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Volume 24,Issue 7,2017 Table of Contents
2017, 24(7):693-699.
DOI: 10.3872/j.issn.1007-385X.2017.07.001
Abstract:
The studies of immune checkpoint represented by programmed death 1(PD-1) have pushed cancer im-munotherapy to a climax, which implies that modulating the negative immune regulatory pathway could create an ef-fective munotherapy strategy. Meanwhile, the tumor icroenvironment plays an important role in suppressing or enhancing immune response. Therefore, it will provide new immunotherapy strategy, and make foundation for indi-vidualized precision medicine, based on the mechanism of interation between immune response and tumor microen-vironment. This review summarized the research progress of cancer immunotherapy from the perspective of how the tumor microenvironment affects immune response, and aimed to propose a new strategy for cancer immunotherapy.
The studies of immune checkpoint represented by programmed death 1(PD-1) have pushed cancer im-munotherapy to a climax, which implies that modulating the negative immune regulatory pathway could create an ef-fective munotherapy strategy. Meanwhile, the tumor icroenvironment plays an important role in suppressing or enhancing immune response. Therefore, it will provide new immunotherapy strategy, and make foundation for indi-vidualized precision medicine, based on the mechanism of interation between immune response and tumor microen-vironment. This review summarized the research progress of cancer immunotherapy from the perspective of how the tumor microenvironment affects immune response, and aimed to propose a new strategy for cancer immunotherapy.
LIU Shengnan
,
XU Fenglou
,
LU Fan
,
DONG Zhiming
,
KUANG Gang
,
GUO Yanli
,
SHEN Supeng
,
LIANG Jia
,
GUO We
2017, 24(7):700-707.
DOI: 10.3872/j.issn.1007-385X.2017.07.002
Abstract:
Objective: To explore effect of long non coding RNA (lonRNA) of XLOC_005009 gene on biological properties, proliferation, migration, invasion, cell cycle and apoptosis in vitro, of esophageal cancer cell. Methods:The surgically resected cancer and para-cancerous tissues of 25 patients with esophageal cancer who hospitalized in the Tumor Institute of the 4 th Hospital of Hebei Medical University during 2015 to 2016 were collected. Expressions of XLOC_005009 gene in human esophageal cancer Eca109 and Kyse170 line cells, the esophageal cancer and para- cancerous tissues were detected by RT-PCR. pcDNA3.1-XLOC_005009 over-expression plasmid was structured and transfected into the Eca109 and Kyse170 cells. MTS , colony forming, scratching, Transwell chamber and flow cytometry assays were used respectively to check proliferation, cloning efficiency, migration, invasion, cell cycle and apoptosis of the cells, before and after transfection of the over-expression plasmid. Results: Expression of XLOC_005009 mRNA in the esophageal cancer tissue was obviously lower than that in the para-cancerous normal tissue (0.06±0.06 vs 0.21±0.19, P＜0.05), and expressions of XLOC_005009 mRNA in the esophageal cancer cells were all lower than that in the control group. In the Eca109 and Kyse170 cells transfected with the over-expression plasmid, expressions of XLOC_005009 gene were higher than those in the control groups (Eca109 cell: 039±0.17 vs 0.02±0.00; Kyse170 cell: 0.35±0.08 vs 0.01±0.01, all P＜0.05). And comparing with the control group, proliferation abilities of the Eca109 and Kyse170 cells with over-expression of XLOC_005009 gene were significantly weakened (P<0.05), their cloning efficiency evidently reduced, transmembrane cell numbers of the cells remarkably decreased (Eca109 cell: 146.40±34.47 vs 193.00±26.33; Kyse170 cell:157.80±32.51 vs 269.00±29.89, all P<0.05), migration efficiency of the Eca109 cell didn’t markly change, but that of the Kyse170 cell obviously reduced; S phase cell ra- tio of the cells increased; effecting on apoptosis of the cells was not obvious. Conclusion: Low-expression of XLOC_005009 might be closely related to occurrence and development of the esophageal cancer. Over-expression of XLOC_005009 could inhibit proliferation, invasion and migration in vitro of the esophageal cancer cells.
Objective: To explore effect of long non coding RNA (lonRNA) of XLOC_005009 gene on biological properties, proliferation, migration, invasion, cell cycle and apoptosis in vitro, of esophageal cancer cell. Methods:The surgically resected cancer and para-cancerous tissues of 25 patients with esophageal cancer who hospitalized in the Tumor Institute of the 4 th Hospital of Hebei Medical University during 2015 to 2016 were collected. Expressions of XLOC_005009 gene in human esophageal cancer Eca109 and Kyse170 line cells, the esophageal cancer and para- cancerous tissues were detected by RT-PCR. pcDNA3.1-XLOC_005009 over-expression plasmid was structured and transfected into the Eca109 and Kyse170 cells. MTS , colony forming, scratching, Transwell chamber and flow cytometry assays were used respectively to check proliferation, cloning efficiency, migration, invasion, cell cycle and apoptosis of the cells, before and after transfection of the over-expression plasmid. Results: Expression of XLOC_005009 mRNA in the esophageal cancer tissue was obviously lower than that in the para-cancerous normal tissue (0.06±0.06 vs 0.21±0.19, P＜0.05), and expressions of XLOC_005009 mRNA in the esophageal cancer cells were all lower than that in the control group. In the Eca109 and Kyse170 cells transfected with the over-expression plasmid, expressions of XLOC_005009 gene were higher than those in the control groups (Eca109 cell: 039±0.17 vs 0.02±0.00; Kyse170 cell: 0.35±0.08 vs 0.01±0.01, all P＜0.05). And comparing with the control group, proliferation abilities of the Eca109 and Kyse170 cells with over-expression of XLOC_005009 gene were significantly weakened (P<0.05), their cloning efficiency evidently reduced, transmembrane cell numbers of the cells remarkably decreased (Eca109 cell: 146.40±34.47 vs 193.00±26.33; Kyse170 cell:157.80±32.51 vs 269.00±29.89, all P<0.05), migration efficiency of the Eca109 cell didn’t markly change, but that of the Kyse170 cell obviously reduced; S phase cell ra- tio of the cells increased; effecting on apoptosis of the cells was not obvious. Conclusion: Low-expression of XLOC_005009 might be closely related to occurrence and development of the esophageal cancer. Over-expression of XLOC_005009 could inhibit proliferation, invasion and migration in vitro of the esophageal cancer cells.
2017, 24(7):708-715.
DOI: 10.3872/j.issn.1007-385X.2017.07.003
Abstract:
Objective: To investigate the methylation status of dishevelled-binding antagonist of beta-catenin 1 (DACT1) gene in CpG islands shore and transcription start site(TSS) regions in esophageal squamous cell cancer (ESCC) cell lines and ESCC samples, and to explore the possible effect on gene transcription and the prognosis of ESCC patients. Methods: MSP and RT-PCR methods were applied respectively to examine the methylation of DACT1 gene in two regions and its mRNAexpression in ESCC cell lines (TE1，TE13，T.Tn，Eca109) andESCC sam- ples which from the high risk area of upper digestive tract cancer in Hebei Province. Results: The negative or weak expression of DACT1 mRNA was detected in four ESCC cell lines. After treated with 5-aza-2'-deoxycytidine (5-aza-dC, a demethylation agent), the expression level of DACT1 mRNA was obviously increased. Meanwhile, The result of MSP showed that the methylation bands were obviously weakened or disappeared. The level of DACT1 mRNA expression had no obviously change after treated with trichostatin A（TSA）. Decreased mRNA expression of DACT1 was observed in ESCC tumor tissues comparing with non-cancerous tissues(P<0.01), and associated with the methylation status of TSS region(P<0.01). The hypermethylation of DACT1 in CpG islands shore region was ob- served both in tumor and corresponding adjacent tissues but wasn’t related to the transcriptional inhibition of DACT1. The result of survival analysis showed that the methylation status of DACT1 in TSS region was associated with ESCC patients’prognosis(P<0.01). Conclusion: The highpermethylation of DACT1 in TSS region was one of the mechanisms causing genes silencing in ESCC and may serve as prognostic methylation biomarkers for ESCC pa- tients.
