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Volume 23,Issue 1,2016 Table of Contents
2016, 23(1):1-10.
DOI: 10.3872/j.issn.1007-385X.2016.01.001
Abstract:
Natural killer (NK) cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for cancer. With the rise of CAR-T technology, potential of CAR modification in NK cells has been also concerned. The research and application of CAR-NK not only inherited some ideas of classic CAR-T, but also achieved a lot of innovations and developments based on biological characteristics of NK cells. Peripheral blood NK cells, NK cells lines and NK cells derived from stem cells exert various biological characteristics and had been widely used in the researches and developments of CAR-NK. A lot of remarkable results have been obtained in the preclinical tests and animal experiments of CAR-NK targeting to hematologic and solid tumors. CAR-NK could make a novel breakthrough in treatment of solid tumor and simplification of imunotherapy, although there is no clinical data supporting the efficacy of CAR-NK till now and some bottleneck problems still need to be overcome.
Natural killer (NK) cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for cancer. With the rise of CAR-T technology, potential of CAR modification in NK cells has been also concerned. The research and application of CAR-NK not only inherited some ideas of classic CAR-T, but also achieved a lot of innovations and developments based on biological characteristics of NK cells. Peripheral blood NK cells, NK cells lines and NK cells derived from stem cells exert various biological characteristics and had been widely used in the researches and developments of CAR-NK. A lot of remarkable results have been obtained in the preclinical tests and animal experiments of CAR-NK targeting to hematologic and solid tumors. CAR-NK could make a novel breakthrough in treatment of solid tumor and simplification of imunotherapy, although there is no clinical data supporting the efficacy of CAR-NK till now and some bottleneck problems still need to be overcome.
2016, 23(1):11-16.
DOI: 10.3872/j.issn.1007-385X.2016.01.002
Abstract:
Objective:To evaluate the safety of multiple antigen stimulating cellular therapy (MASCTTM) in treating patients with hepatocellular carcinoma (HCC). Methods: The clinical datas of 45 HCC patients, who received MASCTTM from January 2012 to December 2014 in the Center of Liver Diseases of Nanfang Hospital, were retrospectively analyzed. These patients did not receive any other immunotherapy before and their latest treatment (surgery,radiotherapy or chemotherapy) was at least one month before receiving MASCTTM. Peripheral blood mononuclear cells (PBMCs) were separated on Day 0，and the adherent cells were induced into mature dendritic cells (mDCs) to load 14 types of antigen peptides, a small part of mDCs was injected intracutaneously into the area of inguinal lymph nodes on Day 8. The un-adherent cells were co-cultured with mDC on Day 7 and induced into cytotoxic T lymphocytes (CTLs); the quality of DCs and CTLs was controlled before injected intravenously into patients on Day 26. The adverse effects, blood routine examination results, and functional changes of liver and kidney were recorded after injection. Results: In mDCs, the percentage of CD80+, CD83+, CD86+ and HLA-DR+ was (98.5±5)%, (88.0±10)%, (98.4±3)%, and (98.8±2)%, respectively; mDC secreted high level of IL-12（985±312） pg/ml and low level of IL-10（53±10） pg/ml. The percentage of CD3+CD8+ and CD3+CD56+ cells in CTLs was (83.0±10)% and (24.0±5)%, respectively; CTL secreted high level of IFN-γ （1 222±650） pg/ml and low level of IL-10（7±5） pg/ml. Most of the 45 patients had alleviation in appetite, sleep and physical condition after MASCTTM treatment. There were 2 patients (4.4%) had moderate fever after infusion with CTLs, but without other severe adverse reactions. There was no significant difference in renal function or blood routine examination before and after treatment. But ATL, AST, TBIL in liver function were increased a little.Conclusion: MASCTTM induced mDC and CTL successfully; it is a feasible treatment for HCC patients with less adverse effects and good clinical safety.
Objective:To evaluate the safety of multiple antigen stimulating cellular therapy (MASCTTM) in treating patients with hepatocellular carcinoma (HCC). Methods: The clinical datas of 45 HCC patients, who received MASCTTM from January 2012 to December 2014 in the Center of Liver Diseases of Nanfang Hospital, were retrospectively analyzed. These patients did not receive any other immunotherapy before and their latest treatment (surgery,radiotherapy or chemotherapy) was at least one month before receiving MASCTTM. Peripheral blood mononuclear cells (PBMCs) were separated on Day 0，and the adherent cells were induced into mature dendritic cells (mDCs) to load 14 types of antigen peptides, a small part of mDCs was injected intracutaneously into the area of inguinal lymph nodes on Day 8. The un-adherent cells were co-cultured with mDC on Day 7 and induced into cytotoxic T lymphocytes (CTLs); the quality of DCs and CTLs was controlled before injected intravenously into patients on Day 26. The adverse effects, blood routine examination results, and functional changes of liver and kidney were recorded after injection. Results: In mDCs, the percentage of CD80+, CD83+, CD86+ and HLA-DR+ was (98.5±5)%, (88.0±10)%, (98.4±3)%, and (98.8±2)%, respectively; mDC secreted high level of IL-12（985±312） pg/ml and low level of IL-10（53±10） pg/ml. The percentage of CD3+CD8+ and CD3+CD56+ cells in CTLs was (83.0±10)% and (24.0±5)%, respectively; CTL secreted high level of IFN-γ （1 222±650） pg/ml and low level of IL-10（7±5） pg/ml. Most of the 45 patients had alleviation in appetite, sleep and physical condition after MASCTTM treatment. There were 2 patients (4.4%) had moderate fever after infusion with CTLs, but without other severe adverse reactions. There was no significant difference in renal function or blood routine examination before and after treatment. But ATL, AST, TBIL in liver function were increased a little.Conclusion: MASCTTM induced mDC and CTL successfully; it is a feasible treatment for HCC patients with less adverse effects and good clinical safety.
2016, 23(1):17-23.
DOI: 10.3872/j.issn.1007-385X.2016.01.003
Abstract:
Objective:To study the role of monocyte chemoatractant protein-1 (MCP-1)/(chemokine \[C-C motif\] receptor 2, CCR2) axis in human umbilical cord mesenchymal stem cells（HUMSCs） homing to lung cancer. Methods: “Tissue explant” method was used to isolate and identify HUMSCs from umbilical cord of healthy newborns. Subcutaneous lung cancer xenograft model was established in nude BALB/c mice. Transwell migration assay in vitro and IVIS Xenogen living imaging system in vivo were applied respectively to investigate the capability of HUMSCs homing to lung cancer. ELISA was utilized to detect the secretion of monocyte chemoatrractant protein-1（MCP-1）in lung cancer A549 cell culture supernatant. After knocking down the MCP-1 expression in lung cancer cells by transfecting shRNA and blocking MCP-1 receptor CCR2 on the surface of HUMSCs by inhibitor RS504393, the migration ability of HUMSCs was determined in vitro and in vivo. Results: HUMSCs were successfully isolated and identified. Subcutaneous lung cancer xenograft model was successfully established in nude BALB/c mice. HUMSCs migrated to lung cancer both in vivo and in vitro（P<0.01）. Lung cancer cells highly expressed MCP-1. Lung cancer A549 cell line with stable low expression of MCP-1 was successfully constructed, compared with control group, number of migrating HUMSCs significantly decreased in shRNA1 and shRNA2 knock down groups （\[80.0±33.0\]，\[94.0±16.0\] vs \[167.0±41.0\]，P<0.05）. Inhibition of CCR2 (receptor of MCP-1) on HUMSCs greatly suppressed the tropism of HUMSCs to lung cancer in vivo and in vitro （P<0.05）. Conclusion: MCP-1/CCR2 axis promoted the migration of HUMSCs to lung cancer.
Objective:To study the role of monocyte chemoatractant protein-1 (MCP-1)/(chemokine \[C-C motif\] receptor 2, CCR2) axis in human umbilical cord mesenchymal stem cells（HUMSCs） homing to lung cancer. Methods: “Tissue explant” method was used to isolate and identify HUMSCs from umbilical cord of healthy newborns. Subcutaneous lung cancer xenograft model was established in nude BALB/c mice. Transwell migration assay in vitro and IVIS Xenogen living imaging system in vivo were applied respectively to investigate the capability of HUMSCs homing to lung cancer. ELISA was utilized to detect the secretion of monocyte chemoatrractant protein-1（MCP-1）in lung cancer A549 cell culture supernatant. After knocking down the MCP-1 expression in lung cancer cells by transfecting shRNA and blocking MCP-1 receptor CCR2 on the surface of HUMSCs by inhibitor RS504393, the migration ability of HUMSCs was determined in vitro and in vivo. Results: HUMSCs were successfully isolated and identified. Subcutaneous lung cancer xenograft model was successfully established in nude BALB/c mice. HUMSCs migrated to lung cancer both in vivo and in vitro（P<0.01）. Lung cancer cells highly expressed MCP-1. Lung cancer A549 cell line with stable low expression of MCP-1 was successfully constructed, compared with control group, number of migrating HUMSCs significantly decreased in shRNA1 and shRNA2 knock down groups （\[80.0±33.0\]，\[94.0±16.0\] vs \[167.0±41.0\]，P<0.05）. Inhibition of CCR2 (receptor of MCP-1) on HUMSCs greatly suppressed the tropism of HUMSCs to lung cancer in vivo and in vitro （P<0.05）. Conclusion: MCP-1/CCR2 axis promoted the migration of HUMSCs to lung cancer.
2016, 23(1):24-29.
