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Volume 24,Issue 4,2017 Table of Contents
2017, 24(4):335-340.
DOI: 10.3872/j.issn.1007-385X.2017.04.001
Abstract:
Tumorigenesis is a complex process involving multistep. Tumor cells escape from immune of the host and promote their proliferation via inhibiting antitumor immune responses of the host. Molecular mechanism of the tumor immune escape is one of core issues about the tumor immune research. Programmed death receptor-1 (PD-1) is a key checkpoint for the inhibit immunity. The tumors can enhance inhibit signal of PD-1 and promote their immune escape through expression of programmed death ligand-1 (PD-L1). Research on how tumor cells regulate expression of PD-L1 can help to expound molecular mechanism of the tumor immune escape. Recently, some researches found tumor cells regulate expression of PD-L1 on multisteps of gene translation, post-transcriptional regulation and post-translational modification of proteins, as well as affect the anti-tumor immune responses through regulating expression of PD-L1. The researches provided novel targets for the immunotherapy of tumors.
Tumorigenesis is a complex process involving multistep. Tumor cells escape from immune of the host and promote their proliferation via inhibiting antitumor immune responses of the host. Molecular mechanism of the tumor immune escape is one of core issues about the tumor immune research. Programmed death receptor-1 (PD-1) is a key checkpoint for the inhibit immunity. The tumors can enhance inhibit signal of PD-1 and promote their immune escape through expression of programmed death ligand-1 (PD-L1). Research on how tumor cells regulate expression of PD-L1 can help to expound molecular mechanism of the tumor immune escape. Recently, some researches found tumor cells regulate expression of PD-L1 on multisteps of gene translation, post-transcriptional regulation and post-translational modification of proteins, as well as affect the anti-tumor immune responses through regulating expression of PD-L1. The researches provided novel targets for the immunotherapy of tumors.
2017, 24(4):341-347.
DOI: 10.3872/j.issn.1007-385X.2017.04.002
Abstract:
With development of novel techniques for targeted therapy, immunotherapy and so on, the tumor diagnosis and treatment have entered a new era of precision treatment. Liquid biopsy played an increasingly important role in the precision treatment of tumors as a convenient and noninvasive assay which could dynamically reflect the whole pictures of tumor gene spectrum. Detection of circulation tumor cells (CTCs) in blood is the earliest liquid biopsy technique and has been widely used in the early diagnosis, prognosis judgment, efficacy evaluation and so on for tumors. At primary stage, the detection of CTCs mainly based on a purely counting. However, a fact that the purely counting cannot really reflect the situations of tumor load and changes was gradually found. With continuous developments of sequencing technique and so on for a single cell, understanding of CTCs is also deepening and the detection of CTCs gradually turned to the advanced stage that is based on analysis of molecular phenotype and function. This paper mainly elaborated a development of CTCs detection from a primary stage to an advanced one and progresses of the research on its application in the precision treatment of tumor, combining with clinical practice for recent years.
With development of novel techniques for targeted therapy, immunotherapy and so on, the tumor diagnosis and treatment have entered a new era of precision treatment. Liquid biopsy played an increasingly important role in the precision treatment of tumors as a convenient and noninvasive assay which could dynamically reflect the whole pictures of tumor gene spectrum. Detection of circulation tumor cells (CTCs) in blood is the earliest liquid biopsy technique and has been widely used in the early diagnosis, prognosis judgment, efficacy evaluation and so on for tumors. At primary stage, the detection of CTCs mainly based on a purely counting. However, a fact that the purely counting cannot really reflect the situations of tumor load and changes was gradually found. With continuous developments of sequencing technique and so on for a single cell, understanding of CTCs is also deepening and the detection of CTCs gradually turned to the advanced stage that is based on analysis of molecular phenotype and function. This paper mainly elaborated a development of CTCs detection from a primary stage to an advanced one and progresses of the research on its application in the precision treatment of tumor, combining with clinical practice for recent years.
2017, 24(4):348-354.
DOI: 10.3872/j.issn.1007-385X.2017.04.003
Abstract:
Objective:To screen specific gene of circulating tumor cells (CTCs) of rectal cancer according to the differentially expressed profile of rectal cancer CTCs and primary tumor tissues. Methods: Four cases of rectal cancer patients treated in Fujian Cancer Hospital from September 2015 to December 2016 were selected to collect tumor tissues and corresponding para-cancerous tissues, in addition, 20 ml of peripheral blood was collected. Moflo XDP cytometry was adopted to identify and sort CTCs; after purification and amplification of sample total RNA, human whole transcriptome microarray chip was used to detect the expression profiles of CTCs and tumor tissue mRNA of corresponding patients, and further to screen the CTCs specific genes. In addition, MAC3.0 bio-informatics software was used for the gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: After sorting and testing, CTCs number sorted from each patient were 67，78，53 and 120.There were 7 755 differentially expressed gene between tumor tissues and normal para-cancerous tissues; there were 567 differentially expressed gene between CTCs and white cells; Combining the two dataset, there were 36 differentially co-expressed gene, including 16 up-regulated genes and 20 down-regulated genes (P<0.05 or P<0.01).GO function of CTCs specific genes were correlated with tumor metastasis and stem cell function, and those specific genes also participated in 22 signaling pathways related to cell migration, stem cell function and immune function. Conclusion: Compared with primary tumor gene, CTCs has a unique mRNA profile, which is the foundation of tumor recurrence and metastasis.
Objective:To screen specific gene of circulating tumor cells (CTCs) of rectal cancer according to the differentially expressed profile of rectal cancer CTCs and primary tumor tissues. Methods: Four cases of rectal cancer patients treated in Fujian Cancer Hospital from September 2015 to December 2016 were selected to collect tumor tissues and corresponding para-cancerous tissues, in addition, 20 ml of peripheral blood was collected. Moflo XDP cytometry was adopted to identify and sort CTCs; after purification and amplification of sample total RNA, human whole transcriptome microarray chip was used to detect the expression profiles of CTCs and tumor tissue mRNA of corresponding patients, and further to screen the CTCs specific genes. In addition, MAC3.0 bio-informatics software was used for the gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: After sorting and testing, CTCs number sorted from each patient were 67，78，53 and 120.There were 7 755 differentially expressed gene between tumor tissues and normal para-cancerous tissues; there were 567 differentially expressed gene between CTCs and white cells; Combining the two dataset, there were 36 differentially co-expressed gene, including 16 up-regulated genes and 20 down-regulated genes (P<0.05 or P<0.01).GO function of CTCs specific genes were correlated with tumor metastasis and stem cell function, and those specific genes also participated in 22 signaling pathways related to cell migration, stem cell function and immune function. Conclusion: Compared with primary tumor gene, CTCs has a unique mRNA profile, which is the foundation of tumor recurrence and metastasis.
XU Yangmei
,
LIU Qiaozhen
,
LIU Qinying
,
WEI Shenghong
,
CHEN Luchuan
,
YING Mingang
,
ZHENG Qiuhong
2017, 24(4):355-361.
