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Volume 22,Issue 2,2015 Table of Contents
2015, 22(2):143-150.
DOI: 10.3872/j.issn.1007-385X.2015.2.002
Abstract:
Tumor microenvironment has attracted significant research attentions worldwide. It is now generally accepted that the immune system is one of major components in tumor microenvironment and is involved in almost all processes of tumor development and progression. Innate immunity plays dual roles in immune surveillance and immune tolerance in the interaction of host and tumors. As the sensors for innate immunity, pattern recognition receptors (PRRs) can recognize virus, bacteria and other pathogens to initiate the immune responses. PRRs are also bifacial in the regulation of tumor immunity. They can inhibit tumorigenesis through maintaining the host-microflora homeostasis and removing the death or mutant cells and recognize danger signals to induce immunogenic tumor cell death to inhibit tumor progression on one hand, they can also contribute to tumorigenesis in settings of chronic inflammation and induction of regulatory cell populations and immunosuppressive cytokines to facilitate tumor growth on the other hand. In addition, tumor cells also express various PRRs, which are involved in tumor development and progression. In this review, we summarize the expression of PRRs and their ligands in tumor microenvironment, with a particular focus on the dual characters of PRRs in tumor immunity.
Tumor microenvironment has attracted significant research attentions worldwide. It is now generally accepted that the immune system is one of major components in tumor microenvironment and is involved in almost all processes of tumor development and progression. Innate immunity plays dual roles in immune surveillance and immune tolerance in the interaction of host and tumors. As the sensors for innate immunity, pattern recognition receptors (PRRs) can recognize virus, bacteria and other pathogens to initiate the immune responses. PRRs are also bifacial in the regulation of tumor immunity. They can inhibit tumorigenesis through maintaining the host-microflora homeostasis and removing the death or mutant cells and recognize danger signals to induce immunogenic tumor cell death to inhibit tumor progression on one hand, they can also contribute to tumorigenesis in settings of chronic inflammation and induction of regulatory cell populations and immunosuppressive cytokines to facilitate tumor growth on the other hand. In addition, tumor cells also express various PRRs, which are involved in tumor development and progression. In this review, we summarize the expression of PRRs and their ligands in tumor microenvironment, with a particular focus on the dual characters of PRRs in tumor immunity.
2015, 22(2):151-158.
DOI: 10.3872/j.issn.1007-385X.2015.2.003
Abstract:
Precision medicine is a novel medical concept and medical model. Its benefits in the treatment of malignant tumors are being increasingly demonstrated in clinical settings. Precision immunotherapy is one of precision medicine strategies. In case of caner treatment, precision immunotherapy involves genetic screening of mutations, identification of the neo-antigen(s) capable of triggering strong immune responses using bioinformatics tools, screening and enrichment of the precision T cells for Neo-Antigen(s) (referred to as PNA-Ts), and amplification of the PNA-Ts in a large scale and transfusion of the PNA-Ts back into the autologous patients. Among the various existing treatment strategies for cancer patients, precision immunotherapy, by virtue of its unique advantages, is expected to become an important breakthrough in the treatment of cancer in China. This paper aims to outline the concept, features, processes, technical difficulties, etc. of precision cancer immunotherapy and compare the cons and pros of precision immunotherapy and chimeric antigen receptor T-cell immunotherapy. We will also discuss the opportunities and challenges of precision immunotherapy in the treatment of cancer, particularly in China.
Precision medicine is a novel medical concept and medical model. Its benefits in the treatment of malignant tumors are being increasingly demonstrated in clinical settings. Precision immunotherapy is one of precision medicine strategies. In case of caner treatment, precision immunotherapy involves genetic screening of mutations, identification of the neo-antigen(s) capable of triggering strong immune responses using bioinformatics tools, screening and enrichment of the precision T cells for Neo-Antigen(s) (referred to as PNA-Ts), and amplification of the PNA-Ts in a large scale and transfusion of the PNA-Ts back into the autologous patients. Among the various existing treatment strategies for cancer patients, precision immunotherapy, by virtue of its unique advantages, is expected to become an important breakthrough in the treatment of cancer in China. This paper aims to outline the concept, features, processes, technical difficulties, etc. of precision cancer immunotherapy and compare the cons and pros of precision immunotherapy and chimeric antigen receptor T-cell immunotherapy. We will also discuss the opportunities and challenges of precision immunotherapy in the treatment of cancer, particularly in China.
2015, 22(2):159-165.
DOI: 10.3872/j.issn.1007-385X.2015.2.004
Abstract:
The author proposed the concept of cancer targeting gene-viro-therapy (CTGVT) in 2001. By inserting an anti-tumor gene into an oncolytic virus (OV), this novel approach combines the advantages of both gene therapy and OV therapy. The anti-tumor effect of CTGVT can be several dozens to hundred times higher than that of either respective cancer gene therapy or OV therapy alone, owing to the fact that OV can target to the cancer cell where both the virus and the inserted gene replicate several tens or hundreds of times faster than usual. Given compensatory or synergetic effects of genes, double gene strategy (CTGVT-DG) has been demonstrated in an animal model of xenograft tumor to be significantly more effective. In our approaches, the OncoAd vector is used. To minimize the OV injection-associated vector degradation, we choose to coat the CTGVT-DG products with nano-particles or to use the OncoPox vector. In the previous studies from the Western countries, only the immune effect of GM-CSF is considered in the OV-Gene system, while the replicative capacity of the gene is often ignored. As a result, our strategies may be able to more effectively eradicate tumors, thereby offering greater clinical potential.
The author proposed the concept of cancer targeting gene-viro-therapy (CTGVT) in 2001. By inserting an anti-tumor gene into an oncolytic virus (OV), this novel approach combines the advantages of both gene therapy and OV therapy. The anti-tumor effect of CTGVT can be several dozens to hundred times higher than that of either respective cancer gene therapy or OV therapy alone, owing to the fact that OV can target to the cancer cell where both the virus and the inserted gene replicate several tens or hundreds of times faster than usual. Given compensatory or synergetic effects of genes, double gene strategy (CTGVT-DG) has been demonstrated in an animal model of xenograft tumor to be significantly more effective. In our approaches, the OncoAd vector is used. To minimize the OV injection-associated vector degradation, we choose to coat the CTGVT-DG products with nano-particles or to use the OncoPox vector. In the previous studies from the Western countries, only the immune effect of GM-CSF is considered in the OV-Gene system, while the replicative capacity of the gene is often ignored. As a result, our strategies may be able to more effectively eradicate tumors, thereby offering greater clinical potential.
2015, 22(2):166-169.
DOI: 10.3872/j.issn.1007-385X.2015.2.005
Abstract:
The antibody has become an important pillar of the bio pharmaceutical industry. The development of the antibody used to cancer biological therapy was discussed on the basis of antibody engineering technology, including antibody humanization, human antibody preparation, effect function improvement, and so on. Furthermore, the novel direction of antibody research was forecasted.
The antibody has become an important pillar of the bio pharmaceutical industry. The development of the antibody used to cancer biological therapy was discussed on the basis of antibody engineering technology, including antibody humanization, human antibody preparation, effect function improvement, and so on. Furthermore, the novel direction of antibody research was forecasted.
