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Volume 26,Issue 1,2019 Table of Contents
2019, 26(1):1-2.
DOI: 10.3872/j.issn.1007-385X.2019.01.001
Abstract:
2019, 26(1):3-6.
DOI: 10.3872/j.issn.1007-385X.2019.01.002
Abstract:
3 Immunotherapy precise targeting tumour microenvironment will become a key strategy of curing cancer
2019, 26(1):7-15.
DOI: 10.3872/j.issn.1007-385X.2019.01.003
Abstract:
[Abstract] The most two advanced development in cancer immunotherapy: (1) Infusion with in vitro activated or gene-modified T cells; (2) Activation of suppressive immune cells by antibodies to exert cytotoxicity. The first one about gene-modified T cells is mainly referred to chimeric antigen receptor-T cells (CAR-T) that have shown the significant efficacy in some haematological malignancies.The latter one about immune checkpoint blockades takes effects on tumors with burden of gene mutations. For cancer patients, however,tumor microenvironment is suppressed highly more than the systemic immune. Normalizing or enhancing the local microenvironment by systemic activation of immune response may cause the overreaction in other normal tissues, even severe damage, for example interstitial lung diseases, acute myocarditis, and severe liver failure. This review summarizes the characterization and classification of tumor immune microenvironment, development of cancer treatment and immunotherapy, and elucidates the importance of targeting tumor immune microenvironment. The key strategy is pointed out to efficiently and precision target tumor immune microenvironment by using self-secreting antibody CAR-T cells (baize T cells), quickly enhancing the immune function in tumor microenvironment, which may eventually cure cancer.
[Abstract] The most two advanced development in cancer immunotherapy: (1) Infusion with in vitro activated or gene-modified T cells; (2) Activation of suppressive immune cells by antibodies to exert cytotoxicity. The first one about gene-modified T cells is mainly referred to chimeric antigen receptor-T cells (CAR-T) that have shown the significant efficacy in some haematological malignancies.The latter one about immune checkpoint blockades takes effects on tumors with burden of gene mutations. For cancer patients, however,tumor microenvironment is suppressed highly more than the systemic immune. Normalizing or enhancing the local microenvironment by systemic activation of immune response may cause the overreaction in other normal tissues, even severe damage, for example interstitial lung diseases, acute myocarditis, and severe liver failure. This review summarizes the characterization and classification of tumor immune microenvironment, development of cancer treatment and immunotherapy, and elucidates the importance of targeting tumor immune microenvironment. The key strategy is pointed out to efficiently and precision target tumor immune microenvironment by using self-secreting antibody CAR-T cells (baize T cells), quickly enhancing the immune function in tumor microenvironment, which may eventually cure cancer.
2019, 26(1):16-21.
DOI: 10.3872/j.issn.1007-385X.2019.01.004
Abstract:
[Abstract] As one of the pivotal immunotherapies, tumor vaccine has increasingly shown its benefits in the treatment of malignant tumors.However, traditional vaccines targeting tumor associated antigen (TAA) are difficult to be promoted on a large scale in clinic, due to immune tolerance and the risk of inducing autoimmune disease. Neoantigen, which doesn’t present in normal cells and originates from tumor somatic mutations, is considered as ideal target for vaccines recently. Personalized neoantigen vaccine developed on the basis of sequencing, which specifically targets neoantigens, is expected to become an important breakthrough in precision medicine of cancer.This paper will elaborate on the concept, characteristics, preparation process and clinical trials of personalized neoantigen vaccine,and we will also discuss the opportunities and challenges that might be encountered during its clinical transformation.
[Abstract] As one of the pivotal immunotherapies, tumor vaccine has increasingly shown its benefits in the treatment of malignant tumors.However, traditional vaccines targeting tumor associated antigen (TAA) are difficult to be promoted on a large scale in clinic, due to immune tolerance and the risk of inducing autoimmune disease. Neoantigen, which doesn’t present in normal cells and originates from tumor somatic mutations, is considered as ideal target for vaccines recently. Personalized neoantigen vaccine developed on the basis of sequencing, which specifically targets neoantigens, is expected to become an important breakthrough in precision medicine of cancer.This paper will elaborate on the concept, characteristics, preparation process and clinical trials of personalized neoantigen vaccine,and we will also discuss the opportunities and challenges that might be encountered during its clinical transformation.
2019, 26(1):22-28.
DOI: 10.3872/j.issn.1007-385X.2019.01.005
Abstract:
[Abstract] Malignant cancer is a kind of fatal disease with severe threat to human health and social development, and seeking a scientific method for the proper diagnosis, treatment and assessment has become one of the most important public health problems in recent years. With the constant development in healthcare industry, traditional methods of tumor screening, prevention and prognosis assessment have made a rapid progress. However, owing to the characteristics of tumor heterogeneity and patient individuation, precision medicine mode in disease screening, diagnosis and treatment will become a general trend in future medical development. As an important part in precision medicine, gene variation detection in the field of tumors involves several aspects, including early screening, recurrence monitoring, guidance on use of targeted drugs and assessment of efficacy and prognosis etc; However, there are still many limitations in its clinical practice. Therefore, further research is needed to promote the development of tumor precision medicine. In this paper,the development history of gene variation detection and its application progress in precision medicine of malignant tumors are comprehensively discussed.
[Abstract] Malignant cancer is a kind of fatal disease with severe threat to human health and social development, and seeking a scientific method for the proper diagnosis, treatment and assessment has become one of the most important public health problems in recent years. With the constant development in healthcare industry, traditional methods of tumor screening, prevention and prognosis assessment have made a rapid progress. However, owing to the characteristics of tumor heterogeneity and patient individuation, precision medicine mode in disease screening, diagnosis and treatment will become a general trend in future medical development. As an important part in precision medicine, gene variation detection in the field of tumors involves several aspects, including early screening, recurrence monitoring, guidance on use of targeted drugs and assessment of efficacy and prognosis etc; However, there are still many limitations in its clinical practice. Therefore, further research is needed to promote the development of tumor precision medicine. In this paper,the development history of gene variation detection and its application progress in precision medicine of malignant tumors are comprehensively discussed.
2019, 26(1):29-35.
DOI: 10.3872/j.issn.1007-385X.2019.01.006
Abstract:
[Abstract] Objective: To investigate the effects of ezrin enhancer knockout on ezrin gene expression, cell proliferation and migration of human esophageal carcinoma Eca-109 cells. Methods: The CRISPR/Cas9 recombinant plasmids targeting upstream/downstream of human ezrin enhancer were co-transfected into human esophageal carcinoma Eca-109 cells, and the cell line Eca-C2 with ezrin enhancer knockout was screened by purinomycin. Then the expression levels of ezrin mRNA and protein in Eca-C2 cells were detected by Real-time quantitative PCR (qPCR) and Western blotting, respectively; The expression levels of MAPK-pathway-related proteins were detected by protein array technology; and the effects of ezrin enhancer knockout on the proliferation and migration of Eca-C2 cells were analyzed by WST-1 method and wound-healing assay, respectively. Results: The human esophageal carcinoma cell line Eca-C2 with stable ezrin enhancer knockout was established successfully. Compared with control cells, the mRNA and protein expressions of ezrin in Eca-C2 cells were significantly reduced (all P<0.05). Among the 17 detected MAPK pathway related proteins in Eca-C2 cells, 9 proteins (AKT, CREB, GSK3b, MKK6, mTOR, P38, P53, P70S6K and RSK1) were down-regulated, and the cell proliferation and migration were significantly inhibited (all P<0.05). Conclusion: ezrin enhancer knockout can significantly inhibit the cell proliferation and migration of human esophageal carcinoma Eca-109 cells.
