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Volume 28,Issue 7,2021 Table of Contents
2021, 28(7):651-658.
Abstract:
Cancer stem cell (CSC) is characterized by unique molecular expression, surface markers, stemness-related signaling pathways, and metabolic patterns. CSC has been the key factor for the growth, metastasis and treatment resistance in various malignancies, as well as the important reason for the tumorigenesis and recurrence due to its high tumorigenicity, metastatic potential and resistance. Normal stem cells can develop gradually into pre-cancerous stem cell (pCSC) and CSC after incurring the first oncogenic mutation. Subsequently, under the co-influence of oncogenic mutations and tumor microenvironments, oncogenic mutations are accumulated in cells, which further aiding up to tumor heterogeneity, and eventually, promote the tumorigenesis, development, relapse, metastasis, and resistance in combination with CSC plasticity transformation. In order to improve clinical outcome in tumor treatment, various therapeutic strategies targeting CSC have been developed, including cell surface markers, signal pathways, microenvironment, and metabolic patterns. Other strategies such as the promotion of CSC differentiation and immunotherapy targeting CSC are also studied. In clinical trials, several new anti-cancer drugs targeting CSC have shown favorable outcomes in patients. However, the failed attempt of some new anti-cancer drugs also holds noteworthy lessons for future development. Therefore, the specific targeting of all heterogeneous CSCs in tumor of patients and the simultaneous elimination of pCSC and progeny tumor cells will be conducive to inhibitting tumor growth, metastasis and recurrence, expecting to bring new hope for tumor therapy.
Cancer stem cell (CSC) is characterized by unique molecular expression, surface markers, stemness-related signaling pathways, and metabolic patterns. CSC has been the key factor for the growth, metastasis and treatment resistance in various malignancies, as well as the important reason for the tumorigenesis and recurrence due to its high tumorigenicity, metastatic potential and resistance. Normal stem cells can develop gradually into pre-cancerous stem cell (pCSC) and CSC after incurring the first oncogenic mutation. Subsequently, under the co-influence of oncogenic mutations and tumor microenvironments, oncogenic mutations are accumulated in cells, which further aiding up to tumor heterogeneity, and eventually, promote the tumorigenesis, development, relapse, metastasis, and resistance in combination with CSC plasticity transformation. In order to improve clinical outcome in tumor treatment, various therapeutic strategies targeting CSC have been developed, including cell surface markers, signal pathways, microenvironment, and metabolic patterns. Other strategies such as the promotion of CSC differentiation and immunotherapy targeting CSC are also studied. In clinical trials, several new anti-cancer drugs targeting CSC have shown favorable outcomes in patients. However, the failed attempt of some new anti-cancer drugs also holds noteworthy lessons for future development. Therefore, the specific targeting of all heterogeneous CSCs in tumor of patients and the simultaneous elimination of pCSC and progeny tumor cells will be conducive to inhibitting tumor growth, metastasis and recurrence, expecting to bring new hope for tumor therapy.
2021, 28(7):659-664.
Abstract:
Objective: To observe the expression level of long non-coding RNA FLJ26245 (lncRNA FLJ26245) in prostate cancer tissues and cells, and to explore its effect on the proliferation and migration of prostate cancer PC-3 cells and the underlying mechanism. Methods: A total of 52 pairs of prostate cancer tissues and corresponding para-cancerous tissues from patients who underwent surgery at Luoyang Central Hospital from March 2017 to May 2019 were collected for this study; in addtion, the prostate cancer cell lines (LNCaP, C4-2B, PC-3, DU-145) and normal prostate epithelial cells (RWPE-1) were also selected. qPCR was used to detect the expression level of FLJ26245 in prostate cancer tissues and cells. FLJ26245 mimics and negative control plasmids (lncR-NC) were transfected into PC-3 cells, respectively. MTT assay and Wound-healing test were used to detect the proliferation and migration ability of prostate cancer cells. Bioinformatics technology was used to predict the targeting relationship among FLJ26245, miR-200a-3p, and tyrosine phosphatase receptor G (PTPRG), which was further validated with Dual luciferase reporter gene assay. qPCR and WB methods were used to detect the expression of FLJ26245 downstream gene and proliferation and migration related proteins, respectively. Results: Compared with para-cancerous tissues, the expression level of FLJ26245 in prostate cancer tissues was significantly downregulaed (P<0.01). Compared with RWPE-1 cells, the expression level of FLJ26245 in prostate cancer cells was also significantly decreased (P<0.01 or P<0.05), with the lowest expression in PC-3 cells (P<0.01). Overexpression of FLJ26245 could significantly inhibit the proliferation and migration ability of PC-3 cells (P<0.05 or P<0.01). FLJ26245 could bind to miR-200a-3p, and miR-200a-3p could bind to PTPRG (all P<0.01). After overexpression of FLJ26245, the expression of miR-200a-3p in PC-3 cells was significantly decreased (P<0.01), the mRNA and protein expressions of PTPRG were significantly increased (all P<0.01), and proliferation and migration related proteins, such as cyclin A, CDK2 and Twist, N-cadherin, were significantly reduced (all P<0.01). Conclusion: FLJ26245 is low expressed in prostate cancer tissues and cells. FLJ26245 may inhibit the proliferation and migration of prostate cancer PC-3 cells by regulating the miR-200a-3p/PTPRG axis.
Objective: To observe the expression level of long non-coding RNA FLJ26245 (lncRNA FLJ26245) in prostate cancer tissues and cells, and to explore its effect on the proliferation and migration of prostate cancer PC-3 cells and the underlying mechanism. Methods: A total of 52 pairs of prostate cancer tissues and corresponding para-cancerous tissues from patients who underwent surgery at Luoyang Central Hospital from March 2017 to May 2019 were collected for this study; in addtion, the prostate cancer cell lines (LNCaP, C4-2B, PC-3, DU-145) and normal prostate epithelial cells (RWPE-1) were also selected. qPCR was used to detect the expression level of FLJ26245 in prostate cancer tissues and cells. FLJ26245 mimics and negative control plasmids (lncR-NC) were transfected into PC-3 cells, respectively. MTT assay and Wound-healing test were used to detect the proliferation and migration ability of prostate cancer cells. Bioinformatics technology was used to predict the targeting relationship among FLJ26245, miR-200a-3p, and tyrosine phosphatase receptor G (PTPRG), which was further validated with Dual luciferase reporter gene assay. qPCR and WB methods were used to detect the expression of FLJ26245 downstream gene and proliferation and migration related proteins, respectively. Results: Compared with para-cancerous tissues, the expression level of FLJ26245 in prostate cancer tissues was significantly downregulaed (P<0.01). Compared with RWPE-1 cells, the expression level of FLJ26245 in prostate cancer cells was also significantly decreased (P<0.01 or P<0.05), with the lowest expression in PC-3 cells (P<0.01). Overexpression of FLJ26245 could significantly inhibit the proliferation and migration ability of PC-3 cells (P<0.05 or P<0.01). FLJ26245 could bind to miR-200a-3p, and miR-200a-3p could bind to PTPRG (all P<0.01). After overexpression of FLJ26245, the expression of miR-200a-3p in PC-3 cells was significantly decreased (P<0.01), the mRNA and protein expressions of PTPRG were significantly increased (all P<0.01), and proliferation and migration related proteins, such as cyclin A, CDK2 and Twist, N-cadherin, were significantly reduced (all P<0.01). Conclusion: FLJ26245 is low expressed in prostate cancer tissues and cells. FLJ26245 may inhibit the proliferation and migration of prostate cancer PC-3 cells by regulating the miR-200a-3p/PTPRG axis.