DOI: 10.3872/j.issn.1007-385X.2017.04.004
Abstract:
Objective:To explore the feasibility and clinical value of indentifying circulating tumor cells (CTCs) and circulating tumor stem cells (CTSCs) by Flow cytometry before and after the radical resection of colorectal carcinoma for the prognosis prediction of colorectal cancerl (CRC) patients. Methods: Altogether 50 colorectal cancer patients without previous chemotherapeutic treatment were recruited. Approximately 15 ml peripheral blood was drawn from each patient before and one week after surgery. Mononuclear cells were isolated and divided into two groups: one was tagged with CTC surface markers (CD45, EpCAM and CK), and the other with CTSC markers (CD45, EpCAM, CD44 and CD133). After examination by Moflo XDP flow cytometry, CTC was difined as CD45-EpCAM+ CK+; and CTSC was categorized into three groups: CD44+CTSC(CD45-EpCAM+CD44+), CD133+ CTSC (CD45-EpCAM+CD133+ ) ,CD44+ CD133+ CTSC (CD45-EpCAM+CD44+CD133+ ). Results: Positive rates of pre-operative CTC and CD44+CTSC were 34% and 44%, respectively, while the positive rates of CD133+ CTSC and CD44+ CD133+ CTSC were 24% and 0%, respectively. Positive rates of post-operative CTC and CD44+CTSC were 38% and 54%, respectively, while the positive rates of CD133+ CTSC and CD44+ CD133+ CTSC were 26% and 0%, respectively. Both pre- and post-operative CTC levels were associated with the T stages of tumor (P<0.05); Moreover, post-operative CTC level had significant correlation with infiltration depth, lymphnode metastasis and distant metastasis (P<0.05). Pre-operative CD44+CTSC level was associated with tumor infiltration depth (P<0.05). Conclusion: Pre- and post-operative CTCs and preoperative CD44+CTSC all have the feasibility and practical value to be the prognostic biomarkers; Postoperative CTC positive rate may serve as a better predictive biomarker for colorectal cancer.
Objective:To explore the feasibility and clinical value of indentifying circulating tumor cells (CTCs) and circulating tumor stem cells (CTSCs) by Flow cytometry before and after the radical resection of colorectal carcinoma for the prognosis prediction of colorectal cancerl (CRC) patients. Methods: Altogether 50 colorectal cancer patients without previous chemotherapeutic treatment were recruited. Approximately 15 ml peripheral blood was drawn from each patient before and one week after surgery. Mononuclear cells were isolated and divided into two groups: one was tagged with CTC surface markers (CD45, EpCAM and CK), and the other with CTSC markers (CD45, EpCAM, CD44 and CD133). After examination by Moflo XDP flow cytometry, CTC was difined as CD45-EpCAM+ CK+; and CTSC was categorized into three groups: CD44+CTSC(CD45-EpCAM+CD44+), CD133+ CTSC (CD45-EpCAM+CD133+ ) ,CD44+ CD133+ CTSC (CD45-EpCAM+CD44+CD133+ ). Results: Positive rates of pre-operative CTC and CD44+CTSC were 34% and 44%, respectively, while the positive rates of CD133+ CTSC and CD44+ CD133+ CTSC were 24% and 0%, respectively. Positive rates of post-operative CTC and CD44+CTSC were 38% and 54%, respectively, while the positive rates of CD133+ CTSC and CD44+ CD133+ CTSC were 26% and 0%, respectively. Both pre- and post-operative CTC levels were associated with the T stages of tumor (P<0.05); Moreover, post-operative CTC level had significant correlation with infiltration depth, lymphnode metastasis and distant metastasis (P<0.05). Pre-operative CD44+CTSC level was associated with tumor infiltration depth (P<0.05). Conclusion: Pre- and post-operative CTCs and preoperative CD44+CTSC all have the feasibility and practical value to be the prognostic biomarkers; Postoperative CTC positive rate may serve as a better predictive biomarker for colorectal cancer.
2017, 24(4):362-366.
DOI: 10.3872/j.issn.1007-385X.2017.04.005
Abstract:
Objective:To explore the significance of peripheral blood circulating tumor cells (CTCs) combined with gastrin releasing peptide (pro-GRP) and neuron specific enolase (NSE) in evaluating the chemotherapy efficacy for small cell lung cancer (SCLC) patients. Methods: Forty SCLC patients treated in the department of respiratory and critical care of Changhai Hospital from October 1, 2015 to November 30, 2016 were included in this study. The peripheral blood was extracted from patients before the chemotherapy of first and third cycle to determine the level of CTCs, pro-GRP and NSE, and to analyze their relationship to the efficacy of chemotherapy. Meanwhile, all patients underwent the chest CT before the first and the third cycle of chemotherapy, to compare the differences between CTCs combined with pro-GRP, NSE evaluation and RECIST standard in judging the efficacy of chemotherapy. In addition, the correlation between CTCs number and clinical characteristics of patients were also analyzed. Results: In 40 SCLC patients, the CTCs positive rates detected at two times were 82.5%, 87.5%, respectively. The more CTCs number decreased after chemotherapy, the better effect of chemotherapy was. According to RECIST criteria, there was significant difference in the change of CTCs number between tumor progression group and tumor control group(P<0.05). According to CTCs number evaluation criteria, tumor control was not significantly correlated with age, sex, smoking, tumor size and tumor stage (P<0.05).There was a consistency in evaluating the efficacy of chemotherapy between CTCs number evaluation criteria and RECIST criteria (P>005). Combined detection of CTCs, pro-GRP and NSE in evaluating the chemotherapy efficacy has the same result as RECIST evaluation (P>0.05), and the joint detection can improve the sensitivity of efficacy judgment. Conclusion:There was a negative correlation between the change of CTCs number and the efficacy of chemotherapy. Combing detection of CTCs, pro-GRP and NSE to evaluate the efficacy of chemotherapy for SCLC patients has a higher sensitivity.
Objective:To explore the significance of peripheral blood circulating tumor cells (CTCs) combined with gastrin releasing peptide (pro-GRP) and neuron specific enolase (NSE) in evaluating the chemotherapy efficacy for small cell lung cancer (SCLC) patients. Methods: Forty SCLC patients treated in the department of respiratory and critical care of Changhai Hospital from October 1, 2015 to November 30, 2016 were included in this study. The peripheral blood was extracted from patients before the chemotherapy of first and third cycle to determine the level of CTCs, pro-GRP and NSE, and to analyze their relationship to the efficacy of chemotherapy. Meanwhile, all patients underwent the chest CT before the first and the third cycle of chemotherapy, to compare the differences between CTCs combined with pro-GRP, NSE evaluation and RECIST standard in judging the efficacy of chemotherapy. In addition, the correlation between CTCs number and clinical characteristics of patients were also analyzed. Results: In 40 SCLC patients, the CTCs positive rates detected at two times were 82.5%, 87.5%, respectively. The more CTCs number decreased after chemotherapy, the better effect of chemotherapy was. According to RECIST criteria, there was significant difference in the change of CTCs number between tumor progression group and tumor control group(P<0.05). According to CTCs number evaluation criteria, tumor control was not significantly correlated with age, sex, smoking, tumor size and tumor stage (P<0.05).There was a consistency in evaluating the efficacy of chemotherapy between CTCs number evaluation criteria and RECIST criteria (P>005). Combined detection of CTCs, pro-GRP and NSE in evaluating the chemotherapy efficacy has the same result as RECIST evaluation (P>0.05), and the joint detection can improve the sensitivity of efficacy judgment. Conclusion:There was a negative correlation between the change of CTCs number and the efficacy of chemotherapy. Combing detection of CTCs, pro-GRP and NSE to evaluate the efficacy of chemotherapy for SCLC patients has a higher sensitivity.
