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Volume 30,Issue 2,2023 Table of Contents
2023, 30(2):99-107.
DOI: 10.3872/j.issn.1007-385X.2023.02.001
Abstract:
PD-1/PD-L1 inhibitors have emerged as an important therapeutic tool in breast cancer immunotherapy. However, certain scientific issues remain to be addressed urgently in immunotherapy for breast cancer, especially for triple-negative breast cancer (TNBC), including the poor efficiency of PD-1/PD-L1 inhibitor monotherapy, the lack of explicit biomarkers to effectively screen treatment-sensitive populations, and the high incidence of immune-related adverse events (irAEs). In order to improve the treatmentefficacy and reduce the incidence of irAEs, it is important to take some measures, such as exploring combined treatment of PD-1/PD-L1 inhibitors and other drugs, using nanotechnology to develop nanocarriers that selectively target tumor cells to reduce the toxicity andincrease the efficacy of antitumor drugs, exploring biomarkers that can predict the response potential of immunotherapy, and early identification and treatment of irAEs and the construction and development of a multidisciplinary team (MDT) model. As these measures are actively promoted and the problems continue to be solved, PD-1/PD-L1 inhibitors will certainly have a broader application prospect in the treatment of breast cancer.
PD-1/PD-L1 inhibitors have emerged as an important therapeutic tool in breast cancer immunotherapy. However, certain scientific issues remain to be addressed urgently in immunotherapy for breast cancer, especially for triple-negative breast cancer (TNBC), including the poor efficiency of PD-1/PD-L1 inhibitor monotherapy, the lack of explicit biomarkers to effectively screen treatment-sensitive populations, and the high incidence of immune-related adverse events (irAEs). In order to improve the treatmentefficacy and reduce the incidence of irAEs, it is important to take some measures, such as exploring combined treatment of PD-1/PD-L1 inhibitors and other drugs, using nanotechnology to develop nanocarriers that selectively target tumor cells to reduce the toxicity andincrease the efficacy of antitumor drugs, exploring biomarkers that can predict the response potential of immunotherapy, and early identification and treatment of irAEs and the construction and development of a multidisciplinary team (MDT) model. As these measures are actively promoted and the problems continue to be solved, PD-1/PD-L1 inhibitors will certainly have a broader application prospect in the treatment of breast cancer.
2023, 30(2):108-113.
DOI: 10.3872/j.issn.1007-385X.2023.02.002
Abstract:
Nicotinic acid belongs to B vitamins and is one of the essential vitamins for humans. In the past, the main cognition of nicotinic acid remained on its nutritional functions, such as participating in the maintenance of neural function, the promotion of metabolism and development, and the protection of cardio cerebral vessels. With the development of researches, in recent years, multiple studies have shown that nicotinic acid and its derivatives play key roles in the prevention and treatment of cancer. Nicotinic acid and its derivatives could affect the biological functions of tumor cells, participate in immune regulation, promote the antitumor efficacy of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, and maintain the genomic stability through a variety of molecular pathways in a poly ADP-ribose polymerase (PARP)-dependent manner. This review summarizes the research approaches and the latest progress in the studies of the role nicotinic acid and its derivatives play in cancer prevention and treatment and assess the prospects of its further research and application direction, with the hope of helping promote the application of nicotinic acid and its derivatives in comprehensive cancer prevention and treatment.
Nicotinic acid belongs to B vitamins and is one of the essential vitamins for humans. In the past, the main cognition of nicotinic acid remained on its nutritional functions, such as participating in the maintenance of neural function, the promotion of metabolism and development, and the protection of cardio cerebral vessels. With the development of researches, in recent years, multiple studies have shown that nicotinic acid and its derivatives play key roles in the prevention and treatment of cancer. Nicotinic acid and its derivatives could affect the biological functions of tumor cells, participate in immune regulation, promote the antitumor efficacy of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, and maintain the genomic stability through a variety of molecular pathways in a poly ADP-ribose polymerase (PARP)-dependent manner. This review summarizes the research approaches and the latest progress in the studies of the role nicotinic acid and its derivatives play in cancer prevention and treatment and assess the prospects of its further research and application direction, with the hope of helping promote the application of nicotinic acid and its derivatives in comprehensive cancer prevention and treatment.
2023, 30(2):114-122.