DOI: 10.3872/j.issn.1007-385X.2016.01.004
Abstract:
Objective:To explore the effect of Notoginsenoside R1 on the apoptosis of human leukemia cell line HL-60 and possible mechanisms. Methods：After HL-60 cells were incubated with different concentrations of Notoginsenoside R1 (10, 20, 40 and 80 μmol/L) for 12, 24, 36 h and 48 h, apoptosis of the HL-60 cells was determined by MTT and Annexin V-FITC flow cytometry assays respectively. The expression of Bcl-2, Bax and cytochrome C (Cyt-C) in the HL-60 cells was determined by Western blotting. The change of mitochondrial membrane potential was assessed by JC-1 dyeing method. Results：The results of MTT and flow cytometry assays showed that Notoginsenoside R1 induced the apoptosis of HL-60 cells in dose-dependent manners, and survival rate of the HL-60 cells decreased with increase of incubation time; after adding Notoginsenoside R1, expression of Bcl-2 protein in the HL-60 cells remarkably decreased (\[0.45±0.03\] vs \[1.00±0.00\]，P<0.05, compared with control group); expression of Bax protein significantly increased (\[1.72±0.08\] vs \[1.00±0.00\]，P<0.05, compared with control group); and the ratio of Bcl-2/Bax decreased (\[0.21±0.01\] vs \[1.00±0.00\]，P<0.05); the mitochondrial membrane potential decreased (\[0.56±009\] vs \[1.00±0.00\]，P<0.05)；and expression level of Cyt-C protein in cytoplasm remarkably decreased (\[0.42±0.03\] vs \[1.00±0.00\]，P<0.05\]. Conclusion：Notoginsenoside R1 can remarkbly incluce apoptosis of HL-60 cells. Mitochondria-dependent pathway may be involved inNotoginsenoside R1-induced apoptosis of HL-60 cells. These findings suggest that Notoginsenoside R1 may be a new strategy for treatment of leukemia.
Objective:To explore the effect of Notoginsenoside R1 on the apoptosis of human leukemia cell line HL-60 and possible mechanisms. Methods：After HL-60 cells were incubated with different concentrations of Notoginsenoside R1 (10, 20, 40 and 80 μmol/L) for 12, 24, 36 h and 48 h, apoptosis of the HL-60 cells was determined by MTT and Annexin V-FITC flow cytometry assays respectively. The expression of Bcl-2, Bax and cytochrome C (Cyt-C) in the HL-60 cells was determined by Western blotting. The change of mitochondrial membrane potential was assessed by JC-1 dyeing method. Results：The results of MTT and flow cytometry assays showed that Notoginsenoside R1 induced the apoptosis of HL-60 cells in dose-dependent manners, and survival rate of the HL-60 cells decreased with increase of incubation time; after adding Notoginsenoside R1, expression of Bcl-2 protein in the HL-60 cells remarkably decreased (\[0.45±0.03\] vs \[1.00±0.00\]，P<0.05, compared with control group); expression of Bax protein significantly increased (\[1.72±0.08\] vs \[1.00±0.00\]，P<0.05, compared with control group); and the ratio of Bcl-2/Bax decreased (\[0.21±0.01\] vs \[1.00±0.00\]，P<0.05); the mitochondrial membrane potential decreased (\[0.56±009\] vs \[1.00±0.00\]，P<0.05)；and expression level of Cyt-C protein in cytoplasm remarkably decreased (\[0.42±0.03\] vs \[1.00±0.00\]，P<0.05\]. Conclusion：Notoginsenoside R1 can remarkbly incluce apoptosis of HL-60 cells. Mitochondria-dependent pathway may be involved inNotoginsenoside R1-induced apoptosis of HL-60 cells. These findings suggest that Notoginsenoside R1 may be a new strategy for treatment of leukemia.
2016, 23(1):30-35.
DOI: 10.3872/j.issn.1007-385X.2016.01.005
Abstract:
Objective:To explore the anti-tumor effect of dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, on gastric cancer cells in vitro.Methods: Gastric cancer cell SGC-7901 and BGC-823 lines cultured in vitro were treated respectively by different concentrations of DCA for 24 h. Viability rates of the gastric cancer cells were evaluated by MTT assay. The synergistic effect of DCA combined with cisplatin (DDP) on the gastric cancer cells was analyzed with the median effect principle. Invasive ability of the gastric cancer cells were then evaluated by Transwell assay. Their apoptotic rates were measured by double staining flow cytometry. Results:DCA (20, 40, 60, 80 and 100 mmol/L) remarkably reduced survival rates of the gastric cancer cells (SGC-7901and BGC-823) in a concentration-dependent manner. The IC50 of DCA for 24 h in SGC-7901 and BGC-823 cells were 60.9 mmol/L and 53.8 mmol/L, respectively. Small-concentrations of DCA (20, 40 mmol/L) in combination with DDP (5, 10 μmol /L) synergistically reduced cell viability in the gastric cancer cells, their combination index was less than 1 both. Compared to control group, the number of invaded SGC-7901 cells in 60, 80 and 100 mmol/L DCA groups significantly decreased (\[99.3±11.7\], \[55.7±60\] and \[38.3±6.7\] vs \[182.7±17.3\], P<0.05\]; the number of invaded BGC-823 cells in the same concentrations of DCA groups also significantly decreased (\[88.7±8.3\], \[49.0±5.7\] and \[42.3±6.7\] vs \[170.7±15.0\], P<0.05\]. In addition, the early apoptotic rates of the SGC-7901 cells in 60, 80 and 100 mmol/L DCA groups significantly increased (\[31.7±5.2\]%, \[35.0±5.4\]%, \[37.8±62\] vs \[8.1±1.3\]%, P<0.05, compared to control group); while the early apoptotic rates of the BGC-823 cells in the same concentrations of DCA groups also significantly increased ( \[24.6±4.6\]%, \[31.9±42\]%, \[40.4 ±5.7\]% vs \[6.6±1.4\]%, P<0.05, compared to control group). Conclusion:DCA can obviously inhibit survial of gastric cancer cells cultrued in vitro, and produce a asynergistic effect with chemotherapetric agents. DCA can inhibit invasiveness of gastric cancer cells and induce their apoptosis. Targeting pyruvate dehydrogenase kinase may be a novel therapuetic method of gastric carcinoma in future.
Objective:To explore the anti-tumor effect of dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, on gastric cancer cells in vitro.Methods: Gastric cancer cell SGC-7901 and BGC-823 lines cultured in vitro were treated respectively by different concentrations of DCA for 24 h. Viability rates of the gastric cancer cells were evaluated by MTT assay. The synergistic effect of DCA combined with cisplatin (DDP) on the gastric cancer cells was analyzed with the median effect principle. Invasive ability of the gastric cancer cells were then evaluated by Transwell assay. Their apoptotic rates were measured by double staining flow cytometry. Results:DCA (20, 40, 60, 80 and 100 mmol/L) remarkably reduced survival rates of the gastric cancer cells (SGC-7901and BGC-823) in a concentration-dependent manner. The IC50 of DCA for 24 h in SGC-7901 and BGC-823 cells were 60.9 mmol/L and 53.8 mmol/L, respectively. Small-concentrations of DCA (20, 40 mmol/L) in combination with DDP (5, 10 μmol /L) synergistically reduced cell viability in the gastric cancer cells, their combination index was less than 1 both. Compared to control group, the number of invaded SGC-7901 cells in 60, 80 and 100 mmol/L DCA groups significantly decreased (\[99.3±11.7\], \[55.7±60\] and \[38.3±6.7\] vs \[182.7±17.3\], P<0.05\]; the number of invaded BGC-823 cells in the same concentrations of DCA groups also significantly decreased (\[88.7±8.3\], \[49.0±5.7\] and \[42.3±6.7\] vs \[170.7±15.0\], P<0.05\]. In addition, the early apoptotic rates of the SGC-7901 cells in 60, 80 and 100 mmol/L DCA groups significantly increased (\[31.7±5.2\]%, \[35.0±5.4\]%, \[37.8±62\] vs \[8.1±1.3\]%, P<0.05, compared to control group); while the early apoptotic rates of the BGC-823 cells in the same concentrations of DCA groups also significantly increased ( \[24.6±4.6\]%, \[31.9±42\]%, \[40.4 ±5.7\]% vs \[6.6±1.4\]%, P<0.05, compared to control group). Conclusion:DCA can obviously inhibit survial of gastric cancer cells cultrued in vitro, and produce a asynergistic effect with chemotherapetric agents. DCA can inhibit invasiveness of gastric cancer cells and induce their apoptosis. Targeting pyruvate dehydrogenase kinase may be a novel therapuetic method of gastric carcinoma in future.
TIAN Jianhui
,
YANG Xiaoxia
,
BI Ling
,
LUO Bin
,
ZHOU Zhiyi
,
WANG Qing
,
HUANG Jianhua
,
LI Hegen
,
LIU Jiaxiang
2016, 23(1):36-43.
