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Volume 23,Issue 4,2016 Table of Contents
2016, 23(4):453-467.
DOI: 10.3872/j.issn.1007-385X.2016.04.001
Abstract:
Trastuzumab is a humanized monoclonal antibody targeting human epidermal growth factor receptor 2(HER2), which combined with chemotherapy drugs could significantly improve progression-free survival of patients. However, primary and acquired resistances of trastuzumab severely limit its curative effect and clinical application. Aberrant activation of PI3K/AKT/mTOR signaling pathway, interaction of HER family members, activation of compensatory survival signals under drug pressure and formation of phenotypes of cancer stem cells could be important mechanisms of the trastuzumab resistance. With deepening of research on mechanisms of trastuzumab resistance, treatments for overcoming trastuzumab resistance is also increasing. Some studies have shown that combination of trastuzumab with another monoclonal antibodies targeting HER2 extracellular domain or other HER family members could increase curative effect of trastuzumab. Application of small-molecule inhibitor of PI3K/AKT/mTOR signaling pathway or specific inhibitors of pro-survival signaling pathway that related to trastuzumab resisitance could effectively reverse the resistance and prolong progression-free survival of patients. In-depth researches on mechanisms of trastuzumab resistance and constant exploration on treatment strategies to reverse the resistance could provide the basis for establishment of individualized treatment plan of breast carcinoma.
Trastuzumab is a humanized monoclonal antibody targeting human epidermal growth factor receptor 2(HER2), which combined with chemotherapy drugs could significantly improve progression-free survival of patients. However, primary and acquired resistances of trastuzumab severely limit its curative effect and clinical application. Aberrant activation of PI3K/AKT/mTOR signaling pathway, interaction of HER family members, activation of compensatory survival signals under drug pressure and formation of phenotypes of cancer stem cells could be important mechanisms of the trastuzumab resistance. With deepening of research on mechanisms of trastuzumab resistance, treatments for overcoming trastuzumab resistance is also increasing. Some studies have shown that combination of trastuzumab with another monoclonal antibodies targeting HER2 extracellular domain or other HER family members could increase curative effect of trastuzumab. Application of small-molecule inhibitor of PI3K/AKT/mTOR signaling pathway or specific inhibitors of pro-survival signaling pathway that related to trastuzumab resisitance could effectively reverse the resistance and prolong progression-free survival of patients. In-depth researches on mechanisms of trastuzumab resistance and constant exploration on treatment strategies to reverse the resistance could provide the basis for establishment of individualized treatment plan of breast carcinoma.
2016, 23(4):468-475.
DOI: 10.3872/j.issn.1007-385X.2016.04.002
Abstract:
Objective:To prepare fusion protein of gonadotropin releasing hormone (GnRH) and M2 (GnRH/M2), and investigate inhibitory effect of DC vaccine sensitized with the fusion protein on melanoma B16F10 cell xenografts. Methods: An expression vector of pET28a-ansB-C-GnRH3-hinge-MVP-M2 plasmid was constructed and transferred into engineering bacteria. Under the induction of lactose, fusion protein of ansB-C-GnRH3-hinge-MVP-M2 was expressed as inclusion body in the transferred engineering bacteria. Then the fusion protein was purified by means of ultrasonic broken, washings and ethanol fractionation precipitation. After purification, protein polypeptide GnRH3-hinge-MVP-M2 was released by acid hydrolysis and isolated with DEAE-52 anion exchange chromatography. DCs were sensitized with the fusion polypeptide to obtain DC vaccine. Mouse models with melanoma B16F10 xenografts were established and divided into cyclophosphamide group (CTX), DC sensitized with GnRH/M2 fusion protein group (GDC), DC sensitized with tumor cell lysate group (BDC), DC sensitized with GnRH/M2 fusion protein plus cyclophosphamide group (GDCTX), DC sensitized with tumor cell lysate plus cyclophosphamide group (BDCTX) and normal saline group (NS), according to different vaccination. Effects of GnRH/M2 vaccine on growth of the xenografts, killing ability of CTL and proliferation of T cells in the mouse models were observed. Results: The pET28a-ansB-C-GnRH3-hinge-MVP-M2 plasmid was successfully constructed and the fusion protein efficiently expressed. Growth of the xenografts in GDC group was more slower than that in NS group obviously (P<0.05), and similar to that in BDC group (P>0.05). Although inhibitory effect on tumor in GDCTX group was further increased, but there not was any significant differences comparing with CTX group (P>0.05). Killing effect on B16F10 cells and proliferation effect on T cells in various treatment groups were significantly better than those in negative control groups (P<0.05 or P<0.01), but differences of them between GDC and BDC groups were not obvious (P>0.05). Conclusion: It was preliminarily proved that the DC vaccine sensitized with the fusion polypeptide GnRH/M2 could effectively inhibit growth of the melanoma B16F10 xenografts in the mouse model.
Objective:To prepare fusion protein of gonadotropin releasing hormone (GnRH) and M2 (GnRH/M2), and investigate inhibitory effect of DC vaccine sensitized with the fusion protein on melanoma B16F10 cell xenografts. Methods: An expression vector of pET28a-ansB-C-GnRH3-hinge-MVP-M2 plasmid was constructed and transferred into engineering bacteria. Under the induction of lactose, fusion protein of ansB-C-GnRH3-hinge-MVP-M2 was expressed as inclusion body in the transferred engineering bacteria. Then the fusion protein was purified by means of ultrasonic broken, washings and ethanol fractionation precipitation. After purification, protein polypeptide GnRH3-hinge-MVP-M2 was released by acid hydrolysis and isolated with DEAE-52 anion exchange chromatography. DCs were sensitized with the fusion polypeptide to obtain DC vaccine. Mouse models with melanoma B16F10 xenografts were established and divided into cyclophosphamide group (CTX), DC sensitized with GnRH/M2 fusion protein group (GDC), DC sensitized with tumor cell lysate group (BDC), DC sensitized with GnRH/M2 fusion protein plus cyclophosphamide group (GDCTX), DC sensitized with tumor cell lysate plus cyclophosphamide group (BDCTX) and normal saline group (NS), according to different vaccination. Effects of GnRH/M2 vaccine on growth of the xenografts, killing ability of CTL and proliferation of T cells in the mouse models were observed. Results: The pET28a-ansB-C-GnRH3-hinge-MVP-M2 plasmid was successfully constructed and the fusion protein efficiently expressed. Growth of the xenografts in GDC group was more slower than that in NS group obviously (P<0.05), and similar to that in BDC group (P>0.05). Although inhibitory effect on tumor in GDCTX group was further increased, but there not was any significant differences comparing with CTX group (P>0.05). Killing effect on B16F10 cells and proliferation effect on T cells in various treatment groups were significantly better than those in negative control groups (P<0.05 or P<0.01), but differences of them between GDC and BDC groups were not obvious (P>0.05). Conclusion: It was preliminarily proved that the DC vaccine sensitized with the fusion polypeptide GnRH/M2 could effectively inhibit growth of the melanoma B16F10 xenografts in the mouse model.
2016, 23(4):476-480.
