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Volume 23,Issue 6,2016 Table of Contents
2016, 23(6):741-744.
DOI: 10.3872/j.issn.1007-385X.2016.06.001
Abstract:
Cellular immunotherapy of cancer is an important approach of cancer immunotherapy which showed a bright prospect for practical application in clinical research. However, with the rapid development of cellular immunotherapy of cancer, it should be aware that the unique characteristics of the therapy have also brought new challenges and difficulties to the design and evaluation of clinical trials. Immune related response criteria (irRC) has been designed to better evaluate curative efficacy of the immunotherapies. In clinical trials, irRC as evaluation standards was widely used, and became a powerful tool in clinical research coordinating with traditional WHO or RECIST evaluation system. And it further offer more choices of clinical trial endpoints for the immunotherapy. In this review, based on the dual attributes of drug and technique for cellular immunotherapy, reagents and other materials used in collection, screen and process of immunocytes as well as key points of technics and product quality control and other aspects were summed up. Uniform technical specification and testing standardsused in multi-centers of clinical trials were also explored. It was sincerely hoped that more convincing evidences of multi-center randomized controlled clinical trials could be provided by workers of cancer celluar immunotherapy in China with continuous innovation, of the celluar immunotherapy, so then to promote vigorous development of the cellular immunotherapy in China.
Cellular immunotherapy of cancer is an important approach of cancer immunotherapy which showed a bright prospect for practical application in clinical research. However, with the rapid development of cellular immunotherapy of cancer, it should be aware that the unique characteristics of the therapy have also brought new challenges and difficulties to the design and evaluation of clinical trials. Immune related response criteria (irRC) has been designed to better evaluate curative efficacy of the immunotherapies. In clinical trials, irRC as evaluation standards was widely used, and became a powerful tool in clinical research coordinating with traditional WHO or RECIST evaluation system. And it further offer more choices of clinical trial endpoints for the immunotherapy. In this review, based on the dual attributes of drug and technique for cellular immunotherapy, reagents and other materials used in collection, screen and process of immunocytes as well as key points of technics and product quality control and other aspects were summed up. Uniform technical specification and testing standardsused in multi-centers of clinical trials were also explored. It was sincerely hoped that more convincing evidences of multi-center randomized controlled clinical trials could be provided by workers of cancer celluar immunotherapy in China with continuous innovation, of the celluar immunotherapy, so then to promote vigorous development of the cellular immunotherapy in China.
2016, 23(6):745-750.
DOI: 10.3872/j.issn.1007-385X.2016.06.002
Abstract:
Chimeric antigen receptor T cell (CAR-T) is an important approach of tumor immunotherapy, which has strong anti-tumor activity, but has clear clinical toxic adverse reactions. Through mechanisms of recognizing tissues with co-expressed target antigens and cross antigens, CAR-T could cause systemic injuries in whole body, namely tumor lysis syndrome (TLS) and cytokine release syndrome (CRS). Effective monitoring and real-time processing are key to prevention and treatment of the toxic adverse reactions. Combining with multiple clinical research results and experiences of CAR-T cellular immunotherapy for cancer the paper reviewed CAR-T cellular immunotherapy for cancer related toxic adverse reactions and its clinical strategies
Chimeric antigen receptor T cell (CAR-T) is an important approach of tumor immunotherapy, which has strong anti-tumor activity, but has clear clinical toxic adverse reactions. Through mechanisms of recognizing tissues with co-expressed target antigens and cross antigens, CAR-T could cause systemic injuries in whole body, namely tumor lysis syndrome (TLS) and cytokine release syndrome (CRS). Effective monitoring and real-time processing are key to prevention and treatment of the toxic adverse reactions. Combining with multiple clinical research results and experiences of CAR-T cellular immunotherapy for cancer the paper reviewed CAR-T cellular immunotherapy for cancer related toxic adverse reactions and its clinical strategies
2016, 23(6):751-758.
DOI: 10.3872/j.issn.1007-385X.2016.06.003
Abstract:
Objective: To explore killing effect of DC-CIK/CTL loaded on membrane microparticles (MMPs) of the colorectal cancer stem cells synergisted with cetuximab (C225) on colorectal cancer cells which are resistent to epidermal growth factor receptor (EGFR)-targeting drug C225, and their mechanisms. Methods: Mutation satus of k-RAS gene for colorectal cancer cell SW480, SW620 and HCT116 line cells were identified by PCR. Cancer stem cells of the SW480 and HCT116 were enriched with serum free suspension cell culture method. Stem cell markers, Sox-2 and Oct-4, were detected by RT-PCR. Pheripheral blood monocuclear cells were extracted to culture DC and CIK, CIK was co-cultured with DC loaded with MMP of the colorectal cancer stem cells. Observation of mophology and MTT assay were respectively used to detect killing effects of DC-CIK/CTL cells, their culture supernatant (DC-CIK/CTL’S) and C225 alone as well as both combination on the SW480, SW620, HCT116 line cells and their stem cells. Exprissions of apoptosis-related gene Fas, epithelial-mesenchymal transition (EMT)-related proteins, E-cadherin and vinmentin, in the SW480, SW620, HCT116 line cells after treatmented by DC-CIK/CTL’S and C225 alone as well as both combination were detected by RT-PCR. Effects of DC-CIK/CTL’S and C225 alone as well as both combination on invasion acts of the colorectal cance cells were detected by a scratch assay. Results: All of the SW480, SW620 and HCT116 cell lines were identified as K-RAS mutation type. Stem cells of the colorectal carcinoma which obtained from enrichment culture had a high expression of the stem cell marker Sox-2 and Oct-4. The DC-CIK/CTL cells loaded with MMPs, thier secretion supernatant and C225 had a synergistic effect on inhibition of colorectal cancer cells. the combination group of C225 with DC-CIK/CTL’S enhanced expressions of Fas and E-cadherin proteins, comparing with groups of C225 and DC-CIK/CTL’S alone. Migration rate of the cells in the combination treatment group was smaller than those in the single treatment groups. Conclusion: The DC-CIK/CTL loaded with the MMPs of colorectal cancer stem cell could be of specific targeting killing effect in vitro on the colorectal cancer cells which are resistant to EGFR-target drug. It could have a obvious synergistic effect with C225. Their mechanisms could be related to reverse of EMT and improvement of apoptosis of the cells.
Objective: To explore killing effect of DC-CIK/CTL loaded on membrane microparticles (MMPs) of the colorectal cancer stem cells synergisted with cetuximab (C225) on colorectal cancer cells which are resistent to epidermal growth factor receptor (EGFR)-targeting drug C225, and their mechanisms. Methods: Mutation satus of k-RAS gene for colorectal cancer cell SW480, SW620 and HCT116 line cells were identified by PCR. Cancer stem cells of the SW480 and HCT116 were enriched with serum free suspension cell culture method. Stem cell markers, Sox-2 and Oct-4, were detected by RT-PCR. Pheripheral blood monocuclear cells were extracted to culture DC and CIK, CIK was co-cultured with DC loaded with MMP of the colorectal cancer stem cells. Observation of mophology and MTT assay were respectively used to detect killing effects of DC-CIK/CTL cells, their culture supernatant (DC-CIK/CTL’S) and C225 alone as well as both combination on the SW480, SW620, HCT116 line cells and their stem cells. Exprissions of apoptosis-related gene Fas, epithelial-mesenchymal transition (EMT)-related proteins, E-cadherin and vinmentin, in the SW480, SW620, HCT116 line cells after treatmented by DC-CIK/CTL’S and C225 alone as well as both combination were detected by RT-PCR. Effects of DC-CIK/CTL’S and C225 alone as well as both combination on invasion acts of the colorectal cance cells were detected by a scratch assay. Results: All of the SW480, SW620 and HCT116 cell lines were identified as K-RAS mutation type. Stem cells of the colorectal carcinoma which obtained from enrichment culture had a high expression of the stem cell marker Sox-2 and Oct-4. The DC-CIK/CTL cells loaded with MMPs, thier secretion supernatant and C225 had a synergistic effect on inhibition of colorectal cancer cells. the combination group of C225 with DC-CIK/CTL’S enhanced expressions of Fas and E-cadherin proteins, comparing with groups of C225 and DC-CIK/CTL’S alone. Migration rate of the cells in the combination treatment group was smaller than those in the single treatment groups. Conclusion: The DC-CIK/CTL loaded with the MMPs of colorectal cancer stem cell could be of specific targeting killing effect in vitro on the colorectal cancer cells which are resistant to EGFR-target drug. It could have a obvious synergistic effect with C225. Their mechanisms could be related to reverse of EMT and improvement of apoptosis of the cells.
4 Two-deoxy glucose enhances killing efficacy of cisplatin on human melanoma cells and its mechanism
2016, 23(6):759-765.