2017, 24(4):367-372.
DOI: 10.3872/j.issn.1007-385X.2017.04.006
Abstract:
非小细胞肺癌（non-small cell lung cancer,NSCLC）是发病率及病死率最高的恶性肿瘤，确诊时大多数NSCLC患者已到疾病晚期，导致患者5年生存率低。随着肿瘤个体化治疗的进展，早期诊断以及对患者病情实时监测尤为重要。循环肿瘤细胞（circulating tumor cell，CTC）作为肿瘤血源性转移的生物学标志物之一，是“液体活检”的重要指标，可用于肿瘤患者实时动态监测。检测CTC有助于早期发现NSCLC微转移、重新确定临床分期、实时监测抗肿瘤治疗疗效、评估预后、制定个体化的治疗策略，不仅如此，对其进一步分子鉴定有助于阐明肿瘤的生物学进程及转移机制。然而，由于检测标准不统一、检测阳性率低等多种因素，现阶段 CTC 仍较难应用到临床工作中。本文对CTC的发展历程及其在NSCLC诊断、治疗及预后等方面的研究新近进展作一综述。
非小细胞肺癌（non-small cell lung cancer,NSCLC）是发病率及病死率最高的恶性肿瘤，确诊时大多数NSCLC患者已到疾病晚期，导致患者5年生存率低。随着肿瘤个体化治疗的进展，早期诊断以及对患者病情实时监测尤为重要。循环肿瘤细胞（circulating tumor cell，CTC）作为肿瘤血源性转移的生物学标志物之一，是“液体活检”的重要指标，可用于肿瘤患者实时动态监测。检测CTC有助于早期发现NSCLC微转移、重新确定临床分期、实时监测抗肿瘤治疗疗效、评估预后、制定个体化的治疗策略，不仅如此，对其进一步分子鉴定有助于阐明肿瘤的生物学进程及转移机制。然而，由于检测标准不统一、检测阳性率低等多种因素，现阶段 CTC 仍较难应用到临床工作中。本文对CTC的发展历程及其在NSCLC诊断、治疗及预后等方面的研究新近进展作一综述。
2017, 24(4):373-379.
DOI: 10.3872/j.issn.1007-385X.2017.04.007
Abstract:
Objective:To explore the effect of Runt-related transcription factor 2 (RUNX2) on apoptosis of mouse breast cancer 4T1 cells under hypoxia and its mechanism. Methods: Western blotting and Real-time PCR were used to measure the effect of hypoxia on the expression levels of RUNX1, RUNX2, RUNX3 mRNA and RUNX2 protein in 4T1 cells; small interference RNA (siRNA) and eukaryotic recombinant plasmid DNA over-expression technique were used to down-or up-regulate the RUNX2 expression in 4T1 cells respectively; Co-immunoprecipitation was used to detect the binding of RUNX2 and other proteins in 4T1 cells; Flow cytometry was used for the detection of the effect of down-/up-regulation of RUNX2 on apoptosis of 4T1 cells under normoxic/hypoxic condition. Results: The mRNA expression levels of RUNX1 and RUNX2 in 4T1 cells were up-regulated under hypoxic condition (P<0.05), and the protein expression of RUNX2 was significantly elevated (P<0.05). Transfection with RUNX2-siRNA-1415 or pcDNA3.1(-)-RUNX2 could significantly decrease or increase the RUNX2 level in 4T1 cells, respectively; Under normoxic/hypoxic condition, apoptosis rate of 4T1 cells that transfected with siRNA-RUNX2-1415 was significantly increased by comparing with negative control group(normoxia: \[12.83±0.2404\]% vs \[9.3±0.5508\]%, P<0.05; hypoxia: \[19.77±0.59\]% vs \[15.13±032\]%, P<0.05); however, the apoptosis rate of 4T1 cells were decreased by over-expressing RUNX2 (normoxia: \[9.967±02728\]% vs \[14.07±0.7965\]%, P<0.05; hypoxia: \[22.43±1.02\]% vs \[34.93±0.71\]%, P<005). Under hypoxic condition, the expression levels of hypoxic induced factor-1α (HIF-1α) and RUNX2 were significantly elevated, and RUNX2 could bind with HIF-1α to form complex. Conclusion: Under the hypoxic micro-environment, 4T1 cells express the high level of RUNX2, in the meanwhile, high level RUNX2 could inhibit the apoptosis of tumor cells by interacting with HIF-1α.
Objective:To explore the effect of Runt-related transcription factor 2 (RUNX2) on apoptosis of mouse breast cancer 4T1 cells under hypoxia and its mechanism. Methods: Western blotting and Real-time PCR were used to measure the effect of hypoxia on the expression levels of RUNX1, RUNX2, RUNX3 mRNA and RUNX2 protein in 4T1 cells; small interference RNA (siRNA) and eukaryotic recombinant plasmid DNA over-expression technique were used to down-or up-regulate the RUNX2 expression in 4T1 cells respectively; Co-immunoprecipitation was used to detect the binding of RUNX2 and other proteins in 4T1 cells; Flow cytometry was used for the detection of the effect of down-/up-regulation of RUNX2 on apoptosis of 4T1 cells under normoxic/hypoxic condition. Results: The mRNA expression levels of RUNX1 and RUNX2 in 4T1 cells were up-regulated under hypoxic condition (P<0.05), and the protein expression of RUNX2 was significantly elevated (P<0.05). Transfection with RUNX2-siRNA-1415 or pcDNA3.1(-)-RUNX2 could significantly decrease or increase the RUNX2 level in 4T1 cells, respectively; Under normoxic/hypoxic condition, apoptosis rate of 4T1 cells that transfected with siRNA-RUNX2-1415 was significantly increased by comparing with negative control group(normoxia: \[12.83±0.2404\]% vs \[9.3±0.5508\]%, P<0.05; hypoxia: \[19.77±0.59\]% vs \[15.13±032\]%, P<0.05); however, the apoptosis rate of 4T1 cells were decreased by over-expressing RUNX2 (normoxia: \[9.967±02728\]% vs \[14.07±0.7965\]%, P<0.05; hypoxia: \[22.43±1.02\]% vs \[34.93±0.71\]%, P<005). Under hypoxic condition, the expression levels of hypoxic induced factor-1α (HIF-1α) and RUNX2 were significantly elevated, and RUNX2 could bind with HIF-1α to form complex. Conclusion: Under the hypoxic micro-environment, 4T1 cells express the high level of RUNX2, in the meanwhile, high level RUNX2 could inhibit the apoptosis of tumor cells by interacting with HIF-1α.
