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Volume 22,Issue 5,2015 Table of Contents
2015, 22(5):413-419.
DOI: 10.3872/j.issn.1007-385X.2015.05.001
Abstract:
In recent years, the breakthroughs of targeting agents for tumor therapies and personalized molecular diagnosis have prompted cancer treatment into the era of precision medicine. However, established assessment for solid tumors treatment such as the WHO or RECIST evaluation criteria could not reflex precisely the efficacy of the targeted therapeutics and the survival benefits they provided to patients. Therefore, it is extremely urgent to explore and establish a new response assessment criteria for targeted tumor therapeutics. This article reviewed the history of the efficacy assessment criteria for anti-tumor drugs and current opinions on the subject. I also introduced the evolution and development of evaluation criteria for various targeted therapeutics toward different tumors, and focused on the new criteria for evaluating immuno-related therapeutics. Finally, I discussed in detail the proposed evaluation criteria, its definition, guiding principle and clinical application. It is conceivable that the continuous improvements in evaluating targeted therapeutics for solid tumors will bring transformation to personalized cancer treatment.
In recent years, the breakthroughs of targeting agents for tumor therapies and personalized molecular diagnosis have prompted cancer treatment into the era of precision medicine. However, established assessment for solid tumors treatment such as the WHO or RECIST evaluation criteria could not reflex precisely the efficacy of the targeted therapeutics and the survival benefits they provided to patients. Therefore, it is extremely urgent to explore and establish a new response assessment criteria for targeted tumor therapeutics. This article reviewed the history of the efficacy assessment criteria for anti-tumor drugs and current opinions on the subject. I also introduced the evolution and development of evaluation criteria for various targeted therapeutics toward different tumors, and focused on the new criteria for evaluating immuno-related therapeutics. Finally, I discussed in detail the proposed evaluation criteria, its definition, guiding principle and clinical application. It is conceivable that the continuous improvements in evaluating targeted therapeutics for solid tumors will bring transformation to personalized cancer treatment.
2015, 22(5):558-565.
DOI: 10.3872/j.issn.1007-385X.2015.05.002
Abstract:
Objective:To investigate roles for focal adhesion kinase (FAK) in the regulation of proliferation, migration, apoptosis, and angiogenesis of human vascular endothelial cells. Methods: Human umbilical vein endothelial cells (HUVECs) were transfected with FAK siRNA or treated with TAE226. FAK mRNA abundance in siRNA-transfected or TAE226-treated HUVECs and malignant pleural mesothelioma cell lines Y-MESO14 and NCI-H290 was determined by Real-time PCR. FAK protein was assessed by Western blotting, cell viability by MTT, apoptosis by flow cytometry, migration by Transwell assay, and capillary structure formation by matrigel-based tube formation assay in control, TAE-treated and FAK siRNA-transfected HUVECs. Results: FAK mRNA was significantly more abundant in HUVECs than in both Y-MESO-14 and NCI-H290 cell lines(P<0.05). rhVEGF treatment significantly increased FAK and pFAK protein levels of HUVECs (P<0.05). FAK siRNA effectively silenced FAK gene expression in the presence of rhVEGF in HUVECs (P<0.01). TAE226 at all concentrations used and FAK mRNA significantly inhibited proliferation, migration, and apoptosis of HUVECs (P<0.01). While rhVEGF significantly promoted angiogenesis, TAE226 and FAK siRNA significantly inhibited capillary structure formation in HUVECs (P<0.01). Conclusion: FAK siRNA plays important regulatory roles in vascular endothelial cell proliferation, migration, apoptosis, and capillary structure formation, and thus offer a novel target for angiogenesis-based cancer therapy.
Objective:To investigate roles for focal adhesion kinase (FAK) in the regulation of proliferation, migration, apoptosis, and angiogenesis of human vascular endothelial cells. Methods: Human umbilical vein endothelial cells (HUVECs) were transfected with FAK siRNA or treated with TAE226. FAK mRNA abundance in siRNA-transfected or TAE226-treated HUVECs and malignant pleural mesothelioma cell lines Y-MESO14 and NCI-H290 was determined by Real-time PCR. FAK protein was assessed by Western blotting, cell viability by MTT, apoptosis by flow cytometry, migration by Transwell assay, and capillary structure formation by matrigel-based tube formation assay in control, TAE-treated and FAK siRNA-transfected HUVECs. Results: FAK mRNA was significantly more abundant in HUVECs than in both Y-MESO-14 and NCI-H290 cell lines(P<0.05). rhVEGF treatment significantly increased FAK and pFAK protein levels of HUVECs (P<0.05). FAK siRNA effectively silenced FAK gene expression in the presence of rhVEGF in HUVECs (P<0.01). TAE226 at all concentrations used and FAK mRNA significantly inhibited proliferation, migration, and apoptosis of HUVECs (P<0.01). While rhVEGF significantly promoted angiogenesis, TAE226 and FAK siRNA significantly inhibited capillary structure formation in HUVECs (P<0.01). Conclusion: FAK siRNA plays important regulatory roles in vascular endothelial cell proliferation, migration, apoptosis, and capillary structure formation, and thus offer a novel target for angiogenesis-based cancer therapy.
2015, 22(5):566-572.
DOI: 10.3872/j.issn.1007-385X.2015.05.003
Abstract:
Objective:To investigate the effect of melanoma antigen gene-A11 (MAGE-A11) on estrogen receptor (ER)-mediated cell proliferation of breast cancer MCF-7 cells.Methods:RT-PCR and Western blotting confirmed ER-positive MCF-7 cells were transfected with pCMV-AC-MAGE-A11-GFP and pCMV-AC-GFP respectively. Wild-type and transfected MCF-7 cells were treated with 17β-estradiol (17β-E). After treatment, estrogen-responsive finger protein (Efp) was assessed by RT-PCR and Western blotting, protein interaction between MAGE-A11 and ER by immunoprecipitation, cell viability by MTT assay and colony-forming capacity by colony formation assay.Results: Treatment with 17β-E significantly increased Efp mRNA and protein proteins in both wild-type and transfected MCF-7 cells (P<0.05). Evident interactions between MAGE-A11 and ER were detected in both wild-type and transfected MCF-7 cells. Estrogen treatment also significantly increased cell viability and colony formation in wild-type and MAGE-A11-transfected MCF-7 cells (P<005). Conclusion: In ER-positive MCF-7 cells, MAGE-A11 is capable of enhancing the expression of the ER target gene Efp and cell proliferation through direct interaction with ER. This finding suggests that MAGE-A11 may offer a potential therapeutic target for resistant ER-positive breast cancer.
