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Volume 28,Issue 6,2021 Table of Contents
2021, 28(6):549-557.
Abstract:
Chimeric antigen receptor-modified T cells (CAR-T cells) refers to the products after transferring genetic material with specific antigen recognition domain and T cell activation signal domains into T cells by gene modification technology, thus rendering the modified T cells activated by binding directly to specific antigens on the surface of tumor cells in the CAR-T cell therapy. In recent years, CAR-T cells have achieved remarkable results in the treatment of hematological diseases, bringing new hope to patients with hematological tumors. CAR-T cell therapy has become one of the most promising tumor immunotherapies, and CAR-T cells have become a hot spot for research and development by major companies. However, due to the side effects such as cytokine storm and poor treatment effect on solid tumors, the clinical application of CAR-T cells still faces challenges. In addition to traditional T cells, other immune cells are being explored for the application of CAR, for example, modifying immune cells such as NK cells, γδT cells, NKT cells, and macrophages to improve the effectiveness of these immune cells in killing tumors, and simultaneously reduce the adverse reactions caused by CAR-T cell immunotherapy. This review compares the advantages and disadvantages of different CAR[1]modified immune cells in tumor therapy and provides new ideas and enlightenments for the clinical development and application of CAR-modified immune cells in tumor immunotherapy.
Chimeric antigen receptor-modified T cells (CAR-T cells) refers to the products after transferring genetic material with specific antigen recognition domain and T cell activation signal domains into T cells by gene modification technology, thus rendering the modified T cells activated by binding directly to specific antigens on the surface of tumor cells in the CAR-T cell therapy. In recent years, CAR-T cells have achieved remarkable results in the treatment of hematological diseases, bringing new hope to patients with hematological tumors. CAR-T cell therapy has become one of the most promising tumor immunotherapies, and CAR-T cells have become a hot spot for research and development by major companies. However, due to the side effects such as cytokine storm and poor treatment effect on solid tumors, the clinical application of CAR-T cells still faces challenges. In addition to traditional T cells, other immune cells are being explored for the application of CAR, for example, modifying immune cells such as NK cells, γδT cells, NKT cells, and macrophages to improve the effectiveness of these immune cells in killing tumors, and simultaneously reduce the adverse reactions caused by CAR-T cell immunotherapy. This review compares the advantages and disadvantages of different CAR[1]modified immune cells in tumor therapy and provides new ideas and enlightenments for the clinical development and application of CAR-modified immune cells in tumor immunotherapy.
2021, 28(6):558-566.
Abstract:
Objective: To explore the molecular mechanism of miR-125a-5p suppressing the migration and invasion of gastric cancer cells by regulating expression of Bcl-2-associated athanogene 4 (BAG4) gene. Method: A total of 82 pairs of gastric cancer tissues and corresponding para-cancer tissues were obtained from gastric cancer patients who received curative surgery at the First Hospital of Lanzhou University during January 2014 to December 2015. Human gastric cancer cell lines (MGC803, BGC823, SGC7901, HGC27) and human gastric epithelium cell line (GES-1) were also collected for this study. Real-time fluorescent quantitative PCR (qPCR) method was used to detect the expression level of miR-125a-5p in gastric cancer tissues, para-cancer tissues and gastric cancer cell lines. miR-125a-5p mimics, miR-125a-5p inhibitor, si-BAG4 (siRNA-BAG4) and negative control plasmids were transiently transfected into gastric cancer cells, respectively. The effect of miR-125a-5p/BAG4 signaling axis on migratory and invasive ability of gastric cancer cells was determined by Wound healing assay and Transwell invasion assay, respectively. WB was used to detect BAG4 protein expression in gastric cancer cells. The targeted regulatory relationship between miR-125a-5p and BAG4 was determined by Luciferase reporter gene assay. Result: miR-125a-5p was down-regulated in gastric cancer tissues and gastric cancer cell lines. The expression level of miR-125a-5p was not correlated with gender (P=0.953), age (P=0.772), tumor location (P=0.867), histological grade (P=0.745) and tumor size (P=0.088) of gastric cancer patients, but significantly correlated with T stage (P=0.003), N stage (P=0.001), M stage (P=0.027) and TNM stage (P=0.035) in gastric cancer patients, and the differences were statistically significant. Low expression of miR-125a-5p was an independent risk factor for overall survival of gastric cancer patients. miR-125a-5p significantly inhibited the migration and invasion of gastric cancer cells (all P<0.01). Knockdown BAG4 could reverse the inhibitory effect of miR-125a-5p inhibitor on migration and invasion of gastric cancer cells. Luciferase reporter gene assay validated that miR[1]125a-5p could bind with BAG4 3'UTR (Untranslated Regions) to suppress its expression. Conclusion: miR-125a-5p inhibits the migration and invasion of gastric cancer cells by down-regulating the expression level of BAG4.
