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Volume 23,Issue 5,2016 Table of Contents
2016, 23(5):589-594.
DOI: 10.3872/j.issn.1007-385X.2016.05.001
Abstract:
Liquid biopsy, as a novel technique of precision therapy, has a very high scientific research value, but also has great potential power to promote clinical practice of precision therapy, which can be applied in more fields of early screening, diagnosis, monitoring, guiding theraputic program and efficacy evaluation of tumor, and so on. Advantages of the liquid biopsy make it become the most development potential approach for diagnosis and therapy of tumor. This article elucidated application prospects of the liquid biopsy in clinical precision therapy of tumor from the views of conceptions, characters, research methods, individualized tumor therapy, clinical applications, research status and so on, and showed huge clinical application value and market prospect of the liquid biopsy.
Liquid biopsy, as a novel technique of precision therapy, has a very high scientific research value, but also has great potential power to promote clinical practice of precision therapy, which can be applied in more fields of early screening, diagnosis, monitoring, guiding theraputic program and efficacy evaluation of tumor, and so on. Advantages of the liquid biopsy make it become the most development potential approach for diagnosis and therapy of tumor. This article elucidated application prospects of the liquid biopsy in clinical precision therapy of tumor from the views of conceptions, characters, research methods, individualized tumor therapy, clinical applications, research status and so on, and showed huge clinical application value and market prospect of the liquid biopsy.
2016, 23(5):595-600.
DOI: 10.3872/j.issn.1007-385X.2016.05.002
Abstract:
Existence and circulation of circulating tumor cell (CTC) in peripheral blood is recognized as a primary reason for distant metastasis of tumor. Compared with the conventional imaging diagnosed methods, CTC detection as a non-invasive detection approach is operation simpler, safer and more accurate. Moreover, CTC technique also helps researchers to explore further the mechanisms of tumor metastasis, recurrence and chemotherapy resistance. Therefore, CTC as a sensitive biomarker has important clinical significance in tumor screening, early diagnosis, prognostic evaluation and monitoring of curative efficiency. “Tumor fisher” developed by CAS is a technology which captures the CTC in peripheral blood using polypeptide nano magnetic beads. At present, the CTC detective technique has been used for clinical research and trial in many advanced public hospitals of China. A lot of clinical data indicated that this technology might have great guide significance for early diagnosis, prognostic judge and monitoring of drug resistance. The article will explain progresses of the CTC research, development and application of the “tumor fisher” technique.
Existence and circulation of circulating tumor cell (CTC) in peripheral blood is recognized as a primary reason for distant metastasis of tumor. Compared with the conventional imaging diagnosed methods, CTC detection as a non-invasive detection approach is operation simpler, safer and more accurate. Moreover, CTC technique also helps researchers to explore further the mechanisms of tumor metastasis, recurrence and chemotherapy resistance. Therefore, CTC as a sensitive biomarker has important clinical significance in tumor screening, early diagnosis, prognostic evaluation and monitoring of curative efficiency. “Tumor fisher” developed by CAS is a technology which captures the CTC in peripheral blood using polypeptide nano magnetic beads. At present, the CTC detective technique has been used for clinical research and trial in many advanced public hospitals of China. A lot of clinical data indicated that this technology might have great guide significance for early diagnosis, prognostic judge and monitoring of drug resistance. The article will explain progresses of the CTC research, development and application of the “tumor fisher” technique.
2016, 23(5):601-608.
DOI: 10.3872/j.issn.1007-385X.2016.05.003
Abstract:
Circulating tumor DNAs (ctDNAs) are small genomic fragments released by tumor cells into circulatory system, which come from all of tumor bearing parts of the patients, have characters of extremely low content, great difference among the patients, a short half-time, homogeneous and carrying tumor-specific genetics and epigenetic mutations, and so on, are closely related to development, evolution, dormancy, drug resistance, metastasis and recurrence of the tumor and are gradually becoming key approach in molecular research field of oncology. At present, there is a wide variety of detection methods and platforms for ctDNA, which are mainly divided into PCR-based assay and next-generation sequencing (NGS) , each of both them has their own advantages and disadvantages, and need to be flexibly selected according to research objective, and uniform standards should be established. ctDNA could become as an ideal hematogenous biomarker for tumor screening, early diagnosis, individually therapy and prognostic assessment with development of related techniques and continuous improvement of laws and regulations. This paper reviewed research progresses of ctDNA in the field of oncology.
Circulating tumor DNAs (ctDNAs) are small genomic fragments released by tumor cells into circulatory system, which come from all of tumor bearing parts of the patients, have characters of extremely low content, great difference among the patients, a short half-time, homogeneous and carrying tumor-specific genetics and epigenetic mutations, and so on, are closely related to development, evolution, dormancy, drug resistance, metastasis and recurrence of the tumor and are gradually becoming key approach in molecular research field of oncology. At present, there is a wide variety of detection methods and platforms for ctDNA, which are mainly divided into PCR-based assay and next-generation sequencing (NGS) , each of both them has their own advantages and disadvantages, and need to be flexibly selected according to research objective, and uniform standards should be established. ctDNA could become as an ideal hematogenous biomarker for tumor screening, early diagnosis, individually therapy and prognostic assessment with development of related techniques and continuous improvement of laws and regulations. This paper reviewed research progresses of ctDNA in the field of oncology.
2016, 23(5):609-612.
DOI: 10.3872/j.issn.1007-385X.2016.05.004
Abstract:
Recently, cytotherapy has become a research hotpoint, which provide a novel therapeutic approach for tumor and other major and refractory disease. In this paper, some ideals and principles on quality research and quality control of the cell preparation products were suggested, including Good Manufacturing Practice (GMP), raw materials for production of the cell preparation, processing technique and process control, quality research and quality control, and so on. It hopes that successful research and development of the cell preparation products were advanced through continuous improvement of quality management.
Recently, cytotherapy has become a research hotpoint, which provide a novel therapeutic approach for tumor and other major and refractory disease. In this paper, some ideals and principles on quality research and quality control of the cell preparation products were suggested, including Good Manufacturing Practice (GMP), raw materials for production of the cell preparation, processing technique and process control, quality research and quality control, and so on. It hopes that successful research and development of the cell preparation products were advanced through continuous improvement of quality management.
YUAN Yuan
,
QIN Yang
,
YOU Fengtao
,
CHEN Dan
,
ZOU Jianxuan
,
ZHU Xuejun
,
LI Bingzong
,
YUAN Lei
,
MENG Huimin
,
HANG Bozhen
,
AN Gangli
,
YANG Lin
2016, 23(5):613-619.
DOI: 10.3872/j.issn.1007-385X.2016.05.005
Abstract:
Objective:To screen and prepare theraputic monoclonal antibody CD19 using hybridoma technique in mice, and to explore killing effect of NK cells modified with pCD19-CAR which made by CD19 scFv sequence on B-cell lymphoma cells. Methods:CD19 monoclonal antibody was prepared in mice immunized with conjugated polypeptide, then sequence of the obtained antibody was obtained by gene sequencing method. The antibody sequence was analyzed and pCD19-CAR fragments were constructed via gene synthesis and molecular cloning PCR-based gene synthesis techniques. Then the pCD19-CAR fragments were cloned into lentiviral vectors, and transfected into NK-92MI cells after packaging preparation. and cloned into lenti-virus using molecular cloning method; and then the positive hybridoma cells were analyzed for scFv sequences. One of the scFv sequence was used to construct CAR (pCD19-CAR).Finally, the killing rates of various pCD19-CAR-NK-92MI cells on B-cell lymphoma cells were examined using Flow cytometry assay. Results: (1) CD19 monoclonal antibody pCD19 with high specificity was successfully screened out. (2) The measurement of the antibody showed that the positive rates of Ramos and Raji cells were 84.3% and 85.6% respectively, which were similar to commercial CD19 antibody. (3) The killing efficacy of pCD19-CAR-NK-92MI cells, of which modification rate was 28.72%, on CD+Ramos cells and CD+Raji cells was apparently higher than those of non-modified NK-92MI cells (\[47.0±1.7\]% vs \[24.7±6.2\]% and \[51.8±7.9\]% vs \[27.6±9.3\]%, all P<0.05). Specific killing effects of unmodified and modified NK-92 cells on CD19- Jurkat cells were not almost found (\[16.1±0.7\]% vs \[17.7±2.9\]%, P>0.05). Conclusion：pCD19-CAR was successfully constructed ; pCD19-CAR-NK-92MI cells could specifically recognize CD19 antigen and kill CD19+ B-cell lymphoma cells.
Objective:To screen and prepare theraputic monoclonal antibody CD19 using hybridoma technique in mice, and to explore killing effect of NK cells modified with pCD19-CAR which made by CD19 scFv sequence on B-cell lymphoma cells. Methods:CD19 monoclonal antibody was prepared in mice immunized with conjugated polypeptide, then sequence of the obtained antibody was obtained by gene sequencing method. The antibody sequence was analyzed and pCD19-CAR fragments were constructed via gene synthesis and molecular cloning PCR-based gene synthesis techniques. Then the pCD19-CAR fragments were cloned into lentiviral vectors, and transfected into NK-92MI cells after packaging preparation. and cloned into lenti-virus using molecular cloning method; and then the positive hybridoma cells were analyzed for scFv sequences. One of the scFv sequence was used to construct CAR (pCD19-CAR).Finally, the killing rates of various pCD19-CAR-NK-92MI cells on B-cell lymphoma cells were examined using Flow cytometry assay. Results: (1) CD19 monoclonal antibody pCD19 with high specificity was successfully screened out. (2) The measurement of the antibody showed that the positive rates of Ramos and Raji cells were 84.3% and 85.6% respectively, which were similar to commercial CD19 antibody. (3) The killing efficacy of pCD19-CAR-NK-92MI cells, of which modification rate was 28.72%, on CD+Ramos cells and CD+Raji cells was apparently higher than those of non-modified NK-92MI cells (\[47.0±1.7\]% vs \[24.7±6.2\]% and \[51.8±7.9\]% vs \[27.6±9.3\]%, all P<0.05). Specific killing effects of unmodified and modified NK-92 cells on CD19- Jurkat cells were not almost found (\[16.1±0.7\]% vs \[17.7±2.9\]%, P>0.05). Conclusion：pCD19-CAR was successfully constructed ; pCD19-CAR-NK-92MI cells could specifically recognize CD19 antigen and kill CD19+ B-cell lymphoma cells.