DOI: 10.3872/j.issn.1007-385X.2016.04.003
Abstract:
Objective:To evaluate the function of melanoma-associated antigen (MAGE)-C2 antigen-specific CD8+T cells in peripheral blood of the patients with esophageal cancer, and analyze its relevance to clinical pathological parameters. Methods:Peripheral blood mononuclear cells (PBMCs) were obtained from 130 patients with esophageal cancer who were collected by Department of thoracic surgery, the First Hospital affiliated to Zhengzhou University during November 2014 and November 2015 with density gradient centrifugation. The patients with co-positive HLA-A2*0201 and MAGE-C2 were selected with flow cytometry and RT-PCR assays. After PBMCs of the patients were cultured for 7 and 14 days and treated with MAGE-C2(336-344) antigen peptide (1 μg/ml), IL-12 (100 μg/ml) and CD3/CD28 Dynabeads (2 μl) to induce amplification of antigen-specific CD8+ T cells, as well as CD107a on surface of CD8+ T cells and IFN-γ in the cells were detected with flow cytometry assay, and their relationships with clinical parameters were analyzed. Results: Fifty two patients with co-positive HLA-A2*0201 and MAGE-C2 were selected out. After their PBMCs were treated with MAGE-C2(336-344), percentage of CD107a+ IFN-γ+ / CD107a+ IFN-γ-/ CD107a-IFN-γ+ in CD8+ T cells of the treatment group was obviously increased (P<0.05). Expression of CD107a in early stage and highly differentiated esophageal cancer patients without lymphatic metastasis was obviously higher than that in advanced and poorly differentiated esophageal cancer patients with lymphatic metastasis (P<005). Expression of IFN-γ in patients with highly differentiated esophageal cancer was higher than that in patients with poorly differentiated esophageal cancer (P<0.05). Conclusion: Amplification of MAGE-C2 antigen-specific CD8+ T cells was successfully introduced, and associations of its function with esophageal cancer staging and lymphatic metastasis were found. It could become an ideal target for immunotherapy of the cancer.
Objective:To evaluate the function of melanoma-associated antigen (MAGE)-C2 antigen-specific CD8+T cells in peripheral blood of the patients with esophageal cancer, and analyze its relevance to clinical pathological parameters. Methods:Peripheral blood mononuclear cells (PBMCs) were obtained from 130 patients with esophageal cancer who were collected by Department of thoracic surgery, the First Hospital affiliated to Zhengzhou University during November 2014 and November 2015 with density gradient centrifugation. The patients with co-positive HLA-A2*0201 and MAGE-C2 were selected with flow cytometry and RT-PCR assays. After PBMCs of the patients were cultured for 7 and 14 days and treated with MAGE-C2(336-344) antigen peptide (1 μg/ml), IL-12 (100 μg/ml) and CD3/CD28 Dynabeads (2 μl) to induce amplification of antigen-specific CD8+ T cells, as well as CD107a on surface of CD8+ T cells and IFN-γ in the cells were detected with flow cytometry assay, and their relationships with clinical parameters were analyzed. Results: Fifty two patients with co-positive HLA-A2*0201 and MAGE-C2 were selected out. After their PBMCs were treated with MAGE-C2(336-344), percentage of CD107a+ IFN-γ+ / CD107a+ IFN-γ-/ CD107a-IFN-γ+ in CD8+ T cells of the treatment group was obviously increased (P<0.05). Expression of CD107a in early stage and highly differentiated esophageal cancer patients without lymphatic metastasis was obviously higher than that in advanced and poorly differentiated esophageal cancer patients with lymphatic metastasis (P<005). Expression of IFN-γ in patients with highly differentiated esophageal cancer was higher than that in patients with poorly differentiated esophageal cancer (P<0.05). Conclusion: Amplification of MAGE-C2 antigen-specific CD8+ T cells was successfully introduced, and associations of its function with esophageal cancer staging and lymphatic metastasis were found. It could become an ideal target for immunotherapy of the cancer.
2016, 23(4):481-485.
DOI: 10.3872/j.issn.1007-385X.2016.04.004
Abstract:
Objective:To study the effect of bridging intergrator-1 (Bin1) gene over-expression on migration and invasion abilities of non-small cell lung cancer A549 line cell, and initially discuss mechanism of its action. Methods: Eukaryotic expression plasmid CMV-MCS-GFP-SV40-Neomycin-Bin1 containing full length Bin1 gene sequence was transfected into the A549 cell using cationic liposomes and gene transfection technology (as Bin1 transfection group), as well as blanck control and empty plasmid transfection groups were set up. Expressions of Bin1mRNA and protein in various treatment groups were detected with PT-PCR and Western blotting assays. Effects of Bin1over-expression on migration and invasion abilities of the A549 cell were examed by scarification and Transwell invasion tests respectively. Western blotting assay was used to detect effects of Bin1over-expression on NF-κB phosphorylation level and expressions of migration-related proteins, E-cadherin, N- cadherin and MMP-9, in the A549 cell.Results: Comparing with blanck control and empty plasmid transfection groups, expressions of Bin1 mRNA and protein in the A549 cell of Bin1 transfection group increased significantly (all P<0.05). Cell abilities of migration and invasion in Bin1transfection group were significantly lower than those in empty plasmid transfection and blanck control groups (number of penetrating cells: \[50.50±3.15\] vs \[124.00±425\], \[130.00±4.37\], all P<0.05). In the A549 cell of Bin1transfection group, expressions of NF-κB and E-cadherin obviously increased (all P<0.05), and expressions of p-NF-κB, N- cadherin and MMP-9 significantly decreased (all P<0.05), compared to empty plasmid transfection and blanck control groups. Conclusion: Over-expression of Bin1 could inhibit abilities of migration and invasion of the A549 cell, and its mechanism might be associated with inactivation of NF-κB pathway and expression changes of cell migration and invasion-related proteins.
Objective:To study the effect of bridging intergrator-1 (Bin1) gene over-expression on migration and invasion abilities of non-small cell lung cancer A549 line cell, and initially discuss mechanism of its action. Methods: Eukaryotic expression plasmid CMV-MCS-GFP-SV40-Neomycin-Bin1 containing full length Bin1 gene sequence was transfected into the A549 cell using cationic liposomes and gene transfection technology (as Bin1 transfection group), as well as blanck control and empty plasmid transfection groups were set up. Expressions of Bin1mRNA and protein in various treatment groups were detected with PT-PCR and Western blotting assays. Effects of Bin1over-expression on migration and invasion abilities of the A549 cell were examed by scarification and Transwell invasion tests respectively. Western blotting assay was used to detect effects of Bin1over-expression on NF-κB phosphorylation level and expressions of migration-related proteins, E-cadherin, N- cadherin and MMP-9, in the A549 cell.Results: Comparing with blanck control and empty plasmid transfection groups, expressions of Bin1 mRNA and protein in the A549 cell of Bin1 transfection group increased significantly (all P<0.05). Cell abilities of migration and invasion in Bin1transfection group were significantly lower than those in empty plasmid transfection and blanck control groups (number of penetrating cells: \[50.50±3.15\] vs \[124.00±425\], \[130.00±4.37\], all P<0.05). In the A549 cell of Bin1transfection group, expressions of NF-κB and E-cadherin obviously increased (all P<0.05), and expressions of p-NF-κB, N- cadherin and MMP-9 significantly decreased (all P<0.05), compared to empty plasmid transfection and blanck control groups. Conclusion: Over-expression of Bin1 could inhibit abilities of migration and invasion of the A549 cell, and its mechanism might be associated with inactivation of NF-κB pathway and expression changes of cell migration and invasion-related proteins.
2016, 23(4):486-491.
DOI: 10.3872/j.issn.1007-385X.2016.04.005
Abstract:
Objective:To establish a gastric cancer cell line with high metastasis and explore biological characteristics of cancer stem cell for the cell line. Methods: The gastric cancer SNU-5 line cells were subcutaneously injected into nude mice. After a xenotransplanted tumor was formed, pulmonary metastasis of the tumor was taken out and repeatedly injected into nude mice by mechanical separation method, as well as the SNU-5-V12 cell line was achieved. Serum free suspension culture and PKH26 staining were used to confirm that there are cancer stem cells in the SNU-5-V12 cells. Expressions of cancer stem cell marker CD44 in the SUN-5 and the SUN-5-V12 cell lines were analyzed with flow cytometry assay. CD44+ cells in the SNU-5 and the SNU-5-V12 cell lines were separated and research in vitro of biological characteristics and tumorigenic experiments in nude mice were performed with the CD44+ cells. Results:The SNU-5-V12 cell line with high metastasis was established. There was a single PKH26 positive cell in spheroids formed by the SNU-5-V12 cells after serum free suspension culture for 11 days. Analysis of flow cytometry shown that ratio of cancer stem cell marker CD44 in SNU-5-V12 cell with high metastasis was significantly higher than that in the SNU-5 cell (\[72.9±1.5\]% vs \[8.96±1.2\]%), and self-renewal capacity of the CD44+ cells in the SNU-5-V12 cells was obviously stronger than that in the SNU-5 cells (forming spheroid rate: \[27.8±1.7\]% vs \[20.4±10\]%, P<0.01), as well as invasion ability of the SNU-5-V12 cells increased 1.6 times (\[329.5±7.5\] vs \[200±20\], P<0.01）, its drug resistant ability also enhanced significantly (IC50: \[0.286 vs 0.196\]μg/ml, P<0.01). At two months of the injection, third one nude mice (2/6) that injected with 2×102 the SNU-5-V12 cells formed xenotransplanted tumor, but only minority nude mice (1/6) that injected with 2×104 the SNU-5 cells formed xenotransplanted tumor. Conclusion:A gastric cancer the SNU-5-V12 cell line with high metastasis was obtained. In vivo and in vitro functions of CD44+ cell in the SNU-5-V12 cell line significantly increased. It could provide a valuable cell model for target therapy of gastric cancer stem cell.