DOI: 10.3872/j.issn.1007-385X.2023.02.003
Abstract:
Objective: To investigate the expression level of hsa_circ_0140180 in esophageal squamous cell carcinoma (ESCC) cells,as well as its effect on malignant biological behavior of ESCC cells and the possible molecular mechanisms. Methods: Six pairs of ESCC tissues and corresponding paracarcinoma tissues resected at the Department of Thoracic Surgery, Central Hospital of Nanchong City between November 2018 and March 2019 were collected for whole-transcriptome sequencing, and hsa_circ_0140180 at a low expression in ESCC tissues was screened out. The TE-1 and KYSE30 cell lines overexpressing hsa_circ_0140180 were established.qPCR was used to detect the expression of hsa_circ_0140180 in human normal esophageal epithelial cells and ESCC cells, as well as the expression of miR-1287-5p in TE-1 and KYSE30 cells overexpressing hsa_circ_0140180. CCK-8 and FCM were used to detect theeffect of hsa_circ_0140180 overexpression on the proliferation and cell cycle of TE-1 and KYSE30 cells. Scratch assay and Transwellassay were used to assess the effects of hsa_circ_0140180 overexpression on migration and invasion of TE-1 and KYSE30 cells. Dual-luciferase reporter assay was used to confirm the targeting relationship between hsa_circ_0140180 and miR-1287-5p. WB assay was used to detect the expression of EMT-related proteins and the phosphorylation level of the PI3K-Akt pathway in TE-1 and KYSE30 cells after hsa_circ_0140180 overexpression. Results: Transcriptome sequencing and qPCR results showed that hsa_circ_0140180 was lowly expressed in ESCC tissues and cells (P<0.05 or P<0.01) and confirmed its closed-loop molecular signature and localization in the cytoplasm. Overexpression of hsa_circ_0140180 could significantly inhibit the migration and invasion of ESCC cells (all P<0.05) but had no significant effect on the proliferation and cell cycle. The results of dual-luciferase reporter gene assay demonstrated that hsa_circ_0140180 targets miR-1287-5p and negatively regulates its expression (P<0.001). Overexpression of hsa_circ_0140180 could significantly increase the expression of E-cadherin and decrease the expression of Snail (both P<0.05) and the phosphorylation level of the PI3K-Akt pathway (P<0.01, P<0.001) in TE-1 and KYSE30 cells. Conclusion: hsa_circ_0140180 is lowly expressed in ESCC cells and tissues; it reduces the phosphorylation levels of PI3K-Akt pathway and suppresses EMT process possibly through regulation of miR-1287-5p expression, thus affecting the migration and invasion abilities of ESCC cells.
Objective: To investigate the expression level of hsa_circ_0140180 in esophageal squamous cell carcinoma (ESCC) cells,as well as its effect on malignant biological behavior of ESCC cells and the possible molecular mechanisms. Methods: Six pairs of ESCC tissues and corresponding paracarcinoma tissues resected at the Department of Thoracic Surgery, Central Hospital of Nanchong City between November 2018 and March 2019 were collected for whole-transcriptome sequencing, and hsa_circ_0140180 at a low expression in ESCC tissues was screened out. The TE-1 and KYSE30 cell lines overexpressing hsa_circ_0140180 were established.qPCR was used to detect the expression of hsa_circ_0140180 in human normal esophageal epithelial cells and ESCC cells, as well as the expression of miR-1287-5p in TE-1 and KYSE30 cells overexpressing hsa_circ_0140180. CCK-8 and FCM were used to detect theeffect of hsa_circ_0140180 overexpression on the proliferation and cell cycle of TE-1 and KYSE30 cells. Scratch assay and Transwellassay were used to assess the effects of hsa_circ_0140180 overexpression on migration and invasion of TE-1 and KYSE30 cells. Dual-luciferase reporter assay was used to confirm the targeting relationship between hsa_circ_0140180 and miR-1287-5p. WB assay was used to detect the expression of EMT-related proteins and the phosphorylation level of the PI3K-Akt pathway in TE-1 and KYSE30 cells after hsa_circ_0140180 overexpression. Results: Transcriptome sequencing and qPCR results showed that hsa_circ_0140180 was lowly expressed in ESCC tissues and cells (P<0.05 or P<0.01) and confirmed its closed-loop molecular signature and localization in the cytoplasm. Overexpression of hsa_circ_0140180 could significantly inhibit the migration and invasion of ESCC cells (all P<0.05) but had no significant effect on the proliferation and cell cycle. The results of dual-luciferase reporter gene assay demonstrated that hsa_circ_0140180 targets miR-1287-5p and negatively regulates its expression (P<0.001). Overexpression of hsa_circ_0140180 could significantly increase the expression of E-cadherin and decrease the expression of Snail (both P<0.05) and the phosphorylation level of the PI3K-Akt pathway (P<0.01, P<0.001) in TE-1 and KYSE30 cells. Conclusion: hsa_circ_0140180 is lowly expressed in ESCC cells and tissues; it reduces the phosphorylation levels of PI3K-Akt pathway and suppresses EMT process possibly through regulation of miR-1287-5p expression, thus affecting the migration and invasion abilities of ESCC cells.
2023, 30(2):123-128.
