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Volume 16,Issue 1,2009 Table of Contents
2009, 16(1):1-1.
DOI: 10.3872/j.issn.1007-385X.2009.1.001
Abstract:
2009, 16(1):2-5.
DOI: 10.3872/j.issn.1007-385X.2009.1.002
Abstract:
The development and differentiation of NK cells are highly noted in recent years. In addition to the peripheral blood, spleen and bone marrow, the liver, lymph nodes and thymus are also considered as important organs for differentiation of NK cell precursors (NKPs) . Human NK cell subset CD56bright is enriched in secondary lymphoid tissues and nonlymph tissues; NK subset cell CD56dim can migrate to peripheral inflammatory region. Activating receptors on NK cells include cytokine receptors, integrin receptors, natural cytotoxic receptors, immunoglobulinlike killer receptors, and many new receptors and ligands different from the aforementioned receptor families. In the process of tumor progression, NK cells can directly recognize malignant cells via “internal recognition” and be activated; they can also be activated by accessory cells such as monocytes, macrophages and dentritic cells. DC cells can trigger the activation of NK cells, in which the reverse signal transduction of IL15RIL15 plays an important role. Great progression has been made in NK cellbased immunotherapy of tumor, in particular there are many new ways in NK cell innate recognitionbased tumor biotherapy
The development and differentiation of NK cells are highly noted in recent years. In addition to the peripheral blood, spleen and bone marrow, the liver, lymph nodes and thymus are also considered as important organs for differentiation of NK cell precursors (NKPs) . Human NK cell subset CD56bright is enriched in secondary lymphoid tissues and nonlymph tissues; NK subset cell CD56dim can migrate to peripheral inflammatory region. Activating receptors on NK cells include cytokine receptors, integrin receptors, natural cytotoxic receptors, immunoglobulinlike killer receptors, and many new receptors and ligands different from the aforementioned receptor families. In the process of tumor progression, NK cells can directly recognize malignant cells via “internal recognition” and be activated; they can also be activated by accessory cells such as monocytes, macrophages and dentritic cells. DC cells can trigger the activation of NK cells, in which the reverse signal transduction of IL15RIL15 plays an important role. Great progression has been made in NK cellbased immunotherapy of tumor, in particular there are many new ways in NK cell innate recognitionbased tumor biotherapy
2009, 16(1):6-11.
DOI: 10.3872/j.issn.1007-385X.2009.1.003
Abstract:
Objective: To explore the role of membranebound stem cell factor (mSCF) in the pathogenesis of leukemia. Methods: The eukaryotic expression plasmid of soluble stem cell factor（sSCF）precursor (pTARGETs) was constructed. Overlap PCR was used to obtain mSCF sequence with the deletion of exon 6, and pTARGETm was constructed. After verified by DNA sequencing, pTARGETm and control pTARGET vector were transfected into K562 cells via Lipofetamine 2000, and the positive cells were screened by G418. K562 cells stably transfected with pTARGETm were verified by RTPCR and Western blotting. Proliferation and colonyformation of these stably transfected cells were studied. Results: The sSCF and mSCF eukaryotic expression vectors were successfully constructed. The stable transfectants K562V, K562S, and K562M were obtained. Under Ubottom culture condition, proliferation ability of K562M cells was significantly stronger than those of K562V or K562S (both P<0.01). Colonyformation ability of K562M was significantly higher than those of K562V and K562S (both P<0.01). Furthermore, the colony size of K562M was larger than those of the other two kinds of cells. Conclusion: mSCF significantly enhances proliferation and colonyformation of leukemia cells by a juxtacrine mechanism.
Objective: To explore the role of membranebound stem cell factor (mSCF) in the pathogenesis of leukemia. Methods: The eukaryotic expression plasmid of soluble stem cell factor（sSCF）precursor (pTARGETs) was constructed. Overlap PCR was used to obtain mSCF sequence with the deletion of exon 6, and pTARGETm was constructed. After verified by DNA sequencing, pTARGETm and control pTARGET vector were transfected into K562 cells via Lipofetamine 2000, and the positive cells were screened by G418. K562 cells stably transfected with pTARGETm were verified by RTPCR and Western blotting. Proliferation and colonyformation of these stably transfected cells were studied. Results: The sSCF and mSCF eukaryotic expression vectors were successfully constructed. The stable transfectants K562V, K562S, and K562M were obtained. Under Ubottom culture condition, proliferation ability of K562M cells was significantly stronger than those of K562V or K562S (both P<0.01). Colonyformation ability of K562M was significantly higher than those of K562V and K562S (both P<0.01). Furthermore, the colony size of K562M was larger than those of the other two kinds of cells. Conclusion: mSCF significantly enhances proliferation and colonyformation of leukemia cells by a juxtacrine mechanism.
2009, 16(1):12-17.
DOI: 10.3872/j.issn.1007-385X.2009.1.004
Abstract:
Objective: To investigate the mechanism by which tumor necrosis factorα (TNFα) induces expression of vascular endothelial growth factor(VEGF) in MCF7 cells. Methods: MCF7 cells were treated with TNFα (20 ng/ml) for different time periods. Western blotting was used to detect the phosphorylation of MAPK pathway proteins (JNK, P38, and ERK) and the expression and phosphorylation of AP1 family members(cJun，JunB，cFos，Fra1，Fra2，JunD). The activation of AP1 was detected by immunoprecipitation(IP). RTPCR and Western blotting were used to detect the VEGF mRNA and protein expression. The VEGF protein expression was also detected after pretreatment with inhibitor of MAPK. ChIP method was used to verify the binding of pcJun to the promoter region of VEGF. Results: TNFα activated AP1 through JNK signal pathway. AP1 existed in the form of pcJuncJun and pcJunJunB homodimer after activation. TNFα increased VEGF transcription by activating transcriptional factor AP1 and result in increased expression of VEGF protein. Pcjun regulated the transcription of VEGF through binding to the AP1 site of VEGF. Conclusion: TNFα can mediate the transcription of VEGF through a AP1dependent pathway.
Objective: To investigate the mechanism by which tumor necrosis factorα (TNFα) induces expression of vascular endothelial growth factor(VEGF) in MCF7 cells. Methods: MCF7 cells were treated with TNFα (20 ng/ml) for different time periods. Western blotting was used to detect the phosphorylation of MAPK pathway proteins (JNK, P38, and ERK) and the expression and phosphorylation of AP1 family members(cJun，JunB，cFos，Fra1，Fra2，JunD). The activation of AP1 was detected by immunoprecipitation(IP). RTPCR and Western blotting were used to detect the VEGF mRNA and protein expression. The VEGF protein expression was also detected after pretreatment with inhibitor of MAPK. ChIP method was used to verify the binding of pcJun to the promoter region of VEGF. Results: TNFα activated AP1 through JNK signal pathway. AP1 existed in the form of pcJuncJun and pcJunJunB homodimer after activation. TNFα increased VEGF transcription by activating transcriptional factor AP1 and result in increased expression of VEGF protein. Pcjun regulated the transcription of VEGF through binding to the AP1 site of VEGF. Conclusion: TNFα can mediate the transcription of VEGF through a AP1dependent pathway.
