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Volume 26,Issue 6,2019 Table of Contents
2019, 26(6):617-622.
DOI: 10.3872/j.issn.1007-385X.2019.06.001
Abstract:
[Abstract] Chimeric antigen receptor modified T (CAR-T) cell therapy is one of the important methods of tumor immunotherapy. The targeting, killing, proliferation and persistence of CAR-T cells are significantly enhanced than that of conventional T cells. After continuous improvement and evolution, CAR-T cell treatment has achieved excellent progress in hematological tumors and has received extensive attention. However, neurotoxicity arising from the treatment, also known as CAR-T cell relevant encephalopathy syndrome (CRES), has affected its clinical application. Exploring the pathogenesis of CRES and high-risk factors, and finding appropriate strategies is therefore critical for the prevention and treatment of CRES. Here, we take CD19-CAR-T cell treatment as example to review the symptoms and pathogenesis of CRES, discuss high-risk factors as well as coping strategies, in an effort to provide a reference for clinical treatment.
[Abstract] Chimeric antigen receptor modified T (CAR-T) cell therapy is one of the important methods of tumor immunotherapy. The targeting, killing, proliferation and persistence of CAR-T cells are significantly enhanced than that of conventional T cells. After continuous improvement and evolution, CAR-T cell treatment has achieved excellent progress in hematological tumors and has received extensive attention. However, neurotoxicity arising from the treatment, also known as CAR-T cell relevant encephalopathy syndrome (CRES), has affected its clinical application. Exploring the pathogenesis of CRES and high-risk factors, and finding appropriate strategies is therefore critical for the prevention and treatment of CRES. Here, we take CD19-CAR-T cell treatment as example to review the symptoms and pathogenesis of CRES, discuss high-risk factors as well as coping strategies, in an effort to provide a reference for clinical treatment.
2019, 26(6):623-631.
DOI: 10.3872/j.issn.1007-385X.2019.06.002
Abstract:
[Abstract] Objective: To investigate the expression of miR-1269a in esophageal squamous cell carcinoma (ESCC) tissues and its effect on the malignant biological behaviors of ESCC KYSE30 cells, as well as to explore the underlying mechanism. Methods: Ninety specimens of ESCC tissues and adjacent para-cancerous tissues were obtained from patients underwent surgery in Fourth Hospital, Hebei Medical University. In addition, normal esophageal immortalized epithelial cells and esophageal cancer cell lines were also collected.The expression level of miR-1269a in above mentioned tissues and cell lines was examined by Real-time fluorescent quantitative PCR.After being transfected with miR-1269a mimics and inhibitors, the effects of miR-1269a on proliferation, migration, invasion and colony formation of KYSE30 cells were detected by MTS, Transwell and colony formation assay, respectively. The bioinformatics tool was used to predict the possible target genes of miR-1269a. Then the regulation effect of miR-1269a on target gene expression was validated by WB and Dual-luciferase reporter assay. After being transfected with SOX6 plasmid, the effects of SOX6 on the proliferation, migration,invasion and colony formation of KYSE30 cells were detected by MTS, Transwell and colony formation assay, respectively. At last, rescue assay was used to confirm the results. Results: The expression level of miR-1269a in ESCC tissues was significantly higher than that in adjacent para-cancerous tissues (P<0.05), and the expression level of miR-1269a in ESCC cell lines was significantly elevated compared with the normal epithelial cells (P<0.05 or P<0.01). The capacities of proliferation, invasion, migration and colony formation of KYSE30 cells in miR-1269a mimics transfection group were obviously higher than those in mimics NC group, while those abilities in miR-1269a inhibitor transfection group were significantly lower than those in inhibitor NC group (P<0.05 or P<0.01). Bioinformatics analysis showed that miR-1269a could combine with 3’UTR region at SOX6 gene; and after miR-1269a over-expression, the expression level of SOX6 and luciferase activity in KYSE30 cells were significantly reduced (P<0.05). Rescue assay showed that miR-1269a over-expression could promote the proliferation, invasion and migration of KYSE 30 cells, while simultaneous transfection of SOX6 could partially reverse the promotion effect of miR-1269a mimics. Conclusion: The expression level of miR-1269a in ESCC tissues and cell lines is significantly increased, and it could enhance proliferation, migration, invasion and colony formation of KYSE30 cell line. And its mechanism may be related to the suppression of its target gene SOX6.
[Abstract] Objective: To investigate the expression of miR-1269a in esophageal squamous cell carcinoma (ESCC) tissues and its effect on the malignant biological behaviors of ESCC KYSE30 cells, as well as to explore the underlying mechanism. Methods: Ninety specimens of ESCC tissues and adjacent para-cancerous tissues were obtained from patients underwent surgery in Fourth Hospital, Hebei Medical University. In addition, normal esophageal immortalized epithelial cells and esophageal cancer cell lines were also collected.The expression level of miR-1269a in above mentioned tissues and cell lines was examined by Real-time fluorescent quantitative PCR.After being transfected with miR-1269a mimics and inhibitors, the effects of miR-1269a on proliferation, migration, invasion and colony formation of KYSE30 cells were detected by MTS, Transwell and colony formation assay, respectively. The bioinformatics tool was used to predict the possible target genes of miR-1269a. Then the regulation effect of miR-1269a on target gene expression was validated by WB and Dual-luciferase reporter assay. After being transfected with SOX6 plasmid, the effects of SOX6 on the proliferation, migration,invasion and colony formation of KYSE30 cells were detected by MTS, Transwell and colony formation assay, respectively. At last, rescue assay was used to confirm the results. Results: The expression level of miR-1269a in ESCC tissues was significantly higher than that in adjacent para-cancerous tissues (P<0.05), and the expression level of miR-1269a in ESCC cell lines was significantly elevated compared with the normal epithelial cells (P<0.05 or P<0.01). The capacities of proliferation, invasion, migration and colony formation of KYSE30 cells in miR-1269a mimics transfection group were obviously higher than those in mimics NC group, while those abilities in miR-1269a inhibitor transfection group were significantly lower than those in inhibitor NC group (P<0.05 or P<0.01). Bioinformatics analysis showed that miR-1269a could combine with 3’UTR region at SOX6 gene; and after miR-1269a over-expression, the expression level of SOX6 and luciferase activity in KYSE30 cells were significantly reduced (P<0.05). Rescue assay showed that miR-1269a over-expression could promote the proliferation, invasion and migration of KYSE 30 cells, while simultaneous transfection of SOX6 could partially reverse the promotion effect of miR-1269a mimics. Conclusion: The expression level of miR-1269a in ESCC tissues and cell lines is significantly increased, and it could enhance proliferation, migration, invasion and colony formation of KYSE30 cell line. And its mechanism may be related to the suppression of its target gene SOX6.
2019, 26(6):632-637.