2017, 24(4):380-388.
DOI: 10.3872/j.issn.1007-385X.2017.04.008
Abstract:
Objective:To explore the effect and molecular mechanism of mediator 19 (Med19) on drug sensitivity of breast cancer cells. Methods: Human breast cancer cell line MCF-7/ADM (adriamycin resistant) and it’s parental cell line MCF-7（NC groups） were selected. Lentivirus-mediated RNA-interference was used to construct MCF-7/ADM and MCF-7 cell lines that stably expressing low Med19 (KD groups), and the infection efficiency was detected by Real-time PCR and Western blotting assays. The change of drug-susceptibility to ADM, cisplatin (DDP) and taxinol (TAX) were examined with CCK-8 assay before and after Med19 knockdown. The effects of Med19 knockdown on the expressions of multidrug resistance gene 1(MDR1), Bcl2, Bax, Caspase-3 and active caspase-3 in breast cancer cells were detected by RT-PCR and Western Blotting assays, respectively. Effect of Med19 down-regulation and ADM treatment on apoptosis rates of MCF-7 and MCF-7/ADM cells were detected with flow cytometry assay. Results: Compared with MCF-7 cells, MCF-7/ADM cells exhibited drug resistance to ADM, DDP and TAX. MCF-7/ADM and MCF-7 cell lines that stably expressing low Med19level were successfully established; their drug-susceptibilities to ADM, DDP, TAX were increased, and the IC50 values of these three cytotoxic agents deceased obviously (all P<0.05). The mRNA and protein expressions of Med19 in MCF-7/ADM cells were significantly higher than those in MCF-7 cells, however, Med19 knockdown significantly inhibited the expressions of MDR1 mRNA and protein in MCF-7/ADM cells (all P<0.05); in addition, it significantly increased the expressions of active caspase-3 and Bax protein in both MCF-7/ADM and MCF-7 cells (all P<0.05) and decreased the expression of Bcl2 protein (all P<0.05). Besides, compared with NC or NC+ADM group, the apoptosis rate of the cells significantly increased in KD group or KD+ADM group (all P<0.05). Conclusions: High Med19 expression plays a particularly important role in chemoresistance of breast cancer, and the mechanism might correlate with Med19 regulating MDR1 expression and affecting apoptosis related genes.
Objective:To explore the effect and molecular mechanism of mediator 19 (Med19) on drug sensitivity of breast cancer cells. Methods: Human breast cancer cell line MCF-7/ADM (adriamycin resistant) and it’s parental cell line MCF-7（NC groups） were selected. Lentivirus-mediated RNA-interference was used to construct MCF-7/ADM and MCF-7 cell lines that stably expressing low Med19 (KD groups), and the infection efficiency was detected by Real-time PCR and Western blotting assays. The change of drug-susceptibility to ADM, cisplatin (DDP) and taxinol (TAX) were examined with CCK-8 assay before and after Med19 knockdown. The effects of Med19 knockdown on the expressions of multidrug resistance gene 1(MDR1), Bcl2, Bax, Caspase-3 and active caspase-3 in breast cancer cells were detected by RT-PCR and Western Blotting assays, respectively. Effect of Med19 down-regulation and ADM treatment on apoptosis rates of MCF-7 and MCF-7/ADM cells were detected with flow cytometry assay. Results: Compared with MCF-7 cells, MCF-7/ADM cells exhibited drug resistance to ADM, DDP and TAX. MCF-7/ADM and MCF-7 cell lines that stably expressing low Med19level were successfully established; their drug-susceptibilities to ADM, DDP, TAX were increased, and the IC50 values of these three cytotoxic agents deceased obviously (all P<0.05). The mRNA and protein expressions of Med19 in MCF-7/ADM cells were significantly higher than those in MCF-7 cells, however, Med19 knockdown significantly inhibited the expressions of MDR1 mRNA and protein in MCF-7/ADM cells (all P<0.05); in addition, it significantly increased the expressions of active caspase-3 and Bax protein in both MCF-7/ADM and MCF-7 cells (all P<0.05) and decreased the expression of Bcl2 protein (all P<0.05). Besides, compared with NC or NC+ADM group, the apoptosis rate of the cells significantly increased in KD group or KD+ADM group (all P<0.05). Conclusions: High Med19 expression plays a particularly important role in chemoresistance of breast cancer, and the mechanism might correlate with Med19 regulating MDR1 expression and affecting apoptosis related genes.
2017, 24(4):389-394.
DOI: 10.3872/j.issn.1007-385X.2017.04.009
Abstract:
Objective:To evaluate the effect of small interfering RNA (siRNA) of CXCR4 and CXCR7 on the growth of endometrial cancer (EC) Ishikawa cells xenografts in nude mice. Methods: EC Ishikawa cells were subcutaneously injected into the right flank of nude mice to establish animal xenograft model. When the diameter of tumors reached 5-7 mm, all tumor-bearing mice were randomly divided into five groups, and treated with intra-tumor injection of CXCR4-siRNA, CXCR7-siRNA, CXCR4-siRNA+CXCR7-siRNA, negative-siRNA, and normal saline, respectively. Growth of xenografts was observed, and the differences in volume and weight of xenografts among five groups were examined. CXCR4 and CXCR7expressions in tumor xenografts were detected by quantitative reverse transcription polymerase chain reaction (QRT-PCR), Western blotting and immunohistochemical technique, respectively. Results: Ishikawa cells xenograft model in nude mice was successfully constructed. The growth of tumor xenografts in CXCR4 siRNA group, CXCR-siRNA group and CXCR4-siRNA+CXCR7-siRNA group were significantly inhibited, compared with those in negative control and blank control group (all P<0.05). The mRNA (P<0.05) and protein (P<0.01) expressions of CXCR4 and CXCR7 were statistically down-regulated by directly injecting siRNA into xenografts. Conclusion: siRNA interfering CXCR4and CXCR7could effectively suppress the growth of human EC Ishikawa xenografts in nude mice.
Objective:To evaluate the effect of small interfering RNA (siRNA) of CXCR4 and CXCR7 on the growth of endometrial cancer (EC) Ishikawa cells xenografts in nude mice. Methods: EC Ishikawa cells were subcutaneously injected into the right flank of nude mice to establish animal xenograft model. When the diameter of tumors reached 5-7 mm, all tumor-bearing mice were randomly divided into five groups, and treated with intra-tumor injection of CXCR4-siRNA, CXCR7-siRNA, CXCR4-siRNA+CXCR7-siRNA, negative-siRNA, and normal saline, respectively. Growth of xenografts was observed, and the differences in volume and weight of xenografts among five groups were examined. CXCR4 and CXCR7expressions in tumor xenografts were detected by quantitative reverse transcription polymerase chain reaction (QRT-PCR), Western blotting and immunohistochemical technique, respectively. Results: Ishikawa cells xenograft model in nude mice was successfully constructed. The growth of tumor xenografts in CXCR4 siRNA group, CXCR-siRNA group and CXCR4-siRNA+CXCR7-siRNA group were significantly inhibited, compared with those in negative control and blank control group (all P<0.05). The mRNA (P<0.05) and protein (P<0.01) expressions of CXCR4 and CXCR7 were statistically down-regulated by directly injecting siRNA into xenografts. Conclusion: siRNA interfering CXCR4and CXCR7could effectively suppress the growth of human EC Ishikawa xenografts in nude mice.
