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Volume 28,Issue 2,2021 Table of Contents
2021, 28(2):103-108.
DOI: 10.3872/j.issn.1007-385x.2021.02.001
Abstract:
In recent years, tumor immunotherapy has developed rapidly, among which T-cell-based adoptive cell therapy has achieved certain clinical effect and become one of the most potential immunotherapeutics. T cell infiltration mainly includes rolling, adhesion, extravasation and chemotaxis etc. However, there are physical barriers, chemokine mismatch, vascular abnormalities, immunosuppressive microenvironment and other factors that limit the efficacy of adoptive cell therapy. The homing ability of T cells can be further improved by optimizing the chemokine receptor on the cell surface, inserting targeted peptide, improving the way of administration, and adopting combined treatment of radiotherapy, immune checkpoint blocker, tumor vaccine and bispecific antibody, etc. This review mainly summarizes the process of T cell infiltration, the influencing factors of T cell targeting tumor site and the relevant treatment strategies, as well as gives a prospection for future research.
In recent years, tumor immunotherapy has developed rapidly, among which T-cell-based adoptive cell therapy has achieved certain clinical effect and become one of the most potential immunotherapeutics. T cell infiltration mainly includes rolling, adhesion, extravasation and chemotaxis etc. However, there are physical barriers, chemokine mismatch, vascular abnormalities, immunosuppressive microenvironment and other factors that limit the efficacy of adoptive cell therapy. The homing ability of T cells can be further improved by optimizing the chemokine receptor on the cell surface, inserting targeted peptide, improving the way of administration, and adopting combined treatment of radiotherapy, immune checkpoint blocker, tumor vaccine and bispecific antibody, etc. This review mainly summarizes the process of T cell infiltration, the influencing factors of T cell targeting tumor site and the relevant treatment strategies, as well as gives a prospection for future research.
2021, 28(2):109-114.
DOI: 10.3872/j.issn.1007-385x.2021.02.002
Abstract:
Objective: To study the role of c-Jun N-terminal kinase (JNK) in vitamin E succinate (VES) activating endoplasmic reticulum stress-induced autophagy in human gastric SGC-7901 cells.Methods: SGC-7901 cells were treated with different doses of VES (5, 10, 15, 20 μg/ml) for 24 h, then, qPCR and WB were used to detect the mRNA and protein expressions of autophagy markers LC3 and Beclin-1; Under the action of reticulum stress inhibitor 4-PBA, the fluorescence intensity and distribution of LC3 were observed under laser confocal microscope, and then qPCR was used to detect the mRNA expression of endoplasmic reticulum stress markers GRP78, GRP94 and autophagy markers LC3, Beclin-1. Under the action of the JNK inhibitor SP600125, WB was used to detect the protein expression changes of p-JNK and autophagy marker proteins LC3 and Beclin-1.Results: Compared with the control group, with the increase of the concentration of VES, the mRNA and protein expressions of Beclin-1 and LC3 showed a gradual increase (all P < 0.05), and LC3-Ⅱ/LC3-Ⅰ ratio also increased significantly (P < 0.01); compared with 20 μg/ml VES group, after pretreatment with endoplasmic reticulum stress inhibitor 4-PBA, mRNA expressions of GRP78, GRP94, LC3 and Beclin-1 decreased (all P < 0.01), and the intensity of LC3 punctate aggregation decreased; after pretreatment with JNK inhibitor SP600125, the protein expression levels of p-JNK, LC3 and Beclin-1 were lower than those of 20 μg/ml VES group (all P < 0.01), these results indicated that inhibition of JNK activity could inhibit the occurrence of autophagy.Conclusion: VES can induce autophagy in SGC-7901cells by activating endoplasmic reticulum stress, and JNK participates in the regulation process of endoplasmic reticulum stress on autophagy.
Objective: To study the role of c-Jun N-terminal kinase (JNK) in vitamin E succinate (VES) activating endoplasmic reticulum stress-induced autophagy in human gastric SGC-7901 cells.Methods: SGC-7901 cells were treated with different doses of VES (5, 10, 15, 20 μg/ml) for 24 h, then, qPCR and WB were used to detect the mRNA and protein expressions of autophagy markers LC3 and Beclin-1; Under the action of reticulum stress inhibitor 4-PBA, the fluorescence intensity and distribution of LC3 were observed under laser confocal microscope, and then qPCR was used to detect the mRNA expression of endoplasmic reticulum stress markers GRP78, GRP94 and autophagy markers LC3, Beclin-1. Under the action of the JNK inhibitor SP600125, WB was used to detect the protein expression changes of p-JNK and autophagy marker proteins LC3 and Beclin-1.Results: Compared with the control group, with the increase of the concentration of VES, the mRNA and protein expressions of Beclin-1 and LC3 showed a gradual increase (all P < 0.05), and LC3-Ⅱ/LC3-Ⅰ ratio also increased significantly (P < 0.01); compared with 20 μg/ml VES group, after pretreatment with endoplasmic reticulum stress inhibitor 4-PBA, mRNA expressions of GRP78, GRP94, LC3 and Beclin-1 decreased (all P < 0.01), and the intensity of LC3 punctate aggregation decreased; after pretreatment with JNK inhibitor SP600125, the protein expression levels of p-JNK, LC3 and Beclin-1 were lower than those of 20 μg/ml VES group (all P < 0.01), these results indicated that inhibition of JNK activity could inhibit the occurrence of autophagy.Conclusion: VES can induce autophagy in SGC-7901cells by activating endoplasmic reticulum stress, and JNK participates in the regulation process of endoplasmic reticulum stress on autophagy.
QI Chunsheng
,
ZHANG Qinghuai
,
QI Lin
,
ZHANG Ping
,
CUI Jifang
,
ZHANG Weihua
,
SU Yanjun
,
ZHANG Chunze
2021, 28(2):115-120.