DOI: 10.3872/j.issn.1007-385X.2016.06.004
Abstract:
Objective:To explore effect of drug combination of 2-deoxy glucose (2-DG) and cisplatin on apoptosis of human melanoma cells and its mechanism. Methods: MTT assay was used to detect viability of the cells; Annexin-V/PI staining and flow cytometry assay detected apoptosis of the cells and Wetern blotting assay detected expressions of related-apoptosis protein. Intracellular ATP content was detected by a bioluminescence kit. Results: Although cisplatin with variou concentrations (5-25 μmol/L) alone inhibited viability of the A375 cells as concentration and time dependenct patterns, cisplatin (except 5 μmol/L) combined with 2-DG (10 μmol/L) all enhanced inhibition effect on viability of the cells. Single 2-DG (10 μmol/L) did not induce apparent death of the A375 cells (<10%), single cisplatin (20 μmol/L) resulted in death of the cells (about 50%) and both of them resulted in death of the cells (>80%), compairing with single drug groups there was a significant difference (P<0.01). Single cisplatin or combination with 2-DG all induced cleavages of Caspase-3 and PARP-1, and inhibited expression of anti-apoptosis protein Mcl-1. Two-DG combined with cisplatin (20 μmol/L) could significantly inhibit expression of hexokinase Ⅱ and content of intracellular ATP was lower than that in the control group (6.3 μmol/mg protein vs 33 μmol/mg protein), that was siginificantly different from those of single drug groups (P<0.01). Two-DG combined with cisplatin did not introduce apoptosis of nornal human melanocytes. In addition, the combination of both drugs also enhanced activity of killing another three human melanoma cells (SK-100, C8161 and Mum-2C). Conclution: Two-DG could specifically enhance susceptibility of cisplatin to induce apoptosis of human melanoma cells, Its mechanism could relate with down-regulating expression of anti-apoptosis protein Mcl-1 as well as inhibiting level of tumor hexokinase and synthesis of ATP.
Objective:To explore effect of drug combination of 2-deoxy glucose (2-DG) and cisplatin on apoptosis of human melanoma cells and its mechanism. Methods: MTT assay was used to detect viability of the cells; Annexin-V/PI staining and flow cytometry assay detected apoptosis of the cells and Wetern blotting assay detected expressions of related-apoptosis protein. Intracellular ATP content was detected by a bioluminescence kit. Results: Although cisplatin with variou concentrations (5-25 μmol/L) alone inhibited viability of the A375 cells as concentration and time dependenct patterns, cisplatin (except 5 μmol/L) combined with 2-DG (10 μmol/L) all enhanced inhibition effect on viability of the cells. Single 2-DG (10 μmol/L) did not induce apparent death of the A375 cells (<10%), single cisplatin (20 μmol/L) resulted in death of the cells (about 50%) and both of them resulted in death of the cells (>80%), compairing with single drug groups there was a significant difference (P<0.01). Single cisplatin or combination with 2-DG all induced cleavages of Caspase-3 and PARP-1, and inhibited expression of anti-apoptosis protein Mcl-1. Two-DG combined with cisplatin (20 μmol/L) could significantly inhibit expression of hexokinase Ⅱ and content of intracellular ATP was lower than that in the control group (6.3 μmol/mg protein vs 33 μmol/mg protein), that was siginificantly different from those of single drug groups (P<0.01). Two-DG combined with cisplatin did not introduce apoptosis of nornal human melanocytes. In addition, the combination of both drugs also enhanced activity of killing another three human melanoma cells (SK-100, C8161 and Mum-2C). Conclution: Two-DG could specifically enhance susceptibility of cisplatin to induce apoptosis of human melanoma cells, Its mechanism could relate with down-regulating expression of anti-apoptosis protein Mcl-1 as well as inhibiting level of tumor hexokinase and synthesis of ATP.
2016, 23(6):766-772.
DOI: 10.3872/j.issn.1007-385X.2016.06.005
Abstract:
Objective:To investigate effect of hypoxic microenviroment in vitro which built by cobalt chloride (CoCl2) on epithelial mesenchymal transition and DNA homologous recombination repair of colorectal cancer SW480 and Caco-2 line cells and to explore their mechanisms. Methods: After the SW480 and Caco-2 cells were treated with various concentrations of CoCl2 for 72 h, proliferation abilities of the cells were detected by CCK8 assay, migration and invasion abilities of the cells detected by scratch test and transwell assay, cell cycles and apoptosis status of the cells detected by flow cytometry (FCM), changes of mRNA and protein levels of associated gene in the cells detected by RT-PCR and Western blotting assays. Results: CCK8 assay prompted that proliferation ability of the cells significantly increased after hypoxia (P<0.05); scratch and transwell tests suggested that under hypoxia, migration and invasion abilities of the cells obviously enhanced (P<0.05); FCM disclosed that after anoxic treatment the cells were maintained at S phage and apoptosis rates of the cells significantly decreased (P<0.05); RT-PCR assay showed that mRNA levels of HIF-1α and RAD51 in the cells after hypoxic treatment raised (P<0.05); Western blotting assay indicated that under hypoxic microenviroment in the cells expression of HIF1-α enhanced (P<0.05), expression of epithelial mesenchymal transition (EMT) associated proteins, namely E-cadherin was down-regulated, expressions of vimentin and transcription inhibitor (snail) were up-regulated (P<0.05), expressions of DNA homologous recombination associated protein BRCA1 and RAD51 were up-regulated (P<0.05), phosphorylation levels of down stream key molecule Akt1 on PI3K/AKT (phosphatidyl inositol-3-hydroxy kinase) signaling pathway and ATM kinase encoded by ataxia-telangiectasia mutant gene were significantly enhanced (P<0.05). Conclusion: Chronic hypoxia enviroment could promote abilities of proliferation, migration and invasion of the colorectal cancer SW480 and Caco-2 cells as well as inhibit apoptosis of the cells. Mechanism of the actions might related to HIF-1α/PI3K and HIF-1α/ATM signaling pathways mediated EMT and DNA homologous recombination repair process.
Objective:To investigate effect of hypoxic microenviroment in vitro which built by cobalt chloride (CoCl2) on epithelial mesenchymal transition and DNA homologous recombination repair of colorectal cancer SW480 and Caco-2 line cells and to explore their mechanisms. Methods: After the SW480 and Caco-2 cells were treated with various concentrations of CoCl2 for 72 h, proliferation abilities of the cells were detected by CCK8 assay, migration and invasion abilities of the cells detected by scratch test and transwell assay, cell cycles and apoptosis status of the cells detected by flow cytometry (FCM), changes of mRNA and protein levels of associated gene in the cells detected by RT-PCR and Western blotting assays. Results: CCK8 assay prompted that proliferation ability of the cells significantly increased after hypoxia (P<0.05); scratch and transwell tests suggested that under hypoxia, migration and invasion abilities of the cells obviously enhanced (P<0.05); FCM disclosed that after anoxic treatment the cells were maintained at S phage and apoptosis rates of the cells significantly decreased (P<0.05); RT-PCR assay showed that mRNA levels of HIF-1α and RAD51 in the cells after hypoxic treatment raised (P<0.05); Western blotting assay indicated that under hypoxic microenviroment in the cells expression of HIF1-α enhanced (P<0.05), expression of epithelial mesenchymal transition (EMT) associated proteins, namely E-cadherin was down-regulated, expressions of vimentin and transcription inhibitor (snail) were up-regulated (P<0.05), expressions of DNA homologous recombination associated protein BRCA1 and RAD51 were up-regulated (P<0.05), phosphorylation levels of down stream key molecule Akt1 on PI3K/AKT (phosphatidyl inositol-3-hydroxy kinase) signaling pathway and ATM kinase encoded by ataxia-telangiectasia mutant gene were significantly enhanced (P<0.05). Conclusion: Chronic hypoxia enviroment could promote abilities of proliferation, migration and invasion of the colorectal cancer SW480 and Caco-2 cells as well as inhibit apoptosis of the cells. Mechanism of the actions might related to HIF-1α/PI3K and HIF-1α/ATM signaling pathways mediated EMT and DNA homologous recombination repair process.
6 miR-33a inhibits invasion and migration of colon cancer cells through down-regulation of lumican
2016, 23(6):773-778.
DOI: 10.3872/j.issn.1007-385X.2016.06.006
Abstract:
Objective:To investigate expression situations of miR-33a and lumican in colon cancer at various stages and to explore effect of miR-33a on invasion and migration of colon cancer cells. Methods: Expression situations of miR-33a and lumican in colon cancer at various sages were detected by Western blotting and qPCR. To up-regulate expression of miR-33a, miR-33a mimic was transfected into colon cancer SW480 line cells. Expressions of miR-33a and lumican mRNAs after the transfection of miR-33a mimic were detected by qPCR. Transwell and scratch assays were used to examine effect of miR-33a on invasion and migration abilities of human colon cancer SW480 line cells respectively. Subcutaneous tumor formation assay in nude mice was used to detect growth of tumor tissues in the colon cancer and survival of the nudemice.Results: With increased tumor stages of the colon cancer, expression of miR-33a obviously decreased, and expression of lumican obviously increased. As increasing pathological stage and grade, expression of miR-33a gradually decreased. Expression of miR-33a evidently decreased in the colon cancer tissues with lymph node metastasis. Using of miR-33a mimic clearly up-regulated expression of miR-33a, which significantly decreased expression of lumican protein. Up-regulation of miR-33a inhibited invasion and migration abilities of the colon cancer cells. Cancer growth extent of the tumor bearing mice in the miR-33a mimic group obviously decreased, and their survival period evidently prolonged. Conclusion: miR-33a could be associated with staging and grading of the colon cancer as well as lymph node metastasis. miR-33a could inhibit invasion and migration of the colon cancer through inhibition of lumican.
