Mobile website
Volume 28,Issue 9,2021 Table of Contents
2021, 28(9):863-868.
DOI: 10.3872/j.issn.1007-385X.2021.09.001
Abstract:
Genetically engineered T cell immunotherapy has made breakthroughs in the field of tumor therapy, including chimeric antigen receptor engineered-T (CAR-T) cells and T cell receptor modified-T (TCR-T) cells. Although CAR-T cell therapy presents an attractive clinical efficacy on treatment of hematological tumors, CAR-T cells can only recognize tumor cell membrane antigens (accounting for approximately 10% of all cellular antigens); However, TCR-T cells can recognize intracellular antigens presented by human leukocyte antigens (HLAs), so TCR-T cells can recognize more types of tumor antigens, and then realize a reasonable supplement to CAR-T cells. TCR-T cells needs to recognize both intracellular antigens and corresponding HLAs, while the HLA types and tumor antigens in different patients may present huge difference, therefore, it is necessary to customize individualized TCR-T cells for each/each type of cancer patient, in which screening the TCR that specifically recognizes tumor antigens is the key point. Currently, there are two main strategies for screening TCR, targeting "known" tumor antigens and targeting "unknown" tumor antigens, and each has its own applicability. A suitable screening method should be developed for each patient to prepare a variety of tumor-specific TCR-T cells, so as to achieve individualized TCR-T cell therapy for tumor treatment.
Genetically engineered T cell immunotherapy has made breakthroughs in the field of tumor therapy, including chimeric antigen receptor engineered-T (CAR-T) cells and T cell receptor modified-T (TCR-T) cells. Although CAR-T cell therapy presents an attractive clinical efficacy on treatment of hematological tumors, CAR-T cells can only recognize tumor cell membrane antigens (accounting for approximately 10% of all cellular antigens); However, TCR-T cells can recognize intracellular antigens presented by human leukocyte antigens (HLAs), so TCR-T cells can recognize more types of tumor antigens, and then realize a reasonable supplement to CAR-T cells. TCR-T cells needs to recognize both intracellular antigens and corresponding HLAs, while the HLA types and tumor antigens in different patients may present huge difference, therefore, it is necessary to customize individualized TCR-T cells for each/each type of cancer patient, in which screening the TCR that specifically recognizes tumor antigens is the key point. Currently, there are two main strategies for screening TCR, targeting "known" tumor antigens and targeting "unknown" tumor antigens, and each has its own applicability. A suitable screening method should be developed for each patient to prepare a variety of tumor-specific TCR-T cells, so as to achieve individualized TCR-T cell therapy for tumor treatment.
2021, 28(9):869-876.
DOI: 10.3872/j.issn.1007-385X.2021.09.002
Abstract:
Objective: To investigate the immunological characteristics and the anti-tumor potential of T cells in the tumor-draining lymph node (TDLN) of colorectal cancer (CRC). Methods: The clinical data and lymph node specimens of 33 CRC patients who were treated in the Affiliated Hospital of Guizhou Medical University from December 2018 to January 2021 were retrospectively collected for this study. Paired TDLN and non-tumor-draining lymph nodes (NTDLN) were collected from CRC patients by using Dye tracer. Flow cytometry was used to examine the immune cell subsets and functional phenotypic differences in TDLN and NTDLN that prepared as single cell suspension. ELISPOT (enzyme-linked immunoSPOT) method was employed to compare the proportion of tumor-reactive T cells in TDLN and NTDLN. The spatial distribution of immune cells in the TDLN and NTDLN was evaluated by multiplexed immunohistochemistry (mIHC). The TDLN-T cells were amplified ex vivo to evaluate the T cell subsets and phenotypic changes as well as tumor immune response capabilities. Results: Compared with NTDLN, there were higher proportions of tumor[1]reactive T cells and regulatory T cells (Tregs), but lower proportion of monocytic myeloid-derived suppressor cells (Mo-MDSCs) in TDLN (P<0.01 or P<0.05 ); in addition, both the activation markers (ICOS, CD28) and suppression markers (PD-1, TIGIT) were elevated (P<0.05 or P<0.01 ). mIHC results showed that Tregs were mainly distributed in the cortex, and follicular helper T (Tfh) cells were located in the germinal center. After the TDLN-T cells were expanded ex vivo, CD8+ T cells were the predominant phenotype （P<0.01), and the expression of ICOS and CD28 and the proportion of tumor-reactive T cells were increased (P<0.05 or P<0.01 ).T cells in colorectal cancer TDLN are activated and highly expresses immune suppression markers. Ex vivo expansion can enhance the activation of TDLN-T cells and increase the proportion of tumor-reactive T cells.