2015, 22(2):170-176.
DOI: 10.3872/j.issn.1007-385X.2015.2.006
Abstract:
Gene therapy is one of the most revolutionary medical technologies developing with the mature of the techniques of recombinant DNA and gene cloning and it is a kind of biomedical treatment based on changing human genetic materials. After nearly thirty years development, gene therapy has expanded from single-gene genetic diseases treatment to the therapy of malignant tumor, infectious diseases, cardiovascular disease, autoimmune disease, metabolic disease and other major diseases and about 2/3 of the gene therapy clinical trials are directed to malignant tumor. This article will mainly focus on the development history of world gene therapy and the development status of tumor gene therapy in China with emphases on the reviews of gene expression vector, gene delivery system, gene therapy clinical trials, the research and development of gene therapy major products and the industrialization development of gene therapy and the recent key breakthroughs in the malignant tumor and genetic diseases gene therapy fields. Besides, this article reviews with emphasis on the development opportunities and challenges of tumor gene therapy in the future from five aspects including gene delivery in vivo, safety of gene therapy, new technology in tumor gene therapy, tumor gene therapy combined with other therapeutic methods and gene detection technology united with gene therapy. We have reasons to believe that along with the continuous breakthroughs of key technologies of gene therapy, the next few years will be an important period of tumor gene therapeutic products coming to the market, which provides new choices for the clinical trials of malignant tumor.
Gene therapy is one of the most revolutionary medical technologies developing with the mature of the techniques of recombinant DNA and gene cloning and it is a kind of biomedical treatment based on changing human genetic materials. After nearly thirty years development, gene therapy has expanded from single-gene genetic diseases treatment to the therapy of malignant tumor, infectious diseases, cardiovascular disease, autoimmune disease, metabolic disease and other major diseases and about 2/3 of the gene therapy clinical trials are directed to malignant tumor. This article will mainly focus on the development history of world gene therapy and the development status of tumor gene therapy in China with emphases on the reviews of gene expression vector, gene delivery system, gene therapy clinical trials, the research and development of gene therapy major products and the industrialization development of gene therapy and the recent key breakthroughs in the malignant tumor and genetic diseases gene therapy fields. Besides, this article reviews with emphasis on the development opportunities and challenges of tumor gene therapy in the future from five aspects including gene delivery in vivo, safety of gene therapy, new technology in tumor gene therapy, tumor gene therapy combined with other therapeutic methods and gene detection technology united with gene therapy. We have reasons to believe that along with the continuous breakthroughs of key technologies of gene therapy, the next few years will be an important period of tumor gene therapeutic products coming to the market, which provides new choices for the clinical trials of malignant tumor.
6 Immunoscore: A prognosis prediction tool based on the immunological characteristics of tumor region
2015, 22(2):177-182.
DOI: 10.3872/j.issn.1007-385X.2015.2.007
Abstract:
Cancer is a major and common public health problem worldwide. Effective prognostic indicators are beneficial in developing personalized therapeutic treatment specific to each individual case, preventing inappropriate and excessive therapies. At present, clinical predictions are primarily based on histopathological evaluations of the primary tumor tissues obtained during surgery, such as the TNM staging system. However, compiling evidence has emerged to suggest that patients in the same TNM stage may exhibit significantly distinct survival after surgery. Recently, scholars around the world have come to a consensus that immunoscore, as a means of statistically and pathologically quantitating the regional immune status around the tumor, may provide better predictions of the survival in colorectal cancer patients. As an important progress in tumor immunopathology, immunoscore provides the basis for determining the “pre-stored immunity” and suitability in receiving personalized immunotherapy in cancer patients. Herein, we will outline the development history and discuss prospective applications, and future directions of this promising prognostic indicator in oncology.
Cancer is a major and common public health problem worldwide. Effective prognostic indicators are beneficial in developing personalized therapeutic treatment specific to each individual case, preventing inappropriate and excessive therapies. At present, clinical predictions are primarily based on histopathological evaluations of the primary tumor tissues obtained during surgery, such as the TNM staging system. However, compiling evidence has emerged to suggest that patients in the same TNM stage may exhibit significantly distinct survival after surgery. Recently, scholars around the world have come to a consensus that immunoscore, as a means of statistically and pathologically quantitating the regional immune status around the tumor, may provide better predictions of the survival in colorectal cancer patients. As an important progress in tumor immunopathology, immunoscore provides the basis for determining the “pre-stored immunity” and suitability in receiving personalized immunotherapy in cancer patients. Herein, we will outline the development history and discuss prospective applications, and future directions of this promising prognostic indicator in oncology.
2015, 22(2):183-190.
DOI: 10.3872/j.issn.1007-385X.2015.2.008
Abstract:
Immunoglobulin (Ig), one of the most important immune molecules, has been considered to be produced only by B lymphocytes. The membrane bound Ig on B cells is responsible for the recognition of antigen, and the secreted Ig (antibody) exerts the immune defense effect via several mechanisms. This is the classic concept that can be found in the contemporary textbooks of immunology. However, in recent years, an emerging large body of evidence has confirmed that in addition to the B cell-derived Ig, there is another class of Ig which is of non-IB cell origin (non B-Igs). The non B-Igs are different from those of the classical Igs about their VHDJH or VκJκ rearrangement pattern, expression regulation and function. Observably, the non B-Igs are frequently over expressed in many cancer cells, and correlated with poor cell differentiation and patients’ prognosis. Importantly, the non B-Igs could promote growth of cancer cells, and play importent role in the mechanism of tumor progression. These findings suggest that the non B-Ig behaves like potential proto-oncogenes, which may be useful for tumor therapy as novel targets.
Immunoglobulin (Ig), one of the most important immune molecules, has been considered to be produced only by B lymphocytes. The membrane bound Ig on B cells is responsible for the recognition of antigen, and the secreted Ig (antibody) exerts the immune defense effect via several mechanisms. This is the classic concept that can be found in the contemporary textbooks of immunology. However, in recent years, an emerging large body of evidence has confirmed that in addition to the B cell-derived Ig, there is another class of Ig which is of non-IB cell origin (non B-Igs). The non B-Igs are different from those of the classical Igs about their VHDJH or VκJκ rearrangement pattern, expression regulation and function. Observably, the non B-Igs are frequently over expressed in many cancer cells, and correlated with poor cell differentiation and patients’ prognosis. Importantly, the non B-Igs could promote growth of cancer cells, and play importent role in the mechanism of tumor progression. These findings suggest that the non B-Ig behaves like potential proto-oncogenes, which may be useful for tumor therapy as novel targets.
2015, 22(2):191-196.