DOI: 10.3872/j.issn.1007-385X.2016.01.006
Abstract:
Objective:To study the preventive and therapeutic effects of Jinfukang decoction on lung carcinoma in immunosenescence mouse induced by D-galactose. Methods:Using SPSS 18.0 software, 10 male C57BL/6J mice were randomly selected as control group and 83 male C57BL/6J mice as model group. In the model group, mice were subcutaneously injected with D-galactose (150 mg/kg/d) in scruff for 42 days to construct immunosenescence mouse model, normal saline and Jinfukang decoction were applied to intervene. After construction of the mouse model, 10 mice in the control group and 20 mice in the model group were selected to detect vitalities of serum superoxide dismutase (SOD) and contents of serum malondialdegyde (MDA),and then removed spleens and thymuses from the mice to calculate index of the organs; Flow cytometry was used to examine the expressions of immunosenscene related membrane molecules in T cells of the spleen and the thymuses. The rest 63 immunosenescence mice in the model group were subcutaneously injected with LL2-Luc-M38 lung cancer cells in the front of the left armpit to construct the model of Lewis lung cancer, and the mice were randomly divided into normal saline group, Jinfukang prevention group and Jinfukang prevention + treatment group. Among them, 30 mice (10 mice each group) were sacrificed at 14th day to measure the tumor mass, and the rest 33 mice were observed for time of tumor formation and survival time. Results: (1) Compared with the control group, the indexes of spleen and thymus in the normal saline group significantly decreased (P<0.05 or P<0.01); expression of CD3+CD45RA+, CD3+CD25+ and CD3+CD28+ in the spleen and the thymus significantly decreased (all P<0.01) while expression of CD3+CD196+ and CD4+CD25+ in the organs significantly increased (P<0.01); the vitalities of serum SOD remarkably decreased (P<0.001) while contents of serum MDA increased (P<0.001). After intervention of Jinfukang decoction, in the model group the spleen indexes increased significantly (P<0.01), expression of CD3+CD45RA+ and CD3+CD28+ increased (P<0.01 or P<0.05) and expression of CD3+CD196+ and CD4+CD25+ decreased (P<001) in the spleen, while expressioin of CD3+CD25+ increased (P<0.01), expression of CD3+CD196+ in the thymus decreased (P<0.05), vitalities of serum SOD increased (P<0.01) and contente of serum MDA decreased (P<0.01) compared with the normal saline group. (2) After the immunosenescence model mice were subcutaneously injected with lung cancer cells ,times of tumor formation and survival in the Jinfukang prevention group were significantly longer than those in the normal saline group (P<005), especially in the Jinfukang prevention + treatment group survival time was more significantly longer than that in the normal saline group (P<0.01); the tumor mass in the Jinfukang prevention + treatment group was smaller than those in the normal saline group (P<0.01) and the Jinfukang prevention group (P<005), but there was no significant difference between the latter two groups (P<0.05). Conclusion: The immunosenescence of mouse can be induced by D-galactose; Jifukang decoction can time-dependently delay the immunosenescence of mouse, by which Jifukang decoction can prevent the occurrence and development of lung cancer, and can prolong survival period of the mice bearing lung umor.
Objective:To study the preventive and therapeutic effects of Jinfukang decoction on lung carcinoma in immunosenescence mouse induced by D-galactose. Methods:Using SPSS 18.0 software, 10 male C57BL/6J mice were randomly selected as control group and 83 male C57BL/6J mice as model group. In the model group, mice were subcutaneously injected with D-galactose (150 mg/kg/d) in scruff for 42 days to construct immunosenescence mouse model, normal saline and Jinfukang decoction were applied to intervene. After construction of the mouse model, 10 mice in the control group and 20 mice in the model group were selected to detect vitalities of serum superoxide dismutase (SOD) and contents of serum malondialdegyde (MDA),and then removed spleens and thymuses from the mice to calculate index of the organs; Flow cytometry was used to examine the expressions of immunosenscene related membrane molecules in T cells of the spleen and the thymuses. The rest 63 immunosenescence mice in the model group were subcutaneously injected with LL2-Luc-M38 lung cancer cells in the front of the left armpit to construct the model of Lewis lung cancer, and the mice were randomly divided into normal saline group, Jinfukang prevention group and Jinfukang prevention + treatment group. Among them, 30 mice (10 mice each group) were sacrificed at 14th day to measure the tumor mass, and the rest 33 mice were observed for time of tumor formation and survival time. Results: (1) Compared with the control group, the indexes of spleen and thymus in the normal saline group significantly decreased (P<0.05 or P<0.01); expression of CD3+CD45RA+, CD3+CD25+ and CD3+CD28+ in the spleen and the thymus significantly decreased (all P<0.01) while expression of CD3+CD196+ and CD4+CD25+ in the organs significantly increased (P<0.01); the vitalities of serum SOD remarkably decreased (P<0.001) while contents of serum MDA increased (P<0.001). After intervention of Jinfukang decoction, in the model group the spleen indexes increased significantly (P<0.01), expression of CD3+CD45RA+ and CD3+CD28+ increased (P<0.01 or P<0.05) and expression of CD3+CD196+ and CD4+CD25+ decreased (P<001) in the spleen, while expressioin of CD3+CD25+ increased (P<0.01), expression of CD3+CD196+ in the thymus decreased (P<0.05), vitalities of serum SOD increased (P<0.01) and contente of serum MDA decreased (P<0.01) compared with the normal saline group. (2) After the immunosenescence model mice were subcutaneously injected with lung cancer cells ,times of tumor formation and survival in the Jinfukang prevention group were significantly longer than those in the normal saline group (P<005), especially in the Jinfukang prevention + treatment group survival time was more significantly longer than that in the normal saline group (P<0.01); the tumor mass in the Jinfukang prevention + treatment group was smaller than those in the normal saline group (P<0.01) and the Jinfukang prevention group (P<005), but there was no significant difference between the latter two groups (P<0.05). Conclusion: The immunosenescence of mouse can be induced by D-galactose; Jifukang decoction can time-dependently delay the immunosenescence of mouse, by which Jifukang decoction can prevent the occurrence and development of lung cancer, and can prolong survival period of the mice bearing lung umor.
2016, 23(1):44-51.
DOI: 10.3872/j.issn.1007-385X.2016.01.007
Abstract:
Objective:To establish a combined therapy of p[5HRE]AFPp-p53/PEI-Fe3O4 magnetic nanoparticle and Magnetic Fluid Hyperthermia (MFH) to treat liver carcinoma and improve the safety and efficacy of the treatment. Methods:Sub-clone was used to construct hepatoma targeted gene p[5HRE]AFPp-p53, which was then confirmed by enzyme digestion and gel electrophoresis. The PEI-Fe3O4 magnetic nanoparticles were prepared by coprecipitation method, and its surface characteristics were examined by transmission electron microscope, particle size analyzer and Fourier transform infrared spectrometer etc. The proliferation of cell lines transfected with p[HRE]AFPp-p53/ PEI-Fe3O4, and the inhibition effect of targeted gene therapy combined with MFH on HepG2 cell proliferation were detected by MTT method. Results: p[5HRE]AFPp-p53/PEI-Fe3O4 magnetic nanoparticles were successfully constructed. Comparing with negative control group and nanoparticles control group, the proliferation activity of HepG2 cells ([0.592±0.041] vs [1.052±0031]，[1.012±0.021], P<0.01) and SMMC772 cells ([0.813±0.042] vs [1.073±0.032], [1.182±0.052], P<0.01) was significantly inhibited in p[5HRE]AFPp-p53/PEI-Fe3O4 mediated gene treatment group, however the proliferation of nonhepatoma cells (L929 and LOVO) was not significantly inhibited (P>0.05). Comparing with MFH group and gene therapy group, the inhibition rate of HegG2 cell proliferation was significantly increased in gene+MFH group (3522%, 42.92% vs 76.11%, P<0.01).Conclusion: p[5HRE]AFPp-p53/PEI-Fe3O4 magnetic nanoparticle has specific killing effect on liver carcinoma cells; it will have synergistic effect when combined with MFH; the combined therapy is an anti-tumor treatment with high selection and good therapeutic effect.
Objective:To establish a combined therapy of p[5HRE]AFPp-p53/PEI-Fe3O4 magnetic nanoparticle and Magnetic Fluid Hyperthermia (MFH) to treat liver carcinoma and improve the safety and efficacy of the treatment. Methods:Sub-clone was used to construct hepatoma targeted gene p[5HRE]AFPp-p53, which was then confirmed by enzyme digestion and gel electrophoresis. The PEI-Fe3O4 magnetic nanoparticles were prepared by coprecipitation method, and its surface characteristics were examined by transmission electron microscope, particle size analyzer and Fourier transform infrared spectrometer etc. The proliferation of cell lines transfected with p[HRE]AFPp-p53/ PEI-Fe3O4, and the inhibition effect of targeted gene therapy combined with MFH on HepG2 cell proliferation were detected by MTT method. Results: p[5HRE]AFPp-p53/PEI-Fe3O4 magnetic nanoparticles were successfully constructed. Comparing with negative control group and nanoparticles control group, the proliferation activity of HepG2 cells ([0.592±0.041] vs [1.052±0031]，[1.012±0.021], P<0.01) and SMMC772 cells ([0.813±0.042] vs [1.073±0.032], [1.182±0.052], P<0.01) was significantly inhibited in p[5HRE]AFPp-p53/PEI-Fe3O4 mediated gene treatment group, however the proliferation of nonhepatoma cells (L929 and LOVO) was not significantly inhibited (P>0.05). Comparing with MFH group and gene therapy group, the inhibition rate of HegG2 cell proliferation was significantly increased in gene+MFH group (3522%, 42.92% vs 76.11%, P<0.01).Conclusion: p[5HRE]AFPp-p53/PEI-Fe3O4 magnetic nanoparticle has specific killing effect on liver carcinoma cells; it will have synergistic effect when combined with MFH; the combined therapy is an anti-tumor treatment with high selection and good therapeutic effect.
2016, 23(1):52-56.