Objective: To investigate the methylation status of dishevelled-binding antagonist of beta-catenin 1 (DACT1) gene in CpG islands shore and transcription start site(TSS) regions in esophageal squamous cell cancer (ESCC) cell lines and ESCC samples, and to explore the possible effect on gene transcription and the prognosis of ESCC patients. Methods: MSP and RT-PCR methods were applied respectively to examine the methylation of DACT1 gene in two regions and its mRNAexpression in ESCC cell lines (TE1，TE13，T.Tn，Eca109) andESCC sam- ples which from the high risk area of upper digestive tract cancer in Hebei Province. Results: The negative or weak expression of DACT1 mRNA was detected in four ESCC cell lines. After treated with 5-aza-2'-deoxycytidine (5-aza-dC, a demethylation agent), the expression level of DACT1 mRNA was obviously increased. Meanwhile, The result of MSP showed that the methylation bands were obviously weakened or disappeared. The level of DACT1 mRNA expression had no obviously change after treated with trichostatin A（TSA）. Decreased mRNA expression of DACT1 was observed in ESCC tumor tissues comparing with non-cancerous tissues(P<0.01), and associated with the methylation status of TSS region(P<0.01). The hypermethylation of DACT1 in CpG islands shore region was ob- served both in tumor and corresponding adjacent tissues but wasn’t related to the transcriptional inhibition of DACT1. The result of survival analysis showed that the methylation status of DACT1 in TSS region was associated with ESCC patients’prognosis(P<0.01). Conclusion: The highpermethylation of DACT1 in TSS region was one of the mechanisms causing genes silencing in ESCC and may serve as prognostic methylation biomarkers for ESCC pa- tients.
2017, 24(7):716-720.
DOI: 10.3872/j.issn.1007-385X.2017.07.004
Abstract:
Objective: To study expression situation of GRHL3 and c-Myc in the neoplastic and para-carcinoma tis- sues of the patients with esophageal squamous cell carcinoma (ESCC) and its clinical significance. Methods: Patho- logical confirmed neoplastic and para-arcinoma tissues of the 64 patients with ESCC who were hospitalized in De- partment of chest surgery, the Fourth Hospital of Hebei Medical University for tumor resection during April 2015 to July 2016 were collected. Real-time PCR and immunohistochemistry assays were used to detect expressions of mRNA and proteins of GRHL3 and c-Myc genes. Relationship of the expressions of mRNA and proteins of GRHL3 and c-Myc genes with clinical features of the patients with ESCC were analyzed. Results: Comparing with the para- carcinoma tissues, positive expression levels of GRHL3mRNA and GRHL3 protein in the ESCC tissue were obvi-ously raised (mRNA: 2.85 ± 2.83 vs 2.06 ± 2.02, protein: 81.30% vs 25.00%, all P<0.01), positive expression levels of cMyc mRNA and cMyc protein in the ESCC tissue also significantly risen (mRNA: 5.13 ± 5.11 vs 2.03 ± 2.00, protein: 42.20% vs 20.30%, all P<0.01). In the ESCC tissue, expression of GRHL3mRNA and expression of cMyc mRNA were positively correlated obviously (P<0.05), expression of GRHL3 protein and expression of cMyc protein were also positively correlated significantly (P<0.01). Expressions of GRHL3 and cMyc proteins were related to tumor in-filtration range, lymph node metastasis, clinical staging and differentiation degree of the patients with ESCC (all P<0.05). Conclusion: Expression levels of GRHL3 and cMyc in the neoplastic tissues of the patients with ESCC were significantly raised, positive correlation was found between the both expressions, the both expressions were closelyrelated to partial clinicopathological features of the patients with ESCC, which could be key factors that affecting pathological process of the ESCC.
Objective: To study expression situation of GRHL3 and c-Myc in the neoplastic and para-carcinoma tis- sues of the patients with esophageal squamous cell carcinoma (ESCC) and its clinical significance. Methods: Patho- logical confirmed neoplastic and para-arcinoma tissues of the 64 patients with ESCC who were hospitalized in De- partment of chest surgery, the Fourth Hospital of Hebei Medical University for tumor resection during April 2015 to July 2016 were collected. Real-time PCR and immunohistochemistry assays were used to detect expressions of mRNA and proteins of GRHL3 and c-Myc genes. Relationship of the expressions of mRNA and proteins of GRHL3 and c-Myc genes with clinical features of the patients with ESCC were analyzed. Results: Comparing with the para- carcinoma tissues, positive expression levels of GRHL3mRNA and GRHL3 protein in the ESCC tissue were obvi-ously raised (mRNA: 2.85 ± 2.83 vs 2.06 ± 2.02, protein: 81.30% vs 25.00%, all P<0.01), positive expression levels of cMyc mRNA and cMyc protein in the ESCC tissue also significantly risen (mRNA: 5.13 ± 5.11 vs 2.03 ± 2.00, protein: 42.20% vs 20.30%, all P<0.01). In the ESCC tissue, expression of GRHL3mRNA and expression of cMyc mRNA were positively correlated obviously (P<0.05), expression of GRHL3 protein and expression of cMyc protein were also positively correlated significantly (P<0.01). Expressions of GRHL3 and cMyc proteins were related to tumor in-filtration range, lymph node metastasis, clinical staging and differentiation degree of the patients with ESCC (all P<0.05). Conclusion: Expression levels of GRHL3 and cMyc in the neoplastic tissues of the patients with ESCC were significantly raised, positive correlation was found between the both expressions, the both expressions were closelyrelated to partial clinicopathological features of the patients with ESCC, which could be key factors that affecting pathological process of the ESCC.
QIAN Li
,
LIU Yang
,
YE Feng
,
LIU Lu
,
WANG Shaoqing
,
JIA Xiaoqin
,
FU Yi
,
GONG Weijuan
,
TIAN Fang
2017, 24(7):721-726.
DOI: 10.3872/j.issn.1007-385X.2017.07.005
Abstract:
Objective: To explore effect of BaF3 primary B lymphocyte that expresses retinoic acid early transcript 1? (RAE1?), ligand of mouse NKG2D, on function of myeloid-derived suppressor cell (MDSC) originated from mouse. Methods: Based on mouse primary B lymphocyte BaF3 line, a BaF3-RAE1? cell that expressed RAE1? and a BaF3-mock control cell with empty plasmid were structured. CD11b + Gr-1 + MDSC was produced through introduc- tion of 4T1 tumor model in situ. Spleen MDSC was respectively co-cultured with BaF3-RAE1? cell and BaF3-mock cell that acted as stimulating cells. Flow cytometry assay was used to detect expressions of CD40, CD80, F4/80 , CD11c and content of reactive oxygen species (ROS) in the MDSC. ELISA assay was used to test contents of IL-10, IL-4 ans IFN-γ in supernatant of the co-culture. Concentration of nitric oxide (NO) in the supernatant was examed by Griess assay. Magnetic beads were used to separate the MDSC in the co-culture system, activity of arginase was detected after splitting. In addition, the separated MDSC co-culture with splenocyte activated by anti-CD3/CD28 an-tibody. Proliferation of the activated CD3 + CD8 + T cell was examed by CFSC assay. Results: The MDSC of mouse spleen derived from 4T1 in situ tumor model was successfully obtained. Comparing with the BaF3-mock cell, effect- ing of the BaF3-RAE1? cell stimulation on amounts of IL-4, IFN-γ, IL-10 and NO secreted by the MDSC was not significant (P>0.05), and on amounts of CD40, CD80, F4/80 ,CD11c and ROS expressed by the MDSC also not sig- nificant (P>0.05). Stimulation of the BaF3-RAE1? cell did more increase activity of arginase in the MDSC than that of the BaF3-mock cell obviously (156.166±1.209 vs 110.135±7.356, P<0.01), and evidently enhanced inhibitory effect of the MDSC on proliferation of CD8 + T cell. Conclusion: RAE1? could enhance inhibitory function in vitro of the MDSC derived from 4T1 mouse with tumor.