2009, 16(1):18-23.
DOI: 10.3872/j.issn.1007-385X.2009.1.005
Abstract:
Objective: To study the antigen specific antitumor effect of cytotoxic T lymphocyte (CTL), which was induced by cancer testis antigen NYESO1impulsed dendritic cells (DCs), against human hepatocellular carcinoma (HCC). Methods: GSTESO1 fusion protein was induced in recombinant pGEXESO1 vector transformed bacteria by IPTG, and the GSTESO1 fusion protein was purified. DCs were induced with granulocyte/macrophage colonystimulating factor (GMCSF) and interleukin4 (IL4) from human peripheral blood mononuclear cells. DCs impulsed with GSTESO protein peptide were cocultured with T lymphocytes, and the resultant CTLs were used as effector cells. NYESO1 positive hepatocellular carcinoma HepG2 cells and NYESO1 negative H2P cells were used as target cells to test the specific antitumor effect of CTL using MTT. Results: Escherichia coli BL21 expressed fusion protein peptide GSTESO1 (Mr 36 000) after transfection with recombinant pGEXESO1 vector. The concentration of GSTESO1 peptide was 50 μg/ml after purification. DCs were successfully induced with GMCSF and IL4 from human peripheral blood mononuclear cells. DCsimpulsed with NYESO1 had high expression of surface molecule such as HLADR(91.4%), CD86(70.5%), CD83(71.2%) and CD80(55.3%). DCsimpulsed with NYESO1 induced production and proliferation of CTL, and this CTL specifically killed NYESO1 positive HepG2 cells. CTL induced by NYESO1 had stronger cytotoxic effect against HepG2 cells compared with GSTimpulsed DCs, unimpulsed DCs (P<0.05). Highest antitumor activity was found when the ratio of effector∶target was 50∶1 (53.23±3.78, P<0.01). Conclusion: DCsimpulsed with NYESO1 can induce production and proliferation of allogenic CTLs, which show antigen specific antitumor effect against NYESO1 positive HCC cells. This result casts new lights on immunotherapy of HCC.
Objective: To study the antigen specific antitumor effect of cytotoxic T lymphocyte (CTL), which was induced by cancer testis antigen NYESO1impulsed dendritic cells (DCs), against human hepatocellular carcinoma (HCC). Methods: GSTESO1 fusion protein was induced in recombinant pGEXESO1 vector transformed bacteria by IPTG, and the GSTESO1 fusion protein was purified. DCs were induced with granulocyte/macrophage colonystimulating factor (GMCSF) and interleukin4 (IL4) from human peripheral blood mononuclear cells. DCs impulsed with GSTESO protein peptide were cocultured with T lymphocytes, and the resultant CTLs were used as effector cells. NYESO1 positive hepatocellular carcinoma HepG2 cells and NYESO1 negative H2P cells were used as target cells to test the specific antitumor effect of CTL using MTT. Results: Escherichia coli BL21 expressed fusion protein peptide GSTESO1 (Mr 36 000) after transfection with recombinant pGEXESO1 vector. The concentration of GSTESO1 peptide was 50 μg/ml after purification. DCs were successfully induced with GMCSF and IL4 from human peripheral blood mononuclear cells. DCsimpulsed with NYESO1 had high expression of surface molecule such as HLADR(91.4%), CD86(70.5%), CD83(71.2%) and CD80(55.3%). DCsimpulsed with NYESO1 induced production and proliferation of CTL, and this CTL specifically killed NYESO1 positive HepG2 cells. CTL induced by NYESO1 had stronger cytotoxic effect against HepG2 cells compared with GSTimpulsed DCs, unimpulsed DCs (P<0.05). Highest antitumor activity was found when the ratio of effector∶target was 50∶1 (53.23±3.78, P<0.01). Conclusion: DCsimpulsed with NYESO1 can induce production and proliferation of allogenic CTLs, which show antigen specific antitumor effect against NYESO1 positive HCC cells. This result casts new lights on immunotherapy of HCC.
2009, 16(1):24-28.
DOI: 10.3872/j.issn.1007-385X.2009.1.006
Abstract:
Objective: To express mSDF1γ/GMCS fusion protein in the Pichia pastoris expression system and investigate its in vivo promoting effects on hematopoiesis function and immune function. Methods: The mSDF1γ/GMCS fusion gene was chemically synthesized and was cloned into pichia expression vector; the vector was then transfected into Pichia pastoris expression system. Then the expressed products were detected by SDSPAGE，Western blotting and purified by ion exchange columns．Rat irradiation model was established by 60Co γ ray and were subcutaneously injected with the fusion protein. The hematopoietic and chemotactic activities of the fusion protein were investigated in vivo. Results: The expression vector pPIC9KSDF1LGMCSF was successfully constructed, and mSDF1γ/GMCS fusion protein was successfully expressed by Pichia pastoris strain GSl15．The molecular weight of the protein was about 32000 D, with a concentration of 78 ng/ml. The numbers of bone marrow mononuclear cells and GMCFU were significantly increased in rats after subcutaneous injection of the fusion protein (P<0.01). The apoptotic rate of bone marrow cells was significantly decreased（P<0.05 or P<0.01）, and the numbers of CD3+CD4+T lymphocytes in the peripheral blood were significantly increased (P<0.05). Conclusion: The mSDF1γ/GMCS fusion protein can improve the hematopoietic function and immune function in irradiated rats, which might be a promising cytokine for regulating hematopoiesis and antitumor immune response．
Objective: To express mSDF1γ/GMCS fusion protein in the Pichia pastoris expression system and investigate its in vivo promoting effects on hematopoiesis function and immune function. Methods: The mSDF1γ/GMCS fusion gene was chemically synthesized and was cloned into pichia expression vector; the vector was then transfected into Pichia pastoris expression system. Then the expressed products were detected by SDSPAGE，Western blotting and purified by ion exchange columns．Rat irradiation model was established by 60Co γ ray and were subcutaneously injected with the fusion protein. The hematopoietic and chemotactic activities of the fusion protein were investigated in vivo. Results: The expression vector pPIC9KSDF1LGMCSF was successfully constructed, and mSDF1γ/GMCS fusion protein was successfully expressed by Pichia pastoris strain GSl15．The molecular weight of the protein was about 32000 D, with a concentration of 78 ng/ml. The numbers of bone marrow mononuclear cells and GMCFU were significantly increased in rats after subcutaneous injection of the fusion protein (P<0.01). The apoptotic rate of bone marrow cells was significantly decreased（P<0.05 or P<0.01）, and the numbers of CD3+CD4+T lymphocytes in the peripheral blood were significantly increased (P<0.05). Conclusion: The mSDF1γ/GMCS fusion protein can improve the hematopoietic function and immune function in irradiated rats, which might be a promising cytokine for regulating hematopoiesis and antitumor immune response．
7 Soluble mucin 1 peptide inhibits proliferation of T lymphoma Jurkat cells and its related mechanisms
MA Jichun
,
ZHAO Xiaoxia
,
GAO Hang
,
FANG Fang
,
ZHOU Jing
,
SONG Xianmei
,
LIU Zhonghui
,
TAI Guixiang
2009, 16(1):29-33.
