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1.
Adv Exp Med Biol ; 1287: 155-168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034031

RESUMO

Thyroid cancer is the most common malignancy of the endocrine system with a steadily rising incidence. The term "thyroid cancer" encompasses a spectrum of subtypes, namely papillary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, and medullary thyroid cancer. Each subtype differs histopathologically and in degrees of cellular differentiation, which may be in part due to signaling of the Notch pathway. The Notch pathway is an evolutionarily conserved signal transduction mechanism that regulates cell proliferation, differentiation, survival, stem cell maintenance, embryonic and adult development, epithelial-mesenchymal transition, and angiogenesis. Its role in cancer biology is controversial, as it has been shown to play both an oncogenic and tumor-suppressive role in many different types of cancers. This discordance holds true for each subtype of thyroid cancer, indicating that Notch signaling is likely cell type and context dependent. Whether oncogenic or not, Notch signaling has proven to be significantly involved in the tumorigenesis of thyroid cancer and has thus earned interest as a therapeutic target. Advancement in the understanding of Notch signaling in thyroid cancer holds great promise for the development of novel treatment strategies to benefit patients.


Assuntos
Receptores Notch/metabolismo , Transdução de Sinais , Neoplasias da Glândula Tireoide/metabolismo , Humanos , Oncogenes , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
3.
Chirurgia (Bucur) ; 115(4): 441-447, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32876017

RESUMO

Background: Receptor-binding cancer antigen (RCAS1) is a membrane protein, regarded as a tumor-associated antigen. Cancer cells evade immune response with RCAS1 up-regulation, inducing apoptosis to tumor infiltrating lymphocytes. Thyroid cancer incidence is rising and its accurate diagnosis in early stage is targeted. The aim of this study is to access RCAS1 expression in benign and malignant thyroid pathology. Methods: This is a retrospective study of 110 patients, who had thyroidectomy in a single tertiary referral centre between January 2008 until December 2014. Immunohistochemistry study for RCAS1 expression was carried out and correlation with clinical and histopathological data is attempted. Results: RCAS1 immunostaining was found positive in 81 out of 110 cases. Notably it was deemed positive in all malignant thyroid tissue samples (p 0.001). In thyroid malignancy, tumor size, thyroid capsule invasion and positive lymph nodes status were positively correlated with moderate and strong expression of RCAS1. For papillary thyroid carcinoma, the vast majority (35/37 cases, 94.6%) were also classified as having moderate or strong RCAS1 expression. Conclusions: RCAS1 expression can aid in differential diagnosis between benign and malignant thyroid pathology, while its strong expression correlates with worse oncological features.


Assuntos
Antígenos de Neoplasias/biossíntese , Neoplasias da Glândula Tireoide/metabolismo , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Resultado do Tratamento
4.
Life Sci ; 259: 118374, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32891613

RESUMO

OBJECTIVE: Dipeptidyl peptidase IV (DPP4) has been indicated as a possible prognostic biomarker in papillary thyroid cancer (PTC). However, the mechanism of DPP4 during metastasis of PTC remains unclear. In this study, we investigated whether lysine acetyltransferase 5 (KAT5) and FBJ murine osteosarcoma viral oncogene homolog B (FosB) synergistically regulate high DPP4 expression in PTC. METHODS: PTC tissues and matched paracancerous tissues were harvested, followed by the establishment of IHH-4 and TPC-1 cells with downregulation of DPP4. The relevance of DPP4 on the metastasis of PTC cells was assessed. Subsequently, the effect of KAT5 on the transcription of DPP4 was verified. The binding relationship between FosB and DPP4 was predicted by a bioinformatics website. Functional rescue experiments were performed to evaluate cell activities after overexpression of KAT5 or FosB in cells with DPP4 knockdown. RESULTS: DPP4 was overexpressed in PTC tissues and cell lines, which was correlated with higher risks for metastases and poorer survival. DPP4 downregulation curtailed cell growth and metastasis. Moreover, KAT5 acetylated DPP4 promoter histone, which promoted transcription activation of DPP4. Subsequently, FosB recruited KAT5 at the DPP4 promoter, thereby enhancing DPP4 transcriptional activation. Further overexpression of KAT5 or FosB in cells with low expression of DPP4 promoted cell activity. Finally, DPP4 expedited p62 nuclear translocation to elevate Keap1/Nrf2 expression, thus facilitating the growth and metastasis of PTC cells. CONCLUSION: FosB enhanced the growth and metastasis of PTC cells by recruiting histone acetyltransferases KAT5 to increase DPP4 transcription and activate the p62/Keap1/Nrf2 signaling.