Objective: To explore effect of BaF3 primary B lymphocyte that expresses retinoic acid early transcript 1? (RAE1?), ligand of mouse NKG2D, on function of myeloid-derived suppressor cell (MDSC) originated from mouse. Methods: Based on mouse primary B lymphocyte BaF3 line, a BaF3-RAE1? cell that expressed RAE1? and a BaF3-mock control cell with empty plasmid were structured. CD11b + Gr-1 + MDSC was produced through introduc- tion of 4T1 tumor model in situ. Spleen MDSC was respectively co-cultured with BaF3-RAE1? cell and BaF3-mock cell that acted as stimulating cells. Flow cytometry assay was used to detect expressions of CD40, CD80, F4/80 , CD11c and content of reactive oxygen species (ROS) in the MDSC. ELISA assay was used to test contents of IL-10, IL-4 ans IFN-γ in supernatant of the co-culture. Concentration of nitric oxide (NO) in the supernatant was examed by Griess assay. Magnetic beads were used to separate the MDSC in the co-culture system, activity of arginase was detected after splitting. In addition, the separated MDSC co-culture with splenocyte activated by anti-CD3/CD28 an-tibody. Proliferation of the activated CD3 + CD8 + T cell was examed by CFSC assay. Results: The MDSC of mouse spleen derived from 4T1 in situ tumor model was successfully obtained. Comparing with the BaF3-mock cell, effect- ing of the BaF3-RAE1? cell stimulation on amounts of IL-4, IFN-γ, IL-10 and NO secreted by the MDSC was not significant (P>0.05), and on amounts of CD40, CD80, F4/80 ,CD11c and ROS expressed by the MDSC also not sig- nificant (P>0.05). Stimulation of the BaF3-RAE1? cell did more increase activity of arginase in the MDSC than that of the BaF3-mock cell obviously (156.166±1.209 vs 110.135±7.356, P<0.01), and evidently enhanced inhibitory effect of the MDSC on proliferation of CD8 + T cell. Conclusion: RAE1? could enhance inhibitory function in vitro of the MDSC derived from 4T1 mouse with tumor.
CHEN Ran
,
WANG Yuming
,
DUAN Yong
,
ZHANG Yanliang
,
SONG Guibo
,
WU Chunyan
,
SUN Yan
,
DU Na
,
XIAO Cheng
2017, 24(7):727-732.
DOI: 10.3872/j.issn.1007-385X.2017.07.006
Abstract:
Objective: To detect expressions of FENDRR long non coding RNA(lncRNA) in the lung adenocarcino-ma XWLC-05 cell line from the Xuanwei area and in the non small cell lung cancer (NSCLC) A549 cell line, and to explore its effect on proliferation, migration and invasion of the cell lines. Methods: Expressions of FENDRR gene in the XWLC-05 and the A549 cells were detected by Real-time quantitative fluorescence PCR. Over-expression plasmid pEX-3-FENDRR and lentiviral vector LV3-FENDRR were structured, then respectively transfected into theXWLC-05 and the A549 cells. After the transfection, expressions of FENDRR in the XWLC-05 and the A549 cells were tested by real-time quantitative fluorescence PCR. MTS assay was used to examine proliferation of the cells and Transwell assay used to test migration and invasion abilities of the cells. Results: Expression of ENDRRgene in the XWLC-05cell was obviously lower than that in the A549 cell. Level of FENDRR mRNA in the XWLC- 05cell transfected with pEX-3-FENDRR was enhanced and, which in the A549 cell transfected with LV3-FENDRR reduced. Comparing with the control group, over-expression of FENDRR could significantly inhibit proliferation of the XWLC-05cell ([1.23±0.13] vs [1.46±0.25], P<0.05), and reduce its abilities of migration and invasion (P< 0.05). Interference of FENDRR expression could promote proliferation ([0.85±0.02] vs [0.77±0.08], P< 0.05), mi- gration and invasion of the A549 cell. Conclusion: Down-regulation of lncRNA FENDRR expression could related with occurrence and development of the uanweilung adenocarcinoma, which could play a role of tumor suppres-sion in the process of tumor malignization and inhibit proliferation and metastasis of the tumor cells.
Objective: To detect expressions of FENDRR long non coding RNA(lncRNA) in the lung adenocarcino-ma XWLC-05 cell line from the Xuanwei area and in the non small cell lung cancer (NSCLC) A549 cell line, and to explore its effect on proliferation, migration and invasion of the cell lines. Methods: Expressions of FENDRR gene in the XWLC-05 and the A549 cells were detected by Real-time quantitative fluorescence PCR. Over-expression plasmid pEX-3-FENDRR and lentiviral vector LV3-FENDRR were structured, then respectively transfected into theXWLC-05 and the A549 cells. After the transfection, expressions of FENDRR in the XWLC-05 and the A549 cells were tested by real-time quantitative fluorescence PCR. MTS assay was used to examine proliferation of the cells and Transwell assay used to test migration and invasion abilities of the cells. Results: Expression of ENDRRgene in the XWLC-05cell was obviously lower than that in the A549 cell. Level of FENDRR mRNA in the XWLC- 05cell transfected with pEX-3-FENDRR was enhanced and, which in the A549 cell transfected with LV3-FENDRR reduced. Comparing with the control group, over-expression of FENDRR could significantly inhibit proliferation of the XWLC-05cell ([1.23±0.13] vs [1.46±0.25], P<0.05), and reduce its abilities of migration and invasion (P< 0.05). Interference of FENDRR expression could promote proliferation ([0.85±0.02] vs [0.77±0.08], P< 0.05), mi- gration and invasion of the A549 cell. Conclusion: Down-regulation of lncRNA FENDRR expression could related with occurrence and development of the uanweilung adenocarcinoma, which could play a role of tumor suppres-sion in the process of tumor malignization and inhibit proliferation and metastasis of the tumor cells.
2017, 24(7):733-741.
DOI: 10.3872/j.issn.1007-385X.2017.07.007
Abstract:
Objective: To explore microRNA-133 (miR-133) controling effect of breast cancer anti-estrogen resis- tance 4（BCAR4）gene on migration and invasion of the breast cancer cells as well as its mechanism. Methods:Breast cancer and corresponding paracancerous tissues from the 80 patients with breast cancr who were hospitalized in Tumor Hospital affiliated to Zhengzhou University for surgical resection treatment during January to December 2016 were collected. Expressions of BCAR4 and miR-133 in the breast cancer and paracancerous tissues were de- tected by RT-PCR. A association between BCAR4 and miR-133 was tested by a dual- luciferase assay. Scratch and Transwell assays were respectively used to examine migration and invasion of the breast cancer MCF-7 cell after si-lencing BCAR4 or silencing BCAR4 and miR-133. Expressions of the Notch1 signaling pathway-related proteins were detected by Western blotting assay. A subcutaneous xenograft tumor experiment in nude mice was used to ex-amine effect of silencing BCAR4 on ability of forming tumor of the MCF-7 cell in vivo. Relationships between ex- pression of BCAR4 and clinicopathological parameters as well as survival rate of the patients with breast cancer were analyzed by biostatistics. Results: Expression of BCAR4 in the breast cancer tissue was significantly higher than that in the para-cancer tissue(P<0.05 ). Result of dual-luciferase assay shown that BCAR4 could manage ex- pression of miR-133. Silencing expression of BCAR4 could inhibit migration and invasion of the MCF-7 cell. Mi- gration rate and transmembrane cell number of the MCF-7 cell in which expressions of miR-133 and BCAR4 were silenced were obviously higher than those of the MCF-7 cell in which only expression of BCAR4 was silenced [mi-gration rate: (92.31±8.64)% vs (52.61±5.12)%, P<0.05; transmembrane cell number:(171.38±12.61) vs (28.54±3.29), P<0.01]. Restrain of miR-133 could reverse inhibition of BCAR4 to migration and invasion of the MCF-7 cell. Volumes and wights of the xenograft tumors of the nude mice in which BCAR4 was silenced were significantly decreased. Expressions of Notch1 signaling pathway-related proteins of the MCF-7 cell in which BCAR4 was si- lenced were remarkably down-regulated. Expression of BCAR4 was significantly related to pathological staging and lymph node metastasis of the patients with breast cancer. Survival rate of the patients with high expression of BCAR4 were lower than that of the patients with low expression of BCAR4. Conclusion: Migration and invasion of the breast cancer MCF-7 cell might be doubly managed by BCAR4 and miR-133. miR-133 could targetly regulate effect of BCAR4 on migration and invasion of the breast cancer cell through the Notch1 signaling pathway, which might give some clues for the molecular targeting therapy of breast cancer and the research on drug resistance mech- anism of breast cancer.