Objective:To investigate expression situations of miR-33a and lumican in colon cancer at various stages and to explore effect of miR-33a on invasion and migration of colon cancer cells. Methods: Expression situations of miR-33a and lumican in colon cancer at various sages were detected by Western blotting and qPCR. To up-regulate expression of miR-33a, miR-33a mimic was transfected into colon cancer SW480 line cells. Expressions of miR-33a and lumican mRNAs after the transfection of miR-33a mimic were detected by qPCR. Transwell and scratch assays were used to examine effect of miR-33a on invasion and migration abilities of human colon cancer SW480 line cells respectively. Subcutaneous tumor formation assay in nude mice was used to detect growth of tumor tissues in the colon cancer and survival of the nudemice.Results: With increased tumor stages of the colon cancer, expression of miR-33a obviously decreased, and expression of lumican obviously increased. As increasing pathological stage and grade, expression of miR-33a gradually decreased. Expression of miR-33a evidently decreased in the colon cancer tissues with lymph node metastasis. Using of miR-33a mimic clearly up-regulated expression of miR-33a, which significantly decreased expression of lumican protein. Up-regulation of miR-33a inhibited invasion and migration abilities of the colon cancer cells. Cancer growth extent of the tumor bearing mice in the miR-33a mimic group obviously decreased, and their survival period evidently prolonged. Conclusion: miR-33a could be associated with staging and grading of the colon cancer as well as lymph node metastasis. miR-33a could inhibit invasion and migration of the colon cancer through inhibition of lumican.
2016, 23(6):779-782.
DOI: 10.3872/j.issn.1007-385X.2016.06.007
Abstract:
Objective: To investigate effect of trypsin inhibitor, sporamin, on expression of Notch4 protein in human pancreatic cancer (PC) cells and proliferation, migration, invasion of the tumor cells. Methods: Effect of the sporamin on proliferation of the PANC-1 and MiaPaCa-2 PC line cells was detected by MTT assay; proliferation and invasion abilities in vitro of the pancreatic cancer cells detected by Transwell assay and effects of various concentrations of the sporamin (0，25，50，75 and 100 μg/ml) on expression level of the Notch4 protein in the human pancreatic cancer cells detected by Western blotting assay. Results: Sporamin significantly inhibited prolilferation, migration and invasion abilities of the PANC-1and MiaPaCa-2 PC line cells, as a patern of concentration-dependence (P<0.05), but not a patern of time-dependence (P>0.05). With increase of the sporamin concentration, expression level of the Notch4 protein also decreased gradually. Conclusion:Trypsin inhibitor sporamin could inhibit proliferation, migration and invasion abilities of the PC cells with a concentration-dependence, and simualtaneously inhibit expression of the Notch4 protein in the PC cells.
Objective: To investigate effect of trypsin inhibitor, sporamin, on expression of Notch4 protein in human pancreatic cancer (PC) cells and proliferation, migration, invasion of the tumor cells. Methods: Effect of the sporamin on proliferation of the PANC-1 and MiaPaCa-2 PC line cells was detected by MTT assay; proliferation and invasion abilities in vitro of the pancreatic cancer cells detected by Transwell assay and effects of various concentrations of the sporamin (0，25，50，75 and 100 μg/ml) on expression level of the Notch4 protein in the human pancreatic cancer cells detected by Western blotting assay. Results: Sporamin significantly inhibited prolilferation, migration and invasion abilities of the PANC-1and MiaPaCa-2 PC line cells, as a patern of concentration-dependence (P<0.05), but not a patern of time-dependence (P>0.05). With increase of the sporamin concentration, expression level of the Notch4 protein also decreased gradually. Conclusion:Trypsin inhibitor sporamin could inhibit proliferation, migration and invasion abilities of the PC cells with a concentration-dependence, and simualtaneously inhibit expression of the Notch4 protein in the PC cells.
ZHAO Fengzhi
,
ZHAO Jianfu
,
SUN Yifan
,
SU Jiamin
,
QUAN Qiang
,
LUO Zhenming
,
XIANG Junjian
,
WANG Hong
,
FU Yuewu
,
TAN Xiaoling
,
XU Meng
2016, 23(6):783-788.
DOI: 10.3872/j.issn.1007-385X.2016.06.008
Abstract:
Objective:To explore effect of monoclonal antibody to basic fibroblast growth factor (bFGF mAb) combined with lobaplatin (LBP) on proliferation and apoptosis of lung adenocarcinama A549 cell and their possible mechanisms. Methods: Effect of the drugs on viability of the A549 cell was detected by CCK8 assay. Annexin V-FITC/PI assay was used to detect apoptosis rates of the A549 cell. Laser scanning confocal microscope was used to observe nuclear morphology of the cells. Expressions of related-apoptosis proteins in the cells were measured by Western blotting assay. Results: Outcomes of CCK8 assay shown that after culturing of the cell for 48 h, proliferations of the cells in bFGF mAb and LBP groups were inhibited, but inhibited proliferation of the cell in combination of both group was obviously higher than those in single LBP and single bFGF mAb groups (P<0.05). Results of Annexin V-FITC/PI assay suggested that early and later apoptosis rate in bFGFmAb combined with LBP group was (27.83±1.23)% and (39.32±1.01)% respectively, comparing with those in bFGF mAb group (\[6.25±0.19\]% and \[14.54±0.25\]%) and those in LBP group (\[1654±0.39\]% and \[21.01±0.98\]%), early and later apoptosis rates of the combination group was significantly higher than those of the single drug groups (P<0.01). The result of laser scanning confocal microscope showed that cytonuclear fragmentation rate of the combination drugs group was more significantly increased than those of the single LBP and the single bFGF mAb groups. Western blotting assay displayed that in the combination group, expressions of BAX, Caspase-3, Caspase-9 and PARPs proteins obviously increased and expressions of Bcl-2, cleaved-Caspase-3, cleaved-Caspase-9 and cleaved-PARP proteins obviously decreased as comparing with those in both of the single drug groups. Conclusion: bFGF mAb combined with LBP could inhibit proliferation of lung adenocarcinama A549 cell and induce apoptosis of the A549 cell via inhibiting expressions of Bcl-2, cleaved-Caspase-3, cleaved-Caspase-9 and cleaved-PARP proteins and up-regulating expression of BAX, Caspase-3, Caspase-9 and PAR proteins.
Objective:To explore effect of monoclonal antibody to basic fibroblast growth factor (bFGF mAb) combined with lobaplatin (LBP) on proliferation and apoptosis of lung adenocarcinama A549 cell and their possible mechanisms. Methods: Effect of the drugs on viability of the A549 cell was detected by CCK8 assay. Annexin V-FITC/PI assay was used to detect apoptosis rates of the A549 cell. Laser scanning confocal microscope was used to observe nuclear morphology of the cells. Expressions of related-apoptosis proteins in the cells were measured by Western blotting assay. Results: Outcomes of CCK8 assay shown that after culturing of the cell for 48 h, proliferations of the cells in bFGF mAb and LBP groups were inhibited, but inhibited proliferation of the cell in combination of both group was obviously higher than those in single LBP and single bFGF mAb groups (P<0.05). Results of Annexin V-FITC/PI assay suggested that early and later apoptosis rate in bFGFmAb combined with LBP group was (27.83±1.23)% and (39.32±1.01)% respectively, comparing with those in bFGF mAb group (\[6.25±0.19\]% and \[14.54±0.25\]%) and those in LBP group (\[1654±0.39\]% and \[21.01±0.98\]%), early and later apoptosis rates of the combination group was significantly higher than those of the single drug groups (P<0.01). The result of laser scanning confocal microscope showed that cytonuclear fragmentation rate of the combination drugs group was more significantly increased than those of the single LBP and the single bFGF mAb groups. Western blotting assay displayed that in the combination group, expressions of BAX, Caspase-3, Caspase-9 and PARPs proteins obviously increased and expressions of Bcl-2, cleaved-Caspase-3, cleaved-Caspase-9 and cleaved-PARP proteins obviously decreased as comparing with those in both of the single drug groups. Conclusion: bFGF mAb combined with LBP could inhibit proliferation of lung adenocarcinama A549 cell and induce apoptosis of the A549 cell via inhibiting expressions of Bcl-2, cleaved-Caspase-3, cleaved-Caspase-9 and cleaved-PARP proteins and up-regulating expression of BAX, Caspase-3, Caspase-9 and PAR proteins.