Objective:To establish a gastric cancer cell line with high metastasis and explore biological characteristics of cancer stem cell for the cell line. Methods: The gastric cancer SNU-5 line cells were subcutaneously injected into nude mice. After a xenotransplanted tumor was formed, pulmonary metastasis of the tumor was taken out and repeatedly injected into nude mice by mechanical separation method, as well as the SNU-5-V12 cell line was achieved. Serum free suspension culture and PKH26 staining were used to confirm that there are cancer stem cells in the SNU-5-V12 cells. Expressions of cancer stem cell marker CD44 in the SUN-5 and the SUN-5-V12 cell lines were analyzed with flow cytometry assay. CD44+ cells in the SNU-5 and the SNU-5-V12 cell lines were separated and research in vitro of biological characteristics and tumorigenic experiments in nude mice were performed with the CD44+ cells. Results:The SNU-5-V12 cell line with high metastasis was established. There was a single PKH26 positive cell in spheroids formed by the SNU-5-V12 cells after serum free suspension culture for 11 days. Analysis of flow cytometry shown that ratio of cancer stem cell marker CD44 in SNU-5-V12 cell with high metastasis was significantly higher than that in the SNU-5 cell (\[72.9±1.5\]% vs \[8.96±1.2\]%), and self-renewal capacity of the CD44+ cells in the SNU-5-V12 cells was obviously stronger than that in the SNU-5 cells (forming spheroid rate: \[27.8±1.7\]% vs \[20.4±10\]%, P<0.01), as well as invasion ability of the SNU-5-V12 cells increased 1.6 times (\[329.5±7.5\] vs \[200±20\], P<0.01）, its drug resistant ability also enhanced significantly (IC50: \[0.286 vs 0.196\]μg/ml, P<0.01). At two months of the injection, third one nude mice (2/6) that injected with 2×102 the SNU-5-V12 cells formed xenotransplanted tumor, but only minority nude mice (1/6) that injected with 2×104 the SNU-5 cells formed xenotransplanted tumor. Conclusion:A gastric cancer the SNU-5-V12 cell line with high metastasis was obtained. In vivo and in vitro functions of CD44+ cell in the SNU-5-V12 cell line significantly increased. It could provide a valuable cell model for target therapy of gastric cancer stem cell.
2016, 23(4):492-497.
DOI: 10.3872/j.issn.1007-385X.2016.04.006
Abstract:
Objective:To confirm cancer stem cell characteristics of CD44+ gastric cancer cell in orthotopic carcinoma xenograft model. Methods: MKN-45 gastric cancer line cells were separated into two cell groups, CD44+ and CD44-, with flow cytometry assay, as well as non-separated MKN-45 gastric cancer cell as control. Proliferation in vitro of CD44+ gastric cancer cell was detected by MTT and colony formation assays and its invasion ability in vitro tested by Transwell assay. The above gastric cancer cells were injected into nude mice by orthotopic tansplantation method. The transplanted nude mice were killed and detected for their rates of tumor formation after breeding for 8 weeks under the same conditions. Their livers were taken out and counted the number of hepatic metastasis. Shapes of gastric tumor and metastatic tumor in liver were observed with H-E staining. Numbers of the CD44+ cell in both the tumors were counted by immunofluorescence assay. Results: Compared with CD44- gastric cancer cell, proliferation and invasion abilities of CD44+ gastric cancer cell obviously enhanced ( all P<0.01), formation of tumor and metastasis more frequently occurred (P<005), but compared with non-separated MKN-45 gastric cancer cell there not were any statistic differences (P>0.05). Whether in primary tumor or in metastatic one, CD44+ gastric cancer cells could all produce CD44- gastric cancer cells, but the latter could not produce the CD44+ cells. Conclusion: Compared with CD44- gastric cancer cells, CD44+ MKN-45 gastric cancer cells could have more stronger proliferation and invasion abilities, and be more likely to become tumor and metastasis, which meet partial characteristics of cancer stem cell. It might be valuable to further investige.
Objective:To confirm cancer stem cell characteristics of CD44+ gastric cancer cell in orthotopic carcinoma xenograft model. Methods: MKN-45 gastric cancer line cells were separated into two cell groups, CD44+ and CD44-, with flow cytometry assay, as well as non-separated MKN-45 gastric cancer cell as control. Proliferation in vitro of CD44+ gastric cancer cell was detected by MTT and colony formation assays and its invasion ability in vitro tested by Transwell assay. The above gastric cancer cells were injected into nude mice by orthotopic tansplantation method. The transplanted nude mice were killed and detected for their rates of tumor formation after breeding for 8 weeks under the same conditions. Their livers were taken out and counted the number of hepatic metastasis. Shapes of gastric tumor and metastatic tumor in liver were observed with H-E staining. Numbers of the CD44+ cell in both the tumors were counted by immunofluorescence assay. Results: Compared with CD44- gastric cancer cell, proliferation and invasion abilities of CD44+ gastric cancer cell obviously enhanced ( all P<0.01), formation of tumor and metastasis more frequently occurred (P<005), but compared with non-separated MKN-45 gastric cancer cell there not were any statistic differences (P>0.05). Whether in primary tumor or in metastatic one, CD44+ gastric cancer cells could all produce CD44- gastric cancer cells, but the latter could not produce the CD44+ cells. Conclusion: Compared with CD44- gastric cancer cells, CD44+ MKN-45 gastric cancer cells could have more stronger proliferation and invasion abilities, and be more likely to become tumor and metastasis, which meet partial characteristics of cancer stem cell. It might be valuable to further investige.
2016, 23(4):498-505.
DOI: 10.3872/j.issn.1007-385X.2016.04.007
Abstract:
Objective:To investigate the effect of celecoxib on chemotherapy sensitivity of T cell lymphoma and the possible mechanism. Methods：The proliferation activities of Jurkat and Hut78 cell lines treated with celecoxib at different concentrations for 24, 48 and 72 h were detected by MTT method. The inhibition effect of chemotherapy drugs \[cisplatinum(DDP), epirubicin (EPI), and vinblastine(VCR)\] associated with celecoxib at different doses on the proliferation of Jurkat and Hut78 cell lines was also detected using MTT method, meanwhile, the IC50 value was calculated. The apoptotic rates of Jurkat and Hut78 cells co-cultured with different chemotherapy drugs associated with celecoxib at different doses were analyzed by Flow Cytometry. Meanwhile, the effect of celecooxib on the expression of MDR1, MRP1, LRP and TopoⅡ at the level of mRNA and protein in Jurkat and Hut78 cells were investigated by Real-time PCR and Western blotting respectively. Results： After the treatment of celecoxib, the proliferation activity of Jurkat and Hut78 cells was inhibited in a dose-and time-dependent manner, and the killing effect of chemotherapy drugs on Jurkat and Hut78 cells was also obviously enhanced (P<0.05); in addition, the apoptotic rate of Jurkat and Hut78 cells was significantly elevated（P<001). The results of Real-time PCR and Western blotting showed that the expressions of MDR1, MRP1 and LRP were down-regulated and TopoⅡ was up-regulated at both mRNA and protein levels in Jurkat and Hut78 cell lines treated with celecoxib at different doses, compared with control group (P<0.05). Conclusion：Celecoxib can enhance the chemotherapy sensitivity of T lymphoma cells by regulating the expression of multidrug resistance（MDR） related genes; Thus, it has a wide application prospect in the clinical treatment of T cell lymphoma.