DOI: 10.3872/j.issn.1007-385X.2016.01.008
Abstract:
Objective:To investigate the effect of Silibinin on hypoxia inducible factor-1α (HIF-1α) expression as well as its possible molecular mechanism. Methods：Gastric carcinoma cell line MGC803 was cultured in vitro under hypoxic condition. After treated with different concentration of Silibinin, the expression of HIF-1α mRNA was detected by Real-time PCR; HIF-1α protein level and phosphorylation of mTOR and Akt were detected by Western blotting. Effect of Silibinin on proliferation of MGC803 cell was analyzed by MTT assay. Results：After 4 h of incubation under hypoxia condition, the expression of HIF-1α protein was significantly increased in MGC803 cells, as compared with the normoxia group ([094±0.16] vs[0.015±0.03], P<0.01). After treatment with 250μmol/L Silibinin, the expression of HIF-1α protein was significantly inhibited as compared to pre-treatment ([0.24±0.09] vs [0.94±0.16], P<0.01). As compare with normoxia group, hypoxia couldn’t increase expression of HIF-1α mRNA ([0.074±0.011] vs [0.07±0.02], P>0.05), even though treatment with 250 μmol/L aqueous Silibinin also couldn’t significantly affect expression of HIF-1α mRNA ([0.081±0.011] vs[0.07±0.02], P>0.05) , but Silibinin could significantly increase the expression of ubiquitinated HIF-1α protein ([0.94±0.16] vs[0.24±0.09], P<0.01). After incubation with Silibinin, phosphorylation of mTOR was significantly inhibited ([0.17±0.06) vs [0.53±0.14], P<0.05), and proliferation of MGC803 cell was significantly inhibited ([52.94±6.15] vs [100±3.2]，P<0.05), as compared with pre-treatment. In contrast, 50 and 100 μmol/L Silibinin had no obvious effect on phosphorylation of Akt ([0.16±009], [0.17±006] vs [0.11±0.04], P<0.05), but 250 μmol/L Silibinin could significantly increase the phosphorylation of Akt in the cells ([0.33±0.06] vs [0.11±0.04], P<0.05). Conclusion：Silibinin could exert antitumor action through to effect on expression of mTOR and HIF-1α.
Objective:To investigate the effect of Silibinin on hypoxia inducible factor-1α (HIF-1α) expression as well as its possible molecular mechanism. Methods：Gastric carcinoma cell line MGC803 was cultured in vitro under hypoxic condition. After treated with different concentration of Silibinin, the expression of HIF-1α mRNA was detected by Real-time PCR; HIF-1α protein level and phosphorylation of mTOR and Akt were detected by Western blotting. Effect of Silibinin on proliferation of MGC803 cell was analyzed by MTT assay. Results：After 4 h of incubation under hypoxia condition, the expression of HIF-1α protein was significantly increased in MGC803 cells, as compared with the normoxia group ([094±0.16] vs[0.015±0.03], P<0.01). After treatment with 250μmol/L Silibinin, the expression of HIF-1α protein was significantly inhibited as compared to pre-treatment ([0.24±0.09] vs [0.94±0.16], P<0.01). As compare with normoxia group, hypoxia couldn’t increase expression of HIF-1α mRNA ([0.074±0.011] vs [0.07±0.02], P>0.05), even though treatment with 250 μmol/L aqueous Silibinin also couldn’t significantly affect expression of HIF-1α mRNA ([0.081±0.011] vs[0.07±0.02], P>0.05) , but Silibinin could significantly increase the expression of ubiquitinated HIF-1α protein ([0.94±0.16] vs[0.24±0.09], P<0.01). After incubation with Silibinin, phosphorylation of mTOR was significantly inhibited ([0.17±0.06) vs [0.53±0.14], P<0.05), and proliferation of MGC803 cell was significantly inhibited ([52.94±6.15] vs [100±3.2]，P<0.05), as compared with pre-treatment. In contrast, 50 and 100 μmol/L Silibinin had no obvious effect on phosphorylation of Akt ([0.16±009], [0.17±006] vs [0.11±0.04], P<0.05), but 250 μmol/L Silibinin could significantly increase the phosphorylation of Akt in the cells ([0.33±0.06] vs [0.11±0.04], P<0.05). Conclusion：Silibinin could exert antitumor action through to effect on expression of mTOR and HIF-1α.
2016, 23(1):57-61.
DOI: 10.3872/j.issn.1007-385X.2016.01.009
Abstract:
Objective:To investigate dihydroartemisinin (DHA)-induced apoptosis of peripheral T lymphocytoma Hut-78 cell line and its possible mechanism. Methods: The effect of DHA 1－30 μg/ml on proliferation of Hut-78 cells was measured by CCK-8 assay. The morphological changes of Hut-78 cell's nuclei induced by DHA were observed by Hochest 33258 staining and confocal microscopy. Flow cytometry was used to examine the apoptosis of Hut-78 cells induced by DHA. After pretreating the Hut-78 cells with 10 mmol/L of reactive oxygen species (ROS) scavenger N-acetyl cysteine C (NAC) , a role of ROS in changes of mitochondrial membrane potential induced by DHA was evaluated. Effect of ROS on release of cytochondrial C induced by DHA during apoptosis of Hut-78 cells was examined with an immunoblotting assay.Results:DHA inhibited proliferation of the Hut-78 cells in a dose-dependent manner, induced nucleus pyknosis and formed apoptotic bodies in the cells. Apoptosis rates of the Hut-78 cells iuduced with 5, 10 and 20 μg/ml of DHA were (25.1±2.8)%, (43,6±3.1)% and (68.9±2.6)% respectively, which were significantly different from that of the control group (all P<0.01 ). Furthermore, treatment with 20 μg/ml of DHA droped mitochondrial membrane potential of the Hut-78 cells by (59.4±2.6)%, and pretreating with ROS scavenger NAC droped the mitochondrial membrane potential by (38.4±2.1)%. DHA can induce release of cytochrome C in mitochondrion, which can be significantly inhibited by pretreatment with NAC. Statistic results further demonstrated this point. Conclutions: DHA can effectively inhibit proliferation of the peripheral T lymphocytoma Hut-78 cells and induce their apoptosis. Its action mechanism may be related to ability of HAD to promote release of ROS-dependent cytochrome C.
Objective:To investigate dihydroartemisinin (DHA)-induced apoptosis of peripheral T lymphocytoma Hut-78 cell line and its possible mechanism. Methods: The effect of DHA 1－30 μg/ml on proliferation of Hut-78 cells was measured by CCK-8 assay. The morphological changes of Hut-78 cell's nuclei induced by DHA were observed by Hochest 33258 staining and confocal microscopy. Flow cytometry was used to examine the apoptosis of Hut-78 cells induced by DHA. After pretreating the Hut-78 cells with 10 mmol/L of reactive oxygen species (ROS) scavenger N-acetyl cysteine C (NAC) , a role of ROS in changes of mitochondrial membrane potential induced by DHA was evaluated. Effect of ROS on release of cytochondrial C induced by DHA during apoptosis of Hut-78 cells was examined with an immunoblotting assay.Results:DHA inhibited proliferation of the Hut-78 cells in a dose-dependent manner, induced nucleus pyknosis and formed apoptotic bodies in the cells. Apoptosis rates of the Hut-78 cells iuduced with 5, 10 and 20 μg/ml of DHA were (25.1±2.8)%, (43,6±3.1)% and (68.9±2.6)% respectively, which were significantly different from that of the control group (all P<0.01 ). Furthermore, treatment with 20 μg/ml of DHA droped mitochondrial membrane potential of the Hut-78 cells by (59.4±2.6)%, and pretreating with ROS scavenger NAC droped the mitochondrial membrane potential by (38.4±2.1)%. DHA can induce release of cytochrome C in mitochondrion, which can be significantly inhibited by pretreatment with NAC. Statistic results further demonstrated this point. Conclutions: DHA can effectively inhibit proliferation of the peripheral T lymphocytoma Hut-78 cells and induce their apoptosis. Its action mechanism may be related to ability of HAD to promote release of ROS-dependent cytochrome C.
2016, 23(1):62-66.
DOI: 10.3872/j.issn.1007-385X.2016.01.010
Abstract:
Objective:To explore the effect of miR-486-5p on gastric cancer xenograft in nude mice and to investigate its probable mechanism. Methods: The subcutaneously transplanted tumor models of human gastric carcinoma (SGC-7901 cell line) in nude mice were established and after treated with miR-486-5p over-expression plasmids, growth situation of cancer xenografts in the nude mice was observed. The expression of NRP2（the target gene of miR-486-5p）were detected by Western blotting and immunohistochemical method. Results：Gastric carcinoma (SGC-7901) xenograft models in nude mice were successfully constructed; miR-486-5p can significantly inhibit the growth of xenografts in nude mice and the expression of miR-486-5p in cancer xenografts of experimental group was significantly higher than that of control group (P＜0.05). Compared to the negative control group and blank control group, the average mass and volume of cancer xenografts in experiment group was significantly less than those in the other groups, mass:(0.404±0.080) g vs (0.748±0.122) g, (0.788±0.176) g, all P＜0.05; volume: (0.333±0.039) cm3 vs (0.597±0.175) cm3, (0.594±0.216) cm3, P＜005, and the inhibition rate of cancer xenografts in experiment group was 46.99%. After treated with miR-486-5p over-expression plasmid in experiment group, the immunohistochemical results showed that NRP2 protein, presenting as yellow particle, mainly existed in the cytoplasm of gastric cancer cells; the IHS score of NRP2 protein in miR-486-5p group was significantly lower than that of NC and blank control groups (\[2.2±0.84\] vs \[6.4±0.89\], \[6.2±1.48\], all P<001); however, there was no significant difference between negative control and blank control groups (P＞005). The results of Western blotting shown that the relative expression of NRP2 protein in cancer xenograft tissues of experiment group was significantly less than that of the other groups (\[0.04±0.006\] vs \[0.70±0.03\], (0.68±002\]，all P<001). The difference in IHS score, inhibition rate of cancer and NRP2 protein expression between NC and blank control groups had no statistical significance (P>0.05). Conclusion: miR-486-5p can remarkably inhibit the growth of gastric cancer xenograft in nude mice. It may associate with inhibiting expression of NRP2.
