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Volume 23,Issue 3,2016 Table of Contents
2016, 23(3):306-307.
DOI: 10.3872/j.issn.1007-385X.2016.03.002
Abstract:
2016, 23(3):308-313.
DOI: 10.3872/j.issn.1007-385X.2016.03.003
Abstract:
Cancer immunotherapy, once one of hottest area in China, has been rapidly cooled-down or even frozen by the “Event of Wei Zexi” nowadays. In view of the situation, we objectively introduced development history and future trends of cancer immunotherapy, and its advantages and disadvantages. Current problems of cancer immunotherapy and their possible countermeasures were analyzed from multiple perspectives including the patients with tumor, regulatory authorities, medical institutions and experts of the industry. It could provide constructive opinions for establishment of cancer immunotherapy development path which is suitable for national conditions of China.
Cancer immunotherapy, once one of hottest area in China, has been rapidly cooled-down or even frozen by the “Event of Wei Zexi” nowadays. In view of the situation, we objectively introduced development history and future trends of cancer immunotherapy, and its advantages and disadvantages. Current problems of cancer immunotherapy and their possible countermeasures were analyzed from multiple perspectives including the patients with tumor, regulatory authorities, medical institutions and experts of the industry. It could provide constructive opinions for establishment of cancer immunotherapy development path which is suitable for national conditions of China.
2016, 23(3):314-317.
DOI: 10.3872/j.issn.1007-385X.2016.03.004
Abstract:
2016, 23(3):318-325.
DOI: 10.3872/j.issn.1007-385X.2016.03.005
Abstract:
Intestinal microbiota plays a critical role in regulating growth, development, nutrition and energy metabolism of a host, as well as immune homeostasis. Accumulating evidences had recently shown that the dysbiosis of the intestinal microbiota was frequently found in the patients with various cancers, especially with colorectal cancer. Alteration of the intestinal microbiota could improve or inhibit occurence and development of intestinal tumor through influencing metabolism, homeostasis and immune function of intestine. Currently, clinical practice of cancer therapy by intervene of the microbiota had shown good curative effects and a great potential. This review aims to discuss role of the intestinal microbiota on occurence and development of the intestinal tumor, and its mechanism, along with current progresses of clinical researches on treatment of the intestinal cancer with the intestinal microbiota.
Intestinal microbiota plays a critical role in regulating growth, development, nutrition and energy metabolism of a host, as well as immune homeostasis. Accumulating evidences had recently shown that the dysbiosis of the intestinal microbiota was frequently found in the patients with various cancers, especially with colorectal cancer. Alteration of the intestinal microbiota could improve or inhibit occurence and development of intestinal tumor through influencing metabolism, homeostasis and immune function of intestine. Currently, clinical practice of cancer therapy by intervene of the microbiota had shown good curative effects and a great potential. This review aims to discuss role of the intestinal microbiota on occurence and development of the intestinal tumor, and its mechanism, along with current progresses of clinical researches on treatment of the intestinal cancer with the intestinal microbiota.
2016, 23(3):326-334.
DOI: 10.3872/j.issn.1007-385X.2016.03.006
Abstract:
Objective:To investigate polymorphism interaction of α1-antitypsin (α1-AT) gene exon 5 and tissue factor pathway inhibitor (TFPI) gene T287C and relationship of the gene polymorphism interation with invasion and metastasis of colon carcinoma. Methods: Each of one hundred eighty patients diagnosed as the TNM Ⅰ,Ⅱ, Ⅲ or Ⅳ stage colon carcinoma received and treated by the First Hospital affiliated to Xinxiang Medical University Henan Province during July 2011 to July 2015 were selected. One hundred eighty patients with the TNM 0 stage colon carcinoma who without involvement of reginol lymph nodes and distant metastasis were selected as control group. Polymorphisms of the both genes in peripheral blood leukocytes of the patients in each group were tested with PCR-RFLP assay. Hardy-Weinberg equilibrium tests were used to analyze the population representativeness of the samples. Polymorphism interaction of the both genes was examed with Khoury and Wagener model. Expressions of the α1-AT and TFPI proteins in serum were tested by ELISA assay. Scratch test and Transwell invasion assay were used to detect the effect of the α1-AT and TFPI on migration and invation abilities of the human colon carcinoma SW480 line cells respectively. Expression levels of cell trypsin, tissue factor (TF) and protease-activated receptor -2 (PAR-2) were tested with Western blotting assay. Results: Risks of invasion and metastasis of the colorectal cancer in the patients with genotypes of α1-AT(MZ), α1-AT(ZZ), TFPI (TC) and TFPI (CC) significantly increased, furthermore there was a positive interaction between α1-AT (MZ) and TFPI (TC), α1-AT (MZ) and TFPI (CC), α1-AT (ZZ) and TFPI (TC), and α1-AT (ZZ) and TFPI (CC) at all (all γ＞1 ). Expressions of the α1-AT and TFPI proteins in the patients with TNM Ⅰ,Ⅱ, Ⅲ,Ⅳ stage were significantly lower than that in the patients with TNM 0 stage, and expressions of serum α1-AT and TFPI proteins among the patients with TNM Ⅰ,Ⅱ, Ⅲ and Ⅳ stage were also obviously different ( P<0.01). In the same group, exoressions of serum α1-AT and TFPI proteins in the patients with mutant genotype were significantly lower than those in the patients with wild genotype (P<001). Cell culture in vitro experiments shown that α1-AT obviously inhibited exoression of cell trypsin in the SW480 cells, but TFPI inhibited expression of TF evidently. As well as both of them could significantly decrease expression of PAR-2 protein and, migration and invasion abilities of the cells. Conclusion: All genotypes of α1-AT (MZ), α1-AT (ZZ), TFPI (TC) and TFPI (CC) might be risk factors for invasion and metastasis of the colon carcinoma. Polymorphisms and interactions of the gnens could increase invasion and metastasis dangers of the colon cancer.
Objective:To investigate polymorphism interaction of α1-antitypsin (α1-AT) gene exon 5 and tissue factor pathway inhibitor (TFPI) gene T287C and relationship of the gene polymorphism interation with invasion and metastasis of colon carcinoma. Methods: Each of one hundred eighty patients diagnosed as the TNM Ⅰ,Ⅱ, Ⅲ or Ⅳ stage colon carcinoma received and treated by the First Hospital affiliated to Xinxiang Medical University Henan Province during July 2011 to July 2015 were selected. One hundred eighty patients with the TNM 0 stage colon carcinoma who without involvement of reginol lymph nodes and distant metastasis were selected as control group. Polymorphisms of the both genes in peripheral blood leukocytes of the patients in each group were tested with PCR-RFLP assay. Hardy-Weinberg equilibrium tests were used to analyze the population representativeness of the samples. Polymorphism interaction of the both genes was examed with Khoury and Wagener model. Expressions of the α1-AT and TFPI proteins in serum were tested by ELISA assay. Scratch test and Transwell invasion assay were used to detect the effect of the α1-AT and TFPI on migration and invation abilities of the human colon carcinoma SW480 line cells respectively. Expression levels of cell trypsin, tissue factor (TF) and protease-activated receptor -2 (PAR-2) were tested with Western blotting assay. Results: Risks of invasion and metastasis of the colorectal cancer in the patients with genotypes of α1-AT(MZ), α1-AT(ZZ), TFPI (TC) and TFPI (CC) significantly increased, furthermore there was a positive interaction between α1-AT (MZ) and TFPI (TC), α1-AT (MZ) and TFPI (CC), α1-AT (ZZ) and TFPI (TC), and α1-AT (ZZ) and TFPI (CC) at all (all γ＞1 ). Expressions of the α1-AT and TFPI proteins in the patients with TNM Ⅰ,Ⅱ, Ⅲ,Ⅳ stage were significantly lower than that in the patients with TNM 0 stage, and expressions of serum α1-AT and TFPI proteins among the patients with TNM Ⅰ,Ⅱ, Ⅲ and Ⅳ stage were also obviously different ( P<0.01). In the same group, exoressions of serum α1-AT and TFPI proteins in the patients with mutant genotype were significantly lower than those in the patients with wild genotype (P<001). Cell culture in vitro experiments shown that α1-AT obviously inhibited exoression of cell trypsin in the SW480 cells, but TFPI inhibited expression of TF evidently. As well as both of them could significantly decrease expression of PAR-2 protein and, migration and invasion abilities of the cells. Conclusion: All genotypes of α1-AT (MZ), α1-AT (ZZ), TFPI (TC) and TFPI (CC) might be risk factors for invasion and metastasis of the colon carcinoma. Polymorphisms and interactions of the gnens could increase invasion and metastasis dangers of the colon cancer.
2016, 23(3):335-342.