YANG Yao
,
ZHANG Chunlei
,
XIA Fangfang
,
LIU Yanlei
,
YANG Meng
,
ZHANG Jingjing
,
FANG Shan
,
CUI Daxiang
2016, 23(6):789-794.
DOI: 10.3872/j.issn.1007-385X.2016.06.009
Abstract:
Objective:Using property of human cytokine-induced killer cells (CIK) targeting gastric cancer cells to achievie local photoacoustic imaging of gastric cancer, to observe distribution of gold nanorods in gastric cancer tissues and to measure concentration changes of cytokines in serum. Methods: Peripheral blood monocuclear cells were extracted from whole blood of healthy volunteers and CIK cells were amplified induced under inductions of multiple cytokines. A seed synthesis method was used to prepare gold nanorods and to modify their surfaces with silicon dioxide(20 nm thick). A nude mouse model with subcutaneous xenograft of gastric tumor was etablished using gastric cancer MGC803 line cells. The CIK cells labeled with gold nanorods were injected into caudal vein of the nude mice with xenograft of gastric cancer and distribution of the CIK cells labeled with gold nanorods in the tumor tissues was observed with photoacoustic imaging at various time points of the injection. After 3 days of the injection, concentrations of IL-2, IL-7 and γ-IFN in serum of the nude mice were detected by ELISA assay. Results:CIK cells and gold nanorods were successfully made. The gold nanorods with 60 nm long and 8 nm wide were swallowed by the human CIK. The human CIK cells labeled with the gold nanorods actively targeted gastric cancer tissues, a large number of them accumulated in the gastric cancer tissues and enhanced signaling of photoacoustic imaging was presented. Concentrations of cytokines IL-2, IL-7 and γ-IFN significantly increased, and were higher than those in the control group (P<0.05). Conclusion: The CIK cells labeled with the gold nanorods could actively target gastric cancer tissues, efficiently collect and present enhanced signaling of photoacoustic imaging. At the same time, cytokine level in blood could be elevated and curative efficacy of the immunotherapy could be enhanced.
Objective:Using property of human cytokine-induced killer cells (CIK) targeting gastric cancer cells to achievie local photoacoustic imaging of gastric cancer, to observe distribution of gold nanorods in gastric cancer tissues and to measure concentration changes of cytokines in serum. Methods: Peripheral blood monocuclear cells were extracted from whole blood of healthy volunteers and CIK cells were amplified induced under inductions of multiple cytokines. A seed synthesis method was used to prepare gold nanorods and to modify their surfaces with silicon dioxide(20 nm thick). A nude mouse model with subcutaneous xenograft of gastric tumor was etablished using gastric cancer MGC803 line cells. The CIK cells labeled with gold nanorods were injected into caudal vein of the nude mice with xenograft of gastric cancer and distribution of the CIK cells labeled with gold nanorods in the tumor tissues was observed with photoacoustic imaging at various time points of the injection. After 3 days of the injection, concentrations of IL-2, IL-7 and γ-IFN in serum of the nude mice were detected by ELISA assay. Results:CIK cells and gold nanorods were successfully made. The gold nanorods with 60 nm long and 8 nm wide were swallowed by the human CIK. The human CIK cells labeled with the gold nanorods actively targeted gastric cancer tissues, a large number of them accumulated in the gastric cancer tissues and enhanced signaling of photoacoustic imaging was presented. Concentrations of cytokines IL-2, IL-7 and γ-IFN significantly increased, and were higher than those in the control group (P<0.05). Conclusion: The CIK cells labeled with the gold nanorods could actively target gastric cancer tissues, efficiently collect and present enhanced signaling of photoacoustic imaging. At the same time, cytokine level in blood could be elevated and curative efficacy of the immunotherapy could be enhanced.
2016, 23(6):795-800.
DOI: 10.3872/j.issn.1007-385X.2016.06.010
Abstract:
Objective:To explore the expressions of Efp and PlK3 in patients with estroen receptor (ER) positive breast cancer and to analyze their clinical significance and possible mechanisms of the actions. Methods: Immuno histochemistry was used to detect expressions of Efp and PlK3 proteins in ER positive breast cancer tissues of 86 cases who were hospitalized in Department of Breast Surgery, the 4th Hospital of Hebei Medical University during January to June, 2010. Correlation between expressions of the both protein and their relationship with clinical pathological features were analyzed. Expressions of ER and Efp mRNAs in breast cancer MCF-7 and MDA-MB-231 line cells were detected by qRT-PCR assay. RT-PCR and Western blotting assays were used to check expression changes of Efp and Plk3 genes in ER positive breast cancer MCF-7 line cell after stimulation of estrogen. Expression changes of Efp and Plk3 proteins in the MCF-7 cell after treatments with estrogen and protease inhibitor MG132 were detected by Western blotting assay. Results:In ER positive breast cancer tissues of the 86 cases, Efp expression of 55 cases was positive (64.0%) and PIk3 expression of 28 cases was positive (32.6%). Positive expression of PIk3 was 23.6% in the tissues of Efp positive expression and that was 48.4% in the tissues of Efp negative expression. There was a significant negative correlation between expressions of Efp protein and Plk3 protein (P<0.05). Expression of Efp protein and lymph node metastasis of the patients with breast cancer were obviously positive correlation (P<0.05), and expression of Plk3 protein and lymph node metastasis of the patients with breast cancer were obviously negative correlation （P<0.05). Expression of ER mRNA in the MCF-7 cell was high, but expression of ER mRNA in the MDA-MB-231 cell was low. After stimulated by estrogen, Efp mRNA expression of the MDA-MB-231 cell did not obviously changed. After stimulated by estrogen, mRNA and protein expressions of Efp gene of the MCF-7 cell significantly increased (P<0.05), however expressions of Plk3 mRNA and its protein did not markedly changed, expression of Plk3 protein was not detected also. After treated by MG132, expression of Plk3 protein in the MCF-7 cell evidently increased. After stimulated by estrogen, treatment of MG132 significantly increased expression of Efp protein and decreased expression of Plk3 protein in the MCF-7 cell (all P<0.05). Conclusion: There was obvious negative correlation between expressions of Efp and Plk3 proteins in the ER positive breast cancer. Efp protein could improve degradation of Plk3 protein, and could involve in drug resistance process of endocrine therapy for patients with ER positive breast cancer.
Objective:To explore the expressions of Efp and PlK3 in patients with estroen receptor (ER) positive breast cancer and to analyze their clinical significance and possible mechanisms of the actions. Methods: Immuno histochemistry was used to detect expressions of Efp and PlK3 proteins in ER positive breast cancer tissues of 86 cases who were hospitalized in Department of Breast Surgery, the 4th Hospital of Hebei Medical University during January to June, 2010. Correlation between expressions of the both protein and their relationship with clinical pathological features were analyzed. Expressions of ER and Efp mRNAs in breast cancer MCF-7 and MDA-MB-231 line cells were detected by qRT-PCR assay. RT-PCR and Western blotting assays were used to check expression changes of Efp and Plk3 genes in ER positive breast cancer MCF-7 line cell after stimulation of estrogen. Expression changes of Efp and Plk3 proteins in the MCF-7 cell after treatments with estrogen and protease inhibitor MG132 were detected by Western blotting assay. Results:In ER positive breast cancer tissues of the 86 cases, Efp expression of 55 cases was positive (64.0%) and PIk3 expression of 28 cases was positive (32.6%). Positive expression of PIk3 was 23.6% in the tissues of Efp positive expression and that was 48.4% in the tissues of Efp negative expression. There was a significant negative correlation between expressions of Efp protein and Plk3 protein (P<0.05). Expression of Efp protein and lymph node metastasis of the patients with breast cancer were obviously positive correlation (P<0.05), and expression of Plk3 protein and lymph node metastasis of the patients with breast cancer were obviously negative correlation （P<0.05). Expression of ER mRNA in the MCF-7 cell was high, but expression of ER mRNA in the MDA-MB-231 cell was low. After stimulated by estrogen, Efp mRNA expression of the MDA-MB-231 cell did not obviously changed. After stimulated by estrogen, mRNA and protein expressions of Efp gene of the MCF-7 cell significantly increased (P<0.05), however expressions of Plk3 mRNA and its protein did not markedly changed, expression of Plk3 protein was not detected also. After treated by MG132, expression of Plk3 protein in the MCF-7 cell evidently increased. After stimulated by estrogen, treatment of MG132 significantly increased expression of Efp protein and decreased expression of Plk3 protein in the MCF-7 cell (all P<0.05). Conclusion: There was obvious negative correlation between expressions of Efp and Plk3 proteins in the ER positive breast cancer. Efp protein could improve degradation of Plk3 protein, and could involve in drug resistance process of endocrine therapy for patients with ER positive breast cancer.
