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Volume 24,Issue 6,2017 Table of Contents
2017, 24(6):575-580.
DOI: 10.3872/j.issn.1007-385X.2017.06.001
Abstract:
In recent years, great breakthrough progresses have been achieved in cancer immunotherapy, cytoimunotherapy with CART as a representative has achieved encouraging clinical efficacy in the treatment of hematologic tumors, immune checkpoint inhibitor, CTLA4 and PD1/PDL1 monoclonal antibodies, have been approved for clinical use in one after another. However, most of the patients with solid tumors did not get benefit from the immunotherapy. This paper summarized key problems that were difficult to resolve in the immunotherapy of solid tumors from aspects of screening individual noval antigen epitopes, maintaining viability of the immune cells , chemotaxis and invasion of the immunocytes, clinical treatment model, evaluation criterion and so on. And their coping strategies were described from the angle of clinical application.
In recent years, great breakthrough progresses have been achieved in cancer immunotherapy, cytoimunotherapy with CART as a representative has achieved encouraging clinical efficacy in the treatment of hematologic tumors, immune checkpoint inhibitor, CTLA4 and PD1/PDL1 monoclonal antibodies, have been approved for clinical use in one after another. However, most of the patients with solid tumors did not get benefit from the immunotherapy. This paper summarized key problems that were difficult to resolve in the immunotherapy of solid tumors from aspects of screening individual noval antigen epitopes, maintaining viability of the immune cells , chemotaxis and invasion of the immunocytes, clinical treatment model, evaluation criterion and so on. And their coping strategies were described from the angle of clinical application.
2 MiR1425p promotes hepatocellular carcinoma cell apoptosis induced by dexorubicin with targetting
2017, 24(6):581-587.
DOI: 10.3872/j.issn.1007-385X.2017.06.002
Abstract:
Objective:To investigate the function and molecular mechanisms of micro RNA1425p ( miR1425p) on the doxorubicin induced apoptosis of primary hepatocellular carcinoma (HCC)．Methods: Paired HCC tissues and adjacent noncancerous tissue specimens (25cm away from the lesion) were surgically collected from 88 patients who were diagnosed with primary HCC in Tumor Hospital Affiliated to Guangxi Medical University between October 2001 and July 2005. qRTPCR was used to detect the miR1425p expressions in those HCC tissues, adjacent noncancerous tissues, normal hepatocellular cell line and HCC cell lines. HCC SMMC7721 cells were transfected with miR1425p mimics, and flow cytometry was used to determine the changes in doxorubicin (1 μg/ml) induced apoptosis of SMMC7721 cells. Bioinformatics predicted that miR1425p could bind with insulinlike growth factor 2 Mrnabinding protein 3 (IGF2BP3), which was then validated by luciferase reporter gene assay. qRTPCR and Western blotting were separately used to detect the mRNA and protein expressions of IGF2BP3 in SMMC7721 cells that overexpress miR1425p. Results: Compared with the adjacent nontumor tissues, miR1425p was significantly lower in HCC tissues (-6.91±261 vs -11.59±259, P<0.01) and this decrease was also found in HCC cell line compared with normal human liver cells (P<0.01); overexpression of miR1425p significantly promoted the doxorubicin induced apoptosis of HCC SMMC7721 cells (\[49.4±3.47\]% vs \[19.50±1.74\]%, P<0.01). miR1425p overexpression could obviously inhibit the mRNA and protein expressions of IGF2BP3 in SMMC7721 cells. Luciferase reporter gene assay also showed that miR1425p overexpression could inhibit the luciferase activity of 3′UTR of IGF2BP3. Conclusion: miR1425p expression significantly decreased in both HCC tissues and HCC cell lines. miR1425p mimics transfection promoted doxorubicin induced apoptosis of HCC cells, and the mechanism probably related with miR1425p targetting IGF2BP3 and further promote the apoptosis of HCC cells.
Objective:To investigate the function and molecular mechanisms of micro RNA1425p ( miR1425p) on the doxorubicin induced apoptosis of primary hepatocellular carcinoma (HCC)．Methods: Paired HCC tissues and adjacent noncancerous tissue specimens (25cm away from the lesion) were surgically collected from 88 patients who were diagnosed with primary HCC in Tumor Hospital Affiliated to Guangxi Medical University between October 2001 and July 2005. qRTPCR was used to detect the miR1425p expressions in those HCC tissues, adjacent noncancerous tissues, normal hepatocellular cell line and HCC cell lines. HCC SMMC7721 cells were transfected with miR1425p mimics, and flow cytometry was used to determine the changes in doxorubicin (1 μg/ml) induced apoptosis of SMMC7721 cells. Bioinformatics predicted that miR1425p could bind with insulinlike growth factor 2 Mrnabinding protein 3 (IGF2BP3), which was then validated by luciferase reporter gene assay. qRTPCR and Western blotting were separately used to detect the mRNA and protein expressions of IGF2BP3 in SMMC7721 cells that overexpress miR1425p. Results: Compared with the adjacent nontumor tissues, miR1425p was significantly lower in HCC tissues (-6.91±261 vs -11.59±259, P<0.01) and this decrease was also found in HCC cell line compared with normal human liver cells (P<0.01); overexpression of miR1425p significantly promoted the doxorubicin induced apoptosis of HCC SMMC7721 cells (\[49.4±3.47\]% vs \[19.50±1.74\]%, P<0.01). miR1425p overexpression could obviously inhibit the mRNA and protein expressions of IGF2BP3 in SMMC7721 cells. Luciferase reporter gene assay also showed that miR1425p overexpression could inhibit the luciferase activity of 3′UTR of IGF2BP3. Conclusion: miR1425p expression significantly decreased in both HCC tissues and HCC cell lines. miR1425p mimics transfection promoted doxorubicin induced apoptosis of HCC cells, and the mechanism probably related with miR1425p targetting IGF2BP3 and further promote the apoptosis of HCC cells.
MA Yanping
,
WANG Nan
,
GUO Dan
,
ZHAO Yangyang
,
LIU Xiaoyan
,
YIN Jing
,
REN Qian
,
LIN Yongmin
,
MA Xiaotong
2017, 24(6):588-594.
DOI: 10.3872/j.issn.1007-385X.2017.06.003
Abstract:
Objective:To investigate the correlation between myeloproliferative leukemia virus oncogene (MPL) and Twist1 in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), and to explore whether MPL contributes to Twist1mediated cell proliferation and drug resistance of leukemia cells. Methods: Bone marrow specimens from 41 patients, who were first diagnosed as AML or CML in Hospital of Blood Diseases Affiliated to Chinese Academy of Medical Sciences between January 2005 and December 2008 (23 cases of AML, 18 cases of CML), were selected in this study. Expressions of Twist1 mRNA and MPL mRNA in hematopoietic tumor cell lines and bone marrow mononuclear cells (BMMCs) of patients with AML or CML were detected by Realtime PCR, and their correlation was analyzed. Lentiviral vector overexpressing MPL (pCDH1MPL) were constructed and transduced into myeloid leukemia cell lines K562 and U937. Effect of MPL on proliferation, colony formation and drug sensitivity of the leukemic cells were evaluated by cell counting, colony formation assay and MTT assay; in addition, whether Twist1 promote the proliferation of leukemia cells via MPL was further confirmed. Results: Overexpression of Twist1 significantly increased the protein expressions of MPL in U937 and K562 cell lines (P<0.05) while knockdown of Twist1 significantly decreased the expression of MPL (P<0.01). The mRNA expressions of Twist1 and MPL showed a significant positive correlation in BMMCs of patients with AML and CML (P<0.05). Overexpression of MPL significantly reduced the drug sensitivity of K562 and U937 cells to daunorubicin and Imatinib (P<0.01). Enforced expression of MPL in U937 and K562 cells promoted the cell growth and colony formation (all P<0.01); Twist1 knockdown with MPL overexpression significantly impaired cell growth and colony formation of leukemia cells (all P<0.01). Conclusion: Twist1 promoted proliferation, survival and chemotherapy resistance in the leukemia cells of AML and CML via MPL.