DOI: 10.3872/j.issn.1007-385X.2009.1.007
Abstract:
Objective: To investigate the inhibitory effect of mucin 1 (MUC1) peptide on the proliferation of T lymphoma Jurkat cells and the related mechanism. Methods: Jurkat cells were cocultured with MUC1 peptide and effects of MUC1 peptide on Jurkat cell growth was examined by Trypan Blue staining. Cell cycle of Jurkat cells and membrane MUC1 protein expression were determined by flow cytometry. The apoptosis of Jurkat cells was examined by Annexin V/PI double staining. To further analyze whether soluble MUC1 peptide interacts with membrane MUC1 protein, MUC1 protein binding sites on the surface of Jurkat cells was blocked by an antiMUC1 polyclonal antibody. Results: Proliferation of Jurkat cells was inhibited by soluble MUC1 peptide in a dosedependent manner (MUC1 at 10, 20, and 40 μg/ml resulted in inhibitory rates of （32±4）%, （37±2）%, and（46±5）%, respectively ). No apoptosis was observed. Soluble MUC1 peptide induced G0/G1 phase cell cycle arrest of Jurkat cells and membrane MUC1 protein was expressed on the surface of Jurkat cells. The inhibition of Jurkat cells by soluble MUC1 peptide was almost totally reversed by antiMUC1 polyclonal antibodies at the concentrations of 5 μg/ml to 25 μg/ml. Conclusion: It is suggested that soluble MUC1 peptide can inhibit proliferation of Jurkat cells by interacting with membrane MUC1 protein on Jurkat cells and inducing G0/G1 phase cell cycle arrest.
Objective: To investigate the inhibitory effect of mucin 1 (MUC1) peptide on the proliferation of T lymphoma Jurkat cells and the related mechanism. Methods: Jurkat cells were cocultured with MUC1 peptide and effects of MUC1 peptide on Jurkat cell growth was examined by Trypan Blue staining. Cell cycle of Jurkat cells and membrane MUC1 protein expression were determined by flow cytometry. The apoptosis of Jurkat cells was examined by Annexin V/PI double staining. To further analyze whether soluble MUC1 peptide interacts with membrane MUC1 protein, MUC1 protein binding sites on the surface of Jurkat cells was blocked by an antiMUC1 polyclonal antibody. Results: Proliferation of Jurkat cells was inhibited by soluble MUC1 peptide in a dosedependent manner (MUC1 at 10, 20, and 40 μg/ml resulted in inhibitory rates of （32±4）%, （37±2）%, and（46±5）%, respectively ). No apoptosis was observed. Soluble MUC1 peptide induced G0/G1 phase cell cycle arrest of Jurkat cells and membrane MUC1 protein was expressed on the surface of Jurkat cells. The inhibition of Jurkat cells by soluble MUC1 peptide was almost totally reversed by antiMUC1 polyclonal antibodies at the concentrations of 5 μg/ml to 25 μg/ml. Conclusion: It is suggested that soluble MUC1 peptide can inhibit proliferation of Jurkat cells by interacting with membrane MUC1 protein on Jurkat cells and inducing G0/G1 phase cell cycle arrest.
2009, 16(1):34-39.
DOI: 10.3872/j.issn.1007-385X.2009.1.008
Abstract:
Objective: To study whether allicin combined with cell cycle specific chemotherapeutic drugs can influence p21，p27 expression in human gastric cancer cell line, so as to discuss the synergistic effect between allicin and cell cycle specific chemotherapeutic drugs and the possible mechanism. Methods： MTT was used to observe the inhibition of gastric cancer cell lines BGC823 and SGC7901 after treatment with vinorelbine(NVB), fluorouracil(5FU) and mitomycin(MMC), and the IC50 was calculated. The change of cell cycle was examined by flow cytometry; SP immunohistochemistry was used to detect the expression of p21 and p27 in BGC823 and SGC7901 cells. Results： Allicin decreased cells in G0/G1 phase and increased cells in G2/M phase in both BGC823 and SGC7901 cells after 24 h. Allicin dose dependently increased expression of p21 and p27 at a serial concentration of 5, 10, 15 and 20 μg/ml. Combination of allicin with NVB increased the expression of both p21 and p27 in both cell lines compared with either allicin or NVB alone（P<001）. Combination of allicin with 5FU or MMC did not further increase the expression of p21 and p27. Conclusion： Combination of allicin with NVB greatly increases expression of p21 and p27 in gastric BGC823 and SGC7901 cells, and subsequently induces cell cycle arrest in G2/M phase.
Objective: To study whether allicin combined with cell cycle specific chemotherapeutic drugs can influence p21，p27 expression in human gastric cancer cell line, so as to discuss the synergistic effect between allicin and cell cycle specific chemotherapeutic drugs and the possible mechanism. Methods： MTT was used to observe the inhibition of gastric cancer cell lines BGC823 and SGC7901 after treatment with vinorelbine(NVB), fluorouracil(5FU) and mitomycin(MMC), and the IC50 was calculated. The change of cell cycle was examined by flow cytometry; SP immunohistochemistry was used to detect the expression of p21 and p27 in BGC823 and SGC7901 cells. Results： Allicin decreased cells in G0/G1 phase and increased cells in G2/M phase in both BGC823 and SGC7901 cells after 24 h. Allicin dose dependently increased expression of p21 and p27 at a serial concentration of 5, 10, 15 and 20 μg/ml. Combination of allicin with NVB increased the expression of both p21 and p27 in both cell lines compared with either allicin or NVB alone（P<001）. Combination of allicin with 5FU or MMC did not further increase the expression of p21 and p27. Conclusion： Combination of allicin with NVB greatly increases expression of p21 and p27 in gastric BGC823 and SGC7901 cells, and subsequently induces cell cycle arrest in G2/M phase.
2009, 16(1):40-44.