KONG Xiao
,
QIN Yang
,
LI Jialu
,
YOU Fengtao
,
ZHU Xuejun
,
YUAN Lei
,
MENG Huimin
,
AN Gangli
,
YANG Lin
2016, 23(5):620-625.
DOI: 10.3872/j.issn.1007-385X.2016.05.006
Abstract:
Objective:To explore killing efficiency of NK-92MI cells modified with chimeric antigen receptor of specific targeting HER2 antigen (HER2-CAR) on HER2+ breast carcinoma cells. Methods: HER2-CAR fragments were obtained by PCR, then built into lentiviral vectors via molecular cloning technology and transfected into NK-92MI cells using the lentiviral particles with HER2-CAR. Flow cytometry assay was used to detect efficiency of the cell transfection and, secretion differences between IFN-γ and granzyme in NK-92MI cells before and after the transfection. Killing efficiency of HER2-CAR-NK92MI cells on breast carcinoma cells in vitro was tested with 7-AAD and flow cytometry assays. Mouse model with breast tumor in situ was constructed and used to detect killing efficiency of the HER2-CAR-NK92MI cells in vivo. Results:Killing efficiencies of the NK-92MI cell modified with HER2-CAR on HER2+ breast carcinoma MCF-7 and T47T cell lines were significantly higher than those of the NK-92MI cell that did not modified with HER2-CAR gene (\[62.4±1.3\]% vs \[22.1±1.2\]%. \[50.0±1.9\]% vs \[16.9±0.6\]%， respectively, all P<0.01). However, there was no obvious difference in killing efficiency of both the modified and un-modified NK-92MI cells on HER2- breast carcinoma MDA-MB-468 cell (\[13.6±1.4\]% vs \[12.7±0.8\]%,P>0.05). At the same time, amount of IFN-γ secreted by the NK-92MI cell modified with HER2-CAR was significantly higher than that secreted by the NK-92MI cell which did not modified with HER2-CAR gene (P<0.01).Conclusion: Killing efficiency of the NK-92MI cell modified with HER2-CAR on HER2+ breast carcinoma cell significantly increased, and could have specific targeting property, which might provide a clinical evidence for the treatment of malignant tumor, such as breast carcinoma and so on.
Objective:To explore killing efficiency of NK-92MI cells modified with chimeric antigen receptor of specific targeting HER2 antigen (HER2-CAR) on HER2+ breast carcinoma cells. Methods: HER2-CAR fragments were obtained by PCR, then built into lentiviral vectors via molecular cloning technology and transfected into NK-92MI cells using the lentiviral particles with HER2-CAR. Flow cytometry assay was used to detect efficiency of the cell transfection and, secretion differences between IFN-γ and granzyme in NK-92MI cells before and after the transfection. Killing efficiency of HER2-CAR-NK92MI cells on breast carcinoma cells in vitro was tested with 7-AAD and flow cytometry assays. Mouse model with breast tumor in situ was constructed and used to detect killing efficiency of the HER2-CAR-NK92MI cells in vivo. Results:Killing efficiencies of the NK-92MI cell modified with HER2-CAR on HER2+ breast carcinoma MCF-7 and T47T cell lines were significantly higher than those of the NK-92MI cell that did not modified with HER2-CAR gene (\[62.4±1.3\]% vs \[22.1±1.2\]%. \[50.0±1.9\]% vs \[16.9±0.6\]%， respectively, all P<0.01). However, there was no obvious difference in killing efficiency of both the modified and un-modified NK-92MI cells on HER2- breast carcinoma MDA-MB-468 cell (\[13.6±1.4\]% vs \[12.7±0.8\]%,P>0.05). At the same time, amount of IFN-γ secreted by the NK-92MI cell modified with HER2-CAR was significantly higher than that secreted by the NK-92MI cell which did not modified with HER2-CAR gene (P<0.01).Conclusion: Killing efficiency of the NK-92MI cell modified with HER2-CAR on HER2+ breast carcinoma cell significantly increased, and could have specific targeting property, which might provide a clinical evidence for the treatment of malignant tumor, such as breast carcinoma and so on.
YU Tiantian
,
ZHANG Fan
,
LU Yao
,
LI Hongxia
,
XIE Min
,
LIU Qingping
,
LU Teng
,
QIN Jianzhong
,
CHI Yan
2016, 23(5):626-632.
DOI: 10.3872/j.issn.1007-385X.2016.05.007
Abstract:
Objective: To explore the effect of deletion of glucose or glutamine on growth and apoptosis of melanoma cells in vitro. Methods: MTT, flow cytometry, chemiluminescence, Western blotting and immunofluorescence staining assays were respectively used to detect primary cilia formation, proliferation, ATP contents, cell cycles and apoptosis of melanoma A375 cell on which effected by deletions of glucose and glutamine. Results: Proliferation rate of the A375 cell in none-glucose (No-Glu) or none-glutamine (No-Gln) culture medium was significantly lower than that in control group (normal culture medium) (No-Glu: \[21.0±1.9\]% vs 100%, P<0.01; No-Gln: \[46.2±9.7\]% vs 100%, P<005). No-Gln culture significantly increased positive rate of cilia formation of the A375 cell (\[16.8±2.3\]% vs \[6.2±9.8\]%, P<0.01), decreased (14.4±6.4)% of the cells at G1 phase (P<0.05) and increased (75.0±19)% of the cells at S phase (P<0.05), compared with control group. No-Glu culture medium had no obvious effect on cilia formation as well as ratios of the cells at G1 and S phases of the A375 cell. In addition, No-Gln medium reduced ATP content in the A375 cell by (64.5±4.9)% (P<0.01), and No-Glu medium only reduced ATP content in the A375 cell by (11.1±2.1)% (P<0.05). No-Glu medium increased apoptosis rate of the A375 cell more highly than that in control group (\[26.1±7.1\]% vs \[6.1±1.5\]%, P<0.01), and increased expression of pro-apoptotic protein Noxa, decreased expression of anti-apoptotic protein Mcl-1. No-Gln medium had no effect on apoptosis, and expressions of Noxa and Mcl-1 proteins. Conclusion: All of No-Glu and No-Gln could inhibit proliferation of the A375 cell, but No-Gln could result in blocking cell cycle of S phase, inhibiting ATP synthesis more obviously, however No-Glu could much more induce apoptosis of the cell.
Objective: To explore the effect of deletion of glucose or glutamine on growth and apoptosis of melanoma cells in vitro. Methods: MTT, flow cytometry, chemiluminescence, Western blotting and immunofluorescence staining assays were respectively used to detect primary cilia formation, proliferation, ATP contents, cell cycles and apoptosis of melanoma A375 cell on which effected by deletions of glucose and glutamine. Results: Proliferation rate of the A375 cell in none-glucose (No-Glu) or none-glutamine (No-Gln) culture medium was significantly lower than that in control group (normal culture medium) (No-Glu: \[21.0±1.9\]% vs 100%, P<0.01; No-Gln: \[46.2±9.7\]% vs 100%, P<005). No-Gln culture significantly increased positive rate of cilia formation of the A375 cell (\[16.8±2.3\]% vs \[6.2±9.8\]%, P<0.01), decreased (14.4±6.4)% of the cells at G1 phase (P<0.05) and increased (75.0±19)% of the cells at S phase (P<0.05), compared with control group. No-Glu culture medium had no obvious effect on cilia formation as well as ratios of the cells at G1 and S phases of the A375 cell. In addition, No-Gln medium reduced ATP content in the A375 cell by (64.5±4.9)% (P<0.01), and No-Glu medium only reduced ATP content in the A375 cell by (11.1±2.1)% (P<0.05). No-Glu medium increased apoptosis rate of the A375 cell more highly than that in control group (\[26.1±7.1\]% vs \[6.1±1.5\]%, P<0.01), and increased expression of pro-apoptotic protein Noxa, decreased expression of anti-apoptotic protein Mcl-1. No-Gln medium had no effect on apoptosis, and expressions of Noxa and Mcl-1 proteins. Conclusion: All of No-Glu and No-Gln could inhibit proliferation of the A375 cell, but No-Gln could result in blocking cell cycle of S phase, inhibiting ATP synthesis more obviously, however No-Glu could much more induce apoptosis of the cell.
2016, 23(5):633-639.
