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Anaplastic thyroid cancer: Unveiling advances in diagnosis andmanagement
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作者 Treshita Dey Budhi Singh Yadav 《World Journal of Clinical Oncology》 2024年第7期786-789,共4页
The review article by Pavlidis et al published in World J Clin Oncol provides a meticulous analysis of the intricacies surrounding anaplastic carcinoma of the thyroid.Thyroid carcinoma encompasses a spectrum of diseas... The review article by Pavlidis et al published in World J Clin Oncol provides a meticulous analysis of the intricacies surrounding anaplastic carcinoma of the thyroid.Thyroid carcinoma encompasses a spectrum of diseases,each charac-terized by distinct behaviors and outcomes.Diagnostic approaches encompass a diverse array of tools.Surgery remains the pivotal treatment for anaplastic thyroid carcinoma.Radiotherapy and chemotherapy offer the best overall sur-vival in aggressive disease.Combinations of immunotherapy with targeted the-rapies,such as dabrafenib-trametinib,demonstrate potential for enhanced effect-iveness and improved survival outcomes.Multifaceted approach fuelled by precision medicine and interdisciplinary collaboration is imperative in charting a course toward improved outcomes in this formidable malignancy. 展开更多
关键词 anaplastic thyroid cancer SURGERY RADIOTHERAPY CHEMOTHERAPY Targeted therapy IMMUNOTHERAPY
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An overview of the contemporary diagnosis and management approaches for anaplastic thyroid carcinoma
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作者 Shu-Yue Zhou Lian-Xiang Luo 《World Journal of Clinical Oncology》 2024年第6期674-676,共3页
Thyroid carcinoma is a complex disease with several types,the most common being well-differentiated and undifferentiated.The latter,“undifferentiated carcinoma”,also known as anaplastic thyroid carcinoma(ATC),is a h... Thyroid carcinoma is a complex disease with several types,the most common being well-differentiated and undifferentiated.The latter,“undifferentiated carcinoma”,also known as anaplastic thyroid carcinoma(ATC),is a highly aggr-essive malignant tumor accounting for less than 0.2%of all thyroid carcinomas and carries a poor prognosis with a median survival of 5 months.BRAF gene mutations are the most common molecular factor associated with this type of thyroid carcinoma.Recent advances in targeted biological agents,immuno-therapy,stem cell therapy,nanotechnology,the dabrafenib/trametinib com-bination therapy,immune checkpoint inhibitors(ICI)and artificial intelligence offer novel treatment options.The combination therapy of dabrafenib and tra-metinib is the current standard treatment for patients with BRAF-V600E gene mutations.Besides,the dabrafenib/trametinib combination therapy,ICI,used alone or in combination with targeted therapies have raised some hopes for improving the prognosis of this deadly disease.Younger age,earlier tumor stage and radiotherapy are all prognostic factors for improved outcomes.Ultimately,therapeutic regimens should be tailored to the individual patient based on surveillance and epidemiological data,and a multidisciplinary approach is ess-ential. 展开更多
关键词 thyroid diseases thyroid cancers anaplastic carcinoma Undifferentiated carcinoma Neck mass Aggressive malignancies
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Clinical Response with Sunitinib Therapy in the Treatment of Anaplastic Thyroid Cancer
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作者 Kenneth M. Wong Theodore Scott Nowicki +4 位作者 Carmelo Puccio Tauseef Ahmed Raj Tiwari Jan Geliebter Augustine Moscatello 《Journal of Cancer Therapy》 2012年第2期132-136,共5页
