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Volume 19,Issue 2,2012 Table of Contents
2012, 19(2):111-115.
DOI: 10.3872/j.issn.1007-385X.2012.2.001
Abstract:
Immune response and inflammation composes two cores of tumor microenvironment. However the relationship between them remains elusive. Studies corroborate the idea that the mission of myeloid derived suppressor cells (MDSCs) and regulatory T cells (Tregs) that migrate to tumor sites is to suppress inflammation rather than mediate tumor immune evasion. Mast cells, however, mediate the crosstalk of immune response and inflammation by regulating MDSCs and Tregs. In addition, Toll-like signaling, as the basic signaling pathway in tumor microenvironment, may directly regulate immune response and inflammation, maintaining inflammatory homeostasis through microparticle pathways. Despite the very complex relationship between immune response and inflammation, we suggest that antitumor immune response and inflammation are negatively correlated and time dependent. At the early stage of tumor, antitumor immune responses are dominant. Later, the bias favors inflammation in tumor microenvironment.
Immune response and inflammation composes two cores of tumor microenvironment. However the relationship between them remains elusive. Studies corroborate the idea that the mission of myeloid derived suppressor cells (MDSCs) and regulatory T cells (Tregs) that migrate to tumor sites is to suppress inflammation rather than mediate tumor immune evasion. Mast cells, however, mediate the crosstalk of immune response and inflammation by regulating MDSCs and Tregs. In addition, Toll-like signaling, as the basic signaling pathway in tumor microenvironment, may directly regulate immune response and inflammation, maintaining inflammatory homeostasis through microparticle pathways. Despite the very complex relationship between immune response and inflammation, we suggest that antitumor immune response and inflammation are negatively correlated and time dependent. At the early stage of tumor, antitumor immune responses are dominant. Later, the bias favors inflammation in tumor microenvironment.
2012, 19(2):116-121.
DOI: 10.3872/j.issn.1007-385X.2012.2.002
Abstract:
In the research area of clinical cancer therapy, the adoptive immunotherapy has been a hot topic. There are natural anticancer CD8+ memory T cells existing in the patient body, which can actively recognize, target and kill cancer cells. These T cells respond rapidly to only a small number of cancer cells re-circulating in the body and act as a long-term cancer surveillance force there. Bone marrow is the major place where the anticancer CD8+ memory T cells reside. If isolated, primed and expanded properly, bone marrow-derived anticancer CD8+ memory T cells can exhibit a giant power in the adoptive immunotherapy. In order to give clinical researchers a clear picture of the biological characteristics and therapeutic values of anticancer CD8+ memory T cells as well as to help them deal with the problems encountered in the clinical application, we reviewed recent research progressions on the application of anticancer CD8+ memory T cells in the cancer immunotherapy
In the research area of clinical cancer therapy, the adoptive immunotherapy has been a hot topic. There are natural anticancer CD8+ memory T cells existing in the patient body, which can actively recognize, target and kill cancer cells. These T cells respond rapidly to only a small number of cancer cells re-circulating in the body and act as a long-term cancer surveillance force there. Bone marrow is the major place where the anticancer CD8+ memory T cells reside. If isolated, primed and expanded properly, bone marrow-derived anticancer CD8+ memory T cells can exhibit a giant power in the adoptive immunotherapy. In order to give clinical researchers a clear picture of the biological characteristics and therapeutic values of anticancer CD8+ memory T cells as well as to help them deal with the problems encountered in the clinical application, we reviewed recent research progressions on the application of anticancer CD8+ memory T cells in the cancer immunotherapy
2012, 19(2):122-127.
DOI: 10.3872/j.issn.1007-385X.2012.2.003
Abstract:
Objective:To screen the monoclonal antibody (McAb) recognizing liver cancer stem cells and study its anticancer effects in vitro so as to provide antibody drug candidates for liver cancer stem cell-targeted therapy. Methods: Serum-free suspension culture and PKH26 staining was used to determine whether there were liver cancer stem cells in human hepatoma cell line MHCC97H. Expressions of 7 cancer stem cell biomarkers in MHCC97H cells and MHCC97H sphere cells, and co-expressions of antigens recognized by CD90 and different McAbs (3G7, 4F11, 11C9, 15B7, 15D2) in MHCC97H cells were examined by flow cytometry assay. The effects of McAb 4F11 on self-renewal and proliferation of MHCC97H cells and MHCC97H sphere cells were identified by serum-free suspension culture and CCK-8 assay. The effects of McAb 4F11 on in vitro invasion and migration of MHCC97 cells was examined by Transwell assay. Results: PKH26 staining results demonstrated that each MHCC97H sphere cell was proliferated and differentiated from one single liver cancer stem cell. The positive rate of CD90 in MHCC97H sphere cells were significantly higher than that in parent MHCC97H cells（\[18.0?7.5\]% vs \[2.3?1.0\]%，P<0.05). McAbs 3G7, 4F11, 11C9, 15B7 and 15D2 all CD90+MHCC97H cells in MHCC97H cells with the recognition rate of McAb 4F11 in CD90+MHCC97H cells was (47.2?44)%. The inhibitory rate of McAb 4F11 on MHCC97H sphere cells was significantly higher than that on MHCC97H cells（\[29.4?3.8\]% vs \[12.0?2.2\]%，P<0.05), and McAb 4F11 extremely suppressed the sphere formation ability of MHCC97H cells and inhibitory rate was (58.0?20.8)%. McAb 4F11 also significantly inhibited invasion and migration of MHCC97H cells in vitro (inhibitory rate: \[48.6?5.1\]% and \[47.6?3.6\]%). Conclusion: Hybridoma McAb 4F11 can specifically recognize CD90+ liver cancer stem cells, and inhibit invasion and migration of liver cancer cells. McAb 4F11 could be a antibody drug candidate for liver cancer stem cell targeted therapy.
Objective:To screen the monoclonal antibody (McAb) recognizing liver cancer stem cells and study its anticancer effects in vitro so as to provide antibody drug candidates for liver cancer stem cell-targeted therapy. Methods: Serum-free suspension culture and PKH26 staining was used to determine whether there were liver cancer stem cells in human hepatoma cell line MHCC97H. Expressions of 7 cancer stem cell biomarkers in MHCC97H cells and MHCC97H sphere cells, and co-expressions of antigens recognized by CD90 and different McAbs (3G7, 4F11, 11C9, 15B7, 15D2) in MHCC97H cells were examined by flow cytometry assay. The effects of McAb 4F11 on self-renewal and proliferation of MHCC97H cells and MHCC97H sphere cells were identified by serum-free suspension culture and CCK-8 assay. The effects of McAb 4F11 on in vitro invasion and migration of MHCC97 cells was examined by Transwell assay. Results: PKH26 staining results demonstrated that each MHCC97H sphere cell was proliferated and differentiated from one single liver cancer stem cell. The positive rate of CD90 in MHCC97H sphere cells were significantly higher than that in parent MHCC97H cells（\[18.0?7.5\]% vs \[2.3?1.0\]%，P<0.05). McAbs 3G7, 4F11, 11C9, 15B7 and 15D2 all CD90+MHCC97H cells in MHCC97H cells with the recognition rate of McAb 4F11 in CD90+MHCC97H cells was (47.2?44)%. The inhibitory rate of McAb 4F11 on MHCC97H sphere cells was significantly higher than that on MHCC97H cells（\[29.4?3.8\]% vs \[12.0?2.2\]%，P<0.05), and McAb 4F11 extremely suppressed the sphere formation ability of MHCC97H cells and inhibitory rate was (58.0?20.8)%. McAb 4F11 also significantly inhibited invasion and migration of MHCC97H cells in vitro (inhibitory rate: \[48.6?5.1\]% and \[47.6?3.6\]%). Conclusion: Hybridoma McAb 4F11 can specifically recognize CD90+ liver cancer stem cells, and inhibit invasion and migration of liver cancer cells. McAb 4F11 could be a antibody drug candidate for liver cancer stem cell targeted therapy.
2012, 19(2):128-132.
DOI: 10.3872/j.issn.1007-385X.2012.2.004
Abstract:
Objective:To isolate and culture human brain glioma stem-like cells (GSLCs), and to determine the invasiveness of GSLC in vitro. Methods: Glioma cell spheres were serum free cultured from 8 surgical specimens of glioma inpatients from October 2008 to January 2009 in the Department of Neurosurgery, First Hospital of China Medical University. CD133 expression was identified by immunocytochemistry assay, and the expressions of GFAP and TU-20 in differentiated glioma cell spheres were detected under an immunofluorescence microscope. With matrigel invasion assay, invasiveness of glioma sphere cells was determined and compared with that of primary glioma cells. Results: Glioma cell spheres were cultured successfully. These cells were proved to express stem cell marker CD133, capable of renewal and proliferation, and can differentiate to glia and neurons with positive expressions of GFAP and TU-20, indicating the characteristics of GSLC. The invasiveness of glioma spheres cells in vitro was higher than that of primary glioma cells (261.23±87.20 vs 116.08±63.88, P<0.01). Moreover, glioma spheres cells preferred to aggregate and reform new spheres after travelling through the matrigel. Conclusion:〗GSLCs are successfully cultured from human glioma tissues, which show higher invasiveness in vitro. GSLC may participate in glioma invasion and metastasis.
