), but remarkably up-regulated Bax expression, and finally resulted in increased caspase-3 activity (all P<0.05). The proliferation and migration of B16 cells were significantly inhibited by pim-3 silencing (all P<0.05); however, there was no obvious change in cell cy-cle. Conclusion: Pim-3-specific gene silencing effectively promoted the apoptosis and inhibited both the prolifera-tion and migration of B16 cells, suggesting that pim-3 may serve as a potential effective gene therapy target for mel-anoma.
2017, 24(10):1070-1075.
DOI: 10.3872/j.issn.1007-385X.2017.10.005
Abstract:
Objective: To investigate the reversal effects of the extracts from stellera chamaejasme L (SCL) on EG-FR-TKI (epidermal growth factor receptor tyrosine kinase inhibitors) resistance in lung adenocarcinoma H1975 cells, and to explore the underlying mechanism. Methods: The inhibitory effects of SCL, gefitinib, and SCL plus ge-fitinib on the proliferation of H1975 cells were evaluated by MTT assay; the effects on apoptosis of H1975 cells were determined by flow cytometry ( FACS); Wound healing assay was performed to examine cell migration; and Western blotting was conducted to detect the expression of p-EGFR and apoptosis-related protein Bcl-2. Nude mice xenograft model was constructed, and the volume of xenografts as well as the overall survival (OS) was observed after treatment with SCL plus gefitinib. Moreover, ELISA was carried out to detect the serum levels of Bcl-2 and p-EGFR. Results: IC 50 of SCL and gefitinib on H1975 cells was (21.35±2.11）mg/ml and (11.21±1.68) μmol/L, re-spectively. Compared with single treatment of SCL(5 mg/ml) or Gefitnib(1 μmol/L), combined treatment of SCL and gefitnib significantly inhibited the proliferation rate of H1975 cells ([49.78±7.09]% vs [12.88±3.64]%, [8.45±2.57]%; all P<0.01), and inhibited the migration of H1975 cells ([22.4±6.5]% vs [70.3±4.9]%, [67.1±10.5]%; all P<0.01). FACS showed that the apoptosis rate in combined treatment group was obviously higher than that in single treatment group ([51.68±6.56]% vs [9.88±2.71]%, [9.48±2.45]%; all P<0.01). Western blotting showed the protein expressions of Bcl-2 and p-EGFR in H1975 cells were remarkably decreased after the combined treatment of SCL and gefitinib (P<0.01)．In vivo xenograft experiment showed that combined treatment of SCL and gefitinib signifi-cantly inhibited progressive tumor growth and promoted the survival time compared with single treatment of SCL or gefitinib (all P<0.01). Conclusion: SCL might reverse the EGFR-TKI resistance in H1975 cells. The potential mech-anism might be related to phosphorylation of EGFR and down-regulation of Bcl-2 expression, which might provide new thoughts of treating lung adenocarcinoma.
Objective: To investigate the reversal effects of the extracts from stellera chamaejasme L (SCL) on EG-FR-TKI (epidermal growth factor receptor tyrosine kinase inhibitors) resistance in lung adenocarcinoma H1975 cells, and to explore the underlying mechanism. Methods: The inhibitory effects of SCL, gefitinib, and SCL plus ge-fitinib on the proliferation of H1975 cells were evaluated by MTT assay; the effects on apoptosis of H1975 cells were determined by flow cytometry ( FACS); Wound healing assay was performed to examine cell migration; and Western blotting was conducted to detect the expression of p-EGFR and apoptosis-related protein Bcl-2. Nude mice xenograft model was constructed, and the volume of xenografts as well as the overall survival (OS) was observed after treatment with SCL plus gefitinib. Moreover, ELISA was carried out to detect the serum levels of Bcl-2 and p-EGFR. Results: IC 50 of SCL and gefitinib on H1975 cells was (21.35±2.11）mg/ml and (11.21±1.68) μmol/L, re-spectively. Compared with single treatment of SCL(5 mg/ml) or Gefitnib(1 μmol/L), combined treatment of SCL and gefitnib significantly inhibited the proliferation rate of H1975 cells ([49.78±7.09]% vs [12.88±3.64]%, [8.45±2.57]%; all P<0.01), and inhibited the migration of H1975 cells ([22.4±6.5]% vs [70.3±4.9]%, [67.1±10.5]%; all P<0.01). FACS showed that the apoptosis rate in combined treatment group was obviously higher than that in single treatment group ([51.68±6.56]% vs [9.88±2.71]%, [9.48±2.45]%; all P<0.01). Western blotting showed the protein expressions of Bcl-2 and p-EGFR in H1975 cells were remarkably decreased after the combined treatment of SCL and gefitinib (P<0.01)．In vivo xenograft experiment showed that combined treatment of SCL and gefitinib signifi-cantly inhibited progressive tumor growth and promoted the survival time compared with single treatment of SCL or gefitinib (all P<0.01). Conclusion: SCL might reverse the EGFR-TKI resistance in H1975 cells. The potential mech-anism might be related to phosphorylation of EGFR and down-regulation of Bcl-2 expression, which might provide new thoughts of treating lung adenocarcinoma.
2017, 24(10):1076-1080.
