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Volume 26,Issue 5,2019 Table of Contents
2019, 26(5):485-491.
DOI: 10.3872/j.issn.1007-385X.2019.05.001
Abstract:
[Abstract] Successful targeting and inhibition of the programmed cell death-1/ programmed cell death-ligand 1 immune checkpoint pathways by monoclonal antibody stimulates an immune response against tumors, has led to a rapidly expanding repertoire of immune checkpoint inhibitors (ICIs) for the treatment of various cancers. Immune checkpoint therapy has dramatically changed the therapeutic landscape of certain types of cancers. However, hyperprogressive disease (HPD) is emerging as a new pattern of progression in cancer patients treated with ICIs, characterized as an absolute increase in the tumor growth rate exceeding 50% per month. This article discusses the concept of HPD, hypotheses as to the underlying biology, and what needs to be done to better understand and identify strategies to prevent or overcome HPD related to checkpoint blockade therapy.
[Abstract] Successful targeting and inhibition of the programmed cell death-1/ programmed cell death-ligand 1 immune checkpoint pathways by monoclonal antibody stimulates an immune response against tumors, has led to a rapidly expanding repertoire of immune checkpoint inhibitors (ICIs) for the treatment of various cancers. Immune checkpoint therapy has dramatically changed the therapeutic landscape of certain types of cancers. However, hyperprogressive disease (HPD) is emerging as a new pattern of progression in cancer patients treated with ICIs, characterized as an absolute increase in the tumor growth rate exceeding 50% per month. This article discusses the concept of HPD, hypotheses as to the underlying biology, and what needs to be done to better understand and identify strategies to prevent or overcome HPD related to checkpoint blockade therapy.
2 Cytotoxic effect of in vitro expanded NK cell-carrying oncolytic reovirus on colorectal cancer cells
2019, 26(5):492-499.
DOI: 10.3872/j.issn.1007-385X.2019.05.002
Abstract:
[Abstract] Objective: To evaluate whether human NK cells expanded in vitro can be used as carrier cells of reovirus and to investigate its clinical application value. Methods: Expansion of human NK cells in vitro, and flow cytometry was used to analyse the purity of CD3-CD56+ cells. Expanded NK cells were loaded with reovirus and observed by confocal microscopy, to determining the location of reovirus on NK cells. CCK-8 assay was used to detect reovirus-induced oncolysis of expanded NK cells carrying reovirus (Reo-NK)to tumor cells in the presence of neutralizing antibodies; Real-time fluorescence quantitative PCR was used to assess the relative expression of viral RNA in tumor cells. Cytotoxicity assay were performed to detect Reo-NK cells against KRAS mutant (DLD-1) and KRAS wild type (CaCo-2, HT29) colorectal cancer cell lines, ELISA matched paired antibodies assay was performed to measure the perforin level released by NK cells. Results: Confocal microscopy demonstrated that NK cells retained reovirus on the surface. Expanded NK cells could delivery reovirus to tumor cells in the presence of neutralizing antibodies, and the reovirus after delivery still had significant oncolytic activity (P<0.01); Corresponding qPCR result displayed that the expression of viral RNA in tumor cells significantly in-creased over time (P<0.01). Compared with NK group, Reo-NK group evidently enhanced the cytotoxicity on colorectal cancer cell lines with both KRAS gene mutant and wild (all P<0.05), and significantly increased the release of perforin (all P<0.05). Conclusion:In vitro expanded NK cells provide a convincing cell carrier for reovirus, while reovirus enhances the cytotoxicity of NK cells, and the combination of the two show a stronger killing effect on colorectal cancer cells，that has important clinical application value.
[Abstract] Objective: To evaluate whether human NK cells expanded in vitro can be used as carrier cells of reovirus and to investigate its clinical application value. Methods: Expansion of human NK cells in vitro, and flow cytometry was used to analyse the purity of CD3-CD56+ cells. Expanded NK cells were loaded with reovirus and observed by confocal microscopy, to determining the location of reovirus on NK cells. CCK-8 assay was used to detect reovirus-induced oncolysis of expanded NK cells carrying reovirus (Reo-NK)to tumor cells in the presence of neutralizing antibodies; Real-time fluorescence quantitative PCR was used to assess the relative expression of viral RNA in tumor cells. Cytotoxicity assay were performed to detect Reo-NK cells against KRAS mutant (DLD-1) and KRAS wild type (CaCo-2, HT29) colorectal cancer cell lines, ELISA matched paired antibodies assay was performed to measure the perforin level released by NK cells. Results: Confocal microscopy demonstrated that NK cells retained reovirus on the surface. Expanded NK cells could delivery reovirus to tumor cells in the presence of neutralizing antibodies, and the reovirus after delivery still had significant oncolytic activity (P<0.01); Corresponding qPCR result displayed that the expression of viral RNA in tumor cells significantly in-creased over time (P<0.01). Compared with NK group, Reo-NK group evidently enhanced the cytotoxicity on colorectal cancer cell lines with both KRAS gene mutant and wild (all P<0.05), and significantly increased the release of perforin (all P<0.05). Conclusion:In vitro expanded NK cells provide a convincing cell carrier for reovirus, while reovirus enhances the cytotoxicity of NK cells, and the combination of the two show a stronger killing effect on colorectal cancer cells，that has important clinical application value.
2019, 26(5):500-505.
DOI: 10.3872/j.issn.1007-385X.2019.05.003
Abstract:
[Abstract] Objective: To investigate the molecular and signal pathway mechanism of Interleukin-27 affecting the anti-tumor effect of NK92 cells. Methods: NK92 cells were cultured with different concentrations of IL-27 (10, 20, 30 and 60 ng/ml) for 24 hours. The cytotoxicity of NK92 cells to target cells was detected by LDH assay. The expressions of NKG2D, NKp30 and NKp46 on the surface of NK92 cells and the secretion of perforin and granzyme B were detected by Flow cytometry. The expression and phosphorylation level of STATs protein was detected by WB. The DU145 cell transplanted tumor model of prostatic carcinoma in NOD-PrkdcscidIl2rgem1/Smoc mice was established and treated with the combination of NK92 cells and IL-27 to evaluate their anti-tumor efficacy. Results: IL-27 at concentrations of 10, 20 and 30 ng/ml could significantly increase the cytotoxicity of NK92 cells to target cells, and 30 ng/ml exerted the best effect (P<0.05 or P<0.01). 30 ng/ml IL-27 could significantly promote the expressions of NKG2D, NKp30 and NKp46 on surface of NK92 cells, as well as elevate the secretion of perforin (all P<0.05), but didn’t affect the secretion of granzyme B (P>0.05);moreover, it also up-regulated the phosphorylation of STAT1, STAT3 and STAT5 protein (all P<0.01). The combined treatment of IL-27 and NK92 cells obviously extended the survival time of tumor-bearing mice (P<0.05). Conclusions: IL-27 can promote the cytotoxicity of NK92 cells against solid tumor cells and blood tumor cells by promoting expressions of NKG2D, NKp30 and NKp46 on the surface of NK92 cells and the secretion of perforin, which might be related with the phosphorylation of STAT1, STAT3 and STAT5 in JAKSTAT pathway.