DOI: 10.3872/j.issn.1007-385X.2019.06.003
Abstract:
[Abstract] Objective: To investigate the effect of ELMOD2 over-expression on the malignant biological behaviors of gastric cancer MGC803 cells, and to study its related molecular mechanism. Methods: GV141-ELMOD2 expression vector was transfected into human gastric cancer MGC803 cells. The mRNA and protein expressions of ELMOD2 were detected by Real-time fluorescent quantitative PCR and WB, respectively. The cell proliferation ability was detected by CCK-8 method. Apoptosis rate was detected by flow cytometry.The cell migration ability was detected by Transwell method. The protein expressions of PCNA, BAX and Bcl-2 and Vimentin were detected by WB. Results: After transfection of ELMOD2 expression vector, the mRNA and protein expressions of ELMOD2 were significantly increased in MGC803 cells (P<0.05). Further studies showed that over-expression of ELMOD2 increased the proliferation and migration ability but reduced the apoptosis rate of MGC803 cells significantly (P<0.05 or P<0.01). The protein levels of PCNA,Vimentin and Bcl-2 in MGC803 cells increased, while the protein level of BAX decreased (P<0.05 or P<0.01). Conclusion: Over-expression of ELMOD2 can promote the proliferation and migration of MGC803 cells and inhibit cell apoptosis. These effects may be achieved by increasing the protein level of PCNA, Vimentin and Bcl-2, and reducing the protein level of BAX.
[Abstract] Objective: To investigate the effect of ELMOD2 over-expression on the malignant biological behaviors of gastric cancer MGC803 cells, and to study its related molecular mechanism. Methods: GV141-ELMOD2 expression vector was transfected into human gastric cancer MGC803 cells. The mRNA and protein expressions of ELMOD2 were detected by Real-time fluorescent quantitative PCR and WB, respectively. The cell proliferation ability was detected by CCK-8 method. Apoptosis rate was detected by flow cytometry.The cell migration ability was detected by Transwell method. The protein expressions of PCNA, BAX and Bcl-2 and Vimentin were detected by WB. Results: After transfection of ELMOD2 expression vector, the mRNA and protein expressions of ELMOD2 were significantly increased in MGC803 cells (P<0.05). Further studies showed that over-expression of ELMOD2 increased the proliferation and migration ability but reduced the apoptosis rate of MGC803 cells significantly (P<0.05 or P<0.01). The protein levels of PCNA,Vimentin and Bcl-2 in MGC803 cells increased, while the protein level of BAX decreased (P<0.05 or P<0.01). Conclusion: Over-expression of ELMOD2 can promote the proliferation and migration of MGC803 cells and inhibit cell apoptosis. These effects may be achieved by increasing the protein level of PCNA, Vimentin and Bcl-2, and reducing the protein level of BAX.
4 Ursolic acid regulates apoptosis and autophagy of gastric cancer cell line MGC-803 and its mechanism
2019, 26(6):638-643.
DOI: 10.3872/j.issn.1007-385X.2019.06.004
Abstract:
[Abstract] Objective: To observe the effect of ursolic acid (UA) on autophagy and apoptosis of gastric cancer cell line MGC-803, and to explore the mechanism of UA-induced autophagy of MGC-803 cells based on PI3K/AKT/mTOR signaling pathway. Methods: Human gastric cancer cell line MGC-803 was cultured in vitro and divided into blank control group, UA intervention group and UA+3-MA group. The cell apoptosis in each group was detected by flow cytometry. Cell autophagy was detected by double fluorescence mRFPeGFP-LC3 plasmid transfection method. The mRNA expression levels of LC3B, BAX and Bcl-2 were detected by qPCR. The protein expression levels of PI3K type I, p-AKT, p-mTOR, ULK1, LC3B, BAX and Bcl-2 were detected by WB. Results: Flow cytometry showed that the cell apoptotic rate of UA intervention group was significantly higher than that of blank control group (P<0.05). Compared with UA intervention group, the apoptotic rate in UA + 3-MA group was significantly reduced (P<0.05). The double fluorescence mRFP-eGFP-LC3 plasmid transfection method showed that the green and red fluorescent bright spots in UA intervention group increased significantly compared with the blank control group (P<0.05), and the green and red fluorescent bright spots in UA+3-MA group were significantly reduced compared with UA intervention group (P<0.05). Real-time quantitative PCR and WB method showed that compared with the blank control group, the mRNA and protein expressions of BAX and LC3B, and ULK1 protein were significantly increased in UA intervention group, while the mRNA and protein expressions of Bcl-2, and the protein expressions of PI3K, p-AKT and p-mTOR were significantly decreased in UA intervention group (all P<0.05); Compared with UA intervention group, mRNA and protein expressions of BAX and LC3B were significantly down-regulated and the mRNA and protein expressions of Bcl-2 were significantly up-regulated in UA+3-MA group (all P<0.05), while protein levels of PI3K, p-AKT, p-mTOR and ULK1 were not significantly changed in UA+3-MA group (P>0.05). Conclusion: UA can promote apoptosis of MGC-803 cells via inducing autophagy, which may be related to UA's involvement in regulating the expressions of PI3K/AKT/mTOR signaling pathway-related proteins.
[Abstract] Objective: To observe the effect of ursolic acid (UA) on autophagy and apoptosis of gastric cancer cell line MGC-803, and to explore the mechanism of UA-induced autophagy of MGC-803 cells based on PI3K/AKT/mTOR signaling pathway. Methods: Human gastric cancer cell line MGC-803 was cultured in vitro and divided into blank control group, UA intervention group and UA+3-MA group. The cell apoptosis in each group was detected by flow cytometry. Cell autophagy was detected by double fluorescence mRFPeGFP-LC3 plasmid transfection method. The mRNA expression levels of LC3B, BAX and Bcl-2 were detected by qPCR. The protein expression levels of PI3K type I, p-AKT, p-mTOR, ULK1, LC3B, BAX and Bcl-2 were detected by WB. Results: Flow cytometry showed that the cell apoptotic rate of UA intervention group was significantly higher than that of blank control group (P<0.05). Compared with UA intervention group, the apoptotic rate in UA + 3-MA group was significantly reduced (P<0.05). The double fluorescence mRFP-eGFP-LC3 plasmid transfection method showed that the green and red fluorescent bright spots in UA intervention group increased significantly compared with the blank control group (P<0.05), and the green and red fluorescent bright spots in UA+3-MA group were significantly reduced compared with UA intervention group (P<0.05). Real-time quantitative PCR and WB method showed that compared with the blank control group, the mRNA and protein expressions of BAX and LC3B, and ULK1 protein were significantly increased in UA intervention group, while the mRNA and protein expressions of Bcl-2, and the protein expressions of PI3K, p-AKT and p-mTOR were significantly decreased in UA intervention group (all P<0.05); Compared with UA intervention group, mRNA and protein expressions of BAX and LC3B were significantly down-regulated and the mRNA and protein expressions of Bcl-2 were significantly up-regulated in UA+3-MA group (all P<0.05), while protein levels of PI3K, p-AKT, p-mTOR and ULK1 were not significantly changed in UA+3-MA group (P>0.05). Conclusion: UA can promote apoptosis of MGC-803 cells via inducing autophagy, which may be related to UA's involvement in regulating the expressions of PI3K/AKT/mTOR signaling pathway-related proteins.
