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1.
Endocr Pract ; 27(3): 216-222, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33779554

RESUMO

OBJECTIVE: The sensitivity of thyroglobulin (Tg) to detect differentiated thyroid cancer recurrence increases with the rise of the thyrotropin level. Since 1998, recombinant human thyrotropin (rhTSH) has been commercially available for this purpose. The traditional protocol for using rhTSH calls for 2 daily injections of rhTSH, followed by the measurement of Tg 72 hours after the second dose. In this study, we compared the performance of rhTSH-stimulated Tg (rhTSH-Tg) obtained at 48 versus 72 hours after the second rhTSH. METHODS: A retrospective chart review of 1088 patients with thyroid cancer was conducted. Two hundred forty-nine rhTSH-Tg, without measurable Tg antibody, were identified, 134 of which were obtained at 48 hours (4-day test) and 115 at 72 hours after the second rhTSH (5-day test). The ability of rhTSH-Tg to identify recurrence or persistence of differentiated thyroid cancer and to predict response to therapy at the end of the study period was compared between the 2 groups. RESULTS: The median duration of follow-up was 8 years. When recurrent/persistent cancer was present based on a combination of unstimulated Tg, imaging and procedures, the ratio of rhTSH-Tg ≥ 1 ng/mL was similar in both groups (P value: .153). The negative predictive value of rhTSH-Tg to predict response to therapy over the long term was 95% or higher in 4-day and 5-day tests. CONCLUSION: Tg measured 48 and 72 hours after the second dose of rhTSH may provide a comparable prognostic value. These results encourage further studies to identify new protocols to obtain rhTSH-Tg.


Assuntos
Tireoglobulina , Neoplasias da Glândula Tireoide , Humanos , Recidiva Local de Neoplasia/diagnóstico , Prognóstico , Proteínas Recombinantes , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Tireotropina
2.
Medicine (Baltimore) ; 100(12): e25191, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761701

RESUMO

RATIONALE: Though the majority of differentiated thyroid cancer (DTC) patients have a good prognosis after careful and standardized therapy, approximately 13% to 15% of DTC cases show surprisingly aggressive behavior and invasion of the surrounding structures, and a few progress to unresectable diseases. In this study, we report a case of an inoperable locally advanced DTC patient who underwent a curative operation after treatment of preoperative monotherapy of apatinib in a short time. PATIENT CONCERNS: A 64-year-old woman complained of dysphagia due to large cervical mass, which severely invaded the left esophagus at the junction of the neck and thorax. DIAGNOSES: The female patient was diagnosed with locally advanced papillary thyroid cancer (PTC) by cytopathology and it was difficult to perform a safe and complete removal. INTERVENTIONS: Apatinib (500 mg orally once a day) was initially used to treat this patient as a neoadjuvant therapy. OUTCOMES: Six weeks later, the tumor dramatically shrunk from 56 × 37 mm to 29 × 26 mm with well-controlled mild hypertension. After a 10-day interval of apatinib withdrawal, complete tumor excision was accomplished through cervical incision without esophageal fistula. Postoperative thyroid stimulating hormone suppression and radioiodine 131I ablation therapy were performed. At the 1-year follow-up evaluation, no tumor recurrence or metastasis was observed. LESSONS: Preoperative short term targeted treatment with apatinib for locally advanced inoperable DTC may become a promising neoadjuvant therapy that, can reduce the tumor size and decrease stage, thus making the complete and safe removal of the lesion feasible.


