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Volume 21,Issue 5,2014 Table of Contents
2014, 21(5):485-492.
DOI: 10.3872/j.issn.1007-385X.2014.5.001
Abstract:
Glioma is one of the most common primary tumors in the central nervous system. Given the presence and unique immune characteristics of the blood-brain barrier, investigations of the relationship between the immune microenvironment of the brain and glioma development are particularly important. In recent years, significant advances have been made in the research on: (1) changes in the immune microenvironment in physiological and pathological states of the brain, (2) the function of various immune cells and immune molecules in the local microenvironment of glioma, (3) the relationship between local immunosuppression and glioma growth, and (4) the regulation and intervention of the glioma immune microenvironment in light of potential treatment of glioma. The aim of this paper is to review these advances.
Glioma is one of the most common primary tumors in the central nervous system. Given the presence and unique immune characteristics of the blood-brain barrier, investigations of the relationship between the immune microenvironment of the brain and glioma development are particularly important. In recent years, significant advances have been made in the research on: (1) changes in the immune microenvironment in physiological and pathological states of the brain, (2) the function of various immune cells and immune molecules in the local microenvironment of glioma, (3) the relationship between local immunosuppression and glioma growth, and (4) the regulation and intervention of the glioma immune microenvironment in light of potential treatment of glioma. The aim of this paper is to review these advances.
2014, 21(5):493-498.
DOI: 10.3872/j.issn.1007-385X.2014.5.002
Abstract:
Objective: To investigate the effect of expanded CD11b + NKT cells isolated from the injured murine liver following poly-I:C challenge on the proliferation and function of normal murine CD8 +T cells in vitro . Methods: Male C57BL/6 mice were treated with poly-I:C at 20 μg/g. CD11b + and CD11b - NKT cells were isolated from the liver 24 h after poly-I:C- treatment. CD8 +T cells were isolated from normal male OT-I mice and co-cultured with the isolated hepatic CD11b + and CD11b - NKT cells, respectively. The proliferation and cytotoxic ability of CD8 +T cells in the co-culture were both assessed by flow cytometry. The concentration of major immunoregulatory cytokines was determined by ELISA. Results: Poly-I:C treatment significantly increased the proportion of CD11b + NKT cells in the liver. After stimulation, CD11b + hepatic NKT cells produced less IFN-γ, IL-4 and IL-10 than CD11b - hepatic NKT cells. CD11b + hepatic NKT cells significantly inhibited both antigen-specific and nonspecific immune responses of CD8 +T cells, while CD11b - hepatic NKT cells showed no inhibitory effect. CD11b + hepatic NKT cells did not significantly alter the cytotoxic ability of activated CD8 +T cells. Conclusion: Poly-I:C-nduced liver injury is associated with the expansion of CD11b + hepatic NKT cells. While these CD11b + hepatic NKT cells have little effect on the cytotoxic activity of activated CD8 +T cells, they significantly inhibit CD8 +T cell proliferation.
Objective: To investigate the effect of expanded CD11b + NKT cells isolated from the injured murine liver following poly-I:C challenge on the proliferation and function of normal murine CD8 +T cells in vitro . Methods: Male C57BL/6 mice were treated with poly-I:C at 20 μg/g. CD11b + and CD11b - NKT cells were isolated from the liver 24 h after poly-I:C- treatment. CD8 +T cells were isolated from normal male OT-I mice and co-cultured with the isolated hepatic CD11b + and CD11b - NKT cells, respectively. The proliferation and cytotoxic ability of CD8 +T cells in the co-culture were both assessed by flow cytometry. The concentration of major immunoregulatory cytokines was determined by ELISA. Results: Poly-I:C treatment significantly increased the proportion of CD11b + NKT cells in the liver. After stimulation, CD11b + hepatic NKT cells produced less IFN-γ, IL-4 and IL-10 than CD11b - hepatic NKT cells. CD11b + hepatic NKT cells significantly inhibited both antigen-specific and nonspecific immune responses of CD8 +T cells, while CD11b - hepatic NKT cells showed no inhibitory effect. CD11b + hepatic NKT cells did not significantly alter the cytotoxic ability of activated CD8 +T cells. Conclusion: Poly-I:C-nduced liver injury is associated with the expansion of CD11b + hepatic NKT cells. While these CD11b + hepatic NKT cells have little effect on the cytotoxic activity of activated CD8 +T cells, they significantly inhibit CD8 +T cell proliferation.
Huang Zhihu
,
Wei Siyu
,
Nong Chaozan
,
Wei Shiyu
,
Nong Shaoyun
,
Guo Lingxiao
,
Li Yumin
,
He Jinhua
,
Yang Linjie
2014, 21(5):499-504.
DOI: 10.3872/j.issn.1007-385X.2014.5.003
Abstract:
Objective: To study the anti-tumor effect of arsenic trioxide (As 2O 3) in combination with overexpression of miR-203 on leukemic K562 cells. Methods: Eukaryotic expression vector of miR-203 (pmiR-203) was transfected into K562 cells. Transcript levels of miR-203 were quantified by real-time quantitative PCR. K562 cells were incubated with different concentrations of As 2O 3 alone or in combination with pmiR-203. Cell viability was measured by MTT assay. Cell apoptosis was analyzed using flow cytometry. Bcr/abl protein contents were assessed by Western blotting. The ability of miR-203 to bind to Bcr/abl 3′UTR was determined by Bcr/abl 3′UTR and Bcr/abl mut-3′UTR dual luciferase report vector assays. Results: Levels of miR-203 transcript were significantly increased in pmiR-203-transfected K562 cells. Overexpression of miR-203 combined with As 2O 3 treatment increased the sensitivity K562 cells to As 2O 3 by up to 4.86-fold alone while the IC 50 was decreased from 3.4 μmol/L to 0.7 μmol/L as compared with As 2O 3. The number of apoptotic cells was increased in pmiR-203-transfected K562 cells treated with As 2O 3 (\[29.97±3.19\]%) compared with As 2O 3 alone (\[10.77±1.71\]%,P <0.05). Overexpression of miR-203 resulted in decreases in Bcr/abl protein levels and Bcr/abl-3′UTR reporter activity without affecting activity of Bcr/abl-mut-3′UTR reporter in K562 cells. A binding site in the sequence of Bcr/abl-mut-3′UTR was identified. Conclusion: Overexpression of miR-203 may enhance the sensitivity of leukemic K562 cells to As 2O 3, at least partially through down-regulation of Bcr/abl expression.
Objective: To study the anti-tumor effect of arsenic trioxide (As 2O 3) in combination with overexpression of miR-203 on leukemic K562 cells. Methods: Eukaryotic expression vector of miR-203 (pmiR-203) was transfected into K562 cells. Transcript levels of miR-203 were quantified by real-time quantitative PCR. K562 cells were incubated with different concentrations of As 2O 3 alone or in combination with pmiR-203. Cell viability was measured by MTT assay. Cell apoptosis was analyzed using flow cytometry. Bcr/abl protein contents were assessed by Western blotting. The ability of miR-203 to bind to Bcr/abl 3′UTR was determined by Bcr/abl 3′UTR and Bcr/abl mut-3′UTR dual luciferase report vector assays. Results: Levels of miR-203 transcript were significantly increased in pmiR-203-transfected K562 cells. Overexpression of miR-203 combined with As 2O 3 treatment increased the sensitivity K562 cells to As 2O 3 by up to 4.86-fold alone while the IC 50 was decreased from 3.4 μmol/L to 0.7 μmol/L as compared with As 2O 3. The number of apoptotic cells was increased in pmiR-203-transfected K562 cells treated with As 2O 3 (\[29.97±3.19\]%) compared with As 2O 3 alone (\[10.77±1.71\]%,P <0.05). Overexpression of miR-203 resulted in decreases in Bcr/abl protein levels and Bcr/abl-3′UTR reporter activity without affecting activity of Bcr/abl-mut-3′UTR reporter in K562 cells. A binding site in the sequence of Bcr/abl-mut-3′UTR was identified. Conclusion: Overexpression of miR-203 may enhance the sensitivity of leukemic K562 cells to As 2O 3, at least partially through down-regulation of Bcr/abl expression.
