The incidence of papillary thyroid carcinoma(PTC)has exponentially increased in recent years.Papillary thyroid microcarcinoma(PTMC)accounts for the majority of the reported cases of PTC.The debates and crucial issues ...The incidence of papillary thyroid carcinoma(PTC)has exponentially increased in recent years.Papillary thyroid microcarcinoma(PTMC)accounts for the majority of the reported cases of PTC.The debates and crucial issues in PTMC management have received researchers'attention.To further improve the clinical management of PTMC in China,展开更多
In recent years, the clinical incidence of thyroid cancer has been increasing year by year, and its risk assessment and clinical management methods have also been accordingly modified and constantly improved. There ar...In recent years, the clinical incidence of thyroid cancer has been increasing year by year, and its risk assessment and clinical management methods have also been accordingly modified and constantly improved. There are great differences between the clinical diagnostic and therapeutic modes and disease management of thyroid cancer employed by various medical institutions in China, particularly with regard to the clinical application of serum marker of thyroid cancer. To this end, the China Anti-Cancer Association Thyroid Cancer Specialized Committee Chinese Association of Thyroid Oncology organized this compilation of ExpertConsensus on Clinical Application of Serum Marker of Thyroid Cancer to help and impel relevant clinical institutions and professionals to standardize clinical diagnosis, treatment, and long-term management of thyroid cancer, and to properly utilize the serum marker for scientific auxiliary clinical diagnosis and assessment of thyroid cancer before and after operation.展开更多
BRAF^(V600E)is the most common genetic alteration and has become a major therapeutic target in thyroid cancers;however,intrinsic feedback mechanism limited clinical use of BRAF^(V600E)specific inhibitors.Synthetic let...BRAF^(V600E)is the most common genetic alteration and has become a major therapeutic target in thyroid cancers;however,intrinsic feedback mechanism limited clinical use of BRAF^(V600E)specific inhibitors.Synthetic lethal is a kind of interaction between two genes,where only simultaneously perturbing both of the genes can lead to lethality.Here,we identified CYP2S1 as a synthetic lethal partner of BRAF^(V600E)in thyroid cancers.First,we found that CYP2S1 was highly expressed in papillary thyroid cancers(PTCs)compared to normal thyroid tissues,particularly in conventional PTCs(CPTCs)and tall-cell PTCs(TCPTCs),and its expression was positively associated with BRAFV600E mutation.CYP2S1 knockdown selectively inhibited cell proliferation,migration,invasion and tumorigenic potential in nude mice,and promoted cell apoptosis in BRAFV600E mutated thyroid cancer cells,but not in BRAF wildtype ones.Mechanistically,BRAF^(V600E)-mediated MAPK/ERK cascade upregulated CYP2S1 expression by an AHR-dependent pathway,while CYP2S1 in turn enhanced transcriptional activity of AHR through its metabolites.This AHR/CYP2S1 feedback loop strongly amplified oncogenic role of BRAF^(V600E)in thyroid cancer cells,thereby causing synthetic lethal interaction between CYP2S1 and BRA^(FV600E).Finally,we demonstrated CYP2S1 as a potential therapeutic target in both BRAF^(V600E)-drived xenograft and transgenic mouse models by targetedly delivering CYP2S1-specific siRNA.Altogether,our data demonstrate CYP2S1 as a synthetic lethal partner of BRAFV600E in thyroid cancers,and indicate that targeting CYP2S1 will provide a new therapeutic strategy for BRAFV600E mutated thyroid cancers.展开更多
Purpose:In recent years,thyroid cancer is a common clinical problem.Since guidelines for the diagnosis and treatment of thyroid nodules and diferentiated thyroid cancer were revised in 2012,signifcant scientifc advanc...Purpose:In recent years,thyroid cancer is a common clinical problem.Since guidelines for the diagnosis and treatment of thyroid nodules and diferentiated thyroid cancer were revised in 2012,signifcant scientifc advances have occurred in the feld.The aim of this guidelines is to inform clinicians,researchers,patients and health policy makers on published evidence and expert consensus relating to the diagnosis and management of thyroid malignancy.Methods:In order to better promote the clinical management of thyroid cancer in China,Chinese Association of Thyroid Oncology(CATO)organized relevant experts to write these guidelines based on latest relevant literatures and clinical experience of multiple centers.The specifc clinical issues and topics addressed in these guidelines were based on published evidence,prior versions of the Chinese guidelines and expert consensus.Results and conclusion:The guidelines provide recommendations for the management of diferent types of thyroid carcinoma,including papillary,follicular,medullary,and anaplastic carcinomas.展开更多
