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Volume 15,Issue 6,2008 Table of Contents
2008, 15(6):501-507.
DOI: 10.3872/j.issn.1007-385X.2008.6.001
Abstract:
Objective:To screen for functional monoclonal antibodies against lung cancer cell membrane antigens, so as to provide candidate targets and drugs for targeted therapy of lung cancer. Methods:Malignant cells separated from lung carcinoma tissues were used to immunize BALB/c mice. The spleen cells of the immunized mouse were fused with SP2/0 cells to construct functional monoclonal antibody library. Several lung cancer cell lines were domesticated to establish functionaloriented differential sub cell lines of proliferation, invasion and migration, then the antibodies of each clone were screened by immunofluorescence with the functional differential sub cell lines to obtain the functional monoclonal antibodies against cell membranes proteins and then screened by in vitro functional assays. Antigens of functional monoclonal antibodies were identified by Western blotting and the inhibitory effects of individual antibodies were tested by tumor treatment experiments in vivo. Results:Totally 2 893 monoclonal antibody clones were obtained by fusion of spleen cells with SP2/0 cells and 309 clones reacted with the lung cancer cell membranes components. Three functionaloriented differential sub cell line models of lung cancer cells, including the proliferation, invasion and migration, were established for primary screening. Twenty clones of monoclonal antibodies significantly suppressed the lung cancer cell proliferation, 10 monoclonal antibodies could inhibit tumor cell invasion in matrigel and 5 inhibited tumor cell migration（P<0.05 or P<001）. Western blotting assay identified 6 target antigens from these functional antibodies above. In vivo assay further demonstrated that 2 of these functional antibodies significantly inhibited lung tumor growth in mice. Conclusion:Combination of functional antibody library and differential functionaloriented cell models can be used to batch screen for functional monoclonal antibodies, which can suppress the malignant behavior of lung cancer cells in vitro and in vivo, providing a new method for screening the targets for the antimalignancy therapy.
Objective:To screen for functional monoclonal antibodies against lung cancer cell membrane antigens, so as to provide candidate targets and drugs for targeted therapy of lung cancer. Methods:Malignant cells separated from lung carcinoma tissues were used to immunize BALB/c mice. The spleen cells of the immunized mouse were fused with SP2/0 cells to construct functional monoclonal antibody library. Several lung cancer cell lines were domesticated to establish functionaloriented differential sub cell lines of proliferation, invasion and migration, then the antibodies of each clone were screened by immunofluorescence with the functional differential sub cell lines to obtain the functional monoclonal antibodies against cell membranes proteins and then screened by in vitro functional assays. Antigens of functional monoclonal antibodies were identified by Western blotting and the inhibitory effects of individual antibodies were tested by tumor treatment experiments in vivo. Results:Totally 2 893 monoclonal antibody clones were obtained by fusion of spleen cells with SP2/0 cells and 309 clones reacted with the lung cancer cell membranes components. Three functionaloriented differential sub cell line models of lung cancer cells, including the proliferation, invasion and migration, were established for primary screening. Twenty clones of monoclonal antibodies significantly suppressed the lung cancer cell proliferation, 10 monoclonal antibodies could inhibit tumor cell invasion in matrigel and 5 inhibited tumor cell migration（P<0.05 or P<001）. Western blotting assay identified 6 target antigens from these functional antibodies above. In vivo assay further demonstrated that 2 of these functional antibodies significantly inhibited lung tumor growth in mice. Conclusion:Combination of functional antibody library and differential functionaloriented cell models can be used to batch screen for functional monoclonal antibodies, which can suppress the malignant behavior of lung cancer cells in vitro and in vivo, providing a new method for screening the targets for the antimalignancy therapy.
JIANG Yunbo
,
LU Yinglin
,
JIA Haiquan
,
XU Yuanji
,
CHEN Huihua
,
LIU Gang
,
WANG Yan
,
DU Zhiyan
2008, 15(6):508-515.
DOI: 10.3872/j.issn.1007-385X.2008.6.002
Abstract:
Objective:To investigate the antitumor effect of exogenous p53regulated apoptosisinducing protein 1（p53AIP1）and the related mechanism, so as to assess the feasibility of using p53AIP1 in tumor gene therapy. Methods: The recombinant replicationdefective adenovirus Adp53AIP1 containing p53AIP1 gene was constructed and transfected into human hepatocellular carcinoma HepG2 cell line. The effects and the relevant mechanisms of exogenous p53AIP1 gene on cell growth were examined by MTT, Western blotting, flow cytometry, rhodamine staining and electron microscopy. Nude mice were subcutaneously inoculated with Adp53AIP1infected mouse breast cancer cell line 4T1 to observe the effect of Adp53AIP1 on tumorigenesis of tumor cells. 4T1 breast cancer xenograft models were established in mice and intratumoral injections of Adp53AIP1 were given to observe the antitumor effect of Adp53AIP1. Results: Overexpression of p53AIP1 protein was confirmed in HepG2 cells infected with Adp53AIP1. Cell growth of HepG2 cells which contain wildtype p53 gene was inhibited by over 50% after infection. Flow cytometry showed transfection with p53AIP1 gene resulted in cell cycle arrest at G2/M. Results of PARP protein examination, rhodamine staining and electron microscopic observation demonstrated that p53AIP1induced obvious apoptosis in tumor cells. Moreover, the infection with Adp53AIP1 significantly inhibited the tumorigenesis of 4T1 cells in vivo （P<0.01）and the growth of tumors in vivo after intratumorial injection（P<0.05）. Furthermore, Western blotting and RTPCR confirmed that Adp53AIP1 had no influence on p53 mRNA expression and downregulated mdm2gene and protein; it also upregulated P53 protein expression. In addition, Adp53AIP1 could regulate cell cyclerelated proteins and apoptosisrelated proteins such as P21. Conclusions: Adp53AIP1 possess obvious tumor inhibitory effect in vitro and in vivo; the mechanism is related to its regulation of P53 protein, cell cycle and apoptosisrelated proteins. p53AIP1 might have a future in tumor gene therapy.