DOI: 10.3872/j.issn.1007-385X.2017.10.006
Abstract:
Objective:To investigate the effect of combined treatment of cortex periplocin (CPP) and tumor necro-sis factor related apoptosis inducing ligand (TRAIL) on gastric cancer cells and to explore the mechanism. Meth-ods: After routine culture, the gastric cancer cell lines (SGC-7901 and MGC-803) were treated with CPP (at concen-trations of 50，100，200 ng/ml) or TRAIL (1 μg/ml) or in combination of these two. The cell proliferation was detect-ed by MTS, the apoptosis was detected by Flow cytometry, and the expression levels of pro-BID，Mcl-1，cleaved caspase-3，DR4 and DR5 were detected by Western blotting. Results: Compared with the control group and each CPP single treatment group, MTS assay demonstrated that CPP (50，100，200 ng/ml) in combination with TRAIL (1 μg/ml) significantly inhibited the proliferation of gastric cancer SGC-7901 and MGC-803 cell lines (all P<0.05 or P<0.01). Flow cytometry demonstrated that the apoptosis rate of gastric cancer cells in combined treatment group was significantly higher than that of control group or each CPP single treatment group (P<0.05 or P<0.01). Western blotting demonstrated that combined treatment for 24 h significantly decreased the expression of pro-BID and Mcl-1 (P<0.05), but increased the expression levels of cleaved caspase-3，DR4 and DR5(P<0.05). Conclusion: CPP in combination with TRAIL could significantly induce the apoptosis of gastric cancer SGC-7901 and MGC-803 cell lines and increase the susceptibility of cancer cells to TRAIL.
Objective:To investigate the effect of combined treatment of cortex periplocin (CPP) and tumor necro-sis factor related apoptosis inducing ligand (TRAIL) on gastric cancer cells and to explore the mechanism. Meth-ods: After routine culture, the gastric cancer cell lines (SGC-7901 and MGC-803) were treated with CPP (at concen-trations of 50，100，200 ng/ml) or TRAIL (1 μg/ml) or in combination of these two. The cell proliferation was detect-ed by MTS, the apoptosis was detected by Flow cytometry, and the expression levels of pro-BID，Mcl-1，cleaved caspase-3，DR4 and DR5 were detected by Western blotting. Results: Compared with the control group and each CPP single treatment group, MTS assay demonstrated that CPP (50，100，200 ng/ml) in combination with TRAIL (1 μg/ml) significantly inhibited the proliferation of gastric cancer SGC-7901 and MGC-803 cell lines (all P<0.05 or P<0.01). Flow cytometry demonstrated that the apoptosis rate of gastric cancer cells in combined treatment group was significantly higher than that of control group or each CPP single treatment group (P<0.05 or P<0.01). Western blotting demonstrated that combined treatment for 24 h significantly decreased the expression of pro-BID and Mcl-1 (P<0.05), but increased the expression levels of cleaved caspase-3，DR4 and DR5(P<0.05). Conclusion: CPP in combination with TRAIL could significantly induce the apoptosis of gastric cancer SGC-7901 and MGC-803 cell lines and increase the susceptibility of cancer cells to TRAIL.
2017, 24(10):1081-1087.
DOI: 10.3872/j.issn.1007-385X.2017.10.007
Abstract:
Objective:To investigate the effects and molecular mechanisms of Suberoylanilide Hydroxamic Acid (SAHA) on the proliferation, cell cycle and apoptosis of colon cancer HCT116 and SW480 cells. Methods: Colon cancer cells (HCT116 and SW480) were treated with a series of concentrations of SAHA．MTT assay was em-ployed to evaluate the effect of SAHA on proliferation of HCT116 and SW480 cells．The cell cycle distribution and apoptosis were determined by flow cytometry．Rhodamine 123 and DCFH-DA were applied to detect the mito-chondrial membrane potential(ΔΨm) and reactive oxygen species (ROS) production．Reverse transcription poly-merase chain reaction (RT-PCR) and Western blotting were used to assess the mRNA and protein expressions of Ac-H3, p21, Cyclin D1, Bax and Bcl-2. Results: After 48 h of SAHA treatment on HCT116 and SW480 cells, the cell proliferation was inhibited，the G1 phase ratio of cells and the apoptosis rate was increased (all P<0.05); moreover,SAHA also reduced ΔΨm and increased cellular ROS production (all P<0.05). Compared with control group, the mRNA expressions of p21 and Bax were higher in SAHA group, while the mRNA expressions of CyclinD1 and Bcl-2 were lower (all P<0.05); Furthermore, the protein expressions of Ac-H3，p21 and Bax were improved，while the protein expressions of CyclinD1 and Bcl-2 were decreased in SAHA group (all P<0.05). Conclusion: SAHA may suppress cell growth, induce apoptosis and cause cell cycle arrest of colon cancer cells by promoting histone acetyla-tion and modulating their related genes of p21, CyclinD1 and Bcl-2 family.
Objective:To investigate the effects and molecular mechanisms of Suberoylanilide Hydroxamic Acid (SAHA) on the proliferation, cell cycle and apoptosis of colon cancer HCT116 and SW480 cells. Methods: Colon cancer cells (HCT116 and SW480) were treated with a series of concentrations of SAHA．MTT assay was em-ployed to evaluate the effect of SAHA on proliferation of HCT116 and SW480 cells．The cell cycle distribution and apoptosis were determined by flow cytometry．Rhodamine 123 and DCFH-DA were applied to detect the mito-chondrial membrane potential(ΔΨm) and reactive oxygen species (ROS) production．Reverse transcription poly-merase chain reaction (RT-PCR) and Western blotting were used to assess the mRNA and protein expressions of Ac-H3, p21, Cyclin D1, Bax and Bcl-2. Results: After 48 h of SAHA treatment on HCT116 and SW480 cells, the cell proliferation was inhibited，the G1 phase ratio of cells and the apoptosis rate was increased (all P<0.05); moreover,SAHA also reduced ΔΨm and increased cellular ROS production (all P<0.05). Compared with control group, the mRNA expressions of p21 and Bax were higher in SAHA group, while the mRNA expressions of CyclinD1 and Bcl-2 were lower (all P<0.05); Furthermore, the protein expressions of Ac-H3，p21 and Bax were improved，while the protein expressions of CyclinD1 and Bcl-2 were decreased in SAHA group (all P<0.05). Conclusion: SAHA may suppress cell growth, induce apoptosis and cause cell cycle arrest of colon cancer cells by promoting histone acetyla-tion and modulating their related genes of p21, CyclinD1 and Bcl-2 family.
