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1.
Endocrine ; 64(3): 622-631, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30826992

RESUMO

PURPOSESS: The purpose of this study was using next-generation sequencing technique to explore the potential association between germline variants of 14 targeted genes and papillary thyroid carcinoma (PTC) predisposition as well as disease progression. METHODS: In all, 516 subjects were enrolled in this study including 416 PTC patients and 100 healthy controls. PTC patients were divided into distant metastasis group and non-distant metastasis group. Patients in distant metastasis group were further divided into radioiodine-refractory PTC (RR-PTC) and non-RR-PTC depending on their response to radioiodine therapy. Genomic DNA was extracted from peripheral blood sample and MiSeq Benchtop Sequencer was used for sequencing. RESULTS: We found rs11246050 in NLRP6 (dominant model, OR/95% CI: 2.028/1.091-3.769, p = 0.025), rs2286742 and rs3740530 in HABP2 (recessive model, OR/95% CI: 9.644/1.307-71.16, p = 0.026 and 3.989/1.413-11.26, p = 0.009), rs2736098 in TERT (recessive model, OR/95% CI: 2.322/1.028-5.242. p = 0.042) and rs62054619 in GAS8-AS1 (recessive model, OR/95% CI: 2.219/1.067-4.617, p = 0.033) were associated with the risk of PTC. rs1137282 in KRAS (dominant model, OR/95% CI: 0.5430/0.3192-0.9236, p = 0.024), rs1347591 and rs4461062 in NUP93 (dominant model, OR/95% CI: 0.6121/0.4128-0.9076, p = 0.015 and 0.6156/0.4157-0.9117, p = 0.015) were associated with low risk of distant metastatic disease in PTC patients. rs33954691 in TERT was associated with the risk of RR-PTC under dominant model (OR/95% CI: 3.161/1.596-6.262). CONCLUSIONS: Germline variants of related genes could be associated with the susceptibility of PTC as well as disease progression (distant metastasis and radioiodine-refractory status). However, these results must be further verified and the potential biological functions of these germline variants in the pathogenesis of PTC remain to be determined in future studies.

2.
Endocr Pract ; 25(3): 279-286, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30913016

RESUMO

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) expression on tumor tissue has been associated with favorable response to anti-programmed cell death-receptor 1/PD-L1 therapy in many human cancers. Studies have reported that PD-L1 is also expressed in thyroid cancer. The objective of this paper is to introduce the potential predictive and therapeutic values of PD-L1 in thyroid cancer. METHODS: A literature search was conducted in the PubMed database using the terms "PD-L1," "B7-H1," and "thyroid cancer." PD-L1 positivity was determined by immunohistochemical assay. RESULTS: The frequency of PD-L1 positivity in different studies ranged from 6.1 to 82.5% in papillary thyroid cancer (PTC) patients and 22.2 to 81.2% in anaplastic thyroid cancer (ATC) patients. PD-L1 positivity rate was higher in ATC than in PTC within the same studies, and its expression intensity was significantly higher in tumor tissue than in the corresponding nontumor thyroid tissues. Moreover, PD-L1 expression was positively associated with the aggressiveness and recurrence of thyroid cancers and negatively associated with the differentiation status and outcomes. PD-L1 checkpoint pathway blockade may emerge as a promising therapeutic target in the treatment of thyroid cancers. CONCLUSION: PD-L1 is a potential biomarker to predict the recurrence and prognosis of thyroid cancers. It is also a novel immunotherapy target for optimizing the management landscape of radioiodine-refractory and ATCs. ABBREVIATIONS: ATC = anaplastic thyroid cancer; DTC = differentiated thyroid cancer; IHC = immunohistochemical; OS = overall survival; PD-1 = programmed cell death-receptor 1; PD-L1 = programmed cell death-ligand 1; PD-L2 = programmed cell death-ligand 2; PTC = papillary thyroid cancer; TNM = tumor-node-metastasis; Treg = regulatory T cell.