Objective:To investigate the antitumor effect of exogenous p53regulated apoptosisinducing protein 1（p53AIP1）and the related mechanism, so as to assess the feasibility of using p53AIP1 in tumor gene therapy. Methods: The recombinant replicationdefective adenovirus Adp53AIP1 containing p53AIP1 gene was constructed and transfected into human hepatocellular carcinoma HepG2 cell line. The effects and the relevant mechanisms of exogenous p53AIP1 gene on cell growth were examined by MTT, Western blotting, flow cytometry, rhodamine staining and electron microscopy. Nude mice were subcutaneously inoculated with Adp53AIP1infected mouse breast cancer cell line 4T1 to observe the effect of Adp53AIP1 on tumorigenesis of tumor cells. 4T1 breast cancer xenograft models were established in mice and intratumoral injections of Adp53AIP1 were given to observe the antitumor effect of Adp53AIP1. Results: Overexpression of p53AIP1 protein was confirmed in HepG2 cells infected with Adp53AIP1. Cell growth of HepG2 cells which contain wildtype p53 gene was inhibited by over 50% after infection. Flow cytometry showed transfection with p53AIP1 gene resulted in cell cycle arrest at G2/M. Results of PARP protein examination, rhodamine staining and electron microscopic observation demonstrated that p53AIP1induced obvious apoptosis in tumor cells. Moreover, the infection with Adp53AIP1 significantly inhibited the tumorigenesis of 4T1 cells in vivo （P<0.01）and the growth of tumors in vivo after intratumorial injection（P<0.05）. Furthermore, Western blotting and RTPCR confirmed that Adp53AIP1 had no influence on p53 mRNA expression and downregulated mdm2gene and protein; it also upregulated P53 protein expression. In addition, Adp53AIP1 could regulate cell cyclerelated proteins and apoptosisrelated proteins such as P21. Conclusions: Adp53AIP1 possess obvious tumor inhibitory effect in vitro and in vivo; the mechanism is related to its regulation of P53 protein, cell cycle and apoptosisrelated proteins. p53AIP1 might have a future in tumor gene therapy.
2008, 15(6):516-521.
DOI: 10.3872/j.issn.1007-385X.2008.6.003
Abstract:
Objective:To investigate the effect of trichostatin A (TSA) and paclitaxel (PTX) on the growth and apoptosis of human endometrial carcinoma KLE cell line. Methods: KLE cells were cultured in the presence of PTX, doxorubicin, carboplatin, histone deacetylase inhibitor TSA or their combination. The growth curve was obtained by trypanblue exclusion assay and cell counting. Cell apoptosis was observed by Annexin V, Hoechst staining and perturbation of mitochondrial membrane potential. The protein expression of PARP, caspase9 and tubulin acetylation was detected by Western blotting. Results: Paclitaxel, doxorubicin, carboplatin, and TSA all significant inhibited the growth of KLE cells. PTX and TSA both induced cell apoptosis; the combined treatment with TSA and PTX induced more severe apoptosis. Western blotting and immunohistochemistry analysis demonstrated that TSA and PTX induced acetylation of tubulin, and a combination of both resulted in more severe acetylation of tubulin. Conclusion: The synergy of TSA and PTX can greatly inhibit the growth of KLE cells and induce their apoptosis.
Objective:To investigate the effect of trichostatin A (TSA) and paclitaxel (PTX) on the growth and apoptosis of human endometrial carcinoma KLE cell line. Methods: KLE cells were cultured in the presence of PTX, doxorubicin, carboplatin, histone deacetylase inhibitor TSA or their combination. The growth curve was obtained by trypanblue exclusion assay and cell counting. Cell apoptosis was observed by Annexin V, Hoechst staining and perturbation of mitochondrial membrane potential. The protein expression of PARP, caspase9 and tubulin acetylation was detected by Western blotting. Results: Paclitaxel, doxorubicin, carboplatin, and TSA all significant inhibited the growth of KLE cells. PTX and TSA both induced cell apoptosis; the combined treatment with TSA and PTX induced more severe apoptosis. Western blotting and immunohistochemistry analysis demonstrated that TSA and PTX induced acetylation of tubulin, and a combination of both resulted in more severe acetylation of tubulin. Conclusion: The synergy of TSA and PTX can greatly inhibit the growth of KLE cells and induce their apoptosis.
2008, 15(6):522-526.
DOI: 10.3872/j.issn.1007-385X.2008.6.004
Abstract:
Objective:To investigate the inhibitory effect of breast cancerassociated antigen 1(BRCAA1) gene silencing on gastric cancer MGC803 cells and the related mechanism. Methods: Plasmid shRNABRCAA1 and shRNAN were constructed and transfected with FuGene HD into gastric cancer cell line MGC803. The transfection efficiency was examined using fluorescent microscope 24 h later. The total RNAs was extracted 48 h after transfection and the expression of BRCAA1 and GAPDH gene were analyzed by realtime PCR. The cell proliferation was assessed by MTT assay 24 h, 48 h, and 72 h after transfection. The cell apoptosis was determined by Annexin VPE/7AAD. The expression of Rb, Bax, Bcl2 and BRCAA1 proteins was analyzed by Western blotting 48 h after transfection. Results:We found that the transfection efficiency of shRNABRCAA1 was （81.2±2.6）％ 24 h after transfection. Fortyeight hours after transfection with shRNABRCAA1 the expression of BRCAA1 mRNA decreased by 61.4%; the inhibition rate of MGC803 cells growth was 45.0%. The cell apoptosis rate of shRNABRCAA1 transfection group was significantly higher than those of untransfected group and mock plasmid transfected group （\[14.4±1.6\]% vs \[5.4±2.0\]％，\[4.4±2.5\]％，P<0.05\]. Cells transfected with shRNABRCAA1 had significantly increased expression of Rb and Bax proteins（P<0.05）, and decreased expression of Bcl2 protein（P<005）. Conclusion: BRCAA1 gene silencing can effectively inhibit the proliferation of MGC803 cells and induce apoptosis, which might be related to the promotion of Rb and Bax proteins, and suppression of Bcl2 protein.
Objective:To investigate the inhibitory effect of breast cancerassociated antigen 1(BRCAA1) gene silencing on gastric cancer MGC803 cells and the related mechanism. Methods: Plasmid shRNABRCAA1 and shRNAN were constructed and transfected with FuGene HD into gastric cancer cell line MGC803. The transfection efficiency was examined using fluorescent microscope 24 h later. The total RNAs was extracted 48 h after transfection and the expression of BRCAA1 and GAPDH gene were analyzed by realtime PCR. The cell proliferation was assessed by MTT assay 24 h, 48 h, and 72 h after transfection. The cell apoptosis was determined by Annexin VPE/7AAD. The expression of Rb, Bax, Bcl2 and BRCAA1 proteins was analyzed by Western blotting 48 h after transfection. Results:We found that the transfection efficiency of shRNABRCAA1 was （81.2±2.6）％ 24 h after transfection. Fortyeight hours after transfection with shRNABRCAA1 the expression of BRCAA1 mRNA decreased by 61.4%; the inhibition rate of MGC803 cells growth was 45.0%. The cell apoptosis rate of shRNABRCAA1 transfection group was significantly higher than those of untransfected group and mock plasmid transfected group （\[14.4±1.6\]% vs \[5.4±2.0\]％，\[4.4±2.5\]％，P<0.05\]. Cells transfected with shRNABRCAA1 had significantly increased expression of Rb and Bax proteins（P<0.05）, and decreased expression of Bcl2 protein（P<005）. Conclusion: BRCAA1 gene silencing can effectively inhibit the proliferation of MGC803 cells and induce apoptosis, which might be related to the promotion of Rb and Bax proteins, and suppression of Bcl2 protein.
2008, 15(6):527-531.