DOI: 10.3872/j.issn.1007-385X.2023.02.004
Abstract:
Objective: To explore the effect of sesamol (SEM) on autophagy and apoptosis of esophageal squamous cell carcinoma (ESCC) Eca109 cells through adenylate activated protein kinase (AMPK)/silencing information regulator 1 (SIRT1)/nuclear factor κB （NF- κB) pathway. Methods: Eca109 cells of ESCC and HEEpiC of human esophageal epithelial cells were treated with different concentrations of SEM (0, 1.562 5, 3.125, 6.25, 12.5, 25, 50, 100, 200, and 400 μmol/L) for 48 hours. Cell viability was detected by CCK-8 method and appropriate SEM concentrations were screened for subsequent experiments. Eca109 cells were grouped into control group (CK group, 0 μmol/L), low-dose SEM group (SEM-L group, 25 μmol/L), medium-dose SEM group (SEM-M group, 50 μmol/L),high-dose SEM group (SEM-M group, 50 μmol/L), high-dose SEM group (SEM-H group, 100 μmol/L) and high-dose SEM+compound C (AMPK inhibitor) group (SEM-H+Compound C group, 100 μmol/L+10 μmol/L). All Eca109 cells were treated at the corresponding drug concentration for 48 hours. CCK-8 assay was applied to detect the proliferation of Eca109 cells; flow cytometry was applied to detect apoptosis; transmission electron microscopy was applied to observe autophagosomes in Eca109 cells and WB assay was applied to detect the protein expressions of microtubule-associated protein 1 light chain 3 (LC3)-Ⅱ/LC3-Ⅰ, Beclin-1, B-lymphoma-2 (Bcl2),Bcl2-associated X protein (BAX), p-AMPK, SIRT1, p-NF-κB p65 in Eca109 cells 2. Results: The SEM concentrations of 25, 50 and 100 μmol/L selected through pre-experiment are used for formal research. Under SEM processing, compared with the CK group, the proliferation levels (24, 48 h) of Eca109 cells, protein expressions of Bcl2 and p-NF-κB p65 in SEM-L group, SEM-M group and SEM-H group decreased significantly while the apoptosis rate, the number of autophagosomes, the protein expressions of LC3Ⅱ-/LC3-Ⅰ,Beclin-1, BAX, p-AMPK and SIRT1 increased significantly, in a dose-dependent manner (all P<0.05); compared with the SEM-H group, the proliferation level (24, 48 h) of Eca109 cells, protein expressions of Bcl2 and p-NF-κB p65 in SEM-H+Compound C group increased significantly while the apoptosis rate, the number of autophagosomes, the protein expressions of LC3Ⅱ-/LC3-Ⅰ, Beclin-1,BAX, p-AMPK and SIRT1 decreased significantly(all P<0.05). Conclusion: SEM may promote autophagy and apoptosis of Eca109 cells by activating AMPK/SIRT1 signaling pathway and inhibiting NF-κB vitality.
Objective: To explore the effect of sesamol (SEM) on autophagy and apoptosis of esophageal squamous cell carcinoma (ESCC) Eca109 cells through adenylate activated protein kinase (AMPK)/silencing information regulator 1 (SIRT1)/nuclear factor κB （NF- κB) pathway. Methods: Eca109 cells of ESCC and HEEpiC of human esophageal epithelial cells were treated with different concentrations of SEM (0, 1.562 5, 3.125, 6.25, 12.5, 25, 50, 100, 200, and 400 μmol/L) for 48 hours. Cell viability was detected by CCK-8 method and appropriate SEM concentrations were screened for subsequent experiments. Eca109 cells were grouped into control group (CK group, 0 μmol/L), low-dose SEM group (SEM-L group, 25 μmol/L), medium-dose SEM group (SEM-M group, 50 μmol/L),high-dose SEM group (SEM-M group, 50 μmol/L), high-dose SEM group (SEM-H group, 100 μmol/L) and high-dose SEM+compound C (AMPK inhibitor) group (SEM-H+Compound C group, 100 μmol/L+10 μmol/L). All Eca109 cells were treated at the corresponding drug concentration for 48 hours. CCK-8 assay was applied to detect the proliferation of Eca109 cells; flow cytometry was applied to detect apoptosis; transmission electron microscopy was applied to observe autophagosomes in Eca109 cells and WB assay was applied to detect the protein expressions of microtubule-associated protein 1 light chain 3 (LC3)-Ⅱ/LC3-Ⅰ, Beclin-1, B-lymphoma-2 (Bcl2),Bcl2-associated X protein (BAX), p-AMPK, SIRT1, p-NF-κB p65 in Eca109 cells 2. Results: The SEM concentrations of 25, 50 and 100 μmol/L selected through pre-experiment are used for formal research. Under SEM processing, compared with the CK group, the proliferation levels (24, 48 h) of Eca109 cells, protein expressions of Bcl2 and p-NF-κB p65 in SEM-L group, SEM-M group and SEM-H group decreased significantly while the apoptosis rate, the number of autophagosomes, the protein expressions of LC3Ⅱ-/LC3-Ⅰ,Beclin-1, BAX, p-AMPK and SIRT1 increased significantly, in a dose-dependent manner (all P<0.05); compared with the SEM-H group, the proliferation level (24, 48 h) of Eca109 cells, protein expressions of Bcl2 and p-NF-κB p65 in SEM-H+Compound C group increased significantly while the apoptosis rate, the number of autophagosomes, the protein expressions of LC3Ⅱ-/LC3-Ⅰ, Beclin-1,BAX, p-AMPK and SIRT1 decreased significantly(all P<0.05). Conclusion: SEM may promote autophagy and apoptosis of Eca109 cells by activating AMPK/SIRT1 signaling pathway and inhibiting NF-κB vitality.
2023, 30(2):129-134.
