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Volume 26,Issue 9,2019 Table of Contents
2019, 26(9):933-940.
DOI: 10.3872/j.issn.1007-385X.2019.09.001
Abstract:
[Abstract] Immune-checkpoint blockade (ICB) therapy, especially PD-1/PD-L1 and CTLA-4 blocking antibodies, has achieved surprising curative effects in advanced cancer patients. The US FDA has approved ICB treatment for melanoma, small cell lung carcinoma,kidney carcinoma, and all solid tumors with microsatellite instability. However, with the expansion and deepening of pre-clinical trials and clinical applications in recent years, the limitations of ICB immunotherapy have gradually emerged. For example, even in well-responded tumor types, the effective rate of ICB therapy is only 20%-30%, and there are even cases with tumor progression and metastasis.Therefore, what factors determine or limit the effectiveness of ICB therapy? What kind of patients can benefit from it? Which biomarkers can be used for screening beneficiary patients, evaluating therapeutic outcomes and prognosis? The clarification of above issues will greatly promote the research in this field. In this review, based on the anti-tumor mechanism of ICB, we discuss the recent progress in this field, with an emphasis on the key factors restricting the efficacy of ICB treatment and the current combined therapeutic strategies with ICB, aiming to reveal which biomarkers can be used in the concomitant diagnosis of ICB therapy and the future application perspective of ICB combined therapies, to provide reference for the precision medicine of ICB anti-tumor therapy.
[Abstract] Immune-checkpoint blockade (ICB) therapy, especially PD-1/PD-L1 and CTLA-4 blocking antibodies, has achieved surprising curative effects in advanced cancer patients. The US FDA has approved ICB treatment for melanoma, small cell lung carcinoma,kidney carcinoma, and all solid tumors with microsatellite instability. However, with the expansion and deepening of pre-clinical trials and clinical applications in recent years, the limitations of ICB immunotherapy have gradually emerged. For example, even in well-responded tumor types, the effective rate of ICB therapy is only 20%-30%, and there are even cases with tumor progression and metastasis.Therefore, what factors determine or limit the effectiveness of ICB therapy? What kind of patients can benefit from it? Which biomarkers can be used for screening beneficiary patients, evaluating therapeutic outcomes and prognosis? The clarification of above issues will greatly promote the research in this field. In this review, based on the anti-tumor mechanism of ICB, we discuss the recent progress in this field, with an emphasis on the key factors restricting the efficacy of ICB treatment and the current combined therapeutic strategies with ICB, aiming to reveal which biomarkers can be used in the concomitant diagnosis of ICB therapy and the future application perspective of ICB combined therapies, to provide reference for the precision medicine of ICB anti-tumor therapy.
2019, 26(9):941-947.
DOI: 10.3872/j.issn.1007-385X.2019.09.002
Abstract:
[Abstract] Lymphocyte-activation gene 3 (LAG-3), also known as CD223, is a 498-amino-acid type I transmembrane protein encoded by LAG-3 gene, which consists of extracellular, transmembrane and intracellular regions.LAG-3 negatively regulates T lymphocyte by binding extracellular domain to ligand, thus avoiding autoimmunitycaused by T cell over-activation. Like programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), LAG-3 is an important immune checkpoint in vivo and plays a balanced regulatory role in human immune system.Tumor cells escape the surveillance of the immune system by over-expressing LAG-3 ligand. With the development in research of immune checkpoints, LAG-3 has become a new generation of immunotherapy targets after PD-1 and CTLA-4. This article reviews the structure and function of LAG-3 and the application of its inhibitors in tumor immunotherapy, in order to provide reference for the further study of LAG-3.
[Abstract] Lymphocyte-activation gene 3 (LAG-3), also known as CD223, is a 498-amino-acid type I transmembrane protein encoded by LAG-3 gene, which consists of extracellular, transmembrane and intracellular regions.LAG-3 negatively regulates T lymphocyte by binding extracellular domain to ligand, thus avoiding autoimmunitycaused by T cell over-activation. Like programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), LAG-3 is an important immune checkpoint in vivo and plays a balanced regulatory role in human immune system.Tumor cells escape the surveillance of the immune system by over-expressing LAG-3 ligand. With the development in research of immune checkpoints, LAG-3 has become a new generation of immunotherapy targets after PD-1 and CTLA-4. This article reviews the structure and function of LAG-3 and the application of its inhibitors in tumor immunotherapy, in order to provide reference for the further study of LAG-3.
2019, 26(9):948-954.
DOI: 10.3872/j.issn.1007-385X.2019.09.003
Abstract:
[Abstract] Objective: To investigate the effects and the underlying mechanisms of betulinic acid (BEA) on sensitizing pancreatic cancer cell lines Panc-1 and Miapaca-2 to gefitinib. Methods: After the cell culture was completed, Panc-1 and Miapaca-2 cells were randomly divided into 4 groups: control group (without treatment), BEA group, gefitinib group and BEA combined with gefitinib group, respectively.The sensitization effect of BEA on gefitinib-insensitive pancreatic cancer cells was detected by MTS assay. The treatment effects of combined treatment of gefitinib and BEA against Panc-1 and Miapaca-2 cells were evaluated by colony formation assay. Flow cytometry was used to examine the effect of BEA on apoptosis of Panc-1 cells while WB was applied to determine the effect of BEA onapoptosis-related proteins. Surface plasmon resonance (SPR) experiment was used to detect the direct combination between signal transducer and activator of transcription 3(STAT3) and BEA; Molecular docking and molecular dynamics simulation experiments were adopted topredict the combining mode between STAT3 and BEA. Results: BEA synergistically enhanced the gefitinib-sensitivity of pancreatic cancer Panc-1 and Miapaca-2 cells (P<0.05), and IC50 of gefitinib on two cells were reduced by over 50%. Compared with single treatment, the combined treatment of BEA and gefitinib promoted the apoptosis and up-regulated the expressions of apoptosis-relatedproteins (cleaved-PARP and Bax), but reduced the apoptosis-inhibitory protein Bcl-2 (all P<0.05 or P<0.01). Moreover, the inhibitory effect of BEA on STAT3 activation in Panc-1 cells was in a dose-dependent mannar (P<0.01). BEA stabilizes its binding to STAT3 by forming hydrogen bonds with Lys-591 and Ser-613 of STAT3; in the meanwhile, BEA stabilized inthebinding site of STAT3,there by blocking STAT3 dimerization to enhance the drug sensitivity. Conclusion: Combined use of BEA and gefitinib could significantly inhibit the proliferation and induce apoptosis of Panc-1 and Miapaca-2 cells, which might be mediated by the inhibition of BEA on STST3.