[Abstract] Objective: To investigate the molecular and signal pathway mechanism of Interleukin-27 affecting the anti-tumor effect of NK92 cells. Methods: NK92 cells were cultured with different concentrations of IL-27 (10, 20, 30 and 60 ng/ml) for 24 hours. The cytotoxicity of NK92 cells to target cells was detected by LDH assay. The expressions of NKG2D, NKp30 and NKp46 on the surface of NK92 cells and the secretion of perforin and granzyme B were detected by Flow cytometry. The expression and phosphorylation level of STATs protein was detected by WB. The DU145 cell transplanted tumor model of prostatic carcinoma in NOD-PrkdcscidIl2rgem1/Smoc mice was established and treated with the combination of NK92 cells and IL-27 to evaluate their anti-tumor efficacy. Results: IL-27 at concentrations of 10, 20 and 30 ng/ml could significantly increase the cytotoxicity of NK92 cells to target cells, and 30 ng/ml exerted the best effect (P<0.05 or P<0.01). 30 ng/ml IL-27 could significantly promote the expressions of NKG2D, NKp30 and NKp46 on surface of NK92 cells, as well as elevate the secretion of perforin (all P<0.05), but didn’t affect the secretion of granzyme B (P>0.05);moreover, it also up-regulated the phosphorylation of STAT1, STAT3 and STAT5 protein (all P<0.01). The combined treatment of IL-27 and NK92 cells obviously extended the survival time of tumor-bearing mice (P<0.05). Conclusions: IL-27 can promote the cytotoxicity of NK92 cells against solid tumor cells and blood tumor cells by promoting expressions of NKG2D, NKp30 and NKp46 on the surface of NK92 cells and the secretion of perforin, which might be related with the phosphorylation of STAT1, STAT3 and STAT5 in JAKSTAT pathway.
2019, 26(5):506-511.
DOI: 10.3872/j.issn.1007-385X.2019.05.004
Abstract:
[Abstract] Objective: To investigate the inhibitory effect of asiatic acid (AA) on malignant biological behaviors of human liver cancer cells and to explore the mechanism. Methods: Human liver cancer cell line (Huh7) was used as research subject, and treated with different concentrations of AA (0, 5, 10, 25, 50, 100 μmol/L) in vitro. The effect of AA on cell proliferation was determined by CCK-8 and EdU assay; the apoptosis and cell cycle distribution were detected by flow cytometry, while the expressions of apoptosis-related proteins (AKT, P-ERK 1/2 , p38, cleaved-caspase3, cleaved-caspase9, BAX, Bcl-2, AKT, ERK, p38, pro-caspase 3 and pro-caspase 9)were examined by WB. Results: AA could inhibit the proliferation of Huh7 cells in a dose- and time-dependent manner (all P<0.05).After being incubated with 10 μmol/L AA for 24 h, the proliferation of Huh7 cells was significantly inhibited (P<0.05), the apoptosis rate was significantly increased (P<0.05), and cell cycle was arrested in G1 phase (P<0.05). AA induced p-p38 expression, but inhibited the expression of p-AKT and p-ERK in a dose-dependent manner (all P<0.05). In addition, as the concentration of AA increased, the levels of cleaved-caspase 3, cleaved-caspase 9 and BAX increased, while the level of Bcl-2 decreased (all P<0.05). Conclusion: AA inhibits the proliferation of human liver cancer cells and promotes its apoptosis, which is associated with the MAPK and PI3K/AKT pathways.
[Abstract] Objective: To investigate the inhibitory effect of asiatic acid (AA) on malignant biological behaviors of human liver cancer cells and to explore the mechanism. Methods: Human liver cancer cell line (Huh7) was used as research subject, and treated with different concentrations of AA (0, 5, 10, 25, 50, 100 μmol/L) in vitro. The effect of AA on cell proliferation was determined by CCK-8 and EdU assay; the apoptosis and cell cycle distribution were detected by flow cytometry, while the expressions of apoptosis-related proteins (AKT, P-ERK 1/2 , p38, cleaved-caspase3, cleaved-caspase9, BAX, Bcl-2, AKT, ERK, p38, pro-caspase 3 and pro-caspase 9)were examined by WB. Results: AA could inhibit the proliferation of Huh7 cells in a dose- and time-dependent manner (all P<0.05).After being incubated with 10 μmol/L AA for 24 h, the proliferation of Huh7 cells was significantly inhibited (P<0.05), the apoptosis rate was significantly increased (P<0.05), and cell cycle was arrested in G1 phase (P<0.05). AA induced p-p38 expression, but inhibited the expression of p-AKT and p-ERK in a dose-dependent manner (all P<0.05). In addition, as the concentration of AA increased, the levels of cleaved-caspase 3, cleaved-caspase 9 and BAX increased, while the level of Bcl-2 decreased (all P<0.05). Conclusion: AA inhibits the proliferation of human liver cancer cells and promotes its apoptosis, which is associated with the MAPK and PI3K/AKT pathways.
2019, 26(5):512-517.
DOI: 10.3872/j.issn.1007-385X.2019.05.005
Abstract:
[Abstract] Objective: To investigate the effects of Wilms’tumor 1-associating protein (WTAP) on proliferation, migration and invasion of human lung adenocarcinoma A549 cells. Methods: Human lung adenocarcinoma cell line A549 and HEK293T cells were chosen for this study. Two sets of shWTAP interference sequences were designed to construct lentiviral vector plasmid. Human lung adenocarcinoma A549 cells were infected after packaging lentivirus in HEK293T cells, and the control group was transfected with 277 empty vector plasmid. The mRNA and protein expression levels of WTAP in A549 cells were detected by qPCR and WB. Changes in proliferation,migration and invasion of A549 cells were detected by BrdU assay, cell scratch healing assay and Transwell assay, respectively.Results: Two plasmids, shWTAP-1 and shWTAP-2, were successfully constructed. Compared with the control group, the mRNA and protein expression levels of WTAP were significantly down-regulated in A549 cells with WTAP knockdown (both P<0.05), and the proliferation,migration and invasion ability of cells were significantly decreased (all P<0.05). Conclusion: Knockdown of WTAP significantly inhibited the proliferation, migration and invasion of human lung adenocarcinoma A549 cells. The expression of WTAP gene is associated with the occurrence and development of lung adenocarcinoma. WTAP may be a potential target for the diagnosis and treatment of lung adenocarcinoma.
[Abstract] Objective: To investigate the effects of Wilms’tumor 1-associating protein (WTAP) on proliferation, migration and invasion of human lung adenocarcinoma A549 cells. Methods: Human lung adenocarcinoma cell line A549 and HEK293T cells were chosen for this study. Two sets of shWTAP interference sequences were designed to construct lentiviral vector plasmid. Human lung adenocarcinoma A549 cells were infected after packaging lentivirus in HEK293T cells, and the control group was transfected with 277 empty vector plasmid. The mRNA and protein expression levels of WTAP in A549 cells were detected by qPCR and WB. Changes in proliferation,migration and invasion of A549 cells were detected by BrdU assay, cell scratch healing assay and Transwell assay, respectively.Results: Two plasmids, shWTAP-1 and shWTAP-2, were successfully constructed. Compared with the control group, the mRNA and protein expression levels of WTAP were significantly down-regulated in A549 cells with WTAP knockdown (both P<0.05), and the proliferation,migration and invasion ability of cells were significantly decreased (all P<0.05). Conclusion: Knockdown of WTAP significantly inhibited the proliferation, migration and invasion of human lung adenocarcinoma A549 cells. The expression of WTAP gene is associated with the occurrence and development of lung adenocarcinoma. WTAP may be a potential target for the diagnosis and treatment of lung adenocarcinoma.
2019, 26(5):518-523.
