Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.Wh...Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.While KIF18B overexpression in osteosarcoma tissue is clearly detected,its specific function in the disease process remains to be established.Methods:K IF18B expression was assessed in osteosarcoma tissues and cells.We additionally evaluated the effects of KIF18B on proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.Results:Our results showed overexpression of KIF18B in osteosarcoma tissues and cells.Knockdown of K IF18B induced G1/S phase arrest and significantly inhibited proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.K IF18B regulated P-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2 and at the post-transcriptional level by interacting with the adenomatous polyposis coli(APC)tumor suppressor gene in osteosarcoma cells.Conclusions:KIF18B plays a carcinogenic role in osteosarcoma by regulating expression ofβ-catenin transcriptionally via decreasing nuclear aggregation of ATF2 or post-transcriptionally through interactions with APC.Our collective findings support the potential utility of KIF18B as a novel prognostic biomarker for osteosarcoma.展开更多
Activating transcription factor 2(ATF2)is a member of the leucine zipper family of DNA binding proteins that are responsible for regulating various genes that play an essential role in major biological and cellular fu...Activating transcription factor 2(ATF2)is a member of the leucine zipper family of DNA binding proteins that are responsible for regulating various genes that play an essential role in major biological and cellular functions.Since ATF2 plays a vital role in cellular proliferation and apoptosis,it is believed that it greatly affects the development of breast cancers.However,its exact role in breast cancer is incompletely understood.It remains a subject of debate,ambiguity,and continuous research.Several studies have suggested the role of ATF2 as an oncogene,promoting cellular proliferation and worsening the outcome of cancers.In contrast,other studies have postulated that ATF2 plays a tumor suppressive role in estrogen receptor-positive breast cancer.The ambiguity surrounding its role in breast cancer is the reason why there is an influx of recent studies and research in this area.In this narrative review,we investigate several studies that have been published about the role of ATF2 in breast cancer.We also explore studies that have examined the association between ATF2 and endocrine therapy resistance.ATF2 has been suggested to modulate estrogen receptor(ER)expression and activity,potentially affecting tamoxifen sensitivity in breast cancer cells.Therefore,the role of ATF2 in DNA repair mechanisms and drug resistance has been deeply explored in this review.Additionally,there are numerous ongoing clinical trials exploring the effect of targeting ATF2 pathways and mechanisms on the outcome of breast cancers,some of which we have discussed.The studies and clinical trials that are being conducted to understand the multifaceted role of ATF2 and its signaling pathways may provide valuable insight for developing efficient targeted therapeutic solutions to enhance the outcomes of breast cancer and overcome endocrine resistance.We suggest further research to elucidate the dual roles of ATF2 in breast cancer and potential therapeutic therapies for its treatment.展开更多
The beam halo is a major issue for interaction region （IR） backgrounds at many colliders, for example, future linear colliders, B factories, and also it is an important problem at ATF2. In this paper, we report on t...The beam halo is a major issue for interaction region （IR） backgrounds at many colliders, for example, future linear colliders, B factories, and also it is an important problem at ATF2. In this paper, we report on the halo propagation along the ATF2 beam line with realistic apertures, the nonlinear optics influence on the increasing number of halo particles input is analyzed, and the transmitted halo particles distribution just before the last BPM is then described, the results from which will benefit the Compton recoil electrons measurement.展开更多
The ATF2 project is the final focus system prototype for the ILC and CLIC linear collider projects, with the purpose of reaching a 37nm vertical beam size at the interaction point. In the nanometer beam size regime, h...The ATF2 project is the final focus system prototype for the ILC and CLIC linear collider projects, with the purpose of reaching a 37nm vertical beam size at the interaction point. In the nanometer beam size regime, higher order multipoles in magnets become a crucial point for consideration. The strength and rotation angle of the ATF2 QEA magnets were reconstructed from the IHEP measurements and compared with the KEK ones to be identical. Based on the study of the skew multipoles sensitivity, we report on the analysis of the possible mitigation of the measured multipoles. A suggestion is given which will benefit the ATF2 present commissioning to reach the goal beam size, and also the reduced β optics in future.展开更多
The ATF2 project is the final focus system prototype for the ILC and CLIC linear collider projects, with a purpose of reaching a 37 nm vertical beam size at the interaction point （IP）. During the initial commissioni...The ATF2 project is the final focus system prototype for the ILC and CLIC linear collider projects, with a purpose of reaching a 37 nm vertical beam size at the interaction point （IP）. During the initial commissioning, we started with larger-than-nominal β-functions at the IP in order to reduce the effects from higher-order optical aberrations and thereby simplifying the optical corrections needed. We report on the simulation studies at two different IP locations developed based on waist scan, dispersion, coupling and β function multiknobs correction in the large β optics of ATF2, in the presence of two kinds of magnet inaccuracies （quadrupole gradient and roll errors） to generate all possible linear optic distortions at the IP. A vertical beam size which is very close to the nominal beam size is obtained based on the simulation study.展开更多
基金grants from the National Natural Science Foundation of China(Grant No.81802689)China International Medical Foundation(Grant No.Z-2014-06-15331)Conflict of interest。
文摘Objective:Osteosarcoma is a common primary highly malignant bone tumor.Kinesin family member 18B(K1F18B)has been identified as a potential oncogene involved in the development and metastasis of several cancer types.While KIF18B overexpression in osteosarcoma tissue is clearly detected,its specific function in the disease process remains to be established.Methods:K IF18B expression was assessed in osteosarcoma tissues and cells.We additionally evaluated the effects of KIF18B on proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.Results:Our results showed overexpression of KIF18B in osteosarcoma tissues and cells.Knockdown of K IF18B induced G1/S phase arrest and significantly inhibited proliferation,migration,and invasion of osteosarcoma cells,both in vitro and in vivo.K IF18B regulated P-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2 and at the post-transcriptional level by interacting with the adenomatous polyposis coli(APC)tumor suppressor gene in osteosarcoma cells.Conclusions:KIF18B plays a carcinogenic role in osteosarcoma by regulating expression ofβ-catenin transcriptionally via decreasing nuclear aggregation of ATF2 or post-transcriptionally through interactions with APC.Our collective findings support the potential utility of KIF18B as a novel prognostic biomarker for osteosarcoma.