Background: Anaplastic thyroid cancer (ATC), while rare, carries a uniformly poor prognosis. Current treatment includes surgery when possible, radiotherapy, and chemotherapy. Multiple chemotherapeutic agents are in th... Background: Anaplastic thyroid cancer (ATC), while rare, carries a uniformly poor prognosis. Current treatment includes surgery when possible, radiotherapy, and chemotherapy. Multiple chemotherapeutic agents are in the process of clinical testing, and promising agents include those in the tyrosine kinase inhibitor family. Our patient represents a novel case of ATC treated with sunitinib, one such tyrosine kinase inhibitor. Methods/Results: We utilized the experimental sunitinib in conjunction with radiation therapy to treat a patient with aggressive ATC in whom curative resection was unable to be achieved due to carotid sheath and tracheal involvement. The patient had marked clinical response and sustained stable disease for 8 months, which coincides with reported data regarding sunitinib to treat other thyroid malignancies. Conclusion: Our case illustrates the efficacy of sunitinib therapy as a possible adjunct in the treatment of ATC. 展开更多
关键词 SUNITINIB anaplastic thyroid cancer TYROSINE KINASE Inhibitor Chemotherapy atc
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Anaplastic thyroid carcinoma:A comprehensive review of current and future therapeutic options 被引量:6
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作者 Francesco Perri Giuseppe Di Lorenzo +1 位作者 Giuseppina Della Vittoria Scarpati Carlo Buonerba 《World Journal of Clinical Oncology》 CAS 2011年第3期150-157,共8页
Anaplastic thyroid carcinoma(ATC)is the rarest,but deadliest histologic type among thyroid malignancies,with a dismal median survival of 3-9 mo.Even though ATC accounts for less than 2%of all thyroid tumors,it is resp... Anaplastic thyroid carcinoma(ATC)is the rarest,but deadliest histologic type among thyroid malignancies,with a dismal median survival of 3-9 mo.Even though ATC accounts for less than 2%of all thyroid tumors,it is responsible for 14%-39%of thyroid carcinoma-related deaths.ATC clinically presents as a rapidly growing mass in the neck,associated with dyspnoea,dysphagia and vocal cord paralysis.It is usually locally advanced and often metastatic at initial presentation.For operable diseases,the combination of radical surgery with adjuvant radiotherapy or chemotherapy,using agents such as doxorubicin and cisplatin,is the best treatment strategy.Cytotoxic drugs for advanced/metastatic ATC are poorly effective.On the other hand,targeted agents might represent a viable therapeutic option.Axitinib,combretastatin A4,sorafenib and imatinib have been tested in small clinical trials of ATC,with a promising disease control rate ranging from 33%to 75%.Other clinical trials of targeted therapy for thyroid carcinoma are currently ongoing.Biological agents that are under investigation include pazopanib,gefitinib and everolimus.With the very limited therapeutic armamentarium available at the present time,targeted therapy constitutes an exciting new horizon for ATC.In future,biological agents will probably represent the standard of care for this aggressive malignancy,in the same fashion as it has recently occurred for other chemo-refractory tumors,such as kidney and hepatic cancer. 展开更多
关键词 anaplastic thyroid cancer TARGETED AGENTS
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Small Cell Carcinoma:a Rare Subtype of Thyroid Cancer with Unanticipated Prognosis 被引量:1
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作者 Wei SHI Qiu-yang ZHAO +2 位作者 Ze-ming LIU Shun-tao WANG Chun-ping LIU 《Current Medical Science》 SCIE CAS 2019年第2期265-269,共5页