Assuntos
Antineoplásicos/uso terapêutico , Terapia Neoadjuvante , Piridinas/uso terapêutico , Câncer Papilífero da Tireoide/tratamento farmacológico , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia , Transtornos de Deglutição/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Câncer Papilífero da Tireoide/complicações , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento
3.
Anticancer Res ; 41(3): 1555-1561, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788749

RESUMO

BACKGROUND/AIM: Anaplastic thyroid carcinoma (ATC) is the least common but most lethal of thyroid cancer, despite various therapeutic options, with limited efficacy. In order to help therapeutic decision-making, the purpose of this study was to develop a new prognostic score providing survival estimates in patients with ATC. PATIENTS AND METHODS: Based on a multivariate analysis of 149 retrospectively analyzed patients diagnosed with ATC from 1968 to 2017 at a referral center, a propensity score was developed. A model was generated providing survival probability at 6 months and median overall survival estimates. RESULTS: The median survival was 96 days. The overall survival rate was 35% at 6 months, 20% at 1 year and 13% at 2 years. Stepwise Cox regression revealed that the most appropriate death prediction model included metastatic spread, tumor size and age class as explanatory variables. This model made it possible to define three categories of patients with different survival profiles. CONCLUSION: Distant metastasis, age and primary tumor size are strong independent factors that affect prognosis in patients with ATC. Using these significant pretreatment factors, we developed a score to predict survival in these patients with poor prognosis.


Assuntos
Carcinoma Anaplásico da Tireoide/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
4.
Anticancer Res ; 41(3): 1683-1691, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788766

RESUMO

BACKGROUND/AIM: Lenvatinib is standard therapy for radioiodine-refractory differentiated thyroid cancer (RR-DTC), although the optimal timing for starting treatment is still controversial. The aim of this study was to evaluate the prognostic impact of baseline tumour size (BTS) in patients with RR-DTC treated with lenvatinib. PATIENTS AND METHODS: Fifty-one RR-DTC patients who had at least one measurable lesion and treated with lenvatinib were retrospectively analysed. BTS was defined as the sum of the longest dimensions of all measurable target lesions. RESULTS: Median progression-free survival (PFS) and overall survival (OS) in the larger BTS (≥42 mm) group were shorter than those in the smaller (<42 mm) group. This result was more significant in patients with fast-growing tumours. BTS was an independent prognostic factor for both PFS and OS. CONCLUSION: Starting lenvatinib at BTS <42 mm should be recommended to achieve good treatment outcomes in patients with RR-DTC.


Assuntos
Radioisótopos do Iodo/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia
5.
Medicine (Baltimore) ; 100(4): e23866, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530180

RESUMO

INTRODUCTION: Metastasis of a papillary thyroid microcarcinoma (PTMC) in the lateral neck is characterized primarily by solid lymphadenopathy, although some cases may rarely present with a cervical cystic mass. We report a case of lateral cervical lymph node metastases of PTMC that appeared as a cystic lymphangioma of the lateral neck. PATIENT CONCERNS: A 55-year-old man with a painless egg-sized mass in the right side of the neck that had been present for 1 month underwent physical examination, ultrasonography, computed tomography (CT), fine needle aspiration biopsy (FNAB), and intraoperative fast-frozen pathological examination, which indicated that the cystic masses in the neck were benign. However, the final pathology report identified the lateral neck masses as lymph node metastases of thyroid carcinoma. DIAGNOSIS: The patient was diagnosed with PTMC of the right lobe of the thyroid gland with lateral neck metastases. INTERVENTIONS: The patient underwent right cervical neck dissection together with a right thyroidectomy, followed by levothyroxine therapy and routine follow-up. OUTCOMES: No postoperative complications were reported, and the thyroid-stimulating hormone inhibition target was <0.1 mmol/L; there was no detectable tumor recurrence on routine clinical follow-up for up to 16 months. CONCLUSIONS: This case report emphasizes the need to consider cervical lymph node metastases of thyroid carcinoma in the differential diagnosis for patients with large, multiple, simple cystic neck masses.