2017, 24(4):395-399.
DOI: 10.3872/j.issn.1007-385X.2017.04.010
Abstract:
Objective:To investigate the effects and mechanisms of genistein (Gen) enhancing radio-sensitivity of Hepatoma Bel-7404 cells. Methods: Bel-7404 cells were divided into four groups: normal control (NC), genistein treatment (G), radiation alone treatment (R) as well as genistein+radiation treatment group (G+R). Except the NC group, the other three groups were treated with genistein (5 μmol/L) and/or X-ray irradiation (8 Gy) at a dose rate of 300 cGy/min, respectively. The effect of Gen and x-ray on cell proliferation, cell cycle and apoptosis of Bel-7404 cells were detected using CCK-8 and flow cytometry, respectively; the expression levels of ATM-Chk2 signal pathway related proteins were detected using Western blotting.Results:The inhibitory rate on cell proliferation in G+R group was significantly higher than that in R group at 24 h after irradiation (\[16.80±2.59\]% vs \[9.76±2.11\]%, P<0.05). And the inhibitory effect was enhanced in a time-dependent manner. Compared with NC group, the cell apoptosis rate and percentage of cells in G2/M phase were all significantly increased in G, R and G+R group (P<0.05 or P<0.01). Combination of Gen with X-ray further increased cell apoptosis compared with X-ray treatment alone group (\[51.86±288\]% vs \[33.18±4.48\]%, P<0.01). Furthermore, the expressions of p-ATM and p-Chk2 were obviously up-regulated in G+R group compared with that of R, G and NC group. Conclusions: Gen could enhance radiosensitivity of hepatoma Bel-7404 cells, and the mechanism might be related with the activation of ATM-Chk2 signal pathway.
Objective:To investigate the effects and mechanisms of genistein (Gen) enhancing radio-sensitivity of Hepatoma Bel-7404 cells. Methods: Bel-7404 cells were divided into four groups: normal control (NC), genistein treatment (G), radiation alone treatment (R) as well as genistein+radiation treatment group (G+R). Except the NC group, the other three groups were treated with genistein (5 μmol/L) and/or X-ray irradiation (8 Gy) at a dose rate of 300 cGy/min, respectively. The effect of Gen and x-ray on cell proliferation, cell cycle and apoptosis of Bel-7404 cells were detected using CCK-8 and flow cytometry, respectively; the expression levels of ATM-Chk2 signal pathway related proteins were detected using Western blotting.Results:The inhibitory rate on cell proliferation in G+R group was significantly higher than that in R group at 24 h after irradiation (\[16.80±2.59\]% vs \[9.76±2.11\]%, P<0.05). And the inhibitory effect was enhanced in a time-dependent manner. Compared with NC group, the cell apoptosis rate and percentage of cells in G2/M phase were all significantly increased in G, R and G+R group (P<0.05 or P<0.01). Combination of Gen with X-ray further increased cell apoptosis compared with X-ray treatment alone group (\[51.86±288\]% vs \[33.18±4.48\]%, P<0.01). Furthermore, the expressions of p-ATM and p-Chk2 were obviously up-regulated in G+R group compared with that of R, G and NC group. Conclusions: Gen could enhance radiosensitivity of hepatoma Bel-7404 cells, and the mechanism might be related with the activation of ATM-Chk2 signal pathway.
2017, 24(4):400-403.
DOI: 10.3872/j.issn.1007-385X.2017.04.011
Abstract:
Objective: To investigate the effects of artesunate (ART) on the proliferation, invasion and migratory ability of human lung cancer A549 cells and its possible mechanisms. Methods: CCK-8 assay was used to analyze the proliferation level of A549 cells after treatment with different concentrations of ART for 24 and 48 h. Transwell assay and wound healing assay were adopted to evaluate the invasion and migration of A549 cells after the treatment of ART at concentration of 30 μg/ml, respectively. Western blotting was used to detect the change in protein expressions of human antigen R (HuR) and MMP-9 in A549 cells after the treatment with ART (30 μg/ml). Results:ART inhibited the proliferation of human lung cancer A549 cells in a dose-dependent manner (P<0.05). Compared with untreated group, number of A549 cells penetrating the membrane in ART group (30μg/ml) was significantly decreased(\[47.11±8.61\] vs \[131.00±1458\], P<001), and the migration distance was remarkably reduced (\[1.08±0.13\] vs \[2.91±0.24\] mm, P<001). In addition, ART significantly inhibited the protein expression of HuR and MMP-9 in A549 cells (P<0.05). Conclusion: ART can inhibit the proliferation, invasion and migration of A549 cells, and this effect may be related to inhibition of HuR expression.
Objective: To investigate the effects of artesunate (ART) on the proliferation, invasion and migratory ability of human lung cancer A549 cells and its possible mechanisms. Methods: CCK-8 assay was used to analyze the proliferation level of A549 cells after treatment with different concentrations of ART for 24 and 48 h. Transwell assay and wound healing assay were adopted to evaluate the invasion and migration of A549 cells after the treatment of ART at concentration of 30 μg/ml, respectively. Western blotting was used to detect the change in protein expressions of human antigen R (HuR) and MMP-9 in A549 cells after the treatment with ART (30 μg/ml). Results:ART inhibited the proliferation of human lung cancer A549 cells in a dose-dependent manner (P<0.05). Compared with untreated group, number of A549 cells penetrating the membrane in ART group (30μg/ml) was significantly decreased(\[47.11±8.61\] vs \[131.00±1458\], P<001), and the migration distance was remarkably reduced (\[1.08±0.13\] vs \[2.91±0.24\] mm, P<001). In addition, ART significantly inhibited the protein expression of HuR and MMP-9 in A549 cells (P<0.05). Conclusion: ART can inhibit the proliferation, invasion and migration of A549 cells, and this effect may be related to inhibition of HuR expression.
ZHAO Jianfu
,
ZHAO Fengzhi
,
CHEN Wenhui
,
QUAN Qiang
,
FAN Jing
,
CHEN Biyun
,
ZHANG Ding
,
XU Meng
2017, 24(4):404-410.