2019, 26(6):644-649.
DOI: 10.3872/j.issn.1007-385X.2019.06.005
Abstract:
[Abstract] Objective: To investigate the effect of high expression of TET1 catalytic domain (TET1-CD) gene on the proliferation and migration of breast cancer MDA-MB-231 cells and its underlying mechanism. Methods: MDA-MB-231 cell line with high TET1-CD expression was established by lentiviral transfection. Real-time quantitative PCR was used to detect the mRNA expression of TET1-CD.Transwell assay and cell scratch assay were used to detect cell migration ability, MTT assay and colony formation assay were used to detect cell proliferation capacity. And WB was adopted to detect the expressions of EMT-related proteins (E-cadherin, Vimentin, MMP2)and Wnt, Hedgehog pathway-related proteins in MDA-MB-231 cells. Results: The MDA-MB-231 cell line with high TET1-CD expression was successfully constructed (all P<0.01). TET1-CD over-expression significantly inhibited the proliferation and migration of breast cancer MDA-MB-231 cells (P<0.01); in addition, TET1-CD over-expression increased the expression of E-cadherin, but down-regulated the expressions of Vimentin, MMP2, β -catenin, Gli1, C-myc and CyclinD1 (all P<0.05). Conclusion: TET1-CD may inhibit the proliferation and migration of breast cancer MDA-MB-231 cells by inhibiting the EMT through Wnt and HH signaling pathway.
[Abstract] Objective: To investigate the effect of high expression of TET1 catalytic domain (TET1-CD) gene on the proliferation and migration of breast cancer MDA-MB-231 cells and its underlying mechanism. Methods: MDA-MB-231 cell line with high TET1-CD expression was established by lentiviral transfection. Real-time quantitative PCR was used to detect the mRNA expression of TET1-CD.Transwell assay and cell scratch assay were used to detect cell migration ability, MTT assay and colony formation assay were used to detect cell proliferation capacity. And WB was adopted to detect the expressions of EMT-related proteins (E-cadherin, Vimentin, MMP2)and Wnt, Hedgehog pathway-related proteins in MDA-MB-231 cells. Results: The MDA-MB-231 cell line with high TET1-CD expression was successfully constructed (all P<0.01). TET1-CD over-expression significantly inhibited the proliferation and migration of breast cancer MDA-MB-231 cells (P<0.01); in addition, TET1-CD over-expression increased the expression of E-cadherin, but down-regulated the expressions of Vimentin, MMP2, β -catenin, Gli1, C-myc and CyclinD1 (all P<0.05). Conclusion: TET1-CD may inhibit the proliferation and migration of breast cancer MDA-MB-231 cells by inhibiting the EMT through Wnt and HH signaling pathway.
CHENG Xianshuo
,
YANG Fang
,
DONG Jian
,
LI Yunfeng
,
YANG Zhibin
,
ZHANG Hongtao
,
SHEN Tao
,
LIU Ping
,
YIN Zhengfeng
,
LI Qiang
2019, 26(6):650-655.
DOI: 10.3872/j.issn.1007-385X.2019.06.006
Abstract:
[Abstract] Objective: To investigate the molecular mechanism of chemokine CCL20/CCR6 in promoting invasion and migration of colon cancer SW480 cells. Methods: Colorectal cancer SW480 cells with high expression of CCR6 receptor were screened by immunochemistry (IHC). After co-culture with recombinant human CCL20, the invasion and migration of SW480 cells were detected by Transwell assay and Wound-Healing assay, respectively. Expressions of EMT markers, AKT signal protein and target protein MMP3 were detected by immunofluorescence (IF) and WB. AKT signaling pathway as the key mechanism was confirmed by MK2206 blocking assay.The expressions of CCL20 and MMP3 in colorectal cancer tissues as well as their correlation were analyzed by TCGA database resources (https://portal.gdc.cancer.gov/). Results: CCL20 promoted the invasion and migration ability of SW480 cells significantly (all P <0.01), and this was induced by activation of AKT signaling and up-regulation of downstream target protein MMP3, instead of EMT.Blocking AKT signaling could significantly inhibit the invasion and migration of SW480 cells, and down-regulate MMP3 expression (P<0.05). TCGA platform data showed that the expressions of CCL20 and MMP3 in colorectal cancer tissues were significantly higher than those in normal mucosa tissues (P<0.05 or P<0.01), and an evidently positive correlation was found between CCL20 and MMP3 (r=0.051, P<0.01). Conclusion: The chemokine CCL20 promotes the invasion and migration of SW480 cells through AKT/MMP3 signal axis, but not the EMT.
[Abstract] Objective: To investigate the molecular mechanism of chemokine CCL20/CCR6 in promoting invasion and migration of colon cancer SW480 cells. Methods: Colorectal cancer SW480 cells with high expression of CCR6 receptor were screened by immunochemistry (IHC). After co-culture with recombinant human CCL20, the invasion and migration of SW480 cells were detected by Transwell assay and Wound-Healing assay, respectively. Expressions of EMT markers, AKT signal protein and target protein MMP3 were detected by immunofluorescence (IF) and WB. AKT signaling pathway as the key mechanism was confirmed by MK2206 blocking assay.The expressions of CCL20 and MMP3 in colorectal cancer tissues as well as their correlation were analyzed by TCGA database resources (https://portal.gdc.cancer.gov/). Results: CCL20 promoted the invasion and migration ability of SW480 cells significantly (all P <0.01), and this was induced by activation of AKT signaling and up-regulation of downstream target protein MMP3, instead of EMT.Blocking AKT signaling could significantly inhibit the invasion and migration of SW480 cells, and down-regulate MMP3 expression (P<0.05). TCGA platform data showed that the expressions of CCL20 and MMP3 in colorectal cancer tissues were significantly higher than those in normal mucosa tissues (P<0.05 or P<0.01), and an evidently positive correlation was found between CCL20 and MMP3 (r=0.051, P<0.01). Conclusion: The chemokine CCL20 promotes the invasion and migration of SW480 cells through AKT/MMP3 signal axis, but not the EMT.
2019, 26(6):656-661.