Objective:To explore the effect of miR-486-5p on gastric cancer xenograft in nude mice and to investigate its probable mechanism. Methods: The subcutaneously transplanted tumor models of human gastric carcinoma (SGC-7901 cell line) in nude mice were established and after treated with miR-486-5p over-expression plasmids, growth situation of cancer xenografts in the nude mice was observed. The expression of NRP2（the target gene of miR-486-5p）were detected by Western blotting and immunohistochemical method. Results：Gastric carcinoma (SGC-7901) xenograft models in nude mice were successfully constructed; miR-486-5p can significantly inhibit the growth of xenografts in nude mice and the expression of miR-486-5p in cancer xenografts of experimental group was significantly higher than that of control group (P＜0.05). Compared to the negative control group and blank control group, the average mass and volume of cancer xenografts in experiment group was significantly less than those in the other groups, mass:(0.404±0.080) g vs (0.748±0.122) g, (0.788±0.176) g, all P＜0.05; volume: (0.333±0.039) cm3 vs (0.597±0.175) cm3, (0.594±0.216) cm3, P＜005, and the inhibition rate of cancer xenografts in experiment group was 46.99%. After treated with miR-486-5p over-expression plasmid in experiment group, the immunohistochemical results showed that NRP2 protein, presenting as yellow particle, mainly existed in the cytoplasm of gastric cancer cells; the IHS score of NRP2 protein in miR-486-5p group was significantly lower than that of NC and blank control groups (\[2.2±0.84\] vs \[6.4±0.89\], \[6.2±1.48\], all P<001); however, there was no significant difference between negative control and blank control groups (P＞005). The results of Western blotting shown that the relative expression of NRP2 protein in cancer xenograft tissues of experiment group was significantly less than that of the other groups (\[0.04±0.006\] vs \[0.70±0.03\], (0.68±002\]，all P<001). The difference in IHS score, inhibition rate of cancer and NRP2 protein expression between NC and blank control groups had no statistical significance (P>0.05). Conclusion: miR-486-5p can remarkably inhibit the growth of gastric cancer xenograft in nude mice. It may associate with inhibiting expression of NRP2.
2016, 23(1):67-72.
DOI: 10.3872/j.issn.1007-385X.2016.01.011
Abstract:
Objective:To explore the effect of histone deacetylase 1 (HDAC1) over-expression on drug resistance of glioma cells. Methods: U87MG cells were infected with a recombinant lentiviral vector pCDH-CMV-MCS-HDAC1-EF1-Puro/over-expressing HDAC1 and a control lentiviral pCDH-CMV-MCS-EF1-Puro, respectively. Cell line U87MG-HDAC1 which stably over expressing HDAC1, and control cell line U87MG-Control were selected with purine gradient concentration and identified by Western blotting. After processed with VM-26 and DDP at different concentrations assessed by MTT of the cells was evaluated by Hoechst/PI double staining assay, and the expressions of Bcl-2、Bax and Caspase-3 were examined by Western blotting.Results: Cell line U87MG-HDAC1 that stably over expressing HDAC1 was successfuly constructed. Compared with U87GM-Control group, the expression of U87MG-HDAC1 protein was significantly increased in U87MG-HDAC1 group (\[1.148±0.024\] vs \[0.580±0.003\], P<0.01). After drug treatment the survival rate of U87MG-HDAC1 cell was remarkably higher (0.1 μg/ml VM-26: \[95.57±0.45\]% vs \[68.8±149\]%, P<001)；(0.08 μg/ml DDP:\[99.20±7.4\]% vs \[72.48±2.03\]%, P<0.01); Number of apoptotic cells decreased (P<0.05); the expression of Caspase-3 protein decreased significantly (P<0.01) and the expression ratio of Bcl-2/Bax proteins was significantly enhanced (P<0.01). Conclusion: The over-expression of HDAC1 in glima cell U87MG remarkably enhance of resistance of the cells to chemotherapeutic drugs, which was may associated with the expressions of Caspase-3 and Bcl-2/Bax.
Objective:To explore the effect of histone deacetylase 1 (HDAC1) over-expression on drug resistance of glioma cells. Methods: U87MG cells were infected with a recombinant lentiviral vector pCDH-CMV-MCS-HDAC1-EF1-Puro/over-expressing HDAC1 and a control lentiviral pCDH-CMV-MCS-EF1-Puro, respectively. Cell line U87MG-HDAC1 which stably over expressing HDAC1, and control cell line U87MG-Control were selected with purine gradient concentration and identified by Western blotting. After processed with VM-26 and DDP at different concentrations assessed by MTT of the cells was evaluated by Hoechst/PI double staining assay, and the expressions of Bcl-2、Bax and Caspase-3 were examined by Western blotting.Results: Cell line U87MG-HDAC1 that stably over expressing HDAC1 was successfuly constructed. Compared with U87GM-Control group, the expression of U87MG-HDAC1 protein was significantly increased in U87MG-HDAC1 group (\[1.148±0.024\] vs \[0.580±0.003\], P<0.01). After drug treatment the survival rate of U87MG-HDAC1 cell was remarkably higher (0.1 μg/ml VM-26: \[95.57±0.45\]% vs \[68.8±149\]%, P<001)；(0.08 μg/ml DDP:\[99.20±7.4\]% vs \[72.48±2.03\]%, P<0.01); Number of apoptotic cells decreased (P<0.05); the expression of Caspase-3 protein decreased significantly (P<0.01) and the expression ratio of Bcl-2/Bax proteins was significantly enhanced (P<0.01). Conclusion: The over-expression of HDAC1 in glima cell U87MG remarkably enhance of resistance of the cells to chemotherapeutic drugs, which was may associated with the expressions of Caspase-3 and Bcl-2/Bax.
2016, 23(1):73-78.
DOI: 10.3872/j.issn.1007-385X.2016.01.012
Abstract:
Objective:To explore the clinical efficacy of dendritic cell vaccine combined with radiofrequency ablation (RFA) for treatment of colorectal liver metastasis (CRLM) patients. Methods: Forty-six patients with comfirmed CRLM underwent RFA in 81st Hospital of PLA from Aug. 2012 to Aug. 2014 were retrospectively analyzed, the patients were randomly divided into 2 groups: DC treatment combined with RFA group (n=26) and treatment group RFA control (n=20). After treatment, the two groups were compared for the recent curative effect, the long-term curative effect, immune function, safety and improvement in quality of life.Results：(1) The significant differences was found in the overall response rate between DC-RFA group and RFA group (92.31% vs 70.00%, P＜0.05); the six month survival rate of DC-RFA group and RFA group was 96.15% and 90.00% respectively. The 1- and 2- year survival rate of DC-RFA groups was slightly less better than that of RFA group（P＞0.05）; (2) in DC-RFA group, percentage of CD3+ and CD4+ the ratio of CD4+/CD8+ in peripheral blood increased significantly (P＜0.05), but CD8+ reduced (P＞0.05) after the treatment ; In the RFA group, percentage of CD3+and CD4+, the ratio of CD4+/CD8+ increased remarkably after treatment(P<005), while CD8+ slightly increased(P＞005). (3) In DC-RFA group, there were 2 cases of fever, 1 case of allergic reaction, and the patients recovered after treatment. (4) The life quality of the patients was improved in the DC-RFA group, especially in the aspects of mental state and pain control. Conclusion:In the treatment of patients with CRLM, DC vaccine combined with RFA can improve the therapeutic effect of RFA treatment, prolong the survival time, improve the immune function, and can effectively improve the quality of life and possess good treatment safety.
Objective:To explore the clinical efficacy of dendritic cell vaccine combined with radiofrequency ablation (RFA) for treatment of colorectal liver metastasis (CRLM) patients. Methods: Forty-six patients with comfirmed CRLM underwent RFA in 81st Hospital of PLA from Aug. 2012 to Aug. 2014 were retrospectively analyzed, the patients were randomly divided into 2 groups: DC treatment combined with RFA group (n=26) and treatment group RFA control (n=20). After treatment, the two groups were compared for the recent curative effect, the long-term curative effect, immune function, safety and improvement in quality of life.Results：(1) The significant differences was found in the overall response rate between DC-RFA group and RFA group (92.31% vs 70.00%, P＜0.05); the six month survival rate of DC-RFA group and RFA group was 96.15% and 90.00% respectively. The 1- and 2- year survival rate of DC-RFA groups was slightly less better than that of RFA group（P＞0.05）; (2) in DC-RFA group, percentage of CD3+ and CD4+ the ratio of CD4+/CD8+ in peripheral blood increased significantly (P＜0.05), but CD8+ reduced (P＞0.05) after the treatment ; In the RFA group, percentage of CD3+and CD4+, the ratio of CD4+/CD8+ increased remarkably after treatment(P<005), while CD8+ slightly increased(P＞005). (3) In DC-RFA group, there were 2 cases of fever, 1 case of allergic reaction, and the patients recovered after treatment. (4) The life quality of the patients was improved in the DC-RFA group, especially in the aspects of mental state and pain control. Conclusion:In the treatment of patients with CRLM, DC vaccine combined with RFA can improve the therapeutic effect of RFA treatment, prolong the survival time, improve the immune function, and can effectively improve the quality of life and possess good treatment safety.
2016, 23(1):79-82.
DOI: 10.3872/j.issn.1007-385X.2016.01.013
Abstract:
Objective:To evaluate the clinical efficacy and safety of trastuzumab combined with paclitaxel and “tegafur gimeracil and oteracil potassium” (S-1) chemotherapy in the second-line treatment for HER-2-positive advanced gastric carcinoma．Methods： Seventeen by gone cases of chemo-refractory advanced gastric carcinoma treated in Affiliated Cancer Hospital of Xinjiang Medical University from January 2012 to March 2014 were included in this study. The patients were previously treated with chemotherapy regimen of oxalipaltin combined with fluorouracil. Therapeutic effect and adverse reactions were evaluated in the second-line treatment with trastuzumab combined with paclitaxel and S-1．Results：The therapeutic effect of all the 17 patients were evaluated with partial alleviated in 4 cases, stable disease in 7 cases and disease progression in 6 cases, the objective effective rate was 4/17 and disease control rate was 11/17；The median progress free survival time (PFS) was 6.5 months (95% CI 4.9-11.1) and median overall survival time (OS) was 11.9 months (95% CI 8.7-13.8)．Among the 17 cases，loss of appetite, neutropenia, fatigue and hair loss were the most frequent adverse events, and most of them were at level 1-2．In the aspect of possible trastuzumab-related adverse events, no obvious decreasing in left ventricular ejection fraction and adverse events related to cardiac was observed. Conclusion:Second-line chemotherapy of trastuzumab combined with paclitaxel and S-1 is effective and safe in treating patients with HER2-positive advanced gastric carcinoma.