The prognosis of small cell thyroid carcinoma(SCTC)in a large cohort has not been well reported in the literature.In this study,we analyzed the mortality of SCTC,in comparison to medullary thyroid cancer(MTC)and anapl... The prognosis of small cell thyroid carcinoma(SCTC)in a large cohort has not been well reported in the literature.In this study,we analyzed the mortality of SCTC,in comparison to medullary thyroid cancer(MTC)and anaplastic thyroid cancer(ATC),based on the Surveillance,Epidemiology,and End Results(SEER)Program of the National Cancer Institute,to determine the prognosis of SCTC.Information regarding patients with a diagnosis of MTC,ATC,or SCTC,between 2004 and 2013,was acquired from the SEER database.Patient survival curves were assessed by Cox proportional hazards regression analyses,Kaplan-Meier analyses,and log-rank tests.In a Kaplan-Meier analysis of the entire cohort of thyroid cancer patients,cancer-specific survival declined sharply for patients with SCTC,but it declined more modestly for patients with MTC.The cancer-specific survival was not significantly different between SCTC and ATC.Unadjusted Cox regression analysis showed that SCTC had a higher cancer-specific mortality than MTC but a similar prognosis as ATC.SCTC showed a higher cancer-specific mortality than MTC and ATC after adjustments for various confounding factors.SCTC was found to have a more highly lethal clinical course than MTC and had a similar death rate to ATC.Therefore,we recommend that aggressive,radical treatment like surgery or radiation should be performed tor these patients. 展开更多
关键词 small cell carcinoma MEDULLARY thyroid cancer anaplastic thyroid cancer
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Update on current diagnosis and management of anaplastic thyroid carcinoma 被引量:3
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作者 Efstathios T Pavlidis Ioannis N Galanis Theodoros E Pavlidis 《World Journal of Clinical Oncology》 2023年第12期570-583,共14页
Well-differentiated thyroid carcinoma has a favorable prognosis with a 5-year survival rate of over 95%.However,the undifferentiated or anaplastic type accounting for<0.2%,usually in elderly individuals,exhibits a ... Well-differentiated thyroid carcinoma has a favorable prognosis with a 5-year survival rate of over 95%.However,the undifferentiated or anaplastic type accounting for<0.2%,usually in elderly individuals,exhibits a dismal prognosis with rapid growth and disappointing outcomes.It is the most aggressive form of thyroid carcinoma,with a median survival of 5 mo and poor quality of life(airway obstruction,dysphagia,hoarseness,persistent pain).Early diagnosis and staging are crucial.Diagnostic tools include biopsy(fine needle aspiration,core needle,open surgery),high-resolution ultrasound,computed tomography,magnetic resonance imaging,[(18)F]fluoro-D-glucose positron emission tomography/computed tomography,liquid biopsy and microRNAs.The BRAF gene(BRAF-V600E and BRAF wild type)is the most often found molecular factor.Others include the genes RET,KRAS,HRAS,and NRAS.Recent management policy is based on surgery,even debulking,chemotherapy(cisplatin or doxorubicin),radiotherapy(adjuvant or definitive),targeted biological agents and immunotherapy.The last two options constitute novel hopeful management modalities improving the overall survival in these otherwise condemned patients.Anti-programmed death-ligand 1 antibody immunotherapy,stem cell targeted therapies,nanotechnology achievements and artificial intelligence implementation provide novel promising alternatives.Genetic mutations determine molecular pathways,thus indicating novel treatment strategies such as anti-BRAF,anti-vascular endothelial growth factor-A,and anti-epidermal growth factor receptor.Treatment with the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib has been approved by the Food and Drug Administration in cases with BRAF-V600E gene mutations and is currently the standard care.This neoadjuvant treatment followed by surgery ensures a twoyear overall survival of 80%.Prognostic factors for improved outcomes have been found to be younger age,earlier tumor stage and radiation therapy.A multidisciplinary approach is necessary,and the therapeutic plan should be individu alized based on surveillance and epidemiology end results. 展开更多