Objective: To investigate the immunological characteristics and the anti-tumor potential of T cells in the tumor-draining lymph node (TDLN) of colorectal cancer (CRC). Methods: The clinical data and lymph node specimens of 33 CRC patients who were treated in the Affiliated Hospital of Guizhou Medical University from December 2018 to January 2021 were retrospectively collected for this study. Paired TDLN and non-tumor-draining lymph nodes (NTDLN) were collected from CRC patients by using Dye tracer. Flow cytometry was used to examine the immune cell subsets and functional phenotypic differences in TDLN and NTDLN that prepared as single cell suspension. ELISPOT (enzyme-linked immunoSPOT) method was employed to compare the proportion of tumor-reactive T cells in TDLN and NTDLN. The spatial distribution of immune cells in the TDLN and NTDLN was evaluated by multiplexed immunohistochemistry (mIHC). The TDLN-T cells were amplified ex vivo to evaluate the T cell subsets and phenotypic changes as well as tumor immune response capabilities. Results: Compared with NTDLN, there were higher proportions of tumor[1]reactive T cells and regulatory T cells (Tregs), but lower proportion of monocytic myeloid-derived suppressor cells (Mo-MDSCs) in TDLN (P<0.01 or P<0.05 ); in addition, both the activation markers (ICOS, CD28) and suppression markers (PD-1, TIGIT) were elevated (P<0.05 or P<0.01 ). mIHC results showed that Tregs were mainly distributed in the cortex, and follicular helper T (Tfh) cells were located in the germinal center. After the TDLN-T cells were expanded ex vivo, CD8+ T cells were the predominant phenotype （P<0.01), and the expression of ICOS and CD28 and the proportion of tumor-reactive T cells were increased (P<0.05 or P<0.01 ).T cells in colorectal cancer TDLN are activated and highly expresses immune suppression markers. Ex vivo expansion can enhance the activation of TDLN-T cells and increase the proportion of tumor-reactive T cells.
2021, 28(9):877-884.
DOI: 10.3872/j.issn.1007-385X.2021.09.003
Abstract:
Objective: To analyze the relationship between the expression of cyclooxygenase-2 (COX-2) and clinicopathological features and prognosis of patients with liver cancer, and to explore the role and mechanism of formononetin (FOR) in the pathogenesis of liver cancer. Methods: The clinical data of 60 patients with liver cancer and 20 pairs of surgically resected cancer tissues and corresponding para-cancerous tissues from liver cancer patients that treated in the Fourth Hospital of Hebei Medical University during January 2021 and May 2021 were collected for this study; in addition, human liver cancer cell lines HepG2 and Bel-7402 were also collected. The expression of COX-2 in liver cancer tissues was detected by qPCR and immunohistochemical staining, and the relationship between COX-2 expression and clinicopathological characteristics and prognosis of patients was analyzed. Diethylnitrosamine-induced mouse model of liver cancer was established to verify the effect of FOR on the incidence of liver cancer. After being treated with 0.003 and 0.006 μmol/ml FOR 48 h, the effects of FOR on proliferation and cell cycle of HepG2 and Bel-7402 cells were detected by CCK-8 and Flow cytometry. The changes in the expression of COX-2, CDK4, CDK6 and cyclin D1 were detected by qPCR and WB. Results: The mRNA expression of COX-2 in liver cancer tissues was significantly higher than that in para cancerous tissues ( P<0.01 ). The positive expression rate of COX-2 in liver cancer tissues was 68.3% (41/60), and the positive expression of COX-2 was correlated with advanced TNM stage, large tumor and short survival (all P<0.05 ). In the xenograft mouse model of induced liver cancer, the incidence of liver cancer in mice treated with FOR was significantly reduced, and the expression of COX-2 in liver tissues was significantly decreased (all P<0.05 ). FOR significantly inhibited the proliferation, increased the proportion of cells at G0/G1 phase, decreased the proportion of cells at S and G2 phase (all P<0.05 ), and inhibited the expression of COX-2 and cyclin D1 in HepG2 and Bel-7402 cells (all P<0.01 ). Conclusion: Liver cancer patients with positive COX-2 expression have an advanced clinical stage and a poor prognosis. FOR can prevent the occurrence and development of liver cancer by inhibiting the expression of COX-2 and cyclin D1.
Objective: To analyze the relationship between the expression of cyclooxygenase-2 (COX-2) and clinicopathological features and prognosis of patients with liver cancer, and to explore the role and mechanism of formononetin (FOR) in the pathogenesis of liver cancer. Methods: The clinical data of 60 patients with liver cancer and 20 pairs of surgically resected cancer tissues and corresponding para-cancerous tissues from liver cancer patients that treated in the Fourth Hospital of Hebei Medical University during January 2021 and May 2021 were collected for this study; in addition, human liver cancer cell lines HepG2 and Bel-7402 were also collected. The expression of COX-2 in liver cancer tissues was detected by qPCR and immunohistochemical staining, and the relationship between COX-2 expression and clinicopathological characteristics and prognosis of patients was analyzed. Diethylnitrosamine-induced mouse model of liver cancer was established to verify the effect of FOR on the incidence of liver cancer. After being treated with 0.003 and 0.006 μmol/ml FOR 48 h, the effects of FOR on proliferation and cell cycle of HepG2 and Bel-7402 cells were detected by CCK-8 and Flow cytometry. The changes in the expression of COX-2, CDK4, CDK6 and cyclin D1 were detected by qPCR and WB. Results: The mRNA expression of COX-2 in liver cancer tissues was significantly higher than that in para cancerous tissues ( P<0.01 ). The positive expression rate of COX-2 in liver cancer tissues was 68.3% (41/60), and the positive expression of COX-2 was correlated with advanced TNM stage, large tumor and short survival (all P<0.05 ). In the xenograft mouse model of induced liver cancer, the incidence of liver cancer in mice treated with FOR was significantly reduced, and the expression of COX-2 in liver tissues was significantly decreased (all P<0.05 ). FOR significantly inhibited the proliferation, increased the proportion of cells at G0/G1 phase, decreased the proportion of cells at S and G2 phase (all P<0.05 ), and inhibited the expression of COX-2 and cyclin D1 in HepG2 and Bel-7402 cells (all P<0.01 ). Conclusion: Liver cancer patients with positive COX-2 expression have an advanced clinical stage and a poor prognosis. FOR can prevent the occurrence and development of liver cancer by inhibiting the expression of COX-2 and cyclin D1.