Assuntos
Dipeptidil Peptidase 4/metabolismo , Lisina Acetiltransferase 5/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Animais , Western Blotting , Linhagem Celular Tumoral , Feminino , Imunofluorescência , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo
5.
Anticancer Res ; 40(7): 3801-3809, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620619

RESUMO

AIM: Cancer stem-like cell (CSC) markers and the role of CSCs derived from papillary thyroid carcinoma (PTC) in pathogenesis are unclear. This study aimed to investigate CSC properties using tumor spheres from passaged PTC cells but without sorting CSCs. MATERIALS AND METHODS: To identify the properties of CSCs derived from PTC, the expression of SRY-box transcription factor 2(SOX2), octamer-binding transcription factor 4 (OCT4), Nanog homeobox (NANOG), thyroglobulin (TG), thyroid-stimulating hormone receptor (TSHR), E-cadherin, YES-associated protein 1 (YAP1), and signal transducer and activator of transcription 3 (STAT3) was investigated in tumor spheres serially passaged without sorting CSCs. RESULTS: The cultured tumor spheres had cancer stemness; high expression of OCT4, SOX2, NANOG, and YAP1; low expression of E-cadherin; and varied expression of TG, TSHR, and STAT3. PTC tumor spheres transfected with small interfering RNA targeting YAP1 had fewer CSC properties than the non-transfected tumor spheres did. CONCLUSION: Tumor spheres derived from PTC cells by passaging without sorting CSCs have more stem-like cell properties, and less differentiation potential. Thus, this simple and cost-effective method can be used for the enrichment of PTC stemness for employment in cell-based models, reducing the need for use of animal models.


Assuntos
Células-Tronco Neoplásicas/patologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Antígenos CD/biossíntese , Antígenos CD/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Caderinas/biossíntese , Caderinas/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Humanos , Células-Tronco Neoplásicas/metabolismo , Fator 3 de Transcrição de Octâmero/biossíntese , Fator 3 de Transcrição de Octâmero/genética , Fator de Transcrição STAT3/biossíntese , Fator de Transcrição STAT3/genética , Esferoides Celulares , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética
6.
Medicine (Baltimore) ; 99(26): e20644, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590739

RESUMO

The present study aimed to investigate the correlation between ultrasonographic features, basic fibroblast growth factor (bFGF), and the local invasiveness of papillary thyroid carcinoma (PTC).A total of 350 samples of thyroid nodules were collected. Routine ultrasonography was performed before the operation and routine pathological diagnosis and bFGF detection were performed after the operation.'These 350 samples of thyroid nodules included 90 samples of nodular goiter, 36 samples of focal thyroiditis, and 224 samples of PTC. A total of 326 thyroid nodules were examined for bFGF. The results revealed that the difference in the expression of bFGF between the benign and malignant groups was statistically significant (P < .05) and the difference in the positive expression of bFGF between the invasive and non-invasive PTC groups was statistically significant (P < .05).Whether the shape of PTC is regular or not and whether there is micro-calcification in PTC and other ultrasonographic features, the size and location of the lesions and the age of the patient help make a preliminary prediction of local invasiveness before the operation. Postoperative detection of bFGF is helpful for further risk assessments of PTC.