3 Effect of lncRNA MAFG-AS1 regulating miR-532-3p expression on glycolysis of lung cancer A549 cells
2021, 28(7):665-671.
Abstract:
Objective: To investigate the effect of lncRNA MAFG antisense RNA1 (lncRNA MAFG-AS1) regulating miR-532-3p on the glycolysis of lung cancer A549 cells. Methods: The expression levels of MAFG-AS1 and miR-532-3p in human lung cancer A549 cells and normal lung epithelial BEAS-2B cells were detected by qPCR. A549 cells with MAFG-AS1 downregulation or miR-532-3p overexpression were constructed by liposome transfection technique, respectively. The glucose consumption and lactate secretion in cell culture supernatant of A549 cells were detected by visible spectrophotometry, and the mRNA and protein expression levels of pyruvate kinase M2 (PKM2) and hexokinase 2 (HK2) in A549 cells were detected using qPCR and WB, respectively. The targeting relationship between MAFG-AS1 and miR-532-3p was verified by Dual luciferase reporter gene assay, and the effects of co-downregulation of MAFG-AS1 and miR-532-3p on glucose uptake, lactate secretion and expression of PKM2 and HK2 in A549 cells were observed. Results: Compared with BEAS-2B cells, the expression of MAFG-AS1 was upregulated while miR-532-3p expression was downregulated in A549 cells (all P<0.01). Glucose consumption, lactate secretion and the protein and mRNA expressions of PKM2 and HK2 were inhibited by MAFG-AS1 downregulation or miR-532-3p overexpression (all P<0.01). miR-532-3p could bind to MAFG-AS1 and inhibit the luciferase activity of wild-type MAFG-AS1 cells (P<0.01). Downregulation of MAFG-AS1 could increase the expression of miR-532-3p (P<0.01)，while the co-downregulation of miR-532-3p could reverse the effect of MAFG-AS1 downregulation on glucose uptake, lactate secretion and the expression of PKM2 and HK2 in A549 cells (all P<0.01). Conclusion: Downregulation of MAFG-AS1 can inhibit the glycolysis of A549 cells by promoting the expression of miR-532-3p.
Objective: To investigate the effect of lncRNA MAFG antisense RNA1 (lncRNA MAFG-AS1) regulating miR-532-3p on the glycolysis of lung cancer A549 cells. Methods: The expression levels of MAFG-AS1 and miR-532-3p in human lung cancer A549 cells and normal lung epithelial BEAS-2B cells were detected by qPCR. A549 cells with MAFG-AS1 downregulation or miR-532-3p overexpression were constructed by liposome transfection technique, respectively. The glucose consumption and lactate secretion in cell culture supernatant of A549 cells were detected by visible spectrophotometry, and the mRNA and protein expression levels of pyruvate kinase M2 (PKM2) and hexokinase 2 (HK2) in A549 cells were detected using qPCR and WB, respectively. The targeting relationship between MAFG-AS1 and miR-532-3p was verified by Dual luciferase reporter gene assay, and the effects of co-downregulation of MAFG-AS1 and miR-532-3p on glucose uptake, lactate secretion and expression of PKM2 and HK2 in A549 cells were observed. Results: Compared with BEAS-2B cells, the expression of MAFG-AS1 was upregulated while miR-532-3p expression was downregulated in A549 cells (all P<0.01). Glucose consumption, lactate secretion and the protein and mRNA expressions of PKM2 and HK2 were inhibited by MAFG-AS1 downregulation or miR-532-3p overexpression (all P<0.01). miR-532-3p could bind to MAFG-AS1 and inhibit the luciferase activity of wild-type MAFG-AS1 cells (P<0.01). Downregulation of MAFG-AS1 could increase the expression of miR-532-3p (P<0.01)，while the co-downregulation of miR-532-3p could reverse the effect of MAFG-AS1 downregulation on glucose uptake, lactate secretion and the expression of PKM2 and HK2 in A549 cells (all P<0.01). Conclusion: Downregulation of MAFG-AS1 can inhibit the glycolysis of A549 cells by promoting the expression of miR-532-3p.
2021, 28(7):672-679.
Abstract:
Objective: To investigate whether purple sweet potato anthocyanin (PSPA) regulates the proliferation, migration and invasion of breast cancer MDA-MB-231 cells through the circ_0003998/miRNA-145 axis. Methods: Breast cancer MDA-MB-231 cells were divided into control group, PSPA groups (200, 400, 800 μg/ml PSPA), pcDNA group, pcDNA-circ_0003998 group, si-NC group, si-circ_0003998 group, si-circ_0003998+anti-miR-145 group, PSPA+pcDNA group, PSPA+pcDNA-circ_0003998 group and PSPA+anti-miR-145 group. The expressions of circ_0003998 and miR-145 in MDA-MB-231 cells were detected by qPCR method. The cell proliferation, migration and invasion abilities were measured by CCK-8 method and Transwell chamber method, respectively. WB was used to detect the protein expressions of Ki-67, MMP-2 and MMP-9 in cells. Dual luciferase reporter gene assay was used to analyze the targeting relationship between circ_0003998 and miR-145. Results: Compared with the control group, the proliferation inhibition rate and miR-145 expression level in MDA-MB-231 cells of various PSPA groups increased significantly, while the expression of circ_0003998 and protein expression levels of Ki-67, MMP-2, MMP-9, as well as the number of migrated and invaded cells were significantly reduced (all P<0.01), all of which were in a concentration-dependent manner. circ_0003998 could target and negatively regulate the expression of miR-145. After inhibiting circ_0003998, the proliferation inhibition rate and the expression level of miR-145 in MDA-MB-231 cells were significantly increased, while the protein expression levels of Ki-67, MMP-2 and MMP-9, and the number of migrated and invaded cells were significantly reduced (all P<0.01). After co-transfection of si-circ_0003998 and anti-miR-145, the suppression effect of circ_0003998 inhibition on the proliferation, migration and invasion of MDA-MB-231 cells were reversed. circ_0003998 overexpression or miR-145 inhibition could reverse the inhibitory effects of PSPA on the proliferation, migration and invasion of MDA-MB-231 cells. Conclusion: PSPA inhibites the proliferation, migration and invasion of breast cancer MDA-MB-231 cells through the circ_0003998/miR-145 axis.