[Abstract] Objective: To investigate the effects and the underlying mechanisms of betulinic acid (BEA) on sensitizing pancreatic cancer cell lines Panc-1 and Miapaca-2 to gefitinib. Methods: After the cell culture was completed, Panc-1 and Miapaca-2 cells were randomly divided into 4 groups: control group (without treatment), BEA group, gefitinib group and BEA combined with gefitinib group, respectively.The sensitization effect of BEA on gefitinib-insensitive pancreatic cancer cells was detected by MTS assay. The treatment effects of combined treatment of gefitinib and BEA against Panc-1 and Miapaca-2 cells were evaluated by colony formation assay. Flow cytometry was used to examine the effect of BEA on apoptosis of Panc-1 cells while WB was applied to determine the effect of BEA onapoptosis-related proteins. Surface plasmon resonance (SPR) experiment was used to detect the direct combination between signal transducer and activator of transcription 3(STAT3) and BEA; Molecular docking and molecular dynamics simulation experiments were adopted topredict the combining mode between STAT3 and BEA. Results: BEA synergistically enhanced the gefitinib-sensitivity of pancreatic cancer Panc-1 and Miapaca-2 cells (P<0.05), and IC50 of gefitinib on two cells were reduced by over 50%. Compared with single treatment, the combined treatment of BEA and gefitinib promoted the apoptosis and up-regulated the expressions of apoptosis-relatedproteins (cleaved-PARP and Bax), but reduced the apoptosis-inhibitory protein Bcl-2 (all P<0.05 or P<0.01). Moreover, the inhibitory effect of BEA on STAT3 activation in Panc-1 cells was in a dose-dependent mannar (P<0.01). BEA stabilizes its binding to STAT3 by forming hydrogen bonds with Lys-591 and Ser-613 of STAT3; in the meanwhile, BEA stabilized inthebinding site of STAT3,there by blocking STAT3 dimerization to enhance the drug sensitivity. Conclusion: Combined use of BEA and gefitinib could significantly inhibit the proliferation and induce apoptosis of Panc-1 and Miapaca-2 cells, which might be mediated by the inhibition of BEA on STST3.
2019, 26(9):955-961.
DOI: 10.3872/j.issn.1007-385X.2019.09.004
Abstract:
[Abstract] Objective: To investigate the effect of miR-135a on the malignant biological behaviors of human laryngeal carcinoma epithelial Hep-2 cells and its sensitivity to oxaliplatin. Methods: Samples of laryngeal carcinoma tissues and para-cancerous tissues were collected from 10 patients who underwent laryngectomy in Nanyang Hospital Affiliated to Zhengzhou University-Nanyang City Center Hospital from January 2018 to June 2018. The expression of miR-135a in laryngeal carcinoma tissues and Hep-2 cells was detected by qPCR. After being transfected with miR-135 inhibitor, cell proliferation viability of Hep-2 cells was measured by CCK-8 assay, cell colony formation ability was detected by colony formation assay, and cell proliferation invasion and migration abilities were detected by Transwell analysis, and the expression of SOX2 protein in Hep-2 cells was detected by WB. Hep-2 cells transfected with miR-135 in-hibitor were further treated with various concentrations (0.5, 1.0, 1.5 and 2.0 μmol/L) of oxaliplatin, and the cell proliferation viability was detected by CCK-8 while cell apoptosis was detected by Annexin-V-FITC/PI double staining flow cytometry. miR-135a inhibitor plasmid, control pcDNA empty vector (SOX2-Con) plasmid, and pcDNA-SOX2 (SOX2-OE) plasmid were transfected into Hep-2 cells to construct the miR-135a inhibitor+SOX2-Con group and miR-135a inhibitor+SOX2-OE group, and the cell viability, cell colony formation ability, cell invasion and migration ability in two groups were detected. Results: Compared with para-cancerous tissues, miR-135a expression in laryngeal cancer tissues was significantly increased (P<0.01). Compared with normal NHP cells, miR-135a expression in Hep-2 cells was significantly increased (P<0.01). miR-135a inhibitor significantly reduced the expression level of miR-135a in Hep-2 cells (P<0.01). miR-135a knockdown significantly reduced the cell proliferation viability, cell colony number, migration, invasion and SOX2 expression in Hep-2 cells (all P <0.01), but significantly enhanced the sensitivity of Hep-2 cells to oxaliplatin (P<0.01).Compared with miR-135a inhibitor+SOX2-Con group, the cell proliferation viability, cell colony number, migration and invasion of Hep-2 cells in miR-135a inhibitor+SOX2-OE group were significantly increased (P<0.01); Meanwhile, the cells of the 2 groups were treated with different concentrations of oxaliplatin, and the results of CCK-8 assay showed that, compared with the miR-135a inhibitor+ SOX2-Con group, the cell proliferation viability of Hep-2 cells in miR-135a inhibitor+SOX2-OE group was significantly increased (P<0.01). Conclusion: miR-135a knockdown inhibits the malignant biological behaviors and promotes oxaliplatin-sensitivity of Hep-2 cells possibly by inhibiting the expression of the transcription factor SOX2.
[Abstract] Objective: To investigate the effect of miR-135a on the malignant biological behaviors of human laryngeal carcinoma epithelial Hep-2 cells and its sensitivity to oxaliplatin. Methods: Samples of laryngeal carcinoma tissues and para-cancerous tissues were collected from 10 patients who underwent laryngectomy in Nanyang Hospital Affiliated to Zhengzhou University-Nanyang City Center Hospital from January 2018 to June 2018. The expression of miR-135a in laryngeal carcinoma tissues and Hep-2 cells was detected by qPCR. After being transfected with miR-135 inhibitor, cell proliferation viability of Hep-2 cells was measured by CCK-8 assay, cell colony formation ability was detected by colony formation assay, and cell proliferation invasion and migration abilities were detected by Transwell analysis, and the expression of SOX2 protein in Hep-2 cells was detected by WB. Hep-2 cells transfected with miR-135 in-hibitor were further treated with various concentrations (0.5, 1.0, 1.5 and 2.0 μmol/L) of oxaliplatin, and the cell proliferation viability was detected by CCK-8 while cell apoptosis was detected by Annexin-V-FITC/PI double staining flow cytometry. miR-135a inhibitor plasmid, control pcDNA empty vector (SOX2-Con) plasmid, and pcDNA-SOX2 (SOX2-OE) plasmid were transfected into Hep-2 cells to construct the miR-135a inhibitor+SOX2-Con group and miR-135a inhibitor+SOX2-OE group, and the cell viability, cell colony formation ability, cell invasion and migration ability in two groups were detected. Results: Compared with para-cancerous tissues, miR-135a expression in laryngeal cancer tissues was significantly increased (P<0.01). Compared with normal NHP cells, miR-135a expression in Hep-2 cells was significantly increased (P<0.01). miR-135a inhibitor significantly reduced the expression level of miR-135a in Hep-2 cells (P<0.01). miR-135a knockdown significantly reduced the cell proliferation viability, cell colony number, migration, invasion and SOX2 expression in Hep-2 cells (all P <0.01), but significantly enhanced the sensitivity of Hep-2 cells to oxaliplatin (P<0.01).Compared with miR-135a inhibitor+SOX2-Con group, the cell proliferation viability, cell colony number, migration and invasion of Hep-2 cells in miR-135a inhibitor+SOX2-OE group were significantly increased (P<0.01); Meanwhile, the cells of the 2 groups were treated with different concentrations of oxaliplatin, and the results of CCK-8 assay showed that, compared with the miR-135a inhibitor+ SOX2-Con group, the cell proliferation viability of Hep-2 cells in miR-135a inhibitor+SOX2-OE group was significantly increased (P<0.01). Conclusion: miR-135a knockdown inhibits the malignant biological behaviors and promotes oxaliplatin-sensitivity of Hep-2 cells possibly by inhibiting the expression of the transcription factor SOX2.