Objective:To isolate and culture human brain glioma stem-like cells (GSLCs), and to determine the invasiveness of GSLC in vitro. Methods: Glioma cell spheres were serum free cultured from 8 surgical specimens of glioma inpatients from October 2008 to January 2009 in the Department of Neurosurgery, First Hospital of China Medical University. CD133 expression was identified by immunocytochemistry assay, and the expressions of GFAP and TU-20 in differentiated glioma cell spheres were detected under an immunofluorescence microscope. With matrigel invasion assay, invasiveness of glioma sphere cells was determined and compared with that of primary glioma cells. Results: Glioma cell spheres were cultured successfully. These cells were proved to express stem cell marker CD133, capable of renewal and proliferation, and can differentiate to glia and neurons with positive expressions of GFAP and TU-20, indicating the characteristics of GSLC. The invasiveness of glioma spheres cells in vitro was higher than that of primary glioma cells (261.23±87.20 vs 116.08±63.88, P<0.01). Moreover, glioma spheres cells preferred to aggregate and reform new spheres after travelling through the matrigel. Conclusion:〗GSLCs are successfully cultured from human glioma tissues, which show higher invasiveness in vitro. GSLC may participate in glioma invasion and metastasis.
2012, 19(2):133-137.
DOI: 10.3872/j.issn.1007-385X.2012.2.005
Abstract:
Objective:To investigate the effect of reovirus on apoptosis of breast cancer mammosphere cells. Methods:MCF-7 and BT474 cells were cultured in stem cell culture medium to generate mammospheres. Then the mammospheres were infected by reovirus or treated with epirubicin, The proportion CD44+CD24-/low cells in the mammosphere cells from MCF-7 and BT474 cells was detected by flow cytometry (FCM); the apoptosis of mammosphere cells was detected by TUNEL; and the expression of Ras in MCF-7 cells and the mammosphere cells was examined by Western blotting. Results: The infection rates of reovirus on MCF-7 and BT474 mammosphere cells were significantly higher than those on MCF-7 and BT474 cells (all P<0.05). The proportions of CD44+CD24-/low cells in the mammosphere cells from MCF-7 and BT474 cells after treatment with epirubicin were improved greatly (\[8.1±0.4\]% vs \[18.0±4.5\]%, P<0.01; \[0.6±0.2\]% vs \[0.9±0.13\]%, P<0.05), while the proportions of CD44+CD24-/low cells in the mammosphere cells after treatment with reovirus were decreased apparently (\[8.1±0.4\]% vs \[0.8±0.2\]%, P<0.05; \[0.6±0.2\]% vs \[0.2±0.1\]%, P<0.05). The apoptosis rates of the mammospheres cells from MCF-7 and BT474 cells rose up from (1.9±0.21)% to (5±1.4)% (P<0.05) and from (0.2±0.1)% to (1.0±0.16)% (P<0.05) after reovirus treatment. Ras levels in MCF-7 cells and the mammosphere cells were almost same high. Conclusion: Compared with that of epirubicin, reovirus has a higher inhibitory effect on breast cancer mammosphere cells, while reovirus distinctively induces apoptosis of mammosphere cells.
Objective:To investigate the effect of reovirus on apoptosis of breast cancer mammosphere cells. Methods:MCF-7 and BT474 cells were cultured in stem cell culture medium to generate mammospheres. Then the mammospheres were infected by reovirus or treated with epirubicin, The proportion CD44+CD24-/low cells in the mammosphere cells from MCF-7 and BT474 cells was detected by flow cytometry (FCM); the apoptosis of mammosphere cells was detected by TUNEL; and the expression of Ras in MCF-7 cells and the mammosphere cells was examined by Western blotting. Results: The infection rates of reovirus on MCF-7 and BT474 mammosphere cells were significantly higher than those on MCF-7 and BT474 cells (all P<0.05). The proportions of CD44+CD24-/low cells in the mammosphere cells from MCF-7 and BT474 cells after treatment with epirubicin were improved greatly (\[8.1±0.4\]% vs \[18.0±4.5\]%, P<0.01; \[0.6±0.2\]% vs \[0.9±0.13\]%, P<0.05), while the proportions of CD44+CD24-/low cells in the mammosphere cells after treatment with reovirus were decreased apparently (\[8.1±0.4\]% vs \[0.8±0.2\]%, P<0.05; \[0.6±0.2\]% vs \[0.2±0.1\]%, P<0.05). The apoptosis rates of the mammospheres cells from MCF-7 and BT474 cells rose up from (1.9±0.21)% to (5±1.4)% (P<0.05) and from (0.2±0.1)% to (1.0±0.16)% (P<0.05) after reovirus treatment. Ras levels in MCF-7 cells and the mammosphere cells were almost same high. Conclusion: Compared with that of epirubicin, reovirus has a higher inhibitory effect on breast cancer mammosphere cells, while reovirus distinctively induces apoptosis of mammosphere cells.
2012, 19(2):138-142.
DOI: 10.3872/j.issn.1007-385X.2012.2.006
Abstract:
Objective: To study the effect of resveratrol (Res) on proliferation, adhesion and invasion of A549 lung adenocarcinoma cells. Methods: A549 cells were treated with different doses of Res. The cell proliferation, cell cycle and apoptosis, adhesive ability, and invasion of A549 cells were examined by methyl thiazolyltetrazolium (MTT) assay, flow cytometry, Boyden chamber assay and Transwell assay respectively (3T3 cells as a normal cell control). The expressions of MMP-2 and TIMP-2 proteins in A549 cells were assayed by immunofluorescent cytochemistry.Results: Res inhibited the proliferation of A549 cells in a dose (20-80 μmol/L) and time (0-72 h) dependent manner. No significant inhibitory effect on 3T3 cell proliferation was observed at the same dose. Res induced the apoptosis of A549 cells with the apoptotic rates of (34.9±0.91)%, (41.33±0.13)%, (45.47±0.87)% and (59.46±0.59)% respectively when Res being 10, 20, 40, 80 μmol/L. A549 cells were arrested at the S phase of cell cycle, and the cell proportion in the S phase was (56.41±167)% when treated with 20 μmol/L Res, the adhesion and invasion ability of A549 cells was effectively decreased after treatment with 20 μmol/L -80 μmol/L Res (P<0.05), accompanied by a significant down-regulation of MMP-2 expressions and up-regulation of TIMP-2 expressions. Conclusion:Res can inhibit the proliferation, adhesion and invasion of A549 lung adenocarcinoma cells, which may be related with the bilateral regulation on MMP-2 and TIMP-2 expressions.
Objective: To study the effect of resveratrol (Res) on proliferation, adhesion and invasion of A549 lung adenocarcinoma cells. Methods: A549 cells were treated with different doses of Res. The cell proliferation, cell cycle and apoptosis, adhesive ability, and invasion of A549 cells were examined by methyl thiazolyltetrazolium (MTT) assay, flow cytometry, Boyden chamber assay and Transwell assay respectively (3T3 cells as a normal cell control). The expressions of MMP-2 and TIMP-2 proteins in A549 cells were assayed by immunofluorescent cytochemistry.Results: Res inhibited the proliferation of A549 cells in a dose (20-80 μmol/L) and time (0-72 h) dependent manner. No significant inhibitory effect on 3T3 cell proliferation was observed at the same dose. Res induced the apoptosis of A549 cells with the apoptotic rates of (34.9±0.91)%, (41.33±0.13)%, (45.47±0.87)% and (59.46±0.59)% respectively when Res being 10, 20, 40, 80 μmol/L. A549 cells were arrested at the S phase of cell cycle, and the cell proportion in the S phase was (56.41±167)% when treated with 20 μmol/L Res, the adhesion and invasion ability of A549 cells was effectively decreased after treatment with 20 μmol/L -80 μmol/L Res (P<0.05), accompanied by a significant down-regulation of MMP-2 expressions and up-regulation of TIMP-2 expressions. Conclusion:Res can inhibit the proliferation, adhesion and invasion of A549 lung adenocarcinoma cells, which may be related with the bilateral regulation on MMP-2 and TIMP-2 expressions.
2012, 19(2):143-147.