DOI: 10.3872/j.issn.1007-385X.2015.2.009
Abstract:
Adoptive cell transfer (ACT) is a passive immunotherapy of cancer. Recently, researchers have observed that durable complete cancer regressions can be achieved in patients with metastatic melanoma after ACT, encouragingly suggesting a great potential for ACT in the treatment of cancer in clinical settings. This potential can be further enhanced when genetic modification of lymphocytes is performed. The key to the success of adoptive cell therapy is the identification of suitable immunologic targets on cancer cells that can be attacked by tumor infiltrating lymphocytes (TIL) or genetically modified lymphocytes without damaging normal tissues. Differentiation antigens overexpressed on cancers, shared non-mutated antigens of cancers, and antigens from tumor stroma are not suitable targets of ACT due to their low level expression in normal tissues. On the contrary, antigens encoded by shared mutations, viral oncogenes, or unique driver mutations may serve as ideal targets of ACT. Further development of ACT will result from new adoptive cell immunotherapy strategies with lymphocytes that recognize mutated antigens, in particular those derived from gene products that are involved in carcinogenesis.
Adoptive cell transfer (ACT) is a passive immunotherapy of cancer. Recently, researchers have observed that durable complete cancer regressions can be achieved in patients with metastatic melanoma after ACT, encouragingly suggesting a great potential for ACT in the treatment of cancer in clinical settings. This potential can be further enhanced when genetic modification of lymphocytes is performed. The key to the success of adoptive cell therapy is the identification of suitable immunologic targets on cancer cells that can be attacked by tumor infiltrating lymphocytes (TIL) or genetically modified lymphocytes without damaging normal tissues. Differentiation antigens overexpressed on cancers, shared non-mutated antigens of cancers, and antigens from tumor stroma are not suitable targets of ACT due to their low level expression in normal tissues. On the contrary, antigens encoded by shared mutations, viral oncogenes, or unique driver mutations may serve as ideal targets of ACT. Further development of ACT will result from new adoptive cell immunotherapy strategies with lymphocytes that recognize mutated antigens, in particular those derived from gene products that are involved in carcinogenesis.
2015, 22(2):197-203.
DOI: 10.3872/j.issn.1007-385X.2015.2.010
Abstract:
Malignant melanoma is one of the most aggressive malignant tumors with a 5-year survival rate of less than 5% in advanced patients who are highly resistant to traditional radiotherapy and chemotherapy. Nevertheless, significant progress has been made in the treatment of metastatic melanoma in the past five years with the introduction of monoclonal antibodies, small molecule compounds, adoptive cells and oncolytic viruses. To date, monoclonal antibodies against CTLA-4 (ipilimumab), PD-1 (pembrolizumab and nivolumab) and inhibitors against BRAF (vemurafinib and dabrafinib) or MEK (trametinib) have been approved by the FDA for the treatment of advanced melanoma patients. Moreover, a variety of autoimmune cell therapy methods such as TIL, CAR-T, and oncolytic virus T-VEC have been developed and there therapies have demonstrated clinical benefits in clinical trials. All these tumor biotherapy strategies have broken the silence of clinical research on melanoma. Although further clinical evidence needs to be generated before a wider application of biotherapy technologies in clinical settings in China, melanoma patients will eventually benefit from the integration of cellular immunology, molecular biology and cancer genetics in their fight against the disease.
Malignant melanoma is one of the most aggressive malignant tumors with a 5-year survival rate of less than 5% in advanced patients who are highly resistant to traditional radiotherapy and chemotherapy. Nevertheless, significant progress has been made in the treatment of metastatic melanoma in the past five years with the introduction of monoclonal antibodies, small molecule compounds, adoptive cells and oncolytic viruses. To date, monoclonal antibodies against CTLA-4 (ipilimumab), PD-1 (pembrolizumab and nivolumab) and inhibitors against BRAF (vemurafinib and dabrafinib) or MEK (trametinib) have been approved by the FDA for the treatment of advanced melanoma patients. Moreover, a variety of autoimmune cell therapy methods such as TIL, CAR-T, and oncolytic virus T-VEC have been developed and there therapies have demonstrated clinical benefits in clinical trials. All these tumor biotherapy strategies have broken the silence of clinical research on melanoma. Although further clinical evidence needs to be generated before a wider application of biotherapy technologies in clinical settings in China, melanoma patients will eventually benefit from the integration of cellular immunology, molecular biology and cancer genetics in their fight against the disease.
2015, 22(2):204-208.
DOI: 10.3872/j.issn.1007-385X.2015.2.011
Abstract:
Objective: To predict genes related to multidrug resistance (MDR) in ovarian cancer based on the microRNA (miRNA) regulatory network. Methods: To identify potential genes associated with multidrug resistance in ovarian cancer based on published miRNAs and miRNA-target genes were identified using a comprehensive bioinformatics approaches including text mining and network researching. Results: Eleven miRNAs related to ovarian cancer chemoresistance were identified, including miR-130a, miR-214, let-7i, miR-125b, miR-376c, miR-199a, miR-93, miR-141, miR-130b, miR-193b* and miR-200c. A total of 47 077 putative targets were predicted using the TargetScan algorithm and 1 675 other targets were predicted using the PicTar algorithm. Neuropilins (NRP1) was the most important Hub-gene found in the cancer miRNA regulatory network. Conclusion: It is an effective method to construct a miRNA regulatory network to predict genes related to MDR in ovarian cancer by utilizing the existing information on miRNAs. Using this approach, we predict that NRP1 may play an important role in ovarian cancer chemoresistance and would be a potential therapeutic target for ovarian cancer.
Objective: To predict genes related to multidrug resistance (MDR) in ovarian cancer based on the microRNA (miRNA) regulatory network. Methods: To identify potential genes associated with multidrug resistance in ovarian cancer based on published miRNAs and miRNA-target genes were identified using a comprehensive bioinformatics approaches including text mining and network researching. Results: Eleven miRNAs related to ovarian cancer chemoresistance were identified, including miR-130a, miR-214, let-7i, miR-125b, miR-376c, miR-199a, miR-93, miR-141, miR-130b, miR-193b* and miR-200c. A total of 47 077 putative targets were predicted using the TargetScan algorithm and 1 675 other targets were predicted using the PicTar algorithm. Neuropilins (NRP1) was the most important Hub-gene found in the cancer miRNA regulatory network. Conclusion: It is an effective method to construct a miRNA regulatory network to predict genes related to MDR in ovarian cancer by utilizing the existing information on miRNAs. Using this approach, we predict that NRP1 may play an important role in ovarian cancer chemoresistance and would be a potential therapeutic target for ovarian cancer.
2015, 22(2):209-213.
DOI: 10.3872/j.issn.1007-385X.2015.2.012
Abstract:
Objective: To determine the effect of Toll-like receptor 4 (TLR4) on lipopolysaccharide (LPS)-induced human lung carcinoma SPCA1 cell proliferation. Methods: SPCA1 cells were treated with LPS (10 μg/ml) to mimic a chronic inflammation microenvironment. TLR4 specific small interfering RNA (TLR4-siRNA) and a negative control interfering RNA (NC-siRNA) were transfected into SPCA1 cells by Lipofectamine. At 24 h after transfection, transfectants were treated with 10 μg/ml LPS. At 48 h after LPS treatment, TLR4 mRNA and protein levels were determined by Real-time PCR and FCM respectively, cell proliferation was assessed by CCK-8 assay and colony formation assay, and the cell cycle distribution was examined by FCM. Results: TLR4 mRNA and protein levels were significantly decreased (P<001), proliferation was significantly suppressed (P<0.01), and colony formation ability was significantly reduced (P<0.01) in SPCA1 cells transfected with TLR4-siRNA as compared with cells transfected with NC-siRNA. The proportion of cells arrested at the G0/G1 phase was significantly higher (P<0.01) in SPCA1 cells transfected with TLR4-siRNA (61.55±0.55)% than in NC-siRNA-transfected (53.59±1.59)% and control (51.72±0.77)%. Conclusion: TLR4-siRNA can effectively silence TLR4 expression in SPCA1 cells, block cell growth and inhibit cell proliferation.