DOI: 10.3872/j.issn.1007-385x.2021.02.003
Abstract:
Objective: To study the effect of micheliolide (MCL) on the sensitivity of colorectal cancer cells to oxaliplatin (OxP) and its possible mechanism.Methods: HCT116 and LoVo cells were treated with 2 μmol/L MCL and 100 μmol/L OxP alone or in combination. The cell viability and colony forming ability in vitro were detected by CCK-8 and plate cloning formation assay, respectively. After being transfected with GFP-LC3 lentivirus, HCT116 cells were respectively treated with 2 μmol/L and 5 μmol/L MCL for 24 h. The aggregation of autophagy bodies in HCT116 cells induced by MCL was observed under fluorescence microscope. The effects of MCL on the expressions of LC3B-Ⅰ, LC3B-Ⅱ, p62 and STAT3 were detected by WB assay; the molecular docking model of MCL and STAT3 was constructed by Autodock version.Results: After the treatment of 2 μmol/L MCL combined with 100 μmol/L OxP, the activity of HCT116 and LoVo cells as well as the colony forming ability of HCT116 cells significantly decreased (all P < 0.01). After HCT116 cells were treated with 2 and 5 μmol/L MCL, the autophagy rate of cells in the treatment groups was significantly higher than that of the control group (all P < 0.01), the LC3B Ⅱ/Ⅰ ratio was 3.25 and 5.78 times that of the control group, the expression level of p62 was 25.5% and 9.8% of the control group, and the phosphorylation level of STAT3 was 2.18 and 3.87 times that of the control group. Molecular docking results showed that MCL might directly bind to STAT3 protein in vivo.Conclusion: MCL may enhance the sensitivity of colorectal cancer cells to OxP by promoting autophagy through STAT3 pathway.
Objective: To study the effect of micheliolide (MCL) on the sensitivity of colorectal cancer cells to oxaliplatin (OxP) and its possible mechanism.Methods: HCT116 and LoVo cells were treated with 2 μmol/L MCL and 100 μmol/L OxP alone or in combination. The cell viability and colony forming ability in vitro were detected by CCK-8 and plate cloning formation assay, respectively. After being transfected with GFP-LC3 lentivirus, HCT116 cells were respectively treated with 2 μmol/L and 5 μmol/L MCL for 24 h. The aggregation of autophagy bodies in HCT116 cells induced by MCL was observed under fluorescence microscope. The effects of MCL on the expressions of LC3B-Ⅰ, LC3B-Ⅱ, p62 and STAT3 were detected by WB assay; the molecular docking model of MCL and STAT3 was constructed by Autodock version.Results: After the treatment of 2 μmol/L MCL combined with 100 μmol/L OxP, the activity of HCT116 and LoVo cells as well as the colony forming ability of HCT116 cells significantly decreased (all P < 0.01). After HCT116 cells were treated with 2 and 5 μmol/L MCL, the autophagy rate of cells in the treatment groups was significantly higher than that of the control group (all P < 0.01), the LC3B Ⅱ/Ⅰ ratio was 3.25 and 5.78 times that of the control group, the expression level of p62 was 25.5% and 9.8% of the control group, and the phosphorylation level of STAT3 was 2.18 and 3.87 times that of the control group. Molecular docking results showed that MCL might directly bind to STAT3 protein in vivo.Conclusion: MCL may enhance the sensitivity of colorectal cancer cells to OxP by promoting autophagy through STAT3 pathway.
2021, 28(2):121-127.
DOI: 10.3872/j.issn.1007-385x.2021.02.004
Abstract:
Objective: To investigate the effects of over-expressing VASH1 on the malignant biological behaviors of human colorectal cancer cells.Methods: Lentivirus was packaged and transfected into human colorectal cancer cells SW680 and SW620 to construct an over-expressed VASH1 cell line, the untransfected cells were used as control. qPCR experiment and WB experiment were used to detect the over-expression effect of VASH1. The effects of VASH1 over-expressed on microangiogenesis, proliferation, colony formation and migration of colorectal cancer cells were detected respectively by tubule formation, CCK-8 assay, soft agar assay, Transwell assay and Wound healing assay in vitro. In addition, tumor growth and lung metastasis were detected in NOD-SCID mice subcutaneously injected with VASH1-overexpressing SW620 cells.Results: Successfully constructed SW480 and SW620 cells over-expressing VASH1. Compared with the control group, the abilities of microangiogenesis, proliferation, colony forming and migration were significantly reduced in colorectal cancer cells over-expressing VASH1 (P<0.05) in vitro. The abilities of subcutaneous tumor growth and lung metastasis of colorectal cancer cells over-expressing VASH1 were also significantly reduced (P<0.05) in vivo.Conclusion: Over-expression of VASH1 can suppress the malignant biological behaviors of human colorectal cancer cells.
Objective: To investigate the effects of over-expressing VASH1 on the malignant biological behaviors of human colorectal cancer cells.Methods: Lentivirus was packaged and transfected into human colorectal cancer cells SW680 and SW620 to construct an over-expressed VASH1 cell line, the untransfected cells were used as control. qPCR experiment and WB experiment were used to detect the over-expression effect of VASH1. The effects of VASH1 over-expressed on microangiogenesis, proliferation, colony formation and migration of colorectal cancer cells were detected respectively by tubule formation, CCK-8 assay, soft agar assay, Transwell assay and Wound healing assay in vitro. In addition, tumor growth and lung metastasis were detected in NOD-SCID mice subcutaneously injected with VASH1-overexpressing SW620 cells.Results: Successfully constructed SW480 and SW620 cells over-expressing VASH1. Compared with the control group, the abilities of microangiogenesis, proliferation, colony forming and migration were significantly reduced in colorectal cancer cells over-expressing VASH1 (P<0.05) in vitro. The abilities of subcutaneous tumor growth and lung metastasis of colorectal cancer cells over-expressing VASH1 were also significantly reduced (P<0.05) in vivo.Conclusion: Over-expression of VASH1 can suppress the malignant biological behaviors of human colorectal cancer cells.