DOI: 10.3872/j.issn.1007-385X.2012.2.007
Abstract:
Objective:To investigate the effects of silencing B7-H4 expression by small interference RNA (siRNA) on proliferation, invasion and migration of human lung adenocarcinoma A549 cells. Methods: Chemically synthesized siRNA targeting B7-H4 (B7-H4-siRNA) was transfected into A549 cells. The proliferation of A549 cells was determined by MTT assay, the cell cycle was detected by flow cytometry, the levels of B7-H4 and Cyclin D1 were verified by Western blotting, and the invasion and migration ability was detected by Transwell assay. Results: B7-H4-siRNA was successfully transfected into A549 cells. Western blotting results showed that B7-H4-siRNA transfection inhibited the expressions of B7-H4 and Cyclin D1 in A549 cells. In the B7-H4-siRNA group, the proliferation of A549 cells was significantly down-regulated, the doubling time was longer than that in the untransfected group, the Ctrl-siRNA group and the empty vector group (\[33.78±0.26\] h vs \[28.69±0.18\], \[27.32±0.13\], \[26.93±0.19\] h，P<0.05), and the cell cycles were arrested in G1 phase. The invasion of A549 cells in the B7-H4-siRNA group was inhibited significantly as compared with the untransfected group (\[89.80±0.99\] vs \[186.20±1.33\], P<0.05), and the migration of A549 cells in the B7-H4-siRNA group was suppressed significantly as compared with the untransfected group, the Ctrl-siRNA group and the empty vector group (\[60.20±0.37\] vs \[102.57±0.52\], \[100.72±0.31\], \[98.65±0.21\], P<0.05). Conclusion: B7-H4-siRNA can silence B7-H4 expression in A549 cells, and inhibit the proliferation, invasion and migration of A549 cells effectively. B7-H4 can be regarded as a candidate gene for lung cancer gene therapy.
Objective:To investigate the effects of silencing B7-H4 expression by small interference RNA (siRNA) on proliferation, invasion and migration of human lung adenocarcinoma A549 cells. Methods: Chemically synthesized siRNA targeting B7-H4 (B7-H4-siRNA) was transfected into A549 cells. The proliferation of A549 cells was determined by MTT assay, the cell cycle was detected by flow cytometry, the levels of B7-H4 and Cyclin D1 were verified by Western blotting, and the invasion and migration ability was detected by Transwell assay. Results: B7-H4-siRNA was successfully transfected into A549 cells. Western blotting results showed that B7-H4-siRNA transfection inhibited the expressions of B7-H4 and Cyclin D1 in A549 cells. In the B7-H4-siRNA group, the proliferation of A549 cells was significantly down-regulated, the doubling time was longer than that in the untransfected group, the Ctrl-siRNA group and the empty vector group (\[33.78±0.26\] h vs \[28.69±0.18\], \[27.32±0.13\], \[26.93±0.19\] h，P<0.05), and the cell cycles were arrested in G1 phase. The invasion of A549 cells in the B7-H4-siRNA group was inhibited significantly as compared with the untransfected group (\[89.80±0.99\] vs \[186.20±1.33\], P<0.05), and the migration of A549 cells in the B7-H4-siRNA group was suppressed significantly as compared with the untransfected group, the Ctrl-siRNA group and the empty vector group (\[60.20±0.37\] vs \[102.57±0.52\], \[100.72±0.31\], \[98.65±0.21\], P<0.05). Conclusion: B7-H4-siRNA can silence B7-H4 expression in A549 cells, and inhibit the proliferation, invasion and migration of A549 cells effectively. B7-H4 can be regarded as a candidate gene for lung cancer gene therapy.
2012, 19(2):148-153.
DOI: 10.3872/j.issn.1007-385X.2012.2.008
Abstract:
Objective:To explore the activation of CD8+T cells of hepatocellular carcinoma (HCC) stimulated by the artificial antigen presenting cells (aAPC) (K32/4-IBBL/CD86). Methods: Peripheral CD8+T cells of HLA-A*0201 positive HCC patients were enriched by MACS separation system. CD8+T cells were cultured with aAPC at different ratios (3∶1, 2∶1 and 1∶1), and CTLs were induced. Growth curve of CTLs was examined by trypan blue exclusion assay; MTS/PMS assay was used to detect the proliferation of CTLs; the IFN-γ secreting CTLs were assayed by FACS; the cytotoxicity of CTLs on a human liver cancer cell line BEL7402 and self-HCC cells was tested using MTT method. Results: The proliferation of peripheral CD8+ T cells stimulated with aAPC was significantly increased. At days 8, the CTL cell numbers of aAPC to CD8+ T cells at 1∶1, 1∶2, 1∶3 groups was significantly higher than those in the control group (\[212±2.5\]×105, \[17.6±3.2\]×105, \[15.3±2.8\]×105 vs \[8.5±0.15\]×105, P<0.01); and the proportion of IFN-γ secreting CTLs in 1∶1, 1∶2, 1∶3 groups was higher than those in the control group (\[26.2±1.91\]%, \[21.3±1.38\]%, \[18.6±1.20\]% vs \[0.1±0.02\]%, P<0.01). The cytotoxicity of aAPC-activated CTLs against BEL7402 cells and self-HCC cells in 1∶3 group was stronger than that in the control group (\[21.8±4.3\]% vs \[3.8±18\]%, P<0.01; \[25.6±3.6\]% vs \[3.8±2.0\]%, P<0.01). A higher cytotoxic rate on BEL7402 cells and self-HCC cells in the 1∶1 group at a ratio of E (effect): T (target) as 50∶1 was achieved compared with that in the 1∶2 and 1∶3 groups (\[568±3.0\]% vs \[44.3±2.6\]%, \[38.9±4.7\]%, P<0.05; \[64.8±4.2\]% vs \[56.1±3.4\]%, \[46.2±47\]%, P<0.05). Conclusion: aAPC can effectively activate CD8+T cells of HCC patients, and the resultant CTLs not only secrete IFN-γ but also efficiently kill human liver cancer BEL7402 cells and self-HCC cells.
Objective:To explore the activation of CD8+T cells of hepatocellular carcinoma (HCC) stimulated by the artificial antigen presenting cells (aAPC) (K32/4-IBBL/CD86). Methods: Peripheral CD8+T cells of HLA-A*0201 positive HCC patients were enriched by MACS separation system. CD8+T cells were cultured with aAPC at different ratios (3∶1, 2∶1 and 1∶1), and CTLs were induced. Growth curve of CTLs was examined by trypan blue exclusion assay; MTS/PMS assay was used to detect the proliferation of CTLs; the IFN-γ secreting CTLs were assayed by FACS; the cytotoxicity of CTLs on a human liver cancer cell line BEL7402 and self-HCC cells was tested using MTT method. Results: The proliferation of peripheral CD8+ T cells stimulated with aAPC was significantly increased. At days 8, the CTL cell numbers of aAPC to CD8+ T cells at 1∶1, 1∶2, 1∶3 groups was significantly higher than those in the control group (\[212±2.5\]×105, \[17.6±3.2\]×105, \[15.3±2.8\]×105 vs \[8.5±0.15\]×105, P<0.01); and the proportion of IFN-γ secreting CTLs in 1∶1, 1∶2, 1∶3 groups was higher than those in the control group (\[26.2±1.91\]%, \[21.3±1.38\]%, \[18.6±1.20\]% vs \[0.1±0.02\]%, P<0.01). The cytotoxicity of aAPC-activated CTLs against BEL7402 cells and self-HCC cells in 1∶3 group was stronger than that in the control group (\[21.8±4.3\]% vs \[3.8±18\]%, P<0.01; \[25.6±3.6\]% vs \[3.8±2.0\]%, P<0.01). A higher cytotoxic rate on BEL7402 cells and self-HCC cells in the 1∶1 group at a ratio of E (effect): T (target) as 50∶1 was achieved compared with that in the 1∶2 and 1∶3 groups (\[568±3.0\]% vs \[44.3±2.6\]%, \[38.9±4.7\]%, P<0.05; \[64.8±4.2\]% vs \[56.1±3.4\]%, \[46.2±47\]%, P<0.05). Conclusion: aAPC can effectively activate CD8+T cells of HCC patients, and the resultant CTLs not only secrete IFN-γ but also efficiently kill human liver cancer BEL7402 cells and self-HCC cells.
2012, 19(2):154-157.
DOI: 10.3872/j.issn.1007-385X.2012.2.009
Abstract:
Objective: To investigate the effect of leptin on the migration and invasion of human glioma U87MG cells, and explore its molecule mechanism. Methods: U87MG cells were treated with leptin, the cell migration was analyzed by cell scratch assay, cell invasion was detected by Transwell, and mRNA and protein expressions of MMP-2 and MMP-9 in U87MG cells were observed by RT-PCR and Western blotting assay. Results: Leptin significantly promoted migration (\[152.42±3.29\] vs \[83.24±2.61\] μm, P<0.05), and invasion (\[31.78±5.04\] vs \[17.03±2.41\]/field, P<0.05) of U87MG cells; the mRNA and protein expressions of MMP-2 and MMP-9 were significantly upregulated by leptin in U87MG cells (mRNA: \[0.76±0.04\] vs \[0.35±0.02\], \[0.84±0.02\] vs \[0.41±0.06\], P<0.05; protein: \[079±0.03\] vs \[0.23±0.01\], \[0.81±0.05\] vs \[0.39±0.03\], P<0.05); MMP inhibitor GM6001 reversed U87MG cell migration (\[82.05±2.98\] vs \[81.76±3.25\] μm, P>0.05\] and invasion (\[19.23±2.46\] vs \[18.02±1.98\]/field, P<0.05) induced by leptin. Conclusion: Leptin can promote the invasion and migration of human glioma U87MG cells, which might related with the upregulation of MMP-2 and MMP-9.