Objective:To investigate the correlation between myeloproliferative leukemia virus oncogene (MPL) and Twist1 in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), and to explore whether MPL contributes to Twist1mediated cell proliferation and drug resistance of leukemia cells. Methods: Bone marrow specimens from 41 patients, who were first diagnosed as AML or CML in Hospital of Blood Diseases Affiliated to Chinese Academy of Medical Sciences between January 2005 and December 2008 (23 cases of AML, 18 cases of CML), were selected in this study. Expressions of Twist1 mRNA and MPL mRNA in hematopoietic tumor cell lines and bone marrow mononuclear cells (BMMCs) of patients with AML or CML were detected by Realtime PCR, and their correlation was analyzed. Lentiviral vector overexpressing MPL (pCDH1MPL) were constructed and transduced into myeloid leukemia cell lines K562 and U937. Effect of MPL on proliferation, colony formation and drug sensitivity of the leukemic cells were evaluated by cell counting, colony formation assay and MTT assay; in addition, whether Twist1 promote the proliferation of leukemia cells via MPL was further confirmed. Results: Overexpression of Twist1 significantly increased the protein expressions of MPL in U937 and K562 cell lines (P<0.05) while knockdown of Twist1 significantly decreased the expression of MPL (P<0.01). The mRNA expressions of Twist1 and MPL showed a significant positive correlation in BMMCs of patients with AML and CML (P<0.05). Overexpression of MPL significantly reduced the drug sensitivity of K562 and U937 cells to daunorubicin and Imatinib (P<0.01). Enforced expression of MPL in U937 and K562 cells promoted the cell growth and colony formation (all P<0.01); Twist1 knockdown with MPL overexpression significantly impaired cell growth and colony formation of leukemia cells (all P<0.01). Conclusion: Twist1 promoted proliferation, survival and chemotherapy resistance in the leukemia cells of AML and CML via MPL.
FAN Dongmei
,
ZHANG Zixiang
,
ZHAO Yingxin
,
YANG Ming
,
ZHANG Yanjun
,
YAN Cihui
,
JIANG Yuan
,
LYU Junqiang
2017, 24(6):595-600.
DOI: 10.3872/j.issn.1007-385X.2017.06.004
Abstract:
Objective:To study the tropism and differentiation of human umbilical cord derived mesenchymal stem cell (HUMSC) to HepG2 orthotopic hepatocarcinoma. Methods: The in vitro hepatic differentiation of HUMSCs was induced by a twostep protocol; the changes in mRNA and protein expression of hepatic alphafetoprotein (AFP) and albumin (ALB) at different time points were examined by Realtime PCR and western blotting; the tropism of HUMSCs stimulated by conditional culture medium with HepG2 cells was identified by transwell assay. Subcutaeousorthotopic transplantation was used to build the HepG2 orthotopic hepatocarcinoma model in athymic BALB/c nude mice. HUMSCs were labeled with MSC.CMVLuc or MSC.AFPLuc through lentivirus transduction before orthotopically injected into hepatic parenchyma; the tropism of MSC.CMVLuc to tumor location as well as the hepatic differentiation of MSC.AFPLuc in tumorbearing liver was monitored by using IVIS living imaging system. Results：The in vitro hepatic differentiation of HUMSCs was successfully induced in vitrowith morphological changes, and the mRNA and protein levels of AFP and ALB significantly elevated after the culture (P<0.05); the tropism of HUMSCs to HepG2 cells was in a dosedependent manner (P<001). MSC.CMVLuc, which injected intravenously, migrated to liver after 48 h; and the luciferase signal in the liver of rats was enhanced on day 5. MSC.AFPLuc developed hepatic differentiation after 24 h of in situ transplantation; at day 7 of posttransplantation, the activity of AFP promoter was at the highest, while, its activity was undetectable at day 9. Conclusion：It was confirmed the tropism and differentiation of HUMSCs to liver by in vitro and in vivo experiments. This study may provide a new strategy of target gene therapy for hepatocarcinoma by using MSCs.
Objective:To study the tropism and differentiation of human umbilical cord derived mesenchymal stem cell (HUMSC) to HepG2 orthotopic hepatocarcinoma. Methods: The in vitro hepatic differentiation of HUMSCs was induced by a twostep protocol; the changes in mRNA and protein expression of hepatic alphafetoprotein (AFP) and albumin (ALB) at different time points were examined by Realtime PCR and western blotting; the tropism of HUMSCs stimulated by conditional culture medium with HepG2 cells was identified by transwell assay. Subcutaeousorthotopic transplantation was used to build the HepG2 orthotopic hepatocarcinoma model in athymic BALB/c nude mice. HUMSCs were labeled with MSC.CMVLuc or MSC.AFPLuc through lentivirus transduction before orthotopically injected into hepatic parenchyma; the tropism of MSC.CMVLuc to tumor location as well as the hepatic differentiation of MSC.AFPLuc in tumorbearing liver was monitored by using IVIS living imaging system. Results：The in vitro hepatic differentiation of HUMSCs was successfully induced in vitrowith morphological changes, and the mRNA and protein levels of AFP and ALB significantly elevated after the culture (P<0.05); the tropism of HUMSCs to HepG2 cells was in a dosedependent manner (P<001). MSC.CMVLuc, which injected intravenously, migrated to liver after 48 h; and the luciferase signal in the liver of rats was enhanced on day 5. MSC.AFPLuc developed hepatic differentiation after 24 h of in situ transplantation; at day 7 of posttransplantation, the activity of AFP promoter was at the highest, while, its activity was undetectable at day 9. Conclusion：It was confirmed the tropism and differentiation of HUMSCs to liver by in vitro and in vivo experiments. This study may provide a new strategy of target gene therapy for hepatocarcinoma by using MSCs.
2017, 24(6):601-607.
DOI: 10.3872/j.issn.1007-385X.2017.06.005
Abstract:
Objective:This study aimed to explore the mechanism of tamoxifen (TAM) resistance caused by IL6 in ovarian cancer cells. Methods: Human ovarian cancer A2780 cell line that endogenously overexpressing IL6 and human ovarian cancer CAOV3 cell line that exogenously depleting IL6 were constructed; exogenous IL6 (50 ng/ml) were used for pretreatment of A2780 cells (A2780/perIL6 cells), and Western blotting was used to detect the effect of endogenous/exogenous IL6 on the phosphorylation level of ERα Ser167 in ovarian cancer cells; IL6 and/or Wortmannin (PI3K inhibitor) were used to treat A2780 cells and western blotting was used to detect their effect on the phosphorylation of Akt and ERα; MTT assay was used to detect the effect of Wortmannin and endogenous/exogenous IL6 on the sensitivity of A2780 cells to TAM; luciferase reporter assay was performed to detect transcription activity of ERα in ovarian cancer cells, and to explore the possible signaling pathway. Results: Both exogenous and endogenous overexpression of IL6 could obviously increase the level of ERα Ser167 phosphorylation in A2780 cells (all P<0.01), while endogenous depletion of IL6 could reduce the level of ERα Ser167 phosphorylation in CAOV3 cells (P<0.01). It also found that wortmannin (PI3K inhibitor) could significantly antagonize IL6induced TAM resistance and phosphorylation of ERα Ser167. IL6 promoted ERa transcription activity, while this activation was not blocked by the PI3Kspecific inhibitor wortmannin. Conclusion: These results indicate that IL6 could induce ERa phosphorylation by triggering PI3K/Akt signaling pathway to activate the ER pathway, and thereby induce the resistance of ovarian cancer cells to TAM.
Objective:This study aimed to explore the mechanism of tamoxifen (TAM) resistance caused by IL6 in ovarian cancer cells. Methods: Human ovarian cancer A2780 cell line that endogenously overexpressing IL6 and human ovarian cancer CAOV3 cell line that exogenously depleting IL6 were constructed; exogenous IL6 (50 ng/ml) were used for pretreatment of A2780 cells (A2780/perIL6 cells), and Western blotting was used to detect the effect of endogenous/exogenous IL6 on the phosphorylation level of ERα Ser167 in ovarian cancer cells; IL6 and/or Wortmannin (PI3K inhibitor) were used to treat A2780 cells and western blotting was used to detect their effect on the phosphorylation of Akt and ERα; MTT assay was used to detect the effect of Wortmannin and endogenous/exogenous IL6 on the sensitivity of A2780 cells to TAM; luciferase reporter assay was performed to detect transcription activity of ERα in ovarian cancer cells, and to explore the possible signaling pathway. Results: Both exogenous and endogenous overexpression of IL6 could obviously increase the level of ERα Ser167 phosphorylation in A2780 cells (all P<0.01), while endogenous depletion of IL6 could reduce the level of ERα Ser167 phosphorylation in CAOV3 cells (P<0.01). It also found that wortmannin (PI3K inhibitor) could significantly antagonize IL6induced TAM resistance and phosphorylation of ERα Ser167. IL6 promoted ERa transcription activity, while this activation was not blocked by the PI3Kspecific inhibitor wortmannin. Conclusion: These results indicate that IL6 could induce ERa phosphorylation by triggering PI3K/Akt signaling pathway to activate the ER pathway, and thereby induce the resistance of ovarian cancer cells to TAM.