2017, 24(10):1088-1092.
DOI: 10.3872/j.issn.1007-385X.2017.10.008
Abstract:
Objective:To investigate the inhibitory effect of bone marrow mesenehymal stem cells (BMMSCs)transfected with ADAM17-shRNA (adisintegrin and metalloprotease 17-shRNA) on the growth of implanted breast cancer MCF-7 cell xenograft in nude mice. Methods: BMMSCs from 3-week-old male SD rats were isolated and cultured with the whole bone marrow adherence method. BMMSCs were transfected with Lentivirus-mediated AD-AM17-shRNA. Breast cancer MCF-7 cell xenograft model was successfully established in 30 nude mice after 14 days implantation of tumor cells.According to the random number table, nude mice were randomly divided into con-trol group (equal volume PBS), BMMSCs group (1×10 6 /ml BMMSCs) and transfection group (1×10 6 /ml BMMSCs transfected with ADAM17-shRNA) with 10 nude mouses in each group. The tumor inhibition test was carried out on the 15 th day by injecting BMMSCs into tail vein (0.1 ml/each, administration was carried every 3 days with a to-tal of 5 times). The growth of implanted tumor was observed every day. All the nude mice were sacrificed on 16 th day after treatment. The expressions of ADAM17 mRNA and ADAM17 protein in tumor tissues were detected by Real- time PCR and Western blotting, respectively. Results：The volume of implanted tumor in control group,BMMSCs group was significantly larger than that of transfection group ([787.15 ± 25.95], [767.02 ± 28.98] vs [361.89±19.75] mm 3 , all P<0.01) on D 30. The tumor inhibition rate of BMMSCs group and transfection group was significantly higher than that of control group (2.57%, 53.89% vs 0.00%, all P<0.05). The expression of ADAM17 mRNA in control group , BMMSCs group was significantly higher than that of transfection group (1.00±0.01, 0.97±0.08 vs 0.30±0.09, P<0.05). The expression of ADAM17 protein in control group, BMMSCs group was significant-ly higher than that of transfection group (0.70±0.09, 0.68±0.02 vs 0.45±0.05, all P<0.05). Conclusion: The tropism of ADAM17-shRNA to breast cancer xenograft in nude mice was accomplished by BMMSCs mediation, which may play an anti-tumor effect.
Objective:To investigate the inhibitory effect of bone marrow mesenehymal stem cells (BMMSCs)transfected with ADAM17-shRNA (adisintegrin and metalloprotease 17-shRNA) on the growth of implanted breast cancer MCF-7 cell xenograft in nude mice. Methods: BMMSCs from 3-week-old male SD rats were isolated and cultured with the whole bone marrow adherence method. BMMSCs were transfected with Lentivirus-mediated AD-AM17-shRNA. Breast cancer MCF-7 cell xenograft model was successfully established in 30 nude mice after 14 days implantation of tumor cells.According to the random number table, nude mice were randomly divided into con-trol group (equal volume PBS), BMMSCs group (1×10 6 /ml BMMSCs) and transfection group (1×10 6 /ml BMMSCs transfected with ADAM17-shRNA) with 10 nude mouses in each group. The tumor inhibition test was carried out on the 15 th day by injecting BMMSCs into tail vein (0.1 ml/each, administration was carried every 3 days with a to-tal of 5 times). The growth of implanted tumor was observed every day. All the nude mice were sacrificed on 16 th day after treatment. The expressions of ADAM17 mRNA and ADAM17 protein in tumor tissues were detected by Real- time PCR and Western blotting, respectively. Results：The volume of implanted tumor in control group,BMMSCs group was significantly larger than that of transfection group ([787.15 ± 25.95], [767.02 ± 28.98] vs [361.89±19.75] mm 3 , all P<0.01) on D 30. The tumor inhibition rate of BMMSCs group and transfection group was significantly higher than that of control group (2.57%, 53.89% vs 0.00%, all P<0.05). The expression of ADAM17 mRNA in control group , BMMSCs group was significantly higher than that of transfection group (1.00±0.01, 0.97±0.08 vs 0.30±0.09, P<0.05). The expression of ADAM17 protein in control group, BMMSCs group was significant-ly higher than that of transfection group (0.70±0.09, 0.68±0.02 vs 0.45±0.05, all P<0.05). Conclusion: The tropism of ADAM17-shRNA to breast cancer xenograft in nude mice was accomplished by BMMSCs mediation, which may play an anti-tumor effect.
2017, 24(10):1093-1100.