Objective: To investigate the effect of leptin on the migration and invasion of human glioma U87MG cells, and explore its molecule mechanism. Methods: U87MG cells were treated with leptin, the cell migration was analyzed by cell scratch assay, cell invasion was detected by Transwell, and mRNA and protein expressions of MMP-2 and MMP-9 in U87MG cells were observed by RT-PCR and Western blotting assay. Results: Leptin significantly promoted migration (\[152.42±3.29\] vs \[83.24±2.61\] μm, P<0.05), and invasion (\[31.78±5.04\] vs \[17.03±2.41\]/field, P<0.05) of U87MG cells; the mRNA and protein expressions of MMP-2 and MMP-9 were significantly upregulated by leptin in U87MG cells (mRNA: \[0.76±0.04\] vs \[0.35±0.02\], \[0.84±0.02\] vs \[0.41±0.06\], P<0.05; protein: \[079±0.03\] vs \[0.23±0.01\], \[0.81±0.05\] vs \[0.39±0.03\], P<0.05); MMP inhibitor GM6001 reversed U87MG cell migration (\[82.05±2.98\] vs \[81.76±3.25\] μm, P>0.05\] and invasion (\[19.23±2.46\] vs \[18.02±1.98\]/field, P<0.05) induced by leptin. Conclusion: Leptin can promote the invasion and migration of human glioma U87MG cells, which might related with the upregulation of MMP-2 and MMP-9.
2012, 19(2):158-162.
DOI: 10.3872/j.issn.1007-385X.2012.2.010
Abstract:
Objective:To investigate the effect of microRNA-7 (miR-7) on the chemosensitivity of non-small cell lung cancer A549 and H1299 cells to epirubicin (EPI) treatment and its molecular mechanism. Methods: After being treated with EPI and transfected with miR-7 mimics alone or in combination, the cell proliferation of A549 and H1299 cells was measured by CCK-8; the cell apoptosis was detected by Annexin V/PI staining; and the expressions of EGFR and Raf-1 mRNA were examined by real-time PCR. Results: Both EPI treatment and miR-7 mimics transfection inhibited the proliferation of A549 and H1299 cells (P<0.05), while EPI (50-400 ng/ml) combined with miR-7 mimics had a stronger inhibitory effect on the proliferation of A549 and H1299 cells than EPI treatment alone (P<0.05). The percentages of apoptotic cells was significantly increased in the combination treatment group by (54.9±0.4)% in A549 cells and (672±0.5)% in H1299 cells (P<0.01) compared with that of the EPI treatment group, and the expressions of EGFR and Raf-1 mRNA were also downregulated by (68.0±6.0)% and (78.2±3.9)% in A549 cells, (94.8±6.2)% and (87.8±4.3)% in H1299 cells after the combination treatment of miR-7 mimics and EPI compared with that of the EPI treatment alone group (P<0.01).Conclusion: miR-7 enhances the inhibitory and pro-apoptosis effect of EPI on A549 and H1299 cells through the downregulation of EGFR and Raf-1 mRNA.
Objective:To investigate the effect of microRNA-7 (miR-7) on the chemosensitivity of non-small cell lung cancer A549 and H1299 cells to epirubicin (EPI) treatment and its molecular mechanism. Methods: After being treated with EPI and transfected with miR-7 mimics alone or in combination, the cell proliferation of A549 and H1299 cells was measured by CCK-8; the cell apoptosis was detected by Annexin V/PI staining; and the expressions of EGFR and Raf-1 mRNA were examined by real-time PCR. Results: Both EPI treatment and miR-7 mimics transfection inhibited the proliferation of A549 and H1299 cells (P<0.05), while EPI (50-400 ng/ml) combined with miR-7 mimics had a stronger inhibitory effect on the proliferation of A549 and H1299 cells than EPI treatment alone (P<0.05). The percentages of apoptotic cells was significantly increased in the combination treatment group by (54.9±0.4)% in A549 cells and (672±0.5)% in H1299 cells (P<0.01) compared with that of the EPI treatment group, and the expressions of EGFR and Raf-1 mRNA were also downregulated by (68.0±6.0)% and (78.2±3.9)% in A549 cells, (94.8±6.2)% and (87.8±4.3)% in H1299 cells after the combination treatment of miR-7 mimics and EPI compared with that of the EPI treatment alone group (P<0.01).Conclusion: miR-7 enhances the inhibitory and pro-apoptosis effect of EPI on A549 and H1299 cells through the downregulation of EGFR and Raf-1 mRNA.
2012, 19(2):163-167.
DOI: 10.3872/j.issn.1007-385X.2012.2.011
Abstract:
Objective:To modify PEGylated cationic liposome was modified by small peptide ligand D4 of epidermal growth factor receptor (EGFR), and study its effect on enhancing the transfection efficiency of plasmid DNA and siRNA in tumor cells. Methods: D4 was conjugated to the end of DSPE-PEG2000 to modify the PEGylated cationic liposome, and the effects of this vector system on transfection efficiency of plasmid DNA in EGFR highly-expressed human non-small lung cancer H1299 cells was examined. Luciferase expression in plasmid DNA tranfected-H1299 cells was observed by Siriu sillumination apparatus, and the fluorescence intensity of FAM-siRNA tranfected-H1299 cells was detected by fluorescence microscopy. Results: In prepared liposome/plasmid DNA, with increasing of electric charge ratios, the particle diameter of complex was gradually decreasing and Zeta electric potential was increasing. Compared with non-targeted liposome, liposome modified by D4 significantly increased the expression of luciferase in H1299 cells after plasmid DNA tranfection (P<0.05, or P<0.01); the transfection efficiency of D4-modified liposome with different electric charge ratios on H1299 cells was significantly increased compared with un-modified liposome (P<0.05, or P<0.01). In addtion, in the transfection of FAM-siRNA, an enhanced fluorescence intensity of FAM was observed in the D4-modified liposome group under a fluorescence microscope. Conclusion: D4-modified cationic liposome can improve the transfection efficiency of plasmid DNA and siRNA in EGFR highly-expressed tumor cells.
Objective:To modify PEGylated cationic liposome was modified by small peptide ligand D4 of epidermal growth factor receptor (EGFR), and study its effect on enhancing the transfection efficiency of plasmid DNA and siRNA in tumor cells. Methods: D4 was conjugated to the end of DSPE-PEG2000 to modify the PEGylated cationic liposome, and the effects of this vector system on transfection efficiency of plasmid DNA in EGFR highly-expressed human non-small lung cancer H1299 cells was examined. Luciferase expression in plasmid DNA tranfected-H1299 cells was observed by Siriu sillumination apparatus, and the fluorescence intensity of FAM-siRNA tranfected-H1299 cells was detected by fluorescence microscopy. Results: In prepared liposome/plasmid DNA, with increasing of electric charge ratios, the particle diameter of complex was gradually decreasing and Zeta electric potential was increasing. Compared with non-targeted liposome, liposome modified by D4 significantly increased the expression of luciferase in H1299 cells after plasmid DNA tranfection (P<0.05, or P<0.01); the transfection efficiency of D4-modified liposome with different electric charge ratios on H1299 cells was significantly increased compared with un-modified liposome (P<0.05, or P<0.01). In addtion, in the transfection of FAM-siRNA, an enhanced fluorescence intensity of FAM was observed in the D4-modified liposome group under a fluorescence microscope. Conclusion: D4-modified cationic liposome can improve the transfection efficiency of plasmid DNA and siRNA in EGFR highly-expressed tumor cells.
FAN Yong-li
,
ZHAO Hua
,
YU Jin-pu
,
LI Hui
,
REN Bao-zhu
,
CAO Shui
,
LIU Liang
,
LI Run-mei
,
ZHANG Nai-ning
,
AN Xiu-mei
,
REN Xiu-bao
2012, 19(2):168-174.
DOI: 10.3872/j.issn.1007-385X.2012.2.012
Abstract:
Objective:To estimate the clinical efficacy of chemotherapy combined with cytokine-induced killer cell（CIK）treatment after curative resection for gastric cancer patients. Methods: 65 gastric cancer patients treated with chemotherapy combined with CIK (chemotherapy combined with CIK group) and 130 patients treated with chemotherapy only after radical gastrectomy (chemotherapy-only group) were included in this study (from March 1999 to December 2007 in Affiliated Cancer Hospital of Tianjin Medical University). The survival rate and live time was compared between two groups. The receiver operating characteristic (ROC) was analyzed, and the periodicity of chemotherapy and the frequency of CIK treatment was determined. The survival curve was made by Kaplan-Meier method, and the survival difference was compared by Log-rank test. Results: The overall 3- and 5-year survival rates of the chemotherapy combined with CIK group were slightly higher than those of the chemotherapy-only group, and without significant difference (60% vs 47%, 55% vs 23%, P>005). The 3- and 5-year progression free survival rates of the chemotherapy combined with CIK group were lower than those of the chemotherapy-only group (48% vs 31%, 47% vs 20%, P<0.05). The median overall survival (OS) of chemotherapy combined with CIK group was 96 months, which was longer than that of 32 months in the chemotherapy-only group (P=0.001). The median progression free survival (PFS) was 36 months in the chemotherapy combined with CIK group and was longer than that of 23 months in the chemotherapy-only group (P=0.011). In univariate analysis, the TNM stage, chemotherapy cycle and CIK frequency were related to OS of the patients; the TNM stage, the modes of surgery and CIK frequency were related to PFS of patients. Multivariate analysis revealed that the chemotherapy cycle independently influenced OS. However, CIK frequency was an independent risk factor of both OS and PFS. Conclusion: OS is significantly longer in the gastric patients treated with chemotherapy combined with CIK than the patients treated with chemotherapy alone, and the higher CIK frequency shows more clinical benefits.