DOI: 10.3872/j.issn.1007-385X.2019.06.007
Abstract:
[Abstract] Objective: To explore the effect of PD-1 gene knockout by CRISPR/Cas9 system on the proliferation and IFN-γ secretion in human T cells. Methods: The sequence of sgRNA targeting PD-1 was designed. The PD-1-sgRNA and Cas9 mRNA were synthesized by T7 RNA polymerase in vitro, and then the mixture of PD-1-sgRNA and Cas9 mRNA was delivered into activated T cells by nucleofection.The efficiency of gene knockout was confirmed by sequencing. The phenotypes of T lymphocytes and the expression of PD-1 after gene knockout were analyzed by Flow cytometry. The proliferation of T lymphocytes was calculated by trypan blue counting.The level of IFN-γ secreted by T lymphocytes was detected by ELISA. Results：PD-1-sgRNA and Cas9 mRNA were successfully synthesized in vitro and delivered into T cells by nucleofection. Sequencing technology confirmed that the PD-1 gene sequence was edited and the editing efficiency was 58.3%. The expression of PD-1 on T lymphocyte surface was down-regulated successfully by CRISPR/Cas9 system [(9.6±1.85)% vs (16.2±2.05)%, P<0.05]. The knockout of PD-1 gene did not affect the proliferation and phenotype of T lymphocytes(P<0.05); However, compared with the control group, the level of IFN- γ secreted by T lymphocytes in the PD-1-sgRNA group was significantly increased (P<0.01). Conclusion: CRISPR/Cas9 system can successfully ablate PD-1 gene in human T lymphocytes, which could block the negative regulation of PD-1／PD-L1 and further promote the IFN-γ secretion in T cells.
[Abstract] Objective: To explore the effect of PD-1 gene knockout by CRISPR/Cas9 system on the proliferation and IFN-γ secretion in human T cells. Methods: The sequence of sgRNA targeting PD-1 was designed. The PD-1-sgRNA and Cas9 mRNA were synthesized by T7 RNA polymerase in vitro, and then the mixture of PD-1-sgRNA and Cas9 mRNA was delivered into activated T cells by nucleofection.The efficiency of gene knockout was confirmed by sequencing. The phenotypes of T lymphocytes and the expression of PD-1 after gene knockout were analyzed by Flow cytometry. The proliferation of T lymphocytes was calculated by trypan blue counting.The level of IFN-γ secreted by T lymphocytes was detected by ELISA. Results：PD-1-sgRNA and Cas9 mRNA were successfully synthesized in vitro and delivered into T cells by nucleofection. Sequencing technology confirmed that the PD-1 gene sequence was edited and the editing efficiency was 58.3%. The expression of PD-1 on T lymphocyte surface was down-regulated successfully by CRISPR/Cas9 system [(9.6±1.85)% vs (16.2±2.05)%, P<0.05]. The knockout of PD-1 gene did not affect the proliferation and phenotype of T lymphocytes(P<0.05); However, compared with the control group, the level of IFN- γ secreted by T lymphocytes in the PD-1-sgRNA group was significantly increased (P<0.01). Conclusion: CRISPR/Cas9 system can successfully ablate PD-1 gene in human T lymphocytes, which could block the negative regulation of PD-1／PD-L1 and further promote the IFN-γ secretion in T cells.
2019, 26(6):662-668.
DOI: 10.3872/j.issn.1007-385X.2019.06.008
Abstract:
[Abstract] Objective: To investigate the effect of over-expression of paired related homoeobox 1 (PRRX1) on apoptosis of hepatocellular carcinoma SMMC7721 cells, and to explore its detailed mechanism. Methods：Lentivirus-mediated PRRX1 over-expression vector (pGMLV-PRRX1) and empty vector (Vector) were respectively infected into SMMC7721 cells, and the mRNA and protein expression levels of PRRX1 in infected cells were detected by qPCR and WB. The effect of PRRX1 over-expression on the cell proliferation and apoptosis of SMMC7721 cells were assessed by CCK-8 assay and Annexin-V FITC/PI double staining flow cytometry assay, respectively.The change of mitochondrial membrane potential of SMMC7721 cells was detected by mitochondrial membrane potential assay kit (JC-10 staining assay). The enzymatic activities of caspase-8 and caspase-9 in infected cells were detected by using caspase activity assay kit (spectrophotometric method). The protein expression levels of p53, Bcl-2, Bax, Fas, Cleaved-caspase-3 and Cty C expressed in mitochondria and cytosol were evaluated by WB. Results：PRRX1 over-expressed SMMC7721 cell line was successfully constructed, and the protein and mRNA expression levels of PRRX1 were significantly increased in lentivirus infected cells (all P<0.01). Compared with control group and vector group, over-expression of PRRX1 significantly inhibited cell proliferation, weakened mitochondrial membrane potential, but increased the rate of apoptosis, elevated the shear level of caspase-3, promoted the release of Cyt C protein from mitochondrial into cytosol and increased the enzymatic activity of caspase-9 (all P<0.05 or P<0.01). In addition,over-expression of PRRX1 also promoted the protein expressions of p53 and Bax but inhibited the protein expression of Bcl-2 (all P<0.05 or P<0.01); however,it had no significant effect on the expression of Fas protein and the enzymatic activity of caspase-8 (all P＞0.05). Conclusion：Over-expression of PRRX1 induces apoptosis in hepatocellular carcinoma SMMC7721 cells, which may be related to the activation of p53-mediated mitochondrial apoptotic pathway.
[Abstract] Objective: To investigate the effect of over-expression of paired related homoeobox 1 (PRRX1) on apoptosis of hepatocellular carcinoma SMMC7721 cells, and to explore its detailed mechanism. Methods：Lentivirus-mediated PRRX1 over-expression vector (pGMLV-PRRX1) and empty vector (Vector) were respectively infected into SMMC7721 cells, and the mRNA and protein expression levels of PRRX1 in infected cells were detected by qPCR and WB. The effect of PRRX1 over-expression on the cell proliferation and apoptosis of SMMC7721 cells were assessed by CCK-8 assay and Annexin-V FITC/PI double staining flow cytometry assay, respectively.The change of mitochondrial membrane potential of SMMC7721 cells was detected by mitochondrial membrane potential assay kit (JC-10 staining assay). The enzymatic activities of caspase-8 and caspase-9 in infected cells were detected by using caspase activity assay kit (spectrophotometric method). The protein expression levels of p53, Bcl-2, Bax, Fas, Cleaved-caspase-3 and Cty C expressed in mitochondria and cytosol were evaluated by WB. Results：PRRX1 over-expressed SMMC7721 cell line was successfully constructed, and the protein and mRNA expression levels of PRRX1 were significantly increased in lentivirus infected cells (all P<0.01). Compared with control group and vector group, over-expression of PRRX1 significantly inhibited cell proliferation, weakened mitochondrial membrane potential, but increased the rate of apoptosis, elevated the shear level of caspase-3, promoted the release of Cyt C protein from mitochondrial into cytosol and increased the enzymatic activity of caspase-9 (all P<0.05 or P<0.01). In addition,over-expression of PRRX1 also promoted the protein expressions of p53 and Bax but inhibited the protein expression of Bcl-2 (all P<0.05 or P<0.01); however,it had no significant effect on the expression of Fas protein and the enzymatic activity of caspase-8 (all P＞0.05). Conclusion：Over-expression of PRRX1 induces apoptosis in hepatocellular carcinoma SMMC7721 cells, which may be related to the activation of p53-mediated mitochondrial apoptotic pathway.
PENG Kenan
,
LI Xiaoya
,
BAI Hanyu
,
WANG Gang
,
DAI Suli
,
YANG Tao
,
LIU Yujing
,
TAN He
,
ZHAO Ming
,
ZHAO Lianmei
,
Shan Baoen
2019, 26(6):669-675.