DOI: 10.3872/j.issn.1007-385X.2023.02.005
Abstract:
Objective: To study the possible mechanism of lung adenocarcinoma- infiltrating CD8+ T cells expressing CD39. Methods: The transcriptomic data of lung adenocarcinoma (LUAD) tissues and normal lung tissues from the TCGA database were used to analyze the differences in CD39 expression in LUAD tissues and normal lung tissues and its impact on patient prognosis, and to analyze the relationship between CD39 expression and T cell infiltration and activation. Mouse subcutaneous transplantation tumor model was established using LUAD Lewis cells. Flow cytometry was used to detect the expression of CD8+CD39+ T cells in lymph nodes, pancreas and transplantation tumor tissues. Lewis cell culture supernatant was collected as conditioned culture medium (CCM). CD8+T cells and CD11b+ cells were sorted by magnetic activated cell sorting (MACS). Then, CCM and mouse recombinant interleukin-6 (IL-6) were added into the supernatant respectively and contact culture and non-contact culture were carried out to explore the possible mechanism of CD39 expression in CD8+ T cells. Result: The expression of CD39 in LUAD tissues was low (P<0.01). Its expression level was all positively correlated with overall survival (OS) of LUAD patients, the infiltration of T cells and the level of activation (P<0.05 or P<0.01). Flow cytometry results showed that the proportion of CD8+CD39+ T cells in transplantation tumor tissues was significantly higher than that in lymph nodes and spleen (P<0.01). Both CCM and IL-6 could not induce CD8+ T cells to express CD39. Non-contact co-culture of CD11b+ cells and CD8+ T cells could not induce CD8+ T cells to express CD39 either. Direct contact co-culture of CD11b+ cells and CD8+ T cells could induce CD8+ T cells to express CD39(P<0.01). Conclusion: CD11b+ cells induced tumor-infiltrating CD8+ T cells to express CD39 through direct contact, and CD39 may act as a molecule marker of LUAD-specific CD8+ T cells.
Objective: To study the possible mechanism of lung adenocarcinoma- infiltrating CD8+ T cells expressing CD39. Methods: The transcriptomic data of lung adenocarcinoma (LUAD) tissues and normal lung tissues from the TCGA database were used to analyze the differences in CD39 expression in LUAD tissues and normal lung tissues and its impact on patient prognosis, and to analyze the relationship between CD39 expression and T cell infiltration and activation. Mouse subcutaneous transplantation tumor model was established using LUAD Lewis cells. Flow cytometry was used to detect the expression of CD8+CD39+ T cells in lymph nodes, pancreas and transplantation tumor tissues. Lewis cell culture supernatant was collected as conditioned culture medium (CCM). CD8+T cells and CD11b+ cells were sorted by magnetic activated cell sorting (MACS). Then, CCM and mouse recombinant interleukin-6 (IL-6) were added into the supernatant respectively and contact culture and non-contact culture were carried out to explore the possible mechanism of CD39 expression in CD8+ T cells. Result: The expression of CD39 in LUAD tissues was low (P<0.01). Its expression level was all positively correlated with overall survival (OS) of LUAD patients, the infiltration of T cells and the level of activation (P<0.05 or P<0.01). Flow cytometry results showed that the proportion of CD8+CD39+ T cells in transplantation tumor tissues was significantly higher than that in lymph nodes and spleen (P<0.01). Both CCM and IL-6 could not induce CD8+ T cells to express CD39. Non-contact co-culture of CD11b+ cells and CD8+ T cells could not induce CD8+ T cells to express CD39 either. Direct contact co-culture of CD11b+ cells and CD8+ T cells could induce CD8+ T cells to express CD39(P<0.01). Conclusion: CD11b+ cells induced tumor-infiltrating CD8+ T cells to express CD39 through direct contact, and CD39 may act as a molecule marker of LUAD-specific CD8+ T cells.
2023, 30(2):135-141.
DOI: 10.3872/j.issn.1007-385X.2023.02.006
Abstract:
Objective: To investigate the expression of cellular retinoic acid binding protein 2 (CRABP2) in endometrial adenocarcinoma tissues and cells and its effects on the proliferation and invasion of endometrial adenocarcinoma cells as well as its molecular mechanism. Methods: A total of 24 pairs of endometrioid adenocarcinoma tissues and matched normal endometrial tissues were collected from Hengshui People's Hospital from June 2020 to April 2021, and human endometrial adenocarcinoma cells (An3ca and KLE) were cultured in vitro. The expression of CRABP2 in human endometrioid adenocarcinoma tissues and normal endometrial tissues was analyzed by immunohistochemistry and WB. The knockdown efficiency of CRABP2 in An3ca and KLE cells was detected by WB method, and the proliferation and invasion ability of An3ca and KLE cells after CRABP2 knockdown was detected by EDU method and Transwell assay, the expressions of key proteins related to Wnt/β-catenin pathway (β-catenin, c-Myc, cyclin-D1, MMP7 and MMP9) in An3ca and KLE cells after CRABP2 knockdown were detected by WB. The effects of CRABP2 on the growth of xenograft tumor and the expression of Ki67 and β-catenin in xenograft tumor tissues were observed in nude mice tumorigenesis assay. Results: Compared with normal endometrial tissue, the expression of CRABP2 was up-regulated in human endometrioid adenocarcinoma tissue. Expression of CRABP2 in An3ca and KLE cells decreased after transfection of shRNA targeting CRABP2 (all P<0.01). The proliferation and invasion ability of An3ca and KLE cells were decreased after CRABP2 knockdown (all P<0.01) and the Wnt/β -catenin pathway was inhibited (P<0.01). The tumor formation experiment showed that the tumor volume of transplanted tumor in nude mice decreased significantly after CRABP2 knockdown (P<0.01). Conclusion: CRABP2 can promote the proliferation and invasion of endometrioid adenocarcinoma cells by regulating the Wnt/β-catenin pathway.