DOI: 10.3872/j.issn.1007-385X.2019.05.006
Abstract:
[Abstract] Objective: To investigate the effects of ginsenoside Rg3 on the formation of vasculogenic mimicry (VM) in gastric cancer cell line SGC7901 and its molecular mechanism. Methods: MTT assay was used to detect the effect of different concentrations of Rg3 on the proliferation of SGC7901 cells. SGC7901 cells were grouped as follows: BML-284 group, XAV-939 group, Rg3 group, Rg3+BML-284 group and blank group. Transwell chamber assay was used to detect cell invasion and migration; the formation of VM was observed by tube formation assay; the secretion of MMP-9 and MMP2 was detected by ELISA; the mRNA expressions of GSK-3β and Wnt2B were detected by qPCR; the expression of β-Catenin protein in cells was analyzed by WB; and nuclear entry of β-Catenin was examined by Immunofluorescence. Results: Ginsenoside Rg3 inhibited the proliferation of SGC7901 cells in a time- and concentrationdependent manner; compared with the blank group, 40 mg/L Rg3 significantly inhibited the invasion and migration of SGC7901 cells (both P<0.05) and VM formation (P<0.05); in the meanwhile, the expressions of intracellular GSK-3β, Wnt2B mRNA and β-catenin protein, as well as the nuclear entry of β-catenin were significantly inhibited (all P<0.05). The invasion, migration and VM formation of SGC7901 cells in Rg3+BML-284 group were not significantly different from those in the blank group (all P>0.05). Conclusion: Rg3 can inhibit cell invasion, migration and VM formation in SGC7901 cells by inhibiting the activation of Wnt/β-Catenin pathway.
[Abstract] Objective: To investigate the effects of ginsenoside Rg3 on the formation of vasculogenic mimicry (VM) in gastric cancer cell line SGC7901 and its molecular mechanism. Methods: MTT assay was used to detect the effect of different concentrations of Rg3 on the proliferation of SGC7901 cells. SGC7901 cells were grouped as follows: BML-284 group, XAV-939 group, Rg3 group, Rg3+BML-284 group and blank group. Transwell chamber assay was used to detect cell invasion and migration; the formation of VM was observed by tube formation assay; the secretion of MMP-9 and MMP2 was detected by ELISA; the mRNA expressions of GSK-3β and Wnt2B were detected by qPCR; the expression of β-Catenin protein in cells was analyzed by WB; and nuclear entry of β-Catenin was examined by Immunofluorescence. Results: Ginsenoside Rg3 inhibited the proliferation of SGC7901 cells in a time- and concentrationdependent manner; compared with the blank group, 40 mg/L Rg3 significantly inhibited the invasion and migration of SGC7901 cells (both P<0.05) and VM formation (P<0.05); in the meanwhile, the expressions of intracellular GSK-3β, Wnt2B mRNA and β-catenin protein, as well as the nuclear entry of β-catenin were significantly inhibited (all P<0.05). The invasion, migration and VM formation of SGC7901 cells in Rg3+BML-284 group were not significantly different from those in the blank group (all P>0.05). Conclusion: Rg3 can inhibit cell invasion, migration and VM formation in SGC7901 cells by inhibiting the activation of Wnt/β-Catenin pathway.
2019, 26(5):524-529.
DOI: 10.3872/j.issn.1007-385X.2019.05.007
Abstract:
[Abstract] Objective: To investigate the expression of ECT2 (epithelial Transforming sequence 2) gene in human pancreatic ductal adenocarcinoma (PDAC) and its effect on the proliferation and apoptosis of pancreatic cancer cells. Methods: Carcinoma tissues and corresponding para-carcinoma tissues from 35 PDAC patients at Changhai Hospital Affiliated to Naval Medical University from July 2018 to March 2019 were collected for this study. The differentially expressed genes in pancreatic cancer were screened out by using Gene Expression Omnibus (GEO) Database. Then, the related gene expression in PDAC and its relation with patients’survival were analyzed by The Cancer Genome Atlas (TCGA) database. QPCR and immunohistochemistry were used to verify the mRNA and protein expressions of ECT2 in human PDAC samples. To explore the effect of ECT2 on the biological behaviors of pancreatic cancer cells, si-RNA was used to silence the ECT2 gene in pancreatic cancer PANC-1 cells, and CCK-8 proliferation assay and Flow cytometry were used to detect the proliferation and apoptosis rate of PANC-1 cells after ECT2 silence. Finally,the expressions of apoptosis-related proteins were detected by WB. Results: The differentially expressed gene-ECT2, was screened out by analyzing the gene expression profiles of human pancreatic cancer in GEO database. TCGA database analysis showed that ECT2 was highly expressed in pancreatic cancer tissues (t=4.005, P<0.05) and significantly correlated with patients’survival (P<0.01). Moreover, it is also verified that ECT2 was highly expressed in PDAC tissues at mRNA (1.01±0.06 vs 4.25±0.12; t=24.09，P<0.01) and protein level. After ECT2 silence in PANC-1 cells, the proliferation rate was decreased (P<0.01), while the Tamoxifeninduced apoptosis rate was increased (P<0.01), and the expressions of apoptosis-related proteins (BAX and Bcl-2) were also affected.Conclusion: ECT2 is highly expressed in human pancreatic ductal adenocarcinoma and is related with patients’survival.ECT2 promotes the proliferation and apoptosis resistance of pancreatic cancer cells, providing the basis for exploring ECT2 as a new target for the prognostic judgment and treatment of pancreatic cancer.
[Abstract] Objective: To investigate the expression of ECT2 (epithelial Transforming sequence 2) gene in human pancreatic ductal adenocarcinoma (PDAC) and its effect on the proliferation and apoptosis of pancreatic cancer cells. Methods: Carcinoma tissues and corresponding para-carcinoma tissues from 35 PDAC patients at Changhai Hospital Affiliated to Naval Medical University from July 2018 to March 2019 were collected for this study. The differentially expressed genes in pancreatic cancer were screened out by using Gene Expression Omnibus (GEO) Database. Then, the related gene expression in PDAC and its relation with patients’survival were analyzed by The Cancer Genome Atlas (TCGA) database. QPCR and immunohistochemistry were used to verify the mRNA and protein expressions of ECT2 in human PDAC samples. To explore the effect of ECT2 on the biological behaviors of pancreatic cancer cells, si-RNA was used to silence the ECT2 gene in pancreatic cancer PANC-1 cells, and CCK-8 proliferation assay and Flow cytometry were used to detect the proliferation and apoptosis rate of PANC-1 cells after ECT2 silence. Finally,the expressions of apoptosis-related proteins were detected by WB. Results: The differentially expressed gene-ECT2, was screened out by analyzing the gene expression profiles of human pancreatic cancer in GEO database. TCGA database analysis showed that ECT2 was highly expressed in pancreatic cancer tissues (t=4.005, P<0.05) and significantly correlated with patients’survival (P<0.01). Moreover, it is also verified that ECT2 was highly expressed in PDAC tissues at mRNA (1.01±0.06 vs 4.25±0.12; t=24.09，P<0.01) and protein level. After ECT2 silence in PANC-1 cells, the proliferation rate was decreased (P<0.01), while the Tamoxifeninduced apoptosis rate was increased (P<0.01), and the expressions of apoptosis-related proteins (BAX and Bcl-2) were also affected.Conclusion: ECT2 is highly expressed in human pancreatic ductal adenocarcinoma and is related with patients’survival.ECT2 promotes the proliferation and apoptosis resistance of pancreatic cancer cells, providing the basis for exploring ECT2 as a new target for the prognostic judgment and treatment of pancreatic cancer.
2019, 26(5):530-535.