DOI: 10.3872/j.issn.1007-385X.2019.06.009
Abstract:
[Abstract] Objective: To investigate the expression of metastasis-associated protein 2 (MTA2) in human bladder cancer tissues and its effect on the malignant biological behaviors of bladder cancer T24 cells, as well as to explore the effect of MTA2 on the progression of bladder cancer. Methods: Sixty-two cases of human bladder cancer tissues and 28 cases of normal bladder tissues (from patients with cystitis, and pathologically confirmed as normal tissue) were collected at People’s Hospital of Hebei Province during December 2012 and December 2014. The expression of MTA2 in bladder cancer tissues and normal bladder tissues was detected by immunohistochemical staining, and the correlation between MTA2 expression and clinicopathological characteristics of patients was also analyzed.The bladder cancer T24 cell line stably expressing MTA2 was constructed. The effects of MTA2 on the proliferation, colony formation,migration and invasion of bladder cancer T24 cells were detected by MTS, clone formation, scratch healing and Transwell assay, respectively.Results: Immunohistochemical staining showed that MTA2 expression was significantly up-regulated in bladder cancer tissues as compared with normal bladder tissues (P<0.01). The high expression of MTA2 in bladder cancer tissues was not related to gender,age and tumor volume (P>0.05), but was associated with higher TNM stage, histological grade, and lymphatic infiltration and metastasis (all P<0.05). After over-expression of MTA2 in bladder cancer T24 cell line, the proliferation activity of the cells was significantly increased (P<0.05), and the colony formation, scratch healing, migration and invasion ability were significantly increased (all P<0.01).Conclusions: MTA2 is up-regulated in human bladder cancer tissues and can promote the proliferation, tumor formation, migration and invasion of T24 cells.
[Abstract] Objective: To investigate the expression of metastasis-associated protein 2 (MTA2) in human bladder cancer tissues and its effect on the malignant biological behaviors of bladder cancer T24 cells, as well as to explore the effect of MTA2 on the progression of bladder cancer. Methods: Sixty-two cases of human bladder cancer tissues and 28 cases of normal bladder tissues (from patients with cystitis, and pathologically confirmed as normal tissue) were collected at People’s Hospital of Hebei Province during December 2012 and December 2014. The expression of MTA2 in bladder cancer tissues and normal bladder tissues was detected by immunohistochemical staining, and the correlation between MTA2 expression and clinicopathological characteristics of patients was also analyzed.The bladder cancer T24 cell line stably expressing MTA2 was constructed. The effects of MTA2 on the proliferation, colony formation,migration and invasion of bladder cancer T24 cells were detected by MTS, clone formation, scratch healing and Transwell assay, respectively.Results: Immunohistochemical staining showed that MTA2 expression was significantly up-regulated in bladder cancer tissues as compared with normal bladder tissues (P<0.01). The high expression of MTA2 in bladder cancer tissues was not related to gender,age and tumor volume (P>0.05), but was associated with higher TNM stage, histological grade, and lymphatic infiltration and metastasis (all P<0.05). After over-expression of MTA2 in bladder cancer T24 cell line, the proliferation activity of the cells was significantly increased (P<0.05), and the colony formation, scratch healing, migration and invasion ability were significantly increased (all P<0.01).Conclusions: MTA2 is up-regulated in human bladder cancer tissues and can promote the proliferation, tumor formation, migration and invasion of T24 cells.
2019, 26(6):676-682.
DOI: 10.3872/j.issn.1007-385X.2019.06.010
Abstract:
[Abstract] Objective: To evaluate the potential associations between the single nucleotide polymorphisms (SNPs) of lncRNA H19 genes and the susceptibility to gastric cancer (GC), especially to EBV-associated gastric cancer (EBVaGC) in Han population in Qingdao.Methods: 225 cases of pathologically confirmed fresh gastric cancer tissues or paraffin embedded gastric cancer tissues during January 2015 and October 2018 were collected from Affiliated Hospital of Qingdao University, as GC group; in the meanwhile, 200 healthy people underwent physical examination at Outpatient were collected as control. The 225 cases of cancer tissues were assigned into two groups according to the transcription result of EBV-encoded small molecule non-polyadenylation (EBER 1) by In situ hybridization:EBVaGC group (70 cases) and EBVnGC group (155 cases). DNA was extracted from the tissues of two groups and peripheral blood of healthy participants. According to the general setting of HaploView software (MAF>0.05, r2>0.8), four TagSNPs (rs217727, rs2735971,rs2839698 and rs3741216) of H19 were screened. Genotyping of each SNP locus was carried out by using Taq-Man MGB allele typing kit, and the gene polymorphisms were examined. Results: H19 SNPs of collected tissue samples were in accordance with the Hardy-Weinberg equilibrium. Compared with control group, patients carrying TT genotype of H19 rs217727 loci had significantly increased susceptibility to gastric cancer (χ2=9.073, P=0.003, OR=1.999, 95% CI=1.271-3.143), so did the T allele (χ2=13.475, P=0.001, OR=1.661, 95% CI=1.266-2.180). In contrast, patients carrying TC and CC genotype of rs2839698 loci had significantly increased susceptibility to gastric cancer (χ2=9.407, P=0.002; χ2=6.517, P=0.011), and patients carrying C allele had obviously increased susceptibility to GC (χ2=6.163, P=0.013, OR=1.417, 95%CI=1.076-1.867; χ2=9.542, P=0.02, OR=2.070, 95%CI=1.298-3.302). As for the rs2735971 and rs3741216, there was no significant difference between the GC group and the control group (all P>0.05). The distribution of 4 H19 SNPs showed no statistical difference in both EBVaGC group and EBVnGC group (all P>0.05). Conclusion: There was an association between H19 gene polymorphism (rs217727 and rs2839698) and gastric carcinoma; patients carrying the TT genotype of rs217727 and C allele of rs2839698 may increase the risk of gastric carcinoma. No significant association was observed between H19 SNP polymorphism and risk of EBVaGC.