2014, 21(5):505-509.
DOI: 10.3872/j.issn.1007-385X.2014.5.004
Abstract:
Objective : To investigate the effects of cytokine-induced killer (CIK) cells co-cultured with dendritic cells (DCs) challenged with hepatoma target peptides on hepatoma cancer cell growth in vitro and in nude mice in vivo . Methods: Peripheral blood mononuclear cells (PBMCs), isolated from healthy volunteer subjects, were induced to differentiate into DCs and CIK cells with different cytokines, respectively. DCs were then stimulated with target peptides or whole cell lysates from human hepatoma HuH-7 cells to develop into DC HuH-7 or DC target which were co-cultured with CIK cells for 6 days to obtain DC HuH-7-CIK or DC target-CIK cells. Concentrations of IL-12 and INF-γ produced by CIK cells, DC-CIK cells, DC HuH-7-CIK or DC target-CIK cells were measured by ELISA. The cytotoxicity of these four types of effector cells against HuH-7 cells respectively was evaluated by CCK-8 assays in vitro and by HuH-7 cell transplantation assays in nude mice in vivo . Results: IL-12 production was significantly increased ( P <0.01) in DC HuH-7-CIK cells (179.33±14.04 pg/ml) and DC target-CIK cells (173.33±6.66 pg/ml) as compared with DCs (59.33±11.84 pg/ml). Similarly, IFN-γ production was significantly increased in CIK cells co-cultured with DC HuH-7 or DC target ( P <0.01) but was not significantly different between DC HuH-7-CIK and DC target-CIK cells ( P >0.05). Compared with untreated CIK cells, DC HuH-7-CIK cells and DC target-CIK cells possessed a similarly higher cytotoxic activity against HuH-7 cells in vitro ( P <0.05) and a similarly stronger inhibitory effect on tumor growth in nude mice bearing hepatoma cancer (\[5469±28.07\] vs \[78.48±1458\]% and \[85.78±15.69\]% respectively, P <0.05). Conclusion: Hepatoma target peptides-sensitized DCs may significantly enhance the cytotoxicity of CIK cells against human hepatoma cells, thus offering a potential strategy to enhance cell-based immunotherapy for liver cancer.
Objective : To investigate the effects of cytokine-induced killer (CIK) cells co-cultured with dendritic cells (DCs) challenged with hepatoma target peptides on hepatoma cancer cell growth in vitro and in nude mice in vivo . Methods: Peripheral blood mononuclear cells (PBMCs), isolated from healthy volunteer subjects, were induced to differentiate into DCs and CIK cells with different cytokines, respectively. DCs were then stimulated with target peptides or whole cell lysates from human hepatoma HuH-7 cells to develop into DC HuH-7 or DC target which were co-cultured with CIK cells for 6 days to obtain DC HuH-7-CIK or DC target-CIK cells. Concentrations of IL-12 and INF-γ produced by CIK cells, DC-CIK cells, DC HuH-7-CIK or DC target-CIK cells were measured by ELISA. The cytotoxicity of these four types of effector cells against HuH-7 cells respectively was evaluated by CCK-8 assays in vitro and by HuH-7 cell transplantation assays in nude mice in vivo . Results: IL-12 production was significantly increased ( P <0.01) in DC HuH-7-CIK cells (179.33±14.04 pg/ml) and DC target-CIK cells (173.33±6.66 pg/ml) as compared with DCs (59.33±11.84 pg/ml). Similarly, IFN-γ production was significantly increased in CIK cells co-cultured with DC HuH-7 or DC target ( P <0.01) but was not significantly different between DC HuH-7-CIK and DC target-CIK cells ( P >0.05). Compared with untreated CIK cells, DC HuH-7-CIK cells and DC target-CIK cells possessed a similarly higher cytotoxic activity against HuH-7 cells in vitro ( P <0.05) and a similarly stronger inhibitory effect on tumor growth in nude mice bearing hepatoma cancer (\[5469±28.07\] vs \[78.48±1458\]% and \[85.78±15.69\]% respectively, P <0.05). Conclusion: Hepatoma target peptides-sensitized DCs may significantly enhance the cytotoxicity of CIK cells against human hepatoma cells, thus offering a potential strategy to enhance cell-based immunotherapy for liver cancer.
2014, 21(5):510-515.
DOI: 10.3872/j.issn.1007-385X.2014.5.005
Abstract:
Objective: To evaluate the effect of microRNA-155 (miR-155) on human lung cancer cell behaviors in vitro . Methods: A plasmid vector (p-miR-155) carrying the pri-miR-155 sequence amplified from genomic RNA of human lung cancer 95D cells by PCR was constructed. Lung cancer 95D cells were transiently transfected with p-miR-155. p-miR-155 mRNA abundance in 95D cells was assessed by real-time PCR before and after transfection. Cell proliferation and migration in control, mock-transfected and transfected 95D cells were assessed by CCK-8 assay wound assay respectively. Results: The abundance of miR-155 mRNA was increased significantly in 95D cells transfected with p-miR-155 than in mock-transfected and control cells (2.045±0.62 vs 0.76±0.62, 1±0.45; P <0.01). The proliferation was markedly inhibited in p-miR-155 transfectants as compared in mock-transfected and control cells (\[4670±689\]% vs \[3.70±1.40\]%, \[1.11±0.75\]%; P <0.01). The number of colonies formed was significantly decreased (\[12±3\] vs \[34±3\], \[35±3\]; P <0.01) and so was migration capability (\[110±5\] vs \[295±5\], \[325±5\]; P ＜0.01) in p-miR-155-transfected cells as compared with mock-transfected and control cells. Conclusion: A eukaryotic expression vector carrying human pri-miR-155 sequence is capable of effectively inhibiting lung cancer cell proliferation and migration, thus having a significant clinical implication.
Objective: To evaluate the effect of microRNA-155 (miR-155) on human lung cancer cell behaviors in vitro . Methods: A plasmid vector (p-miR-155) carrying the pri-miR-155 sequence amplified from genomic RNA of human lung cancer 95D cells by PCR was constructed. Lung cancer 95D cells were transiently transfected with p-miR-155. p-miR-155 mRNA abundance in 95D cells was assessed by real-time PCR before and after transfection. Cell proliferation and migration in control, mock-transfected and transfected 95D cells were assessed by CCK-8 assay wound assay respectively. Results: The abundance of miR-155 mRNA was increased significantly in 95D cells transfected with p-miR-155 than in mock-transfected and control cells (2.045±0.62 vs 0.76±0.62, 1±0.45; P <0.01). The proliferation was markedly inhibited in p-miR-155 transfectants as compared in mock-transfected and control cells (\[4670±689\]% vs \[3.70±1.40\]%, \[1.11±0.75\]%; P <0.01). The number of colonies formed was significantly decreased (\[12±3\] vs \[34±3\], \[35±3\]; P <0.01) and so was migration capability (\[110±5\] vs \[295±5\], \[325±5\]; P ＜0.01) in p-miR-155-transfected cells as compared with mock-transfected and control cells. Conclusion: A eukaryotic expression vector carrying human pri-miR-155 sequence is capable of effectively inhibiting lung cancer cell proliferation and migration, thus having a significant clinical implication.