文摘Activating transcription factor 2(ATF2)is a member of the leucine zipper family of DNA binding proteins that are responsible for regulating various genes that play an essential role in major biological and cellular functions.Since ATF2 plays a vital role in cellular proliferation and apoptosis,it is believed that it greatly affects the development of breast cancers.However,its exact role in breast cancer is incompletely understood.It remains a subject of debate,ambiguity,and continuous research.Several studies have suggested the role of ATF2 as an oncogene,promoting cellular proliferation and worsening the outcome of cancers.In contrast,other studies have postulated that ATF2 plays a tumor suppressive role in estrogen receptor-positive breast cancer.The ambiguity surrounding its role in breast cancer is the reason why there is an influx of recent studies and research in this area.In this narrative review,we investigate several studies that have been published about the role of ATF2 in breast cancer.We also explore studies that have examined the association between ATF2 and endocrine therapy resistance.ATF2 has been suggested to modulate estrogen receptor(ER)expression and activity,potentially affecting tamoxifen sensitivity in breast cancer cells.Therefore,the role of ATF2 in DNA repair mechanisms and drug resistance has been deeply explored in this review.Additionally,there are numerous ongoing clinical trials exploring the effect of targeting ATF2 pathways and mechanisms on the outcome of breast cancers,some of which we have discussed.The studies and clinical trials that are being conducted to understand the multifaceted role of ATF2 and its signaling pathways may provide valuable insight for developing efficient targeted therapeutic solutions to enhance the outcomes of breast cancer and overcome endocrine resistance.We suggest further research to elucidate the dual roles of ATF2 in breast cancer and potential therapeutic therapies for its treatment.
基金Supported by National Natural Science Foundation of China (11175192)Agence Nationale de la Recherche of the French Ministry of Research (Programme Blanc, Project ATF2-IN2P3-KEK, contract, ANR-06-BLAN-0027)
文摘The beam halo is a major issue for interaction region （IR） backgrounds at many colliders, for example, future linear colliders, B factories, and also it is an important problem at ATF2. In this paper, we report on the halo propagation along the ATF2 beam line with realistic apertures, the nonlinear optics influence on the increasing number of halo particles input is analyzed, and the transmitted halo particles distribution just before the last BPM is then described, the results from which will benefit the Compton recoil electrons measurement.
基金Supported by Agence Nationale de la Recherche of the French Ministry of Research(Programme Blanc,Project ATF2-IN2P3-KEK,contract,ANR-06-BLAN-0027)National Natural Science Foundation of China(11175192)support in part by the USDepartment of Energy(DE-AC02-76SF00515)
文摘The ATF2 project is the final focus system prototype for the ILC and CLIC linear collider projects, with the purpose of reaching a 37nm vertical beam size at the interaction point. In the nanometer beam size regime, higher order multipoles in magnets become a crucial point for consideration. The strength and rotation angle of the ATF2 QEA magnets were reconstructed from the IHEP measurements and compared with the KEK ones to be identical. Based on the study of the skew multipoles sensitivity, we report on the analysis of the possible mitigation of the measured multipoles. A suggestion is given which will benefit the ATF2 present commissioning to reach the goal beam size, and also the reduced β optics in future.
基金Supported by Agence Nationale de la Recherche of the French Ministry of Research (Programme Blanc, Project ATF2-IN2P3-KEK, contract ANR-06-BLAN-0027)National Natural Science Foundation of China (10775154, 10525525)
文摘The ATF2 project is the final focus system prototype for the ILC and CLIC linear collider projects, with a purpose of reaching a 37 nm vertical beam size at the interaction point （IP）. During the initial commissioning, we started with larger-than-nominal β-functions at the IP in order to reduce the effects from higher-order optical aberrations and thereby simplifying the optical corrections needed. We report on the simulation studies at two different IP locations developed based on waist scan, dispersion, coupling and β function multiknobs correction in the large β optics of ATF2, in the presence of two kinds of magnet inaccuracies （quadrupole gradient and roll errors） to generate all possible linear optic distortions at the IP. A vertical beam size which is very close to the nominal beam size is obtained based on the simulation study.