DOI: 10.3872/j.issn.1007-385X.2017.10.009
Abstract:
Objective:To explore effect of miRNA-24 on proliferation and apoptosis of the gastric cancer AGS cell and its potential mechanism. Methods: Expressions of miRNA-24 in gastric cancer AGS, MKN and HGC27 cells as well as gastric mucosal epithelium GES-1 cell were detected by qRT-PCR. The AGS cell line with over-expression of miRNA-24 was constructed. CCK-8, flow cytometry and Western blotting assays were respectively used to mea-sure proliferation vibility of the cells, cell cycle and apoptosis, and expressions of cell cycle and apoptosis-related cyclin D1, CDK2, Bcl-2, p-IκB-α/IκB-α, p-Rb/Rb proteins. Possible target gene of miRNA-24 was forecasted and verified with dual luciferase report gene assay. Results: Expressions of miRNA-24 in the gastric cells was obvious-ly lower than that in the GES-1 cell (P<0.05). Proliferation vibility of the AGS cell at 48 h in the transfected with miRNA-24 mimic (miR-24 ) group was remarkably lower than that in the control miR-NC group ([119.62 ± 12.63]% vs [147.79 ± 11.89]%, P<0.05), an arrest of cell cycle occurred, and its early and later apoptosis rates were evidently more increased than those in the miR-NC group（early apoptosis rate:[11.32+2.27]% vs [0.57 ± 0.08]%; later apopto-sis rate:([15.56 ± 2.27]% vs [0.85 ± 0.16]%, all P<0.05). In the miRNA-24 group, expression levels of cyclin D1,CDK2, Bcl2 and p-Rb proteins were all obviously lower than those in the miR-NC group, and expression level of p-IκB-α protein was obviously higher than that in the miR-NC group. In co-transfection of miRNA-24 mimic and over-expression plasmid of CARMA3 that may be action target of miRNA-24 (miR-24+pcDNA-CARMA3) group,CARMA3 protein expression of the AGS cell was significantly higher than that in the miR-24 group (1.74 ± 0.09 vs 1.03 ± 0.06, P<0.05). Proliferation vibility of the AGS cell at 48 h in the miR-24+pcDNA-CARMA3 group was obvi-ously higher than that in the miR-24 group ([137.85 ± 15.34]% vs [102.31 ± 11.23]%, P<0.05), however, early and lat-er apoptosis rates of the AGS cell in the miR-24+pcDNA-CARMA3 group were all lower than those in the miR-24 group (early apoptosis rate: [4.24 ± 0.56]% vs [11.32 ± 2.27]%, later apoptosis rate: [6.38+0.63]% vs [15.56 ± 2.27]%,all P<0.05). Effect of miRNA-24 on proliferation of apoptosis of the gastric cancer AGS cell can be partially re-versed by over-expression of CARMA3. Conclusion: miRNA-24 could inhibit proliferation of the gastric caner cells and promote their apoptosis through targeting CARMA3.
Objective:To explore effect of miRNA-24 on proliferation and apoptosis of the gastric cancer AGS cell and its potential mechanism. Methods: Expressions of miRNA-24 in gastric cancer AGS, MKN and HGC27 cells as well as gastric mucosal epithelium GES-1 cell were detected by qRT-PCR. The AGS cell line with over-expression of miRNA-24 was constructed. CCK-8, flow cytometry and Western blotting assays were respectively used to mea-sure proliferation vibility of the cells, cell cycle and apoptosis, and expressions of cell cycle and apoptosis-related cyclin D1, CDK2, Bcl-2, p-IκB-α/IκB-α, p-Rb/Rb proteins. Possible target gene of miRNA-24 was forecasted and verified with dual luciferase report gene assay. Results: Expressions of miRNA-24 in the gastric cells was obvious-ly lower than that in the GES-1 cell (P<0.05). Proliferation vibility of the AGS cell at 48 h in the transfected with miRNA-24 mimic (miR-24 ) group was remarkably lower than that in the control miR-NC group ([119.62 ± 12.63]% vs [147.79 ± 11.89]%, P<0.05), an arrest of cell cycle occurred, and its early and later apoptosis rates were evidently more increased than those in the miR-NC group（early apoptosis rate:[11.32+2.27]% vs [0.57 ± 0.08]%; later apopto-sis rate:([15.56 ± 2.27]% vs [0.85 ± 0.16]%, all P<0.05). In the miRNA-24 group, expression levels of cyclin D1,CDK2, Bcl2 and p-Rb proteins were all obviously lower than those in the miR-NC group, and expression level of p-IκB-α protein was obviously higher than that in the miR-NC group. In co-transfection of miRNA-24 mimic and over-expression plasmid of CARMA3 that may be action target of miRNA-24 (miR-24+pcDNA-CARMA3) group,CARMA3 protein expression of the AGS cell was significantly higher than that in the miR-24 group (1.74 ± 0.09 vs 1.03 ± 0.06, P<0.05). Proliferation vibility of the AGS cell at 48 h in the miR-24+pcDNA-CARMA3 group was obvi-ously higher than that in the miR-24 group ([137.85 ± 15.34]% vs [102.31 ± 11.23]%, P<0.05), however, early and lat-er apoptosis rates of the AGS cell in the miR-24+pcDNA-CARMA3 group were all lower than those in the miR-24 group (early apoptosis rate: [4.24 ± 0.56]% vs [11.32 ± 2.27]%, later apoptosis rate: [6.38+0.63]% vs [15.56 ± 2.27]%,all P<0.05). Effect of miRNA-24 on proliferation of apoptosis of the gastric cancer AGS cell can be partially re-versed by over-expression of CARMA3. Conclusion: miRNA-24 could inhibit proliferation of the gastric caner cells and promote their apoptosis through targeting CARMA3.
2017, 24(10):1101-1106.