文摘The incidence of papillary thyroid carcinoma(PTC)has exponentially increased in recent years.Papillary thyroid microcarcinoma(PTMC)accounts for the majority of the reported cases of PTC.The debates and crucial issues in PTMC management have received researchers'attention.To further improve the clinical management of PTMC in China,
文摘In recent years, the clinical incidence of thyroid cancer has been increasing year by year, and its risk assessment and clinical management methods have also been accordingly modified and constantly improved. There are great differences between the clinical diagnostic and therapeutic modes and disease management of thyroid cancer employed by various medical institutions in China, particularly with regard to the clinical application of serum marker of thyroid cancer. To this end, the China Anti-Cancer Association Thyroid Cancer Specialized Committee Chinese Association of Thyroid Oncology organized this compilation of ExpertConsensus on Clinical Application of Serum Marker of Thyroid Cancer to help and impel relevant clinical institutions and professionals to standardize clinical diagnosis, treatment, and long-term management of thyroid cancer, and to properly utilize the serum marker for scientific auxiliary clinical diagnosis and assessment of thyroid cancer before and after operation.
基金supported by the National Natural Science Foundation of China(No.81572627,81672645 and 81770787)Innovation Talent Promotion Plan in Shaanxi Province(No.2018TD-006).
文摘BRAF^(V600E)is the most common genetic alteration and has become a major therapeutic target in thyroid cancers;however,intrinsic feedback mechanism limited clinical use of BRAF^(V600E)specific inhibitors.Synthetic lethal is a kind of interaction between two genes,where only simultaneously perturbing both of the genes can lead to lethality.Here,we identified CYP2S1 as a synthetic lethal partner of BRAF^(V600E)in thyroid cancers.First,we found that CYP2S1 was highly expressed in papillary thyroid cancers(PTCs)compared to normal thyroid tissues,particularly in conventional PTCs(CPTCs)and tall-cell PTCs(TCPTCs),and its expression was positively associated with BRAFV600E mutation.CYP2S1 knockdown selectively inhibited cell proliferation,migration,invasion and tumorigenic potential in nude mice,and promoted cell apoptosis in BRAFV600E mutated thyroid cancer cells,but not in BRAF wildtype ones.Mechanistically,BRAF^(V600E)-mediated MAPK/ERK cascade upregulated CYP2S1 expression by an AHR-dependent pathway,while CYP2S1 in turn enhanced transcriptional activity of AHR through its metabolites.This AHR/CYP2S1 feedback loop strongly amplified oncogenic role of BRAF^(V600E)in thyroid cancer cells,thereby causing synthetic lethal interaction between CYP2S1 and BRA^(FV600E).Finally,we demonstrated CYP2S1 as a potential therapeutic target in both BRAF^(V600E)-drived xenograft and transgenic mouse models by targetedly delivering CYP2S1-specific siRNA.Altogether,our data demonstrate CYP2S1 as a synthetic lethal partner of BRAFV600E in thyroid cancers,and indicate that targeting CYP2S1 will provide a new therapeutic strategy for BRAFV600E mutated thyroid cancers.
基金funded by National Natural Science Foundation of China (81872170[Minghua Ge]).
文摘Purpose:In recent years,thyroid cancer is a common clinical problem.Since guidelines for the diagnosis and treatment of thyroid nodules and diferentiated thyroid cancer were revised in 2012,signifcant scientifc advances have occurred in the feld.The aim of this guidelines is to inform clinicians,researchers,patients and health policy makers on published evidence and expert consensus relating to the diagnosis and management of thyroid malignancy.Methods:In order to better promote the clinical management of thyroid cancer in China,Chinese Association of Thyroid Oncology(CATO)organized relevant experts to write these guidelines based on latest relevant literatures and clinical experience of multiple centers.The specifc clinical issues and topics addressed in these guidelines were based on published evidence,prior versions of the Chinese guidelines and expert consensus.Results and conclusion:The guidelines provide recommendations for the management of diferent types of thyroid carcinoma,including papillary,follicular,medullary,and anaplastic carcinomas.