Assuntos
Fator 2 de Crescimento de Fibroblastos/metabolismo , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/metabolismo , Adulto , Fatores Etários , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Bócio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Prospectivos , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/metabolismo , Tireoidite/metabolismo , Ultrassonografia , Adulto Jovem
7.
Zhonghua Zhong Liu Za Zhi ; 42(6): 463-468, 2020 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-32575941

RESUMO

Objective: To explore the differential protein expressions in papillary thyroid carcinoma (PTC) with or without Hashimoto's thyroiditis (HT). Methods: Tissue microarray was prepared and the protein expression levels of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), vascular endothelial growth factor (VEGF), cyclinD1, mesothelial cell (MC) , CD56 and Galectin3 in the PTC tissues with or without HT were detected by immunohistochemical staining. Results: The positive expression rates of BRAF protein in the PTC tissues with or without HT groups were 55.4% (36/65) and 63.6% (42/66), respectively, without significant difference (P=0.336). The positive expression rates of VEGF protein in the PTC tissues with or without HT groups were 25.7% (19/74) and 25.8%(17/66), respectively, without significant difference (P=0.991). The positive expression rates of cyclin D1 protein in the PTC tissues with or without HT groups were 93.4% (71/76) and 97.6% (80/82), without significant difference (P=0.206). The positive expression rates of MC protein in the PTC tissues with or without HT groups were 86.1% (62/72) and 83.5%(71/85), without significant difference (P=0.654). The positive expression rates of Galectin3 protein in the PTC tissues with or without HT groups were 98.7% (76/77) and 97.5% (78/80), without significant difference (P=0.583). The positive expression rates of CD56 in the PTC tissues and adjacent thyroid follicular epithelial cells were 27.4% (32/117) and 65.0% (76/117), respectively, and the difference was statistically significant (P=0.001). The positive expression rates of CD56 in PTC tissues with or without HT were 35.5% (24/68) and 16.5% (13/79), respectively, and the difference was statistically significant (P=0.009). Conclusions: There are no significant differences in the expressions of BRAF, VEGF, CyclinD1, MC and Galectin3 between the PTC tissues with or without HT. However, the significantly differential expression of CD56 between the two group suggests that CD56 may be related to the pathogenesis of PTC with HT. CD56 may be used as a potential molecular marker in PTC diagnosis.


Assuntos
Adenocarcinoma Papilar/genética , Antígeno CD56/metabolismo , Carcinoma Papilar/patologia , Doença de Hashimoto/genética , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/patologia , Animais , Biomarcadores/análise , Carcinoma Papilar/metabolismo , Ciclina D1/genética , Galectinas , Doença de Hashimoto/metabolismo , Doença de Hashimoto/patologia , Humanos , Camundongos , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas B-raf/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Análise Serial de Tecidos , Fator A de Crescimento do Endotélio Vascular/genética
8.
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
9.
Eur J Histochem ; 64(2)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32363847

RESUMO

To develop a new therapeutic strategy against thyroid cancer (TC), the expression of both substance P (SP) and neurokinin-1 receptor (NK-1R) must be demonstrated in TC cells. This study aims to examine by immunohistochemistry, the localization of SP and the NK-1R in human TC samples (papillary, follicular, medullary, anaplastic), in metastasis and in healthy thyroid samples. SP and the NK-1R were expressed in all normal and TC samples. In healthy glands, SP was located in follicular cells (nucleus) and colloid and NK-1R in follicular cells (cytoplasm) and stroma. In TC samples, SP was visualized in follicular cells (nucleus and cytoplasm), stroma and colloid and NK-1R in follicular cells (cytoplasm), stroma and colloid. A semiquantitative scoring system (Allred Unit Scoring System) was applied. The expression (Allred total score) of SP and NK-1R was weaker in normal thyroid glands than in TC. In comparison with TC samples, a lower intensity/proportion of SP (nucleus and cytoplasm of follicular cells; stroma) was observed in normal samples. By contrast, in the colloid of TC samples the presence of SP was lower than in normal samples. In comparison with TC samples, the presence of the NK-1R in the cytoplasm of follicular cells and colloid was lower in normal thyroid samples, whereas the expression of this receptor in the stroma was higher. The results reported in this study suggest that the NK-1R could be a new target for the treatment of TC and use of the NK-1R antagonists could serve as a new anti-TC therapeutic strategy.