DOI: 10.3872/j.issn.1007-385X.2016.05.008
Abstract:
Objective:To explore the inhibitory effect of recombinant adenovirus Ad5-CCL20 combined with hyperthermia on the growth of mouse colon carcinoma CT-26 cells in mice transplanted tumor.Methods: Colon carcinoma CT-26 cells were transfected with recombinant adenovirus Ad5-CCL20, the expression of chemokine CCL20 was assessed by ELISA method and its chemotaxis to dendritic cell(DC) was detected by chemotaxis assays.Western blotting was performed to detect the expression of HSP70 and GP96 after CT-26 cells heated. DC were induced with protein exosomes from heat-shock CT-26 cells(heat group), control group and negative group as controls. Phenotypes of DC were detected by flow cytometry. The CT-26 cells were subcutaneous inoculated into BALB/c mice, then the BALB/c mice was immunotherapyed by intramuscular injection of recombinant adenovirus Ad5-CCL20 combined with treatment of heat (combined therapy group), and simultaneitily set hyperthermia alone heat group, Ad5-CCL20 alone group, Ad5-GFP group and control group. The tumor volumes and survival rate of tumor-bearing in each group was observed. ELISAPOT method was used to examine the IFN-γ production of spleen-derived T lymphocytes and the activity of cytotoxic T lymphocytes (CTL) was measured by lactate dehydrogenase (LDH) method. The infiltration of DC at the tumor site was examined with immunohistochemistry. Results:The CT-26 cells highly expressed chemokine CCL20 after the transfection of recombinant adenovirus Ad5-CCL20. CCL20 showed obviously chemotaxis activity both to iDC and mDC, especially iDC (P<0.05). Western blotting results showed that the expression of HSP70 and GP96 were detected in CT-26 cells after heat shock, but not in pure CT-26 cells. Compared with control and unheat group, flow cytometry demonstrated that the protein from heat-shocked CT-26 cells could significantly up-regulate expressions of CD80,CD86,CCR6 and MHC-Ⅱ molecules on the DC(P<0.01). Compared with all other groups, the growth of tumor in Ad5-CCL20/heat group was significantly inhibited (\[876.8±108.7\] vs \[2 862±85.52\], \[2 660±142.6\], \[2 447±100.6\], \[1 608±135.3\] mm3,P<0.01),and the survival time of tumor-bearing mice was prolonged(P<0.05). Results of ELISAPOT and LDH respectively showed that the CTL activity of spleen-derived T lymphocytes in Ad5-CCL20/heat group was higher as compared with all other groups (P<0.05).The immunohistochemical assay also showed that the infiltration proportion of CD11c+ DC was obviously increased in the Ad5-CCL20/heat group compared with Control group, Ad5-GFP group, Ad5-CCL20 group and Hyperthermia group(P<0.05). Conclusion: Recombinant adenovirus Ad5-CCL20 combined with hyperthermia significantly inhibited tumor growth and prolonged the survival time of tumor-bearing mice by recruiting and promoting DC maturation and antigen presentation, which could be a potential therapy for colon cancer.
Objective:To explore the inhibitory effect of recombinant adenovirus Ad5-CCL20 combined with hyperthermia on the growth of mouse colon carcinoma CT-26 cells in mice transplanted tumor.Methods: Colon carcinoma CT-26 cells were transfected with recombinant adenovirus Ad5-CCL20, the expression of chemokine CCL20 was assessed by ELISA method and its chemotaxis to dendritic cell(DC) was detected by chemotaxis assays.Western blotting was performed to detect the expression of HSP70 and GP96 after CT-26 cells heated. DC were induced with protein exosomes from heat-shock CT-26 cells(heat group), control group and negative group as controls. Phenotypes of DC were detected by flow cytometry. The CT-26 cells were subcutaneous inoculated into BALB/c mice, then the BALB/c mice was immunotherapyed by intramuscular injection of recombinant adenovirus Ad5-CCL20 combined with treatment of heat (combined therapy group), and simultaneitily set hyperthermia alone heat group, Ad5-CCL20 alone group, Ad5-GFP group and control group. The tumor volumes and survival rate of tumor-bearing in each group was observed. ELISAPOT method was used to examine the IFN-γ production of spleen-derived T lymphocytes and the activity of cytotoxic T lymphocytes (CTL) was measured by lactate dehydrogenase (LDH) method. The infiltration of DC at the tumor site was examined with immunohistochemistry. Results:The CT-26 cells highly expressed chemokine CCL20 after the transfection of recombinant adenovirus Ad5-CCL20. CCL20 showed obviously chemotaxis activity both to iDC and mDC, especially iDC (P<0.05). Western blotting results showed that the expression of HSP70 and GP96 were detected in CT-26 cells after heat shock, but not in pure CT-26 cells. Compared with control and unheat group, flow cytometry demonstrated that the protein from heat-shocked CT-26 cells could significantly up-regulate expressions of CD80,CD86,CCR6 and MHC-Ⅱ molecules on the DC(P<0.01). Compared with all other groups, the growth of tumor in Ad5-CCL20/heat group was significantly inhibited (\[876.8±108.7\] vs \[2 862±85.52\], \[2 660±142.6\], \[2 447±100.6\], \[1 608±135.3\] mm3,P<0.01),and the survival time of tumor-bearing mice was prolonged(P<0.05). Results of ELISAPOT and LDH respectively showed that the CTL activity of spleen-derived T lymphocytes in Ad5-CCL20/heat group was higher as compared with all other groups (P<0.05).The immunohistochemical assay also showed that the infiltration proportion of CD11c+ DC was obviously increased in the Ad5-CCL20/heat group compared with Control group, Ad5-GFP group, Ad5-CCL20 group and Hyperthermia group(P<0.05). Conclusion: Recombinant adenovirus Ad5-CCL20 combined with hyperthermia significantly inhibited tumor growth and prolonged the survival time of tumor-bearing mice by recruiting and promoting DC maturation and antigen presentation, which could be a potential therapy for colon cancer.
2016, 23(5):640-645.
DOI: 10.3872/j.issn.1007-385X.2016.05.009
Abstract:
Objective:To explore effect of down-regulating miR-221 expression on malignant biologic behaviors of cervical cancer cells and its mechanism. Methods: Liposome 2000 transfection method was used to transfect miR-221 inhibitor and negative control nucleotide fragment (NC) into cervical cancer HeLa, C33A, SiHa and Caski line cells. Protein expression levels of ARIDIA (target protein of miR-221), cleaved caspase 3, caspase 3, cleaved PARP, PARP, MMP-9, MMP-13 and TIMP-3, as well as expression levels of miR-221, MMP-9, MMP-13, TIMP-3 mRNAs were respectively detected by Western blotting and Real-time PCR assays. Proliferation of the cells, clone formation rate and apoptosis rate of the cells were separately determined by MTT assay, clone formation experiment and flow cytometry assay plus AnnexinV-FITC/PI staining.Results: Comparing with the control group, (1) expression amounts of miR-221 in HeLa, CC3A, SiHa and Caski cells which transfected with miR-221 inhibitor were significantly decreased (\[0.23±0.01\], \[0.34±002\], \[0.34±0.01\] and \[0.37±0.02\], F=25.44, P<0.05); (2) survival rates of the transfected cells gradually decreased with increase of culture time, and had a time dependent effect, survival rates of the cells were significantly lower than that of the negative control group after culture for 48 h (F=37.42, P<0.05); clone formation rates of the cells obviously reduced (F=43.58, P<0.05); as culture for 72 h, apoptosis rates of the cells were (27.92±3.47)% for HeLa, (20.84±4.31)% for C33A, (18.81±2.18)% for SiHa and (19.86±3.82)% for Caski, obviously higher than that of the control group (F=54.78,P<0.05); (3) after expression of miR-221 in the transfected cells was down-regulated, expressions of cleaved caspase 3, cleaved PARP and TIMP-3 proteins were promoted, expression of MMP-13 protein was inhibited, expression of MMP-13 mRNA was depressed (t=37.5, P<0.05), and expression of TIMP-3 mRNA was increased (t=46.3, P<0.05). Conclusion: Down-regulation of miR-221 could inhibit malignant biologic behaviors of cervical cancer cells, its mechanism might be associated with activation of caspase signaling pathway which could induce apoptosis of the cancer cells and related with regulating and controlling expressions of MMP-13 and TIMP-3 proteins.
Objective:To explore effect of down-regulating miR-221 expression on malignant biologic behaviors of cervical cancer cells and its mechanism. Methods: Liposome 2000 transfection method was used to transfect miR-221 inhibitor and negative control nucleotide fragment (NC) into cervical cancer HeLa, C33A, SiHa and Caski line cells. Protein expression levels of ARIDIA (target protein of miR-221), cleaved caspase 3, caspase 3, cleaved PARP, PARP, MMP-9, MMP-13 and TIMP-3, as well as expression levels of miR-221, MMP-9, MMP-13, TIMP-3 mRNAs were respectively detected by Western blotting and Real-time PCR assays. Proliferation of the cells, clone formation rate and apoptosis rate of the cells were separately determined by MTT assay, clone formation experiment and flow cytometry assay plus AnnexinV-FITC/PI staining.Results: Comparing with the control group, (1) expression amounts of miR-221 in HeLa, CC3A, SiHa and Caski cells which transfected with miR-221 inhibitor were significantly decreased (\[0.23±0.01\], \[0.34±002\], \[0.34±0.01\] and \[0.37±0.02\], F=25.44, P<0.05); (2) survival rates of the transfected cells gradually decreased with increase of culture time, and had a time dependent effect, survival rates of the cells were significantly lower than that of the negative control group after culture for 48 h (F=37.42, P<0.05); clone formation rates of the cells obviously reduced (F=43.58, P<0.05); as culture for 72 h, apoptosis rates of the cells were (27.92±3.47)% for HeLa, (20.84±4.31)% for C33A, (18.81±2.18)% for SiHa and (19.86±3.82)% for Caski, obviously higher than that of the control group (F=54.78,P<0.05); (3) after expression of miR-221 in the transfected cells was down-regulated, expressions of cleaved caspase 3, cleaved PARP and TIMP-3 proteins were promoted, expression of MMP-13 protein was inhibited, expression of MMP-13 mRNA was depressed (t=37.5, P<0.05), and expression of TIMP-3 mRNA was increased (t=46.3, P<0.05). Conclusion: Down-regulation of miR-221 could inhibit malignant biologic behaviors of cervical cancer cells, its mechanism might be associated with activation of caspase signaling pathway which could induce apoptosis of the cancer cells and related with regulating and controlling expressions of MMP-13 and TIMP-3 proteins.
ZHENG Jianbao
,
LI Xiaobin
,
SUN Xuejun
,
WANG Xiaolong
,
WANG Wei
,
WEI Guangbing
,
CHEN Nanzheng
,
WANG Kai
2016, 23(5):646-650.