Objective: To investigate the expression of cellular retinoic acid binding protein 2 (CRABP2) in endometrial adenocarcinoma tissues and cells and its effects on the proliferation and invasion of endometrial adenocarcinoma cells as well as its molecular mechanism. Methods: A total of 24 pairs of endometrioid adenocarcinoma tissues and matched normal endometrial tissues were collected from Hengshui People's Hospital from June 2020 to April 2021, and human endometrial adenocarcinoma cells (An3ca and KLE) were cultured in vitro. The expression of CRABP2 in human endometrioid adenocarcinoma tissues and normal endometrial tissues was analyzed by immunohistochemistry and WB. The knockdown efficiency of CRABP2 in An3ca and KLE cells was detected by WB method, and the proliferation and invasion ability of An3ca and KLE cells after CRABP2 knockdown was detected by EDU method and Transwell assay, the expressions of key proteins related to Wnt/β-catenin pathway (β-catenin, c-Myc, cyclin-D1, MMP7 and MMP9) in An3ca and KLE cells after CRABP2 knockdown were detected by WB. The effects of CRABP2 on the growth of xenograft tumor and the expression of Ki67 and β-catenin in xenograft tumor tissues were observed in nude mice tumorigenesis assay. Results: Compared with normal endometrial tissue, the expression of CRABP2 was up-regulated in human endometrioid adenocarcinoma tissue. Expression of CRABP2 in An3ca and KLE cells decreased after transfection of shRNA targeting CRABP2 (all P<0.01). The proliferation and invasion ability of An3ca and KLE cells were decreased after CRABP2 knockdown (all P<0.01) and the Wnt/β -catenin pathway was inhibited (P<0.01). The tumor formation experiment showed that the tumor volume of transplanted tumor in nude mice decreased significantly after CRABP2 knockdown (P<0.01). Conclusion: CRABP2 can promote the proliferation and invasion of endometrioid adenocarcinoma cells by regulating the Wnt/β-catenin pathway.
2023, 30(2):142-149.
DOI: 10.3872/j.issn.1007-385X.2023.02.007
Abstract:
Objective: To investigate the correlation between programmed death-ligand 1 (PD-L1) and sialic acid-binding Ig-like lectin 15 (Siglec-15）in ovarian cancer (OC) and its prognostic significance and their effects on the proliferation, migration and invasion of ovarian cancer SKOV3 cells.Methods: A total of 50 paraffin samples of ovarian cancer tissues and tissues of ipsilateral oviducts resected from patients with OC from January 2017 to December 2019 were collected from the Second Attached Hospital of Fujian Medical University. The expression levels of PD-L1 and Siglec-15 of cancer tissues and oviduct tissues were detected by immunohistochemical staining Envision method. Kaplan-Meier survival and Logistic regression analysis were used to analyze the relationship between the expressions of PD-L1and Siglec-15, and the prognosis of OC patients. Si-PD-L1 and si-NC were respectively transfected in ovarian cancer cells SKOV3 by transient transfection technology. The effect of PD-L1 expression on Siglec-15 in ovarian cancer cells SKOV3 was detected by qPCR and WB assays. CCK-8 and Transwell assays were used to verify the effect of PD-L1 and Siglec-15 expressions on the proliferation, migration and invasion of SKOV3 cells. Results: In the 50 cases of ovarian cancer, PD-L1 and Siglec-15 were highly expressed (50.00% and 42.00%). The expression of PD-L1 is significantly correlated with tumor pathological type, ascites, lymph node metastasis, FIGO stage and recurrence (all P<0.05). The expression of Siglec-15 is significantly correlated with lymph node metastasis and FIGO stage (both P<0.05). Ovarian cancer cell lines with low expression of PD-L1 were successfully constructed.Knockdown of the expression of PD-L1 could increase the expression of Siglec-15. Conclusion: PD-L1 and Siglec-15 have a high positive expression in ovarian cancer tissues. PD-L1 is an independent risk factor for disease recurrence. The expression of PD-L1 is negatively correlated with that of Siglec-15. Knocking down the expression of PD-L1 could increase the expression of Siglec-15, and inhibit the proliferation, migration and invasion of SKOV3 cells.
