MET gene alterations in lung cancer patients mainly include exon 14 skipping and gene amplification,which are the key therapeutic targets and drive resistance to tyrosine kinase inhibitors(TKls).1 However,the structur...MET gene alterations in lung cancer patients mainly include exon 14 skipping and gene amplification,which are the key therapeutic targets and drive resistance to tyrosine kinase inhibitors(TKls).1 However,the structural variants of MET,such as MET fusions,are much rarer(0.26%),as reported in a Chinese non-small cell lung cancer(NSCLC)cohort.2 Several recurrent MET fusions,such as KIF5B-MET and HLADRB1-MET,were reported as oncogenic drivers and showed favorable responses to crizotinib.展开更多
Distraction osteogenesis(DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immun...Distraction osteogenesis(DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.展开更多
Dear Editor,Lung cancer is one of the most common cancers worldwide and is associated with high mortality.Anaplastic lymphoma kinase(ALK)rearrangement,an oncogenic driver,has been identified in 5%to 6%of patients with...Dear Editor,Lung cancer is one of the most common cancers worldwide and is associated with high mortality.Anaplastic lymphoma kinase(ALK)rearrangement,an oncogenic driver,has been identified in 5%to 6%of patients with non-small cell lung cancer(NSCLC)[1].The first identified and the most common ALK fusion partner is echinoderm microtubule-associated protein-like 4(EML4)[2].With the broad application of next-generation sequencing(NGS),an increasing number of novel ALK fusions have been reported.Many ALK tyrosine kinase inhibitors(ALKTKIs),including crizotinib,brigatinib,ceritinib,and ensartinib,have been approved to treat ALK-positive NSCLC patients,and their efficacy may be affected by different ALK fusion variants[3].Here,we report two novel ALK fusions,MAPRE3-ALK and PKNOX2-ALK,detected by an NGS panel targeting 425 cancer-related genes(Nanjing Geneseeq Technology Inc.,Nanjing,Jiangsu,China)[4]in two metastatic lung adenocarcinoma patients who then received ALK-TKI treatments.The drug efficacy of the two novel fusions reported here could have significant referential value and provide useful therapeutic strategies for treating ALK-positive patients.展开更多
Neuroendocrine neoplasm of the pancreas is a rare tumor with limited treatment options.Among such tumors,treatment for pancreatic neuroendocrine tumor(PanNET)G3 is the most difficult.Temozolomide(TMZ)is commonly used ...Neuroendocrine neoplasm of the pancreas is a rare tumor with limited treatment options.Among such tumors,treatment for pancreatic neuroendocrine tumor(PanNET)G3 is the most difficult.Temozolomide(TMZ)is commonly used to treat PanNET.However,TMZ may cause tumor gene alkylation,which induces drug resistance and rapid disease progression.Herein,we present a case of a female who was diagnosed with PanNET G3 and achieved a partial response to toripalimab,an anti-programmed cell death-ligand 1(anti-PD-L1)monoclonal antibody,after multiple cycles of TMZ treatment.Genomic profiling revealed that compared with the patient’s samples collected at baseline,the postTMZ-treatment samples had markedly higher levels of tumor mutational burden(TMB)associated with characteristic alkylating mutational signature representing a positive correlation with favorable response to anti-PD-1 treatment.In addition,we observed a germline truncating mutation of MUTYH(W156*)that was considered to be pathogenic and potentially conferred to genomic instability.This case suggests that anti-PD-1 therapy could be a treatment option for PanNET patients with increased TMB after TMZ-based treatment.展开更多
基金approved by the Ethics Committee for the First Hospital of China Medical University(No.20180551230).
文摘MET gene alterations in lung cancer patients mainly include exon 14 skipping and gene amplification,which are the key therapeutic targets and drive resistance to tyrosine kinase inhibitors(TKls).1 However,the structural variants of MET,such as MET fusions,are much rarer(0.26%),as reported in a Chinese non-small cell lung cancer(NSCLC)cohort.2 Several recurrent MET fusions,such as KIF5B-MET and HLADRB1-MET,were reported as oncogenic drivers and showed favorable responses to crizotinib.
基金supported by grants from the National Key R&D Program of China (2016YFC1102800)National Natural Science Foundation of China (81879741, 51872332)+1 种基金Natural Science Foundation of Liaoning Province (20170541040)China Postdoctoral Science Foundation Grant (2020M681020)
文摘Distraction osteogenesis(DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.
文摘Dear Editor,Lung cancer is one of the most common cancers worldwide and is associated with high mortality.Anaplastic lymphoma kinase(ALK)rearrangement,an oncogenic driver,has been identified in 5%to 6%of patients with non-small cell lung cancer(NSCLC)[1].The first identified and the most common ALK fusion partner is echinoderm microtubule-associated protein-like 4(EML4)[2].With the broad application of next-generation sequencing(NGS),an increasing number of novel ALK fusions have been reported.Many ALK tyrosine kinase inhibitors(ALKTKIs),including crizotinib,brigatinib,ceritinib,and ensartinib,have been approved to treat ALK-positive NSCLC patients,and their efficacy may be affected by different ALK fusion variants[3].Here,we report two novel ALK fusions,MAPRE3-ALK and PKNOX2-ALK,detected by an NGS panel targeting 425 cancer-related genes(Nanjing Geneseeq Technology Inc.,Nanjing,Jiangsu,China)[4]in two metastatic lung adenocarcinoma patients who then received ALK-TKI treatments.The drug efficacy of the two novel fusions reported here could have significant referential value and provide useful therapeutic strategies for treating ALK-positive patients.
文摘Neuroendocrine neoplasm of the pancreas is a rare tumor with limited treatment options.Among such tumors,treatment for pancreatic neuroendocrine tumor(PanNET)G3 is the most difficult.Temozolomide(TMZ)is commonly used to treat PanNET.However,TMZ may cause tumor gene alkylation,which induces drug resistance and rapid disease progression.Herein,we present a case of a female who was diagnosed with PanNET G3 and achieved a partial response to toripalimab,an anti-programmed cell death-ligand 1(anti-PD-L1)monoclonal antibody,after multiple cycles of TMZ treatment.Genomic profiling revealed that compared with the patient’s samples collected at baseline,the postTMZ-treatment samples had markedly higher levels of tumor mutational burden(TMB)associated with characteristic alkylating mutational signature representing a positive correlation with favorable response to anti-PD-1 treatment.In addition,we observed a germline truncating mutation of MUTYH(W156*)that was considered to be pathogenic and potentially conferred to genomic instability.This case suggests that anti-PD-1 therapy could be a treatment option for PanNET patients with increased TMB after TMZ-based treatment.