[Abstract] Objective: To investigate the effects of ezrin enhancer knockout on ezrin gene expression, cell proliferation and migration of human esophageal carcinoma Eca-109 cells. Methods: The CRISPR/Cas9 recombinant plasmids targeting upstream/downstream of human ezrin enhancer were co-transfected into human esophageal carcinoma Eca-109 cells, and the cell line Eca-C2 with ezrin enhancer knockout was screened by purinomycin. Then the expression levels of ezrin mRNA and protein in Eca-C2 cells were detected by Real-time quantitative PCR (qPCR) and Western blotting, respectively; The expression levels of MAPK-pathway-related proteins were detected by protein array technology; and the effects of ezrin enhancer knockout on the proliferation and migration of Eca-C2 cells were analyzed by WST-1 method and wound-healing assay, respectively. Results: The human esophageal carcinoma cell line Eca-C2 with stable ezrin enhancer knockout was established successfully. Compared with control cells, the mRNA and protein expressions of ezrin in Eca-C2 cells were significantly reduced (all P<0.05). Among the 17 detected MAPK pathway related proteins in Eca-C2 cells, 9 proteins (AKT, CREB, GSK3b, MKK6, mTOR, P38, P53, P70S6K and RSK1) were down-regulated, and the cell proliferation and migration were significantly inhibited (all P<0.05). Conclusion: ezrin enhancer knockout can significantly inhibit the cell proliferation and migration of human esophageal carcinoma Eca-109 cells.
2019, 26(1):36-41.
DOI: 10.3872/j.issn.1007-385X.2019.01.007
Abstract:
[Abstract] Objective: To investigate the effects of tumor-associated macrophages (TAM) on proliferation, migration, invation and apoptosis of gastric cancer MGC-803 cells and the possible mechanisms. Methods: Human monocyte THP-1 was cultured in vitro. After being added with PMA and IL-4, the levels of interleukin-12 (IL-12) and interleukin-10 (IL-10) in cell supernatant were detected by enzyme-linked immunosorbent assay (ELISA). MGC-803 cells at logarithmic phase and M2-type TAM cells were divided into single cell culture group, non-contact co-culture group and contact co-culture group according to different culture methods. MTT assay was used to detect the proliferation of MGC-803 cells, Transwell assay was used to detect cell migration and invasion, and Annexin V-FITC/PI staining flow cytometry was used to examine the apoptosis and cell cycle changes of MGC-803 cells; In addition, the mRNA and protein expressions of matrix metalloproteinase-9 (MMP-9) and MMP-2 were detected by Real-time fluorescence quantitative PCR (qPCR)and Western blotting. Results: Compared with PMA group, the level of IL-12 in cell supernatant of PMA+IL-4 group decreased significantly while the level of IL-10 increased significantly (all P<0.05), indicating THP-1 cells were successfully induced to differentiate into M2-type TAM. Compared with the single cell culture group, the non-contact co-culture group and the contact co-culture group exhibited: (1) significantly increased proliferation rate of MGC-803 cells (P<0.05)；(2) increased number of migrated and invaded cells (all P < 0.05)；(3) significantly decreased apoptotic rate (P<0.05)；(4) increased proportion of S, G2 phase cells and decreased proportion of G1 phase cells (all P<0.05)；and (5) significantly increased mRNA and protein expressions of MMP-9 and MMP-2 (all P<0.05).Conclusion: TAM can promote the proliferation, migration and invasion of gastric cancer MGC-803 cells, relieve G1 phase arrest and reduce cell apoptosis, which may be related to the up-regulation of MMP-9 and MMP-2 expression in gastric cancer cells.
[Abstract] Objective: To investigate the effects of tumor-associated macrophages (TAM) on proliferation, migration, invation and apoptosis of gastric cancer MGC-803 cells and the possible mechanisms. Methods: Human monocyte THP-1 was cultured in vitro. After being added with PMA and IL-4, the levels of interleukin-12 (IL-12) and interleukin-10 (IL-10) in cell supernatant were detected by enzyme-linked immunosorbent assay (ELISA). MGC-803 cells at logarithmic phase and M2-type TAM cells were divided into single cell culture group, non-contact co-culture group and contact co-culture group according to different culture methods. MTT assay was used to detect the proliferation of MGC-803 cells, Transwell assay was used to detect cell migration and invasion, and Annexin V-FITC/PI staining flow cytometry was used to examine the apoptosis and cell cycle changes of MGC-803 cells; In addition, the mRNA and protein expressions of matrix metalloproteinase-9 (MMP-9) and MMP-2 were detected by Real-time fluorescence quantitative PCR (qPCR)and Western blotting. Results: Compared with PMA group, the level of IL-12 in cell supernatant of PMA+IL-4 group decreased significantly while the level of IL-10 increased significantly (all P<0.05), indicating THP-1 cells were successfully induced to differentiate into M2-type TAM. Compared with the single cell culture group, the non-contact co-culture group and the contact co-culture group exhibited: (1) significantly increased proliferation rate of MGC-803 cells (P<0.05)；(2) increased number of migrated and invaded cells (all P < 0.05)；(3) significantly decreased apoptotic rate (P<0.05)；(4) increased proportion of S, G2 phase cells and decreased proportion of G1 phase cells (all P<0.05)；and (5) significantly increased mRNA and protein expressions of MMP-9 and MMP-2 (all P<0.05).Conclusion: TAM can promote the proliferation, migration and invasion of gastric cancer MGC-803 cells, relieve G1 phase arrest and reduce cell apoptosis, which may be related to the up-regulation of MMP-9 and MMP-2 expression in gastric cancer cells.
2019, 26(1):42-49.