Objective:To investigate the effect of melanoma antigen gene-A11 (MAGE-A11) on estrogen receptor (ER)-mediated cell proliferation of breast cancer MCF-7 cells.Methods:RT-PCR and Western blotting confirmed ER-positive MCF-7 cells were transfected with pCMV-AC-MAGE-A11-GFP and pCMV-AC-GFP respectively. Wild-type and transfected MCF-7 cells were treated with 17β-estradiol (17β-E). After treatment, estrogen-responsive finger protein (Efp) was assessed by RT-PCR and Western blotting, protein interaction between MAGE-A11 and ER by immunoprecipitation, cell viability by MTT assay and colony-forming capacity by colony formation assay.Results: Treatment with 17β-E significantly increased Efp mRNA and protein proteins in both wild-type and transfected MCF-7 cells (P<0.05). Evident interactions between MAGE-A11 and ER were detected in both wild-type and transfected MCF-7 cells. Estrogen treatment also significantly increased cell viability and colony formation in wild-type and MAGE-A11-transfected MCF-7 cells (P<005). Conclusion: In ER-positive MCF-7 cells, MAGE-A11 is capable of enhancing the expression of the ER target gene Efp and cell proliferation through direct interaction with ER. This finding suggests that MAGE-A11 may offer a potential therapeutic target for resistant ER-positive breast cancer.
2015, 22(5):573-577.
DOI: 10.3872/j.issn.1007-385X.2015.05.004
Abstract:
Objective:To investigate if and how chromosome region maintenance 1 (CRM1) inhibitor S109 affects the proliferation of human lung cancer cells in vitro. Methods: Non-small cell lung cancer (NSLC) H197 and H1650 cells were treated with S109 at 0.04, 0.2, 1, 5, 25, 50 μmol/L. After treatment for 72 h, cell viability, proliferation and colony formation were examined by CCK-8, EdU and clonogenic assays, respectively. Cell cycle arrest and subcellular localization of RanBP1 were analyzed by flow cytometry and fluorescence microscopy respectively. CRM1 and Cyclin D1 protein contents were assessed by Western blotting. Results: S109 inhibited the growth of H1975 and H1650 cells in a dose-dependent manner and the IC50 in these two cell lines was 1.4 and 1.2 μmol/L, respectively. Compared with control, S109 reduced H1975 cell proliferation by （51.3±2.8）% at 2 μmol/L and by (23.2±2.1)% at 4 μmol/L (P<0.05) and reduced colony formation by (43.6±3.2)% at 2 μmol/L and by (26.8±2.8)% at 4 μmol/L (P<0.05). S109 treatment increased the G1 fraction from 50.5% to 74.9% in H1975 cells (P<0.05), specifically inhibited nuclear export of RanBP1 and induced degradation of CRM1. Conclusion: S109 is able to suppress the proliferation and induces cell cycle arrest of NSLC cells, at least partially, via inhibiting nuclear export of RanBP1.
Objective:To investigate if and how chromosome region maintenance 1 (CRM1) inhibitor S109 affects the proliferation of human lung cancer cells in vitro. Methods: Non-small cell lung cancer (NSLC) H197 and H1650 cells were treated with S109 at 0.04, 0.2, 1, 5, 25, 50 μmol/L. After treatment for 72 h, cell viability, proliferation and colony formation were examined by CCK-8, EdU and clonogenic assays, respectively. Cell cycle arrest and subcellular localization of RanBP1 were analyzed by flow cytometry and fluorescence microscopy respectively. CRM1 and Cyclin D1 protein contents were assessed by Western blotting. Results: S109 inhibited the growth of H1975 and H1650 cells in a dose-dependent manner and the IC50 in these two cell lines was 1.4 and 1.2 μmol/L, respectively. Compared with control, S109 reduced H1975 cell proliferation by （51.3±2.8）% at 2 μmol/L and by (23.2±2.1)% at 4 μmol/L (P<0.05) and reduced colony formation by (43.6±3.2)% at 2 μmol/L and by (26.8±2.8)% at 4 μmol/L (P<0.05). S109 treatment increased the G1 fraction from 50.5% to 74.9% in H1975 cells (P<0.05), specifically inhibited nuclear export of RanBP1 and induced degradation of CRM1. Conclusion: S109 is able to suppress the proliferation and induces cell cycle arrest of NSLC cells, at least partially, via inhibiting nuclear export of RanBP1.
2015, 22(5):578-583.
DOI: 10.3872/j.issn.1007-385X.2015.05.005
Abstract:
Objective:The aim of this study was to investigate the possible mechanisms underlying the effect of miR-145 on the proliferation in nasopharyngeal carcinoma (NPC) cells.Methods: Protein and mRNA levels of miR-145 and c-Myc mRNA and protein were determined in 3 NPC cell lines (CNE-1, CNE-2 and CNE-2Z) and one immortalised nasopharyngeal epithelial cell line (NP69) by Western blotting and Real-time PCR respectively. To evaluate the effect of miR-145 on c-Myc transcript and proliferation in NPCs, CNE-1 cells were transfected with microRNA mimics and small interfering RNA using LipofectamineTM 2000. Transfectants were subjected to proliferative activity assessment using Cell Counting Kit-8 assay and cell cycle arrest analysis by propyliodide organism (PI) staining.Results: The expression of miR-145 in was down regulated but c-Myc expression was up-regulated in all NPC cell lines studied as compared with NP69 cells. After Transfection of miR-145 mimics resulted in significant growth-suppression(P<0.01) and a significant increase in cell cycle arrest in G1 phase (P<0.05). Knock down of c-Myc significantly inhibited CNE-1 cell proliferation (P<001), and resulted in increased accumulation of CNE-1 cells in G1 phase (P<0.05). Furthermore, miR-145 inhibited c-Myc expression in CNE-1 cells by directly affecting the 3’ untranslated region (3' UTR) of the c-Myc gene. Conclusion: miR-145 may inhibit NPC cell proliferation, possibly through a direct effect on the c-Myc 3’ UTR region. This observation may have significant implications in the diagnose and treatment of NPC.
Objective:The aim of this study was to investigate the possible mechanisms underlying the effect of miR-145 on the proliferation in nasopharyngeal carcinoma (NPC) cells.Methods: Protein and mRNA levels of miR-145 and c-Myc mRNA and protein were determined in 3 NPC cell lines (CNE-1, CNE-2 and CNE-2Z) and one immortalised nasopharyngeal epithelial cell line (NP69) by Western blotting and Real-time PCR respectively. To evaluate the effect of miR-145 on c-Myc transcript and proliferation in NPCs, CNE-1 cells were transfected with microRNA mimics and small interfering RNA using LipofectamineTM 2000. Transfectants were subjected to proliferative activity assessment using Cell Counting Kit-8 assay and cell cycle arrest analysis by propyliodide organism (PI) staining.Results: The expression of miR-145 in was down regulated but c-Myc expression was up-regulated in all NPC cell lines studied as compared with NP69 cells. After Transfection of miR-145 mimics resulted in significant growth-suppression(P<0.01) and a significant increase in cell cycle arrest in G1 phase (P<0.05). Knock down of c-Myc significantly inhibited CNE-1 cell proliferation (P<001), and resulted in increased accumulation of CNE-1 cells in G1 phase (P<0.05). Furthermore, miR-145 inhibited c-Myc expression in CNE-1 cells by directly affecting the 3’ untranslated region (3' UTR) of the c-Myc gene. Conclusion: miR-145 may inhibit NPC cell proliferation, possibly through a direct effect on the c-Myc 3’ UTR region. This observation may have significant implications in the diagnose and treatment of NPC.