Objective:To investigate the effect of celecoxib on chemotherapy sensitivity of T cell lymphoma and the possible mechanism. Methods：The proliferation activities of Jurkat and Hut78 cell lines treated with celecoxib at different concentrations for 24, 48 and 72 h were detected by MTT method. The inhibition effect of chemotherapy drugs \[cisplatinum(DDP), epirubicin (EPI), and vinblastine(VCR)\] associated with celecoxib at different doses on the proliferation of Jurkat and Hut78 cell lines was also detected using MTT method, meanwhile, the IC50 value was calculated. The apoptotic rates of Jurkat and Hut78 cells co-cultured with different chemotherapy drugs associated with celecoxib at different doses were analyzed by Flow Cytometry. Meanwhile, the effect of celecooxib on the expression of MDR1, MRP1, LRP and TopoⅡ at the level of mRNA and protein in Jurkat and Hut78 cells were investigated by Real-time PCR and Western blotting respectively. Results： After the treatment of celecoxib, the proliferation activity of Jurkat and Hut78 cells was inhibited in a dose-and time-dependent manner, and the killing effect of chemotherapy drugs on Jurkat and Hut78 cells was also obviously enhanced (P<0.05); in addition, the apoptotic rate of Jurkat and Hut78 cells was significantly elevated（P<001). The results of Real-time PCR and Western blotting showed that the expressions of MDR1, MRP1 and LRP were down-regulated and TopoⅡ was up-regulated at both mRNA and protein levels in Jurkat and Hut78 cell lines treated with celecoxib at different doses, compared with control group (P<0.05). Conclusion：Celecoxib can enhance the chemotherapy sensitivity of T lymphoma cells by regulating the expression of multidrug resistance（MDR） related genes; Thus, it has a wide application prospect in the clinical treatment of T cell lymphoma.
2016, 23(4):506-509.
DOI: 10.3872/j.issn.1007-385X.2016.04.008
Abstract:
Objective:To observe effect of down-regulating microRNA-214 (miR-214) expression on migration and invasion of ovarian carcinoma SKOV-3 cells and explore its possible mechanism. Methods: miR-214 inhibitors were transfected into human ovarian carcinoma SKOV-3 cells by liposome. Expressions of miR-214, nuclear factor-κB (NF-κB) and urokinase-type plasminogen activator (uridylyl phosphate adenosine \[uPA\]) gene mRNA, as well as NF-κB and uPA proteins in the cells were respectively detected by Real-time PCR and Western blotting assays. Scarification test and transwell assay were used to detect abilities of migration and invasion of the cells respectively. Results: After transfection of miR-214 inhibitor, expression of miR-214 in human carcinoma SKOV-3 cells decreased, and migration and invasion abilities of the cells reduced. At the same time, expressions of NF-κB and uPA gene mRNA and proteins also depressed. Conclusion: Down-regulation of miR-214 expression in human ovarian carcinoma SKOV-3 cells could inhibit migration and invasion abilities of the cells, and down-regulation of NF-κB and uPA gene expressions might be its possible mechanism.
Objective:To observe effect of down-regulating microRNA-214 (miR-214) expression on migration and invasion of ovarian carcinoma SKOV-3 cells and explore its possible mechanism. Methods: miR-214 inhibitors were transfected into human ovarian carcinoma SKOV-3 cells by liposome. Expressions of miR-214, nuclear factor-κB (NF-κB) and urokinase-type plasminogen activator (uridylyl phosphate adenosine \[uPA\]) gene mRNA, as well as NF-κB and uPA proteins in the cells were respectively detected by Real-time PCR and Western blotting assays. Scarification test and transwell assay were used to detect abilities of migration and invasion of the cells respectively. Results: After transfection of miR-214 inhibitor, expression of miR-214 in human carcinoma SKOV-3 cells decreased, and migration and invasion abilities of the cells reduced. At the same time, expressions of NF-κB and uPA gene mRNA and proteins also depressed. Conclusion: Down-regulation of miR-214 expression in human ovarian carcinoma SKOV-3 cells could inhibit migration and invasion abilities of the cells, and down-regulation of NF-κB and uPA gene expressions might be its possible mechanism.
2016, 23(4):510-514.
DOI: 10.3872/j.issn.1007-385X.2016.04.009
Abstract:
Objective:To investigate the expression changes of IFN-γ，TGF-β1 and indoleamine-2,3-dioxygenase (IDO) in tumor microenvironment of non-small cell lung cancer(NSCLC) patients at different clinical stages, as well as the correlation between IDO expression and the expressions of IFN-γ，TGF-β1. Methods: 107 NSCLC tissue samples (experiment group) were obtained from patients who underwent surgical therapy or bronchoscopy biopsy at the Department of Thoracic Surgery of The 1st Affiliated Hospital of Kunming Medical University From January 2013 to June 2015, and 19 normal lung tissues (control group) were obtained from lung injury patients. The samples of experiment group were divided into four groups according to the 7th edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) system. Group 1: patients with stage Ⅰ (28 patients), group 2: patients with stage Ⅱ (26 patients), group 3: patients with stage Ⅲ (28 patients) and group 4: patients with stage Ⅳ (25 patients). The protein concentrations of IFN-γ, TGF-β1 and IDO were detected by ELISA and the IDO expression in tissues was assessed by immunohistochemistry. At same time, the correlations between IDO expression and IFN-γ, TGF-β1 expression in cancer tissues were evaluated. Results: Compared with control group, the IFN-γ expression in tissues of group 1 was significantly elevated（P<005), while its expressions in group 3 and group 4 were significantly decreased（P<0.05). Moreover, the IFN-γ expression in tissues of group 4 was significantly less than that of group 3（P<0.05). Similar to TGF-β1, the IDO expression in group1 was not significantly different with control group (P>0.05); but the TGF-β1 and IDO expressions in group 2, 3 and 4 were higher than those of normal tissues（P<0.05). Furthermore, The TGF-β1 and IDO expressions increased as the tumor stage went higher. Pearson correlation analysis showed that the IDO expressions in control group and group1 were directly correlate with IFN-γ（r=0.969, P<0.01, r=0.853, P<0.01）, but not correlate with TGF-β1. However, in group 2, 3 and 4, the IDO expressions were directly correlate with TGF-β1 （r=0.678, P<0.01, r=0810, P<0.01, r=0.630, P=0.01）, but not correlate with IFN-γ. Conclusion: Expression of IFN-γ in immune microenviroment of NSCLC patients increased at early stage, then with the progress of the disease, the immune function of patients was weakened and the expression of IFN-γ was reduced while the expressions of IDO and TGF-β1 were increased, indicating that IDO expression might be relate to IFN-γ at early stage of NSCLC, and relate to TGF-β1 at late stage.