LI Fenga
,
ZHANG Yanb
,
ZHANG Qionga
,
TAO Jina
,
BAI Shutongc
,
SONG Naa
,
SUN Minglinga
,
DUAN Yatingb
2019, 26(9):962-968.
DOI: 10.3872/j.issn.1007-385X.2019.09.005
Abstract:
[Abstract] Objective: To investigate the role of exosome (EXO) transporting Let-7a to regulate MYC gene in the malignant biological behaviors of triple negative breast cancer (TNBC) cell, and to explore the underlying mechanism. Methods: After the completion of cell culture, the gene and protein expressions of MYC and Let-7a in TNBC MDA-MB-231cells were detected by qPCR and WB, respectively.Recombinant lenti-virus vector carrying Let-7a and Crisper / Cas-9 system with MYC knockdown were transfected into MDA-MB-231 cells; MTT assay, Transwell assay and Scratch healing assay were performed to examine the proliferation, invasion and migration of MDA-MB-231 cells. Luciferase activity assay was performed to validate the binding between MYC and Let-7a. EXO was isolated and identified by transmission electron microscopy and WB assay in wild-type and Let-7a over-expressed MDA-MB-231 cells,respectively. After co-incubation of two types of EXO and MDA-MB-231 cells, the effects of Let-7a on biological behaviors of MDAMB-231 cells via EXO were detected by qPCR, WB, MTT and Transwell etc. Results: Let-7a was negatively correlated with MYC in breast cancer tissues and cell lines (all P<0.05); MYC promoted while Let-7a inhibited the proliferation, migration and invasion of breast cancer cells (all P< .01); Let-7a silenced MYC by acting on 3'UTR of MYC gene, thereby reducing the expression of MYC protein (P<0.05); Let-7a was enveloped by EXO and transported to cancer cells, there by inhibiting the proliferation, migration and invasion of MDA-MB-231 cells. Conclusion: EXO some mediated Let-7a silences MYC gene by acting on its 3'UTR region, thus inhibiting the proliferation, migration and invasion of MDA-MB-231 cells.
[Abstract] Objective: To investigate the role of exosome (EXO) transporting Let-7a to regulate MYC gene in the malignant biological behaviors of triple negative breast cancer (TNBC) cell, and to explore the underlying mechanism. Methods: After the completion of cell culture, the gene and protein expressions of MYC and Let-7a in TNBC MDA-MB-231cells were detected by qPCR and WB, respectively.Recombinant lenti-virus vector carrying Let-7a and Crisper / Cas-9 system with MYC knockdown were transfected into MDA-MB-231 cells; MTT assay, Transwell assay and Scratch healing assay were performed to examine the proliferation, invasion and migration of MDA-MB-231 cells. Luciferase activity assay was performed to validate the binding between MYC and Let-7a. EXO was isolated and identified by transmission electron microscopy and WB assay in wild-type and Let-7a over-expressed MDA-MB-231 cells,respectively. After co-incubation of two types of EXO and MDA-MB-231 cells, the effects of Let-7a on biological behaviors of MDAMB-231 cells via EXO were detected by qPCR, WB, MTT and Transwell etc. Results: Let-7a was negatively correlated with MYC in breast cancer tissues and cell lines (all P<0.05); MYC promoted while Let-7a inhibited the proliferation, migration and invasion of breast cancer cells (all P< .01); Let-7a silenced MYC by acting on 3'UTR of MYC gene, thereby reducing the expression of MYC protein (P<0.05); Let-7a was enveloped by EXO and transported to cancer cells, there by inhibiting the proliferation, migration and invasion of MDA-MB-231 cells. Conclusion: EXO some mediated Let-7a silences MYC gene by acting on its 3'UTR region, thus inhibiting the proliferation, migration and invasion of MDA-MB-231 cells.
KONG Lei
,
WANG Junjie
,
WANG Jidong
,
YU Yonghua
,
ZHANG Yingdong
,
CUI Di
,
ZHANG Yong
,
FU Zhixue
2019, 26(9):969-975.
DOI: 10.3872/j.issn.1007-385X.2019.09.006
Abstract:
[Abstract] Objective: To investigate the mechanism of miR-503 modulates radio-resistance of esophageal squamous cell carcinoma (ESCC) by targeting excision-repair cross-complementing 1 (ERCC1). Methods: The expression level of miR-503 in radio-resistant ESCC tumor tissues and KYSE140 and KYSE140R cells was detected by qPCR. The miR-503 mimic, miR-503 inhibitor or si-ERCC1 was transfected into KYSE140 and KYSE140R cells. After radiation treatment, the colony formation assay and CCK-8 assay were used to detect the proliferation of KYSE140R cells. Flow cytometry was used to detect apoptosis of KYSE140R cells. WB was used to detect changes in protein expression of ERCC1. Dual luciferase reporter gene assay was used to validate the targeting relationship between miR-503 and ERCC1. Results: The expression level of miR-503 was down-regulated in radio-resistant tissues and ESCC cell lines (all P<0.01). Over-expression of miR-503 significantly inhibited cell proliferation and promoted apoptosis of KYSE140R cells (all P<0.01). Dual-luciferase reporter assay validated that ERCC1 was a target gene of miR-503, and miR-503 negatively regulated the expression of ERCC1. Over-expression of miR-503 significantly down-regulated the expression of ERCC1 in KYSE140 and KYSE140R cells (both P<0.01), inhibited cell proliferation (both P<0.01), but significantly increased apoptosis rate (all P<0.01); knockdown of ERCC1 exhibited a similar effect, while knockdown of both ERCC1 and miR-503 reversed the above effects. Conclusion: Over-expression of miR-503 up-regulated the radio-sensitivity of KYSE140R cells by targeting ERCC1.