Objective:To estimate the clinical efficacy of chemotherapy combined with cytokine-induced killer cell（CIK）treatment after curative resection for gastric cancer patients. Methods: 65 gastric cancer patients treated with chemotherapy combined with CIK (chemotherapy combined with CIK group) and 130 patients treated with chemotherapy only after radical gastrectomy (chemotherapy-only group) were included in this study (from March 1999 to December 2007 in Affiliated Cancer Hospital of Tianjin Medical University). The survival rate and live time was compared between two groups. The receiver operating characteristic (ROC) was analyzed, and the periodicity of chemotherapy and the frequency of CIK treatment was determined. The survival curve was made by Kaplan-Meier method, and the survival difference was compared by Log-rank test. Results: The overall 3- and 5-year survival rates of the chemotherapy combined with CIK group were slightly higher than those of the chemotherapy-only group, and without significant difference (60% vs 47%, 55% vs 23%, P>005). The 3- and 5-year progression free survival rates of the chemotherapy combined with CIK group were lower than those of the chemotherapy-only group (48% vs 31%, 47% vs 20%, P<0.05). The median overall survival (OS) of chemotherapy combined with CIK group was 96 months, which was longer than that of 32 months in the chemotherapy-only group (P=0.001). The median progression free survival (PFS) was 36 months in the chemotherapy combined with CIK group and was longer than that of 23 months in the chemotherapy-only group (P=0.011). In univariate analysis, the TNM stage, chemotherapy cycle and CIK frequency were related to OS of the patients; the TNM stage, the modes of surgery and CIK frequency were related to PFS of patients. Multivariate analysis revealed that the chemotherapy cycle independently influenced OS. However, CIK frequency was an independent risk factor of both OS and PFS. Conclusion: OS is significantly longer in the gastric patients treated with chemotherapy combined with CIK than the patients treated with chemotherapy alone, and the higher CIK frequency shows more clinical benefits.
2012, 19(2):175-179.
DOI: 10.3872/j.issn.1007-385X.2012.2.013
Abstract:
Objective:To investigate the expression of TFIIB-related factor 2 (BRF2) in human esophageal squamous cell carcinoma tissues, adjacent esophageal cell carcinoma tissues and normal esophageal tissues, so as to analyze the role of BRF2 in the development and progression of esophageal squamous cell carcinoma. Methods: Samples were obtained from 74 esophageal squamous cell carcinoma patients who had been surgically treated during Jan. 2007 to Jan. 2008 in Qilu Hospital of Shandong University. Immunohistochemisty and RT-PCR were applied to detect BRF2 expression in esophageal squamous cell carcinoma tissues, adjacent esophageal squamous cell carcinoma tissues and normal esophageal tissues. Results: The expression of BRF2 mRNA in esophageal squamous cell carcinoma and adjacent esophageal squamous cell carcinoma tissues was significantly higher than that in normal esophageal tissues. The positive expression rates of BRF2 protein in esophageal squamous cell carcinoma, adjacent esophageal squamous cell carcinoma and normal esophageal tissues were 54.55%, 32.5% and 7.5%, respectively, with a rate in esophageal squamous cell carcinoma and adjacent esophageal squamous cell carcinoma tissues higher than that in normal esophageal tissues (P<0.05). The BRF2 positive expression rate in esophageal squamous cell carcinoma tissues was decreased with the increase in differentiation grade of esophageal squamous cell carcinoma (P<0.05), and the expression rate in grade Ⅲ and Ⅳ of esophageal squamous cell carcinoma significantly higher than that in gradeⅠ and Ⅱ ( 72.7%, 73.3% vs 35.7%, 34.8%， P<0.05). The BRF2 expression rate in the patients who survived less than 3 years was markedly higher than that in the patients who survived longer than 3 years (69.2% vs 38.2%, P<0.05); and smoking patients had a markedly higher expression rate than non-smokers (61.1% vs 30.4%, P<0.05). Conclusion: mRNA and protein of BRF2 gene are highly expressed in esophageal squamous cell carcinoma, which is correlated with poor prognosis of patients, and may be used in evaluating the prognosis of esophageal carcinoma patients.
Objective:To investigate the expression of TFIIB-related factor 2 (BRF2) in human esophageal squamous cell carcinoma tissues, adjacent esophageal cell carcinoma tissues and normal esophageal tissues, so as to analyze the role of BRF2 in the development and progression of esophageal squamous cell carcinoma. Methods: Samples were obtained from 74 esophageal squamous cell carcinoma patients who had been surgically treated during Jan. 2007 to Jan. 2008 in Qilu Hospital of Shandong University. Immunohistochemisty and RT-PCR were applied to detect BRF2 expression in esophageal squamous cell carcinoma tissues, adjacent esophageal squamous cell carcinoma tissues and normal esophageal tissues. Results: The expression of BRF2 mRNA in esophageal squamous cell carcinoma and adjacent esophageal squamous cell carcinoma tissues was significantly higher than that in normal esophageal tissues. The positive expression rates of BRF2 protein in esophageal squamous cell carcinoma, adjacent esophageal squamous cell carcinoma and normal esophageal tissues were 54.55%, 32.5% and 7.5%, respectively, with a rate in esophageal squamous cell carcinoma and adjacent esophageal squamous cell carcinoma tissues higher than that in normal esophageal tissues (P<0.05). The BRF2 positive expression rate in esophageal squamous cell carcinoma tissues was decreased with the increase in differentiation grade of esophageal squamous cell carcinoma (P<0.05), and the expression rate in grade Ⅲ and Ⅳ of esophageal squamous cell carcinoma significantly higher than that in gradeⅠ and Ⅱ ( 72.7%, 73.3% vs 35.7%, 34.8%， P<0.05). The BRF2 expression rate in the patients who survived less than 3 years was markedly higher than that in the patients who survived longer than 3 years (69.2% vs 38.2%, P<0.05); and smoking patients had a markedly higher expression rate than non-smokers (61.1% vs 30.4%, P<0.05). Conclusion: mRNA and protein of BRF2 gene are highly expressed in esophageal squamous cell carcinoma, which is correlated with poor prognosis of patients, and may be used in evaluating the prognosis of esophageal carcinoma patients.
2012, 19(2):180-185.
DOI: 10.3872/j.issn.1007-385X.2012.2.014
Abstract:
Objective:To investigate the expressions of different Smad genes in gastric cardia adenocarcinoma (GCA) and to explore their correlation and clinical significance. Methods: 110 cases of pathologically confirmed GCA were included from the Fourth Hospital of Hebei Medical University during 2004-2009 year. RT-PCR and immunohistochemistry methods was used to respectively detect the mRNA and protein expressions of Smad2, Smad3, Smad4 and Smad7 in GCA. Their correlations with clinical pathological characteristics of GCA were analyzed. Results: The expressions of Smad2, Smad3 and Smad4 mRNA in GCA tissues were significantly reduced with comparison to the paired normal tissues (\[0.4956±0.1862\] vs \[0.8611±0.2914\], P<0.01; \[0.4713±0.1712\] vs \[0.8314±0.2811\], P<0.01; \[05145±0.1987\] vs \[0.8954±0.2856\], P<0.01), and Smad7 mRNA expression in GCA tissues was significantly increased with comparison to the paired normal tissues (\[0.5114±0.1962\] vs \[0.2012±01006\], P<0.01). The positive protein expression rate of p-Smad2/3 and Smad4 in GCA tissues was significantly lower than that in the paired normal tissues (42.7% vs 93.6%, P<0.01; 45.5% vs 95.5%, P<0.01). The protein expressions of p-Smad2/3 and Smad4 were associated with TNM stage and pathological differentiation (P<0.05). The positive protein expression rate of Smad7 in GCA tissues (48.2%) was significantly higher than that in the paired normal tissues (3.6%) and was associated with pathological differentiation (P<0.05). The protein expression of p-Smad2/3 and Smad4 was positively correlated, while p-Smad2/3 and Smad4 did not show any correlation with Smad7. Conclusion: Decreased expression of Smad2, Smad3 and Smad4 and increased expression of Smad7 in GCA may be associated with the occurrence and development of GCA.