2016, 23(6):801-805.
DOI: 10.3872/j.issn.1007-385X.2016.06.011
Abstract:
Objective:To analyze structures of specific glycans in breast carcinoma, in order to provide potential early diagnostic markers for breast carcinoma.Methods: Fifteen specimens of breast carcinoma and five specimens of tissues adjacent to the carcinoma margin 3-5 cm surgical resected from the patients with breast cancer who were hospitalized in Department of Galactophore, Tumor Hospital of Shaanxi Province during May 2014 to September 2014 were collected. In addition, four specimens of breast lobular hyperplasia tissues were selected. Tissue proteins were extracted. Using filter membrane assisted method for the release of glycoprotein glycans, N-linked glycans were obtained. Type distributions and content changes of glycoprotein N-linked glycans in breast carcinoma, adjacent breast carcinoma and normal breast tissues were analyzed by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) technique. Results: hirtyeight,thirty four and twentytwo N-linked glycans were respectively identified in the breast cancer tissues, the adjacent tissues, and the normal breast tissues. Comparing with the paracarcinoma tissues and the normal breast tissues, contents of complex, high mannose, bisecting, fucosylated and two attenna types of N-linked glycans in the breast carcinoma tissues significantly decreased except for that content of high mannose type N-linked glycans obviously increased (P<0.05 or P<0.01). In the breast carcinoma tissue, contents of two types of high mannose type N-linked glycans, relative molecular masses of that were 1 580.455 and 1 742.490 respectively, were significantly higher than those in the normal breast tissues (P<0.05 or P<0.01), and contents of two types of complex type N-linked glycans, relative molecular masses of that were 1 647.473 and 1 850.583 respectively, were obviously lower than those in the normal breast tissues (P<0.05 or P<0.01). ROC curve analysis showed that the 4 kinds of N-linked glycanshave high detection accuracy (P<0.05 or P<0.01). Conclusion: Four types of specific N-linked glycans found in the breast carcinoma could be expected to become potential markers for early diagnosis and target therapy of the breast carcinoma.
Objective:To analyze structures of specific glycans in breast carcinoma, in order to provide potential early diagnostic markers for breast carcinoma.Methods: Fifteen specimens of breast carcinoma and five specimens of tissues adjacent to the carcinoma margin 3-5 cm surgical resected from the patients with breast cancer who were hospitalized in Department of Galactophore, Tumor Hospital of Shaanxi Province during May 2014 to September 2014 were collected. In addition, four specimens of breast lobular hyperplasia tissues were selected. Tissue proteins were extracted. Using filter membrane assisted method for the release of glycoprotein glycans, N-linked glycans were obtained. Type distributions and content changes of glycoprotein N-linked glycans in breast carcinoma, adjacent breast carcinoma and normal breast tissues were analyzed by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) technique. Results: hirtyeight,thirty four and twentytwo N-linked glycans were respectively identified in the breast cancer tissues, the adjacent tissues, and the normal breast tissues. Comparing with the paracarcinoma tissues and the normal breast tissues, contents of complex, high mannose, bisecting, fucosylated and two attenna types of N-linked glycans in the breast carcinoma tissues significantly decreased except for that content of high mannose type N-linked glycans obviously increased (P<0.05 or P<0.01). In the breast carcinoma tissue, contents of two types of high mannose type N-linked glycans, relative molecular masses of that were 1 580.455 and 1 742.490 respectively, were significantly higher than those in the normal breast tissues (P<0.05 or P<0.01), and contents of two types of complex type N-linked glycans, relative molecular masses of that were 1 647.473 and 1 850.583 respectively, were obviously lower than those in the normal breast tissues (P<0.05 or P<0.01). ROC curve analysis showed that the 4 kinds of N-linked glycanshave high detection accuracy (P<0.05 or P<0.01). Conclusion: Four types of specific N-linked glycans found in the breast carcinoma could be expected to become potential markers for early diagnosis and target therapy of the breast carcinoma.
2016, 23(6):806-812.
DOI: 10.3872/j.issn.1007-385X.2016.06.012
Abstract:
Objective:To explore effect abnormal expression of serine-threonine kinase receptor-associated protein (STRAP) on differentiation of gastriic cancer cells. Methods: Two hundred fifty three cases of surgically resected gastric carcinoma specimens in Department of Digestive Tumor Surgery, Tumor Hospital of Peking University during January 1991 to January 2009 were collected. At the same time, 103 cases of carcinoma adjacent tissue from the same lot of the patients with gastric carcinoma were collected as control. Tissue microarrays were prepared. Immuno histochemistry assay was used to detect expressions of STRAP protein in the gastric carcinoma tissues and the carcinoma adjacent tissues, and relationship between expressions of the STRAP protein and clinical pathological factors, namely differentiation of gastric carcinoma cells, clinical staging and so on was analyzed. Relationship between abnormal expression of STRAP protein and prognosis of the patients with gastric carcinoma was analyzed by Kaplan-Meier survival analysis. STRAP eukaryotic expression vectors were transfected into gastric carcinoma SGC7901 line cells. After the transfection, expressions of STRAP protein in the SGC7901 cells were examined by Western blotting, proliferation abilities of the SGC7901 cells were detected by MTT test, expressions of the gastric cancer cell differentiation associated-protein pepsinogen C (PGC) in the SGC7901 cells were checked by immuno fluorescence staining assay. Meanwhile activity of alkaline phosphatases (AKP）in the cells with excessive expression of STRAP was analyzed. Results: Positive expression rate of STRAP protein in the gastric carcinoma tissues was obviously lower than that in the carcinoma adjacent tissues (33.6% \[75/223\] vs 59.3% \[51/86\], P<001), and the expression level of STRAP was closely related to defferentiation grade of the gastric carcinoma cells (P<0.05), prognosis survival of the patients with high expression of STRAP protein was evidently longer than that of the patients with low expression of the protein (P<0.05). After overexpression of STRAP protein in the gastirc carcinoma SGC7901 cells, proliferation ability of the cells significantly attenuated (P<0.05), expression of the PGC obviously increased (P<0.05), and activity of the AKP evidently decreased (P<0.05). Conclusion: There could be a strong link between expression level of STRAP protein in the gastric carcinoma tissues and differentiation of the gastric carcinoma cells, the STRAP protein as a molecualr marker might have a good clinical value for differentiation grade of the gastric carcinoma cells and supplementary judgment of prognosis in the patients with gastric carcinoma.
Objective:To explore effect abnormal expression of serine-threonine kinase receptor-associated protein (STRAP) on differentiation of gastriic cancer cells. Methods: Two hundred fifty three cases of surgically resected gastric carcinoma specimens in Department of Digestive Tumor Surgery, Tumor Hospital of Peking University during January 1991 to January 2009 were collected. At the same time, 103 cases of carcinoma adjacent tissue from the same lot of the patients with gastric carcinoma were collected as control. Tissue microarrays were prepared. Immuno histochemistry assay was used to detect expressions of STRAP protein in the gastric carcinoma tissues and the carcinoma adjacent tissues, and relationship between expressions of the STRAP protein and clinical pathological factors, namely differentiation of gastric carcinoma cells, clinical staging and so on was analyzed. Relationship between abnormal expression of STRAP protein and prognosis of the patients with gastric carcinoma was analyzed by Kaplan-Meier survival analysis. STRAP eukaryotic expression vectors were transfected into gastric carcinoma SGC7901 line cells. After the transfection, expressions of STRAP protein in the SGC7901 cells were examined by Western blotting, proliferation abilities of the SGC7901 cells were detected by MTT test, expressions of the gastric cancer cell differentiation associated-protein pepsinogen C (PGC) in the SGC7901 cells were checked by immuno fluorescence staining assay. Meanwhile activity of alkaline phosphatases (AKP）in the cells with excessive expression of STRAP was analyzed. Results: Positive expression rate of STRAP protein in the gastric carcinoma tissues was obviously lower than that in the carcinoma adjacent tissues (33.6% \[75/223\] vs 59.3% \[51/86\], P<001), and the expression level of STRAP was closely related to defferentiation grade of the gastric carcinoma cells (P<0.05), prognosis survival of the patients with high expression of STRAP protein was evidently longer than that of the patients with low expression of the protein (P<0.05). After overexpression of STRAP protein in the gastirc carcinoma SGC7901 cells, proliferation ability of the cells significantly attenuated (P<0.05), expression of the PGC obviously increased (P<0.05), and activity of the AKP evidently decreased (P<0.05). Conclusion: There could be a strong link between expression level of STRAP protein in the gastric carcinoma tissues and differentiation of the gastric carcinoma cells, the STRAP protein as a molecualr marker might have a good clinical value for differentiation grade of the gastric carcinoma cells and supplementary judgment of prognosis in the patients with gastric carcinoma.
GONG Fusheng
,
CHEN Luchuan
,
YANG Jianwei
,
WEI Shenghong
,
XIE Yunqing
,
LIN Xiaowei
,
YING Mingang
,
ZHENG Qiuhong
2016, 23(6):813-818.