DOI: 10.3872/j.issn.1007-385X.2019.05.008
Abstract:
[Abstract] Objective: To investigate the relationship between PET/CT metabolic parameters and pathological features and prognosis in esophageal squamous cell carcinoma (ESCC) patients with intramural gastric metastasis (IGM). Methods: Totally 86 cases of ESCC IGM patients treated in Anhui Provincial Hospital Affiliated to Anhui Medical University from January 2008 to December 2014 were selected for this study. The patients received the imaging examination by positron emission tomography and computed tomography (PET/CT). The metabolic parameters including maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), PET tumor length (PTL) and mean standard uptake value (SUVmean) were examined to calculate the total lesion glycolysis (TLG). The survival of the patients during 5-year follow-up was recorded, and the relationship between metabolic parameters and clinical pathological features and prognosis was analyzed. Results: SUVmax and SUVmean of IGM patients were related to the diameter of the primary tumor (all P<0.05); MTV was associated with the tumor diameter, lymph node metastasis, and TNM staging (all P<0.05); TLG was associated with the tumor diameter, lymph node metastasis, TNM stage, and tissue differentiation (all P<0.05). During the 5-year follow-up, 6 patients were lost to follow-up, 36 patients died and 44 patients survived; SUVmax, MTV, TLG, PTL, SUVmean, and TNM staging were predictors for patients’prognosis (all P<0.05); MTV, TLG, PTL, SUVmean, and TNM staging were risk factors for prognosis (all P<0.05). Conclusion: The metabolic parameters including SUVmax, MTV, TLG, PTL and SUVmean in ESCC patients with IGM are related to the pathological characteristics of patients; moreover, MTV, TLG, PTL, SUVmean and TNM staging are risk factors for prognosis;so, PET/CT examination has certain clinical value for the prognosis assessment in ESCC patients with IGM.
[Abstract] Objective: To investigate the relationship between PET/CT metabolic parameters and pathological features and prognosis in esophageal squamous cell carcinoma (ESCC) patients with intramural gastric metastasis (IGM). Methods: Totally 86 cases of ESCC IGM patients treated in Anhui Provincial Hospital Affiliated to Anhui Medical University from January 2008 to December 2014 were selected for this study. The patients received the imaging examination by positron emission tomography and computed tomography (PET/CT). The metabolic parameters including maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), PET tumor length (PTL) and mean standard uptake value (SUVmean) were examined to calculate the total lesion glycolysis (TLG). The survival of the patients during 5-year follow-up was recorded, and the relationship between metabolic parameters and clinical pathological features and prognosis was analyzed. Results: SUVmax and SUVmean of IGM patients were related to the diameter of the primary tumor (all P<0.05); MTV was associated with the tumor diameter, lymph node metastasis, and TNM staging (all P<0.05); TLG was associated with the tumor diameter, lymph node metastasis, TNM stage, and tissue differentiation (all P<0.05). During the 5-year follow-up, 6 patients were lost to follow-up, 36 patients died and 44 patients survived; SUVmax, MTV, TLG, PTL, SUVmean, and TNM staging were predictors for patients’prognosis (all P<0.05); MTV, TLG, PTL, SUVmean, and TNM staging were risk factors for prognosis (all P<0.05). Conclusion: The metabolic parameters including SUVmax, MTV, TLG, PTL and SUVmean in ESCC patients with IGM are related to the pathological characteristics of patients; moreover, MTV, TLG, PTL, SUVmean and TNM staging are risk factors for prognosis;so, PET/CT examination has certain clinical value for the prognosis assessment in ESCC patients with IGM.
2019, 26(5):536-543.
DOI: 10.3872/j.issn.1007-385X.2019.05.009
Abstract:
[Abstract] Objective: To investigate the relationship between Ki-67 and PD-L1 in patients with non-small cell lung cancer (NSCLC)and their effects on prognosis. Methods: A total of 401patients, who were pathologically diagnosed as NSCLC in Changhai Hospital from January 2012 to August 2018, were enrolled as study subjects; and the patients were immunohistochemically tested for PD-L1 and Ki-67. The clinical and pathological data were collected, and the follow-up was performed regularly. The correlation between Ki-67 and PD-L1 and their effects on postoperative DFS and post-chemotherapy PFS were statistically analyzed. Results: Positive rates of PD-L1 and Ki-67 in NSCLC tissues were 37.9% (152/401) and 96.3% (386/401), respectively. Univariate analysis showed that Ki-67 was an influencing factor for PD-L1 expression (OR=0.33, 95%CI=0.28-0.39, P<0.0001); Curve Fitting analysis showed a positive correlation between Ki-67 and PD-L1; threshold effect analysis, segmentation multivariate logistic and ROC curve analysis showed 14% is a relatively suitable threshold for Ki-67 to be combined with PD-L1. Kaplan-Meier analysis showed that patients in Ki-67 high expression group had a significantly shorter post-operative DFS than those in Ki-67 low expression group ([21.88±11.25] vs [41.22±16.25]m, P<0.0001), patients in PD-L1 positive group had a significantly shorter DFS than those in PD-L1 negative group ([24.75±14.59] vs [38.27±16.75]m, P<0.0001)], and patients in Ki-67 high /PD-L1 positive group had the shortest DFS as compared to the other three groups ([20.57±11.33] vs [24.11±10.79], [36.00±16.79], [42.91±15.77]m, P<0.0001). As for post-chemotherapy PFS, patients in Ki-67 high ex-pression group was significantly longer than those in Ki-67 low expression group [(7.70±3.01) vs (5.80±2.99)m, P=0.016), but there was no significant difference between PD-L1 positive group and PD-L1 negative group [(7.04±3.21) vs (6.33±3.06)m, P=0.22); for combined evaluation with Ki-67 and PD-L1, the PFS of two Ki-67 high expression groups was significantly longer than the other two Ki-67 low expression groups [(7.74±3.25) vs (7.43±2.38) vs (4.91±1.97) vs (6.02±3.19)m, P=0.041). Conclusion: Ki-67 is positively correlated with PD-L1 in NSCLC patients, and Ki-67 14% is a suitable threshold for combined use with PD-L1. Both Ki-67 and PD-L1 are predictors of poor prognosis. The combination of the two has an "additive effect" on the prediction of poor prognosis, and patients with high Ki-67 expression are more sensitive to chemotherapy.
[Abstract] Objective: To investigate the relationship between Ki-67 and PD-L1 in patients with non-small cell lung cancer (NSCLC)and their effects on prognosis. Methods: A total of 401patients, who were pathologically diagnosed as NSCLC in Changhai Hospital from January 2012 to August 2018, were enrolled as study subjects; and the patients were immunohistochemically tested for PD-L1 and Ki-67. The clinical and pathological data were collected, and the follow-up was performed regularly. The correlation between Ki-67 and PD-L1 and their effects on postoperative DFS and post-chemotherapy PFS were statistically analyzed. Results: Positive rates of PD-L1 and Ki-67 in NSCLC tissues were 37.9% (152/401) and 96.3% (386/401), respectively. Univariate analysis showed that Ki-67 was an influencing factor for PD-L1 expression (OR=0.33, 95%CI=0.28-0.39, P<0.0001); Curve Fitting analysis showed a positive correlation between Ki-67 and PD-L1; threshold effect analysis, segmentation multivariate logistic and ROC curve analysis showed 14% is a relatively suitable threshold for Ki-67 to be combined with PD-L1. Kaplan-Meier analysis showed that patients in Ki-67 high expression group had a significantly shorter post-operative DFS than those in Ki-67 low expression group ([21.88±11.25] vs [41.22±16.25]m, P<0.0001), patients in PD-L1 positive group had a significantly shorter DFS than those in PD-L1 negative group ([24.75±14.59] vs [38.27±16.75]m, P<0.0001)], and patients in Ki-67 high /PD-L1 positive group had the shortest DFS as compared to the other three groups ([20.57±11.33] vs [24.11±10.79], [36.00±16.79], [42.91±15.77]m, P<0.0001). As for post-chemotherapy PFS, patients in Ki-67 high ex-pression group was significantly longer than those in Ki-67 low expression group [(7.70±3.01) vs (5.80±2.99)m, P=0.016), but there was no significant difference between PD-L1 positive group and PD-L1 negative group [(7.04±3.21) vs (6.33±3.06)m, P=0.22); for combined evaluation with Ki-67 and PD-L1, the PFS of two Ki-67 high expression groups was significantly longer than the other two Ki-67 low expression groups [(7.74±3.25) vs (7.43±2.38) vs (4.91±1.97) vs (6.02±3.19)m, P=0.041). Conclusion: Ki-67 is positively correlated with PD-L1 in NSCLC patients, and Ki-67 14% is a suitable threshold for combined use with PD-L1. Both Ki-67 and PD-L1 are predictors of poor prognosis. The combination of the two has an "additive effect" on the prediction of poor prognosis, and patients with high Ki-67 expression are more sensitive to chemotherapy.