DOI: 10.3872/j.issn.1007-385X.2009.1.009
Abstract:
Objective: To study the inhibitory effect of IL27 against human tumor angiogenesis and the related mechanisms. Methods: Human esophageal carcinoma cells (Eca109/IL27) stably transfected with IL27 gene were injected into nude mice to establish tumorbearing mouse model. The survival time and tumor growth were observed. IFNγ level secreted by splenocytes was measured by ELISA. Expression of VEGF and CD34 was detected by immunohistochemistry method and MVD was calculated according to CD34 level. RTPCR was used to detect the expression of IP10 and MIG mRNA in the tumor tissues. Results: The survival time of mice injected with Eca109/IL27 cells was significantly longer than those of mice injected with wide type Eca109 or Eca109/LXSN (blank vector) cells (P<0.05). Expression of VEGF and CD34 in Eca109/IL27inoculated mice was lower than those in Eca109 or Eca109/LXSN groups. Production of IFNγ by splenocytes in mice injected with Eca109/IL27 cells was higher than those with Eca109 and Eca109/LXSN (P<0.05). MIG and IP10 mRNA expression was also higher than those in Eca109 or Eca109/LXSN injected mice (P<005). Conclusion: IL27 can inhibit tumor angiogenesis in nude mice through upregulating the expression of MIG and IP10, and thus exerts antitumor effect
Objective: To study the inhibitory effect of IL27 against human tumor angiogenesis and the related mechanisms. Methods: Human esophageal carcinoma cells (Eca109/IL27) stably transfected with IL27 gene were injected into nude mice to establish tumorbearing mouse model. The survival time and tumor growth were observed. IFNγ level secreted by splenocytes was measured by ELISA. Expression of VEGF and CD34 was detected by immunohistochemistry method and MVD was calculated according to CD34 level. RTPCR was used to detect the expression of IP10 and MIG mRNA in the tumor tissues. Results: The survival time of mice injected with Eca109/IL27 cells was significantly longer than those of mice injected with wide type Eca109 or Eca109/LXSN (blank vector) cells (P<0.05). Expression of VEGF and CD34 in Eca109/IL27inoculated mice was lower than those in Eca109 or Eca109/LXSN groups. Production of IFNγ by splenocytes in mice injected with Eca109/IL27 cells was higher than those with Eca109 and Eca109/LXSN (P<0.05). MIG and IP10 mRNA expression was also higher than those in Eca109 or Eca109/LXSN injected mice (P<005). Conclusion: IL27 can inhibit tumor angiogenesis in nude mice through upregulating the expression of MIG and IP10, and thus exerts antitumor effect
2009, 16(1):45-49.
DOI: 10.3872/j.issn.1007-385X.2009.1.010
Abstract:
Objective: To study the proliferation inhibition and apoptosis promotion effect of mda7/IL24 in transplanted hepatocellular cancer cells in nude mice, and to study the related mechanism. Methods: Recombinant vector Ad.mda7 was constructed. BALB/c nude mice liver cancer model was established by subcutaneous implanting of HepG2 cells. Nude mice were administered with Ad.GFP, Ad.mda7 or ALLN+Ad.mda7 via intratumor single point injection. The changes of tumor size and weight were observed. Activation of caspase3, apoptosis of cancer cells, cell proliferationassociated antigen ki67 and microvascular density were assessed by immunohistochemistry and TUNEL method. Caspase12, caspase3 and Bax expression was examined via Western blotting. Results: The tumor sizes of Ad.mda7 treated mice and Ad.GFP treated mice were (312.6±30.24) mm3 vs (520.6±30.00) mm3 (P<0.05), and the weights were (0.321±0.031) g vs (0.534±0.030) g, respectively (P<0.05). Ad.mda7 inhibited expression of ki67 and CD31, and induced activation of caspase3 in subcutaneous tumor xenografts. ALLN reversed the apoptosis inducing effect of Ad.mda7 （P<0.05）， downregulated the expression of caspase12, caspase3 and Bax induced by Ad. Mda7. Conclusion: mda7/IL24 can obviously inhibit proliferation and angiogenesis of transplanted hepatocellular cancer cells, and induce apoptosis of hepatocellular cancer cells through activating the endoplasmic reticulum stress pathway.
Objective: To study the proliferation inhibition and apoptosis promotion effect of mda7/IL24 in transplanted hepatocellular cancer cells in nude mice, and to study the related mechanism. Methods: Recombinant vector Ad.mda7 was constructed. BALB/c nude mice liver cancer model was established by subcutaneous implanting of HepG2 cells. Nude mice were administered with Ad.GFP, Ad.mda7 or ALLN+Ad.mda7 via intratumor single point injection. The changes of tumor size and weight were observed. Activation of caspase3, apoptosis of cancer cells, cell proliferationassociated antigen ki67 and microvascular density were assessed by immunohistochemistry and TUNEL method. Caspase12, caspase3 and Bax expression was examined via Western blotting. Results: The tumor sizes of Ad.mda7 treated mice and Ad.GFP treated mice were (312.6±30.24) mm3 vs (520.6±30.00) mm3 (P<0.05), and the weights were (0.321±0.031) g vs (0.534±0.030) g, respectively (P<0.05). Ad.mda7 inhibited expression of ki67 and CD31, and induced activation of caspase3 in subcutaneous tumor xenografts. ALLN reversed the apoptosis inducing effect of Ad.mda7 （P<0.05）， downregulated the expression of caspase12, caspase3 and Bax induced by Ad. Mda7. Conclusion: mda7/IL24 can obviously inhibit proliferation and angiogenesis of transplanted hepatocellular cancer cells, and induce apoptosis of hepatocellular cancer cells through activating the endoplasmic reticulum stress pathway.
2009, 16(1):50-54.
DOI: 10.3872/j.issn.1007-385X.2009.1.011
Abstract:
Objective: To explore the expression of B71, B72 and B7H1 on tumorinfiltrating dendritic cells (TIDC) and on splenic dendritic cells (SDC) , and to investigate TIDCmediated and SDCmediated Tcell function after blocking B7H1 expression in these dendritic cells. Methods: The TIDCs and SDCs were isolated from tumorbearing mice using antimouse CD11c magnetic beads. The expression of B71, B72 and B7H1 on TIDC and SDC was analyzed using flow cytometer. T cells were cocultured with TIDCs or SDCs for the mixed lymphocyte reaction (MLR), and monoclonal antibodies to B7H1 or the isotype control antibodies were added to the MLR cultures. Tcell proliferation was assessed using XTT method and the secretion of IL10 was detected using ELISA. Results: B71 and B72 positive TIDCs were significantly less than SDCs (P<0.01). B7H1 was moderately expressed on both TIDCs and SDCs (P>0.05). Tcell proliferation stimulated by TIDCs was weaker than that stimulated by SDCs; T cells produced more IL10 after TIDCs stimulation than after SDCs stimulation（P<0.01）. After blocking B7H1 on DCs, TIDCs showed a stronger stimulating ability on T cell proliferation compared with control antibodies, while SDCs did not have significant effect on T cell proliferation and production of IL10. Conclusion: Blocking B7H1 on TIDCs can significantly enhance their ability to activate T cells, and may elimilate TIDCmediated tumor immunosuppression.