2021, 28(9):885-892.
DOI: 10.3872/j.issn.1007-385X.2021.09.004
Abstract:
Objective: To investigate the effect of miR-153-3p on the proliferation, invasion and migration of gastric cancer SGC7901 cells and its molecular mechanism. Methods: A total of 60 pairs of cancer tissues and corresponding para-cancerous tissues of gastric cancer patients who were treated in the General Hospital of Ningxia Medical University during May 2018 and June 2020 were collected for this study; in addition, human gastric cancer cell lines (NCI-N87, AGS, SNU-5, SGC7901) and normal gastric epithelial GES-1 cells were also collected. The expression level of miR-153-3p in gastric cancer tissues and cells was detected by qRT-PCR. miR-153-3p mimics and mimic control were transfected into SGC7901 cells, respectively. The effects of miR-153-3p overexpression on proliferation, apoptosis, invasion and migration of gastric cancer SGC7901 cells were respectively determined using CCK-8, Clone formation assay, Flow cytometry, TUNEL, Transwell and Wound-healing assay. SGC7901 cell transplanted xenograft tumor model in nude mice was established to explore the effect of miR-153-3p on tumor growth. The targeting relationship between miR-153-3p and FZD3 was predicted and verified by bioinformatics database and Dual-luciferase reporter gene assay, respectively. The effects of miR-153-3p on expression of FZD3 protein and Wnt/β-catenin pathway related proteins were determined by Western blotting. Results: The expression level of miR-153-3p in gastric cancer tissues and cells was significantly lower than that in para-cancerous tissues and gastric epithelial cells, with the lowest expression in SGC7901 cells (all P<0.01). Up-regulation of miR-153-3p significantly inhibited the proliferation, invasion and migration abilities of SGC7901 cells, and increased the rate of apoptotic cells (all P<0.01). In addition, up-regulation of miR-153-3p significantly promoted the expression of E-cadherin but significantly suppressed the expression of N-cadherin, matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) (all P<0.01). In vivo experiments showed that intravenous injection of miR-153-3p mimics significantly reduced tumor size and Ki-67 expression, but significantly increased the expression of P57 in tumor tissues (all P<0.01). The mechanism analysis showed that miR-153-3p could bind to the 3'UTR region of FZD3 mRNA, and up-regulation of miR-153-3p inhibited the expression of FZD3 and increased the levels of β -catenin, TCF-4 and cyclin D1 (all P<0.01). Conclusion: MiR-153-3p regulates the proliferation, invasion and migration of gastric cancer SGC7901 cells via targeting FZD3 gene and regulating Wnt/β-catenin signaling pathway.
Objective: To investigate the effect of miR-153-3p on the proliferation, invasion and migration of gastric cancer SGC7901 cells and its molecular mechanism. Methods: A total of 60 pairs of cancer tissues and corresponding para-cancerous tissues of gastric cancer patients who were treated in the General Hospital of Ningxia Medical University during May 2018 and June 2020 were collected for this study; in addition, human gastric cancer cell lines (NCI-N87, AGS, SNU-5, SGC7901) and normal gastric epithelial GES-1 cells were also collected. The expression level of miR-153-3p in gastric cancer tissues and cells was detected by qRT-PCR. miR-153-3p mimics and mimic control were transfected into SGC7901 cells, respectively. The effects of miR-153-3p overexpression on proliferation, apoptosis, invasion and migration of gastric cancer SGC7901 cells were respectively determined using CCK-8, Clone formation assay, Flow cytometry, TUNEL, Transwell and Wound-healing assay. SGC7901 cell transplanted xenograft tumor model in nude mice was established to explore the effect of miR-153-3p on tumor growth. The targeting relationship between miR-153-3p and FZD3 was predicted and verified by bioinformatics database and Dual-luciferase reporter gene assay, respectively. The effects of miR-153-3p on expression of FZD3 protein and Wnt/β-catenin pathway related proteins were determined by Western blotting. Results: The expression level of miR-153-3p in gastric cancer tissues and cells was significantly lower than that in para-cancerous tissues and gastric epithelial cells, with the lowest expression in SGC7901 cells (all P<0.01). Up-regulation of miR-153-3p significantly inhibited the proliferation, invasion and migration abilities of SGC7901 cells, and increased the rate of apoptotic cells (all P<0.01). In addition, up-regulation of miR-153-3p significantly promoted the expression of E-cadherin but significantly suppressed the expression of N-cadherin, matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) (all P<0.01). In vivo experiments showed that intravenous injection of miR-153-3p mimics significantly reduced tumor size and Ki-67 expression, but significantly increased the expression of P57 in tumor tissues (all P<0.01). The mechanism analysis showed that miR-153-3p could bind to the 3'UTR region of FZD3 mRNA, and up-regulation of miR-153-3p inhibited the expression of FZD3 and increased the levels of β -catenin, TCF-4 and cyclin D1 (all P<0.01). Conclusion: MiR-153-3p regulates the proliferation, invasion and migration of gastric cancer SGC7901 cells via targeting FZD3 gene and regulating Wnt/β-catenin signaling pathway.
2021, 28(9):893-899.