Objective:To evaluate the clinical efficacy and safety of trastuzumab combined with paclitaxel and “tegafur gimeracil and oteracil potassium” (S-1) chemotherapy in the second-line treatment for HER-2-positive advanced gastric carcinoma．Methods： Seventeen by gone cases of chemo-refractory advanced gastric carcinoma treated in Affiliated Cancer Hospital of Xinjiang Medical University from January 2012 to March 2014 were included in this study. The patients were previously treated with chemotherapy regimen of oxalipaltin combined with fluorouracil. Therapeutic effect and adverse reactions were evaluated in the second-line treatment with trastuzumab combined with paclitaxel and S-1．Results：The therapeutic effect of all the 17 patients were evaluated with partial alleviated in 4 cases, stable disease in 7 cases and disease progression in 6 cases, the objective effective rate was 4/17 and disease control rate was 11/17；The median progress free survival time (PFS) was 6.5 months (95% CI 4.9-11.1) and median overall survival time (OS) was 11.9 months (95% CI 8.7-13.8)．Among the 17 cases，loss of appetite, neutropenia, fatigue and hair loss were the most frequent adverse events, and most of them were at level 1-2．In the aspect of possible trastuzumab-related adverse events, no obvious decreasing in left ventricular ejection fraction and adverse events related to cardiac was observed. Conclusion:Second-line chemotherapy of trastuzumab combined with paclitaxel and S-1 is effective and safe in treating patients with HER2-positive advanced gastric carcinoma.
2016, 23(1):83-88.
DOI: 10.3872/j.issn.1007-385X.2016.01.014
Abstract:
Objective:To investigate the clinical efficacy and safety of autologous tumor antigen-pulsed DC-CIK (dendritic cell-cytokine induced killer cell) combined with chemotherapy in treatment of advanced lung adenocarcinoma.Methods: 120 patients with advanced lung adenocarcinoma treated in the Affiliated Tumor Hospital of Xinjiang Medical University from Jan 2013 to December 2013 were selected in this study; 60 patients were treated with autologous tumor antigen-pulsed DC-CIK combined with chemotherapy (combination group), the other 60 patients were treated with chemotherapy only (chemotherapy group); the immune function, curative effect, adverse reactions, quality of life (QOL), progression free survival (PFS) and overall survival (OS) after treatment were separately evaluated in the two groups . Results: Compared to the values of pre-treatment, there was no significant difference in peripheral blood T cell subsets in combination group (P>0.05); Compared to pre-treatment value, the post-treatment percentage of CD3+, CD3+CD4+, CD3+CD8+ and CD3-CD56+ in peripheral blood decreased significantly in chemotherapy group, and it was significant lower than that of combination group (P<0.05); the incidences of nausea and vomiting, Ⅲ-Ⅳ degree myelosuppression in combination group were less than that of chemotherapy group, and the difference was statistically significant (P<005); after treatment, compared with chemotherapy group, the combination of sleep, appetite and physical strength in combination group was significantly improved (P<0.05). There was no significant difference in PFS between combination group and chemotherapy group (6 months vs 4.5 months, P>0.05), however, the OS of combination group was longer than that of chemotherapy group (16 months vs 11.5 months, P<0.05). Conclusion:Autologous tumor antigen-pulsed DC-CIK combination with chemotherapy, compared with chemotherapy alone, can obviously optimize the immune function of the patients, improve their life quality, reduce the adverse reactions, prolonged overall survival periods, and improve the overall curative effects.
Objective:To investigate the clinical efficacy and safety of autologous tumor antigen-pulsed DC-CIK (dendritic cell-cytokine induced killer cell) combined with chemotherapy in treatment of advanced lung adenocarcinoma.Methods: 120 patients with advanced lung adenocarcinoma treated in the Affiliated Tumor Hospital of Xinjiang Medical University from Jan 2013 to December 2013 were selected in this study; 60 patients were treated with autologous tumor antigen-pulsed DC-CIK combined with chemotherapy (combination group), the other 60 patients were treated with chemotherapy only (chemotherapy group); the immune function, curative effect, adverse reactions, quality of life (QOL), progression free survival (PFS) and overall survival (OS) after treatment were separately evaluated in the two groups . Results: Compared to the values of pre-treatment, there was no significant difference in peripheral blood T cell subsets in combination group (P>0.05); Compared to pre-treatment value, the post-treatment percentage of CD3+, CD3+CD4+, CD3+CD8+ and CD3-CD56+ in peripheral blood decreased significantly in chemotherapy group, and it was significant lower than that of combination group (P<0.05); the incidences of nausea and vomiting, Ⅲ-Ⅳ degree myelosuppression in combination group were less than that of chemotherapy group, and the difference was statistically significant (P<005); after treatment, compared with chemotherapy group, the combination of sleep, appetite and physical strength in combination group was significantly improved (P<0.05). There was no significant difference in PFS between combination group and chemotherapy group (6 months vs 4.5 months, P>0.05), however, the OS of combination group was longer than that of chemotherapy group (16 months vs 11.5 months, P<0.05). Conclusion:Autologous tumor antigen-pulsed DC-CIK combination with chemotherapy, compared with chemotherapy alone, can obviously optimize the immune function of the patients, improve their life quality, reduce the adverse reactions, prolonged overall survival periods, and improve the overall curative effects.
2016, 23(1):89-94.
DOI: 10.3872/j.issn.1007-385X.2016.01.015
Abstract:
Objective:To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) and epithelial growth factor receptor (EGFR) and their relationship to clinicopathological features and prognosis of gastric cancer. Methods: 116 cases of gastric carcinoma tissues and 20 cases of tumor-adjacent tissues, resected from July 2008 to July 2010 in the First Affiliated Hospital of Nanyang Medical College, were analyzed for the expression of HIF-1α and EGFR by immnohistochemical staining, as well as their correlation with clinicopathological factors and survival time. Results:The positive rates of HIF-1α (63.8%) and EGFR (68.1%) in cancer tissues were significantly higher than those in tumor-adjacent tissues (P<0.01). The rate for both HIF-1α+ and EGFR+ was 50.9%. The expression of HIF-1α was correlated with T staging (P=0.014), and the co-expression of HIF-1α+ and EGFR+ was correlated with invasion depth and TNM stage (P=0.006 and P=0.023). Spearman rank correlation analysis illustrated that there was a significant positive correlation between HIF-1α and EGFR (r=0.331，P=0.000). Kaplan-Meier survival analysis showed that the survival time of patients with positive EGFR expression was significantly shorter than those with negative expression （29.6 months vs 48.4 months，P＜0.019）. The multivariate Cox regression analysis demonstrated that EGFR positivity, as an independent factor, could predict poor prognosis for patients with gastric cancer. Conclusion: HIF-1α and EGFR were highly expressed in the tissues of gastric cancer; HIF-1α and EGFR were closely related with each other, and may play important roles in development and progression of gastric carcinoma. EGFR positivity may be used as important index to evaluate the prognosis of gastric carcinoma.
Objective:To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) and epithelial growth factor receptor (EGFR) and their relationship to clinicopathological features and prognosis of gastric cancer. Methods: 116 cases of gastric carcinoma tissues and 20 cases of tumor-adjacent tissues, resected from July 2008 to July 2010 in the First Affiliated Hospital of Nanyang Medical College, were analyzed for the expression of HIF-1α and EGFR by immnohistochemical staining, as well as their correlation with clinicopathological factors and survival time. Results:The positive rates of HIF-1α (63.8%) and EGFR (68.1%) in cancer tissues were significantly higher than those in tumor-adjacent tissues (P<0.01). The rate for both HIF-1α+ and EGFR+ was 50.9%. The expression of HIF-1α was correlated with T staging (P=0.014), and the co-expression of HIF-1α+ and EGFR+ was correlated with invasion depth and TNM stage (P=0.006 and P=0.023). Spearman rank correlation analysis illustrated that there was a significant positive correlation between HIF-1α and EGFR (r=0.331，P=0.000). Kaplan-Meier survival analysis showed that the survival time of patients with positive EGFR expression was significantly shorter than those with negative expression （29.6 months vs 48.4 months，P＜0.019）. The multivariate Cox regression analysis demonstrated that EGFR positivity, as an independent factor, could predict poor prognosis for patients with gastric cancer. Conclusion: HIF-1α and EGFR were highly expressed in the tissues of gastric cancer; HIF-1α and EGFR were closely related with each other, and may play important roles in development and progression of gastric carcinoma. EGFR positivity may be used as important index to evaluate the prognosis of gastric carcinoma.
2016, 23(1):95-101.