Objective:To investigate the expression changes of IFN-γ，TGF-β1 and indoleamine-2,3-dioxygenase (IDO) in tumor microenvironment of non-small cell lung cancer(NSCLC) patients at different clinical stages, as well as the correlation between IDO expression and the expressions of IFN-γ，TGF-β1. Methods: 107 NSCLC tissue samples (experiment group) were obtained from patients who underwent surgical therapy or bronchoscopy biopsy at the Department of Thoracic Surgery of The 1st Affiliated Hospital of Kunming Medical University From January 2013 to June 2015, and 19 normal lung tissues (control group) were obtained from lung injury patients. The samples of experiment group were divided into four groups according to the 7th edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) system. Group 1: patients with stage Ⅰ (28 patients), group 2: patients with stage Ⅱ (26 patients), group 3: patients with stage Ⅲ (28 patients) and group 4: patients with stage Ⅳ (25 patients). The protein concentrations of IFN-γ, TGF-β1 and IDO were detected by ELISA and the IDO expression in tissues was assessed by immunohistochemistry. At same time, the correlations between IDO expression and IFN-γ, TGF-β1 expression in cancer tissues were evaluated. Results: Compared with control group, the IFN-γ expression in tissues of group 1 was significantly elevated（P<005), while its expressions in group 3 and group 4 were significantly decreased（P<0.05). Moreover, the IFN-γ expression in tissues of group 4 was significantly less than that of group 3（P<0.05). Similar to TGF-β1, the IDO expression in group1 was not significantly different with control group (P>0.05); but the TGF-β1 and IDO expressions in group 2, 3 and 4 were higher than those of normal tissues（P<0.05). Furthermore, The TGF-β1 and IDO expressions increased as the tumor stage went higher. Pearson correlation analysis showed that the IDO expressions in control group and group1 were directly correlate with IFN-γ（r=0.969, P<0.01, r=0.853, P<0.01）, but not correlate with TGF-β1. However, in group 2, 3 and 4, the IDO expressions were directly correlate with TGF-β1 （r=0.678, P<0.01, r=0810, P<0.01, r=0.630, P=0.01）, but not correlate with IFN-γ. Conclusion: Expression of IFN-γ in immune microenviroment of NSCLC patients increased at early stage, then with the progress of the disease, the immune function of patients was weakened and the expression of IFN-γ was reduced while the expressions of IDO and TGF-β1 were increased, indicating that IDO expression might be relate to IFN-γ at early stage of NSCLC, and relate to TGF-β1 at late stage.
JING Na
,
ZHANG Jinchao
,
YANG Yanli
,
WU Qiong
,
SUN Xuedong
,
ZHANG Xiaoyan
,
ZHAO Laiwei
,
PAN Xin
,
JIANG Hao
,
DING Guoliang
,
WANG Danhong
,
CHEN Hu
2016, 23(4):515-518.
DOI: 10.3872/j.issn.1007-385X.2016.04.010
Abstract:
Objective:To observe and evaluate the clinical efficacy and safety of natural killer cells (NK) on advanced hepatocellular carcinoma (HCC), as well as its influence on the activities of lymphocyte subsets and natural killer (NK) cells in peripheral blood of HCC patients. Methods: We collected peripheral blood (PB) from 30 patients with advanced hepatocellular carcinoma from September 2013 to September 2015 at No. 307 Hospital of PLA. The NK cells were generated through cultivation and induction in vitro, and were re-transfused into patients at the 14th and the 15th day. Two consecutive transfusions were regarded as one cycle, and there were totally two cycles. We detected the activities of lymphocyte subsets and NK cells in peripheral blood at pre-treatment and 2 weeks post-treatment for each cycle, respectively, and observed the activity changes of the lymphocyte subsets and NK cells before and after the treatment as well as its relationship to clinical efficacy. Results: Among the 30 HCC patients, there were 4 cases of PR, 19 cases of SD and 7 cases of PD after NK treatment; the objective response rate and disease control rate were 13.3% and 76.7 % respectively. The lymphocyte subsets didn't show obvious change, but the NK cell activity increased significantly after the treatment (\[5.06±4.46\]% vs \[6.68±3.83\] %, P<0.05). None of the 30 patients had adverse effects. Conclusion:The NK cell immunotherapy can improve the anti-tumor and immunity effect of body and slow-down the disease progression; it is a new and safe treatment approach for HCC patients.
Objective:To observe and evaluate the clinical efficacy and safety of natural killer cells (NK) on advanced hepatocellular carcinoma (HCC), as well as its influence on the activities of lymphocyte subsets and natural killer (NK) cells in peripheral blood of HCC patients. Methods: We collected peripheral blood (PB) from 30 patients with advanced hepatocellular carcinoma from September 2013 to September 2015 at No. 307 Hospital of PLA. The NK cells were generated through cultivation and induction in vitro, and were re-transfused into patients at the 14th and the 15th day. Two consecutive transfusions were regarded as one cycle, and there were totally two cycles. We detected the activities of lymphocyte subsets and NK cells in peripheral blood at pre-treatment and 2 weeks post-treatment for each cycle, respectively, and observed the activity changes of the lymphocyte subsets and NK cells before and after the treatment as well as its relationship to clinical efficacy. Results: Among the 30 HCC patients, there were 4 cases of PR, 19 cases of SD and 7 cases of PD after NK treatment; the objective response rate and disease control rate were 13.3% and 76.7 % respectively. The lymphocyte subsets didn't show obvious change, but the NK cell activity increased significantly after the treatment (\[5.06±4.46\]% vs \[6.68±3.83\] %, P<0.05). None of the 30 patients had adverse effects. Conclusion:The NK cell immunotherapy can improve the anti-tumor and immunity effect of body and slow-down the disease progression; it is a new and safe treatment approach for HCC patients.
11 Clinical curative effect of DC-CIK immunocyte therapy for the patients with advanced breast cancer
YAO Lu
,
ZHANG Yan
,
HUANG Weiqian
,
AI Yueqin
,
ZHENG Jie
,
GAO Yanrong
,
ZHANG Chuang
,
ZHAO Hua
,
HU Jianhua
,
JIANG Longwei
,
JIA Shaochang
2016, 23(4):519-524.
DOI: 10.3872/j.issn.1007-385X.2016.04.011
Abstract:
Objective:To evaluate the clinical efficacy and safety of dendritic cells (DCs) combined with cytokine-induced killer (CIK) cells in the treatment of advanced breast cancer, and to investigate the relevant prognostic factors. Methods: The clinical documents of 42 patients with advanced breast cancer that received DC/CIK treatment in 81st Hospital of PLA from August 2011 to December 2014 were retrospectively analyzed. Short-term curative effect was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) and the safety of DC-CIK therapy was observed. Overall survival of 42 patients was analyzed to evaluate the long-term curative effect. Univariate and multivariate analyses were used to analyze prognostic factors. The immunologic function was evaluated by paired T-test. Results: After the DC-CIK therapy, the overall response rate was 38.1% (16/42), the disease control rate was 61.9% (26/42), and the one-year, two-year and three-year survival rates were 59%, 48% and 48%, respectively. CA153 was significantly decreased after the treatment. In addition to a significant increase in the CD4+ level, the other peripheral blood lymphocyte subsets didn’t change significantly. Univariate analysis showed that the onset area (P=0.012) and the CA153 value before treatment (P=0.000) were the influence factors for the prognosis of cell immune therapy. Multivariate analysis showed that the CA153 value before treatment was an independent influence factor for the prognosis of cell immune therapy. Conclusion: The DC-CIK therapy is a safe and feasible therapeutic approach. It may improve the long-term survival rate of patients with advanced breast cancer.
Objective:To evaluate the clinical efficacy and safety of dendritic cells (DCs) combined with cytokine-induced killer (CIK) cells in the treatment of advanced breast cancer, and to investigate the relevant prognostic factors. Methods: The clinical documents of 42 patients with advanced breast cancer that received DC/CIK treatment in 81st Hospital of PLA from August 2011 to December 2014 were retrospectively analyzed. Short-term curative effect was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) and the safety of DC-CIK therapy was observed. Overall survival of 42 patients was analyzed to evaluate the long-term curative effect. Univariate and multivariate analyses were used to analyze prognostic factors. The immunologic function was evaluated by paired T-test. Results: After the DC-CIK therapy, the overall response rate was 38.1% (16/42), the disease control rate was 61.9% (26/42), and the one-year, two-year and three-year survival rates were 59%, 48% and 48%, respectively. CA153 was significantly decreased after the treatment. In addition to a significant increase in the CD4+ level, the other peripheral blood lymphocyte subsets didn’t change significantly. Univariate analysis showed that the onset area (P=0.012) and the CA153 value before treatment (P=0.000) were the influence factors for the prognosis of cell immune therapy. Multivariate analysis showed that the CA153 value before treatment was an independent influence factor for the prognosis of cell immune therapy. Conclusion: The DC-CIK therapy is a safe and feasible therapeutic approach. It may improve the long-term survival rate of patients with advanced breast cancer.