DOI: 10.3872/j.issn.1007-385X.2021.09.005
Abstract:
Objective: To explore the mechanism of circ_0001821 regulating the proliferation, apoptosis, migration and invasion of cutaneous squamous cell carcinoma (CSCC) A431 cells by targeting miR-203. Methods: The cancer and para-cancerous tissues of 39 patients with CSCC treated in the Second Affiliated Hospital of Hainan Medical University from February 2018 to August 2019, as well as the human CSCC cell line A431, were collected for this study. The qPCR method was used to detect the expression level of circ_0001821 in CSCC tissues and para-cancerous tissues. Using liposome transfection technology, si-circ_0001821, si-NC, miR-203 mimic, miR-NC, si-circ_0001821+anti-miR-NC and si-circ_0001821+anti-miR-203 were transfected into A431 cells, respectively. qPCR was used to detect the expression of circ_0001821 and miR-203 in the transfected cells. MTT method, Flow cytometry and Transwell chamber assay were used to detect the proliferation, apoptosis, migration and invasion of transfected A431 cells. WB was used to detect the expression of proteins related to proliferation, apoptosis, migration and invasion. Circinteractome database was utilized to predict the binding site between circ_0001821 and miR-203, which was further validated by Dual-luciferase reporter gene assay. Results: Compared with para-cancerous tissues, the expression level of circ_0001821 in CSCC tissues was significantly increased (P<0.01). Transfection of si-circ_0001821 could significantly reduce the expression of circ_0001821 (P<0.01), increase the apoptosis rate (P<0.01), and reduce the proliferation, migration and invasion abilities of A431 cells (all P<0.01). Dual-luciferase report gene assay confirmed that circ_0001821 could targetedly bind with miR-203. Transfection of miR-203 mimics could significantly reduce the proliferation, migration and invasion abilities but increase the apoptosis rate of A431 cells (all P<0.01). . Co-transfection of si-circ_0001821 and anti-miR-203 could significantly reverse the effects of si-circ_0001821 transfection on the proliferation, migration, invasion and apoptosis of A431 cells. Conclusion: circ_0001821 regulates the proliferation, migration, invasion and apoptosis of CSCC A431 cells by targeting miR-203.
Objective: To explore the mechanism of circ_0001821 regulating the proliferation, apoptosis, migration and invasion of cutaneous squamous cell carcinoma (CSCC) A431 cells by targeting miR-203. Methods: The cancer and para-cancerous tissues of 39 patients with CSCC treated in the Second Affiliated Hospital of Hainan Medical University from February 2018 to August 2019, as well as the human CSCC cell line A431, were collected for this study. The qPCR method was used to detect the expression level of circ_0001821 in CSCC tissues and para-cancerous tissues. Using liposome transfection technology, si-circ_0001821, si-NC, miR-203 mimic, miR-NC, si-circ_0001821+anti-miR-NC and si-circ_0001821+anti-miR-203 were transfected into A431 cells, respectively. qPCR was used to detect the expression of circ_0001821 and miR-203 in the transfected cells. MTT method, Flow cytometry and Transwell chamber assay were used to detect the proliferation, apoptosis, migration and invasion of transfected A431 cells. WB was used to detect the expression of proteins related to proliferation, apoptosis, migration and invasion. Circinteractome database was utilized to predict the binding site between circ_0001821 and miR-203, which was further validated by Dual-luciferase reporter gene assay. Results: Compared with para-cancerous tissues, the expression level of circ_0001821 in CSCC tissues was significantly increased (P<0.01). Transfection of si-circ_0001821 could significantly reduce the expression of circ_0001821 (P<0.01), increase the apoptosis rate (P<0.01), and reduce the proliferation, migration and invasion abilities of A431 cells (all P<0.01). Dual-luciferase report gene assay confirmed that circ_0001821 could targetedly bind with miR-203. Transfection of miR-203 mimics could significantly reduce the proliferation, migration and invasion abilities but increase the apoptosis rate of A431 cells (all P<0.01). . Co-transfection of si-circ_0001821 and anti-miR-203 could significantly reverse the effects of si-circ_0001821 transfection on the proliferation, migration, invasion and apoptosis of A431 cells. Conclusion: circ_0001821 regulates the proliferation, migration, invasion and apoptosis of CSCC A431 cells by targeting miR-203.
2021, 28(9):900-907.
DOI: 10.3872/j.issn.1007-385X.2021.09.006
Abstract:
Objective: To investigate the expression of lncRNA LINC01140 in esophageal squamous cell carcinoma (ESCC) tissues and cell lines, and to explore its effect on the proliferation and invasion of Eca109 cells as well as the possible molecular mechanism. Methods: The clinical data of 133 ESCC patients who were treated in the Fourth Hospital of Hebei Medical University from March 2012 to May 2015 and the data of 182 ESCC tissues and 286 normal esophageal mucosa tissues included in GEPIA database, as well as ESCC cell lines (Kyse150, Eca109, TE13) were collected for this study. The expression level of LINC01140 in ESCC tissues and cell lines was detected by qPCR method, and the relationship between its expression level and clinicopathological features as well as the prognosis of ESCC patients was further analyzed. pcDNA3.1-LINC01140, negative control (pcDNA3.1-NC) or miR-452-5p mimics and negative control (miR-NC) were respectively transfected into Eca109 cells. Then, MTS and Transwell assay were performed to assess the effect of LINC01140 on proliferation and invasion of transfected cells. The interaction between LINC01140 and miR-452-5p, as well as the effect of LINC01140 on the activation of Wnt/β-catenin pathway was detected by Dual-luciferase reporter gene assay and TOP/FOP reporter gene system. Results: The expression of LINC01140 was downregulated in ESCC tissues and cell lines (all P<0.01). Low expression of LINC01140 was closely correlated with the age, lymph node metastasis, TNM stage and the OS of ESCC patients (all P <0.01). Overexpression of LINC01140 significantly reduced the proliferation and invasion ability of Eca109 cells (all P<0.01). Mechanistic analysis indicated that LINC01140 affected the activation of Wnt/β-catenin signaling pathway possibly via competitively sponging miR-452-5p to further regulate the malignant biological behaviors of Eca109 cells. Conclusion: LINC01140 affects proliferation and invasion of ESCC cells via regulating miR-452-5p/Wnt/β-catenin axis. LINC01140 is expected to be a potential target for the targeted therapy and the molecular marker for the prognosis evaluation of ESCC patients.