2014, 21(5):516-520.
DOI: 10.3872/j.issn.1007-385X.2014.5.006
Abstract:
Objective: To investigate the effects of all-transretinoic acid (ATRA) and C-phycocyanin (C-PC), either each alone or two in combination on cervical cancer cell growth and apoptosis in vitro . Methods: Immortalized human cervical cancer HeLa cells were treated with ATRA and C-CP, either each at various concentrations or two in various dose combinations. After treatment for 48 h, cell viability was assessed by MTT assay, apoptosis by TUNEL assay, and changes in Caspase-3 and Bcl-2 protein contents by Western blotting and immunohistochemistry staining, respectively. Results: C-PC and ATRA each alone significantly inhibited the growth of HeLa cells; and IC 50 was 0.158±0.036 mmol/L for C-CP and 192.75±5.79 μg/L for ATRA ( P <0.05). When ATRA was combined with C-PC, the IC 50 was significantly lower than that when ATRA was used alone. Compared with non-treatment control, C-PC and ATRA each alone induced significant HeLa cell apoptosis ( P <0.05), and in the apoptotic effect was more pronounced when C-PC and ATRA were used together ( P <0.01). ATRA and C-PC each alone significantly decreased Bcl-2 protein content ( P <0.01) but significantly increased Caspase-3 protein content ( P <0.01) in Hela cells, and both changes became more significant when ATRT and C-CP were used together ( P <0.01). Conclusion: C-PC combined with ATRA may induce cervical cancer cell apoptosis by down-regulation of Bcl-2 gene and up-regulation of Caspase-3 gene more effectively than each alone.
Objective: To investigate the effects of all-transretinoic acid (ATRA) and C-phycocyanin (C-PC), either each alone or two in combination on cervical cancer cell growth and apoptosis in vitro . Methods: Immortalized human cervical cancer HeLa cells were treated with ATRA and C-CP, either each at various concentrations or two in various dose combinations. After treatment for 48 h, cell viability was assessed by MTT assay, apoptosis by TUNEL assay, and changes in Caspase-3 and Bcl-2 protein contents by Western blotting and immunohistochemistry staining, respectively. Results: C-PC and ATRA each alone significantly inhibited the growth of HeLa cells; and IC 50 was 0.158±0.036 mmol/L for C-CP and 192.75±5.79 μg/L for ATRA ( P <0.05). When ATRA was combined with C-PC, the IC 50 was significantly lower than that when ATRA was used alone. Compared with non-treatment control, C-PC and ATRA each alone induced significant HeLa cell apoptosis ( P <0.05), and in the apoptotic effect was more pronounced when C-PC and ATRA were used together ( P <0.01). ATRA and C-PC each alone significantly decreased Bcl-2 protein content ( P <0.01) but significantly increased Caspase-3 protein content ( P <0.01) in Hela cells, and both changes became more significant when ATRT and C-CP were used together ( P <0.01). Conclusion: C-PC combined with ATRA may induce cervical cancer cell apoptosis by down-regulation of Bcl-2 gene and up-regulation of Caspase-3 gene more effectively than each alone.
2014, 21(5):521-525.
DOI: 10.3872/j.issn.1007-385X.2014.5.007
Abstract:
Objective: To study the differential expression of ovarian cancer stem cell specific markers in the side population (SP) and non-SP of human epithelial ovarian cancer SKOV3 cells. Methods: The SP of SKOV3 cells was identified and sorted by flow cytometry using the blue fluorescent dye Hoechst 33342. The expression of CD133, CD117, CD44, ABCG2 and ALDH2 at the protein level in SP and non-SP cells was assessed by flow cytometry. The expression of ALDH1, ABCG2, NANOG, OCT4, SOX2, CD133 and CD117 at the mRNA level in SP and non-SP cells was assessed by RT-PCR. Results: In SKOV3 cells, SP accounted for (1.56±0.35)%. ALDH1 and ABCG2 proteins were detected in (87.3±5.76)% and (29.48±4.43)% of SP cells respectively, both significantly higher than those in non-SP cells ( P <0.05). CD44 protein was detected in greater than 99% of cells in both subpopulations ( P >0.05). Neither CD133 nor CD117 protein was detected in both subpopulations. The mRNA levels of ALDH1, ABCG2, NANOG, OCT4 and SOX2 in SP cells were increased by 21.03 ( P =0.001), 3.14( P =0.001), 23.94 ( P =0.001), 10.73 ( P =0.009), 21.46 ( P =0.001) folds , respectively, as compared with the levels in Non-SP cells. CD133 and CD117 transcripts were detected in neither sub-population of SKOV 3 cells. Conclusion: There is a SP in human ovarian cancer SKOV3 cells expressing stem cell markers ALDH1 and ABCG2 at the protein level and NANOG, OCT4 , and SOX2 at the mRNA level like ovarian cancer stem cells. This SP of SKOV3 cells may offer a very useful tool for ovarian cancer stem cell research.
Objective: To study the differential expression of ovarian cancer stem cell specific markers in the side population (SP) and non-SP of human epithelial ovarian cancer SKOV3 cells. Methods: The SP of SKOV3 cells was identified and sorted by flow cytometry using the blue fluorescent dye Hoechst 33342. The expression of CD133, CD117, CD44, ABCG2 and ALDH2 at the protein level in SP and non-SP cells was assessed by flow cytometry. The expression of ALDH1, ABCG2, NANOG, OCT4, SOX2, CD133 and CD117 at the mRNA level in SP and non-SP cells was assessed by RT-PCR. Results: In SKOV3 cells, SP accounted for (1.56±0.35)%. ALDH1 and ABCG2 proteins were detected in (87.3±5.76)% and (29.48±4.43)% of SP cells respectively, both significantly higher than those in non-SP cells ( P <0.05). CD44 protein was detected in greater than 99% of cells in both subpopulations ( P >0.05). Neither CD133 nor CD117 protein was detected in both subpopulations. The mRNA levels of ALDH1, ABCG2, NANOG, OCT4 and SOX2 in SP cells were increased by 21.03 ( P =0.001), 3.14( P =0.001), 23.94 ( P =0.001), 10.73 ( P =0.009), 21.46 ( P =0.001) folds , respectively, as compared with the levels in Non-SP cells. CD133 and CD117 transcripts were detected in neither sub-population of SKOV 3 cells. Conclusion: There is a SP in human ovarian cancer SKOV3 cells expressing stem cell markers ALDH1 and ABCG2 at the protein level and NANOG, OCT4 , and SOX2 at the mRNA level like ovarian cancer stem cells. This SP of SKOV3 cells may offer a very useful tool for ovarian cancer stem cell research.
2014, 21(5):526-531.