DOI: 10.3872/j.issn.1007-385X.2017.04.012
Abstract:
Objective:To investigate the antitumor activity and the mechanism of cytokine-induced killer (CIK) cells combined with bevacizumab against hepatocellular carcinoma HepG2 cells in vitro and in vivo. Methods: Peripheral blood mononuclear cells (PBMCs) from healthy blood donors were isolated and cultured in the presence of different cytokines to promote the maturation of CIK cells; and the immune phenotypes of CIK cells were analyzed by flow cytometry. The inhibitory effect on HepG2 cells of CIK cells combining with or without bevacizumab were analyzed by CCK-8 assay. Cell migration and invasion of HepG2 cells were detected by scratch assay and transwell assay. The phosphorylation levels of Erk/Akt signaling pathway related proteins were detected by Western blotting. HepG2 cell xenograft tumor model was established in nude mice. Tumor bearing mice were divided into normal saline control group, CIK group, bevacizumab group and CIK+bevacizumab group. On the 28th day after drug administration, the mice were sacrificed and tumors were isolated. Immunohistochemical staining was used to analyze the expressions of CD31 and Ki67. Results: Human PBMCs were stimulated for 14 days, and the CIK cell phenotype analysis showed that the amplification of CD3+CD56+ CIK cells reached (36.33±2.58)%. The inhibition rate of CIK cells combined with bevacizumab was significantly enhanced by comparing with CIK/bevacizumab alone groups (all P<0.05). CIK cells combined with bevacizumab showed a more intensive inhibition on cell migration(\[75.6±9.53\] vs \[304.8±45.73\], \[359.8±38.10\], P<0.01) and invasion (\[29.35±8.14\]% vs \[55.07±6.27\]%, \[60.50±9.73\]%, P<0.05\] by comparing with those two single treatment groups; CIK cell treatment, bevacizumab treatment and the combined treatment could all decrease the phosphorylation level of Erk and Akt; the combined treatment significantly inhibited the tumor growth, mean vessel density (MVD) and Ki67 expression, which had statistical significance when compared with the other groups (P<0.05). Conclusion: The current study suggested that CIK cells combined with bevacizumab inhibited HepG2 cells proliferation, invasion and migration both in vitro and in vivo, which significantly precede the treatment efficacy of single treatment groups.
Objective:To investigate the antitumor activity and the mechanism of cytokine-induced killer (CIK) cells combined with bevacizumab against hepatocellular carcinoma HepG2 cells in vitro and in vivo. Methods: Peripheral blood mononuclear cells (PBMCs) from healthy blood donors were isolated and cultured in the presence of different cytokines to promote the maturation of CIK cells; and the immune phenotypes of CIK cells were analyzed by flow cytometry. The inhibitory effect on HepG2 cells of CIK cells combining with or without bevacizumab were analyzed by CCK-8 assay. Cell migration and invasion of HepG2 cells were detected by scratch assay and transwell assay. The phosphorylation levels of Erk/Akt signaling pathway related proteins were detected by Western blotting. HepG2 cell xenograft tumor model was established in nude mice. Tumor bearing mice were divided into normal saline control group, CIK group, bevacizumab group and CIK+bevacizumab group. On the 28th day after drug administration, the mice were sacrificed and tumors were isolated. Immunohistochemical staining was used to analyze the expressions of CD31 and Ki67. Results: Human PBMCs were stimulated for 14 days, and the CIK cell phenotype analysis showed that the amplification of CD3+CD56+ CIK cells reached (36.33±2.58)%. The inhibition rate of CIK cells combined with bevacizumab was significantly enhanced by comparing with CIK/bevacizumab alone groups (all P<0.05). CIK cells combined with bevacizumab showed a more intensive inhibition on cell migration(\[75.6±9.53\] vs \[304.8±45.73\], \[359.8±38.10\], P<0.01) and invasion (\[29.35±8.14\]% vs \[55.07±6.27\]%, \[60.50±9.73\]%, P<0.05\] by comparing with those two single treatment groups; CIK cell treatment, bevacizumab treatment and the combined treatment could all decrease the phosphorylation level of Erk and Akt; the combined treatment significantly inhibited the tumor growth, mean vessel density (MVD) and Ki67 expression, which had statistical significance when compared with the other groups (P<0.05). Conclusion: The current study suggested that CIK cells combined with bevacizumab inhibited HepG2 cells proliferation, invasion and migration both in vitro and in vivo, which significantly precede the treatment efficacy of single treatment groups.
2017, 24(4):411-416.
DOI: 10.3872/j.issn.1007-385X.2017.04.013
Abstract:
Objective:To indentify the differentially expressed proteins in serum among patients of breast cancer with and without axillary lymph node metastasis, and to screen the diagnostic biomarkers and therapeutic targets that related to breast cancer metastasis.Methods: Quantitative proteomics TMT（tandem mass tag）technology was used to detect and quantitatively analyze serum proteins of breast cancer patients with and without axillary lymph node metastasis (14 cases in each group), and to further screen significant differentially expressed proteins. Uniprot database and proteome discoverer software were applied to analyze the bioinformatics. Results:One hundred and nineteen differentially expressed proteins were identified, and 6 proteins were significantly up-regulated,113 proteins were significantly down-regulated. Gene ontology (GO) annotation and functional cluster analyses showed that these differentially expressed proteins are locate at extracellular domain, and correlate with biosynthesis, cell proliferation and angiogenesis of tumor. Western boltting and qRT-PCR verified that the expressions of K1C19 (down-regulated by 0.11 times) and PSME2 (up-regulated by 2.02 times). Conclusion: TMT quantitative proteomics is a compelling way to discover differentially expressed proteins of breast cancer patients with and without axillary lymph node metastasis, and K1C19 and PSME2 are the potential serum biomarkers that deserve further exploration.
Objective:To indentify the differentially expressed proteins in serum among patients of breast cancer with and without axillary lymph node metastasis, and to screen the diagnostic biomarkers and therapeutic targets that related to breast cancer metastasis.Methods: Quantitative proteomics TMT（tandem mass tag）technology was used to detect and quantitatively analyze serum proteins of breast cancer patients with and without axillary lymph node metastasis (14 cases in each group), and to further screen significant differentially expressed proteins. Uniprot database and proteome discoverer software were applied to analyze the bioinformatics. Results:One hundred and nineteen differentially expressed proteins were identified, and 6 proteins were significantly up-regulated,113 proteins were significantly down-regulated. Gene ontology (GO) annotation and functional cluster analyses showed that these differentially expressed proteins are locate at extracellular domain, and correlate with biosynthesis, cell proliferation and angiogenesis of tumor. Western boltting and qRT-PCR verified that the expressions of K1C19 (down-regulated by 0.11 times) and PSME2 (up-regulated by 2.02 times). Conclusion: TMT quantitative proteomics is a compelling way to discover differentially expressed proteins of breast cancer patients with and without axillary lymph node metastasis, and K1C19 and PSME2 are the potential serum biomarkers that deserve further exploration.
PAN Na
,
REN Hongliang
,
ZHAO Ning
,
SHEN Xuejie
,
WEI Feng
,
WANG Yang
,
ZHENG Yu
,
JIN Hao
,
WU Zhanbo
,
CAO Shui
2017, 24(4):417-422.