2016, 23(4):525-530.
DOI: 10.3872/j.issn.1007-385X.2016.04.012
Abstract:
Objective:To detect expressions of mRNAs and proteins for EMT-assosiated factors, E-cadherin and vimentin, and stem cell factor OCT4 in invasive breast cancer and correlation of OCT4 with E-cadherin and vimentin. Method: Fourty samples of invasive breast cancer tissues were collected. Expressions of mRNAs and proteins for EMT-assosiated factors, E-cadherin and vimentin, and stem cell factor OCT4 were respectively detected by Real-time quantitative PCR and immune histochemistry assay. Relationship between expressions of the mRNA and the proteins, and survival rates and clinical pathological features of the patients with invasive breast cancer, and correlation of OCT4 with E-cadherin and vimentin, were analyzed. Results:In the invasive breast cancer tissues, expression rates of OCT4, E-cadherin and vimentin were 30% (12/40), 55% (22/40), and 65% (26/40) respectively. The expression of OCT4 was correlated with age, histological grade, lymph node metastasis and Her-2 expression of the patients with invasive breast cancer. Expression of E-cadherin was related with lymph node metastasis and expression of vimentin was related with histological grade and lymph node metastasis. Expressions of mRNA and protein for OCT4 and E-cadherin were negatively correlated. Expressions of mRNA and protein for OCT4 and vimentin were positively correlated. Also expressions of mRNA and protein for E-cadherin and vimentin were negatively correlated. Survival rates of the patients with positive expression of OCT4 were significantly lower than those of the patients with negative expression of OCT4 (P<0.05). However there were no significant differences between expressions of E-cadherin and vimentin, and survival rates of the patients (P>0.05). Conclusion: Stem cells factor OCT4 might promote metastasis of the invasive breast cancer cells via EMT, and might be a factor affecting prognosis of the invasive breast cancer.
Objective:To detect expressions of mRNAs and proteins for EMT-assosiated factors, E-cadherin and vimentin, and stem cell factor OCT4 in invasive breast cancer and correlation of OCT4 with E-cadherin and vimentin. Method: Fourty samples of invasive breast cancer tissues were collected. Expressions of mRNAs and proteins for EMT-assosiated factors, E-cadherin and vimentin, and stem cell factor OCT4 were respectively detected by Real-time quantitative PCR and immune histochemistry assay. Relationship between expressions of the mRNA and the proteins, and survival rates and clinical pathological features of the patients with invasive breast cancer, and correlation of OCT4 with E-cadherin and vimentin, were analyzed. Results:In the invasive breast cancer tissues, expression rates of OCT4, E-cadherin and vimentin were 30% (12/40), 55% (22/40), and 65% (26/40) respectively. The expression of OCT4 was correlated with age, histological grade, lymph node metastasis and Her-2 expression of the patients with invasive breast cancer. Expression of E-cadherin was related with lymph node metastasis and expression of vimentin was related with histological grade and lymph node metastasis. Expressions of mRNA and protein for OCT4 and E-cadherin were negatively correlated. Expressions of mRNA and protein for OCT4 and vimentin were positively correlated. Also expressions of mRNA and protein for E-cadherin and vimentin were negatively correlated. Survival rates of the patients with positive expression of OCT4 were significantly lower than those of the patients with negative expression of OCT4 (P<0.05). However there were no significant differences between expressions of E-cadherin and vimentin, and survival rates of the patients (P>0.05). Conclusion: Stem cells factor OCT4 might promote metastasis of the invasive breast cancer cells via EMT, and might be a factor affecting prognosis of the invasive breast cancer.
GU Lina
,
SANG Meixiang
,
YIN Danjing
,
LIU Fei
,
LIU Shina
,
HUANG Weina
,
FAN Xiaojie
,
LIAN Yishui
,
SHAN Baoen
2016, 23(4):531-536.
DOI: 10.3872/j.issn.1007-385X.2016.04.013
Abstract:
Objective:To investigate the expressions of melanoma antigen (MAGE)-As in esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcioma (GCA), and to explore its correlation with clinical biological indicators and the prognosis in patients with ESCC and GCA. Methods: Cancerous (n=60) tissue samples and corresponding normal (n=60) adjacent tissues with normal morphology that 5 cm away from the lesions were collected from 60 patients with ESCC or GCA, who were surgically treated in Fourth Hospital of Hebei Medical University between September and November of 2010. In the meanwhile, testicular tissues (n=5) were collected from Men with prostate cancer as the positive control. Immunohistochemical staining was performed to assess the expressions of MAGE-As in carcinoma tissues and adjacent normal tissues. Results: The expression rates of MAGE-As protein in the tissues from ESCC and GCA were 6833% (41/60) and 58.33% (35/60) respectively, but it was not expressed in adjacent normal tissues. No correlation was found between MAGE-As protein expression and the age, gender, histological grade, clinical stage, tumor size, lymph node metastasis in patients with esophageal squamous cell carcinomas (P>0.05). MAGE-As protein expression was not correlated to the gender, age, clinical stage, tumor size, lymph node metastasis in patients with gastric cardia adenocarciomas (P>0.05), but positively related to the histological grade (P<0.05). Log-rank test showed that the survival time of ESCC patient (P=0.036) and GCA patients (P=0.045) with positive MAGE-As expression were significantly lower than those of the patients with negative expressions. Conclusion:MAGE-As proteins are the ESCC and GCA associated antigen. It may be regarded as a potential diagnostic and prognostic index in clinical settings.
Objective:To investigate the expressions of melanoma antigen (MAGE)-As in esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcioma (GCA), and to explore its correlation with clinical biological indicators and the prognosis in patients with ESCC and GCA. Methods: Cancerous (n=60) tissue samples and corresponding normal (n=60) adjacent tissues with normal morphology that 5 cm away from the lesions were collected from 60 patients with ESCC or GCA, who were surgically treated in Fourth Hospital of Hebei Medical University between September and November of 2010. In the meanwhile, testicular tissues (n=5) were collected from Men with prostate cancer as the positive control. Immunohistochemical staining was performed to assess the expressions of MAGE-As in carcinoma tissues and adjacent normal tissues. Results: The expression rates of MAGE-As protein in the tissues from ESCC and GCA were 6833% (41/60) and 58.33% (35/60) respectively, but it was not expressed in adjacent normal tissues. No correlation was found between MAGE-As protein expression and the age, gender, histological grade, clinical stage, tumor size, lymph node metastasis in patients with esophageal squamous cell carcinomas (P>0.05). MAGE-As protein expression was not correlated to the gender, age, clinical stage, tumor size, lymph node metastasis in patients with gastric cardia adenocarciomas (P>0.05), but positively related to the histological grade (P<0.05). Log-rank test showed that the survival time of ESCC patient (P=0.036) and GCA patients (P=0.045) with positive MAGE-As expression were significantly lower than those of the patients with negative expressions. Conclusion:MAGE-As proteins are the ESCC and GCA associated antigen. It may be regarded as a potential diagnostic and prognostic index in clinical settings.
2016, 23(4):537-544.