Assuntos
Receptores da Neurocinina-1/metabolismo , Substância P/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Estatísticas não Paramétricas , Células Epiteliais da Tireoide/metabolismo , Glândula Tireoide/citologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
10.
PLoS One ; 15(5): e0232480, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32365074

RESUMO

A five-compartmental biokinetic model of I-131 radioiodine based on in-vivo gamma camera scanning results was developed and successfully applied to nine thyroid cancer patients who were administered 1,110 MBq I-131 in capsules for the residual thyroid gland ablation. The I-131 solution activity among internal organs was analyzed via the revised biokinetic model of iodine recommended by the ICRP-30 and -56 reports. Accordingly, a five-compartmental (stomach, body fluid, thyroid, whole body, and excretion) model was established to simulate the metabolic mechanism of I-131 in thyroid cancer patients, whereas the respective four simultaneous differential equations were solved via a self-developed program run in MATLAB. This made it possible to provide a close correlation between MATLAB simulation results and empirical data. The latter data were collected through in-vivo gamma camera scans of nine patients obtained after 1, 4, 24, 48, 72, and 168 hours after radioactive I-131 administration. The average biological half-life values for the stomach, body fluid, thyroid, and whole body of thyroid cancer patients under study were 0.54±0.32, 12.6±1.8, 42.8±5.1, and 12.6±1.8 h, respectively. The corresponding branching ratios I12, I23, I25, I34, I42, and I45 as denoted in the biokinetic model of iodine were 1.0, 0.21±0.14, 0.79±0.14, 1.0, 0.1, and 0.9, respectively. The average values of the AT dimensionless index used to verify the agreement between empirical and numerical simulation results were 0.056±0.017, 0.017±0.014, 0.044±0.023, and 0.045±0.009 for the stomach, thyroid, body fluid + whole body, and total, respectively. The results obtained were considered quite instrumental in the elucidation of metabolic mechanisms in the human body, particularly in thyroid cancer patients.


Assuntos
Radioisótopos do Iodo/farmacocinética , Modelos Biológicos , Compostos Radiofarmacêuticos/farmacocinética , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/metabolismo , Adulto , Idoso , Simulação por Computador , Feminino , Câmaras gama , Meia-Vida , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Distribuição Tecidual
11.
Gene ; 750: 144681, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32304784

RESUMO

Thyroid cancer (THCA) is one of the most common endocrine tumors and keeps rapidly increasing worldwide. Acidic nuclear phosphoprotein 32 family member E (ANP32E) is a H2A.Z histone chaperone that regulates the expression of various genes. It has been shown that ANP32E promotes breast cancer development, whereas its role in THCA remains unknown. In this study, we found that ANP32E was significantly overexpressed in THCA tissues. Down-regulation of ANP32E inhibited the growth, cell cycle progression, DNA synthesis, glycolysis, migration and increased apoptosis in K1 and TPC-1 cells. Opposite results were observed in ANP32E-overexpressing THCA cells. At the molecular level, ANP32E up-regulated MMP9 and MMP13, and activated AKT/mTOR/HK2 signaling in THCA cells. Positive correlation between ANP32E and HK2 was found in THCA tissues. Importantly, silencing of HK2 repressed glycolysis. Inhibition of AKT/mTOR reduced cell proliferation, cell cycle progression and migration in THCA cells. Our findings suggest that ANP32E promotes THCA cell proliferation and migration via potentiating AKT/mTOR/HK2-mediated glycolysis.