2019, 26(5):544-549.
DOI: 10.3872/j.issn.1007-385X.2019.05.010
Abstract:
[Abstract] Objective: To evaluate the expression of CKLF-like MARVEL transmembrane domain containing member 6 (CMTM6) in lung adenocarcinoma tissues, and to explore its correlation with the clinicopathologic features and prognosis of patients. Methods:Eighty-six pairs of cancer tissues and para-cancer tissues from patients that pathologically confirmed with lung adenocarcinoma were collected during September 2004 and June 2009 at the Third Affiliated Hospital of Soochow University. The expression levels of CMTM6 in above mentioned tissues were detected by immunohistochemistry. Serum of 52 patients with confirmed lung adenocarcinoma was collected before and after surgery, and serum of 32 healthy subjects was also collected. The levels of CMTM6 and PD-L1 in peripheral blood before and after surgery were measured and analyzed by ELISA. Chi-square test was used to analyze the relationship between CMTM6 expression and clinicopathological features; Kaplan-Meier method and Log-Rank test were used to analyze the survival data of patients. Results: CMTM6 was widely expressed in lung adenocarcinoma tissues; 30% of the tumor tissues showed an up-regulation as compared with para-cancer tissues, and 70% showed no difference. CMTM6 expression was associated with clinical stage and distant metastasis (all P<0.05), but not significantly associated with age, gender, tumor size, and T stage (P>0.05). Kaplan-Meier survival analysis showed the survival rate of patients with high CMTM6 expression was significantly lower than those with stable expression (P=0.014), and among patients at stage Ⅲ, the survival rate of patients with high CMTM6 expression was significantly lower than those with stable CMTM6 expression (P=0.001). Cox regression model analysis of multiple factors showed CMTM6 expression was an independent risk factor for the prognosis of patients with lung adenocarcinoma. CMTM6 expression in pre-surgery serum, post-surgery serum and healthy donors’serum showed statistically significant differences (P<0.05), which was significantly correlated with tumor size and age of the patients. Spearman correlation analysis showed a significant correlation between serum CMTM6 and PD-L1 expression level (r=0.623, P<0.01). Conclusion: CMTM6 is an independent risk factor for the prognosis of lung adenocarcinoma patients. It plays an important role in the occurrence and development of lung adenocarcinoma and it is a potential tumor suppressor gene.
[Abstract] Objective: To evaluate the expression of CKLF-like MARVEL transmembrane domain containing member 6 (CMTM6) in lung adenocarcinoma tissues, and to explore its correlation with the clinicopathologic features and prognosis of patients. Methods:Eighty-six pairs of cancer tissues and para-cancer tissues from patients that pathologically confirmed with lung adenocarcinoma were collected during September 2004 and June 2009 at the Third Affiliated Hospital of Soochow University. The expression levels of CMTM6 in above mentioned tissues were detected by immunohistochemistry. Serum of 52 patients with confirmed lung adenocarcinoma was collected before and after surgery, and serum of 32 healthy subjects was also collected. The levels of CMTM6 and PD-L1 in peripheral blood before and after surgery were measured and analyzed by ELISA. Chi-square test was used to analyze the relationship between CMTM6 expression and clinicopathological features; Kaplan-Meier method and Log-Rank test were used to analyze the survival data of patients. Results: CMTM6 was widely expressed in lung adenocarcinoma tissues; 30% of the tumor tissues showed an up-regulation as compared with para-cancer tissues, and 70% showed no difference. CMTM6 expression was associated with clinical stage and distant metastasis (all P<0.05), but not significantly associated with age, gender, tumor size, and T stage (P>0.05). Kaplan-Meier survival analysis showed the survival rate of patients with high CMTM6 expression was significantly lower than those with stable expression (P=0.014), and among patients at stage Ⅲ, the survival rate of patients with high CMTM6 expression was significantly lower than those with stable CMTM6 expression (P=0.001). Cox regression model analysis of multiple factors showed CMTM6 expression was an independent risk factor for the prognosis of patients with lung adenocarcinoma. CMTM6 expression in pre-surgery serum, post-surgery serum and healthy donors’serum showed statistically significant differences (P<0.05), which was significantly correlated with tumor size and age of the patients. Spearman correlation analysis showed a significant correlation between serum CMTM6 and PD-L1 expression level (r=0.623, P<0.01). Conclusion: CMTM6 is an independent risk factor for the prognosis of lung adenocarcinoma patients. It plays an important role in the occurrence and development of lung adenocarcinoma and it is a potential tumor suppressor gene.
2019, 26(5):550-556.
DOI: 10.3872/j.issn.1007-385X.2019.05.011
Abstract:
[Abstract] Objective: To explore the effect of miR-195/TLR4 axis on the proliferation, invasion and migration of liver cancer cells via regulating NF-κB pathway. Methods: Twenty-five pairs of liver cancer tissues and corresponding adjacent tissues surgically resected at the Second Affiliated Hospital of Kunming Medical University from March 2016 to January 2017 were collected for this study. Liver cancer HepG2 cells were cultured and then randomly divided into four groups: control group (NC), miR-195 mimic group (miR-195),TLR4 knockdown group (si-TLR4), and miR-195 inhibitor combined with TRL4 knockdown group (si-TLR4+miR-195 inhibitor). qRTPCR was used to detect the expression of miR-195 in liver cancer tissues and cell lines. CCK-8 assay was used to evaluate the cell viability of each group. Transwell and Wound healing assay were applied to detect the invasion and migration ability of HepG2 cells, respectively.Dual-luciferase reporter gene assay was used to verify the targeted regulation of TLR4 by miR-195. WB was applied to analyze the protein expressions of TLR4 and NF-κB p65. Results: miR-195 was down-regulated in the liver cancer tissues compared with adjacent tissues (P<0.01). Compared with human hepatic epithelial cells (THLE-3), the expression of miR-193 in liver cancer cell lines (HepG2 and Huh-7) was down-regulated (P<0.01), and the expression level in HepG2 cells was the lowest. The proliferation, invasion and migration of HepG2 cells was significantly suppressed after over-expression of miR-195 (all P<0.01). Moreover, over-expression of miR-195 significantly down-regulated TLR4 protein expression (P<0.05), and TLR4 was negatively correlated with miR-195 (R2=0.602, P<0.0001). Furthermore, miR-195 over-expression inhibited proliferation, invasion and migration of HepG2 cells by targeting TLR4 expression and blocking NF- κB pathway (P<0.05 or P<0.01). Conclusion: miR-195 over-expression can inhibit the proliferation,invasion and migration of HepG2 cells. The mechanism may be related with targeting TLR4 and blocking the NF-κB pathway to affect cell biological behaviors.