DOI: 10.3872/j.issn.1007-385X.2008.6.005
Abstract:
Objective:To investigate the inhibitory effect of inhibitor of differentiation 3 (Id3) on growth of human lung adenocarcinoma cell line A549. Methods: Recombinant eukaryotic expression vector pEGFP/Id3 was constructed and transfected into A549 cells by liposomemediated method. Expression of pEGFP/Id3 in A549 cells was analyzed by flow cytometry (FCM), fluorescence microscopy, semiquantitative RTPCR and immunocytochemistry. The growth inhibitory rate of A549 cells was examined by MTT assay; cell cycle change was evaluated by PI (propidium iodide) staining method. Cell apoptotic rate and nuclear morphology were detected by Annexin V/7AAD and Hoechst33258 staining. Results: The recombinant eukaryotic expression vector pEGFP/Id3 was successfully constructed. The expression of EGFP reached the peak 4872 h after transfection; the expresion of pEGFPtransfected group was higher than that of the pEGFP/Id3 group. RTPCR and immunocytochemistry staining showed that Id3 mRNA and protein were effectively expressed in pEGFP/Id3transfected A549 cells. The growth of cells in pEGFP/Id3 transfected cells was significantly inhibited 4872 h after transfection（P<0.01）. More cells were blocked in G0/G1 phase in pEGFP/Id3transfected group compared with pEGFP group（P<0.05）. Annexin V/7AAD showed that the apoptotic rate of pEGFP/Id3 group （\[10.67±2.60\]%）were significantly higher than those of the control group（\[2.35 ± 0.95\]%）and pEGFP group（\[3.39±2.21\] %）（P<0.05）. Hoechst33258 staining also showed that the cells in pEGFP/Id3 group had typical apoptotic morphology.Conclusion: Exogenous Id3 gene expression in A549 cells can induce cell growth inhibition and apoptosis of A549 cells.
Objective:To investigate the inhibitory effect of inhibitor of differentiation 3 (Id3) on growth of human lung adenocarcinoma cell line A549. Methods: Recombinant eukaryotic expression vector pEGFP/Id3 was constructed and transfected into A549 cells by liposomemediated method. Expression of pEGFP/Id3 in A549 cells was analyzed by flow cytometry (FCM), fluorescence microscopy, semiquantitative RTPCR and immunocytochemistry. The growth inhibitory rate of A549 cells was examined by MTT assay; cell cycle change was evaluated by PI (propidium iodide) staining method. Cell apoptotic rate and nuclear morphology were detected by Annexin V/7AAD and Hoechst33258 staining. Results: The recombinant eukaryotic expression vector pEGFP/Id3 was successfully constructed. The expression of EGFP reached the peak 4872 h after transfection; the expresion of pEGFPtransfected group was higher than that of the pEGFP/Id3 group. RTPCR and immunocytochemistry staining showed that Id3 mRNA and protein were effectively expressed in pEGFP/Id3transfected A549 cells. The growth of cells in pEGFP/Id3 transfected cells was significantly inhibited 4872 h after transfection（P<0.01）. More cells were blocked in G0/G1 phase in pEGFP/Id3transfected group compared with pEGFP group（P<0.05）. Annexin V/7AAD showed that the apoptotic rate of pEGFP/Id3 group （\[10.67±2.60\]%）were significantly higher than those of the control group（\[2.35 ± 0.95\]%）and pEGFP group（\[3.39±2.21\] %）（P<0.05）. Hoechst33258 staining also showed that the cells in pEGFP/Id3 group had typical apoptotic morphology.Conclusion: Exogenous Id3 gene expression in A549 cells can induce cell growth inhibition and apoptosis of A549 cells.
2008, 15(6):532-537.
DOI: 10.3872/j.issn.1007-385X.2008.6.006
Abstract:
Objective:To observe the inhibitory effects of survivinspecific siRNA on human lung cancer cell lines with different P53 statuses, and to analyse the relationship between P53and survivin in vitro. Methods: A549 (wildtype P53) and H1299 (P53absent) cells were transfected with chemosynthetic survivin siRNA. The effect of siRNA on cell proliferation was analysed by MTT assay. The changes of cell cycle and apoptosis were examined by flow cytometry. The expression of survivin mRNA was detected by RTPCR. The protein expression of survivin, P53, P21 and PARP was examined by Western blotting. Results:Endogenous survivin level in A549 cells was lower than that in H1299 cells. The mRNA and protein expression of survivin was significantly lower in siRNA group than in blank control group and nonsilencing siRNA group (P<0.01). Survivinspecific siRNA significantly inhibited the growth and proliferation of both A549 and H1299 cells in a concentration dependent manner (P<0.05), but the inhibitory effect was earlier and more efficient in A549 cells than in H1299 cells. Survivinspecific siRNA produced an increase in the G1 fraction and a decrease in S fraction in the two cell lines, with the changes in the latter more evident. Apoptosis was found in A549 cells; PARP was cleaved and P21 and P53 protein was increased in A549 cells. The above changes were not obvious in H1299 cells. Conclusion: Endogenous survivin levels in A549 (wildtype P53) cells is lower than that in H1299 (without P53) cells. Inhibition of survivin by transfecting survivin siRNA can significantly upregulate P53 protein expression in A549 cells. The effects of survivin siRNA on the cell growth, apoptosis and expression of some proteins are more prominent in A549 than in H1299 cells, suggesting that survivin and P53 might inhibit each other.
Objective:To observe the inhibitory effects of survivinspecific siRNA on human lung cancer cell lines with different P53 statuses, and to analyse the relationship between P53and survivin in vitro. Methods: A549 (wildtype P53) and H1299 (P53absent) cells were transfected with chemosynthetic survivin siRNA. The effect of siRNA on cell proliferation was analysed by MTT assay. The changes of cell cycle and apoptosis were examined by flow cytometry. The expression of survivin mRNA was detected by RTPCR. The protein expression of survivin, P53, P21 and PARP was examined by Western blotting. Results:Endogenous survivin level in A549 cells was lower than that in H1299 cells. The mRNA and protein expression of survivin was significantly lower in siRNA group than in blank control group and nonsilencing siRNA group (P<0.01). Survivinspecific siRNA significantly inhibited the growth and proliferation of both A549 and H1299 cells in a concentration dependent manner (P<0.05), but the inhibitory effect was earlier and more efficient in A549 cells than in H1299 cells. Survivinspecific siRNA produced an increase in the G1 fraction and a decrease in S fraction in the two cell lines, with the changes in the latter more evident. Apoptosis was found in A549 cells; PARP was cleaved and P21 and P53 protein was increased in A549 cells. The above changes were not obvious in H1299 cells. Conclusion: Endogenous survivin levels in A549 (wildtype P53) cells is lower than that in H1299 (without P53) cells. Inhibition of survivin by transfecting survivin siRNA can significantly upregulate P53 protein expression in A549 cells. The effects of survivin siRNA on the cell growth, apoptosis and expression of some proteins are more prominent in A549 than in H1299 cells, suggesting that survivin and P53 might inhibit each other.
2008, 15(6):538-542.