2017, 24(6):608-614.
DOI: 10.3872/j.issn.1007-385X.2017.06.006
Abstract:
Objective:Lung adenocarcinoma SPCA1 cell line that stably overexpresses microsomal glutathione Stransferase 1 (MGST1) was constructed to explore the function and mechanism of MGST1 in lung adenocarcinoma.Methods:The recombinant plasmid pcDNA3MGST1 and the empty vector pcDNA3 were transfected into SPCA1 by Lipofectaminemediated method; after being screened by G418, stably transfected cells were labeled and divided into pcDNA3MGST1 group and empty vector pcDNA3 group. qRTPCR and Western blotting were used to detect the expression of MGST1 at mRNA and protein level in stable cells. MTS was used to detect the viability of cells. Flow cytometry and Western blotting were used to detect the cell apoptotic rate and the downstream apoptotic proteins induced by H2O2, respectively. Results: The results of sequencing showed that the recombinant plasmid pcDNA3MGST1 was successfully constructed, and the stable cell line with G418 resistance was obtained. The mRNA and protein level of MGST1 in pcDNA3MGST1 group were all significantly elevated (P<0.01), and the cell viability was significantly increased (P<0.05). Under the induction of H2O2, the early apoptosis rate of pcDNA3MGST1 group was significantly lower than that of pcDNA3 group (\[3.30±0.40\]% vs \[6.50±0.95\]%, P<0.05). The expressions of apoptotic proteins (caspase 9, caspase3 and PARP) increased, and the expressions of cleavedcaspase 9, cleavedcaspase 3 and cleavedPARP were significantly decreased in pcDNA3MGST1 group. Conclusion: The lung adenocarcinoma cell line SPCA1, which stably overexpresses human MGST1, has been successfully established. It was found that MGST1 could inhibit the apoptosis of lung adenocarcinoma cells by regulating caspase apoptosis pathway, which laid the experimental foundation for the followup study.
Objective:Lung adenocarcinoma SPCA1 cell line that stably overexpresses microsomal glutathione Stransferase 1 (MGST1) was constructed to explore the function and mechanism of MGST1 in lung adenocarcinoma.Methods:The recombinant plasmid pcDNA3MGST1 and the empty vector pcDNA3 were transfected into SPCA1 by Lipofectaminemediated method; after being screened by G418, stably transfected cells were labeled and divided into pcDNA3MGST1 group and empty vector pcDNA3 group. qRTPCR and Western blotting were used to detect the expression of MGST1 at mRNA and protein level in stable cells. MTS was used to detect the viability of cells. Flow cytometry and Western blotting were used to detect the cell apoptotic rate and the downstream apoptotic proteins induced by H2O2, respectively. Results: The results of sequencing showed that the recombinant plasmid pcDNA3MGST1 was successfully constructed, and the stable cell line with G418 resistance was obtained. The mRNA and protein level of MGST1 in pcDNA3MGST1 group were all significantly elevated (P<0.01), and the cell viability was significantly increased (P<0.05). Under the induction of H2O2, the early apoptosis rate of pcDNA3MGST1 group was significantly lower than that of pcDNA3 group (\[3.30±0.40\]% vs \[6.50±0.95\]%, P<0.05). The expressions of apoptotic proteins (caspase 9, caspase3 and PARP) increased, and the expressions of cleavedcaspase 9, cleavedcaspase 3 and cleavedPARP were significantly decreased in pcDNA3MGST1 group. Conclusion: The lung adenocarcinoma cell line SPCA1, which stably overexpresses human MGST1, has been successfully established. It was found that MGST1 could inhibit the apoptosis of lung adenocarcinoma cells by regulating caspase apoptosis pathway, which laid the experimental foundation for the followup study.
2017, 24(6):615-619.
DOI: 10.3872/j.issn.1007-385X.2017.06.007
Abstract:
Objective:To study the mechanism of ginsenoside Rg3 inhibiting the proliferation of breast cancer MDAMB231 cells via regulation of mammaglobinA (MGBA) expression. Methods: MTT assay and flow cytometry was used to detect the effect of different concentrations (5,10,15 μg/ml) of Rg3 on the proliferation and apoptosis of breast cancer cells; Western blotting was used to detect the expression of MGBA in breast cancer cells. MDAMB231 cells were treated with Rg3 and/or siRNAMGBA; MTT and Flow cytometry were used to detect their effect on the proliferation and apoptosis of treated cells while Western blotting was used to detect the expression of MGBA in cells; sulfur electrode assay was used to detect H2S secretion in breast cancer MDAMB231 cells. Results:48 h after cell treatment, the inhibitory rates on proliferation of MDAMB231 cells in Rg3 groups (5,10,15 μg/ml) were significantly higher than that of control group (\[18.78±0.82\]%, \[33.25±1.17\]%, \[35.11±0.94\]% vs \[9.72±0.91\]%, all P<0.05\]; Rg3 promoted the apoptosis of MDAMB231 cells (P<0.05), and significantly enhanced the expression of MGBA protein in MDAMB231 cells (P<0.05); Compared with the control group, the inhibitory rate on proliferation of MDAMB231 cells in Rg3 group was significantly increased (\[30.12±1.01)% vs (10.66±0.59)%, P<0.05\], while the inhibitory rates in Rg3+siRNAMGBA and siRNAMGBA group were significantly reduced (\[6.61±0.63\]%, \[702±0.46\]% vs \[1066±0.59\]%, all P<0.05); The expression of MGBA and cystathionineγ lyase (CSE) as well as the secretion of H2S in Rg3 group were significantly enhanced; however, their expressions in Rg3 + siRNAMGBA group and siRNAMGBA group were significantly inhibited（all P<0.05）. Conclusion: Rg3 can significantly inhibit the growth of MDAMB231 breast cancer cells and promote its apoptosis, and this effect may be realized by enhancing MGBA expression and activating H2S/CSE system.
Objective:To study the mechanism of ginsenoside Rg3 inhibiting the proliferation of breast cancer MDAMB231 cells via regulation of mammaglobinA (MGBA) expression. Methods: MTT assay and flow cytometry was used to detect the effect of different concentrations (5,10,15 μg/ml) of Rg3 on the proliferation and apoptosis of breast cancer cells; Western blotting was used to detect the expression of MGBA in breast cancer cells. MDAMB231 cells were treated with Rg3 and/or siRNAMGBA; MTT and Flow cytometry were used to detect their effect on the proliferation and apoptosis of treated cells while Western blotting was used to detect the expression of MGBA in cells; sulfur electrode assay was used to detect H2S secretion in breast cancer MDAMB231 cells. Results:48 h after cell treatment, the inhibitory rates on proliferation of MDAMB231 cells in Rg3 groups (5,10,15 μg/ml) were significantly higher than that of control group (\[18.78±0.82\]%, \[33.25±1.17\]%, \[35.11±0.94\]% vs \[9.72±0.91\]%, all P<0.05\]; Rg3 promoted the apoptosis of MDAMB231 cells (P<0.05), and significantly enhanced the expression of MGBA protein in MDAMB231 cells (P<0.05); Compared with the control group, the inhibitory rate on proliferation of MDAMB231 cells in Rg3 group was significantly increased (\[30.12±1.01)% vs (10.66±0.59)%, P<0.05\], while the inhibitory rates in Rg3+siRNAMGBA and siRNAMGBA group were significantly reduced (\[6.61±0.63\]%, \[702±0.46\]% vs \[1066±0.59\]%, all P<0.05); The expression of MGBA and cystathionineγ lyase (CSE) as well as the secretion of H2S in Rg3 group were significantly enhanced; however, their expressions in Rg3 + siRNAMGBA group and siRNAMGBA group were significantly inhibited（all P<0.05）. Conclusion: Rg3 can significantly inhibit the growth of MDAMB231 breast cancer cells and promote its apoptosis, and this effect may be realized by enhancing MGBA expression and activating H2S/CSE system.
