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Volume 29,Issue 6,2022 Table of Contents
2022, 29(6):509-518.
DOI: 10.3872/j.issn.1007-385X.2022.06.001
Abstract:
In recent years, neoantigens have started a new chapter of individualized immunotherapy. As an important component of neoantigen-based individualized immunotherapy, neoantigen-specific T-cell adoptive transfer (ACT) has attracted much attention. This paper will first introduce the current development of neoantigen-specific T-cell ACT therapy, an emerging precision immunotherapy, in terms of application strategies and current clinical applications of neoantigen-specific T-cell ACT therapy. Then, the obstacles and challenges faced by neoantigen-specific T-cell ACT therapy will be systematically summarized in terms of neoantigen prediction, neoantigen-specific T-cell screening, and expansion. Finally, future development opportunities and research directions will be highlighted in five aspects, including optimizing neoantigen prediction, increasing the number and diversity of neoantigen-specific T cells, and preventing excessive differentiation or death of neoantigen-specific T cells, shortening the production cycle and reducing production cost, and exploring combination therapy modalities.
In recent years, neoantigens have started a new chapter of individualized immunotherapy. As an important component of neoantigen-based individualized immunotherapy, neoantigen-specific T-cell adoptive transfer (ACT) has attracted much attention. This paper will first introduce the current development of neoantigen-specific T-cell ACT therapy, an emerging precision immunotherapy, in terms of application strategies and current clinical applications of neoantigen-specific T-cell ACT therapy. Then, the obstacles and challenges faced by neoantigen-specific T-cell ACT therapy will be systematically summarized in terms of neoantigen prediction, neoantigen-specific T-cell screening, and expansion. Finally, future development opportunities and research directions will be highlighted in five aspects, including optimizing neoantigen prediction, increasing the number and diversity of neoantigen-specific T cells, and preventing excessive differentiation or death of neoantigen-specific T cells, shortening the production cycle and reducing production cost, and exploring combination therapy modalities.
2022, 29(6):519-526.
DOI: 10.3872/j.issn.1007-385X.2022.06.002
Abstract:
Attenuated Salmonella has shown broad tumor targeting specificity against solid tumors. By activating host antitumor response and modifying tumor immune microenvironment, attenuated Salmonella can suppress tumor development. Meanwhile, the high tumor targeting specificity enables the attenuated Salmonella to be used as the ideal expression and delivery vector for therapeutic drugs and imaging probes, realizing the integration of tumor diagnosis and treatment. Attenuated Salmonella has been widely studied and applied in basic and clinical fields, showing good application prospects and promising future. In this article, we will first investigate the attenuated Salmonella-related antitumor mechanism, application status, current problems and challenges and then explore how to improve its biosafety, tumor targeting specificity, and antitumor efficacy by using genetic biotechnology, thus to promote the translational application of attenuated Salmonella and realize the cross-integration of immunology, biotechnology and other disciplines, which may provide a new strategy and direction for future clinical tumor biotherapy.
Attenuated Salmonella has shown broad tumor targeting specificity against solid tumors. By activating host antitumor response and modifying tumor immune microenvironment, attenuated Salmonella can suppress tumor development. Meanwhile, the high tumor targeting specificity enables the attenuated Salmonella to be used as the ideal expression and delivery vector for therapeutic drugs and imaging probes, realizing the integration of tumor diagnosis and treatment. Attenuated Salmonella has been widely studied and applied in basic and clinical fields, showing good application prospects and promising future. In this article, we will first investigate the attenuated Salmonella-related antitumor mechanism, application status, current problems and challenges and then explore how to improve its biosafety, tumor targeting specificity, and antitumor efficacy by using genetic biotechnology, thus to promote the translational application of attenuated Salmonella and realize the cross-integration of immunology, biotechnology and other disciplines, which may provide a new strategy and direction for future clinical tumor biotherapy.
2022, 29(6):527-533.
DOI: 10.3872/j.issn.1007-385X.2022.06.003
Abstract:
Objective: To investigate the expression of circular circ_0000615 in cholangiocarcinoma cells and its effect on the proliferation, migration and invasion ability of tumor cells as well as the possible regulatory mechanism. Methods: The expression level of circ_0000615 in cholangiocarcinoma cells (TFK-1, RBE, CCLP-1 and QBC939) and normal bile duct epithelium HIBEC cells was detected by qPCR. The targeting relationship between circ_0000615 and miR-432-5p was verified by the Dual-luciferase reporter gene assay. si-NC, si-circ_0000615 (si-circ-1, si-circ-2), inhibitor-NC and inhibitor-miR-432-5p were separately or jointly transfected into CCLP-1 and QBC939 cells, namely si-NC group, si-circ-1 group, si-circ-2 group, si-NC+inh-NC group, si-NC+inh-miR-432-5p group, and si-circ-1+inh-miR-432-5p group. The proliferation, migration and invasion of cholangiocarcinoma cells in each group were detected by CCK-8, EdU and Transwell experiments. Results: circ_0000615 was highly expressed while miR-432-5p was lowly expressed in cholangiocarcinoma tumor cells (P
Objective: To investigate the expression of circular circ_0000615 in cholangiocarcinoma cells and its effect on the proliferation, migration and invasion ability of tumor cells as well as the possible regulatory mechanism. Methods: The expression level of circ_0000615 in cholangiocarcinoma cells (TFK-1, RBE, CCLP-1 and QBC939) and normal bile duct epithelium HIBEC cells was detected by qPCR. The targeting relationship between circ_0000615 and miR-432-5p was verified by the Dual-luciferase reporter gene assay. si-NC, si-circ_0000615 (si-circ-1, si-circ-2), inhibitor-NC and inhibitor-miR-432-5p were separately or jointly transfected into CCLP-1 and QBC939 cells, namely si-NC group, si-circ-1 group, si-circ-2 group, si-NC+inh-NC group, si-NC+inh-miR-432-5p group, and si-circ-1+inh-miR-432-5p group. The proliferation, migration and invasion of cholangiocarcinoma cells in each group were detected by CCK-8, EdU and Transwell experiments. Results: circ_0000615 was highly expressed while miR-432-5p was lowly expressed in cholangiocarcinoma tumor cells (P
2022, 29(6):534-540.