Objective: To explore the molecular mechanism of miR-125a-5p suppressing the migration and invasion of gastric cancer cells by regulating expression of Bcl-2-associated athanogene 4 (BAG4) gene. Method: A total of 82 pairs of gastric cancer tissues and corresponding para-cancer tissues were obtained from gastric cancer patients who received curative surgery at the First Hospital of Lanzhou University during January 2014 to December 2015. Human gastric cancer cell lines (MGC803, BGC823, SGC7901, HGC27) and human gastric epithelium cell line (GES-1) were also collected for this study. Real-time fluorescent quantitative PCR (qPCR) method was used to detect the expression level of miR-125a-5p in gastric cancer tissues, para-cancer tissues and gastric cancer cell lines. miR-125a-5p mimics, miR-125a-5p inhibitor, si-BAG4 (siRNA-BAG4) and negative control plasmids were transiently transfected into gastric cancer cells, respectively. The effect of miR-125a-5p/BAG4 signaling axis on migratory and invasive ability of gastric cancer cells was determined by Wound healing assay and Transwell invasion assay, respectively. WB was used to detect BAG4 protein expression in gastric cancer cells. The targeted regulatory relationship between miR-125a-5p and BAG4 was determined by Luciferase reporter gene assay. Result: miR-125a-5p was down-regulated in gastric cancer tissues and gastric cancer cell lines. The expression level of miR-125a-5p was not correlated with gender (P=0.953), age (P=0.772), tumor location (P=0.867), histological grade (P=0.745) and tumor size (P=0.088) of gastric cancer patients, but significantly correlated with T stage (P=0.003), N stage (P=0.001), M stage (P=0.027) and TNM stage (P=0.035) in gastric cancer patients, and the differences were statistically significant. Low expression of miR-125a-5p was an independent risk factor for overall survival of gastric cancer patients. miR-125a-5p significantly inhibited the migration and invasion of gastric cancer cells (all P<0.01). Knockdown BAG4 could reverse the inhibitory effect of miR-125a-5p inhibitor on migration and invasion of gastric cancer cells. Luciferase reporter gene assay validated that miR[1]125a-5p could bind with BAG4 3'UTR (Untranslated Regions) to suppress its expression. Conclusion: miR-125a-5p inhibits the migration and invasion of gastric cancer cells by down-regulating the expression level of BAG4.
2021, 28(6):567-573.
Abstract:
Objective: To explore the effect of miR-1207-5p on the proliferation, migration and invasion of breast cancer T47D stem cells and its possible mechanism. Methods: Breast cancer T47D stem cells were induced and enriched with IGF-1, EGF and bFGF and cultured into spheroids. The stem cells were separated by Flow cytometry, and molecular markers of stem cells were detected by WB. qPCR was used to detect the expression level of miR-1207-5p in stem cells, and Dual luciferase reporter gene assay was used to analyze the targeting relationship between miR-1207-5p and LIMD1. CCK-8, Transwell and Cell scratch test were used to detect the proliferation, migration and invasion ability of T47D stem cells. WB was used to detect the expression level of LIMD1 protein in stem cells. Results: The isolated stem cells could form cell spheres, and the volume of the cell spheres increased with the increase of culture days. The expressions of stem cell molecular markers ALDH1, ESA and OCT4 were significantly higher than those of the parental T47D cells (P<0.05 or P<0.01 ), and miR-1207-5p was highly expressed in stem cells (P<0.01). Overexpression of miR-1207-5p significantly promoted the proliferation, migration and invasion of T47D stem cells (all P<0.01), and knockdown of miR-1207-5p significantly inhibited the proliferation, migration and invasion of T47D stem cell (all P<0.01). miR-1207-5p targetedly downregulated the expression of LIMD1 (P<0.01), by which it promoted the proliferation, migration and invasion of breast cancer T47D stem cells (P<0.05 or P<0.01). Conclusion: miR-1207-5p promotes the proliferation, migration and invasion of breast cancer T47D stem cells by targeted downregulation of the expression of LIMD1.
Objective: To explore the effect of miR-1207-5p on the proliferation, migration and invasion of breast cancer T47D stem cells and its possible mechanism. Methods: Breast cancer T47D stem cells were induced and enriched with IGF-1, EGF and bFGF and cultured into spheroids. The stem cells were separated by Flow cytometry, and molecular markers of stem cells were detected by WB. qPCR was used to detect the expression level of miR-1207-5p in stem cells, and Dual luciferase reporter gene assay was used to analyze the targeting relationship between miR-1207-5p and LIMD1. CCK-8, Transwell and Cell scratch test were used to detect the proliferation, migration and invasion ability of T47D stem cells. WB was used to detect the expression level of LIMD1 protein in stem cells. Results: The isolated stem cells could form cell spheres, and the volume of the cell spheres increased with the increase of culture days. The expressions of stem cell molecular markers ALDH1, ESA and OCT4 were significantly higher than those of the parental T47D cells (P<0.05 or P<0.01 ), and miR-1207-5p was highly expressed in stem cells (P<0.01). Overexpression of miR-1207-5p significantly promoted the proliferation, migration and invasion of T47D stem cells (all P<0.01), and knockdown of miR-1207-5p significantly inhibited the proliferation, migration and invasion of T47D stem cell (all P<0.01). miR-1207-5p targetedly downregulated the expression of LIMD1 (P<0.01), by which it promoted the proliferation, migration and invasion of breast cancer T47D stem cells (P<0.05 or P<0.01). Conclusion: miR-1207-5p promotes the proliferation, migration and invasion of breast cancer T47D stem cells by targeted downregulation of the expression of LIMD1.
2021, 28(6):574-581.