DOI: 10.3872/j.issn.1007-385X.2014.5.008
Abstract:
Objective: This study aimed to determine the expression of filamin A (FLNA) in nasopharyngeal carcinoma and evaluate the effect of FLNA overexpression on nasopharyngeal cancer cell proliferation and migration in vitro . Methods: Fresh nasopharyngeal cancer (NPC, n =63) and non-cancer nasopharyngeal tissue surrounding but at least 2 cm from the tumor proper ( n =21) specimens were collected from NPC patients who were treat in the Department of Pathology in Tangshan Municipal People’s Hospital between January, 2008 and December, 2008. The presence and quantity of FLNA protein in these specimens was assessed by immunohistochemistry and Western blotting analysis. To evaluate the effect of FLNA on NPC cell proliferation and migration in vitro and elucidate the possible underlying mechanisms, nasopharyngeal cancer CNE2 cells were infected with a lentiviral vector carrying the human FLNA gene (pLenti6-FLNA) or a control lentiviral vector and the cell viability, migration capacity and MMP-9 protein content of the vector-infected cells were assessed by MTT assay, Transwell assay and Western blotting analysis respectively. Result: FLNA protein was detected positive in 35.6% (23/63) of nasopharyngeal carcinoma specimens and 66.7% (14/21) of non-carcinoma specimens ( P <0.05). The relative amount of FLNA protein in nasopharyngeal cancer tissue was significantly lower than in normal nasopharyngeal tissue ( P <0.05). The level of FLNA protein was correlated with T stages, lymph node metastasis, clinic stage and histological grade ( P <0.05). Overexpression of FLNA resulted in significant decreases in proliferation, migration and invasion, and MMP-9 protein content CNE2 cells in vitro ( P <0.05). Conclusion: FLNA may be a negative regulator to nasopharyngeal cancer growth and invasion. This negative effect of FLNA is mediated, at least partially, by an MMP-9-dependent mechanism.
Objective: This study aimed to determine the expression of filamin A (FLNA) in nasopharyngeal carcinoma and evaluate the effect of FLNA overexpression on nasopharyngeal cancer cell proliferation and migration in vitro . Methods: Fresh nasopharyngeal cancer (NPC, n =63) and non-cancer nasopharyngeal tissue surrounding but at least 2 cm from the tumor proper ( n =21) specimens were collected from NPC patients who were treat in the Department of Pathology in Tangshan Municipal People’s Hospital between January, 2008 and December, 2008. The presence and quantity of FLNA protein in these specimens was assessed by immunohistochemistry and Western blotting analysis. To evaluate the effect of FLNA on NPC cell proliferation and migration in vitro and elucidate the possible underlying mechanisms, nasopharyngeal cancer CNE2 cells were infected with a lentiviral vector carrying the human FLNA gene (pLenti6-FLNA) or a control lentiviral vector and the cell viability, migration capacity and MMP-9 protein content of the vector-infected cells were assessed by MTT assay, Transwell assay and Western blotting analysis respectively. Result: FLNA protein was detected positive in 35.6% (23/63) of nasopharyngeal carcinoma specimens and 66.7% (14/21) of non-carcinoma specimens ( P <0.05). The relative amount of FLNA protein in nasopharyngeal cancer tissue was significantly lower than in normal nasopharyngeal tissue ( P <0.05). The level of FLNA protein was correlated with T stages, lymph node metastasis, clinic stage and histological grade ( P <0.05). Overexpression of FLNA resulted in significant decreases in proliferation, migration and invasion, and MMP-9 protein content CNE2 cells in vitro ( P <0.05). Conclusion: FLNA may be a negative regulator to nasopharyngeal cancer growth and invasion. This negative effect of FLNA is mediated, at least partially, by an MMP-9-dependent mechanism.
2014, 21(5):532-536.
DOI: 10.3872/j.issn.1007-385X.2014.5.009
Abstract:
Objective: To determine the effect of silencing nucleostemin ( NS ) gene expression on proliferation and apoptosis of non-small cell lung cancer (NSCLC) A549 cells in vitro . Methods: The recombinant pcDNA4/C-NS-silencer targeting the NS gene was constructed. Human NSCLS A549 cells were transfected with pcDNA4/C-NS-silencer or the control vectorpcDNA4/C. NS mRNA abundance was assessed by real-time RT-PCR, cell proliferation by CCK-8 assay, and cell cycle progress and apoptosis by flow cytometric assay with Hoechst33258 staining in untransfected and transfected A549 cells. Results: Compared with control vector-transfected and untransfected A549 cells, A549 cells transfected with pcDNA4/C-NS-silencer had significantly lower NS mRNA abundance (0.166±0.024 vs 0.497±0.022, 0.505±0032, P <0.01) and a significantly lower proliferation activity (0.518±0.107 vs 0.855±0.102, 0.832±0.158, P <005). NS gene silencing resulted significant increases in the percentage of cells in G1/G0 phase, in chromatin condensation and fragmentation, and in apoptosis (\[34.80±6.77\]% vs \[9.70±1.50\]%, \[8.16±2.01\]% P <0.01), as compared with control vector-transfected and untransfected A549 cells. Conclusion: RNAi-mediated silencing of the NS gene results in human non-small cell lung cancer cell proliferation, G-1 arrest and apoptosis, thereby possessing a therapeutic potential.
Objective: To determine the effect of silencing nucleostemin ( NS ) gene expression on proliferation and apoptosis of non-small cell lung cancer (NSCLC) A549 cells in vitro . Methods: The recombinant pcDNA4/C-NS-silencer targeting the NS gene was constructed. Human NSCLS A549 cells were transfected with pcDNA4/C-NS-silencer or the control vectorpcDNA4/C. NS mRNA abundance was assessed by real-time RT-PCR, cell proliferation by CCK-8 assay, and cell cycle progress and apoptosis by flow cytometric assay with Hoechst33258 staining in untransfected and transfected A549 cells. Results: Compared with control vector-transfected and untransfected A549 cells, A549 cells transfected with pcDNA4/C-NS-silencer had significantly lower NS mRNA abundance (0.166±0.024 vs 0.497±0.022, 0.505±0032, P <0.01) and a significantly lower proliferation activity (0.518±0.107 vs 0.855±0.102, 0.832±0.158, P <005). NS gene silencing resulted significant increases in the percentage of cells in G1/G0 phase, in chromatin condensation and fragmentation, and in apoptosis (\[34.80±6.77\]% vs \[9.70±1.50\]%, \[8.16±2.01\]% P <0.01), as compared with control vector-transfected and untransfected A549 cells. Conclusion: RNAi-mediated silencing of the NS gene results in human non-small cell lung cancer cell proliferation, G-1 arrest and apoptosis, thereby possessing a therapeutic potential.
2014, 21(5):537-542.
DOI: 10.3872/j.issn.1007-385X.2014.5.010
Abstract:
Objective: To evaluate the effects of K562 cells overexpression of IL-15, 4-1BBL and IL-18 combined with IL-2 ex vivo expansion on NK cell activation and cytotoxicity. Methods: K562 cells were engineered to overexpress IL-15, 4-1BBL and IL-18 on the cell membrane. Peripheral blood mononuclear cells (PBMCs) were prepared from venous blood collected from both healthy volunteers and cancer patients. NK cells were purified from PBMCs and expanded ex vivo by co-culture with engineered K562 cells in the presence of IL-2 and/or Hsp70 peptide (TKD) for 21 days. The purity and surface marker expression of the expanded NK cells were analyzed by flow cytometry. The cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) of the expanded NK cells were assessed by a Cell Counting Ki-8-based colorimetric assay. Results: In the cell preparations from healthy subjects, ex vivo expansion for 3 weeks by co-culture with engineered K562 cells in the presence of IL-2 and/or TKD increased the purity of NK cells to (93±3)%, increased the proportion of cells expressing killer activation receptors, NKG2D, CD94, NKp46, NKp30, and NKp44, by 60%, 40%, 20%, 40%, and 63% respectively with no effect on the proportion of cells expressing inhibitory receptors (CD158b, NKB1 and NKAT2), increased the ADCC by 32%, and increased the cytotoxicity against K562, A549, 7721, MCF tumor cells by 19%, 29%, 26% and 28% respectively. In the cell preparations from cancer patients, ex vivo expansion induce the percentage of NK cells increase to (90.0±8.0)% and the cytotoxicity against K562 cells by 17%.Conclusion: Co-culture with engineered K562 cells overexpressing IL-15, 4-1BBL and IL-18 in the presence of IL-2 and/or TKD may offer an effective approach to expand the NK cell population ex vivo and enhance the NK cell cytotoxicity.