[Abstract] Objective: To evaluate the potential associations between the single nucleotide polymorphisms (SNPs) of lncRNA H19 genes and the susceptibility to gastric cancer (GC), especially to EBV-associated gastric cancer (EBVaGC) in Han population in Qingdao.Methods: 225 cases of pathologically confirmed fresh gastric cancer tissues or paraffin embedded gastric cancer tissues during January 2015 and October 2018 were collected from Affiliated Hospital of Qingdao University, as GC group; in the meanwhile, 200 healthy people underwent physical examination at Outpatient were collected as control. The 225 cases of cancer tissues were assigned into two groups according to the transcription result of EBV-encoded small molecule non-polyadenylation (EBER 1) by In situ hybridization:EBVaGC group (70 cases) and EBVnGC group (155 cases). DNA was extracted from the tissues of two groups and peripheral blood of healthy participants. According to the general setting of HaploView software (MAF>0.05, r2>0.8), four TagSNPs (rs217727, rs2735971,rs2839698 and rs3741216) of H19 were screened. Genotyping of each SNP locus was carried out by using Taq-Man MGB allele typing kit, and the gene polymorphisms were examined. Results: H19 SNPs of collected tissue samples were in accordance with the Hardy-Weinberg equilibrium. Compared with control group, patients carrying TT genotype of H19 rs217727 loci had significantly increased susceptibility to gastric cancer (χ2=9.073, P=0.003, OR=1.999, 95% CI=1.271-3.143), so did the T allele (χ2=13.475, P=0.001, OR=1.661, 95% CI=1.266-2.180). In contrast, patients carrying TC and CC genotype of rs2839698 loci had significantly increased susceptibility to gastric cancer (χ2=9.407, P=0.002; χ2=6.517, P=0.011), and patients carrying C allele had obviously increased susceptibility to GC (χ2=6.163, P=0.013, OR=1.417, 95%CI=1.076-1.867; χ2=9.542, P=0.02, OR=2.070, 95%CI=1.298-3.302). As for the rs2735971 and rs3741216, there was no significant difference between the GC group and the control group (all P>0.05). The distribution of 4 H19 SNPs showed no statistical difference in both EBVaGC group and EBVnGC group (all P>0.05). Conclusion: There was an association between H19 gene polymorphism (rs217727 and rs2839698) and gastric carcinoma; patients carrying the TT genotype of rs217727 and C allele of rs2839698 may increase the risk of gastric carcinoma. No significant association was observed between H19 SNP polymorphism and risk of EBVaGC.
2019, 26(6):683-688.
DOI: 10.3872/j.issn.1007-385X.2019.06.011
Abstract:
[Abstract] Objective: To explore the association between the single nucleotide polymorphism (SNP) of rs175048 in ataxia telangiectasia mutated (ATM) gene and lung cancer susceptibility in Han population. Methods: A total of 225 cases of blood samples from lung cancer patients treated in Hospital of Traditional Chinese Medicine of Hengyang City and the Affiliated First Hospital of Nanhua University from October 2015 to August 2016 were collected as case group, and 128 cases of blood samples from healthy people were collected as the control. The polymorphisms of ATM rs175048 of above mentioned participants were detected by using the SNP sensitive On/ Off Switch technique. The genotypes and allele frequencies were analyzed to compare the distribution difference between case group and control group as well as its association to the clinical features of lung cancer. Results: The genotype frequencies of AA, AT and TT of ATM rs175048 were 24.9%, 52.9%, 22.2% in case group and 42.2%, 42.2%, 15.6% in control group, respectively (all P<0.01). Moreover, the frequencies of alleles A and T were 51.0%, 49.0% in case group, and 63.0%, 37.0% in control group (all P<0.01).Genotype TT might increase while genotype AT might decrease the risk of lung cancer. rs175048 SNP was significantly correlated with smoking, age, sex and family history (all P<0.05). Conclusion: rs175048 SNP is significantly associated with lung cancer, and TT genotype may increase the risk of lung cancer.
[Abstract] Objective: To explore the association between the single nucleotide polymorphism (SNP) of rs175048 in ataxia telangiectasia mutated (ATM) gene and lung cancer susceptibility in Han population. Methods: A total of 225 cases of blood samples from lung cancer patients treated in Hospital of Traditional Chinese Medicine of Hengyang City and the Affiliated First Hospital of Nanhua University from October 2015 to August 2016 were collected as case group, and 128 cases of blood samples from healthy people were collected as the control. The polymorphisms of ATM rs175048 of above mentioned participants were detected by using the SNP sensitive On/ Off Switch technique. The genotypes and allele frequencies were analyzed to compare the distribution difference between case group and control group as well as its association to the clinical features of lung cancer. Results: The genotype frequencies of AA, AT and TT of ATM rs175048 were 24.9%, 52.9%, 22.2% in case group and 42.2%, 42.2%, 15.6% in control group, respectively (all P<0.01). Moreover, the frequencies of alleles A and T were 51.0%, 49.0% in case group, and 63.0%, 37.0% in control group (all P<0.01).Genotype TT might increase while genotype AT might decrease the risk of lung cancer. rs175048 SNP was significantly correlated with smoking, age, sex and family history (all P<0.05). Conclusion: rs175048 SNP is significantly associated with lung cancer, and TT genotype may increase the risk of lung cancer.
2019, 26(6):689-694.
DOI: 10.3872/j.issn.1007-385X.2019.06.012
Abstract:
[Abstract] Objective: To investigate the expression of HOXA13 in non-small cell lung cancer (NSCLC) tissues, and to explore the effect of silencing HOXA13 gene on the growth of A549 cells in vitro and xenograft in nude mice. Methods: A total of 112 pairs of NSCLC tissues and corresponding adjacent normal tissues from patients, who underwent surgical resection at the Department of Thoracic surgery, Central Hospital of Jiaozuo Coal Industry Group from March 2014 to April 2016, were selected for this study. Real-time fluorescence quantitative PCR was used to detect the expressions of HOXA13 in NSCLC tissues and adjacent tissues. A549 cells were cultured and divided into siRNA-HOXA13 group, negative control group and control group. Real-time quantitative PCR was used to detect the expression of HOXA13 in cells, CCK-8 was used to detect cell proliferation, and Transwell assay was used to detect cell invasion.Xenograft model in nude mice was constructed, and the growth of nude mice was observed. After 5 weeks, the mice was sacrificed and weighed, and the tumor-inhibition rate was calculated. Real-time fluorescence quantitative PCR(qPCR) was used to detect the expression of HOXA13 in xenograft tissues. Results: The relative expression level of HOXA13 mRNA in NSCLC tissues was significantly higher than that in the adjacent tissues (1.83±0.13 vs 1.12±0.10, t=47.008, P=0.000), and its expression was correlated to TNM staging,differentiation and lymph node metastasis (all P<0.05). The relative expression level of HOXA13 mRNA in cells of siRNAHOXA13 group was lower than that in the negative control group and the control group (P<0.05). The cell proliferation level (D values)at 24, 48, 72 and 96 h in the siRNA-HOXA13 group were significantly lower than those in the negative control group and control group (F=30.727, 5.427, 13.816 and 24.454, all P<0.05 or P<0.01); the number of invasive cells in the siRNA-HOXA13 group was lower than that in the negative control group and the control group (all P<0.05). The mass of xenograft in nude mice at week 5 in the siRNA-HOXA13 group was smaller than that in the negative control group and control group, while the tumor-inhibition rate was higher than the negative control group (all P<0.05). The relative mRNA expression level of HOXA13 in xenograft tumor tissue in the siRNA-HOXA13 group was lower than that in the negative control group and the control group (all P<0.01). Conclusion: HOXA13 was highly expressed in the non-small cell lung cancer tissues, and was related to oncogenesis, progression and metastasis of cancer. Specific silencing of HOXA13 gene expression could inhibit the proliferation and invasion of tumor cells and suppress the growth of xenograft in nude mice.