DOI: 10.3872/j.issn.1007-385X.2022.06.004
Abstract:
Objective: To explore the effect of lncRNA SNHG14 on the malignant biological behaviors of thyroid cancer SW579 cells and its mechanism. Methods: The cancer tissue and paracancerous tissue samples of 20 patients with thyroid cancer admitted to Qinghai Provincial People's Hospital from October 2017 to December 2018 were collected. The expression of SNHG14 and miR-433-3p in thyroid carcinoma tissues and corresponding paracancerous tissues was determined by qPCR. Depending on the transfectant, SW579 cells were divided into the si-NC group (transfected with si-NC), si-SNHG14 group (transfected with si-SNHG14), miR-NC group (transfected with miR-NC), and miR-433-3p mimic group (transfected with miR-433-3p mimic), si-SNHG14+anti-miR-NC group (co-transfected with si-SNHG14 and anti-miR-NC), and si-SNHG14+anti-miR-433-3p group (co-transfected with si-SNHG14 and anti-miR-433-3p). MTT method, FCM, and Transwell test were used to detect the changes in proliferation, cell cycle, apoptosis rate, migration, and invasion ability of SW579 cells after transfection, respectively. The dual-luciferase reporter gene assay was employed to analyze whether SNHG14 could bind to miR-433- 3p, and the regulation relationship between SNHG14 and miR-433-3p was detected by qPCR. Results: Compared with the paracancerous tissues, the expression of SNHG14 in thyroid carcinoma tissues was significantly increased while the expression level of miR-433-3p was obviously decreased (all PObjective: To explore the effect of lncRNA SNHG14 on the malignant biological behaviors of thyroid cancer SW579 cells and its mechanism. Methods: The cancer tissue and paracancerous tissue samples of 20 patients with thyroid cancer admitted to Qinghai Provincial People's Hospital from October 2017 to December 2018 were collected. The expression of SNHG14 and miR-433-3p in thyroid carcinoma tissues and corresponding paracancerous tissues was determined by qPCR. Depending on the transfectant, SW579 cells were divided into the si-NC group (transfected with si-NC), si-SNHG14 group (transfected with si-SNHG14), miR-NC group (transfected with miR-NC),and miR-433-3p mimic group (transfected with miR-433-3p mimic), si-SNHG14+anti-miR-NC group (co-transfected with si-SNHG14 and anti-miR-NC), and si-SNHG14+anti-miR-433-3p group (co-transfected with si-SNHG14 and anti-miR-433-3p). MTT method, FCM,and Transwell test were used to detect the changes in proliferation, cell cycle, apoptosis rate, migration, and invasion ability of SW579 cells after transfection, respectively. The dual-luciferase reporter gene assay was employed to analyze whether SNHG14 could bind to miR-433-3p, and the regulation relationship between SNHG14 and miR-433-3p was detected by qPCR. Results: Compared with the paracancerous tissues, the expression of SNHG14 in thyroid carcinoma tissues was significantly increased while the expression level of miR-433-3p was obviously decreased (all P<0.05). SNHG14 inhibition or miR-433-3p overexpression could reduce cell proliferation, the number of migrated and invaded cells (P<0.05), increase the rate of apoptosis (P<0.05) and the proportion of cells in the G1 phase (P<0.05), and decrease the proportion of cells in the S phase (P<0.05). Dual-luciferase reporter gene assay demonstrated that SNHG14 could bind to miR-433-3p, and inhibition of SNHG14 expression could promote the expression of miR-433-3p in SW579 cells (all P<0.05). Simultaneous inhibition of miR-433-3p expression partialy reversed the inhibitory effect of SNHG14 downregulation on cell proliferation, apoptosis, migration, and invasion of SW579 cells (all P<0.05). Conclusion: lncRNA SNHG14 is highly expressed while miR-433-3p is lowly expressed in thyroid cancer tissues. lncRNA SNHG14 can promote the proliferation, migration and invasion and inhibit apoptosis of thyroid cancer SW579 cells by targeted binding to miR-433-3p.