Abstract:
Objective: To investigate the effect of long intergene non-coding RNA 00519 (LINC00519) on the proliferation, apoptosis, migration and invasion of gastric cancer HGC-27 cells by regulating the miR-876-3p / high mobility group protein A1 (HMGA1) axis. Methods: The expression levels of LINC00519 in gastric cancer HGC-27 cells and gastric mucosal epithelial GES-1 cells were detected by qPCR. HGC-27 cells were divided into si-NC, si-LINC00519, si-LINC00519+anti-miR-NC, and si-LINC00519 + anti-miR[1]876-3p groups according to transfection treatment. Colony formation test was applied to detect cell cloning ability; Flow cytometry was used to detect apoptosis and cell cycle distribution; Transwell assay was selected to measure cell migration and invasion. Dual luciferase reporter gene assay and qPCR were applied to confirm the interaction between LINC00519 and miR-876-3p as well as between miR-876-3p and HMGA1. Results: The expression of LINC00519 in HGC-27 cells was significantly higher than that in GES[1] 1 cells (P <0.05). After siRNA transfection, the expression level of LINC00519 in HGC-27 cells of the si-LINC00519 group was significantly lower than that of the si-NC group (t=47.294, P<0.01). Compared with the si-NC group, the number of HGC-27 cell clones, the number of migrated and invaded cells, and proportion of S-phase cells in the si-LINC00519 group were significantly decreased (all P<0.01), while the apoptosis rate and the proportion of G0/G1 phase cells were significantly increased (all P <0.01). Compared with the si-LINC00519+anti-miR-NC group, the number of HGC-27 cell clones, the number of migrated and invaded cells, proportion of S-phase cells were significantly increased (all P<0.01), while the apoptosis rate and the proportion of G0/G1 phase cells in the si-LINC00519 + anti-miR-876-3p group were significantly decreased (all P<0.01), LINC00519 could target and negatively regulate miR-876-3p expression. miR-876-3p could target and negatively regulate HMGA1 expression. Conclusion: Knocking down LINC00519 could inhibit the proliferation, migration and invasion of gastric cancer HGC-27 cells and induce apoptosis by regulating the miR-876-3p/HMGA1 axis.
Objective: To investigate the effect of long intergene non-coding RNA 00519 (LINC00519) on the proliferation, apoptosis, migration and invasion of gastric cancer HGC-27 cells by regulating the miR-876-3p / high mobility group protein A1 (HMGA1) axis. Methods: The expression levels of LINC00519 in gastric cancer HGC-27 cells and gastric mucosal epithelial GES-1 cells were detected by qPCR. HGC-27 cells were divided into si-NC, si-LINC00519, si-LINC00519+anti-miR-NC, and si-LINC00519 + anti-miR[1]876-3p groups according to transfection treatment. Colony formation test was applied to detect cell cloning ability; Flow cytometry was used to detect apoptosis and cell cycle distribution; Transwell assay was selected to measure cell migration and invasion. Dual luciferase reporter gene assay and qPCR were applied to confirm the interaction between LINC00519 and miR-876-3p as well as between miR-876-3p and HMGA1. Results: The expression of LINC00519 in HGC-27 cells was significantly higher than that in GES[1] 1 cells (P <0.05). After siRNA transfection, the expression level of LINC00519 in HGC-27 cells of the si-LINC00519 group was significantly lower than that of the si-NC group (t=47.294, P<0.01). Compared with the si-NC group, the number of HGC-27 cell clones, the number of migrated and invaded cells, and proportion of S-phase cells in the si-LINC00519 group were significantly decreased (all P<0.01), while the apoptosis rate and the proportion of G0/G1 phase cells were significantly increased (all P <0.01). Compared with the si-LINC00519+anti-miR-NC group, the number of HGC-27 cell clones, the number of migrated and invaded cells, proportion of S-phase cells were significantly increased (all P<0.01), while the apoptosis rate and the proportion of G0/G1 phase cells in the si-LINC00519 + anti-miR-876-3p group were significantly decreased (all P<0.01), LINC00519 could target and negatively regulate miR-876-3p expression. miR-876-3p could target and negatively regulate HMGA1 expression. Conclusion: Knocking down LINC00519 could inhibit the proliferation, migration and invasion of gastric cancer HGC-27 cells and induce apoptosis by regulating the miR-876-3p/HMGA1 axis.
2021, 28(6):582-589.