Assuntos
Carcinoma Papilar/patologia , Neoplasias de Cabeça e Pescoço/secundário , Linfangioma/patologia , Metástase Linfática , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar/tratamento farmacológico , Carcinoma Papilar/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Terapia de Reposição Hormonal , Humanos , Linfangioma/cirurgia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Tiroxina/uso terapêutico
6.
Mol Carcinog ; 60(3): 201-212, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33595872

RESUMO

Mutations in the BRAF gene are highly prevalent in thyroid cancer. However, the response rate of thyroid tumors to BRAF-directed therapies has been mixed. Increasingly, combination therapies inhibiting the MAPK pathway at multiple nodes have shown promise. Recently developed ERK1/2 inhibitors are of interest for use in combination therapies as they have the advantage of inhibiting the most downstream node of the MAPK pathway, therefore preventing pathway reactivation. Here, we examined the effect of combined BRAF inhibition (dabrafenib) and ERK1/2 inhibition (SCH772984) on the growth and survival of a panel of BRAF-mutant thyroid cancer cell lines using in vitro and in vivo approaches. We found that resistance due to MAPK pathway reactivation occurs quickly with single-agent BRAF inhibition, but can be prevented with combined BRAF and ERK1/2 inhibition. Combined inhibition also results in synergistic growth inhibition, decreased clonogenic survival, and enhanced induction of apoptosis in a subset of BRAF-mutant thyroid cancer cells. Finally, combined inhibition of BRAF and ERK1/2 results in enhanced inhibition of tumor growth in an anaplastic thyroid cancer in vivo model. These results provide key rationale to pursue combined BRAF and ERK1/2 inhibition as an alternative therapeutic strategy for BRAF-mutant advanced thyroid cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias da Glândula Tireoide/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Indazóis/administração & dosagem , Indazóis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Nus , Mutação , Oximas/administração & dosagem , Oximas/farmacologia , Piperazinas/administração & dosagem , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
J Cancer Res Clin Oncol ; 147(2): 323-337, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33387037

RESUMO

The incidence of papillary thyroid cancer (PTC), the major type of thyroid cancer, is increasing rapidly around the world, and its pathogenesis is still unclear. There is poor prognosis for PTC involved in rapidly progressive tumors and resistance to radioiodine therapy. Kinase gene fusions have been discovered to be present in a wide variety of malignant tumors, and an increasing number of novel types have been detected in PTC, especially progressive tumors. As a tumor-driving event, kinase fusions are constitutively activated or overexpress their kinase function, conferring oncogenic potential, and their frequency is second only to BRAFV600E mutation in PTC. Diverse forms of kinase fusions have been observed and are associated with specific pathological features of PTC (usually at an advanced stage), and clinical trials of therapeutic strategies targeting kinase gene fusions are feasible for radioiodine-resistant PTC. This review summarizes the roles of kinase gene fusions in PTC and the value of clinical therapy of targeting fusions in progressive or refractory PTC, and discusses the future perspectives and challenges related to kinase gene fusions in PTC patients.


Assuntos
Fusão Gênica , Proteínas Quinases/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Quinase do Linfoma Anaplásico/genética , Fusão Gênica/efeitos dos fármacos , Fusão Gênica/fisiologia , Humanos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-ret/genética , Receptor trkA/genética , Câncer Papilífero da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico
8.
Gan To Kagaku Ryoho ; 48(1): 148-150, 2021 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-33468750

RESUMO

An 82-year-old woman who underwent total thyroidectomy and left cervical lymph node dissection 21 years ago admitted our hospital because of left cervical pain. Neck CT scan showed a 6 cm tumor on the left clavicle. Pathological diagnosis by needle biopsy revealed poorly differentiated to undifferentiated carcinoma, positive for TTF-1, and diagnosed as thyroid cancer lymph node metastasis anaplastic transformation. Administration of lenvatinib was started after radiation therapy. Since thrombocytopenia was observed, lenvatinib was gradually reduced from 14 mg and the dose was continued at 4 mg. The tumor shrinked and the effect of chemotherapy was partial response. She survived for 3 years while continuing lenvatinib. We reported long-term survival due to radiation therapy and lenvatinib of anaplastic transformation of thyroid cancer in lymph node metastasis due to radiation therapy and lenvatinib.