DOI: 10.3872/j.issn.1007-385X.2016.03.007
Abstract:
Objective:To explore effect of the adenovirus vector (Ad.RGD-ING4-PTEN) modified with RGD and co-expressing with double genes coding inhibitor of growth 4 (ING4) and phosphatase and tensin homologue deleted on chromosome ten (PTEN) on proliferation, apoptosis and invasion of human neuroglioma cells in vitro.Methods: Neuroglioma U87 cells were in vitro infected with Ad.RGD-ING4-PTEN as experimental group, Ad.RGD-ING4/-PTEN as monogenge control group and PBS, Ad.RGD/RGD-GPF as blank control group. Expressions of the target genes, ING4 and PTEN in the U87 cells were detected by Western blotting. Effect of infection with the Ad.RGD-ING4-PTEN of experimental group on proliferation of the U87 cell was detected by MTT assay. Changes in apoptosis of the neuroglioma cells and expressions of apoptosis-related genes, Bcl-2, Bax, caspase-3 and HIF-1α, were respectively examined with flow cytometry and Real-time PCR assays. Effects of infection with the Ad.RGD-ING4-PTEN of experimental group on migration and invasion abilities were detected with scratch and Transwell assays respectively. Expression of invasion-associated genes, MMP-2 and MMP-9, was detected by Real-time PCR. Results: Expressions of ING4 and PTEN were successfully detected only in the experimental group and the corresponding monogene control groups. Inhibitory and apoptosis rate of the U87 cell on 5th day in experimental group were (83.1±4.6)% and (40.7±4.3)%, respectively, compared to the blank control and monogene control groups, the differences were statistically significant (P<0.05). In the experimental group, expressions of apoptosis-related proteins, Bax and caspase-3, were remarkably up-regulated, while expressions of HIF-1α and Bcl-2 proteins down-regulated in the U87 cells (all P<0.05), and expressions of invasion-associated molecules MMP-2 and MMP-9 also down-regulated significantly (all P<0.05 ). Migration distances(\[70.1±6.2\] μm) of the cells and number of the penetrated cells (\[266±3.5\] cell) in the experiment group were significantly lesser than those in the monogene control and blank control groups(all P<0.05). Conclusion: The adenovirus with double-gene ING4 and PTEN (Ad.RGD-ING4-PTEN) could more significantly inhibit proliferation and induce apoptosis of the neuroglioma U87 cells, compared to those in the adenovirus with monogene, and also could inhibit migration and invasion abilities of the U87 cells.
Objective:To explore effect of the adenovirus vector (Ad.RGD-ING4-PTEN) modified with RGD and co-expressing with double genes coding inhibitor of growth 4 (ING4) and phosphatase and tensin homologue deleted on chromosome ten (PTEN) on proliferation, apoptosis and invasion of human neuroglioma cells in vitro.Methods: Neuroglioma U87 cells were in vitro infected with Ad.RGD-ING4-PTEN as experimental group, Ad.RGD-ING4/-PTEN as monogenge control group and PBS, Ad.RGD/RGD-GPF as blank control group. Expressions of the target genes, ING4 and PTEN in the U87 cells were detected by Western blotting. Effect of infection with the Ad.RGD-ING4-PTEN of experimental group on proliferation of the U87 cell was detected by MTT assay. Changes in apoptosis of the neuroglioma cells and expressions of apoptosis-related genes, Bcl-2, Bax, caspase-3 and HIF-1α, were respectively examined with flow cytometry and Real-time PCR assays. Effects of infection with the Ad.RGD-ING4-PTEN of experimental group on migration and invasion abilities were detected with scratch and Transwell assays respectively. Expression of invasion-associated genes, MMP-2 and MMP-9, was detected by Real-time PCR. Results: Expressions of ING4 and PTEN were successfully detected only in the experimental group and the corresponding monogene control groups. Inhibitory and apoptosis rate of the U87 cell on 5th day in experimental group were (83.1±4.6)% and (40.7±4.3)%, respectively, compared to the blank control and monogene control groups, the differences were statistically significant (P<0.05). In the experimental group, expressions of apoptosis-related proteins, Bax and caspase-3, were remarkably up-regulated, while expressions of HIF-1α and Bcl-2 proteins down-regulated in the U87 cells (all P<0.05), and expressions of invasion-associated molecules MMP-2 and MMP-9 also down-regulated significantly (all P<0.05 ). Migration distances(\[70.1±6.2\] μm) of the cells and number of the penetrated cells (\[266±3.5\] cell) in the experiment group were significantly lesser than those in the monogene control and blank control groups(all P<0.05). Conclusion: The adenovirus with double-gene ING4 and PTEN (Ad.RGD-ING4-PTEN) could more significantly inhibit proliferation and induce apoptosis of the neuroglioma U87 cells, compared to those in the adenovirus with monogene, and also could inhibit migration and invasion abilities of the U87 cells.
2016, 23(3):343-349.
DOI: 10.3872/j.issn.1007-385X.2016.03.008
Abstract:
Objective:To investigate the effect of extra cellular signal-regulated kinase （ERK） knockdown on melanoma cell apoptosis mediated by TNF related apoptosis inducing ligand (TRAIL) and the underlying mechanisms. Methods: A375 cells were infected with lentivirus carrying either scramble shRNA (SC shRNA) or ERK (shRNA) for 48 hours and then treated with recombinant TRAIL protein (100 μg/ml) for another 6 hours. Cells were harvested and stained with PI; Flow cytometry was used to detect cell cycle, apoptosis, and the expression of TRAIL receptor; Western blotting was used to measure the expression level of relevant proteins. Results: Knockdown of either ERK1 or ERK2 by isotype specific shRNA resulted in G1-phase growth arrest of A375 cells（cell percentageat G1-phase in control group was 71%, compared to 85%, 90%, 81% respectively in ERK1, ERK2 and ERK1+2 shRNA groups, P<0.01). Accordingly, the A375 cell percentage at S-phase was 11% in control group, compared to around 2% in various ERK shRNA groups (P<0.001); the G2/M cell percentage was 17% in control group, compared to the around 3% in various ERK shRNA groups (P<0.01). The change of cell cycle was accompanied by up-regulation of P21 and P27 proteins, and down-regulation of cyclin D1 level, however no obvious cell apoptosis was observed. Treatment of scramble shRNA together with TRAIL caused about 15% of cell apoptosis,in contrast, the combined treatment of ERK shRNA and TRAIL increased cell apoptosis rate up to 40%~60% (P<0.01). Silencing of ERK enhanced DR4 expression on TRAIL receptor (from 32% to 75%~80%, P<0.01), but not DR5 expression. Furthermore, directly silencing ERK resulted in inhibited expression of Glut 1 and hexokinase Ⅱ, which are involved in the unique glucose metabolism of tumor cells. Conclusion: Directly silencing ERK with specific shRNA inhibited tumor cell growth and enhanced tumor cell apoptosis mediated by TRAIL. A combination of increased DR4 expression and impaired glucose metabolism is likely to contribute to the synergistic effect seen with TRAIL and ERK shRNA treatment in melanoma cells.
Objective:To investigate the effect of extra cellular signal-regulated kinase （ERK） knockdown on melanoma cell apoptosis mediated by TNF related apoptosis inducing ligand (TRAIL) and the underlying mechanisms. Methods: A375 cells were infected with lentivirus carrying either scramble shRNA (SC shRNA) or ERK (shRNA) for 48 hours and then treated with recombinant TRAIL protein (100 μg/ml) for another 6 hours. Cells were harvested and stained with PI; Flow cytometry was used to detect cell cycle, apoptosis, and the expression of TRAIL receptor; Western blotting was used to measure the expression level of relevant proteins. Results: Knockdown of either ERK1 or ERK2 by isotype specific shRNA resulted in G1-phase growth arrest of A375 cells（cell percentageat G1-phase in control group was 71%, compared to 85%, 90%, 81% respectively in ERK1, ERK2 and ERK1+2 shRNA groups, P<0.01). Accordingly, the A375 cell percentage at S-phase was 11% in control group, compared to around 2% in various ERK shRNA groups (P<0.001); the G2/M cell percentage was 17% in control group, compared to the around 3% in various ERK shRNA groups (P<0.01). The change of cell cycle was accompanied by up-regulation of P21 and P27 proteins, and down-regulation of cyclin D1 level, however no obvious cell apoptosis was observed. Treatment of scramble shRNA together with TRAIL caused about 15% of cell apoptosis,in contrast, the combined treatment of ERK shRNA and TRAIL increased cell apoptosis rate up to 40%~60% (P<0.01). Silencing of ERK enhanced DR4 expression on TRAIL receptor (from 32% to 75%~80%, P<0.01), but not DR5 expression. Furthermore, directly silencing ERK resulted in inhibited expression of Glut 1 and hexokinase Ⅱ, which are involved in the unique glucose metabolism of tumor cells. Conclusion: Directly silencing ERK with specific shRNA inhibited tumor cell growth and enhanced tumor cell apoptosis mediated by TRAIL. A combination of increased DR4 expression and impaired glucose metabolism is likely to contribute to the synergistic effect seen with TRAIL and ERK shRNA treatment in melanoma cells.
2016, 23(3):350-354.