DOI: 10.3872/j.issn.1007-385X.2008.6.007
Abstract:
Objective:To screen for specific CpG ODN sequence which can enhance the radiosensitivity of nasopharyngeal carcinoma cell line CNE2 cells to βray and to observe the sensitivityenhancing characters of the screened CpG ODN sequence, so as to provide evidence for searching novel sensitizer of nasopharyngeal carcinoma to radiation. Methods: MTT assay was used to select the strongest sequence to sensitize CNE2 cells to βray irradiation from 21 CpG ODN sequences. The effect of the selected sequence combined with βray irradiation were used to treat CNE2 cells and the proliferation, colony forming, cell migration, cell cycle and apoptosis were all observed. Results: Screen assay found CpG ODN107 had the highest SER (1.59±0.06) for CNE2 cells. CpG ODN107 combined with βray irradiation inhibited CNE2 cell proliferation in a dose-dependent manner, and the inhibitory effect was significantly higher than that of radiation alone (P<0.05, P<0.01). CpG ODN107 combined with βray irradiation significantly inhibited the formation and migration of CNE2 cell colony, and induced G0/G1 arrest and significantly increased cell apoptosis compared with that of radiation alone (P<0.05 or 0.01). Conclusion：Our results suggest that CpG ODN107 can greatly enhance the radiosensitivities of human nasopharyngeal carcinoma cell line CNE2 to βray radiation, which might be related to the induction of cell cycle arrest and apoptosis.
Objective:To screen for specific CpG ODN sequence which can enhance the radiosensitivity of nasopharyngeal carcinoma cell line CNE2 cells to βray and to observe the sensitivityenhancing characters of the screened CpG ODN sequence, so as to provide evidence for searching novel sensitizer of nasopharyngeal carcinoma to radiation. Methods: MTT assay was used to select the strongest sequence to sensitize CNE2 cells to βray irradiation from 21 CpG ODN sequences. The effect of the selected sequence combined with βray irradiation were used to treat CNE2 cells and the proliferation, colony forming, cell migration, cell cycle and apoptosis were all observed. Results: Screen assay found CpG ODN107 had the highest SER (1.59±0.06) for CNE2 cells. CpG ODN107 combined with βray irradiation inhibited CNE2 cell proliferation in a dose-dependent manner, and the inhibitory effect was significantly higher than that of radiation alone (P<0.05, P<0.01). CpG ODN107 combined with βray irradiation significantly inhibited the formation and migration of CNE2 cell colony, and induced G0/G1 arrest and significantly increased cell apoptosis compared with that of radiation alone (P<0.05 or 0.01). Conclusion：Our results suggest that CpG ODN107 can greatly enhance the radiosensitivities of human nasopharyngeal carcinoma cell line CNE2 to βray radiation, which might be related to the induction of cell cycle arrest and apoptosis.
2008, 15(6):543-547.
DOI: 10.3872/j.issn.1007-385X.2008.6.008
Abstract:
Objective:To explore the antitumor and hypoxia regulatory effect of HIF1α siRNA in tumor tissues. Methods:The HIF1α siRNA adenovirus vectors targeting HIF1α were constructed and the rabbit VX2 tumor model was established. The constructed vectors were injected into rabbits through ear vein; noninterference sequence was injected as control. PET (positron emission computed tomography) was used to observe the changes of hypoxia and necrosis in tumor tissues. The tumors were removed and the tumor volumes were measured. HE staining was used to observe the degree of the necrosis; RTPCR was used to detect the change of HIF1α expression in tumor tissues. Results: The recombinant HIF1α siRNA adenovirus vectors were successfully constructed, with a titre of 1.1×1010 pfu/mL. PET imaging showed that the SUV of 18FFDG was significantly decreased in HIF1α siRNA injected group than that in the control group (\[351±0.36\]％ vs \[8.73±0.83\]％, P<0.01). Images showed that the tumor tissue had obvious hypoxia and necrosis. The sizes of the tumors of HIF1α siRNA injected group were significantly smaller than that of the control group (P<0.01); the necrosis areas in the tumors of HIF1α siRNA injected group were significantly larger than that of control group (P<0.01). RTPCR demonstrated that the expression of HIF1α mRNA in HIF1α siRNA injected group was significantly lower than that in the control group (P<0.01). Conclusion: HIF1α specific siRNA can reduce HIF1α expression in tumor tissues and aggregate the hypoxia and necrosis of tumor tissue, therefore producing obvious antitumor effect.
Objective:To explore the antitumor and hypoxia regulatory effect of HIF1α siRNA in tumor tissues. Methods:The HIF1α siRNA adenovirus vectors targeting HIF1α were constructed and the rabbit VX2 tumor model was established. The constructed vectors were injected into rabbits through ear vein; noninterference sequence was injected as control. PET (positron emission computed tomography) was used to observe the changes of hypoxia and necrosis in tumor tissues. The tumors were removed and the tumor volumes were measured. HE staining was used to observe the degree of the necrosis; RTPCR was used to detect the change of HIF1α expression in tumor tissues. Results: The recombinant HIF1α siRNA adenovirus vectors were successfully constructed, with a titre of 1.1×1010 pfu/mL. PET imaging showed that the SUV of 18FFDG was significantly decreased in HIF1α siRNA injected group than that in the control group (\[351±0.36\]％ vs \[8.73±0.83\]％, P<0.01). Images showed that the tumor tissue had obvious hypoxia and necrosis. The sizes of the tumors of HIF1α siRNA injected group were significantly smaller than that of the control group (P<0.01); the necrosis areas in the tumors of HIF1α siRNA injected group were significantly larger than that of control group (P<0.01). RTPCR demonstrated that the expression of HIF1α mRNA in HIF1α siRNA injected group was significantly lower than that in the control group (P<0.01). Conclusion: HIF1α specific siRNA can reduce HIF1α expression in tumor tissues and aggregate the hypoxia and necrosis of tumor tissue, therefore producing obvious antitumor effect.
CAI Xiaoshan
,
REN Ruimei
,
ZHANG Shinuan
,
LI Wentong
,
ZHU Hongguang
,
DOU Jianxin
,
LIU Jing
2008, 15(6):548-551.
DOI: 10.3872/j.issn.1007-385X.2008.6.009
Abstract:
Objective:To investigate the influence of Bifidobacterium adolescence on the expression of HIF1α and VEGF in rabbit VX2 tumor. Methods: Rabbit VX2 tumor models were established and were divided into two groups (n=10). Animals in the experimental group were injected with Bifidobacterium adolescence and those in the control group received normal saline via ear vein. Animals were sacrificed and the liver, kidney, spleen, heart, lung and tumor tissues were removed, cultured and Gram stained. The changes of tumor tissue were observed by HE staining; immunohistochemistry was used to detect the expression of HIF1α and VEGF in tumor tissues. Results:Bifidobacterium adolescence could target the tumor tissue. HE staining showed the necrotic area was obviously enlarged after treatment with Bifidobacterium. Immunohistochemistry demonstrated that the positive rates of HIF1α and VEGF in the experimental group were significantly lower than those of the control group(P<0.05), and the expression of the HIF1α and VEGF in two groups was positively correlated (r=0.86). Conclusion:Bifidobacterium adolescence can specifically target rabbit VX2 tumors tissues, and decrease the expression of HIF1α and VEGF.