Assuntos
Quinolinas , Neoplasias da Glândula Tireoide , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Compostos de Fenilureia , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
9.
Am J Nurs ; 121(2): 63-67, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33497131

RESUMO

ABSTRACT: The release of radioactive iodine after a nuclear disaster, such as those that occurred at the Fukushima Daiichi Nuclear Power Plant in Japan 10 years ago and Three Mile Island in Pennsylvania in 1979, increases thyroid cancer risk among people who are exposed. Certain populations are especially vulnerable, including pregnant and breastfeeding women, children, and neonates. Potassium iodide (KI) can effectively block radioactive iodine from being absorbed by the thyroid gland if taken immediately after a radiation release. This article examines lessons learned from Fukushima to enhance disaster readiness and nursing actions. Nurses should be directly involved in vulnerability assessments, emergency planning, and in ensuring the availability, accessibility, and distribution of KI within U.S. nuclear power plant emergency planning zones before a crisis occurs.


Assuntos
Acidente Nuclear de Fukushima , Iodeto de Potássio/uso terapêutico , Exposição à Radiação/prevenção & controle , Exposição Ambiental/prevenção & controle , Humanos , Japão , Iodeto de Potássio/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/prevenção & controle
10.
J Formos Med Assoc ; 120(1 Pt 1): 189-195, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32402521

RESUMO

BACKGROUND: Sorafenib has been shown to prolong the progression free survival (PFS) of advanced radioiodine (RAI) refractory differentiated thyroid cancer (DTC) and has been approved by the FDA as the result of the phase III DECISION trial. Sorafenib has been reimbursed for the treatment of RAI refractory DTC in Taiwan since Jan 2017. High percentage of adverse events (AE) was noted in DECISION trial. We conducted a study to show the real-world experience of sorafenib in Taiwan. METHODS: We retrospectively collected the clinical data, including dose, AE, and PFS of sorafenib, of the DTC patients who received sorafenib treatment in National Cheng Kung University Hospital and China Medical University Hospital by chart review from 2012 to 2018. RESULTS: Thirty-six advanced DTC patients with progression were included in this study. The starting dose of sorafenib in most patients was 200 mg twice daily and the mean daily maintenance dose was 433 mg. Five patients had partial response (13.9%) and 28 patients had stable disease (77.8%). The median PFS was 17.3 months (95% confidence interval: 11.9-33.6 months). Daily maintenance dose ≥ 600 mg was associated with better PFS (median PFS, not reached). The most common toxicity of sorafenib was hand foot skin reaction (69%), followed by diarrhea (42%), and skin rash (33%). Most of the toxicities were grade I/II. CONCLUSION: Higher maintenance dose of sorafenib is associated with longer PFS while starting from half dose is feasible to minimize the incidence of high grade toxicities in the real-world use of sorafenib.


Assuntos
Neoplasias da Glândula Tireoide , Antineoplásicos/efeitos adversos , China , Humanos , Radioisótopos do Iodo/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Estudos Retrospectivos , Sorafenibe/uso terapêutico , Taiwan , Neoplasias da Glândula Tireoide/tratamento farmacológico
11.
PLoS One ; 15(9): e0239315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970704

RESUMO

Anaplastic thyroid cancer (ATC) is a rare, but nearly uniformly fatal disease that is typically resistant to chemotherapy and radiation. Alternative strategies to target this cancer at a molecular level are necessary in order to improve dismal outcomes for ATC patients. We examined the effects of flavopiridol, a CDK inhibitor, in a panel of ATC cell lines. When cell lines were treated over a ten-point concentration range, CAL62, KMH2 and BHT-101 cell lines had a sub micromolar half-maximal inhibitory concentration, while no effect was seen in the non-cancerous cell line IMR-90. Flavopiridol treatment resulted in decreased levels of the cell cycle proteins CDK9 and MCL1, and induced cell cycle arrest. Flavopiridol also decreased the in vitro ability of ATC cells to form colonies and impeded migration using a transwell migration assay. In vivo, flavopiridol decreased tumor weight and tumor volume over time in a patient-derived xenograft model of ATC. Given the observed in vitro and in vivo activity, flavopiridol warrants further investigation for treatment of ATC.