Objective: To investigate whether purple sweet potato anthocyanin (PSPA) regulates the proliferation, migration and invasion of breast cancer MDA-MB-231 cells through the circ_0003998/miRNA-145 axis. Methods: Breast cancer MDA-MB-231 cells were divided into control group, PSPA groups (200, 400, 800 μg/ml PSPA), pcDNA group, pcDNA-circ_0003998 group, si-NC group, si-circ_0003998 group, si-circ_0003998+anti-miR-145 group, PSPA+pcDNA group, PSPA+pcDNA-circ_0003998 group and PSPA+anti-miR-145 group. The expressions of circ_0003998 and miR-145 in MDA-MB-231 cells were detected by qPCR method. The cell proliferation, migration and invasion abilities were measured by CCK-8 method and Transwell chamber method, respectively. WB was used to detect the protein expressions of Ki-67, MMP-2 and MMP-9 in cells. Dual luciferase reporter gene assay was used to analyze the targeting relationship between circ_0003998 and miR-145. Results: Compared with the control group, the proliferation inhibition rate and miR-145 expression level in MDA-MB-231 cells of various PSPA groups increased significantly, while the expression of circ_0003998 and protein expression levels of Ki-67, MMP-2, MMP-9, as well as the number of migrated and invaded cells were significantly reduced (all P<0.01), all of which were in a concentration-dependent manner. circ_0003998 could target and negatively regulate the expression of miR-145. After inhibiting circ_0003998, the proliferation inhibition rate and the expression level of miR-145 in MDA-MB-231 cells were significantly increased, while the protein expression levels of Ki-67, MMP-2 and MMP-9, and the number of migrated and invaded cells were significantly reduced (all P<0.01). After co-transfection of si-circ_0003998 and anti-miR-145, the suppression effect of circ_0003998 inhibition on the proliferation, migration and invasion of MDA-MB-231 cells were reversed. circ_0003998 overexpression or miR-145 inhibition could reverse the inhibitory effects of PSPA on the proliferation, migration and invasion of MDA-MB-231 cells. Conclusion: PSPA inhibites the proliferation, migration and invasion of breast cancer MDA-MB-231 cells through the circ_0003998/miR-145 axis.
LU Hongjian
,
ZHANG Ronghua
,
HUO Xiaoju
,
HAN Xiangyang
,
WANG Yuan
,
YANG Chen
,
MA Ruixue
,
ZHANG Guangling
2021, 28(7):680-688.
Abstract:
Objective: To investigate the effects of miR-203a-3p on the proliferation, migration and invasion ability of pancreatic cancer BxPC-3 cells. Methods: The Cancer Genome Atlas (TCGA) database was used to screen the differentially expressed miRNAs between pancreatic cancer tissues and paracancerous tissues, and to analyze the survival rate and clinical stage of pancreatic cancer patients with high or low miRNA expression; TarBase was used for the cancer related GO function and KEGG pathway analysis of the miRNAs, DIANATools, miRDB and TargetScan websites were used to predict the target genes of miR-203a-3p. miR-203a-3p mimic and NC mimic, miR-203a-3p inhibitor and NC inhibitor were transfected into BxPC-3 cells. The expression levels of miR-203a-3p, miR-192-5p and miR-451a in normal pancreatic epithelial HPNE cells and pancreatic cancer cells were detected by qPCR. The proliferation, migration, invasion and colony formation abilities of BxPC-3 cells were detected by CCK-8, Transwell chamber assay and Colony formation assay, respectively. Results: A total of 18 differentially expressed miRNAs in pancreatic cancer tissues were screened out by TCGA database, among which miR-203a[1]3p, miR-192-5p and miR-451a were species-conservative and significantly correlated with clinical cancer stage, cell cycle and survival rate of pancreatic cancer patients (all P<0.05); Bioinformatics tool predicted that PPM1A might be the candidate target gene of miR[1] 203a-3p and could interact with multiple genes. miR-203a-3p, miR-192-5p and miR-451a were highly expressed in BxPC-3 and Aspc[1] cells (all P<0.001). In miR-203a-3p mimic group, the expression level of miR-203a-3p and the proliferation, migration and invasion ability of BxPC-3 cells were significantly increased (all P<0.01); however, in miR-203a-3p inhibitor group, the expression level of miR-203a-3p and the ability of cell proliferation, migration and invasion were significantly decreased (all P<0.01). Conclusion: miR-203a-3p is highly expressed in pancreatic cancer tissues and cells, and its expression is related to the survival and clinical stage of patients. miR-203a-3p may regulate the proliferation, migration and invasion of BxPC-3 cells.
Objective: To investigate the effects of miR-203a-3p on the proliferation, migration and invasion ability of pancreatic cancer BxPC-3 cells. Methods: The Cancer Genome Atlas (TCGA) database was used to screen the differentially expressed miRNAs between pancreatic cancer tissues and paracancerous tissues, and to analyze the survival rate and clinical stage of pancreatic cancer patients with high or low miRNA expression; TarBase was used for the cancer related GO function and KEGG pathway analysis of the miRNAs, DIANATools, miRDB and TargetScan websites were used to predict the target genes of miR-203a-3p. miR-203a-3p mimic and NC mimic, miR-203a-3p inhibitor and NC inhibitor were transfected into BxPC-3 cells. The expression levels of miR-203a-3p, miR-192-5p and miR-451a in normal pancreatic epithelial HPNE cells and pancreatic cancer cells were detected by qPCR. The proliferation, migration, invasion and colony formation abilities of BxPC-3 cells were detected by CCK-8, Transwell chamber assay and Colony formation assay, respectively. Results: A total of 18 differentially expressed miRNAs in pancreatic cancer tissues were screened out by TCGA database, among which miR-203a[1]3p, miR-192-5p and miR-451a were species-conservative and significantly correlated with clinical cancer stage, cell cycle and survival rate of pancreatic cancer patients (all P<0.05); Bioinformatics tool predicted that PPM1A might be the candidate target gene of miR[1] 203a-3p and could interact with multiple genes. miR-203a-3p, miR-192-5p and miR-451a were highly expressed in BxPC-3 and Aspc[1] cells (all P<0.001). In miR-203a-3p mimic group, the expression level of miR-203a-3p and the proliferation, migration and invasion ability of BxPC-3 cells were significantly increased (all P<0.01); however, in miR-203a-3p inhibitor group, the expression level of miR-203a-3p and the ability of cell proliferation, migration and invasion were significantly decreased (all P<0.01). Conclusion: miR-203a-3p is highly expressed in pancreatic cancer tissues and cells, and its expression is related to the survival and clinical stage of patients. miR-203a-3p may regulate the proliferation, migration and invasion of BxPC-3 cells.
2021, 28(7):689-695.