Objective: To determine the effect of Toll-like receptor 4 (TLR4) on lipopolysaccharide (LPS)-induced human lung carcinoma SPCA1 cell proliferation. Methods: SPCA1 cells were treated with LPS (10 μg/ml) to mimic a chronic inflammation microenvironment. TLR4 specific small interfering RNA (TLR4-siRNA) and a negative control interfering RNA (NC-siRNA) were transfected into SPCA1 cells by Lipofectamine. At 24 h after transfection, transfectants were treated with 10 μg/ml LPS. At 48 h after LPS treatment, TLR4 mRNA and protein levels were determined by Real-time PCR and FCM respectively, cell proliferation was assessed by CCK-8 assay and colony formation assay, and the cell cycle distribution was examined by FCM. Results: TLR4 mRNA and protein levels were significantly decreased (P<001), proliferation was significantly suppressed (P<0.01), and colony formation ability was significantly reduced (P<0.01) in SPCA1 cells transfected with TLR4-siRNA as compared with cells transfected with NC-siRNA. The proportion of cells arrested at the G0/G1 phase was significantly higher (P<0.01) in SPCA1 cells transfected with TLR4-siRNA (61.55±0.55)% than in NC-siRNA-transfected (53.59±1.59)% and control (51.72±0.77)%. Conclusion: TLR4-siRNA can effectively silence TLR4 expression in SPCA1 cells, block cell growth and inhibit cell proliferation.
2015, 22(2):214-219.
DOI: 10.3872/j.issn.1007-385X.2015.2.013
Abstract:
Objective: To explore the influence and the mechanism of matrix metalloproteinase-3 (MMP-3) on invasion and metastasis of osteosarcoma. Methods: 40 cases of patients with osteosarcoma in No. 184 Hospital of PLA from January 1, 2013 to November 1, 2013 and 40 cases of healthy people were collected , and the serum of the patients with osteosarcoma and the healthy people were collected and the content of MMP-3 was detected with ELISA. And, the correlation between MMP-3 and the pathogenesis of osteosarcoma was also analyzed by SPSS. The mRNA levels of MMP-3 were detected by the method of RT-PCR in different osteosarcoma cell lines such as U2-OS，HOS-143b，MG-63cell lines. The proliferation of MG-63 after given different concentration of MMP-3 or knockdown MMP-3 was detected using MTT assay. And the invasion ability was detected by Transwell. Finally, the MMP-3 promotes the invasion and metastasis related proteins of osteosarcoma such as p-AKT, NF-κB were detected by Western blotting. Results: MMP-3 was highly expression in the serum of the patients with osteosarcoma (F=186.4, P=0.000), and there was a strong positive correlation between MMP-3 exepression and Enneking stage in osteosarcoma(r=0.736, P=0.043). MMP-3 was highly expression in the cell lines of MG-63 (P<0.05). The overexpression of MMP-3 stimulated by MMP-3 cultivation increased the expression of p-AKT and the intranuclear NF-κB, then promoted the proliferation and invasion ability of MG-63 cells (P<0.05); In contrast, MMP-3- shRNA transfection knockdown the MMP-3, result in reduction of the expression of p-AKT and the intranuclear NF-κB, then suppressed the proliferation and invasion ability of MG-63 cells (P<0.05). Conclusion: MMP-3 promotes the invasion and metastasis of osteosarcoma may via increasing the phosphorylation of AKT and promoting the translocation of NF-κB1.
Objective: To explore the influence and the mechanism of matrix metalloproteinase-3 (MMP-3) on invasion and metastasis of osteosarcoma. Methods: 40 cases of patients with osteosarcoma in No. 184 Hospital of PLA from January 1, 2013 to November 1, 2013 and 40 cases of healthy people were collected , and the serum of the patients with osteosarcoma and the healthy people were collected and the content of MMP-3 was detected with ELISA. And, the correlation between MMP-3 and the pathogenesis of osteosarcoma was also analyzed by SPSS. The mRNA levels of MMP-3 were detected by the method of RT-PCR in different osteosarcoma cell lines such as U2-OS，HOS-143b，MG-63cell lines. The proliferation of MG-63 after given different concentration of MMP-3 or knockdown MMP-3 was detected using MTT assay. And the invasion ability was detected by Transwell. Finally, the MMP-3 promotes the invasion and metastasis related proteins of osteosarcoma such as p-AKT, NF-κB were detected by Western blotting. Results: MMP-3 was highly expression in the serum of the patients with osteosarcoma (F=186.4, P=0.000), and there was a strong positive correlation between MMP-3 exepression and Enneking stage in osteosarcoma(r=0.736, P=0.043). MMP-3 was highly expression in the cell lines of MG-63 (P<0.05). The overexpression of MMP-3 stimulated by MMP-3 cultivation increased the expression of p-AKT and the intranuclear NF-κB, then promoted the proliferation and invasion ability of MG-63 cells (P<0.05); In contrast, MMP-3- shRNA transfection knockdown the MMP-3, result in reduction of the expression of p-AKT and the intranuclear NF-κB, then suppressed the proliferation and invasion ability of MG-63 cells (P<0.05). Conclusion: MMP-3 promotes the invasion and metastasis of osteosarcoma may via increasing the phosphorylation of AKT and promoting the translocation of NF-κB1.
2015, 22(2):220-224.
DOI: 10.3872/j.issn.1007-385X.2015.2.014
Abstract:
Objective: To isolate and characterize side population (SP) cells in human hepatocellular carcinoma (HCC) cells. Methods: Four HCC cell lines with a metastatic potential in an order of HCCLM3 > MHCC97-H>MHCC97-L>Huh7 were cultivated in routine culture conditions. Single cell suspensions were made for these lines and incubated with different concentrations of Hoechst33342 either alone or with 50 μmol/l verapamil. The proportion of SP cells in these suspensions was analyzed by flow cytometry. SP cells and main population (MP) cells in the single cell suspension of cell line HCCLM3 were sorted. The HCCLM3-derived SP cells and MP cells were then comparatively assessed for tumorsphere formation, migration and invasion in vitro, for tumorigenicity in vivo and for the expression of stem cell-related genes at the mRNA level. Results: The proportion of SP proportion was significantly different among HCCLM3 (16.9±18)%, MHCC97-H (8.4±0.7)%, MHCC97-L (4.6±0.5)% and Huh7 (1.0±0.2) (P<0.05). HCCLM3-derived SP cells but not MP cells displayed many characteristics of cancer stem cells including more sphere formation (253±5.1)% vs (11.2±2.6)%, P<0.05), higher invasion ability in vitro and stronger tumorigenicity in nude mice. The mRNA levels of ABCG2, CD13, CD44, Nanog, Sox2 and Klf4 in SP cells were 5.64, 2.26, 2.10, 378, 237, 2.92 times of those respectively in MP cells (all P<0.05). Conclusion: In the HCCLM3 cell line there is an enriched population of SP cells with liver cancer stem cell-like properties, which may be related to the highly metastatic potential of HCCLM3 cells.