Assuntos
Pontos de Checagem do Ciclo Celular , Flavonoides/uso terapêutico , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Quinase 9 Dependente de Ciclina/genética , Quinase 9 Dependente de Ciclina/metabolismo , Flavonoides/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Transplante Heterólogo
12.
N Engl J Med ; 383(9): 825-835, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32846061

RESUMO

BACKGROUND: RET mutations occur in 70% of medullary thyroid cancers, and RET fusions occur rarely in other thyroid cancers. In patients with RET-altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown. METHODS: We enrolled patients with RET-mutant medullary thyroid cancer with or without previous vandetanib or cabozantinib treatment, as well as those with previously treated RET fusion-positive thyroid cancer, in a phase 1-2 trial of selpercatinib. The primary end point was an objective response (a complete or partial response), as determined by an independent review committee. Secondary end points included the duration of response, progression-free survival, and safety. RESULTS: In the first 55 consecutively enrolled patients with RET-mutant medullary thyroid cancer who had previously received vandetanib, cabozantinib, or both, the percentage who had a response was 69% (95% confidence interval [CI], 55 to 81), and 1-year progression-free survival was 82% (95% CI, 69 to 90). In 88 patients with RET-mutant medullary thyroid cancer who had not previously received vandetanib or cabozantinib, the percentage who had a response was 73% (95% CI, 62 to 82), and 1-year progression-free survival was 92% (95% CI, 82 to 97). In 19 patients with previously treated RET fusion-positive thyroid cancer, the percentage who had a response was 79% (95% CI, 54 to 94), and 1-year progression-free survival was 64% (95% CI, 37 to 82). The most common adverse events of grade 3 or higher were hypertension (in 21% of the patients), increased alanine aminotransferase level (in 11%), increased aspartate aminotransferase level (in 9%), hyponatremia (in 8%), and diarrhea (in 6%). Of all 531 patients treated, 12 (2%) discontinued selpercatinib owing to drug-related adverse events. CONCLUSIONS: In this phase 1-2 trial, selpercatinib showed durable efficacy with mainly low-grade toxic effects in patients with medullary thyroid cancer with and without previous vandetanib or cabozantinib treatment. (Funded by Loxo Oncology and others; LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.).


Assuntos
Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas c-ret/antagonistas & inibidores , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipertensão/induzido quimicamente , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-ret/análise , Proteínas Proto-Oncogênicas c-ret/genética , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Transaminases/sangue , Resultado do Tratamento , Adulto Jovem
14.
Medicine (Baltimore) ; 99(28): e21190, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664162

RESUMO

The effects of thyrotropin (TSH) suppressive therapy on autonomic regulation and ventricular repolarization in patients with differentiated thyroid cancer (DTC) have not been elucidated. The aim of present study was to evaluate variation in heart rate variability (HRV) and QT dispersion after TSH suppressive therapy in patients with DTC.Cases, defined as 271 patients with DTC within 1 year of exogenous levothyroxine, and all patients underwent a full history, physical examination, including standard 12 lead electrocardiogram (ECG), and 24 h ambulatory ECG monitoring (Holter) with normal free thyroxine (FT4) and free triiodothyronine (FT3) with levothyroxine. To evaluate effects of TSH suppressive therapy on HRV and QT dispersion, patients were divided into three groups according to different levels of TSH: TSH < 0.1 mIU/L group and 0.1 ≤ TSH < 0.5 mIU/L group were as TSH suppression groups, and 0.5 ≤ TSH < 2.0 mIU/L group was as TSH replacement group.Comparing with 0.5 ≤ TSH < 2.0 mIU/L group, significant changes in both time and frequency domain of HRV and QT dispersion were observed in TSH < 0.1 mIU/L group (P < .001: SDNN, SDANN, HF, LF/HF, QTd, and QTcd; P < .05: rMSSD) and 0.1 ≤ TSH < 0.5 mIU/L group (P < .001: SDNN, HF, LF/HF, QTd, and QTcd), and especially were more pronounced in TSH < 0.1 mIU/L group. Moreover, we found that TSH level was proportional to SDNN (ß = 15.829, P < .001), but inversely proportional to LF/HF (ß = -0.671, P < .001), QTd (ß = -16.674, P < .001) and QTcd (ß = -18.314, P < .001) in DTC patients with exogenous levothyroxine.Compared with euthyroid state, patients with suppressed serum TSH have increased sympathetic activity in the presence of diminished vagal tone, ultimately showed sympathovagal imbalance and with an increased inhomogeneity of ventricular recovery times. These findings revealed that TSH suppression therapy had a significant impact on cardiovascular system and had certain guiding role in the treatment and management of patients with DTC.