Abstract:
Objective: To explore the effects of miR-206 on the proliferation and invasion of ER-α36-positive gastric cancer (GC) BGC-823 cells induced by estrogen and its related mechanisms. Methods: ER- α36-positive BGC-823 cells were stimulated with estradiol (E2) at different concentrations (1, 10 and 100 pmol/L), then, the expression level of miR-206 was detected by qPCR, the proliferation and invasion were respectively determined by MTT and Transwell assays, and the expression of cyclin-dependent kinase 14 (CDK14) protein was detected by WB. After transfecting miR-206 mimic, miR-NC, pcDNA-CDK14 or pcDNA-vector into ER-α36 positive BGC-823 cells and stimulating them with 100 pmol/L E2, the proliferation and invasion ability of the cells were respectively detected by MTT assay and Transwell assays, and the expression of CDK14 was detected by WB assay. The targeting relationship between miR-206 and CDK14 was verified by Dual luciferase reporter gene assay. Results: E2 significantly decreased the expression level of miR-206 (P<0.05 or P<0.01), enhanced the proliferation and invasion (P<0.05 or P<0.01), and up-regulated the expression level of CDK14 （P<0.01) in ER-α36-positive BGC-823 cells. Overexpression of miR-206 could significantly reduce the proliferation and invasion ability of ER-α36-positive BGC-823 cells induced by E2 (all P<0.01). miR-206 negatively regulated the expression of CDK14 by directly binding to the 3'-UTR of CDK14 mRNA, thereby inhibiting the proliferation and invasion of ER- α -positive BGC-823 cells (all P<0.01). Conclusion: miR-206 inhibits the proliferation and invasion of estrogen-induced ER- α36-positive GC cells by targeting CDK14.
Objective: To explore the effects of miR-206 on the proliferation and invasion of ER-α36-positive gastric cancer (GC) BGC-823 cells induced by estrogen and its related mechanisms. Methods: ER- α36-positive BGC-823 cells were stimulated with estradiol (E2) at different concentrations (1, 10 and 100 pmol/L), then, the expression level of miR-206 was detected by qPCR, the proliferation and invasion were respectively determined by MTT and Transwell assays, and the expression of cyclin-dependent kinase 14 (CDK14) protein was detected by WB. After transfecting miR-206 mimic, miR-NC, pcDNA-CDK14 or pcDNA-vector into ER-α36 positive BGC-823 cells and stimulating them with 100 pmol/L E2, the proliferation and invasion ability of the cells were respectively detected by MTT assay and Transwell assays, and the expression of CDK14 was detected by WB assay. The targeting relationship between miR-206 and CDK14 was verified by Dual luciferase reporter gene assay. Results: E2 significantly decreased the expression level of miR-206 (P<0.05 or P<0.01), enhanced the proliferation and invasion (P<0.05 or P<0.01), and up-regulated the expression level of CDK14 （P<0.01) in ER-α36-positive BGC-823 cells. Overexpression of miR-206 could significantly reduce the proliferation and invasion ability of ER-α36-positive BGC-823 cells induced by E2 (all P<0.01). miR-206 negatively regulated the expression of CDK14 by directly binding to the 3'-UTR of CDK14 mRNA, thereby inhibiting the proliferation and invasion of ER- α -positive BGC-823 cells (all P<0.01). Conclusion: miR-206 inhibits the proliferation and invasion of estrogen-induced ER- α36-positive GC cells by targeting CDK14.
2021, 28(7):696-701.
Abstract:
Objective: To investigate the effects of 1,25(OH)2D3 (1,25-dihydroxy vitamin D3) on the proliferation, migration and cell cycle of esophageal squamous cell carcinoma (ESCC) cells and its mechanism. Methods: Human ESCC cells (TE-1, KYSE30, TE-11 and KYSE510) were treated with different concentrations of 1,25(OH)2D3, and the proliferation was detected by CCK-8. TE-11 and KYSE30 cells were treated with 1,25(OH)2D3 at concentrations of 0, 0.1, 0.15, and 0.2 μmol/L, respectively. Scratch healing test was used to detect cell migration ability, Flow cytometry was used to detect cell cycle distribution, and WB was used to detect the protein expressions of cyclin D1, P27, ERK and p-ERK. Results: 1,25(OH)2D3 significantly inhibited the proliferation of TE-11, KYSE30 cells in a concentration- and time-dependent manner (P<0.05 or P<0.01). As compared with control group, TE-11 and KYSE30 cells that treated with 0.1 and 0.2 μmol/L 1,25(OH)2D3 for 48 h exhibited significantly inhibited migration ability (P<0.05 or P<0.01)，increased cell population at G0/G1 phase (P<0.05 or P<0.01)，decreased protein expressions of cyclin D1 and p-ERK (P<0.05 or P<0.01)，and increased expression of P27 protein (P<0.05 or P<0.01)；however, there was no significant difference in total ERK level. Conclusion: 1,25(OH)2D3 can significantly inhibit the proliferation, migration and block the cell cycle of ESCC cells, which may be through the regulation of ERK signal pathway.
Objective: To investigate the effects of 1,25(OH)2D3 (1,25-dihydroxy vitamin D3) on the proliferation, migration and cell cycle of esophageal squamous cell carcinoma (ESCC) cells and its mechanism. Methods: Human ESCC cells (TE-1, KYSE30, TE-11 and KYSE510) were treated with different concentrations of 1,25(OH)2D3, and the proliferation was detected by CCK-8. TE-11 and KYSE30 cells were treated with 1,25(OH)2D3 at concentrations of 0, 0.1, 0.15, and 0.2 μmol/L, respectively. Scratch healing test was used to detect cell migration ability, Flow cytometry was used to detect cell cycle distribution, and WB was used to detect the protein expressions of cyclin D1, P27, ERK and p-ERK. Results: 1,25(OH)2D3 significantly inhibited the proliferation of TE-11, KYSE30 cells in a concentration- and time-dependent manner (P<0.05 or P<0.01). As compared with control group, TE-11 and KYSE30 cells that treated with 0.1 and 0.2 μmol/L 1,25(OH)2D3 for 48 h exhibited significantly inhibited migration ability (P<0.05 or P<0.01)，increased cell population at G0/G1 phase (P<0.05 or P<0.01)，decreased protein expressions of cyclin D1 and p-ERK (P<0.05 or P<0.01)，and increased expression of P27 protein (P<0.05 or P<0.01)；however, there was no significant difference in total ERK level. Conclusion: 1,25(OH)2D3 can significantly inhibit the proliferation, migration and block the cell cycle of ESCC cells, which may be through the regulation of ERK signal pathway.
2021, 28(7):702-708.
Abstract:
Objective: To explore the synergistic effect of Fe3O4 nanoparticles (PION), as a drug carrier, on enhancing the effect of chlorin e6 (Ce6) in glioma. Methods: PEG-Fe3O4@Ce6 composite nanoparticles (PION@E6) were prepared by high temperature degradation method and phase transfer method, and then verified by hydrated particle size analysis, transmission electron microscopy, colloidal stability analysis and ultraviolet-visible light absorption spectroscopy, etc. CCK-8 method was used to detect the proliferation activity of glioma U251 cells, Flow cytometry was used to detect the apoptosis of the cells, and the DCFH-DA probe method was used to detect the level of reactive oxygen species (ROS) in the cells. Glioma U251 cell transplanted tumor model was constructed on BALB/c-nu nude mice. The retention time of PION@E6 and Ce6 in transplanted tumors was observed with animal fluorescence imaging technology and magnetic resonance imaging (MRI), and the survival and tumor volume on the 28th day in the PION@E6 sonodynamic therapy group and Ce6 sonodynamic therapy group were compared. Results: Transmission electron microscopy and hydrated particle size analysis showed that the core particle size of PION@E6 was 10 nm and the hydrated particle size was (37.86±12.90) nm; colloidal stability analysis showed that PION@E6 had good water solubility and stability; and the absorption spectrum and XRD atlas showed that Ce6 had been loaded on Fe3O4 nanoparticles. Compared with the Ce6 sonodynamic group, the proliferation activity of U251 cells in the PION@E6 sonodynamic group was significantly decreased (P<0.05)， the apoptosis rate was significantly increased (all P<0.05)，and the level of ROS in the cells was significantly increased (P<0.05). In vivo experiments on nude mice bearing glioma U251 cell transplanted tumors showed that compared with Ce6 sonodynamic therapy group, the retention time of Ce6 in the transplanted tumor tissues of the PION@E6 sonodynamic therapy group was significantly prolonged (P<0.05)，the number of survived nude mice was significant increased, and the transplanted tumor volume was significantly reduced (P<0.01). Conclusion: Fe3O4 nanoparticles have a significant synergistic effect on Ce6-mediated sonodynamic therapy of glioma U251 cells.