关键词 thyroid diseases thyroid cancers anaplastic carcinoma Undifferentiated carcinoma Neck mass Aggressive malignancies
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Diagnosis and Treatment of Anaplastic Thyroid Carcinoma
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作者 Patorn Piromchai Teeraporn Ratanaanekchai Pornthep Kasemsiri 《International Journal of Clinical Medicine》 2012年第1期69-73,共5页
Anaplastic thyroid carcinoma (ATC) is a poorly differentiated thyroid cancer. It cannot uptake iodine or synthesis thyroglobulin. The incidence is low;about 2% - 5% of thyroid cancer. The peak age incidence is 60 - 70... Anaplastic thyroid carcinoma (ATC) is a poorly differentiated thyroid cancer. It cannot uptake iodine or synthesis thyroglobulin. The incidence is low;about 2% - 5% of thyroid cancer. The peak age incidence is 60 - 70 years and it is more common in females (55% - 77% of all patients). In recent years, the incidence has declined;however, it may be higher in areas of endemic goiter. ATC may occur with a coexisting carcinoma and may represent transformation of a well-differentiated thyroid cancer. Patients typically present with a rapidly growing anterior neck mass and aggressive symptoms. The most reliable tool in detecting thyroid malignancies is fine-needle aspiration cytology (FNAC). Sensitivity of FNAC for thyroid malignancy ranged from 61% to 97.7%. Fine-needle aspiration can diagnose ATC by the demonstration of spindled or giant cells, bizarre neoplastic cells that may be multinucleated, or atypical cells with high mitotic activity. A syncytial pattern is the predominant cellular pattern of anaplastic thyroid carcinoma. Other laboratory tests, including tumor markers (cytokeratin, vimentin, and carcinoembryogenic antigen) are helpful in diagnosis and follow-up of the patients. Multimodality therapy (surgery, external beam radiation, and chemotherapy) is the recommended treatment and it seems to have slightly improved outcomes. The prognosis is not as bad in younger patients with smaller tumors. The most common cause of death is lung metastasis. The mean survival time is less than 6 months from the time of diagnosis. The prompt diagnosis and aggressive treatment are essential modality to achieve optimal outcomes. 展开更多
关键词 anaplastic thyroid CARCINOMA thyroid cancer
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Long Term Survival in a Patient with Anaplastic Thyroid Carcinoma Treated with Cricotracheal Resection
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作者 Gregory Sayer Douglas Sidell Joel A. Sercarz 《International Journal of Otolaryngology and Head & Neck Surgery》 2012年第2期39-43,共5页
Anaplastic thyroid cancer is an uncommon malignancy with a poor prognosis. Elderly patients are most commonly afflicted and survival past 3 years occurs in less than 5% of patients. Management of these patients is cha... Anaplastic thyroid cancer is an uncommon malignancy with a poor prognosis. Elderly patients are most commonly afflicted and survival past 3 years occurs in less than 5% of patients. Management of these patients is challenging, and the importance of palliation, airway protection, and aggressive resection is debated. In this report, we describe a patient with anaplastic thyroid carcinoma who presented with respiratory distress due to invasion of the tracheal cartilage. The patient was managed with cricotracheal resection, total thyroidectomy and thyrotracheal anastomosis. The patient is currently disease free 3.5 years after resection and postoperative radiation therapy with interval neck dissection. 展开更多