Objective:To investigate the expressions of different Smad genes in gastric cardia adenocarcinoma (GCA) and to explore their correlation and clinical significance. Methods: 110 cases of pathologically confirmed GCA were included from the Fourth Hospital of Hebei Medical University during 2004-2009 year. RT-PCR and immunohistochemistry methods was used to respectively detect the mRNA and protein expressions of Smad2, Smad3, Smad4 and Smad7 in GCA. Their correlations with clinical pathological characteristics of GCA were analyzed. Results: The expressions of Smad2, Smad3 and Smad4 mRNA in GCA tissues were significantly reduced with comparison to the paired normal tissues (\[0.4956±0.1862\] vs \[0.8611±0.2914\], P<0.01; \[0.4713±0.1712\] vs \[0.8314±0.2811\], P<0.01; \[05145±0.1987\] vs \[0.8954±0.2856\], P<0.01), and Smad7 mRNA expression in GCA tissues was significantly increased with comparison to the paired normal tissues (\[0.5114±0.1962\] vs \[0.2012±01006\], P<0.01). The positive protein expression rate of p-Smad2/3 and Smad4 in GCA tissues was significantly lower than that in the paired normal tissues (42.7% vs 93.6%, P<0.01; 45.5% vs 95.5%, P<0.01). The protein expressions of p-Smad2/3 and Smad4 were associated with TNM stage and pathological differentiation (P<0.05). The positive protein expression rate of Smad7 in GCA tissues (48.2%) was significantly higher than that in the paired normal tissues (3.6%) and was associated with pathological differentiation (P<0.05). The protein expression of p-Smad2/3 and Smad4 was positively correlated, while p-Smad2/3 and Smad4 did not show any correlation with Smad7. Conclusion: Decreased expression of Smad2, Smad3 and Smad4 and increased expression of Smad7 in GCA may be associated with the occurrence and development of GCA.
2012, 19(2):186-190.
DOI: 10.3872/j.issn.1007-385X.2012.2.015
Abstract:
Objective:To discuss the expression and significance of v-raf murine sarcoma viral oncogene homolog B1(BRAF) and erythropoietin-producing hepatoma cell line B2 (EphB2) in human colorectal serrated adenomas. Methods: Collect 10 paraffin specimens of normal mucosa, 21 cases of hyperplastic polyp, 22 cases of serrated adenomas and 55 cases of traditional colorectal adenomas (18 tubular adenomas, 16 tubulovillous adenomas, 21 villous adenomas) in the Affiliated Hospital of Binzhou Medical College between Jan. 1996 to May. 2008. The expression levels and sites of BRAF and EphB2 protein were examined by immunohistochemical method. Results:Most BRAF protein positive cells in hyperplastic polyp were located in the lower crypt, those in adenomatous polyp located in upper crypt, and those in serrated adenomas almost expressed in the whole crypt. The expression of BRAF protein was similar in serrated adenomas and adenomatous polyp (0.129±0030 vs 0.130±0.026, P>0.05), while more higher than that in hyperplastic polyp (0.129±0.030 vs 0.102±0.014, P<0.01). There was no significant difference in BRAF protein expression among the serrated adenomas, tubular adenomas, tubulovillous adenomas and villous adenomas (0.129±0.030 vs 0.116±0.019, 0.119±0.037, 0.122±0.008, P>0.05). The EphB2 protein positive cells in hyperplastic polyp was almost located in the membrane of the middle and lower region of crypt, those in adenomatous polyp located in the upper crypt, and those in serrated adenomas expressed in the whole crypt. The EphB2 protein expression in serrated adenomas and adenomatous polyp was similar (0.138±0.024 vs 0.139±0.025, P>0.05)，but much higher than that in hyperplastic polyp (0.138±0.024 vs 0.169±0.018, P<0.01). No significant difference was found in EphB2 among serrated adenomas, tubular adenomas, tubulovillous adenomas and villous adenomas (0.138±0.024 vs 0.143±0.027, 0.139±0.028, 0.133±0021, P>0.05). Conclusion: BRAF and EphB2 proteins both in hyperplastic polyp and adenomatous polyp are expressed partly in crypt, while those in colorectal serrated adenomas are expressed in the whole crypt, indicating that serrated adenomas may be an independent tumor difference from adenomatous polyp.
Objective:To discuss the expression and significance of v-raf murine sarcoma viral oncogene homolog B1(BRAF) and erythropoietin-producing hepatoma cell line B2 (EphB2) in human colorectal serrated adenomas. Methods: Collect 10 paraffin specimens of normal mucosa, 21 cases of hyperplastic polyp, 22 cases of serrated adenomas and 55 cases of traditional colorectal adenomas (18 tubular adenomas, 16 tubulovillous adenomas, 21 villous adenomas) in the Affiliated Hospital of Binzhou Medical College between Jan. 1996 to May. 2008. The expression levels and sites of BRAF and EphB2 protein were examined by immunohistochemical method. Results:Most BRAF protein positive cells in hyperplastic polyp were located in the lower crypt, those in adenomatous polyp located in upper crypt, and those in serrated adenomas almost expressed in the whole crypt. The expression of BRAF protein was similar in serrated adenomas and adenomatous polyp (0.129±0030 vs 0.130±0.026, P>0.05), while more higher than that in hyperplastic polyp (0.129±0.030 vs 0.102±0.014, P<0.01). There was no significant difference in BRAF protein expression among the serrated adenomas, tubular adenomas, tubulovillous adenomas and villous adenomas (0.129±0.030 vs 0.116±0.019, 0.119±0.037, 0.122±0.008, P>0.05). The EphB2 protein positive cells in hyperplastic polyp was almost located in the membrane of the middle and lower region of crypt, those in adenomatous polyp located in the upper crypt, and those in serrated adenomas expressed in the whole crypt. The EphB2 protein expression in serrated adenomas and adenomatous polyp was similar (0.138±0.024 vs 0.139±0.025, P>0.05)，but much higher than that in hyperplastic polyp (0.138±0.024 vs 0.169±0.018, P<0.01). No significant difference was found in EphB2 among serrated adenomas, tubular adenomas, tubulovillous adenomas and villous adenomas (0.138±0.024 vs 0.143±0.027, 0.139±0.028, 0.133±0021, P>0.05). Conclusion: BRAF and EphB2 proteins both in hyperplastic polyp and adenomatous polyp are expressed partly in crypt, while those in colorectal serrated adenomas are expressed in the whole crypt, indicating that serrated adenomas may be an independent tumor difference from adenomatous polyp.
WANG Shao-kai
,
WANG Wei-dong
,
TAO Chen-jie
,
HU Meng
,
YANG Jin-song
,
XU Zhi
,
HONG Ling-zhi
,
WEI Xiao-wei
,
TANG Cui-ju
,
GUO Yu-wu
,
GONG Yong-ling
2012, 19(2):191-195.
DOI: 10.3872/j.issn.1007-385X.2012.2.016
Abstract:
Objective:To observe the levels of plasma lysophosphatidic acid (LPA) in patients with pancreatic carcinoma, and to evaluate its clinical potential of diagnosis. Methods: Plasma LPA and serum CA19-9, AFP and CEA levels were measured in 50 patients with pancreatic carcinoma and 32 patients with benign pancreatic lesions hospitalized in Nanjing First Hospital during June of 2006 and October of 2010, and 36 healthy donors by phosphate determination method. Immunohistochemistry (IHC) was used to determine the expression of LPA2 receptor both in surgically resected pancreatic carcinomas and adjacent non tumor tissues. The correlation between LPA levels with clinical pathological features of pancreatic carcinoma patients was analyzed. Results: Plasma LPA concentration was significantly higher in pancreatic carcinoma patients than in patients with benign lesions and controls (\[4.10±2.03\] vs \[328±1.26\], \[2.27±1.02\] μmol/L, P＜0.05). Plasma LPA concentration was correlated with serum CA19-9 level (r=0.9070, P＜0.01) in patients with pancreatic carcinoma. The positive rate of LPA2 receptor in pancreatic carcinoma tissues was significantly higher than that in adjacent non tumor tissues (88% vs 4%, P＜0.05). Higher plasma LPA level showed a significant correlation with invasion and metastasis of pancreatic carcinoma. Conclusion: Plasma LPA level might be a potential indicator of the diagnosis and prognosis of pancreatic carcinoma.
Objective:To observe the levels of plasma lysophosphatidic acid (LPA) in patients with pancreatic carcinoma, and to evaluate its clinical potential of diagnosis. Methods: Plasma LPA and serum CA19-9, AFP and CEA levels were measured in 50 patients with pancreatic carcinoma and 32 patients with benign pancreatic lesions hospitalized in Nanjing First Hospital during June of 2006 and October of 2010, and 36 healthy donors by phosphate determination method. Immunohistochemistry (IHC) was used to determine the expression of LPA2 receptor both in surgically resected pancreatic carcinomas and adjacent non tumor tissues. The correlation between LPA levels with clinical pathological features of pancreatic carcinoma patients was analyzed. Results: Plasma LPA concentration was significantly higher in pancreatic carcinoma patients than in patients with benign lesions and controls (\[4.10±2.03\] vs \[328±1.26\], \[2.27±1.02\] μmol/L, P＜0.05). Plasma LPA concentration was correlated with serum CA19-9 level (r=0.9070, P＜0.01) in patients with pancreatic carcinoma. The positive rate of LPA2 receptor in pancreatic carcinoma tissues was significantly higher than that in adjacent non tumor tissues (88% vs 4%, P＜0.05). Higher plasma LPA level showed a significant correlation with invasion and metastasis of pancreatic carcinoma. Conclusion: Plasma LPA level might be a potential indicator of the diagnosis and prognosis of pancreatic carcinoma.