Assuntos
Neoplasias da Glândula Tireoide , Antígeno B7-H1 , Biomarcadores Tumorais , Morte Celular , Humanos , Radioisótopos do Iodo , Recidiva Local de Neoplasia , Prognóstico
3.
J Foot Ankle Surg ; 58(3): 434-440, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30876811

RESUMO

Both osteoarthritis and impingement syndrome are the disorders commonly observed in sports medicine. However, failure in pain alleviation by surgical intervention introduces challenges in the diagnosis and decision-making for orthopedists. Hybrid single photon emission computed tomography/computed tomography (SPECT/CT) provides both functional and structural information of ankle pathology. The purpose of this retrospective study was to evaluate whether bone tracer uptake by ankle SPECT/CT is related to the lesion type and visual analog scale (VAS) pain score for patients with osteoarthritis and bony impingement. Fifty individuals with chronic ankle pain who underwent pretreatment ankle SPECT/CT were included in the current study. The median follow-up period was 2.5 (range 1.8 to 3.2) years. The lesion types were categorized by the positions of anatomical changes and bone tracer uptake. The VAS pain score was recorded 2 weeks before and 1.5 year after surgical intervention. Twenty-nine (58%) of 50 patients had osseous impingement. Among them, 16 (55.2%), 4 (13.8%), and 9 (31%) patients had anterior, posterior, and both types of ankle impingement, respectively. The uptake grade of bone tracer was significantly related to the lesion type of ankle impingement (p < .001). The VAS pain score was significantly correlated with bone tracer uptake before treatment (p < .001). Bone tracer uptake was related to the lesion type of impingement detected by SPECT/CT and was confirmed by surgical findings. The VAS pain score was significantly correlated with the bone tracer uptake. Preoperative ankle SPECT/CT may be helpful to clinically correlate the VAS pain score in the pre- and postsurgical periods for patients with osteoarthritis and bony impingement syndrome.

4.
Clin Nucl Med ; 43(11): e412-e413, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30106862

RESUMO

Extraskeletal osteosarcomas are uncommon entities in clinical practice, which account for 1% to 2% of all soft tissue sarcomas. We here reported a case of multiple extraskeletal osteosarcomas and nuclear medicine imaging findings of this disease in Tc-MDP bone scan as well as F-FDG PET/CT.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Fluordesoxiglucose F18 , Osteossarcoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Medronato de Tecnécio Tc 99m , Feminino , Humanos , Pessoa de Meia-Idade
5.
Endocrine ; 62(1): 149-158, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30022382

RESUMO

PURPOSE: Papillary thyroid carcinoma (PTC) with pulmonary metastases is rare in children and adolescents. Unlike adults, limited data are available on children with this disease. Thus, this study evaluated the therapeutic efficacy and prognostic factors of individuals less than 21 years of age with pulmonary metastases from PTC. METHODS: Seventy-six children and adolescents with pulmonary metastases from PTC treated with 131I were retrospectively analyzed. Therapeutic efficacy was evaluated by changes in serum thyroglobulin (Tg) and chest computed tomography (CT). Factors predictive of progression-free survival and overall survival were measured by the Kaplan-Meier method. RESULTS: Among the 76 patients included in this study, 22.4% (17 of 76) were less than 15 years old and 65.8% (50 of 76) were female. Under the evaluation of stimulated serum Tg levels, RAI treatment were effective in 55.9% (38 of 68), stable in 26.5% (18 of 68) and ineffectvie in 17.6% (12 of 68) of patients. Changes on anatomical imaging suggested complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) in 8.5, 62.0, 15.5, and 14.1% of individuals, respectively. Univariate analysis showed that size and tumor doubling time of pulmonary metastases were independent factors affecting therapeutic efficacy. Extra-thyroidal extension, tumor diameter of pulmonary metastases and tumor doubling time were significant independent factors regarding progression-free survival rates, while only tumor doubling time and tumor diameter were significant risk factors associated with overall survival rate. CONCLUSIONS: Radioactive iodine therapy is an effective treatment for children and adolescents with pulmonary metastases from PTC. Extra-thyroid extension was associated with disease progression while did not show significant influence on overall survival. Tumor doubling time and tumor diameter were the main factors influencing both progression-free survival and overall survival.