Assuntos
Doenças do Sistema Nervoso Autônomo/induzido quimicamente , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Neoplasias da Glândula Tireoide/fisiopatologia , Tiroxina/efeitos adversos , Adulto , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/tratamento farmacológico , Tireotropina/sangue
15.
Eur J Endocrinol ; 183(4): 411-417, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32688334

RESUMO

Objective: At present, recombinant TSH cannot be used for the treatment of metastatic differentiated thyroid cancer patients. The aim of this study was to evaluate if the type of TSH stimulation, recombinant or endogenous, had an impact on the outcome of these patients. Design and methods: We compared the outcome of two propensity score-matched groups of metastatic patients, stimulated by either only recombinant TSH (n = 43) or only endogenous TSH (n = 34). Results: As expected from the matching procedure, the clinical-pathological features and the cumulative 131-I activities administered to the two groups were very similar. After 4 years of follow-up, 4% of patients were cured, 3% had biochemical disease and 93% had structural disease. However, 91% of patients obtained a clinical benefit from this therapy in terms of stabilization of the disease or complete remission or partial response. When considering the two groups separately, we did not find any difference in their outcome. When considering the response to 131-I therapy of the single type of metastases, 8% of lymph node metastases and 8% of lung metastases disappeared but none of the bone metastases. The response to 131-I therapy of the single type of metastases was similar when we looked at the two groups separately. Conclusions: This study shows (i) an overall clinical benefit of the 131-I therapy, since the majority of patients remained affected but with a stable disease, and (ii) that the preparation with either recombinant or endogenous TSH has no impact on the 131-I therapy efficacy and the outcome of our two groups of patients.


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Tireotropina/uso terapêutico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Quimioterapia Adjuvante , Criança , Terapia Combinada , Feminino , Seguimentos , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Pontuação de Propensão , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Resultado do Tratamento , Adulto Jovem
16.
Eur J Endocrinol ; 183(3): P1-P10, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32508309

RESUMO

The incidence of differentiated thyroid carcinoma (DTC) has increased rapidly over the past several years. Thus far, the only conclusively established risk factor for developing DTC is exposure to ionizing radiation, especially when the exposure occurs in childhood. Since the number of childhood cancer survivors (CCS) is increasing due to improvements in treatment and supportive care, the number of patients who will develop DTC after surviving childhood cancer (secondary thyroid cancer) is also expected to rise. Currently, there are no recommendations for management of thyroid cancer specifically for patients who develop DTC as a consequence of cancer therapy during childhood. Since complications or late effects from prior cancer treatment may elevate the risk of toxicity from DTC therapy, the medical history of CCS should be considered carefully in choosing DTC treatment. In this paper, we emphasize how the occurrence and treatment of the initial childhood malignancy affects the medical and psychosocial factors that will play a role in the diagnosis and treatment of a secondary DTC. We present considerations for clinicians to use in the management of patients with secondary DTC, based on the available evidence combined with experience-based opinions of the authors.