2017, 24(6):620-626.
DOI: 10.3872/j.issn.1007-385X.2017.06.008
Abstract:
Objective:Toinvestigate the effect of melatonin (MT) on humanlaryngeal cancercells and its ability to enhance the sensitivity of humanlaryngeal cancercells tocisplatin (DDP) treatment, this study was performed. Methods: Hep2 human laryngeal cancer cells were treated with various concentrations of MT and/or DDP in vitro for various times. Then cells proliferation was detected by CCK8 assays and cell apoptosis or cell cycle was assayed by flow cytometry. The coefficient of drug interaction (CDI) was used to evaluate whether MT could affect the sensitivity of Hep2 cells to DDP. Results：It was demonstrated by CCK8 assays that MT or DDP used alone inhibited the proliferation of Hep2 cells in a dosedependent manner.Combined treatment with MT and DDP synergistically inhibited the proliferation of Hep2 cells with the synergism between two drugs (CDI<1). Furthermore,flow cytometry results showed that MT promoted apoptotic cells and the proportion of cells in subG1 phase in Hep2 cells, and cotreatment with MT and DDP increased apoptotic cells （the apoptotic rate of cells in the 0.5 mmol/L MT and 20 μg/ml DDP combination group was significantly higher than that in 20 μg/ml DDP group, \[40.9±3.0\]% vs \[11.0±09\]%, P<0.01) and the proportion of cells in subG1 phase (the proportion of cells in subG1 phase in the 0.5 mmol/L MT and 20 μg/ml DDP combination group was significantly higher than that in 20 μg/ml DDP group, \[73.0±2.4\]% vs \[40.4±3.0\]%, P<0.01). Caspase inhibitor ZVADfmk reversed the suppression of Hep2 cell proliferation and the induction of Hep2 cell apoptosis by MT and/or DDP (both P<0.01). Conclusions：Our findings demonstrate that melatonin can induce Hep2 human laryngeal cancer cell apoptosis in caspasedependent manners, thereby synergistically enhancing the suppressive effects of cisplatin on human laryngealcancercellproliferation.
Objective:Toinvestigate the effect of melatonin (MT) on humanlaryngeal cancercells and its ability to enhance the sensitivity of humanlaryngeal cancercells tocisplatin (DDP) treatment, this study was performed. Methods: Hep2 human laryngeal cancer cells were treated with various concentrations of MT and/or DDP in vitro for various times. Then cells proliferation was detected by CCK8 assays and cell apoptosis or cell cycle was assayed by flow cytometry. The coefficient of drug interaction (CDI) was used to evaluate whether MT could affect the sensitivity of Hep2 cells to DDP. Results：It was demonstrated by CCK8 assays that MT or DDP used alone inhibited the proliferation of Hep2 cells in a dosedependent manner.Combined treatment with MT and DDP synergistically inhibited the proliferation of Hep2 cells with the synergism between two drugs (CDI<1). Furthermore,flow cytometry results showed that MT promoted apoptotic cells and the proportion of cells in subG1 phase in Hep2 cells, and cotreatment with MT and DDP increased apoptotic cells （the apoptotic rate of cells in the 0.5 mmol/L MT and 20 μg/ml DDP combination group was significantly higher than that in 20 μg/ml DDP group, \[40.9±3.0\]% vs \[11.0±09\]%, P<0.01) and the proportion of cells in subG1 phase (the proportion of cells in subG1 phase in the 0.5 mmol/L MT and 20 μg/ml DDP combination group was significantly higher than that in 20 μg/ml DDP group, \[73.0±2.4\]% vs \[40.4±3.0\]%, P<0.01). Caspase inhibitor ZVADfmk reversed the suppression of Hep2 cell proliferation and the induction of Hep2 cell apoptosis by MT and/or DDP (both P<0.01). Conclusions：Our findings demonstrate that melatonin can induce Hep2 human laryngeal cancer cell apoptosis in caspasedependent manners, thereby synergistically enhancing the suppressive effects of cisplatin on human laryngealcancercellproliferation.
2017, 24(6):627-631.
DOI: 10.3872/j.issn.1007-385X.2017.06.009
Abstract:
Objective:Objective: To investigate the effects of 5AzaCdR on expression of excision repair cross complementation group 1 (ERCC1) in ovarian cancer cell line SKOV3 and its possible mechanism.Methods: shRNA that specifically targeting DNA methyltransferase 1 (DNMT1) was constructed and transfected into SKOV3 cells. Western blotting was applied to determine the expressions of DNMT1 and ERCC1 in SKOV3 cells; Ovarian cancer cell line SKOV3 was treated with 5AzaCdR of various concentrations for different time courses, and Western blotting was used to determine the protein changes of DNMT1 and ERCC1 before and after the treatment; and the methylation level of ERCC1 promoter was tested by Sodium Bisulfite method. Results: After being treated with 5AzaCdR (at the concentrations of 0.5, 1.0, 20, 4.0 μmol/L), the expression of DNMT1 protein in SKOV3 cells was decreased in a dosedependent manner while the ERCC1 protein was increased in a timedependent manner; With the treatment of 5AzaCdR (concentration of 1.0 μmol/L) for 12, 24 and 36 h, the expression of DNMT1 protein was decreased and the ERCC1 protein was increased in SKOV3 cells, and the expression both changed in a timedependent manner. Sodium Bisulfite method indicated that the methylation of ERCC1 promoter was at high level before the treatment; However, after the treatment of 5AzaCdR at concentration of 1.0 μmol/L, the promoter of ERCC1 showed demethylation．Conclusion: 5AzaCdR regulates the methylation of ERCC1 promoter and its expression in SKOV3 cells via.
Objective:Objective: To investigate the effects of 5AzaCdR on expression of excision repair cross complementation group 1 (ERCC1) in ovarian cancer cell line SKOV3 and its possible mechanism.Methods: shRNA that specifically targeting DNA methyltransferase 1 (DNMT1) was constructed and transfected into SKOV3 cells. Western blotting was applied to determine the expressions of DNMT1 and ERCC1 in SKOV3 cells; Ovarian cancer cell line SKOV3 was treated with 5AzaCdR of various concentrations for different time courses, and Western blotting was used to determine the protein changes of DNMT1 and ERCC1 before and after the treatment; and the methylation level of ERCC1 promoter was tested by Sodium Bisulfite method. Results: After being treated with 5AzaCdR (at the concentrations of 0.5, 1.0, 20, 4.0 μmol/L), the expression of DNMT1 protein in SKOV3 cells was decreased in a dosedependent manner while the ERCC1 protein was increased in a timedependent manner; With the treatment of 5AzaCdR (concentration of 1.0 μmol/L) for 12, 24 and 36 h, the expression of DNMT1 protein was decreased and the ERCC1 protein was increased in SKOV3 cells, and the expression both changed in a timedependent manner. Sodium Bisulfite method indicated that the methylation of ERCC1 promoter was at high level before the treatment; However, after the treatment of 5AzaCdR at concentration of 1.0 μmol/L, the promoter of ERCC1 showed demethylation．Conclusion: 5AzaCdR regulates the methylation of ERCC1 promoter and its expression in SKOV3 cells via.
GU Lina
,
SANG Meixiang
,
YIN Danjing
,
LIU Fei
,
LIU Shina
,
HUANG Weina
,
WANG Pengyu
,
LIAN Yishui
,
SHAN Baoen
2017, 24(6):632-639.