DOI: 10.3872/j.issn.1007-385X.2016.04.014
Abstract:
Objective:To investigate the promoter methylation status of Ras-association domain family 5A (RASSF5A) gene and its mRNA expression level in in the peripheral blood of patients with lymphoma and normal people as well as its correlation to clinical manifestations. Methods：Methylation-specific PCR (MSP) and Reverse Transcriptase-PCR(RT-PCR) method were used to examine the methylation status and the mRNA expression of RASSF5A gene in peripheral blood of patients with diffused large B cell lymphoma or T cell lymphoma and healthy participants. The relationship between RASSF5Agene methylation and clinical data was further analyzed. Results: The methylation frequencies of RASSF5A in diffused large B cell lymphoma and T cell lymphoma (64.9% \[48/74\] and 73.8% \[31/42\]) were significantly higher than that of healthy participants (7.1% \[3/42\], all P<0.05). The mRNA expressions of RASSF5A gene in diffused large B cell lymphoma and peripheral T cell lymphoma were (0.54±0.17) and (0.52±0.18), respectively, which were significantly lower than that of healthy participants (0.86±0.10) (P<0.05). The mRNA expression of RASSF5A gene with positive promoter methylation (\[0.51±0.18\]; \[0.50±0.15\]) was significantly lower than that of the gene with negative methylation (\[0.60±0.17\]; \[0.63±0.12\]) (all P<0.05) in both diffused large B cell lymphoma and T cell lymphoma. Methylation frequency of RASSF5A gene was associated with LDH, IPI, and Ki-67 (P<0.05) in diffused large B cell lymphoma, and associated with clinical stage, extranodal involvement and Ki-67 (P<0.05) in T cell lymphoma. The mRNA expression of RASSF5A gene was correlated with IPI score, extranodal involvement (P<0.05) in diffused large B cell lymphoma, and correlated with clinical stage and extranodal involvement (P<0.05) in T cell lymphoma. Conclusion: The methylation of RASSF5A gene may be associated with the occurrence of diffused large B cell lymphoma and T cell lymphoma, and mRNA expression silencing might be one of the mechanisms of epigenetics. RASSF5A gene may act as a tumor suppressor gene in diffused large B cell lymphoma and T cell lymphoma, which may be associated with tumor invasiveness, tumor malignant process and tumor prognosis.
Objective:To investigate the promoter methylation status of Ras-association domain family 5A (RASSF5A) gene and its mRNA expression level in in the peripheral blood of patients with lymphoma and normal people as well as its correlation to clinical manifestations. Methods：Methylation-specific PCR (MSP) and Reverse Transcriptase-PCR(RT-PCR) method were used to examine the methylation status and the mRNA expression of RASSF5A gene in peripheral blood of patients with diffused large B cell lymphoma or T cell lymphoma and healthy participants. The relationship between RASSF5Agene methylation and clinical data was further analyzed. Results: The methylation frequencies of RASSF5A in diffused large B cell lymphoma and T cell lymphoma (64.9% \[48/74\] and 73.8% \[31/42\]) were significantly higher than that of healthy participants (7.1% \[3/42\], all P<0.05). The mRNA expressions of RASSF5A gene in diffused large B cell lymphoma and peripheral T cell lymphoma were (0.54±0.17) and (0.52±0.18), respectively, which were significantly lower than that of healthy participants (0.86±0.10) (P<0.05). The mRNA expression of RASSF5A gene with positive promoter methylation (\[0.51±0.18\]; \[0.50±0.15\]) was significantly lower than that of the gene with negative methylation (\[0.60±0.17\]; \[0.63±0.12\]) (all P<0.05) in both diffused large B cell lymphoma and T cell lymphoma. Methylation frequency of RASSF5A gene was associated with LDH, IPI, and Ki-67 (P<0.05) in diffused large B cell lymphoma, and associated with clinical stage, extranodal involvement and Ki-67 (P<0.05) in T cell lymphoma. The mRNA expression of RASSF5A gene was correlated with IPI score, extranodal involvement (P<0.05) in diffused large B cell lymphoma, and correlated with clinical stage and extranodal involvement (P<0.05) in T cell lymphoma. Conclusion: The methylation of RASSF5A gene may be associated with the occurrence of diffused large B cell lymphoma and T cell lymphoma, and mRNA expression silencing might be one of the mechanisms of epigenetics. RASSF5A gene may act as a tumor suppressor gene in diffused large B cell lymphoma and T cell lymphoma, which may be associated with tumor invasiveness, tumor malignant process and tumor prognosis.
2016, 23(4):545-549.
DOI: 10.3872/j.issn.1007-385X.2016.04.015
Abstract:
帕妥珠单抗（pertuzumab)作为一种新的抗人表皮生长因子受体-2（human epidermal growth factor receptor，HER-2）治疗药物，其作用区域不同于曲妥珠单抗，两者联合可以发挥更全面的HER-2抑制作用，基础和临床转化研究均证实帕妥珠单抗和曲妥珠单抗有协同的抗肿瘤作用。Ⅱ期和Ⅲ期临床转化试验结果显示，抗HER-2两药治疗（帕妥珠单抗+曲妥珠单抗）联合化疗可使HER-2阳性晚期乳腺癌的中位无疾病进展时间（progression-free survival，PFS）延长到18个月以上，中位总生存时间（overall survival，OS）接近5年（56.5个月），显著改善了晚期HER-2阳性乳腺癌患者的预后。两项Ⅱ期新辅助治疗临床转化研究也确认帕妥珠单抗联合曲妥珠单抗的协同作用疗效同样突出，病理完全缓解（pathological complete response，pCR）率最高可达66.2%。安全性分析发现，即使是与蒽环类药物联用，加用帕妥珠单抗治疗也并未增加心脏毒性。本文对帕妥珠单抗在 HER-2阳性乳腺癌治疗中的上述相关临床转化研究进行综述。
帕妥珠单抗（pertuzumab)作为一种新的抗人表皮生长因子受体-2（human epidermal growth factor receptor，HER-2）治疗药物，其作用区域不同于曲妥珠单抗，两者联合可以发挥更全面的HER-2抑制作用，基础和临床转化研究均证实帕妥珠单抗和曲妥珠单抗有协同的抗肿瘤作用。Ⅱ期和Ⅲ期临床转化试验结果显示，抗HER-2两药治疗（帕妥珠单抗+曲妥珠单抗）联合化疗可使HER-2阳性晚期乳腺癌的中位无疾病进展时间（progression-free survival，PFS）延长到18个月以上，中位总生存时间（overall survival，OS）接近5年（56.5个月），显著改善了晚期HER-2阳性乳腺癌患者的预后。两项Ⅱ期新辅助治疗临床转化研究也确认帕妥珠单抗联合曲妥珠单抗的协同作用疗效同样突出，病理完全缓解（pathological complete response，pCR）率最高可达66.2%。安全性分析发现，即使是与蒽环类药物联用，加用帕妥珠单抗治疗也并未增加心脏毒性。本文对帕妥珠单抗在 HER-2阳性乳腺癌治疗中的上述相关临床转化研究进行综述。
2016, 23(4):550-554.
DOI: 10.3872/j.issn.1007-385X.2016.04.016
Abstract:
肺癌是中国发病率首位的癌症，虽然组织学活检和细胞学检测可以确诊肺癌，但其检出时病情多已处于较晚期，且检出率并不理想。SHOX2基因甲基化检测为解决这个问题提供了一个较为有效的选项，多项临床试验证明其与组织学或细胞学检测联合使用提高了确诊率，是辅助确诊肺癌的有效工具。本文回顾了此检测在辅助确诊肺癌方面所进行的临床试验的结果，并对未来的使用方法和研究方向提出建议。
肺癌是中国发病率首位的癌症，虽然组织学活检和细胞学检测可以确诊肺癌，但其检出时病情多已处于较晚期，且检出率并不理想。SHOX2基因甲基化检测为解决这个问题提供了一个较为有效的选项，多项临床试验证明其与组织学或细胞学检测联合使用提高了确诊率，是辅助确诊肺癌的有效工具。本文回顾了此检测在辅助确诊肺癌方面所进行的临床试验的结果，并对未来的使用方法和研究方向提出建议。
2016, 23(4):555-559.