Assuntos
Carcinoma Papilar/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Sobreviventes de Câncer , Carcinoma Papilar/tratamento farmacológico , Carcinoma Papilar/cirurgia , Criança , Feminino , Humanos , Masculino , Fatores de Risco , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia
17.
Life Sci ; 256: 117925, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32522570

RESUMO

AIMS: This study aims to explore the effect and underlying mechanism of zoledronic acid (ZA) on the incidence of thyroid cancer (TC) tumorigenesis. MATERIALS AND METHODS: Human mononuclear cells THP-1 were differentiated into M2-like tumor associated macrophages (TAMs) by incubation with PMA followed by additional incubation of IL-4 and IL-13. TC cells TPC-1 and IHH4 were co-cultured with M2-like TAMs. Identification of M2-like TAMs markers were determined by immunohistochemistry or flow cytometry. Cell proliferation, stemness and migration/invasion ability were measured by colony, sphere formation assay and transwell assay, respectively. The expression levels of cell stemness, EMT and Wnt/ß-catenin pathway-related factors were verified by qRT-PCR, Western blotting, and immunofluorescence. A subcutaneous tumor model was established in nude mice to examine the in vivo effects of ZA. KEY FINDINGS: M2-like TAMs were enriched in TC tissues, and they promoted the colony/sphere formation, accompanied with a down-regulated expression in E-cadherin and an up-regulated expression in N-cadherin, Vimentin and other stemness-associated markers (CD133, Oct4, c-Myc) in TC cells. The effects were suppressed when ZA co-treatment was given, because ZA inhibited the polarization of M2-like TAMs and ß-catenin entry into the nucleus. Moreover, in agreement with in vitro data, ZA also limited subcutaneous tumor formation and macrophage enrichment in nude mice. SIGNIFICANCE: ZA suppressed M2-like TAMs induced TC cell proliferation, stemness and metastasis through inhibiting M2-like TAMs polarization and Wnt/ß-catenin pathway, which sheds light on the mechanisms of TC and provides avenues for the development of clinical therapy to TC.


Assuntos
Macrófagos/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Ácido Zoledrônico/farmacologia , beta Catenina/metabolismo , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Carcinogênese/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Transdução de Sinais , Células THP-1/metabolismo , Microambiente Tumoral , Via de Sinalização Wnt
18.
Arch Biochem Biophys ; 689: 108461, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32531316

RESUMO

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the development of papillary thyroid cancer. While rapamycin has been shown to exhibit anti-tumor effects, it may also activate AKT, resulting in increased cell survival and drug resistance, thereby limiting its anti-tumor effects. Resveratrol can also inhibit tumor growth by regulating the PI3K/AKT/mTOR signaling pathway. The present study investigated the anti-tumor effects of the combined use of rapamycin and resveratrol in papillary thyroid cancer. We first treated two human papillary thyroid cancer cell lines (KTC-1 and TPC-1) with single or combined administration, and examined the effects on proliferation, the cell cycle, apoptosis, and invasion/migration of papillary thyroid cancer cells. A mouse xenograft model was induced with KTC-1 and TPC-1 cells followed by treatment with single or combined administration. Body weight and tumor size were monitored to assess the toxicity of each compound. The phosphorylation of AKT and the mTORC1 target p70S6 kinase (p70S6K) in tumors was also examined. Both rapamycin and resveratrol inhibited proliferation, altered the cell cycle, and induced apoptosis of papillary thyroid cancer cells. Invasion and migration were also reduced, as was the tumor growth rate in the xenograft model. Co-administration significantly enhanced the anti-tumor effects than use of any one drug, and significantly reduced the phosphorylation of AKT and p70S6K compared to treatment with rapamycin alone. Overall, compared to single use of rapamycin or resveratrol, co-administration had a synergistic effect in inhibiting proliferation and invasion/migration of papillary thyroid cancer cells and inducing apoptosis. Resveratrol is sensitizing the anti-tumor effects of rapamycin and the PI3K/AKT/mTOR signaling is involved. Although further animal and clinical studies are needed to clarify the mechanism and assess drug safety, the present study suggests that the combination of rapamycin and resveratrol may be a promising strategy for the treatment of papillary thyroid cancer.