Objective: To investigate the expression of lncRNA LINC01140 in esophageal squamous cell carcinoma (ESCC) tissues and cell lines, and to explore its effect on the proliferation and invasion of Eca109 cells as well as the possible molecular mechanism. Methods: The clinical data of 133 ESCC patients who were treated in the Fourth Hospital of Hebei Medical University from March 2012 to May 2015 and the data of 182 ESCC tissues and 286 normal esophageal mucosa tissues included in GEPIA database, as well as ESCC cell lines (Kyse150, Eca109, TE13) were collected for this study. The expression level of LINC01140 in ESCC tissues and cell lines was detected by qPCR method, and the relationship between its expression level and clinicopathological features as well as the prognosis of ESCC patients was further analyzed. pcDNA3.1-LINC01140, negative control (pcDNA3.1-NC) or miR-452-5p mimics and negative control (miR-NC) were respectively transfected into Eca109 cells. Then, MTS and Transwell assay were performed to assess the effect of LINC01140 on proliferation and invasion of transfected cells. The interaction between LINC01140 and miR-452-5p, as well as the effect of LINC01140 on the activation of Wnt/β-catenin pathway was detected by Dual-luciferase reporter gene assay and TOP/FOP reporter gene system. Results: The expression of LINC01140 was downregulated in ESCC tissues and cell lines (all P<0.01). Low expression of LINC01140 was closely correlated with the age, lymph node metastasis, TNM stage and the OS of ESCC patients (all P <0.01). Overexpression of LINC01140 significantly reduced the proliferation and invasion ability of Eca109 cells (all P<0.01). Mechanistic analysis indicated that LINC01140 affected the activation of Wnt/β-catenin signaling pathway possibly via competitively sponging miR-452-5p to further regulate the malignant biological behaviors of Eca109 cells. Conclusion: LINC01140 affects proliferation and invasion of ESCC cells via regulating miR-452-5p/Wnt/β-catenin axis. LINC01140 is expected to be a potential target for the targeted therapy and the molecular marker for the prognosis evaluation of ESCC patients.
2021, 28(9):908-913.
DOI: 10.3872/j.issn.1007-385X.2021.09.007
Abstract:
Objective: To investigate the effect of lncRNA LINC01410 on the proliferation, apoptosis and temozolomide (TMZ) sensitivity of glioma A172 cells and the underlying mechanism. Methods: qPCR method was used to determine the expression of LINC01410 in glioma cell lines (H4, SHG-44, A172) and normal astrocytes (HA1800). LINC01410 shRNA, shRNA control and miR-205-5p inhibitor and inhibitor control were respectively transfected into A172 cells, which were then treated with 400 μmol/L TMZ. Then, MTT assay and Flow cytometry were used to detect proliferation and apoptosis, and WB was used to detect protein expression of Bax, Bcl-2, cyclin D1 and p27 in transfected A172 cells. The target gene of LINC01410 was predicted by the online bioinformatic software LncBase, and the Dual-luciferase reporter gene system was used to verify the targeting relationship between LINC01410 and miR-205-5p. Results: The expression level of LINC01410 in three glioma cells was higher than that in normal astrocytes HA1800 cells (all P <0.01) with the highest expression level in A172 cells (P<0.01). After LINC01410 shRNA transfection and TMZ treatment, the proliferation decreased while the apoptosis rate increased in A172 cells, and the proportion of cells at G1 phase increased (all P<0.01); moreover, the protein expression level of Bax and p27 increased (all P<0.01), and the expression level of Bcl-2 and cyclin D1 decreased in A172 cells (all P<0.01). Dual-luciferase reporter gene assay verified that LINC01410 could targetedly bind with miR-205-5p, and down-regulation of LINC01410 promoted miR-205-5p expression. Transfection of miR-205-5p inhibitor could reverse the effects of down-regulation of LINC01410 and TMZ treatment on the proliferation, cell cycle and apoptosis of A172 cells. Conclusion: Down-regulation of lncRNA LINC01410 can inhibit proliferation, block cell cycle, induce cell apoptosis, and improve TMZ sensitivity of glioma A172 cells, the mechanism of which may be related with its targeted regulation of miR-205-5p.