Abstract:
Objective: To investigate whether long intergene non-coding RNA (LINC) 01018 regulates the proliferation, apoptosis and radiosensitivity of gastric cancer HGC-27 cells by inhibiting miR-297. Methods: The cancer tissues and para-cancerous tissues from gastric cancer patients (21 cases) who underwent surgery or chemo-resistant gastric cancer patients (19 cases) in the Fifth People's Hospital of Qinghai Province were collected, and the expressions of LINC01018 and miR-297 in gastric cancer tissues, chemo-resistant gastric cancer tissues and gastric cancer HGC-27 cells were detected by qPCR. Dual luciferase reporter gene assay was used to verify the targeting relationship between LINC01018 and miR-297. The LINC01018 overexpression plasmid pcDNA-LINC01018, miR-297 inhibitor, or pcDNA-LINC01018+miR-297 mimic was transfected into HGC-27 cells, and the transfection efficiency was verified by qPCR. MTT and Clone formation experiment were employed to assess the proliferation viability and the clone formation ability of HGC-27 cells after transfection. The apoptosis rate of HGC-27 cells was evaluated by Flow cytometry, and the radiosensitivity of HGC-27 cells after transfection in each group was determined with Clone formation experiment. WB was used to detect the protein expressions of Ki67, cleaved-caspase3 and pro-caspase3 in the cells. Results: Compared with para-cancerous tissues or normal gastric mucosal epithelial GES-1 cells, the expression level of LINC01018 decreased while the expression level of miR-297 increased in gastric cancer tissues, chemo-resistant gastric cancer tissues and gastric cancer HGC-27 cells (all P<0.01). LINC01018 had a targeted binding relationship with miR-297, and LINC01018 negatively regulated the expression of miR-297. LINC01018 overexpression or miR-297 knockdown inhibited the proliferation viability, clone formation and cell survival of HGC-27 cells, down-regulated the protein expression level of Ki67 and pro-caspase3, but promoted the apoptosis and radiosensitivity of HGC-27 cells as well as up-regulated the expression level of cleaved-caspase3 protein (all P<0.01). Co-transfection of pcDNA-LINC01018 and miR-297 mimic could reverse all the above-mentioned effects of LINC01018 overexpression on HGC-27 cells, especially its radio-sensitization effect on HGC-27 cells (P<0.05 or P<0.01). Conclusion: LINC01018 inhibits the proliferation of gastric cancer HGC-27 cells by down-regulating the expression of miR-297 to promote apoptosis and enhance the radiosensitivity of cells, which may be related to the expression of Ki67 and caspase3.
Objective: To investigate whether long intergene non-coding RNA (LINC) 01018 regulates the proliferation, apoptosis and radiosensitivity of gastric cancer HGC-27 cells by inhibiting miR-297. Methods: The cancer tissues and para-cancerous tissues from gastric cancer patients (21 cases) who underwent surgery or chemo-resistant gastric cancer patients (19 cases) in the Fifth People's Hospital of Qinghai Province were collected, and the expressions of LINC01018 and miR-297 in gastric cancer tissues, chemo-resistant gastric cancer tissues and gastric cancer HGC-27 cells were detected by qPCR. Dual luciferase reporter gene assay was used to verify the targeting relationship between LINC01018 and miR-297. The LINC01018 overexpression plasmid pcDNA-LINC01018, miR-297 inhibitor, or pcDNA-LINC01018+miR-297 mimic was transfected into HGC-27 cells, and the transfection efficiency was verified by qPCR. MTT and Clone formation experiment were employed to assess the proliferation viability and the clone formation ability of HGC-27 cells after transfection. The apoptosis rate of HGC-27 cells was evaluated by Flow cytometry, and the radiosensitivity of HGC-27 cells after transfection in each group was determined with Clone formation experiment. WB was used to detect the protein expressions of Ki67, cleaved-caspase3 and pro-caspase3 in the cells. Results: Compared with para-cancerous tissues or normal gastric mucosal epithelial GES-1 cells, the expression level of LINC01018 decreased while the expression level of miR-297 increased in gastric cancer tissues, chemo-resistant gastric cancer tissues and gastric cancer HGC-27 cells (all P<0.01). LINC01018 had a targeted binding relationship with miR-297, and LINC01018 negatively regulated the expression of miR-297. LINC01018 overexpression or miR-297 knockdown inhibited the proliferation viability, clone formation and cell survival of HGC-27 cells, down-regulated the protein expression level of Ki67 and pro-caspase3, but promoted the apoptosis and radiosensitivity of HGC-27 cells as well as up-regulated the expression level of cleaved-caspase3 protein (all P<0.01). Co-transfection of pcDNA-LINC01018 and miR-297 mimic could reverse all the above-mentioned effects of LINC01018 overexpression on HGC-27 cells, especially its radio-sensitization effect on HGC-27 cells (P<0.05 or P<0.01). Conclusion: LINC01018 inhibits the proliferation of gastric cancer HGC-27 cells by down-regulating the expression of miR-297 to promote apoptosis and enhance the radiosensitivity of cells, which may be related to the expression of Ki67 and caspase3.
2021, 28(6):590-597.
