Granulocyte colony-stimulating factor （G-CSF） is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells （MDSCs） promote neoplastic progression...Granulocyte colony-stimulating factor （G-CSF） is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells （MDSCs） promote neoplastic progression through multiple mechanisms by immune suppression. Despite the findings of G-CSF function in colon cancer progression, the precise mechanism of G-CSF on MDSCs regulation and its blockade effects on tumor growth remains a worthy area of investigation. In this study we observed an overexpression of G-CSF in a mouse colitis-associated cancer （CAC） model, which was consistent with the accumulation of MDSCs in mouse colon tissues. Further in vitro studies demonstrated that G-CSF could promote MDSCs survival and activation through signal transducer and activator of transcription 3 （STAT3） signaling pathway. Moreover, compared with isotype control, anti-G-CSF mAb treatment demonstrated reduced MDSC accumulation, which led to a marked decrease in neoplasm size and number in mice. Our results indicated that G-CSF is a critical regulating molecule in the migration, proliferation and function maintenance of MDSCs, which could be a potential therapeutic target for cancer.展开更多
This study includes three aspects:(1) we have reported some novel or rare mutations of SOD1(Cu/Zn superoxide dismutase) gene in Chinese families of ALS/MND,and found quite different features from Western patients in p...This study includes three aspects:(1) we have reported some novel or rare mutations of SOD1(Cu/Zn superoxide dismutase) gene in Chinese families of ALS/MND,and found quite different features from Western patients in polymorphisms with some candidate genes such as vascular endothelial growth factor(VEGF) in sporadic ALS/MND in China.Meanwhile,we have so for established a complete clinical database with more than 1 200 cases;(2) we have established some neurophysiologic techniques of diagnosis and differential diagnosis at early-stage for ALS/MND,which include trigemino-cervical response,sternocleidomastoid and rectus electromyography,contact heat evoked potentials,and motor unit number estimate;(3) we have attempted some experimental and clinical treatments for ALS/MND,which include gene and stem cell therapies in animal models,and a pilot clinical trial of granulocyte colony stimulating factor(G-CSF) for ALS/MND patients(NCT00397423).Abstract:SUMM ARY This study includes three aspects:(1) we have reported some novel or rare mutations of SOD1(Cu /Zn superoxide d ismutase) gene in Chinese fam ilies ofALS /MND,and found quite d ifferent features from W estern patients in polymorphisms with some cand idate genes such as vascular endothelial growth factor(VEGF) in sporad ic ALS /MND in China.Meanwhile,we have so for established a com-plete clinical database with more than 1 200 cases;(2) we have established some neurophysiologic tech-niques of d iagnosis and d ifferential d iagnosis at early-stage forALS /MND,which include trigem ino-cervi-cal response,sternocleidomastoid and rectus electromyography,contact heat evoked potentials,and motor unit number estimate;(3) we have attempted some experimental and clinical treatments forALS /MND,which include gene and stem cell therapies in animalmodels,and a pilot clinical trial of granulocyte colo-ny stimulating factor(G-CSF) forALS /MND patients(NCT00397423).展开更多
Granulocyte-macrophage colony-stimulating factor （GM-CSF） is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukoc...Granulocyte-macrophage colony-stimulating factor （GM-CSF） is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukocytes. It is produced by a variety of cell types including T cells, macrophages, endothelial cells and fibroblasts upon receiving immune stimuli. Although GM-CSF is produced locally, it can act in a paracrine fashion to recruit circulating neutrophils, monocytes and lymphocytes to enhance their functions in host defense. Recent intensive investigations are centered on the application of GM-CSF as an immune adjuvant for its ability to increase dendritic cell （DC） maturation and function as well as macrophage activity. It is used clinically to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. Interestingly, the hematopoietic system of GM-CSF-deficient mice appears to be normal; the most significant changes are in some specific T cell responses. Although molecular cloning of GM-CSF was carried out using cDNA library oft cells and it is well known that the T cells produce GM-CSF after activation, there is a lack of systematic investigation of this cytokine in production by T cells and its effect on T cell function. In this article, we will focus mainly on the immunobiology of GM-CSF in T cells.展开更多
基金We thank all study participants for their contributions to this project. This work was supported by the National Basic Research Program （973 Program） （No. 2014CB542103）, Beijing Natural Science Foundation of China （Grant no.7144237）, The Beijing Training Project for The Leading Talents （Z131107000513001）, Beijing Nova Program （Z131107000413066） and the National Natural Science Foundation of China （Grant No. 81541154）.