DOI: 10.3872/j.issn.1007-385X.2017.04.014
Abstract:
Objective:To investigate the correlation between Tregs infiltration in non-small cell lung carcinoma (NSCLC) tissues and SUVmax for primary lesion in PET-CT, and its effect on prognosis of NSCLC. Methods: One hundred and twenty two samples of primary NSCLC patients diagnosed in Cancer Institute and Hospital affiliated to Tianjin Medical University during March 2008 to October 2014 were collected, as well as their imaging, clinical and pathological data and follow-up information. Immunohistochemistry was used to detect the Tregs infiltration of carcinoma tissues. Survival outcomes were analyzed using the Kaplan-Meier method. Correlations between Tregs infiltration and SUVmax of primary lesions, as well as other clinicopathological factors were analyzed using Pearson correlation analysis and Spearman rank correlation analysis. Results: There was a positive correlation between Tregs infiltration and SUVmax (r=0.291, P=0.001). Tregs and SUVmax were divided into two groups respectively at the level of cut off value. Univariate analysis showed that Tregs and SUVmax were risk factors for the prognosis of patients. Clinical data also demonstrated that there was positive correlation between Tregs and tumor size, TNM stage (P<0.05). Multivariate Cox analysis demonstrated that tumor TNM stage (HR=7.537, 95% CI:1.191-2.855, P=0.006) was independent predictors for survival. Conclusion: There was a positive correlation between Tregs infiltration and SUVmax; PET/CT SUVmax may indicate Tregs infiltration in the tumor microenvironment of NSCLC patients, and it may play important role in predicting clinical prognosis and guiding treatment for NSCLC patients.
Objective:To investigate the correlation between Tregs infiltration in non-small cell lung carcinoma (NSCLC) tissues and SUVmax for primary lesion in PET-CT, and its effect on prognosis of NSCLC. Methods: One hundred and twenty two samples of primary NSCLC patients diagnosed in Cancer Institute and Hospital affiliated to Tianjin Medical University during March 2008 to October 2014 were collected, as well as their imaging, clinical and pathological data and follow-up information. Immunohistochemistry was used to detect the Tregs infiltration of carcinoma tissues. Survival outcomes were analyzed using the Kaplan-Meier method. Correlations between Tregs infiltration and SUVmax of primary lesions, as well as other clinicopathological factors were analyzed using Pearson correlation analysis and Spearman rank correlation analysis. Results: There was a positive correlation between Tregs infiltration and SUVmax (r=0.291, P=0.001). Tregs and SUVmax were divided into two groups respectively at the level of cut off value. Univariate analysis showed that Tregs and SUVmax were risk factors for the prognosis of patients. Clinical data also demonstrated that there was positive correlation between Tregs and tumor size, TNM stage (P<0.05). Multivariate Cox analysis demonstrated that tumor TNM stage (HR=7.537, 95% CI:1.191-2.855, P=0.006) was independent predictors for survival. Conclusion: There was a positive correlation between Tregs infiltration and SUVmax; PET/CT SUVmax may indicate Tregs infiltration in the tumor microenvironment of NSCLC patients, and it may play important role in predicting clinical prognosis and guiding treatment for NSCLC patients.
2017, 24(4):423-428.
DOI: 10.3872/j.issn.1007-385X.2017.04.015
Abstract:
Objective:To investigate the expression of ubiquitin specific peptidose 53（USP53） in colorectal cancer tissues and its over-expression on human colorectal cancer(CRC) HCT116 cells. Methods: Real-time PCR and IHC were used to examine the expression level of USP53 in colorectal cancerous tissues and the para-cancerous tissues; TCGA database, provided by UCSC CANCER BROWSER, was used to validate the relationship between USP53 mRNA expression and clinical characteristics as well as prognosis; After over-expressing USP53in HCT116, the changes in cell proliferation were measured by CCK-8 assay and colony formation assay. Results: IHC showed that the expression level of USP53 was higher in the normal para-cancerous tissues than that in cancerous tissues (91.67%\[44/48\] vs 18.75% \[9/48\], P<001); the same was also found in the mRNA level (\[0.46±0.27\] vs \[0.85±0.32\], F=0.925, P<0.05). The mRNA level of USP53in CRC was negatively correlated with the prognosis (P<0.05); Over-expression of USP53 in HCT116 cell significantly decreased the colony formation (\[123±27.22\] vs \[338±55.24\]，P<0.01); CCK-8 assay also showed that over-expression of USP53 also significantly inhibited the proliferation of HCT116 cells (\[0.14±0.01\] vs \[0.18±0.04\]，P<0.05, \[0.23±0.01\] vs \[0.32±0.01\]，P<0.01，\[0.45±0.03\] vs \[0.80±0.05\]，P<001，\[0.83±0.03\] vs \[1.18±0.10\]，P<0.01). Conclusion: USP53 was downregulated in CRC, which is correlated with the poor prognosis; and up-regulation of USP53 could inhibit the proliferation of HCT116 cells in vitro, indicating USP53 could be used as a diagnostic and therapeutic target for colorectal cancer.
Objective:To investigate the expression of ubiquitin specific peptidose 53（USP53） in colorectal cancer tissues and its over-expression on human colorectal cancer(CRC) HCT116 cells. Methods: Real-time PCR and IHC were used to examine the expression level of USP53 in colorectal cancerous tissues and the para-cancerous tissues; TCGA database, provided by UCSC CANCER BROWSER, was used to validate the relationship between USP53 mRNA expression and clinical characteristics as well as prognosis; After over-expressing USP53in HCT116, the changes in cell proliferation were measured by CCK-8 assay and colony formation assay. Results: IHC showed that the expression level of USP53 was higher in the normal para-cancerous tissues than that in cancerous tissues (91.67%\[44/48\] vs 18.75% \[9/48\], P<001); the same was also found in the mRNA level (\[0.46±0.27\] vs \[0.85±0.32\], F=0.925, P<0.05). The mRNA level of USP53in CRC was negatively correlated with the prognosis (P<0.05); Over-expression of USP53 in HCT116 cell significantly decreased the colony formation (\[123±27.22\] vs \[338±55.24\]，P<0.01); CCK-8 assay also showed that over-expression of USP53 also significantly inhibited the proliferation of HCT116 cells (\[0.14±0.01\] vs \[0.18±0.04\]，P<0.05, \[0.23±0.01\] vs \[0.32±0.01\]，P<0.01，\[0.45±0.03\] vs \[0.80±0.05\]，P<001，\[0.83±0.03\] vs \[1.18±0.10\]，P<0.01). Conclusion: USP53 was downregulated in CRC, which is correlated with the poor prognosis; and up-regulation of USP53 could inhibit the proliferation of HCT116 cells in vitro, indicating USP53 could be used as a diagnostic and therapeutic target for colorectal cancer.
2017, 24(4):429-435.