DOI: 10.3872/j.issn.1007-385X.2019.01.008
Abstract:
[Abstract] Objective: To explore the effect of miR-424/HMGA1 (high mobility protein A1) axis on the radio-sensitivity of breast cancer cells and the possible mechanism. Methods: A total of 50 cases of breast cancer tissues from patients, who underwent surgical resection at the Department of Oncological Radiotherapy, Wuxi Fourth People’s Hospital from April 2014 to April 2017, were collected for this study. Real-time quantitative polymerase chain reaction (qPCR) and Western blotting were performed to evaluate the mRNA and protein expressions of miR-424 and HMGA1 in breast cancer tissues of radiation sensitive and insensitive patients. After being treated with different doses of 60Co γ - ray radiation (0, 2, 4, 6 and 8 Gy), the expression changes of miR-424 and HMGA1 in breast cancer MDA-MB-468 cells were observed. Subsequently, miR-424 mimic/inhibitor and pcDNA-HMGA1 were transfected into MDA-MB-468 cells, and the effect of miR-424 on cell proliferation, invasion and apoptosis of radiation-treated MDA-MB-468 cells were evaluated by colony formation assay, MTT assay, Transwell assay and Annexin V-FITC/PI double staining flow cytometry assay, respectively. Furthermore,dual luciferase reporter gene assay was used to verify whether HMGA1 was a target gene of miR-424. Results: The patients in radio-sensitive group exhibited higher miR-424 expression but lower HMGA1 expression than the patients in insensitive group (all P<0.01). Compared with the cells treated with 0, 2 and 4 Gy radiation, the cells treated with 6 and 8Gy radiation exhibited significantly higher apoptosis rate and miR-424 expression but lower HMGA1 expression and cell invasion (all P<0.01). Moreover, luciferase reporter gene assay confirmed that miR-424 down-regulated HMGA1 expression. Mechanistically, miR-424 significantly inhibited cell proliferation, invasion and induced apoptosis of MDA-MB-468 cells (all P<0.01) via targeted down-regulating HMGA1, and further upregulated the radio-sensitivity of breast cancer cells. Conclusion: miR-424/HMGA1 axis regulates the radio-sensitivity of breast cancer,and over-expression of miR-424 may increase the sensitivity of MDA-MB-468 cells to γ-ray radiation therapy.
[Abstract] Objective: To explore the effect of miR-424/HMGA1 (high mobility protein A1) axis on the radio-sensitivity of breast cancer cells and the possible mechanism. Methods: A total of 50 cases of breast cancer tissues from patients, who underwent surgical resection at the Department of Oncological Radiotherapy, Wuxi Fourth People’s Hospital from April 2014 to April 2017, were collected for this study. Real-time quantitative polymerase chain reaction (qPCR) and Western blotting were performed to evaluate the mRNA and protein expressions of miR-424 and HMGA1 in breast cancer tissues of radiation sensitive and insensitive patients. After being treated with different doses of 60Co γ - ray radiation (0, 2, 4, 6 and 8 Gy), the expression changes of miR-424 and HMGA1 in breast cancer MDA-MB-468 cells were observed. Subsequently, miR-424 mimic/inhibitor and pcDNA-HMGA1 were transfected into MDA-MB-468 cells, and the effect of miR-424 on cell proliferation, invasion and apoptosis of radiation-treated MDA-MB-468 cells were evaluated by colony formation assay, MTT assay, Transwell assay and Annexin V-FITC/PI double staining flow cytometry assay, respectively. Furthermore,dual luciferase reporter gene assay was used to verify whether HMGA1 was a target gene of miR-424. Results: The patients in radio-sensitive group exhibited higher miR-424 expression but lower HMGA1 expression than the patients in insensitive group (all P<0.01). Compared with the cells treated with 0, 2 and 4 Gy radiation, the cells treated with 6 and 8Gy radiation exhibited significantly higher apoptosis rate and miR-424 expression but lower HMGA1 expression and cell invasion (all P<0.01). Moreover, luciferase reporter gene assay confirmed that miR-424 down-regulated HMGA1 expression. Mechanistically, miR-424 significantly inhibited cell proliferation, invasion and induced apoptosis of MDA-MB-468 cells (all P<0.01) via targeted down-regulating HMGA1, and further upregulated the radio-sensitivity of breast cancer cells. Conclusion: miR-424/HMGA1 axis regulates the radio-sensitivity of breast cancer,and over-expression of miR-424 may increase the sensitivity of MDA-MB-468 cells to γ-ray radiation therapy.
2019, 26(1):50-57.
DOI: 10.3872/j.issn.1007-385X.2019.01.009
Abstract:
[Abstract] Objective: To investigate the degree and distribution of tissue-resident CD8+ T cell (CD103+CD8+T cells) infiltration in colorectal cancer (CRC) tissues, and to analyze its relationship to patients’clinicopathological features and prognosis. Methods: Tissue chips of 88 cases of colon cancer tissues (No.HColA180Su14) and 77 cases of rectal cancer tissues (No. HRec-Ade180Sur-03) were obtained from Shanghai Outdo Biotech Co.,Ltd. Immunofluorescence staining was performed to examine the infiltration pattern and degree of CD103+CD8+T cells in the collected CRC tissues and their para-cancerous tissues. Wilcoxon rank test was used to compare CD103+CD8+T cell infiltration degree in CRC tissues and the para-cancerous tissues. Chi-square test was used to analyze the relationship between CD103+CD8+T cell infiltration in CRC and patients’clinicopathological features. Kaplan-Meier survival analysis was conducted to explore the correlation between CD103+CD8+T cell infiltration and patients’prognosis. Cox model was applied to analyze the correlation between different clinical parameters and patients’prognosis. Results: CD103+CD8+T cell infiltration presented no signifi-cant differences between CRC and para-cancer tissues (P>0.05). Patients with distant metastasis had significantly lower CD103+CD8+T cell infiltration rate than patients without distant metastasis (P<0.01). There was no significant correlation between the infiltration of CD103+CD8+T cells and other clinicopathological features (P>0.05). Kaplan-Meier survival analysis showed that the overall survival (OS) of patients with high CD103+CD8+T cell infiltration was significantly longer than that of the patients with low infiltration (54.42%vs 25.00%, P<0.05). Multivariate Cox model analysis indicated that pathological grade (P<0.01) and high CD103+CD8+T cell infiltration (P<0.05) were independent prognostic factors for CRC. Conclusion：CD103+CD8+T cell infiltration in CRC is associated with patients’prognosis,suggesting that CD103+CD8+T cell plays an important role in the initiation and development of CRC.
[Abstract] Objective: To investigate the degree and distribution of tissue-resident CD8+ T cell (CD103+CD8+T cells) infiltration in colorectal cancer (CRC) tissues, and to analyze its relationship to patients’clinicopathological features and prognosis. Methods: Tissue chips of 88 cases of colon cancer tissues (No.HColA180Su14) and 77 cases of rectal cancer tissues (No. HRec-Ade180Sur-03) were obtained from Shanghai Outdo Biotech Co.,Ltd. Immunofluorescence staining was performed to examine the infiltration pattern and degree of CD103+CD8+T cells in the collected CRC tissues and their para-cancerous tissues. Wilcoxon rank test was used to compare CD103+CD8+T cell infiltration degree in CRC tissues and the para-cancerous tissues. Chi-square test was used to analyze the relationship between CD103+CD8+T cell infiltration in CRC and patients’clinicopathological features. Kaplan-Meier survival analysis was conducted to explore the correlation between CD103+CD8+T cell infiltration and patients’prognosis. Cox model was applied to analyze the correlation between different clinical parameters and patients’prognosis. Results: CD103+CD8+T cell infiltration presented no signifi-cant differences between CRC and para-cancer tissues (P>0.05). Patients with distant metastasis had significantly lower CD103+CD8+T cell infiltration rate than patients without distant metastasis (P<0.01). There was no significant correlation between the infiltration of CD103+CD8+T cells and other clinicopathological features (P>0.05). Kaplan-Meier survival analysis showed that the overall survival (OS) of patients with high CD103+CD8+T cell infiltration was significantly longer than that of the patients with low infiltration (54.42%vs 25.00%, P<0.05). Multivariate Cox model analysis indicated that pathological grade (P<0.01) and high CD103+CD8+T cell infiltration (P<0.05) were independent prognostic factors for CRC. Conclusion：CD103+CD8+T cell infiltration in CRC is associated with patients’prognosis,suggesting that CD103+CD8+T cell plays an important role in the initiation and development of CRC.