DOI: 10.3872/j.issn.1007-385X.2017.10.010
Abstract:
Objective:To explore the promoting effect of rhPDCD5 (recombinant human programmed cell death protein 5) on paclitaxel (PTX) chemotherapy in endometrial carcinoma cells. Methods: After routine culture, endo-metrial carcinoma KLE cells were treated with rhPDCD5 (20 μg/ml), and then treated with PTX at different concen-trations (0, 1.0, 5.0, 10.0 and 50 μmol/L) for 24 hours or 10 μmol/L PTX for different time periods (0，12，24，48 h).The proliferation of KLE cells was determined by CCK, the apoptosis was examined by Flow cytometry, the PDCD5 mRNA was determined by Real-time quantitative (qPCR), and the changes of apoptosis-related genes (Bax,Bcl2, caspase 3) at protein and mRNA level were detected by western blotting and q-PCR, respectively. Results:The promoting effect of PTX on PDCD5 expression was dose- and time- dependent. The optimal concentration of PTX was 10 μmol/L and the best treatment duration was 24 hours. rhPDCD5 significantly promoted the inhibitory effect of PTX on KLE cells. CCK-8 assay and Flow cytometry confirmed that the proliferation inhibitory rate and apoptosis rate were significantly enhanced in PTX+rhPDCD5 group, compared with PTX group (P<0.01); In the presence of PTX and rhPDCD5, the expression level of pro-caspase 3 was significantly increased (P<0.01); more-over, the ratio of Bax to Bcl2 was significantly higher in PTX+rhPDCD5 group than that in other groups (P<0.01).Conclusion: rhPDCD5 can enhance the inhibitory effect of PTX on proliferation of KLE cells, promote cell apopto-sis and significantly enhance the PTX susceptibility of KLE cells.
Objective:To explore the promoting effect of rhPDCD5 (recombinant human programmed cell death protein 5) on paclitaxel (PTX) chemotherapy in endometrial carcinoma cells. Methods: After routine culture, endo-metrial carcinoma KLE cells were treated with rhPDCD5 (20 μg/ml), and then treated with PTX at different concen-trations (0, 1.0, 5.0, 10.0 and 50 μmol/L) for 24 hours or 10 μmol/L PTX for different time periods (0，12，24，48 h).The proliferation of KLE cells was determined by CCK, the apoptosis was examined by Flow cytometry, the PDCD5 mRNA was determined by Real-time quantitative (qPCR), and the changes of apoptosis-related genes (Bax,Bcl2, caspase 3) at protein and mRNA level were detected by western blotting and q-PCR, respectively. Results:The promoting effect of PTX on PDCD5 expression was dose- and time- dependent. The optimal concentration of PTX was 10 μmol/L and the best treatment duration was 24 hours. rhPDCD5 significantly promoted the inhibitory effect of PTX on KLE cells. CCK-8 assay and Flow cytometry confirmed that the proliferation inhibitory rate and apoptosis rate were significantly enhanced in PTX+rhPDCD5 group, compared with PTX group (P<0.01); In the presence of PTX and rhPDCD5, the expression level of pro-caspase 3 was significantly increased (P<0.01); more-over, the ratio of Bax to Bcl2 was significantly higher in PTX+rhPDCD5 group than that in other groups (P<0.01).Conclusion: rhPDCD5 can enhance the inhibitory effect of PTX on proliferation of KLE cells, promote cell apopto-sis and significantly enhance the PTX susceptibility of KLE cells.
2017, 24(10):1107-1111.
DOI: 10.3872/j.issn.1007-385X.2017.10.011
Abstract:
Objective:To observe the interfering and regulating effect of gemcitabine (GEM) on the immune mi-croenvironment of ovarian tumor bearing mice. Methods: C57BL/6 mice were inoculated subcutaneousely with ID8 cells to construct ovarian cancer xenograft model. The mice in the experimental group were injected with GEM intraperitoneally and the control group was injected with saline. Growth of the tumor was observed. The percentage of the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in spleen and tumor tissues of the mice were detected by FCM. RT-qPCR was used to detect the mRNA expression of arginase-1 (Arg-1) and Foxp3 in tumor tissues. The ratio of CD8 + T cells in spleen of the mice was detected by FCM. The serum IFN-γ and IL-2 level was detected by ELISA assay. Results: Tumor growth in tumor-bearing mice was significantly inhibited after GEM treatment ([366.8±44.88] vs [499.3±24.14] mm 3 , P<0.01). Tregs ratio in tumor tissues and spleen were significantly lower than controls, respectively ([12.71±2.31]% vs [20.36±2.65]%, [10.09±1.69]% vs [13.79±1.31]%; all P<0.01).The mRNA levels of Foxp3 ([4.30±0.46] vs [6.35±0.58], P<0.01) and Arg-1 ([13.26±0.37] vs [16.32±0.38], P<0.01)in the treatment group were significantly lower than that in the control group. Percentage of the CD8 + T lymphocytes in treatment and control groups had no significant difference ([11.08±1.29]% vs [11.12±1.06]%; P>0.05), but the se-rum level of IFN-γ ([71.90±2.28] vs [53.91±3.91] pg/ml，P<0.01) and IL-2 ([51.46±1.69] vs [40.90±1.50] pg/ml; P<0.01) was significantly increased compared with control group. Conclusion: GEM down-regulated immunosuppres-sive activity and up-regulated anti-cancer immunogenicity of tumor-bearing mice, which might provide the experi-mental basis of GEM serving as immunotherapy intervention for ovarian cancer.