2021, 28(2):128-134.
DOI: 10.3872/j.issn.1007-385x.2021.02.005
Abstract:
Objective: To explore whether PDGF-BB can be transmitted through exosome and verify its angiogenic function in human osteosarcoma.Methods: Exosomes from a variety of human osteosarcoma cells were isolated. The expression of PDGF-BB in cells and exosomes was detected by WB. Exosomes derived from osteosarcoma SJSA-1 cells were co-incubated with HUVEC, and the pattern of exosomal PDGF-BB entering HUVEC was observed using Immunofluorescence and confocal scanning microscope. SJSA-1 cell lines with PDGF-BB over-expression or knockdown were constructed by lentiviral infection, and the exosomes derived from transfected SJSA-1 cells were isolated and incubated with HUVEC. Microtubule formation experiment was conducted to detect their effects on angiogenesis; SJSA-1 cell transplanted xenograft model was established in nude mice, and the exosomes derived from SJSA-1 cells with PDGF-BB over-expression or knockdown were infused into nude mice to observe their effects on tumor growth.Results: The exosomes derived from osteosarcoma cells were successfully isolated, in which a large amount of PDGF-BB was confirmed. The exosomes entered HUVEC by endocytosis. The SJSA-1 cell lines with PDGF-BB over-expression or knockdown were successfully constructed, and the corresponding exosomes were isolated. Compared with the control group, exosomes with high PDGF-BB content significantly promoted HUVEC angiogenesis (P < 0.01 , t=13.51) and tumor growth (P < 0.01 ), while exosomes with low PDGF-BB content reduced the angiogenesis ability of HUVEC (P < 0.01 , t=8.226) and inhibited tumor growth (P < 0.01 ).Conclusion: The exosomal PDGF-BB secreted by osteosarcoma cells can be directly absorbed by HUVEC and induce tumor angiogenesis, further promoting the growth of osteosarcoma.
Objective: To explore whether PDGF-BB can be transmitted through exosome and verify its angiogenic function in human osteosarcoma.Methods: Exosomes from a variety of human osteosarcoma cells were isolated. The expression of PDGF-BB in cells and exosomes was detected by WB. Exosomes derived from osteosarcoma SJSA-1 cells were co-incubated with HUVEC, and the pattern of exosomal PDGF-BB entering HUVEC was observed using Immunofluorescence and confocal scanning microscope. SJSA-1 cell lines with PDGF-BB over-expression or knockdown were constructed by lentiviral infection, and the exosomes derived from transfected SJSA-1 cells were isolated and incubated with HUVEC. Microtubule formation experiment was conducted to detect their effects on angiogenesis; SJSA-1 cell transplanted xenograft model was established in nude mice, and the exosomes derived from SJSA-1 cells with PDGF-BB over-expression or knockdown were infused into nude mice to observe their effects on tumor growth.Results: The exosomes derived from osteosarcoma cells were successfully isolated, in which a large amount of PDGF-BB was confirmed. The exosomes entered HUVEC by endocytosis. The SJSA-1 cell lines with PDGF-BB over-expression or knockdown were successfully constructed, and the corresponding exosomes were isolated. Compared with the control group, exosomes with high PDGF-BB content significantly promoted HUVEC angiogenesis (P < 0.01 , t=13.51) and tumor growth (P < 0.01 ), while exosomes with low PDGF-BB content reduced the angiogenesis ability of HUVEC (P < 0.01 , t=8.226) and inhibited tumor growth (P < 0.01 ).Conclusion: The exosomal PDGF-BB secreted by osteosarcoma cells can be directly absorbed by HUVEC and induce tumor angiogenesis, further promoting the growth of osteosarcoma.
2021, 28(2):135-142.
DOI: 10.3872/j.issn.1007-385x.2021.02.006
Abstract:
Objective: To analyze the expression level of miR-224 in cancer tissues and plasma of hepatocellular carcinoma (HCC) patients, and its correlation with clinicopathological characteristics, diagnosis and prognosis of HCC patients, and to further analyze its mechanism of action in the occurrence and development of liver cancer through bioinformatics analysis and in vitro experiments.Methods: The expression level of miR-224 in HCC tissues and normal tissues was analyzed using large sample data from Gene Expression Omnibus (GEO). qPCR method was used to verify the expression level of miR-224 in the tumor tissues and corresponding adjacent tissues that surgically resected from 80 HCC patients in Hebei Provincial People’s Hospital from January 2017 to January 2020; in addition, the miR-224 level was also examined in plasma samples from 30 HCC patients. The Kaplan-Meier plotter database was used to analyze the correlation between the miR-224 expression and the overall survival time of HCC patients. The biological processes and signal pathways involving miR-224 were analyzed using bioinformatics tools. Hepatocellular carcinoma HepG2 cells were transfected with miR-224 inhibitor, and then Clone formation experiment, Transwell chamber experiment, qPCR and WB methods were used to detect the effect of miR-224 knockdown on the proliferation and invasion of HepG2 cells and the expression level of EMT-related molecules.Results: The results of GEO database analysis showed that the expression level of miR-224 in HCC tissues was significantly higher than that in normal tissues. The results of clinical specimen verification showed that the expression level of miR-224 in the tumor tissues and plasma of HCC patients was significantly higher than that in the corresponding adjacent tissues and plasma from healthy controls (all P<0.01). The expression level of miR-224 was significantly correlated with the TNM stage, lymph node metastasis status and tumor size of HCC patients (P<0.05 or P<0.01). ROC analysis indicated that miR-224 showed a prominent diagnostic value in liver cancer, and the increased expression level of miR-224 was significantly related to the poor prognosis of HCC patients (P<0.05). Functional enrichment analysis revealed that miR-224 was mainly involved in the mTOR signaling pathway, AGE-RAGE signaling pathway, Rap1 signaling pathway, Ras signaling pathway, ErbB signaling pathway, HIF-1 signaling pathway and p53 signaling pathway and other signaling pathways related to tumor occurrence and development. Knockdown of miR-224 could significantly inhibit the colony formation and invasion of HepG2 cells and affect the expression of EMT-related markers (P<0.05 or P<0.01).Conclusion: miR-224 is highly expressed in HCC tissues and plasma and is significantly related to the poor prognosis of HCC patients. Knockdown of miR-224 expression can inhibit the colony formation, invasion and EMT process of liver cancer HepG2 cells.