DOI: 10.3872/j.issn.1007-385X.2017.06.010
Abstract:
Objective:To investigate the expression of melanoma antigen (MAGE)As in nonsmall cell carcinoma (NSCLC), and to explore its correlation with clinical pathological indicators and the prognosis. Methods: NSCLC tissue samples (n=90) and paracarcinoma tissue samples (n=90) were collected from 90 patients with NSCLC who were surgically treated in Fourth Hospital of Hebei Medical University between September of 2005 and March of 2006. The expression of MAGEAs protein in the 90 paired tissues was detected by immunohistochemistry assay, and its correlation to NSCLC clinical pathological indicators was analyzed. In addition, EGFR amplification and ALK rearrangements of NSCLC patients were detected by fluorescent in situ hybridization, and the association between MAGEAs expression and EGFR amplification and ALK rearrangements was analyzed with Spearman correlation analysis. The survival of NSCLC patients with positive MAGEAs expression was analyzed by KaplanMeier method. Cox regression model was used for univariate analysis and multivariate analysis of correlations between positive expression of MAGEAs and clinical pathological indicators. Results: The positive rates of MAGEAs protein in NSCLC were significantly higher than that of noncancerous tissues (P<0.05). MAGEAs expression was not correlated with clinical pathological indicators of NSCLC patients, EGFR amplification and ALK rearrangements(P>0.05). Logrank test showed that the survival time of NSCLC patients with positive MAGEAs expression were lower than those with negative expression (P<0.05); However, EGFR amplification and ALK rearrangements were not associated with the overall survival of NSCLC patients. Results from multivariate analyses showed that the expression of MAGEAs, clinical stage, lymph node metastasis were independent risk factors of NSCLC. Conclusion: MAGEAs proteins are NSCLCassociated antigens, thus having potential diagnostic and prognostic significance in clinical settings.
Objective:To investigate the expression of melanoma antigen (MAGE)As in nonsmall cell carcinoma (NSCLC), and to explore its correlation with clinical pathological indicators and the prognosis. Methods: NSCLC tissue samples (n=90) and paracarcinoma tissue samples (n=90) were collected from 90 patients with NSCLC who were surgically treated in Fourth Hospital of Hebei Medical University between September of 2005 and March of 2006. The expression of MAGEAs protein in the 90 paired tissues was detected by immunohistochemistry assay, and its correlation to NSCLC clinical pathological indicators was analyzed. In addition, EGFR amplification and ALK rearrangements of NSCLC patients were detected by fluorescent in situ hybridization, and the association between MAGEAs expression and EGFR amplification and ALK rearrangements was analyzed with Spearman correlation analysis. The survival of NSCLC patients with positive MAGEAs expression was analyzed by KaplanMeier method. Cox regression model was used for univariate analysis and multivariate analysis of correlations between positive expression of MAGEAs and clinical pathological indicators. Results: The positive rates of MAGEAs protein in NSCLC were significantly higher than that of noncancerous tissues (P<0.05). MAGEAs expression was not correlated with clinical pathological indicators of NSCLC patients, EGFR amplification and ALK rearrangements(P>0.05). Logrank test showed that the survival time of NSCLC patients with positive MAGEAs expression were lower than those with negative expression (P<0.05); However, EGFR amplification and ALK rearrangements were not associated with the overall survival of NSCLC patients. Results from multivariate analyses showed that the expression of MAGEAs, clinical stage, lymph node metastasis were independent risk factors of NSCLC. Conclusion: MAGEAs proteins are NSCLCassociated antigens, thus having potential diagnostic and prognostic significance in clinical settings.
2017, 24(6):640-644.
DOI: 10.3872/j.issn.1007-385X.2017.06.011
Abstract:
Objective:To investigate the effect of nonA5.1 type MHC class Ⅰrelated molecules A (MICA) transmembrane allele on the treatment efficacy of chemotherapy combined with NK cell immunotherapy in advanced esophageal cancer patients. Methods: One hundred and fiftytwo patients with advanced esophageal cancer (TNM ⅢⅣa) underwent systemic chemotherapy after palliative surgery between April, 2013 and October, 2015 were included in this study. According to whether the MICA transmembrane allele was A5.1, patients were divided into four groups to observe the clinical efficacy: A5.1 chemotherapy + NK cell therapy (A5.1+NK group); A5.1 chemotherapy alone (A5.1 group); nonA5.1 chemotherapy+NK cell therapy (non A5.1+NK group); nonA5.1 chemotherapy alone (non A5.1 group). Eukaryotic expression vector pTE1A5.1 carrying MICA allele A5.1 was constructed and used to transfect esophageal cancer TE1 cell line. Western blotting was used to detect the effect of pTE1A5.1 transfection on the expression of MICA protein in TE1 cells. The sensitivity change of TE1 cells to NK cells before and after the transfection was detected by LDH. ELISA was used to detect the soluble MICA in serum of esophageal cancer patients and the soluble MICA content in the supernatant of TE1 cells before and after transfection with pTE1A5.1. Results: After 3 years of followup, the medium overall survival (mOS) of A5.1+NK group, A5.1group, non A5.1+NK group and non A5.1 group were 15.0 months, 16.0 months, 22.4 months and 16.0 months, respectively. The mOS of non A5.1+NK group was significantly longer than that of other groups (P<0.05). There was no significant correlation between age, sex, ECOG score, genotype and prognosis by Cox multivariate regression analysis (P>0.05). The cross analysis of genotype and NK therapy showed that the mOS of non A5.1+NK group was significantly longer than that of the other three groups (P<0.05). The expression of MICA in TE1 cells was significantly increased after transfection with pTE1A5.1, and the soluble MICA secretion in culture supernatant was significantly increased (\[256.2±45.3\] vs \[45.3±11.5\] pg/ml, P<0.01). Compared with pretransfection, the killing rate of NK cells on TE1 cells overexpressing MICA was significantly decreased (\[29.5±7.2\]% vs \[42.5±7.1\]%, P<0.05).Conclusion: Compared with esophageal patients with MICAA5.1 allele, the efficacy of combined treatment of NK cell therapy and chemotherapy for patients with MICAnon A5.1 is better, which is closely related to low level of soluble MICA.
Objective:To investigate the effect of nonA5.1 type MHC class Ⅰrelated molecules A (MICA) transmembrane allele on the treatment efficacy of chemotherapy combined with NK cell immunotherapy in advanced esophageal cancer patients. Methods: One hundred and fiftytwo patients with advanced esophageal cancer (TNM ⅢⅣa) underwent systemic chemotherapy after palliative surgery between April, 2013 and October, 2015 were included in this study. According to whether the MICA transmembrane allele was A5.1, patients were divided into four groups to observe the clinical efficacy: A5.1 chemotherapy + NK cell therapy (A5.1+NK group); A5.1 chemotherapy alone (A5.1 group); nonA5.1 chemotherapy+NK cell therapy (non A5.1+NK group); nonA5.1 chemotherapy alone (non A5.1 group). Eukaryotic expression vector pTE1A5.1 carrying MICA allele A5.1 was constructed and used to transfect esophageal cancer TE1 cell line. Western blotting was used to detect the effect of pTE1A5.1 transfection on the expression of MICA protein in TE1 cells. The sensitivity change of TE1 cells to NK cells before and after the transfection was detected by LDH. ELISA was used to detect the soluble MICA in serum of esophageal cancer patients and the soluble MICA content in the supernatant of TE1 cells before and after transfection with pTE1A5.1. Results: After 3 years of followup, the medium overall survival (mOS) of A5.1+NK group, A5.1group, non A5.1+NK group and non A5.1 group were 15.0 months, 16.0 months, 22.4 months and 16.0 months, respectively. The mOS of non A5.1+NK group was significantly longer than that of other groups (P<0.05). There was no significant correlation between age, sex, ECOG score, genotype and prognosis by Cox multivariate regression analysis (P>0.05). The cross analysis of genotype and NK therapy showed that the mOS of non A5.1+NK group was significantly longer than that of the other three groups (P<0.05). The expression of MICA in TE1 cells was significantly increased after transfection with pTE1A5.1, and the soluble MICA secretion in culture supernatant was significantly increased (\[256.2±45.3\] vs \[45.3±11.5\] pg/ml, P<0.01). Compared with pretransfection, the killing rate of NK cells on TE1 cells overexpressing MICA was significantly decreased (\[29.5±7.2\]% vs \[42.5±7.1\]%, P<0.05).Conclusion: Compared with esophageal patients with MICAA5.1 allele, the efficacy of combined treatment of NK cell therapy and chemotherapy for patients with MICAnon A5.1 is better, which is closely related to low level of soluble MICA.
2017, 24(6):645-649.