Objective:To observe the interfering and regulating effect of gemcitabine (GEM) on the immune mi-croenvironment of ovarian tumor bearing mice. Methods: C57BL/6 mice were inoculated subcutaneousely with ID8 cells to construct ovarian cancer xenograft model. The mice in the experimental group were injected with GEM intraperitoneally and the control group was injected with saline. Growth of the tumor was observed. The percentage of the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in spleen and tumor tissues of the mice were detected by FCM. RT-qPCR was used to detect the mRNA expression of arginase-1 (Arg-1) and Foxp3 in tumor tissues. The ratio of CD8 + T cells in spleen of the mice was detected by FCM. The serum IFN-γ and IL-2 level was detected by ELISA assay. Results: Tumor growth in tumor-bearing mice was significantly inhibited after GEM treatment ([366.8±44.88] vs [499.3±24.14] mm 3 , P<0.01). Tregs ratio in tumor tissues and spleen were significantly lower than controls, respectively ([12.71±2.31]% vs [20.36±2.65]%, [10.09±1.69]% vs [13.79±1.31]%; all P<0.01).The mRNA levels of Foxp3 ([4.30±0.46] vs [6.35±0.58], P<0.01) and Arg-1 ([13.26±0.37] vs [16.32±0.38], P<0.01)in the treatment group were significantly lower than that in the control group. Percentage of the CD8 + T lymphocytes in treatment and control groups had no significant difference ([11.08±1.29]% vs [11.12±1.06]%; P>0.05), but the se-rum level of IFN-γ ([71.90±2.28] vs [53.91±3.91] pg/ml，P<0.01) and IL-2 ([51.46±1.69] vs [40.90±1.50] pg/ml; P<0.01) was significantly increased compared with control group. Conclusion: GEM down-regulated immunosuppres-sive activity and up-regulated anti-cancer immunogenicity of tumor-bearing mice, which might provide the experi-mental basis of GEM serving as immunotherapy intervention for ovarian cancer.
ZHOU Xinliang
,
ZHAO Riyang
,
HAN Jing
,
FAN Zhisong
,
LI Dan
,
ZHAO Lianmei
,
SANG Meixiang
,
SHAN Baoen
2017, 24(10):1112-1117.
DOI: 10.3872/j.issn.1007-385X.2017.10.012
Abstract:
Objective:To investigate the relationship between miR-141-3p expression and prognosis and the clini-cal parameters of gastric cancer patients through detecting the expression of miR-141-3p in gastric cancer tissues and plasma. Methods: Tissue specimens and preoperative periphery venous blood specimens from 44 gastric cancer patients were collected during radical resection of gastric cancer at the Fourth Hospital of Hebei Medical University from May 2012 to January 2013; each tissue sample included cancer tissue (non-necrosis part) and the correspond-ing non-cancerous tissue. qRT-PCR was adopted to detect the expression of miR-141-3p in gastric cancer tissues,normal para-cancerous tissues and plasma of gastric cancer patients as well as healthy volunteers (25 cases). The re-lationship between miR-141-3p expression and DFS and clinical parameters were also investigated. Results: miR-141-3p was dramatically decreased in gastric cancer tissues but significantly increased in plasma (all P<0.01). In re-gard of tissue sample examination, DFS of high miR-141-3p expression group was significantly longer than that of low expression group (21.8 vs 10.3 months, P<0.01), and miR-141-3p expression was positively correlated with DFS of patients (P<0.01). In regard of plasma sample examination, DFS of high miR-141-3p expression group was significantly shorter than that of low expression group (9.1 vs 21.0 months, P<0.01), and miR-141-3p expression was negatively correlated with DFS (P<0.01). The plasma miR-141-3p expression was associated with TNM stage,lymph node metastasis and venous obstruction (P<0.01). Conclusion: miR-141-3p was dramatically decreased in gastric cancer tissues and positively correlated with the prognosis; while its expression was significantly increased in plasma and negatively correlated with prognosis of patients, indicating that miR-141-3p could serve as a potential target for the timely treatment and the prognosis prediction of gastric cancer.
Objective:To investigate the relationship between miR-141-3p expression and prognosis and the clini-cal parameters of gastric cancer patients through detecting the expression of miR-141-3p in gastric cancer tissues and plasma. Methods: Tissue specimens and preoperative periphery venous blood specimens from 44 gastric cancer patients were collected during radical resection of gastric cancer at the Fourth Hospital of Hebei Medical University from May 2012 to January 2013; each tissue sample included cancer tissue (non-necrosis part) and the correspond-ing non-cancerous tissue. qRT-PCR was adopted to detect the expression of miR-141-3p in gastric cancer tissues,normal para-cancerous tissues and plasma of gastric cancer patients as well as healthy volunteers (25 cases). The re-lationship between miR-141-3p expression and DFS and clinical parameters were also investigated. Results: miR-141-3p was dramatically decreased in gastric cancer tissues but significantly increased in plasma (all P<0.01). In re-gard of tissue sample examination, DFS of high miR-141-3p expression group was significantly longer than that of low expression group (21.8 vs 10.3 months, P<0.01), and miR-141-3p expression was positively correlated with DFS of patients (P<0.01). In regard of plasma sample examination, DFS of high miR-141-3p expression group was significantly shorter than that of low expression group (9.1 vs 21.0 months, P<0.01), and miR-141-3p expression was negatively correlated with DFS (P<0.01). The plasma miR-141-3p expression was associated with TNM stage,lymph node metastasis and venous obstruction (P<0.01). Conclusion: miR-141-3p was dramatically decreased in gastric cancer tissues and positively correlated with the prognosis; while its expression was significantly increased in plasma and negatively correlated with prognosis of patients, indicating that miR-141-3p could serve as a potential target for the timely treatment and the prognosis prediction of gastric cancer.
2017, 24(10):1118-1123.