Assuntos
Antineoplásicos/uso terapêutico , Resveratrol/uso terapêutico , Sirolimo/uso terapêutico , Câncer Papilífero da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resveratrol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo
19.
Int J Clin Oncol ; 25(7): 1278-1284, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32347432

RESUMO

BACKGROUND: Proteinuria induced by lenvatinib is a class effect that occurs secondary to VEGFR suppression. Withholding of lenvatinib is required in cases with severe proteinuria. Urine protein-creatinine ratio (UPCR, g/gCre) has recently attracted attention as an alternative to 24-h urine collection for assessing proteinuria. The aim of this study was to examine the correlation between the results of proteinuria assessed by the dipstick test and UPCR, and to investigate the influence of proteinuria grading with UPCR on lenvatinib dose adjustment compared to that with only the dipstick test. METHOD: Three hundred and ten urine samples from 63 patients with advanced thyroid cancer under treatment with lenvatinib, which were tested by both the dipstick test and UPCR were analyzed. Lenvatinib was withheld when there was evidence of CTCAE grade 3 proteinuria, and restarted when it resolved. The frequency of proteinuria, correlation between the results of the dipstick test and UPCR test, and the effect of dose withholding in cases with results of 3 + in the dipstick test were calculated. RESULTS: Proteinuria was seen in 56 (88.9%) patients. Of the 154 dipstick 3 + samples, only 56 (36.4%) were judged as more than 3.5 g/gCre by UPCR (grade 3 proteinuria), although none of the 1 + and only 3.7% of 2 + samples were judged as grade 3 proteinuria. We were able to prevent unnecessary lenvatinib interruption due to proteinuria in 63.6% of dipstick 3 + samples by assessment of UPCR. CONCLUSIONS: Urinalysis by combination of the dipstick test and UPCR assessment might be a better strategy for preventing unnecessary interruption of lenvatinib.


Assuntos
Antineoplásicos/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Proteinúria/induzido quimicamente , Quinolinas/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Urinálise/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Creatinina/urina , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Proteinúria/diagnóstico , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/urina
20.
Medicine (Baltimore) ; 99(11): e19408, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176066

RESUMO

Some thyroid cancer patients experience a rapid disease progression after the discontinuation of tyrosine kinase inhibitors (TKIs), which is called flare phenomenon. The incidence of the flare phenomenon of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) ranged from 4% to 11.1% and the median time to occurrence of the flare phenomenon ranged from 7 to 12 days in previous reports. In this study, we investigate the timing and incidence of the flare phenomenon in thyroid cancer patients treated with lenvatinib.The records of patients treated with lenvatinib were retrospectively reviewed. The primary outcomes were the incidence rate and timing of the flare phenomenon after the discontinuation of lenvatinib. The flare phenomenon was defined as death, hospitalization attributable to tumor progression, or unexpected event (e.g., pleural drainage) within 1 month of lenvatinib cessation. We excluded patients with progression of underlying diseases other than thyroid cancer or infection, those in whom the disease progressed, or those who died without achieving a clinical response (stable disease, partial response, or complete response).In total, 8 (14.3%) of the 56 patients experienced the flare phenomenon. The median time from lenvatinib cessation to the flare phenomenon was 9 (range, 4-30) days. Three patients in the flare group died within 1 month of lenvatinib cessation without an imaging evaluation. The remaining 5 patients had dyspnea and pleural effusion, and pleural drainage was performed in 3 of the 5 patients. Lenvatinib was resumed in 4 of the 8 patients in the flare group. Median overall survival (OS) was 15.1 months in the flare group and 41.9 months in the non-flare group. The OS tended to be poor in the flare group than in the non-flare group; however, this difference was not statistically significant (P = .051).In lenvatinib treatment for thyroid cancer, the incidence and timing of the flare phenomenon were similar to those observed with other TKIs. OS tended to be poor in the flare group than in the non-flare group. Further studies are needed to determine the mechanism of the flare phenomenon and establish measures and treatment policies.


Assuntos
Antineoplásicos/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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