2019, 26(1):58-66.
DOI: 10.3872/j.issn.1007-385X.2019.01.010
Abstract:
[Abstract] Objective: To investigate the expression of long non-coding RNA SNHG16 (lncRNA SNHG16) in colorectal cancer (CRC)tissues and cells, and to explore the mechanism of its regulation on the expression of mitochondrial glycerol-3-phosphate acyltransferase (GPAM) via sponging miR-128-3p. Methods: Sixty pairs of colorectal cancerous tissues and para-cancerous tissues that resected from CRC patients, who underwent surgery in the Department of Anorectal Surgery, Gansu Provincial People’s Hospital during Jan.2014 and Jan. 2017, were collected for this study; In addition, CRC cell lines (SW480, SW620, HCT116, Caco-2,DLD-1, HT29) and colonic epithelial cell line CCD841 were also collected for the study. The expression of SNHG16 in collected tissues and cell lines was determined by Real-time quantitative PCR (qPCR), and its correlation to the clinicopathological features of CRC patients was also analyzed.SW480 cells were transfected with miR-128-3p mimic, miR-128-3p inhibitor, and si-SNHG16, respectively, and then the mRNA expressions of miR-128-3p and SNHG16 were detected by qPCR, the protein expression of GPAM was determined by Western blotting,and the cell proliferation, apoptosis and invasion were detected by CCK-8 assay, colony formation assay, cell apoptosis assay and Transwell chamber assay, respectively. The binding between SNHG16 and miR-128-3p was validated with dual luciferase reporter gene assay and RNA Immunoprecipitation assay. For in vivo experiment, mouse model of SW480 cell exnograft was constructed, and the ef-fect of SNHG16 knockdown on the growth of exnograft was observed. Results: SNHG16 was found to highly expressed in human CRC tissues and cell lines (all P<0.01), and SNHG16 expression level was associated with lymph node metastasis, Duke's stage and patients’survival (all P<0.01). Knockdown of SNHG16 significantly inhibited CRC cell proliferation and invasion, and induced apoptosis (all P<0.01); After SNHG16 knockdown, the volume of exnograft was obviously reduced (P<0.05). Dual luciferase reporter gene assay and RNA Immunoprecipitation assay validated the interaction between miR-128-3p and SNHG16, and they were negatively correlated with each other in CRC patients (P<0.01). The SNHG16 regulated the expression of its down-stream gene GPAM via endogenously sponging miR-128-3p. Conclusion: SNHG16 regulates GPAM expression in CRC cells by sponging miR-128-3p, and SNHG16 and miR-128-3p may serve as potential targets for the diagnosis and treatment of CRC.
[Abstract] Objective: To investigate the expression of long non-coding RNA SNHG16 (lncRNA SNHG16) in colorectal cancer (CRC)tissues and cells, and to explore the mechanism of its regulation on the expression of mitochondrial glycerol-3-phosphate acyltransferase (GPAM) via sponging miR-128-3p. Methods: Sixty pairs of colorectal cancerous tissues and para-cancerous tissues that resected from CRC patients, who underwent surgery in the Department of Anorectal Surgery, Gansu Provincial People’s Hospital during Jan.2014 and Jan. 2017, were collected for this study; In addition, CRC cell lines (SW480, SW620, HCT116, Caco-2,DLD-1, HT29) and colonic epithelial cell line CCD841 were also collected for the study. The expression of SNHG16 in collected tissues and cell lines was determined by Real-time quantitative PCR (qPCR), and its correlation to the clinicopathological features of CRC patients was also analyzed.SW480 cells were transfected with miR-128-3p mimic, miR-128-3p inhibitor, and si-SNHG16, respectively, and then the mRNA expressions of miR-128-3p and SNHG16 were detected by qPCR, the protein expression of GPAM was determined by Western blotting,and the cell proliferation, apoptosis and invasion were detected by CCK-8 assay, colony formation assay, cell apoptosis assay and Transwell chamber assay, respectively. The binding between SNHG16 and miR-128-3p was validated with dual luciferase reporter gene assay and RNA Immunoprecipitation assay. For in vivo experiment, mouse model of SW480 cell exnograft was constructed, and the ef-fect of SNHG16 knockdown on the growth of exnograft was observed. Results: SNHG16 was found to highly expressed in human CRC tissues and cell lines (all P<0.01), and SNHG16 expression level was associated with lymph node metastasis, Duke's stage and patients’survival (all P<0.01). Knockdown of SNHG16 significantly inhibited CRC cell proliferation and invasion, and induced apoptosis (all P<0.01); After SNHG16 knockdown, the volume of exnograft was obviously reduced (P<0.05). Dual luciferase reporter gene assay and RNA Immunoprecipitation assay validated the interaction between miR-128-3p and SNHG16, and they were negatively correlated with each other in CRC patients (P<0.01). The SNHG16 regulated the expression of its down-stream gene GPAM via endogenously sponging miR-128-3p. Conclusion: SNHG16 regulates GPAM expression in CRC cells by sponging miR-128-3p, and SNHG16 and miR-128-3p may serve as potential targets for the diagnosis and treatment of CRC.
2019, 26(1):67-72.
DOI: 10.3872/j.issn.1007-385X.2019.01.011
Abstract:
[Abstract] Objective: To investigate the effect of VEGFR2 gene polymorphism V297I on the clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with bevacizumab combining with chemotherapy. Methods: A total of 135 patients with advanced NSCLC, who were treated by bevacizumab plus platinum-based chemotherapy for first-line regimen, were included in this study. PCR-RFLP assay was used to detect the VEGFR2 genotypes in peripheral blood of patients and qPCR was used to detect the VEGFR2 mRNA in the cancer tissues of NSCLC patients. Logistic regression analysis was used to analyze the correlation between gene polymorphism and other variants, Kaplan-Meier assay to analyze the correlation between genotype and prognosis, and Cox regression model to analyze the risk factors for patients’PFS. Results: Of the polymorphisms analyzed, only polymorphism V297I was found to be of clinical significance. V297I locates in the coding region of VEGFR2, and it’s prevalence in the study population was as follows: CC genotype in 99 cases (73.33%), CT genotype in 33 cases (24.44%) and TT genotype in 3 cases (2.23%); the frequency of minor allele was 0.14, and the distribution of three genotypes was in accordance with Hardy-Weinberg equilibrium (P>0.05). The overall objective remission rate (ORR) of the 135 patients was 45.93%, the median progression free survival (mPFS) was 8.2 months and the median overall survival (mOS) was 20.8 months. The ORR, mPFS and mOS of patients with CT/TT genotype and CC genotype were 41.67%, 6.2 months, 18.9 months and 47.47%, 8.9 months and 21.5 months, respectively (all P<0.05). Additionally, the mRNA expression of VEGFR2 in cancer tissues of the patients with CT/TT genotype was significantly higher than those with CC genotype (P<0.01). The risk factors for patients’PFS included V297I, gender and ECOG score. Conclusion: Among advanced NSCLC patients treated by bevacizumab plus platinum-based chemotherapy, the polymorphism V297I of VEGFR2 may impact the clinical outcomes and prognosis of NSCLC patients treated with bevacizumab first line treatment by influencing the mRNA expression of VEGFR2.