[Abstract] Objective: To investigate the expression of HOXA13 in non-small cell lung cancer (NSCLC) tissues, and to explore the effect of silencing HOXA13 gene on the growth of A549 cells in vitro and xenograft in nude mice. Methods: A total of 112 pairs of NSCLC tissues and corresponding adjacent normal tissues from patients, who underwent surgical resection at the Department of Thoracic surgery, Central Hospital of Jiaozuo Coal Industry Group from March 2014 to April 2016, were selected for this study. Real-time fluorescence quantitative PCR was used to detect the expressions of HOXA13 in NSCLC tissues and adjacent tissues. A549 cells were cultured and divided into siRNA-HOXA13 group, negative control group and control group. Real-time quantitative PCR was used to detect the expression of HOXA13 in cells, CCK-8 was used to detect cell proliferation, and Transwell assay was used to detect cell invasion.Xenograft model in nude mice was constructed, and the growth of nude mice was observed. After 5 weeks, the mice was sacrificed and weighed, and the tumor-inhibition rate was calculated. Real-time fluorescence quantitative PCR(qPCR) was used to detect the expression of HOXA13 in xenograft tissues. Results: The relative expression level of HOXA13 mRNA in NSCLC tissues was significantly higher than that in the adjacent tissues (1.83±0.13 vs 1.12±0.10, t=47.008, P=0.000), and its expression was correlated to TNM staging,differentiation and lymph node metastasis (all P<0.05). The relative expression level of HOXA13 mRNA in cells of siRNAHOXA13 group was lower than that in the negative control group and the control group (P<0.05). The cell proliferation level (D values)at 24, 48, 72 and 96 h in the siRNA-HOXA13 group were significantly lower than those in the negative control group and control group (F=30.727, 5.427, 13.816 and 24.454, all P<0.05 or P<0.01); the number of invasive cells in the siRNA-HOXA13 group was lower than that in the negative control group and the control group (all P<0.05). The mass of xenograft in nude mice at week 5 in the siRNA-HOXA13 group was smaller than that in the negative control group and control group, while the tumor-inhibition rate was higher than the negative control group (all P<0.05). The relative mRNA expression level of HOXA13 in xenograft tumor tissue in the siRNA-HOXA13 group was lower than that in the negative control group and the control group (all P<0.01). Conclusion: HOXA13 was highly expressed in the non-small cell lung cancer tissues, and was related to oncogenesis, progression and metastasis of cancer. Specific silencing of HOXA13 gene expression could inhibit the proliferation and invasion of tumor cells and suppress the growth of xenograft in nude mice.
2019, 26(6):695-699.
DOI: 10.3872/j.issn.1007-385X.2019.06.013
Abstract:
[Abstract] Objective: To evaluate the long-term clinical efficacy and follow-up of dendritic cell (DC) vaccines in combination with cytokine-induced killer cell (CIK) treatment in metastatic renal cell carcinoma. Methods: From January 2011 to December 2013, 29 patients with metastatic renal cell carcinoma (pathologically confirmed as renal clear cell carcinoma) were treated by DC vaccines-CIK at the Department of Hematopoietic Stem Cell Transplantation, the Fifth Medical Center of Chinese PLA General Hospital. The 29 patients included 24 male and 5 female, with a median age of 57(32-81) years old. Mature DC vaccine was obtained by gene transfection technology and CIK cells were obtained by in vitro culture; and DC vaccine-CIK was infused back to patients through lymphatic drainage area and vein by each course. Twelve patients received first line treatment, 6 patients received second line treatment after the disease progression by targeted drug therapy or cytokine therapy, and 11 patients received third-linetreatment or above. The long-term clinical efficacy and overall survival rate were evaluated. Results: The median follow-up time was 5 (1-7) years. Treatment cycle was over 2 (2-23) cycles. One case (3.4%) achieved complete remission, 9 cases (31%) achieved partial responses, 13 cases (44.8%) demonstrated stable disease over 3 months and 6 patients (20.7%) developed progressive disease. The objective response rate was 34.4%,and the disease control rate was 79.2%. Stable disease for more than one year realized in 19 cases (65.5%). The 1-, 3- and 5-year survival rates were 93.1% (27/29), 65.5% (20/29) and 51.7% (15 / 29), respectively. Neither the median progression-free survival (PFS) nor the median survival time was achieved. No adverse reactions above grade 3 were observed during treatment. Conclusion: DC vaccines-CIK therapy for the treatment of metastatic renal cell carcinoma is affirmative; it achieved good disease control and long-term survival with controllable safety, and prolonged the survival time for advanced renal cell carcinoma patients.
[Abstract] Objective: To evaluate the long-term clinical efficacy and follow-up of dendritic cell (DC) vaccines in combination with cytokine-induced killer cell (CIK) treatment in metastatic renal cell carcinoma. Methods: From January 2011 to December 2013, 29 patients with metastatic renal cell carcinoma (pathologically confirmed as renal clear cell carcinoma) were treated by DC vaccines-CIK at the Department of Hematopoietic Stem Cell Transplantation, the Fifth Medical Center of Chinese PLA General Hospital. The 29 patients included 24 male and 5 female, with a median age of 57(32-81) years old. Mature DC vaccine was obtained by gene transfection technology and CIK cells were obtained by in vitro culture; and DC vaccine-CIK was infused back to patients through lymphatic drainage area and vein by each course. Twelve patients received first line treatment, 6 patients received second line treatment after the disease progression by targeted drug therapy or cytokine therapy, and 11 patients received third-linetreatment or above. The long-term clinical efficacy and overall survival rate were evaluated. Results: The median follow-up time was 5 (1-7) years. Treatment cycle was over 2 (2-23) cycles. One case (3.4%) achieved complete remission, 9 cases (31%) achieved partial responses, 13 cases (44.8%) demonstrated stable disease over 3 months and 6 patients (20.7%) developed progressive disease. The objective response rate was 34.4%,and the disease control rate was 79.2%. Stable disease for more than one year realized in 19 cases (65.5%). The 1-, 3- and 5-year survival rates were 93.1% (27/29), 65.5% (20/29) and 51.7% (15 / 29), respectively. Neither the median progression-free survival (PFS) nor the median survival time was achieved. No adverse reactions above grade 3 were observed during treatment. Conclusion: DC vaccines-CIK therapy for the treatment of metastatic renal cell carcinoma is affirmative; it achieved good disease control and long-term survival with controllable safety, and prolonged the survival time for advanced renal cell carcinoma patients.
2019, 26(6):700-704.