Objective: To explore the synergistic effect of Fe3O4 nanoparticles (PION), as a drug carrier, on enhancing the effect of chlorin e6 (Ce6) in glioma. Methods: PEG-Fe3O4@Ce6 composite nanoparticles (PION@E6) were prepared by high temperature degradation method and phase transfer method, and then verified by hydrated particle size analysis, transmission electron microscopy, colloidal stability analysis and ultraviolet-visible light absorption spectroscopy, etc. CCK-8 method was used to detect the proliferation activity of glioma U251 cells, Flow cytometry was used to detect the apoptosis of the cells, and the DCFH-DA probe method was used to detect the level of reactive oxygen species (ROS) in the cells. Glioma U251 cell transplanted tumor model was constructed on BALB/c-nu nude mice. The retention time of PION@E6 and Ce6 in transplanted tumors was observed with animal fluorescence imaging technology and magnetic resonance imaging (MRI), and the survival and tumor volume on the 28th day in the PION@E6 sonodynamic therapy group and Ce6 sonodynamic therapy group were compared. Results: Transmission electron microscopy and hydrated particle size analysis showed that the core particle size of PION@E6 was 10 nm and the hydrated particle size was (37.86±12.90) nm; colloidal stability analysis showed that PION@E6 had good water solubility and stability; and the absorption spectrum and XRD atlas showed that Ce6 had been loaded on Fe3O4 nanoparticles. Compared with the Ce6 sonodynamic group, the proliferation activity of U251 cells in the PION@E6 sonodynamic group was significantly decreased (P<0.05)， the apoptosis rate was significantly increased (all P<0.05)，and the level of ROS in the cells was significantly increased (P<0.05). In vivo experiments on nude mice bearing glioma U251 cell transplanted tumors showed that compared with Ce6 sonodynamic therapy group, the retention time of Ce6 in the transplanted tumor tissues of the PION@E6 sonodynamic therapy group was significantly prolonged (P<0.05)，the number of survived nude mice was significant increased, and the transplanted tumor volume was significantly reduced (P<0.01). Conclusion: Fe3O4 nanoparticles have a significant synergistic effect on Ce6-mediated sonodynamic therapy of glioma U251 cells.
2021, 28(7):709-713.
Abstract:
Objective: To investigate the prognostic value of microenvironmental typing in patients with malignant melanoma (MM). Methods: Next generation sequencing (NGS) was performed on 87 cases of primary MM tissues that had been surgically removed in Nanjing Drum Tower Hospital from July 2010 to May 2017. Immunohistochemistry was carried out to detect the expressions of PD-1, PD-L1, CD3+TIL, MSH2, MSH6, PMS2 and MLH1. The survival of these patients was followed up. Then, the effects of different immune microenvironment types on prognosis and gene expression profile of patients were analyzed. Results: According to the expression level of PD-L1 and TIL, MM patients were divided into 4 immune microenvironment subtypes, including PD-L1+TIL+ group (15/87, 17.24%), PD-L1+ TIL- group (15/87, 17.24%), PD-L1- TIL+ group (20/87, 22.99%), and PD-L1- TIL- group (37/87, 42.53%). The median disease free survival (DFS) time of PD-L1+ TIL+ patients was significantly longer than that of PD-L1- TIL- patients (P<0.05)， which might be related with more copy number amplification of poor prognosis-associated genes in PD-L1- TIL- patients, such as CDK4, MCL1, MYC, AKT2, CCND1 and FGF19. It was found that the expression of PD-1 in PD-L1+ TIL+ patients was significantly higher than that in PD-L1- TIL- ones (P<0.01)，which may be related to the co-expression or un-expression of PD-L1 and PD-1 as well as TIL and PD-1. Conclusion: The microenvironment of MM patients can be divided into four subtypes according to the expression of PD-L1 and TIL, which can distinguish the prognosis of MM patients. The PD-L1- TIL- patients have more copy number amplification of poor prognosis related genes.
Objective: To investigate the prognostic value of microenvironmental typing in patients with malignant melanoma (MM). Methods: Next generation sequencing (NGS) was performed on 87 cases of primary MM tissues that had been surgically removed in Nanjing Drum Tower Hospital from July 2010 to May 2017. Immunohistochemistry was carried out to detect the expressions of PD-1, PD-L1, CD3+TIL, MSH2, MSH6, PMS2 and MLH1. The survival of these patients was followed up. Then, the effects of different immune microenvironment types on prognosis and gene expression profile of patients were analyzed. Results: According to the expression level of PD-L1 and TIL, MM patients were divided into 4 immune microenvironment subtypes, including PD-L1+TIL+ group (15/87, 17.24%), PD-L1+ TIL- group (15/87, 17.24%), PD-L1- TIL+ group (20/87, 22.99%), and PD-L1- TIL- group (37/87, 42.53%). The median disease free survival (DFS) time of PD-L1+ TIL+ patients was significantly longer than that of PD-L1- TIL- patients (P<0.05)， which might be related with more copy number amplification of poor prognosis-associated genes in PD-L1- TIL- patients, such as CDK4, MCL1, MYC, AKT2, CCND1 and FGF19. It was found that the expression of PD-1 in PD-L1+ TIL+ patients was significantly higher than that in PD-L1- TIL- ones (P<0.01)，which may be related to the co-expression or un-expression of PD-L1 and PD-1 as well as TIL and PD-1. Conclusion: The microenvironment of MM patients can be divided into four subtypes according to the expression of PD-L1 and TIL, which can distinguish the prognosis of MM patients. The PD-L1- TIL- patients have more copy number amplification of poor prognosis related genes.
2021, 28(7):714-720.