关键词 anaplastic thyroid cancer SURVIVAL Treatment SURGERY
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Pattern of Thyroid Cancer at King Abdulaziz University Hospital, Jeddah: A 10-Year Retrospective Study
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作者 Amani Alhozali Aisha Al-Ghamdi Jawaher Alahmadi 《Open Journal of Endocrine and Metabolic Diseases》 2016年第3期121-125,共5页
Background and objective: Thyroid cancer is the most common endocrine malignancy. This report aims to describe the pattern of thyroid cancer presentations at King Abdulaziz University Hospital, Jeddah. Methods: This w... Background and objective: Thyroid cancer is the most common endocrine malignancy. This report aims to describe the pattern of thyroid cancer presentations at King Abdulaziz University Hospital, Jeddah. Methods: This was a retrospect chart review of all thyroid cancer cases diagnosed between 2001 and 2010 at King Abdulaziz University Hospital, Jeddah. We documented patients’ demographic and clinical data, including age at diagnosis, tumor type and size, extrathyroidal extension, and metastasis. Results: A total of 114 thyroid cancer cases were diagnosed from 2001 through 2010. Females comprise the majority of cases (female to male ratio of 4:1). The mean ages of patients diagnosed with different thyroid cancers were: papillary thyroid cancer, 39.6 years;follicular thyroid cancer, 43.2 years;medullary thyroid cancer, 55.8 years;and anaplastic thyroid cancer, 46.0 years. Papillary thyroid cancer was diagnosed in 88 cases (77%), follicular thyroid cancer in 19 cases (17%), medullary thyroid cancer in 5 cases (4%), and anaplastic thyroid cancer in 2 cases (2%). Conclusion: Thyroid cancers are more common among females. The disease is diagnosed at a relatively young age among our patients (40 years). Papillary thyroid cancer is the most common type of thyroid cancer. 展开更多
关键词 anaplastic thyroid cancer Follicular thyroid cancer Medullary thyroid cancer Papillary thyroid cancer Endocrine Malignancy
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甲状腺未分化癌的靶向治疗进展
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作者 殷德涛 刘维豪 《肿瘤防治研究》 CAS 2024年第8期617-624,共8页
甲状腺未分化癌是一种极其罕见的甲状腺恶性肿瘤,因其侵袭性强、预后差,是目前甲状腺癌的主要致死原因。甲状腺未分化癌的手术难度通常较大,且传统放化疗的意义不够明确,而靶向治疗的出现彻底改变了传统的肿瘤治疗模式。靶向治疗通过特... 甲状腺未分化癌是一种极其罕见的甲状腺恶性肿瘤,因其侵袭性强、预后差,是目前甲状腺癌的主要致死原因。甲状腺未分化癌的手术难度通常较大,且传统放化疗的意义不够明确,而靶向治疗的出现彻底改变了传统的肿瘤治疗模式。靶向治疗通过特异性作用于肿瘤相关的特定分子和信号通路来实现抗肿瘤效应。与传统化疗相比,靶向治疗可以更精确地攻击肿瘤细胞,并减少对正常细胞的损伤。随着靶向治疗临床试验的深入,发现应用靶向药物治疗对提高甲状腺未分化癌患者总生存期有明显效果,靶向治疗以及肿瘤相关信号通路逐渐成为甲状腺未分化癌治疗的研究热点之一。本文结合现阶段靶向药物在甲状腺未分化癌治疗方面的研究,对甲状腺未分化癌靶向治疗的进展作一综述。 展开更多
关键词 甲状腺未分化癌 靶向治疗 信号通路 基因突变
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未分化甲状腺癌去分化过程的分子研究进展
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作者 王帅 王宽宇 +1 位作者 孔祥定 李承 《中国肿瘤外科杂志》 CAS 2024年第2期196-200,共5页
未分化甲状腺癌(ATC)是罕见但极具侵略性的甲状腺癌,对多数患者而言是致命的。随着分子检测常规化及分子靶向药物的不断研发,分子靶向治疗已成为未分化甲状腺癌的一种重要治疗手段。然而,ATC的分子和遗传特征存在广泛的异质性,这使得AT... 未分化甲状腺癌(ATC)是罕见但极具侵略性的甲状腺癌,对多数患者而言是致命的。随着分子检测常规化及分子靶向药物的不断研发,分子靶向治疗已成为未分化甲状腺癌的一种重要治疗手段。然而,ATC的分子和遗传特征存在广泛的异质性,这使得ATC靶向治疗变得更加困难。许多研究证明ATC来源于分化型甲状腺癌(DTC),通过特定分子事件触发去分化过程,但触发这一过程并维持ATC侵袭性的分子机制尚不完全明确。该文讨论从DTC至ATC的分子进化轨迹,对相关分子机制进行综述,这对于未分化甲状腺癌的诊断和治疗具有指导意义。 展开更多
关键词 甲状腺癌 未分化甲状腺癌 分化型甲状腺癌 分子机制 靶向治疗
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NKX2-1-AS1介导miR-96-5p/PRDM16轴对未分化甲状腺癌细胞增殖、迁移和侵袭的影响
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作者 郭宏鹏 李尤 +3 位作者 刘奇 张睿 孙成林 潘星合 《中国医科大学学报》 CAS 北大核心 2024年第6期547-554,共8页