Objective:To investigate the influence of Bifidobacterium adolescence on the expression of HIF1α and VEGF in rabbit VX2 tumor. Methods: Rabbit VX2 tumor models were established and were divided into two groups (n=10). Animals in the experimental group were injected with Bifidobacterium adolescence and those in the control group received normal saline via ear vein. Animals were sacrificed and the liver, kidney, spleen, heart, lung and tumor tissues were removed, cultured and Gram stained. The changes of tumor tissue were observed by HE staining; immunohistochemistry was used to detect the expression of HIF1α and VEGF in tumor tissues. Results:Bifidobacterium adolescence could target the tumor tissue. HE staining showed the necrotic area was obviously enlarged after treatment with Bifidobacterium. Immunohistochemistry demonstrated that the positive rates of HIF1α and VEGF in the experimental group were significantly lower than those of the control group(P<0.05), and the expression of the HIF1α and VEGF in two groups was positively correlated (r=0.86). Conclusion:Bifidobacterium adolescence can specifically target rabbit VX2 tumors tissues, and decrease the expression of HIF1α and VEGF.
2008, 15(6):552-556.
DOI: 10.3872/j.issn.1007-385X.2008.6.010
Abstract:
Objective:To investigate the promoting effect of silencing mitogenactivated protein/ERK kinase kinase 3 ( MEKK3 )gene on TRAIL-induced apoptosis of breast cancer MCF7 cells, so as to search for a novel clinical treatment strategy for breast cancer. Methods: TRAIL was used to treat MCF7 cells and the growth inhibition of MCF7 cells was determined by a methyl thiazolyl tetrazolium ( MTT ) assay．Chemically synthesized small interfering RNA ( siRNA ) targeting MEKK3 was transfected into MCF7 cells using DharmaFECT Transfection reagent, and the expression of MEKK3mRNA and protein was detected by RTPCR and Western blotting. The proliferation and apoptosis of MCF7 cells were analyzed by MTT and flow cytometry ( FCM ) after treatment with MEKK3siRNA combined with TRAIL．Results: TRAIL inhibited the proliferation of MCF7 cells, but the inhibitory effect was weak. Transfection with MEKK3siRNA effectively and stably inhibited the expression of MEKK3mRNA and protein expression (P<0.01). Combination of TRAIL and MEKK3siRNA more severely inhibited the proliferation of MCF7 cells compared with TRAIL alone (P<0.05); besides, the combination also increased the apoptosis rate of MCF7 cells (P<0.05). Conclusion: Silencing of MEKK3gene with siRNA can greatly promote TRAILinduced apoptosis of breast cancer cells MCF7, which lays an experimental foundation for new treatment method of breast cancer.
Objective:To investigate the promoting effect of silencing mitogenactivated protein/ERK kinase kinase 3 ( MEKK3 )gene on TRAIL-induced apoptosis of breast cancer MCF7 cells, so as to search for a novel clinical treatment strategy for breast cancer. Methods: TRAIL was used to treat MCF7 cells and the growth inhibition of MCF7 cells was determined by a methyl thiazolyl tetrazolium ( MTT ) assay．Chemically synthesized small interfering RNA ( siRNA ) targeting MEKK3 was transfected into MCF7 cells using DharmaFECT Transfection reagent, and the expression of MEKK3mRNA and protein was detected by RTPCR and Western blotting. The proliferation and apoptosis of MCF7 cells were analyzed by MTT and flow cytometry ( FCM ) after treatment with MEKK3siRNA combined with TRAIL．Results: TRAIL inhibited the proliferation of MCF7 cells, but the inhibitory effect was weak. Transfection with MEKK3siRNA effectively and stably inhibited the expression of MEKK3mRNA and protein expression (P<0.01). Combination of TRAIL and MEKK3siRNA more severely inhibited the proliferation of MCF7 cells compared with TRAIL alone (P<0.05); besides, the combination also increased the apoptosis rate of MCF7 cells (P<0.05). Conclusion: Silencing of MEKK3gene with siRNA can greatly promote TRAILinduced apoptosis of breast cancer cells MCF7, which lays an experimental foundation for new treatment method of breast cancer.
2008, 15(6):561-565.
DOI: 10.3872/j.issn.1007-385X.2008.6.012
Abstract:
Objective:To construct a small interfering RNA (siRNA) expression vector (psiRNAVEGFR3) targeting vascular endothelial growth factor receptor 3 (VEGFR3) and to investigate the effects of VEGFR3 siRNA on the adherence and invasion of human colon cancer cells. Methods: A siRNA expression vector (psiRNAVEGFR3) targeting VEGFR3were constructed and was used to transfect LoVo cells via lipofectamine 2000. The mRNA and protein expression of VEGFR3were examined after transfection by reverse transcriptase polymerase chain reaction (RTPCR) and Western blotting, respectively. The tumor adhesion ability was detected by cellmatrix adhesion experiment and the invasion ability of tumor cells was evaluated by millicell chamber model. Results: The VEGFR3 siRNA expression vector was successfully constructed. The expression of VEGFR3mRNA and protein was inhibited after psiRNAVEGFR3 transfection. Seventytwo hours after psiRNAVEGFR3 transfection, Western blotting assay showed that the expression of VEGFR3 protein was decreased from (1.26±0.19) to (0.39±0.12)(P＜0.05), the adhesion ability of LoVo cells was also significantly decreased compared with the untransfected group and negative control group (0.407±0029 vs 0.626±0.047,0.621±0.068, P<0.01). The invasion assay demonstrated that the number of LoVo cells penetrating the membrane in the transfection group was significantly lower than those in the untransfected and negative control group (6.38±3.25 vs 24.82±3.44, 23.58±3.73, P<0.05). Conclusion: The siRNA of VEGFR3gene can effectively inhibit the mRNA and protein expression of VEGFR3 in LoVo cells, therefore restraining the adhesion and invasion ability of LoVo cells.