Objective: To investigate the effect of lncRNA LINC01410 on the proliferation, apoptosis and temozolomide (TMZ) sensitivity of glioma A172 cells and the underlying mechanism. Methods: qPCR method was used to determine the expression of LINC01410 in glioma cell lines (H4, SHG-44, A172) and normal astrocytes (HA1800). LINC01410 shRNA, shRNA control and miR-205-5p inhibitor and inhibitor control were respectively transfected into A172 cells, which were then treated with 400 μmol/L TMZ. Then, MTT assay and Flow cytometry were used to detect proliferation and apoptosis, and WB was used to detect protein expression of Bax, Bcl-2, cyclin D1 and p27 in transfected A172 cells. The target gene of LINC01410 was predicted by the online bioinformatic software LncBase, and the Dual-luciferase reporter gene system was used to verify the targeting relationship between LINC01410 and miR-205-5p. Results: The expression level of LINC01410 in three glioma cells was higher than that in normal astrocytes HA1800 cells (all P <0.01) with the highest expression level in A172 cells (P<0.01). After LINC01410 shRNA transfection and TMZ treatment, the proliferation decreased while the apoptosis rate increased in A172 cells, and the proportion of cells at G1 phase increased (all P<0.01); moreover, the protein expression level of Bax and p27 increased (all P<0.01), and the expression level of Bcl-2 and cyclin D1 decreased in A172 cells (all P<0.01). Dual-luciferase reporter gene assay verified that LINC01410 could targetedly bind with miR-205-5p, and down-regulation of LINC01410 promoted miR-205-5p expression. Transfection of miR-205-5p inhibitor could reverse the effects of down-regulation of LINC01410 and TMZ treatment on the proliferation, cell cycle and apoptosis of A172 cells. Conclusion: Down-regulation of lncRNA LINC01410 can inhibit proliferation, block cell cycle, induce cell apoptosis, and improve TMZ sensitivity of glioma A172 cells, the mechanism of which may be related with its targeted regulation of miR-205-5p.
2021, 28(9):914-919.
DOI: 10.3872/j.issn.1007-385X.2021.09.008
Abstract:
Objective: To screen the enhancer RNAs (eRNAs) and their corresponding target genes related to the prognosis hepatocellular carcinoma (HCC), and to explore their regulatory effect and function. Methods: The transcript data and clinical data of HCC were downloaded from UCSC database to extract the expression matrix of eRNAs and their predicted corresponding target genes. Kaplan-Meier and Spearman correlation analysis were used to screen HCC prognosis-related eRNAs and the target genes, and the least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox multiple regression analysis were utilized to construct a HCC prognostic risk scoring system. A short interfering RNA (siRNA) targeting eRNA AP003469.2 was designed and synthesized to transfect liver cancer SMMC-7721 cells. Then, RT-PCR was used to verify the knockdown efficiency, qPCR was used to detect the expression of the target gene YWHAZ, and CCK-8 was adopted to examine the proliferation of SMMC-7721 cells after transfection. Results: Four prognosis-related genes were screened, including two eRNAs (AP003469.2 and SPRY4-AS1) and two target genes (PPARGC1A and SLC2A1) (P<0.05). Among them, the high expression of PPARGC1A indicated a better prognosis, while the high expression of AP003469.2, SPRY4-AS1 and SLC2A1 genes indicated a poor prognosis. The prognostic risk scoring system constructed based on the 4 genes exhibited AUC of 0.730, 0.699 and 0.679 at the 1st, 3rd and the 5th year respectively, indicating good predictive performance of the system. After AP003469.2 knockdown in SMMC-7721 cells, the expression of its predicted target gene YWHAZ did not change significantly, and it had no significant effect on the proliferation of SMMC-7721 cells. Conclusion: Among the 4 key genes were screened out based on bioinformatics analysis, eRNA AP003469.2 is a biomarker with high prognostic performance for HCC; however, it has no cancer-promoting function or regulatory effect on YWHAZ.
Objective: To screen the enhancer RNAs (eRNAs) and their corresponding target genes related to the prognosis hepatocellular carcinoma (HCC), and to explore their regulatory effect and function. Methods: The transcript data and clinical data of HCC were downloaded from UCSC database to extract the expression matrix of eRNAs and their predicted corresponding target genes. Kaplan-Meier and Spearman correlation analysis were used to screen HCC prognosis-related eRNAs and the target genes, and the least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox multiple regression analysis were utilized to construct a HCC prognostic risk scoring system. A short interfering RNA (siRNA) targeting eRNA AP003469.2 was designed and synthesized to transfect liver cancer SMMC-7721 cells. Then, RT-PCR was used to verify the knockdown efficiency, qPCR was used to detect the expression of the target gene YWHAZ, and CCK-8 was adopted to examine the proliferation of SMMC-7721 cells after transfection. Results: Four prognosis-related genes were screened, including two eRNAs (AP003469.2 and SPRY4-AS1) and two target genes (PPARGC1A and SLC2A1) (P<0.05). Among them, the high expression of PPARGC1A indicated a better prognosis, while the high expression of AP003469.2, SPRY4-AS1 and SLC2A1 genes indicated a poor prognosis. The prognostic risk scoring system constructed based on the 4 genes exhibited AUC of 0.730, 0.699 and 0.679 at the 1st, 3rd and the 5th year respectively, indicating good predictive performance of the system. After AP003469.2 knockdown in SMMC-7721 cells, the expression of its predicted target gene YWHAZ did not change significantly, and it had no significant effect on the proliferation of SMMC-7721 cells. Conclusion: Among the 4 key genes were screened out based on bioinformatics analysis, eRNA AP003469.2 is a biomarker with high prognostic performance for HCC; however, it has no cancer-promoting function or regulatory effect on YWHAZ.
2021, 28(9):920-925.