Objective: To analyze the expression level of miR-224 in cancer tissues and plasma of hepatocellular carcinoma (HCC) patients, and its correlation with clinicopathological characteristics, diagnosis and prognosis of HCC patients, and to further analyze its mechanism of action in the occurrence and development of liver cancer through bioinformatics analysis and in vitro experiments.Methods: The expression level of miR-224 in HCC tissues and normal tissues was analyzed using large sample data from Gene Expression Omnibus (GEO). qPCR method was used to verify the expression level of miR-224 in the tumor tissues and corresponding adjacent tissues that surgically resected from 80 HCC patients in Hebei Provincial People’s Hospital from January 2017 to January 2020; in addition, the miR-224 level was also examined in plasma samples from 30 HCC patients. The Kaplan-Meier plotter database was used to analyze the correlation between the miR-224 expression and the overall survival time of HCC patients. The biological processes and signal pathways involving miR-224 were analyzed using bioinformatics tools. Hepatocellular carcinoma HepG2 cells were transfected with miR-224 inhibitor, and then Clone formation experiment, Transwell chamber experiment, qPCR and WB methods were used to detect the effect of miR-224 knockdown on the proliferation and invasion of HepG2 cells and the expression level of EMT-related molecules.Results: The results of GEO database analysis showed that the expression level of miR-224 in HCC tissues was significantly higher than that in normal tissues. The results of clinical specimen verification showed that the expression level of miR-224 in the tumor tissues and plasma of HCC patients was significantly higher than that in the corresponding adjacent tissues and plasma from healthy controls (all P<0.01). The expression level of miR-224 was significantly correlated with the TNM stage, lymph node metastasis status and tumor size of HCC patients (P<0.05 or P<0.01). ROC analysis indicated that miR-224 showed a prominent diagnostic value in liver cancer, and the increased expression level of miR-224 was significantly related to the poor prognosis of HCC patients (P<0.05). Functional enrichment analysis revealed that miR-224 was mainly involved in the mTOR signaling pathway, AGE-RAGE signaling pathway, Rap1 signaling pathway, Ras signaling pathway, ErbB signaling pathway, HIF-1 signaling pathway and p53 signaling pathway and other signaling pathways related to tumor occurrence and development. Knockdown of miR-224 could significantly inhibit the colony formation and invasion of HepG2 cells and affect the expression of EMT-related markers (P<0.05 or P<0.01).Conclusion: miR-224 is highly expressed in HCC tissues and plasma and is significantly related to the poor prognosis of HCC patients. Knockdown of miR-224 expression can inhibit the colony formation, invasion and EMT process of liver cancer HepG2 cells.
2021, 28(2):143-150.
DOI: 10.3872/j.issn.1007-385x.2021.02.007
Abstract:
Objective: To investigate the effect and mechanism of miR-449b-5p on the proliferation of ovarian cancer cells.Methods: Cancer tissue and corresponding para-cancerous tissue specimens from 20 patients who underwent surgery in the Department of Obstetrics and Gynecology of Sichuan Provincial People's Hospital from June 2018 to June 2020 were collected for this study; in addition, normal ovarian epithelial cell line (HOSEpiC) and six human cervical cancer cell lines (SKOV3, ES-2, OVCAR-3, HO8910, CaOV-3 and A2780) were also selected. mRNA expressions of miR-449b-5p and CCNE2 in ovarian cancer tissues and cells were detected by qPCR. The plasmids miR-NC, miR-499b-5p mimic, miR-499b-5p inhibitor and pc-CCNE2 were transfected into SKOV3 cells separately or in combination. Cell growth and cell cycle were measured by the CCK-8 method and Flow cytometry, the expression of CCNE2 protein was detected by WB assay, respectively. The targeting relationship between miR-449b-5p and CCNE2 was verified by Dual luciferase reporter assay. miR-499b-5p transfected SKOV3 cells were injected subcutaneously in nude mice to construct xenograft model, and the tumor volume was measured weekly. Nude mice were sacrificed at day 42. The weight of the subcutaneous tumors was weighed by an electronic balance, and the expressions of CCNE2 and Ki67 were detected by immunohistochemistry.Results: Compared with normal ovarian tissues and epithelial cell line HOSEpiC, miR-499b expression was significantly down-regulated in human cervical cancer tissues and cell lines SKOV3, ES-2, OVCAR-3, HO8910, CaOV-3 and A2780 (P<0.01). Compared with the Control group, the proliferation of SKOV3 cells in the miR-499b mimic group was significantly reduced (P<0.01) and the cell proportion in G0/G1 phase was significantly increased ( P<0.01); while the proliferation of SKOV3 cells in the miR-499b inhibitor group was significantly increased (P<0.01) and the cell proportion in G0/G1 phase was significantly reduced (P<0.01). Over-expression of miR-499b-5p significantly inhibited the luciferase activity of wild type CCNE2 plasmid (P<0.01) but had no effect on the luciferase activity of the mutant CCNE2 plasmid. Compared with the miR-499b mimic group, the growth of SKOV3 cells in the miR-499b mimic+pc-CCNE2 group was significantly increased (P<0.01) and the cell proportion in G0/G1 phase was significantly reduced (P<0.01). Compared with the miR-NC group, the tumor volume and weight of nude mice in the miR-499b mimic group were significantly reduced (all P<0.01), and the proportion of CCNE2 and Ki67 positive cells was significantly decreased (P<0.01).Conclusion: miR-449b-5p inhibits the growth and cell cycle progression of ovarian cancer cells by targeting Cyclin E2.