[Abstract] Objective: To investigate the effect of VEGFR2 gene polymorphism V297I on the clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with bevacizumab combining with chemotherapy. Methods: A total of 135 patients with advanced NSCLC, who were treated by bevacizumab plus platinum-based chemotherapy for first-line regimen, were included in this study. PCR-RFLP assay was used to detect the VEGFR2 genotypes in peripheral blood of patients and qPCR was used to detect the VEGFR2 mRNA in the cancer tissues of NSCLC patients. Logistic regression analysis was used to analyze the correlation between gene polymorphism and other variants, Kaplan-Meier assay to analyze the correlation between genotype and prognosis, and Cox regression model to analyze the risk factors for patients’PFS. Results: Of the polymorphisms analyzed, only polymorphism V297I was found to be of clinical significance. V297I locates in the coding region of VEGFR2, and it’s prevalence in the study population was as follows: CC genotype in 99 cases (73.33%), CT genotype in 33 cases (24.44%) and TT genotype in 3 cases (2.23%); the frequency of minor allele was 0.14, and the distribution of three genotypes was in accordance with Hardy-Weinberg equilibrium (P>0.05). The overall objective remission rate (ORR) of the 135 patients was 45.93%, the median progression free survival (mPFS) was 8.2 months and the median overall survival (mOS) was 20.8 months. The ORR, mPFS and mOS of patients with CT/TT genotype and CC genotype were 41.67%, 6.2 months, 18.9 months and 47.47%, 8.9 months and 21.5 months, respectively (all P<0.05). Additionally, the mRNA expression of VEGFR2 in cancer tissues of the patients with CT/TT genotype was significantly higher than those with CC genotype (P<0.01). The risk factors for patients’PFS included V297I, gender and ECOG score. Conclusion: Among advanced NSCLC patients treated by bevacizumab plus platinum-based chemotherapy, the polymorphism V297I of VEGFR2 may impact the clinical outcomes and prognosis of NSCLC patients treated with bevacizumab first line treatment by influencing the mRNA expression of VEGFR2.
2019, 26(1):73-78.
DOI: 10.3872/j.issn.1007-385X.2019.01.012
Abstract:
[Abstract] Objective: To explore the expression of IQGAP1 (Ras GTPase-activating-like protein containing IQ domain) in esophageal squamous cell carcinoma (ESCC) tissues and cell lines and its effect on the proliferation and invasion of TE-2 cell. Methods: Totally 125 pairs of cancer tissues and para-cancerous tissues from ESCC patients, who underwent surgical resection in Affiliated Tumor Hospital of Zhengzhou University from January 2015 to December 2016, were included in this study; in addition, ESCC cell lines (TE-2, TE-3, ECA109) and normal esophageal epithelial cell line Het-1A were also collected. The expression of IQGAP1 was detected by immunohistochemical staining and its relationship with cliniopathological features was also analyzed. IQGAP1 mRNA and protein expressions in ESCC cell lines were detected by Real-time quantitative PCR (qPCR) and Western blotting, respectively. TE-2 cells were transfected with si-IQGAP1 (positive transfection group) and si-CTRL (negative control group) plasmids, and the effects of IQGAP1 silencing on the proliferation and invasion of TE-2 cells were detected by MTT and Transwell assay. The expressions of E-cadherin and Ncadherin were detected by Western blotting. Results: The positive expression rate of IQGAP1 in ESCC tissues was significantly higher than that in para-cancerous tissues (P<0.05), which was closely related to tumor stage and histologic grade (all P<0.05). The mRNA and protein expressions of IQGAP1 in TE-2, TE-3 and ECA109 cells were significantly higher than those in Het-1A cells (all P<0.05). After IQGAP1 was silenced, compared with the negative control group and the blank group, the expression of IQGAP1 mRNA and protein in the positive transfection group significantly decreased (all P<0.05); the proliferation and invasiveness of TE-2 cells significantly decreased (all P<0.05); E-cardherin was up-regulated while N-cardherin was down-regulated (all P<0.05) in the positive interference group. Conclusion: IQGAP1 is highly expressed in ESCC tissues, and si-IQGAP1 can inhibit the proliferation and invasion of TE-2 cells, which plays an important role in the occurrence and development of ESCC.
[Abstract] Objective: To explore the expression of IQGAP1 (Ras GTPase-activating-like protein containing IQ domain) in esophageal squamous cell carcinoma (ESCC) tissues and cell lines and its effect on the proliferation and invasion of TE-2 cell. Methods: Totally 125 pairs of cancer tissues and para-cancerous tissues from ESCC patients, who underwent surgical resection in Affiliated Tumor Hospital of Zhengzhou University from January 2015 to December 2016, were included in this study; in addition, ESCC cell lines (TE-2, TE-3, ECA109) and normal esophageal epithelial cell line Het-1A were also collected. The expression of IQGAP1 was detected by immunohistochemical staining and its relationship with cliniopathological features was also analyzed. IQGAP1 mRNA and protein expressions in ESCC cell lines were detected by Real-time quantitative PCR (qPCR) and Western blotting, respectively. TE-2 cells were transfected with si-IQGAP1 (positive transfection group) and si-CTRL (negative control group) plasmids, and the effects of IQGAP1 silencing on the proliferation and invasion of TE-2 cells were detected by MTT and Transwell assay. The expressions of E-cadherin and Ncadherin were detected by Western blotting. Results: The positive expression rate of IQGAP1 in ESCC tissues was significantly higher than that in para-cancerous tissues (P<0.05), which was closely related to tumor stage and histologic grade (all P<0.05). The mRNA and protein expressions of IQGAP1 in TE-2, TE-3 and ECA109 cells were significantly higher than those in Het-1A cells (all P<0.05). After IQGAP1 was silenced, compared with the negative control group and the blank group, the expression of IQGAP1 mRNA and protein in the positive transfection group significantly decreased (all P<0.05); the proliferation and invasiveness of TE-2 cells significantly decreased (all P<0.05); E-cardherin was up-regulated while N-cardherin was down-regulated (all P<0.05) in the positive interference group. Conclusion: IQGAP1 is highly expressed in ESCC tissues, and si-IQGAP1 can inhibit the proliferation and invasion of TE-2 cells, which plays an important role in the occurrence and development of ESCC.
2019, 26(1):79-84.