6.
Cell Physiol Biochem ; 48(2): 718-730, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30025398

RESUMO

BACKGROUND/AIMS: As biomarkers, circulating tumor cells (CTCs) from solid tumors can predict metastases and prognoses, and help monitor treatment efficacy. However, conventional CellSearch methods have low sensitivity to differentiated thyroid cancer (DTC) CTCs. In this study, for the first time, we used negative enriching (NE) immunofluorescence-in situ hybridization (iFISH) of chromosome 8 to capture and identify CTCs in DTC patients; and investigated how CTCs correlate with clinicopathological factors and prognosis in DTC patients with distant metastases (DM). METHODS: In this prospective study, we enrolled 72 patients with DTC before they underwent 131I treatment, and 30 healthy controls (HC). Their CTCs were measured in 7.5 ml peripheral blood using the NE-iFISH technique. CTC was defined by the aneuploidy. RESULTS: We detected CTCs in 62 (86.1%) of the 72 subjects with DTC. The mean number of CTCs in patients with DTC with DM (DM+) was significantly higher than in the HC group (P< 0.001) and DTC patients without DM (DM-; P=0.0016). We found CTCs ≥ 5 was significantly associated with DM+ DTC (P=0.009; sensitivity: 64.3%; specificity: 83.8%); CTCs ≥ 7 was related to poor response to 131I treatment (sensitivity: 73.7 %; specificity: 69.6 %), and was also associated with worse prognosis in DM+ DTC (P< 0.001). CONCLUSION: We found CTCs ≥ 5 to be a potential predictive index for DM+ DTC; and CTCs ≥7 as a possible indicator of poor response to 131I treatment and worse prognosis in DM+ DTC.


Assuntos
Células Neoplásicas Circulantes/metabolismo , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Aneuploidia , Área Sob a Curva , Criança , Feminino , Humanos , Radioisótopos do Iodo/química , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/mortalidade , Adulto Jovem
7.
Oncotarget ; 8(41): 71188-71196, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-29050355

RESUMO

The purpose of this study was to evaluate the diagnostic potential of dual time-point18F-FDG PET/CT imaging with multiple metabolic parameters in malignancy-suspected bone/joint lesions. Fifty seven consecutive patients were recruited. PET parameters including SUVmax, SUVmean, metabolic tumor volume (MTV), total lesional glycolysis (TLG) and retention indexes (RIs) were obtained. Thirty five malignant and 22 benign lesions were confirmed by pathology. In all, 48 receiver operating characteristic (ROC) curves were derived. For SUVmax, MTV2.0, TLG2.0, MTV2.5 and TLG2.5, areas under the curves (AUCs) of early time-point imaging were similar to those of delayed time (P > 0.05), while higher than those of dual time (P< 0.05). For MTV50%max, TLG50%max, MTV75%max and TLG75%max, AUCs of early time-point imaging were lower than those of delayed time (P< 0.05), while similar to those of dual time (P> 0.05). In conclusion, dual time-point18F-FDG PET/CT imaging shows limited value in the differential diagnosis of malignancy-suspected bone/joint lesions. However, MTV and TLG at a fixed SUV threshold (50% or 75% of SUVmax) in delayed time-point imaging may provide better diagnostic accuracy.

8.
Endocrine ; 58(1): 176-183, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28884426

RESUMO

PURPOSE: The relationship between thyroid autoimmunity and thyroid cancer remains controversial. The objective of this study is to comprehensively analyze the association between thyroid autoimmune antibodies and disease statuses of papillary thyroid carcinoma (PTC). METHODS: Patients were divided into different groups according to their final diagnoses after radioiodine therapy as well as their serum anti-thyroglobulin antibody (TgAb) and anti-thyroidperoxidase antibody (TPOAb) titers. Clinicopathologic characteristics were then compared between groups. RESULTS: In all, 1126 PTC patients met the inclusion criteria. When compared with thyroid autoimmune antibody negative group, patients in positive group were young female predominant. After age and gender adjusted, patients in thyroid autoimmune antibody positive group had much more cervical metastatic node count and this effect was limited to the central compartment but not to the lateral compartment. Antibody positivity rate was much lower in patients with distant metastasis and multivariable logistic regression analysis showed positive status of antibody was a protective factor of distant metastasis of PTC with an OR value of 0.403 (95% CI 0.216-0.622, p < 0.001). Additionally, subgroup analysis demonstrated single TgAb positivity and combined positivity of TgAb and TPOAb were shown to be related to less distant metastatic disease. CONCLUSIONS: Positive thyroid auto-antibody status could be a risk factor of more metastatic cervical lymph nodes while a protective factor of distant metastatic disease in PTC patients. The association between thyroid autoimmunity and thyroid cancer can be patient and antibody specific. A systemic immunosupression status may exist in PTC patients with distant metastasis.