Objective: To evaluate the effects of K562 cells overexpression of IL-15, 4-1BBL and IL-18 combined with IL-2 ex vivo expansion on NK cell activation and cytotoxicity. Methods: K562 cells were engineered to overexpress IL-15, 4-1BBL and IL-18 on the cell membrane. Peripheral blood mononuclear cells (PBMCs) were prepared from venous blood collected from both healthy volunteers and cancer patients. NK cells were purified from PBMCs and expanded ex vivo by co-culture with engineered K562 cells in the presence of IL-2 and/or Hsp70 peptide (TKD) for 21 days. The purity and surface marker expression of the expanded NK cells were analyzed by flow cytometry. The cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) of the expanded NK cells were assessed by a Cell Counting Ki-8-based colorimetric assay. Results: In the cell preparations from healthy subjects, ex vivo expansion for 3 weeks by co-culture with engineered K562 cells in the presence of IL-2 and/or TKD increased the purity of NK cells to (93±3)%, increased the proportion of cells expressing killer activation receptors, NKG2D, CD94, NKp46, NKp30, and NKp44, by 60%, 40%, 20%, 40%, and 63% respectively with no effect on the proportion of cells expressing inhibitory receptors (CD158b, NKB1 and NKAT2), increased the ADCC by 32%, and increased the cytotoxicity against K562, A549, 7721, MCF tumor cells by 19%, 29%, 26% and 28% respectively. In the cell preparations from cancer patients, ex vivo expansion induce the percentage of NK cells increase to (90.0±8.0)% and the cytotoxicity against K562 cells by 17%.Conclusion: Co-culture with engineered K562 cells overexpressing IL-15, 4-1BBL and IL-18 in the presence of IL-2 and/or TKD may offer an effective approach to expand the NK cell population ex vivo and enhance the NK cell cytotoxicity.
2014, 21(5):543-547.
DOI: 10.3872/j.issn.1007-385X.2014.5.011
Abstract:
Objective : To investigate the relationship between estrogen receptor 1 gene ( ER-1 ) single nucleotide polymorphism(SNP) and susceptibility to hepatocellular carcinoma (HCC) in liver cancer family pedigrees of Zhuang population in Fusui county of Guangxi. Methods: This was a case-control study involving 85 members of 21 HCC high incidence families and 39 members of 10 normal control families in Fusui County, Guangxi Province. Genotype frequencies and restriction fragment length polymorphisms of the ER-1 gene were determined by PCR. Correlation between the ER-1 gene polymorphisms and HCC risk was evaluated by non-conditional logistic regression analysis. Results: The frequencies of genotypes AA, AG, GG among the normal controls and HCC high incidence families was 74.36 vs 83.53%, 17.95 vs 11.76%, and 7 69 vs 4.71%, respectively. Age and sex distributions did not differ significantly between the two groups ( P >0.05) and genotype distributions conformed to Hardy-Weinberg equilibrium. In the normal control families, the risk of HCC for members with AG and GG was 0.218 (95% CI =0.025-1.917, P =0.170) and 0.509 (95% CI =0.049-5.260, P =0.571) times that of members with AA respectively. In the high HCC incidence families, the risk of HCC for members with AG and GG was respectively 0.298 (95% CI =0.035-2.515, P =0.266) and 0.671 (95% CI =0070-6391, P =0.729) times that of members with AA. Conclusion: There is no correlation between ESR1 gene rs3798757 polymorphism and susceptibility to HCC in families with high incidence of liver cancer in Fusui County of Guangxi Province.
Objective : To investigate the relationship between estrogen receptor 1 gene ( ER-1 ) single nucleotide polymorphism(SNP) and susceptibility to hepatocellular carcinoma (HCC) in liver cancer family pedigrees of Zhuang population in Fusui county of Guangxi. Methods: This was a case-control study involving 85 members of 21 HCC high incidence families and 39 members of 10 normal control families in Fusui County, Guangxi Province. Genotype frequencies and restriction fragment length polymorphisms of the ER-1 gene were determined by PCR. Correlation between the ER-1 gene polymorphisms and HCC risk was evaluated by non-conditional logistic regression analysis. Results: The frequencies of genotypes AA, AG, GG among the normal controls and HCC high incidence families was 74.36 vs 83.53%, 17.95 vs 11.76%, and 7 69 vs 4.71%, respectively. Age and sex distributions did not differ significantly between the two groups ( P >0.05) and genotype distributions conformed to Hardy-Weinberg equilibrium. In the normal control families, the risk of HCC for members with AG and GG was 0.218 (95% CI =0.025-1.917, P =0.170) and 0.509 (95% CI =0.049-5.260, P =0.571) times that of members with AA respectively. In the high HCC incidence families, the risk of HCC for members with AG and GG was respectively 0.298 (95% CI =0.035-2.515, P =0.266) and 0.671 (95% CI =0070-6391, P =0.729) times that of members with AA. Conclusion: There is no correlation between ESR1 gene rs3798757 polymorphism and susceptibility to HCC in families with high incidence of liver cancer in Fusui County of Guangxi Province.
2014, 21(5):554-558.
DOI: 10.3872/j.issn.1007-385X.2014.5.013
Abstract:
Objective : To investigate the possible involvement of Golgi phosphoprotein 3 (GOLPH3) in the development and progression of non-small cell lung cancer (NSCLC) by examining the expression of GOLPH3 in cancerous versus noncancerous lung tissue. Methods: Cancerous ( n =116) and para-carcinoma ( n =43, at least 5 cm from the tumor proper) lung tissue specimens were collected from 116 patients with NSCLC who were surgically treated between February, 2004 and February, 2006 in Qilu Hospital of Shandong University． GOLPH3 protein in these specimens was assessed by immunohistochemistry. Possible correlations of the intensity of the immunoreactive GOLPH3 protein signal were various clinical and pathologic variables were analyzed by Cox regression analysis. Results: GOLPH3 protein was detected in 57 8% (67/116) of the cancerous specimens and in 28.0% (12/43) of the non-cancerous specimens ( P ＜0.01). The intensity of the immunoreactive GOLPH3 protein signal was not significantly correlated with any of the clinical and pathological variables assessed ( P >0.05). In addition, univariate and multivariate analysis demonstrated that BRF2 protein overexpression were significantly associated with tumor relapse and prognosis. Conclusion: GOLPH3 is present in a robustly higher rate in cancerous tissue than in non-cancerous lung tissue of patients with NSCLS. The diagnostic and prognostic value of GOLPH3 for NSCLS warrants further investigations.