DOI: 10.3872/j.issn.1007-385X.2016.03.009
Abstract:
Objective:This study was designed to estimate the role of platycodin D (PD), a natural monomeric compound derived from platycodin grandiflorum, in apoptosis of highly metastatic breast cancer cell line MDA-MB-231 and to primarily explore the possible mechanisms. Methods: MDA-MB-231 cells were treated with different concentrations of PD (0, 2.5, 5, 10 μmol/L), cell proliferation rate was detected by MTT and IC50 value was calculated; cell apoptosis was evaluated by Flow cytometry, and the expressions of apoptosis-related proteins were assessed by Western blotting. Results: PD significantly inhibited MDA-MB-231 cell proliferation (P＜0.01) in a dose-dependent manner with a IC50 value of (7.30±2.67) μmol/L at 72 h. Compared with control group, 10 μmol/L PD could significantly promote the apoptosis of MDA-MB-231 cells (P<0.05). PD increased the caspase protein activity by up-regulating active cleaved caspase-3, -8 and -9 and down-regulating inactive caspase-8 and -9. PD also decreased the expression level of Bcl-2 and increased Bax expression, resulting in the decrease of Bcl-2/Bax ratio in MDA-MB-231 cells. The protein expression of mutant P53 was down-regulated after treated with PD; otherwise, the expression of E2F1 was up-regulated. Conclusion：PD had an obvious anticancer effect by inhibiting breast cancer cell proliferation, and inducing apoptosis might be a potential mechanism of anti-cancer effects.
Objective:This study was designed to estimate the role of platycodin D (PD), a natural monomeric compound derived from platycodin grandiflorum, in apoptosis of highly metastatic breast cancer cell line MDA-MB-231 and to primarily explore the possible mechanisms. Methods: MDA-MB-231 cells were treated with different concentrations of PD (0, 2.5, 5, 10 μmol/L), cell proliferation rate was detected by MTT and IC50 value was calculated; cell apoptosis was evaluated by Flow cytometry, and the expressions of apoptosis-related proteins were assessed by Western blotting. Results: PD significantly inhibited MDA-MB-231 cell proliferation (P＜0.01) in a dose-dependent manner with a IC50 value of (7.30±2.67) μmol/L at 72 h. Compared with control group, 10 μmol/L PD could significantly promote the apoptosis of MDA-MB-231 cells (P<0.05). PD increased the caspase protein activity by up-regulating active cleaved caspase-3, -8 and -9 and down-regulating inactive caspase-8 and -9. PD also decreased the expression level of Bcl-2 and increased Bax expression, resulting in the decrease of Bcl-2/Bax ratio in MDA-MB-231 cells. The protein expression of mutant P53 was down-regulated after treated with PD; otherwise, the expression of E2F1 was up-regulated. Conclusion：PD had an obvious anticancer effect by inhibiting breast cancer cell proliferation, and inducing apoptosis might be a potential mechanism of anti-cancer effects.
2016, 23(3):355-359.
DOI: 10.3872/j.issn.1007-385X.2016.03.010
Abstract:
Objective:To investigate the effect of advanced glycation end products(AGEs) on epithelial-mesenchymal transition (EMT) and cancer stem cell associated marker CD133 in human colon cancer cell line SW620 and their mechanism of actions. Methods:After the SW620 cells were treated with AGEs at different concentrations of 0,50,100,200μg/ml, migration and invasion abilities of the SW620 cells were detected by wound healing test and Transwell chamber assay, respectively, percentage of CD133+ cells was tested by flow cytometry, and protein expression levels of receptor of AGEs(RAGE), E-cadherin, Vimentin, ERK1/2, p-ERK1/2 and CD133 were detected by Western blotting. Results: After the treatment of AGEs, compared with the control group (0 μg/ml), cellular migration distances in experiment groups (50, 100, 200 μg/ml) were significantly improved after 24 h (\[1.55±0.15\], \[1.58±0.19\], \[1.75±0.21\] vs \[0.95±0.18\] mm，all P<0.05) and 48 h （\[1.60±0.24\], \[2.11±0.22\], \[2.68±0.23\] vs \[1.60±0.24\] mm, all P<005). In addition, treating the cells with AGEs (50,100, 200 μg/ml) for 48 h remarkably increased number of the cells crossed Matrigel in vitro（ \[176±19.52\], \[194±17.70\], \[220±25.50\] vs \[125±26.06\]，all P＜0.05\] and percentages of CD133+ cell （\[4.75±1.49\], \[10.34±1.54\], \[14.45±2.41\]% vs \[0.77±0.41\]%，all P＜0.05). Expressions of RAGE, Vimentin, p-ERK1/2 and CD133 proteins were significantly increased in the treatment groups comparing with control group; however, the expression of E-cadherin protein was decreased, while that of ERK1/2 protein had not obvious change. Conclusion: AGEs could enhance migration and invasion abilities of the SW620 cells in vitro, promote occurrence of EMT, and induce tumorigenesis of cancer stem cells. Activating ligand of AGE-RAGE, up-regulating p-ERK1/2 prtein and regulating expression of the EMT protein might be a possible mechanism for tumorigenesis of cancer stem cells.
Objective:To investigate the effect of advanced glycation end products(AGEs) on epithelial-mesenchymal transition (EMT) and cancer stem cell associated marker CD133 in human colon cancer cell line SW620 and their mechanism of actions. Methods:After the SW620 cells were treated with AGEs at different concentrations of 0,50,100,200μg/ml, migration and invasion abilities of the SW620 cells were detected by wound healing test and Transwell chamber assay, respectively, percentage of CD133+ cells was tested by flow cytometry, and protein expression levels of receptor of AGEs(RAGE), E-cadherin, Vimentin, ERK1/2, p-ERK1/2 and CD133 were detected by Western blotting. Results: After the treatment of AGEs, compared with the control group (0 μg/ml), cellular migration distances in experiment groups (50, 100, 200 μg/ml) were significantly improved after 24 h (\[1.55±0.15\], \[1.58±0.19\], \[1.75±0.21\] vs \[0.95±0.18\] mm，all P<0.05) and 48 h （\[1.60±0.24\], \[2.11±0.22\], \[2.68±0.23\] vs \[1.60±0.24\] mm, all P<005). In addition, treating the cells with AGEs (50,100, 200 μg/ml) for 48 h remarkably increased number of the cells crossed Matrigel in vitro（ \[176±19.52\], \[194±17.70\], \[220±25.50\] vs \[125±26.06\]，all P＜0.05\] and percentages of CD133+ cell （\[4.75±1.49\], \[10.34±1.54\], \[14.45±2.41\]% vs \[0.77±0.41\]%，all P＜0.05). Expressions of RAGE, Vimentin, p-ERK1/2 and CD133 proteins were significantly increased in the treatment groups comparing with control group; however, the expression of E-cadherin protein was decreased, while that of ERK1/2 protein had not obvious change. Conclusion: AGEs could enhance migration and invasion abilities of the SW620 cells in vitro, promote occurrence of EMT, and induce tumorigenesis of cancer stem cells. Activating ligand of AGE-RAGE, up-regulating p-ERK1/2 prtein and regulating expression of the EMT protein might be a possible mechanism for tumorigenesis of cancer stem cells.
2016, 23(3):360-365.
DOI: 10.3872/j.issn.1007-385X.2016.03.011
Abstract:
Objective:To explore inhibitory effects of sophoridine on DNA topoisomerase I (DNA TOP I), epidermal growth factor receptor-tyrosine kinase (EGFR-TK), matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (APN), and the machanism for that growth and invasion of neuroglioma U87 cells were inhibited by the sophoridine. Methods: Sophoridine at different concentrations were added into brain neuroglioma U87 line cells. Inhibitory effect of the sophoridine on growths of the U87 cells and HEB human brain astrocytes was determined with MTT assay, activity of the sophoridine on apoptosis-associated protein caspase-3 in the U87 cells was detected by enzyme-linked turbidimetry assay, Transwell tests were used to determe effect of the sophoridine on invasion ability of the U87 cells. Expression of NF-κB in the U87 cells was examed by a non radioactive EMSA reagent kit.Results: Growth inhibitory rate of the neuroglioma U87 cells increased constantly with increase of sophoridine concentration (5, 10, 25, 50 and 100μmol/L), but growth rate of the HEB cells did not inhibited obviously (\[11.23±1.18\]% vs \[2.43±0.29\]%, \[22.48±3.21\]% vs \[3.65±042\]%, \[43.21±4.09\]% vs \[4.03±0.55\]%, \[57.31±5.09\]% vs \[5.21±0.43\]%, \[77.98±6.9\]% vs \[722±0.78\]%，all P<0.05). Compared with the blank control group, invasion ability of the U87 cells was significantly inhibited as presence of the sorphoridine (\[87.43±7.33\]%, \[65.12±6.16\]%, \[50.63±4.56\]%, \[35.32±4.04\]%, \[23.46±2.32\]% vs \[120.32±932\]%, all P<0.05). Half inhibitory rates (IC50) of the sorphoridin on DNA TOP I, EGFR-TPK, APN and MMP-2 were (\[22.43±2.21\], \[31.25±3.09\], \[6.32±0.32\] and \[8.23±0.63\] μmol/L) respectively. But activity of apoptosis protein caspase-3 in the U87 cell was enhanced and the sorphoridin down-regulated expression of NF-κB signaling. Conclution: The sorphoridin with low toxicity could reduce activities of DNA TOP I, EGFR-TPK, APN and MMP-2, down-regulate NF-κB signal pathway and activate apoptosis protein caspase-3, by which invasion and proliferation of the neuroglioma U87 cell and its signaling pathway could be inhibited.