DOI: 10.3872/j.issn.1007-385X.2016.05.010
Abstract:
Objective:To establish a liver metastasis model of human colorectal cancer in nude mice，and to investigate the effect of interfering CDX2 gene on the metastasis of colorectal cancer in vivo. Methods： Lentiviral vector particles were used to infect human colorectal cancer HT29 and SW480 cells; CDX2 gene interfering cell lines (SW480-KD、HT29-KD) and negative shRNA were screened and established; cell lines with CDX2 gene interfering (SW480-KD,HT29-KD),cell lines with negative shRNA (SW480-NC, HT29-NC) and blank control cells (SW480-CON, HT29-CON) were injected into the spleen of nude mice, respectively; the ingestion, movement and mental status of the mice were observed everyday and the weight of nude mice were measured every days. The nude mice were sacrificed on D50 to observe the liver metastasis by visual and microscopic observation. Results：The liver metastasis model of human colorectal cancer in nude mice was successfully constructed and confirmed by H-E staining. The weight of rats in knockdown group (SW480-KD, HT29-KD) was significantly lower than that of the blank control group (SW480-CON, HT29-CON) and negative control group (SW480-NC, HT29-NC）(SW480：\[15.02±2.00\] g vs \[18.00±2.48\] g, \[18.03±2.05\] g, F=3.761, P<0.05; HT29: \[15.39±2.16\] g vs \[17.96±2.48\] g, \[18.30±1.87\] g, F=3.721, P<0.05). The number of liver metastatic tumors in SW480-KD group was significantly more than that of the SW480-CON group and SW480-NC group (\[5783±22.56\] vs \[29.50±16.90\], \[28.20±15.40\], F=4.197, P<0.05). The number of liver metastatic tumors in HT29-KD group was significantly more than that of the HT29-CON group and HT29-NC group (\[56.83±2916\] vs \[2640±12.76\] , \[21.00±11.50\]， F=4.467，P<0.05). Conclusion： The liver metastasis model in nude mice established by the spleen injection was an ideal model to study the geng function in vivo; the CDX2 gene interfering could promote the metastasis of CRC SW480 cells and HT29 cells in nude mice.
Objective:To establish a liver metastasis model of human colorectal cancer in nude mice，and to investigate the effect of interfering CDX2 gene on the metastasis of colorectal cancer in vivo. Methods： Lentiviral vector particles were used to infect human colorectal cancer HT29 and SW480 cells; CDX2 gene interfering cell lines (SW480-KD、HT29-KD) and negative shRNA were screened and established; cell lines with CDX2 gene interfering (SW480-KD,HT29-KD),cell lines with negative shRNA (SW480-NC, HT29-NC) and blank control cells (SW480-CON, HT29-CON) were injected into the spleen of nude mice, respectively; the ingestion, movement and mental status of the mice were observed everyday and the weight of nude mice were measured every days. The nude mice were sacrificed on D50 to observe the liver metastasis by visual and microscopic observation. Results：The liver metastasis model of human colorectal cancer in nude mice was successfully constructed and confirmed by H-E staining. The weight of rats in knockdown group (SW480-KD, HT29-KD) was significantly lower than that of the blank control group (SW480-CON, HT29-CON) and negative control group (SW480-NC, HT29-NC）(SW480：\[15.02±2.00\] g vs \[18.00±2.48\] g, \[18.03±2.05\] g, F=3.761, P<0.05; HT29: \[15.39±2.16\] g vs \[17.96±2.48\] g, \[18.30±1.87\] g, F=3.721, P<0.05). The number of liver metastatic tumors in SW480-KD group was significantly more than that of the SW480-CON group and SW480-NC group (\[5783±22.56\] vs \[29.50±16.90\], \[28.20±15.40\], F=4.197, P<0.05). The number of liver metastatic tumors in HT29-KD group was significantly more than that of the HT29-CON group and HT29-NC group (\[56.83±2916\] vs \[2640±12.76\] , \[21.00±11.50\]， F=4.467，P<0.05). Conclusion： The liver metastasis model in nude mice established by the spleen injection was an ideal model to study the geng function in vivo; the CDX2 gene interfering could promote the metastasis of CRC SW480 cells and HT29 cells in nude mice.
2016, 23(5):651-655.
DOI: 10.3872/j.issn.1007-385X.2016.05.011
Abstract:
Objective:To construct a eukaryotic expression vector containing human cannabinoid receptor 2 (hCB2R) gene and investigate its effect on the apoptosis of cervical cancer HeLa cells as well as the possible mechanism. Methods：cDNA of human brain tissues was selected as template for the amplification of hCB2R gene by RT-PCR; recombinant plasmid GV230-hCB2R was constructed to transfect HeLa cells, and the empty vector GV230 was used as control vector. Western blotting and immunofluorescence staining combined with laser scanning and co-confocal microscope technology were used to detect hCB2R expression and intra-cecullar localization; Flow cytometry was used to determine the apoptosis of HeLa cells; Western blotting and real-time fluorescence quantitative PCR were used for the detection of expression of hCB2R, Bcl-2, Bax and Bad in HeLa cells. Results: Compared with empty plasmid group, GV230-hCB2R transfected HeLa cells expressed hCB2R protein with relative molecular weight (Mr) 40 000, on both cell membrane and cytoplasm; cell apoptosis rate of GV230-hCB2R group was significantly higher than that of the GV230 empty plasmid group (\[14.51±4.51\]% vs \[6.29±0.57\]%, t=1.72, P<0.05). Compared with the control group, the expression levels of Bax and Bad were significantly increased (P<0.05) while the expression of Bcl-2 was significantly decreased (P<0.05) in GV230-hCB2R group. Conclusion:hCB2R has a significant inhibitory effect on the growth of cervical cancer HeLa cell line, and its mechanism may be directly related to the involvement of hCB2R in the expression of apoptosis related proteins.
Objective:To construct a eukaryotic expression vector containing human cannabinoid receptor 2 (hCB2R) gene and investigate its effect on the apoptosis of cervical cancer HeLa cells as well as the possible mechanism. Methods：cDNA of human brain tissues was selected as template for the amplification of hCB2R gene by RT-PCR; recombinant plasmid GV230-hCB2R was constructed to transfect HeLa cells, and the empty vector GV230 was used as control vector. Western blotting and immunofluorescence staining combined with laser scanning and co-confocal microscope technology were used to detect hCB2R expression and intra-cecullar localization; Flow cytometry was used to determine the apoptosis of HeLa cells; Western blotting and real-time fluorescence quantitative PCR were used for the detection of expression of hCB2R, Bcl-2, Bax and Bad in HeLa cells. Results: Compared with empty plasmid group, GV230-hCB2R transfected HeLa cells expressed hCB2R protein with relative molecular weight (Mr) 40 000, on both cell membrane and cytoplasm; cell apoptosis rate of GV230-hCB2R group was significantly higher than that of the GV230 empty plasmid group (\[14.51±4.51\]% vs \[6.29±0.57\]%, t=1.72, P<0.05). Compared with the control group, the expression levels of Bax and Bad were significantly increased (P<0.05) while the expression of Bcl-2 was significantly decreased (P<0.05) in GV230-hCB2R group. Conclusion:hCB2R has a significant inhibitory effect on the growth of cervical cancer HeLa cell line, and its mechanism may be directly related to the involvement of hCB2R in the expression of apoptosis related proteins.
2016, 23(5):656-662.
DOI: 10.3872/j.issn.1007-385X.2016.05.012
Abstract:
Objective:To explore the effect of heparanase (HPSE) on adhesion with vascular endothelial cell and trans-endothelial migration of hepatocellular carcinoma (HCC) cells. Methods:Human normal umbilical vein endothelial cell HUVEC-C line , hepatic LO-2 cells, and hepatic carcinoma HepG2, BEL-7402 and HCCLM3 cells were selected to use. HCC cells with high expression of HPSE were screened using Real-time PCR. Four RNA interference (RNAi) sequences of HPSE gene were designed, and the corresponding plasmids were constructed respectively, and the RNAi plasmids with the highest efficiency were screened out, which were transfected into HCC cells with high expression of HPSE. At the same time, blank control (BC) group, negative control (NC) group and untransfected HCC cell group were set up. Adhesion test was used to detect adhesion situation of HCC cell and HUVEC-C cell in each group and Transwell assay was performed to determine the trans-HUVEC-C cell migration of HCC cells. The HCC cells were stained with 0.25% Rose Bengal and observed under inverted microscope. After decolorization, D values of the HCC cells in each group were determined and compared using an enzyme-labeled instrument. Results: Expression level of HPSE mRNA in the HCCLM3 cells was significantly higher than those in hepatic LO-2, HepG-2 and Bel-7402 cells (\[5.72±0.62\] vs \[1.05±009\], \[2.65±0.31\] and \[3.43±0.58\], all P<0.01 ). Of the designed 4 RNAi plasmids of HPSE, siHPSE-3158 plasmid showed the best inhibitory effect on expression of HPSE gene (P<0.05). The adhesion rate of HCCLM3 cells and HUVEC-C cells in RNAi group was significantly lower than those in BC, NC and untransfected HCCLM3 cell groups (\[031±0.04\] vs \[0.46±0.06\], \[0.45±0.05\] and \[0.64±0.09\], all P<0.01). The trans-HUVEC-C cell migration rate of HCCLM3 cell in RNAi group was also significantly lower than those in BC, NC and untransfected HCCLM3 cell group (\[0.284±0.029\] vs \[0.41±0.04\], \[0.41±0.05\] and \[0.43±0.05\], all P<0.05). Conclusion: HPSE might be involved in mediating the adhesion of HCC cells and vascular endothelial cells as well as trans-endothelial cells migration, which could be a key factor in the adhesion to vascular endothelial cells and hematogenous metastasis of HCC cells.