Assuntos
Autoanticorpos/imunologia , Carcinoma Papilar/imunologia , Doenças da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/imunologia , Adulto , Idoso , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/radioterapia , Feminino , Humanos , Iodeto Peroxidase/imunologia , Radioisótopos do Iodo/uso terapêutico , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Metástase Linfática/radioterapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Caracteres Sexuais , Tireoglobulina/imunologia , Câncer Papilífero da Tireoide , Doenças da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/secundário
9.
Am J Nucl Med Mol Imaging ; 7(3): 92-104, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28721303

RESUMO

Although fibrous dysplasia is not considered a potentially premalignant disorder, malignant transformation occurs. Because of its rarity, radiographic features of malignantly transformed fibrous dysplasia on cross-sectional imaging modalities are less recognized, making diagnosis and differential diagnosis of the disease quite difficult in clinical practice. In this study, we analyzed the clinical characteristics, imaging features, pathology findings and surgery strategies of 19 malignantly transformed fibrous dysplasia. We found that there was significant male predominance in this specific cohort (13/6). While osteosarcoma (63.2%) was the most frequently occurring neoplasm secondary to fibrous dysplasia, other less commonly malignantly changed types included fasciculated sarcoma, malignant fibrous histiocytoma, fibrosarcoma and chondrosarcoma. We found that the diagnostic value of single modality imaging method, like conventional X-ray, computed tomography or non-contrast magnetic resonance imaging, was limited mainly because of a lack of whole-body metabolic information. In contrast, we highlighted that 99mTc-MDP SPECT/CT and/or 18F-FDG PET/CT scanning could exert a pivotal role in the management of malignantly transformed fibrous dysplasia by guiding precise biopsy and optimizing surgery options.

10.
Clin Nucl Med ; 42(9): e405-e406, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28719445

RESUMO

Adefovir-induced hypophosphatemic osteomalacia in the context of hepatocarcinoma is rare and needs to be differentiated from metastatic hepatocarcinoma. We here report a case of severe osteomalacia whose focal uptakes of radiotracer on the Tc-MDP SPECT/CT images mimicked that of metastatic hepatocarcinoma.


Assuntos
Adenina/análogos & derivados , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Hipofosfatemia/complicações , Neoplasias Hepáticas/patologia , Organofosfonatos/efeitos adversos , Osteomalacia/induzido quimicamente , Osteomalacia/diagnóstico , Adenina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Osteomalacia/complicações , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único
11.
Clin Endocrinol (Oxf) ; 87(6): 844-852, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28755525

RESUMO

BACKGROUND: Although the incidence rate for thyroid cancer seems to have begun stabilizing in recent years, an increased rate of advanced stage of this disease has been reported. Additionally, distant metastasis is one of the most important prognostic factors of patients with papillary thyroid carcinoma (PTC). Unfortunately, the underlying mechanisms of distant metastasis, as well as cell status like metabolism changes in distant metastatic tumours have not been clearly elucidated. OBJECTIVE: To identify serum metabolic signature of distant metastatic PTC. DESIGN, PATIENTS AND MEASUREMENTS: In this study, gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) was used to analyse the serum from 77 patients diagnosed with PTC (37 in distant metastasis group and 40 in ablation group). Principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) scores plots were used to analyse the data. RESULTS: Principal component analysis and OPLS-DA analyses demonstrated an evident trend of separation between 40 serum samples from the ablation group and 37 samples from distant metastasis group. A total of 31 metabolites were identified, which are related to amino acid, lipid, glucose, vitamin metabolism and diet/gut microbiota interaction. Pathway analysis showed "alanine, aspartate and glutamate metabolism" and "inositol phosphate metabolism" were the most relevant pathways. CONCLUSION: Serum metabolomics profiling could significantly discriminate papillary thyroid cancer patients according to distant metastasis. Potential metabolic aberration in distant metastatic PTC could be involved in different biological behaviours of tumour cells including proliferation, invasion/migration and immune escape. Diet/gut microbiota-produced metabolites could play an important role in these effects. This work may provide new clues to find the underlying mechanisms regarding the distant metastasis of PTC as well as potential adjuvant therapy targets.