Objective: To explore microRNA-133 (miR-133) controling effect of breast cancer anti-estrogen resis- tance 4（BCAR4）gene on migration and invasion of the breast cancer cells as well as its mechanism. Methods:Breast cancer and corresponding paracancerous tissues from the 80 patients with breast cancr who were hospitalized in Tumor Hospital affiliated to Zhengzhou University for surgical resection treatment during January to December 2016 were collected. Expressions of BCAR4 and miR-133 in the breast cancer and paracancerous tissues were de- tected by RT-PCR. A association between BCAR4 and miR-133 was tested by a dual- luciferase assay. Scratch and Transwell assays were respectively used to examine migration and invasion of the breast cancer MCF-7 cell after si-lencing BCAR4 or silencing BCAR4 and miR-133. Expressions of the Notch1 signaling pathway-related proteins were detected by Western blotting assay. A subcutaneous xenograft tumor experiment in nude mice was used to ex-amine effect of silencing BCAR4 on ability of forming tumor of the MCF-7 cell in vivo. Relationships between ex- pression of BCAR4 and clinicopathological parameters as well as survival rate of the patients with breast cancer were analyzed by biostatistics. Results: Expression of BCAR4 in the breast cancer tissue was significantly higher than that in the para-cancer tissue(P<0.05 ). Result of dual-luciferase assay shown that BCAR4 could manage ex- pression of miR-133. Silencing expression of BCAR4 could inhibit migration and invasion of the MCF-7 cell. Mi- gration rate and transmembrane cell number of the MCF-7 cell in which expressions of miR-133 and BCAR4 were silenced were obviously higher than those of the MCF-7 cell in which only expression of BCAR4 was silenced [mi-gration rate: (92.31±8.64)% vs (52.61±5.12)%, P<0.05; transmembrane cell number:(171.38±12.61) vs (28.54±3.29), P<0.01]. Restrain of miR-133 could reverse inhibition of BCAR4 to migration and invasion of the MCF-7 cell. Volumes and wights of the xenograft tumors of the nude mice in which BCAR4 was silenced were significantly decreased. Expressions of Notch1 signaling pathway-related proteins of the MCF-7 cell in which BCAR4 was si- lenced were remarkably down-regulated. Expression of BCAR4 was significantly related to pathological staging and lymph node metastasis of the patients with breast cancer. Survival rate of the patients with high expression of BCAR4 were lower than that of the patients with low expression of BCAR4. Conclusion: Migration and invasion of the breast cancer MCF-7 cell might be doubly managed by BCAR4 and miR-133. miR-133 could targetly regulate effect of BCAR4 on migration and invasion of the breast cancer cell through the Notch1 signaling pathway, which might give some clues for the molecular targeting therapy of breast cancer and the research on drug resistance mech- anism of breast cancer.
2017, 24(7):742-747.
DOI: 10.3872/j.issn.1007-385X.2017.07.008
Abstract:
Objective: To observe effect of miR-134-5p transfection on proliferation and apoptosis of cervical carci-noma cell and to verify its possible molecular mechanism. Methods: Eight pairs of cervical cancer and para-cancer-ous tissuesfrom the patients with cervical cancer who hospitalized in Center of Oncology, Renmin Hospital, Hubei University of Medicine during May to August 2016 were collected. miR-134-5p mimics were transfected into cervi-cal carcinoma Hela and SiHa cells by lipofectomin 2000. MTT and colony formation assays were used to detect pro-liferation of cells. Flow cytometry (FCM）assay was used to test cell cycles and apoptosis of cells. Expressions of miR-134-5p mRNA in cervical carcinoma tissue and cell, and expression of EGFR mRNA in cervical carcinoma cell were detected by qRT-PCR assay. Expressions of EGFR pathway-related proteins in cervical carcinoma cell were examed by Western blotting assay. Results: Expression of miR-134-5p mRNA in cervical carcinoma tissue was significantly lower than that in para-carcinoma tissue (P<0.01). Comparing with the Hela and SiHa cells that transfected with miR-NC, expressions of miR-134-5p mRNA in the Hela and SiHa cells that transfected with miR-134-5p mimics were obviously increased, proliferation abilities of the cells significantly reduced (at the 5th day of the transfection, Hela cell:1.06 ± 0.13 vs 1.32 ± 0.07; SiHa cell: 1.12 ± 0.10 vs 1.42 ± 0.12, all P<0.05), apoptosis rates of the cells obviously increased (Hela cell: [26.53 ± 13.48]% vs [3.25 ± 1.74]%; SiHa cell: [30.49 ± 12.04]% vs [5.12 ±2.86]%, all P<0.05), number of formed colony decreased, ratio of G0/G1 phase cells increased, ratio of the cells in Sand G2/M phase decreased, apoptosis rate of the cells enhanced (all P<0.05), expressions of EGFR mRNA and EG-FR protein in the cells were remarkably down-regulated, among which EGFR mRNA in the the Hela cell down 58%(P<0.01) and in the the SiHa cell down 41% (P<0.05), expressions of downstream target protein for EGFR, p-AKT,p-ERK/2 and Cyclin D1, as well as pEGFR proteins were evidently down-regulated. Conclusion: miR-134-5p couldsignificantly inhibit proliferation of the cervical carcinoma cells and promote their apoptosis, of which possible mo-lecular mechanism might be inhibit activation of EGFR pathway through inhibiting expression of EGFR gene.
Objective: To observe effect of miR-134-5p transfection on proliferation and apoptosis of cervical carci-noma cell and to verify its possible molecular mechanism. Methods: Eight pairs of cervical cancer and para-cancer-ous tissuesfrom the patients with cervical cancer who hospitalized in Center of Oncology, Renmin Hospital, Hubei University of Medicine during May to August 2016 were collected. miR-134-5p mimics were transfected into cervi-cal carcinoma Hela and SiHa cells by lipofectomin 2000. MTT and colony formation assays were used to detect pro-liferation of cells. Flow cytometry (FCM）assay was used to test cell cycles and apoptosis of cells. Expressions of miR-134-5p mRNA in cervical carcinoma tissue and cell, and expression of EGFR mRNA in cervical carcinoma cell were detected by qRT-PCR assay. Expressions of EGFR pathway-related proteins in cervical carcinoma cell were examed by Western blotting assay. Results: Expression of miR-134-5p mRNA in cervical carcinoma tissue was significantly lower than that in para-carcinoma tissue (P<0.01). Comparing with the Hela and SiHa cells that transfected with miR-NC, expressions of miR-134-5p mRNA in the Hela and SiHa cells that transfected with miR-134-5p mimics were obviously increased, proliferation abilities of the cells significantly reduced (at the 5th day of the transfection, Hela cell:1.06 ± 0.13 vs 1.32 ± 0.07; SiHa cell: 1.12 ± 0.10 vs 1.42 ± 0.12, all P<0.05), apoptosis rates of the cells obviously increased (Hela cell: [26.53 ± 13.48]% vs [3.25 ± 1.74]%; SiHa cell: [30.49 ± 12.04]% vs [5.12 ±2.86]%, all P<0.05), number of formed colony decreased, ratio of G0/G1 phase cells increased, ratio of the cells in Sand G2/M phase decreased, apoptosis rate of the cells enhanced (all P<0.05), expressions of EGFR mRNA and EG-FR protein in the cells were remarkably down-regulated, among which EGFR mRNA in the the Hela cell down 58%(P<0.01) and in the the SiHa cell down 41% (P<0.05), expressions of downstream target protein for EGFR, p-AKT,p-ERK/2 and Cyclin D1, as well as pEGFR proteins were evidently down-regulated. Conclusion: miR-134-5p couldsignificantly inhibit proliferation of the cervical carcinoma cells and promote their apoptosis, of which possible mo-lecular mechanism might be inhibit activation of EGFR pathway through inhibiting expression of EGFR gene.