目的探讨长链非编码RNA(lncRNA)NK2同源异形盒1-反义RNA 1(NKX2-1-AS1)介导微RNA(miR)-96-5p/含有PR结构域的蛋白16(PRDM16)轴对未分化甲状腺癌(ATC)细胞体外增殖、迁移和侵袭以及体内移植瘤生长的影响。方法基于生物信息学筛选ATC组织... 目的探讨长链非编码RNA(lncRNA)NK2同源异形盒1-反义RNA 1(NKX2-1-AS1)介导微RNA(miR)-96-5p/含有PR结构域的蛋白16(PRDM16)轴对未分化甲状腺癌(ATC)细胞体外增殖、迁移和侵袭以及体内移植瘤生长的影响。方法基于生物信息学筛选ATC组织及细胞中差异表达的lncRNA NKX2-1-AS1,并进一步筛选其靶基因miR-96-5p和下游靶基因PRDM16。双荧光素酶报告基因实验验证NKX2-1-AS1与miR-96-5p以及miR-96-5p与PRDM16之间的关系。Western blotting检测过表达miR-96-5p对NKX2-1-AS1过表达的CAL-62细胞PRDM16表达的影响。平板克隆形成实验、划痕实验和Transwell实验分别检测敲减PRDM16对过表达NKX2-1-AS1的CAL-62细胞增殖、迁移和侵袭的影响。裸鼠皮下注射CAL-62细胞,观察敲减PRDM16对NKX2-1-AS1过表达的CAL-62细胞移植瘤生长的影响。结果基于生物信息学筛选出参与调节ATC发展的NKX2-1-AS1/miR-96-5p/PRDM16轴。双荧光素酶报告基因实验验证结果显示NKX2-1-AS1与miR-96-5p、miR-96-5p与PRDM16结合。过表达NKX2-1-AS1上调CAL-62细胞中PRDM16蛋白表达;而过表达miR-96-5p可逆转此上调作用。过表达NKX2-1-AS1抑制CAL-62细胞体外增殖、迁移和侵袭以及体内移植瘤生长;而敲减PRDM16可逆转此抑制作用。结论NKX2-1-AS1可能作为竞争性内源性RNA与miR-96-5p竞争结合下游靶基因PRDM16,上调PRDM16表达,从而抑制ATC细胞体外增殖、迁移和侵袭以及体内移植瘤生长。 展开更多
关键词 NKX2-1-AS1 miR-96-5p PRDM16 未分化甲状腺癌
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HBB通过调控Wnt/β-catenin信号通路抑制甲状腺未分化癌发展
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作者 郭宏鹏 张凤坤 +6 位作者 李尤 张金辉 潘星合 张睿 张艺彤 刘俊良 孙成林 《沈阳医学院学报》 2024年第6期570-574,596,共6页
目的:探究HBB在甲状腺未分化癌(anaplastic thyroid cancer,ATC)细胞中表达情况及其对ATC细胞增殖、侵袭、迁移和凋亡的调控作用和潜在机制。方法:通过TIMER数据库分析HBB在甲状腺癌及癌旁组织中表达情况;通过KM-plotter数据库分析HBB... 目的:探究HBB在甲状腺未分化癌(anaplastic thyroid cancer,ATC)细胞中表达情况及其对ATC细胞增殖、侵袭、迁移和凋亡的调控作用和潜在机制。方法:通过TIMER数据库分析HBB在甲状腺癌及癌旁组织中表达情况;通过KM-plotter数据库分析HBB表达与甲状腺癌患者总生存期相关性;通过RT-qPCR检测HBB mRNA在ATC细胞中表达情况;将HBB敲减或过表达质粒转染甲状腺未分化癌细胞,通过Western blot检测细胞HBB蛋白表达,通过CCK-8检测细胞增殖活力,通过Transwell检测细胞迁移和侵袭能力,通过流式细胞术检测细胞凋亡,通过Western blot检测细胞中β-catenin表达。结果:HBB在甲状腺癌组织中低表达,且其高表达患者总生存期高。HBB蛋白在ATC细胞中表达下调。敲减HBB增加甲状腺未分化癌细胞增殖、迁移和侵袭能力及β-catenin蛋白表达水平,抑制凋亡;而过表达HBB降低甲状腺未分化癌细胞增殖、迁移和侵袭能力及β-catenin蛋白表达水平,促进凋亡。结论:HBB高表达与甲状腺癌患者较高的总生存期相关。其可能通过Wnt/β-catenin信号通路抑制ATC细胞增殖、迁移和侵袭,促进凋亡。 展开更多
关键词 甲状腺未分化癌 HBB 增殖 迁移和侵袭 凋亡 WNT/Β-CATENIN信号通路
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E2F7介导CXCL5转录促进未分化甲状腺癌发展
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作者 潘星合 郭宏鹏 +1 位作者 李尤 孙成林 《中国医科大学学报》 CAS 北大核心 2024年第10期907-913,共7页
目的探讨转录因子E2F7对未分化甲状腺癌细胞体外增殖、迁移和侵袭及体内肿瘤生长的促进作用。方法慢病毒转染建立稳定敲减E2F7的CAL-62细胞,实时PCR检测细胞中E2F7表达以验证转染效率。将CAL-62细胞分为sh-NC组和sh-E2F7组,CCK-8法检测... 目的探讨转录因子E2F7对未分化甲状腺癌细胞体外增殖、迁移和侵袭及体内肿瘤生长的促进作用。方法慢病毒转染建立稳定敲减E2F7的CAL-62细胞,实时PCR检测细胞中E2F7表达以验证转染效率。将CAL-62细胞分为sh-NC组和sh-E2F7组,CCK-8法检测细胞增殖能力,Transwell实验检测细胞的迁移和侵袭能力。将CAL-62细胞皮下注射入裸鼠并观察肿瘤生长。EPD网站在线预测CXCL5启动子的E2F7结合位点,双荧光素酶报告基因实验检测敲减E2F7对CXCL5启动子荧光素酶活性的影响。实时PCR和ELISA检测敲减E2F7对CAL-62细胞CXCL5水平的影响。将CAL-62细胞分为sh-E2F7+空载体组和sh-E2F7+CXCL5组,进一步检测在敲减E2F7的基础上过表达CXCL5对CAL-62细胞增殖、迁移和侵袭以及CXCR2/ERK信号通路的影响。结果敲减E2F7抑制CAL-62细胞体外增殖、迁移和侵袭及体内肿瘤生长。CXCL5启动子存在E2F7的结合位点,敲减E2F7降低了CXCL5启动子的荧光素酶活性。在敲减E2F7的基础上过表达CXCL5逆转了敲减E2F7对CAL-62细胞体外增殖、迁移和侵袭的抑制作用。在敲减E2F7的基础上过表达CXCL5还逆转了敲减E2F7对CAL-62细胞CXCR2/ERK信号通路激活的抑制作用。结论E2F7能够促进未分化甲状腺癌细胞体外增殖、迁移、侵袭和体内肿瘤生长,其机制可能与促进CXCL5转录介导的CXCL5/CXCR2/ERK信号通路的激活有关。 展开更多
关键词 E2F7 未分化甲状腺癌 CXCL5/CXCR2/ERK信号通路 增殖 迁移和侵袭 肿瘤生长
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甲状腺未分化癌分子机制和治疗的研究进展
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作者 李尤 郭宏鹏 +4 位作者 张艺彤 刘俊良 俞建华 张金辉 孙成林 《沈阳医学院学报》 2024年第3期309-315,共7页
甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)是最具侵袭性的恶性肿瘤,预后极差。ATC发病机制复杂,目前尚无有效的治疗手段。近年来,随着对驱动ATC遗传(如BRAF V600E、TP53、TERT、PIK3CA突变等)和表观遗传(如组蛋白甲基化、组蛋... 甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)是最具侵袭性的恶性肿瘤,预后极差。ATC发病机制复杂,目前尚无有效的治疗手段。近年来,随着对驱动ATC遗传(如BRAF V600E、TP53、TERT、PIK3CA突变等)和表观遗传(如组蛋白甲基化、组蛋白去乙酰化、microRNA调节通路等)改变的深入了解,分子靶向治疗为ATC患者带来新的希望。本文综述了ATC发病分子机制、靶向治疗和其他治疗的最新成果。 展开更多
关键词 甲状腺未分化癌 基因突变 靶向治疗
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Is the incidence of anaplastic thyroid cancer increasing: A population based epidemiology study 被引量:2