Objective:To construct a small interfering RNA (siRNA) expression vector (psiRNAVEGFR3) targeting vascular endothelial growth factor receptor 3 (VEGFR3) and to investigate the effects of VEGFR3 siRNA on the adherence and invasion of human colon cancer cells. Methods: A siRNA expression vector (psiRNAVEGFR3) targeting VEGFR3were constructed and was used to transfect LoVo cells via lipofectamine 2000. The mRNA and protein expression of VEGFR3were examined after transfection by reverse transcriptase polymerase chain reaction (RTPCR) and Western blotting, respectively. The tumor adhesion ability was detected by cellmatrix adhesion experiment and the invasion ability of tumor cells was evaluated by millicell chamber model. Results: The VEGFR3 siRNA expression vector was successfully constructed. The expression of VEGFR3mRNA and protein was inhibited after psiRNAVEGFR3 transfection. Seventytwo hours after psiRNAVEGFR3 transfection, Western blotting assay showed that the expression of VEGFR3 protein was decreased from (1.26±0.19) to (0.39±0.12)(P＜0.05), the adhesion ability of LoVo cells was also significantly decreased compared with the untransfected group and negative control group (0.407±0029 vs 0.626±0.047,0.621±0.068, P<0.01). The invasion assay demonstrated that the number of LoVo cells penetrating the membrane in the transfection group was significantly lower than those in the untransfected and negative control group (6.38±3.25 vs 24.82±3.44, 23.58±3.73, P<0.05). Conclusion: The siRNA of VEGFR3gene can effectively inhibit the mRNA and protein expression of VEGFR3 in LoVo cells, therefore restraining the adhesion and invasion ability of LoVo cells.
WU Xiaojun
,
LU Yicheng
,
CHEN Huairui
,
CHEN Juxiang
,
HUANG Chenguang
,
YANG ZhiRong
,
PAN Jinwei
,
LUO Chun
,
HU Guohan
,
LOU Meiqing
,
HAN Xi
,
LIU Ping
,
RUI Yaocheng
2008, 15(6):566-570.
DOI: 10.3872/j.issn.1007-385X.2008.6.013
Abstract:
Objective: To explore the expression of NogoB in brain gliomas and its relationship with the pathological grades of gliomas. Methods: The expression of NogoB was investigated in 10 normal brain tissues and 36 brain glioma specimens, which were confirmed after surgery during 2005-2008 in Changzheng Hospital, using immunohistochemical method, realtime PCR and Western blotting assay．The relationship between NogoB expression and pathological grades were analyzed. Results:Tissue NogoB immunohistochemical staining in gliomas specimens suggested the involvement of NogoB in the proliferation of gliomas. The realtime PCR demonstrated that NogoB mRNA expression level in gliomas was obviously decreased in gliomas of high pathological grades, and the expression was stable in normal brain tissues. The expression of NogoB was negatively correlated with the malignancy of glioma. The expression in gliomas of grade Ⅲ decreased by 90% compared with the normal brain tissues (P<0.01). Western blotting showed that NogoB protein expression was stable in normal brain tissues and obviously decreased in glioma tissues of high grade; the decrease was negatively correlated with the malignancy of gliomas. Immunohistochemical analysis showed NogoB expression was scattered in the normal brain tissues (100%) and greatly decreased in human gliomas. The expression of NogoB was decreased with the increase of the malignancy in our 36 specimens, being 88.2%，42.9%，and 25.0% in ⅠⅡ,Ⅲ, and Ⅳ grades, respectively (P<0.01)．Conclusion: NogoB is decreases in human glioma at both protein and mRNA level. NogoB participats in the development and progression of bliomas, and its downregulation is closely related to the malignancy of tumors.
Objective: To explore the expression of NogoB in brain gliomas and its relationship with the pathological grades of gliomas. Methods: The expression of NogoB was investigated in 10 normal brain tissues and 36 brain glioma specimens, which were confirmed after surgery during 2005-2008 in Changzheng Hospital, using immunohistochemical method, realtime PCR and Western blotting assay．The relationship between NogoB expression and pathological grades were analyzed. Results:Tissue NogoB immunohistochemical staining in gliomas specimens suggested the involvement of NogoB in the proliferation of gliomas. The realtime PCR demonstrated that NogoB mRNA expression level in gliomas was obviously decreased in gliomas of high pathological grades, and the expression was stable in normal brain tissues. The expression of NogoB was negatively correlated with the malignancy of glioma. The expression in gliomas of grade Ⅲ decreased by 90% compared with the normal brain tissues (P<0.01). Western blotting showed that NogoB protein expression was stable in normal brain tissues and obviously decreased in glioma tissues of high grade; the decrease was negatively correlated with the malignancy of gliomas. Immunohistochemical analysis showed NogoB expression was scattered in the normal brain tissues (100%) and greatly decreased in human gliomas. The expression of NogoB was decreased with the increase of the malignancy in our 36 specimens, being 88.2%，42.9%，and 25.0% in ⅠⅡ,Ⅲ, and Ⅳ grades, respectively (P<0.01)．Conclusion: NogoB is decreases in human glioma at both protein and mRNA level. NogoB participats in the development and progression of bliomas, and its downregulation is closely related to the malignancy of tumors.
LIU Zhaolong
,
HAN Ceran
,
YAN Bo
,
LUO Yunbao
,
WANG Yongbing
,
SONG An
,
ZHU Zhenya
,
YU Guanzhen
2008, 15(6):571-574.
DOI: 10.3872/j.issn.1007-385X.2008.6.014
Abstract:
Objective:To investigate the expression of phosphorylatemammalian target of rapamycin, pmTOR, in human gallbladder carcinoma and its clinical significance. Methods: Six chronic cholecystitis tissues, 7 adjacent gallbladder carcinoma tissues and 59 gallbladder carcinoma tissues, obtained from Department of General Surgery, People′s Hospital of Pudong New Area and Department of Oncology of Changzheng Hospital from 2004 to 2007, were evaluated by immunohistochemistry and tissue microarray for pmTOR expression. The correlations among pmTOR expression with gallbladder carcinoma invasion, differentiation and Nevin stage were analyzed. Results: The positive rates of pmTOR in chronic cholevstitis, adjacentneoplatic gallbladder carcinoma and gallbladder carcinoma tissue were 0, 0 and 47.5%, respectively (P<0.01). The positive rates of pmTOR in with well, moderately and poorlydifferentiated gallbladder carcinoma tissues were 21.4%, 48.1% and 66.7%, respectively; there were a significant differences among the three groups（P<0.01）. The positive rates in gallbladder carcinoma tissue with mucosa and muscle invasion, serous membrane invasion and peripheral tissue invasion were 30%, 35.7% and 71.40%, respectively（P<0.01）. The positive rates in Ⅰ/Ⅱ, Ⅲ/Ⅳ and Ⅴ stage gallbladder carcinoma tissues were 11.1%, 46.4% and 66.7%, respectively, showing a significant increasing trend（P<0.01）. Conclusion:The expression of pmTOR is closely related with low differentiation, invasion and clinical stage (Nevin stage) of gallbladder carcinoma and may participate in the development and progression of gallbladder carcinoma.