DOI: 10.3872/j.issn.1007-385X.2021.09.009
Abstract:
Objective: To investigate the level and clinical significance of programmed death ligand-1 (PD-L1) and tumor-infiltrating lymphocyte (TIL) in triple-negative breast cancer (TNBC) tissues. Methods: A total of 61 postoperative paraffin samples of tumor tissues and para-cancerous tissues from TNBC patients who underwent surgical resection during January 2015 and January 2019 were collected from the Second Affiliated Hospital of Fujian Medical University. The PD-L1 expression and CD8+ TIL level were detected by Immunohistochemistry. The relationship between the levels of PD-L1 and CD8+ TIL in TNBC tissues and the clinicopathological features as well as the prognosis of TNBC patients was analyzed by Chi-square test. Results: The positive rate of PD-L1 and CD8+ TIL in TNBC tissues was 63.9% (39/61) and 32.8% (20/61), respectively. The expression of PD-L1 was significantly correlated with tumor diameter, lymph node metastasis, TNM staging and recurrence (all P<0.05), but not significantly correlated with the age of patients, differentiation degree, vascular invasion and Ki67 expression (all P>0.05). The level of CD8+ TIL was significantly correlated with tumor diameter, differentiation degree, lymph node metastasis, TNM staging and recurrence (all P<0.05), but not significantly correlated with the age of patients, vascular invasion and Ki67 expression (all P>0.05). The levels of PD-L1 and CD8+ TIL were significantly correlated with progression-free survival (PFS) and overall survival (OS) of patients (both P<0.05). Positive PD-L1 expression or lack of CD8+ TIL were associated with tumor invasiveness and worse PFS and OS of patients (both P<0.05). Conclusion: High levels of PD-L1 and CD8+ TIL are present in TNBC tissues. The positive expression PD-L1 and lack of CD8+ TIL are both associated with increased tumor invasiveness and worse PFS and OS of patients
Objective: To investigate the level and clinical significance of programmed death ligand-1 (PD-L1) and tumor-infiltrating lymphocyte (TIL) in triple-negative breast cancer (TNBC) tissues. Methods: A total of 61 postoperative paraffin samples of tumor tissues and para-cancerous tissues from TNBC patients who underwent surgical resection during January 2015 and January 2019 were collected from the Second Affiliated Hospital of Fujian Medical University. The PD-L1 expression and CD8+ TIL level were detected by Immunohistochemistry. The relationship between the levels of PD-L1 and CD8+ TIL in TNBC tissues and the clinicopathological features as well as the prognosis of TNBC patients was analyzed by Chi-square test. Results: The positive rate of PD-L1 and CD8+ TIL in TNBC tissues was 63.9% (39/61) and 32.8% (20/61), respectively. The expression of PD-L1 was significantly correlated with tumor diameter, lymph node metastasis, TNM staging and recurrence (all P<0.05), but not significantly correlated with the age of patients, differentiation degree, vascular invasion and Ki67 expression (all P>0.05). The level of CD8+ TIL was significantly correlated with tumor diameter, differentiation degree, lymph node metastasis, TNM staging and recurrence (all P<0.05), but not significantly correlated with the age of patients, vascular invasion and Ki67 expression (all P>0.05). The levels of PD-L1 and CD8+ TIL were significantly correlated with progression-free survival (PFS) and overall survival (OS) of patients (both P<0.05). Positive PD-L1 expression or lack of CD8+ TIL were associated with tumor invasiveness and worse PFS and OS of patients (both P<0.05). Conclusion: High levels of PD-L1 and CD8+ TIL are present in TNBC tissues. The positive expression PD-L1 and lack of CD8+ TIL are both associated with increased tumor invasiveness and worse PFS and OS of patients
2021, 28(9):926-932.
DOI: 10.3872/j.issn.1007-385X.2021.09.010
Abstract:
长链非编码RNA（lncRNA）ARSR（lncARSR）作为lncRNA家族中的成员之一，近年来受到医学界的广泛关注。随着 lncARSR相关基础及临床研究的逐渐深入，发现其不仅在多种生物学过程包括脂代谢中起重要的调控作用，同时在恶性肿瘤的 发生、发展及治疗过程的耐药性中均发挥类似癌基因的功能。研究发现，lncARSR在多种类型肿瘤患者的血清、组织及细胞中呈 高表达，而且通过调控靶基因进而促进肿瘤细胞增殖、侵袭及转移，抑制肿瘤细胞凋亡，增强肿瘤耐药性，与肿瘤的分期及预后密 切相关，为肿瘤的早期诊断及生物治疗提供了新的思路。综述中论述了lncARSR在结直肠癌、卵巢癌、非小细胞肺癌、膀胱癌、肾 细胞癌、肝细胞癌和骨肉瘤等恶性肿瘤中的作用及其机制的相关性研究进展。
长链非编码RNA（lncRNA）ARSR（lncARSR）作为lncRNA家族中的成员之一，近年来受到医学界的广泛关注。随着 lncARSR相关基础及临床研究的逐渐深入，发现其不仅在多种生物学过程包括脂代谢中起重要的调控作用，同时在恶性肿瘤的 发生、发展及治疗过程的耐药性中均发挥类似癌基因的功能。研究发现，lncARSR在多种类型肿瘤患者的血清、组织及细胞中呈 高表达，而且通过调控靶基因进而促进肿瘤细胞增殖、侵袭及转移，抑制肿瘤细胞凋亡，增强肿瘤耐药性，与肿瘤的分期及预后密 切相关，为肿瘤的早期诊断及生物治疗提供了新的思路。综述中论述了lncARSR在结直肠癌、卵巢癌、非小细胞肺癌、膀胱癌、肾 细胞癌、肝细胞癌和骨肉瘤等恶性肿瘤中的作用及其机制的相关性研究进展。
2021, 28(9):933-941.