DOI: 10.3872/j.issn.1007-385X.2017.06.012
Abstract:
Objective:To investigate the expression and clinical significance of lncRNA AC007009.1 in tissue samples of nonsmall cell lung cancer (NSCLC). Methods: The expression of lncRNA AC007009.1 in 105 NSCLC tissue samples, 72 adjacent normal tissue samples and 33 normal tissue samples was detected by qRTPCR method; and the relationship between lncRNA AC007009.1 expression and clinical pathological characteristics of NSCLC was analyzed; in addition, the correlation between lncRNAAC007009.1 expression and the OS and PFS of NSCLC patients was also analyzed. Results: Expression of lncRNAAC007009.1 was significantly increased in tumor tissues than that in noncancerous tissues (5.30±1.96 vs 1.01±0.33, 0.99±0.29，P<0.01). AC007009.1 expression was positively correlated with disease stage，distant metastasis，pathological type and survival status (P<0.05); Moreover, the OS and PFS of patients with high lncRNAAC007009.1 expression were significantly shorter than the patients with low expression (P<0.01). Cox multivariate analysis also indicated that lncRNAAC007009.1 expression, disease stage, distant metastasis were the independent prognostic markers for NSCLC (all P<0.05). Conclusion: LncRNA AC007009.1 is involved in the development of NSCLC, and can be used as a molecular marker for the diagnosis and prognosis of nonsmall cell lung cancer.
Objective:To investigate the expression and clinical significance of lncRNA AC007009.1 in tissue samples of nonsmall cell lung cancer (NSCLC). Methods: The expression of lncRNA AC007009.1 in 105 NSCLC tissue samples, 72 adjacent normal tissue samples and 33 normal tissue samples was detected by qRTPCR method; and the relationship between lncRNA AC007009.1 expression and clinical pathological characteristics of NSCLC was analyzed; in addition, the correlation between lncRNAAC007009.1 expression and the OS and PFS of NSCLC patients was also analyzed. Results: Expression of lncRNAAC007009.1 was significantly increased in tumor tissues than that in noncancerous tissues (5.30±1.96 vs 1.01±0.33, 0.99±0.29，P<0.01). AC007009.1 expression was positively correlated with disease stage，distant metastasis，pathological type and survival status (P<0.05); Moreover, the OS and PFS of patients with high lncRNAAC007009.1 expression were significantly shorter than the patients with low expression (P<0.01). Cox multivariate analysis also indicated that lncRNAAC007009.1 expression, disease stage, distant metastasis were the independent prognostic markers for NSCLC (all P<0.05). Conclusion: LncRNA AC007009.1 is involved in the development of NSCLC, and can be used as a molecular marker for the diagnosis and prognosis of nonsmall cell lung cancer.
2017, 24(6):650-655.
DOI: 10.3872/j.issn.1007-385X.2017.06.013
Abstract:
Objective:To detect the expressions of 21 cytokines (ITAC\[IFNinducible T cell α chemoattractant\], GMCSF, Fractalkine, IFNγ, L10, MIP3α \[macrophage inflammatory protein3α\], IL12(p70), IL13, IL17A, IL1β, IL2, IL4, IL21, IL23, IL5, IL6, IL7, IL8, MIP1α, MIP1β and TNFα) in serum of patients with lung cancer, and analyze their clinical significance. Methods: Thirty healthy controls and forty newly diagnosed patients with lung cancer before treatment were enrolled for the detection of serum levels of 21 cytokines by liquid chip. The correlations between clinical characteristics of lung cancer and these cytokines were analyzed; in addition, the correlations between significantly differentiallyexpressed cytokines were also analyzed.Results: The expressions of 11 cytokines, including GMCSF, IFNγ, IL12(P70), IL1β, IL2, IL6, IL7, TNFα, Fractalkine, IL8, and MIP3α(P<0.05 or P<0.01) in serum of patients with lung cancer were significantly higher than those in control group. However, there was no significant difference in the serum levels of 21 cytokines between nonmetastasis group and metastasis group of lung cancer patients. The serum expressions of IFNγ(P<0.05) and MIP1β(P<0.05) in lung adenocarcinoma (AC) patients were significantly higher than that in squamous cell carcinoma (SCC) patients. And the expression of ITAC (P<005) in SCC group was significantly higher than that in small cell lung carcinoma group (SCLC group). The 11 highly expressed cytokines showed different correlations in two groups. Conclusion: The expressions of 11 cytokines were significantly increased in patients with lung cancer, including IL6 and IL8 etc. It suggested that they may be involved in the development of lung cancer. These highly expressed cytokines may be used for the diagnosis of lung cancer, and may provide new targeting for the research of lung cancer treatment.
Objective:To detect the expressions of 21 cytokines (ITAC\[IFNinducible T cell α chemoattractant\], GMCSF, Fractalkine, IFNγ, L10, MIP3α \[macrophage inflammatory protein3α\], IL12(p70), IL13, IL17A, IL1β, IL2, IL4, IL21, IL23, IL5, IL6, IL7, IL8, MIP1α, MIP1β and TNFα) in serum of patients with lung cancer, and analyze their clinical significance. Methods: Thirty healthy controls and forty newly diagnosed patients with lung cancer before treatment were enrolled for the detection of serum levels of 21 cytokines by liquid chip. The correlations between clinical characteristics of lung cancer and these cytokines were analyzed; in addition, the correlations between significantly differentiallyexpressed cytokines were also analyzed.Results: The expressions of 11 cytokines, including GMCSF, IFNγ, IL12(P70), IL1β, IL2, IL6, IL7, TNFα, Fractalkine, IL8, and MIP3α(P<0.05 or P<0.01) in serum of patients with lung cancer were significantly higher than those in control group. However, there was no significant difference in the serum levels of 21 cytokines between nonmetastasis group and metastasis group of lung cancer patients. The serum expressions of IFNγ(P<0.05) and MIP1β(P<0.05) in lung adenocarcinoma (AC) patients were significantly higher than that in squamous cell carcinoma (SCC) patients. And the expression of ITAC (P<005) in SCC group was significantly higher than that in small cell lung carcinoma group (SCLC group). The 11 highly expressed cytokines showed different correlations in two groups. Conclusion: The expressions of 11 cytokines were significantly increased in patients with lung cancer, including IL6 and IL8 etc. It suggested that they may be involved in the development of lung cancer. These highly expressed cytokines may be used for the diagnosis of lung cancer, and may provide new targeting for the research of lung cancer treatment.
2017, 24(6):656-659.
DOI: 10.3872/j.issn.1007-385X.2017.06.014
Abstract:
Objective:To determine the change of serum anterior gradient2 (AGR2) level before and after surgery in bladder cancer patients, and to investigate its significance in predicting prognosis. Methods:The peripheral venous blood samples were collected from 40 patients with bladder cancer who accepted surgery (bladder cancer group) and 20 healthy controls (control group).The level of serum AGR2 was detected by enzyme linked immunosorbent assay (ELISA). The relationship between the level of serum AGR2 and clinicopathologic characteristics as well as prognosis prediction of bladder cancer was analyzed. Results: The level of serum AGR2 in the patients with bladder cancer was significantly higher than that in normal controls (\[28.93±6.03\] vs \[10.20±3.76\] ng/ml, P<0.01\]. The preoperative level of serum AGR2 in the patients was significantly lower than that of postoperative level (\[16.63±4.31\] vs \[28.93±6.03\] ng/ml, P<0.01). The preoperative level of serum AGR2 was closely correlated with lymph node metastasis and clinical pathologic staging (P<0.01 or P<0.05). The median progression free survival (PFS) and median overall survival (OS) in high level of serum AGR2 group (AGR2＞27.90 ng/mL group) were lower than those in low level of serum AGR2 group (AGR2≤27.90 ng/ml group), respectively (all P<0.05). COX multivariance regression model showed that clinical stages, lymph node metastasis and different level of serum AGR2 were independent risk factors that influence the prognosis of bladder cancer patients (P<0.05). Conclusion: Serum AGR2 in bladder cancer patients was higher, which closely related to malignant biological behavior of bladder cancer. It is of clinical significance to detect the level of serum AGR2 before operation for judging the prognosis of patients with bladder cancer.