Objective: To explore the expression of B71, B72 and B7H1 on tumorinfiltrating dendritic cells (TIDC) and on splenic dendritic cells (SDC) , and to investigate TIDCmediated and SDCmediated Tcell function after blocking B7H1 expression in these dendritic cells. Methods: The TIDCs and SDCs were isolated from tumorbearing mice using antimouse CD11c magnetic beads. The expression of B71, B72 and B7H1 on TIDC and SDC was analyzed using flow cytometer. T cells were cocultured with TIDCs or SDCs for the mixed lymphocyte reaction (MLR), and monoclonal antibodies to B7H1 or the isotype control antibodies were added to the MLR cultures. Tcell proliferation was assessed using XTT method and the secretion of IL10 was detected using ELISA. Results: B71 and B72 positive TIDCs were significantly less than SDCs (P<0.01). B7H1 was moderately expressed on both TIDCs and SDCs (P>0.05). Tcell proliferation stimulated by TIDCs was weaker than that stimulated by SDCs; T cells produced more IL10 after TIDCs stimulation than after SDCs stimulation（P<0.01）. After blocking B7H1 on DCs, TIDCs showed a stronger stimulating ability on T cell proliferation compared with control antibodies, while SDCs did not have significant effect on T cell proliferation and production of IL10. Conclusion: Blocking B7H1 on TIDCs can significantly enhance their ability to activate T cells, and may elimilate TIDCmediated tumor immunosuppression.
2009, 16(1):55-58.
DOI: 10.3872/j.issn.1007-385X.2009.1.012
Abstract:
Objective: To study whether interleukin(IL)18 can promote tumor antigenpulsed dendritic cells (DCs) to induce specific CTL against hepatocellular carcinoma(HCC) in vitro. Methods: The recombinant adenovirus expression plasmid AdIL18 was transfected into DCs pulsed by HepG2 lysates (AdIL18HepG2/DC). The surface molecules of AdIL18HepG2/DCs were analyzed by flow cytometry. IL18 levels in culture supernatant of AdIL18HepG2/DCs were measured by ELISA. The ability of AdIL18HepG2/DC to induce proliferation of autologous T lymphocytes was evaluated by 3HTdR assay. The in vitro CTL antitumor activity induced by AdIL18HepG2/DC on HepG2 cell was detected by MTT. Results: IL18 promoted expression of CD1a, CD11c, CD80, CD86 and HLADR on HepG2/DCs compared with untransfected DCs. AdIL18HepG2/DCs secreted more IL18 in vitro compared with untransfected DCs. AdIL18HepG2/DC effectively stimulated proliferation of autologous T cells ( CPM being 228 018 ±1 079); the stimulating effect was significantly higher than those of AdIL18DC, HepG2/DC, AdlzcZ/DC, and DC（all P＜0.05）. CTL induced by TAA pulsed/IL18 modified DC had significantly higher cytotoxicity against HepG2 cells compared with that induced by other DCs. Conclusion: AdIL18HepG2/DCs have enhanced ability to induce specific CTL in killing hepatocellular carcinoma HepG2 cell line.
Objective: To study whether interleukin(IL)18 can promote tumor antigenpulsed dendritic cells (DCs) to induce specific CTL against hepatocellular carcinoma(HCC) in vitro. Methods: The recombinant adenovirus expression plasmid AdIL18 was transfected into DCs pulsed by HepG2 lysates (AdIL18HepG2/DC). The surface molecules of AdIL18HepG2/DCs were analyzed by flow cytometry. IL18 levels in culture supernatant of AdIL18HepG2/DCs were measured by ELISA. The ability of AdIL18HepG2/DC to induce proliferation of autologous T lymphocytes was evaluated by 3HTdR assay. The in vitro CTL antitumor activity induced by AdIL18HepG2/DC on HepG2 cell was detected by MTT. Results: IL18 promoted expression of CD1a, CD11c, CD80, CD86 and HLADR on HepG2/DCs compared with untransfected DCs. AdIL18HepG2/DCs secreted more IL18 in vitro compared with untransfected DCs. AdIL18HepG2/DC effectively stimulated proliferation of autologous T cells ( CPM being 228 018 ±1 079); the stimulating effect was significantly higher than those of AdIL18DC, HepG2/DC, AdlzcZ/DC, and DC（all P＜0.05）. CTL induced by TAA pulsed/IL18 modified DC had significantly higher cytotoxicity against HepG2 cells compared with that induced by other DCs. Conclusion: AdIL18HepG2/DCs have enhanced ability to induce specific CTL in killing hepatocellular carcinoma HepG2 cell line.
2009, 16(1):59-62.
DOI: 10.3872/j.issn.1007-385X.2009.1.013
Abstract:
Objective: To study the safety of tissuespecific cytosine deaminase /5fluorocytosine (CD/5FC) system thermochemotherapy in treatment of a liver metastasis model of colon cancer in nude mice. Methods: Liver metastasis model was established by intravenously injection of LOVO cell lines harboring tissuespecific CD gene in 30 nude mice. The mice were then randomly divide into three groups, namely, a control group, a thermochemotherapy group, and a chemotherapy group; the three groups were intraperitoneally injected with sodium saline, 43 ℃ prodrug 5 FC or prodrug 5FC, respectively. After 21 days, the animals were sacrificed and the pathological changes of liver, stomach, lung, pancreas, small intestine, and large intestine were examined by HE staining. RTPCR was used to study the expression of CD gene. Results: The growth of tumor cells in the control group grew actively, and the growth in the 43 ℃ prodrug 5 FC group was greatly inhibited compared with those in the prodrug 5FC and normal saline groups. The normal liver, stomach, lung, pancreas, small intestine and large intestine tissues showed no pathological changes and no CD expression. RTPCR examination revealed stable CD gene expression in the 3 groups. Conclusion: Tissuespecific CD/5FC system thermochemotherapy can improve the specificity of CD gene expression, and reduces the damages to the normal tissues by the thermochemotherapy.
Objective: To study the safety of tissuespecific cytosine deaminase /5fluorocytosine (CD/5FC) system thermochemotherapy in treatment of a liver metastasis model of colon cancer in nude mice. Methods: Liver metastasis model was established by intravenously injection of LOVO cell lines harboring tissuespecific CD gene in 30 nude mice. The mice were then randomly divide into three groups, namely, a control group, a thermochemotherapy group, and a chemotherapy group; the three groups were intraperitoneally injected with sodium saline, 43 ℃ prodrug 5 FC or prodrug 5FC, respectively. After 21 days, the animals were sacrificed and the pathological changes of liver, stomach, lung, pancreas, small intestine, and large intestine were examined by HE staining. RTPCR was used to study the expression of CD gene. Results: The growth of tumor cells in the control group grew actively, and the growth in the 43 ℃ prodrug 5 FC group was greatly inhibited compared with those in the prodrug 5FC and normal saline groups. The normal liver, stomach, lung, pancreas, small intestine and large intestine tissues showed no pathological changes and no CD expression. RTPCR examination revealed stable CD gene expression in the 3 groups. Conclusion: Tissuespecific CD/5FC system thermochemotherapy can improve the specificity of CD gene expression, and reduces the damages to the normal tissues by the thermochemotherapy.
2009, 16(1):63-66.