Objective:To investigate the expression of phosphorylatemammalian target of rapamycin, pmTOR, in human gallbladder carcinoma and its clinical significance. Methods: Six chronic cholecystitis tissues, 7 adjacent gallbladder carcinoma tissues and 59 gallbladder carcinoma tissues, obtained from Department of General Surgery, People′s Hospital of Pudong New Area and Department of Oncology of Changzheng Hospital from 2004 to 2007, were evaluated by immunohistochemistry and tissue microarray for pmTOR expression. The correlations among pmTOR expression with gallbladder carcinoma invasion, differentiation and Nevin stage were analyzed. Results: The positive rates of pmTOR in chronic cholevstitis, adjacentneoplatic gallbladder carcinoma and gallbladder carcinoma tissue were 0, 0 and 47.5%, respectively (P<0.01). The positive rates of pmTOR in with well, moderately and poorlydifferentiated gallbladder carcinoma tissues were 21.4%, 48.1% and 66.7%, respectively; there were a significant differences among the three groups（P<0.01）. The positive rates in gallbladder carcinoma tissue with mucosa and muscle invasion, serous membrane invasion and peripheral tissue invasion were 30%, 35.7% and 71.40%, respectively（P<0.01）. The positive rates in Ⅰ/Ⅱ, Ⅲ/Ⅳ and Ⅴ stage gallbladder carcinoma tissues were 11.1%, 46.4% and 66.7%, respectively, showing a significant increasing trend（P<0.01）. Conclusion:The expression of pmTOR is closely related with low differentiation, invasion and clinical stage (Nevin stage) of gallbladder carcinoma and may participate in the development and progression of gallbladder carcinoma.
2008, 15(6):575-580.
DOI: 10.3872/j.issn.1007-385X.2008.6.015
Abstract:
Objective:To investigate the expression of latent membrane protein1 (LMP1) , NET1, and vascular endothelial growth factor (VEGF) in nonkeratin nasopharyngeal carcinoma (NKNPC) and its clinical significance. Methods:Sixty biopsy specimens from pathologicallyconfirmed NKNPC patients, who were treated in the Affilitated Hospital of Nantong University from May 1999 to May 2003, were included in the present study. Using immunohistochemical techniques (Envison twostep), we examined the expression of LMP1, NET1 and VEGF protein in the specimens. The relationship between their expression and clnicopathological parameters and the prognosis was anayzed. Ten specimens of chronic nasopharyngitis served as control. Results:(1) The positive rates of LMP1, NET1 and VEGF in NKNPC were significantly higher than those in the chronic nasopharyngitis (P<0．05). (2) The LMP1 expression in NKNPC specimens were positively correlated with distant metastasis of NKNPC (P<0．05)，and not correlated with the sex，age，T stages and N stages (P＞0．05)． (3) NET1 and VEGF expression in NKNPC specimens were positively correlated with lymph node metastasis and distant metastasis (P<0.05), and not correlated with the sex，age，and T stages． (4) The expression of LMP1, NET1, and VEGF was correlated with each other (P<0.05)．(5) Kaplan-Meier survival curve analysis showed that the expression of LMP1, VEGF was significantly correlated with the prognosis of NKNPC patients (P<005)．Conclusion: Combined examination of LMP1, NET1, and VEGF can help to predict NPC metastasis and prognosis. LMP1 and VEGF might be used as an indicator for prognosis of NKNPC．
Objective:To investigate the expression of latent membrane protein1 (LMP1) , NET1, and vascular endothelial growth factor (VEGF) in nonkeratin nasopharyngeal carcinoma (NKNPC) and its clinical significance. Methods:Sixty biopsy specimens from pathologicallyconfirmed NKNPC patients, who were treated in the Affilitated Hospital of Nantong University from May 1999 to May 2003, were included in the present study. Using immunohistochemical techniques (Envison twostep), we examined the expression of LMP1, NET1 and VEGF protein in the specimens. The relationship between their expression and clnicopathological parameters and the prognosis was anayzed. Ten specimens of chronic nasopharyngitis served as control. Results:(1) The positive rates of LMP1, NET1 and VEGF in NKNPC were significantly higher than those in the chronic nasopharyngitis (P<0．05). (2) The LMP1 expression in NKNPC specimens were positively correlated with distant metastasis of NKNPC (P<0．05)，and not correlated with the sex，age，T stages and N stages (P＞0．05)． (3) NET1 and VEGF expression in NKNPC specimens were positively correlated with lymph node metastasis and distant metastasis (P<0.05), and not correlated with the sex，age，and T stages． (4) The expression of LMP1, NET1, and VEGF was correlated with each other (P<0.05)．(5) Kaplan-Meier survival curve analysis showed that the expression of LMP1, VEGF was significantly correlated with the prognosis of NKNPC patients (P<005)．Conclusion: Combined examination of LMP1, NET1, and VEGF can help to predict NPC metastasis and prognosis. LMP1 and VEGF might be used as an indicator for prognosis of NKNPC．
15 Expression of indoleamine 2,3dioxygenase in hepatocellular carcinoma and its clinical significance
2008, 15(6):585-587.
DOI: 10.3872/j.issn.1007-385X.2008.6.017
Abstract:
目的: 探讨吲哚胺2,3双加氧酶(indoleamine 2,3dioxygenase，IDO)在原发性肝癌细胞、癌旁肝细胞及肿瘤浸润淋巴细胞中的表达及其临床意义。方法：选择经临床确诊的21例原发性肝癌患者的手术切除和（或）肝穿刺所取肝癌组织及癌旁组织标本，通过免疫组织化学染色法检测肝癌及癌旁组织IDO的表达, 并分析其与临床病理特征的关系。结果：IDO在原发性肝癌细胞与肿瘤浸润淋巴细胞的表达水平相对较低，在癌旁肝硬变细胞中表达明显增高（P<0.01）。IDO表达强度与患者的年龄、性别、TNM分期无关（P＞0.05）；与患者大体病理分型有一定的相关性，浸润型IDO表达强度较块状型明显增高（P<0.05）；有血管浸润及癌栓形成患者IDO也呈高表达状态（P<0.05）；IDO的表达还与病理组织学分化情况相关，低分化肿瘤组织IDO的表达强度明显增高（P<0.05）。结论：IDO的表达与肝细胞癌恶性有一定的相关，故IDO拟可以作肝癌预后差的一个参考指标。
目的: 探讨吲哚胺2,3双加氧酶(indoleamine 2,3dioxygenase，IDO)在原发性肝癌细胞、癌旁肝细胞及肿瘤浸润淋巴细胞中的表达及其临床意义。方法：选择经临床确诊的21例原发性肝癌患者的手术切除和（或）肝穿刺所取肝癌组织及癌旁组织标本，通过免疫组织化学染色法检测肝癌及癌旁组织IDO的表达, 并分析其与临床病理特征的关系。结果：IDO在原发性肝癌细胞与肿瘤浸润淋巴细胞的表达水平相对较低，在癌旁肝硬变细胞中表达明显增高（P<0.01）。IDO表达强度与患者的年龄、性别、TNM分期无关（P＞0.05）；与患者大体病理分型有一定的相关性，浸润型IDO表达强度较块状型明显增高（P<0.05）；有血管浸润及癌栓形成患者IDO也呈高表达状态（P<0.05）；IDO的表达还与病理组织学分化情况相关，低分化肿瘤组织IDO的表达强度明显增高（P<0.05）。结论：IDO的表达与肝细胞癌恶性有一定的相关，故IDO拟可以作肝癌预后差的一个参考指标。
2008, 15(6):588-590.