Objective: To isolate and characterize side population (SP) cells in human hepatocellular carcinoma (HCC) cells. Methods: Four HCC cell lines with a metastatic potential in an order of HCCLM3 > MHCC97-H>MHCC97-L>Huh7 were cultivated in routine culture conditions. Single cell suspensions were made for these lines and incubated with different concentrations of Hoechst33342 either alone or with 50 μmol/l verapamil. The proportion of SP cells in these suspensions was analyzed by flow cytometry. SP cells and main population (MP) cells in the single cell suspension of cell line HCCLM3 were sorted. The HCCLM3-derived SP cells and MP cells were then comparatively assessed for tumorsphere formation, migration and invasion in vitro, for tumorigenicity in vivo and for the expression of stem cell-related genes at the mRNA level. Results: The proportion of SP proportion was significantly different among HCCLM3 (16.9±18)%, MHCC97-H (8.4±0.7)%, MHCC97-L (4.6±0.5)% and Huh7 (1.0±0.2) (P<0.05). HCCLM3-derived SP cells but not MP cells displayed many characteristics of cancer stem cells including more sphere formation (253±5.1)% vs (11.2±2.6)%, P<0.05), higher invasion ability in vitro and stronger tumorigenicity in nude mice. The mRNA levels of ABCG2, CD13, CD44, Nanog, Sox2 and Klf4 in SP cells were 5.64, 2.26, 2.10, 378, 237, 2.92 times of those respectively in MP cells (all P<0.05). Conclusion: In the HCCLM3 cell line there is an enriched population of SP cells with liver cancer stem cell-like properties, which may be related to the highly metastatic potential of HCCLM3 cells.
2015, 22(2):225-229.
DOI: 10.3872/j.issn.1007-385X.2015.2.015
Abstract:
Objective: To study whether and how ginsenoside Rg3 regulate apoptosis of gastric cancer BGC-823 cells. Methods: BGC-823 cells were treated with vehicle (control), Rg3 (50 μg/ml), Ad-CaM, and Rg3 (50 μg/ml) plus Ad-CaM, respectively. At 48 hours after treatment, cell viability was assessed by MTT assay, cell apoptosis by flow cytometry, cell invasive capacity by trans-well assay, CaM, Iκ B, CaMKⅡ and NF-κ B protein contents by Western blotting analysis. Results: Compared with vehicle control, Rg3 significantly promoted apoptosis and inhibited proliferation and invasion of BGC-823 cells (P<0.05), while Ad-CaM and Rg3+Ad-CaM significantly inhibited apoptosis and promoted proliferation and invasion of BGC-823 cells (P<0.05). At the protein level, the expression of NF-κ B and CaMKⅡ was significantly downregulated whereas the expression of IκBα was significantly in Rg3-treated BGC-823 cells (P<0.05), and the expression of NF-κ B and CaMKⅡ was significantly enhanced whereas the expression of IκBα was significantly inhibited in cells treated with Ad-CaM and Rg3 plus Ad-CaM respectively (P<0.05), as compared with control cells. Conclusion: Rg3 may inhibit proliferation and invasion and promote apoptosis of gastric cancer cells through downregulation of CaM kinase expression and inactivation of NF-κ B.
Objective: To study whether and how ginsenoside Rg3 regulate apoptosis of gastric cancer BGC-823 cells. Methods: BGC-823 cells were treated with vehicle (control), Rg3 (50 μg/ml), Ad-CaM, and Rg3 (50 μg/ml) plus Ad-CaM, respectively. At 48 hours after treatment, cell viability was assessed by MTT assay, cell apoptosis by flow cytometry, cell invasive capacity by trans-well assay, CaM, Iκ B, CaMKⅡ and NF-κ B protein contents by Western blotting analysis. Results: Compared with vehicle control, Rg3 significantly promoted apoptosis and inhibited proliferation and invasion of BGC-823 cells (P<0.05), while Ad-CaM and Rg3+Ad-CaM significantly inhibited apoptosis and promoted proliferation and invasion of BGC-823 cells (P<0.05). At the protein level, the expression of NF-κ B and CaMKⅡ was significantly downregulated whereas the expression of IκBα was significantly in Rg3-treated BGC-823 cells (P<0.05), and the expression of NF-κ B and CaMKⅡ was significantly enhanced whereas the expression of IκBα was significantly inhibited in cells treated with Ad-CaM and Rg3 plus Ad-CaM respectively (P<0.05), as compared with control cells. Conclusion: Rg3 may inhibit proliferation and invasion and promote apoptosis of gastric cancer cells through downregulation of CaM kinase expression and inactivation of NF-κ B.
2015, 22(2):230-235.
DOI: 10.3872/j.issn.1007-385X.2015.2.016
Abstract:
Objective: To determine the effect of the growth differentiation factor 15 (GDF15) gene in resistance of glioma cells to chemotherapeutic agents cisplatin (DDP) and teniposide (Vumon, VM-26) in vitro. Methods: Glioma U373 cells were infected with a lentiviral vector expressing a small hairpin RNA targeting the GDF15 gene (LV-GDF15-RNAi) and a control lentiviral vector (LV-RNAi), respectively. Stably infected cells were then treated with VM-26 (01, 0.5, 2.5 and 12.5 μg/ml) and DDP (0.08, 0.4, 2 and 10 μg/ml). After treatment for 48 h, cell viability was assessed by MTT assay and Hoechst/PI staining to evaluate differences in resistance to VM-26 and DDP, and changes in Bcl-2, Bcl-xL, P53 and caspase-3 proteins were analyzed by Western blotting. Results: GDF15 protein content was significantly lower in LV-GDF15-RNAi-infected U373 cells (0.013±0.001) than in LV-RNAi-infected (0.622±0.068) and wild-type U373 cells (0.601±0.004) (P<0.01); survival rate was significantly different between LV-GDF15-RNAi-infected (91.84±2.64)% and LV-RNAi-infected (80.71±2.66)% in the presence of VM-26 and DDP at the lowest concentrations used (P<0.01) and the difference became more significant as the concentrations were increasing. Under the treatment with VM-26 or DDP at the same concentration, the number of apoptotic cells was significantly lower in LV-GDF15-RNAi-infected cells than that in LV-RNAi-infected cells (P<0.05). In association with changes in apoptosis, protein levels of Bcl-2 and Bcl-xL were significantly higher (P<0.05) but protein levels of P53 and caspase-3 were significantly lower (P<0.01) in LV-GFD 15-RNAi-infected cells than in LV-RNAi-infected cells. Conclusion: Down-regulation of the GDF15 gene may increase the resistance of glioma cells to VM-26 and DDP, possibly through regulating the expression of Bcl-2, Bcl-xL, P53and caspase-3.