Assuntos
Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Adulto , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Glicólise , Hexoquinase/metabolismo , Humanos , Masculino , Proteínas Nucleares/genética , Nucleossomos/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Glândula Tireoide/patologia , Ativação Transcricional
12.
World Neurosurg ; 139: 310-313, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32339726

RESUMO

BACKGROUND: Pituitary blastoma is a malignant neoplasm of the pituitary gland that was recognized by the World Health Organization in 2017. It is commonly diagnosed in children before 24 months of age. Here, we report the first case of a young adult patient who was diagnosed with pituitary blastoma with increased levels of growth hormone instead of adrenocorticotropic hormone and provide a review of the literature. CASE DESCRIPTION: A 19-year-old woman presented to our hospital with visual disturbance. She had a medical history of Wilms' tumor and multinodular goiter. The brain imaging showed a 3.2 × 2.5 × 1.8-cm solid sellar and suprasellar cystic mass that upwardly displaced the optic chiasm. She had an elevated level of growth hormone but a normal level of adrenocorticotropic hormone, cortisol, and prolactin. The mass was subtotally removed through the left pterional craniotomy. The pathologic examination suggested a pituitary blastoma. Thereafter, the patient was treated with chemotherapy and radiotherapy. At 4-year follow-up postsurgery, her overall well-being is good. CONCLUSIONS: Although in this case the patient was a young adult, pituitary blastoma should be taken into consideration when children have an enhanced sellar and suprasellar mass with peripherally located cysts.


Assuntos
Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias da Glândula Tireoide/patologia , Feminino , Bócio Nodular , Hormônio do Crescimento/metabolismo , Humanos , Neoplasias Renais , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/cirurgia , Segunda Neoplasia Primária/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/cirurgia , Tumor de Wilms , Adulto Jovem
13.
Sci Rep ; 10(1): 4142, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139737

RESUMO

We aimed to investigate the role of RORγt (Retinoic acid-related orphan receptor gamma) in the tumor microenvironment of differentiated thyroid carcinoma. We retrospectively analyzed 56 patients (48 papillary and 8 follicular thyroid carcinomas). Immunohistochemical expression of RORγt was compared to other immune markers previously investigated by our group, clinical and pathological information. All patients presented cytoplasmic expression of RORγt in thyroid tumor cells. Seven (12.5%) patients presented no nuclear expression of RORγt. Positivity was few (up to 10%) in 14 patients; 10 to 50% in 5 patients (8.9%); and more than 50% in 30 patients (53.6%). Nuclear RORγt positivity was associated with absence of distant metastasis at diagnosis (p = 0.013) and the need of less cumulative doses of radioactive iodine (p = 0.039). Patients whose tumors were positive for nuclear RORγt presented higher 10-years relapse-free survival rate than those patients who were negative for RORγt (p = 0.023). We classified the patients according to the clustering of immunological immunohistochemical markers. We were able to distinguish a subset (A) of 38 patients who presented high expression of nuclear RORγt and tended to be scarce in proinflammatory immune markers. Other 16 patients integrated a second subset (B) whose tumor microenvironment accumulated proinflammatory markers and presented low expression of nuclear nuclear RORγt. Distant metastasis at diagnosis were more frequent among patients from cluster B than from cluster A (p = 0.008). Our results reinforce that the expression of RORγt together with other immune markers might help predict the prognosis of patients with thyroid cancer and help individualize clinical management.


Assuntos
Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Adulto , Análise por Conglomerados , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/mortalidade
14.
Life Sci ; 250: 117519, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32147429

RESUMO

OBJECTIVE: Papillary thyroid cancer (PTC) is the most ordinary type of thyroid cancer. Studies pivoting on the mechanisms of microRNAs (miRNAs) are adequately explored but not much on miR-448 in PTC. Thus, this study is proposed to bring forward the uncovered mechanisms of miR-448 in PTC. METHODS: Lysine specific demethylase 5B (KDM5B), miR-448 and transforming growth factor ß-induced factor 1 (TGIF1) expression in PTC tissues and cell lines were detected. The connection between miR-448 expression and clinicopathological characteristics of PTC patients was determined. PTC cell lines TPC-1 and K-1 were transfected with sh-KDM5B, si-TGIF1 or miR-448 mimic to explore their roles in PTC cell progression. Tumor xenografts in nude mice was performed to detect tumor volume and weight. RESULTS: KDM5B and TGIF1 were increased and miR-448 was declined in PTC tissues and cell lines. MiR-448 expression was connected with N stage, lymph node metastasis and advanced tumor node metastasis stage of PTC patients. KDM5B knockdown or TGIF1 reduction or miR-448 elevation undermined PTC cell progression and inhibited tumor growth of nude mice. Down-regulation of miR-448 followed by KDM5B knockdown reversed the effect of decreased KDM5B on the proliferation inhibition and apoptosis promotion of PTC cells. CONCLUSION: Our study elaborates that KDM5B-mediated miR-448 up-regulation restrains PTC cell progression and slows down tumor growth via TGIF1 repression, which provides a novel reference for treatment of PTC.