Objective:To explore the effect of heparanase (HPSE) on adhesion with vascular endothelial cell and trans-endothelial migration of hepatocellular carcinoma (HCC) cells. Methods:Human normal umbilical vein endothelial cell HUVEC-C line , hepatic LO-2 cells, and hepatic carcinoma HepG2, BEL-7402 and HCCLM3 cells were selected to use. HCC cells with high expression of HPSE were screened using Real-time PCR. Four RNA interference (RNAi) sequences of HPSE gene were designed, and the corresponding plasmids were constructed respectively, and the RNAi plasmids with the highest efficiency were screened out, which were transfected into HCC cells with high expression of HPSE. At the same time, blank control (BC) group, negative control (NC) group and untransfected HCC cell group were set up. Adhesion test was used to detect adhesion situation of HCC cell and HUVEC-C cell in each group and Transwell assay was performed to determine the trans-HUVEC-C cell migration of HCC cells. The HCC cells were stained with 0.25% Rose Bengal and observed under inverted microscope. After decolorization, D values of the HCC cells in each group were determined and compared using an enzyme-labeled instrument. Results: Expression level of HPSE mRNA in the HCCLM3 cells was significantly higher than those in hepatic LO-2, HepG-2 and Bel-7402 cells (\[5.72±0.62\] vs \[1.05±009\], \[2.65±0.31\] and \[3.43±0.58\], all P<0.01 ). Of the designed 4 RNAi plasmids of HPSE, siHPSE-3158 plasmid showed the best inhibitory effect on expression of HPSE gene (P<0.05). The adhesion rate of HCCLM3 cells and HUVEC-C cells in RNAi group was significantly lower than those in BC, NC and untransfected HCCLM3 cell groups (\[031±0.04\] vs \[0.46±0.06\], \[0.45±0.05\] and \[0.64±0.09\], all P<0.01). The trans-HUVEC-C cell migration rate of HCCLM3 cell in RNAi group was also significantly lower than those in BC, NC and untransfected HCCLM3 cell group (\[0.284±0.029\] vs \[0.41±0.04\], \[0.41±0.05\] and \[0.43±0.05\], all P<0.05). Conclusion: HPSE might be involved in mediating the adhesion of HCC cells and vascular endothelial cells as well as trans-endothelial cells migration, which could be a key factor in the adhesion to vascular endothelial cells and hematogenous metastasis of HCC cells.
2016, 23(5):663-669.
DOI: 10.3872/j.issn.1007-385X.2016.05.013
Abstract:
Objective:To explore the inhibitory effect of γ-aminobutyric acid (GABA) on colorectal cancer cells (SW480 and HCT116 lines) and its chemosensitization. Methods: The effects of GABA and its combination with anticancer drugs 5-fluorouracil (5-FU) or oxaliplatin (OXA) on proliferation of colorectal cancer cells (SW480, HCT116) were determined using CCK-8 assay; the effects of GABA on cell cycles of SW480 and CT116 were analyzed using Flow cytometry assay; the tumor weight and size were investigated in experiment of tumor-bearing nude mice; the expression of Ki67 protein in cancer tissues of the nude mice and the apoptosis of colorectal cancer cells in the nude mice were observed using immunohistochemistry and TUNEL staining assays respectively; the effect of GABA combined with OXA on growth of the tumor cells was observed with experiment in vivo. Results: GABA (100 μmol/L) significantly inhibited the proliferation of SW480 and HCT116 cells, their inhibition rates were (37.38±262)% and (15.54±1.33)%, respectively. Further increasing of the GABA concentration to 200 μmol/L did not obviously enhance the inhibitory rate. GABA decreased the number of SW480 and HCT116 cells at S phase by 11.8% and 10.7%, respectively. Inhibitory rates of the ISW480 cell in GABA combined with 5-FU or OXA groups were higher than those in 5-FU or OXA groups (combined with 5-FU: \[72.76±1.07\]% vs \[63.82±3.29\]%, q=4.079, P<005; combined with OXA: \[65.60±1.19\]% vs \[57.09±1.25\]%, q=4.128, P<0.05); inhibitory rates of HCT116 cells in GABA combined with 5-FU or OXA groups were higher than those in 5-FU or OXA alone groups (combined with 5-FU: \[79.53±1.12\]% vs \[69.71±009\]%, q=4.569, P<0.05; combined with OXA: \[73.19±0.07\]% vs \[64.65±199\]%, q=4.561, P<005). At end of the experiment, the tumor weight and size of the nude miceinthe combined group of GABA and OXA were significantly lower than those in control group and the oxaliplatin alone group (\[0.20±0016\] g vs \[0.42±0.039\] g, \[0.36±0.030\]g; \[250±27\] mm3 vs \[780±60\] mm3, \[520±46\] mm3, P<0.01). The combination of GABA with OXA also significantly inhibited the expression of Ki67 protein in the tumor tissues and promoted apoptosis of the tumor cells in tumor tissues. Conclusion: GABA couldhave strong inhibitory effect on proliferation of the colorectal cancer cells and its combination use with 5-FU or OXA could enhance efficacy of chemotherapy.
Objective:To explore the inhibitory effect of γ-aminobutyric acid (GABA) on colorectal cancer cells (SW480 and HCT116 lines) and its chemosensitization. Methods: The effects of GABA and its combination with anticancer drugs 5-fluorouracil (5-FU) or oxaliplatin (OXA) on proliferation of colorectal cancer cells (SW480, HCT116) were determined using CCK-8 assay; the effects of GABA on cell cycles of SW480 and CT116 were analyzed using Flow cytometry assay; the tumor weight and size were investigated in experiment of tumor-bearing nude mice; the expression of Ki67 protein in cancer tissues of the nude mice and the apoptosis of colorectal cancer cells in the nude mice were observed using immunohistochemistry and TUNEL staining assays respectively; the effect of GABA combined with OXA on growth of the tumor cells was observed with experiment in vivo. Results: GABA (100 μmol/L) significantly inhibited the proliferation of SW480 and HCT116 cells, their inhibition rates were (37.38±262)% and (15.54±1.33)%, respectively. Further increasing of the GABA concentration to 200 μmol/L did not obviously enhance the inhibitory rate. GABA decreased the number of SW480 and HCT116 cells at S phase by 11.8% and 10.7%, respectively. Inhibitory rates of the ISW480 cell in GABA combined with 5-FU or OXA groups were higher than those in 5-FU or OXA groups (combined with 5-FU: \[72.76±1.07\]% vs \[63.82±3.29\]%, q=4.079, P<005; combined with OXA: \[65.60±1.19\]% vs \[57.09±1.25\]%, q=4.128, P<0.05); inhibitory rates of HCT116 cells in GABA combined with 5-FU or OXA groups were higher than those in 5-FU or OXA alone groups (combined with 5-FU: \[79.53±1.12\]% vs \[69.71±009\]%, q=4.569, P<0.05; combined with OXA: \[73.19±0.07\]% vs \[64.65±199\]%, q=4.561, P<005). At end of the experiment, the tumor weight and size of the nude miceinthe combined group of GABA and OXA were significantly lower than those in control group and the oxaliplatin alone group (\[0.20±0016\] g vs \[0.42±0.039\] g, \[0.36±0.030\]g; \[250±27\] mm3 vs \[780±60\] mm3, \[520±46\] mm3, P<0.01). The combination of GABA with OXA also significantly inhibited the expression of Ki67 protein in the tumor tissues and promoted apoptosis of the tumor cells in tumor tissues. Conclusion: GABA couldhave strong inhibitory effect on proliferation of the colorectal cancer cells and its combination use with 5-FU or OXA could enhance efficacy of chemotherapy.
14 Peripheral blood sCTLA-4: prognostic factor of patients with advanced non-small cell lung cancer
2016, 23(5):670-674.
DOI: 10.3872/j.issn.1007-385X.2016.05.014
Abstract:
Objective:To explore the relationship between soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) and the survival time of advanced NSCLC patients by examine its expressions in peripheral blood of patients. Methods: The research collected the peripheral blood of 58 advanced NSCLC patients confirmed by oncology department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2010 to June 2013, and also collected the peripheral blood from 30 healthy persons during the same time period. Researcher used ELISA to test the sCTLA-4 content in the blood, and obtained the data of survival time through telephone follow-up or collected from Shanghai Municipal Center for Disease Control and Prevention, to analyze the relationship between sCTLA-4 and survival time. Results: The sCTLA-4 in peripheral blood of NSCLC patients was higher than that of healthy people (70.7% vs 6.7%， χ2=32.44，P<001); the median survival time of the patients with over-expressed sCTLA-4 was shorter (41.63 months vs 31. 57 months, χ2=7.77，P<0.01) than those patients with low expression, indicating a higher death risk （RR=305， χ2=8.01, P<0.01). Conclusion: sCTLA-4 was highly expressed in the peripheral blood of advanced NSCLC patients, and it could be used as one of the prognostic factors for patients with advanced NSCLC.
Objective:To explore the relationship between soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) and the survival time of advanced NSCLC patients by examine its expressions in peripheral blood of patients. Methods: The research collected the peripheral blood of 58 advanced NSCLC patients confirmed by oncology department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2010 to June 2013, and also collected the peripheral blood from 30 healthy persons during the same time period. Researcher used ELISA to test the sCTLA-4 content in the blood, and obtained the data of survival time through telephone follow-up or collected from Shanghai Municipal Center for Disease Control and Prevention, to analyze the relationship between sCTLA-4 and survival time. Results: The sCTLA-4 in peripheral blood of NSCLC patients was higher than that of healthy people (70.7% vs 6.7%， χ2=32.44，P<001); the median survival time of the patients with over-expressed sCTLA-4 was shorter (41.63 months vs 31. 57 months, χ2=7.77，P<0.01) than those patients with low expression, indicating a higher death risk （RR=305， χ2=8.01, P<0.01). Conclusion: sCTLA-4 was highly expressed in the peripheral blood of advanced NSCLC patients, and it could be used as one of the prognostic factors for patients with advanced NSCLC.
LIANG Jia
,
KUANG Gang
,
LIU Shengnan
,
GUO Wei
,
SHEN Supeng
,
DING Chunyan
,
LI Huijie
,
DONG Zhiming
2016, 23(5):675-681.