[Abstract] Objective: To explore the effect of miR-195/TLR4 axis on the proliferation, invasion and migration of liver cancer cells via regulating NF-κB pathway. Methods: Twenty-five pairs of liver cancer tissues and corresponding adjacent tissues surgically resected at the Second Affiliated Hospital of Kunming Medical University from March 2016 to January 2017 were collected for this study. Liver cancer HepG2 cells were cultured and then randomly divided into four groups: control group (NC), miR-195 mimic group (miR-195),TLR4 knockdown group (si-TLR4), and miR-195 inhibitor combined with TRL4 knockdown group (si-TLR4+miR-195 inhibitor). qRTPCR was used to detect the expression of miR-195 in liver cancer tissues and cell lines. CCK-8 assay was used to evaluate the cell viability of each group. Transwell and Wound healing assay were applied to detect the invasion and migration ability of HepG2 cells, respectively.Dual-luciferase reporter gene assay was used to verify the targeted regulation of TLR4 by miR-195. WB was applied to analyze the protein expressions of TLR4 and NF-κB p65. Results: miR-195 was down-regulated in the liver cancer tissues compared with adjacent tissues (P<0.01). Compared with human hepatic epithelial cells (THLE-3), the expression of miR-193 in liver cancer cell lines (HepG2 and Huh-7) was down-regulated (P<0.01), and the expression level in HepG2 cells was the lowest. The proliferation, invasion and migration of HepG2 cells was significantly suppressed after over-expression of miR-195 (all P<0.01). Moreover, over-expression of miR-195 significantly down-regulated TLR4 protein expression (P<0.05), and TLR4 was negatively correlated with miR-195 (R2=0.602, P<0.0001). Furthermore, miR-195 over-expression inhibited proliferation, invasion and migration of HepG2 cells by targeting TLR4 expression and blocking NF- κB pathway (P<0.05 or P<0.01). Conclusion: miR-195 over-expression can inhibit the proliferation,invasion and migration of HepG2 cells. The mechanism may be related with targeting TLR4 and blocking the NF-κB pathway to affect cell biological behaviors.
TAN Linyan
,
LIU Min△
,
GE Fei
,
CHEN Wenlin
,
HUANG Saijun
,
LI Yunqian
,
YE Younan
,
WANG Xi
,
ZHANG Yong
2019, 26(5):557-562.
DOI: 10.3872/j.issn.1007-385X.2019.05.012
Abstract:
[Abstract] Objective:To investigate the role of cyclo-oxygenase-2 (COX-2) in breast cancer metastasis and its possible mechanism. Methods: A total of 45 cases of primary breast cancer tissues and brain metastatic breast cancer tissues were collected from patients,who underwent mastectomy in Yunnan Cancer Hospital from October 2015 to April 2018, including 30 cases of primary lesions and 15 cases of brain metastasis. qPCR was used to detect the expression of COX-2 in breast cancer tissues and brain metastatic breast cancer tissues. Recombinant viruses with COX-2 over-expression (LV6-COX2) or COX-2 knockdown (LV3-COX2 shRNA1, LV3-COX2 shRNA2) were transfected into human breast cancer MDA-MB-231 cells; After obtaining the stable expression cell lines, the effect of COX-2 expression on the proliferation of MDA-MB-231 cells was detected by CCK-8, and the effects of COX-2 expression on the migration and invasion of MDA-MB-231 cells were detected by scratch test and Transwell assay, respectively. The mRNA and protein expressions of COX-2 in each group were examined by qPCR and WB, respectively. The effect of COX-2 expression on the expression of EMT-related genes in MDA-MB-231 cells was analyzed by qPCR. Results: The expression of COX-2 in tissues of patients with brain metastases was significantly higher than that in patients with primary breast cancer tissues (P<0.01), and it was correlated with tumor TMN stage in breast cancer patients. MDA-MB-231 cell lines with stable COX-2 over-expression/knockout were successfully construct-ed. Over-expression of COX-2 promoted the migration and invasion of MDA-MB-231 cells (all P<0.01), and significantly increased the expressions of MMP2, MMP1, N-cadherin and vimentin (all P<0.01), but exerted insignificant effect on cell proliferation. The effect of COX-2 silence exerted the opposite effect and promoted cell proliferation (P<0.05). Conclusion: COX-2 is highly expressed in brain metastatic breast cancer tissues, which may promote the migration and invasion of breast cancer MDA-MB-231 cells by regulating EMT processes.
[Abstract] Objective:To investigate the role of cyclo-oxygenase-2 (COX-2) in breast cancer metastasis and its possible mechanism. Methods: A total of 45 cases of primary breast cancer tissues and brain metastatic breast cancer tissues were collected from patients,who underwent mastectomy in Yunnan Cancer Hospital from October 2015 to April 2018, including 30 cases of primary lesions and 15 cases of brain metastasis. qPCR was used to detect the expression of COX-2 in breast cancer tissues and brain metastatic breast cancer tissues. Recombinant viruses with COX-2 over-expression (LV6-COX2) or COX-2 knockdown (LV3-COX2 shRNA1, LV3-COX2 shRNA2) were transfected into human breast cancer MDA-MB-231 cells; After obtaining the stable expression cell lines, the effect of COX-2 expression on the proliferation of MDA-MB-231 cells was detected by CCK-8, and the effects of COX-2 expression on the migration and invasion of MDA-MB-231 cells were detected by scratch test and Transwell assay, respectively. The mRNA and protein expressions of COX-2 in each group were examined by qPCR and WB, respectively. The effect of COX-2 expression on the expression of EMT-related genes in MDA-MB-231 cells was analyzed by qPCR. Results: The expression of COX-2 in tissues of patients with brain metastases was significantly higher than that in patients with primary breast cancer tissues (P<0.01), and it was correlated with tumor TMN stage in breast cancer patients. MDA-MB-231 cell lines with stable COX-2 over-expression/knockout were successfully construct-ed. Over-expression of COX-2 promoted the migration and invasion of MDA-MB-231 cells (all P<0.01), and significantly increased the expressions of MMP2, MMP1, N-cadherin and vimentin (all P<0.01), but exerted insignificant effect on cell proliferation. The effect of COX-2 silence exerted the opposite effect and promoted cell proliferation (P<0.05). Conclusion: COX-2 is highly expressed in brain metastatic breast cancer tissues, which may promote the migration and invasion of breast cancer MDA-MB-231 cells by regulating EMT processes.
2019, 26(5):563-568.
DOI: 10.3872/j.issn.1007-385X.2019.05.013
Abstract:
[Abstract] Objective: To explore the effect of miR-141-3p on the proliferation, invasion and apoptosis of ovarian cancer cells via targeting PTEN and regulating PI3K/Akt pathway. Methods: Collecting twenty-eight cases pairs of ovarian cancerovarian cancer patients with tumor tissues and adjacent tissues were collected from patients, who from April 2014 to October 2017 were treated in the Department of Obstetrics and Gynecology. qPCR was applied to detect the expression of miR-141-3p in ovarian cancer tissues and cell lines.The relationship between miR-141-3p and PTEN was verified by dual-luciferase reporter gene assay. After over-expression or knockdown of miR-141 and PTEN genes, the cell viability, invasion and apoptosis of ovarian cancer A2780 cells were examined by CCK-8 assay, Transwell assay and Annexin V-FITC/PI double staining flow cytometry assay, respectively. Furthermore, the effect of miR-141-3p on PTEN-PI3K/Akt signaling pathway was measured by WB. Results: miR-141-3p is was highly expressed in ovarian cancer tissues and cell lines (P<0.05 or P<0.01). The dual luciferase reporter gene assay confirmed that miR-141-3p targets PTEN was a target of miR-141-3p and downregulates its expression level was down-regulated (P<0.01). Compared with the control group, after knockdown of miR-141-3p, the proliferation of A2780 cells was significantly inhibited after knockdown of miR-141-3p (at 48 h, 0.36±0.04 vs 0.82±0.06, P<0.05), and the invasive ability of A2780 cells was significantly reduced (number of transmembrane cells: 215.32±16.04 vs 45.14±7.88, P<0.01), while the apoptotic rate was significantly increased ([1.85±0.26]% vs [9.29±0.65]%, P<0.01). Over-expression of PTEN significantly inhibited the expression of p-Akt and cell proliferation and invasion in A2780 cells (all P<0.01), inhibited cell pro-liferation and invasion (all P<0.01) and significantly promoted apoptosis (all P<0.01). However, simultaneous over-expression of miR-141-3p or addition of IGF-1 wile over-expressing PTEN can offset the above effects. Conclusion: miR-141-3p facilitates the proliferation,invasion and decreases apoptosis of A2780 cells. The mechanism may be related to targeted regulation of PTEN and activation of PI3K/Akt pathway.