DOI: 10.3872/j.issn.1007-385X.2021.09.011
Abstract:
近年来，随着肿瘤微环境（tumor microenvironment，TME）和免疫治疗的研究不断深入，TME 中肿瘤浸润免疫细胞 （tumor infiltrating immune cell，TIC）已成为研究人员关注的热点。对TIC进行量化分析有助于了解免疫系统在人类恶性肿瘤中 的作用及其机制，并对肿瘤免疫治疗提供新的见解和帮助。在传统的肿瘤组织测序分析结果中，基因表达往往忽略了组织中的 细胞组成和类型，因此肿瘤组织中低丰度细胞的基因表达情况会被掩盖。随着分析算法的不断发展，越来越多的工具被开发应 用于分析肿瘤组织中免疫细胞的基因表达情况，实现对肿瘤组织中免疫细胞的成分进行计算和量化。
近年来，随着肿瘤微环境（tumor microenvironment，TME）和免疫治疗的研究不断深入，TME 中肿瘤浸润免疫细胞 （tumor infiltrating immune cell，TIC）已成为研究人员关注的热点。对TIC进行量化分析有助于了解免疫系统在人类恶性肿瘤中 的作用及其机制，并对肿瘤免疫治疗提供新的见解和帮助。在传统的肿瘤组织测序分析结果中，基因表达往往忽略了组织中的 细胞组成和类型，因此肿瘤组织中低丰度细胞的基因表达情况会被掩盖。随着分析算法的不断发展，越来越多的工具被开发应 用于分析肿瘤组织中免疫细胞的基因表达情况，实现对肿瘤组织中免疫细胞的成分进行计算和量化。
2021, 28(9):942-946.
DOI: 10.3872/j.issn.1007-385X.2021.09.012
Abstract:
目前，新型冠状病毒肺炎（coronavirus disease 2019，COVID-19）疫情仍在世界范围内肆虐，其传染性强、病情进展迅 速，造成了重大的生命与财产损失，已成为国际上最受关注的严重突发公共卫生事件。恶性肿瘤患者由于免疫力低下成为 COVID-19的重点高危人群，其罹患COVID-19的风险高，感染后的重症和死亡的风险高、预后差。但是，目前抗肿瘤相关治疗尤 其是肿瘤免疫治疗与COVID-19的关系仍不明确。因此，了解COVID-19肿瘤患者的临床特征，阐明COVID-19感染与肿瘤免疫 学及免疫治疗的关系，制定COVID-19疫情下的肿瘤免疫治疗策略，已成为亟待解决的问题。
目前，新型冠状病毒肺炎（coronavirus disease 2019，COVID-19）疫情仍在世界范围内肆虐，其传染性强、病情进展迅 速，造成了重大的生命与财产损失，已成为国际上最受关注的严重突发公共卫生事件。恶性肿瘤患者由于免疫力低下成为 COVID-19的重点高危人群，其罹患COVID-19的风险高，感染后的重症和死亡的风险高、预后差。但是，目前抗肿瘤相关治疗尤 其是肿瘤免疫治疗与COVID-19的关系仍不明确。因此，了解COVID-19肿瘤患者的临床特征，阐明COVID-19感染与肿瘤免疫 学及免疫治疗的关系，制定COVID-19疫情下的肿瘤免疫治疗策略，已成为亟待解决的问题。
2021, 28(9):947-952.
DOI: 10.3872/j.issn.1007-385X.2021.09.013
Abstract:
甲状腺未分化癌（anaplastic thyroid carcinoma，ATC）是一种高侵袭性、高致死性的甲状腺恶性肿瘤，其发生率低、生长 速度快，确诊时常常已经处在晚期和远处转移，确诊患者病死率达100%，中位生存期仅为3~6个月。因ATC的罕见性以及其恶 性程度高、侵袭性强，确诊ATC的患者常遵循个体化治疗原则，目前尚无标准化的治疗方案，因此多种方式联合生物治疗成为了 目前关注的重点，如基因靶向治疗。既往研究表明，完全切除可延长ATC 患者的生存期，而术后联合放疗可达到完全缓解和部分 缓解，目前放疗已被证实可控制局部疾病，提高生活质量，但个体差异较大，其预后受多种因素影响，如年龄较大、高白细胞、甲状 腺外侵犯、诊断时远处转移、不完全切除和放疗剂量等。
甲状腺未分化癌（anaplastic thyroid carcinoma，ATC）是一种高侵袭性、高致死性的甲状腺恶性肿瘤，其发生率低、生长 速度快，确诊时常常已经处在晚期和远处转移，确诊患者病死率达100%，中位生存期仅为3~6个月。因ATC的罕见性以及其恶 性程度高、侵袭性强，确诊ATC的患者常遵循个体化治疗原则，目前尚无标准化的治疗方案，因此多种方式联合生物治疗成为了 目前关注的重点，如基因靶向治疗。既往研究表明，完全切除可延长ATC 患者的生存期，而术后联合放疗可达到完全缓解和部分 缓解，目前放疗已被证实可控制局部疾病，提高生活质量，但个体差异较大，其预后受多种因素影响，如年龄较大、高白细胞、甲状 腺外侵犯、诊断时远处转移、不完全切除和放疗剂量等。
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
您是第位访问者
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.