DOI: 10.3872/j.issn.1007-385X.2016.01.016
Abstract:
Objective:To investigate the expression of retinoblastoma (Rb) and phosphate retinoblastoma (P-Rb) in human breast cancer tissues and their significance during the process of epithelial-mesenchymal transition (EMT). Methods: 65 samples from patients with breast cancer that surgically removed in the Fourth Clinical Hospital of Hebei Medical University from Jan. to Aug. 2009 were retrospectively examined in this study. Immunohistochemistry was used to examine the expression of Rb, P-Rb, CDH1 and Vimentin in the breast cancer tissues of 65 cases. The correlation between their expression and clinicopathological parameters and prognosis of the case wih breast cancer was analyzed. Real-time PCR and Western blotting were used to examine the expression change of Rb and P-Rb in TGFβ-induced EMT. Results: Expression rates of Rb and P-Rb in the breast cancer tissues were 55.38% and 50.77%, respectively. Expression of P-Rb was positively correlated with tumor size, clinical stages and lymph node metastasis. Expression rates of CDH1 and Vimentin in the breast cancer were 76.92% and 43.08% respectively. Expression of CDH1 negatively correlates with tumor size, clinical stages and lymph node metastasis, while expression of Vimentin positively correlates with tumor size, clinical stages and lymph node metastasis. Both expressions of Rb and P-Rb positively correlates with expression of CDH1, but negatively correlates with expression of Vimentin. Overall 5 years survival rate of patients with P-Rb positive breast cancer was significantly lower than that of patients with P-Rb negative breast cancer; overall 5 years survival rate of patients with CDH1 positive breast cancer was significantly higher than that of patients with CDH1 negative breast cancer; overall 5 years survival rate of patients with Vimentin positive breast cancer was significantly lower than that of patients with Vimentin negative breast cancer. Expression of Rb was down regulated and that of P-Rb up regulated in TGFβ induced EMT of HEML cells.Conclusion: Inactivation of Rb with phosphorylation affected EMT and correlated with breast cancer metastasis.
Objective:To investigate the expression of retinoblastoma (Rb) and phosphate retinoblastoma (P-Rb) in human breast cancer tissues and their significance during the process of epithelial-mesenchymal transition (EMT). Methods: 65 samples from patients with breast cancer that surgically removed in the Fourth Clinical Hospital of Hebei Medical University from Jan. to Aug. 2009 were retrospectively examined in this study. Immunohistochemistry was used to examine the expression of Rb, P-Rb, CDH1 and Vimentin in the breast cancer tissues of 65 cases. The correlation between their expression and clinicopathological parameters and prognosis of the case wih breast cancer was analyzed. Real-time PCR and Western blotting were used to examine the expression change of Rb and P-Rb in TGFβ-induced EMT. Results: Expression rates of Rb and P-Rb in the breast cancer tissues were 55.38% and 50.77%, respectively. Expression of P-Rb was positively correlated with tumor size, clinical stages and lymph node metastasis. Expression rates of CDH1 and Vimentin in the breast cancer were 76.92% and 43.08% respectively. Expression of CDH1 negatively correlates with tumor size, clinical stages and lymph node metastasis, while expression of Vimentin positively correlates with tumor size, clinical stages and lymph node metastasis. Both expressions of Rb and P-Rb positively correlates with expression of CDH1, but negatively correlates with expression of Vimentin. Overall 5 years survival rate of patients with P-Rb positive breast cancer was significantly lower than that of patients with P-Rb negative breast cancer; overall 5 years survival rate of patients with CDH1 positive breast cancer was significantly higher than that of patients with CDH1 negative breast cancer; overall 5 years survival rate of patients with Vimentin positive breast cancer was significantly lower than that of patients with Vimentin negative breast cancer. Expression of Rb was down regulated and that of P-Rb up regulated in TGFβ induced EMT of HEML cells.Conclusion: Inactivation of Rb with phosphorylation affected EMT and correlated with breast cancer metastasis.
2016, 23(1):102-105.
DOI: 10.3872/j.issn.1007-385X.2016.01.017
Abstract:
Objective:To investigate the expression and clinical significance of connective tissue growth factor (CTGF) in ovarian cancer. Methods: The expression levels of CTGF in 20 cases of normal ovarian tissues，30 cases of benign ovarian tumor tissues and 105 cases of ovarian cancer tissues were examined by RT-PCR and immunohistochemical staining, and the correlation between CTGF expression and clinicopathological significance of ovarian cancer was analyzed. Results: The positive rate of CTGF expression in normal ovarian tissues, benign ovarian tumor tissues and ovarian cancer tissues were 95.00%（19/20），93.33%(28/30) and 53.33%（56/105）respectively; the positive rate of CTGF in ovarian cancer tissues was significantly lower than that of normal ovarian tissues（χ2=12.15, P=0.00) and benign ovarian tumor tissues（χ2=15.88, P=0.00）; there was no significant difference in the positive rate between normal ovarian tissues and benign ovarian tumor tissues（χ2=15.88, P=0.00）. The CTGF mRNA expression in ovarian cancer tissue was lower than that in normal ovarian tissue and benign ovarian tumor tissue showed by RT-PCR ( F=3.39，P=0.039）. Data was processed by χ2 analysis, and the results showed that the expression of CTGF was correlated with clinical stages, lymph node metastasis（P<005）, but not correlated with age, pathologic type，pathologic grade and positive rate of ascites tumor cells (P>0.05）. Conclusion：CTGF was low expressed in overian cancer tissues and correlate with the occurrence and progression of ovarian cancer.
Objective:To investigate the expression and clinical significance of connective tissue growth factor (CTGF) in ovarian cancer. Methods: The expression levels of CTGF in 20 cases of normal ovarian tissues，30 cases of benign ovarian tumor tissues and 105 cases of ovarian cancer tissues were examined by RT-PCR and immunohistochemical staining, and the correlation between CTGF expression and clinicopathological significance of ovarian cancer was analyzed. Results: The positive rate of CTGF expression in normal ovarian tissues, benign ovarian tumor tissues and ovarian cancer tissues were 95.00%（19/20），93.33%(28/30) and 53.33%（56/105）respectively; the positive rate of CTGF in ovarian cancer tissues was significantly lower than that of normal ovarian tissues（χ2=12.15, P=0.00) and benign ovarian tumor tissues（χ2=15.88, P=0.00）; there was no significant difference in the positive rate between normal ovarian tissues and benign ovarian tumor tissues（χ2=15.88, P=0.00）. The CTGF mRNA expression in ovarian cancer tissue was lower than that in normal ovarian tissue and benign ovarian tumor tissue showed by RT-PCR ( F=3.39，P=0.039）. Data was processed by χ2 analysis, and the results showed that the expression of CTGF was correlated with clinical stages, lymph node metastasis（P<005）, but not correlated with age, pathologic type，pathologic grade and positive rate of ascites tumor cells (P>0.05）. Conclusion：CTGF was low expressed in overian cancer tissues and correlate with the occurrence and progression of ovarian cancer.
2016, 23(1):106-113.
DOI: 10.3872/j.issn.1007-385X.2016.01.018
Abstract:
真核生物由于双层核膜的存在，蛋白及大分子物质需依赖核质转运受体进行跨核膜转运。核输出蛋白1（exportin 1, XPO1)是最重要的出核转运受体之一，负责多种蛋白和RNAs的出核转运。XPO1往往在肿瘤细胞中过量表达，导致多种抑癌基因蛋白及生长调节蛋白亚细胞定位及功能的紊乱，从而促进了肿瘤的发生发展。XPO1不仅可作为肿瘤患者预后判断的指标，还是抗肿瘤治疗的潜在靶标。近年来，一系列XPO1小分子抑制剂的研发，尤其是高效低毒的SINE系列抑制剂的抗肿瘤临床研究，揭示了XPO1抑制剂在治疗难治性、耐药性、转移复发性血液恶性肿瘤及实体肿瘤的独特疗效，并引起广泛关注。本文就出核转运抑制剂的临床转化研究进展进行综述。
真核生物由于双层核膜的存在，蛋白及大分子物质需依赖核质转运受体进行跨核膜转运。核输出蛋白1（exportin 1, XPO1)是最重要的出核转运受体之一，负责多种蛋白和RNAs的出核转运。XPO1往往在肿瘤细胞中过量表达，导致多种抑癌基因蛋白及生长调节蛋白亚细胞定位及功能的紊乱，从而促进了肿瘤的发生发展。XPO1不仅可作为肿瘤患者预后判断的指标，还是抗肿瘤治疗的潜在靶标。近年来，一系列XPO1小分子抑制剂的研发，尤其是高效低毒的SINE系列抑制剂的抗肿瘤临床研究，揭示了XPO1抑制剂在治疗难治性、耐药性、转移复发性血液恶性肿瘤及实体肿瘤的独特疗效，并引起广泛关注。本文就出核转运抑制剂的临床转化研究进展进行综述。
2016, 23(1):114-118.
DOI: 10.3872/j.issn.1007-385X.2016.01.019
Abstract:
上皮间质转化（epithelial to mesenchymal transition，EMT）指上皮细胞向间质细胞转变的现象，其在组织损伤修复等生命过程中是必需的。研究发现，EMT在肿瘤细胞侵袭和转移中发挥至关重要的作用，EMT不仅使肿瘤细胞获得迁移、侵袭、转移能力，同时还与肿瘤细胞抑制衰老和凋亡、抵抗放化疗和形成肿瘤干细胞（cancer stem cells, CSCs）密切相关，因此抑制EMT成为抑制肿瘤转移的新策略。肿瘤细胞EMT受到表观遗传的复杂调控，DNA甲基化、组蛋白修饰、非编码RNA在EMT发生中扮演十分重要的角色，因此肿瘤细胞EMT的表观遗传调控已经成为国内外的研究热点。本文就肿瘤细胞EMT表观遗传调控机制的研究进展予以综述。
上皮间质转化（epithelial to mesenchymal transition，EMT）指上皮细胞向间质细胞转变的现象，其在组织损伤修复等生命过程中是必需的。研究发现，EMT在肿瘤细胞侵袭和转移中发挥至关重要的作用，EMT不仅使肿瘤细胞获得迁移、侵袭、转移能力，同时还与肿瘤细胞抑制衰老和凋亡、抵抗放化疗和形成肿瘤干细胞（cancer stem cells, CSCs）密切相关，因此抑制EMT成为抑制肿瘤转移的新策略。肿瘤细胞EMT受到表观遗传的复杂调控，DNA甲基化、组蛋白修饰、非编码RNA在EMT发生中扮演十分重要的角色，因此肿瘤细胞EMT的表观遗传调控已经成为国内外的研究热点。本文就肿瘤细胞EMT表观遗传调控机制的研究进展予以综述。
2016, 23(1):119-123.