2015, 22(5):584-589.
DOI: 10.3872/j.issn.1007-385X.2015.05.006
Abstract:
Objective:To investigate the expression of miRNA-101(miR-101) in lung cancer specimens and lung cancer cell lines as well as its impact on the proliferative, colony-forming and tumorigenic capacities of human lung cancer cells. Methods: Cyclooxygenase-2 (COX-2) and miR-101 mRNA and protein levels were assessed, respectively, by RT-PCR and Western blotting in clinical specimens (lung cancer tissue and the surrounding normal tissue) collected from 10 patients, human lung cancer cell lines A549 and NCI-H226, and human diploid MRC-5 fibroblasts. A549 and NCI-H226 cells were transfected with miR-NC and miR-101 respectively. The transfectants were assessed for COX-2 protein content by Western blotting, proliferative activity by CCK-8, colony-forming capacity by colony formation experiments, and tumorigenic capacity in vivo by xenograft experiments in nude BAL B/C mice. Results: COX-2 protein content was significantly higher in cancer tissue specimens than in both para-cancer tissue specimens (t=20.03, P=0.001) and human diploid MRC-5 fibroblasts (t=14.59, P=0.012). In contrast, the expression of miR-101 was down-regulated in lung cancer tissue specimens and cell lines as compared with para-cancer tissue specimens (t=18.33, P=0.002) and human diploid MRC-5 fibroblasts (t=28.95, P=0.000). Overexpression of miR101 resulted in a significant decreases in COX-2 expression (t=26.03, P=0.000) and proliferative (F=5.783, P=0.017) and colony-forming (Dunnett t test I-J=－0.28, P=0.035) capacities of A549 and NCI-H226 lung cancer cells in vitro. A549 cells overexpressing miR101 had a remarkably reduced tumorigenic capacity in nude BALB/c mice in vivo (F=14.8, P=0.003). Conclusion:MicroR-101 is downregulated whereas COX-2 is up-regulated in lung cancer. Over-expression of miR-101 results in significant inhibition of proliferation, colony formation and tumorigenesis of lung cancer cells through down-regulation of COX-2 and thus may offer a potential therapeutic option for lung cancer.
Objective:To investigate the expression of miRNA-101(miR-101) in lung cancer specimens and lung cancer cell lines as well as its impact on the proliferative, colony-forming and tumorigenic capacities of human lung cancer cells. Methods: Cyclooxygenase-2 (COX-2) and miR-101 mRNA and protein levels were assessed, respectively, by RT-PCR and Western blotting in clinical specimens (lung cancer tissue and the surrounding normal tissue) collected from 10 patients, human lung cancer cell lines A549 and NCI-H226, and human diploid MRC-5 fibroblasts. A549 and NCI-H226 cells were transfected with miR-NC and miR-101 respectively. The transfectants were assessed for COX-2 protein content by Western blotting, proliferative activity by CCK-8, colony-forming capacity by colony formation experiments, and tumorigenic capacity in vivo by xenograft experiments in nude BAL B/C mice. Results: COX-2 protein content was significantly higher in cancer tissue specimens than in both para-cancer tissue specimens (t=20.03, P=0.001) and human diploid MRC-5 fibroblasts (t=14.59, P=0.012). In contrast, the expression of miR-101 was down-regulated in lung cancer tissue specimens and cell lines as compared with para-cancer tissue specimens (t=18.33, P=0.002) and human diploid MRC-5 fibroblasts (t=28.95, P=0.000). Overexpression of miR101 resulted in a significant decreases in COX-2 expression (t=26.03, P=0.000) and proliferative (F=5.783, P=0.017) and colony-forming (Dunnett t test I-J=－0.28, P=0.035) capacities of A549 and NCI-H226 lung cancer cells in vitro. A549 cells overexpressing miR101 had a remarkably reduced tumorigenic capacity in nude BALB/c mice in vivo (F=14.8, P=0.003). Conclusion:MicroR-101 is downregulated whereas COX-2 is up-regulated in lung cancer. Over-expression of miR-101 results in significant inhibition of proliferation, colony formation and tumorigenesis of lung cancer cells through down-regulation of COX-2 and thus may offer a potential therapeutic option for lung cancer.
2015, 22(5):590-596.
DOI: 10.3872/j.issn.1007-385X.2015.05.007
Abstract:
Objective:To evaluate the cytotoxic effects of the cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) loaded with alpha-fetoprotein (AFP) in different approaches. Methods:Peripheral blood monocytes were isolated from healthy donors. The adhesive precursor DCs were cultured in the presence of rhGM-CSF and rhIL-4 for 6 d. The cytokine-treated DCs were then left untreated as a control, infected with recombinant AFP-carrying adeno-associated viral vector (rAAV/AFP), or loaded respectively with AFP peptide, HepG2 cell lysate, and HepG2-derived exosomes (T-exo). Changes in CD83, CD86, ICAM-1,CD58 And CD 40 in DCs before and after AFP loading were assessed by Western botting Autologous T cells were co-cultured with the various AFP-loaded DCs loaded at a ratio of 10∶1 for 48 h. The proliferative activity and cytotoxicity against HepG2 cells of DC-induced T cells were assessed by flow cytometry.Results: AFP antigen induced maturation of DCs. The expression of surface molecules CD83,CD86, ICAM-1,CD58 and CD40 in DCs infected with the rAAV/AFP vector was significantly increased compared with the nave DCs (P<0.05). AFP-loaded DCs increased the proliferation of T cells. The cytotoxic activity against HepG2 cells was (41.40±2.87)%, (44.9±4.12)%, (28.42±3.29)%, and (24.28±1.79)% for T cells after induction by T-exo-loaded DCs, rAAV/AFP-infected DCs, AFP peptide-loaded DCs and HepG2 lysate-treated DCs respectively (P<0.05). Conclusions：AFP and T-exsome are capable of increasing the proliferative activity of DCs and the cytotoxic activity of CTL against HepG2 cells. Our finding may have significant implications in the development of DC-based vaccines for liver cancer.