Assuntos
Carcinoma Papilar/sangue , Neoplasias da Glândula Tireoide/sangue , Adolescente , Adulto , Carcinoma/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide , Adulto Jovem
12.
Sci Rep ; 7(1): 2849, 2017 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-28588229

RESUMO

Differentiated thyroid cancer (DTC) patients with negative serum thyroglobulin (Tg), negative 131I whole-body scintigraphy (131I-WBS) at first post-ablation and progressively increased TgAb level are a relatively rare entity in the follow-up after total thyroidectomy and radioactive iodine therapy. The value of 18F-FDG PET/CT in detecting the recurrence of disease in these patients has only been reported in a small case series. The goal of this study was to investigate the diagnostic accuracy of 18F-FDG PET/CT in detecting recurrent disease in these specific PTC patients and to identify risk factors for patients with positive 18F-FDG PET/CT results. Eighty-two PTC patients who had 18F-FDG PET/CT scans with negative Tg, negative 131I-WBS at first post-ablation and progressively increased TgAb levels were included. We found that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18F-FDG PET/CT in this patient group were determined as 84%, 72%, 92%, 57% and 82%, respectively. 18F-FDG PET/CT scan had a good diagnostic performance and should be performed routinely in PTC patients with negative Tg, negative 131I-WBS at first postablation and progressively increased TgAb level, especially when span for progressively increased TgAb level ≥ 3 years and/or progressively increased TgAb value up to 150 IU/mL.

13.
Theranostics ; 7(4): 987-1001, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28382170

RESUMO

Although the prognosis of differentiated thyroid cancer (DTC) is relatively good, 30-40% of patients with distant metastases develop resistance to radioactive iodine therapy due to tumor dedifferentiation. For DTC patients harboring BRAFV600E mutation, Vemurafenib, a BRAF kinase inhibitor, has dramatically changed the therapeutic landscape, but side effects and drug resistance often lead to termination of the single agent treatment. In the present study, we showed that either LY3009120 or Obatoclax (GX15-070) efficiently inhibited cell cycle progression and induced massive death of DTC cells. We established that BRAF/CRAF dimerization was an underlying mechanism for Vemurafenib resistance. LY3009120, the newly discovered pan-RAF inhibitor, successfully overcame Vemurafenib resistance and suppressed the growth of DTC cells in vitro and in vivo. We also observed that expression of anti-apoptotic Bcl-2 increased substantially following BRAF inhibitor treatment in Vemurafenib-resistant K1 cells, and both Obatoclax and LY3009120 efficiently induced apoptosis of these resistant cells. Specifically, Obatoclax exerted its anti-cancer activity by inducing loss of mitochondrial membrane potential (ΔΨm), dysfunction of mitochondrial respiration, reduction of cellular glycolysis, autophagy, neutralization of lysosomes, and caspase-related apoptosis. Furthermore, the cancer killing effects of LY3009120 and Obatoclax extended to two more Vemurafenib-resistant DTC cell lines, KTC-1 and BCPAP. Taken together, our results highlighted the potential value of LY3009120 for both Vemurafenib-sensitive and -resistant DTC and provided evidence for the combination therapy using Vemurafenib and Obatoclax for radioiodine-refractory DTC.


Assuntos
Antineoplásicos/administração & dosagem , Resistência a Medicamentos , Indóis/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Pirimidinas/administração & dosagem , Pirróis/administração & dosagem , Sulfonamidas/administração & dosagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Xenoenxertos , Humanos , Camundongos Nus , Multimerização Proteica , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas c-raf/metabolismo , Resultado do Tratamento , Vemurafenib
14.
J Mol Endocrinol ; 58(1): 15-23, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27920093