Abstract:
Objective：To investigate the effect of Helicobacter pylori (Hp) infection on gene expression of ataxia-telangiectasia mutant (ATM) in gastric cancer cells and its clinical significance. Methods: The gastric cancer related RNAseq data was obtained from the TCGA database to compare the differential expressions of ATM. The correlation between ATM expression and clinicopathological parameters as well as the prognostic value of ATM was analyzed. Kaplan-Meier method was used for survival analysis, LinkedOmics database was utilized to analyze ATM-related genes, and R language was used for GO and KEGG enrichment analysis. Twelve pairs of gastric cancer tissues and para-cancerous tissues resected in the Affiliated Hospital of Guizhou Medical University from March 2019 to December 2019 as well as gastric cancer cell lines (AGS and BGC823) were collected for this study. Bacterial Hp GZ7 at a MOI (multiplicity of infection) of 40∶1 was used to infect the cells. The protein expression of ATM in gastric cancer tissues was detected using immunohistochemical staining, and the mRNA expression of ATM in gastric cancer tissues and cells was determined using qPCR. Results: TCGA data showed that the miRNA expression of ATM in gastric cancer tissues and Hp-infected gastric cancer tissues was significantly higher than that in para-cancerous tissues (all P<0.01). The miRNA expression of ATM in the gastric cancer tissues was positively correlated with pathological parameters such as T and AJCC staging (all P<0.05) ; High ATM expression was accompanied with significantly reduced survival rate (P<0.05). Experiment results showed that the protein expression of ATM in gastric cancer tissues was significantly higher than that in para-cancerous tissues (P<0.01)，and the miRNA expression of ATM in Hp-infected gastric cancer cells was significantly higher than that in the uninfected gastric cancer cells (P<0.01). In gastric cancer, ATM gene was positively correlated with 12 461 genes such as NPAT (P<0.05)，and negatively correlated with 7 764 genes such as MIF (P<0.05).The GO and KEGG enrichment analyses showed that ATM is enriched in the pathways such as DNA repair complexes, transcription disorders in cancer. Conclusion: ATM gene is highly expressed in GC tissues, and its high expression results in decreased survival rate of patients. ATM gene is associated with pathological parameters such as patient's T stage and AJCC stage, and the increase in ATM expression level caused by Hp infection may be one of the reasons for Hp caused gastric cancer.
Objective：To investigate the effect of Helicobacter pylori (Hp) infection on gene expression of ataxia-telangiectasia mutant (ATM) in gastric cancer cells and its clinical significance. Methods: The gastric cancer related RNAseq data was obtained from the TCGA database to compare the differential expressions of ATM. The correlation between ATM expression and clinicopathological parameters as well as the prognostic value of ATM was analyzed. Kaplan-Meier method was used for survival analysis, LinkedOmics database was utilized to analyze ATM-related genes, and R language was used for GO and KEGG enrichment analysis. Twelve pairs of gastric cancer tissues and para-cancerous tissues resected in the Affiliated Hospital of Guizhou Medical University from March 2019 to December 2019 as well as gastric cancer cell lines (AGS and BGC823) were collected for this study. Bacterial Hp GZ7 at a MOI (multiplicity of infection) of 40∶1 was used to infect the cells. The protein expression of ATM in gastric cancer tissues was detected using immunohistochemical staining, and the mRNA expression of ATM in gastric cancer tissues and cells was determined using qPCR. Results: TCGA data showed that the miRNA expression of ATM in gastric cancer tissues and Hp-infected gastric cancer tissues was significantly higher than that in para-cancerous tissues (all P<0.01). The miRNA expression of ATM in the gastric cancer tissues was positively correlated with pathological parameters such as T and AJCC staging (all P<0.05) ; High ATM expression was accompanied with significantly reduced survival rate (P<0.05). Experiment results showed that the protein expression of ATM in gastric cancer tissues was significantly higher than that in para-cancerous tissues (P<0.01)，and the miRNA expression of ATM in Hp-infected gastric cancer cells was significantly higher than that in the uninfected gastric cancer cells (P<0.01). In gastric cancer, ATM gene was positively correlated with 12 461 genes such as NPAT (P<0.05)，and negatively correlated with 7 764 genes such as MIF (P<0.05).The GO and KEGG enrichment analyses showed that ATM is enriched in the pathways such as DNA repair complexes, transcription disorders in cancer. Conclusion: ATM gene is highly expressed in GC tissues, and its high expression results in decreased survival rate of patients. ATM gene is associated with pathological parameters such as patient's T stage and AJCC stage, and the increase in ATM expression level caused by Hp infection may be one of the reasons for Hp caused gastric cancer.
2021, 28(7):721-727.
Abstract:
Objective: To investigate the expression of miR-17-5p in gastrointestinal stromal tumor (GIST) tissues and its effect on proliferation and apoptosis of GIST882 cells. Methods: Twenty pairs of GIST tissues and corresponding paratumoral tissues form patients who underwent gastrointestinal surgery in the Fourth Affiliated Hospital of Guangxi Medical University from May 2019 to May 2020 were selected for this study; at the same time, GIST882 cells and human intestinal epithelial cells (HIECs) were also collected for this study. The KIT gene mutations in GIST tissue samples were detected by fluorescence PCR-capillary electrophoresis sequencing. The miR-17-5p mimics and pc-KIT plasmids were transfected into GIST882 cells, respectively. The targeting relationship between miR-17-5p and KIT was verified by Dual-luciferase reporter gene assay. The mRNA and protein expressions of miR-17-5p and KIT in GIST tissues and GIST882 cells were detected by qPCR and WB, respectively; and the proliferation, apoptosis and cell cycle progression of the cells were detected by CCK-8 and Flow cytometry. Results: KIT gene mutations occurred in 15 GIST patients (15/20). Compared with paratumoral tissues, miR-17-5p expression was significantly decreased while KIT mRNA expression was significantly increased in GIST tissues (all P<0.01); compared with HIEC cells, miR-17-5p expression was significantly decreased while mRNA and protein expressions of KIT were significantly increased in GIST882 cells (all P<0.01). Overexpression of miR-17-5p significantly decreased the proliferation ability and increased the apoptosis rate of GIST882 cells (P<0.01 or P<0.05), increased the proportion of cells in sub-G1 and S phases (P<0.05), and decreased the expression level of KIT protein (P<0.01). Dual-luciferase reporter gene assay confirmed that KIT is a downstream target gene of miR-17-5p. Simultaneous overexpression of miR-17-5p and KIT did not produce significant effects on the proliferation, cell cycle progression and apoptotic levels of GIST882 cells. Conclusion: Overexpression of miR-17-5p can significantly inhibit the proliferation and induce apoptosis of GIST882 cells and downregulate the expression of KIT protein. miR-17-5p may be a potential target in the treatment of GIST.