[Abstract] Objective: To investigate the mechanism of miR-503 modulates radio-resistance of esophageal squamous cell carcinoma (ESCC) by targeting excision-repair cross-complementing 1 (ERCC1). Methods: The expression level of miR-503 in radio-resistant ESCC tumor tissues and KYSE140 and KYSE140R cells was detected by qPCR. The miR-503 mimic, miR-503 inhibitor or si-ERCC1 was transfected into KYSE140 and KYSE140R cells. After radiation treatment, the colony formation assay and CCK-8 assay were used to detect the proliferation of KYSE140R cells. Flow cytometry was used to detect apoptosis of KYSE140R cells. WB was used to detect changes in protein expression of ERCC1. Dual luciferase reporter gene assay was used to validate the targeting relationship between miR-503 and ERCC1. Results: The expression level of miR-503 was down-regulated in radio-resistant tissues and ESCC cell lines (all P<0.01). Over-expression of miR-503 significantly inhibited cell proliferation and promoted apoptosis of KYSE140R cells (all P<0.01). Dual-luciferase reporter assay validated that ERCC1 was a target gene of miR-503, and miR-503 negatively regulated the expression of ERCC1. Over-expression of miR-503 significantly down-regulated the expression of ERCC1 in KYSE140 and KYSE140R cells (both P<0.01), inhibited cell proliferation (both P<0.01), but significantly increased apoptosis rate (all P<0.01); knockdown of ERCC1 exhibited a similar effect, while knockdown of both ERCC1 and miR-503 reversed the above effects. Conclusion: Over-expression of miR-503 up-regulated the radio-sensitivity of KYSE140R cells by targeting ERCC1.
2019, 26(9):976-982.
DOI: 10.3872/j.issn.1007-385X.2019.09.007
Abstract:
[Abstract] Objective: To explore the influence of circ_0023642 on the proliferation and metastasis of gastric cancer GMC-803 cells by modulating miR-508-3p/ERBB4 axis. Methods: Cancer tissues and corresponding para-cancer normal tissues from 31 gastric cancer patients, who underwent surgical resection at the Second People's Hospital of Nantong City from May 2015 to March 2018, were collected for this study; meanwhile, gastric cancer cell lines (MGC-803, MKN-45 and MKN-28) were also collected. qPCR was performed to determine the expression levels of circ_0023642 and miR-508-3p in above mentioned tissues and cell lines. WB was applied to measure the expressions of ERBB4, E-cadherin, N-cadherin and Vimentin in MGC-803 cells. CCK-8 assay and Transwell assay were used to evaluate the effects of circ_0023462 and miR-508-3p expression on proliferation, migration and invasion of MGC-803 cells. Dual-luciferase reporter gene was carried out to validate whether miR-508-3p could bind to the 3' UTR of circ_0023642 and ERBB4. Results:Compared with para-cancer tissues or normal gastric mucosal cells, the expression of circ_0023642 was significantly up-regulated in gastric cancer tissues and cells lines, and the expression was highest in MGC-803 cells (P<0.05 or P<0.01). Silencing circ_0023642 dramatically decreased the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of MGC-803 cells (P<0.05 or P<0.01). Both circ_0023642 and ERBB4 could target the binding sites of miR-508-3p. Further experiments confirmed that circ_0023642 promoted the proliferation, migration, invasion and EMT of MGC-803 cells by sponging miR-508-3p (P<0.05 or P<0.01).Conclusion: circ_0023642, by competing ERBB4 to bind with miR-508-3p, promotes the proliferation and metastasis of gastric cancer MGC-803 cells, thus could be used as a marker for the clinical diagnosis of gastric cancer.
[Abstract] Objective: To explore the influence of circ_0023642 on the proliferation and metastasis of gastric cancer GMC-803 cells by modulating miR-508-3p/ERBB4 axis. Methods: Cancer tissues and corresponding para-cancer normal tissues from 31 gastric cancer patients, who underwent surgical resection at the Second People's Hospital of Nantong City from May 2015 to March 2018, were collected for this study; meanwhile, gastric cancer cell lines (MGC-803, MKN-45 and MKN-28) were also collected. qPCR was performed to determine the expression levels of circ_0023642 and miR-508-3p in above mentioned tissues and cell lines. WB was applied to measure the expressions of ERBB4, E-cadherin, N-cadherin and Vimentin in MGC-803 cells. CCK-8 assay and Transwell assay were used to evaluate the effects of circ_0023462 and miR-508-3p expression on proliferation, migration and invasion of MGC-803 cells. Dual-luciferase reporter gene was carried out to validate whether miR-508-3p could bind to the 3' UTR of circ_0023642 and ERBB4. Results:Compared with para-cancer tissues or normal gastric mucosal cells, the expression of circ_0023642 was significantly up-regulated in gastric cancer tissues and cells lines, and the expression was highest in MGC-803 cells (P<0.05 or P<0.01). Silencing circ_0023642 dramatically decreased the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of MGC-803 cells (P<0.05 or P<0.01). Both circ_0023642 and ERBB4 could target the binding sites of miR-508-3p. Further experiments confirmed that circ_0023642 promoted the proliferation, migration, invasion and EMT of MGC-803 cells by sponging miR-508-3p (P<0.05 or P<0.01).Conclusion: circ_0023642, by competing ERBB4 to bind with miR-508-3p, promotes the proliferation and metastasis of gastric cancer MGC-803 cells, thus could be used as a marker for the clinical diagnosis of gastric cancer.
2019, 26(9):983-987.