RESUMO

More aggressive thyroid cancer cells show a higher activity of glycometabolism. Targeting cancer cell metabolism has emerged as a novel approach to prevent or treat malignant tumors. Glucose metabolism regulation effect of metformin in papillary thyroid cancer was investigated in the current study. Human papillary thyroid carcinoma (PTC) cell lines BCPAP and KTC1 were used. Cell viability was detected by CCK8 assay. Glucose uptake and relative gene expression were measured in metformin (0-10 mM for 48 h)-treated cells by 18F-FDG uptake assay and western blotting analysis, respectively. MicroPET/CT imaging was performed to detect 18F-FDG uptake in vivo After treatment with metformin at 0, 2.5, 5 and 10 mM for 48 h, the ratio of p-AMPK to total AMPK showed significant rising in a dose-dependent manner in both BCPAP and KTC1, whereas p-AKT and p-mTOR expression level were downregulated. 18F-FDG uptake reduced after metformin treatment in a dose-dependent manner, corresponding to the reduced expression level of HK2 and GLUT1 in vitro Xenograft model of PTC using BCPAP cells was achieved successfully. MicroPET/CT imaging showed that in vivo 18F-FDG uptake decreased after treatment with metformin. Immunohistochemistry staining further confirmed the reduction of HK2 and GLUT1 expression in the tumor tissue of metformin-treated PTC xenograft model. In conclusion, metformin could reduce glucose metabolism of PTC in vitro and in vivo Metformin, by targeting glycometabolism of cancer cells, could be a promising adjuvant therapy alternative in the treatment modality of advanced thyroid carcinoma.


Assuntos
Carcinoma Papilar/metabolismo , Glucose/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Metformina/farmacologia , Neoplasias da Glândula Tireoide/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Linhagem Celular Tumoral , Sobrevivência Celular , Modelos Animais de Doenças , Feminino , Fluordesoxiglucose F18 , Expressão Gênica , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Xenoenxertos , Hexoquinase/genética , Hexoquinase/metabolismo , Humanos , Imuno-Histoquímica , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia
15.
Cell Physiol Biochem ; 40(6): 1377-1390, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27997908

RESUMO

PURPOSE: The aims of the current study were to explore plasma lncRNAs as a novel biomarker panel for the diagnosis of non-131I-avid lung metastases of PTC and to investigate the plasma lncRNA expression levels associated with survival in PTC patients with lung metastases. METHODS: The expression of lncRNAs was examined using an lncRNA microarray chip. The lncRNAs with the most significant difference in expression between PTC patients with non-131I-avid lung metastases and PTC patients with 131I-avid lung metastases were verified by quantitative reverse-transcription polymerase chain reaction. The Kaplan-Meier method was used to determine whether the plasma lncRNA levels might be indicative of patient prognosis. RESULTS: Compared with 131I-avid lung metastases, we discovered that two lncRNAs (ENST00000462717 andENST00000415582) were upregulated and two (TCONS_00024700 and NR_028494) were downregulated in the non-131I-avid lung metastases of PTC. Receiver operating characteristic curve (ROC) analyses indicated that the use of these four lncRNAs had high diagnostic sensitivity and specificity for predicting non-131I-avid lung metastases of PTC. The merged areas under the curve for ENST00000462717, ENST00000415582, TCONS_00024700,and NR_028494 in the training and validation sets were 0.890, 0.936, 0.975, and 0.918, respectively. Low (ENST00000462717 and ENST00000415582) and high plasma lncRNA levels(TCONS_00024700and NR_028494) were also found to be associated with better prognosis of PTC patients with lung metastases(P<0.001). CONCLUSIONS: ENST00000462717, ENST00000415582, TCONS_00024700, and NR_028494 may be used as novel and minimally invasive markers for the diagnosis and prognostic assessment of non-131I-avid lung metastases from PTC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma/diagnóstico por imagem , Carcinoma/mortalidade , Radioisótopos do Iodo/metabolismo , Neoplasias Pulmonares/secundário , RNA Longo não Codificante/sangue , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/mortalidade , Biomarcadores Tumorais/genética , Carcinoma/sangue , Carcinoma Papilar , Estudos de Casos e Controles , Demografia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Longo não Codificante/genética , Curva ROC , Reprodutibilidade dos Testes , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/sangue
16.
Oncol Rep ; 36(3): 1576-84, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27432558