Objective: To investigate the effect and mechanism of miR-449b-5p on the proliferation of ovarian cancer cells.Methods: Cancer tissue and corresponding para-cancerous tissue specimens from 20 patients who underwent surgery in the Department of Obstetrics and Gynecology of Sichuan Provincial People's Hospital from June 2018 to June 2020 were collected for this study; in addition, normal ovarian epithelial cell line (HOSEpiC) and six human cervical cancer cell lines (SKOV3, ES-2, OVCAR-3, HO8910, CaOV-3 and A2780) were also selected. mRNA expressions of miR-449b-5p and CCNE2 in ovarian cancer tissues and cells were detected by qPCR. The plasmids miR-NC, miR-499b-5p mimic, miR-499b-5p inhibitor and pc-CCNE2 were transfected into SKOV3 cells separately or in combination. Cell growth and cell cycle were measured by the CCK-8 method and Flow cytometry, the expression of CCNE2 protein was detected by WB assay, respectively. The targeting relationship between miR-449b-5p and CCNE2 was verified by Dual luciferase reporter assay. miR-499b-5p transfected SKOV3 cells were injected subcutaneously in nude mice to construct xenograft model, and the tumor volume was measured weekly. Nude mice were sacrificed at day 42. The weight of the subcutaneous tumors was weighed by an electronic balance, and the expressions of CCNE2 and Ki67 were detected by immunohistochemistry.Results: Compared with normal ovarian tissues and epithelial cell line HOSEpiC, miR-499b expression was significantly down-regulated in human cervical cancer tissues and cell lines SKOV3, ES-2, OVCAR-3, HO8910, CaOV-3 and A2780 (P<0.01). Compared with the Control group, the proliferation of SKOV3 cells in the miR-499b mimic group was significantly reduced (P<0.01) and the cell proportion in G0/G1 phase was significantly increased ( P<0.01); while the proliferation of SKOV3 cells in the miR-499b inhibitor group was significantly increased (P<0.01) and the cell proportion in G0/G1 phase was significantly reduced (P<0.01). Over-expression of miR-499b-5p significantly inhibited the luciferase activity of wild type CCNE2 plasmid (P<0.01) but had no effect on the luciferase activity of the mutant CCNE2 plasmid. Compared with the miR-499b mimic group, the growth of SKOV3 cells in the miR-499b mimic+pc-CCNE2 group was significantly increased (P<0.01) and the cell proportion in G0/G1 phase was significantly reduced (P<0.01). Compared with the miR-NC group, the tumor volume and weight of nude mice in the miR-499b mimic group were significantly reduced (all P<0.01), and the proportion of CCNE2 and Ki67 positive cells was significantly decreased (P<0.01).Conclusion: miR-449b-5p inhibits the growth and cell cycle progression of ovarian cancer cells by targeting Cyclin E2.
WANG Xuan
,
KONG Yan
,
CUI Chuanliang
,
CHI Zhihong
,
SHENG Xinan
,
SI Lu
,
LIAN Bin
,
MAO Lili
,
TANG Bixia
,
YAN Xieqiao
,
ZHOU Li
,
BAI Xue
,
LI Siming
,
JI Qing
,
TIAN Hui
,
GUO Jun
2021, 28(2):151-156.
DOI: 10.3872/j.issn.1007-385x.2021.02.008
Abstract:
Objective: Elevated levels of soluble PD-L1 (sPD-L1) are associated with worse prognosis of renal cell carcinoma and multiple myeloma. However, the regulatory roles and functions of sPD-L1 in advanced melanoma are not fully understood. This study was designed to evaluate the association between circulating sPD-L1 concentrations and prognosis of patients with advanced acral or mucosal melanoma.Methods: A total of 102 untreated patients with advanced acral and mucosal melanoma admitted to Peking University Cancer Hospital between January 2012 and December 2015 were enrolled in this study. In the meanwhile, peripheral blood samples were obtained from 40 healthy donors. Circulating sPD-L1 concentrations were determined using an enzyme-linked immunosorbent assay.Results: The advanced melanoma cohort included 58 acral melanoma patients and 44 mucosal melanoma patients. The pre-treatment concentration of sPD-L1 (2.91±2.23 ng/ml) in plasma of patients group was elevated as compared with that in healthy donors (0.59 ng/ml). The concentration of sPD-L1 in serum was significantly upregulated in 39/102 (38.2%) patients and significantly associated with increased LDH level (P=0.021) and number of Tregs (P=0.017). The overall survival rates of patients with high or low concentrations of sPD-L1 were statistically different (8.5 months [high level] vs 11.6 months [low level], P=0.022).Conclusion: sPD-L1 concentration is elevated in patients with advanced acral or mucosal melanoma, which may play an important role in predicting prognosis.
