Hepatocellular carcinoma(HCC)is the main cause of cancer-related deaths in adult men under the age of 60 years in China.^([1])Liver transplantation(LT)is generally recognized as one of the most effective therapeutic a...Hepatocellular carcinoma(HCC)is the main cause of cancer-related deaths in adult men under the age of 60 years in China.^([1])Liver transplantation(LT)is generally recognized as one of the most effective therapeutic approaches for end-stage liver diseases.LT guidelines for HCC were firstly launched in 2014 and were updated in 2018.Recently,further updates are required to adapt to the new situation of LT in China and to continue advancing the recommendations.(Full version in Supplementary file,http://links.lww.com/CM9/B362).展开更多
Lenvatinib is a targeted drug used for first-line treatment of hepatocellular carcinoma(HCC).A deeper insight into the resistance mechanism of HCC against lenvatinib is urgently needed.In this study,we aimed to dissec...Lenvatinib is a targeted drug used for first-line treatment of hepatocellular carcinoma(HCC).A deeper insight into the resistance mechanism of HCC against lenvatinib is urgently needed.In this study,we aimed to dissect the underlying mechanism of lenvatinib resistance(LR)and provide effective treatment strategies.We established an HCC model of acquired LR.Cell counting,migration,self-renewal ability,chemoresistance and expression of stemness genes were used to detect the stemness of HCC cells.Molecular and biochemical strategies such as RNA-sequencing,immunoprecipitation,mass spectrometry and ubiquitination assays were used to explore the underlying mechanisms.Patient-derived HCC models and HCC samples from patients were used to demonstrate clinical significance.We identified that increased cancer stemness driven by the hypoxia-inducible factor-1α(HIF-1α)pathway activation is responsible for acquired LR in HCC.Phosphorylated non-muscle myosin heavy chain 9(MYH9)at Ser1943,p-MYH9(Ser1943),could recruit ubiquitin-specific protease 22(USP22)to deubiquitinate and stabilize HIF-1αin lenvatinib-resistant HCC.Clinically,p-MYH9(Ser1943)expression was upregulated in HCC samples,which predicted poor prognosis and LR.A casein kinase-2(CK2)inhibitor and a USP22 inhibitor effectively reversed LR in vivo and in vitro.Therefore,the p-MYH9(Ser1943)/USP22/HIF-1αaxis is critical for LR and cancer stemness.For the diagnosis and treatment of LR in HCC,p-MYH9(Ser1943),USP22,and HIF-1αmight be valuable as novel biomarkers and targets.展开更多
As a radical treatment for hepatocellular carcinoma(HCC),liver transplantation(LT)has become an ideal treatment option for certain HCC patients.For patients beyond the Milan criteria,high HCC recurrence risk is a vita...As a radical treatment for hepatocellular carcinoma(HCC),liver transplantation(LT)has become an ideal treatment option for certain HCC patients.For patients beyond the Milan criteria,high HCC recurrence risk is a vital factor affecting the prognosis.Sirolimus,a firstgeneration mammalian target of rapamycin(mTOR)inhibitor,decreased recurrence rates and prolonged overall survival(OS)compared with calcineurin inhibitors(CNI)-based mTOR inhibitor-free immunosuppression.[1]However,some patients taking sirolimus after LT regularly do still have HCC recurrence in clinical practice.Thus,predicting the efficacy of sirolimus from the perspective of molecular pathology is expected to break through this bottleneck.展开更多
Transplant oncology refers to the implementation of transplant surgery in cancer treatment,with the core understanding of replacing diseased organs with healthy ones to solve cancer fundamentally.Early in 2004,dermato...Transplant oncology refers to the implementation of transplant surgery in cancer treatment,with the core understanding of replacing diseased organs with healthy ones to solve cancer fundamentally.Early in 2004,dermatologic surgeons presented“transplant oncology”,originally referring to de novo malignancies(DNMs)of skin after organ transplantation.展开更多
To the Editor:Liver cancer is estimated to be the sixth most lethal tumor,representing approximately 5.0%of all cancer-related deaths.[1]Mainly due to the high rate of infection with hepatitis B virus,liver cancer rem...To the Editor:Liver cancer is estimated to be the sixth most lethal tumor,representing approximately 5.0%of all cancer-related deaths.[1]Mainly due to the high rate of infection with hepatitis B virus,liver cancer remains a serious health concern in China,severely limiting the extension of human life expectancy.In China,the number of new cases and deaths from liver cancer is projected to exceed 400,000 in 2022.[2]Hepatocellular carcinoma(HCC)is the major histological type of liver cancer and is a complex and highly heterogeneous disease.Due to the lack of early symptoms,patients with HCC are usually diagnosed at an advanced stage,thus losing the opportunity for surgical resection or liver transplantation.Tumor recurrence and metastasis are major bafflements that limit the efficiency of surgical therapeutics.It is urgent to explore the molecular mechanism of HCC to develop effective methods for early diagnosis and identify patients at high risk of tumor recurrence and metastasis.展开更多
文摘Hepatocellular carcinoma(HCC)is the main cause of cancer-related deaths in adult men under the age of 60 years in China.^([1])Liver transplantation(LT)is generally recognized as one of the most effective therapeutic approaches for end-stage liver diseases.LT guidelines for HCC were firstly launched in 2014 and were updated in 2018.Recently,further updates are required to adapt to the new situation of LT in China and to continue advancing the recommendations.(Full version in Supplementary file,http://links.lww.com/CM9/B362).