[Abstract] Objective: To explore the effect of miR-141-3p on the proliferation, invasion and apoptosis of ovarian cancer cells via targeting PTEN and regulating PI3K/Akt pathway. Methods: Collecting twenty-eight cases pairs of ovarian cancerovarian cancer patients with tumor tissues and adjacent tissues were collected from patients, who from April 2014 to October 2017 were treated in the Department of Obstetrics and Gynecology. qPCR was applied to detect the expression of miR-141-3p in ovarian cancer tissues and cell lines.The relationship between miR-141-3p and PTEN was verified by dual-luciferase reporter gene assay. After over-expression or knockdown of miR-141 and PTEN genes, the cell viability, invasion and apoptosis of ovarian cancer A2780 cells were examined by CCK-8 assay, Transwell assay and Annexin V-FITC/PI double staining flow cytometry assay, respectively. Furthermore, the effect of miR-141-3p on PTEN-PI3K/Akt signaling pathway was measured by WB. Results: miR-141-3p is was highly expressed in ovarian cancer tissues and cell lines (P<0.05 or P<0.01). The dual luciferase reporter gene assay confirmed that miR-141-3p targets PTEN was a target of miR-141-3p and downregulates its expression level was down-regulated (P<0.01). Compared with the control group, after knockdown of miR-141-3p, the proliferation of A2780 cells was significantly inhibited after knockdown of miR-141-3p (at 48 h, 0.36±0.04 vs 0.82±0.06, P<0.05), and the invasive ability of A2780 cells was significantly reduced (number of transmembrane cells: 215.32±16.04 vs 45.14±7.88, P<0.01), while the apoptotic rate was significantly increased ([1.85±0.26]% vs [9.29±0.65]%, P<0.01). Over-expression of PTEN significantly inhibited the expression of p-Akt and cell proliferation and invasion in A2780 cells (all P<0.01), inhibited cell pro-liferation and invasion (all P<0.01) and significantly promoted apoptosis (all P<0.01). However, simultaneous over-expression of miR-141-3p or addition of IGF-1 wile over-expressing PTEN can offset the above effects. Conclusion: miR-141-3p facilitates the proliferation,invasion and decreases apoptosis of A2780 cells. The mechanism may be related to targeted regulation of PTEN and activation of PI3K/Akt pathway.
2019, 26(5):569-576.
DOI: 10.3872/j.issn.1007-385X.2019.05.014
Abstract:
[Abstract] Objection: To analyze the factors affecting the prognosis of patients with gastric neuroendocrine neoplasms (G-NENs) by using the surveillance of National Cancer Institute (NCI) of America, Epidemiology and End Results (SEER) database, and to construct a prognostic Nomogram model for individualized prediction of prognosis in patients with G-NENs. Methods: The clinical data of 2720 G-NENs patients with complete follow-up data from 2010 to 2015 in the SEER database were collected. The prognostic Nomogram model was constructed based on independent risk factors determined by survival analysis. The consistency index (C-index) and calibration curve were used to evaluate its accuracy. Area under the curve (AUC) was used to compare the evaluation value between the Nomogram and the 7th edition of AJCC TNM staging. Results: The 1-, 3-, and 5-year survival rates of 2,720 patients with G-NENs were 88.14%, 79.09%, and 71.86%, respectively. Multivariate COX regression analysis showed that gender, age, marital status, other associated tumors, histological type, tumor grade, T stage, M stage, and surgery were independent risk factors affecting survival time of GNENs patients. The C-index of newly constructed Nomogram prediction model was 0.816, which was significantly higher than 0.702 of the 7th AJCC TNM staging (P<0.001), and the 1-, 3- and 5-year calibration curves showed a good agreement between predicted survival and actual survival. The AUC for 1-, 3- and 5-year survival by Nomogram prognostic model was 0.800, 0.811, and 0.820,which was higher than 0.650, 0.688 and 0.698 of the 7th AJCC TNM staging, and the differences were statistically significant (Z=6.600, 8.085, 9.632, all P<0.0001). Conclusion: The Nomogram prediction model drawn in this study has a high prognostic value and can individually predict the survival rate of G-NENs patients, which is helpful for clinical treatment decision-making and clinical research options.
[Abstract] Objection: To analyze the factors affecting the prognosis of patients with gastric neuroendocrine neoplasms (G-NENs) by using the surveillance of National Cancer Institute (NCI) of America, Epidemiology and End Results (SEER) database, and to construct a prognostic Nomogram model for individualized prediction of prognosis in patients with G-NENs. Methods: The clinical data of 2720 G-NENs patients with complete follow-up data from 2010 to 2015 in the SEER database were collected. The prognostic Nomogram model was constructed based on independent risk factors determined by survival analysis. The consistency index (C-index) and calibration curve were used to evaluate its accuracy. Area under the curve (AUC) was used to compare the evaluation value between the Nomogram and the 7th edition of AJCC TNM staging. Results: The 1-, 3-, and 5-year survival rates of 2,720 patients with G-NENs were 88.14%, 79.09%, and 71.86%, respectively. Multivariate COX regression analysis showed that gender, age, marital status, other associated tumors, histological type, tumor grade, T stage, M stage, and surgery were independent risk factors affecting survival time of GNENs patients. The C-index of newly constructed Nomogram prediction model was 0.816, which was significantly higher than 0.702 of the 7th AJCC TNM staging (P<0.001), and the 1-, 3- and 5-year calibration curves showed a good agreement between predicted survival and actual survival. The AUC for 1-, 3- and 5-year survival by Nomogram prognostic model was 0.800, 0.811, and 0.820,which was higher than 0.650, 0.688 and 0.698 of the 7th AJCC TNM staging, and the differences were statistically significant (Z=6.600, 8.085, 9.632, all P<0.0001). Conclusion: The Nomogram prediction model drawn in this study has a high prognostic value and can individually predict the survival rate of G-NENs patients, which is helpful for clinical treatment decision-making and clinical research options.
2019, 26(5):577-582.
DOI: 10.3872/j.issn.1007-385X.2019.05.015
Abstract:
[摘要] 程序性细胞死亡是多细胞生物死亡的重要生物学过程，其调控方式复杂，对维持细胞内环境稳定十分重要。在过去的几年中，除了凋亡之外，对程序性细胞死亡的非凋亡形式的研究也取得了进展。p53 作为经典的肿瘤抑制因子，除了控制细胞增殖和凋亡外，也参与非典型细胞死亡调控。p53 通过对其下游靶点的转录调控以及与关键蛋白的直接作用，直接或间接调节细胞的非典型死亡。本文对p53 在凋亡、铁中毒、细胞程序性坏死、自噬性细胞死亡、有丝分裂灾难、副凋亡等几种非典型细胞死亡模式中的作用作一综述，为肿瘤抑制机制的阐明及癌症药物研制提供相应参考。
[摘要] 程序性细胞死亡是多细胞生物死亡的重要生物学过程，其调控方式复杂，对维持细胞内环境稳定十分重要。在过去的几年中，除了凋亡之外，对程序性细胞死亡的非凋亡形式的研究也取得了进展。p53 作为经典的肿瘤抑制因子，除了控制细胞增殖和凋亡外，也参与非典型细胞死亡调控。p53 通过对其下游靶点的转录调控以及与关键蛋白的直接作用，直接或间接调节细胞的非典型死亡。本文对p53 在凋亡、铁中毒、细胞程序性坏死、自噬性细胞死亡、有丝分裂灾难、副凋亡等几种非典型细胞死亡模式中的作用作一综述，为肿瘤抑制机制的阐明及癌症药物研制提供相应参考。
2019, 26(5):583-590.
