According to the 2019 World Health Organization(WHO)classification,welldifferentiated grade 3(G3)gastroenteropancreatic(GEP)neuroendocrine tumors(NETs)are a new category of cancer of the digestive system.G3 GEP-NET re...According to the 2019 World Health Organization(WHO)classification,welldifferentiated grade 3(G3)gastroenteropancreatic(GEP)neuroendocrine tumors(NETs)are a new category of cancer of the digestive system.G3 GEP-NET research and treatment are not as robust as those of lower grade(G1/2)NETs and poorly differentiated neuroendocrine carcinomas(NECs).Previously,the management of high-grade NETs was mainly based on NEC therapies,as highgrade NETs were classified as NECs under the previous WHO classification.Despite this,G3 GEP-NETs are significantly less responsive to platinum-based chemotherapy regimens than NECs,due to their distinct molecular pathogenesis and course of pathological grade transition.Patients with advanced G3 GEPNETs,who have progressed or are intolerant to chemotherapy regimens such as capecitabine plus temozolomide,have limited treatment choices.Immunotherapy has helped patients with a variety of cancers attain long-term survival through the use of immune checkpoint inhibitors.Immunotherapies,either alone or in combination with other therapies,do not have a clear function in the treatment of G3 GEP-NETs.Currently,the majority of immunotherapy studies,both prospective and retrospective,do not reliably differentiate G3 GEP-NETs from NECs.By contrast,a significant number of studies include non-GEP neuroendocrine neoplasms(NENs).Therefore,there is an urgent need to summarize and evaluate these data to provide more effective therapeutic approaches for patients with this rare tumor.The purpose of this mini-review was to screen and summarize information on G3 GEP-NETs from all studies on NENs immunotherapy.展开更多
Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration(IDD).Current limitations of stem cells include with their insufficient cell source,poor proliferation capacity,l...Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration(IDD).Current limitations of stem cells include with their insufficient cell source,poor proliferation capacity,low nucleus pulposus(NP)-specific differentiation potential,and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation.To address these challenges,embryo-derived long-term expandable nucleus pulposus progenitor cells(NPPCs)and esterase-responsive ibuprofen nano-micelles(PEG-PIB)were prepared for synergistic transplantation.In this study,we propose a biomaterial pre-modification cell strategy;the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis.The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro;their further synergistic transplantation yielded effective functional recovery,histological regeneration,and inhibition of pyroptosis during IDD regeneration.Herein,we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.展开更多
文摘According to the 2019 World Health Organization(WHO)classification,welldifferentiated grade 3(G3)gastroenteropancreatic(GEP)neuroendocrine tumors(NETs)are a new category of cancer of the digestive system.G3 GEP-NET research and treatment are not as robust as those of lower grade(G1/2)NETs and poorly differentiated neuroendocrine carcinomas(NECs).Previously,the management of high-grade NETs was mainly based on NEC therapies,as highgrade NETs were classified as NECs under the previous WHO classification.Despite this,G3 GEP-NETs are significantly less responsive to platinum-based chemotherapy regimens than NECs,due to their distinct molecular pathogenesis and course of pathological grade transition.Patients with advanced G3 GEPNETs,who have progressed or are intolerant to chemotherapy regimens such as capecitabine plus temozolomide,have limited treatment choices.Immunotherapy has helped patients with a variety of cancers attain long-term survival through the use of immune checkpoint inhibitors.Immunotherapies,either alone or in combination with other therapies,do not have a clear function in the treatment of G3 GEP-NETs.Currently,the majority of immunotherapy studies,both prospective and retrospective,do not reliably differentiate G3 GEP-NETs from NECs.By contrast,a significant number of studies include non-GEP neuroendocrine neoplasms(NENs).Therefore,there is an urgent need to summarize and evaluate these data to provide more effective therapeutic approaches for patients with this rare tumor.The purpose of this mini-review was to screen and summarize information on G3 GEP-NETs from all studies on NENs immunotherapy.
基金Nature Science Foundation of Zhejiang Province(Y20H060063,LY19H060005,LQ18H060003,LZ22H090003)National Natural Science Foundation of China(NO.82072465,NO.81772379,NO.81972096,NO.82172457,NO.82002327)+1 种基金China Postdoctoral Science Foundation(2017M612011)Scientific Research Fund of Zhejiang Provincial Education Department(Y201941476).
文摘Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration(IDD).Current limitations of stem cells include with their insufficient cell source,poor proliferation capacity,low nucleus pulposus(NP)-specific differentiation potential,and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation.To address these challenges,embryo-derived long-term expandable nucleus pulposus progenitor cells(NPPCs)and esterase-responsive ibuprofen nano-micelles(PEG-PIB)were prepared for synergistic transplantation.In this study,we propose a biomaterial pre-modification cell strategy;the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis.The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro;their further synergistic transplantation yielded effective functional recovery,histological regeneration,and inhibition of pyroptosis during IDD regeneration.Herein,we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.