Objective: Elevated levels of soluble PD-L1 (sPD-L1) are associated with worse prognosis of renal cell carcinoma and multiple myeloma. However, the regulatory roles and functions of sPD-L1 in advanced melanoma are not fully understood. This study was designed to evaluate the association between circulating sPD-L1 concentrations and prognosis of patients with advanced acral or mucosal melanoma.Methods: A total of 102 untreated patients with advanced acral and mucosal melanoma admitted to Peking University Cancer Hospital between January 2012 and December 2015 were enrolled in this study. In the meanwhile, peripheral blood samples were obtained from 40 healthy donors. Circulating sPD-L1 concentrations were determined using an enzyme-linked immunosorbent assay.Results: The advanced melanoma cohort included 58 acral melanoma patients and 44 mucosal melanoma patients. The pre-treatment concentration of sPD-L1 (2.91±2.23 ng/ml) in plasma of patients group was elevated as compared with that in healthy donors (0.59 ng/ml). The concentration of sPD-L1 in serum was significantly upregulated in 39/102 (38.2%) patients and significantly associated with increased LDH level (P=0.021) and number of Tregs (P=0.017). The overall survival rates of patients with high or low concentrations of sPD-L1 were statistically different (8.5 months [high level] vs 11.6 months [low level], P=0.022).Conclusion: sPD-L1 concentration is elevated in patients with advanced acral or mucosal melanoma, which may play an important role in predicting prognosis.
BAI Xue
,
LI Caili
,
MAO Lili
,
WEI Xiaoting
,
QI Zhonghui
,
SHENG Xinan
,
CUI Chuanliang
,
CHI Zhihong
,
LIAN Bin
,
WANG Xuan
,
YAN Xieqiao
,
TANG Bixia
,
ZHOU Li
,
LI Siming
,
DUAN Rong
,
XU Huayan
,
GUO Jun
,
SI Lu
2021, 28(2):157-164.
DOI: 10.3872/j.issn.1007-385x.2021.02.009
Abstract:
Abstract: To explore the expression patterns of melanoma lineage antigens and nuclear antigen Ki-67 and their correlations with survival in melanoma patients.Methods: A retrospective analysis was conducted to analyze the pathological data of melanoma patients treated at the Department of Melanoma, Peking University Cancer Hospital from February 2008 to August 2020, mainly including the expression patterns of melanoma lineage antigens (S-100, HMB-45, Melan-A) and Ki-67, demographics, clinical features and survival. The correlation between expression patterns of melanoma lineage antigens, Ki-67 and melanoma-specific survival (MSS) was analyzed.Results: In total, 603 patients were included in this study. The median follow-up time was 47.4 months. The positive rates of S-100, HMB, and Melan-A were 92.8%, 92.1% and 90.0%, respectively. The percentages of patients with melanoma lineage antigen scores(S-100, HMB-45 and Melan-A was scored each, as 1 when positive and 0 when negative) of 0, 1, 2, and 3 were 0.5%, 5.0%, 15.6%, and 78.8%, respectively. The percentages of patients with Ki-67 scores of 0, 1, 2, and 3 were 43.0%, 36.3%, 16.3%, and 4.5%, respectively. Ki-67 was highly expressed in mucosal and progressive melanomas. In a multivariate analysis, Ki-67 expression was an independent prognostic factor for poorer MSS (HR=1.506, 95%CI: 1.248-1.818, P<0.001) as the incidence of MSS event increased by 50% per 25% increase in Ki-67 expression, whereas there was no statistical correlation between melanoma lineage antigen expression and MSS (HR=0.991, 95%CI: 0.759-1.293, P=0.94).Conclusion: High expressions melanoma lineage antigens are ubiquitous in melanoma tissues, and Ki-67 is an independent prognostic factor for MSS.
Abstract: To explore the expression patterns of melanoma lineage antigens and nuclear antigen Ki-67 and their correlations with survival in melanoma patients.Methods: A retrospective analysis was conducted to analyze the pathological data of melanoma patients treated at the Department of Melanoma, Peking University Cancer Hospital from February 2008 to August 2020, mainly including the expression patterns of melanoma lineage antigens (S-100, HMB-45, Melan-A) and Ki-67, demographics, clinical features and survival. The correlation between expression patterns of melanoma lineage antigens, Ki-67 and melanoma-specific survival (MSS) was analyzed.Results: In total, 603 patients were included in this study. The median follow-up time was 47.4 months. The positive rates of S-100, HMB, and Melan-A were 92.8%, 92.1% and 90.0%, respectively. The percentages of patients with melanoma lineage antigen scores(S-100, HMB-45 and Melan-A was scored each, as 1 when positive and 0 when negative) of 0, 1, 2, and 3 were 0.5%, 5.0%, 15.6%, and 78.8%, respectively. The percentages of patients with Ki-67 scores of 0, 1, 2, and 3 were 43.0%, 36.3%, 16.3%, and 4.5%, respectively. Ki-67 was highly expressed in mucosal and progressive melanomas. In a multivariate analysis, Ki-67 expression was an independent prognostic factor for poorer MSS (HR=1.506, 95%CI: 1.248-1.818, P<0.001) as the incidence of MSS event increased by 50% per 25% increase in Ki-67 expression, whereas there was no statistical correlation between melanoma lineage antigen expression and MSS (HR=0.991, 95%CI: 0.759-1.293, P=0.94).Conclusion: High expressions melanoma lineage antigens are ubiquitous in melanoma tissues, and Ki-67 is an independent prognostic factor for MSS.
2021, 28(2):165-170.
DOI: 10.3872/j.issn.1007-385x.2021.02.010
Abstract:
Objective: To investigate the effects of antibiotics on the treatment efficacy of immune checkpoint inhibitors in NSCLC (non-small cell lung cancer) with Meta-analysis.Methods: Literatures regarding the effects of antibiotics on the treatment efficacy of immune checkpoint inhibitors in NSCLC were searched in Pubmed, Cochrane Library, Embase, EBSCO, Chinese Biomedical Literature Database(CBM) and Chinese Journal Full-text Database(CNKI). RevMan 5.3 software was used in this Meta-analysis.Results: Fourteen articles involving 2 505 NSCLC patients were included in this study. Meta-analysis showed that the application of antibiotics could significantly shorten the PFS (HR=1.14, 95%CI =1.04-1.26, P=0.005) and OS (HR=1.30, 95%CI =1.14-1.47, P<0.0001) of NSCLC patients treated with immune checkpoint inhibitors.Conclusion: Application of antibiotics before, concurrently or after immune checkpoint inhibitors in the treatment of NSCLC may significantly shorten PFS and OS, resulting in adverse effect on treatment efficacy.