Objective: To investigate the expression of miR-17-5p in gastrointestinal stromal tumor (GIST) tissues and its effect on proliferation and apoptosis of GIST882 cells. Methods: Twenty pairs of GIST tissues and corresponding paratumoral tissues form patients who underwent gastrointestinal surgery in the Fourth Affiliated Hospital of Guangxi Medical University from May 2019 to May 2020 were selected for this study; at the same time, GIST882 cells and human intestinal epithelial cells (HIECs) were also collected for this study. The KIT gene mutations in GIST tissue samples were detected by fluorescence PCR-capillary electrophoresis sequencing. The miR-17-5p mimics and pc-KIT plasmids were transfected into GIST882 cells, respectively. The targeting relationship between miR-17-5p and KIT was verified by Dual-luciferase reporter gene assay. The mRNA and protein expressions of miR-17-5p and KIT in GIST tissues and GIST882 cells were detected by qPCR and WB, respectively; and the proliferation, apoptosis and cell cycle progression of the cells were detected by CCK-8 and Flow cytometry. Results: KIT gene mutations occurred in 15 GIST patients (15/20). Compared with paratumoral tissues, miR-17-5p expression was significantly decreased while KIT mRNA expression was significantly increased in GIST tissues (all P<0.01); compared with HIEC cells, miR-17-5p expression was significantly decreased while mRNA and protein expressions of KIT were significantly increased in GIST882 cells (all P<0.01). Overexpression of miR-17-5p significantly decreased the proliferation ability and increased the apoptosis rate of GIST882 cells (P<0.01 or P<0.05), increased the proportion of cells in sub-G1 and S phases (P<0.05), and decreased the expression level of KIT protein (P<0.01). Dual-luciferase reporter gene assay confirmed that KIT is a downstream target gene of miR-17-5p. Simultaneous overexpression of miR-17-5p and KIT did not produce significant effects on the proliferation, cell cycle progression and apoptotic levels of GIST882 cells. Conclusion: Overexpression of miR-17-5p can significantly inhibit the proliferation and induce apoptosis of GIST882 cells and downregulate the expression of KIT protein. miR-17-5p may be a potential target in the treatment of GIST.
2021, 28(7):728-731.
Abstract:
恶性肿瘤是严重威胁人类生命的疾病之一，近年来免疫治疗已经成为肿瘤治疗的焦点，解决免疫治疗只对部分患者 有效的问题迫在眉睫。在肿瘤微环境（tumor microenvironment，TME）中趋化因子介导细胞的定向移动，同时具有多种调节功能， 既可以作用于免疫细胞，也可直接作用于肿瘤细胞，发挥了复杂的生物学作用。CXC趋化因子受体3（CXC chemokine receptor 3， CXCR3）通过与其同源CXC趋化因子配体9（CXC chemokine ligand 9，CXCL9）/10/11结合，不仅参与了肿瘤发生、侵袭并促进肿 瘤相关血管的形成，同时也介导了免疫细胞向肿瘤组织中浸润，为无免疫反应性或免疫反应性差的“冷肿瘤”转变为免疫反应性 的“热肿瘤”提供了新的思路，并且可能成为治疗的新靶点。这种抗肿瘤和促肿瘤的双重作用，似乎与CXCR3变体（CXCR3-A、 CXCR3-B）发挥相反的作用密切相关。本文就近年来CXCR3变体CXCR3-A、CXCR3-B及其配体CXCL9/10/11在TME中作用的 研究进展展开综述。
恶性肿瘤是严重威胁人类生命的疾病之一，近年来免疫治疗已经成为肿瘤治疗的焦点，解决免疫治疗只对部分患者 有效的问题迫在眉睫。在肿瘤微环境（tumor microenvironment，TME）中趋化因子介导细胞的定向移动，同时具有多种调节功能， 既可以作用于免疫细胞，也可直接作用于肿瘤细胞，发挥了复杂的生物学作用。CXC趋化因子受体3（CXC chemokine receptor 3， CXCR3）通过与其同源CXC趋化因子配体9（CXC chemokine ligand 9，CXCL9）/10/11结合，不仅参与了肿瘤发生、侵袭并促进肿 瘤相关血管的形成，同时也介导了免疫细胞向肿瘤组织中浸润，为无免疫反应性或免疫反应性差的“冷肿瘤”转变为免疫反应性 的“热肿瘤”提供了新的思路，并且可能成为治疗的新靶点。这种抗肿瘤和促肿瘤的双重作用，似乎与CXCR3变体（CXCR3-A、 CXCR3-B）发挥相反的作用密切相关。本文就近年来CXCR3变体CXCR3-A、CXCR3-B及其配体CXCL9/10/11在TME中作用的 研究进展展开综述。
2021, 28(7):732-737.
Abstract:
程序性死亡蛋白-1（programmed death protein 1，PD-1）是表达在T细胞表面的一种重要的免疫抑制穿膜蛋白，在限制慢 性炎症、感染或肿瘤中T细胞的活性方面起重要作用。可溶性PD-1（soluble PD-1，sPD-1）是由PD-1缺失3号外显子的转录剪接体 转录翻译而来，无法形成穿膜区，但其具有胞外结构域，具有与配体PD-L1/PD-L2结合的能力，能激活T细胞并促进DC成熟，而发 挥抗肿瘤作用。随着免疫疗法及免疫检查点阻断治疗的出现并逐渐成为肿瘤治疗的新兴手段，关于PD-1及其抗体的基础及临床 转化研究也成为肿瘤研究的热点之一。不同形式的PD-1被发现，意味着PD-1可能在机体中发挥着更加复杂及多面的功能，因此对 于sPD-1的研究也逐渐展开及深入。本文就sPD-1作为肿瘤诊断、疗效预测及预后评估的潜在标志物及联合抗肿瘤免疫治疗中的 临床应用研究进展作一综述，以期了解sPD-1在抗肿瘤治疗中的重要作用，为肿瘤免疫治疗提供新思路、新方法和新策略。
程序性死亡蛋白-1（programmed death protein 1，PD-1）是表达在T细胞表面的一种重要的免疫抑制穿膜蛋白，在限制慢 性炎症、感染或肿瘤中T细胞的活性方面起重要作用。可溶性PD-1（soluble PD-1，sPD-1）是由PD-1缺失3号外显子的转录剪接体 转录翻译而来，无法形成穿膜区，但其具有胞外结构域，具有与配体PD-L1/PD-L2结合的能力，能激活T细胞并促进DC成熟，而发 挥抗肿瘤作用。随着免疫疗法及免疫检查点阻断治疗的出现并逐渐成为肿瘤治疗的新兴手段，关于PD-1及其抗体的基础及临床 转化研究也成为肿瘤研究的热点之一。不同形式的PD-1被发现，意味着PD-1可能在机体中发挥着更加复杂及多面的功能，因此对 于sPD-1的研究也逐渐展开及深入。本文就sPD-1作为肿瘤诊断、疗效预测及预后评估的潜在标志物及联合抗肿瘤免疫治疗中的 临床应用研究进展作一综述，以期了解sPD-1在抗肿瘤治疗中的重要作用，为肿瘤免疫治疗提供新思路、新方法和新策略。
2021, 28(7):738-745.