DOI: 10.3872/j.issn.1007-385X.2019.09.008
Abstract:
[Abstract] Objective: To investigate the effect of serine and arginine rich splicing factor 1 (SRSF1) on proliferation and cell cycle of U87 cells and to explore the underlying mechanisms. Methods: Gene silencing technology was used to knockdown SRSF1, and stable SRSF1 knockdown cell lines with two different targeting sites (shSRSF1-1 and shSRSF1-2) were obtained. Cell counting kit (CCK-8) was performed to detect proliferation of U87, and flow cytometry was performed to detect cell cycle of U87 with or without SRSF1 knockdown. qPCR and WB were used to detect the mRNA and protein expressions of cell division related genes (CEP70 and SMC4). WB was performed to detect the effect of SRSF1 knockdown on phosphorylation of translation initiation protein 4E-BP1. Results: Compared with control group, the protein level of SRSF1 was significantly decreased in U87 cells of shSRSF1-1 and shSRSF1-2 groups (P<0.01), and the proliferation was significantly decreased (P<0.01); in addition,U87 cells were remarkably arrested at G2 phasein shSRSF1-1 and shSRSF1-2 groups (P<0.01). Although the mRNA levels of CEP70 and SMC4 did not change significantly (P>0.05), the protein levels of CEP70 and SMC4 were lower in U87 cells of shSRSF1-1 and shSRSF1-2 groupsas compared with control group (all P<0.01). And the levels of phosphorylated 4E-BP1 were also inhibited in U87 cellsof shSRSF1-1 and shSRSF1-2 groups as compared with control group (P<0.01). Conclusion: SRSF1 knockdown decreased the phosphorylation of 4EBP1 and inhibited the translation process of CEP70 and SMC4, there by resulting in cell cycle retardant in G2 phase and proliferation repression of glioma U87 cells.
[Abstract] Objective: To investigate the effect of serine and arginine rich splicing factor 1 (SRSF1) on proliferation and cell cycle of U87 cells and to explore the underlying mechanisms. Methods: Gene silencing technology was used to knockdown SRSF1, and stable SRSF1 knockdown cell lines with two different targeting sites (shSRSF1-1 and shSRSF1-2) were obtained. Cell counting kit (CCK-8) was performed to detect proliferation of U87, and flow cytometry was performed to detect cell cycle of U87 with or without SRSF1 knockdown. qPCR and WB were used to detect the mRNA and protein expressions of cell division related genes (CEP70 and SMC4). WB was performed to detect the effect of SRSF1 knockdown on phosphorylation of translation initiation protein 4E-BP1. Results: Compared with control group, the protein level of SRSF1 was significantly decreased in U87 cells of shSRSF1-1 and shSRSF1-2 groups (P<0.01), and the proliferation was significantly decreased (P<0.01); in addition,U87 cells were remarkably arrested at G2 phasein shSRSF1-1 and shSRSF1-2 groups (P<0.01). Although the mRNA levels of CEP70 and SMC4 did not change significantly (P>0.05), the protein levels of CEP70 and SMC4 were lower in U87 cells of shSRSF1-1 and shSRSF1-2 groupsas compared with control group (all P<0.01). And the levels of phosphorylated 4E-BP1 were also inhibited in U87 cellsof shSRSF1-1 and shSRSF1-2 groups as compared with control group (P<0.01). Conclusion: SRSF1 knockdown decreased the phosphorylation of 4EBP1 and inhibited the translation process of CEP70 and SMC4, there by resulting in cell cycle retardant in G2 phase and proliferation repression of glioma U87 cells.
2019, 26(9):988-992.
DOI: 10.3872/j.issn.1007-385X.2019.09.009
Abstract:
[Abstract] Objective: To investigate the effect of ginsenoside Rg3 combined with TRAIL on the apoptosis of lung cancer H358 cells and its possible mechanism. Methods: After the completion of cell culture, H538 cells were treated with TRAIL (0, 50, 100, 200 ng/ml ) or Rg3 (0, 25, 50, 100 μmol/L) for 48 h, and the cells were grouped according to different treatments, namely control group, 50 μmol/L Rg3 group, 100 ng/ml TRAIL group and 50 μmol/L Rg3+100 ng/ml TRAIL group. The effects of Rg3 and/or TRAIL on the proliferation of H358 cells were detected by MTT assay. The effects of Rg3 and/or TRAIL on the morphological changes of H358 cells were observed by DAPI staining. Theapoptosis of H358 cells in each group was detected by flow cytometry. The effects of Rg3 and/or TRAIL on the expressions of death receptor 5 (DR5) and caspase-8 in H358 cells were detected by WB. Results: Compared with the other groups, the proliferation of lung cancer H358 cells was significantly inhibited, while the apoptosis was significantly elevated in the 50 μmol/L Rg3+100 ng/ml TRAIL group (P<0.05). After color developing, cells in 50 μmol/L Rg3+100 ng/ml TRAIL group had nuclear shrinkage, chromatin condensation, increased fluorescence intensity, and late morphological changes such as saturation fragmentation.Compared with the other groups, the expression levels of DR5 and caspase-3 ,8 in the cells of 50 μmol/L Rg3+100 ng/ml TRAIL group were significantly increased (P<0.05). Conclusion: Ginsenoside Rg3 combined with TRAIL can synergistically inhibit the proliferation and induce apoptosis of lung cancer H358 cells. The mechanism may be related to the up-regulation of DR5 and caspase-8 by ginsenoside Rg3.
[Abstract] Objective: To investigate the effect of ginsenoside Rg3 combined with TRAIL on the apoptosis of lung cancer H358 cells and its possible mechanism. Methods: After the completion of cell culture, H538 cells were treated with TRAIL (0, 50, 100, 200 ng/ml ) or Rg3 (0, 25, 50, 100 μmol/L) for 48 h, and the cells were grouped according to different treatments, namely control group, 50 μmol/L Rg3 group, 100 ng/ml TRAIL group and 50 μmol/L Rg3+100 ng/ml TRAIL group. The effects of Rg3 and/or TRAIL on the proliferation of H358 cells were detected by MTT assay. The effects of Rg3 and/or TRAIL on the morphological changes of H358 cells were observed by DAPI staining. Theapoptosis of H358 cells in each group was detected by flow cytometry. The effects of Rg3 and/or TRAIL on the expressions of death receptor 5 (DR5) and caspase-8 in H358 cells were detected by WB. Results: Compared with the other groups, the proliferation of lung cancer H358 cells was significantly inhibited, while the apoptosis was significantly elevated in the 50 μmol/L Rg3+100 ng/ml TRAIL group (P<0.05). After color developing, cells in 50 μmol/L Rg3+100 ng/ml TRAIL group had nuclear shrinkage, chromatin condensation, increased fluorescence intensity, and late morphological changes such as saturation fragmentation.Compared with the other groups, the expression levels of DR5 and caspase-3 ,8 in the cells of 50 μmol/L Rg3+100 ng/ml TRAIL group were significantly increased (P<0.05). Conclusion: Ginsenoside Rg3 combined with TRAIL can synergistically inhibit the proliferation and induce apoptosis of lung cancer H358 cells. The mechanism may be related to the up-regulation of DR5 and caspase-8 by ginsenoside Rg3.