Assuntos
Carcinoma Papilar/metabolismo , Proteínas de Homeodomínio/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , MicroRNAs/genética , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Idoso , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Transplante de Neoplasias , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima
15.
Oncol Res ; 28(4): 345-355, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32138807

RESUMO

Anaplastic thyroid carcinoma (ATC) is resistant to standard therapies and has no effective treatment. Eukaryotic translation initiation factor 5A2 (EIF5A2) has shown to be upregulated in many malignant tumors and proposed to be a critical gene involved in tumor metastasis. In this study, we aimed to investigate the expression status of EIF5A2 in human ATC tissues and to study the role and mechanisms of EIF5A2 in ATC tumorigenesis in vitro and in vivo. Expression of EIF5A2 protein was analyzed in paraffin-embedded human ATC tissues and adjacent nontumorous tissues (ANCT) (n=24) by immunochemistry. Expressions of EIF5A2 mRNA and protein were analyzed in fresh-matched ATC and ANCT (n=23) and ATC cell lines by real-time polymerase chain reaction (PCR) and Western blotting. The effect of targeting EIF5A2 with short hairpin RNA (shRNA) or EIF5A2 overexpression on the ATC tumorigenesis and TGF-/Smad2/3 signals in vitro and in vivo was investigated. Expression of EIF5A2 was significantly upregulated in ATC tissues and cell lines compared with ANCT and normal follicular epithelial cell line. Functional studies found that targeting EIF5A2 induced SW1736 cell death in vitro and in vivo, followed by significantly downregulated phosphorylation of Smad2/3 (p-Smad2/3) in SW1736 cells at the protein level. Ectopic expression of EIF5A2 could promote 8505C cell growth in vitro and in vivo, followed by significantly upregulated p-Smad3 at the protein level. Recombinant human TGF-1 (hTGF-1) treatment decreased the antiproliferative activity of the EIF5A2 downexpressing 8505C cells through reversing pSmad2/3. Using the specific inhibitor SB431542 to block TGF- pathway or Smad3 siRNA to knock down Smad3 increased the antiproliferative activity of the EIF5A2-overexpressing 8505C cells through inhibiting pSmad2/3. Our findings indicated that EIF5A2 controled cell growth in ATC cells, and EIF5A/TGF-/Smad2/3 signal may be a potential therapeutic target for ATC treatment.


Assuntos
Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Carcinoma Anaplásico da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Apoptose , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Humanos , Fatores de Iniciação de Peptídeos/genética , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Regulação para Cima
16.
Sci Rep ; 10(1): 3639, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107431

RESUMO

There is concern among residents that their children might suffer from thyroid cancer in the near future after the Fukushima Daiichi nuclear power station (FDNPS) accident. However, the demographic and geographical distribution of thyroid equivalent doses was not thoroughly evaluated, and direct thyroid measurements were conducted only for 1,200 children, whose individual thyroid doses were assessed on the basis of those measurements accounting for the dynamics of radioiodine intake. We conducted hierarchical clustering analyses of 100 or 300 randomly sampled behavioural questionnaire sheets of children from each of seven municipalities in the evacuation area to reconstruct evacuation scenarios associated with high or low exposures to plumes. In total 896 behaviour records in the Fukushima Health Management Survey were analysed to estimate thyroid equivalent doses via inhalation, using a spatiotemporal radionuclides concentration database constructed by atmospheric dispersion simulations. After a decontamination factor for sheltering and a modifying factor for the dose coefficient-to reflect lower iodine uptake rate in Japanese-were applied, estimated thyroid equivalent doses were close to those estimated from direct thyroid measurement. The median and 95th percentile of thyroid equivalent doses of 1-year-old children ranged from 0.6 to 16 mSv and from 7.5 to 30 mSv, respectively. These results are useful for future epidemiological studies of thyroid cancer in Fukushima.