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作者 Tyler A.Janz David M.Neskey +1 位作者 Shaun A.Nguyen Eric J.Lentsch 《World Journal of Otorhinolaryngology-Head and Neck Surgery》 2019年第1期34-40,共7页
Objective:To provide an understanding of the incidence of anaplastic thyroid cancer within the United States.Methods:Patients in the Surveillance,Epidemiology,and End Results (SEER) database were included from 1973 to... Objective:To provide an understanding of the incidence of anaplastic thyroid cancer within the United States.Methods:Patients in the Surveillance,Epidemiology,and End Results (SEER) database were included from 1973 to 2014 based on a diagnosis of anaplastic thyroid cancer using ICDO-3 codes.Patients were categorized into cohorts based on their year of diagnosis.Results:1527 patients were diagnosed with anaplastic thyroid cancer within the SEER 18 registries.The age-adjusted incidence rate was 0.2 per 1,000,000 people (95% CI:0.0-0.5) in 1973 and was 1.2 per 1,000,000 people (95% Cl:0.8-1.6) in 2014 (average annual percent change:3.0% [95% CI:2.2%-3.7%]).Patients tended to be of older age (mean age:70.5 [range 15.0-102.0]),of female sex (62.8%),and Caucasian (81.1%).Finally,survival over time remained the same,as median disease specific survival months was 4.00 (95% CI:2.26-5.74) from 1995 to 1999 and 4.00 (95% Cl:3.26-4.74) from 2010 to 2014.Conclusions:The incidence rate of anaplastic thyroid cancer has increased from 1973 to 2014.Interestingly,median survival in months did not greatly change overtime.Based on this increasing incidence,physicians must act appropriately to identify patients with anaplastic thyroid cancer as it possesses a high morbidity and mortality. 展开更多
关键词 anaplastic thyroid cancer thyroid cancer HEAD and NECK HEAD and NECK ENDOCRINE surgery HEAD and NECK oncology
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化学合成DFV-紫杉烷类化合物对未分化甲状腺癌细胞的抗肿瘤作用研究
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作者 王美晨 王昌伟 +1 位作者 冯超 Iwao Ojima 《肿瘤药学》 CAS 2024年第2期179-185,共7页
目的探索化学合成DFV-紫杉烷类化合物对未分化甲状腺癌细胞的抗肿瘤作用及可能机制。方法噻唑蓝(MTT)实验测定DFV-紫杉烷类化合物对肿瘤细胞增殖及细胞活性的影响;紫外分光光度计测定新型紫杉烷类化合物处理后肿瘤细胞的存活情况;克隆... 目的探索化学合成DFV-紫杉烷类化合物对未分化甲状腺癌细胞的抗肿瘤作用及可能机制。方法噻唑蓝(MTT)实验测定DFV-紫杉烷类化合物对肿瘤细胞增殖及细胞活性的影响;紫外分光光度计测定新型紫杉烷类化合物处理后肿瘤细胞的存活情况;克隆形成实验评价新型紫杉烷类化合物对肿瘤细胞增殖能力的敏感性;结晶紫染色计数存活克隆数;流式细胞仪检测新型紫杉烷类化合物对肿瘤细胞周期分布的影响。结果甲状腺癌细胞系8505C和8305C经四种不同的DFV-紫杉烷类化合物处理后,IC_(50)在0.5~5.5 nmol·L^(-1)之间;不同药物处理后,甲状腺癌细胞的增殖能力显著降低(P<0.001);不同浓度的DFV-紫杉烷类化合物可不同程度地抑制甲状腺癌细胞的克隆形成能力(P<0.001);DFV-紫杉烷类化合物可诱导甲状腺癌细胞G_(2)/M期周期阻滞(P<0.001),从而抑制甲状腺癌细胞的生长。结论四种化学合成DFV-紫杉烷类化合物对未分化甲状腺癌细胞具有生长抑制和抗肿瘤作用。 展开更多
关键词 DFV-紫杉烷类化合物 未分化甲状腺癌 抗肿瘤作用
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RIP1、MLKL蛋白在未分化甲状腺癌中的表达及临床意义
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作者 姜燕 郭越 +2 位作者 王芳 张学 牛彦斌 《新疆医科大学学报》 CAS 2024年第2期238-243,共6页
目的探讨受体相互作用蛋白激酶1(RIP1)、混合系激酶区域样蛋白(MLKL)在未分化甲状腺癌(ATC)中的表达及其临床意义。方法选取48例ATC患者为研究对象,检测手术标本组织中RIP1、MLKL的表达,收集患者临床病理参数并随访,统计分析RIP1、MLKL... 目的探讨受体相互作用蛋白激酶1(RIP1)、混合系激酶区域样蛋白(MLKL)在未分化甲状腺癌(ATC)中的表达及其临床意义。方法选取48例ATC患者为研究对象,检测手术标本组织中RIP1、MLKL的表达,收集患者临床病理参数并随访,统计分析RIP1、MLKL在ATC组织标本中的表达模式及对患者预后的影响。培养人未分化型甲状腺癌THJ-11T、THJ-16T、THJ-21T、ASH-3、BHT101细胞系、分化型甲状腺癌细胞系CAL-62、PDTC-1、正常人甲状腺细胞系Nthy-ori 3-1、HTORI-3,利用Western blot法及RT-PCR检测细胞系中RIP1、MLKL的蛋白mRNA的表达水平。结果(1)RT-PCR及Western blot检测显示,与正常人甲状腺细胞系及分化型甲状腺癌细胞系相比,未分化甲状腺癌细胞系中RIP1、MLKL蛋白和mRNA相对表达水平明显更高。(2)48例ATC患者中,14例起源于乳头状甲状腺癌(PTC),34例起源于滤泡状甲状腺癌(FTC)。肿瘤细胞表现出明显的多形性。形态学特征包括梭形细胞为主的肉瘤样及鳞状细胞样。(3)免疫组化染色显示,RIP1表达主要定位于ATC细胞膜。48例ATCs中有24例(50.0%)RIP1染色阳性。组织中含有混合岛状或低分化癌成分。MLKL阳性细胞核表达清晰,48例ATC患者中有29例(60.4%)患者MLKL染色阳性。(4)Kaplan-Meier生存分析显示,RIP1和MLKL过度表达会缩短ATC患者的无病生存期(DFS)(P<0.05),但对患者的总体生存率(OS)无明显影响(P>0.05)。Cox多因素分析显示,RIP1高表达、MLKL高表达、N分期、M分期均是影响ATC患者DFS的独立性危险因素(P<0.05)。结论RIP1、MLKL高表达与ATC的发生及DFS密切相关,或可作为ATC潜在的治疗靶点及预后预测的生物学标记物。 展开更多
关键词 甲状腺未分化癌 受体相互作用蛋白激酶1(RIP1) 混合系激酶区域样蛋白(MLKL)