RESUMO

Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective ß-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study. Broad ß-blocker propranolol and ß2-specific antagonist ICI118551, but not ß1-specific antagonist atenolol, inhibited the growth of 8505C and K1 cells. Propranolol treatment inhibited growth and induced apoptosis of 8505C cells in vitro and in vivo, which are closely associated with decreased expressions of cyclin D1 and anti-apoptotic Bcl-2. Expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) also decreased following propranolol intervention. 18F-FDG PET/CT imaging of the 8505C xenografts validated shrinkage of the tumors in the propranolol-treated group when compared to the phosphate­buffered saline treated group. Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. Our present results suggest that propranolol has potential activity against thyroid cancers and investigation of the combination with targeted molecular therapy for progressive thyroid cancers could be beneficial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Indóis/farmacologia , Propranolol/farmacologia , Sulfonamidas/farmacologia , Neoplasias da Glândula Tireoide/patologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , Vemurafenib , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Exp Clin Cancer Res ; 35(1): 101, 2016 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-27342319

RESUMO

BACKGROUND: Serum miRNAs profiles between papillary thyroid carcinoma (PTC) patients with non-(131)I and (131)I-avid lung metastases are differentially expressed. These miRNAs have to be further validated and the role of these miRNAs in the molecular function level of thyroid cancer cell lines has not been investigated. METHODS: Expression levels of six identified miRNAs were assessed via quantitative real-time PCR (qRT-PCR) in the serum of eligible patients. Dual-luciferase reporter assay was used to determine the potential target of miR-106a. Cell viability and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively. The change of gene expression was detected by qRT-PCR and western blotting analysis. In vitro iodine uptake assay was conducted by a γ-counter. RESULTS: Compared to PTC patients with (131)I-avid lung metastases, miR-106a was up-regulated in the serum of patients with non-(131)I-avid lung metastases. The results of dual-luciferase reporter assay demonstrated that miR-106a directly targeted retinoic acid receptor beta (RARB) 3'-UTR. miR-106a-RARB promoted viability of thyroid cancer cells by regulating MEKK2-ERK1/2 and MEKK2-ERK5 pathway. miR-106a-RARB inhibited apoptosis of thyroid cancer cells by regulating ASK1-p38 pathway. Moreover, miR-106a-RARB could regulate the expression of sodium iodide symporter, TSH receptor and alter the iodine uptake function of thyroid cancer cells. CONCLUSIONS: miRNA-106a, directly targeting RARB, associates with the viability, apoptosis, differentiation and the iodine uptake function of thyroid cancer cell lines by regulating MAPK signaling pathway in vitro. These findings in the present study may provide new strategies for the diagnosis and treatment in radioiodine-refractory differentiated thyroid carcinoma.


Assuntos
Carcinoma Papilar/genética , Neoplasias Pulmonares/secundário , MicroRNAs/genética , Receptores do Ácido Retinoico/genética , Simportadores/metabolismo , Neoplasias da Glândula Tireoide/genética , Regiões 3' não Traduzidas , Adulto , Carcinoma Papilar/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Iodo/metabolismo , Neoplasias Pulmonares/genética , Sistema de Sinalização das MAP Quinases , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Receptores da Tireotropina/metabolismo , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Regulação para Cima
18.
Mol Cell Endocrinol ; 434: 108-15, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27329154

RESUMO

Circulating afamin (AFM) concentrations have been investigated as a tumor biomarker in various types of carcinomas. However, suitable cell lines expressing human afamin have not yet been reported and current knowledge of the functions of afamin, particularly at the mechanistic molecular level, is very limited. In the current study, thyroid cancer cell lines 8505c and K1 were used to investigate the potential functions of afamin. AFM over-expression models and vector controls of 8505c (8505c + AFM and 8505c + NC) and K1 (K1 + AFM and K1 + NC) were successfully established by Lenti-LV5-AFM and Lenti-LV5-NC transfection. The change of gene expression was detected by qRT-PCR and western blotting analysis. (18)F-FDG imaging in xenografts model was performed using a micro PET/CT. We found that protein level of GAPDH, GLUT1, HK2, p-AKT, AKT, p-mTOR and PARP1 were up-regulated in K1 + AFM cells when compared to K1 and K1 + NC. While in 8505c, 8505c + NC and 8505c cells, the expression level of these genes were not significantly changed. (18)F-FDG uptake was much higher in K1 + AFM cells when compared to K1 and K1 + NC in vitro and in vivo. In conclusion, afamin could promote glycometabolism by up-regulating the glucose metabolism key enzymes in papillary thyroid carcinoma. These findings reveal new clues of the molecular function of AFM.