DOI: 10.3872/j.issn.1007-385X.2016.01.020
Abstract:
SETD2是哺乳动物中唯一的组蛋白H3K36的特异性三甲基转移酶，它的编码基因位于第三号染色体的3p21.31区域。SETD2蛋白是一个230 kD、含有SET结构域的蛋白，最早是由人造血干细胞分离的，也被认为是与亨廷顿病的发病机制相关。它是生物转录延伸过程中的重要组成部分，能够与RNA聚合酶Ⅱ的最大亚基Rbp1结合，参与基因的转录延伸。SETD2还能通过编码区的去乙酰化抑制转录起始的频率以保证基因转录的高保真度，从而预防肿瘤的发生；同时SETD2也能激活转录因子〖STBX〗p53〖STBZ〗及下游凋亡靶基因发挥抑癌作用。SETD2在DNA修复方面也具有重要作用，它是人错配基因修复和人同源基因修复过程中不可缺少的重要部分。已经有研究表明在多种肿瘤中SETD2均发生了突变，包括肾透明细胞癌、小儿晚期神经胶质瘤、急性T淋巴细胞白血病等，对某些特定肿瘤的分期和预后也有显著影响。本文将介绍SETD2在人体内的多种功能，并对其在肿瘤发生发展中的作用机制进行综述。
SETD2是哺乳动物中唯一的组蛋白H3K36的特异性三甲基转移酶，它的编码基因位于第三号染色体的3p21.31区域。SETD2蛋白是一个230 kD、含有SET结构域的蛋白，最早是由人造血干细胞分离的，也被认为是与亨廷顿病的发病机制相关。它是生物转录延伸过程中的重要组成部分，能够与RNA聚合酶Ⅱ的最大亚基Rbp1结合，参与基因的转录延伸。SETD2还能通过编码区的去乙酰化抑制转录起始的频率以保证基因转录的高保真度，从而预防肿瘤的发生；同时SETD2也能激活转录因子〖STBX〗p53〖STBZ〗及下游凋亡靶基因发挥抑癌作用。SETD2在DNA修复方面也具有重要作用，它是人错配基因修复和人同源基因修复过程中不可缺少的重要部分。已经有研究表明在多种肿瘤中SETD2均发生了突变，包括肾透明细胞癌、小儿晚期神经胶质瘤、急性T淋巴细胞白血病等，对某些特定肿瘤的分期和预后也有显著影响。本文将介绍SETD2在人体内的多种功能，并对其在肿瘤发生发展中的作用机制进行综述。
2016, 23(1):124-129.
DOI: 10.3872/j.issn.1007-385X.2016.01.021
Abstract:
近年来，黑素瘤的免疫治疗取得了较大的突破，提高了其临床疗效，成为当前研究热点。大量研究发现，黑素瘤中存在干性细胞，它们具有特殊的分子表型、信号通路和肿瘤微环境，与肿瘤的增殖、侵袭、转移、复发和放化疗抵抗等密切相关，参与黑素瘤的发生发展。令人感兴趣的是，黑素瘤干细胞样细胞（melanoma tumor stem-like cells，MTSCs）代表了难治性和耐药性肿瘤细胞的主体，针对MTSCs的免疫治疗显示出较好的临床疗效和远期预后，成为黑素瘤免疫治疗的新方向。本文主要综述黑素瘤干细胞样细胞特异性表面标记分子及其分选方法、异常信号通路特征、免疫耐受性肿瘤微环境及其相关靶向免疫治疗的新进展，以期为研发黑素瘤免疫治疗新方法提供理论指导。
近年来，黑素瘤的免疫治疗取得了较大的突破，提高了其临床疗效，成为当前研究热点。大量研究发现，黑素瘤中存在干性细胞，它们具有特殊的分子表型、信号通路和肿瘤微环境，与肿瘤的增殖、侵袭、转移、复发和放化疗抵抗等密切相关，参与黑素瘤的发生发展。令人感兴趣的是，黑素瘤干细胞样细胞（melanoma tumor stem-like cells，MTSCs）代表了难治性和耐药性肿瘤细胞的主体，针对MTSCs的免疫治疗显示出较好的临床疗效和远期预后，成为黑素瘤免疫治疗的新方向。本文主要综述黑素瘤干细胞样细胞特异性表面标记分子及其分选方法、异常信号通路特征、免疫耐受性肿瘤微环境及其相关靶向免疫治疗的新进展，以期为研发黑素瘤免疫治疗新方法提供理论指导。
2016, 23(1):130-134.
DOI: 10.3872/j.issn.1007-385X.2016.01.022
Abstract:
白介素10（interleukin-10, IL-10）是一种主要由效应T细胞产生的免疫调节因子，它最初被认为是具有免疫抑制作用的抗炎分子，通过直接和间接抑制T细胞的活化作用促进肿瘤的生长。近年来的研究发现IL-10还具有免疫活化作用，可以通过对T细胞和自然杀伤细胞（natural killer cell, NK）的免疫活化作用促进肿瘤特异性免疫监视并减少致病性炎症反应的发生，表明IL-10能够发挥双向免疫调节作用。由于IL-10在免疫反应中发挥双向免疫调节功能并处于免疫调节的核心地位，使得它在肿瘤免疫中的作用仍存在许多可探讨之处。对IL-10功能的深入研究将有利于人们对肿瘤免疫的认识。本文就IL-10在肿瘤免疫中的双向调节作用作一综述。
白介素10（interleukin-10, IL-10）是一种主要由效应T细胞产生的免疫调节因子，它最初被认为是具有免疫抑制作用的抗炎分子，通过直接和间接抑制T细胞的活化作用促进肿瘤的生长。近年来的研究发现IL-10还具有免疫活化作用，可以通过对T细胞和自然杀伤细胞（natural killer cell, NK）的免疫活化作用促进肿瘤特异性免疫监视并减少致病性炎症反应的发生，表明IL-10能够发挥双向免疫调节作用。由于IL-10在免疫反应中发挥双向免疫调节功能并处于免疫调节的核心地位，使得它在肿瘤免疫中的作用仍存在许多可探讨之处。对IL-10功能的深入研究将有利于人们对肿瘤免疫的认识。本文就IL-10在肿瘤免疫中的双向调节作用作一综述。
2016, 23(1):135-139.
DOI: 10.3872/j.issn.1007-385X.2016.01.023
Abstract:
B淋巴细胞作为体液和细胞免疫的重要组成部分，能够通过多种调控方式发挥正性免疫调节作用。然而，越来越多的研究表明，B淋巴细胞亦可通过多种途径参与机体的免疫抑制调节，其中在肿瘤中以免疫抑制作用为主。目前研究多关注于B淋巴细胞特殊亚型-调节性B细胞（regulatory B cells, Bregs)在肿瘤中发挥的免疫抑制性作用,并通过分泌多种细胞因子、调控T细胞的作用以及直接作用于恶性肿瘤细胞等多途径影响肿瘤的发生发展进程。本文就B淋巴细胞在肿瘤免疫抑制机制研究的最新进展作一综述，为B淋巴细胞作为抗肿瘤潜在治疗靶点及治疗策略提供新的思路。
B淋巴细胞作为体液和细胞免疫的重要组成部分，能够通过多种调控方式发挥正性免疫调节作用。然而，越来越多的研究表明，B淋巴细胞亦可通过多种途径参与机体的免疫抑制调节，其中在肿瘤中以免疫抑制作用为主。目前研究多关注于B淋巴细胞特殊亚型-调节性B细胞（regulatory B cells, Bregs)在肿瘤中发挥的免疫抑制性作用,并通过分泌多种细胞因子、调控T细胞的作用以及直接作用于恶性肿瘤细胞等多途径影响肿瘤的发生发展进程。本文就B淋巴细胞在肿瘤免疫抑制机制研究的最新进展作一综述，为B淋巴细胞作为抗肿瘤潜在治疗靶点及治疗策略提供新的思路。
2016, 23(1):140-144.
DOI: 10.3872/j.issn.1007-385X.2016.01.024
Abstract:
临床医生如何在繁重的临床工作中兼顾科研一直是一个难题，其实在临床工作中有许多可供研究的临床课题，临床医生应该从临床遇到的问题中寻找科研选题，努力寻找答案以解决这些问题。临床医生应该牢记科研的目的是为了使患者从研究中真正获得益处，因此只要贴近临床，从临床诊疗过程中发现问题及提出问题、最终解决问题，就可以进行有价值的临床研究。总之，临床工作与临床科研并不矛盾，正确的科研思维，有助于临床医生更好地总结经验、探究规律、提高疗效及最终造福患者。希望“大处着眼、小处着手，勤于思考、善于反思、精于总结”这20个字对临床医生做好科研工作能够有所帮助。笔者以自己的切身经验着重介绍临床研究的选题和设计思路，包括开展个案报道、回顾性病例系列研究、诊断性试验（指标诊断和症状诊断）和随机对照试验等一系列有临床价值的研究。
临床医生如何在繁重的临床工作中兼顾科研一直是一个难题，其实在临床工作中有许多可供研究的临床课题，临床医生应该从临床遇到的问题中寻找科研选题，努力寻找答案以解决这些问题。临床医生应该牢记科研的目的是为了使患者从研究中真正获得益处，因此只要贴近临床，从临床诊疗过程中发现问题及提出问题、最终解决问题，就可以进行有价值的临床研究。总之，临床工作与临床科研并不矛盾，正确的科研思维，有助于临床医生更好地总结经验、探究规律、提高疗效及最终造福患者。希望“大处着眼、小处着手，勤于思考、善于反思、精于总结”这20个字对临床医生做好科研工作能够有所帮助。笔者以自己的切身经验着重介绍临床研究的选题和设计思路，包括开展个案报道、回顾性病例系列研究、诊断性试验（指标诊断和症状诊断）和随机对照试验等一系列有临床价值的研究。
联系方式
- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.