Objective:To explore inhibitory effects of sophoridine on DNA topoisomerase I (DNA TOP I), epidermal growth factor receptor-tyrosine kinase (EGFR-TK), matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (APN), and the machanism for that growth and invasion of neuroglioma U87 cells were inhibited by the sophoridine. Methods: Sophoridine at different concentrations were added into brain neuroglioma U87 line cells. Inhibitory effect of the sophoridine on growths of the U87 cells and HEB human brain astrocytes was determined with MTT assay, activity of the sophoridine on apoptosis-associated protein caspase-3 in the U87 cells was detected by enzyme-linked turbidimetry assay, Transwell tests were used to determe effect of the sophoridine on invasion ability of the U87 cells. Expression of NF-κB in the U87 cells was examed by a non radioactive EMSA reagent kit.Results: Growth inhibitory rate of the neuroglioma U87 cells increased constantly with increase of sophoridine concentration (5, 10, 25, 50 and 100μmol/L), but growth rate of the HEB cells did not inhibited obviously (\[11.23±1.18\]% vs \[2.43±0.29\]%, \[22.48±3.21\]% vs \[3.65±042\]%, \[43.21±4.09\]% vs \[4.03±0.55\]%, \[57.31±5.09\]% vs \[5.21±0.43\]%, \[77.98±6.9\]% vs \[722±0.78\]%，all P<0.05). Compared with the blank control group, invasion ability of the U87 cells was significantly inhibited as presence of the sorphoridine (\[87.43±7.33\]%, \[65.12±6.16\]%, \[50.63±4.56\]%, \[35.32±4.04\]%, \[23.46±2.32\]% vs \[120.32±932\]%, all P<0.05). Half inhibitory rates (IC50) of the sorphoridin on DNA TOP I, EGFR-TPK, APN and MMP-2 were (\[22.43±2.21\], \[31.25±3.09\], \[6.32±0.32\] and \[8.23±0.63\] μmol/L) respectively. But activity of apoptosis protein caspase-3 in the U87 cell was enhanced and the sorphoridin down-regulated expression of NF-κB signaling. Conclution: The sorphoridin with low toxicity could reduce activities of DNA TOP I, EGFR-TPK, APN and MMP-2, down-regulate NF-κB signal pathway and activate apoptosis protein caspase-3, by which invasion and proliferation of the neuroglioma U87 cell and its signaling pathway could be inhibited.
11 The effect of Yiqijianpi anticancer on expression of PKC, PKCδ and PKCε in mice colon cancer tissues
2016, 23(3):366-370.
DOI: 10.3872/j.issn.1007-385X.2016.03.012
Abstract:
Objective:To study the influence of Yiqijianpi anticancer method on the expression of PKC (protein kinase C) and its subtypes (PKCδ and PKCε) in transplanted colon cancer tissues. Methods: After the establishment of subcutaneous xenograft model (human colon cancer cell line HT-29), the mice were randomly divided into 3 groups: model group, Yiqijianpi group, Yiqijianpi anticancer group. The Chinese herbs used in Yiqijianpi group were composed of Radix pseudostellariae, Poria, Atractylodes, Licorice root, Pinellia and dried orange peel etc. In addition to these, the herbs used in replenishing and anticancer group had additional Iphigenia, Tuckahoe, Zhejiang fritillaria, and Hedyotis diffusa willd. After 14 days of administration, the protein and mRNA expressions of PKC, PKCδ and PKCε were detected by RT-PCR and Western blotting. Results: （1） The mRNA and protein expressions of PKC were lower in the xenograft tissues of Yiqijianpi anticancer group than those of the model group and Yiqijianpi group (\[0.412±0.040\] vs \[0.596±0021\], \[0.540±0.015\] and \[0.261±0.019\] vs \[0.665±0.016\], \[0.498±0.018\]，P<0.05 , P<0.01)；（2）the mRNA and protein expressions of PKCδ were higher than those of the model group and Yiqijianpi group （\[0.410±0030\] vs \[0.233±0025\], \[0.261±0.034\] and \[0.516±0.029\] vs \[0.301±0.041\], \[0.361±0.044\]，all P<0.01);（3）the mRNA and protein expressions of PKCε were lower than those of the model group and Yiqijianpi group (\[0.215±0021\] vs \[0.362±0.021\], \[0.314±0.031\] and \[0.224±0.029\] vs \[0.368±0.044\], \[0.359±0029)，both P<0.01\].Conclusion: Yiqijianpi anticancer method had an inhibitory effect on PKC, PKCε and a promotive effect on PKCδ in transplanted colon cancer tissues, and this may be one of the mechanisms that this anticancer method works on colon cancer.
Objective:To study the influence of Yiqijianpi anticancer method on the expression of PKC (protein kinase C) and its subtypes (PKCδ and PKCε) in transplanted colon cancer tissues. Methods: After the establishment of subcutaneous xenograft model (human colon cancer cell line HT-29), the mice were randomly divided into 3 groups: model group, Yiqijianpi group, Yiqijianpi anticancer group. The Chinese herbs used in Yiqijianpi group were composed of Radix pseudostellariae, Poria, Atractylodes, Licorice root, Pinellia and dried orange peel etc. In addition to these, the herbs used in replenishing and anticancer group had additional Iphigenia, Tuckahoe, Zhejiang fritillaria, and Hedyotis diffusa willd. After 14 days of administration, the protein and mRNA expressions of PKC, PKCδ and PKCε were detected by RT-PCR and Western blotting. Results: （1） The mRNA and protein expressions of PKC were lower in the xenograft tissues of Yiqijianpi anticancer group than those of the model group and Yiqijianpi group (\[0.412±0.040\] vs \[0.596±0021\], \[0.540±0.015\] and \[0.261±0.019\] vs \[0.665±0.016\], \[0.498±0.018\]，P<0.05 , P<0.01)；（2）the mRNA and protein expressions of PKCδ were higher than those of the model group and Yiqijianpi group （\[0.410±0030\] vs \[0.233±0025\], \[0.261±0.034\] and \[0.516±0.029\] vs \[0.301±0.041\], \[0.361±0.044\]，all P<0.01);（3）the mRNA and protein expressions of PKCε were lower than those of the model group and Yiqijianpi group (\[0.215±0021\] vs \[0.362±0.021\], \[0.314±0.031\] and \[0.224±0.029\] vs \[0.368±0.044\], \[0.359±0029)，both P<0.01\].Conclusion: Yiqijianpi anticancer method had an inhibitory effect on PKC, PKCε and a promotive effect on PKCδ in transplanted colon cancer tissues, and this may be one of the mechanisms that this anticancer method works on colon cancer.
2016, 23(3):371-377.
DOI: 10.3872/j.issn.1007-385X.2016.03.013
Abstract:
Objective:To analyze expressions of the mismatch repair proteins, MLH1, MSH2 and MSH6, and infiltration of T lymphocytes in tissues of non-small cell lung cancer (NSCLC) and to explore a relationship of microsatellite instability (MSI) with infiltration of T lymphocytes in NSCLC. Methods:One hundred samples of NSCLC tissues diagnosed in Cancer Institute and Hospital, Tianjin Medical University between 2004 and 2010 were collected. Expressions of the MLH1, MSH2 and MSH6, and infiltration of T lymphocytes in the carcinoma tissues were examined with immunohistochemical assay. The carcinoma tissues with one negative expression among the above proteins were determined as MSI, and clinical pathologic characteristics of MSI NSCLC were analyzed. Results: Petection rate of MSI in NSCLC tissues was 24%, that was lower than that in MSS. Infiltration of T lymphocytes in the tissues of MSI NSCLC was obviously higher than that in MSS. Results of the immunohistochemical assays showed that numbers of CD3+, CD4+ and CD8+ T lymphocytes infiltrated in the tissues of MSI NSCLC were significantly higher than those in the tissues of MSS NSCLC (P<005). MSI situation in the cases was related with their age (P<0.05) but not with their gender, pathological type of tumor, primary tumor size, involvement of regional lymph node and distant metastasis (P>005). Conclusion: MSI affects the tumor immune microenvironment of NSCLC, which might provide a novel predictive indicator for immunotherapy of NSCLC.
Objective:To analyze expressions of the mismatch repair proteins, MLH1, MSH2 and MSH6, and infiltration of T lymphocytes in tissues of non-small cell lung cancer (NSCLC) and to explore a relationship of microsatellite instability (MSI) with infiltration of T lymphocytes in NSCLC. Methods:One hundred samples of NSCLC tissues diagnosed in Cancer Institute and Hospital, Tianjin Medical University between 2004 and 2010 were collected. Expressions of the MLH1, MSH2 and MSH6, and infiltration of T lymphocytes in the carcinoma tissues were examined with immunohistochemical assay. The carcinoma tissues with one negative expression among the above proteins were determined as MSI, and clinical pathologic characteristics of MSI NSCLC were analyzed. Results: Petection rate of MSI in NSCLC tissues was 24%, that was lower than that in MSS. Infiltration of T lymphocytes in the tissues of MSI NSCLC was obviously higher than that in MSS. Results of the immunohistochemical assays showed that numbers of CD3+, CD4+ and CD8+ T lymphocytes infiltrated in the tissues of MSI NSCLC were significantly higher than those in the tissues of MSS NSCLC (P<005). MSI situation in the cases was related with their age (P<0.05) but not with their gender, pathological type of tumor, primary tumor size, involvement of regional lymph node and distant metastasis (P>005). Conclusion: MSI affects the tumor immune microenvironment of NSCLC, which might provide a novel predictive indicator for immunotherapy of NSCLC.