DOI: 10.3872/j.issn.1007-385X.2019.01.013
Abstract:
[Abstract] Objective: To investigate the mechanisms of miR-375 affecting the proliferation and invasion of hepatoma cells via targeting YAP (Yes-associated protein). Methods: The cancerous tissues and corresponding para-cancerous tissues of 70 patients with hepatocellular carcinoma (HCC) who underwent surgical resection at the Second Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2015 to December 2016, as well as the hepatoma cell lines SMMC-7721, Hb611, HepG2 and BEL-7405 were collected for this study. qPCR method was used to detect the expression level of miR-375 in collected HCC tissues and different hepatoma cell lines; Dual luciferase reporter gene assay was used to verify the interaction between miR-375 and YAP; The relationship between miR-375 and clinicopathological features of HCC patients was also analyzed; MTT assay was used to detect the effect of miR-375 on the proliferation of hepatoma cells; Transwell invasion assay was used to detect the invasive ability of hepatoma cells after inhibiting the expression of miR-375; Western blotting was used to detect the expression of YAP in HepG2 cells. The nude mouse model of subcutaneously transplanted xenograft was established, and the tumor volume and mass of transplanted hepatoma cells were detected after inhibiting the expression of miR-375. The expression of YAP in xenograft of nude mice was detected by immunohistochemistry and Western blotting. Results: The expression of miR-375 and YAP in HCC tissues was significantly higher than that in para-cancerous tissues (all P<0.05). The expression of miR-375 in HepG2 cells was the highest (P<0.05). miR-375 could specifically bind to the 3' UTR of YAP and regulate the expression activity of YAP. After inhibiting the expression of miR-375, the proliferation and invasion abilities of HepG2 cells were reduced (all P<0.05); The tumor volume and mass of transplanted xenografts were significantly reduced (both P<0.05); The expression of YAP protein in the transplanted xenografts was down-regulated (P<0.05). Conclusion: miR-375 plays an important role in the occurrence and development of liver cancer, and can influence the malignant biological behaviors of hepatoma cells by targeting and regulating the expression of YAP.
[Abstract] Objective: To investigate the mechanisms of miR-375 affecting the proliferation and invasion of hepatoma cells via targeting YAP (Yes-associated protein). Methods: The cancerous tissues and corresponding para-cancerous tissues of 70 patients with hepatocellular carcinoma (HCC) who underwent surgical resection at the Second Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2015 to December 2016, as well as the hepatoma cell lines SMMC-7721, Hb611, HepG2 and BEL-7405 were collected for this study. qPCR method was used to detect the expression level of miR-375 in collected HCC tissues and different hepatoma cell lines; Dual luciferase reporter gene assay was used to verify the interaction between miR-375 and YAP; The relationship between miR-375 and clinicopathological features of HCC patients was also analyzed; MTT assay was used to detect the effect of miR-375 on the proliferation of hepatoma cells; Transwell invasion assay was used to detect the invasive ability of hepatoma cells after inhibiting the expression of miR-375; Western blotting was used to detect the expression of YAP in HepG2 cells. The nude mouse model of subcutaneously transplanted xenograft was established, and the tumor volume and mass of transplanted hepatoma cells were detected after inhibiting the expression of miR-375. The expression of YAP in xenograft of nude mice was detected by immunohistochemistry and Western blotting. Results: The expression of miR-375 and YAP in HCC tissues was significantly higher than that in para-cancerous tissues (all P<0.05). The expression of miR-375 in HepG2 cells was the highest (P<0.05). miR-375 could specifically bind to the 3' UTR of YAP and regulate the expression activity of YAP. After inhibiting the expression of miR-375, the proliferation and invasion abilities of HepG2 cells were reduced (all P<0.05); The tumor volume and mass of transplanted xenografts were significantly reduced (both P<0.05); The expression of YAP protein in the transplanted xenografts was down-regulated (P<0.05). Conclusion: miR-375 plays an important role in the occurrence and development of liver cancer, and can influence the malignant biological behaviors of hepatoma cells by targeting and regulating the expression of YAP.
2019, 26(1):85-89.
DOI: 10.3872/j.issn.1007-385X.2019.01.014
Abstract:
[Abstract] Objective: To investigate the expression of microRNA-380-5p (miR-380-5p) in cervical cancer tissues and cell lines, and to explore the mechanism of miR-380-5p inhibiting the proliferation and migration of cervical cancer cells. Methods: 16 pairs of cervical cancerous tissues and corresponding para-cancerous tissues were collected from the Department of Obstetrics and Gynecology, the Affiliated Wuhan Central Hospital of Tongji Medical College from December 2016 to July 2017; in addition, cervical cancer cell lines (HCC94, C33A, Hela, SiHa) and human cervical epithelial immortalized H8 cells were also collected for this study. The expression of miR-380-5p in above mentioned tissues and cell lines was detected by Real-time quantitative polymerase chain reaction (qPCR). miR-380-5p mimic (experimental group) and miR-NC (negative control group) were transiently transfected into C33A cells by lipofection,and qPCR was used to detect the expression of miR-380-5p in the transfected cells. Cell proliferation and migration were evaluated by cell counting kit (CCK-8) and Transwell assay. Bioinformatics software TargetScan predicted the downstream genes of miR-380-5p,and dual luciferase reporter assay was used to verify the binding of miR-380-5p to the downstream gene RHOA (Ras homolog gene family member A). qPCR and Western blotting were used to detect the expression of miR-380-5p downstream gene-RHOA. Results:The expression level of miR-380-5p in cervical cancer tissues and cell lines was significantly lower than that in para-cancerous tissues and normal cervical epithelial H8 cells (P<0.01); and the expression in C33A cells was the lowest (P<0.01). Compared with the negative control group, the miR-380-5p mimic transfection singnificantly inhibited the proliferation (P<0.05) and migration ability of C33A cells (P<0.01), and down-regulated protein expressions of RHOA, ROCK1, ROCK2, CDK2 and N-cadherin (all P<0.01). Bioinformatics software predicted that RHOA may be a downstream gene of miR-380-5p, and dual luciferase reporter assay proved the specific binding of miR-380-5p to the 3'UTR of RHOA (P<0.01). miR-380-5p could significantly down-regulate RHOA gene expression (P<0.01). Conclusion: miR-380-5p is low-expressed in cervical cancer cell lines. Over-expression of miR-380-5p may inhibit the proliferation and migration of cervical cancer C33A cells by down-regulating the expression of RHOA gene and its downstream proteins.
[Abstract] Objective: To investigate the expression of microRNA-380-5p (miR-380-5p) in cervical cancer tissues and cell lines, and to explore the mechanism of miR-380-5p inhibiting the proliferation and migration of cervical cancer cells. Methods: 16 pairs of cervical cancerous tissues and corresponding para-cancerous tissues were collected from the Department of Obstetrics and Gynecology, the Affiliated Wuhan Central Hospital of Tongji Medical College from December 2016 to July 2017; in addition, cervical cancer cell lines (HCC94, C33A, Hela, SiHa) and human cervical epithelial immortalized H8 cells were also collected for this study. The expression of miR-380-5p in above mentioned tissues and cell lines was detected by Real-time quantitative polymerase chain reaction (qPCR). miR-380-5p mimic (experimental group) and miR-NC (negative control group) were transiently transfected into C33A cells by lipofection,and qPCR was used to detect the expression of miR-380-5p in the transfected cells. Cell proliferation and migration were evaluated by cell counting kit (CCK-8) and Transwell assay. Bioinformatics software TargetScan predicted the downstream genes of miR-380-5p,and dual luciferase reporter assay was used to verify the binding of miR-380-5p to the downstream gene RHOA (Ras homolog gene family member A). qPCR and Western blotting were used to detect the expression of miR-380-5p downstream gene-RHOA. Results:The expression level of miR-380-5p in cervical cancer tissues and cell lines was significantly lower than that in para-cancerous tissues and normal cervical epithelial H8 cells (P<0.01); and the expression in C33A cells was the lowest (P<0.01). Compared with the negative control group, the miR-380-5p mimic transfection singnificantly inhibited the proliferation (P<0.05) and migration ability of C33A cells (P<0.01), and down-regulated protein expressions of RHOA, ROCK1, ROCK2, CDK2 and N-cadherin (all P<0.01). Bioinformatics software predicted that RHOA may be a downstream gene of miR-380-5p, and dual luciferase reporter assay proved the specific binding of miR-380-5p to the 3'UTR of RHOA (P<0.01). miR-380-5p could significantly down-regulate RHOA gene expression (P<0.01). Conclusion: miR-380-5p is low-expressed in cervical cancer cell lines. Over-expression of miR-380-5p may inhibit the proliferation and migration of cervical cancer C33A cells by down-regulating the expression of RHOA gene and its downstream proteins.