WU Siwei
,
AO Xiang
,
GUO Wei
,
XING Wei
,
AN Tianchen
,
AO Luoquan
,
HU Xueting
,
LI Zhan
,
XU Xiang
2017, 24(7):748-755.
DOI: 10.3872/j.issn.1007-385X.2017.07.009
Abstract:
Objective: To construct chimeric antigen receptor (CAR)-modified T cell (CAR-T) which targets GPC3 positive hepatoma cell, and to assess its killing efficacy to the GPC3 positive hepatoma cell. Methods: To enhance expression efficiency of the CAR molecule, technique for favored codon and modification of gene sequence were se-ected. CAR gene targeting GPC3 antigen was designed and lentiviral vector carrying GPC3-CAR gene, pCDH-GPC3-CAR, was constructed, which was transfected into T cell. Western blotting, flow cytometry, real-time cellanal-ysis (RTCA) and ELISA assays were used respectively to detect expression of GPC3-CAR molecule in the CAR-T cell, infection efficiency of the lentivirus to T cells, killing activity and specificity of the GPC3-CAR-T cell to the GPC3 positive hepatoma cell. Results: The gene segment in the pCDH-GPC3-CAR recombinant lentivirus plasmid,molecular mass of which is the same as the GPC3-CAR molecule, was found in a result of double enzyme digestion,indicating that the pCDH-GPC3-CAR lentivirus plasmid was successfully constructed. About 54.38% of the GPC3-T cell expressing GPC3-CAR molecule were celled as the GPC3-CAR-T cell. Killing efficacy of the GPC3-CAR-T cell to the GPC3 positive Huh-7 hepatoma cell was higher than that to the GPC3 negative SK-HEP-1 cell ([78.96±4.76]% vs [6.87±3.15]%). IFN-γ secretion efficiency of the GPC3-CAR-T cell co-cultured with the GPC3 positive Huh-7 hepatoma cell in the CAR-T group was higher than that in the Mock group ([21 371.4±1 808.3]pg/ml vs [152.8±12.5] pg/ml), which could be one of the mechanisms of high efficacy in killing hepatoma cells. Conclusion:The GPC3-CAR-T cell targeting hepatoma cells might have high efficacy ability to secrete cytokine IFN-γ and spe-cific, higher efficient ability to kill the GPC3 positive hepatoma cell, which would lay a foundation to carry further forward pre-clinical and clinical research on the GPC3-CAR-T cell.
Objective: To construct chimeric antigen receptor (CAR)-modified T cell (CAR-T) which targets GPC3 positive hepatoma cell, and to assess its killing efficacy to the GPC3 positive hepatoma cell. Methods: To enhance expression efficiency of the CAR molecule, technique for favored codon and modification of gene sequence were se-ected. CAR gene targeting GPC3 antigen was designed and lentiviral vector carrying GPC3-CAR gene, pCDH-GPC3-CAR, was constructed, which was transfected into T cell. Western blotting, flow cytometry, real-time cellanal-ysis (RTCA) and ELISA assays were used respectively to detect expression of GPC3-CAR molecule in the CAR-T cell, infection efficiency of the lentivirus to T cells, killing activity and specificity of the GPC3-CAR-T cell to the GPC3 positive hepatoma cell. Results: The gene segment in the pCDH-GPC3-CAR recombinant lentivirus plasmid,molecular mass of which is the same as the GPC3-CAR molecule, was found in a result of double enzyme digestion,indicating that the pCDH-GPC3-CAR lentivirus plasmid was successfully constructed. About 54.38% of the GPC3-T cell expressing GPC3-CAR molecule were celled as the GPC3-CAR-T cell. Killing efficacy of the GPC3-CAR-T cell to the GPC3 positive Huh-7 hepatoma cell was higher than that to the GPC3 negative SK-HEP-1 cell ([78.96±4.76]% vs [6.87±3.15]%). IFN-γ secretion efficiency of the GPC3-CAR-T cell co-cultured with the GPC3 positive Huh-7 hepatoma cell in the CAR-T group was higher than that in the Mock group ([21 371.4±1 808.3]pg/ml vs [152.8±12.5] pg/ml), which could be one of the mechanisms of high efficacy in killing hepatoma cells. Conclusion:The GPC3-CAR-T cell targeting hepatoma cells might have high efficacy ability to secrete cytokine IFN-γ and spe-cific, higher efficient ability to kill the GPC3 positive hepatoma cell, which would lay a foundation to carry further forward pre-clinical and clinical research on the GPC3-CAR-T cell.
2017, 24(7):756-761.
DOI: 10.3872/j.issn.1007-385X.2017.07.010
Abstract:
Objective: To explore inhibitory effect of dentritic cell (DC) transfected with mucin 1 (MUC1) gene on xenograft tumor of human breast carcinoma MCF7 cell in nude mouse. Methods: DC of healthy adults were in-duced-cultured in vitro. Plasmid with human pcDNA3.1-MUC1 gene were transfected into the DC by a lipofection assay. ELISA assay was used to detect secretion ability of cytokines IL-12 and TNF-α by the transfected DC. LDH release assay was used to exam killing activity of specific cytotoxic T lymphocytes (CTL) induced by the transfect-ed DC to the breast carcinoma MCF7 cell. The xenograft tumors of human breast carcinoma MCF7 cell in nude mice were treated by the DC transfected with MUC1 gene, the DC transfected with empty plasmid and normal sa-line in subcutaneous injection, and growth inhibition of the xenograft tumors in nude mice were observed. Results:Secretion abilities of IL-12 and TNF-α by the DC transfected with pcDNA3.1-MUC1 gene were obviously more en-hanced than those by the DC transfected with empty plasmid ( IL-12:[202.52±29.61] vs [10.83±1.02] pg/ml; TNF-α:[349.07±79.42] vs [9.26±1.52] pg/ml, all P<0.01). Killing activity of the specific CTL induced by the DC transfect-ed with pcDNA3.1-MUC1 genewas more obvious than that by the CTL of the control group, and the killing rates at effector/targetor ratio of 10:1, 5:1 and 2.5:1 were 56.2%, 38.9% and 25.8% respectively (all P<0.01). Inhibitory ef-fect of the DC transfected with MUC1 gene on the xenograft tumors of breast carcinoma MCF7 cell in nude mice was significantly stronger than that of the DC transfected with empty plasmid (P<0.05). Conclusion: The DC trans-fected with MUC1 gene might induce specific CTL, which might have stronger anti-tumor immuno effect on the breast carcinoma MCF7 cell.
Objective: To explore inhibitory effect of dentritic cell (DC) transfected with mucin 1 (MUC1) gene on xenograft tumor of human breast carcinoma MCF7 cell in nude mouse. Methods: DC of healthy adults were in-duced-cultured in vitro. Plasmid with human pcDNA3.1-MUC1 gene were transfected into the DC by a lipofection assay. ELISA assay was used to detect secretion ability of cytokines IL-12 and TNF-α by the transfected DC. LDH release assay was used to exam killing activity of specific cytotoxic T lymphocytes (CTL) induced by the transfect-ed DC to the breast carcinoma MCF7 cell. The xenograft tumors of human breast carcinoma MCF7 cell in nude mice were treated by the DC transfected with MUC1 gene, the DC transfected with empty plasmid and normal sa-line in subcutaneous injection, and growth inhibition of the xenograft tumors in nude mice were observed. Results:Secretion abilities of IL-12 and TNF-α by the DC transfected with pcDNA3.1-MUC1 gene were obviously more en-hanced than those by the DC transfected with empty plasmid ( IL-12:[202.52±29.61] vs [10.83±1.02] pg/ml; TNF-α:[349.07±79.42] vs [9.26±1.52] pg/ml, all P<0.01). Killing activity of the specific CTL induced by the DC transfect-ed with pcDNA3.1-MUC1 genewas more obvious than that by the CTL of the control group, and the killing rates at effector/targetor ratio of 10:1, 5:1 and 2.5:1 were 56.2%, 38.9% and 25.8% respectively (all P<0.01). Inhibitory ef-fect of the DC transfected with MUC1 gene on the xenograft tumors of breast carcinoma MCF7 cell in nude mice was significantly stronger than that of the DC transfected with empty plasmid (P<0.05). Conclusion: The DC trans-fected with MUC1 gene might induce specific CTL, which might have stronger anti-tumor immuno effect on the breast carcinoma MCF7 cell.