DOI: 10.3872/j.issn.1007-385X.2019.05.016
Abstract:
[摘要] 以PD-1/PD-L1 抑制剂为代表的免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）疗法改变了以往手术、放疗或化疗的常规癌症治疗方法，甚至已成为部分癌症的一线治疗方式。然而，PD-1/PD-L1 抑制剂并不能使大部分肿瘤患者获益，甚至部分患者接受治疗后出现了肿瘤暴发性进展现象。在PD-1/PD-L1 抑制剂治疗前，对相关疗效标志物进行检测，可以筛选出可能获益的人群，从而有效避免延误治疗无效患者的病情及不必要的经济损失。为进一步指导临床，本文就PD-1/PD-L1 抑制剂的疗效标志物作一系统综述。
[摘要] 以PD-1/PD-L1 抑制剂为代表的免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）疗法改变了以往手术、放疗或化疗的常规癌症治疗方法，甚至已成为部分癌症的一线治疗方式。然而，PD-1/PD-L1 抑制剂并不能使大部分肿瘤患者获益，甚至部分患者接受治疗后出现了肿瘤暴发性进展现象。在PD-1/PD-L1 抑制剂治疗前，对相关疗效标志物进行检测，可以筛选出可能获益的人群，从而有效避免延误治疗无效患者的病情及不必要的经济损失。为进一步指导临床，本文就PD-1/PD-L1 抑制剂的疗效标志物作一系统综述。
2019, 26(5):591-596.
DOI: 10.3872/j.issn.1007-385X.2019.05.017
Abstract:
[摘要] Lynch 综合征（Lynch syndrome，LS）是一种常染色体显性遗传病，是由于几种DNA 错配修复（mismatch repair，MMR）基因（MLH1、MSH2、MSH6、PMS2）中的一种出现种系突变，或由于EPCAM基因缺失导致MSH2 表达丢失引起。LS是遗传性结直肠癌（colorectal cancer，CRC）最常见的原因，其特征为患CRC和子宫内膜癌（endometrial cancer，EC）的风险显著增加，且存在发生其他几种恶性肿瘤的风险。对于LS 的诊断，目前几种临床病理学标准（如阿姆斯特丹标准等）已被用于识别存在Lynch 综合征风险的个体。然而，这些标准的敏感性及特异性有限，仍有赖于临床医生对LS的警惕并关注其家族史。伴有MMR基因变异的LS相关肿瘤通常具有微卫星高度不稳定的特征，由于移码突变新抗原的存在，可以激发强大而持久的免疫反应和肿瘤浸润淋巴细胞浸润，所以对于LS患者，免疫检查点抑制剂将会是一种很有前景的治疗方法。由于LS是一种基因遗传病，与DNA错配修复缺陷具有独特关系，对其的充分理解对相关肿瘤的诊断、预防和治疗具有重要的临床意义。
[摘要] Lynch 综合征（Lynch syndrome，LS）是一种常染色体显性遗传病，是由于几种DNA 错配修复（mismatch repair，MMR）基因（MLH1、MSH2、MSH6、PMS2）中的一种出现种系突变，或由于EPCAM基因缺失导致MSH2 表达丢失引起。LS是遗传性结直肠癌（colorectal cancer，CRC）最常见的原因，其特征为患CRC和子宫内膜癌（endometrial cancer，EC）的风险显著增加，且存在发生其他几种恶性肿瘤的风险。对于LS 的诊断，目前几种临床病理学标准（如阿姆斯特丹标准等）已被用于识别存在Lynch 综合征风险的个体。然而，这些标准的敏感性及特异性有限，仍有赖于临床医生对LS的警惕并关注其家族史。伴有MMR基因变异的LS相关肿瘤通常具有微卫星高度不稳定的特征，由于移码突变新抗原的存在，可以激发强大而持久的免疫反应和肿瘤浸润淋巴细胞浸润，所以对于LS患者，免疫检查点抑制剂将会是一种很有前景的治疗方法。由于LS是一种基因遗传病，与DNA错配修复缺陷具有独特关系，对其的充分理解对相关肿瘤的诊断、预防和治疗具有重要的临床意义。
2019, 26(5):597-601.
DOI: 10.3872/j.issn.1007-385X.2019.05.018
Abstract:
[摘要] 积雪草酸是一种天然存在的乌苏烷型五环三萜酸。近年研究表明积雪草酸能够通过多种机制途径对肿瘤细胞进行抑制，包括抑制肿瘤细胞增殖与诱导凋亡、阻滞肿瘤细胞周期、抑制肿瘤血管细胞生成、抑制肿瘤细胞侵袭迁移、辅助化疗增强其疗效。积雪草酸可以多靶向地抑制肿瘤细胞，但其作用靶点仍未明确；对于积雪草酸的临床前研究以及毒性研究尚少，积雪草酸的抗肿瘤作用仍有很大的研究空间。
[摘要] 积雪草酸是一种天然存在的乌苏烷型五环三萜酸。近年研究表明积雪草酸能够通过多种机制途径对肿瘤细胞进行抑制，包括抑制肿瘤细胞增殖与诱导凋亡、阻滞肿瘤细胞周期、抑制肿瘤血管细胞生成、抑制肿瘤细胞侵袭迁移、辅助化疗增强其疗效。积雪草酸可以多靶向地抑制肿瘤细胞，但其作用靶点仍未明确；对于积雪草酸的临床前研究以及毒性研究尚少，积雪草酸的抗肿瘤作用仍有很大的研究空间。
2019, 26(5):602-608.
DOI: 10.3872/j.issn.1007-385X.2019.05.019
Abstract:
[摘要] 近年来，免疫治疗在肿瘤治疗中取得了突破性的进展，为晚期肿瘤患者带来生存获益。在免疫治疗的应用中，部分患者可以获得显著的疗效，仍有部分患者在疾病缓解的一段时间后出现疾病进展，提示存在免疫耐药。本文主要从原发性耐药及获得性耐药两方面对肿瘤免疫治疗的耐药机制进行综述，同时分析了目前应用较为广泛的两种免疫治疗方法：免疫检查点抑制剂及CAR-T 细胞治疗，为克服耐药取得更好疗效提供参考。
[摘要] 近年来，免疫治疗在肿瘤治疗中取得了突破性的进展，为晚期肿瘤患者带来生存获益。在免疫治疗的应用中，部分患者可以获得显著的疗效，仍有部分患者在疾病缓解的一段时间后出现疾病进展，提示存在免疫耐药。本文主要从原发性耐药及获得性耐药两方面对肿瘤免疫治疗的耐药机制进行综述，同时分析了目前应用较为广泛的两种免疫治疗方法：免疫检查点抑制剂及CAR-T 细胞治疗，为克服耐药取得更好疗效提供参考。
2019, 26(5):609-611.
DOI: 10.3872/j.issn.1007-385X.2019.05.020
Abstract:
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
- 国内定价： ￥20元/册
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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.