DOI: 10.3872/j.issn.1007-385X.2017.04.016
Abstract:
肿瘤的发生、发展涉及细胞内众多基因表达异常和分子间相互作用的改变。其中，异常表达的长链非编码RNA(long non-coding RNA)通过与蛋白质相互作用，在信号转导、基因表达、蛋白功能等各个层面调控癌基因、抑癌基因的表达与功能，进而影响肿瘤的发生和发展。本文将围绕着肿瘤细胞中lncRNA-蛋白质相互作用的最新研究进展，结合相关技术，阐明其分子机制，并结合临床研究前沿热点，讨论如何阻断肿瘤中lncRNA-蛋白质相互作用，及在肿瘤治疗中的应用。
肿瘤的发生、发展涉及细胞内众多基因表达异常和分子间相互作用的改变。其中，异常表达的长链非编码RNA(long non-coding RNA)通过与蛋白质相互作用，在信号转导、基因表达、蛋白功能等各个层面调控癌基因、抑癌基因的表达与功能，进而影响肿瘤的发生和发展。本文将围绕着肿瘤细胞中lncRNA-蛋白质相互作用的最新研究进展，结合相关技术，阐明其分子机制，并结合临床研究前沿热点，讨论如何阻断肿瘤中lncRNA-蛋白质相互作用，及在肿瘤治疗中的应用。
2017, 24(4):436-441.
DOI: 10.3872/j.issn.1007-385X.2017.04.017
Abstract:
基因修饰T细胞（CAR-T，TCR-T）赋予其肿瘤靶向性、更强的杀伤活性和持久的生命力，在恶性血液肿瘤和实体瘤的临床试验中取得了可喜的效果。然而，不断积累的的临床资料也发现了安全性担忧：炎症细胞因子级联反应引发的肿瘤靶向毒性；抗原识别相关的脱靶效应、非肿瘤靶向效应、移植物抗宿主病等，不仅难以预见而且复杂难治，促使研究人员以毒性发生机制为切入点，尝试应用自杀基因开关、细胞内凋亡酶调控、分离式CAR受体、抑制性CAR受体等调控策略，实现对基因修饰T细胞时间和空间的精准控制，预防毒性反应的发生。本文综述基因修饰T细胞的安全问题及应对策略。
基因修饰T细胞（CAR-T，TCR-T）赋予其肿瘤靶向性、更强的杀伤活性和持久的生命力，在恶性血液肿瘤和实体瘤的临床试验中取得了可喜的效果。然而，不断积累的的临床资料也发现了安全性担忧：炎症细胞因子级联反应引发的肿瘤靶向毒性；抗原识别相关的脱靶效应、非肿瘤靶向效应、移植物抗宿主病等，不仅难以预见而且复杂难治，促使研究人员以毒性发生机制为切入点，尝试应用自杀基因开关、细胞内凋亡酶调控、分离式CAR受体、抑制性CAR受体等调控策略，实现对基因修饰T细胞时间和空间的精准控制，预防毒性反应的发生。本文综述基因修饰T细胞的安全问题及应对策略。
2017, 24(4):442-446.
DOI: 10.3872/j.issn.1007-385X.2017.04.018
Abstract:
Cullin7 （Cul7）作为核心支架蛋白与ROC1、Skp1和Fbxw8一起构成SCF（Skp1-Cullin-F-box） E3泛素连接酶复合物。Cul7是对人和小鼠生长发育具有重要调控作用的基因。Cul7对细胞转化、p53活性调节、细胞衰老以及细胞凋亡的调控作用，说明其具有癌基因的特征。Cul7在乳腺癌、肺癌、肝细胞癌、胰腺癌、卵巢癌等多种恶性肿瘤中高表达，通过参与细胞转化和抑制细胞凋亡等机制促进肿瘤的发生发展。
Cullin7 （Cul7）作为核心支架蛋白与ROC1、Skp1和Fbxw8一起构成SCF（Skp1-Cullin-F-box） E3泛素连接酶复合物。Cul7是对人和小鼠生长发育具有重要调控作用的基因。Cul7对细胞转化、p53活性调节、细胞衰老以及细胞凋亡的调控作用，说明其具有癌基因的特征。Cul7在乳腺癌、肺癌、肝细胞癌、胰腺癌、卵巢癌等多种恶性肿瘤中高表达，通过参与细胞转化和抑制细胞凋亡等机制促进肿瘤的发生发展。
2017, 24(4):447-452.
DOI: 10.3872/j.issn.1007-385X.2017.04.019
Abstract:
胆囊癌是一类具有高度恶性、女性高发、高致死性等特点的肿瘤，传统的化疗和放疗对晚期患者疗效欠佳。随着对ErbB信号通路的深入研究，其在胆囊癌靶向治疗方面表现出了良好的应用前景。ErbB信号通路是目前胆囊癌分子机制研究中的热点，特别是EGFR/ ErbB1在胆囊腺癌高表达，而HER2/ErbB2在胆囊癌前病变中高表达，均与不良预后相关，是胆囊癌最具前景的治疗靶标；ErbB信号通路靶基因的异常激活能增强胆囊癌细胞增殖和侵袭力，是胆囊癌的关键性驱动基因。靶向治疗药物干预ErbB信号通路分子可以提高疾病控制率，延长晚期胆囊癌的生存期（PFS和OS）。本文就ErbB信号通路在胆囊癌中发生发展中的作用及其靶向治疗药物的新进展做一综述。
胆囊癌是一类具有高度恶性、女性高发、高致死性等特点的肿瘤，传统的化疗和放疗对晚期患者疗效欠佳。随着对ErbB信号通路的深入研究，其在胆囊癌靶向治疗方面表现出了良好的应用前景。ErbB信号通路是目前胆囊癌分子机制研究中的热点，特别是EGFR/ ErbB1在胆囊腺癌高表达，而HER2/ErbB2在胆囊癌前病变中高表达，均与不良预后相关，是胆囊癌最具前景的治疗靶标；ErbB信号通路靶基因的异常激活能增强胆囊癌细胞增殖和侵袭力，是胆囊癌的关键性驱动基因。靶向治疗药物干预ErbB信号通路分子可以提高疾病控制率，延长晚期胆囊癌的生存期（PFS和OS）。本文就ErbB信号通路在胆囊癌中发生发展中的作用及其靶向治疗药物的新进展做一综述。
2017, 24(4):453-457.
DOI: 10.3872/j.issn.1007-385X.2017.04.020
Abstract:
卵巢癌是妇科恶性肿瘤中导致女性死亡的主要原因，目前主要治疗手段是手术切除并辅助以铂类为基础的化疗，但疗效受耐药性影响。顺铂耐药的机制尚不十分清楚，目前普遍认为核苷酸切除修复(nucleotide excision repair，NER)是顺铂耐药的重要机制之一。切除修复交叉互补基因 1(excision repair cross-complementation gene group 1, ERCC1)是NER途径的限速酶，ERCC1表达与卵巢癌临床病理因素无明显相关性，ERCCl的表达与顺铂耐受性相关，下调ERCCI的表达可克服顺铂耐药性。
卵巢癌是妇科恶性肿瘤中导致女性死亡的主要原因，目前主要治疗手段是手术切除并辅助以铂类为基础的化疗，但疗效受耐药性影响。顺铂耐药的机制尚不十分清楚，目前普遍认为核苷酸切除修复(nucleotide excision repair，NER)是顺铂耐药的重要机制之一。切除修复交叉互补基因 1(excision repair cross-complementation gene group 1, ERCC1)是NER途径的限速酶，ERCC1表达与卵巢癌临床病理因素无明显相关性，ERCCl的表达与顺铂耐受性相关，下调ERCCI的表达可克服顺铂耐药性。
联系方式
- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.