DOI: 10.3872/j.issn.1007-385X.2016.05.015
Abstract:
Objective:To investigate the expression and methylation status of long non-coding RNA XLOC_002319 (lncRNA XLOC_002319) in esophageal squamous cell carcinoma (ESCC), and to elucidate its role in the progression of ESCC. Methods: Reverse transcription polymerase chain reaction (RT-PCR) and methylation specific PCR (MSP) were used respectively to detect the expression and methylation status of XLOC_002319 in esophageal cancer cell lines (TE1, TE13, Yes-2, Eca109, T.TN) treated or untreated with DNA methyltransferase inhibitor 5-aza-2′-detoxycytidine (5-aza-dC), and in cancer-adjacent normal tissues, esophageal intraepithelial neoplasia (EIN) tissues and ESCC tissues. Results:Negative or weak positive expression of XLOC_002319 was detected in the five esophageal cancer cell lines untreated with 5-aza-dC; however, after the treatment with 5-aza-dC, the expression of XLOC_002319 was enhanced. The methylation status of XLOC_002319 was highly expressed in esophageal cancer cell lines before the treatment of 5-aza-dc, however, after the treatment, the methylation level was decreased in Eca109 and T.TN cell lines, while the status in other three cell lines was negative. The expression of XLOC_002319 gene in ESCC tissues was significantly reduced compared to cancer-adjacent tissues and EIN tissues (P<0.01), and was closely associated with pathological differentiation and TNM stage (P<0.05). The methylation frequency of XLOC_002319promoter in ESCC tissues(63.75% \[51/80\]) was significantly higher than that in EIN tissues and adjacent normal tissues (P<0.01), and it was also associated with lymph node metastasis, pathological differentiation and TNM stage (P<0.05). The expressions of XLOC_002319 in ESCC tumor tissues with methylation of the gene was significantly lower than that in tumor tissues with unmethylation of the gene (P<0.01). Conclusion: Aberrant low expression of lncRNA XLOC_002319 was closely related to the development and occurrence of ESCC, and promoter methylation might be one of the mechanisms for inactivation of XLOC_002319 in ESCC.
Objective:To investigate the expression and methylation status of long non-coding RNA XLOC_002319 (lncRNA XLOC_002319) in esophageal squamous cell carcinoma (ESCC), and to elucidate its role in the progression of ESCC. Methods: Reverse transcription polymerase chain reaction (RT-PCR) and methylation specific PCR (MSP) were used respectively to detect the expression and methylation status of XLOC_002319 in esophageal cancer cell lines (TE1, TE13, Yes-2, Eca109, T.TN) treated or untreated with DNA methyltransferase inhibitor 5-aza-2′-detoxycytidine (5-aza-dC), and in cancer-adjacent normal tissues, esophageal intraepithelial neoplasia (EIN) tissues and ESCC tissues. Results:Negative or weak positive expression of XLOC_002319 was detected in the five esophageal cancer cell lines untreated with 5-aza-dC; however, after the treatment with 5-aza-dC, the expression of XLOC_002319 was enhanced. The methylation status of XLOC_002319 was highly expressed in esophageal cancer cell lines before the treatment of 5-aza-dc, however, after the treatment, the methylation level was decreased in Eca109 and T.TN cell lines, while the status in other three cell lines was negative. The expression of XLOC_002319 gene in ESCC tissues was significantly reduced compared to cancer-adjacent tissues and EIN tissues (P<0.01), and was closely associated with pathological differentiation and TNM stage (P<0.05). The methylation frequency of XLOC_002319promoter in ESCC tissues(63.75% \[51/80\]) was significantly higher than that in EIN tissues and adjacent normal tissues (P<0.01), and it was also associated with lymph node metastasis, pathological differentiation and TNM stage (P<0.05). The expressions of XLOC_002319 in ESCC tumor tissues with methylation of the gene was significantly lower than that in tumor tissues with unmethylation of the gene (P<0.01). Conclusion: Aberrant low expression of lncRNA XLOC_002319 was closely related to the development and occurrence of ESCC, and promoter methylation might be one of the mechanisms for inactivation of XLOC_002319 in ESCC.
ZHENG Jie
,
JIANG Longwei
,
YAO Lu
,
LU Xiao
,
YANG Aizhen
,
AI Yueqin
,
ZHANG Yan
,
ZHANG Chuang
,
HUANG Weiqian
,
GAO Yanrong
,
ZHAO Hua
,
HU Jianhua
,
JIA Shaochang
2016, 23(5):682-687.
DOI: 10.3872/j.issn.1007-385X.2016.05.016
Abstract:
Objective:To evaluate clinical efficacy and safety of patients with advanced ovarian cancer treated with autogenous DC-CIK cytotherapy.Methods:Peripheral blood mononuclear cells of 28 patients with Ⅳ stage ovarian cancer who hospitalized in the Department of Tumor Biotherapy, the 81th Hospital of PLA during August, 2011 to January, 2016 were collected, from which DC and CIK were obtained with culture in vitro. DC sensitized by lysate of ovarian cancer HO-8910 line cell and CIK were transfused into the patients with ovarian cancer. Before and after the treatment, clinical efficacy and safety of the patients were observed. Results: After 28 patients with advanced ovarian cancer treated by DC-CIK immunotherapy, overall response rate (ORR) and disease control rate (DCR) of the patents were 7.1% (2/28) and 643(18/28) respectively, overall survival (OS) for 12, 36 and 50 months were 75%, 54% and 42% respectively. After treatment of DC-CIK immunotherapy, proportion of CD3+CD8+ in peripheral blood of the patients significantly increased compared to before the treatment (\[23.35±7.52\]% vs \[29.49±8.16\]%; t=-3.340, P<0.01), CD4+/CD8+ ratio obviously decreased (\[1.61±0.84\]% vs \[1.21±0.74\]%; t= 2.785, P<0.05), proportion of CD3+, CD3+CD4+, CD3-CD56+ , CD4+CD25+ cells and levels of CA125, CA199, TSGF did not significantly change (all P>0.05). There not were any obvious adverse reaction in all the patients after the treatment. Conclusion: DC-CIK cytotherapy could be as a safe and feasible theraputic approach which might improve immune status of the patients with advanced ovarian cancer, increase mid long term survival rate of the patients, and any obvious adverse reaction did not found in the patients treated with the immunotherapy.
Objective:To evaluate clinical efficacy and safety of patients with advanced ovarian cancer treated with autogenous DC-CIK cytotherapy.Methods:Peripheral blood mononuclear cells of 28 patients with Ⅳ stage ovarian cancer who hospitalized in the Department of Tumor Biotherapy, the 81th Hospital of PLA during August, 2011 to January, 2016 were collected, from which DC and CIK were obtained with culture in vitro. DC sensitized by lysate of ovarian cancer HO-8910 line cell and CIK were transfused into the patients with ovarian cancer. Before and after the treatment, clinical efficacy and safety of the patients were observed. Results: After 28 patients with advanced ovarian cancer treated by DC-CIK immunotherapy, overall response rate (ORR) and disease control rate (DCR) of the patents were 7.1% (2/28) and 643(18/28) respectively, overall survival (OS) for 12, 36 and 50 months were 75%, 54% and 42% respectively. After treatment of DC-CIK immunotherapy, proportion of CD3+CD8+ in peripheral blood of the patients significantly increased compared to before the treatment (\[23.35±7.52\]% vs \[29.49±8.16\]%; t=-3.340, P<0.01), CD4+/CD8+ ratio obviously decreased (\[1.61±0.84\]% vs \[1.21±0.74\]%; t= 2.785, P<0.05), proportion of CD3+, CD3+CD4+, CD3-CD56+ , CD4+CD25+ cells and levels of CA125, CA199, TSGF did not significantly change (all P>0.05). There not were any obvious adverse reaction in all the patients after the treatment. Conclusion: DC-CIK cytotherapy could be as a safe and feasible theraputic approach which might improve immune status of the patients with advanced ovarian cancer, increase mid long term survival rate of the patients, and any obvious adverse reaction did not found in the patients treated with the immunotherapy.
2016, 23(5):688-691.
DOI: 10.3872/j.issn.1007-385X.2016.05.017
Abstract:
Objective:To examine expression level of human plasmacytoma variant translocation 1 (PVT1) gene and content of clinical commonly used tumor markers in blood of the patients with gastric cancer and to explore the relationship between PVT1 as well as tumor markers and clinical stages. Methods: Peripheral venous bloods of 51 cases with gastric cancer and 63 cases with chronic atrophic gastritis who hospitalized in the First Hospital Affiliated to School of Medicine, Shihezi University during January to December, 2015 as well as 54 normal persons were collected, from which total blood RNA was extracted. Real-time quatitative PCR (qRT-PCR) was used to detect expression levels of PVT1 mRNA in the bloods; contents of AFP, CEA and CA19-9 in the bloods of the patients with gastric cancer were examined by electrochemical luminescence assay. Results: Expression amounts of PVT1 mRNA in bloods of the patients with gastric cancer and chronic atrophic gastritis were higher, there was statistical difference of PVT1 mRNA expression amounts between gastric cancer group and normal group (t=0.000,P<0.01), there also was statistical difference of PVT1mRNA expression amounts between chronic atrophic gastritis group and normal group (t=0.000, P<0.01), but there was no statistic difference of PVT1 mRNA expression amounts between gastric cancer group and chronic atrophic gastritis group (t=0459, P>0.05). In addition, expression of PVT1 mRNAand serum tumor marker CA19-9 had correlation (r=0.429, P<0.01). Conclusion: Expression of PVT1 mRNA in blood of the patients with gastric cancer and chronic atrophic gastritis could be higher than that in blood of normal persons, and which might be correlated with CA19-9, indicating that PVT1mRNA might be as one of molecular markers for early diagnosis and prognosis.