Abstract:
肿瘤干细胞（cancer stem cell，CSC）与正常干细胞生物学特征相似，具有自我更新、无限增殖和抗化学毒物损伤的能力， 与肿瘤的发生、治疗、预后、复发和转移关系极为密切。在肿瘤发生初期，虽然机体的免疫监视系统可以有效地对肿瘤细胞进行识 别和清除，但CSC可通过下调抗原加工和提呈机制成分、分泌免疫抑制因子、高表达免疫检查点分子以及激活免疫耐受信号通路等 机制调控免疫细胞功能，或促进抑制性免疫微环境的建立以逃避免疫系统对其的清除，从而使肿瘤得以进展。目前，靶向CSC与免 疫系统相互作用的多种方法正在被积极研究中，一些靶向CSC的新型免疫疗法正处于临床研发阶段。本文综述了近年来CSC相关 免疫逃逸机制及针对免疫逃逸的可能有效的治疗手段（包括DC疫苗、CAR-T细胞、免疫检查点抑制剂等）的研究进展。
肿瘤干细胞（cancer stem cell，CSC）与正常干细胞生物学特征相似，具有自我更新、无限增殖和抗化学毒物损伤的能力， 与肿瘤的发生、治疗、预后、复发和转移关系极为密切。在肿瘤发生初期，虽然机体的免疫监视系统可以有效地对肿瘤细胞进行识 别和清除，但CSC可通过下调抗原加工和提呈机制成分、分泌免疫抑制因子、高表达免疫检查点分子以及激活免疫耐受信号通路等 机制调控免疫细胞功能，或促进抑制性免疫微环境的建立以逃避免疫系统对其的清除，从而使肿瘤得以进展。目前，靶向CSC与免 疫系统相互作用的多种方法正在被积极研究中，一些靶向CSC的新型免疫疗法正处于临床研发阶段。本文综述了近年来CSC相关 免疫逃逸机制及针对免疫逃逸的可能有效的治疗手段（包括DC疫苗、CAR-T细胞、免疫检查点抑制剂等）的研究进展。
2021, 28(7):746-750.
Abstract:
胰腺癌是病死率极高的消化系统恶性肿瘤，其发病隐匿且进展迅速，多数患者确诊时已为晚期，常规化疗、放疗效果 不佳，患者5年生存率不到10%。近年来肿瘤免疫治疗已成为肿瘤精准治疗的热门方向，主要包括过继性细胞治疗、肿瘤疫苗及 免疫检查点抑制剂等。基因指导下的个体化免疫治疗是进一步提高免疫治疗效果的主要方法。在众多致病因素中，KRAS突变 是胰腺癌发生发展和耐药的主要驱动因素，接近90%的胰腺癌患者存在KRAS突变，到目前为止仍然没有一种针对KRAS突变 的靶向药物或者免疫治疗获得大样本临床研究阳性数据。近几年随着免疫学机制和免疫治疗基础研究的深入，针对KRAS突变 的个体化免疫治疗获得了一些可喜的结果，包括TIL、TCR-T、CAR-T、个体化肿瘤疫苗以及免疫检查点抑制剂等。本文就近几年 针对KRAS突变的个体化免疫治疗在胰腺癌中的研究进展作一综述。
胰腺癌是病死率极高的消化系统恶性肿瘤，其发病隐匿且进展迅速，多数患者确诊时已为晚期，常规化疗、放疗效果 不佳，患者5年生存率不到10%。近年来肿瘤免疫治疗已成为肿瘤精准治疗的热门方向，主要包括过继性细胞治疗、肿瘤疫苗及 免疫检查点抑制剂等。基因指导下的个体化免疫治疗是进一步提高免疫治疗效果的主要方法。在众多致病因素中，KRAS突变 是胰腺癌发生发展和耐药的主要驱动因素，接近90%的胰腺癌患者存在KRAS突变，到目前为止仍然没有一种针对KRAS突变 的靶向药物或者免疫治疗获得大样本临床研究阳性数据。近几年随着免疫学机制和免疫治疗基础研究的深入，针对KRAS突变 的个体化免疫治疗获得了一些可喜的结果，包括TIL、TCR-T、CAR-T、个体化肿瘤疫苗以及免疫检查点抑制剂等。本文就近几年 针对KRAS突变的个体化免疫治疗在胰腺癌中的研究进展作一综述。
2021, 28(7):751-754.
Abstract:
骨肉瘤是一种好发于青少年、高度恶性、侵袭性强、易转移的成骨恶性肿瘤。新辅助化疗结合外科治疗使骨肉瘤患者 5年生存期超过50%，但针对合并复发和转移的骨肉瘤患者治疗效果仍不理想。免疫治疗被证明是一种行之有效的治疗人类恶 性肿瘤的策略。逃避免疫监测被认为是肿瘤恶性进展的主要因素，免疫检查点在调控抗肿瘤免疫效果中发挥重要作用，因此针 对这些免疫检查点的阻断剂或抑制剂已成为肿瘤患者有效的治疗手段。本文就近年来PD-1/PD-L1通路抑制剂在难治性骨肉瘤 治疗中的作用及机制、临床应用、疗效与安全性等的研究进展进行综述。
骨肉瘤是一种好发于青少年、高度恶性、侵袭性强、易转移的成骨恶性肿瘤。新辅助化疗结合外科治疗使骨肉瘤患者 5年生存期超过50%，但针对合并复发和转移的骨肉瘤患者治疗效果仍不理想。免疫治疗被证明是一种行之有效的治疗人类恶 性肿瘤的策略。逃避免疫监测被认为是肿瘤恶性进展的主要因素，免疫检查点在调控抗肿瘤免疫效果中发挥重要作用，因此针 对这些免疫检查点的阻断剂或抑制剂已成为肿瘤患者有效的治疗手段。本文就近年来PD-1/PD-L1通路抑制剂在难治性骨肉瘤 治疗中的作用及机制、临床应用、疗效与安全性等的研究进展进行综述。
2021, 28(7):755-760.
Abstract:
肿瘤一直是人类医疗健康领域的巨大难题，其早期诊断和治疗是解决这一难题的关键。癌-睾丸抗原（cancer-testis antigen, CTA）是一类多功能蛋白家族，在男性精子细胞及肿瘤细胞中特异性表达，而在其他健康体细胞中无表达。研究发现 CTA参与肿瘤的发生发展，且部分CTA具有免疫原性，为肿瘤免疫治疗提供了可能。临床试验中已针对CTA家族中黑色素瘤相 关抗原1（MAGE1）和纽约食管鳞状上皮细胞癌1（NY-ESO-1）抗原进行多种肿瘤疫苗研究，展现了一定的临床疗效及良好的生物 安全性；CTA在正常组织和肿瘤细胞中的表达差异及功能研究有利于推动肿瘤标志物的筛选及新的免疫疗法的开发。本文主要 综述了CTA的生物学特性及其在肿瘤诊断和免疫治疗中作用的研究进展。
肿瘤一直是人类医疗健康领域的巨大难题，其早期诊断和治疗是解决这一难题的关键。癌-睾丸抗原（cancer-testis antigen, CTA）是一类多功能蛋白家族，在男性精子细胞及肿瘤细胞中特异性表达，而在其他健康体细胞中无表达。研究发现 CTA参与肿瘤的发生发展，且部分CTA具有免疫原性，为肿瘤免疫治疗提供了可能。临床试验中已针对CTA家族中黑色素瘤相 关抗原1（MAGE1）和纽约食管鳞状上皮细胞癌1（NY-ESO-1）抗原进行多种肿瘤疫苗研究，展现了一定的临床疗效及良好的生物 安全性；CTA在正常组织和肿瘤细胞中的表达差异及功能研究有利于推动肿瘤标志物的筛选及新的免疫疗法的开发。本文主要 综述了CTA的生物学特性及其在肿瘤诊断和免疫治疗中作用的研究进展。
2021, 28(7):761-764.
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.