DOI: 10.3872/j.issn.1007-385X.2009.1.014
Abstract:
Objective: To investigate the inhibitory effect of antisense human telomerase RNA (hTR) gene on implanted hepatocellular carcinoma in nude mice. Methods: HepG2 cells were subcutaneously inoculated into BALB/c nude mice at the axilla to establish implanted hepatocellular carcinoma model. The retrovirus plasmid containing antisense telomerse RNA (PLXSNhTRBamHⅠ) was injected into the tumor (0.2 ml every time, 5 times). Retrovirus plasmid containing sense telomerase RNA (PLXSNhTREcoRⅠ) and normal saline were inoculated as control groups. Tumor volume was determined and the inhibitory rate was calculated. Tumor necrosis was observed by histological analysis and cell apoptosis was analyzed by terminal transferase dUTP nick end labeling (TUNEL). Results: Tumor growth in antisense hTR group was significantly inhibited compared with the two control groups. The tumor inhibitory rate (26.78%) of antisense hTR group was significantly higher than that of sense hTR group (1.93%, P＜0.01）). The tumor necrosis area and apoptotic rate in the antisense hTR group were significantly higher than those of the other two groups(P＜0.01）. Conclusion: Antisense hTR can inhibit the growth of implanted hepatocellular carcinoma and promote cell apoptosis.
Objective: To investigate the inhibitory effect of antisense human telomerase RNA (hTR) gene on implanted hepatocellular carcinoma in nude mice. Methods: HepG2 cells were subcutaneously inoculated into BALB/c nude mice at the axilla to establish implanted hepatocellular carcinoma model. The retrovirus plasmid containing antisense telomerse RNA (PLXSNhTRBamHⅠ) was injected into the tumor (0.2 ml every time, 5 times). Retrovirus plasmid containing sense telomerase RNA (PLXSNhTREcoRⅠ) and normal saline were inoculated as control groups. Tumor volume was determined and the inhibitory rate was calculated. Tumor necrosis was observed by histological analysis and cell apoptosis was analyzed by terminal transferase dUTP nick end labeling (TUNEL). Results: Tumor growth in antisense hTR group was significantly inhibited compared with the two control groups. The tumor inhibitory rate (26.78%) of antisense hTR group was significantly higher than that of sense hTR group (1.93%, P＜0.01）). The tumor necrosis area and apoptotic rate in the antisense hTR group were significantly higher than those of the other two groups(P＜0.01）. Conclusion: Antisense hTR can inhibit the growth of implanted hepatocellular carcinoma and promote cell apoptosis.
2009, 16(1):67-70.
DOI: 10.3872/j.issn.1007-385X.2009.1.015
Abstract:
Objective: To investigate the effects of sodium phenylbutyrate (NaPB) on the matrix metalloproteinase9(MMP9) and tissue inhibitor of metalloproteinase1(TIMP1) expression and invasive ability of human thyroid follicular carcinoma cell line CGTHW1. Methods: CGTHW1 cells were treated with different concentrations of NaPB, then the invasive ability of CGTHW1 cells was assessed using Transwell assay. The expression of MMP9 and TIMP1 was examined by immunocytochemistry staining and RTPCR in CGTHW1 cells. Results: After treatment with NaPB (4 mmol/L) for 72 h, CGTHW1 cells passing the Transwell were significantly reduced\[(29.8±1.77) vs (11.00±2.59)，P<005\]. Immunocytochemistry staining and RTPCR demonstrated that protein and mRNA expression of MMP9 and TIMP1 were significantly downregulated in CGTHW1 cells after NaPB treatment (4, 6 mmol/L) (all P<005).Conclusion: NaPB can inhibit CGTHW1 cell invasion by downregulating MMP9 and TIMP1 expression.
Objective: To investigate the effects of sodium phenylbutyrate (NaPB) on the matrix metalloproteinase9(MMP9) and tissue inhibitor of metalloproteinase1(TIMP1) expression and invasive ability of human thyroid follicular carcinoma cell line CGTHW1. Methods: CGTHW1 cells were treated with different concentrations of NaPB, then the invasive ability of CGTHW1 cells was assessed using Transwell assay. The expression of MMP9 and TIMP1 was examined by immunocytochemistry staining and RTPCR in CGTHW1 cells. Results: After treatment with NaPB (4 mmol/L) for 72 h, CGTHW1 cells passing the Transwell were significantly reduced\[(29.8±1.77) vs (11.00±2.59)，P<005\]. Immunocytochemistry staining and RTPCR demonstrated that protein and mRNA expression of MMP9 and TIMP1 were significantly downregulated in CGTHW1 cells after NaPB treatment (4, 6 mmol/L) (all P<005).Conclusion: NaPB can inhibit CGTHW1 cell invasion by downregulating MMP9 and TIMP1 expression.
2009, 16(1):71-74.
DOI: 10.3872/j.issn.1007-385X.2009.1.016
Abstract:
Objective: To study the influence of mesenchymal stem cells (MSC) infected by AdIL12 on the proliferation of C6 glioma cells. Methods: The MSCs were cultured from rat bone marrow and verified by immunohistochemistry and flow cytometry. Recombinant adenovirus vectors harboring IL12 (AdEasyIL12) were infected into MSCs to construct AdIL12MSC containing exogenous IL12. RTPCR and Western Blotting were used to detect IL12 mRNA and protein expression in AdIL12MSC. MTT method was used to detect the effect of AdIL12MSC supernatant on the proliferation of C6 glioma cells. Results: Exogenous IL12 gene was effectively transfected into MSCs by recombinant adenovirus vectors. IL12 was expressed in MSCs at both mRNA and protein levels as detected by RTPCR and Western Blotting. The supernatant of AdIL12MSC significantly inhibited the proliferation of C6 glioma cells compared with MSC supernatant（P<0.05）. Conclusion: MSCs tansfected with IL2 gene (AdIL12MSC) can express IL12 at mRNA and protein levels and inhibit the proliferation of C6 glioma cells.
Objective: To study the influence of mesenchymal stem cells (MSC) infected by AdIL12 on the proliferation of C6 glioma cells. Methods: The MSCs were cultured from rat bone marrow and verified by immunohistochemistry and flow cytometry. Recombinant adenovirus vectors harboring IL12 (AdEasyIL12) were infected into MSCs to construct AdIL12MSC containing exogenous IL12. RTPCR and Western Blotting were used to detect IL12 mRNA and protein expression in AdIL12MSC. MTT method was used to detect the effect of AdIL12MSC supernatant on the proliferation of C6 glioma cells. Results: Exogenous IL12 gene was effectively transfected into MSCs by recombinant adenovirus vectors. IL12 was expressed in MSCs at both mRNA and protein levels as detected by RTPCR and Western Blotting. The supernatant of AdIL12MSC significantly inhibited the proliferation of C6 glioma cells compared with MSC supernatant（P<0.05）. Conclusion: MSCs tansfected with IL2 gene (AdIL12MSC) can express IL12 at mRNA and protein levels and inhibit the proliferation of C6 glioma cells.
2009, 16(1):75-79.