2012, 19(2):196-200.
DOI: 10.3872/j.issn.1007-385X.2012.2.017
Abstract:
Objective:To systematically evaluate the association between hepatitis B virus (HBV) infection and non-Hodgkin lymphoma (NHL). Methods: Case-control studies on the association of HBV infection with NHL were collected from Medline, EMBASE, PubMed, the Cochrane Library, Chinese Biomedical Literature Database, Chinese Scientific Journal Full-text Database, and Chinese Journal Full-text Database. The data extraction and Meta-analysis (STATA 110) was performed by two reviewers independently. Results: 15 case-control studies and 8 nested case-control studies were included in the present study. The Meta results showed that odd radio (OR) of HBV infection in NHL when compared with the control population was 2.44 (95% CI, 2.25-2.63) in the fixed effect model and 2.49 (95% CI, 1.95-3.18) in the random effect model. There was evidence of statistical heterogeneity in all included studies (I2=86.8%，P<0.05), which disappeared in the subgroup nested case-control studies (I2=15.9%，P>0.05). OR was 2.49 (95% CI, 1.95-3.18) in the random effect model, suggesting a higher prevalence of HBV carrier state in NHL than controls. Conclusion: There is a possible causal relation between HBV infection and NHL, which needs to be confirmed by experimental and epidemiological studies.
Objective:To systematically evaluate the association between hepatitis B virus (HBV) infection and non-Hodgkin lymphoma (NHL). Methods: Case-control studies on the association of HBV infection with NHL were collected from Medline, EMBASE, PubMed, the Cochrane Library, Chinese Biomedical Literature Database, Chinese Scientific Journal Full-text Database, and Chinese Journal Full-text Database. The data extraction and Meta-analysis (STATA 110) was performed by two reviewers independently. Results: 15 case-control studies and 8 nested case-control studies were included in the present study. The Meta results showed that odd radio (OR) of HBV infection in NHL when compared with the control population was 2.44 (95% CI, 2.25-2.63) in the fixed effect model and 2.49 (95% CI, 1.95-3.18) in the random effect model. There was evidence of statistical heterogeneity in all included studies (I2=86.8%，P<0.05), which disappeared in the subgroup nested case-control studies (I2=15.9%，P>0.05). OR was 2.49 (95% CI, 1.95-3.18) in the random effect model, suggesting a higher prevalence of HBV carrier state in NHL than controls. Conclusion: There is a possible causal relation between HBV infection and NHL, which needs to be confirmed by experimental and epidemiological studies.
2012, 19(2):201-205.
DOI: 10.3872/j.issn.1007-385X.2012.2.018
Abstract:
Objective:To establish a multidrug resistance cell line from human laryngeal cancer cells by 5-fluorouracil (5-Fu), and provide a research model of drug resistance mechanisms of laryngeal cancer. Methods: A multidrug resistance cell line from human laryngeal Hep-2 cancer cells (Hep-2/5-FU) was established by a high dosage intermittent increase gradient method. The morphology and cell doubling time of Hep-2 and Hep-2/5-FU cells was compared; the IC50 and drug resistance fold was detected by MTT assay; the cell cycle distribution and rhodamine accumulation in Hep-2 and Hep-2/5-Fu cells was studied by flow cytometry; and the MDR1 mRNA and the corresponding MDR1-P protein expressions were detected by real-time quantitative RT-PCR or Western blotting.Results: Hep-2/5-Fu cells was established，which had a stable resistance to 5-Fu; Hep-2/5-Fu cells exhibited cross resistance to chemotherapeutic agents like cisplatin and vincristine, and its doubling time was prolonged as compared with Hep-2 cells (\[31.25±4.37\] h vs \[25.62±353\] h, P<0.05). The proportion of cells in G0/G1 phase was increased (\[45.6±3.4\]% vs \[30.5±1.2\]%, P<0.05), while decreased in S phase (\[32.1±4.2\]% vs \[52.4±3.6\]%, P<0.05) in Hep-2/5-Fu cells as compared with those in Hep-2 cells; rhodamine accumulation in Hep-2 cells was much higher than that in Hep-2/5-Fu cells(\[89.83±0.52\]% vs \[14.38±0.48\]%, P<0.01); and the expressions of MDR1 mRNA (\[13.69±1.12\] vs \[1782±061\], P<0.05) and the corresponding MDR1-P protein were increased in Hep-2/5-Fu cells than those in Hep-2 cells. Conclusion: The Hep-2/5-Fu cell line shows the typical and stable multidrug resistance, and may serve as a research model of laryngeal cancer resistance mechanism.
Objective:To establish a multidrug resistance cell line from human laryngeal cancer cells by 5-fluorouracil (5-Fu), and provide a research model of drug resistance mechanisms of laryngeal cancer. Methods: A multidrug resistance cell line from human laryngeal Hep-2 cancer cells (Hep-2/5-FU) was established by a high dosage intermittent increase gradient method. The morphology and cell doubling time of Hep-2 and Hep-2/5-FU cells was compared; the IC50 and drug resistance fold was detected by MTT assay; the cell cycle distribution and rhodamine accumulation in Hep-2 and Hep-2/5-Fu cells was studied by flow cytometry; and the MDR1 mRNA and the corresponding MDR1-P protein expressions were detected by real-time quantitative RT-PCR or Western blotting.Results: Hep-2/5-Fu cells was established，which had a stable resistance to 5-Fu; Hep-2/5-Fu cells exhibited cross resistance to chemotherapeutic agents like cisplatin and vincristine, and its doubling time was prolonged as compared with Hep-2 cells (\[31.25±4.37\] h vs \[25.62±353\] h, P<0.05). The proportion of cells in G0/G1 phase was increased (\[45.6±3.4\]% vs \[30.5±1.2\]%, P<0.05), while decreased in S phase (\[32.1±4.2\]% vs \[52.4±3.6\]%, P<0.05) in Hep-2/5-Fu cells as compared with those in Hep-2 cells; rhodamine accumulation in Hep-2 cells was much higher than that in Hep-2/5-Fu cells(\[89.83±0.52\]% vs \[14.38±0.48\]%, P<0.01); and the expressions of MDR1 mRNA (\[13.69±1.12\] vs \[1782±061\], P<0.05) and the corresponding MDR1-P protein were increased in Hep-2/5-Fu cells than those in Hep-2 cells. Conclusion: The Hep-2/5-Fu cell line shows the typical and stable multidrug resistance, and may serve as a research model of laryngeal cancer resistance mechanism.
2012, 19(2):206-209.
DOI: 10.3872/j.issn.1007-385X.2012.2.019
Abstract:
目的：检测食管鳞状细胞癌患者外周血中辅助性T细胞17（T helper 17，Th17）和调节性T细胞（regulatory T cell，Treg）的表达，探讨食管鳞状细胞癌中Th17/Treg比例的变化与食管鳞状细胞癌转移的关系。方法：收集山东大学齐鲁医院2009年9月至2010年5月食管鳞状细胞癌患者37例，其中男22例、女15例，平均年龄（61±7.85）岁；23例健康志愿者为对照。流式细胞术检测外周血Th17的表达情况，分析Th17占CD3+T细胞的比例，同样流式细胞术检测外周血Treg的表达及其占CD4+T细胞的比例。分析Th17/Treg比例变化与食管鳞状细胞癌病理特征的相关性。结果：食管鳞状细胞癌患者外周血中Th17占CD3+T细胞的比例显著升高\[（2.11±0.66）% vs（0.84±0.19）%，P<0.01\]，Treg占CD4+T细胞的比例也显著升高\[（6.21±1.48）% vs（4.43±0.78）%，P<0.01\]；食管鳞状细胞癌患者转移组与未转移组相比，Th17比例明显升高\[（242±0.55）% vs（1.61±0.51）%，P<0.01\]，而Treg比例无明显差异。食管鳞状细胞癌患者外周血中Th17/Treg比例显著高于正常对照组\[（0.35±0.13）% vs（0.19±0.04）%，P<0.01\]；食管鳞状细胞癌患者淋巴结转移组与未转移组相比，Th17/Treg比例显著升高\[（0.39±0.13）% vs（0.29±0.10）%，P<0.05\]。结论：食管鳞状细胞癌患者外周血中Th17/Treg比例显著升高，可能参与食管鳞状细胞癌的浸润和转移。
目的：检测食管鳞状细胞癌患者外周血中辅助性T细胞17（T helper 17，Th17）和调节性T细胞（regulatory T cell，Treg）的表达，探讨食管鳞状细胞癌中Th17/Treg比例的变化与食管鳞状细胞癌转移的关系。方法：收集山东大学齐鲁医院2009年9月至2010年5月食管鳞状细胞癌患者37例，其中男22例、女15例，平均年龄（61±7.85）岁；23例健康志愿者为对照。流式细胞术检测外周血Th17的表达情况，分析Th17占CD3+T细胞的比例，同样流式细胞术检测外周血Treg的表达及其占CD4+T细胞的比例。分析Th17/Treg比例变化与食管鳞状细胞癌病理特征的相关性。结果：食管鳞状细胞癌患者外周血中Th17占CD3+T细胞的比例显著升高\[（2.11±0.66）% vs（0.84±0.19）%，P<0.01\]，Treg占CD4+T细胞的比例也显著升高\[（6.21±1.48）% vs（4.43±0.78）%，P<0.01\]；食管鳞状细胞癌患者转移组与未转移组相比，Th17比例明显升高\[（242±0.55）% vs（1.61±0.51）%，P<0.01\]，而Treg比例无明显差异。食管鳞状细胞癌患者外周血中Th17/Treg比例显著高于正常对照组\[（0.35±0.13）% vs（0.19±0.04）%，P<0.01\]；食管鳞状细胞癌患者淋巴结转移组与未转移组相比，Th17/Treg比例显著升高\[（0.39±0.13）% vs（0.29±0.10）%，P<0.05\]。结论：食管鳞状细胞癌患者外周血中Th17/Treg比例显著升高，可能参与食管鳞状细胞癌的浸润和转移。
2012, 19(2):210-214.