Objective:To evaluate the cytotoxic effects of the cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) loaded with alpha-fetoprotein (AFP) in different approaches. Methods:Peripheral blood monocytes were isolated from healthy donors. The adhesive precursor DCs were cultured in the presence of rhGM-CSF and rhIL-4 for 6 d. The cytokine-treated DCs were then left untreated as a control, infected with recombinant AFP-carrying adeno-associated viral vector (rAAV/AFP), or loaded respectively with AFP peptide, HepG2 cell lysate, and HepG2-derived exosomes (T-exo). Changes in CD83, CD86, ICAM-1,CD58 And CD 40 in DCs before and after AFP loading were assessed by Western botting Autologous T cells were co-cultured with the various AFP-loaded DCs loaded at a ratio of 10∶1 for 48 h. The proliferative activity and cytotoxicity against HepG2 cells of DC-induced T cells were assessed by flow cytometry.Results: AFP antigen induced maturation of DCs. The expression of surface molecules CD83,CD86, ICAM-1,CD58 and CD40 in DCs infected with the rAAV/AFP vector was significantly increased compared with the nave DCs (P<0.05). AFP-loaded DCs increased the proliferation of T cells. The cytotoxic activity against HepG2 cells was (41.40±2.87)%, (44.9±4.12)%, (28.42±3.29)%, and (24.28±1.79)% for T cells after induction by T-exo-loaded DCs, rAAV/AFP-infected DCs, AFP peptide-loaded DCs and HepG2 lysate-treated DCs respectively (P<0.05). Conclusions：AFP and T-exsome are capable of increasing the proliferative activity of DCs and the cytotoxic activity of CTL against HepG2 cells. Our finding may have significant implications in the development of DC-based vaccines for liver cancer.
2015, 22(5):597-602.
DOI: 10.3872/j.issn.1007-385X.2015.05.008
Abstract:
Objective:To study whether and how Th1-type cytokine IFN-γ and Th2-type cytokine IL-4 regulating tumorigenicity and adhesion of human breast cancer cells. Methods: Human breast cancer MCF-7 cells were treated with rhIFN-γ at 100 ng/ml or rhIL-4 at 10 ng/ml. At 96 hours after treatment, VEGF mRNA and protein levels were determined by semi-quantitative RT-PCR and Western blotting analysis, tumorigenicity by double layer soft-agar colony formation test and cell adhesion by matrigel adhesion assay respectively.Results: IFN-γ inhibited while IL-4 enhanced significantly tumorigenic and adhesive activities of MCF-7 cells. Compared with the control, rhIFN-γ significantly decreased mRNA and protein levels of VEGF and MMP-9 and down-regulated the Raf/MEK/ERK signaling pathway. On the contrary, rhIL-4 significantly increased mRNA and protein levels of VEGF, MMP-2 and MMP-9 and up-regulated the PI3K/AKT and Raf/MEK/ERK signaling pathways. Conclusion：IFN-γ and IL-4 may regulate human breast cancer cell adhesion and tumorigenicity, at least partially, through regulation of PI3K/AKT and Raf/MEK/ERK signal pathways.
Objective:To study whether and how Th1-type cytokine IFN-γ and Th2-type cytokine IL-4 regulating tumorigenicity and adhesion of human breast cancer cells. Methods: Human breast cancer MCF-7 cells were treated with rhIFN-γ at 100 ng/ml or rhIL-4 at 10 ng/ml. At 96 hours after treatment, VEGF mRNA and protein levels were determined by semi-quantitative RT-PCR and Western blotting analysis, tumorigenicity by double layer soft-agar colony formation test and cell adhesion by matrigel adhesion assay respectively.Results: IFN-γ inhibited while IL-4 enhanced significantly tumorigenic and adhesive activities of MCF-7 cells. Compared with the control, rhIFN-γ significantly decreased mRNA and protein levels of VEGF and MMP-9 and down-regulated the Raf/MEK/ERK signaling pathway. On the contrary, rhIL-4 significantly increased mRNA and protein levels of VEGF, MMP-2 and MMP-9 and up-regulated the PI3K/AKT and Raf/MEK/ERK signaling pathways. Conclusion：IFN-γ and IL-4 may regulate human breast cancer cell adhesion and tumorigenicity, at least partially, through regulation of PI3K/AKT and Raf/MEK/ERK signal pathways.
2015, 22(5):603-606.
DOI: 10.3872/j.issn.1007-385X.2015.05.009
Abstract:
Objective:To design and construct a vector expressing a human epidermal growth factor receptor variant Ⅲ (EGFRvⅢ)-specific third generation chimeric antigen receptor (CAR) for potential use in adoptive immunotherapy of cancer. Methods:An anti-EGFRvⅢ CAR, referred to as EGFRvⅢ/3CAR, comprising the variable fragment ( EGFRvⅢscFv), hinge region/transmembrane region, CD28 & CD137 intracellular signal region, and CD3ζ chain of a monoclonal antibody against human EGFvⅢ was generated and inserted in frame into pCDH-CMV-MCS-EF-copGFP EcoR1 and BamH1 sites. The integrity of the resultant recombinant vector was confirmed by restriction enzyme mapping and sequence analysis. For further functional integrity verification, the recombinant vector was transfected into 293T cells and the fusion protein expression was assessed by Western blotting. Results:DNA sequencing and restriction enzyme mapping demonstrated the sequence of EGFRvⅢ/3CAR was corret. Western blotting detected EGFRvⅢ/3CAR protein at approximately 58 kD in 293T cells transfected with the EGFRvⅢ/3CAR construct. Conclusion: We have successfully designed and constructed a recombinant vector expressing a human EGFRvⅢ-specific third generation CAR, which may prove usefull in further studies on CAR-based cancer immunotherapy.
Objective:To design and construct a vector expressing a human epidermal growth factor receptor variant Ⅲ (EGFRvⅢ)-specific third generation chimeric antigen receptor (CAR) for potential use in adoptive immunotherapy of cancer. Methods:An anti-EGFRvⅢ CAR, referred to as EGFRvⅢ/3CAR, comprising the variable fragment ( EGFRvⅢscFv), hinge region/transmembrane region, CD28 & CD137 intracellular signal region, and CD3ζ chain of a monoclonal antibody against human EGFvⅢ was generated and inserted in frame into pCDH-CMV-MCS-EF-copGFP EcoR1 and BamH1 sites. The integrity of the resultant recombinant vector was confirmed by restriction enzyme mapping and sequence analysis. For further functional integrity verification, the recombinant vector was transfected into 293T cells and the fusion protein expression was assessed by Western blotting. Results:DNA sequencing and restriction enzyme mapping demonstrated the sequence of EGFRvⅢ/3CAR was corret. Western blotting detected EGFRvⅢ/3CAR protein at approximately 58 kD in 293T cells transfected with the EGFRvⅢ/3CAR construct. Conclusion: We have successfully designed and constructed a recombinant vector expressing a human EGFRvⅢ-specific third generation CAR, which may prove usefull in further studies on CAR-based cancer immunotherapy.
2015, 22(5):607-611.