DOI: 10.3872/j.issn.1007-385X.2009.1.017
Abstract:
Objective: To observe the expression of Clusterin in colorectal cancer tissues and study its relationship with the development and progression of colorectal cancer. Methods： Fiftyeight colorectal cancer tissues samples (32 rectal cancer tissues, 26 colon carcinoma tissues) of patients with completed clinic data were obtained after surgery from the Affiliated Hospital of Guangdong Medical College. Immunohistochemical staining (SP method) was used to detect the expression of Clusterin in colorectal cancer tissue, adjacent normal tissue of colorectal cancer and normal tissue. Flow cytometry was used to examine the apoptosis of colorectal cancer cells. Results： The expression of Clusterin in colorectal cancer tissues was significantly higher than those in the adjacent tissues of colorectal cancer and normal colorectal tissue（P＜005); besides, the expression of Clusterin in the colorectal cancer tissue was correlated with the differentiation, Dukes stages and lymphatic metastasis of colorectal cancer. Apoptosis of colorectal cancer cells was found correlated with the clinical stage and lymphatic metastasis; Clusterin expression in colorectal cancer tissue was negatively correlated with apoptosis of colorectal cancer cells (r=-0.381, P<0.05). Conclusion： Clusterin may play important roles in the development and progression of colorectal cancer by inhibiting apoptosis of tumor cells, which may pave a way for immunotherapy of colorectal cancer.
Objective: To observe the expression of Clusterin in colorectal cancer tissues and study its relationship with the development and progression of colorectal cancer. Methods： Fiftyeight colorectal cancer tissues samples (32 rectal cancer tissues, 26 colon carcinoma tissues) of patients with completed clinic data were obtained after surgery from the Affiliated Hospital of Guangdong Medical College. Immunohistochemical staining (SP method) was used to detect the expression of Clusterin in colorectal cancer tissue, adjacent normal tissue of colorectal cancer and normal tissue. Flow cytometry was used to examine the apoptosis of colorectal cancer cells. Results： The expression of Clusterin in colorectal cancer tissues was significantly higher than those in the adjacent tissues of colorectal cancer and normal colorectal tissue（P＜005); besides, the expression of Clusterin in the colorectal cancer tissue was correlated with the differentiation, Dukes stages and lymphatic metastasis of colorectal cancer. Apoptosis of colorectal cancer cells was found correlated with the clinical stage and lymphatic metastasis; Clusterin expression in colorectal cancer tissue was negatively correlated with apoptosis of colorectal cancer cells (r=-0.381, P<0.05). Conclusion： Clusterin may play important roles in the development and progression of colorectal cancer by inhibiting apoptosis of tumor cells, which may pave a way for immunotherapy of colorectal cancer.
2009, 16(1):80-83.
DOI: 10.3872/j.issn.1007-385X.2009.1.018
Abstract:
Objective: To investigate the expression of adrenomedullin (ADM) in breast cancer tissues and its relationship with differentialtion and metastasis of breast cancer. Methods: RTPCR was used to examine ADM mRNA expression in 32 breast cancer tissues (the patients were treated in the Fourth Affiliated Hospital of Hebei Medical University from March 2005 to April 2005) and the corresponding adjacent tissues (5 cm away from tumors), as well as in MCF7 cell line. Expressions of ER， PR and CerbB2 in breast cancer were examined by immunohistochemical staining. Results: Human breast cancer cell line MCF7 was positive of ADM. ADM mRNA expression was detected in 75% (24/32) breast cancer samples, which was significantly higher than that in the corresponding adjacent tissues (0%, 0/32, P<0.01). We found that ADM expression was correlated with the differentialtion degree and lymph node metastasis of breast cancer (P<0.01 and P<0.05, respectively), and was not correlated with the expression of EP, PR or CerbB2, the tumor size, TNM staging, or the pathological types. Conclusion: The expression of ADM is increased in breast cancer tissues, which is correlated with the poor differentiation and lymph node metastasis of the breast cancer.
Objective: To investigate the expression of adrenomedullin (ADM) in breast cancer tissues and its relationship with differentialtion and metastasis of breast cancer. Methods: RTPCR was used to examine ADM mRNA expression in 32 breast cancer tissues (the patients were treated in the Fourth Affiliated Hospital of Hebei Medical University from March 2005 to April 2005) and the corresponding adjacent tissues (5 cm away from tumors), as well as in MCF7 cell line. Expressions of ER， PR and CerbB2 in breast cancer were examined by immunohistochemical staining. Results: Human breast cancer cell line MCF7 was positive of ADM. ADM mRNA expression was detected in 75% (24/32) breast cancer samples, which was significantly higher than that in the corresponding adjacent tissues (0%, 0/32, P<0.01). We found that ADM expression was correlated with the differentialtion degree and lymph node metastasis of breast cancer (P<0.01 and P<0.05, respectively), and was not correlated with the expression of EP, PR or CerbB2, the tumor size, TNM staging, or the pathological types. Conclusion: The expression of ADM is increased in breast cancer tissues, which is correlated with the poor differentiation and lymph node metastasis of the breast cancer.
19 Establishment of a human hepatocellular carcinoma cell line EH-H1 and its biological characteristics
QIAN Yanzhen
,
LI Jiang
,
LI Linfang
,
LIU Hui
,
LIU Tao
,
JIANG Lihua
,
SHI Lehua
,
SU Changqing
,
WU Mengchao
,
QIAN Qijun
2009, 16(1):84-87.
DOI: 10.3872/j.issn.1007-385X.2009.1.019
Abstract:
Objective:To establish a human hepatocellular carcinoma cell line EHH1 by primary culture and to investigate its biological characteristics. Methods: Tumor tissues obtained from patients treated in our hospital were made into singlecell suspension and were primary cultured, passaged in DMEM medium supplemented with 10% fetal bovine serum. The morphology of the cells was observed under light and electronic microscope; the cell growth curve was plotted. Radioimmunoassay was employed to examine the AFP and HBV expression. Cytogenetic study was performed with the cell line using Gbanding chromosome analysis. The tumorigenicity of the cell line was studied in nude mice by subcutaneous injection.Results: We have successfully established a novel hepatocellular carcinoma cell line EHH1, which could be passaged for over 80 generations with unchanged morphology and growth cycle (24 h). Radioimmunoassay results demonstrated that all EHH1 cells were HBV negative with slight AFP expression (0.6 μg/L). G banding results indicated that EHH1 cells were aneuploid cells, primarily hyperdiploid. Tumors were formed in all the 10 mice subcutaneously inoculated with EHH1 cells. The pathological types and differentiation degrees of the newly formed tumors were identical to their parental hepatocellular carcinoma. Conclusion: The established EHH1 cell line in this study maintaines the biologic characteristics of its original carcinoma, and might be a stable cell line of human hepatocellular carcinoma.