Objective: To investigate the effects of antibiotics on the treatment efficacy of immune checkpoint inhibitors in NSCLC (non-small cell lung cancer) with Meta-analysis.Methods: Literatures regarding the effects of antibiotics on the treatment efficacy of immune checkpoint inhibitors in NSCLC were searched in Pubmed, Cochrane Library, Embase, EBSCO, Chinese Biomedical Literature Database(CBM) and Chinese Journal Full-text Database(CNKI). RevMan 5.3 software was used in this Meta-analysis.Results: Fourteen articles involving 2 505 NSCLC patients were included in this study. Meta-analysis showed that the application of antibiotics could significantly shorten the PFS (HR=1.14, 95%CI =1.04-1.26, P=0.005) and OS (HR=1.30, 95%CI =1.14-1.47, P<0.0001) of NSCLC patients treated with immune checkpoint inhibitors.Conclusion: Application of antibiotics before, concurrently or after immune checkpoint inhibitors in the treatment of NSCLC may significantly shorten PFS and OS, resulting in adverse effect on treatment efficacy.
11 The relationship between EGFR-TKI resistance and PD-L1 expression in the treatment of lung cancer
2021, 28(2):171-175.
DOI: 10.3872/j.issn.1007-385x.2021.02.011
Abstract:
表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitor，EGFR-TKI）的上市，使治疗EGFR突变的晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）患者的客观有效率达到79%，取得了显著的抗肿瘤治疗效果。然而，耐药是EGFR-TKIs治疗的瓶颈，对耐药机制的研究以及耐药后的治疗策略，成为肺癌治疗的难点和热点问题。随着免疫治疗的兴起，越来越多的证据发现，PD-L1不仅与EGFR基因突变之间存在调节关系，而且PD-L1表达和EGFR-TKIs耐药也显示出新的相关性。探究PD-L1表达与EGFR-TKIs耐药之间的关系对寻找EGFR-TKIs耐药后治疗策略具有重要意义。
表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitor，EGFR-TKI）的上市，使治疗EGFR突变的晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）患者的客观有效率达到79%，取得了显著的抗肿瘤治疗效果。然而，耐药是EGFR-TKIs治疗的瓶颈，对耐药机制的研究以及耐药后的治疗策略，成为肺癌治疗的难点和热点问题。随着免疫治疗的兴起，越来越多的证据发现，PD-L1不仅与EGFR基因突变之间存在调节关系，而且PD-L1表达和EGFR-TKIs耐药也显示出新的相关性。探究PD-L1表达与EGFR-TKIs耐药之间的关系对寻找EGFR-TKIs耐药后治疗策略具有重要意义。
2021, 28(2):176-183.
DOI: 10.3872/j.issn.1007-385x.2021.02.012
Abstract:
溶瘤病毒能够在肿瘤细胞内大量增殖并最终裂解肿瘤细胞，同时还具有对肿瘤微环境的调控作用，激发宿主抗肿瘤免疫反应。但是溶瘤病毒经静脉注射后引发的机体抗病毒免疫应答以及溶瘤病毒的肿瘤靶向性差，使得临床上对肿瘤的疗效不佳。间充质干细胞具有肿瘤趋向性、免疫抑制功能和旁分泌效应。间充质干细胞运载溶瘤病毒既可以保护病毒不被免疫系统清除又可精准将病毒递送到肿瘤病变部位，同时病毒感染可改变间充质干细胞分泌的细胞因子谱，促进机体抗肿瘤免疫反应。因此，间充质干细胞运载溶瘤病毒是治疗复发/难治性实体肿瘤的理想选择。本文结合临床前及临床研究的有关进展，对间充质干细胞运载溶瘤病毒治疗实体肿瘤进行综述，为间充质干细胞运载溶瘤病毒的临床应用提供了理论依据。
溶瘤病毒能够在肿瘤细胞内大量增殖并最终裂解肿瘤细胞，同时还具有对肿瘤微环境的调控作用，激发宿主抗肿瘤免疫反应。但是溶瘤病毒经静脉注射后引发的机体抗病毒免疫应答以及溶瘤病毒的肿瘤靶向性差，使得临床上对肿瘤的疗效不佳。间充质干细胞具有肿瘤趋向性、免疫抑制功能和旁分泌效应。间充质干细胞运载溶瘤病毒既可以保护病毒不被免疫系统清除又可精准将病毒递送到肿瘤病变部位，同时病毒感染可改变间充质干细胞分泌的细胞因子谱，促进机体抗肿瘤免疫反应。因此，间充质干细胞运载溶瘤病毒是治疗复发/难治性实体肿瘤的理想选择。本文结合临床前及临床研究的有关进展，对间充质干细胞运载溶瘤病毒治疗实体肿瘤进行综述，为间充质干细胞运载溶瘤病毒的临床应用提供了理论依据。
2021, 28(2):184-190.