DOI: 10.3872/j.issn.1007-385X.2015.05.010
Abstract:
Objective:The purpose of this study was to evaluate the effect of cyclosporine A (CsA) plus cisplatin (DDP) on lung cancer growth in vivo. Methods: Lewis lung carcinoma 3LL cells (100 μl of 5×106/ml) were injected subcutaneously into female nude (C57BL/6) mice. Two days after xenograft injection, animals were randomized to four treatment groups (n=10): Control, cisplatin (DDP), cyclosporine A (CsA), and DDP + CsA. DDP and CsA were intraperitoneally administered initially at 2 mg/kg, q3d for 3 times and at 5 mg/kg, q2d for 3 times, respectively, and once a week afterwards. Tumor size was examined every three days. The weight of tumor mass was calculated. Animals were sacrificed 35 days after xenograft implantation. Tumors were collected and weighed. Tumor tissue specimens were subjected to H-E staining immunohistochemical assessment of Ki-67 expression. Results:Compared with the control, all drug treatments significantly reduced tumor size (P<0.01), tumor weight (P<0.05), cell density and mitotic count (P<005)and Ki-67 expression (P<0.05), but DDP together with CsA was significantly more effective than DDP and CsA each alone (P<0.05). Conclusion:The combined use of CsA and DDP may increase the sensitivity of lung carcinoma cells to DDP and thus have a synergistic effect against lung cancer.
Objective:The purpose of this study was to evaluate the effect of cyclosporine A (CsA) plus cisplatin (DDP) on lung cancer growth in vivo. Methods: Lewis lung carcinoma 3LL cells (100 μl of 5×106/ml) were injected subcutaneously into female nude (C57BL/6) mice. Two days after xenograft injection, animals were randomized to four treatment groups (n=10): Control, cisplatin (DDP), cyclosporine A (CsA), and DDP + CsA. DDP and CsA were intraperitoneally administered initially at 2 mg/kg, q3d for 3 times and at 5 mg/kg, q2d for 3 times, respectively, and once a week afterwards. Tumor size was examined every three days. The weight of tumor mass was calculated. Animals were sacrificed 35 days after xenograft implantation. Tumors were collected and weighed. Tumor tissue specimens were subjected to H-E staining immunohistochemical assessment of Ki-67 expression. Results:Compared with the control, all drug treatments significantly reduced tumor size (P<0.01), tumor weight (P<0.05), cell density and mitotic count (P<005)and Ki-67 expression (P<0.05), but DDP together with CsA was significantly more effective than DDP and CsA each alone (P<0.05). Conclusion:The combined use of CsA and DDP may increase the sensitivity of lung carcinoma cells to DDP and thus have a synergistic effect against lung cancer.
Zhong Wu
,
Jiang Zhiyuan
,
Zhong Shibiao
,
Zhang Leichang
,
Huang Jiahao
,
Zhang Sen
,
Chen Lisheng
,
Cao Yunfei
2015, 22(5):612-618.
DOI: 10.3872/j.issn.1007-385X.2015.05.011
Abstract:
Objective:This study aimed: (1) to determine the distribution of LAP+CD4+T cells in the tumor microenvironment of colorectal cancer (CRC); (2) to analyze the associations of LAP+CD4+T cells with CD4+CD25+Treg and clinicopathological variables; and (3) to evaluate the role for LAP+CD4+T cells in CRC development and progression. Methods: Clinicopathologic data of 50 CRC patients who were hospitalized and received surgical treatment in the Colorectal and Anal Department of Guangxi Medical University-Affiliated First Hospital of between January, 2014 and March, 2014 were collected. Preoperative peripheral blood, intraoperative tumor tissue and corresponding para-carcinoma tissue (over 10 cm from the tumor margins) specimens were collected for all patients. Peripheral blood samples were collected from 25 healthy volunteers for the purpose of control. Proportions of LAP+CD4+T cells and CD4+CD25+Treg in all samples were determined by flow cytometry. Associations of LAP+CD4+T cells with CD4+CD25+Treg and clinicopathological variables were analyzed. Results: The proportion of LAP+CD4+ T cells in the peripheral blood was significantly higher in CRC patients (9.44±3.18%) than in healthy controls (1.49±1.00%) (P=0.000), and was also significantly higher in tumor tissue (11.76±3.74%) than in the corresponding para-carcinoma tissue (3.87±1.64%) in CRC patients (P=0.000). LAP+CD4+T cells were positively correlated with CD4+CD25+Treg cells in tumor tissues (r=0.327, P=0.02) and also with TNM staging, distant metastasis and CEA levels (P<0.05). Conclusion: LAP+CD4+T cells are prone to aggregate in the CRC tissue, thus promoting CRC growth and metastasis.
Objective:This study aimed: (1) to determine the distribution of LAP+CD4+T cells in the tumor microenvironment of colorectal cancer (CRC); (2) to analyze the associations of LAP+CD4+T cells with CD4+CD25+Treg and clinicopathological variables; and (3) to evaluate the role for LAP+CD4+T cells in CRC development and progression. Methods: Clinicopathologic data of 50 CRC patients who were hospitalized and received surgical treatment in the Colorectal and Anal Department of Guangxi Medical University-Affiliated First Hospital of between January, 2014 and March, 2014 were collected. Preoperative peripheral blood, intraoperative tumor tissue and corresponding para-carcinoma tissue (over 10 cm from the tumor margins) specimens were collected for all patients. Peripheral blood samples were collected from 25 healthy volunteers for the purpose of control. Proportions of LAP+CD4+T cells and CD4+CD25+Treg in all samples were determined by flow cytometry. Associations of LAP+CD4+T cells with CD4+CD25+Treg and clinicopathological variables were analyzed. Results: The proportion of LAP+CD4+ T cells in the peripheral blood was significantly higher in CRC patients (9.44±3.18%) than in healthy controls (1.49±1.00%) (P=0.000), and was also significantly higher in tumor tissue (11.76±3.74%) than in the corresponding para-carcinoma tissue (3.87±1.64%) in CRC patients (P=0.000). LAP+CD4+T cells were positively correlated with CD4+CD25+Treg cells in tumor tissues (r=0.327, P=0.02) and also with TNM staging, distant metastasis and CEA levels (P<0.05). Conclusion: LAP+CD4+T cells are prone to aggregate in the CRC tissue, thus promoting CRC growth and metastasis.
Wang Hongyan
,
Wang Yu
,
Wang Jiali
,
Han Xiaonan
,
Wang Xuexiao
,
Wang Miao
,
Jia Yunlong
,
Liu Lihua
2015, 22(5):619-624.
DOI: 10.3872/j.issn.1007-385X.2015.05.012
Abstract:
Objective:To study changes in serum levels of interleukin (IL)-6 and vascular endothelial growth factor (VEGF) in associations with tumor invasion and lymphatic metastasis in patients with esophageal squamous cell cancer (ESCC). Methods: Tumor and peri-tumor tissue specimens and peripheral blood samples were collected from 52 ESCC patients who underwent surgical resection in the Department of Chest Surgery, Hebei Medical University-Affiliated Fourth Hospital between January, 2014 and January, 2015. Blood samples were collected from 52 healthy subjects for the purpose of control. IL-6 levels in the blood samples were determined by enzyme-linked immunosorbent assay (ELISA). VEGF protein in the tumor and peri-tumor specimens was assessed by immunohistochemistry. IL-6 and VEGF mRNA abundance was assessed by semi-quantitative RT-PCR. Results: Serum levels of IL-6 were significantly higher in ESCC patients (116.71±25.98) pg/ml than in control subjects (78.43±9.36) pg/ml (P<0.05). In ESCC patients, serum levels of IL-6 were associated to patient TNM stage, tumor invasion depth, tumor differentiation and lymph node metastasis (P<0.05). VEGF protein was detected in 67.31% of tumor specimens and the intensity of the immunoreactive protein signal was associated to TNM stage, tumor invasion depth, tumor differentiation and lymph node metastasis. Tumor tissue VEGF was associated to serum level of IL-6 (P<0.05). IL-6 and VEGF mRNA levels were positively correlated in the tumor tissue (r=7.113, P<0.05). Conclusion: IL-6 is positively correlated with VEGF in ESCC patients. This finding suggests that IL-6 and VEGF may play key roles ESCC invasion and lymph node metastasis.