2017, 24(7):762-766.
DOI: 10.3872/j.issn.1007-385X.2017.07.011
Abstract:
Objective: To explore relationship between single nucleotide polymorphism (SNP) of programmed death ligand 1 (PD-L1) gene, an immune checkpoint molecule,3’untranslated region (3’UTR) and onset risk, clini-cal pathological features of bladder urothelial carcinoma (BUC). Methods: A case-control study was used. Poly-merase chain reaction-ligase detection reaction (PCR-LDR) assay was used to detect the genotype distribution fre-quency of rs4143815 and rs2297136 locus in PD-L1 gene 3’UTR of the 213 patients with BUC who were hospital-ized in Department of Urology Surgery, the Affiliated Hospital of Qingdao University for surgical treatment during June 2013 to December 2015 and the 251 individuals for health examination during the same stage. A relationship between different genotypes and onset risk of BUC as well as clinicopathological features of the patients with BUC was analyzed by chi-square test and unconditionalmultivariate Logistic regression assay. Results: Significant differ-ences of genotype frequencies at the rs4143815loci were found between BUC cases and controls. Onset risk of BUC in the individuals carring GG genotype was 2.83 times (95%CI: 1.82-4.64, P<0.01) of the individuals carring CC genotype and onset risk of BUC in the individuals carring G mutation gene (CG/GG genotype) was 1.53 times (95% CI:1.01-2.24, P<0.01) of the individuals carring CC genotype. Furthermore in the BUC group, frequency of carring G mutation gene at the rs4143815loci was significantly correlated to pathological grade of BUC and clinical staging of the patients with BUC (P<0.05，P<0.01). However at the rs2297136 loci, any significant difference of gnotype distribution frequency between the BUC group and the control group was not found. Onset risks of BUC among the individuals carring CC, CT and TT genotypes were not obviously different. Conclusion: SNP of rs4143815loci in PD-L1 gene 3’UTR could closely related to onset rick and malignant progression of BUC.
Objective: To explore relationship between single nucleotide polymorphism (SNP) of programmed death ligand 1 (PD-L1) gene, an immune checkpoint molecule,3’untranslated region (3’UTR) and onset risk, clini-cal pathological features of bladder urothelial carcinoma (BUC). Methods: A case-control study was used. Poly-merase chain reaction-ligase detection reaction (PCR-LDR) assay was used to detect the genotype distribution fre-quency of rs4143815 and rs2297136 locus in PD-L1 gene 3’UTR of the 213 patients with BUC who were hospital-ized in Department of Urology Surgery, the Affiliated Hospital of Qingdao University for surgical treatment during June 2013 to December 2015 and the 251 individuals for health examination during the same stage. A relationship between different genotypes and onset risk of BUC as well as clinicopathological features of the patients with BUC was analyzed by chi-square test and unconditionalmultivariate Logistic regression assay. Results: Significant differ-ences of genotype frequencies at the rs4143815loci were found between BUC cases and controls. Onset risk of BUC in the individuals carring GG genotype was 2.83 times (95%CI: 1.82-4.64, P<0.01) of the individuals carring CC genotype and onset risk of BUC in the individuals carring G mutation gene (CG/GG genotype) was 1.53 times (95% CI:1.01-2.24, P<0.01) of the individuals carring CC genotype. Furthermore in the BUC group, frequency of carring G mutation gene at the rs4143815loci was significantly correlated to pathological grade of BUC and clinical staging of the patients with BUC (P<0.05，P<0.01). However at the rs2297136 loci, any significant difference of gnotype distribution frequency between the BUC group and the control group was not found. Onset risks of BUC among the individuals carring CC, CT and TT genotypes were not obviously different. Conclusion: SNP of rs4143815loci in PD-L1 gene 3’UTR could closely related to onset rick and malignant progression of BUC.
2017, 24(7):767-772.
DOI: 10.3872/j.issn.1007-385X.2017.07.012
Abstract:
Objective ：To test expression levels of programmed death-1(PD-1) and costimulatory 4-1BB mole-cules on surface of T cells in peripheral blood of the patients with nasopharyngeal carcinoma and to explore their clinical significance in immunotherapy of the patients with nasopharyngeal carcinoma. Methods: Thirty patients with nasopharyngeal carcinoma who were pathological diagnosed and hospitalized in Cancer Hospital of Fujian Province during October to November 2016 were selected as objects of the research, and 30 healthy individuals who are similar to the research objects in gender and age and took physical examination in a medical examination center of the same hospital during the same period as a control group. Expressions of PD-1 and 4-1BB on surface of T cells in peripheral blood as well as ratio of T lymphocyte subgroups were detected by a flow cytometry as-say. Using nuclear magnetic resonance scanning, volumes of the primary carcinoma were measured. Results: Ra-tio of CD8 + T cell in peripheral blood of the patients with Ⅲ stage of nasopharyngeal carcinoma was obviously lower than that of the patients with Ⅳ stage of nasopharyneal carcinoma ([13.1 ± 6.2]% vs [18.7 ±5.5]%,P<0.05).Comparing with the control group, positive expression rate of PD-1 on CD4 + T cell in the research group was sig-nificantly up-regulated([8.7 ± 6.5]% vs [3.87 ± 3.0] %, P<0.05). Expression levels of PD-1 and 4-1BB on surface of T cells in peripheral blood of the patients with nasopharyngeal carcinoma did not obviously correlated with clini-cal staging, tumor load, gender and age of the patient (P>0.05). Conclusion: There could be a synergistic effect between the two costimulatory molecules, PD-1 and 4-1BB, in an immune escape process of tumor. Joint interven-ing a signaling pathway of these two co-stimulation molecules might have more effective and durable antitumor effects，which might provide a novel ideal for an immunotherapy of the nasopharyngeal carcinoma.
Objective ：To test expression levels of programmed death-1(PD-1) and costimulatory 4-1BB mole-cules on surface of T cells in peripheral blood of the patients with nasopharyngeal carcinoma and to explore their clinical significance in immunotherapy of the patients with nasopharyngeal carcinoma. Methods: Thirty patients with nasopharyngeal carcinoma who were pathological diagnosed and hospitalized in Cancer Hospital of Fujian Province during October to November 2016 were selected as objects of the research, and 30 healthy individuals who are similar to the research objects in gender and age and took physical examination in a medical examination center of the same hospital during the same period as a control group. Expressions of PD-1 and 4-1BB on surface of T cells in peripheral blood as well as ratio of T lymphocyte subgroups were detected by a flow cytometry as-say. Using nuclear magnetic resonance scanning, volumes of the primary carcinoma were measured. Results: Ra-tio of CD8 + T cell in peripheral blood of the patients with Ⅲ stage of nasopharyngeal carcinoma was obviously lower than that of the patients with Ⅳ stage of nasopharyneal carcinoma ([13.1 ± 6.2]% vs [18.7 ±5.5]%,P<0.05).Comparing with the control group, positive expression rate of PD-1 on CD4 + T cell in the research group was sig-nificantly up-regulated([8.7 ± 6.5]% vs [3.87 ± 3.0] %, P<0.05). Expression levels of PD-1 and 4-1BB on surface of T cells in peripheral blood of the patients with nasopharyngeal carcinoma did not obviously correlated with clini-cal staging, tumor load, gender and age of the patient (P>0.05). Conclusion: There could be a synergistic effect between the two costimulatory molecules, PD-1 and 4-1BB, in an immune escape process of tumor. Joint interven-ing a signaling pathway of these two co-stimulation molecules might have more effective and durable antitumor effects，which might provide a novel ideal for an immunotherapy of the nasopharyngeal carcinoma.