Objective: To explore the effect of lncRNA SNHG14 on the malignant biological behaviors of thyroid cancer SW579 cells and its mechanism. Methods: The cancer tissue and paracancerous tissue samples of 20 patients with thyroid cancer admitted to Qinghai Provincial People's Hospital from October 2017 to December 2018 were collected. The expression of SNHG14 and miR-433-3p in thyroid carcinoma tissues and corresponding paracancerous tissues was determined by qPCR. Depending on the transfectant, SW579 cells were divided into the si-NC group (transfected with si-NC), si-SNHG14 group (transfected with si-SNHG14), miR-NC group (transfected with miR-NC), and miR-433-3p mimic group (transfected with miR-433-3p mimic), si-SNHG14+anti-miR-NC group (co-transfected with si-SNHG14 and anti-miR-NC), and si-SNHG14+anti-miR-433-3p group (co-transfected with si-SNHG14 and anti-miR-433-3p). MTT method, FCM, and Transwell test were used to detect the changes in proliferation, cell cycle, apoptosis rate, migration, and invasion ability of SW579 cells after transfection, respectively. The dual-luciferase reporter gene assay was employed to analyze whether SNHG14 could bind to miR-433- 3p, and the regulation relationship between SNHG14 and miR-433-3p was detected by qPCR. Results: Compared with the paracancerous tissues, the expression of SNHG14 in thyroid carcinoma tissues was significantly increased while the expression level of miR-433-3p was obviously decreased (all PObjective: To explore the effect of lncRNA SNHG14 on the malignant biological behaviors of thyroid cancer SW579 cells and its mechanism. Methods: The cancer tissue and paracancerous tissue samples of 20 patients with thyroid cancer admitted to Qinghai Provincial People's Hospital from October 2017 to December 2018 were collected. The expression of SNHG14 and miR-433-3p in thyroid carcinoma tissues and corresponding paracancerous tissues was determined by qPCR. Depending on the transfectant, SW579 cells were divided into the si-NC group (transfected with si-NC), si-SNHG14 group (transfected with si-SNHG14), miR-NC group (transfected with miR-NC),and miR-433-3p mimic group (transfected with miR-433-3p mimic), si-SNHG14+anti-miR-NC group (co-transfected with si-SNHG14 and anti-miR-NC), and si-SNHG14+anti-miR-433-3p group (co-transfected with si-SNHG14 and anti-miR-433-3p). MTT method, FCM,and Transwell test were used to detect the changes in proliferation, cell cycle, apoptosis rate, migration, and invasion ability of SW579 cells after transfection, respectively. The dual-luciferase reporter gene assay was employed to analyze whether SNHG14 could bind to miR-433-3p, and the regulation relationship between SNHG14 and miR-433-3p was detected by qPCR. Results: Compared with the paracancerous tissues, the expression of SNHG14 in thyroid carcinoma tissues was significantly increased while the expression level of miR-433-3p was obviously decreased (all P<0.05). SNHG14 inhibition or miR-433-3p overexpression could reduce cell proliferation, the number of migrated and invaded cells (P<0.05), increase the rate of apoptosis (P<0.05) and the proportion of cells in the G1 phase (P<0.05), and decrease the proportion of cells in the S phase (P<0.05). Dual-luciferase reporter gene assay demonstrated that SNHG14 could bind to miR-433-3p, and inhibition of SNHG14 expression could promote the expression of miR-433-3p in SW579 cells (all P<0.05). Simultaneous inhibition of miR-433-3p expression partialy reversed the inhibitory effect of SNHG14 downregulation on cell proliferation, apoptosis, migration, and invasion of SW579 cells (all P<0.05). Conclusion: lncRNA SNHG14 is highly expressed while miR-433-3p is lowly expressed in thyroid cancer tissues. lncRNA SNHG14 can promote the proliferation, migration and invasion and inhibit apoptosis of thyroid cancer SW579 cells by targeted binding to miR-433-3p.
2022, 29(6):541-548.
DOI: 10.3872/j.issn.1007-385X.2022.06.005
Abstract:
Objective: To explore the expression of miR-323a-3p and transmembrane 4 super family member 1 (TM4SF1) in lung cancer tissues and cells, and the target regulatory relationship between them, and to observe their effects on the proliferation, migration and invasion of lung cancer A549 cells, as well as their effects on the growth of A549 cell transplanted tumors in nude mice. Methods:Twenty pairs of lung cancer tissues and their corresponding paracancerous tissues were collected from January 2014 to December 2014 in Qinghai Provincial People's Hospital. The expressions of miR-323a-3p, mRNA and TM4SF1 expression of TM4SF1 in lung cancer tissues were detected by qPCR and WB methods. A549 cells were transfected with miR-323a-3p mimic, and the effects of miR-323a-3p overexpression on cell proliferation, migration and invasion as well as protein expression of TM4SF1, cyclin D1, p21, MMP-2 and MMP-9 were detected by MTT method, Transwell method and WB method, respectively. The targeting relationship between miR-323a3p and TM4SF1 was analyzed using the bioinformatics prediction tool StarBase and dual-luciferase reporter gene experiments. A549 cells were transfected with si-TM4SF1, miR-323a-3p+pcDNA or miR-323a-3p+pcDNA-TM4SF1, respectively, and the changes in proliferation, migration and invasion of A549 cells were evaluated. In the meanwhile, xenograft model was established in BALB/c nude mice by transplanting A549 cells with various treatment, and the xenograft volume was measured and calculated on day 14, 21 and 28.Results: Compared with paracancerous tissues, the expression levels of miR-323a-3p in lung cancer tissues were significantly downregulated, while the mRNA and protein levels of TM4SF1 were significantly up-regulated (all P<0.01). Overexpression of miR-323a-3por inhibition of TM4SF1 expression reduced the proliferation, migration, and invasion of A549 cells, as well as the expression of cyclin D1, MMP-2, and MMP-9 proteins, but promoted the expression of p21 protein (all P<0.01). StarBase prediction and dual-luciferase gene reporter experiment showed that miR-323a-3p could complimentarily bind with TM4SF1 and regulate its expression. After upregulation of TM4SF1 expression, the inhibitory effects of miR-323a-3p overexpression on malignant biological behaviors of A549 cells and protein expression of cyclin D1, MMP-2 and MMP-9, as well as tumor growth in nude mice were reversed (all P<0.01);moreover, the promotive effect of miR-323a-3p overexpression on the protein expression of p21 was also reversed (P<0.01).Conclusion: miR-323a-3p inhibits proliferation, migration and invasion of A549 cells and suppresses xenograft growth in nude mice by downregulating TM4SF1 expression.