Objective:To examine expression level of human plasmacytoma variant translocation 1 (PVT1) gene and content of clinical commonly used tumor markers in blood of the patients with gastric cancer and to explore the relationship between PVT1 as well as tumor markers and clinical stages. Methods: Peripheral venous bloods of 51 cases with gastric cancer and 63 cases with chronic atrophic gastritis who hospitalized in the First Hospital Affiliated to School of Medicine, Shihezi University during January to December, 2015 as well as 54 normal persons were collected, from which total blood RNA was extracted. Real-time quatitative PCR (qRT-PCR) was used to detect expression levels of PVT1 mRNA in the bloods; contents of AFP, CEA and CA19-9 in the bloods of the patients with gastric cancer were examined by electrochemical luminescence assay. Results: Expression amounts of PVT1 mRNA in bloods of the patients with gastric cancer and chronic atrophic gastritis were higher, there was statistical difference of PVT1 mRNA expression amounts between gastric cancer group and normal group (t=0.000,P<0.01), there also was statistical difference of PVT1mRNA expression amounts between chronic atrophic gastritis group and normal group (t=0.000, P<0.01), but there was no statistic difference of PVT1 mRNA expression amounts between gastric cancer group and chronic atrophic gastritis group (t=0459, P>0.05). In addition, expression of PVT1 mRNAand serum tumor marker CA19-9 had correlation (r=0.429, P<0.01). Conclusion: Expression of PVT1 mRNA in blood of the patients with gastric cancer and chronic atrophic gastritis could be higher than that in blood of normal persons, and which might be correlated with CA19-9, indicating that PVT1mRNA might be as one of molecular markers for early diagnosis and prognosis.
WANG Fangzheng
,
JIANG Chuner
,
YE Zhimin
,
SUN Quanquan
,
YAN Fengqin
,
WANG Lei
,
QIN Weifeng
,
LI Bin
,
HU Fujun
,
FU Zhenfu
2016, 23(5):692-697.
DOI: 10.3872/j.issn.1007-385X.2016.05.018
Abstract:
Objective:To evaluate the efficacy and safety of nimotuzumab combined with intensity-modulated radiotherapy and chemotherapy (IMRT) for long-term in treatment of the patients with local advanced nasopharyngeal carcinoma. Methods: Thirty nine patients who diagnosed as Ⅲ-Ⅳ stages nanopharyngeal carcinoma in the Zhejiang Cancer Hospital during November, 2008 to March, 2014 were analyzed, among them 29 cases are male and 10 cases female, 20 cases are at Ⅲ stage, 14 cases at Ⅳ a stage and 5 cases at Ⅳ b stage. All the patients received a long-term treatment of nimotuzumab (200 mg at a time, one time per week) combined with IMRT for 9-18 weeks. Curative efficacy and toxic side effects of the long-term treatment of nimotuzumab combined with IMRT were observed, as well as the acute and chronic toxic side effects of the patients were analyzed according to the criteria of Radiation Therapy Oncology Group (RTOG). Accumulated survival rates of the patients were calculated and analyzed by Kaplan-Meier method and Log-rank test. Results: With a median follw-up period of 46 months (22-86 months), after the long-term treatment of nimotuzumab combined with IMRT for more then nine months local recurrence free survival rate (LRFS), regional recurrence free survival rate (RRFS), distant metastasis free survival rate (DMFS), progression free survival rate (PFS) and overall survival rate (OS) for three years of all the patients were 92.1%, 89.7%, 82.5%, 77.6% and 86.8% respectively. Univariate analysis showed that clinical stages and cycle of new adjuvant chemotherapy have key effect on the survival rates, DMFS for three years of the patients at Ⅲ stage and Ⅳ stage were 100.0% and 63.2% respectively (P<0.01), LRFS for three years of the patients received the treatment 1-2 cycles and 3-4 cycles 75.0% and 96.8% respectively (P<0.05). Conclusion:The long-term treatment of nimotuzumab combined with intensity-modulated radiotherapy and chemotherapy could improve curative efficacy of the patients with local advanced nasopharyngeal carcinoma, but not increase toxic side effect. However long-term curative efficacy of the treatment might wait on results of follow up for a long period.
Objective:To evaluate the efficacy and safety of nimotuzumab combined with intensity-modulated radiotherapy and chemotherapy (IMRT) for long-term in treatment of the patients with local advanced nasopharyngeal carcinoma. Methods: Thirty nine patients who diagnosed as Ⅲ-Ⅳ stages nanopharyngeal carcinoma in the Zhejiang Cancer Hospital during November, 2008 to March, 2014 were analyzed, among them 29 cases are male and 10 cases female, 20 cases are at Ⅲ stage, 14 cases at Ⅳ a stage and 5 cases at Ⅳ b stage. All the patients received a long-term treatment of nimotuzumab (200 mg at a time, one time per week) combined with IMRT for 9-18 weeks. Curative efficacy and toxic side effects of the long-term treatment of nimotuzumab combined with IMRT were observed, as well as the acute and chronic toxic side effects of the patients were analyzed according to the criteria of Radiation Therapy Oncology Group (RTOG). Accumulated survival rates of the patients were calculated and analyzed by Kaplan-Meier method and Log-rank test. Results: With a median follw-up period of 46 months (22-86 months), after the long-term treatment of nimotuzumab combined with IMRT for more then nine months local recurrence free survival rate (LRFS), regional recurrence free survival rate (RRFS), distant metastasis free survival rate (DMFS), progression free survival rate (PFS) and overall survival rate (OS) for three years of all the patients were 92.1%, 89.7%, 82.5%, 77.6% and 86.8% respectively. Univariate analysis showed that clinical stages and cycle of new adjuvant chemotherapy have key effect on the survival rates, DMFS for three years of the patients at Ⅲ stage and Ⅳ stage were 100.0% and 63.2% respectively (P<0.01), LRFS for three years of the patients received the treatment 1-2 cycles and 3-4 cycles 75.0% and 96.8% respectively (P<0.05). Conclusion:The long-term treatment of nimotuzumab combined with intensity-modulated radiotherapy and chemotherapy could improve curative efficacy of the patients with local advanced nasopharyngeal carcinoma, but not increase toxic side effect. However long-term curative efficacy of the treatment might wait on results of follow up for a long period.
2016, 23(5):698-702.
DOI: 10.3872/j.issn.1007-385X.2016.05.019
Abstract:
Objective:Advanced lacrimal gland carcinomais rare andthere is rate and there is no standard treatment regimen. To analyze the clinical presentation and treatment of advanced lacrimal gland carcinoma, in order to improve the understanding of this rare disease. Methods: Six patients with advanced lacrimal gland carcinoma were treated in our hospital between October 2007 and March 2016. The clinical and follow-up data were analyzed retrospectively. Results: All the patients were male (33-66 years old), including four cases of moderately or poorly differentiated adenocarcinoma and two cases of adenoid cystic carcinoma. The averagelongest diameter of lacrimal gland tumorwas (3.3±0.5) cm, and in four cases the tumor infiltrated the bone of orbital wall. After complete resection of lacrimal gland lesions, distant metastasis appeard in all 6 cases. Bone metastasis was observed in five cases, lung in four,distant lymph node in 2, and skin and liver in 1 case, respectively. Chemotherapy was documented in 6 patients, from whom 5 received cisplantin plus paclitaxel regimen as the first-line chemotherapy and partial response was observed in 1, stable disease in 2 and progression disease in 3. One patient failed threelines of chemotherapy regimens was treated with apatinib as the fourth line therapy and achieved a partial response with a progression-free survival of 6.1 months. The adverse events related with apatinib were hand-foot syndrome, hypertension, diarrheaand hemoptysis, which were all manageable. Conclusion: Poor differentiation and wide local invasion are the risk factors for distant metastases in lachrymal gland carcinoma patients. Bone and lung were common sites of metastases. For patients with metastatic disease, chemotherapy has a limited role, but apatinib may represent an effective therapeutic option and deserves further study.
Objective:Advanced lacrimal gland carcinomais rare andthere is rate and there is no standard treatment regimen. To analyze the clinical presentation and treatment of advanced lacrimal gland carcinoma, in order to improve the understanding of this rare disease. Methods: Six patients with advanced lacrimal gland carcinoma were treated in our hospital between October 2007 and March 2016. The clinical and follow-up data were analyzed retrospectively. Results: All the patients were male (33-66 years old), including four cases of moderately or poorly differentiated adenocarcinoma and two cases of adenoid cystic carcinoma. The averagelongest diameter of lacrimal gland tumorwas (3.3±0.5) cm, and in four cases the tumor infiltrated the bone of orbital wall. After complete resection of lacrimal gland lesions, distant metastasis appeard in all 6 cases. Bone metastasis was observed in five cases, lung in four,distant lymph node in 2, and skin and liver in 1 case, respectively. Chemotherapy was documented in 6 patients, from whom 5 received cisplantin plus paclitaxel regimen as the first-line chemotherapy and partial response was observed in 1, stable disease in 2 and progression disease in 3. One patient failed threelines of chemotherapy regimens was treated with apatinib as the fourth line therapy and achieved a partial response with a progression-free survival of 6.1 months. The adverse events related with apatinib were hand-foot syndrome, hypertension, diarrheaand hemoptysis, which were all manageable. Conclusion: Poor differentiation and wide local invasion are the risk factors for distant metastases in lachrymal gland carcinoma patients. Bone and lung were common sites of metastases. For patients with metastatic disease, chemotherapy has a limited role, but apatinib may represent an effective therapeutic option and deserves further study.
CAO Zhongyuan
,
ZHAO Zhenkai
,
XIANG Geng
,
NI Qingrong
,
CAI Yanhui
,
XI Yujing
,
ZHAO Jing
,
YAN Bo
2016, 23(5):703-707.
DOI: 10.3872/j.issn.1007-385X.2016.05.020
Abstract:
Objective:To establish an endogastric xenograft tumor model in nude mice which can be dynamically monitored by in vivo fluorescence imaging system. Methods: The SGC-7901fLuc+ cell line stably expressing luciferase was injected subcutaneously into nude mice to develop transplanted tumor. Subcutaneously transplanted tumor (with diameter of 0.5 cm) was collected and orthotopically overlapping sutured into lesser gastric curvature of nude mice. Tumor growth in rats was monitored using in vivo fluorescence imaging system every 4 days. At 3 weeks post-tumor implantation, the fluorescence-positive mice were sacrificed and H-E staining was performed to observe the morphology of endogastric xenograft tumor. Results:Using in vivo fluorescence imaging system, gradually enhanced fluorescence signal could be detected on the gastric area of tumor bearing nude mice. Tumor block grew locally around the lesser gastric curvature, with typical gastric carcinoma morphology as assessed by H-E staining. The diameter of the tumor block was 0.5-1 cm. The boundary of tumor and adjacent tissue was clear. No adhesion, no metastasis was found in the abdominal cavity, and no formation of ascites was found. The successful rate of endogastric xenograft tumor model of human gastric carcinoma in nude mice was 95% (19/20). Conclusion: The endogastric xenograft tumor model in nude mice was successfully established. This model provided an ideal experimental tool for studying the mechanism of human gastric carcinoma and the development of anticancer drugs.