Objective:To study changes in serum levels of interleukin (IL)-6 and vascular endothelial growth factor (VEGF) in associations with tumor invasion and lymphatic metastasis in patients with esophageal squamous cell cancer (ESCC). Methods: Tumor and peri-tumor tissue specimens and peripheral blood samples were collected from 52 ESCC patients who underwent surgical resection in the Department of Chest Surgery, Hebei Medical University-Affiliated Fourth Hospital between January, 2014 and January, 2015. Blood samples were collected from 52 healthy subjects for the purpose of control. IL-6 levels in the blood samples were determined by enzyme-linked immunosorbent assay (ELISA). VEGF protein in the tumor and peri-tumor specimens was assessed by immunohistochemistry. IL-6 and VEGF mRNA abundance was assessed by semi-quantitative RT-PCR. Results: Serum levels of IL-6 were significantly higher in ESCC patients (116.71±25.98) pg/ml than in control subjects (78.43±9.36) pg/ml (P<0.05). In ESCC patients, serum levels of IL-6 were associated to patient TNM stage, tumor invasion depth, tumor differentiation and lymph node metastasis (P<0.05). VEGF protein was detected in 67.31% of tumor specimens and the intensity of the immunoreactive protein signal was associated to TNM stage, tumor invasion depth, tumor differentiation and lymph node metastasis. Tumor tissue VEGF was associated to serum level of IL-6 (P<0.05). IL-6 and VEGF mRNA levels were positively correlated in the tumor tissue (r=7.113, P<0.05). Conclusion: IL-6 is positively correlated with VEGF in ESCC patients. This finding suggests that IL-6 and VEGF may play key roles ESCC invasion and lymph node metastasis.
2015, 22(5):625-629.
DOI: 10.3872/j.issn.1007-385X.2015.05.013
Abstract:
Objective:To investigate the expression profile of heat shock protein-47 (HSP47) in glioma and evaluate the diagnostic and prognostic significance of HSP47 in clinical settings.Methods: Biopsy specimens were collected from 92 patients diagnosed with glioma and 10 patients diagnosed with gliosis between January, 2008 and December, 2009 at General Hospital of Shenyang Military Command. Additional 15 frozen glioma specimens collected between May, 2014 and June, 2014 were obtained. Immunoreactive HSP47 protein signals in these specimens were assessed by immunohistochemical staining and Western blotting. The prognostic significance of HSP47 was assessed by Kaplan-Meier survival analysis. Results:HSP47 was positive in 52.17% of glioma specimens but was undetectable in non-glioma specimens (χ2=9.855, P=0.002). In HSP47-positive Ⅲ、Ⅳ-grade glioma specimens, the immunoreative HSP47 protein signal was mainly located the cytoplasm of vascular endothelial cells. HSP47 expression was significantly associated with the pathological grade of the lesion (P<0.05) but not with gender (P=0.423) and age (P=0.820). The medium survival time was significantly longer in patients with low levels of HSP47 (43 months, 95 % CI, 22.4～63.6) than in patients with high levels of HSP47 (17 months, 95 % CI, 14.5～19.5) (P<0.001). Conclusion:HSP47 is overexpressed in glioma and its expression level is positively correlated with the pathological grade of the lesion. Our obervations suggest taht HSP47 may serve as a prognostic factor and a therapeutic target.
Objective:To investigate the expression profile of heat shock protein-47 (HSP47) in glioma and evaluate the diagnostic and prognostic significance of HSP47 in clinical settings.Methods: Biopsy specimens were collected from 92 patients diagnosed with glioma and 10 patients diagnosed with gliosis between January, 2008 and December, 2009 at General Hospital of Shenyang Military Command. Additional 15 frozen glioma specimens collected between May, 2014 and June, 2014 were obtained. Immunoreactive HSP47 protein signals in these specimens were assessed by immunohistochemical staining and Western blotting. The prognostic significance of HSP47 was assessed by Kaplan-Meier survival analysis. Results:HSP47 was positive in 52.17% of glioma specimens but was undetectable in non-glioma specimens (χ2=9.855, P=0.002). In HSP47-positive Ⅲ、Ⅳ-grade glioma specimens, the immunoreative HSP47 protein signal was mainly located the cytoplasm of vascular endothelial cells. HSP47 expression was significantly associated with the pathological grade of the lesion (P<0.05) but not with gender (P=0.423) and age (P=0.820). The medium survival time was significantly longer in patients with low levels of HSP47 (43 months, 95 % CI, 22.4～63.6) than in patients with high levels of HSP47 (17 months, 95 % CI, 14.5～19.5) (P<0.001). Conclusion:HSP47 is overexpressed in glioma and its expression level is positively correlated with the pathological grade of the lesion. Our obervations suggest taht HSP47 may serve as a prognostic factor and a therapeutic target.
2015, 22(5):630-636.
DOI: 10.3872/j.issn.1007-385X.2015.05.014
Abstract:
Objective:To investigate the expression of melanoma antigen (MAGE)-A9 and MAGE-A11 in esophageal squamous cell carcinomas in association with major clinical and biological variables. Methods: Cancerous (n=60）and adjacent (n=60) esophageal tissue specimens were collected from 60 patients with esophageal squamous cell carcinomas who underwent surgery in Hebei Medical University-Affiliated Fourth Hospital between September and November 2010. Testicular tissue specimens were collected from 5 prostate cancer patients in the same time as positive controls. MAGE-A9 and MAGE-A11 in these tissue specimens were assessed by immmuohistochemical staining. Correlations of MAGE-A9 and MAGE-A11 levels with patients' major clinical and demographic variables were determined. Results:MAGE-A9 and -A11 were positive in 45% (27/60) and 66.67% (40/60) of cancerous tissue specimens respectively but were both negative in tumor-adjacent tissue specimens. While MAGE-A9 protein was not correlated with age, clinical stage, tumor size, and lymph node metastasis(P>0.05), it was significantly correlated with the histological grade of the lesion in patients with esophageal squamous cell carcinoma (P<0.05). While MAGE-A11 protein was not correlated with age, histological grade, lymph node metastasis (P>0.05), it was significantly correlated with clinical stage and tumor size (P<0.05) in patients with esophageal squamous cell carcinoma. Log-rank test showed that the survival time was significantly shorter in MAGE-A9-positive (P=0.037) and MAGE-A11 positive (P=0.039) patients than in MAGE-A9-negative and MAGE-A11-negative patients. Cox multivariate analysis suggested that MAGE-A9 protein (P=0.026), MAGE-A11 protein (P=0.038), histological grade (P=0.026), TNM stage (P=0.008) and lymph node metastasis (P=0.010) were independent prognostic factors for overall survival. Conclusion: MAGE-A9 and -A11 are esophageal squamous cell carcinoma-specific antigens, thus having potential diagnostic and prognostic significance in clinical settings.