2019, 26(1):90-95.
DOI: 10.3872/j.issn.1007-385X.2019.01.015
Abstract:
[Abstract] Objective: To evaluate the expression of leucine zipper tumor suppressor 2 (LZTS2) in human breast cancer tissues and cell lines, and to investigate the effects and mechanisms of LZTS2 over-expression on proliferation, invasion and epithelial-mesenchymal transition (EMT) of breast cancer cells. Methods: Fifty pairs of cancerous tissues and para-cancerous tissues resected from breast cancer patients in Department of Breast Surgery of Kaifeng Central Hospital from January, 2016 to December, 2016, as well as breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-468) and normal mammary epithelial HBL-100 cells were collected for this study;and Real-time quantitative PCR (qPCR) and Western blotting were used to determine the mRNA and protein expressions of LZTS2 in collected tissues and cell lines. MCF-7 cells were transfected with pcDNA-LZTS2 or pcDNA3.1 (negative control) using lipofectamineTM 2000, and the protein expression of LZTS2 at 49-72 h after transfection was measured by Western blotting; Then, the effects of LZTS2 over-expression on proliferation, migration and invasion of MCF-7 cells were detected by MTT assay and Transwell assay, respectively;Furthermore, Western blotting was performed to detect the expressions of EMT associated proteins (Cyclin D1, Vimentin, Ncadherin,E-cadherin) and PI3K/AKT signaling pathways-related molecules. Results: The mRNA and protein expressions of LZTS2 were down-regulated in breast cancerous tissues and cell lines (MCF-7, MDA-MB-468 and MDA-MB-231) as compared with paired para-cancerous tissues or normal mammary epithelial HBL-100 cells (P<0.05 or P<0.01). Compared with and blank control or pcDNA3.1 group, the protein expression of LZTS2 in MCF-7 cells of pcDNA-LZTS2 group significantly increased (P<0.01), while the proliferation,migration and invasion of MCF-7 cells significantly reduced (P<0.05 or P<0.01). In addition, forced expression of LZTS2 significantly down-regulated the protein expressions of Cyclin D1, Vimentin and N-cadherin (P<0.05 or P<0.01) but up-regulated the expression of E-cadherin in MCF-7 cells (P<0.01), indicating LZTS2 over-expression suppressed PI3K / AKT signaling pathway through inhibiting the expression p-PI3K and p-AKT. Conclusion: The findings collectively demonstrated that the expression of LZTS2 was decreased in breast cancer, and over-expression of LZTS2 efficiently inhibited the proliferation, migration and invasion of breast cancer cells, which might be related with the suppression of PI3K/AKT signaling pathway involved in EMT.
[Abstract] Objective: To evaluate the expression of leucine zipper tumor suppressor 2 (LZTS2) in human breast cancer tissues and cell lines, and to investigate the effects and mechanisms of LZTS2 over-expression on proliferation, invasion and epithelial-mesenchymal transition (EMT) of breast cancer cells. Methods: Fifty pairs of cancerous tissues and para-cancerous tissues resected from breast cancer patients in Department of Breast Surgery of Kaifeng Central Hospital from January, 2016 to December, 2016, as well as breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-468) and normal mammary epithelial HBL-100 cells were collected for this study;and Real-time quantitative PCR (qPCR) and Western blotting were used to determine the mRNA and protein expressions of LZTS2 in collected tissues and cell lines. MCF-7 cells were transfected with pcDNA-LZTS2 or pcDNA3.1 (negative control) using lipofectamineTM 2000, and the protein expression of LZTS2 at 49-72 h after transfection was measured by Western blotting; Then, the effects of LZTS2 over-expression on proliferation, migration and invasion of MCF-7 cells were detected by MTT assay and Transwell assay, respectively;Furthermore, Western blotting was performed to detect the expressions of EMT associated proteins (Cyclin D1, Vimentin, Ncadherin,E-cadherin) and PI3K/AKT signaling pathways-related molecules. Results: The mRNA and protein expressions of LZTS2 were down-regulated in breast cancerous tissues and cell lines (MCF-7, MDA-MB-468 and MDA-MB-231) as compared with paired para-cancerous tissues or normal mammary epithelial HBL-100 cells (P<0.05 or P<0.01). Compared with and blank control or pcDNA3.1 group, the protein expression of LZTS2 in MCF-7 cells of pcDNA-LZTS2 group significantly increased (P<0.01), while the proliferation,migration and invasion of MCF-7 cells significantly reduced (P<0.05 or P<0.01). In addition, forced expression of LZTS2 significantly down-regulated the protein expressions of Cyclin D1, Vimentin and N-cadherin (P<0.05 or P<0.01) but up-regulated the expression of E-cadherin in MCF-7 cells (P<0.01), indicating LZTS2 over-expression suppressed PI3K / AKT signaling pathway through inhibiting the expression p-PI3K and p-AKT. Conclusion: The findings collectively demonstrated that the expression of LZTS2 was decreased in breast cancer, and over-expression of LZTS2 efficiently inhibited the proliferation, migration and invasion of breast cancer cells, which might be related with the suppression of PI3K/AKT signaling pathway involved in EMT.
2019, 26(1):96-102.