Abstract:
Objective: To investigate the effect and mechanism of p-hydroxycinnamaldehyde (CMSP) momomer compounds extract from the Cochinchina momordica seeds on the growth and metastasis of melanoma transplanted tumors in mice with in vivo and in vitro experiments. Methods: A tumor-bearing mouse model was established, and 18 C57BL/6 mice were randomly divided into 3 groups (6 mice in each group): a control group (intraperitoneal injection of 0.1 ml normal saline) and two CMSP treatment groups (intraperitoneal injection of 1 and 2 mg/ml CMSP of 0.1 ml). From the 5th day of drug administration, the transplanted tumor in mice was measured with calipers and the volume was calculated before each administration. At the end of the experiment, the mass of transplanted tumor was weighed. The pathological changes of liver tissues were observed under light microscope after H-E staining. The expressions of E-cadherin and vimentin in the transplanted tumor tissues were detected by SP immunohistochemical method. The metastatic ability of melanoma B16 cells in the CMSP group (10, 20 μg/ml) was detected by cell scratch test and Transwell test after treatment for 24 and 48 h. The expressions of EMT-related mRNAs in B16 cells after treatment with CMSP for 24 h were detected by qPCR. The protein expression levels of β-catenin, p-β-catenin (Ser675), vimentin and E-cadherin in B16 cells treated with CMSP for 48 h were detected by Western blotting(WB). Results: The mean tumor volume and tumor mass of the mice in CMSP treatment group were significantly decreased (all P<0.05). The number of liver metastases in the control group was significantly higher than that in the CMSP (1 and 2 mg/ kg) groups (all P<0.05); moreover, no obvious metastases were found in the liver tissues of the 2 mg/kg CMSP treatment group. The expression level of E-cadherin protein in CMSP group (1 and 2 mg/kg) was significantly higher than that in the control group (all P<0.05), while the expression level of vimentin protein was significantly lower than that in the control group (all P<0.01). For the in vitro experiments, the scratch healing rate of B16 cells in CMSP groups (10, 20 μg/ml) after treatment for 24 and 48 h was significantly lower than that in control group (all P<0.05). The number of B16 cells passing through Transwell compartment in the 20 μg/ml CMSP treatment group was significantly decreased as compared with the control group (all P<0.01). The mRNA expression level of β-catenin in B16 cells treated with CMSP (10, 20 μg/ ml) was significantly lower than that in control group (all P<0.01), while the mRNA expression level of E-cadherin was significantly increased (all P<0.05); However, the mRNA expression level of vimentin in the 10 μg/ml treatment group was not significantly different from that in the control group (P>0.05), but it was significantly decreased in the 20 μg/ml treatment group (P<0.01). Compared with the control group, the protein expressions of β-catenin, p-β-catenin and vimentin in B16 cells of CMSP groups (10 and 20 μg/ml) were significantly decreased (all P<0.01), while the protein expression of E-cadherin was significantly increased (all P<0.01). Conclusion: CMSP can inhibit the growth and metastasis of melanoma transplanted tumors in mice, and its mechanism may be related to the activity of wnt/β-catenin pathway.
Objective: To investigate the effect and mechanism of p-hydroxycinnamaldehyde (CMSP) momomer compounds extract from the Cochinchina momordica seeds on the growth and metastasis of melanoma transplanted tumors in mice with in vivo and in vitro experiments. Methods: A tumor-bearing mouse model was established, and 18 C57BL/6 mice were randomly divided into 3 groups (6 mice in each group): a control group (intraperitoneal injection of 0.1 ml normal saline) and two CMSP treatment groups (intraperitoneal injection of 1 and 2 mg/ml CMSP of 0.1 ml). From the 5th day of drug administration, the transplanted tumor in mice was measured with calipers and the volume was calculated before each administration. At the end of the experiment, the mass of transplanted tumor was weighed. The pathological changes of liver tissues were observed under light microscope after H-E staining. The expressions of E-cadherin and vimentin in the transplanted tumor tissues were detected by SP immunohistochemical method. The metastatic ability of melanoma B16 cells in the CMSP group (10, 20 μg/ml) was detected by cell scratch test and Transwell test after treatment for 24 and 48 h. The expressions of EMT-related mRNAs in B16 cells after treatment with CMSP for 24 h were detected by qPCR. The protein expression levels of β-catenin, p-β-catenin (Ser675), vimentin and E-cadherin in B16 cells treated with CMSP for 48 h were detected by Western blotting(WB). Results: The mean tumor volume and tumor mass of the mice in CMSP treatment group were significantly decreased (all P<0.05). The number of liver metastases in the control group was significantly higher than that in the CMSP (1 and 2 mg/ kg) groups (all P<0.05); moreover, no obvious metastases were found in the liver tissues of the 2 mg/kg CMSP treatment group. The expression level of E-cadherin protein in CMSP group (1 and 2 mg/kg) was significantly higher than that in the control group (all P<0.05), while the expression level of vimentin protein was significantly lower than that in the control group (all P<0.01). For the in vitro experiments, the scratch healing rate of B16 cells in CMSP groups (10, 20 μg/ml) after treatment for 24 and 48 h was significantly lower than that in control group (all P<0.05). The number of B16 cells passing through Transwell compartment in the 20 μg/ml CMSP treatment group was significantly decreased as compared with the control group (all P<0.01). The mRNA expression level of β-catenin in B16 cells treated with CMSP (10, 20 μg/ ml) was significantly lower than that in control group (all P<0.01), while the mRNA expression level of E-cadherin was significantly increased (all P<0.05); However, the mRNA expression level of vimentin in the 10 μg/ml treatment group was not significantly different from that in the control group (P>0.05), but it was significantly decreased in the 20 μg/ml treatment group (P<0.01). Compared with the control group, the protein expressions of β-catenin, p-β-catenin and vimentin in B16 cells of CMSP groups (10 and 20 μg/ml) were significantly decreased (all P<0.01), while the protein expression of E-cadherin was significantly increased (all P<0.01). Conclusion: CMSP can inhibit the growth and metastasis of melanoma transplanted tumors in mice, and its mechanism may be related to the activity of wnt/β-catenin pathway.
2021, 28(6):598-604.