DOI: 10.3872/j.issn.1007-385X.2016.06.013
Abstract:
Objective:To explore the curative effect and safety of autologous tumor antigen loaded dendritic cells combined with cytokine-induced killer (DC-CIK) cells in the treatment of patients with gastric cancer. Methods: Two hundred seventy patients who received operative resection of gastric cancer in Fujian Provincial Cancer Hospital during January, 2005 to January, 2010 were retrospectively analyzed. Acording to wether receiving DC-CIK therapy, the patients were divided into DC-CIK treatment group (120 cases) and control group (150 cases). Flow cytometry assay was used to analyze phenotype of DC-CIK cells. Overall survival (OS) between both groups was compared. Advers reactions of the DC-CIK therapy were observed. And prognostic factors of the gastric cancer were analyzed by Cox regression model. Results: In the mature DC, the percentages of HLA-DR+, CD8+, CD83+ and CD86+ cells were（96.16±151）%, （96.58±2.66）%, （96.44±2.20）%, and （98.74±0.76）% respectively. In CIK cells. the proportions of CD3+，CD3+CD4+，CD3+CD8+ and CD3+CD16+/CD56+ cells were （91.98±5.9）%，（25.19±10.5）%，（71.15±7.8）% and （18.73±7.4）% respectively. The median OS was 77 months in the DC-CIK treatment group and compared to OS median of 51 months in the control group, the difference was significant (χ2＝4.431，P<0.05). DC-CIK therapy, adjuvant chemotherapy and TNM stage are independent prognostic factors for gastric cancer. Common adverse reactions are fever, chill and weakness in the DC-CIK therapy. Conclusion: Autologous tumor antigen-loaded DC-CIK therapy could prolong OS of patients with gastric cancer after operation of gastric cancer, and have little adverse reactions as well as be safety and effective.
Objective:To explore the curative effect and safety of autologous tumor antigen loaded dendritic cells combined with cytokine-induced killer (DC-CIK) cells in the treatment of patients with gastric cancer. Methods: Two hundred seventy patients who received operative resection of gastric cancer in Fujian Provincial Cancer Hospital during January, 2005 to January, 2010 were retrospectively analyzed. Acording to wether receiving DC-CIK therapy, the patients were divided into DC-CIK treatment group (120 cases) and control group (150 cases). Flow cytometry assay was used to analyze phenotype of DC-CIK cells. Overall survival (OS) between both groups was compared. Advers reactions of the DC-CIK therapy were observed. And prognostic factors of the gastric cancer were analyzed by Cox regression model. Results: In the mature DC, the percentages of HLA-DR+, CD8+, CD83+ and CD86+ cells were（96.16±151）%, （96.58±2.66）%, （96.44±2.20）%, and （98.74±0.76）% respectively. In CIK cells. the proportions of CD3+，CD3+CD4+，CD3+CD8+ and CD3+CD16+/CD56+ cells were （91.98±5.9）%，（25.19±10.5）%，（71.15±7.8）% and （18.73±7.4）% respectively. The median OS was 77 months in the DC-CIK treatment group and compared to OS median of 51 months in the control group, the difference was significant (χ2＝4.431，P<0.05). DC-CIK therapy, adjuvant chemotherapy and TNM stage are independent prognostic factors for gastric cancer. Common adverse reactions are fever, chill and weakness in the DC-CIK therapy. Conclusion: Autologous tumor antigen-loaded DC-CIK therapy could prolong OS of patients with gastric cancer after operation of gastric cancer, and have little adverse reactions as well as be safety and effective.
LIU Xiaojun
,
HOU Xiaoming
,
ZHANG Jian
,
LI Chunmei
,
YANG Tianning
,
WANG Jinming
,
ZHAO Da
,
LI Xun
2016, 23(6):819-823.
DOI: 10.3872/j.issn.1007-385X.2016.06.014
Abstract:
Objective:To retrospectively evaluatethe efficacy, quality of life and safety of autologous DC-CIK cells in patients with advanced gastric cancer. Methods: Seventy patientswith advanced gastric cancer who received autologous DC-CIK immunotherapy plus chemotherapy, defined as combination group, were analyzed. Another seventy gastric cancer patients with similar clinical characteristics and received chemotherapy alone, defined as control group,were also selected. The response rate, survival, quality of life and toxicities were respectively analyzed for two groups. Results: In combination group and control group, the response rate was 37.8% versus 29.5% (P>0.05), disease control rate 80.0% versus 59.1% (P<0.05), progression-free survival 7.0 months versus 5.0 months (HR 0.62,95%CI 0.41-0.92, P<0.05) and overall survival 13.0 months versus 10.8 months (HR 0.68,95%CI 0.45-1.02, P>0.05). Compared to that in control group, the quality of life did not decrease obviously after chemotheray in combination group. No severe toxicity was observed after infusion of DC-CIK cells. Conclusion: DC-CIK immunotherapy in combination with chemotherapy demonstrated some clinical benefits, and no severe toxicity appeared in patients with advanced gastric cancer.
Objective:To retrospectively evaluatethe efficacy, quality of life and safety of autologous DC-CIK cells in patients with advanced gastric cancer. Methods: Seventy patientswith advanced gastric cancer who received autologous DC-CIK immunotherapy plus chemotherapy, defined as combination group, were analyzed. Another seventy gastric cancer patients with similar clinical characteristics and received chemotherapy alone, defined as control group,were also selected. The response rate, survival, quality of life and toxicities were respectively analyzed for two groups. Results: In combination group and control group, the response rate was 37.8% versus 29.5% (P>0.05), disease control rate 80.0% versus 59.1% (P<0.05), progression-free survival 7.0 months versus 5.0 months (HR 0.62,95%CI 0.41-0.92, P<0.05) and overall survival 13.0 months versus 10.8 months (HR 0.68,95%CI 0.45-1.02, P>0.05). Compared to that in control group, the quality of life did not decrease obviously after chemotheray in combination group. No severe toxicity was observed after infusion of DC-CIK cells. Conclusion: DC-CIK immunotherapy in combination with chemotherapy demonstrated some clinical benefits, and no severe toxicity appeared in patients with advanced gastric cancer.
2016, 23(6):824-829.
DOI: 10.3872/j.issn.1007-385X.2016.06.015
Abstract:
Objective:To explore expressions of galectin-9 in esophageal squamous cell cancer (ESCC) and para-carcinoma tissues and its effect on migration and invasion abilities of ESCC cells. Methods: Eighty nine samples of ESCC tissues and twenty samples of para-carcinoma tissues that are far from the the carcinoma tissue margin 5 cm or more which were resected from the patients with ESCC in Department of Thoracic Surgery, Ji’nan Central Hospital affiliated to Shandong University during January, 2012 to January, 2013 were collected. Immunohistochemistry assay was used to detect expressions of galectin-9 protein in the ESCC and the para-carcinoma tissues. Their relationships with clinical pathological features of the patients, such as genders, ages, invasion depths, tumor sizes, differentiated degrees, pathological stages (pTNM), lymphatic metastasis and so on were analyzed. pcDNA3.1-galectin-9 was transfected into human esophageal carcinoma EC9706 line cells with liposome mediated method. Effect of up-regulation expression of galectin-9 on migration and invasion abilities of the EC9706 cells were detected by cell scratch healing test and Transwell invasion assay. Results: Positive rate of galectin-9 protein expression in the ESCC tissues was obviously lower than that in the para-carcinoma tissues (25.8% \[23/89\] vs 50% \[10/20\], P<0.05). Expressions of galectin-9 protein and carcinoma differentiated degrees, lymphatic metastasis in the patients with ESCC related (all P<0.05), and genders, ages, tumor sizes, invasion depths, pTMN in the patients with ESCC did not related (P>0.05). After over expression of galectin-9 protein in the EC9706 cells, invasion and migration abilities of the carcinoma cells decreased significantly, comparing with negative control group (invasion ability: \[45.0±8.0\] vs \[160.0±12.0\], P<0.01; migration ability: \[20.6±2.1\] vs \[87.6±4.9\], P<0.05). Conclusion:Absence of galectin-9 expression might involve in occurrence and development of the esophageal carcinoma, galectin-9 could inhibit invasion and migration of the ESCC cells.