Objective:To investigate the expression of melanoma antigen (MAGE)-A9 and MAGE-A11 in esophageal squamous cell carcinomas in association with major clinical and biological variables. Methods: Cancerous (n=60）and adjacent (n=60) esophageal tissue specimens were collected from 60 patients with esophageal squamous cell carcinomas who underwent surgery in Hebei Medical University-Affiliated Fourth Hospital between September and November 2010. Testicular tissue specimens were collected from 5 prostate cancer patients in the same time as positive controls. MAGE-A9 and MAGE-A11 in these tissue specimens were assessed by immmuohistochemical staining. Correlations of MAGE-A9 and MAGE-A11 levels with patients' major clinical and demographic variables were determined. Results:MAGE-A9 and -A11 were positive in 45% (27/60) and 66.67% (40/60) of cancerous tissue specimens respectively but were both negative in tumor-adjacent tissue specimens. While MAGE-A9 protein was not correlated with age, clinical stage, tumor size, and lymph node metastasis(P>0.05), it was significantly correlated with the histological grade of the lesion in patients with esophageal squamous cell carcinoma (P<0.05). While MAGE-A11 protein was not correlated with age, histological grade, lymph node metastasis (P>0.05), it was significantly correlated with clinical stage and tumor size (P<0.05) in patients with esophageal squamous cell carcinoma. Log-rank test showed that the survival time was significantly shorter in MAGE-A9-positive (P=0.037) and MAGE-A11 positive (P=0.039) patients than in MAGE-A9-negative and MAGE-A11-negative patients. Cox multivariate analysis suggested that MAGE-A9 protein (P=0.026), MAGE-A11 protein (P=0.038), histological grade (P=0.026), TNM stage (P=0.008) and lymph node metastasis (P=0.010) were independent prognostic factors for overall survival. Conclusion: MAGE-A9 and -A11 are esophageal squamous cell carcinoma-specific antigens, thus having potential diagnostic and prognostic significance in clinical settings.
2015, 22(5):637-645.
DOI: 10.3872/j.issn.1007-385X.2015.05.015
Abstract:
血管内皮细胞生长因子（vascular endothelial growth factor, VEGF）及其受体VEGFR（VEGF receptor）所介导的“出芽式血管生成（sprouting angiogenesis）”，在生理及病理性血管生成中均扮演着重要的角色，尤其在肿瘤血管生成方面起到关键的作用。靶向VEGF以及VEGFR的药物正在不断被开发出来，如bevacizumab、sorafenib、aflibercept等，这些药物以不同的方式抑制VEGF/VEGFR信号通路，在临床上已被证明能有效抑制多种肿瘤的生长，成功实现了相关药物的临床转化。但随着临床研究的不断推进，抗VEGF/VEGFR靶向治疗的局限性逐渐显露出来，包括肿瘤对药物的抵抗性以及药物带来的不同程度的毒性作用，这些问题同时也是转化医学面临的重要问题，故新靶点以及新药物的研发迫在眉睫。本文对抗VEGF/VEGFR抗癌药物研发和治疗的背景、现状以及面临的挑战等问题进行了系统的综述，并为相关药物临床转化的推进作出了展望。
血管内皮细胞生长因子（vascular endothelial growth factor, VEGF）及其受体VEGFR（VEGF receptor）所介导的“出芽式血管生成（sprouting angiogenesis）”，在生理及病理性血管生成中均扮演着重要的角色，尤其在肿瘤血管生成方面起到关键的作用。靶向VEGF以及VEGFR的药物正在不断被开发出来，如bevacizumab、sorafenib、aflibercept等，这些药物以不同的方式抑制VEGF/VEGFR信号通路，在临床上已被证明能有效抑制多种肿瘤的生长，成功实现了相关药物的临床转化。但随着临床研究的不断推进，抗VEGF/VEGFR靶向治疗的局限性逐渐显露出来，包括肿瘤对药物的抵抗性以及药物带来的不同程度的毒性作用，这些问题同时也是转化医学面临的重要问题，故新靶点以及新药物的研发迫在眉睫。本文对抗VEGF/VEGFR抗癌药物研发和治疗的背景、现状以及面临的挑战等问题进行了系统的综述，并为相关药物临床转化的推进作出了展望。
2015, 22(5):646-650.
DOI: 10.3872/j.issn.1007-385X.2015.05.016
Abstract:
树突状细胞（dendritic cell, DC）是体内功能最强的抗原提呈细胞，能将肿瘤抗原提呈给T细胞，是抗肿瘤免疫的启动者。DC疫苗的肿瘤免疫治疗虽已取得丰硕成果，但在其临床转化过程中还有很多问题需要解决，选择何种抗原负载方式则是其中之一。目前临床试验中常用的有肿瘤细胞裂解物负载DC、重组肿瘤相关抗原负载DC及携带肿瘤相关抗原信息的mRNA转染DC三种方法。本文对此三种方法在临床试验中的应用做一综述，为树突状细胞疫苗的临床应用提供参考。
树突状细胞（dendritic cell, DC）是体内功能最强的抗原提呈细胞，能将肿瘤抗原提呈给T细胞，是抗肿瘤免疫的启动者。DC疫苗的肿瘤免疫治疗虽已取得丰硕成果，但在其临床转化过程中还有很多问题需要解决，选择何种抗原负载方式则是其中之一。目前临床试验中常用的有肿瘤细胞裂解物负载DC、重组肿瘤相关抗原负载DC及携带肿瘤相关抗原信息的mRNA转染DC三种方法。本文对此三种方法在临床试验中的应用做一综述，为树突状细胞疫苗的临床应用提供参考。
2015, 22(5):651-656.
