Objective： Imatinib has dramatically altered the options for management of patients with gastrointestinal stromal turnouts. However, it has become clear that secondary resistance to the drug develops during long- ter...Objective： Imatinib has dramatically altered the options for management of patients with gastrointestinal stromal turnouts. However, it has become clear that secondary resistance to the drug develops during long- term therapy. The purpose of our study was to retrospectively analyze safety and long-term outcomes in Chinese patients with recurrent or metastatic GISTs treated with imatinib preoperatively. Methods： Between June 2003 and June 2011, 22 patients underwent surgery for recurrent or metastatic GISTs after preoperative treatment with imatinib. Results： Complete resection was accomplished in 8 of the 10 responsive disease （RD） patients （80%）, and in 3 of the 12 patients （25%） who had progression disease （PD）. The amount of blood loss during the operation in PD patients was higher than in RD patients. There was 1 hospital death in PD group related to surgery, while the other patients recovered with conservative therapy because complications were mild. The difference in median PFS between patients with RD and those with PD was significant （24.8 vs. 2.81 months, P〈0.001）. The difference in 2-year OS rate between patients with RE） and those with PD was not significant （100% vs. 87.5%, P〉0.05）. Conclusions： Our study indicates that surgical intervention can improve the PFS of Chinese patients with recurrent or metastatic GISTs responsive to imatinib, but does not prolong OS as well as in patients who develop imatinib resistance. Surgical resection following imatinib treatment is feasible and can be considered for patients with advanced GISTs responsive to imatinib.展开更多
SP100 is an antiviral protein that restricts the productive stage of human papillomavirus(HPV)and multiple other viruses,and viruses in turn block sUMO-1-mediated stabilization of SP100 and promotes its degradation(Ta...SP100 is an antiviral protein that restricts the productive stage of human papillomavirus(HPV)and multiple other viruses,and viruses in turn block sUMO-1-mediated stabilization of SP100 and promotes its degradation(Table S1).Interferon(IFN)signaling could still produce more SP100 through transcription to counteract viruses.1 Viruses also disable the transcriptional up-regulation of SP100 to achieve persistent infection in hosts.展开更多
Metastasis is a pivotal event that accelerates the prognosis of cancer patients towards mortality.Therapies that aim to induce cell death in metastatic cells require a more detailed understanding of the metastasis for...Metastasis is a pivotal event that accelerates the prognosis of cancer patients towards mortality.Therapies that aim to induce cell death in metastatic cells require a more detailed understanding of the metastasis for better mitigation.Towards this goal,we discuss the details of two distinct but overlapping pathways of metastasis:a classical reversible epithelial-to-mesenchymal transition(hybrid-EMT)-driven transport pathway and an alternative cell death process-driven blebbishield metastatic-witch(BMW)transport pathway involving reversible cell death process.The knowledge about the EMT and BMW pathways is important for the therapy of metastatic cancers as these pathways confer drug resistance coupled to immune evasion/suppression.We initiallydiscuss the EMT pathway and compare it with the BMW pathway in the contexts of coordinated oncogenic,metabolic,immunologic,and cell biological events that drive metastasis.In particular,we discuss how the cell death environment involving apoptosis,ferroptosis,necroptosis,and NETosis in BMW or EMT pathways recruits immune cells,fuses with it,migrates,permeabilizes vasculature,and settles at distant sites to establish metastasis.Finally,we discuss the therapeutic targets that are common to both EMT and BMW pathways.展开更多
文摘Objective： Imatinib has dramatically altered the options for management of patients with gastrointestinal stromal turnouts. However, it has become clear that secondary resistance to the drug develops during long- term therapy. The purpose of our study was to retrospectively analyze safety and long-term outcomes in Chinese patients with recurrent or metastatic GISTs treated with imatinib preoperatively. Methods： Between June 2003 and June 2011, 22 patients underwent surgery for recurrent or metastatic GISTs after preoperative treatment with imatinib. Results： Complete resection was accomplished in 8 of the 10 responsive disease （RD） patients （80%）, and in 3 of the 12 patients （25%） who had progression disease （PD）. The amount of blood loss during the operation in PD patients was higher than in RD patients. There was 1 hospital death in PD group related to surgery, while the other patients recovered with conservative therapy because complications were mild. The difference in median PFS between patients with RD and those with PD was significant （24.8 vs. 2.81 months, P〈0.001）. The difference in 2-year OS rate between patients with RE） and those with PD was not significant （100% vs. 87.5%, P〉0.05）. Conclusions： Our study indicates that surgical intervention can improve the PFS of Chinese patients with recurrent or metastatic GISTs responsive to imatinib, but does not prolong OS as well as in patients who develop imatinib resistance. Surgical resection following imatinib treatment is feasible and can be considered for patients with advanced GISTs responsive to imatinib.
基金supported in part by the National Institutes of Health under award number K08CA255933.
文摘SP100 is an antiviral protein that restricts the productive stage of human papillomavirus(HPV)and multiple other viruses,and viruses in turn block sUMO-1-mediated stabilization of SP100 and promotes its degradation(Table S1).Interferon(IFN)signaling could still produce more SP100 through transcription to counteract viruses.1 Viruses also disable the transcriptional up-regulation of SP100 to achieve persistent infection in hosts.
文摘Metastasis is a pivotal event that accelerates the prognosis of cancer patients towards mortality.Therapies that aim to induce cell death in metastatic cells require a more detailed understanding of the metastasis for better mitigation.Towards this goal,we discuss the details of two distinct but overlapping pathways of metastasis:a classical reversible epithelial-to-mesenchymal transition(hybrid-EMT)-driven transport pathway and an alternative cell death process-driven blebbishield metastatic-witch(BMW)transport pathway involving reversible cell death process.The knowledge about the EMT and BMW pathways is important for the therapy of metastatic cancers as these pathways confer drug resistance coupled to immune evasion/suppression.We initiallydiscuss the EMT pathway and compare it with the BMW pathway in the contexts of coordinated oncogenic,metabolic,immunologic,and cell biological events that drive metastasis.In particular,we discuss how the cell death environment involving apoptosis,ferroptosis,necroptosis,and NETosis in BMW or EMT pathways recruits immune cells,fuses with it,migrates,permeabilizes vasculature,and settles at distant sites to establish metastasis.Finally,we discuss the therapeutic targets that are common to both EMT and BMW pathways.