Objective:To establish a human hepatocellular carcinoma cell line EHH1 by primary culture and to investigate its biological characteristics. Methods: Tumor tissues obtained from patients treated in our hospital were made into singlecell suspension and were primary cultured, passaged in DMEM medium supplemented with 10% fetal bovine serum. The morphology of the cells was observed under light and electronic microscope; the cell growth curve was plotted. Radioimmunoassay was employed to examine the AFP and HBV expression. Cytogenetic study was performed with the cell line using Gbanding chromosome analysis. The tumorigenicity of the cell line was studied in nude mice by subcutaneous injection.Results: We have successfully established a novel hepatocellular carcinoma cell line EHH1, which could be passaged for over 80 generations with unchanged morphology and growth cycle (24 h). Radioimmunoassay results demonstrated that all EHH1 cells were HBV negative with slight AFP expression (0.6 μg/L). G banding results indicated that EHH1 cells were aneuploid cells, primarily hyperdiploid. Tumors were formed in all the 10 mice subcutaneously inoculated with EHH1 cells. The pathological types and differentiation degrees of the newly formed tumors were identical to their parental hepatocellular carcinoma. Conclusion: The established EHH1 cell line in this study maintaines the biologic characteristics of its original carcinoma, and might be a stable cell line of human hepatocellular carcinoma.
2009, 16(1):88-92.
DOI: 10.3872/j.issn.1007-385X.2009.1.020
Abstract:
免疫球蛋白（IgSF）超家族成员在免疫与炎症中作用与机制研究一直是生物医学领域的热点，IgSF超家族的鼠CMRF35样分子（CMRF35like malecule,CLM）家族成员分子及CLM相对应的人源CD300家族成员分子的结构与功能备受关注。CLM/CD300家族成员在单核细胞、巨噬细胞、淋巴细胞、粒细胞等免疫细胞表面广泛地表达。CLM家族含有9个成员，其中，CLM1和CLM5为配对的抑制性和活化性受体，交联活化CLM1后能抑制CLM5介导的肥大细胞及中性粒细胞活化；CLM8和CLM4亦为配对的抑制性和活化性受体；其他活化性受体如CLM2交联活化后能诱导单核细胞TNFα的产生；CLM7能促进肥大细胞分泌细胞因子并促进细胞存活、脱颗粒以及细胞黏附等。CLM在免疫与炎症过程及其调控中起重要作用。有关CLM/CD300家族成员结构与功能的研究将为免疫应答的调控机制与相关疾病的防治提供新的思路和靶点。
免疫球蛋白（IgSF）超家族成员在免疫与炎症中作用与机制研究一直是生物医学领域的热点，IgSF超家族的鼠CMRF35样分子（CMRF35like malecule,CLM）家族成员分子及CLM相对应的人源CD300家族成员分子的结构与功能备受关注。CLM/CD300家族成员在单核细胞、巨噬细胞、淋巴细胞、粒细胞等免疫细胞表面广泛地表达。CLM家族含有9个成员，其中，CLM1和CLM5为配对的抑制性和活化性受体，交联活化CLM1后能抑制CLM5介导的肥大细胞及中性粒细胞活化；CLM8和CLM4亦为配对的抑制性和活化性受体；其他活化性受体如CLM2交联活化后能诱导单核细胞TNFα的产生；CLM7能促进肥大细胞分泌细胞因子并促进细胞存活、脱颗粒以及细胞黏附等。CLM在免疫与炎症过程及其调控中起重要作用。有关CLM/CD300家族成员结构与功能的研究将为免疫应答的调控机制与相关疾病的防治提供新的思路和靶点。
2009, 16(1):93-96.
DOI: 10.3872/j.issn.1007-385X.2009.1.021
Abstract:
γ氨基丁酸(γaminobutyric acid , GABA)是一种哺乳动物中枢神经系统重要的抑制性神经递质，GABA通过与不同类型的GABA受体（GABA receptor,GABAR）结合对机体多种功能发挥特异性调节作用。近年来研究发现，GABA与GABAR还广泛存在于外周组织，参与细胞间的信息传递，与细胞的分化和成熟密切相关。此外，GABA及其受体还可通过特定的信号转导通路影响某些肿瘤的增殖和侵袭转移等恶性潜能。某些肿瘤伴随GABA及其受体的高表达，阻断GABAR信号则可抑制肿瘤细胞的增殖。GABA与GABAR结合后可通过上调MMP表达、提高胞内钙离子浓度、活化MAPK激酶链等途径促进肿瘤的侵袭和转移。随着研究的深入，GABA及其受体信号通路蛋白分子有可能成为肿瘤诊断与治疗的潜在靶点。
γ氨基丁酸(γaminobutyric acid , GABA)是一种哺乳动物中枢神经系统重要的抑制性神经递质，GABA通过与不同类型的GABA受体（GABA receptor,GABAR）结合对机体多种功能发挥特异性调节作用。近年来研究发现，GABA与GABAR还广泛存在于外周组织，参与细胞间的信息传递，与细胞的分化和成熟密切相关。此外，GABA及其受体还可通过特定的信号转导通路影响某些肿瘤的增殖和侵袭转移等恶性潜能。某些肿瘤伴随GABA及其受体的高表达，阻断GABAR信号则可抑制肿瘤细胞的增殖。GABA与GABAR结合后可通过上调MMP表达、提高胞内钙离子浓度、活化MAPK激酶链等途径促进肿瘤的侵袭和转移。随着研究的深入，GABA及其受体信号通路蛋白分子有可能成为肿瘤诊断与治疗的潜在靶点。
2009, 16(1):97-100.
DOI: 10.3872/j.issn.1007-385X.2009.1.022
Abstract:
肿瘤生物治疗（cancer biotherapy）已经成为继手术、放疗和化疗三大经典肿瘤治疗模式后的第四模式。在肿瘤生物治疗中，表皮生长因子受体（epidermal growth factor receptor，EGFR）靶点扮演着重要角色。EGFR为一种相对分子质量为170 000的酪氨酸蛋白激酶型受体，在多种恶性肿瘤存在过表达，在肿瘤发生、发展中起着重要作用。靶向EGFR的肿瘤生物治疗方法主要包括：基因沉默治疗、显性负性治疗、单克隆抗体（monoclonal antibody,McAb）治疗、生物“导弹”治疗、EGFR酪氨酸激酶抑制剂（EGFR tyrosine kinase inhibitor,EGFR TKI）治疗、双特异性抗体（bispecific antibody,BsAb）治疗方法等。目前靶向EGFR的肿瘤生物治疗研究已经取得较大进展，随着研究的进一步深入，肿瘤的治疗必将跨入一个全新的时代。
肿瘤生物治疗（cancer biotherapy）已经成为继手术、放疗和化疗三大经典肿瘤治疗模式后的第四模式。在肿瘤生物治疗中，表皮生长因子受体（epidermal growth factor receptor，EGFR）靶点扮演着重要角色。EGFR为一种相对分子质量为170 000的酪氨酸蛋白激酶型受体，在多种恶性肿瘤存在过表达，在肿瘤发生、发展中起着重要作用。靶向EGFR的肿瘤生物治疗方法主要包括：基因沉默治疗、显性负性治疗、单克隆抗体（monoclonal antibody,McAb）治疗、生物“导弹”治疗、EGFR酪氨酸激酶抑制剂（EGFR tyrosine kinase inhibitor,EGFR TKI）治疗、双特异性抗体（bispecific antibody,BsAb）治疗方法等。目前靶向EGFR的肿瘤生物治疗研究已经取得较大进展，随着研究的进一步深入，肿瘤的治疗必将跨入一个全新的时代。
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.