Objective:To determine the change of serum anterior gradient2 (AGR2) level before and after surgery in bladder cancer patients, and to investigate its significance in predicting prognosis. Methods:The peripheral venous blood samples were collected from 40 patients with bladder cancer who accepted surgery (bladder cancer group) and 20 healthy controls (control group).The level of serum AGR2 was detected by enzyme linked immunosorbent assay (ELISA). The relationship between the level of serum AGR2 and clinicopathologic characteristics as well as prognosis prediction of bladder cancer was analyzed. Results: The level of serum AGR2 in the patients with bladder cancer was significantly higher than that in normal controls (\[28.93±6.03\] vs \[10.20±3.76\] ng/ml, P<0.01\]. The preoperative level of serum AGR2 in the patients was significantly lower than that of postoperative level (\[16.63±4.31\] vs \[28.93±6.03\] ng/ml, P<0.01). The preoperative level of serum AGR2 was closely correlated with lymph node metastasis and clinical pathologic staging (P<0.01 or P<0.05). The median progression free survival (PFS) and median overall survival (OS) in high level of serum AGR2 group (AGR2＞27.90 ng/mL group) were lower than those in low level of serum AGR2 group (AGR2≤27.90 ng/ml group), respectively (all P<0.05). COX multivariance regression model showed that clinical stages, lymph node metastasis and different level of serum AGR2 were independent risk factors that influence the prognosis of bladder cancer patients (P<0.05). Conclusion: Serum AGR2 in bladder cancer patients was higher, which closely related to malignant biological behavior of bladder cancer. It is of clinical significance to detect the level of serum AGR2 before operation for judging the prognosis of patients with bladder cancer.
2017, 24(6):660-664.
DOI: 10.3872/j.issn.1007-385X.2017.06.015
Abstract:
Objective:To explore the clinical efficacy and safety of chemotherapy combined with autologous tumor antigen load dendritic cellscytokininduced killer (AgDCCIK) cell therapy in the treatment of gastric cancer patients after D2 surgery. Methods: The present study enrolled 60 patients with gastric cancer in progressive stage (stage Ⅱ, stage Ⅲ) who underwent D2 surgery in the department of gastrointestinal surgery, Jingzhou Central Hospital during January, 2013 to March, 2014. The patients were randomly divided into chemotherapy group (FOLFOX regimen for 6 cycles) and combined treatment group (FOLFOX chemotherapy for 6 cycles+AgDCCIK cell therapy). The patients were followed up for two years. The twoyear overall survival (OS) and progression free survival (PFS), the levels of T cell subsets in the peripheral blood (CD3+ , CD4+, CD8+, CD3+CD56+), quality of life and adverse reactions were evaluated in the two groups. Results: Compared to the chemotherapy group, the twoyear OS and PFS were significantly higher in combined treatment group (both P<005). There was no significant difference in level of T cell subsets in peripheral blood of patients between pretreatment and posttreatment in combined treatment group (P>0.05); however, the level of T cell subsets in the peripheral blood of patients of chemotherapy group decreased significantly (P<0.05), and it was significant lower than that of combined treatment group (P<0.05). Compared to the chemotherapy group, the combined treatment group had higher quality of life (\[7.25±1.56\] vs \[5.54±1.27\], P<0.05) and lower adverse reactions (100% vs 20.0%, P<0.05). Conclusion: AgDCCIK cell therapy in combination with chemotherapy, compared with chemotherapy alone, can obviously increase the twoyear OS and PFS, protect the immune function of patients, reduce the adverse reactions and improve quality of life for gastric cancer patients.
Objective:To explore the clinical efficacy and safety of chemotherapy combined with autologous tumor antigen load dendritic cellscytokininduced killer (AgDCCIK) cell therapy in the treatment of gastric cancer patients after D2 surgery. Methods: The present study enrolled 60 patients with gastric cancer in progressive stage (stage Ⅱ, stage Ⅲ) who underwent D2 surgery in the department of gastrointestinal surgery, Jingzhou Central Hospital during January, 2013 to March, 2014. The patients were randomly divided into chemotherapy group (FOLFOX regimen for 6 cycles) and combined treatment group (FOLFOX chemotherapy for 6 cycles+AgDCCIK cell therapy). The patients were followed up for two years. The twoyear overall survival (OS) and progression free survival (PFS), the levels of T cell subsets in the peripheral blood (CD3+ , CD4+, CD8+, CD3+CD56+), quality of life and adverse reactions were evaluated in the two groups. Results: Compared to the chemotherapy group, the twoyear OS and PFS were significantly higher in combined treatment group (both P<005). There was no significant difference in level of T cell subsets in peripheral blood of patients between pretreatment and posttreatment in combined treatment group (P>0.05); however, the level of T cell subsets in the peripheral blood of patients of chemotherapy group decreased significantly (P<0.05), and it was significant lower than that of combined treatment group (P<0.05). Compared to the chemotherapy group, the combined treatment group had higher quality of life (\[7.25±1.56\] vs \[5.54±1.27\], P<0.05) and lower adverse reactions (100% vs 20.0%, P<0.05). Conclusion: AgDCCIK cell therapy in combination with chemotherapy, compared with chemotherapy alone, can obviously increase the twoyear OS and PFS, protect the immune function of patients, reduce the adverse reactions and improve quality of life for gastric cancer patients.
2017, 24(6):665-669.
DOI: 10.3872/j.issn.1007-385X.2017.06.016
Abstract:
Objective:To evaluate the clinical efficacy of adjuvant dendrtic cell (DC)cytokineinduced killer (CIK) cells immunotherapy and the effect of DCCIK cells treatment courses on the prognosis of patients with renal clear cell carcinoma. Methods: One hundred patients with renal clear cell carcinoma treated in Fujian Provincial Tumor Hospital from Jan, 2004 to Jun, 2011 were included in this retrospective study; 63 patients received DCCIK cells immunotherapy combined with conventional therapy were regarded as DCCIK cells treatment group, while the other 37 patients didn't receive DCCIK cells therapy were regarded as control group. The 5year DFS and OS of the two groups were compared. The treatment group was further subgrouped according to the course > 3 and course ≤3, and the 5year DFS and OS were further compared between the two subgroups. Results: Survival analysis showed the 5years overall survival (OS) rate was significantly higher in the DCCIK group compared with the control group (81.05% vs 60.29%, P<0.05), however, there was no significant difference in 5year DFS rate between two groups. Further subgroup analysis stratified according to the course of DCCIK cells treatment showed that the 5years OS was significantly improved in the group with course greater than 3 (P<0.05), although there was no significant difference in 5years DFS rate between two subgroups (P>0.05). Conclusion: Our results demonstrated that renal carcinoma patients could benefit from autologous DCCIK cells immunotherapy in combination with conventional therapies in terms of increasing overall survival. And the course of DCCIK cells treatment is closely related with the prognosis of patients with renal cell carcinoma.
Objective:To evaluate the clinical efficacy of adjuvant dendrtic cell (DC)cytokineinduced killer (CIK) cells immunotherapy and the effect of DCCIK cells treatment courses on the prognosis of patients with renal clear cell carcinoma. Methods: One hundred patients with renal clear cell carcinoma treated in Fujian Provincial Tumor Hospital from Jan, 2004 to Jun, 2011 were included in this retrospective study; 63 patients received DCCIK cells immunotherapy combined with conventional therapy were regarded as DCCIK cells treatment group, while the other 37 patients didn't receive DCCIK cells therapy were regarded as control group. The 5year DFS and OS of the two groups were compared. The treatment group was further subgrouped according to the course > 3 and course ≤3, and the 5year DFS and OS were further compared between the two subgroups. Results: Survival analysis showed the 5years overall survival (OS) rate was significantly higher in the DCCIK group compared with the control group (81.05% vs 60.29%, P<0.05), however, there was no significant difference in 5year DFS rate between two groups. Further subgroup analysis stratified according to the course of DCCIK cells treatment showed that the 5years OS was significantly improved in the group with course greater than 3 (P<0.05), although there was no significant difference in 5years DFS rate between two subgroups (P>0.05). Conclusion: Our results demonstrated that renal carcinoma patients could benefit from autologous DCCIK cells immunotherapy in combination with conventional therapies in terms of increasing overall survival. And the course of DCCIK cells treatment is closely related with the prognosis of patients with renal cell carcinoma.