Objective: To investigate the correlation between programmed death-ligand 1 (PD-L1) and sialic acid-binding Ig-like lectin 15 (Siglec-15）in ovarian cancer (OC) and its prognostic significance and their effects on the proliferation, migration and invasion of ovarian cancer SKOV3 cells.Methods: A total of 50 paraffin samples of ovarian cancer tissues and tissues of ipsilateral oviducts resected from patients with OC from January 2017 to December 2019 were collected from the Second Attached Hospital of Fujian Medical University. The expression levels of PD-L1 and Siglec-15 of cancer tissues and oviduct tissues were detected by immunohistochemical staining Envision method. Kaplan-Meier survival and Logistic regression analysis were used to analyze the relationship between the expressions of PD-L1and Siglec-15, and the prognosis of OC patients. Si-PD-L1 and si-NC were respectively transfected in ovarian cancer cells SKOV3 by transient transfection technology. The effect of PD-L1 expression on Siglec-15 in ovarian cancer cells SKOV3 was detected by qPCR and WB assays. CCK-8 and Transwell assays were used to verify the effect of PD-L1 and Siglec-15 expressions on the proliferation, migration and invasion of SKOV3 cells. Results: In the 50 cases of ovarian cancer, PD-L1 and Siglec-15 were highly expressed (50.00% and 42.00%). The expression of PD-L1 is significantly correlated with tumor pathological type, ascites, lymph node metastasis, FIGO stage and recurrence (all P<0.05). The expression of Siglec-15 is significantly correlated with lymph node metastasis and FIGO stage (both P<0.05). Ovarian cancer cell lines with low expression of PD-L1 were successfully constructed.Knockdown of the expression of PD-L1 could increase the expression of Siglec-15. Conclusion: PD-L1 and Siglec-15 have a high positive expression in ovarian cancer tissues. PD-L1 is an independent risk factor for disease recurrence. The expression of PD-L1 is negatively correlated with that of Siglec-15. Knocking down the expression of PD-L1 could increase the expression of Siglec-15, and inhibit the proliferation, migration and invasion of SKOV3 cells.
2023, 30(2):150-155.
DOI: 10.3872/j.issn.1007-385X.2023.02.008
Abstract:
Objective: To determine the cost-effectiveness of adding PD-1 inhibitors to standard chemotherapy as the first-line treatment in patients with advanced, relapsed or metastatic esophageal squamous cell carcinoma (ESCC). Methods: Based on four first-line phase Ⅲ clinical trials of advanced ESCC: JUPITER-06, ESCORT-1st, ORIENT-15 and KEYNOTE-590 studies, Treeage Pro 2011 was used to establish traditional Markov model. The Markov model included three states: progression-free survival (PFS), progressive disease (PD) and death. Health outcomes were measured in quality-adjusted life years (QALYs) and incremental cost effectiveness ratio (ICER) was used to evaluate the economic benefits of treatment strategies. The sensitivity analysis was employed to further validate the above listed results. Results: The total cost of toripalizumab-chemotherapy group, camrelizumab-chemotherapy group, sintilimab-chemotherapy group, pembrolizumab-chemotherapy group and placebo-chemotherapy group were 66 327.58, 63 473.64, 62 268.18,295 515.26, and 32 753.79 yuan, respectively. The utility values were 0.648, 0.605, 0.673, 0.585, and 0.536 QALY, respectively. Among them, the ICER value of sintilimab-chemotherapy group was 217 018.13 yuan/QALY, which was lower than the Chinese willingness-to-pay (WTP) threshold (242 928 yuan/QALY), and it was a comparatively acceptable treatment strategy. Sensitivity analysis showed that the discount rate and the cost of sintilimab had the greatest influence on the model. Conclusion: Under the current economic situation in China, sintilimab combined with chemotherapy is an acceptable first-line PD-1 inhibitors immunotherapy strategy for the treatment of advanced ESCC.
Objective: To determine the cost-effectiveness of adding PD-1 inhibitors to standard chemotherapy as the first-line treatment in patients with advanced, relapsed or metastatic esophageal squamous cell carcinoma (ESCC). Methods: Based on four first-line phase Ⅲ clinical trials of advanced ESCC: JUPITER-06, ESCORT-1st, ORIENT-15 and KEYNOTE-590 studies, Treeage Pro 2011 was used to establish traditional Markov model. The Markov model included three states: progression-free survival (PFS), progressive disease (PD) and death. Health outcomes were measured in quality-adjusted life years (QALYs) and incremental cost effectiveness ratio (ICER) was used to evaluate the economic benefits of treatment strategies. The sensitivity analysis was employed to further validate the above listed results. Results: The total cost of toripalizumab-chemotherapy group, camrelizumab-chemotherapy group, sintilimab-chemotherapy group, pembrolizumab-chemotherapy group and placebo-chemotherapy group were 66 327.58, 63 473.64, 62 268.18,295 515.26, and 32 753.79 yuan, respectively. The utility values were 0.648, 0.605, 0.673, 0.585, and 0.536 QALY, respectively. Among them, the ICER value of sintilimab-chemotherapy group was 217 018.13 yuan/QALY, which was lower than the Chinese willingness-to-pay (WTP) threshold (242 928 yuan/QALY), and it was a comparatively acceptable treatment strategy. Sensitivity analysis showed that the discount rate and the cost of sintilimab had the greatest influence on the model. Conclusion: Under the current economic situation in China, sintilimab combined with chemotherapy is an acceptable first-line PD-1 inhibitors immunotherapy strategy for the treatment of advanced ESCC.
9 Construction and functional identification of CD19-CAR vector based on PiggyBac transposable system
2023, 30(2):156-160.