Objective: To explore the expression of miR-323a-3p and transmembrane 4 super family member 1 (TM4SF1) in lung cancer tissues and cells, and the target regulatory relationship between them, and to observe their effects on the proliferation, migration and invasion of lung cancer A549 cells, as well as their effects on the growth of A549 cell transplanted tumors in nude mice. Methods:Twenty pairs of lung cancer tissues and their corresponding paracancerous tissues were collected from January 2014 to December 2014 in Qinghai Provincial People's Hospital. The expressions of miR-323a-3p, mRNA and TM4SF1 expression of TM4SF1 in lung cancer tissues were detected by qPCR and WB methods. A549 cells were transfected with miR-323a-3p mimic, and the effects of miR-323a-3p overexpression on cell proliferation, migration and invasion as well as protein expression of TM4SF1, cyclin D1, p21, MMP-2 and MMP-9 were detected by MTT method, Transwell method and WB method, respectively. The targeting relationship between miR-323a3p and TM4SF1 was analyzed using the bioinformatics prediction tool StarBase and dual-luciferase reporter gene experiments. A549 cells were transfected with si-TM4SF1, miR-323a-3p+pcDNA or miR-323a-3p+pcDNA-TM4SF1, respectively, and the changes in proliferation, migration and invasion of A549 cells were evaluated. In the meanwhile, xenograft model was established in BALB/c nude mice by transplanting A549 cells with various treatment, and the xenograft volume was measured and calculated on day 14, 21 and 28.Results: Compared with paracancerous tissues, the expression levels of miR-323a-3p in lung cancer tissues were significantly downregulated, while the mRNA and protein levels of TM4SF1 were significantly up-regulated (all P<0.01). Overexpression of miR-323a-3por inhibition of TM4SF1 expression reduced the proliferation, migration, and invasion of A549 cells, as well as the expression of cyclin D1, MMP-2, and MMP-9 proteins, but promoted the expression of p21 protein (all P<0.01). StarBase prediction and dual-luciferase gene reporter experiment showed that miR-323a-3p could complimentarily bind with TM4SF1 and regulate its expression. After upregulation of TM4SF1 expression, the inhibitory effects of miR-323a-3p overexpression on malignant biological behaviors of A549 cells and protein expression of cyclin D1, MMP-2 and MMP-9, as well as tumor growth in nude mice were reversed (all P<0.01);moreover, the promotive effect of miR-323a-3p overexpression on the protein expression of p21 was also reversed (P<0.01).Conclusion: miR-323a-3p inhibits proliferation, migration and invasion of A549 cells and suppresses xenograft growth in nude mice by downregulating TM4SF1 expression.
2022, 29(6):549-556.
DOI: 10.3872/j.issn.1007-385X.2022.06.006
Abstract:
Objective: To analyze the expression level of integrin-linked kinase (ILK) gene in esophageal squamous cell carcinoma (ESCC) tissues and its relationship with the clinicopathological characteristics of patients, and to explore its effect on KYSE-150 cell proliferation, apoptosis and the growth of subcutaneous xenograft tumor in nude mice. Methods: The cancer tissues and paired paracancerous tissues of 75 patients with ESCC who had surgical resection and confirmed by pathological examination from January 2012 to December 2014 were selected. Tissue chip technology and immunohistochemical staining were used to detect the expression of ILK in ESCC tissues and para-cancerous tissues; qPCR was used to detect the ILK expression in ESCC cell ECA109, TE-1, EC9706 and KYSE-150, and the KYSE-150 cells with the highest ILK expression was selected for subsequent cell functional studies. The KYSE-150 cells were transfected with ILK interference lentivirus to down-regulate the expression of ILK, and the knockdown efficiency was verified by qPCR and WB methods; the effects of interfering ILK expression on the proliferation and apoptosis of KYSE-150 cells were detected by MTT assay, clone formation assay and FACS; subcutaneous tumorigenesis assay in nude mice was used to detect the effect of interfering ILK on the growth of KYSE-150 cells transplanted tumors. Results: The positive rate of ILK protein in ESCC tissues was higher than that in para-cancerous tissues (P<0.05), and the high expression of ILK was associated with lymph node metastasis (P<0.05). The mRNA expression of ILK in shILK-infected KYSE-150 cells was significantly inhibited (P<0.05)and the expression of ILK protein was significantly down-regulated in the shILK group, which indicated the successful knockdown of ILK. Compared with the cells transfected with shCtrl, the proliferation ability and colony formation number of KYSE-150 cells in the shILK group were significantly reduced (both P<0.05), but the apoptosis rate was significantly increased (P<0.05). Compared with the NC group, the growth of transplanted tumors in the nude mice of the KD group was slower, and the weight and volume of the tumor were smaller (both P<0.05). Conclusion: The expression of ILK in ESCC tissues is higher than that in para-cancerous tissues, and the high ILK expression is associated with lymph node metastasis. Silencing ILK gene can inhibit the proliferation but promote the apoptosis of KYSE-150 cells and inhibit tumorigenesis in nude mice.