Objective : To investigate the possible involvement of Golgi phosphoprotein 3 (GOLPH3) in the development and progression of non-small cell lung cancer (NSCLC) by examining the expression of GOLPH3 in cancerous versus noncancerous lung tissue. Methods: Cancerous ( n =116) and para-carcinoma ( n =43, at least 5 cm from the tumor proper) lung tissue specimens were collected from 116 patients with NSCLC who were surgically treated between February, 2004 and February, 2006 in Qilu Hospital of Shandong University． GOLPH3 protein in these specimens was assessed by immunohistochemistry. Possible correlations of the intensity of the immunoreactive GOLPH3 protein signal were various clinical and pathologic variables were analyzed by Cox regression analysis. Results: GOLPH3 protein was detected in 57 8% (67/116) of the cancerous specimens and in 28.0% (12/43) of the non-cancerous specimens ( P ＜0.01). The intensity of the immunoreactive GOLPH3 protein signal was not significantly correlated with any of the clinical and pathological variables assessed ( P >0.05). In addition, univariate and multivariate analysis demonstrated that BRF2 protein overexpression were significantly associated with tumor relapse and prognosis. Conclusion: GOLPH3 is present in a robustly higher rate in cancerous tissue than in non-cancerous lung tissue of patients with NSCLS. The diagnostic and prognostic value of GOLPH3 for NSCLS warrants further investigations.
Jia Yunlong
,
Wang Yu
,
Wang Tingting
,
Duan Yuqing
,
Wang Miao
,
Wang Hongyan
,
Meng Xianli
,
Liu Lihua
2014, 21(5):559-564.
DOI: 10.3872/j.issn.1007-385X.2014.5.014
Abstract:
Objective : To investigate the expression of c-Myc and Bin1 in association with clinical characteristic in patients with esophageal squamous cell cancer (ESCC). Methods: Carcinoma and para-carcinoma tissue specimens were collected from 54 patients with esophageal squamous cell cancer who underwent esophagectomy in Fourth Hospital of Hebei Medical University between April, 2013 and March, 2014. Bin1 and c-Myc mRNA and protein levels were determined by RT-PCR and immunohistochemistry respectively. The associations between c-Myc and Bin1 protein levels and clinical features were analyzed. Results: Compared with para-carcinoma tissue specimens, carcinoma tissue specimens had significantly higher c-Myc mRNA abundance (0.34±0.29 vs 0.17±0.16, P <0.001) and a significantly higher percentage of c-Myc protein-positive tests (55.56% vs 33.33%, P =0.033). In contrast, Bin1 mRNA abundance was significantly decreased ( P <0.001) in carcinoma tissue specimens (0.25±0.19) as compared with para-carcinoma tissue specimens (0.33±0.20) and the percentage of Bin1 protein-positive tests was significantly lower in carcinoma specimens than in para-carcinoma specimens 57.41% vs (84.48%, P =0.007). The abundance of c-Myc mRNA was negatively correlated with Bin1 mRNA abundance ( r =-0.790, P <0.001) and c-Myc protein level was negatively correlated with Bin1 protein level ( P =0.019). Both c-Myc and Bin1 proteins were associated with TNM stage, tumor invasion depth, tumor differentiation and lymph node metastasis. Conclusion: In ESCC tissue, the expression of c-Myc is up-regualted while the expression of Bin1 is down-regulated. Bin1 is negatively correlated with c-Myc at both mRNA and protein levels. The aberrations in both c-Myc and Bin1 is closely associated with tumor invasion and lymph node metastasis of ESCC.
Objective : To investigate the expression of c-Myc and Bin1 in association with clinical characteristic in patients with esophageal squamous cell cancer (ESCC). Methods: Carcinoma and para-carcinoma tissue specimens were collected from 54 patients with esophageal squamous cell cancer who underwent esophagectomy in Fourth Hospital of Hebei Medical University between April, 2013 and March, 2014. Bin1 and c-Myc mRNA and protein levels were determined by RT-PCR and immunohistochemistry respectively. The associations between c-Myc and Bin1 protein levels and clinical features were analyzed. Results: Compared with para-carcinoma tissue specimens, carcinoma tissue specimens had significantly higher c-Myc mRNA abundance (0.34±0.29 vs 0.17±0.16, P <0.001) and a significantly higher percentage of c-Myc protein-positive tests (55.56% vs 33.33%, P =0.033). In contrast, Bin1 mRNA abundance was significantly decreased ( P <0.001) in carcinoma tissue specimens (0.25±0.19) as compared with para-carcinoma tissue specimens (0.33±0.20) and the percentage of Bin1 protein-positive tests was significantly lower in carcinoma specimens than in para-carcinoma specimens 57.41% vs (84.48%, P =0.007). The abundance of c-Myc mRNA was negatively correlated with Bin1 mRNA abundance ( r =-0.790, P <0.001) and c-Myc protein level was negatively correlated with Bin1 protein level ( P =0.019). Both c-Myc and Bin1 proteins were associated with TNM stage, tumor invasion depth, tumor differentiation and lymph node metastasis. Conclusion: In ESCC tissue, the expression of c-Myc is up-regualted while the expression of Bin1 is down-regulated. Bin1 is negatively correlated with c-Myc at both mRNA and protein levels. The aberrations in both c-Myc and Bin1 is closely associated with tumor invasion and lymph node metastasis of ESCC.
2014, 21(5):565-569.
DOI: 10.3872/j.issn.1007-385X.2014.5.015
Abstract:
Objective : To determine the expression profile of lysine-rich CEACAM1 coisolated (LYRIC) in hepatocellular carcinoma (HCC) and matched adjacent normal liver tissue. Methods: Matched biopsy specimens of the tumor proper and the corresponding adjacent normal mucosa were collected from 87 HCC patients who underwent surgical resection in China Medical University-Affiliated Shengjing Hospital and General Hospital of Shenyang Military Region. LYRIC mRNA and protein in these specimens were assessed by realtime PCR and immunohistochemical staining. The potential significance of LYRIC mRNA and protein level measurements in the prognosis of HCC were evaluated by multivariate analysis. Results: In 56 (64.7%) of the 87 matched specimens, LYRIC mRNA was significantly higher in HCC than in the adjacent mucosa. LYRIC protein was detected in both HCC and adjacent normal tissue in all 87 cases, but the level was significantly higher ( P <0.001) in HCC (2.16±0.87) than in adjacent normal tissue (1.63±0.88). Enhanced LYRIC expression was associated with poor prognosis (Log-rank10.236， P =0.001). Metastasis (HR=2.44), elevated LYRIC expression (HR=2.19) in HCC and tumor stage(HR=2.01) were independent risk factors of overall survival. In contrast, overall survival was not associated with tumor diameters and virus infection. Conclusion: LYRIC expression is significantly up-regulated in HCC as compared with normal liver tissue. Both LYRIC mRNA and protein levels in HCC are closely associated with the molecular subtype and staging of the tumor, prognosis, suggesting that LYRIC may serve as a potential prognostic factor of liver cancer.