Abstract:
Objective: To explore the effect of circ_0072088 on the malignant biological behaviors of thyroid cancer IHH4 cells and its possible mechanism. Method: From April 2015 to March 2019, the thyroid cancer tissues and corresponding adjacent tissues from 48 patients who were diagnosed as thyroid cancer and underwent resection without any previous treatment in the Affiliated Hospital of Qinghai University were collected. The differentially expressed circRNAs in papillary thyroid cancer were identified by GEO database (GSE93522). The expression pattern of circ_0072088 was determined using quantitative real-time polymerase chain reaction (qRT-PCR) in thyroid cancer samples and cell lines. CCK-8 and Transwell assays were performed to assess the effects of circ_0072088 and miR-532-3p on proliferation, migration, and invasion of thyroid cancer IHH4 cells. Bioinformatics analysis and dual-luciferase reporter assays were used to explore the correlation between circ_0072088 and miR-532-3p as well as between miR-532-3p and WEE1 gene in thyroid cancer cells. Results: circ_0072088 expression was upregulated in thyroid cancer tissues and cell lines ( P<0.05 or P<0.01). Overexpression of circ_0072088 promoted the proliferation, migration, and invasion of thyroid cancer cells (P<0.05 or P<0.01), while transfection of miR-532-3p mimics weakened this effect (P<0.05 or P<0.01). Mechanistically, circ_0072088 could bind to miR-532-3p. Besides, WEE1 was proved to be the downstream target gene of miR-532-3p. Conclusion: Circ_0072088 promotes the proliferation, migration and invasion of IHH4 cells through regulating WEE1/miR-532-3p axis.
Objective: To explore the effect of circ_0072088 on the malignant biological behaviors of thyroid cancer IHH4 cells and its possible mechanism. Method: From April 2015 to March 2019, the thyroid cancer tissues and corresponding adjacent tissues from 48 patients who were diagnosed as thyroid cancer and underwent resection without any previous treatment in the Affiliated Hospital of Qinghai University were collected. The differentially expressed circRNAs in papillary thyroid cancer were identified by GEO database (GSE93522). The expression pattern of circ_0072088 was determined using quantitative real-time polymerase chain reaction (qRT-PCR) in thyroid cancer samples and cell lines. CCK-8 and Transwell assays were performed to assess the effects of circ_0072088 and miR-532-3p on proliferation, migration, and invasion of thyroid cancer IHH4 cells. Bioinformatics analysis and dual-luciferase reporter assays were used to explore the correlation between circ_0072088 and miR-532-3p as well as between miR-532-3p and WEE1 gene in thyroid cancer cells. Results: circ_0072088 expression was upregulated in thyroid cancer tissues and cell lines ( P<0.05 or P<0.01). Overexpression of circ_0072088 promoted the proliferation, migration, and invasion of thyroid cancer cells (P<0.05 or P<0.01), while transfection of miR-532-3p mimics weakened this effect (P<0.05 or P<0.01). Mechanistically, circ_0072088 could bind to miR-532-3p. Besides, WEE1 was proved to be the downstream target gene of miR-532-3p. Conclusion: Circ_0072088 promotes the proliferation, migration and invasion of IHH4 cells through regulating WEE1/miR-532-3p axis.
2021, 28(6):605-610.
Abstract:
Objective: To investigate the predictive value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to[1]lymphocyte ratio (PLR) in perioperative period on the prognosis of patients with intrahepatic cholangiocarcinoma (ICCA). Methods: Ninety-seven cases of ICCA patients underwent liver resection surgery in Songjiang District Central Hospital from January 2015 to January 2018 were chosen as the ICCA group, and 100 healthy volunteers who underwent physical examination in the hospital during the same period were selected as the control group. The NLR and PLR on preoperative day 1, postoperative day 3 and day 7 were compared between the two groups. Univariate and multivariate analyses were performed to determine the risk factors for mortality during postoperative follow-up in patients with ICCA. Kaplan-Meier survival curve was used to analyze the influence of postoperative day 3 NLR and PLR on the survival time of patients with ICCA. ROC curve was used to analyze the predictive value of postoperative day 3 NLR and PLR on the mortality during postoperative follow-up. Results: Peripheral blood NLR and PLR in the ICCA group were higher than those in the normal control group on preoperative day 1 and postoperative day 3, 7 (all P<0.05). In the ICCA group, the peripheral blood NLR and PLR on preoperative day 1 and postoperative day 7 showed no statistical difference (P>0.05); however, the levels on postoperative day 3 was the highest (P<0.05). Multiple tumors, lymph node metastasis, TNM staging Ⅲ - Ⅳ , increased carbohydrate antigen 199 (CA199) level and higher NLR and PLR on postoperative day 3 were the independent risk factors of mortality during postoperative follow-up in ICCA patients (all P<0.05). The ROC showed that NLR and PLR on postoperative day 3 had predictive value for the survival time of patients with ICCA. Kaplan-Meier survival curve showed that the survival time of patients in low NLR group was longer than those in high NLR group [(50.32±3.69) months vs (30.12±2.36) months], and the survival time of patients in low PLR group was longer than those in high PLR group [(53.6±3.75) months vs (37.6±2.96) months] (all P<0.05). Conclusion: Abnormal elevation in NLR and PLR on postoperative day 3 is an independent risk factor for death after liver resection surgery in patients with ICCA, which has early predictive value for patients’survival.