2016, 23(3):378-381.
DOI: 10.3872/j.issn.1007-385X.2016.03.014
Abstract:
Objective:To observe the expression of Beclin1 in the tissues of non-small cell lung cancer (NSCLC) and to investigate its correlation with EGFR mutation. Methods: Immunohistochemistry and DNA sequencing were used to detect the expression of Beclin1 and EGFR mutation in 42 patients with NSCLC, respectively. The clinical significance and their correlations were analyzed. Results: he expression levels of Beclin1 were significantly higher in NSCLC tissues than that in the para-carcinoma normal tissues（71.4% vs 30.9%, P<0.01). The expression of Beclin1 in NSCLC was associated with smoking history and histological type (P=0.005, P=0.025). There were 14 cases with EGFR mutation, among which 11 cases expressed high level of Beclin1 and 2 cases expressed low level of Beclin1, with a mutation rate of 57.9% (11/19) vs 16.7% (2/12). EGFR mutation and the expression of Beclin1 had a significant correlation (r=0416, P=0009).Conclusion: EGFR mutation in NSCLC patients was positively correlated with Beclin1 expression. Beclin1 could help to determine EGFR mutation in NSCLC patients at certain level, and could provide a meaningful evidence to determine EGFR mutation.
Objective:To observe the expression of Beclin1 in the tissues of non-small cell lung cancer (NSCLC) and to investigate its correlation with EGFR mutation. Methods: Immunohistochemistry and DNA sequencing were used to detect the expression of Beclin1 and EGFR mutation in 42 patients with NSCLC, respectively. The clinical significance and their correlations were analyzed. Results: he expression levels of Beclin1 were significantly higher in NSCLC tissues than that in the para-carcinoma normal tissues（71.4% vs 30.9%, P<0.01). The expression of Beclin1 in NSCLC was associated with smoking history and histological type (P=0.005, P=0.025). There were 14 cases with EGFR mutation, among which 11 cases expressed high level of Beclin1 and 2 cases expressed low level of Beclin1, with a mutation rate of 57.9% (11/19) vs 16.7% (2/12). EGFR mutation and the expression of Beclin1 had a significant correlation (r=0416, P=0009).Conclusion: EGFR mutation in NSCLC patients was positively correlated with Beclin1 expression. Beclin1 could help to determine EGFR mutation in NSCLC patients at certain level, and could provide a meaningful evidence to determine EGFR mutation.
2016, 23(3):382-386.
DOI: 10.3872/j.issn.1007-385X.2016.03.015
Abstract:
Objective:To detect the methylation status of Bin1 gene promoter and its mRNA expression in cancer tissues and para-carcinoma normal tissues from patients with esophageal squamous cell cancer (ESCC), and to explore its clinical significance. Methods: The expression level of Bin1 mRNA and its methylation status in ESCC tissues and the corresponding para-carcinoma normal tissues from 58 patients were determined by real-time quantitative RT-PCR (qRT-PCR) and methylation specific PCR (MSP). The relationship between Bin1 methylation status and clinical pathological staging was compared. Results: The methylation frequency of Bin1 in ESCC tissues was significantly higher than that in the corresponding para-carcinoma normal tissues (58.62% vs 25.86%, P<0.01), and the Bin1 methylation status was closely correlated with TNM stage, tumor invasion depth, tumor differentiation and lymph node metastasis (all P<0.05). Compared with para-carcinoma tissue specimens, the expression of Bin1mRNA in ESCC tissues was significantly lower (\[0.78±0.05\] vs \[1.03±0.03\], t=9.643, P<0.01) . The expression of Bin1 mRNA in ESCC tissues with methylation was significantly lower than that in ESCC tissues without methylation (\[0.68±0.04\] vs \[0.85±0.07\], t=2476, P＜0.05). Conclusion: Aberrant promoter methylation of Bin1 might be closely related to the development of ESCC, and it is one of the possible mechanisms that leads low expression or deletion of Bin1 in ESCC. The DNA methylation of Bin1 might be closely associated with tumor invasion and lymph node metastasis of ESCC.
Objective:To detect the methylation status of Bin1 gene promoter and its mRNA expression in cancer tissues and para-carcinoma normal tissues from patients with esophageal squamous cell cancer (ESCC), and to explore its clinical significance. Methods: The expression level of Bin1 mRNA and its methylation status in ESCC tissues and the corresponding para-carcinoma normal tissues from 58 patients were determined by real-time quantitative RT-PCR (qRT-PCR) and methylation specific PCR (MSP). The relationship between Bin1 methylation status and clinical pathological staging was compared. Results: The methylation frequency of Bin1 in ESCC tissues was significantly higher than that in the corresponding para-carcinoma normal tissues (58.62% vs 25.86%, P<0.01), and the Bin1 methylation status was closely correlated with TNM stage, tumor invasion depth, tumor differentiation and lymph node metastasis (all P<0.05). Compared with para-carcinoma tissue specimens, the expression of Bin1mRNA in ESCC tissues was significantly lower (\[0.78±0.05\] vs \[1.03±0.03\], t=9.643, P<0.01) . The expression of Bin1 mRNA in ESCC tissues with methylation was significantly lower than that in ESCC tissues without methylation (\[0.68±0.04\] vs \[0.85±0.07\], t=2476, P＜0.05). Conclusion: Aberrant promoter methylation of Bin1 might be closely related to the development of ESCC, and it is one of the possible mechanisms that leads low expression or deletion of Bin1 in ESCC. The DNA methylation of Bin1 might be closely associated with tumor invasion and lymph node metastasis of ESCC.
2016, 23(3):387-391.
DOI: 10.3872/j.issn.1007-385X.2016.03.016
Abstract:
Objective:To evaluate the relationship between epidermal growth factor receptor（EGFR） mutations and brain metastasis（BM）in non-small cell lung cancer（NSCLC）. Methods： 90 cases of patients who were pathologically diagnosed as NSCLC in the department of thoracic surgery and oncology of Huashan Hospital, Fudan University, from January 1, 2008 to October 31, 2013 were selected in this study, and we collected the lung cancer tissues. Among them, 30 patients with brain metastasis (BM) were assigned in observation group, and the rest 60 patients with no brain metastasis (NBM) were assigned in control group. The EGFR mutation status was detected by direct sequencing. Results: The patients with BM had more EGFR mutations than the patients with NBMs (46.7% vs 15.0%, P＜0.05), no matter in adenocarcinoma or squamous carcinoma. Conclusion: EGFR mutations increasing may be associated with BM in NSCLC.
Objective:To evaluate the relationship between epidermal growth factor receptor（EGFR） mutations and brain metastasis（BM）in non-small cell lung cancer（NSCLC）. Methods： 90 cases of patients who were pathologically diagnosed as NSCLC in the department of thoracic surgery and oncology of Huashan Hospital, Fudan University, from January 1, 2008 to October 31, 2013 were selected in this study, and we collected the lung cancer tissues. Among them, 30 patients with brain metastasis (BM) were assigned in observation group, and the rest 60 patients with no brain metastasis (NBM) were assigned in control group. The EGFR mutation status was detected by direct sequencing. Results: The patients with BM had more EGFR mutations than the patients with NBMs (46.7% vs 15.0%, P＜0.05), no matter in adenocarcinoma or squamous carcinoma. Conclusion: EGFR mutations increasing may be associated with BM in NSCLC.
2016, 23(3):392-396.
DOI: 10.3872/j.issn.1007-385X.2016.03.017
Abstract:
Objective:To culture peripheral blood mononuclear cell (PBMC) derived DCs of cancer patients in vitro and investigate the effect of VEGF-C/VEGFR3 signaling pathway on the functions of DCs.Methods: DCs were cultured using GM-CSF and IL-4 co-stimulating method, and then induced by VEGF-C (VEGF-C-DC), LPS (LPS-DC) or LPS+VEGF-C (LPS+VEGF-C-DC), respectively; and immature DCs (imDCs) was used as control group. The expressions of CD80, CD83, VEGFR3 and TLR4 on DCs surface were evaluated by flow cytometry. The expression of VEGFR3 was detected by immunofluorescence method. The secretions of IL-6, TNF-α and IL-12 in different treatment groups were detected by ELISA method. Results: VEGFR3 was highly expressed in LPS-DC. The expressions of CD80 and CD83 on LPS-DC and LPS+VEGF-C-DC were much higher than that on imDC and VEGF-C-DC (18.56 % vs 8.52 %，P＜005), and showed phenotypic characteristics of mature DCs. Moreover, compared with LPS-DC, the expression of TLR4 on LPS+VEGF-C-DC was down-regulated, and the secretion of IL-6, TNF-α and IL-12 in LPS+VEGF-C-DC supernatant were also decreased. Conclusion: The VEGF-C/VEGFR3 signaling pathway can decrease DCs cytokine secretion through down-regulating TLR4 expression and act as a negative regulator of DCs immune response.