DOI: 10.3872/j.issn.1007-385X.2017.10.013
Abstract:
Objective：To evaluate the expressionlevelsofprogrammeddeath-1 (PD-1), programmeddeathligand-1 (PD-L1) and IFN-γ in the peripheral blood of patients with esophageal squamous cell carcinoma (ESCC), and to ex-plore their clinical implications. Methods：A total of 90 ESCC patients (including 50 patients that underwent surgi-cal treatment) and 40 healthy controls were enrolled in the study. The periphery blood samples of the participants were collected and the expression levels of soluble PD-1 (sPD-1), soluble PD-L1 (sPD-L1) and IFN-γ in the serum were tested by enzyme-link immunology method. The data were tested and analyzed with SPSS 24.0 software. Re-sults：The expression levels of sPD-1,sPD-L1 and IFN-γ in the blood of ESCC group were significantly higher than those in the healthy controls (P<0.05); the preoperative level of sPD-L1 and IFN-γ in ESCC patients was significant-ly higher than that of postoperative level (P<0.05), whereas no significant difference was observed in the expression levels of sPD-1 before and after the surgery (P>0.05). sPD-1 and sPD-L1 expression had no remarkable correlation with clinicopathological manifestations (P>0.05); however, IFN-γ expression was related to lymph node metastasis (P<0.05), but not with other manifestations (T stage, TNM stage, tumor size, tumor location, tumor cell differentia-tion, sex, and age) (P>0.05). The expression level of sPD-L1 had no significant correlation with IFN-γ (P>0.05).Conclusion：The serum level of sPD-L1 was higher in ESCC patients than that in healthy controls, and the post-op-erative sPD-L1 level was decreased compared with pre-operative level, indicating sPD-L1 may be associated with ESCC development.
Objective：To evaluate the expressionlevelsofprogrammeddeath-1 (PD-1), programmeddeathligand-1 (PD-L1) and IFN-γ in the peripheral blood of patients with esophageal squamous cell carcinoma (ESCC), and to ex-plore their clinical implications. Methods：A total of 90 ESCC patients (including 50 patients that underwent surgi-cal treatment) and 40 healthy controls were enrolled in the study. The periphery blood samples of the participants were collected and the expression levels of soluble PD-1 (sPD-1), soluble PD-L1 (sPD-L1) and IFN-γ in the serum were tested by enzyme-link immunology method. The data were tested and analyzed with SPSS 24.0 software. Re-sults：The expression levels of sPD-1,sPD-L1 and IFN-γ in the blood of ESCC group were significantly higher than those in the healthy controls (P<0.05); the preoperative level of sPD-L1 and IFN-γ in ESCC patients was significant-ly higher than that of postoperative level (P<0.05), whereas no significant difference was observed in the expression levels of sPD-1 before and after the surgery (P>0.05). sPD-1 and sPD-L1 expression had no remarkable correlation with clinicopathological manifestations (P>0.05); however, IFN-γ expression was related to lymph node metastasis (P<0.05), but not with other manifestations (T stage, TNM stage, tumor size, tumor location, tumor cell differentia-tion, sex, and age) (P>0.05). The expression level of sPD-L1 had no significant correlation with IFN-γ (P>0.05).Conclusion：The serum level of sPD-L1 was higher in ESCC patients than that in healthy controls, and the post-op-erative sPD-L1 level was decreased compared with pre-operative level, indicating sPD-L1 may be associated with ESCC development.
2017, 24(10):1124-1128.
DOI: 10.3872/j.issn.1007-385X.2017.10.014
Abstract:
Objective:To examine the application value of preoperative blood neutrophil to lymphocyte ratio (NLR) in the diagnosis and recurrence prediction of epithelial ovarian cancer (EOC). Methods: The complete clini-cal and pathological information of 147 patients with benign ovarian tumor and 134 patients with EOC that treated in Affiliated Hospital of Qingdao University between January 2003 and January 2011 were retrospectively studied.The optimum cut-off value of the preoperative NLR to diagnose EOC was identified through receiver operator char-acteristic (ROC) curve, and the patients were then classified into two groups according to this cut-off value. Univari-ate and multivariate analyses were performed to assess the high risk factors for the relapse of EOC within 5 years.Results: The optimal cut-off value of NLR was 2.04 to diagnose EOC. There were statistically significant differenc-es in age, CA125 levels, FIGO staging, lymphatic metastasis and ascites formation between the NLR<2.04 group and the NLR≥2.04 group (P<0.05), but no significant discrimination was observed in pathological type and differen-tiation level (P>0.05). Univariate and multivariate analyses revealed that NLR ≥2.04 was a risk factor the relapse of EOC within 5 years (P<0.05). Conclusion: An elevated preoperative NLR value was correlated with EOC and mul-tiple clinical indicators, which is an important independent relapse predictor for patients with EOC.
Objective:To examine the application value of preoperative blood neutrophil to lymphocyte ratio (NLR) in the diagnosis and recurrence prediction of epithelial ovarian cancer (EOC). Methods: The complete clini-cal and pathological information of 147 patients with benign ovarian tumor and 134 patients with EOC that treated in Affiliated Hospital of Qingdao University between January 2003 and January 2011 were retrospectively studied.The optimum cut-off value of the preoperative NLR to diagnose EOC was identified through receiver operator char-acteristic (ROC) curve, and the patients were then classified into two groups according to this cut-off value. Univari-ate and multivariate analyses were performed to assess the high risk factors for the relapse of EOC within 5 years.Results: The optimal cut-off value of NLR was 2.04 to diagnose EOC. There were statistically significant differenc-es in age, CA125 levels, FIGO staging, lymphatic metastasis and ascites formation between the NLR<2.04 group and the NLR≥2.04 group (P<0.05), but no significant discrimination was observed in pathological type and differen-tiation level (P>0.05). Univariate and multivariate analyses revealed that NLR ≥2.04 was a risk factor the relapse of EOC within 5 years (P<0.05). Conclusion: An elevated preoperative NLR value was correlated with EOC and mul-tiple clinical indicators, which is an important independent relapse predictor for patients with EOC.
2017, 24(10):1129-1133.