Objective:To explore expressions of galectin-9 in esophageal squamous cell cancer (ESCC) and para-carcinoma tissues and its effect on migration and invasion abilities of ESCC cells. Methods: Eighty nine samples of ESCC tissues and twenty samples of para-carcinoma tissues that are far from the the carcinoma tissue margin 5 cm or more which were resected from the patients with ESCC in Department of Thoracic Surgery, Ji’nan Central Hospital affiliated to Shandong University during January, 2012 to January, 2013 were collected. Immunohistochemistry assay was used to detect expressions of galectin-9 protein in the ESCC and the para-carcinoma tissues. Their relationships with clinical pathological features of the patients, such as genders, ages, invasion depths, tumor sizes, differentiated degrees, pathological stages (pTNM), lymphatic metastasis and so on were analyzed. pcDNA3.1-galectin-9 was transfected into human esophageal carcinoma EC9706 line cells with liposome mediated method. Effect of up-regulation expression of galectin-9 on migration and invasion abilities of the EC9706 cells were detected by cell scratch healing test and Transwell invasion assay. Results: Positive rate of galectin-9 protein expression in the ESCC tissues was obviously lower than that in the para-carcinoma tissues (25.8% \[23/89\] vs 50% \[10/20\], P<0.05). Expressions of galectin-9 protein and carcinoma differentiated degrees, lymphatic metastasis in the patients with ESCC related (all P<0.05), and genders, ages, tumor sizes, invasion depths, pTMN in the patients with ESCC did not related (P>0.05). After over expression of galectin-9 protein in the EC9706 cells, invasion and migration abilities of the carcinoma cells decreased significantly, comparing with negative control group (invasion ability: \[45.0±8.0\] vs \[160.0±12.0\], P<0.01; migration ability: \[20.6±2.1\] vs \[87.6±4.9\], P<0.05). Conclusion:Absence of galectin-9 expression might involve in occurrence and development of the esophageal carcinoma, galectin-9 could inhibit invasion and migration of the ESCC cells.
2016, 23(6):830-834.
DOI: 10.3872/j.issn.1007-385X.2016.06.016
Abstract:
Objective:To explore clinical efficacy of autologous CIK cell combined radiotherapy and chemotherapy for intermediate-advanced cervical cancer. Methods: In the randomized and controlled trial, 89 patients with intermediated-advanced cervical cancer, who were hospitalized in the center of tumor Diagnosis and Treatment, Kaifeng Center Hospital during October 2010 to July 2015, were divided into treatment group (44 cases for CIK cell combined radiatherapy and chemotherapy) and control group (45 cases for radiatherapy and chemotherapy alone) acording to ratio of 1∶1. Effective rates, survival periods, immunofunctions and qualities of life of the patients in the two groups were compared and analyzed. Results: Total effective rate of the patients in the treatment group was 88.64%, which was obviously higher than 68.89% in the control group (P<0.05). Survival rates for 1, 2 and 3 years in the treatment group were 93.18%, 72.27% and 4773% respectively, which were higher than 88.88%, 68.89% and 42.22% in the control group, but the differences were not statistically significant (P>0.05). Comparing with pre-treatment, peripheral blood CD3+ and CD4+/CD8+ of the patients in the treatment group at post-treatment significantly increased (P<0.05), and peripheral blood CD3+ and CD4+/CD8+ of the patients in the contol group at post-treatment significantly decreased (P<0.05). In the treatment group, as comparing post-treatment 25th day (T25) with pre-treatment 1st day (B1) only one item feeling had significant difference (t=2.0976, P<0.05), however in the contol group as comparing T25 with B1, body, role, social and holistic health had obvious differences (t=3.3463, 3.4080, 2.3402 and 3.3010. P<0.05 and 001). Comparison between the two groups at T25, body, social and holistic health had significant differences (t=28262, 2.5797 and 19923, P<0.05 and 0.01). Conclusion: Short-term efficacy of CIK cell combined radiotherapy and chemotherapy for the patients with intermediate-advanced cervical cancer might be better than that of radiotherapy and chemotherapy alone, which could obviously enhance immunofunction and improve life quality of the patients, but the benefit of prolonging the survival period of the patients has not yet been seen.
Objective:To explore clinical efficacy of autologous CIK cell combined radiotherapy and chemotherapy for intermediate-advanced cervical cancer. Methods: In the randomized and controlled trial, 89 patients with intermediated-advanced cervical cancer, who were hospitalized in the center of tumor Diagnosis and Treatment, Kaifeng Center Hospital during October 2010 to July 2015, were divided into treatment group (44 cases for CIK cell combined radiatherapy and chemotherapy) and control group (45 cases for radiatherapy and chemotherapy alone) acording to ratio of 1∶1. Effective rates, survival periods, immunofunctions and qualities of life of the patients in the two groups were compared and analyzed. Results: Total effective rate of the patients in the treatment group was 88.64%, which was obviously higher than 68.89% in the control group (P<0.05). Survival rates for 1, 2 and 3 years in the treatment group were 93.18%, 72.27% and 4773% respectively, which were higher than 88.88%, 68.89% and 42.22% in the control group, but the differences were not statistically significant (P>0.05). Comparing with pre-treatment, peripheral blood CD3+ and CD4+/CD8+ of the patients in the treatment group at post-treatment significantly increased (P<0.05), and peripheral blood CD3+ and CD4+/CD8+ of the patients in the contol group at post-treatment significantly decreased (P<0.05). In the treatment group, as comparing post-treatment 25th day (T25) with pre-treatment 1st day (B1) only one item feeling had significant difference (t=2.0976, P<0.05), however in the contol group as comparing T25 with B1, body, role, social and holistic health had obvious differences (t=3.3463, 3.4080, 2.3402 and 3.3010. P<0.05 and 001). Comparison between the two groups at T25, body, social and holistic health had significant differences (t=28262, 2.5797 and 19923, P<0.05 and 0.01). Conclusion: Short-term efficacy of CIK cell combined radiotherapy and chemotherapy for the patients with intermediate-advanced cervical cancer might be better than that of radiotherapy and chemotherapy alone, which could obviously enhance immunofunction and improve life quality of the patients, but the benefit of prolonging the survival period of the patients has not yet been seen.
2016, 23(6):835-839.
DOI: 10.3872/j.issn.1007-385X.2016.06.017
Abstract:
Objective: To explore relationship between polymorphism of rs283526 and rs8647 loci in ATF5 gene and genetic susceptibility of hepatocellular carcinoma (HCC) in Zhuang population of Fusui County, Guangxi Zhuang Autonomous Region. Methods: With case-control study, 79 cases of HCC family (observation group) and 40 cases of normal family (control group) in Zhuang population were selected from Fusui Country of Guangxi Zhuang Autonomous Region, mass spectrometry assay was used to examine distribution frequency of rs283526 and rs8647 loci in ATF5 gene among them. Correlation between various genotypes and onset risk of HCC were analyzed by unconditional Logistic regression method. Results: In population of the control group, HCC onset risks of individuals with rs283526 locus CT, TT genotype of ATF5 gene were 0.181 times (P<0.05) and 0.348 times (P<0.05) of individuals with CC genotype respectively, HCC onset risk of individuals with rs283526 locus T allele genotype was 0.405 times (P<0.01) of individuals with C allele genotype. In control population with rs8647 locus of ATF5 gene, HCC onset risks of individuals with GA, AA genotype were 1.022 times and 1.949 times, HCC onset risk of individuals with rs8647 A allele genotype was 0.925 times of individuals with G allele genotype, but all the differences were not statistically significant (P>0.05). Conclusion: There could be correlation between polymorphism of rs283526 locus of ATF5 gene and genetic susceptibility of HCC in Fusui Country of Guangxi Zhuang Autonomous Region, T allele genotype of ATF5 gene might be a protective factor of HCC.
Objective: To explore relationship between polymorphism of rs283526 and rs8647 loci in ATF5 gene and genetic susceptibility of hepatocellular carcinoma (HCC) in Zhuang population of Fusui County, Guangxi Zhuang Autonomous Region. Methods: With case-control study, 79 cases of HCC family (observation group) and 40 cases of normal family (control group) in Zhuang population were selected from Fusui Country of Guangxi Zhuang Autonomous Region, mass spectrometry assay was used to examine distribution frequency of rs283526 and rs8647 loci in ATF5 gene among them. Correlation between various genotypes and onset risk of HCC were analyzed by unconditional Logistic regression method. Results: In population of the control group, HCC onset risks of individuals with rs283526 locus CT, TT genotype of ATF5 gene were 0.181 times (P<0.05) and 0.348 times (P<0.05) of individuals with CC genotype respectively, HCC onset risk of individuals with rs283526 locus T allele genotype was 0.405 times (P<0.01) of individuals with C allele genotype. In control population with rs8647 locus of ATF5 gene, HCC onset risks of individuals with GA, AA genotype were 1.022 times and 1.949 times, HCC onset risk of individuals with rs8647 A allele genotype was 0.925 times of individuals with G allele genotype, but all the differences were not statistically significant (P>0.05). Conclusion: There could be correlation between polymorphism of rs283526 locus of ATF5 gene and genetic susceptibility of HCC in Fusui Country of Guangxi Zhuang Autonomous Region, T allele genotype of ATF5 gene might be a protective factor of HCC.
2016, 23(6):840-845.