Objective: To investigate the predictive value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to[1]lymphocyte ratio (PLR) in perioperative period on the prognosis of patients with intrahepatic cholangiocarcinoma (ICCA). Methods: Ninety-seven cases of ICCA patients underwent liver resection surgery in Songjiang District Central Hospital from January 2015 to January 2018 were chosen as the ICCA group, and 100 healthy volunteers who underwent physical examination in the hospital during the same period were selected as the control group. The NLR and PLR on preoperative day 1, postoperative day 3 and day 7 were compared between the two groups. Univariate and multivariate analyses were performed to determine the risk factors for mortality during postoperative follow-up in patients with ICCA. Kaplan-Meier survival curve was used to analyze the influence of postoperative day 3 NLR and PLR on the survival time of patients with ICCA. ROC curve was used to analyze the predictive value of postoperative day 3 NLR and PLR on the mortality during postoperative follow-up. Results: Peripheral blood NLR and PLR in the ICCA group were higher than those in the normal control group on preoperative day 1 and postoperative day 3, 7 (all P<0.05). In the ICCA group, the peripheral blood NLR and PLR on preoperative day 1 and postoperative day 7 showed no statistical difference (P>0.05); however, the levels on postoperative day 3 was the highest (P<0.05). Multiple tumors, lymph node metastasis, TNM staging Ⅲ - Ⅳ , increased carbohydrate antigen 199 (CA199) level and higher NLR and PLR on postoperative day 3 were the independent risk factors of mortality during postoperative follow-up in ICCA patients (all P<0.05). The ROC showed that NLR and PLR on postoperative day 3 had predictive value for the survival time of patients with ICCA. Kaplan-Meier survival curve showed that the survival time of patients in low NLR group was longer than those in high NLR group [(50.32±3.69) months vs (30.12±2.36) months], and the survival time of patients in low PLR group was longer than those in high PLR group [(53.6±3.75) months vs (37.6±2.96) months] (all P<0.05). Conclusion: Abnormal elevation in NLR and PLR on postoperative day 3 is an independent risk factor for death after liver resection surgery in patients with ICCA, which has early predictive value for patients’survival.
2021, 28(6):611-615.
Abstract:
西达苯胺（Chidamide）是近年来我国自主研发且具有独立知识产权的一类抗癌新药，也是全球首个获准上市的亚型 选择性组蛋白去乙酰化酶抑制剂。研究显示，该药物可以阻滞肿瘤细胞周期、促进肿瘤细胞分化、诱导肿瘤细胞的自噬和凋亡， 以及抑制新生血管形成；同时还具有调节机体免疫能力，影响肿瘤细胞的能量代谢等多方面的功能。本文就西达苯胺发挥抗肿 瘤活性的多种作用机制作一综述。
西达苯胺（Chidamide）是近年来我国自主研发且具有独立知识产权的一类抗癌新药，也是全球首个获准上市的亚型 选择性组蛋白去乙酰化酶抑制剂。研究显示，该药物可以阻滞肿瘤细胞周期、促进肿瘤细胞分化、诱导肿瘤细胞的自噬和凋亡， 以及抑制新生血管形成；同时还具有调节机体免疫能力，影响肿瘤细胞的能量代谢等多方面的功能。本文就西达苯胺发挥抗肿 瘤活性的多种作用机制作一综述。
2021, 28(6):616-623.
Abstract:
长散布元件-1（long interspersed nuclear element-1，LINE-1）逆转录转座子是肿瘤中染色体不稳定、基因组不稳定和遗 传异质性的主要标志，并已成为许多疾病发生、发展和不良预后的标志物之一。LINE-1也参与调控免疫系统，并通过多种方式影 响免疫微环境。LINE-1逆转录转座子的异常表达可对先天免疫应答产生强烈刺激，激活免疫系统，引发自身免疫和炎症反应。 因此，抑制LINE-1的活性已成为多种肿瘤的潜在治疗策略。本文主要综述了LINE-1的调控机制、LINE-1与肿瘤和免疫的相关 性以及LINE-1的多种抑制剂，为LINE-1的研究提供了新的认识。
长散布元件-1（long interspersed nuclear element-1，LINE-1）逆转录转座子是肿瘤中染色体不稳定、基因组不稳定和遗 传异质性的主要标志，并已成为许多疾病发生、发展和不良预后的标志物之一。LINE-1也参与调控免疫系统，并通过多种方式影 响免疫微环境。LINE-1逆转录转座子的异常表达可对先天免疫应答产生强烈刺激，激活免疫系统，引发自身免疫和炎症反应。 因此，抑制LINE-1的活性已成为多种肿瘤的潜在治疗策略。本文主要综述了LINE-1的调控机制、LINE-1与肿瘤和免疫的相关 性以及LINE-1的多种抑制剂，为LINE-1的研究提供了新的认识。
2021, 28(6):624-628.
Abstract:
人类婆罗双树样基因4（spalt-like transcription factor 4，SALL4）是一种新发现的癌胚基因，也是维持胚胎干细胞自我 更新和多向分化潜能的锌指蛋白转录因子。SALL4基因的表达随发育成熟的过程逐渐下调甚至在大多数正常的成体组织中不 表达。然而，近年来的研究表明，SALL4在多种肿瘤包括实体肿瘤和血液系统肿瘤中异常高表达，且SALL4表达水平与肿瘤发 生发展及肿瘤患者的不良预后、生存期相关，因而成为肿瘤预测的生物学标志。由于SALL4表达模式的特异性及其在肿瘤发生 发展中的作用使其成为肿瘤治疗的潜在靶点。本文就SALL4在肿瘤发生发展中的作用、调控肿瘤发生发展的机制及SALL4在 疾病诊疗中的意义等方面作一综述。
人类婆罗双树样基因4（spalt-like transcription factor 4，SALL4）是一种新发现的癌胚基因，也是维持胚胎干细胞自我 更新和多向分化潜能的锌指蛋白转录因子。SALL4基因的表达随发育成熟的过程逐渐下调甚至在大多数正常的成体组织中不 表达。然而，近年来的研究表明，SALL4在多种肿瘤包括实体肿瘤和血液系统肿瘤中异常高表达，且SALL4表达水平与肿瘤发 生发展及肿瘤患者的不良预后、生存期相关，因而成为肿瘤预测的生物学标志。由于SALL4表达模式的特异性及其在肿瘤发生 发展中的作用使其成为肿瘤治疗的潜在靶点。本文就SALL4在肿瘤发生发展中的作用、调控肿瘤发生发展的机制及SALL4在 疾病诊疗中的意义等方面作一综述。
2021, 28(6):629-635.