2017, 24(6):670-674.
DOI: 10.3872/j.issn.1007-385X.2017.06.017
Abstract:
Objective:To investigate the efficacy of WAVE bioreactorin the culture and amplification of cytokine induced killer (CIK) cells and their killing activity on tumor cells. Methods: Peripheral blood mononuclear cells (PBMCs) from 8 cancer patients were isolated and cultured by using traditional CIK amplification method (CIK group) and WAVE bioreactors (WAVE group)respectively. Trypan blue staining was used for cell counting, and Flow cytomery was used to comparethe amplification efficiency, functionality and subtype compositionbetween two groups; K562 cell, as the target cell, was used to detect the killing activity of amplified CIK cells of two methods. Results: The proliferated number of CIK cells in WAVE groupwassignificantly higher than that of CIK group(P<0.05 or P<0.01); the proportions of CD3+CD8+ cells and CD3+CD56+ cells in WAVE group were significantly higher than those in CIK group on Day 14 (\[78.56±2.99\]% vs \[74.54±3.02\]%, \[48.33±7.01\]% vs \[40.69±6.43\]%, all P<0.05); However, the proportion of Tregs cell was significantly decreased (P<0.05) in WAVE group. Moreover, it was observed that CIK cells culturedin the WAVE bioreactor group displayed a significantly higher cytotoxic capacitythan that in CIK group at the E/T ratio of 10∶1 and 20∶1, and the proportion of CD3+CD8+CD107a+ in CIK cells of WAVE group was significantly higher （\[29.43±4.97\]% vs \[25.19±4.91\]%, P<0.05). Conclusion: WAVE bioreactor system could produce more CIK cells with high purity, andCD3+CD8+ cells and CD3+CD56+NKT cells account higher proportion; CIK cells amplified by WAVE bioreactor exhibited higher killing effect on tumor K562 cells compared to the CIK cells amplified by traditional culture technique.
Objective:To investigate the efficacy of WAVE bioreactorin the culture and amplification of cytokine induced killer (CIK) cells and their killing activity on tumor cells. Methods: Peripheral blood mononuclear cells (PBMCs) from 8 cancer patients were isolated and cultured by using traditional CIK amplification method (CIK group) and WAVE bioreactors (WAVE group)respectively. Trypan blue staining was used for cell counting, and Flow cytomery was used to comparethe amplification efficiency, functionality and subtype compositionbetween two groups; K562 cell, as the target cell, was used to detect the killing activity of amplified CIK cells of two methods. Results: The proliferated number of CIK cells in WAVE groupwassignificantly higher than that of CIK group(P<0.05 or P<0.01); the proportions of CD3+CD8+ cells and CD3+CD56+ cells in WAVE group were significantly higher than those in CIK group on Day 14 (\[78.56±2.99\]% vs \[74.54±3.02\]%, \[48.33±7.01\]% vs \[40.69±6.43\]%, all P<0.05); However, the proportion of Tregs cell was significantly decreased (P<0.05) in WAVE group. Moreover, it was observed that CIK cells culturedin the WAVE bioreactor group displayed a significantly higher cytotoxic capacitythan that in CIK group at the E/T ratio of 10∶1 and 20∶1, and the proportion of CD3+CD8+CD107a+ in CIK cells of WAVE group was significantly higher （\[29.43±4.97\]% vs \[25.19±4.91\]%, P<0.05). Conclusion: WAVE bioreactor system could produce more CIK cells with high purity, andCD3+CD8+ cells and CD3+CD56+NKT cells account higher proportion; CIK cells amplified by WAVE bioreactor exhibited higher killing effect on tumor K562 cells compared to the CIK cells amplified by traditional culture technique.
2017, 24(6):675-679.
DOI: 10.3872/j.issn.1007-385X.2017.06.018
Abstract:
CRISPR/Cas基因编辑技术是一种强大的新技术，可以精确编辑细胞基因组。该技术在实验室应用的基础上，引入至肿瘤研究领域，成为目前肿瘤治疗研究领域的热点。肺癌的综合治疗已经进入了分子靶向时代，表皮生长因子受体（epidermal growth factor receptor，EGFR）基因突变是肺腺癌最主要、最重要的驱动基因之一，表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptortyrosinekinase inhibitors ,EGFRTKI）治疗EGFR突变肺腺癌有显著疗效，但随之而来的原发性和继发性耐药现象成为当前迫切需要解决的问题。应用CRISPR/Cas基因组编辑技术进行个性化分子手术可有效地纠正或破坏EGFR突变，从而抑制肿瘤生长和进展。随着CRISPR/Cas基因重组技术的日臻完善与成熟，分子手术方法联合传统外科手术、放疗和/或TKI靶向药物治疗必将为携带EGFR突变的肺腺癌患者带来很好的希望。
CRISPR/Cas基因编辑技术是一种强大的新技术，可以精确编辑细胞基因组。该技术在实验室应用的基础上，引入至肿瘤研究领域，成为目前肿瘤治疗研究领域的热点。肺癌的综合治疗已经进入了分子靶向时代，表皮生长因子受体（epidermal growth factor receptor，EGFR）基因突变是肺腺癌最主要、最重要的驱动基因之一，表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptortyrosinekinase inhibitors ,EGFRTKI）治疗EGFR突变肺腺癌有显著疗效，但随之而来的原发性和继发性耐药现象成为当前迫切需要解决的问题。应用CRISPR/Cas基因组编辑技术进行个性化分子手术可有效地纠正或破坏EGFR突变，从而抑制肿瘤生长和进展。随着CRISPR/Cas基因重组技术的日臻完善与成熟，分子手术方法联合传统外科手术、放疗和/或TKI靶向药物治疗必将为携带EGFR突变的肺腺癌患者带来很好的希望。
2017, 24(6):680-684.
DOI: 10.3872/j.issn.1007-385X.2017.06.019
Abstract:
肿瘤的发生发展是一个受多因素影响的逐步发展的过程，其中全基因组低甲基化和局部性高甲基化是肿瘤产生的重要原因。LAMA3基因作为层黏连蛋白的编码基因，被证实参与肿瘤的发生发展。基因启动子区的高甲基化往往使得LAMA3低表达甚至沉默，miRNA与RNA可变剪接等表观遗传修饰也调控肿瘤细胞中LAMA3的表达。LAMA3的异常表达还与黏着斑和细胞外基质受体两条信号通路密切相关，从而影响肿瘤细胞的侵袭和转移。本文就LAMA3在肿瘤发生发展过程中的作用及其在肿瘤中异常表达与表观遗传学的关系作一综述。
肿瘤的发生发展是一个受多因素影响的逐步发展的过程，其中全基因组低甲基化和局部性高甲基化是肿瘤产生的重要原因。LAMA3基因作为层黏连蛋白的编码基因，被证实参与肿瘤的发生发展。基因启动子区的高甲基化往往使得LAMA3低表达甚至沉默，miRNA与RNA可变剪接等表观遗传修饰也调控肿瘤细胞中LAMA3的表达。LAMA3的异常表达还与黏着斑和细胞外基质受体两条信号通路密切相关，从而影响肿瘤细胞的侵袭和转移。本文就LAMA3在肿瘤发生发展过程中的作用及其在肿瘤中异常表达与表观遗传学的关系作一综述。
2017, 24(6):685-688.
DOI: 10.3872/j.issn.1007-385X.2017.06.020
Abstract:
肿瘤相关巨噬细胞（tumorassociated macrophage，TAM）是肿瘤微环境中的重要组成成分，在促进肿瘤发生发展等方面发挥着重要作用。本文从TAM在甲状腺癌中的募集、对甲状腺癌预后的影响以及TAM相关信号通路在促进甲状腺癌增殖与转移的作用进行综述，为甲状腺癌的靶向治疗提供新的方向。
肿瘤相关巨噬细胞（tumorassociated macrophage，TAM）是肿瘤微环境中的重要组成成分，在促进肿瘤发生发展等方面发挥着重要作用。本文从TAM在甲状腺癌中的募集、对甲状腺癌预后的影响以及TAM相关信号通路在促进甲状腺癌增殖与转移的作用进行综述，为甲状腺癌的靶向治疗提供新的方向。
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- 《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
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- 刊号：ISSN 1007-385X
- CN 31-1725/R
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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.