Objective: To analyze the expression level of integrin-linked kinase (ILK) gene in esophageal squamous cell carcinoma (ESCC) tissues and its relationship with the clinicopathological characteristics of patients, and to explore its effect on KYSE-150 cell proliferation, apoptosis and the growth of subcutaneous xenograft tumor in nude mice. Methods: The cancer tissues and paired paracancerous tissues of 75 patients with ESCC who had surgical resection and confirmed by pathological examination from January 2012 to December 2014 were selected. Tissue chip technology and immunohistochemical staining were used to detect the expression of ILK in ESCC tissues and para-cancerous tissues; qPCR was used to detect the ILK expression in ESCC cell ECA109, TE-1, EC9706 and KYSE-150, and the KYSE-150 cells with the highest ILK expression was selected for subsequent cell functional studies. The KYSE-150 cells were transfected with ILK interference lentivirus to down-regulate the expression of ILK, and the knockdown efficiency was verified by qPCR and WB methods; the effects of interfering ILK expression on the proliferation and apoptosis of KYSE-150 cells were detected by MTT assay, clone formation assay and FACS; subcutaneous tumorigenesis assay in nude mice was used to detect the effect of interfering ILK on the growth of KYSE-150 cells transplanted tumors. Results: The positive rate of ILK protein in ESCC tissues was higher than that in para-cancerous tissues (P<0.05), and the high expression of ILK was associated with lymph node metastasis (P<0.05). The mRNA expression of ILK in shILK-infected KYSE-150 cells was significantly inhibited (P<0.05)and the expression of ILK protein was significantly down-regulated in the shILK group, which indicated the successful knockdown of ILK. Compared with the cells transfected with shCtrl, the proliferation ability and colony formation number of KYSE-150 cells in the shILK group were significantly reduced (both P<0.05), but the apoptosis rate was significantly increased (P<0.05). Compared with the NC group, the growth of transplanted tumors in the nude mice of the KD group was slower, and the weight and volume of the tumor were smaller (both P<0.05). Conclusion: The expression of ILK in ESCC tissues is higher than that in para-cancerous tissues, and the high ILK expression is associated with lymph node metastasis. Silencing ILK gene can inhibit the proliferation but promote the apoptosis of KYSE-150 cells and inhibit tumorigenesis in nude mice.
2022, 29(6):557-566.
DOI: 10.3872/j.issn.1007-385X.2022.06.007
Abstract:
Objective: To explore the effect of miR-32-5p on the malignant biological behaviors of pancreatic cancer PANC-1 cells via targeting zeste gene enhancer human homolog 2 (EZH2) and its molecular mechanism. Methods: The GEPIA database was used to analyze the expression level of EZH2 in pancreatic cancer tissues and its relationship with the prognostic survival of patients. The association between miR-32-5p expression and clinicopathological features of patients was also analyzed. qPCR was used to detect the expression of miR-32-5p and EZH2 mRNA in pancreatic cancer cells (PANC-1, AsPC-1, SW1990) and normal pancreatic HPDE6-C7 cells. With LipofectamineTM 2000, miR-NC, miR-32-5p mimic, miR-32-5p inhibitor, pcDNA-NC and pcDNA EZH2 plasmids were separately or jointly transfected into pancreatic cancer PANC-1 cells, namely control group (untransfected)，miR-NC group (transfected with miR-NC), miR-32-5p mimic group (transfected with miR-32-5p mimic), anti-miR-32-5p group (transfected with miR-32-5p inhibitor); miR-NC+pcDNA-NC group (transfected with miR-NC+pcDNA-NC), miR-NC+pcDNA EZH2 group (transfected with miR-NC+pcDNA EZH2), miR-32-5p mimic+pcDNA-NC group (transfected with miR-32-5p mimic+pcDNA-NC), and miR-32-5p mimic+pcDNA EZH2 group (transfected with miR-32-5p mimic+pcDNA EZH2). Dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-32-5p and EZH2. MTT method and the clone formation assay were used to detect proliferation ability of the cells in each group; scratch healing test was used to detect cell migration ability; Transwell chamber test was used to detect cell invasion; Western blotting method was adopted to detect the expression of EZH2, epithelial cadherin (E-cadherin)and neural cadherin (N-cadherin) in cells. The tumorigenicity experiment in nude mice was used to detect the development of transplanted tumors; and the expression of Ki67 and metal matrix protease-2 (MMP-2) in tumor tissues was observed by immunohistochemical staining. Results: The GEPIA database showed that the expression level of EZH2 in pancreatic cancer tissues was higher than that in para-cancerous tissues, and the prognostic survival was negatively correlated with the expression level of EZH2 (all P<0.05). The miR-32-5p expression was significantly correlated with the nerve infiltration, tumor differentiation, TNM staging, lymph node metastasis of pancreatic cancer (all P<0.05). Compared with HPDE6-C7 cells, miR-32-5p was up-regulated and EZH2 mRNA was down-regulated in pancreatic cancer cells (PANC-1, AsPC-1, SW1990), and the level of miR-32-5p was negatively correlated with the level of EZH2. miR-32-5p targeted and down-regulated the expression of EZH2 (all P<0.05). Over-expression of miR-32-5p could down-regulate the expression levels of Ki67, MMP-2 and N-cadherin, up-regulate the level of E-cadherin, inhibit proliferation, migration and invasion of PANC-1 cells as well as the volume and weight of transplanted tumors (all P<0.05).Conclusion: miR-32-5p can inhibit the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) of pancreatic cancer PANC-1 cells as well as the development of nude mice transplanted tumors in vivo through targeting EZH2.