Assuntos
Acidente Nuclear de Fukushima , Neoplasias Induzidas por Radiação , Doses de Radiação , Inquéritos e Questionários , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Japão/epidemiologia , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/metabolismo , Monitoramento de Radiação , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/metabolismo
17.
Biochemistry (Mosc) ; 85(1): 108-118, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32079522

RESUMO

The MAPK (RAS/BRAF/MEK/ERK) signaling pathway is a kinase cascade involved in the regulation of cell proliferation, differentiation, and survival in response to external stimuli. The V600E mutation in the BRAF gene has been detected in various tumors, resulting in a 500-fold increase in BRAF kinase activity. However, monotherapy with selective BRAF V600E inhibitors often leads to reactivation of MAPK signaling cascade and emergence of drug resistance. Therefore, new targets are being developed for the inhibition of components of the aberrantly activated cascade. It was recently discovered that resistance to BRAF V600E inhibitors may be associated with the activity of the tyrosine phosphatase SHP-2 encoded by the PTPN11 gene. In this paper, we analyzed transcriptional effects of PTPN11 gene knockdown and selective suppression of BRAF V600E in a model of thyroid follicular epithelium. We found that the siRNA-mediated knockdown of PTPN11 after vemurafenib treatment prevented an increase in the expression CCNA1 and NOTCH4 genes involved in the formation of drug resistance of tumors. On the other hand, downregulation of PTPN11 expression blocked the transcriptional activation of genes (p21, p15, p16, RB1, and IGFBP7) involved in cell cycle regulation and oncogene-induced senescence in response to BRAF V600E expression. Therefore, it can be assumed that SHP-2 participates not only in emergence of drug resistance in cancer cells, but also in oncogene-induced cell senescence.


Assuntos
Proteína Tirosina Fosfatase não Receptora Tipo 11/fisiologia , Proteínas Proto-Oncogênicas B-raf/metabolismo , Células Epiteliais da Tireoide , Neoplasias da Glândula Tireoide/metabolismo , Ciclo Celular , Linhagem Celular , Senescência Celular , Resistencia a Medicamentos Antineoplásicos/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Células Epiteliais da Tireoide/citologia , Células Epiteliais da Tireoide/metabolismo , Glândula Tireoide/citologia , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Vemurafenib/uso terapêutico
18.
J Clin Ultrasound ; 48(4): 227-230, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32045024

RESUMO

Metastases to the submandibular gland are extremely rare; a literature search retuned only three previously reported cases from a thyroid gland primary site. Herein, we report two cases of metastatic thyroid carcinoma to the submandibular gland in a 64-year-old woman with PTC and a 70-year-old-woman with medullary thyroid carcinoma (MTC). The metastases were identified on CT and PET/CT in one case and on CT in the other case, but both were diagnosed with ultrasound-guided fine-needle aspiration. Our cases highlight that while rare, both PTC and MTC can metastasize to the submandibular gland.