Objective:To establish an endogastric xenograft tumor model in nude mice which can be dynamically monitored by in vivo fluorescence imaging system. Methods: The SGC-7901fLuc+ cell line stably expressing luciferase was injected subcutaneously into nude mice to develop transplanted tumor. Subcutaneously transplanted tumor (with diameter of 0.5 cm) was collected and orthotopically overlapping sutured into lesser gastric curvature of nude mice. Tumor growth in rats was monitored using in vivo fluorescence imaging system every 4 days. At 3 weeks post-tumor implantation, the fluorescence-positive mice were sacrificed and H-E staining was performed to observe the morphology of endogastric xenograft tumor. Results:Using in vivo fluorescence imaging system, gradually enhanced fluorescence signal could be detected on the gastric area of tumor bearing nude mice. Tumor block grew locally around the lesser gastric curvature, with typical gastric carcinoma morphology as assessed by H-E staining. The diameter of the tumor block was 0.5-1 cm. The boundary of tumor and adjacent tissue was clear. No adhesion, no metastasis was found in the abdominal cavity, and no formation of ascites was found. The successful rate of endogastric xenograft tumor model of human gastric carcinoma in nude mice was 95% (19/20). Conclusion: The endogastric xenograft tumor model in nude mice was successfully established. This model provided an ideal experimental tool for studying the mechanism of human gastric carcinoma and the development of anticancer drugs.
2016, 23(5):708-713.
DOI: 10.3872/j.issn.1007-385X.2016.05.021
Abstract:
随着医学的不断发展，研究人员对肿瘤发生、转移机制的研究不断深入，临床治疗中对恶性肿瘤治疗的要求也越来越高。手术、化疗、放疗等传统手段已不能满足临床上对肿瘤的个体化精准治疗。近年来，小分子靶向抗肿瘤药物受到研究者的广泛关注并逐渐应用于临床。本文从肿瘤精准医疗的背景、分子靶向抗肿瘤药物现状两方面予以综述，旨在为靶向抗肿瘤药物的研发提供参考。
随着医学的不断发展，研究人员对肿瘤发生、转移机制的研究不断深入，临床治疗中对恶性肿瘤治疗的要求也越来越高。手术、化疗、放疗等传统手段已不能满足临床上对肿瘤的个体化精准治疗。近年来，小分子靶向抗肿瘤药物受到研究者的广泛关注并逐渐应用于临床。本文从肿瘤精准医疗的背景、分子靶向抗肿瘤药物现状两方面予以综述，旨在为靶向抗肿瘤药物的研发提供参考。
2016, 23(5):714-719.
DOI: 10.3872/j.issn.1007-385X.2016.05.022
Abstract:
以嵌合抗原受体-T细胞（chimeric antigen receptor-T cell，CAR-T）治疗和卡控点（check point）阻断为代表的一系列研究和临床应用表明，自体或移植的特异T细胞可以清除已发生的肿瘤，标志着肿瘤免疫治疗进入了新的阶段。近期研究发现，借助于新一代测序、蛋白质组学及生物信息技术，可以鉴别出肿瘤细胞通过MHC提呈的突变特异性的新抗原，这些抗原或抗原组合具有高度的个体和肿瘤特异性。实验表明，新抗原能通过主动免疫在动物模型中产生抗肿瘤的作用，也可作为过继转移抗原特异性T细胞、TCR转染T细胞和CAR-T所识别的目标。这些重要进展为进一步开展肿瘤临床的精准免疫治疗奠定了理论和实践基础。
以嵌合抗原受体-T细胞（chimeric antigen receptor-T cell，CAR-T）治疗和卡控点（check point）阻断为代表的一系列研究和临床应用表明，自体或移植的特异T细胞可以清除已发生的肿瘤，标志着肿瘤免疫治疗进入了新的阶段。近期研究发现，借助于新一代测序、蛋白质组学及生物信息技术，可以鉴别出肿瘤细胞通过MHC提呈的突变特异性的新抗原，这些抗原或抗原组合具有高度的个体和肿瘤特异性。实验表明，新抗原能通过主动免疫在动物模型中产生抗肿瘤的作用，也可作为过继转移抗原特异性T细胞、TCR转染T细胞和CAR-T所识别的目标。这些重要进展为进一步开展肿瘤临床的精准免疫治疗奠定了理论和实践基础。
2016, 23(5):720-726.
DOI: 10.3872/j.issn.1007-385X.2016.05.023
Abstract:
在过去的20多年中，CIK细胞已逐步从实验室研究走向临床应用研究并展现了一定的抗瘤效果。然而，CIK细胞存在缺乏抗原特异性、靶向性不足、体内存活时间短等问题限制了其在临床上的应用。随着嵌合抗原受体（chimeric antigen receptor, CAR）修饰的T细胞（CAR-T）技术的兴起，CIK细胞的CAR修饰潜力也倍受关注。本文就CAR-CIK细胞的构建思路、效应细胞来源和简化治疗优势、基础研究和临床转化现状以及目前CAR-CIK面临的瓶颈问题等的研究进展作一综述。
在过去的20多年中，CIK细胞已逐步从实验室研究走向临床应用研究并展现了一定的抗瘤效果。然而，CIK细胞存在缺乏抗原特异性、靶向性不足、体内存活时间短等问题限制了其在临床上的应用。随着嵌合抗原受体（chimeric antigen receptor, CAR）修饰的T细胞（CAR-T）技术的兴起，CIK细胞的CAR修饰潜力也倍受关注。本文就CAR-CIK细胞的构建思路、效应细胞来源和简化治疗优势、基础研究和临床转化现状以及目前CAR-CIK面临的瓶颈问题等的研究进展作一综述。
2016, 23(5):727-732.
DOI: 10.3872/j.issn.1007-385X.2016.05.024
Abstract:
肿瘤是危害人类健康最严重的疾病之一，并且我国的肿瘤死亡率呈逐年上升趋势。肿瘤免疫治疗作为手术、放疗和化疗之后第4种治疗手段被临床广泛应用。肿瘤免疫治疗通过激发或调动机体的免疫系统，增强肿瘤微环境的抗肿瘤免疫力，从而控制和杀伤肿瘤细胞，是当前肿瘤治疗领域最具前景的研究方向之一。表观遗传学是研究DNA序列未改变而基因表达发生变化的一种可遗传改变，其调节机制主要包括DNA甲基化、组蛋白修饰和非编码RNA调节等。表观遗传修饰在免疫应答及肿瘤免疫治疗中的调控作用越来越受到重视。本文综述了表观遗传修饰对机体免疫细胞的调控以及通过干预进行肿瘤免疫治疗的相关研究和应用前景。
肿瘤是危害人类健康最严重的疾病之一，并且我国的肿瘤死亡率呈逐年上升趋势。肿瘤免疫治疗作为手术、放疗和化疗之后第4种治疗手段被临床广泛应用。肿瘤免疫治疗通过激发或调动机体的免疫系统，增强肿瘤微环境的抗肿瘤免疫力，从而控制和杀伤肿瘤细胞，是当前肿瘤治疗领域最具前景的研究方向之一。表观遗传学是研究DNA序列未改变而基因表达发生变化的一种可遗传改变，其调节机制主要包括DNA甲基化、组蛋白修饰和非编码RNA调节等。表观遗传修饰在免疫应答及肿瘤免疫治疗中的调控作用越来越受到重视。本文综述了表观遗传修饰对机体免疫细胞的调控以及通过干预进行肿瘤免疫治疗的相关研究和应用前景。
2016, 23(5):733-738.
DOI: 10.3872/j.issn.1007-385X.2016.05.025
Abstract:
缺氧代谢是恶性肿瘤重要的代谢特征之一。肿瘤微环境的缺氧代谢调控参与多项肿瘤恶性进程，如肿瘤周围血管形成、细胞周期和能量代谢等。新近研究发现，非编码小RNA（microRNA）通过转录后调节作用，在肿瘤的缺氧代谢中发挥着至关重要的作用。其中，最为重要的缺氧相关microRNA 为microRNA-210（miR-210）。miR-210的诱导上调是多种恶性肿瘤组织在缺氧状态下的共同特征，其参与肿瘤细胞周期、线粒体氧化代谢、DNA修复等多方面的调控，其高水平表达能够监测肿瘤患者复发以及预后。因此，靶向抑制miR-210可能会抑制多项肿瘤恶性进程，为肿瘤靶向治疗提供新的思路。本文对miR-210在肿瘤微环境及肿瘤恶性进程中的作用作一综述。
缺氧代谢是恶性肿瘤重要的代谢特征之一。肿瘤微环境的缺氧代谢调控参与多项肿瘤恶性进程，如肿瘤周围血管形成、细胞周期和能量代谢等。新近研究发现，非编码小RNA（microRNA）通过转录后调节作用，在肿瘤的缺氧代谢中发挥着至关重要的作用。其中，最为重要的缺氧相关microRNA 为microRNA-210（miR-210）。miR-210的诱导上调是多种恶性肿瘤组织在缺氧状态下的共同特征，其参与肿瘤细胞周期、线粒体氧化代谢、DNA修复等多方面的调控，其高水平表达能够监测肿瘤患者复发以及预后。因此，靶向抑制miR-210可能会抑制多项肿瘤恶性进程，为肿瘤靶向治疗提供新的思路。本文对miR-210在肿瘤微环境及肿瘤恶性进程中的作用作一综述。
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.