Objective:To culture peripheral blood mononuclear cell (PBMC) derived DCs of cancer patients in vitro and investigate the effect of VEGF-C/VEGFR3 signaling pathway on the functions of DCs.Methods: DCs were cultured using GM-CSF and IL-4 co-stimulating method, and then induced by VEGF-C (VEGF-C-DC), LPS (LPS-DC) or LPS+VEGF-C (LPS+VEGF-C-DC), respectively; and immature DCs (imDCs) was used as control group. The expressions of CD80, CD83, VEGFR3 and TLR4 on DCs surface were evaluated by flow cytometry. The expression of VEGFR3 was detected by immunofluorescence method. The secretions of IL-6, TNF-α and IL-12 in different treatment groups were detected by ELISA method. Results: VEGFR3 was highly expressed in LPS-DC. The expressions of CD80 and CD83 on LPS-DC and LPS+VEGF-C-DC were much higher than that on imDC and VEGF-C-DC (18.56 % vs 8.52 %，P＜005), and showed phenotypic characteristics of mature DCs. Moreover, compared with LPS-DC, the expression of TLR4 on LPS+VEGF-C-DC was down-regulated, and the secretion of IL-6, TNF-α and IL-12 in LPS+VEGF-C-DC supernatant were also decreased. Conclusion: The VEGF-C/VEGFR3 signaling pathway can decrease DCs cytokine secretion through down-regulating TLR4 expression and act as a negative regulator of DCs immune response.
2016, 23(3):397-402.
DOI: 10.3872/j.issn.1007-385X.2016.03.018
Abstract:
Objective:To evaluate the safety and clinical effects of chemotherapy combined with dendritic cells and cytokine-induced killer cells (DC-CIKs) in the treatment of colon cancer patients after complete mesocolic excision (CME). Methods: The present study enrolled 82 patients with colon cancer (stageⅢ) who underwent CME in the Department of Surgery, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine of Hebei Province between June 2012 and December 2013. The patients were randomly divided into chemotherapy group and combined therapeutic group. Chemotherapy group consisted of 42 cases, who received 6 cycles of chemotherapy with the protocol of CapeOX. Combined therapeutic group consisted of 40 cases, who were given DC loaded with autologous tumor antigen and autologous CIK cells, in addition to the same chemotherapeutical protocol. The changes in carcino-embryonic antigen (CEA), cellular immune indicators (percentage of CD3+, CD4+, CD8+, CD19+, CD56+, and CD4+ CD25+ FOXP3+ Treg in peripheral blood) and side effects of drugs were recorded, and the 2-year recurrence rate of both groups were compared. Results:The values of CEA decreased significantly at 2 weeks after the procedures in both groups (P<0.05). There were no differences in the values of CEA before and after the treatment as well as 1 year after surgery in both groups (P>0.05). The values of CEA at 2 years after surgery in chemotherapy group were notably higher than those of post-treatment and those of combined therapeutic group (both P<0.05). The proportion of CD8+ and Tregs was reduced significantly after the treatment in chemotherapy group (P<0.05), and other indicators showed no significant differences. The proportion of CD3+, CD4+, CD8+, CD19+ and CD3+CD56+ was increased markedly (P<0.05), whereas the proportion of Tregs was reduced significantly after the treatment in the combined therapeutic group (P<0.05). Fewer side effects (including bone marrow suppression, nausea and vomiting, diarrhea, peripheral nerve toxicity and hand-foot syndrome) were observed in the combined therapeutic group, as compared with the chemotherapy group (all P<0.05). The 2-year recurrence rates in the chemotherapy group and the combined therapeutic group were 23.81% and 7.5%, respectively, with significant difference between two groups (P<0.05). Conclusion: Sequential DC injection and autologous CIK cells transfusion combined with chemotherapy may improve the therapeutic effect in colon cancer patients with CME surgery by enhancing the autoimmune function. Therefore, it can improve the life quality, reduce side effects caused by drugs and more importantly, reduce the 2-year recurrence rate.
Objective:To evaluate the safety and clinical effects of chemotherapy combined with dendritic cells and cytokine-induced killer cells (DC-CIKs) in the treatment of colon cancer patients after complete mesocolic excision (CME). Methods: The present study enrolled 82 patients with colon cancer (stageⅢ) who underwent CME in the Department of Surgery, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine of Hebei Province between June 2012 and December 2013. The patients were randomly divided into chemotherapy group and combined therapeutic group. Chemotherapy group consisted of 42 cases, who received 6 cycles of chemotherapy with the protocol of CapeOX. Combined therapeutic group consisted of 40 cases, who were given DC loaded with autologous tumor antigen and autologous CIK cells, in addition to the same chemotherapeutical protocol. The changes in carcino-embryonic antigen (CEA), cellular immune indicators (percentage of CD3+, CD4+, CD8+, CD19+, CD56+, and CD4+ CD25+ FOXP3+ Treg in peripheral blood) and side effects of drugs were recorded, and the 2-year recurrence rate of both groups were compared. Results:The values of CEA decreased significantly at 2 weeks after the procedures in both groups (P<0.05). There were no differences in the values of CEA before and after the treatment as well as 1 year after surgery in both groups (P>0.05). The values of CEA at 2 years after surgery in chemotherapy group were notably higher than those of post-treatment and those of combined therapeutic group (both P<0.05). The proportion of CD8+ and Tregs was reduced significantly after the treatment in chemotherapy group (P<0.05), and other indicators showed no significant differences. The proportion of CD3+, CD4+, CD8+, CD19+ and CD3+CD56+ was increased markedly (P<0.05), whereas the proportion of Tregs was reduced significantly after the treatment in the combined therapeutic group (P<0.05). Fewer side effects (including bone marrow suppression, nausea and vomiting, diarrhea, peripheral nerve toxicity and hand-foot syndrome) were observed in the combined therapeutic group, as compared with the chemotherapy group (all P<0.05). The 2-year recurrence rates in the chemotherapy group and the combined therapeutic group were 23.81% and 7.5%, respectively, with significant difference between two groups (P<0.05). Conclusion: Sequential DC injection and autologous CIK cells transfusion combined with chemotherapy may improve the therapeutic effect in colon cancer patients with CME surgery by enhancing the autoimmune function. Therefore, it can improve the life quality, reduce side effects caused by drugs and more importantly, reduce the 2-year recurrence rate.
2016, 23(3):403-407.
DOI: 10.3872/j.issn.1007-385X.2016.03.019
Abstract:
Objective:To evaluate the safety and efficacy of dentritic cell (DC)-cytokine induced killer cells(CIKs) immune therapy combined with chemotherapy in treatment of extensive-stage small cell lung cancer(SCLC). Methods：Fifteen extensive-stage SCLC patients, who were admitted to Shanghai Eastern Hepatobiliary Surgery Hospital from June 2012 to January 2015，received DC-CIKs immune therapy after 3-5 days of EP chemotherapy（VP16+DDP)，three weeks for one cycle. The changes in T cell subsets in peripheral blood of patients before and after the combined treatment, clinical efficacy, life quality, and adverse events were observed. Results：All the 15 patients responded to the combined treatment，among them, 3 achieved CR，8 cases of PR，3 cases of SD and 1 cases of PD. The response rate (RR) and disease control rate (DCR) were 73.3% and 93.3%, respectively. The median progression free survival (PFS) and overall survival (OS) was 6.8 months and 14.9 months, respectively. The OS of the two patients obtained CR was 29.1 months and 37.2 months, respectively. Compared to pre-treatment, regulatory T cell (Treg) and CD4+T cells decreased（ \[5.42±0.70\]% vs \[6.16±0.77\]%，P<0.05；\[28.74±1.92\]% vs \[33.06±2.69\]%，P<0.05)，〖JP2〗while CIKs and CD8+T cells increased （\[5.58±0.94\]% vs \[4.94±0.77\]%，P<0.05；\[43.26±3.87\]% vs \[39.92±2.78\]%，P<0.01) after the combined treatment，and the CD4+/CD8+T cells ratio declined significantly (\[0.67±0.09\]% vs \[0.83±0.10\]%，P<0.01). 2 patients improved with 20 scores and 9 improved with 10 scores in KPS evaluation with a effective rate of 73.3%. The side effects mainly were mild myelosuppression and gastrointestinal reaction，patients could recover after symptomatic treatment.Conclusion：DC-CIK combined with chemotherapy can improve the clinical remission rate of extensive-stage SCLC, prolong the survival time, and improve quality of life and immune function, it is safe and effective that deserves further study．
Objective:To evaluate the safety and efficacy of dentritic cell (DC)-cytokine induced killer cells(CIKs) immune therapy combined with chemotherapy in treatment of extensive-stage small cell lung cancer(SCLC). Methods：Fifteen extensive-stage SCLC patients, who were admitted to Shanghai Eastern Hepatobiliary Surgery Hospital from June 2012 to January 2015，received DC-CIKs immune therapy after 3-5 days of EP chemotherapy（VP16+DDP)，three weeks for one cycle. The changes in T cell subsets in peripheral blood of patients before and after the combined treatment, clinical efficacy, life quality, and adverse events were observed. Results：All the 15 patients responded to the combined treatment，among them, 3 achieved CR，8 cases of PR，3 cases of SD and 1 cases of PD. The response rate (RR) and disease control rate (DCR) were 73.3% and 93.3%, respectively. The median progression free survival (PFS) and overall survival (OS) was 6.8 months and 14.9 months, respectively. The OS of the two patients obtained CR was 29.1 months and 37.2 months, respectively. Compared to pre-treatment, regulatory T cell (Treg) and CD4+T cells decreased（ \[5.42±0.70\]% vs \[6.16±0.77\]%，P<0.05；\[28.74±1.92\]% vs \[33.06±2.69\]%，P<0.05)，〖JP2〗while CIKs and CD8+T cells increased （\[5.58±0.94\]% vs \[4.94±0.77\]%，P<0.05；\[43.26±3.87\]% vs \[39.92±2.78\]%，P<0.01) after the combined treatment，and the CD4+/CD8+T cells ratio declined significantly (\[0.67±0.09\]% vs \[0.83±0.10\]%，P<0.01). 2 patients improved with 20 scores and 9 improved with 10 scores in KPS evaluation with a effective rate of 73.3%. The side effects mainly were mild myelosuppression and gastrointestinal reaction，patients could recover after symptomatic treatment.Conclusion：DC-CIK combined with chemotherapy can improve the clinical remission rate of extensive-stage SCLC, prolong the survival time, and improve quality of life and immune function, it is safe and effective that deserves further study．
2016, 23(3):408-412.