DOI: 10.3872/j.issn.1007-385X.2008.6.018
Abstract:
抗新生血管治疗是实体肿瘤治疗中的有效策略，近年来抗VEGFA和VEGFR2受体治疗出现了耐药现象。Notch信号转导是一种细胞间信号通路，在肿瘤新生血管生成中起重要作用。在Notch通路中，Delta样配体4（Deltalike ligand 4，DLL4）在影响肿瘤新生血管生成方面起着重要的作用，它能抑制新生血管分支形成，促进新生血管的成熟;阻断DLL4能增加无功能新生血管数量，加剧恶性肿瘤缺血缺氧，抑制肿瘤的生长。对DLL4蛋白的深入研究为肿瘤新生血管分子靶向治疗 提供新的策略和新的靶标，DLL4有可能成为继VEGF后肿瘤血管分子靶向治疗的重要靶点。
抗新生血管治疗是实体肿瘤治疗中的有效策略，近年来抗VEGFA和VEGFR2受体治疗出现了耐药现象。Notch信号转导是一种细胞间信号通路，在肿瘤新生血管生成中起重要作用。在Notch通路中，Delta样配体4（Deltalike ligand 4，DLL4）在影响肿瘤新生血管生成方面起着重要的作用，它能抑制新生血管分支形成，促进新生血管的成熟;阻断DLL4能增加无功能新生血管数量，加剧恶性肿瘤缺血缺氧，抑制肿瘤的生长。对DLL4蛋白的深入研究为肿瘤新生血管分子靶向治疗 提供新的策略和新的靶标，DLL4有可能成为继VEGF后肿瘤血管分子靶向治疗的重要靶点。
2008, 15(6):591-593.
DOI: 10.3872/j.issn.1007-385X.2008.6.019
Abstract:
内皮祖细胞(endothelial progenitor cell, EPC)是存在于骨髓和循环外周血的祖细胞亚群，具有在体内外分化为成熟内皮细胞的能力，参与血管发生和血管稳态。恶性肿瘤细胞产生多种细胞因子,使骨髓中的EPC动员至外周血,并募集到肿瘤组织的血管床,参与肿瘤血管生成、肿瘤生长和转移。外周血EPC水平与肿瘤的体积、抗新生血管治疗的反应性和预后等密切相关，因此EPC可作为肿瘤血管新生的生物标记物。EPC还可作为靶向肿瘤的细胞载体负载自杀基因、毒素或药物，为抗肿瘤治疗提供了新的途径。
内皮祖细胞(endothelial progenitor cell, EPC)是存在于骨髓和循环外周血的祖细胞亚群，具有在体内外分化为成熟内皮细胞的能力，参与血管发生和血管稳态。恶性肿瘤细胞产生多种细胞因子,使骨髓中的EPC动员至外周血,并募集到肿瘤组织的血管床,参与肿瘤血管生成、肿瘤生长和转移。外周血EPC水平与肿瘤的体积、抗新生血管治疗的反应性和预后等密切相关，因此EPC可作为肿瘤血管新生的生物标记物。EPC还可作为靶向肿瘤的细胞载体负载自杀基因、毒素或药物，为抗肿瘤治疗提供了新的途径。
2008, 15(6):594-597.
DOI: 10.3872/j.issn.1007-385X.2008.6.020
Abstract:
弥漫性大B细胞淋巴瘤（diffuse large B cell lymphema,DLBCL）在形态学、临床表现及其治疗反应上都表现出异质性，明确DLBCL的预后影响因素有利于实施个体化治疗。根据免疫表型分组，DLBCL分为GCB组和非GCB组，GCB组患者预后明显优于非GCB组，其分组的准确性甚至优于基因检测；相关免疫表型如bcl2、 bcl6对于不同组的预后影响不同，利妥昔单抗的应用减少了细胞来源和相关免疫表型对于预后的不良影响。特定转录因子可以作为预后预测因子，如FOXP1阴性组预后好于阳性组、LMO2高表达的患者具有较高生存率等。抑制PI3K/AKT通路可使淋巴瘤细胞发生凋亡，且pAKT阴性组预后较阳性组好。谷胱甘肽过氧化物酶1（GXP1）低表达组预后较好；而在GXP1低表达组中，ABC转运体MDR1低表达组预后明显好于高表达组。此外，EB病毒感染、骨髓浸润的一致性、肿瘤大小、肿瘤血管形成均同预后有关，都有可能作为预后预测因子。
弥漫性大B细胞淋巴瘤（diffuse large B cell lymphema,DLBCL）在形态学、临床表现及其治疗反应上都表现出异质性，明确DLBCL的预后影响因素有利于实施个体化治疗。根据免疫表型分组，DLBCL分为GCB组和非GCB组，GCB组患者预后明显优于非GCB组，其分组的准确性甚至优于基因检测；相关免疫表型如bcl2、 bcl6对于不同组的预后影响不同，利妥昔单抗的应用减少了细胞来源和相关免疫表型对于预后的不良影响。特定转录因子可以作为预后预测因子，如FOXP1阴性组预后好于阳性组、LMO2高表达的患者具有较高生存率等。抑制PI3K/AKT通路可使淋巴瘤细胞发生凋亡，且pAKT阴性组预后较阳性组好。谷胱甘肽过氧化物酶1（GXP1）低表达组预后较好；而在GXP1低表达组中，ABC转运体MDR1低表达组预后明显好于高表达组。此外，EB病毒感染、骨髓浸润的一致性、肿瘤大小、肿瘤血管形成均同预后有关，都有可能作为预后预测因子。
2008, 15(6):598-600.
DOI: 10.3872/j.issn.1007-385X.2008.6.021
Abstract:
研究表明，硒是一种具有防癌、抗癌作用的微量元素，适量补硒能使癌症的发病率和病死率下降。硒的防癌、抗癌机制是多方面的,主要包括抗氧化损伤、调控基因表达促进癌细胞凋亡、调节细胞周期促进癌细胞凋亡、稳定DNA的结构抵御组织癌变、提高机体免疫功能抵御组织癌变、硒介入某些化学致癌剂的代谢等。但也应指出，硒的生物学效应具有双重性，一方面缺硒会引起异常反应，另一方面高浓度的硒又可引起中毒反应。硒防癌、抗癌机制的阐明将可能为未来肿瘤治疗开辟一条新的途径。
研究表明，硒是一种具有防癌、抗癌作用的微量元素，适量补硒能使癌症的发病率和病死率下降。硒的防癌、抗癌机制是多方面的,主要包括抗氧化损伤、调控基因表达促进癌细胞凋亡、调节细胞周期促进癌细胞凋亡、稳定DNA的结构抵御组织癌变、提高机体免疫功能抵御组织癌变、硒介入某些化学致癌剂的代谢等。但也应指出，硒的生物学效应具有双重性，一方面缺硒会引起异常反应，另一方面高浓度的硒又可引起中毒反应。硒防癌、抗癌机制的阐明将可能为未来肿瘤治疗开辟一条新的途径。
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.