DOI: 10.3872/j.issn.1007-385X.2015.05.017
Abstract:
NDR（nuclear Dbf2-related）蛋白激酶家族是蛋白激酶AGC家族的一个亚家族，属于进化上高度保守的丝氨酸/苏氨酸(Ser／Thr)蛋白激酶家族成员，目前发现的人类NDR激酶家族包括NDR1/STK38(serine/threonine kinase 38)、NDR2/STK38L(serine/threonine kinase 38-like protein)、LATS1 (large tumor suppressor-1) 和LATS2四个成员。NDR蛋白激酶表达较为广泛，其主要通过激酶活性来调节细胞的功能，参与细胞增殖与分化。NDR蛋白激酶活化异常可导致其下游基因的异常活化，尤其调控一些原癌基因，如LATS1/2可通过经典HIPPO信号通路调控原癌基因Yorkie转录活性，发挥抑癌作用；NDR1/2一方面通过调控中心体复制、染色体校正参与稳定染色体组、凋亡信号等发挥抑癌作用，另一方面通过增强原癌基因C-myc的稳定性发挥促癌作用，值得关注的是NDR1/2亦可通过调节P21的稳定性而发挥抑癌和促癌的双重作用。本文主要综述近年来NDR蛋白激酶家族在肿瘤研究领域中的研究进展，以期为靶向蛋白激酶的抗肿瘤治疗策略提供新的靶标。
NDR（nuclear Dbf2-related）蛋白激酶家族是蛋白激酶AGC家族的一个亚家族，属于进化上高度保守的丝氨酸/苏氨酸(Ser／Thr)蛋白激酶家族成员，目前发现的人类NDR激酶家族包括NDR1/STK38(serine/threonine kinase 38)、NDR2/STK38L(serine/threonine kinase 38-like protein)、LATS1 (large tumor suppressor-1) 和LATS2四个成员。NDR蛋白激酶表达较为广泛，其主要通过激酶活性来调节细胞的功能，参与细胞增殖与分化。NDR蛋白激酶活化异常可导致其下游基因的异常活化，尤其调控一些原癌基因，如LATS1/2可通过经典HIPPO信号通路调控原癌基因Yorkie转录活性，发挥抑癌作用；NDR1/2一方面通过调控中心体复制、染色体校正参与稳定染色体组、凋亡信号等发挥抑癌作用，另一方面通过增强原癌基因C-myc的稳定性发挥促癌作用，值得关注的是NDR1/2亦可通过调节P21的稳定性而发挥抑癌和促癌的双重作用。本文主要综述近年来NDR蛋白激酶家族在肿瘤研究领域中的研究进展，以期为靶向蛋白激酶的抗肿瘤治疗策略提供新的靶标。
2015, 22(5):657-662.
DOI: 10.3872/j.issn.1007-385X.2015.05.018
Abstract:
肝细胞癌是原发性肝癌中最常见的一种，其全球发病率和病死率分别位居恶性肿瘤中的第六位和第三位。血管生成是促进肝细胞癌发生、发展的关键生物学过程，其涉及多种肿瘤微环境的细胞和分子组分。其中细胞组分包括肝细胞癌内皮细胞、周皮细胞、肝脏星形细胞和肿瘤浸润的淋巴细胞等；分子组分则包括VEGF、FGF、血管生成素等生长因子和细胞因子。这些血管生成相关的细胞和分子机制的阐明，不仅可以加深对肝细胞癌生物学特征的理解，也能为肝细胞癌的抗血管生成治疗提供潜在的药物靶标和新的生物治疗标记物，从而完善或建立新的肝细胞癌治疗方案。本文就目前血管生成在肝细胞癌发生、发展过程中的作用及其相关的细胞、分子机制做一综述，同时简述肝细胞癌治疗的相关进展。
肝细胞癌是原发性肝癌中最常见的一种，其全球发病率和病死率分别位居恶性肿瘤中的第六位和第三位。血管生成是促进肝细胞癌发生、发展的关键生物学过程，其涉及多种肿瘤微环境的细胞和分子组分。其中细胞组分包括肝细胞癌内皮细胞、周皮细胞、肝脏星形细胞和肿瘤浸润的淋巴细胞等；分子组分则包括VEGF、FGF、血管生成素等生长因子和细胞因子。这些血管生成相关的细胞和分子机制的阐明，不仅可以加深对肝细胞癌生物学特征的理解，也能为肝细胞癌的抗血管生成治疗提供潜在的药物靶标和新的生物治疗标记物，从而完善或建立新的肝细胞癌治疗方案。本文就目前血管生成在肝细胞癌发生、发展过程中的作用及其相关的细胞、分子机制做一综述，同时简述肝细胞癌治疗的相关进展。
2015, 22(5):663-667.
DOI: 10.3872/j.issn.1007-385X.2015.05.019
Abstract:
Wnt信号通路与多种肿瘤的发生相关，研究表明Wnt通路抑制因子的异常甲基化可使Wnt信号通路异常激活，从而诱导肿瘤的形成。垂体腺瘤作为颅内常见的肿瘤之一，临床症状主要由垂体激素过度分泌（或）缺乏和（或）肿瘤占位效应引起，其发病机制至今不完全清楚，部分研究表明垂体腺瘤的发生与Wnt通路抑制因子的异常甲基化相关。本文对垂体腺瘤中Wnt通路抑制因子作用的研究进行综述，为垂体腺瘤中去甲基化治疗提供一定的理论依据。
Wnt信号通路与多种肿瘤的发生相关，研究表明Wnt通路抑制因子的异常甲基化可使Wnt信号通路异常激活，从而诱导肿瘤的形成。垂体腺瘤作为颅内常见的肿瘤之一，临床症状主要由垂体激素过度分泌（或）缺乏和（或）肿瘤占位效应引起，其发病机制至今不完全清楚，部分研究表明垂体腺瘤的发生与Wnt通路抑制因子的异常甲基化相关。本文对垂体腺瘤中Wnt通路抑制因子作用的研究进行综述，为垂体腺瘤中去甲基化治疗提供一定的理论依据。
2015, 22(5):668-672.
DOI: 10.3872/j.issn.1007-385X.2015.05.020
Abstract:
急性髓细胞白血病严重威胁人类健康，其与肿瘤抑制因子 p53 存在一定的相关性： p53基因 异常参与急性髓细胞白血病尤其是复杂核型急性髓细胞白血病的发病过程，并提示预后差以及对化疗和移植的治疗反应差；而 p53 抑制因子MDM2蛋白的过表达、多态性以及p53蛋白自身的多态性也在一定程度上影响急性髓细胞白血病的发病风险以及临床预后。以 p53 为靶点的药物主要包括抑制 p53 功能类和恢复 p53 功能类，均已在急性髓细胞白血病的治疗研究中显示出巨大的潜能，部分还进入了临床试验。为全面了解 p53 与急性髓细胞白血病的研究进展，本文就相关文献进行综述。
急性髓细胞白血病严重威胁人类健康，其与肿瘤抑制因子 p53 存在一定的相关性： p53基因 异常参与急性髓细胞白血病尤其是复杂核型急性髓细胞白血病的发病过程，并提示预后差以及对化疗和移植的治疗反应差；而 p53 抑制因子MDM2蛋白的过表达、多态性以及p53蛋白自身的多态性也在一定程度上影响急性髓细胞白血病的发病风险以及临床预后。以 p53 为靶点的药物主要包括抑制 p53 功能类和恢复 p53 功能类，均已在急性髓细胞白血病的治疗研究中显示出巨大的潜能，部分还进入了临床试验。为全面了解 p53 与急性髓细胞白血病的研究进展，本文就相关文献进行综述。
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.