ZHANG Conga
,
BAI Hanyua
,
WANG Yaojiea
,
TIAN Guob
,
LIU Dongxin
,
DAI Sulia
,
LIU Qingweic
,
ZHAO Lianmeia
,
SHAN Baoena
2019, 26(9):993-998.
DOI: 10.3872/j.issn.1007-385X.2019.09.010
Abstract:
[Abstract] Objective: To detect the expression of non-coding RNA snord105b in gastric cancer (GC) tissues, sera and cell lines, and its correlation with clinicopathological characteristics of patients with GC as well as its effect on the proliferation of GC cells. Methods:One hundred and twenty pairs of GC tissues and corresponding para-cancerous tissues from patients, who underwent surgery at Department of Surgery, the Fourth Hospital of Hebei Medical University between 2016 and 2017, were collected for this study. The presurgical sera samples from GC patients (n=50) and peripheral venous blood samples from healthy donors (n=30), as well as five gastric cancer cell lines (SGC-7901, AGS, MGC-803, BGC-823, HGC-27) and gastric mucosa normal epithelial GES-1 cells were also obtained. qPCR assay was adopted to detect the expression of snord105b in GC tissues, sera and cell lines. The correlation between snord105b and patients’clinicopathological features was investigated. MTS assay was adopted to detect the effect of snord105b silence or over-expressionon in vitro proliferation of four GC cells. Results: qPCR assay demonstrated that the expression of snord105b in GC tissues, sera and cell lines were significantly higher than that of para-cancerous tissues, sera from healthy donors and GES-1 cells (all P<0.05). Expression level of snord105b was obviously associated with age,tumor size, differentiation and TNM stages of patients (all P<0.05). MTS assay demonstrated that knockdown of snord105b could suppress the proliferation of GC cells (P< 0.05), while forced-expression of snord105b could promote the proliferation of GC cells (P< 0.05). Conclusion: non-coding RNA snord105b aberrantly expressed in GC tissues, sera, and cells, and its expression was obviously correlated with patients’age, tumor size, differentiation and TNM stages. Snord105b could significantly promote the proliferation of GC cells, which may be used as a potential clinical biomaker for early diagnosis and prognosis of GC.
[Abstract] Objective: To detect the expression of non-coding RNA snord105b in gastric cancer (GC) tissues, sera and cell lines, and its correlation with clinicopathological characteristics of patients with GC as well as its effect on the proliferation of GC cells. Methods:One hundred and twenty pairs of GC tissues and corresponding para-cancerous tissues from patients, who underwent surgery at Department of Surgery, the Fourth Hospital of Hebei Medical University between 2016 and 2017, were collected for this study. The presurgical sera samples from GC patients (n=50) and peripheral venous blood samples from healthy donors (n=30), as well as five gastric cancer cell lines (SGC-7901, AGS, MGC-803, BGC-823, HGC-27) and gastric mucosa normal epithelial GES-1 cells were also obtained. qPCR assay was adopted to detect the expression of snord105b in GC tissues, sera and cell lines. The correlation between snord105b and patients’clinicopathological features was investigated. MTS assay was adopted to detect the effect of snord105b silence or over-expressionon in vitro proliferation of four GC cells. Results: qPCR assay demonstrated that the expression of snord105b in GC tissues, sera and cell lines were significantly higher than that of para-cancerous tissues, sera from healthy donors and GES-1 cells (all P<0.05). Expression level of snord105b was obviously associated with age,tumor size, differentiation and TNM stages of patients (all P<0.05). MTS assay demonstrated that knockdown of snord105b could suppress the proliferation of GC cells (P< 0.05), while forced-expression of snord105b could promote the proliferation of GC cells (P< 0.05). Conclusion: non-coding RNA snord105b aberrantly expressed in GC tissues, sera, and cells, and its expression was obviously correlated with patients’age, tumor size, differentiation and TNM stages. Snord105b could significantly promote the proliferation of GC cells, which may be used as a potential clinical biomaker for early diagnosis and prognosis of GC.
2019, 26(9):999-1005.
DOI: 10.3872/j.issn.1007-385X.2019.09.011
Abstract:
[Abstract] Objective: To investigate the role of long chain non-coding RNA00707 (lncRNA 00707) and micro RNA-613 (miR-613) in regulating the proliferation and metastasis of gastric cancer cells and its underlying mechanisms. Methods: Eighty-nine pairs of primary gastric cancer tissues and corresponding prar-cancerous tissues were collected from the Department of Surgical Oncology, Qinghai Provincial People's Hospital during January 2014 and June 2018 for this study. The expressions of lncRNA 00707 and miR-613 in gastric cancer tissues and cells were detected by qPCR. The lncRNA 00707 low expression and over-expression models of MGC-803 and SGC-7901 cells were established; The proliferation of gastric cancer cells was monitored by CCK-8 assay, and Transwell assay was performed to determine the migration and invasion of gastric cancer cells. Dual luciferase gene reporter assay was adopted to validate the relationship between lncRNA 00707 and miR-613. Results: Compared with para-cancerous tissues and normal cell line GES-1, the expression of lncRNA 00707 was significantly up-regulated in cancer tissues and cell lines, and the expression of lncRNA 00707 was positively correlated with WHO stage (all P<0.05). Down-regulation of lncRNA 00707 significantly inhibited the proliferation and migration of SGC-7901 cells, while overexpression of lncRNA00707 exerted the opposite effect (all P<0.05). Compared with negative control group, lncRNA00707 over-expression significantly reduced the luciferase activity of miR-613; in the contrary, the luciferase activity of miR-163 was significantly increased in MGC-803 and SGC-7901 cells with lncRNA 00707 knockdown (all P<0.01). Conclusion: lncRNA 00707 facilitates the proliferation,migration and invasion of gastric cancer cells by inhibiting the function of miR-613, which exerts a protumorigenic effect in gastric cancer.