Objective: To determine the effect of the growth differentiation factor 15 (GDF15) gene in resistance of glioma cells to chemotherapeutic agents cisplatin (DDP) and teniposide (Vumon, VM-26) in vitro. Methods: Glioma U373 cells were infected with a lentiviral vector expressing a small hairpin RNA targeting the GDF15 gene (LV-GDF15-RNAi) and a control lentiviral vector (LV-RNAi), respectively. Stably infected cells were then treated with VM-26 (01, 0.5, 2.5 and 12.5 μg/ml) and DDP (0.08, 0.4, 2 and 10 μg/ml). After treatment for 48 h, cell viability was assessed by MTT assay and Hoechst/PI staining to evaluate differences in resistance to VM-26 and DDP, and changes in Bcl-2, Bcl-xL, P53 and caspase-3 proteins were analyzed by Western blotting. Results: GDF15 protein content was significantly lower in LV-GDF15-RNAi-infected U373 cells (0.013±0.001) than in LV-RNAi-infected (0.622±0.068) and wild-type U373 cells (0.601±0.004) (P<0.01); survival rate was significantly different between LV-GDF15-RNAi-infected (91.84±2.64)% and LV-RNAi-infected (80.71±2.66)% in the presence of VM-26 and DDP at the lowest concentrations used (P<0.01) and the difference became more significant as the concentrations were increasing. Under the treatment with VM-26 or DDP at the same concentration, the number of apoptotic cells was significantly lower in LV-GDF15-RNAi-infected cells than that in LV-RNAi-infected cells (P<0.05). In association with changes in apoptosis, protein levels of Bcl-2 and Bcl-xL were significantly higher (P<0.05) but protein levels of P53 and caspase-3 were significantly lower (P<0.01) in LV-GFD 15-RNAi-infected cells than in LV-RNAi-infected cells. Conclusion: Down-regulation of the GDF15 gene may increase the resistance of glioma cells to VM-26 and DDP, possibly through regulating the expression of Bcl-2, Bcl-xL, P53and caspase-3.
2015, 22(2):236-239.
DOI: 10.3872/j.issn.1007-385X.2015.2.017
Abstract:
Objective: To create a mouse xenograft model of esophageal squamous cancer by coinjection of tumor cells with matrigel and to determine the anti-tumor and anti-angiogenic effects of PI-88 using this model. Methods: Nude mice were co-injected with human esophageal cancer TE-13 cells and matrigel subcutaneously. They were then randomized to receive subcutaneously physical saline (n=4, 20 ml/\[kg?day\]) as controls and PI-88 (n=4, 20 mg/\[kg?day\]) as test treatment, respectively. At day 2, 6, 10, 14 d after the last dose, contrast enhanced CT scans were performed on the xenograft region and xenograft tumor specimens were collected for analyses of heparanase (HPSE) and vascular endothelial growth factor(VEGF), respectively, by S-P staining and histoimmunological staining. Results: Xenograft tumors were formed on the same day of tumor cell injection in 8 mice. On post-treatment d 14, the volume of xenograft tumors was significantly reduced in the PI-88 treatment group (70.25±6.85 mm3) than in the I-88 treatment group (143.13±1718) (P<0.05). On d 15, CT value was significantly lower in the PI-88 treatment group (15.18±0.91 mm2) than in the control group (19.23±2.03 mm2) (P<0.05), and staining signals for both HPSE (28.70±6.39 vs 87.55±22.03, P<0.01) and VEGF (47.10±8.18 vs 94.40±14.47, P<0.01) in the control group than in the treat group. Conclusions: Co-injection of xenograft tumor cells with matrigel may offer a reliable and more efficient approach of establishing animal models of esophageal cancer. PI-88 may inhibit esophageal tumor growth and angiogenesis, possibly, through VEGF- and HPSE-dependent mechanisms.
Objective: To create a mouse xenograft model of esophageal squamous cancer by coinjection of tumor cells with matrigel and to determine the anti-tumor and anti-angiogenic effects of PI-88 using this model. Methods: Nude mice were co-injected with human esophageal cancer TE-13 cells and matrigel subcutaneously. They were then randomized to receive subcutaneously physical saline (n=4, 20 ml/\[kg?day\]) as controls and PI-88 (n=4, 20 mg/\[kg?day\]) as test treatment, respectively. At day 2, 6, 10, 14 d after the last dose, contrast enhanced CT scans were performed on the xenograft region and xenograft tumor specimens were collected for analyses of heparanase (HPSE) and vascular endothelial growth factor(VEGF), respectively, by S-P staining and histoimmunological staining. Results: Xenograft tumors were formed on the same day of tumor cell injection in 8 mice. On post-treatment d 14, the volume of xenograft tumors was significantly reduced in the PI-88 treatment group (70.25±6.85 mm3) than in the I-88 treatment group (143.13±1718) (P<0.05). On d 15, CT value was significantly lower in the PI-88 treatment group (15.18±0.91 mm2) than in the control group (19.23±2.03 mm2) (P<0.05), and staining signals for both HPSE (28.70±6.39 vs 87.55±22.03, P<0.01) and VEGF (47.10±8.18 vs 94.40±14.47, P<0.01) in the control group than in the treat group. Conclusions: Co-injection of xenograft tumor cells with matrigel may offer a reliable and more efficient approach of establishing animal models of esophageal cancer. PI-88 may inhibit esophageal tumor growth and angiogenesis, possibly, through VEGF- and HPSE-dependent mechanisms.
2015, 22(2):240-245.
DOI: 10.3872/j.issn.1007-385X.2015.2.018
Abstract:
Objective: To evaluate changes in and prognostic value of CD8+ T cells in the peripheral blood of melanoma patients treated with GM-CSF modified tumor cell vaccine (GVAX). Methods: Fifty-six patients with melanoma who underwent GVAX treatment in the Cancer Institute of Tianjing Medical University between October, 2007 and December, 2012 were enrolled in the study. Proportions of CD3+ lymphocytes, CD4+ T cells, CD8+ T cells, regulatory T lymphocytes (Treg), natural killer cells(NK) and dendritic cell (DC1,DC2) before and after GVAX vaccination treatment were determined by flow cytometry. The relationship between the proportion of CD8+ T cells and other immune cells with patient survival at different post-treatment time points was analyzed. Results: The proportion of CD8+ T cells in peripheral blood was significantly higher (P=0.006) after GVAX treatment (37.56±12.76%) than that before the treatment (3471±12.30%). GVAX treatment resulted in significant decreases in the proportion of CD4+ T cells (P=0.017) and the ratio of CD4+ /CD8+ (P=0.009) but showed no significant effect on the proportions of NK cells, Treg cells, DC1 and DC2 cells (P>0.05). Advanced melanoma patients with a proportion of CD8+ T cells above the mean value before vaccination had better overall survival (29.16 months) compared with those with a lower proportion of CD8+ T cells (1334 months) (P=0.012). Conclusion: GVAX can enhance the ability of CD8+ T cells to induce antitumor immunity. A high proportion of CD8+ T cells before GVAX vaccination is a predictor of better prognosis for patients with advanced melanoma.