DOI: 10.3872/j.issn.1007-385X.2016.06.018
Abstract:
嵌合抗原受体T细胞（chimeric antigen receptor-T cells，CAR-T细胞）是应用基因工程技术修饰后培养的T细胞，因其不受主要组织相容性复合体（major histocompatibility complex，MHC）的限制，具有特异性识别肿瘤抗原并杀伤肿瘤细胞的能力，可减少免疫耐受及免疫逃逸的发生，针对某种肿瘤抗原构建的CAR-T细胞可以广泛应用于临床治疗恶性肿瘤，目前已在一些血液系统肿瘤治疗中获得了满意的疗效。
嵌合抗原受体T细胞（chimeric antigen receptor-T cells，CAR-T细胞）是应用基因工程技术修饰后培养的T细胞，因其不受主要组织相容性复合体（major histocompatibility complex，MHC）的限制，具有特异性识别肿瘤抗原并杀伤肿瘤细胞的能力，可减少免疫耐受及免疫逃逸的发生，针对某种肿瘤抗原构建的CAR-T细胞可以广泛应用于临床治疗恶性肿瘤，目前已在一些血液系统肿瘤治疗中获得了满意的疗效。
2016, 23(6):846-851.
DOI: 10.3872/j.issn.1007-385X.2016.06.019
Abstract:
Runt相关转录因子(Runt-related transcription factor, RUNX)作为细胞信号传导的一类重要的转录因子，在发育、细胞增殖分化以及凋亡中起着关键的作用。近年的研究表明，RUNX与肿瘤的发生发展过程密切相关，不同的RUNX蛋白具有不同的组织表达特异性，能在不同的细胞环境中通过与不同的关键信号途径相互作用，发挥独特的生物学功能。深入了解RUNX在肿瘤中的表达和作用机制，探究其在肿瘤发生发展中的作用，将为肿瘤的早期诊断、治疗和预后提供可靠的依据。本文综述了RUNX的结构和活性调节，重点分析了近年来RUNX异常表达与肿瘤的关系，对RUNX相关的致癌信号通路，及其在肿瘤缺氧微环境中的作用的研究进展进行了总结。
Runt相关转录因子(Runt-related transcription factor, RUNX)作为细胞信号传导的一类重要的转录因子，在发育、细胞增殖分化以及凋亡中起着关键的作用。近年的研究表明，RUNX与肿瘤的发生发展过程密切相关，不同的RUNX蛋白具有不同的组织表达特异性，能在不同的细胞环境中通过与不同的关键信号途径相互作用，发挥独特的生物学功能。深入了解RUNX在肿瘤中的表达和作用机制，探究其在肿瘤发生发展中的作用，将为肿瘤的早期诊断、治疗和预后提供可靠的依据。本文综述了RUNX的结构和活性调节，重点分析了近年来RUNX异常表达与肿瘤的关系，对RUNX相关的致癌信号通路，及其在肿瘤缺氧微环境中的作用的研究进展进行了总结。
2016, 23(6):852-857.
DOI: 10.3872/j.issn.1007-385X.2016.06.020
Abstract:
溃疡性结肠炎作为一种慢性炎症性疾病，在严重降低患者生活质量的同时，其难治性与易癌变的特性也给医学研究带来了相当大的挑战。目前的研究表明，其炎症反应在肿瘤形成的不同阶段均发挥着极为重要的作用，包括肿瘤的出现，生长、侵袭和转移。深入探究和揭示炎症向肿瘤转变的细胞与分子机制，将为设计和开发治疗溃疡性结肠炎癌变的新方案奠定理论基础，本文就溃疡性结肠炎相关结直肠癌形成机制研究的最新进展作一综述。
溃疡性结肠炎作为一种慢性炎症性疾病，在严重降低患者生活质量的同时，其难治性与易癌变的特性也给医学研究带来了相当大的挑战。目前的研究表明，其炎症反应在肿瘤形成的不同阶段均发挥着极为重要的作用，包括肿瘤的出现，生长、侵袭和转移。深入探究和揭示炎症向肿瘤转变的细胞与分子机制，将为设计和开发治疗溃疡性结肠炎癌变的新方案奠定理论基础，本文就溃疡性结肠炎相关结直肠癌形成机制研究的最新进展作一综述。
2016, 23(6):858-864.
DOI: 10.3872/j.issn.1007-385X.2016.06.021
Abstract:
近年来神经胶质瘤的治疗正寻找新的途径，研究发现非编码小RNA（microRNA, miRNA）参与了与肿瘤相关的所有过程，包括增殖、凋亡、转移、血管生成、免疫应答等，通过抑制信号网络中特定分子表达，发挥促癌或抑癌作用；某些miRNA可以分泌至外周血血清参与循环，这些为神经胶质瘤分子靶向治疗及诊断预后提供基础。本文就近几年来神经胶质瘤中新发现的、且报道较多的miRNA进行综述。
近年来神经胶质瘤的治疗正寻找新的途径，研究发现非编码小RNA（microRNA, miRNA）参与了与肿瘤相关的所有过程，包括增殖、凋亡、转移、血管生成、免疫应答等，通过抑制信号网络中特定分子表达，发挥促癌或抑癌作用；某些miRNA可以分泌至外周血血清参与循环，这些为神经胶质瘤分子靶向治疗及诊断预后提供基础。本文就近几年来神经胶质瘤中新发现的、且报道较多的miRNA进行综述。
2016, 23(6):865-868.
DOI: 10.3872/j.issn.1007-385X.2016.06.022
Abstract:
非编码短序列RNA（microRNA，miRNA）是一类长度约为21～22个核苷酸的短序列、非编码、具有调控作用的单链RNA分子，可以在转录水平后调控mRNA的表达。作为一个重要的基因调节因子，miRNA在肿瘤中发挥癌基因或抑癌基因样作用，与肿瘤癌细胞的增殖、凋亡、转移、耐药等机制密切相关。卵巢癌是严重威胁女性健康的常见恶性肿瘤之一，在女性肿瘤中病死率居第5位，因病灶隐匿，不易早期发现，故发现时多为晚期，5年生存率低。随着miRNA在肿瘤中的深入研究，miRNA在卵巢癌中存在差异表达，其与卵巢癌的作用日渐明朗，有望成为新一代敏感的肿瘤标志物，并通过对其靶基因的研究，最终达到早期诊断及提高卵巢癌治疗效果的目的。
非编码短序列RNA（microRNA，miRNA）是一类长度约为21～22个核苷酸的短序列、非编码、具有调控作用的单链RNA分子，可以在转录水平后调控mRNA的表达。作为一个重要的基因调节因子，miRNA在肿瘤中发挥癌基因或抑癌基因样作用，与肿瘤癌细胞的增殖、凋亡、转移、耐药等机制密切相关。卵巢癌是严重威胁女性健康的常见恶性肿瘤之一，在女性肿瘤中病死率居第5位，因病灶隐匿，不易早期发现，故发现时多为晚期，5年生存率低。随着miRNA在肿瘤中的深入研究，miRNA在卵巢癌中存在差异表达，其与卵巢癌的作用日渐明朗，有望成为新一代敏感的肿瘤标志物，并通过对其靶基因的研究，最终达到早期诊断及提高卵巢癌治疗效果的目的。
2016, 23(6):869-873.
DOI: 10.3872/j.issn.1007-385X.2016.06.023
Abstract:
趋化因子（chemokine, CK）和循环肿瘤细胞（circulating tumor cells, CTC）在肿瘤定向转移中发挥重要作用。CK通过诱导肿瘤细胞上调基质金属蛋白酶（matrix metalloproteinase, MMP），降解细胞外周基质（extracellular matrix, ECM），发生上皮间质转化（epithelial-mesenchymal transition, EMT），抵抗失巢凋亡（anoikis）和免疫逃避等机制，最终形成CTC，发生“信号”归巢和器官定植，其中每一个步骤都有不同CK的正向或反向参与，其中有共性，也有差异。本文综合阐述CK在CTC的形成及其完成转移过程中的作用及可能机制；分析CK在CTC中的作用差异；探讨靶向CK信号轴个体化治疗肿瘤的研究现状及主要方向；为建立基于靶向CK信号轴治疗肿瘤的个体化治疗模式提供理论基础。
趋化因子（chemokine, CK）和循环肿瘤细胞（circulating tumor cells, CTC）在肿瘤定向转移中发挥重要作用。CK通过诱导肿瘤细胞上调基质金属蛋白酶（matrix metalloproteinase, MMP），降解细胞外周基质（extracellular matrix, ECM），发生上皮间质转化（epithelial-mesenchymal transition, EMT），抵抗失巢凋亡（anoikis）和免疫逃避等机制，最终形成CTC，发生“信号”归巢和器官定植，其中每一个步骤都有不同CK的正向或反向参与，其中有共性，也有差异。本文综合阐述CK在CTC的形成及其完成转移过程中的作用及可能机制；分析CK在CTC中的作用差异；探讨靶向CK信号轴个体化治疗肿瘤的研究现状及主要方向；为建立基于靶向CK信号轴治疗肿瘤的个体化治疗模式提供理论基础。
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.