2017, 24(7):773-777.
DOI: 10.3872/j.issn.1007-385X.2017.07.013
Abstract:
Objective: To explore expression of long non-coding RNA (lncRNA) RP5-1185K9.17 in colorectal can-cer tissue and its clinical significance. Methods: Expression of lncRNA RP5-1185K9.17 in surgery removed cancer tissues and corresponding paracancerous tissues of the patients with colorectal cancer who hospitalized in the Sich-uan Provincial People's Hospital during January 2011 to June 2016 were detected by qRT-PCR assay. Chi-Square in-spection, Kaplan-Meier assay and Cox proportional analysis model were used respectively to analyze relationships of the lncRNA RP5-1185K9.17 expression with clinicopathological parameters, survival time and prognosis of the patients with colorectal cancer as well as factors effecting prognosis of the patients. Results: Expressions of ln-cRNA RP5-1185K9.17 in the colorectal cancer tissues were more significantly heightened than that in paracancer-ous normal tissues ([colon cancer: 6.850±0.420; rectal cancer: 7.180±0.380] vs [paracancerous tissue: 1.080±0.220;normal tissue: 0.980±0.140], P<0.01). The expression of lncRNA RP5-1185K9.17 was obviously related to TNM staging, lymph node metastasis, distant metastasis, tumor differentiation, serum CEA level and survival state of the patients (all P<0.05), but not related to gender, age and tumor location of the patients (all P>0.05). Overall survival (OS) and progression free survival (PFS) of the patients with high expression of lncRNA RP5-1185K9.17 were obvi-ously shorten than those of the patients with low expression of lncRNA RP5-1185K9.17 (OS:[25.45±4.28] month vs [42.69±3.72] months; PFS:[13.88±2.97] months vs [26.65±5.33] months, all P<0.01). Expression of lncRNA RP5-1185K9.17, distant metastasis, TNM staging and serum CEA level were independent factors effecting prognosis of the patients (all P<0.05). Conclusion: lncRNA RP5-1185K9.17 could be involved in occurrence and development of the colorectal cancer, and might be a potential molecular marker of diagnosis and prognosis of the patients with colorectal.
Objective: To explore expression of long non-coding RNA (lncRNA) RP5-1185K9.17 in colorectal can-cer tissue and its clinical significance. Methods: Expression of lncRNA RP5-1185K9.17 in surgery removed cancer tissues and corresponding paracancerous tissues of the patients with colorectal cancer who hospitalized in the Sich-uan Provincial People's Hospital during January 2011 to June 2016 were detected by qRT-PCR assay. Chi-Square in-spection, Kaplan-Meier assay and Cox proportional analysis model were used respectively to analyze relationships of the lncRNA RP5-1185K9.17 expression with clinicopathological parameters, survival time and prognosis of the patients with colorectal cancer as well as factors effecting prognosis of the patients. Results: Expressions of ln-cRNA RP5-1185K9.17 in the colorectal cancer tissues were more significantly heightened than that in paracancer-ous normal tissues ([colon cancer: 6.850±0.420; rectal cancer: 7.180±0.380] vs [paracancerous tissue: 1.080±0.220;normal tissue: 0.980±0.140], P<0.01). The expression of lncRNA RP5-1185K9.17 was obviously related to TNM staging, lymph node metastasis, distant metastasis, tumor differentiation, serum CEA level and survival state of the patients (all P<0.05), but not related to gender, age and tumor location of the patients (all P>0.05). Overall survival (OS) and progression free survival (PFS) of the patients with high expression of lncRNA RP5-1185K9.17 were obvi-ously shorten than those of the patients with low expression of lncRNA RP5-1185K9.17 (OS:[25.45±4.28] month vs [42.69±3.72] months; PFS:[13.88±2.97] months vs [26.65±5.33] months, all P<0.01). Expression of lncRNA RP5-1185K9.17, distant metastasis, TNM staging and serum CEA level were independent factors effecting prognosis of the patients (all P<0.05). Conclusion: lncRNA RP5-1185K9.17 could be involved in occurrence and development of the colorectal cancer, and might be a potential molecular marker of diagnosis and prognosis of the patients with colorectal.
2017, 24(7):778-783.
DOI: 10.3872/j.issn.1007-385X.2017.07.014
Abstract:
Objective: To explore expression of long strand non-coding ribonucleic acid (lonRNA) AK093987 in colon carcinoma tissues and its clinical significance. Methods: Cancer and para-cancer tissues of the 65 patients with carcinoma of colon who hospitalized in the 1 st People’s Hospital of Neijiang, Sichuan, during January 2011 to December 2015, as well as normal colon tissues of the 15 patients with congenital dilatation of colon, and perfora-tion of colon, colonal twist and incarcerated hernia caused by various reasons were collected. Expressions of ln-cRNAAK093987 in cancer and para-cancer tissues of the 65 patients with carcinoma of colon and the colon cancer cells were detected by RT-PCR assay. Proliferation of the colon cancer LoVo cells that were transfected with siRNA AK093987 to down-regulate expression of lncRNAAK093987 was tested by CCK8 assay. Cji-Square test and Ka-plan-Meier assay were used respectively to analyze association of expression of lncRNA AK093987 with clinical features, survival and prognosis of the patients with carcinoma of colon. The factors affecting DFS and OS of the pa-tients with carcinoma of colon were analyzed by Cox regression analysis. Results: Expression of lncRNA AK093987 in the cancer tissues of colon was obviously higher than those in the para-cancer tissue and the normal colon tissues (7.125±1.398 vs 1.058±0.070 and 1.092±0.049, all P<0.01). Proliferation of the LoVo cells down-regu-lating expression of lncRNA AK093987 significantly reduced (P<0.05). Expression of lncRNA AK093987 was re-markably related to clinical staging, metastasis of lymph node, distant metastasis, differentiation of tumor, serum CEA level and survival status of the patients with carcinoma of colon (all P<0.05). DFS and OS medians of the pa-tients with high expression of lncRNA AK093987 were significantly shortened than those in the patients with low expression of lncRNAAK093987 (DFS: [13.00±1.49] months vs [27.01±1.87] months; OS: [27.00±3.32] months vs [43.72±3.08] months, all P<0.01). Expression of lncRNA AK093987, distant metastasis and clinical staging were the independent prognostic factors of the patients with colon cancer (P<0.05). In addition, down-regulation of ln-cRNA AK093987 did evidently inhibit proliferation of the colon cancer LoVo cells. Conclusion: lncRNA AK093987 might involve in development of the colon cancer. Expression of lncRNAAK093987 could be obviously correlated to clinical staging, metastasis of lymph node, distant metastasis, differentiation of tumor, serum CEA lev-el and survival status of the patients with colon cancer, which might be a potential molecular marker for diagnosis and prognosis assessment of the colon carcinoma.