DOI: 10.3872/j.issn.1007-385X.2023.02.009
Abstract:
Objective: To develop an electroporation CAR-T cell preparation method based on PiggyBac (PB) transposable system and to characterize its anti-cancer function in vitro. Methods: Healthy human peripheral blood mononuclear cells (PBMCs) were used to obtain T cells. The CD19 gene was cloned into PB plasmid (transposon) by molecular cloning technique. Then, the transposon and transposase plasmid were introduced into activated T cells by electroporation, and the transfection efficiency was measured. Finally, the ability of prepared CAR-T cells to kill human Burkitt's lymphoma Raji cells was evaluated by flow cytometry and luciferase luminescence assay. Results: The transfection efficiency of CD19 CAR-T cells prepared by electroporation was high (>60%) in a dose-dependent manner, and CAR-T cells had a significantly higher cytotoxicity to Raji cells relative to the Pan-T cell group (P<0.05).Conclusion: The developed PB transposable system is feasible for electrotransfection and has the potential for clinical application inCD19 CAR-T cell preparation due to its significant in vitro cancer cell killing ability.
Objective: To develop an electroporation CAR-T cell preparation method based on PiggyBac (PB) transposable system and to characterize its anti-cancer function in vitro. Methods: Healthy human peripheral blood mononuclear cells (PBMCs) were used to obtain T cells. The CD19 gene was cloned into PB plasmid (transposon) by molecular cloning technique. Then, the transposon and transposase plasmid were introduced into activated T cells by electroporation, and the transfection efficiency was measured. Finally, the ability of prepared CAR-T cells to kill human Burkitt's lymphoma Raji cells was evaluated by flow cytometry and luciferase luminescence assay. Results: The transfection efficiency of CD19 CAR-T cells prepared by electroporation was high (>60%) in a dose-dependent manner, and CAR-T cells had a significantly higher cytotoxicity to Raji cells relative to the Pan-T cell group (P<0.05).Conclusion: The developed PB transposable system is feasible for electrotransfection and has the potential for clinical application inCD19 CAR-T cell preparation due to its significant in vitro cancer cell killing ability.
2023, 30(2):161-166.
DOI: 10.3872/j.issn.1007-385X.2023.02.010
Abstract:
C5AR1是补体激活片段C5a的受体，主要在粒细胞、单核细胞、树突状细胞和髓源性抑制细胞（MDSC）以及肿瘤细胞上表达。C5a可以刺激中性粒细胞产生炎性介质，也可以募集MDSC等免疫抑制细胞形成免疫抑制微环境，促进肿瘤的生长和转移，从而在肿瘤的发生发展中起到重要的作用。C5AR1已成为肿瘤治疗的新靶点，C5AR1靶向药与免疫检查点抑制剂联用能够起到协同抑制肿瘤的作用。就C5AR1的基本信息，促进肿瘤发生、生长和转移的机制，以及以C5AR1为靶点的抗肿瘤药的开发现状进行综述，以期为后续的机制研究、药物开发提供参考。
C5AR1是补体激活片段C5a的受体，主要在粒细胞、单核细胞、树突状细胞和髓源性抑制细胞（MDSC）以及肿瘤细胞上表达。C5a可以刺激中性粒细胞产生炎性介质，也可以募集MDSC等免疫抑制细胞形成免疫抑制微环境，促进肿瘤的生长和转移，从而在肿瘤的发生发展中起到重要的作用。C5AR1已成为肿瘤治疗的新靶点，C5AR1靶向药与免疫检查点抑制剂联用能够起到协同抑制肿瘤的作用。就C5AR1的基本信息，促进肿瘤发生、生长和转移的机制，以及以C5AR1为靶点的抗肿瘤药的开发现状进行综述，以期为后续的机制研究、药物开发提供参考。
2023, 30(2):167-172.
DOI: 10.3872/j.issn.1007-385X.2023.02.011
Abstract:
驱动蛋白KIF14是一种马达蛋白，依靠ATP水解酶的活性，向微管正极末端运动。在细胞内，KIF14参与物质运输、纤毛发生和细胞有丝分裂等过程。近年来的研究表明，在细胞质分裂的不同阶段KIF14 通过与多种蛋白质相互作用来调控有丝分裂的进程。KIF14 的表达异常会导致细胞有丝分裂失常，造成细胞基因组不稳定，而基因组的不稳定是导致肿瘤发生的重要原因。KIF14与多种肿瘤的发生发展密切相关，并且与肿瘤细胞的迁移、侵袭和对药物的敏感性有关，其已成为肿瘤早期诊断、治疗和预后评估的潜在靶点，因此，开发靶向KIF14的抑制剂，将为肿瘤的临床治疗提供新药物。
驱动蛋白KIF14是一种马达蛋白，依靠ATP水解酶的活性，向微管正极末端运动。在细胞内，KIF14参与物质运输、纤毛发生和细胞有丝分裂等过程。近年来的研究表明，在细胞质分裂的不同阶段KIF14 通过与多种蛋白质相互作用来调控有丝分裂的进程。KIF14 的表达异常会导致细胞有丝分裂失常，造成细胞基因组不稳定，而基因组的不稳定是导致肿瘤发生的重要原因。KIF14与多种肿瘤的发生发展密切相关，并且与肿瘤细胞的迁移、侵袭和对药物的敏感性有关，其已成为肿瘤早期诊断、治疗和预后评估的潜在靶点，因此，开发靶向KIF14的抑制剂，将为肿瘤的临床治疗提供新药物。
2023, 30(2):173-177.