[Abstract] Objective: To investigate the role of long chain non-coding RNA00707 (lncRNA 00707) and micro RNA-613 (miR-613) in regulating the proliferation and metastasis of gastric cancer cells and its underlying mechanisms. Methods: Eighty-nine pairs of primary gastric cancer tissues and corresponding prar-cancerous tissues were collected from the Department of Surgical Oncology, Qinghai Provincial People's Hospital during January 2014 and June 2018 for this study. The expressions of lncRNA 00707 and miR-613 in gastric cancer tissues and cells were detected by qPCR. The lncRNA 00707 low expression and over-expression models of MGC-803 and SGC-7901 cells were established; The proliferation of gastric cancer cells was monitored by CCK-8 assay, and Transwell assay was performed to determine the migration and invasion of gastric cancer cells. Dual luciferase gene reporter assay was adopted to validate the relationship between lncRNA 00707 and miR-613. Results: Compared with para-cancerous tissues and normal cell line GES-1, the expression of lncRNA 00707 was significantly up-regulated in cancer tissues and cell lines, and the expression of lncRNA 00707 was positively correlated with WHO stage (all P<0.05). Down-regulation of lncRNA 00707 significantly inhibited the proliferation and migration of SGC-7901 cells, while overexpression of lncRNA00707 exerted the opposite effect (all P<0.05). Compared with negative control group, lncRNA00707 over-expression significantly reduced the luciferase activity of miR-613; in the contrary, the luciferase activity of miR-163 was significantly increased in MGC-803 and SGC-7901 cells with lncRNA 00707 knockdown (all P<0.01). Conclusion: lncRNA 00707 facilitates the proliferation,migration and invasion of gastric cancer cells by inhibiting the function of miR-613, which exerts a protumorigenic effect in gastric cancer.
2019, 26(9):1006-1011.
DOI: 10.3872/j.issn.1007-385X.2019.09.012
Abstract:
[Abstract] Objective: To investigate the expression of survivin, fibronectin-1, vascular endothelial growth factor (VEGF) and ezrin in thyroid tumors and their relationship with the pathological characteristics of thyroid tumors. Methods: Ninety patients with thyroid tumors admitted to the third affiliated hospital of Zunyi Medical University and the first hospital during Oct. 2016 and Oct. 2018 were selected as the observation group. Seventy-five patients with normal thyroid confirmed by pathology in the same period were selected as the control group. The protein levels of survivin, fibronectin-1, VEGF and ezrin were detected by immunohistochemical method.Results: The positive rates of survivin, fibronectin-1, VEGF and Ezrin in the control group were 2.67%, l4.00%, 1.33% and 1.33%,which were lower than 97.78%, 96.67%, 93.33% and 95.56% in the observation group, respectively (all P<0.05 or P<0.01). The expressions of survivin, fibronectin-1, VEGF and ezrin were significantly correlated with TNM staging, tumor diameter, extrathyroid invasion and lymphatic metastasis (all P<0.05). Conclusion: Survivin, fibronectin-1, VEGF and ezrin proteins are all involved in the occurrence and development of thyroid tumors. The combined detection of these four indicators is of great significance in the diagnosis, treatment and prognosis of thyroid tumors.
[Abstract] Objective: To investigate the expression of survivin, fibronectin-1, vascular endothelial growth factor (VEGF) and ezrin in thyroid tumors and their relationship with the pathological characteristics of thyroid tumors. Methods: Ninety patients with thyroid tumors admitted to the third affiliated hospital of Zunyi Medical University and the first hospital during Oct. 2016 and Oct. 2018 were selected as the observation group. Seventy-five patients with normal thyroid confirmed by pathology in the same period were selected as the control group. The protein levels of survivin, fibronectin-1, VEGF and ezrin were detected by immunohistochemical method.Results: The positive rates of survivin, fibronectin-1, VEGF and Ezrin in the control group were 2.67%, l4.00%, 1.33% and 1.33%,which were lower than 97.78%, 96.67%, 93.33% and 95.56% in the observation group, respectively (all P<0.05 or P<0.01). The expressions of survivin, fibronectin-1, VEGF and ezrin were significantly correlated with TNM staging, tumor diameter, extrathyroid invasion and lymphatic metastasis (all P<0.05). Conclusion: Survivin, fibronectin-1, VEGF and ezrin proteins are all involved in the occurrence and development of thyroid tumors. The combined detection of these four indicators is of great significance in the diagnosis, treatment and prognosis of thyroid tumors.
2019, 26(9):1012-1018.
DOI: 10.3872/j.issn.1007-385X.2019.09.013
Abstract:
[摘要] 肿瘤的生长需要血管的生成，不同于正常的血管，异常的肿瘤血管通过改变肿瘤微环境来抑制机体的免疫功能，从而使肿瘤发生免疫逃逸。抗血管生成治疗可以使肿瘤血管正常化，进而改善机体的免疫功能。免疫检查点抑制剂通过改变肿瘤微环境，不仅可以提高机体的免疫功能，同时也可以促进肿瘤血管的正常化。本文综述了抗血管生成治疗联合免疫检查点抑制剂治疗恶性肿瘤的理论依据以及相关的临床数据，为恶性肿瘤的治疗提供更多的治疗策略。
[摘要] 肿瘤的生长需要血管的生成，不同于正常的血管，异常的肿瘤血管通过改变肿瘤微环境来抑制机体的免疫功能，从而使肿瘤发生免疫逃逸。抗血管生成治疗可以使肿瘤血管正常化，进而改善机体的免疫功能。免疫检查点抑制剂通过改变肿瘤微环境，不仅可以提高机体的免疫功能，同时也可以促进肿瘤血管的正常化。本文综述了抗血管生成治疗联合免疫检查点抑制剂治疗恶性肿瘤的理论依据以及相关的临床数据，为恶性肿瘤的治疗提供更多的治疗策略。
14 Basic research and clinical transformation of GPC3-targeted immune-targeted therapy for solid tumors
2019, 26(9):1019-1025.
DOI: 10.3872/j.issn.1007-385X.2019.09.014
Abstract:
[摘要] 磷脂酰肌醇蛋白聚糖3(glypican-3，GPC3)是一种锚定在细胞膜上的硫酸乙酰肝素(heparan sulfate，HS)蛋白多糖的家族成员之一。GPC3 激活经典的Wnt/β-连环蛋白(β-catenin)途径在肝癌(hepatocellular carcinoma，HCC)中表现出促癌基因的作用。尽管GPC3 在胎肝中含量丰富，在多种实体肿瘤中高表达，然而在成人正常组织中含量极少。选择靶点是肿瘤免疫治疗的关键。迄今为止靶向GPC3 的MRI、PET和近红外成像已被用于早期HCC检测。针对GPC3+实体瘤也已经开发了各种免疫治疗方案，一种是基于抗GPC3 抗体包括单克隆抗体、多肽疫苗、免疫毒素、双特异性抗体等，一种是靶向GPC3 的CAR-T/NK疗法，其中部分已进入I/II 期临床试验。靶向GPC3 有可能为实体瘤治疗提供新的工具。本文概述GPC3 的结构、功能等生物学特性，介绍基于抗GPC3抗体、CAR-T细胞开发的新策略，提供GPC3免疫疗法靶向实体瘤的证据。
[摘要] 磷脂酰肌醇蛋白聚糖3(glypican-3，GPC3)是一种锚定在细胞膜上的硫酸乙酰肝素(heparan sulfate，HS)蛋白多糖的家族成员之一。GPC3 激活经典的Wnt/β-连环蛋白(β-catenin)途径在肝癌(hepatocellular carcinoma，HCC)中表现出促癌基因的作用。尽管GPC3 在胎肝中含量丰富，在多种实体肿瘤中高表达，然而在成人正常组织中含量极少。选择靶点是肿瘤免疫治疗的关键。迄今为止靶向GPC3 的MRI、PET和近红外成像已被用于早期HCC检测。针对GPC3+实体瘤也已经开发了各种免疫治疗方案，一种是基于抗GPC3 抗体包括单克隆抗体、多肽疫苗、免疫毒素、双特异性抗体等，一种是靶向GPC3 的CAR-T/NK疗法，其中部分已进入I/II 期临床试验。靶向GPC3 有可能为实体瘤治疗提供新的工具。本文概述GPC3 的结构、功能等生物学特性，介绍基于抗GPC3抗体、CAR-T细胞开发的新策略，提供GPC3免疫疗法靶向实体瘤的证据。
2019, 26(9):1026-1034.