基金National Key Research and Development Program of China(2022YFA1106800),National Natural Science Foundation of China(82203070,82200726,82200727,92159202 and 82273270)Project of Medical and Health Technology Program in Zhejiang Province(2024KY853).
文摘Lenvatinib is a targeted drug used for first-line treatment of hepatocellular carcinoma(HCC).A deeper insight into the resistance mechanism of HCC against lenvatinib is urgently needed.In this study,we aimed to dissect the underlying mechanism of lenvatinib resistance(LR)and provide effective treatment strategies.We established an HCC model of acquired LR.Cell counting,migration,self-renewal ability,chemoresistance and expression of stemness genes were used to detect the stemness of HCC cells.Molecular and biochemical strategies such as RNA-sequencing,immunoprecipitation,mass spectrometry and ubiquitination assays were used to explore the underlying mechanisms.Patient-derived HCC models and HCC samples from patients were used to demonstrate clinical significance.We identified that increased cancer stemness driven by the hypoxia-inducible factor-1α(HIF-1α)pathway activation is responsible for acquired LR in HCC.Phosphorylated non-muscle myosin heavy chain 9(MYH9)at Ser1943,p-MYH9(Ser1943),could recruit ubiquitin-specific protease 22(USP22)to deubiquitinate and stabilize HIF-1αin lenvatinib-resistant HCC.Clinically,p-MYH9(Ser1943)expression was upregulated in HCC samples,which predicted poor prognosis and LR.A casein kinase-2(CK2)inhibitor and a USP22 inhibitor effectively reversed LR in vivo and in vitro.Therefore,the p-MYH9(Ser1943)/USP22/HIF-1αaxis is critical for LR and cancer stemness.For the diagnosis and treatment of LR in HCC,p-MYH9(Ser1943),USP22,and HIF-1αmight be valuable as novel biomarkers and targets.
基金supported by grants from the National Natural Science Foundation of China(Nos.92159202,82273270,and 32171368)National Science and Technology Major Project of China(No.2017ZX10203205).
文摘As a radical treatment for hepatocellular carcinoma(HCC),liver transplantation(LT)has become an ideal treatment option for certain HCC patients.For patients beyond the Milan criteria,high HCC recurrence risk is a vital factor affecting the prognosis.Sirolimus,a firstgeneration mammalian target of rapamycin(mTOR)inhibitor,decreased recurrence rates and prolonged overall survival(OS)compared with calcineurin inhibitors(CNI)-based mTOR inhibitor-free immunosuppression.[1]However,some patients taking sirolimus after LT regularly do still have HCC recurrence in clinical practice.Thus,predicting the efficacy of sirolimus from the perspective of molecular pathology is expected to break through this bottleneck.
基金supported by grants from the program of the National Natural Science Funds(Nos.82200726 and U23A20451).
文摘Transplant oncology refers to the implementation of transplant surgery in cancer treatment,with the core understanding of replacing diseased organs with healthy ones to solve cancer fundamentally.Early in 2004,dermatologic surgeons presented“transplant oncology”,originally referring to de novo malignancies(DNMs)of skin after organ transplantation.
基金the grants from the National Science and Technology Major Project of China(No.2017ZX10203205)the Major Research Plan of the National Natural Science Foundation of China(No.92159202)+2 种基金Key Program of National Natural Science Foundation of China(No.81930016)Key Research and Development Plan of Zhejiang Province(No.2019C03050)Hangzhou Municipal Social Development Independent Declaration Project(No.20180533B34).
文摘To the Editor:Liver cancer is estimated to be the sixth most lethal tumor,representing approximately 5.0%of all cancer-related deaths.[1]Mainly due to the high rate of infection with hepatitis B virus,liver cancer remains a serious health concern in China,severely limiting the extension of human life expectancy.In China,the number of new cases and deaths from liver cancer is projected to exceed 400,000 in 2022.[2]Hepatocellular carcinoma(HCC)is the major histological type of liver cancer and is a complex and highly heterogeneous disease.Due to the lack of early symptoms,patients with HCC are usually diagnosed at an advanced stage,thus losing the opportunity for surgical resection or liver transplantation.Tumor recurrence and metastasis are major bafflements that limit the efficiency of surgical therapeutics.It is urgent to explore the molecular mechanism of HCC to develop effective methods for early diagnosis and identify patients at high risk of tumor recurrence and metastasis.