Objective: To explore the effect of miR-32-5p on the malignant biological behaviors of pancreatic cancer PANC-1 cells via targeting zeste gene enhancer human homolog 2 (EZH2) and its molecular mechanism. Methods: The GEPIA database was used to analyze the expression level of EZH2 in pancreatic cancer tissues and its relationship with the prognostic survival of patients. The association between miR-32-5p expression and clinicopathological features of patients was also analyzed. qPCR was used to detect the expression of miR-32-5p and EZH2 mRNA in pancreatic cancer cells (PANC-1, AsPC-1, SW1990) and normal pancreatic HPDE6-C7 cells. With LipofectamineTM 2000, miR-NC, miR-32-5p mimic, miR-32-5p inhibitor, pcDNA-NC and pcDNA EZH2 plasmids were separately or jointly transfected into pancreatic cancer PANC-1 cells, namely control group (untransfected)，miR-NC group (transfected with miR-NC), miR-32-5p mimic group (transfected with miR-32-5p mimic), anti-miR-32-5p group (transfected with miR-32-5p inhibitor); miR-NC+pcDNA-NC group (transfected with miR-NC+pcDNA-NC), miR-NC+pcDNA EZH2 group (transfected with miR-NC+pcDNA EZH2), miR-32-5p mimic+pcDNA-NC group (transfected with miR-32-5p mimic+pcDNA-NC), and miR-32-5p mimic+pcDNA EZH2 group (transfected with miR-32-5p mimic+pcDNA EZH2). Dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-32-5p and EZH2. MTT method and the clone formation assay were used to detect proliferation ability of the cells in each group; scratch healing test was used to detect cell migration ability; Transwell chamber test was used to detect cell invasion; Western blotting method was adopted to detect the expression of EZH2, epithelial cadherin (E-cadherin)and neural cadherin (N-cadherin) in cells. The tumorigenicity experiment in nude mice was used to detect the development of transplanted tumors; and the expression of Ki67 and metal matrix protease-2 (MMP-2) in tumor tissues was observed by immunohistochemical staining. Results: The GEPIA database showed that the expression level of EZH2 in pancreatic cancer tissues was higher than that in para-cancerous tissues, and the prognostic survival was negatively correlated with the expression level of EZH2 (all P<0.05). The miR-32-5p expression was significantly correlated with the nerve infiltration, tumor differentiation, TNM staging, lymph node metastasis of pancreatic cancer (all P<0.05). Compared with HPDE6-C7 cells, miR-32-5p was up-regulated and EZH2 mRNA was down-regulated in pancreatic cancer cells (PANC-1, AsPC-1, SW1990), and the level of miR-32-5p was negatively correlated with the level of EZH2. miR-32-5p targeted and down-regulated the expression of EZH2 (all P<0.05). Over-expression of miR-32-5p could down-regulate the expression levels of Ki67, MMP-2 and N-cadherin, up-regulate the level of E-cadherin, inhibit proliferation, migration and invasion of PANC-1 cells as well as the volume and weight of transplanted tumors (all P<0.05).Conclusion: miR-32-5p can inhibit the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) of pancreatic cancer PANC-1 cells as well as the development of nude mice transplanted tumors in vivo through targeting EZH2.
2022, 29(6):567-570.
DOI: 10.3872/j.issn.1007-385X.2022.06.008
Abstract:
Objective: To review the clinicopathological features of real-world multiple primary cancers (MPCs) and their traditional combine with biological treatment strategies, in order to improve the diagnosis and treatment of MPCs. Methods: The clinical data of tumor patients admitted to the Department of Oncology of Nanjing First Hospital and the General Surgery Department of Jiangsu Hospital of Traditional Chinese Medicine from January 2016 to December 2021 were retrospectively analyzed. All the patients were diagnosed as malignant tumors after pathological examination, and the incidence, pathological characteristics, clinical treatment and prognosis of MPCs were summarized and analyzed. Results: Among the 2 550 patients with malignancy, there were 24 patients with MPCs, with an overall incidence of 0.94% (24/2 550); specifically, the incidence of double cancer was 0.86% (22/2 550) and the incidence of triple cancer was 0.08% (2/2 550). There were 15 cases (62.5%, 15/24) having the second primary cancer within 3 years and 18 cases (75%, 18/24) within 5 years, with a maximum interval of 30 years. Digestive tumors are the most common ones in both the first and second primary cancers, followed by respiratory tumors. The 3- and 5- year survival rates after surgery, radiotherapy or chemotherapy was 58.3% (14/24) and 45.8% (11/24), respectively. Conclusion: By improving the understanding of the clinicopathological features and the traditional combined with biological treatment strategies of MPCs, we can achieve early diagnosis and treatment (avoid missed diagnosis) of MPCs to prolong the survival of patients and improve their quality of life.