DOI: 10.3872/j.issn.1007-385X.2016.03.020
Abstract:
Objective:To evaluate efficacy and safety of DC-CIK cell combined with EGFR-TKI (tyrosine kinase inhibitor), erlotinib or gefitinib, treatment for progressive non-small cell lung cancer (NSCLC) patients with EGFR-mutation positive through a retrospective analysis of the patients. Methods: All of selected 34 patients were pathologically diagnosed as progressive NSCLC with EGFR-mutation positive, and treated with erlotinib (150 mg/d) or gefitinib (250 mg/d). Among them, 17 cases accepted the combined DC-CIK cell treatment. Curative effect and changes of peripheral blood CD3+, CD4+ and CD8+ T cell subsets were compared between the combined treatment and mono-drug groups. Results: In the combined treatment group, 7 patients (41.2%) had achieved PR, 8 patients (47.1%) achieved SD, and 2 patients (11.8%) emerged disease progress. Objective remission rate was 41.2%, and disease control rate 88.2%. Incidence of diarrhea in the combined treatment group, was obviously lower than that in the mono-drug group (P<0.05). Peripheral blood CD3+, CD4+ and CD8+ T cell subsets didn’t show any obvious changes before and after the treatment in the mono-drug group. However, in the combined treatment group after the treatment peripheral blood CD3+ and CD4+ T cell subsets were significantly increased (P<0.05) and peripheral blood CD8+ T cell subset decreased (P<0.05). Conclusion: The treatment of DC-CIK cell combined with erlotinib or gefitinib for progressive NSCLC patients with EGFR mutation positive had good efficacy. T cell immune status of the patients in the combined treatment group was significantly improved and adverse reactions tolerable.
Objective:To evaluate efficacy and safety of DC-CIK cell combined with EGFR-TKI (tyrosine kinase inhibitor), erlotinib or gefitinib, treatment for progressive non-small cell lung cancer (NSCLC) patients with EGFR-mutation positive through a retrospective analysis of the patients. Methods: All of selected 34 patients were pathologically diagnosed as progressive NSCLC with EGFR-mutation positive, and treated with erlotinib (150 mg/d) or gefitinib (250 mg/d). Among them, 17 cases accepted the combined DC-CIK cell treatment. Curative effect and changes of peripheral blood CD3+, CD4+ and CD8+ T cell subsets were compared between the combined treatment and mono-drug groups. Results: In the combined treatment group, 7 patients (41.2%) had achieved PR, 8 patients (47.1%) achieved SD, and 2 patients (11.8%) emerged disease progress. Objective remission rate was 41.2%, and disease control rate 88.2%. Incidence of diarrhea in the combined treatment group, was obviously lower than that in the mono-drug group (P<0.05). Peripheral blood CD3+, CD4+ and CD8+ T cell subsets didn’t show any obvious changes before and after the treatment in the mono-drug group. However, in the combined treatment group after the treatment peripheral blood CD3+ and CD4+ T cell subsets were significantly increased (P<0.05) and peripheral blood CD8+ T cell subset decreased (P<0.05). Conclusion: The treatment of DC-CIK cell combined with erlotinib or gefitinib for progressive NSCLC patients with EGFR mutation positive had good efficacy. T cell immune status of the patients in the combined treatment group was significantly improved and adverse reactions tolerable.
2016, 23(3):413-415.
DOI: 10.3872/j.issn.1007-385X.2016.03.021
Abstract:
目的：探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者外周血细胞程序性死亡蛋白1(programmed cell death protein 1-ligand l,PD-L1)的表达水平和淋巴细胞亚群比例与NSCLC临床分期的关系及其临床意义。方法：收集2014年3月至12月承德医学院附属医院肿瘤科收治的38例肺腺癌、35例肺鳞癌患者为实验组，以30例健康体检者作为对照组。采集受试者晨起外周血5 ml，用ELISA法检测血清PD-1的表达水平；流式细胞术检测CD4+、CD8+、CD19+、NK细胞比例。结果：实验组血中PD-1表达水平高于对照组\[(104.98±20.76)、(109.13±24.65) vs (50.80±14.38)pg/ml,P<0.01\]；实验组外周血中CD4+、NK细胞比例低于对照组(P<0.001)，CD8+细胞比例高于对照组(P＜0.01)；Ⅲ、Ⅳ期肺癌CD4+细胞比例和NK细胞比例均低于Ⅰ、Ⅱ期（P<0.01），PD-1表达水平CD8+细胞比例均高于Ⅰ、Ⅱ期（P<0.01)；CD19+比例差异无统计学意义(P>0.05)；PD-1的表达水平与NK细胞比例呈负相关(P<0.01)，与CD8+细胞比例呈正相关(P＜0.01)，与CD4+、CD19+无相关性(P＞0.05)。结论: NSCLC患者外周血PD-1的表达水平较健康体检者明显上调，检测外周血PD-1表达水平和淋巴细胞亚群比例对NSCLC患者病情监测及预后判断有重要意义。
目的：探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者外周血细胞程序性死亡蛋白1(programmed cell death protein 1-ligand l,PD-L1)的表达水平和淋巴细胞亚群比例与NSCLC临床分期的关系及其临床意义。方法：收集2014年3月至12月承德医学院附属医院肿瘤科收治的38例肺腺癌、35例肺鳞癌患者为实验组，以30例健康体检者作为对照组。采集受试者晨起外周血5 ml，用ELISA法检测血清PD-1的表达水平；流式细胞术检测CD4+、CD8+、CD19+、NK细胞比例。结果：实验组血中PD-1表达水平高于对照组\[(104.98±20.76)、(109.13±24.65) vs (50.80±14.38)pg/ml,P<0.01\]；实验组外周血中CD4+、NK细胞比例低于对照组(P<0.001)，CD8+细胞比例高于对照组(P＜0.01)；Ⅲ、Ⅳ期肺癌CD4+细胞比例和NK细胞比例均低于Ⅰ、Ⅱ期（P<0.01），PD-1表达水平CD8+细胞比例均高于Ⅰ、Ⅱ期（P<0.01)；CD19+比例差异无统计学意义(P>0.05)；PD-1的表达水平与NK细胞比例呈负相关(P<0.01)，与CD8+细胞比例呈正相关(P＜0.01)，与CD4+、CD19+无相关性(P＞0.05)。结论: NSCLC患者外周血PD-1的表达水平较健康体检者明显上调，检测外周血PD-1表达水平和淋巴细胞亚群比例对NSCLC患者病情监测及预后判断有重要意义。
2016, 23(3):419-426.
DOI: 10.3872/j.issn.1007-385X.2016.03.023
Abstract:
NK细胞是过继免疫治疗(adoptive immunotherapy, AIT)肿瘤中的一种独特免疫效应细胞,具有短期内大量增殖、调节机体免疫力、抗肿瘤、抗菌、抗病毒、抗衰老等特点，受到普遍关注,临床应用也显示出巨大潜力和广阔前景。本文仅就国际上有关ＮＫ细胞抗肿瘤生物学机制、培养和扩增方法、免疫调节作用，以及NK细胞和其他临床肿瘤治疗方法的联合应用，特别是近几年抗肿瘤临床转化的研究现状和进展作一简要综述，并对目前国际上NK细胞治疗中存在的问题和对策进行了有益的探讨。
NK细胞是过继免疫治疗(adoptive immunotherapy, AIT)肿瘤中的一种独特免疫效应细胞,具有短期内大量增殖、调节机体免疫力、抗肿瘤、抗菌、抗病毒、抗衰老等特点，受到普遍关注,临床应用也显示出巨大潜力和广阔前景。本文仅就国际上有关ＮＫ细胞抗肿瘤生物学机制、培养和扩增方法、免疫调节作用，以及NK细胞和其他临床肿瘤治疗方法的联合应用，特别是近几年抗肿瘤临床转化的研究现状和进展作一简要综述，并对目前国际上NK细胞治疗中存在的问题和对策进行了有益的探讨。
2016, 23(3):427-431.