DOI: 10.3872/j.issn.1007-385X.2019.09.015
Abstract:
[摘要] 树突状细胞（DC）是体内功能强大的抗原提呈细胞（APC），在机体抗肿瘤免疫反应的过程中起着关键的作用。成熟DC具有激活T淋巴细胞并激活抗肿瘤免疫反应的功能，以DC为基础的抗肿瘤免疫疗法显示出良好的应用前景。免疫检查点疗法是肿瘤免疫治疗的另一强有力手段，以PD-1 和CTLA-4 为代表的免疫检查点分子在肿瘤微环境中起着免疫调节的作用，同时也对DC的成熟和功能起着重要的调控作用。肿瘤微环境中的未成熟DC和免疫检查点分子是肿瘤免疫逃逸的重要因素。因此探究免疫检查点分子对DC成熟及功能的调控机制对于抗肿瘤治疗的研究具有非常重要的意义。本文从DC的视角，阐述了肿瘤微环境中免疫检查点分子对DC成熟及功能的调控机制以及免疫检查点靶向药物联合DC疫苗应用于肿瘤临床实验的最新研究进展。
[摘要] 树突状细胞（DC）是体内功能强大的抗原提呈细胞（APC），在机体抗肿瘤免疫反应的过程中起着关键的作用。成熟DC具有激活T淋巴细胞并激活抗肿瘤免疫反应的功能，以DC为基础的抗肿瘤免疫疗法显示出良好的应用前景。免疫检查点疗法是肿瘤免疫治疗的另一强有力手段，以PD-1 和CTLA-4 为代表的免疫检查点分子在肿瘤微环境中起着免疫调节的作用，同时也对DC的成熟和功能起着重要的调控作用。肿瘤微环境中的未成熟DC和免疫检查点分子是肿瘤免疫逃逸的重要因素。因此探究免疫检查点分子对DC成熟及功能的调控机制对于抗肿瘤治疗的研究具有非常重要的意义。本文从DC的视角，阐述了肿瘤微环境中免疫检查点分子对DC成熟及功能的调控机制以及免疫检查点靶向药物联合DC疫苗应用于肿瘤临床实验的最新研究进展。
2019, 26(9):1035-1041.
DOI: 10.3872/j.issn.1007-385X.2019.09.016
Abstract:
[摘要] 表皮生长因子受体(EGFR)突变型非小细胞肺癌（NSCLC）容易出现脑转移，EGFR 酪氨酸激酶抑制剂(TKI)(EGFRTKI)则为此类患者的治疗带来极大获益。但第一、二代靶向药物脑穿透力弱和最终获得性耐药，导致颅内疾病进展，是脑转移治疗的主要挑战。近年来，随着第三代EGFR-TKI、免疫检查点抑制剂（ICB）的深入研发，EGFR突变型NSCLC脑转移的治疗发生了极大变化。本文将回顾脑转移的靶向治疗及免疫治疗方面取得的进展，并对目前存在的问题及未来发展方向进行探讨。
[摘要] 表皮生长因子受体(EGFR)突变型非小细胞肺癌（NSCLC）容易出现脑转移，EGFR 酪氨酸激酶抑制剂(TKI)(EGFRTKI)则为此类患者的治疗带来极大获益。但第一、二代靶向药物脑穿透力弱和最终获得性耐药，导致颅内疾病进展，是脑转移治疗的主要挑战。近年来，随着第三代EGFR-TKI、免疫检查点抑制剂（ICB）的深入研发，EGFR突变型NSCLC脑转移的治疗发生了极大变化。本文将回顾脑转移的靶向治疗及免疫治疗方面取得的进展，并对目前存在的问题及未来发展方向进行探讨。
2019, 26(9):1042-1048.
DOI: 10.3872/j.issn.1007-385X.2019.09.017
Abstract:
［摘要］ 可变剪接指从单个基因产生多种mRNA同种型，是转录后调控的重要方式之一。可变剪接不仅影响人体正常生长发育过程，而且在包括癌症在内的多种疾病发生发展中扮演重要角色。癌组织的剪接变化通常是全局的而不是基因特异性的，异常的剪接模式控制癌症的主要特征。遗传、表观遗传、剪接因子网络差异表达及选择性转录起始或终止等多种途径巩固了特定促癌或抑癌同种型的优势表达，进而影响癌症进程。此外，近年来研究，证明呈组织或阶段特异性表达的剪接同种型有作为癌症生物标志物及治疗靶标的潜能。本文通过全局剪接变化影响肿瘤进展、可变剪接影响癌症进展的途径及可变剪接提示癌症监控和治疗新策略3 个方面进行综述。
［摘要］ 可变剪接指从单个基因产生多种mRNA同种型，是转录后调控的重要方式之一。可变剪接不仅影响人体正常生长发育过程，而且在包括癌症在内的多种疾病发生发展中扮演重要角色。癌组织的剪接变化通常是全局的而不是基因特异性的，异常的剪接模式控制癌症的主要特征。遗传、表观遗传、剪接因子网络差异表达及选择性转录起始或终止等多种途径巩固了特定促癌或抑癌同种型的优势表达，进而影响癌症进程。此外，近年来研究，证明呈组织或阶段特异性表达的剪接同种型有作为癌症生物标志物及治疗靶标的潜能。本文通过全局剪接变化影响肿瘤进展、可变剪接影响癌症进展的途径及可变剪接提示癌症监控和治疗新策略3 个方面进行综述。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.