DOI: 10.3872/j.issn.1007-385X.2017.10.015
Abstract:
肺癌是世界上发病率和病死率最高的恶性肿瘤，其中非小细胞肺癌（non-small cell lung cancer，NSCLC）占85%以上。随着精准医疗的出现和高通量测序技术的进步，晚期NSCLC可治疗的靶点明显增多，再加上新药上市速度的不断加快，靶向治疗已成为一线治疗方式。应用针对EGFR、ALK和ROS1的小分子酪氨酸激酶抑制剂已经将晚期NSCLC的PFS突破了18个月；抗PD1的单克隆抗体一线治疗的PFS也达到了10.3个月，联合化疗后PFS可延长至13个月。一些临床较少应用的靶点，如BRAF、MET、RET和HER2在指南中也建议检测，并推荐了相应的靶向药物。本文将晚期NSCLC一线靶向治疗药物（免疫检查点抑制剂、间变淋巴瘤激酶抑制剂 、表皮生长因子受体抑制剂、ROS1抑制剂、血管生成抑制剂等）应用的相关临床研究进展进行综述。
肺癌是世界上发病率和病死率最高的恶性肿瘤，其中非小细胞肺癌（non-small cell lung cancer，NSCLC）占85%以上。随着精准医疗的出现和高通量测序技术的进步，晚期NSCLC可治疗的靶点明显增多，再加上新药上市速度的不断加快，靶向治疗已成为一线治疗方式。应用针对EGFR、ALK和ROS1的小分子酪氨酸激酶抑制剂已经将晚期NSCLC的PFS突破了18个月；抗PD1的单克隆抗体一线治疗的PFS也达到了10.3个月，联合化疗后PFS可延长至13个月。一些临床较少应用的靶点，如BRAF、MET、RET和HER2在指南中也建议检测，并推荐了相应的靶向药物。本文将晚期NSCLC一线靶向治疗药物（免疫检查点抑制剂、间变淋巴瘤激酶抑制剂 、表皮生长因子受体抑制剂、ROS1抑制剂、血管生成抑制剂等）应用的相关临床研究进展进行综述。
2017, 24(10):1134-1138.
DOI: 10.3872/j.issn.1007-385X.2017.10.016
Abstract:
程序性死亡受体-1(programmed death 1，PD-1)与其配体(programmed death-ligand 1，PD-L1)是目前免疫治疗中关注的焦点。PD-1与其配体PD-L1结合导致肿瘤微环境中T细胞衰竭及免疫逃逸，阻断PD-1与PD-L1结合是有效的治疗靶点。针对阻断PD-1/PD-L1通路的单克隆抗体通过美国FDA的审批已应用于临床，并已证实在恶性黑色素瘤、肺癌、膀胱癌、胃癌、霍奇金淋巴瘤、乳腺癌等多种恶性肿瘤的治疗中取得了显著效果，目前该疗法在结直肠癌（colorectal cancer，CRC）的治疗研究中也显示出了良好的疗效。本文对当前PD-1/PD-L1的分子结构、肿瘤免疫中的生物学功能和在结直肠癌微环境中的特点、临床病理分子特点、PD-1/PD-L1抑制剂治疗与耐药及预后方面的研究进展作一综述。
程序性死亡受体-1(programmed death 1，PD-1)与其配体(programmed death-ligand 1，PD-L1)是目前免疫治疗中关注的焦点。PD-1与其配体PD-L1结合导致肿瘤微环境中T细胞衰竭及免疫逃逸，阻断PD-1与PD-L1结合是有效的治疗靶点。针对阻断PD-1/PD-L1通路的单克隆抗体通过美国FDA的审批已应用于临床，并已证实在恶性黑色素瘤、肺癌、膀胱癌、胃癌、霍奇金淋巴瘤、乳腺癌等多种恶性肿瘤的治疗中取得了显著效果，目前该疗法在结直肠癌（colorectal cancer，CRC）的治疗研究中也显示出了良好的疗效。本文对当前PD-1/PD-L1的分子结构、肿瘤免疫中的生物学功能和在结直肠癌微环境中的特点、临床病理分子特点、PD-1/PD-L1抑制剂治疗与耐药及预后方面的研究进展作一综述。
2017, 24(10):1139-1143.
DOI: 10.3872/j.issn.1007-385X.2017.10.017
Abstract:
胰岛素样生长因子(insulin 1ike growth factor, IGF)是一类具有胰岛素样结构的细胞因子，可在受体及结合蛋白的调节下参与细胞的增殖、分化和凋亡。多项研究发现，IGF系统在包括横纹肌肉瘤(rhabdomyosarcoma，RMS) 在内的多种恶性肿瘤疾病的进展中扮演着重要角色。近年来对RMS患者血液与组织中的IGF系统进行基础和临床研究的结果显示，IGF系统可能在RMS的发展和预后中发挥作用，探索其受体信号通路可能为RMS的综合治疗提供新靶点。本文就IGF系统的生物学活性和信号转导通路、IGF家族与RMS的关系、IGF信号通路靶向治疗RMS的最新研究进展进行综述。
胰岛素样生长因子(insulin 1ike growth factor, IGF)是一类具有胰岛素样结构的细胞因子，可在受体及结合蛋白的调节下参与细胞的增殖、分化和凋亡。多项研究发现，IGF系统在包括横纹肌肉瘤(rhabdomyosarcoma，RMS) 在内的多种恶性肿瘤疾病的进展中扮演着重要角色。近年来对RMS患者血液与组织中的IGF系统进行基础和临床研究的结果显示，IGF系统可能在RMS的发展和预后中发挥作用，探索其受体信号通路可能为RMS的综合治疗提供新靶点。本文就IGF系统的生物学活性和信号转导通路、IGF家族与RMS的关系、IGF信号通路靶向治疗RMS的最新研究进展进行综述。
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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
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.