Objective : To determine the expression profile of lysine-rich CEACAM1 coisolated (LYRIC) in hepatocellular carcinoma (HCC) and matched adjacent normal liver tissue. Methods: Matched biopsy specimens of the tumor proper and the corresponding adjacent normal mucosa were collected from 87 HCC patients who underwent surgical resection in China Medical University-Affiliated Shengjing Hospital and General Hospital of Shenyang Military Region. LYRIC mRNA and protein in these specimens were assessed by realtime PCR and immunohistochemical staining. The potential significance of LYRIC mRNA and protein level measurements in the prognosis of HCC were evaluated by multivariate analysis. Results: In 56 (64.7%) of the 87 matched specimens, LYRIC mRNA was significantly higher in HCC than in the adjacent mucosa. LYRIC protein was detected in both HCC and adjacent normal tissue in all 87 cases, but the level was significantly higher ( P <0.001) in HCC (2.16±0.87) than in adjacent normal tissue (1.63±0.88). Enhanced LYRIC expression was associated with poor prognosis (Log-rank10.236， P =0.001). Metastasis (HR=2.44), elevated LYRIC expression (HR=2.19) in HCC and tumor stage(HR=2.01) were independent risk factors of overall survival. In contrast, overall survival was not associated with tumor diameters and virus infection. Conclusion: LYRIC expression is significantly up-regulated in HCC as compared with normal liver tissue. Both LYRIC mRNA and protein levels in HCC are closely associated with the molecular subtype and staging of the tumor, prognosis, suggesting that LYRIC may serve as a potential prognostic factor of liver cancer.
2014, 21(5):570-573.
DOI: 10.3872/j.issn.1007-385X.2014.5.016
Abstract:
Objective : To evaluate the efficacy and safety of dendritic cell (DC)-induced cytotoxic T lymphocytes (CTLs) in the treatment of patients with HPV-positive cervical cancer (CC). Method: Peripheral blood mononuclear cells (PBMCs) were collected from 8 HPV-infection CC patients who were admitted to our institute between November, 2010 and May, 2012. CTLs were generated by infecting the isolated PBMCs with adenoviral vector carrying HPV16/18 E6/E7 together with sequential stimulations with GM-CSF IL-4, TNF-α, IL-2 and IL-7 for once two weeks as an infusion. Patients were each treated with their own adenovirus-infected DC-CTLs through intravenous infusion twice a week for 3 weeks. Follow-up was performed for 6-27 months, during which patients’ response and adverse events were assessed. Result: Out of the 6 patients with partial remission/stable disease prior to treatment, 5 became HPV-negative. Adenovirus-infected DC-CTLs resulted in complete remission in 1 patient with partial remission prior to treatment but showed little effect in the 2 patients with a progressive disease prior to treatment. No significant adverse events were observed in any of the patients. Conclusion: Autologous transfusion of CTLs induced by DCs overexpressing HPV16/18 E6/E7 may offer a novel efficient and safe treatment for HPV-positive CC patients under a partial remission/stable disease state.
Objective : To evaluate the efficacy and safety of dendritic cell (DC)-induced cytotoxic T lymphocytes (CTLs) in the treatment of patients with HPV-positive cervical cancer (CC). Method: Peripheral blood mononuclear cells (PBMCs) were collected from 8 HPV-infection CC patients who were admitted to our institute between November, 2010 and May, 2012. CTLs were generated by infecting the isolated PBMCs with adenoviral vector carrying HPV16/18 E6/E7 together with sequential stimulations with GM-CSF IL-4, TNF-α, IL-2 and IL-7 for once two weeks as an infusion. Patients were each treated with their own adenovirus-infected DC-CTLs through intravenous infusion twice a week for 3 weeks. Follow-up was performed for 6-27 months, during which patients’ response and adverse events were assessed. Result: Out of the 6 patients with partial remission/stable disease prior to treatment, 5 became HPV-negative. Adenovirus-infected DC-CTLs resulted in complete remission in 1 patient with partial remission prior to treatment but showed little effect in the 2 patients with a progressive disease prior to treatment. No significant adverse events were observed in any of the patients. Conclusion: Autologous transfusion of CTLs induced by DCs overexpressing HPV16/18 E6/E7 may offer a novel efficient and safe treatment for HPV-positive CC patients under a partial remission/stable disease state.
2014, 21(5):574-577.
DOI: 10.3872/j.issn.1007-385X.2014.5.017
Abstract:
Objective : To establish a mouse model of intrahepatic recurrence and metastasis of circulating hepatocellular carcinoma cells transplanted via rapid and vast tail vein injection. Methods: C57BL/6J mice were randomly divided into a control group ( n =20) and an experimental group ( n =20). Animals in the control group were given 2×10 6 human hepatoma Hepa1-6 cells/0.2 ml through conventional speed (30 s) tail vein injection and those in the experimental group were given 2×10 6 Hepa1-6 cells/0.2 ml through rapid (5 s) and vast tail vein injection. Four weeks later, animals were sacrificed, liver, lung, kidney and spleen were collected for H-E staining, and tumor formation was evaluated grossly and microscopically. Results: In the control group, tumor nodules were seen in 19 (95%) mice and the metastatic lesions occurred only in the lung but not in liver, spleen and kidneys. In the experimental group, tumor nodules were present in the lungs in 18 (94.7%) mice and in the liver in 19 (100%) mice while no metastatic tumors were found in the spleen and kidneys. Conclusion: Rapid and vast tail vein injection of hepatoma carcinoma cells in to nude mice may mimic the process of hematogenous dissemination of the residual circulating hepatocellular carcinoma cells after curative resection, thus offering a potentially useful, simple, efficient and safe animal model to study the metastasis of the circulating residential hepatoma carcinoma cells after resection.
Objective : To establish a mouse model of intrahepatic recurrence and metastasis of circulating hepatocellular carcinoma cells transplanted via rapid and vast tail vein injection. Methods: C57BL/6J mice were randomly divided into a control group ( n =20) and an experimental group ( n =20). Animals in the control group were given 2×10 6 human hepatoma Hepa1-6 cells/0.2 ml through conventional speed (30 s) tail vein injection and those in the experimental group were given 2×10 6 Hepa1-6 cells/0.2 ml through rapid (5 s) and vast tail vein injection. Four weeks later, animals were sacrificed, liver, lung, kidney and spleen were collected for H-E staining, and tumor formation was evaluated grossly and microscopically. Results: In the control group, tumor nodules were seen in 19 (95%) mice and the metastatic lesions occurred only in the lung but not in liver, spleen and kidneys. In the experimental group, tumor nodules were present in the lungs in 18 (94.7%) mice and in the liver in 19 (100%) mice while no metastatic tumors were found in the spleen and kidneys. Conclusion: Rapid and vast tail vein injection of hepatoma carcinoma cells in to nude mice may mimic the process of hematogenous dissemination of the residual circulating hepatocellular carcinoma cells after curative resection, thus offering a potentially useful, simple, efficient and safe animal model to study the metastasis of the circulating residential hepatoma carcinoma cells after resection.
2014, 21(5):578-563.
DOI: 10.3872/j.issn.1007-385X.2014.5.018
Abstract:
死亡受体5属于肿瘤坏死因子受体超家族，在多种肿瘤细胞中均有表达，它通过与肿瘤细胞表面相应的配体结合而迅速诱导细胞凋亡。死亡受体5在正常细胞很少或几乎不表达，因此其对正常细胞没有作用。近年来有学者认为可以将死亡受体5作为一个肿瘤生物治疗的新靶点，为研究出更有效的抗肿瘤药物提供帮助。目前重组人TRAIL、抗DR5单克隆抗体等相关药物已进入临床试验阶段，而小分子DR5活化剂的发现，更进一步拓展了人们对于DR5在肿瘤生物治疗中的认识。因此，对死亡受体5研究的进一步深入，可能为未来肿瘤生物治疗提供新的策略。本文就DR5的作用机制及其在肿瘤治疗中的研究及应用做一综述。
死亡受体5属于肿瘤坏死因子受体超家族，在多种肿瘤细胞中均有表达，它通过与肿瘤细胞表面相应的配体结合而迅速诱导细胞凋亡。死亡受体5在正常细胞很少或几乎不表达，因此其对正常细胞没有作用。近年来有学者认为可以将死亡受体5作为一个肿瘤生物治疗的新靶点，为研究出更有效的抗肿瘤药物提供帮助。目前重组人TRAIL、抗DR5单克隆抗体等相关药物已进入临床试验阶段，而小分子DR5活化剂的发现，更进一步拓展了人们对于DR5在肿瘤生物治疗中的认识。因此，对死亡受体5研究的进一步深入，可能为未来肿瘤生物治疗提供新的策略。本文就DR5的作用机制及其在肿瘤治疗中的研究及应用做一综述。
2014, 21(5):584-588.