Objective: To review the clinicopathological features of real-world multiple primary cancers (MPCs) and their traditional combine with biological treatment strategies, in order to improve the diagnosis and treatment of MPCs. Methods: The clinical data of tumor patients admitted to the Department of Oncology of Nanjing First Hospital and the General Surgery Department of Jiangsu Hospital of Traditional Chinese Medicine from January 2016 to December 2021 were retrospectively analyzed. All the patients were diagnosed as malignant tumors after pathological examination, and the incidence, pathological characteristics, clinical treatment and prognosis of MPCs were summarized and analyzed. Results: Among the 2 550 patients with malignancy, there were 24 patients with MPCs, with an overall incidence of 0.94% (24/2 550); specifically, the incidence of double cancer was 0.86% (22/2 550) and the incidence of triple cancer was 0.08% (2/2 550). There were 15 cases (62.5%, 15/24) having the second primary cancer within 3 years and 18 cases (75%, 18/24) within 5 years, with a maximum interval of 30 years. Digestive tumors are the most common ones in both the first and second primary cancers, followed by respiratory tumors. The 3- and 5- year survival rates after surgery, radiotherapy or chemotherapy was 58.3% (14/24) and 45.8% (11/24), respectively. Conclusion: By improving the understanding of the clinicopathological features and the traditional combined with biological treatment strategies of MPCs, we can achieve early diagnosis and treatment (avoid missed diagnosis) of MPCs to prolong the survival of patients and improve their quality of life.
2022, 29(6):571-579.
DOI: 10.3872/j.issn.1007-385X.2022.06.009
Abstract:
目前国际上取得重大进展的四类过继性细胞免疫治疗（ACT）技术主要包括肿瘤浸润淋巴细胞（TIL）、CAR-T细胞、 TCR-T细胞和CAR-NK细胞治疗。乳腺癌相关研究结果表明，TIL能预测乳腺癌的预后，间质TIL增加与良好的预后相关；CAR-T 细胞免疫治疗在血液系统肿瘤治疗中取得巨大突破后，现已用于靶向实体肿瘤治疗，并在乳腺癌的治疗中开展了多种靶点的临 床试验；TCR-T细胞疗法依赖于MHC，可以识别MHC分子呈递的任何抗原，具有更广泛的靶抗原，在治疗实体瘤方面更有前景， 多项乳腺癌TCR-T细胞治疗临床试验正在进行中；CAR-NK细胞治疗是通过借鉴CAR-T细胞的结构而设计的，具有出色的抗肿 瘤能力，比CAR-T细胞疗法更安全，可能将为肿瘤免疫治疗带来新的更大发展。ACT在乳腺癌的研究和临床应用领域仍具挑 战，其中TIL疗法难以产生足量的特异性T细胞，CAR-T和CAR-NK细胞疗法均不同程度存在细胞的持久性、快速归巢到肿瘤 床、毒性和转导效率等问题。尽管存在不足，但随着基因工程、肿瘤免疫学和分子生物学等多学科的迅速发展，相信ACT技术有 望为乳腺癌患者治疗带来新的希望。
目前国际上取得重大进展的四类过继性细胞免疫治疗（ACT）技术主要包括肿瘤浸润淋巴细胞（TIL）、CAR-T细胞、 TCR-T细胞和CAR-NK细胞治疗。乳腺癌相关研究结果表明，TIL能预测乳腺癌的预后，间质TIL增加与良好的预后相关；CAR-T 细胞免疫治疗在血液系统肿瘤治疗中取得巨大突破后，现已用于靶向实体肿瘤治疗，并在乳腺癌的治疗中开展了多种靶点的临 床试验；TCR-T细胞疗法依赖于MHC，可以识别MHC分子呈递的任何抗原，具有更广泛的靶抗原，在治疗实体瘤方面更有前景， 多项乳腺癌TCR-T细胞治疗临床试验正在进行中；CAR-NK细胞治疗是通过借鉴CAR-T细胞的结构而设计的，具有出色的抗肿 瘤能力，比CAR-T细胞疗法更安全，可能将为肿瘤免疫治疗带来新的更大发展。ACT在乳腺癌的研究和临床应用领域仍具挑 战，其中TIL疗法难以产生足量的特异性T细胞，CAR-T和CAR-NK细胞疗法均不同程度存在细胞的持久性、快速归巢到肿瘤 床、毒性和转导效率等问题。尽管存在不足，但随着基因工程、肿瘤免疫学和分子生物学等多学科的迅速发展，相信ACT技术有 望为乳腺癌患者治疗带来新的希望。
2022, 29(6):580-586.