DOI: 10.3872/j.issn.1007-385X.2019.01.016
Abstract:
[摘要] 乳腺癌是中国女性最常见的恶性肿瘤，传统治疗方法存在一定副作用，而免疫治疗为攻克乳腺癌提供了新途径，尤以晚期乳腺癌及三阴性乳腺癌（triple-negative breast cancer, TNBC）患者的PD-1/PD-L1 抑制剂治疗最具发展前景。随着乳腺癌免疫治疗相关临床试验的开展，以HER2/nue 疫苗、MUC-1 疫苗等为代表的肿瘤疫苗已观察到可以改善患者的无病生存期（DFS）和总生存期（OS）。曲妥珠单抗、帕妥珠单抗、T-DM1、MM-111 等单克隆抗体也显示出较好疗效，CIK、TIL、CAR-T等过继性细胞治疗具有较强的肿瘤杀伤能力且安全性良好，而抗PD-1/PD-L1 抗体、抗CTLA-4 抗体、抗LAG-3 抗体等免疫负调控抑制剂能够抑制肿瘤逃逸，为乳腺癌的治疗提供了新策略，这些突破性的成果推动了乳腺癌治疗实现“个体化”的进程。
[摘要] 乳腺癌是中国女性最常见的恶性肿瘤，传统治疗方法存在一定副作用，而免疫治疗为攻克乳腺癌提供了新途径，尤以晚期乳腺癌及三阴性乳腺癌（triple-negative breast cancer, TNBC）患者的PD-1/PD-L1 抑制剂治疗最具发展前景。随着乳腺癌免疫治疗相关临床试验的开展，以HER2/nue 疫苗、MUC-1 疫苗等为代表的肿瘤疫苗已观察到可以改善患者的无病生存期（DFS）和总生存期（OS）。曲妥珠单抗、帕妥珠单抗、T-DM1、MM-111 等单克隆抗体也显示出较好疗效，CIK、TIL、CAR-T等过继性细胞治疗具有较强的肿瘤杀伤能力且安全性良好，而抗PD-1/PD-L1 抗体、抗CTLA-4 抗体、抗LAG-3 抗体等免疫负调控抑制剂能够抑制肿瘤逃逸，为乳腺癌的治疗提供了新策略，这些突破性的成果推动了乳腺癌治疗实现“个体化”的进程。
2019, 26(1):103-108.
DOI: 10.3872/j.issn.1007-385X.2019.01.017
Abstract:
[摘要] 消化系统肿瘤是人类常见的恶性肿瘤，其中胃癌、结直肠癌、胰腺癌的发病率和病死率均较高。免疫治疗作为一种新的治疗方法，正逐步成为多种肿瘤的有效治疗策略之一。CTLA-4 和PD-1 是通过不同机制负调控T细胞活化的关键免疫检查点分子。针对这些免疫检查点抑制剂，已经显示出临床疗效，并已获美国FDA批准用于多种实体瘤的治疗。其中，纳武单抗在延长晚期肝癌患者生存期方面超过了索拉非尼，派姆单抗在PD-L1 阳性晚期食管癌有效率可达30%，纳武单抗与伊匹单抗联合治疗dMMR/MSI-H晚期结直肠癌的客观缓解率达到55%。本文就近年来免疫检查点抑制剂在消化系统肿瘤治疗中的研究进展进行综述。
[摘要] 消化系统肿瘤是人类常见的恶性肿瘤，其中胃癌、结直肠癌、胰腺癌的发病率和病死率均较高。免疫治疗作为一种新的治疗方法，正逐步成为多种肿瘤的有效治疗策略之一。CTLA-4 和PD-1 是通过不同机制负调控T细胞活化的关键免疫检查点分子。针对这些免疫检查点抑制剂，已经显示出临床疗效，并已获美国FDA批准用于多种实体瘤的治疗。其中，纳武单抗在延长晚期肝癌患者生存期方面超过了索拉非尼，派姆单抗在PD-L1 阳性晚期食管癌有效率可达30%，纳武单抗与伊匹单抗联合治疗dMMR/MSI-H晚期结直肠癌的客观缓解率达到55%。本文就近年来免疫检查点抑制剂在消化系统肿瘤治疗中的研究进展进行综述。
2019, 26(1):109-115.
DOI: 10.3872/j.issn.1007-385X.2019.01.018
Abstract:
[摘要] 侵袭与转移是影响恶性肿瘤患者预后最重要的因素之一，也一直是预测肿瘤预后和改善患者生存的热点与难点。上皮钙黏蛋白（E-cadherin）低表达是恶性肿瘤最常见的表型之一，在多种肿瘤的侵袭、转移中发挥重要作用。上调上皮钙黏蛋白表达可以降低恶性肿瘤的侵袭与转移能力，甚至改善肿瘤患者的预后，为肿瘤患者的治疗提供有效措施。近年来，以RNA诱导的基因激活（RNAa）为代表的基因调控技术的发展为肿瘤精准治疗提供更多可能，为特异、有效地上调上皮钙黏蛋白表达提供新的途径。本文就上皮钙黏蛋白与RNAa技术近年来的研究进展及小激活RNA（saRNA）上调上皮钙黏蛋白表达的分子机制与生物学意义作一综述。
[摘要] 侵袭与转移是影响恶性肿瘤患者预后最重要的因素之一，也一直是预测肿瘤预后和改善患者生存的热点与难点。上皮钙黏蛋白（E-cadherin）低表达是恶性肿瘤最常见的表型之一，在多种肿瘤的侵袭、转移中发挥重要作用。上调上皮钙黏蛋白表达可以降低恶性肿瘤的侵袭与转移能力，甚至改善肿瘤患者的预后，为肿瘤患者的治疗提供有效措施。近年来，以RNA诱导的基因激活（RNAa）为代表的基因调控技术的发展为肿瘤精准治疗提供更多可能，为特异、有效地上调上皮钙黏蛋白表达提供新的途径。本文就上皮钙黏蛋白与RNAa技术近年来的研究进展及小激活RNA（saRNA）上调上皮钙黏蛋白表达的分子机制与生物学意义作一综述。
2019, 26(1):116-120.
DOI: 10.3872/j.issn.1007-385X.2019.01.019
Abstract:
[摘要] 结直肠癌（colorectal cancer，CRC）是常见的消化系统恶性肿瘤之一，其发病率和病死率处于各类肿瘤的第3 位。环状RNA（circular RNA，circRNA）是一种新型长链非编码RNA（long non-coding RNA，lncRNA），早期被当作剪切过程中的副产物且无生物学意义和功能。近年来研究发现，环状RNA不具有5’末端和3’末端的闭合环状，其结构较其他非编码RNA稳定，能作为RNA的海绵体以及调控剪切和转录，也能影响蛋白质以及核糖体，参与肿瘤的发生、发展和预后，在肿瘤的早期诊断、分型和分期中也具有一定的潜能。随着研究的深入，环状RNA在肿瘤组织的差异表达与CRC的发生、发展以及预后存在密切的关系，为CRC的诊断、治疗及预后提供了可观的发展前景。本文对环状RNA作为CRC生物标志物近年来的研究进展作一综述。
[摘要] 结直肠癌（colorectal cancer，CRC）是常见的消化系统恶性肿瘤之一，其发病率和病死率处于各类肿瘤的第3 位。环状RNA（circular RNA，circRNA）是一种新型长链非编码RNA（long non-coding RNA，lncRNA），早期被当作剪切过程中的副产物且无生物学意义和功能。近年来研究发现，环状RNA不具有5’末端和3’末端的闭合环状，其结构较其他非编码RNA稳定，能作为RNA的海绵体以及调控剪切和转录，也能影响蛋白质以及核糖体，参与肿瘤的发生、发展和预后，在肿瘤的早期诊断、分型和分期中也具有一定的潜能。随着研究的深入，环状RNA在肿瘤组织的差异表达与CRC的发生、发展以及预后存在密切的关系，为CRC的诊断、治疗及预后提供了可观的发展前景。本文对环状RNA作为CRC生物标志物近年来的研究进展作一综述。
2019, 26(1):121-123.
DOI: 10.3872/j.issn.1007-385X.2019.01.020
Abstract:
联系方式
- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.