DOI: 10.3872/j.issn.1007-385X.2012.2.020
Abstract:
胸腺肽β4（thymosin β4，Tβ4）是一个由43个氨基酸残基组成的水溶性多肽，但并非是一个真正的胸腺激素，而是一个主要的肌动蛋白隐蔽蛋白。作为细胞骨架的结构元件，Tβ4具有多种生物学活性，其中最显著的功能是抑制炎症、促进皮肤创伤愈合、角膜修复和血管生成。Tβ4在多种类型肿瘤中表达增高，与肿瘤发生、发展及转移有密切关系；其机制可能涉及刺激肿瘤血管生成，促进肿瘤细胞上皮间质转化，增强肿瘤细胞迁移、侵袭和转移能力，以及诱导肿瘤细胞抗凋亡和耐药等。Tβ4是肿瘤转移的关键调节因子，在肿瘤分子诊断、靶向治疗方面的研究和应用正受到越来越多的关注，可能成为多种恶性肿瘤转移和预后的分子标志。
胸腺肽β4（thymosin β4，Tβ4）是一个由43个氨基酸残基组成的水溶性多肽，但并非是一个真正的胸腺激素，而是一个主要的肌动蛋白隐蔽蛋白。作为细胞骨架的结构元件，Tβ4具有多种生物学活性，其中最显著的功能是抑制炎症、促进皮肤创伤愈合、角膜修复和血管生成。Tβ4在多种类型肿瘤中表达增高，与肿瘤发生、发展及转移有密切关系；其机制可能涉及刺激肿瘤血管生成，促进肿瘤细胞上皮间质转化，增强肿瘤细胞迁移、侵袭和转移能力，以及诱导肿瘤细胞抗凋亡和耐药等。Tβ4是肿瘤转移的关键调节因子，在肿瘤分子诊断、靶向治疗方面的研究和应用正受到越来越多的关注，可能成为多种恶性肿瘤转移和预后的分子标志。
2012, 19(2):215-218.
DOI: 10.3872/j.issn.1007-385X.2012.2.021
Abstract:
免疫脂质体具有主动靶向性、降低肿瘤药物的治疗毒性、提高药物治疗指数等特点，在肿瘤治疗研究中被广泛使用作为肿瘤化疗和放疗药物、基因治疗和肿瘤影像学诊断治疗的载体。作为常见肿瘤药物治疗靶向载体，免疫脂质体可提高药物疗效，降低毒性；作为肿瘤基因治疗载体，免疫脂质体可提高siRNA的稳定性与靶向性；作为放射治疗的载体，免疫脂质体可在细胞或者亚细胞水平对肿瘤组织进行靶向显影，具有影像监测和放射性治疗的双重潜能。随着功能结构复合化、靶标优化筛选等方面的进展，免疫脂质体在肿瘤治疗领域将有更广阔的应用前景。
免疫脂质体具有主动靶向性、降低肿瘤药物的治疗毒性、提高药物治疗指数等特点，在肿瘤治疗研究中被广泛使用作为肿瘤化疗和放疗药物、基因治疗和肿瘤影像学诊断治疗的载体。作为常见肿瘤药物治疗靶向载体，免疫脂质体可提高药物疗效，降低毒性；作为肿瘤基因治疗载体，免疫脂质体可提高siRNA的稳定性与靶向性；作为放射治疗的载体，免疫脂质体可在细胞或者亚细胞水平对肿瘤组织进行靶向显影，具有影像监测和放射性治疗的双重潜能。随着功能结构复合化、靶标优化筛选等方面的进展，免疫脂质体在肿瘤治疗领域将有更广阔的应用前景。
2012, 19(2):219-223.
DOI: 10.3872/j.issn.1007-385X.2012.2.022
Abstract:
热激蛋白（heat shock protein，HSP）作为分子伴侣，在蛋白质的折叠、装配、转运和降解、机体免疫、细胞凋亡等方面发挥重要作用。HSP在多发性骨髓瘤细胞中高表达，在骨髓瘤硼替佐米耐药的发生、发展中起极为重要的作用，并已成为多发性骨髓瘤治疗的一个新靶点。与骨髓瘤患者耐药相关的HSP主要包括HSP90、HSP70、HSP27。HSP90主要通过直接与其分子伴侣结合，扰乱客户蛋白（client protein）以及影响正常的凋亡途径发挥作用，临床上HSP90抑制剂正处于广泛研究中，并发现其可逆转骨髓瘤耐药。HSP70、HSP27亦与骨髓瘤耐药相关，但具体机制尚待进一步深入研究。本文主要介绍HSP家族在骨髓瘤硼替佐米耐药中的作用，对部分机制进行探讨，并对今后的研究重点进行展望。
热激蛋白（heat shock protein，HSP）作为分子伴侣，在蛋白质的折叠、装配、转运和降解、机体免疫、细胞凋亡等方面发挥重要作用。HSP在多发性骨髓瘤细胞中高表达，在骨髓瘤硼替佐米耐药的发生、发展中起极为重要的作用，并已成为多发性骨髓瘤治疗的一个新靶点。与骨髓瘤患者耐药相关的HSP主要包括HSP90、HSP70、HSP27。HSP90主要通过直接与其分子伴侣结合，扰乱客户蛋白（client protein）以及影响正常的凋亡途径发挥作用，临床上HSP90抑制剂正处于广泛研究中，并发现其可逆转骨髓瘤耐药。HSP70、HSP27亦与骨髓瘤耐药相关，但具体机制尚待进一步深入研究。本文主要介绍HSP家族在骨髓瘤硼替佐米耐药中的作用，对部分机制进行探讨，并对今后的研究重点进行展望。
2012, 19(2):224-228.
DOI: 10.3872/j.issn.1007-385X.2012.2.023
Abstract:
细胞周期检测点激酶2（cell cycle checkpoint kinase 2，CHK2）是由抑癌基因CHEK2编码的丝氨酸/苏氨酸激酶，是DNA双链断裂后参与DNA修复应答反应的重要的信号转导蛋白。CHK2被毛细血管扩张性共济失调突变基因（ataxia telangiectasia mutated，ATM）磷酸化后，CHK2可磷酸化多个底物，包括细胞分裂周期25同源物（cell division cycle 25 homolog，Cdc25）、P53、乳腺癌遗传易感基因1（breast cancer 1, early onset，BRCA1）蛋白、E2F-1转录因子和早幼粒细胞白血病（promyelocytic leukemia，PML）蛋白，使细胞周期进程发生阻滞，促进细胞对DNA损伤进行修复或诱导凋亡。细胞在没有DNA损伤时，CHK2也可以将BRCA1磷酸化，这一过程对保持有丝分裂纺锤体组装的正确性以及染色体稳定性十分必要。基于在DNA损伤和细胞有丝分裂中的作用，CHK2有望成为抗肿瘤治疗的靶点。
细胞周期检测点激酶2（cell cycle checkpoint kinase 2，CHK2）是由抑癌基因CHEK2编码的丝氨酸/苏氨酸激酶，是DNA双链断裂后参与DNA修复应答反应的重要的信号转导蛋白。CHK2被毛细血管扩张性共济失调突变基因（ataxia telangiectasia mutated，ATM）磷酸化后，CHK2可磷酸化多个底物，包括细胞分裂周期25同源物（cell division cycle 25 homolog，Cdc25）、P53、乳腺癌遗传易感基因1（breast cancer 1, early onset，BRCA1）蛋白、E2F-1转录因子和早幼粒细胞白血病（promyelocytic leukemia，PML）蛋白，使细胞周期进程发生阻滞，促进细胞对DNA损伤进行修复或诱导凋亡。细胞在没有DNA损伤时，CHK2也可以将BRCA1磷酸化，这一过程对保持有丝分裂纺锤体组装的正确性以及染色体稳定性十分必要。基于在DNA损伤和细胞有丝分裂中的作用，CHK2有望成为抗肿瘤治疗的靶点。
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.