DOI: 10.3872/j.issn.1007-385x.2021.02.013
Abstract:
肿瘤腹膜转移常见于癌症晚期患者，由于腹腔内血供及其他脉管系统丰富，肿瘤病灶可广泛存在于腹膜腔区域，临床预后较差。近年来研究者提出多种诊疗策略以延缓肿瘤进展，但由于腹腔内直接注射药物的滞留时间短、无肿瘤靶向性等原因，抑瘤效果不佳。肿瘤靶向穿透肽是一类多功能短肽，不仅对肿瘤组织有特异性亲和力，还兼有向其深部渗入的特性，可修饰于抗肿瘤药物、纳米载体、免疫细胞及显像探针等，促进药物特异性富集于肿瘤深部，增强抗肿瘤作用。以肿瘤靶向穿透肽修饰介导的腹膜转移靶向治疗显示出良好应用前景，本文总结了靶向穿透肽在肿瘤腹膜转移中的应用进展。
肿瘤腹膜转移常见于癌症晚期患者，由于腹腔内血供及其他脉管系统丰富，肿瘤病灶可广泛存在于腹膜腔区域，临床预后较差。近年来研究者提出多种诊疗策略以延缓肿瘤进展，但由于腹腔内直接注射药物的滞留时间短、无肿瘤靶向性等原因，抑瘤效果不佳。肿瘤靶向穿透肽是一类多功能短肽，不仅对肿瘤组织有特异性亲和力，还兼有向其深部渗入的特性，可修饰于抗肿瘤药物、纳米载体、免疫细胞及显像探针等，促进药物特异性富集于肿瘤深部，增强抗肿瘤作用。以肿瘤靶向穿透肽修饰介导的腹膜转移靶向治疗显示出良好应用前景，本文总结了靶向穿透肽在肿瘤腹膜转移中的应用进展。
2021, 28(2):191-198.
DOI: 10.3872/j.issn.1007-385x.2021.02.014
Abstract:
囊泡转运是细胞间沟通的重要方式。随着蛋白质组学、代谢组学、RNA组学等多组学联合研究的发展和进步，研究人员发现外泌体是细胞间通讯的重要信号转导媒介和介质。外泌体携带大量生物活性分子，对细胞生物学功能的发挥具有重要的调控作用，影响肿瘤细胞的特性。越来越多的证据表明，外泌体的功能与其来源的细胞及其内含物成分密切相关。肿瘤来源外泌体以自分泌和旁分泌的方式诱导癌细胞和基质细胞生理功能和代谢状态的改变，基质细胞来源外泌体参与建立、支持和营养肿瘤细胞的肿瘤微环境，并且不同免疫细胞来源外泌体可能呈现截然相反的功能。本文就不同细胞来源外泌体在肿瘤微环境中的作用和机制进行综述，为外泌体在肿瘤诊断、治疗及预后评估中的应用提供参考。
囊泡转运是细胞间沟通的重要方式。随着蛋白质组学、代谢组学、RNA组学等多组学联合研究的发展和进步，研究人员发现外泌体是细胞间通讯的重要信号转导媒介和介质。外泌体携带大量生物活性分子，对细胞生物学功能的发挥具有重要的调控作用，影响肿瘤细胞的特性。越来越多的证据表明，外泌体的功能与其来源的细胞及其内含物成分密切相关。肿瘤来源外泌体以自分泌和旁分泌的方式诱导癌细胞和基质细胞生理功能和代谢状态的改变，基质细胞来源外泌体参与建立、支持和营养肿瘤细胞的肿瘤微环境，并且不同免疫细胞来源外泌体可能呈现截然相反的功能。本文就不同细胞来源外泌体在肿瘤微环境中的作用和机制进行综述，为外泌体在肿瘤诊断、治疗及预后评估中的应用提供参考。
2021, 28(2):199-210.
DOI: 10.3872/j.issn.1007-385x.2021.02.015
Abstract:
食管癌是常见的消化道恶性肿瘤，易转移及复发的性质常常导致病人呈现出明显的致死性风险。国内一些地区食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）的发病率相对较高，严重威胁着人类的健康和生命而成为肿瘤研究的重要方向。食管鳞状细胞癌的发生发展是一系列因素累积及相互作用的复杂过程，其克隆性增殖会造成肿瘤细胞内微观水平的表达异常和信号传导通路级联反应效应的改变，形成具有不同性质的细胞亚群。肿瘤细胞间不同细胞亚群在细胞分子水平甚至基因表达层面呈现出比较明显的异质性，由此引发肿瘤细胞对药物的敏感性下降及抗药性现象的出现。很多食管癌移植模型被用于了解肿瘤的性质和病理生理学特点，有助于探索肿瘤细胞内的发生机制，为推动肿瘤研究和治疗提供了重要的价值。随着肿瘤类器官培养技术获得突破性进展，肿瘤细胞的3D培养模型能够重现亲代肿瘤细胞的生物学性质，成为探索肿瘤发生机制和基因序列异常表达的工具，为肿瘤的研究提供了重要的平台，并推动肿瘤研究和治疗向前迈进及取得重要进展。本文对常用的ESCC的研究模型作一综述。
食管癌是常见的消化道恶性肿瘤，易转移及复发的性质常常导致病人呈现出明显的致死性风险。国内一些地区食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）的发病率相对较高，严重威胁着人类的健康和生命而成为肿瘤研究的重要方向。食管鳞状细胞癌的发生发展是一系列因素累积及相互作用的复杂过程，其克隆性增殖会造成肿瘤细胞内微观水平的表达异常和信号传导通路级联反应效应的改变，形成具有不同性质的细胞亚群。肿瘤细胞间不同细胞亚群在细胞分子水平甚至基因表达层面呈现出比较明显的异质性，由此引发肿瘤细胞对药物的敏感性下降及抗药性现象的出现。很多食管癌移植模型被用于了解肿瘤的性质和病理生理学特点，有助于探索肿瘤细胞内的发生机制，为推动肿瘤研究和治疗提供了重要的价值。随着肿瘤类器官培养技术获得突破性进展，肿瘤细胞的3D培养模型能够重现亲代肿瘤细胞的生物学性质，成为探索肿瘤发生机制和基因序列异常表达的工具，为肿瘤的研究提供了重要的平台，并推动肿瘤研究和治疗向前迈进及取得重要进展。本文对常用的ESCC的研究模型作一综述。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.