Assuntos
Carcinoma Neuroendócrino/secundário , Neoplasias da Glândula Submandibular/secundário , Câncer Papilífero da Tireoide/secundário , Neoplasias da Glândula Tireoide/patologia , Idoso , Biópsia por Agulha Fina , Calcitonina/metabolismo , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Glândula Submandibular/diagnóstico por imagem , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/secundário , Tireoidectomia , Tomografia Computadorizada por Raios X , Ultrassonografia
19.
Am J Otolaryngol ; 41(3): 102434, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32093976

RESUMO

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a refractory and poor prognosis tumor Present study aimed to investigate the underlying biological functions and pathways involved in the development of ATC and to identify potential hub genes and candidate biomarkers of ATC. MATERIALS AND METHODS: Bioinformatics analyses were performed to identify the differentially expressed genes (DEGs) between ATC tissue samples and adjacent normal tissue samples. Protein-protein interaction (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval of Interacting Genes online tool and Cytoscape software and divided into sub-networks using the Molecular Complex Detection (MCODE) plug-in. DEGs in each module was analyzed by enrichment analysis of the KEGG Orthology Based Annotation System (KOBAS) web software version 3.0. Eventually, the hub genes from bioinformatics analysis were verified by qRT-PCR assay in different ATC cell lines. RESULTS: Thirty hub genes were selected and three modules were built by the Cytoscape software from the PPI network. Seven genes (CDK1, CCNB2, BUB1B, CDC20, RRM2, CHEK1 and CDC45) were screened from thirty hub genes. Enrichment analysis showed that these hub genes were primarily accumulated in 'cell cycle', 'p53 signaling pathway', 'viral carcinogenesis', 'pyrimidine metabolism' and 'ubiquitin mediated proteolysis'. The results of qRT-PCR indicated that seven hub genes were unregulated in three ATC cell lines compared with normal thyroid gland cell. CONCLUSIONS: These findings suggest that CDK1, CCNB2, BUB1B, CDC20, RRM2, CHEK1 and CDC45 may serve as novel diagnosis biomarkers and potential therapeutic target for ATC.


Assuntos
Proteína Quinase CDC2/genética , Proteínas de Ciclo Celular/genética , Biologia Computacional/métodos , Ciclina B2/genética , Estudos de Associação Genética/métodos , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Proteínas Cdc20 , Ciclo Celular/genética , Linhagem Celular Tumoral , Quinase 1 do Ponto de Checagem/genética , Marcadores Genéticos , Humanos , Terapia de Alvo Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ribonucleosídeo Difosfato Redutase/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia
20.
Mol Biol Rep ; 47(3): 2161-2169, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32072403

RESUMO

FSCN1 gene encodes an actin-bundling protein, FSCN1, which is involved in formation of actin-based structures that contribute to cell migration. High levels of FSCN1 expression is observed in cells with extended membranes and protrusions. Moreover, up-regulation of FSCN1 has been reported in several epithelial carcinomas. Therefore, FSCN1 is thought to play a role in cell movement and invasion. However, the mechanism behind FSCN1 up-regulation is not known. We investigated the expression of FSCN1 using immunohistochemistry. Methylation-specific PCR was adopted to analyze the methylation status of FSCN1 promoter as a potential regulatory mechanism in FSCN1 expression. The samples included papillary thyroid carcinoma, follicular thyroid carcinoma and goiter samples (controls). Methylation of FSCN1 promoter was observed in 50% of follicular, 48.6% of papillary and 60% of controls. The promoter was unmethylated in 16.7% of follicular samples, 5.7% of papillary samples and 26.7% of controls. In the remaining 33.3% of follicular and 45.7% of papillary samples as well as 13.3% of controls, both methylated and unmethylated alleles were amplified, a condition referred to as semi-methylation. The results showed that FSCN1 promoter was significantly hypomethylated in papillary cases while the methylation status was not significantly altered in follicular cases. On the other hand, FSCN1 was expressed in only nine papillary samples. Regarding protein expression and methylation status, we suggest that hypomethylation of FSCN1 promoter in papillary thyroid carcinoma does not lead to overexpression of FSCN1 and that there might be other regulatory mechanisms involved in FSCN1 up-regulation.


Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Regiões Promotoras Genéticas , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Biomarcadores Tumorais , Linhagem Celular Tumoral , Ilhas de CpG , Feminino , Humanos , Imuno-Histoquímica , Masculino , Gradação de Tumores , Neoplasias da Glândula Tireoide/diagnóstico
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