Objective: To explore expression of long strand non-coding ribonucleic acid (lonRNA) AK093987 in colon carcinoma tissues and its clinical significance. Methods: Cancer and para-cancer tissues of the 65 patients with carcinoma of colon who hospitalized in the 1 st People’s Hospital of Neijiang, Sichuan, during January 2011 to December 2015, as well as normal colon tissues of the 15 patients with congenital dilatation of colon, and perfora-tion of colon, colonal twist and incarcerated hernia caused by various reasons were collected. Expressions of ln-cRNAAK093987 in cancer and para-cancer tissues of the 65 patients with carcinoma of colon and the colon cancer cells were detected by RT-PCR assay. Proliferation of the colon cancer LoVo cells that were transfected with siRNA AK093987 to down-regulate expression of lncRNAAK093987 was tested by CCK8 assay. Cji-Square test and Ka-plan-Meier assay were used respectively to analyze association of expression of lncRNA AK093987 with clinical features, survival and prognosis of the patients with carcinoma of colon. The factors affecting DFS and OS of the pa-tients with carcinoma of colon were analyzed by Cox regression analysis. Results: Expression of lncRNA AK093987 in the cancer tissues of colon was obviously higher than those in the para-cancer tissue and the normal colon tissues (7.125±1.398 vs 1.058±0.070 and 1.092±0.049, all P<0.01). Proliferation of the LoVo cells down-regu-lating expression of lncRNA AK093987 significantly reduced (P<0.05). Expression of lncRNA AK093987 was re-markably related to clinical staging, metastasis of lymph node, distant metastasis, differentiation of tumor, serum CEA level and survival status of the patients with carcinoma of colon (all P<0.05). DFS and OS medians of the pa-tients with high expression of lncRNA AK093987 were significantly shortened than those in the patients with low expression of lncRNAAK093987 (DFS: [13.00±1.49] months vs [27.01±1.87] months; OS: [27.00±3.32] months vs [43.72±3.08] months, all P<0.01). Expression of lncRNA AK093987, distant metastasis and clinical staging were the independent prognostic factors of the patients with colon cancer (P<0.05). In addition, down-regulation of ln-cRNA AK093987 did evidently inhibit proliferation of the colon cancer LoVo cells. Conclusion: lncRNA AK093987 might involve in development of the colon cancer. Expression of lncRNAAK093987 could be obviously correlated to clinical staging, metastasis of lymph node, distant metastasis, differentiation of tumor, serum CEA lev-el and survival status of the patients with colon cancer, which might be a potential molecular marker for diagnosis and prognosis assessment of the colon carcinoma.
2017, 24(7):784-790.
DOI: 10.3872/j.issn.1007-385X.2017.07.015
Abstract:
程序性死亡受体-1(programmed death receptor-1, PD-1)是T细胞上主要存在的一种抑制性受体，与程序性死亡受体配体-1 （programmed death receptor ligand-1, PD-L1）相互作用，可抑制T细胞增殖、活化。在正常机体中，PD-1/PD-L1信号通路对维持机体的免疫耐受具有重要作用；而在肿瘤发生时，PD-1/PD-L1信号通路能抑制T细胞的免疫反应而促进肿瘤免疫逃逸的发生。本文从PD-1/PD-L1的发现及其结构、信号通路的作用机制、PD-1/PD-L1抗体在肿瘤免疫治疗中的应用等方面进行综述。
程序性死亡受体-1(programmed death receptor-1, PD-1)是T细胞上主要存在的一种抑制性受体，与程序性死亡受体配体-1 （programmed death receptor ligand-1, PD-L1）相互作用，可抑制T细胞增殖、活化。在正常机体中，PD-1/PD-L1信号通路对维持机体的免疫耐受具有重要作用；而在肿瘤发生时，PD-1/PD-L1信号通路能抑制T细胞的免疫反应而促进肿瘤免疫逃逸的发生。本文从PD-1/PD-L1的发现及其结构、信号通路的作用机制、PD-1/PD-L1抗体在肿瘤免疫治疗中的应用等方面进行综述。
2017, 24(7):791-798.
DOI: 10.3872/j.issn.1007-385X.2017.07.016
Abstract:
细胞表皮生长因子受体(epidermal growth factor receptor, EGFR)是调节细胞周期的关键因子，EGFR突变或过表达与多种肿瘤的发生、发展密切相关。EGFR也是外源信号介导细胞内信号通路级联反应的关键衔接蛋白，EGFR介导的细胞下游信号通路广泛参与调控细胞的增殖、凋亡与自噬。本文就有关EGFR介导的自噬在肿瘤发生、发展与治疗抵抗中的作用的最新研究进展作一综述，以期为以EGFR为靶点的抗肿瘤治疗与新药研发提供参考。
细胞表皮生长因子受体(epidermal growth factor receptor, EGFR)是调节细胞周期的关键因子，EGFR突变或过表达与多种肿瘤的发生、发展密切相关。EGFR也是外源信号介导细胞内信号通路级联反应的关键衔接蛋白，EGFR介导的细胞下游信号通路广泛参与调控细胞的增殖、凋亡与自噬。本文就有关EGFR介导的自噬在肿瘤发生、发展与治疗抵抗中的作用的最新研究进展作一综述，以期为以EGFR为靶点的抗肿瘤治疗与新药研发提供参考。
2017, 24(7):799-804.
DOI: 10.3872/j.issn.1007-385X.2017.07.017
Abstract:
长链非编码RNA(long chain non-coding RNA, lncRNA)的表达具有组织特异性和时空特异性，许多lncRNA具有保守的二级结构，提示lncRNAs具有重要的生物学功能。近些年来研究发现，超过80%的肿瘤相关单核苷酸多态性位点在基因组的非编码区域，lncRNA具有功能蛋白质的信号、引导、诱饵或支架分子等多种功能。目前在胃癌组织中发现了较多的基因在肿瘤发生、发展、转移及预后中起到了重要的作用，但仍有许多的lncRNA功能并不清楚，需要大量的研究来探明其结构、作用方式、机制及对胃癌的作用和影响。而在lncRNA中去发现胃癌有效的肿瘤标志物及治疗靶点将是今后研究的热点，同时lncRNA具有直接、特定的调节功能，也极有可能成为胃癌的肿瘤标志物和治疗靶点。
长链非编码RNA(long chain non-coding RNA, lncRNA)的表达具有组织特异性和时空特异性，许多lncRNA具有保守的二级结构，提示lncRNAs具有重要的生物学功能。近些年来研究发现，超过80%的肿瘤相关单核苷酸多态性位点在基因组的非编码区域，lncRNA具有功能蛋白质的信号、引导、诱饵或支架分子等多种功能。目前在胃癌组织中发现了较多的基因在肿瘤发生、发展、转移及预后中起到了重要的作用，但仍有许多的lncRNA功能并不清楚，需要大量的研究来探明其结构、作用方式、机制及对胃癌的作用和影响。而在lncRNA中去发现胃癌有效的肿瘤标志物及治疗靶点将是今后研究的热点，同时lncRNA具有直接、特定的调节功能，也极有可能成为胃癌的肿瘤标志物和治疗靶点。
2017, 24(7):805-808.
DOI: 10.3872/j.issn.1007-385X.2017.07.018
Abstract:
胶质瘤是中枢神经系统最常见的肿瘤，具有发病率、复发率、病死率均较高等特点，临床亟待寻找参与胶质瘤恶性生物学行为的分子标记物，为胶质瘤的诊断、治疗和预后判断提供参考。少突胶质细胞转录因子2 (oligodendrocyte transcription fac-tor 2, Olig2)是胶质细胞特异性转录因子。Olig2几乎在所有胶质瘤中都有表达，参与胶质瘤的发生发展。Olig2维持GSC干性，促进胶质瘤的形成；调节GSC上皮间质转化，促进胶质瘤侵袭；调节GSC表型，促进不同亚型胶质瘤的发生。本文就Olig2在少突胶质瘤诊断及预后判断中的价值，胶质瘤发生发展中的作用机制以及治疗胶质瘤药物的设计和筛选中的应用作一综述。
胶质瘤是中枢神经系统最常见的肿瘤，具有发病率、复发率、病死率均较高等特点，临床亟待寻找参与胶质瘤恶性生物学行为的分子标记物，为胶质瘤的诊断、治疗和预后判断提供参考。少突胶质细胞转录因子2 (oligodendrocyte transcription fac-tor 2, Olig2)是胶质细胞特异性转录因子。Olig2几乎在所有胶质瘤中都有表达，参与胶质瘤的发生发展。Olig2维持GSC干性，促进胶质瘤的形成；调节GSC上皮间质转化，促进胶质瘤侵袭；调节GSC表型，促进不同亚型胶质瘤的发生。本文就Olig2在少突胶质瘤诊断及预后判断中的价值，胶质瘤发生发展中的作用机制以及治疗胶质瘤药物的设计和筛选中的应用作一综述。
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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.