Objective: To evaluate changes in and prognostic value of CD8+ T cells in the peripheral blood of melanoma patients treated with GM-CSF modified tumor cell vaccine (GVAX). Methods: Fifty-six patients with melanoma who underwent GVAX treatment in the Cancer Institute of Tianjing Medical University between October, 2007 and December, 2012 were enrolled in the study. Proportions of CD3+ lymphocytes, CD4+ T cells, CD8+ T cells, regulatory T lymphocytes (Treg), natural killer cells(NK) and dendritic cell (DC1,DC2) before and after GVAX vaccination treatment were determined by flow cytometry. The relationship between the proportion of CD8+ T cells and other immune cells with patient survival at different post-treatment time points was analyzed. Results: The proportion of CD8+ T cells in peripheral blood was significantly higher (P=0.006) after GVAX treatment (37.56±12.76%) than that before the treatment (3471±12.30%). GVAX treatment resulted in significant decreases in the proportion of CD4+ T cells (P=0.017) and the ratio of CD4+ /CD8+ (P=0.009) but showed no significant effect on the proportions of NK cells, Treg cells, DC1 and DC2 cells (P>0.05). Advanced melanoma patients with a proportion of CD8+ T cells above the mean value before vaccination had better overall survival (29.16 months) compared with those with a lower proportion of CD8+ T cells (1334 months) (P=0.012). Conclusion: GVAX can enhance the ability of CD8+ T cells to induce antitumor immunity. A high proportion of CD8+ T cells before GVAX vaccination is a predictor of better prognosis for patients with advanced melanoma.
2015, 22(2):246-251.
DOI: 10.3872/j.issn.1007-385X.2015.2.019
Abstract:
Objective: To establish a nude mice xenograft model of fluorescently tagged-colorectal cancer overexpression of hypoxia-inducible factor-1α (HIF-1α). Methods: Four human colorectal cancer cell lines, SW480, SW620, LOVO and HCT116, were treated with CoCl2, and the one that remained HIF-1α-negative under CoCl2 induction was chosen. The selected cell line was infected with a lentiviral vector overexpressing HIF-1α and EGFP, Lenti-HIF1α-EGFP. Infected cells underwent puromycin selection. Cells stably expressing HIF-1α and EGFP. HIF-1α, confirmed by Western blotting, were used in transwell assay of migration in vitro and injected intraperitoneally into nude mice to create a xenograft model of colorectal cancer in vivo. Results: After CoCl2 induction, only SW480 remained HIF-1α-negative and was thus selected. SW480 cells stably overexpressing HIF-1α and EGFP had enhanced migration ability (250±11) as compared with control Sw480 cells (50±5) (P<0.01). The number of tumor nodules formed on the abdominal wall was significantly higher in mice injected with SW480 cells overexpressing HIF-1α (15±4) than in mice injected with control cells (4±1) (P<0.05). Conclusion: Injection of endogenously HIF-1α-negative colorectal cancer SW480 cells infected by a lentiviral vector overexpressing HIF-1α and EGFP into nude mice would provide a feasible approach of creating a xenograft model of fluorescently visible colorectal cancer for investigations on the function of HIF-1α in the pathogenesis of colorectal cancer.
Objective: To establish a nude mice xenograft model of fluorescently tagged-colorectal cancer overexpression of hypoxia-inducible factor-1α (HIF-1α). Methods: Four human colorectal cancer cell lines, SW480, SW620, LOVO and HCT116, were treated with CoCl2, and the one that remained HIF-1α-negative under CoCl2 induction was chosen. The selected cell line was infected with a lentiviral vector overexpressing HIF-1α and EGFP, Lenti-HIF1α-EGFP. Infected cells underwent puromycin selection. Cells stably expressing HIF-1α and EGFP. HIF-1α, confirmed by Western blotting, were used in transwell assay of migration in vitro and injected intraperitoneally into nude mice to create a xenograft model of colorectal cancer in vivo. Results: After CoCl2 induction, only SW480 remained HIF-1α-negative and was thus selected. SW480 cells stably overexpressing HIF-1α and EGFP had enhanced migration ability (250±11) as compared with control Sw480 cells (50±5) (P<0.01). The number of tumor nodules formed on the abdominal wall was significantly higher in mice injected with SW480 cells overexpressing HIF-1α (15±4) than in mice injected with control cells (4±1) (P<0.05). Conclusion: Injection of endogenously HIF-1α-negative colorectal cancer SW480 cells infected by a lentiviral vector overexpressing HIF-1α and EGFP into nude mice would provide a feasible approach of creating a xenograft model of fluorescently visible colorectal cancer for investigations on the function of HIF-1α in the pathogenesis of colorectal cancer.
2015, 22(2):252-254.
DOI: 10.3872/j.issn.1007-385X.2015.2.020
Abstract:
2015, 22(2):255-258.
DOI: 10.3872/j.issn.1007-385X.2015.2.021
Abstract:
肿瘤干细胞（cancer stem cell，CSC）是肿瘤组织中一小部分具有自我更新、无限增殖能力和多向分化潜能的肿瘤细胞，是肿瘤发生、发展的根源，也可能是起始肿瘤转移发生的根本原因。由细胞外基质（extra cellular matrix，ECM）、血管微环境和骨髓微环境等组成了复杂的CSC微环境，为CSC的生长提供条件；同时，CSC还能招募、激活间充质干细胞等特殊类型的细胞形成适合CSC生长的微环境。并且，CSC微环境能分泌低氧诱导因子（hypoxia-inducible factor，HIF）、IL-1β等细胞因子，激活相关信号通路，通过诱导血管生成及抑制免疫等途径参与CSC的侵袭、转移等。近年来，靶向CSC微环境治疗肿瘤转移逐渐引起了研究人员的注意，尝试靶向一些分子和通路，如IL-6、IL-8及其受体、核因子-κB（nuclear factor-κB，NF-κB）和乙醛脱氢酶1（aldehyde dehydrogenase 1，ALDH1）等，借此抑制卵巢癌、乳腺癌中CSC的增殖，已经取得了一定成果。因此，针对CSC及其微环境的干扰的治疗将可能成为肿瘤治疗的新方向。
肿瘤干细胞（cancer stem cell，CSC）是肿瘤组织中一小部分具有自我更新、无限增殖能力和多向分化潜能的肿瘤细胞，是肿瘤发生、发展的根源，也可能是起始肿瘤转移发生的根本原因。由细胞外基质（extra cellular matrix，ECM）、血管微环境和骨髓微环境等组成了复杂的CSC微环境，为CSC的生长提供条件；同时，CSC还能招募、激活间充质干细胞等特殊类型的细胞形成适合CSC生长的微环境。并且，CSC微环境能分泌低氧诱导因子（hypoxia-inducible factor，HIF）、IL-1β等细胞因子，激活相关信号通路，通过诱导血管生成及抑制免疫等途径参与CSC的侵袭、转移等。近年来，靶向CSC微环境治疗肿瘤转移逐渐引起了研究人员的注意，尝试靶向一些分子和通路，如IL-6、IL-8及其受体、核因子-κB（nuclear factor-κB，NF-κB）和乙醛脱氢酶1（aldehyde dehydrogenase 1，ALDH1）等，借此抑制卵巢癌、乳腺癌中CSC的增殖，已经取得了一定成果。因此，针对CSC及其微环境的干扰的治疗将可能成为肿瘤治疗的新方向。
2015, 22(2):259-264.