DOI: 10.3872/j.issn.1007-385X.2014.5.019
Abstract:
在我国，结直肠癌是最常见的恶性肿瘤之一，且是癌症相关死亡因素的第三大主要原因。近年来，结直肠癌的发病率和病死率呈逐年上升的趋势。在结直肠癌的发生、发展过程中，PI3K/Akt/mTOR信号通路的异常活化起到十分重要的作用。其中，Akt作为该通路的中间信号分子,在蛋白质合成、细胞代谢、细胞增殖与分化、抗凋亡及血管新生等事件中均起到十分关键的作用。本文就Akt信号分子及其在结直肠癌发生发展中的作用以及对结直肠癌预后和生存的影响进行综述。
在我国，结直肠癌是最常见的恶性肿瘤之一，且是癌症相关死亡因素的第三大主要原因。近年来，结直肠癌的发病率和病死率呈逐年上升的趋势。在结直肠癌的发生、发展过程中，PI3K/Akt/mTOR信号通路的异常活化起到十分重要的作用。其中，Akt作为该通路的中间信号分子,在蛋白质合成、细胞代谢、细胞增殖与分化、抗凋亡及血管新生等事件中均起到十分关键的作用。本文就Akt信号分子及其在结直肠癌发生发展中的作用以及对结直肠癌预后和生存的影响进行综述。
2014, 21(5):589-594.
DOI: 10.3872/j.issn.1007-385X.2014.5.020
Abstract:
结直肠癌发病率位居全球恶性肿瘤第三位，早期诊断和治疗可以大大降低结直肠癌的病死率。由于目前临床较普遍使用的粪便潜血和结肠镜检查患者依从性低，所以外周血Septin9(SEPT9)基因甲基化检测为结直肠癌早期诊断和筛查提供了一个较为有前景的选项。截至目前有数项临床试验证明此检测对结直肠癌的灵敏度和特异性较高，与癌分期有一定相关性，其检测效果优于化学法粪便潜血检测及糖蛋白类肿瘤标志物，与免疫学粪便潜血检测和粪便DNA检测相比，也具备一定优势。此检测对结直肠癌前病变如腺瘤的检测效果仍有待观察，但其有可能成为结直肠癌治疗效果、复发和转移的监测指标，并对肿瘤的分期和分型有辅助作用。本文将简要介绍此检测的原理，重点回顾以此方法检测结直肠癌的临床研究，并与其他方法进行比较，最后简述其未来可能的应用方向。
结直肠癌发病率位居全球恶性肿瘤第三位，早期诊断和治疗可以大大降低结直肠癌的病死率。由于目前临床较普遍使用的粪便潜血和结肠镜检查患者依从性低，所以外周血Septin9(SEPT9)基因甲基化检测为结直肠癌早期诊断和筛查提供了一个较为有前景的选项。截至目前有数项临床试验证明此检测对结直肠癌的灵敏度和特异性较高，与癌分期有一定相关性，其检测效果优于化学法粪便潜血检测及糖蛋白类肿瘤标志物，与免疫学粪便潜血检测和粪便DNA检测相比，也具备一定优势。此检测对结直肠癌前病变如腺瘤的检测效果仍有待观察，但其有可能成为结直肠癌治疗效果、复发和转移的监测指标，并对肿瘤的分期和分型有辅助作用。本文将简要介绍此检测的原理，重点回顾以此方法检测结直肠癌的临床研究，并与其他方法进行比较，最后简述其未来可能的应用方向。
2014, 21(5):595-599.
DOI: 10.3872/j.issn.1007-385X.2014.5.021
Abstract:
结直肠癌因早期诊断率低，大多数患者在发现时已处于中晚期，治疗难度大，预后极差，化疗已成为转移性或局部晚期结直肠癌主要的治疗手段，但是疗效不甚理想。西妥昔单抗（cetuximab，C225）作为一种重要的靶向药物，为晚期结直肠癌患者的生物治疗打开了一扇新的大门。西妥昔单抗在细胞水平、基因水平等多个层面上发挥着抗肿瘤作用，其作用靶点表皮生长因子受体(epithelial growth factor receptor, EGFR)在多种癌组织中高表达，尤其是结直肠癌中。根据FOLFIR I (伊立替康+亚叶酸钙+氟尿嘧啶 )、FOLFOX (奥沙利铂+亚叶酸钙+氟尿嘧啶 )、CapeOx（奥沙利铂+卡培他滨）等联合化疗药物临床试验结果，上述方案都是晚期结直肠癌患者可供选择的，每个方案各有利弊，有效率及适用指征略有不同。单药西妥昔单抗可用于耐受不了高强度化疗或已进行常规化疗后需要维持治疗的患者。目前有很多研究致力于探索具有临床应用前景的疗效预测指标如皮疹、EGFR表达、基因拷贝数（gene copy number，GCN)及基因多态性标志物等，其中大鼠肉瘤病毒癌基因同源物（kirsten rat sarcoma viral oncogene homolog， KRAS ）基因突变研究最为广泛和深入，多项临床试验证实KRAS基因检测可以预测西妥昔单抗的疗效并在临床上已开始应用。通过基因检测等手段找到敏感而特异的西妥昔单抗预后标志物是实现个体化治疗结直肠癌的一大趋势。
结直肠癌因早期诊断率低，大多数患者在发现时已处于中晚期，治疗难度大，预后极差，化疗已成为转移性或局部晚期结直肠癌主要的治疗手段，但是疗效不甚理想。西妥昔单抗（cetuximab，C225）作为一种重要的靶向药物，为晚期结直肠癌患者的生物治疗打开了一扇新的大门。西妥昔单抗在细胞水平、基因水平等多个层面上发挥着抗肿瘤作用，其作用靶点表皮生长因子受体(epithelial growth factor receptor, EGFR)在多种癌组织中高表达，尤其是结直肠癌中。根据FOLFIR I (伊立替康+亚叶酸钙+氟尿嘧啶 )、FOLFOX (奥沙利铂+亚叶酸钙+氟尿嘧啶 )、CapeOx（奥沙利铂+卡培他滨）等联合化疗药物临床试验结果，上述方案都是晚期结直肠癌患者可供选择的，每个方案各有利弊，有效率及适用指征略有不同。单药西妥昔单抗可用于耐受不了高强度化疗或已进行常规化疗后需要维持治疗的患者。目前有很多研究致力于探索具有临床应用前景的疗效预测指标如皮疹、EGFR表达、基因拷贝数（gene copy number，GCN)及基因多态性标志物等，其中大鼠肉瘤病毒癌基因同源物（kirsten rat sarcoma viral oncogene homolog， KRAS ）基因突变研究最为广泛和深入，多项临床试验证实KRAS基因检测可以预测西妥昔单抗的疗效并在临床上已开始应用。通过基因检测等手段找到敏感而特异的西妥昔单抗预后标志物是实现个体化治疗结直肠癌的一大趋势。
联系方式
- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.