DOI: 10.3872/j.issn.1007-385X.2019.06.014
Abstract:
[摘要] 胃癌患者具有相对较高的突变负荷、新抗原基数和肿瘤浸润淋巴细胞，表明其对免疫治疗可能具有潜在应答性，但多项研究显示，免疫检查点程序性死亡受体1（programmed death protein1, PD-1）抑制剂单药治疗应答率仅为10%~26%。近期，人们对化疗对机体免疫系统的影响进行了深入探究，证实化疗药物可通过不同免疫调节机制对肿瘤免疫应答产生影响。多项研究显示，免疫治疗联合化疗药物在提高患者客观缓解率（ORR）和延长生存期方面具有一定成效，联合方案逐渐成为目前晚期胃癌研究的热点。本文主要阐述化疗药物对肿瘤免疫应答的影响、免疫治疗联合化疗在晚期胃癌中的应用及预测疗效的生物标记物的进展，以期为胃癌的临床治疗提供参考。
[摘要] 胃癌患者具有相对较高的突变负荷、新抗原基数和肿瘤浸润淋巴细胞，表明其对免疫治疗可能具有潜在应答性，但多项研究显示，免疫检查点程序性死亡受体1（programmed death protein1, PD-1）抑制剂单药治疗应答率仅为10%~26%。近期，人们对化疗对机体免疫系统的影响进行了深入探究，证实化疗药物可通过不同免疫调节机制对肿瘤免疫应答产生影响。多项研究显示，免疫治疗联合化疗药物在提高患者客观缓解率（ORR）和延长生存期方面具有一定成效，联合方案逐渐成为目前晚期胃癌研究的热点。本文主要阐述化疗药物对肿瘤免疫应答的影响、免疫治疗联合化疗在晚期胃癌中的应用及预测疗效的生物标记物的进展，以期为胃癌的临床治疗提供参考。
2019, 26(6):705-709.
DOI: 10.3872/j.issn.1007-385X.2019.06.015
Abstract:
[摘要] 自然杀伤（NK）细胞为体内固有免疫细胞，无需抗原致敏即可直接识别并杀伤肿瘤细胞等。随着对NK细胞抗肿瘤机制深入认识、NK细胞扩增方法优化等方面的进展，以NK细胞为基础的血液肿瘤过继免疗法越来受到关注，尤其异体NK细胞过继性免疫治疗急性髓细胞性白血病（AML）疗效显著。随着精准医学发展、NK 细胞抗肿瘤机制的深入研究以及大样本多中心临床研究逐步开展，相信不久的将来更为有效的异体NK 细胞过继性免疫治疗方案会使更多的AML患者获益。本文就NK 细胞生物学特点、细胞的制备方法、在非移植背景下AML中的临床应用及在AML造血干细胞移植（HSCT）中的应用进行阐述，以期为后续的深入研究和临床治疗提供参考。
[摘要] 自然杀伤（NK）细胞为体内固有免疫细胞，无需抗原致敏即可直接识别并杀伤肿瘤细胞等。随着对NK细胞抗肿瘤机制深入认识、NK细胞扩增方法优化等方面的进展，以NK细胞为基础的血液肿瘤过继免疗法越来受到关注，尤其异体NK细胞过继性免疫治疗急性髓细胞性白血病（AML）疗效显著。随着精准医学发展、NK 细胞抗肿瘤机制的深入研究以及大样本多中心临床研究逐步开展，相信不久的将来更为有效的异体NK 细胞过继性免疫治疗方案会使更多的AML患者获益。本文就NK 细胞生物学特点、细胞的制备方法、在非移植背景下AML中的临床应用及在AML造血干细胞移植（HSCT）中的应用进行阐述，以期为后续的深入研究和临床治疗提供参考。
2019, 26(6):710-714.
DOI: 10.3872/j.issn.1007-385X.2019.06.016
Abstract:
[摘要] 肺癌是目前全世界发病率及病死率均居前列的恶性肿瘤。近年来，基于驱动基因的分子靶向精准治疗彻底改变了晚期肺癌患者的治疗模式，新型抗肿瘤药物层出不穷。安罗替尼（AL3818，anlotinib）是中国自主研发的一种新型小分子多靶点酪氨酸激酶抑制剂（tyrosine kinase inhibition，TKI），其具有抗肿瘤血管生成和抑制肿瘤细胞生长的作用，且安全性较好，目前已被国家食品药品监督管理局（China Food and Drug Administration，cFDA）批准用于肺癌的三线及以上治疗。本文就安罗替尼抗肿瘤作用机制、相关临床研究、寻找预测疗效的标志物及不良反应等方面在肺癌中的研究进展作一综述。
[摘要] 肺癌是目前全世界发病率及病死率均居前列的恶性肿瘤。近年来，基于驱动基因的分子靶向精准治疗彻底改变了晚期肺癌患者的治疗模式，新型抗肿瘤药物层出不穷。安罗替尼（AL3818，anlotinib）是中国自主研发的一种新型小分子多靶点酪氨酸激酶抑制剂（tyrosine kinase inhibition，TKI），其具有抗肿瘤血管生成和抑制肿瘤细胞生长的作用，且安全性较好，目前已被国家食品药品监督管理局（China Food and Drug Administration，cFDA）批准用于肺癌的三线及以上治疗。本文就安罗替尼抗肿瘤作用机制、相关临床研究、寻找预测疗效的标志物及不良反应等方面在肺癌中的研究进展作一综述。
2019, 26(6):715-719.
DOI: 10.3872/j.issn.1007-385X.2019.06.017
Abstract:
[摘要] 卵巢癌是女性生殖器官常见的恶性妇科肿瘤之一。由于缺乏有效的生物标志物用于诊断和个性化治疗，超过70％的卵巢癌患者诊断时已是晚期，并且5 年生存率低于30％。因此，迫切需要新的诊断和预后标志物来推进和启动更个性化的治疗，最终提高患者的存活率。miRNA是一类小的非编码RNA，主要通过转录后抑制负调节基因表达。近年来，一些研究表明，miRNA在卵巢癌组织中表达失调，有可能作为卵巢癌的诊断和预后生物标志物。另外，最近的研究显示，miRNA还可以作为化疗敏感性的预测因子和治疗靶点。本文主要从miRNA在卵巢癌组织中的差异表达、miRNA与卵巢癌的诊断和miRNA与卵巢癌的预后3 个方面进行阐述，为推进和启动卵巢癌患者的诊断和个性化治疗提供借鉴。
[摘要] 卵巢癌是女性生殖器官常见的恶性妇科肿瘤之一。由于缺乏有效的生物标志物用于诊断和个性化治疗，超过70％的卵巢癌患者诊断时已是晚期，并且5 年生存率低于30％。因此，迫切需要新的诊断和预后标志物来推进和启动更个性化的治疗，最终提高患者的存活率。miRNA是一类小的非编码RNA，主要通过转录后抑制负调节基因表达。近年来，一些研究表明，miRNA在卵巢癌组织中表达失调，有可能作为卵巢癌的诊断和预后生物标志物。另外，最近的研究显示，miRNA还可以作为化疗敏感性的预测因子和治疗靶点。本文主要从miRNA在卵巢癌组织中的差异表达、miRNA与卵巢癌的诊断和miRNA与卵巢癌的预后3 个方面进行阐述，为推进和启动卵巢癌患者的诊断和个性化治疗提供借鉴。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.