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柴胡皂苷D通过NLRP3介导细胞焦亡抑制未分化甲状腺癌细胞增殖的机制研究
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作者 高芳 李君 +1 位作者 郭艳霞 李红 《湖南中医药大学学报》 CAS 2024年第10期1794-1800,共7页
目的研究柴胡皂苷D通过NOD样受体蛋白3(NOD-like receptor protein 3,NLRP3)介导细胞焦亡,抑制未分化甲状腺癌细胞增殖的作用及机制。方法培养未分化甲状腺癌细胞株HTh83和KMH2,不同浓度柴胡皂苷D(1、4、7、10、13、16、19、22、25、28... 目的研究柴胡皂苷D通过NOD样受体蛋白3(NOD-like receptor protein 3,NLRP3)介导细胞焦亡,抑制未分化甲状腺癌细胞增殖的作用及机制。方法培养未分化甲状腺癌细胞株HTh83和KMH2,不同浓度柴胡皂苷D(1、4、7、10、13、16、19、22、25、28、31、34、37μmol/L)作用48 h后检测细胞存活率,计算半数抑制浓度(50%inhibition concentration,IC50);细胞分为对照组(0μmol/L柴胡皂苷D)、低浓度组(2.2μmol/L柴胡皂苷D)、中浓度组(11μmol/L柴胡皂苷D)、高浓度组(22μmol/L柴胡皂苷D)、si-NC组(转染NC siRNA)、高浓度+si-NC组(22μmol/L柴胡皂苷D联合转染NC siRNA)、高浓度+si-NLRP3组(22μmol/L柴胡皂苷D联合转染NLRP3 siRNA),处理48 h后检测克隆形成数目,NLRP3、裂解型Caspase-1、GSDMD氨基末端片段(GSDMD N terminal fragment,GSDMD-N)的表达水平及培养基中白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-18(interleukin-18,IL-18)的水平。结果柴胡皂苷D以浓度依赖的方式降低HTh83细胞和KMH2细胞的存活率(P<0.05);低浓度组、中浓度组、高浓度组的细胞克隆数目低于对照组(P<0.05),NLRP3、裂解型Caspase-1、GSDMD-N的表达水平及培养基中IL-1β、IL-18的水平高于对照组(P<0.05);高浓度+si-NLRP3组细胞的存活率及克隆数目高于高浓度+si-NC组(P<0.05),NLRP3、裂解型Caspase-1、GSDMD-N的表达水平及培养基中IL-1β、IL-18的水平低于高浓度+si-NC组(P<0.05)。结论柴胡皂苷D能显著抑制未分化甲状腺癌细胞增殖,其作用机制可能与激活NLRP3,介导细胞焦亡有关。 展开更多
关键词 未分化甲状腺癌 柴胡皂苷D 增殖 NOD样受体蛋白3 焦亡
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Targeting transcriptional regulators for treatment of anaplastic thyroid cancer
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作者 Woo Kyung Lee Sheue-Yann Cheng 《Journal of Cancer Metastasis and Treatment》 2021年第1期381-398,共18页
Dysregulation of genes perpetuates cancer progression.During carcinogenesis,cancer cells acquire dependency of aberrant transcriptional programs(known as“transcription addiction”)to meet the high demands for uncontr... Dysregulation of genes perpetuates cancer progression.During carcinogenesis,cancer cells acquire dependency of aberrant transcriptional programs(known as“transcription addiction”)to meet the high demands for uncontrolled proliferation.The needs for particular transcription programs for cancer growth could be cancer-type-selective.The dependencies of certain transcription regulators could be exploited for therapeutic benefits.Anaplastic thyroid cancer(ATC)is an extremely aggressive human cancer for which new treatment modalities are urgently needed.Its resistance to conventional treatments and the lack of therapeutic options for improving survival might have been attributed to extensive genetic heterogeneity due to subsequent evolving genetic alterations and clonal selections during carcinogenesis.Despite this genetic complexity,mounting evidence has revealed a characteristic transcriptional addiction of ATC cells resulting in evolving diverse oncogenic signaling for cancer cell survival.The transcriptional addiction has presented a huge challenge for effective targeting as shown by the failure of previous targeted therapies.However,an emerging notion is that many different oncogenic signaling pathways activated by multiple upstream driver mutations might ultimately converge on the transcriptional responses,which would provide an opportunity to target transcriptional regulators for treatment of ATC.Here,we review the current understanding of how genetic alterations in cancer distorted the transcription program,leading to acquisition of transcriptional addiction.We also highlight recent findings from studies aiming to exploit the opportunity for targeting transcription regulators as potential therapeutics for ATC. 展开更多
关键词 Transcriptional addiction TRANSCRIPTION oncogene addiction cancer stem cell thyroid hormone receptors steroid receptor coactivators BET inhibitor anaplastic thyroid cancer
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