DOI: 10.3872/j.issn.1007-385X.2015.2.022
Abstract:
近年来，非小细胞肺癌（non small cell lung cancer, NSCLC）在手术、放疗、化疗等方面均取得了很大进展，但NSCLC患者5年生存率仍只有15%，因此探索NSCLC新的治疗模式尤为重要。免疫治疗以其低毒、高效等特点成为当前肿瘤治疗的重要手段。检查点抑制剂作为新型抗肿瘤免疫治疗药物，通过阻断T细胞的负性信号传递使其大量活化增值，增强机体的抗肿瘤免疫功能，显现出了良好的抗瘤效果。目前，细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte associated antigen 4, CTLA-4)、程序性细胞死亡蛋白1（programmed death-1，PD-1)及其受体PD-L1、淋巴细胞活化基因-3分子(lymphocyte activation gene- 3, LAG-3, CD223)和T细胞免疫球蛋白3（T-cell immunoglobulin and mucin-domain-containing molecule 3, TIM-3)等分子的抑制剂均在NSCLC中开展了广泛的研究。在治疗NSCLC的临床试验中，检查点抑制剂Ipilimumab、Nivoluma等取得了一定的成功，前景值得期待。
近年来，非小细胞肺癌（non small cell lung cancer, NSCLC）在手术、放疗、化疗等方面均取得了很大进展，但NSCLC患者5年生存率仍只有15%，因此探索NSCLC新的治疗模式尤为重要。免疫治疗以其低毒、高效等特点成为当前肿瘤治疗的重要手段。检查点抑制剂作为新型抗肿瘤免疫治疗药物，通过阻断T细胞的负性信号传递使其大量活化增值，增强机体的抗肿瘤免疫功能，显现出了良好的抗瘤效果。目前，细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte associated antigen 4, CTLA-4)、程序性细胞死亡蛋白1（programmed death-1，PD-1)及其受体PD-L1、淋巴细胞活化基因-3分子(lymphocyte activation gene- 3, LAG-3, CD223)和T细胞免疫球蛋白3（T-cell immunoglobulin and mucin-domain-containing molecule 3, TIM-3)等分子的抑制剂均在NSCLC中开展了广泛的研究。在治疗NSCLC的临床试验中，检查点抑制剂Ipilimumab、Nivoluma等取得了一定的成功，前景值得期待。
2015, 22(2):265-271.
DOI: 10.3872/j.issn.1007-385X.2015.2.023
Abstract:
目前，对包括多形性成胶质细胞瘤在内的脑肿瘤的治疗效果不佳。血脑屏障限制了放化疗药物以有效的浓度到达肿瘤细胞。常用的方法是通过外科手术切除大部分肿块及对浸润部分的辅助治疗，以多功能纳米粒子为基础的药物输送系统（drug delivery system, DDS）的发展为实体脑肿瘤的诊断和治疗提供了新的思路。以氧化铁、量子点等为代表的纳米粒子可以作为核磁共振成像（magnetic resonance imaging，MRI）探针、光学探针以及结合多种成像方法的探针为实体脑肿瘤的诊断提供更加敏感的分辨能力和更加清晰的成像。此外，多柔比星、紫杉醇等化疗药物的肿瘤内输送，也从最初的脂质体转运系统和多聚物组成的非磷脂纳米粒逐步发展到兼具多种功能的新型纳米粒子转运治疗系统。通过改变其大小、组成和表面化学性质，纳米粒子能够发展成为结合检测、成像、药物靶向导入的多功能平台，尤其是靶向分子修饰的纳米粒子，在实体脑肿瘤的治疗中具有极大的发展前景。本文针对利用纳米粒子进行诊断和治疗脑肿瘤的最新研究进展作一综述，并展望其在肿瘤治疗领域的发展前景。
目前，对包括多形性成胶质细胞瘤在内的脑肿瘤的治疗效果不佳。血脑屏障限制了放化疗药物以有效的浓度到达肿瘤细胞。常用的方法是通过外科手术切除大部分肿块及对浸润部分的辅助治疗，以多功能纳米粒子为基础的药物输送系统（drug delivery system, DDS）的发展为实体脑肿瘤的诊断和治疗提供了新的思路。以氧化铁、量子点等为代表的纳米粒子可以作为核磁共振成像（magnetic resonance imaging，MRI）探针、光学探针以及结合多种成像方法的探针为实体脑肿瘤的诊断提供更加敏感的分辨能力和更加清晰的成像。此外，多柔比星、紫杉醇等化疗药物的肿瘤内输送，也从最初的脂质体转运系统和多聚物组成的非磷脂纳米粒逐步发展到兼具多种功能的新型纳米粒子转运治疗系统。通过改变其大小、组成和表面化学性质，纳米粒子能够发展成为结合检测、成像、药物靶向导入的多功能平台，尤其是靶向分子修饰的纳米粒子，在实体脑肿瘤的治疗中具有极大的发展前景。本文针对利用纳米粒子进行诊断和治疗脑肿瘤的最新研究进展作一综述，并展望其在肿瘤治疗领域的发展前景。
2015, 22(2):272-275.
DOI: 10.3872/j.issn.1007-385X.2015.2.024
Abstract:
2型转谷氨酰胺酶 (transglutaminase 2, TG2)是转谷氨酰胺酶家族成员之一，其作为一种多功能酶可通过激活多条信号通路（如PI3K/AKT途径、NF-κB途径、mTOR途径、RAS/MAPK途径等）调控肿瘤（如胰腺癌、肠癌、肝癌等）发生、发展、侵袭及耐药，在妇科肿瘤尤其是宫颈癌及卵巢癌的病理生理进程中可能也扮演了重要的角色，但具体机制尚不清楚。故本文通过对TG2结构和分布、活性调控以及当前关于TG2在宫颈癌和卵巢癌的研究进展进行综述，为宫颈癌及卵巢癌的治疗提供一些新的思路。
2型转谷氨酰胺酶 (transglutaminase 2, TG2)是转谷氨酰胺酶家族成员之一，其作为一种多功能酶可通过激活多条信号通路（如PI3K/AKT途径、NF-κB途径、mTOR途径、RAS/MAPK途径等）调控肿瘤（如胰腺癌、肠癌、肝癌等）发生、发展、侵袭及耐药，在妇科肿瘤尤其是宫颈癌及卵巢癌的病理生理进程中可能也扮演了重要的角色，但具体机制尚不清楚。故本文通过对TG2结构和分布、活性调控以及当前关于TG2在宫颈癌和卵巢癌的研究进展进行综述，为宫颈癌及卵巢癌的治疗提供一些新的思路。
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.