DOI: 10.3872/j.issn.1007-385X.2023.02.012
Abstract:
液体活检作为精准医疗的新兴焦点，在肺癌脑转移患者靶向治疗中发挥着重要作用。循环肿瘤DNA（ctDNA）、循环肿瘤细胞（CTC）和微小RNA（miRNA）是液体活检的主要检测标志物，它们可以从脑脊液和其它体液中被分离出来。而在中枢神经系统中，脑脊液易获得且是最能反映肿瘤遗传特征的液体介质，通过分析脑脊液中的基因组数据可以获得患者肿瘤特征的详细信息。目前已经开展多项脑脊液液体活检对肺癌脑转移患者靶向治疗作用的研究，利用靶向治疗前脑脊液液体活检标志物基因组特征，以及对脑脊液进行连续采样分析脑脊液活检标志物在治疗过程中的变化，能够监测患者病情活动、预测对靶向治疗的反应和检测耐药性等，从而临床指导患者进行个性化治疗。因此，脑脊液液体活检技术在肺癌脑转移患者精准治疗中已经显示出重要的临床应用价值和巨大潜力，针对脑脊液液体活检的分析可能成为转移性脑肿瘤靶向治疗的新型治疗手段。
液体活检作为精准医疗的新兴焦点，在肺癌脑转移患者靶向治疗中发挥着重要作用。循环肿瘤DNA（ctDNA）、循环肿瘤细胞（CTC）和微小RNA（miRNA）是液体活检的主要检测标志物，它们可以从脑脊液和其它体液中被分离出来。而在中枢神经系统中，脑脊液易获得且是最能反映肿瘤遗传特征的液体介质，通过分析脑脊液中的基因组数据可以获得患者肿瘤特征的详细信息。目前已经开展多项脑脊液液体活检对肺癌脑转移患者靶向治疗作用的研究，利用靶向治疗前脑脊液液体活检标志物基因组特征，以及对脑脊液进行连续采样分析脑脊液活检标志物在治疗过程中的变化，能够监测患者病情活动、预测对靶向治疗的反应和检测耐药性等，从而临床指导患者进行个性化治疗。因此，脑脊液液体活检技术在肺癌脑转移患者精准治疗中已经显示出重要的临床应用价值和巨大潜力，针对脑脊液液体活检的分析可能成为转移性脑肿瘤靶向治疗的新型治疗手段。
2023, 30(2):178-182.
DOI: 10.3872/j.issn.1007-385X.2023.02.013
Abstract:
嗜酸性粒细胞是进化上相对保守的多效性白细胞。嗜酸性粒细胞可浸润于多种肿瘤组织，合成和分泌大量可溶介质和效应分子，抑制肿瘤细胞生长、直接对肿瘤细胞造成杀伤作用。还可作为抗原提呈细胞促进T细胞发挥抗肿瘤效应、作为免疫功能的调节细胞改善肿瘤特异性CD8+ T细胞的浸润，以及促进肿瘤血管正常化抑制肿瘤的发生发展，从而间接对肿瘤细胞造成杀伤作用。同时有研究发现，嗜酸性粒细胞可通过塑造肿瘤组织免疫微环境影响肿瘤免疫治疗的结局，如在非霍奇金淋巴瘤等血液肿瘤以及在胃癌、结直肠癌、黑色素瘤和非小细胞肺癌等实体肿瘤的免疫治疗中发挥着重要作用。嗜酸性粒细胞有望成为未来评估相关肿瘤患者免疫治疗预后的生物标志物。深入探究嗜酸性粒细胞在肿瘤免疫治疗中的作用机制，有望为肿瘤治疗及预后评估提供新策略、新方法。
嗜酸性粒细胞是进化上相对保守的多效性白细胞。嗜酸性粒细胞可浸润于多种肿瘤组织，合成和分泌大量可溶介质和效应分子，抑制肿瘤细胞生长、直接对肿瘤细胞造成杀伤作用。还可作为抗原提呈细胞促进T细胞发挥抗肿瘤效应、作为免疫功能的调节细胞改善肿瘤特异性CD8+ T细胞的浸润，以及促进肿瘤血管正常化抑制肿瘤的发生发展，从而间接对肿瘤细胞造成杀伤作用。同时有研究发现，嗜酸性粒细胞可通过塑造肿瘤组织免疫微环境影响肿瘤免疫治疗的结局，如在非霍奇金淋巴瘤等血液肿瘤以及在胃癌、结直肠癌、黑色素瘤和非小细胞肺癌等实体肿瘤的免疫治疗中发挥着重要作用。嗜酸性粒细胞有望成为未来评估相关肿瘤患者免疫治疗预后的生物标志物。深入探究嗜酸性粒细胞在肿瘤免疫治疗中的作用机制，有望为肿瘤治疗及预后评估提供新策略、新方法。
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- 《中国肿瘤生物治疗杂志》
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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.