DOI: 10.3872/j.issn.1007-385X.2022.06.010
Abstract:
热激蛋白70（HSP70）有维持细胞生存和功能的重要作用，在包括结直肠癌（CRC）在内的多种恶性肿瘤细胞中过表 达。HSP70抑制剂VER-155008可以通过抑制HSP70 ATP酶活性或与HSP70的不同结构域相互作用发挥抗肿瘤作用，纳米给药 系统为增强其疗效提供了可能。此外，钌（Ⅱ/Ⅲ）复合物与多种天然化合物对HSP70家族成员也能发挥抑制作用，参与调节CRC 发生发展中关键的信号通路，抑制CRC细胞的增殖和迁移。苯乙基磺酰胺衍生物、咪唑衍生物、MKT-077类抑制剂、藜芦碱、青 蒿素衍生物等通过不同途径诱导CRC细胞凋亡或降低其活性，亚甲蓝通过抑制HSP70发挥抗癌活性。以上抑制剂因其各自特 性，存在临床运用上的困难，还需探索以发挥作用或增强疗效。
热激蛋白70（HSP70）有维持细胞生存和功能的重要作用，在包括结直肠癌（CRC）在内的多种恶性肿瘤细胞中过表 达。HSP70抑制剂VER-155008可以通过抑制HSP70 ATP酶活性或与HSP70的不同结构域相互作用发挥抗肿瘤作用，纳米给药 系统为增强其疗效提供了可能。此外，钌（Ⅱ/Ⅲ）复合物与多种天然化合物对HSP70家族成员也能发挥抑制作用，参与调节CRC 发生发展中关键的信号通路，抑制CRC细胞的增殖和迁移。苯乙基磺酰胺衍生物、咪唑衍生物、MKT-077类抑制剂、藜芦碱、青 蒿素衍生物等通过不同途径诱导CRC细胞凋亡或降低其活性，亚甲蓝通过抑制HSP70发挥抗癌活性。以上抑制剂因其各自特 性，存在临床运用上的困难，还需探索以发挥作用或增强疗效。
2022, 29(6):587-595.
DOI: 10.3872/j.issn.1007-385X.2022.06.011
Abstract:
近十年来，针对人表皮生长因子受体2（HER2）阳性的乳腺癌亚型，已有6款新型靶向药物获批上市，分别为帕妥珠单 抗、T-DM1、吡咯替尼、来那替尼、图卡替尼和马吉妥昔单抗。临床试验证明这些药物可以显著改善HER2阳性乳腺癌患者的生存 和预后。其他靶向HER2相关信号通路的药物包括双特异单克隆抗体、抗体-药物偶联物、mTOR/PI3K/Akt信号抑制剂、CDK4/6 抑制剂、HER2疫苗和免疫检查点阻滞剂等已进入临床测试阶段。其中T-Dxd（即DS-8201a）、ARX788、SYD985、布帕尼西和GP2 疫苗，在安全性和疗效方面显示了进入临床应用的良好潜力。
近十年来，针对人表皮生长因子受体2（HER2）阳性的乳腺癌亚型，已有6款新型靶向药物获批上市，分别为帕妥珠单 抗、T-DM1、吡咯替尼、来那替尼、图卡替尼和马吉妥昔单抗。临床试验证明这些药物可以显著改善HER2阳性乳腺癌患者的生存 和预后。其他靶向HER2相关信号通路的药物包括双特异单克隆抗体、抗体-药物偶联物、mTOR/PI3K/Akt信号抑制剂、CDK4/6 抑制剂、HER2疫苗和免疫检查点阻滞剂等已进入临床测试阶段。其中T-Dxd（即DS-8201a）、ARX788、SYD985、布帕尼西和GP2 疫苗，在安全性和疗效方面显示了进入临床应用的良好潜力。
2022, 29(6):596-599.
DOI: 10.3872/j.issn.1007-385X.2022.06.012
Abstract:
前列腺相关基因4（PAGE4）是近年来发现的与前列腺癌相关的一种应激反应蛋白，其对前列腺癌的影响是动态的调节 过程。在前列腺癌进展初期，PAGE4减弱雄激素受体的异常激活，抑制肿瘤细胞的EMT进程，同时干扰间质细胞与肿瘤细胞的 交互作用；而在疾病进展期，PAGE4的应激保护功能可减少细胞凋亡，促进肿瘤细胞存活。此外，PAGE4作为癌/睾丸抗原（CTA） 家族成员之一，仅在胚胎组织及成熟睾丸组织中表达，但在前列腺癌组织中表达则异常增高，使得PAGE4在前列腺癌诊疗中具有 一定应用价值。多项研究表明，PAGE4在前列腺癌组织中的高表达与前列腺癌术后的生存率呈正相关。因此，PAGE4在前列腺 癌的发生发展及其诊疗中具有潜在的临床应用价值，其分子机制和功能值得进一步探研。
前列腺相关基因4（PAGE4）是近年来发现的与前列腺癌相关的一种应激反应蛋白，其对前列腺癌的影响是动态的调节 过程。在前列腺癌进展初期，PAGE4减弱雄激素受体的异常激活，抑制肿瘤细胞的EMT进程，同时干扰间质细胞与肿瘤细胞的 交互作用；而在疾病进展期，PAGE4的应激保护功能可减少细胞凋亡，促进肿瘤细胞存活。此外，PAGE4作为癌/睾丸抗原（CTA） 家族成员之一，仅在胚胎组织及成熟睾丸组织中表达，但在前列腺癌组织中表达则异常增高，使得PAGE4在前列腺癌诊疗中具有 一定应用价值。多项研究表明，PAGE4在前列腺癌组织中的高表达与前列腺癌术后的生存率呈正相关。因此，PAGE4在前列腺 癌的发生发展及其诊疗中具有潜在的临床应用价值，其分子机制和功能值得进一步探研。
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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.