DOI: 10.3872/j.issn.1007-385X.2016.04.017
Abstract:
自然杀伤（natural killer，NK）细胞作为固有免疫细胞成员之一，不仅能够通过细胞毒作用直接杀伤肿瘤细胞，还可通过释放细胞因子（如趋化因子）调节多种免疫细胞的功能，支持机体后续的适应性免疫应答。然而肿瘤细胞会通过多种机制成功规避NK细胞的识别，肿瘤微环境还能诱导多种免疫细胞功能异常，如髓系来源的抑制细胞（myeloid derived suppressor cells，MDSCs）、M2型肿瘤相关巨噬细胞（M2-tumor-associated macrophage，M2-TAM）、树突状细胞（dendritic cells，DCs）和调节性T细胞（regulatory T cells，Treg）等，通过干扰NK细胞活化相关信号通路或者受体表达，抑制NK细胞的活化和抗肿瘤活性，造成肿瘤免疫逃逸。本文从NK细胞的视角，在讨论NK细胞功能的转录调控机制同时，重点综述肿瘤微环境中多种类型细胞对NK细胞功能调节的最新研究进展。
自然杀伤（natural killer，NK）细胞作为固有免疫细胞成员之一，不仅能够通过细胞毒作用直接杀伤肿瘤细胞，还可通过释放细胞因子（如趋化因子）调节多种免疫细胞的功能，支持机体后续的适应性免疫应答。然而肿瘤细胞会通过多种机制成功规避NK细胞的识别，肿瘤微环境还能诱导多种免疫细胞功能异常，如髓系来源的抑制细胞（myeloid derived suppressor cells，MDSCs）、M2型肿瘤相关巨噬细胞（M2-tumor-associated macrophage，M2-TAM）、树突状细胞（dendritic cells，DCs）和调节性T细胞（regulatory T cells，Treg）等，通过干扰NK细胞活化相关信号通路或者受体表达，抑制NK细胞的活化和抗肿瘤活性，造成肿瘤免疫逃逸。本文从NK细胞的视角，在讨论NK细胞功能的转录调控机制同时，重点综述肿瘤微环境中多种类型细胞对NK细胞功能调节的最新研究进展。
2016, 23(4):560-565.
DOI: 10.3872/j.issn.1007-385X.2016.04.018
Abstract:
恶性肿瘤转移是导致肿瘤患者死亡的重要原因。现有资料表明，循环肿瘤细胞（circulating tumor cells，CTCs）是肿瘤通过血道转移的根源，其中由两个或两个以上的CTCs聚集成团的循环肿瘤微栓（circulating tumor microemboli，CTM）作为一种特殊类型的CTCs更容易在血循环中生存，比CTCs具有更强的远处转移倾向，是不良预后和化疗抵抗的一个重要因素。本文从CTM的分离方法、构成成分、形成机制、生物学特性及其临床意义等方面综述CTM相关的研究进展，并指出有待解决的科学问题和今后的研究方向。
恶性肿瘤转移是导致肿瘤患者死亡的重要原因。现有资料表明，循环肿瘤细胞（circulating tumor cells，CTCs）是肿瘤通过血道转移的根源，其中由两个或两个以上的CTCs聚集成团的循环肿瘤微栓（circulating tumor microemboli，CTM）作为一种特殊类型的CTCs更容易在血循环中生存，比CTCs具有更强的远处转移倾向，是不良预后和化疗抵抗的一个重要因素。本文从CTM的分离方法、构成成分、形成机制、生物学特性及其临床意义等方面综述CTM相关的研究进展，并指出有待解决的科学问题和今后的研究方向。
2016, 23(4):566-570.
DOI: 10.3872/j.issn.1007-385X.2016.04.019
Abstract:
滤泡性淋巴瘤（follicular lymphoma，FL）是最常见的惰性非霍奇金淋巴瘤（non-Hodgkin’s lymphoma，NHL），其发病率逐年增高，但它是对放疗和化疗最敏感的恶性肿瘤之一。FL在不同发病阶段采取不同治疗方案：在早期阶段，主要为放射治疗；在疾病进展至中晚期时，进行联合化疗或免疫治疗。免疫治疗中，嵌合抗原受体（chimeric antigen receptor，CAR）修饰T细胞（CAR-T）是从基因层面研究出来的精准靶向治疗的新方法，组蛋白去乙酰化酶（histone deacetylase ，HDAC）抑制剂与肿瘤细胞存活关系密切，使用肿瘤疫苗可增强FL的抗肿瘤免疫，免疫调节剂调节肿瘤生存的免疫微环境并同传统化疗药物起到协同作用，新型单克隆抗体的研究将突破原有单克隆抗体的局限性而发挥更好疗效。上述治疗研究仍处于临床试验阶段，需进一步研究发挥治疗作用。本文就FL免疫治疗方面的新进展，如使用CAR-T细胞、HDAC抑制剂、肿瘤疫苗、免疫调节剂和新型单克隆抗体等进行治疗作一综述。
滤泡性淋巴瘤（follicular lymphoma，FL）是最常见的惰性非霍奇金淋巴瘤（non-Hodgkin’s lymphoma，NHL），其发病率逐年增高，但它是对放疗和化疗最敏感的恶性肿瘤之一。FL在不同发病阶段采取不同治疗方案：在早期阶段，主要为放射治疗；在疾病进展至中晚期时，进行联合化疗或免疫治疗。免疫治疗中，嵌合抗原受体（chimeric antigen receptor，CAR）修饰T细胞（CAR-T）是从基因层面研究出来的精准靶向治疗的新方法，组蛋白去乙酰化酶（histone deacetylase ，HDAC）抑制剂与肿瘤细胞存活关系密切，使用肿瘤疫苗可增强FL的抗肿瘤免疫，免疫调节剂调节肿瘤生存的免疫微环境并同传统化疗药物起到协同作用，新型单克隆抗体的研究将突破原有单克隆抗体的局限性而发挥更好疗效。上述治疗研究仍处于临床试验阶段，需进一步研究发挥治疗作用。本文就FL免疫治疗方面的新进展，如使用CAR-T细胞、HDAC抑制剂、肿瘤疫苗、免疫调节剂和新型单克隆抗体等进行治疗作一综述。
2016, 23(4):571-574.
DOI: 10.3872/j.issn.1007-385X.2016.04.020
Abstract:
外泌体是各种细胞分泌的具有脂质双分子层膜结构囊泡状物质，广泛分布于机体组织中，同时也存在于肿瘤的微环境中，其对肿瘤的发生发展具有重要作用。由于细胞来源不同，外泌体在肿瘤的产生和进展中可发挥正向或负向调节作用。虽然目前对于这种截然相反现象的产生机制知之甚少，但是将具有抗肿瘤作用的外泌体应用于肿瘤治疗已经取得较大进展。本文就外泌体在肿瘤生物治疗研究中的进展作一综述，为外泌体作为抗肿瘤治疗的潜在载体及策略提供新的思路。
外泌体是各种细胞分泌的具有脂质双分子层膜结构囊泡状物质，广泛分布于机体组织中，同时也存在于肿瘤的微环境中，其对肿瘤的发生发展具有重要作用。由于细胞来源不同，外泌体在肿瘤的产生和进展中可发挥正向或负向调节作用。虽然目前对于这种截然相反现象的产生机制知之甚少，但是将具有抗肿瘤作用的外泌体应用于肿瘤治疗已经取得较大进展。本文就外泌体在肿瘤生物治疗研究中的进展作一综述，为外泌体作为抗肿瘤治疗的潜在载体及策略提供新的思路。
2016, 23(4):575-577.
DOI: 10.3872/j.issn.1007-385X.2016.04.021
Abstract:
2016, 23(4):578-580.
DOI: 10.3872/j.issn.1007-385X.2016.04.022
Abstract:
2016, 23(4):581-584.
DOI: 10.3872/j.issn.1007-385X.2016.04.023
Abstract:
英文摘要在体现论文的学术水平和国际学术交流中具有重要作用。目前我国医学论文的英文摘要因受母语影响等原因存在一定问题，影响了我国医学科研成果的传播和国际学术交流。笔者简要介绍医学论文英文摘要的写作方法和技巧，举例分析了常见错误并指出订正方式，希望能引导医学论文英文摘要的规范写作，提高论文摘要的英文表达水平和规范化质量。
英文摘要在体现论文的学术水平和国际学术交流中具有重要作用。目前我国医学论文的英文摘要因受母语影响等原因存在一定问题，影响了我国医学科研成果的传播和国际学术交流。笔者简要介绍医学论文英文摘要的写作方法和技巧，举例分析了常见错误并指出订正方式，希望能引导医学论文英文摘要的规范写作，提高论文摘要的英文表达水平和规范化质量。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.