文摘Granulocyte colony-stimulating factor （G-CSF） is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells （MDSCs） promote neoplastic progression through multiple mechanisms by immune suppression. Despite the findings of G-CSF function in colon cancer progression, the precise mechanism of G-CSF on MDSCs regulation and its blockade effects on tumor growth remains a worthy area of investigation. In this study we observed an overexpression of G-CSF in a mouse colitis-associated cancer （CAC） model, which was consistent with the accumulation of MDSCs in mouse colon tissues. Further in vitro studies demonstrated that G-CSF could promote MDSCs survival and activation through signal transducer and activator of transcription 3 （STAT3） signaling pathway. Moreover, compared with isotype control, anti-G-CSF mAb treatment demonstrated reduced MDSC accumulation, which led to a marked decrease in neoplasm size and number in mice. Our results indicated that G-CSF is a critical regulating molecule in the migration, proliferation and function maintenance of MDSCs, which could be a potential therapeutic target for cancer.
文摘This study includes three aspects:(1) we have reported some novel or rare mutations of SOD1(Cu/Zn superoxide dismutase) gene in Chinese families of ALS/MND,and found quite different features from Western patients in polymorphisms with some candidate genes such as vascular endothelial growth factor(VEGF) in sporadic ALS/MND in China.Meanwhile,we have so for established a complete clinical database with more than 1 200 cases;(2) we have established some neurophysiologic techniques of diagnosis and differential diagnosis at early-stage for ALS/MND,which include trigemino-cervical response,sternocleidomastoid and rectus electromyography,contact heat evoked potentials,and motor unit number estimate;(3) we have attempted some experimental and clinical treatments for ALS/MND,which include gene and stem cell therapies in animal models,and a pilot clinical trial of granulocyte colony stimulating factor(G-CSF) for ALS/MND patients(NCT00397423).Abstract:SUMM ARY This study includes three aspects:(1) we have reported some novel or rare mutations of SOD1(Cu /Zn superoxide d ismutase) gene in Chinese fam ilies ofALS /MND,and found quite d ifferent features from W estern patients in polymorphisms with some cand idate genes such as vascular endothelial growth factor(VEGF) in sporad ic ALS /MND in China.Meanwhile,we have so for established a com-plete clinical database with more than 1 200 cases;(2) we have established some neurophysiologic tech-niques of d iagnosis and d ifferential d iagnosis at early-stage forALS /MND,which include trigem ino-cervi-cal response,sternocleidomastoid and rectus electromyography,contact heat evoked potentials,and motor unit number estimate;(3) we have attempted some experimental and clinical treatments forALS /MND,which include gene and stem cell therapies in animalmodels,and a pilot clinical trial of granulocyte colo-ny stimulating factor(G-CSF) forALS /MND patients(NCT00397423).
文摘Granulocyte-macrophage colony-stimulating factor （GM-CSF） is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukocytes. It is produced by a variety of cell types including T cells, macrophages, endothelial cells and fibroblasts upon receiving immune stimuli. Although GM-CSF is produced locally, it can act in a paracrine fashion to recruit circulating neutrophils, monocytes and lymphocytes to enhance their functions in host defense. Recent intensive investigations are centered on the application of GM-CSF as an immune adjuvant for its ability to increase dendritic cell （DC） maturation and function as well as macrophage activity. It is used clinically to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. Interestingly, the hematopoietic system of GM-CSF-deficient mice appears to be normal; the most significant changes are in some specific T cell responses. Although molecular cloning of GM-CSF was carried out using cDNA library oft cells and it is well known that the T cells produce GM-CSF after activation, there is a lack of systematic investigation of this cytokine in production by T cells and its effect on T cell function. In this article, we will focus mainly on the immunobiology of GM-CSF in T cells.