DOI: 10.3872/j.issn.1007-385X.2016.03.024
Abstract:
结直肠癌是最常见的恶性肿瘤之一，发病率逐年上升。研究表明肠道菌群失衡在结直肠癌的发生中可能发挥重要作用，肠道菌群可能通过肠道黏膜屏障受损、慢性炎症反应、细菌酶和毒性代谢产物作用等多种机制促进肿瘤的发生。近年来通过无菌动物实验、基因敲除动物实验以及新一代的高通量测序使人们对肠道菌群和大肠癌间关系的认识不断深化，继而从不同角度提出肠道菌群失衡导致结直肠癌发病的作用模式，本文将结合相关作用模式从肠道菌群先后影响结直肠癌不同发病阶段的角度阐述结直肠癌发生、发展过程中的相关机制，为进一步认识结直肠癌的发病机制和结直肠癌的早期诊疗提供新的思路。
结直肠癌是最常见的恶性肿瘤之一，发病率逐年上升。研究表明肠道菌群失衡在结直肠癌的发生中可能发挥重要作用，肠道菌群可能通过肠道黏膜屏障受损、慢性炎症反应、细菌酶和毒性代谢产物作用等多种机制促进肿瘤的发生。近年来通过无菌动物实验、基因敲除动物实验以及新一代的高通量测序使人们对肠道菌群和大肠癌间关系的认识不断深化，继而从不同角度提出肠道菌群失衡导致结直肠癌发病的作用模式，本文将结合相关作用模式从肠道菌群先后影响结直肠癌不同发病阶段的角度阐述结直肠癌发生、发展过程中的相关机制，为进一步认识结直肠癌的发病机制和结直肠癌的早期诊疗提供新的思路。
2016, 23(3):432-436.
DOI: 10.3872/j.issn.1007-385X.2016.03.025
Abstract:
恶性肿瘤已成为当今严重威胁人类健康的疾病之一，存在早发现难、治愈率低和预后差等三大难点。虽然，化疗是癌症治疗的主要手段，但由此产生的耐药也是当今影响疗效的最棘手问题之一，从而使患者面对无药可用的尴尬境地。外泌体（exosomes）作为细胞间信息传递的重要通讯员，在肿瘤耐药传递方面发挥重要作用。研究发现，肿瘤细胞和肿瘤微环境（tumor microenvironment，TME）中的基质细胞均可分泌携带耐药相关分子（包括蛋白质和miRNAs等）的外泌体，并通过外泌体在TME中相互作用，传递耐药分子，从而增强肿瘤细胞对药物的耐受性；同时肿瘤细胞外泌体还可以介导药物外排，从而影响药效；基质细胞也可与肿瘤细胞相互作用影响肿瘤细胞对药物的敏感性。同时，这些机制的发现也为克服肿瘤耐药提供了新思路，研究表明通过去除或抑制含耐药分子的外泌体，或者通过改变外泌体的成分（减少耐药分子或增加抗耐药分子），可在一定程度上逆转耐药。本文就肿瘤及肿瘤基质细胞释放的外泌体在肿瘤耐药中的作用以及由此而来的耐药逆转的研究进展作一综述。
恶性肿瘤已成为当今严重威胁人类健康的疾病之一，存在早发现难、治愈率低和预后差等三大难点。虽然，化疗是癌症治疗的主要手段，但由此产生的耐药也是当今影响疗效的最棘手问题之一，从而使患者面对无药可用的尴尬境地。外泌体（exosomes）作为细胞间信息传递的重要通讯员，在肿瘤耐药传递方面发挥重要作用。研究发现，肿瘤细胞和肿瘤微环境（tumor microenvironment，TME）中的基质细胞均可分泌携带耐药相关分子（包括蛋白质和miRNAs等）的外泌体，并通过外泌体在TME中相互作用，传递耐药分子，从而增强肿瘤细胞对药物的耐受性；同时肿瘤细胞外泌体还可以介导药物外排，从而影响药效；基质细胞也可与肿瘤细胞相互作用影响肿瘤细胞对药物的敏感性。同时，这些机制的发现也为克服肿瘤耐药提供了新思路，研究表明通过去除或抑制含耐药分子的外泌体，或者通过改变外泌体的成分（减少耐药分子或增加抗耐药分子），可在一定程度上逆转耐药。本文就肿瘤及肿瘤基质细胞释放的外泌体在肿瘤耐药中的作用以及由此而来的耐药逆转的研究进展作一综述。
2016, 23(3):437-440.
DOI: 10.3872/j.issn.1007-385X.2016.03.026
Abstract:
甲状腺乳头状癌（papillary thyroid cancer，PTC）是甲状腺癌中最为常见的亚型，尽管大多数PTC预后较好，但仍有少部分预后较差。随着近年来基因组学研究和精准医疗的迅速发展，越来越多与PTC相关的基因组学改变被发现，包括单核苷酸的突变、基因异位与融合、基因拷贝数变化等。这些变化一方面能加深对PTC发生、发展和转归机制的理解，另一方面从临床诊治角度解读这些信息具有重大临床价值：促成对PTC的分子分型，弥补目前常规检查项目的不足，从而提高PTC的诊断效能和预后判断，为新的靶向药物的研发及应用提供理论依据。本文就近年来PTC基因组学研究领域的主要进展及其临床意义进行综述。
甲状腺乳头状癌（papillary thyroid cancer，PTC）是甲状腺癌中最为常见的亚型，尽管大多数PTC预后较好，但仍有少部分预后较差。随着近年来基因组学研究和精准医疗的迅速发展，越来越多与PTC相关的基因组学改变被发现，包括单核苷酸的突变、基因异位与融合、基因拷贝数变化等。这些变化一方面能加深对PTC发生、发展和转归机制的理解，另一方面从临床诊治角度解读这些信息具有重大临床价值：促成对PTC的分子分型，弥补目前常规检查项目的不足，从而提高PTC的诊断效能和预后判断，为新的靶向药物的研发及应用提供理论依据。本文就近年来PTC基因组学研究领域的主要进展及其临床意义进行综述。
2016, 23(3):441-445.
DOI: 10.3872/j.issn.1007-385X.2016.03.027
Abstract:
子宫颈癌是女性最常见的恶性肿瘤之一，发病率逐年上升且呈年轻化趋势。全球每年新发病例达到50万以上，死亡人数过半。相对于传统的化疗而言，肿瘤的靶向治疗是针对肿瘤细胞中特殊的分子进行的治疗，能特异性地与致癌位点相结合发生作用，具有专一性高、疗效好和毒副作用小等明显优越性，因此也将成为未来子宫颈癌治疗的主要趋势。本文总结了近年来国内外子宫颈癌分子靶向治疗研究的现状及其作用机制，旨在为开发更好的抗肿瘤治疗方法和肿瘤靶向治疗的临床应用提供理论依据。
子宫颈癌是女性最常见的恶性肿瘤之一，发病率逐年上升且呈年轻化趋势。全球每年新发病例达到50万以上，死亡人数过半。相对于传统的化疗而言，肿瘤的靶向治疗是针对肿瘤细胞中特殊的分子进行的治疗，能特异性地与致癌位点相结合发生作用，具有专一性高、疗效好和毒副作用小等明显优越性，因此也将成为未来子宫颈癌治疗的主要趋势。本文总结了近年来国内外子宫颈癌分子靶向治疗研究的现状及其作用机制，旨在为开发更好的抗肿瘤治疗方法和肿瘤靶向治疗的临床应用提供理论依据。
2016, 23(3):446-451.
DOI: 10.3872/j.issn.1007-385X.2016.03.028
Abstract:
肺癌的发病率和病死率位居世界恶性肿瘤之首，每年新确诊肺癌患者中约有85%为非小细胞肺癌（non-small cell lung cancer，NSCLC），探讨NSCLC发生发展的机制及寻找有效诊断方法尤为重要。MicroRNA（miRNA）是一类长度约为18～23个碱基、内源性非编码的小分子RNA，在成熟过程中其碱基可能发生突变或其对应靶基因碱基序列会发生变异，这个现象称为单核苷酸多态性（single nucleotide polymorphism，SNP）。近年来研究发现，miRNA及其SNP可作为癌基因或抑癌基因在NSCLC的发生发展中起重要作用，在NSCLC患者血液、血清、组织、唾液、尿液、痰液和胸腔体液中都有异常表达，miRNA及其SNP有望成为新型的生物标记物。本文就近年来有关miRNA及其相关SNP在NSCLC易感性和诊断中的作用作一综述。
肺癌的发病率和病死率位居世界恶性肿瘤之首，每年新确诊肺癌患者中约有85%为非小细胞肺癌（non-small cell lung cancer，NSCLC），探讨NSCLC发生发展的机制及寻找有效诊断方法尤为重要。MicroRNA（miRNA）是一类长度约为18～23个碱基、内源性非编码的小分子RNA，在成熟过程中其碱基可能发生突变或其对应靶基因碱基序列会发生变异，这个现象称为单核苷酸多态性（single nucleotide polymorphism，SNP）。近年来研究发现，miRNA及其SNP可作为癌基因或抑癌基因在NSCLC的发生发展中起重要作用，在NSCLC患者血液、血清、组织、唾液、尿液、痰液和胸腔体液中都有异常表达，miRNA及其SNP有望成为新型的生物标记物。本文就近年来有关miRNA及其相关SNP在NSCLC易感性和诊断中的作用作一综述。
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.