Assuntos
Carcinoma Papilar/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Glucose/metabolismo , Glicoproteínas/genética , Glicoproteínas/metabolismo , Albumina Sérica/genética , Albumina Sérica/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Animais , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/genética , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Células HEK293 , Hexoquinase/genética , Hexoquinase/metabolismo , Humanos , Camundongos , Transplante de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Albumina Sérica Humana , Transdução de Sinais , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/genética
19.
Endocrine ; 51(2): 283-90, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26093847

RESUMO

Metastatic differentiated thyroid carcinoma (DTC) with positive (131)I scintigraphy, but negative stimulated Tg (sTg) is relatively rare in clinical practice. The clinical characteristics of these patients were analyzed in the current study. A total of 3367 consecutive histologically proven DTC patients were analyzed retrospectively from January 2007 to June 2013. Tg negativity was defined as a sTg level of <2 ng/mL without positive anti-Tg antibody (TgAb level of <100 IU/mL) under thyroid-stimulating hormone stimulation (TSH level of ≥30 mIU/L). Analyses were performed using the Statistical Package for the Social Sciences, version 20.0 (SPSS, Chicago, IL, USA). Seventy-one patients (median age 45 years, range 17-68 years) were post-therapeutic (131)I-SPECT/CT positive and sTg negative (PTP-TN) constituting 2.1 % of all patients. Of these 71 patients, 2 (2.8 %) had bone metastasis, 11 (15.5 %) had lung metastasis, and 59 (83.1 %) had lymph node metastasis. Fifty-six patients had cervical lymph node metastasis (cLNM), and US was positive in 15 patients (26.8 %), while negative in 41 patients (73.2 %). When compared to patients with concordant positive results for sTg and (131)I scintigraphy, US showed a relatively lower positive rate in the detection of cLNM in PTP-TN patients (28.8 vs. 53.8 %; χ (2) = 6.70; P = 0.01). In conclusion, even with sTg <2 ng/mL, there is a low risk of metastatic DTC. US had limitations in PTP-TN patients, while post-therapy (131)I-SPECT/CT demonstrated an advantage in the detection of functioning metastasis despite low sTg levels in patients with metastatic DTC.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adolescente , Adulto , Idoso , Neoplasias Ósseas/secundário , Feminino , Humanos , Radioisótopos do Iodo , Neoplasias Pulmonares/secundário , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Imagem Corporal Total , Adulto Jovem
20.
Clin Endocrinol (Oxf) ; 84(1): 127-33, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25510178

RESUMO

OBJECTIVE: Thyroid cancer is the most common endocrine malignancy, and its incidence has been increasing over the last 30 years. Several studies have suggested that miRNAs may play a significant role in the differential diagnosis of indeterminate thyroid nodules. To systematically evaluate the utility of miRNAs in discriminating malignant thyroid nodules from benign ones on fine-needle aspiration biopsy (FNAB) samples, a systematic review and meta-analysis of the published literatures were carried out. PATIENTS AND DESIGN: Three hundred and sixty-one samples, obtained from 341 patients, were included in the research, and summary sensitivities (SEN), specificities (SPE), positive likelihood ratios, negative likelihood ratios and diagnostic odds ratio were calculated. Then, summary receiver operating characteristic curves (SROCs) and areas under the SROC curves (AUCs) were calculated to further estimate the overall diagnostic value of miRNAs in thyroid cancer. RESULTS: The overall pooled SEN, SPE and AUC are 0·75, 0·81 and 0·89, respectively. For multiple miRNAs assays, the pooled SEN, SPE and AUC are 0·87, 0·75 and 0·68, respectively. For single miRNA assays, the corresponding results are 0·71, 0·84 and 0·87, respectively. The corresponding statistical results for differentiating indeterminate FNAB samples are 0·92, 0·68 and 0·86, respectively. CONCLUSION: Our current meta-analysis suggests that miRNAs may serve as a novel diagnostic tool in distinguishing malignant thyroid nodules from benign ones on FNAB specimens. In addition, subgroup analysis suggests that a panel of miRNAs may have a higher sensitivity but a relatively lower specificity than that of single miRNA in distinguishing thyroid nodules.


Assuntos
MicroRNAs/genética , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Biomarcadores Tumorais/genética , Biópsia por Agulha Fina , Diagnóstico Diferencial , Regulação Neoplásica da Expressão Gênica , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
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