Abstract:
嵌合抗原受体基因修饰T淋巴细胞（CAR-T）免疫治疗尤其在复发/难治性恶性血液病的临床应用中显示出卓越的疗 效，被认为是最有前景的肿瘤治疗方法之一，但是 CAR-T 免疫治疗中可引发独特的毒性作用，其中细胞因子释放综合征 （cytokine release syndrome，CRS）和免疫效应细胞相关神经毒性综合征（immune effector cell-associated neurotoxicity syndrome， ICANS）在临床应用中最为常见，并具有潜在的致死性，使得CRA-T疗法的广泛应用受到一定的限制，因此如何最大程度地利用 CAR-T免疫治疗的同时努力减少或预防CRS和ICANS的发生是目前临床研究的重点，深入了解CRS和ICANS的发生机制能为 新的预防措施提供思路。早期识别相关危险因素及鉴定生物预测标志物，熟悉其分级与治疗措施，有利于规范CAR-T免疫疗法 的临床应用和患者安全管理。本文就CRS和ICANS的危险因素、发生机制、临床表现、分级与治疗和预防措施等方面进行综述， 旨在为CAR-T疗法常见毒性作用的规范管理提供帮助。
嵌合抗原受体基因修饰T淋巴细胞（CAR-T）免疫治疗尤其在复发/难治性恶性血液病的临床应用中显示出卓越的疗 效，被认为是最有前景的肿瘤治疗方法之一，但是 CAR-T 免疫治疗中可引发独特的毒性作用，其中细胞因子释放综合征 （cytokine release syndrome，CRS）和免疫效应细胞相关神经毒性综合征（immune effector cell-associated neurotoxicity syndrome， ICANS）在临床应用中最为常见，并具有潜在的致死性，使得CRA-T疗法的广泛应用受到一定的限制，因此如何最大程度地利用 CAR-T免疫治疗的同时努力减少或预防CRS和ICANS的发生是目前临床研究的重点，深入了解CRS和ICANS的发生机制能为 新的预防措施提供思路。早期识别相关危险因素及鉴定生物预测标志物，熟悉其分级与治疗措施，有利于规范CAR-T免疫疗法 的临床应用和患者安全管理。本文就CRS和ICANS的危险因素、发生机制、临床表现、分级与治疗和预防措施等方面进行综述， 旨在为CAR-T疗法常见毒性作用的规范管理提供帮助。
2021, 28(6):636-642.
Abstract:
表皮生长因子受体（epidermal growth factor receptor，EGFR）在头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）的发生、发展中起着至关重要的作用。作为一种跨膜受体，EGFR参与多种信号通路，且在头颈部鳞状细胞癌 组织中高表达。目前，围绕EGFR设计的HNSCC靶向治疗药物已经广泛应用于临床，但随之产生的耐药问题也日益受到关注。 本文重点从信号通路、靶向药物治疗和耐药等方面综述EGFR在治疗头颈部鳞状细胞癌的最新研究进展，并探讨其发展前景。
表皮生长因子受体（epidermal growth factor receptor，EGFR）在头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）的发生、发展中起着至关重要的作用。作为一种跨膜受体，EGFR参与多种信号通路，且在头颈部鳞状细胞癌 组织中高表达。目前，围绕EGFR设计的HNSCC靶向治疗药物已经广泛应用于临床，但随之产生的耐药问题也日益受到关注。 本文重点从信号通路、靶向药物治疗和耐药等方面综述EGFR在治疗头颈部鳞状细胞癌的最新研究进展，并探讨其发展前景。
2021, 28(6):643-646.
Abstract:
多发性骨髓瘤（multiple myeloma，MM）是一种恶性浆细胞增殖性疾病，随着免疫调节剂和蛋白酶体抑制剂等药物的 广泛应用，患者的生存期现已得到显著延长，但最终还会因耐药、复发等而发生死亡。靶向CD38的单克隆抗体达雷妥尤单抗 （daratumumab, DARA）作为一种新型生物制剂，在一系列临床研究中其对MM的治疗均显示出良好的疗效，本文就DARA单药 或联合化疗治疗MM的研究进展作一综述。
多发性骨髓瘤（multiple myeloma，MM）是一种恶性浆细胞增殖性疾病，随着免疫调节剂和蛋白酶体抑制剂等药物的 广泛应用，患者的生存期现已得到显著延长，但最终还会因耐药、复发等而发生死亡。靶向CD38的单克隆抗体达雷妥尤单抗 （daratumumab, DARA）作为一种新型生物制剂，在一系列临床研究中其对MM的治疗均显示出良好的疗效，本文就DARA单药 或联合化疗治疗MM的研究进展作一综述。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.