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1.
Cell Death Dis ; 12(4): 347, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795650

RESUMO

Papillary thyroid carcinoma (PTC) is one of the most common kinds of endocrine-related cancer and has a heterogeneous prognosis. Metabolic reprogramming is one of the hallmarks of cancers. Aberrant glucose metabolism is associated with malignant biological behavior. However, the functions and mechanisms of glucose metabolism genes in PTC are not fully understood. Thus, data from The Cancer Genome Atlas database were analyzed, and lactate dehydrogenase A (LDHA) was determined to be a potential novel diagnostic and therapeutic target for PTCs. The research objective was to investigate the expression of LDHA in PTCs and to explore the main functions and relative mechanisms of LDHA in PTCs. Higher expression levels of LDHA were found in PTC tissues than in normal thyroid tissues at both the mRNA and protein levels. Higher expression levels of LDHA were correlated with aggressive clinicopathological features and poor prognosis. Moreover, we found that LDHA not only promoted PTC migration and invasion but also enhanced tumor growth both in vitro and in vivo. In addition, we revealed that the metabolic products of LDHA catalyzed induced the epithelial-mesenchymal transition process by increasing the relative gene H3K27 acetylation. Moreover, LDHA knockdown activated the AMPK pathway and induced protective autophagy. An autophagy inhibitor significantly enhanced the antitumor effect of FX11. These results suggested that LDHA enhanced the cell metastasis and proliferation of PTCs and may therefore become a potential therapeutic target for PTCs.

2.
Endocrine ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33822318

RESUMO

PURPOSE: This study aimed to develop a clinically predictive nomogram model to predict the survival probability of differentiated thyroid carcinoma patients and compare the value of this model with that of the eighth edition AJCC cancer staging system. METHODS: We selected 59,876 differentiated thyroid carcinoma patients diagnosed between 2004 and 2015 from the SEER database and separated those patients into a training set (70%) and a validation set (30%) randomly. We used Cox regression analysis to build the nomogram model (model 1) and the eighth edition AJCC cancer staging model (model 2). Then we compared the predictive accuracy, discrimination, and clinical usage of both models by calculating AUC (Area under the curve), C-index, as well as analyzing DCA (Decision Curve Analysis) performance respectively. RESULTS: AUCs of all predicted time points (12-month, 36-month, 60-month, and 120-month) of model 1 were 0.933, 0.913, 0.879, and 0.868 for the training set; 0.933, 0.926, 0.916, and 0.894 for the validation set. As for model 2, data were 0.938, 0.906, 0.866, and 0.847 for the training set; 0.924, 0.925, 0.912, and 0.867 for the validation set. C-indices of model 1 were higher than those of model 2 (0.923 vs. 0.918 for the training set, 0.938 vs. 0.930 for the validation set). DCA comparison showed that the net benefit of model 1 was bigger when comparing with that of model 2. CONCLUSIONS: Model 1 provided with both better predictive accuracy and clinical usage compared with those of model 2 and might be able to predict the survival probability of differentiated thyroid carcinoma patients visually and accurately with a higher net benefit.

3.
Clin Cancer Res ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33832949

RESUMO

PURPOSE: Medullary thyroid cancer (MTC) accounts for about 2% of all thyroid cancer, but has a relatively poor prognosis compared with differentiated thyroid cancer. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR and c-Kit. This multicenter, randomized, double-blind, placebo-controlled phase ⅡB study (ALTER 01031, NCT02586350) was conducted to investigate the efficacy and safety of anlotinib in MTC. PATIENTS AND METHODS: Patients with histopathologically confirmed, unresectable locally advanced or metastatic MTC were enrolled and randomly assigned in a 2:1 ratio to receive anlotinib (12mg once daily from day 1 to 14 every 3 weeks) or placebo. Patients in placebo group were allowed to receive open-label anlotinib after disease progression. The primary end point was progression-free survival (PFS); secondary end points included objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: 91 patients were enrolled. At data cutoff date, the median PFS was significantly prolonged in anlotinib group than in placebo group (20.7 months vs. 11.1 months, P = 0.029, HR = 0.53 [95% CI, 0.30-0.95]). The ORR of anlotinib treatment was 48.4%. The incidence of treatment related adverse events (TRAE) was 100% and 89.7% in anlotinib and placebo groups. The most common TRAE of all grades in the anlotinib group were palmar-plantar erythrodysesthesia syndrome (62.9%), proteinuria (61.3%) and hypertriglyceridemia (48.4%). CONCLUSION: Anlotinib demonstrates its efficacy and safety in this phase ⅡB trial for the treatment of MTC and may become a new choice for this rare disease, especially for Chinese patients.

4.
Cancer Imaging ; 21(1): 33, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836831

RESUMO

BACKGROUND: Medullary thyroid cancer (MTC) has more aggressive behavior and poor prognosis. Ultrasound (US) has facilitated the qualitative diagnosis of thyroid nodules, however, some MTC may be diagnosed as a benign nodule on ultrasound because ultrasound features of malignancy are lacking. The aim of the study was to investigate the association between ultrasound features and biological behavior of MTC. METHODS: Ultrasound findings and medical records of patients with MTC between Jan 2015 to Jun 2017 were retrospectively reviewed at Tianjin Medical University Cancer Institute and Hospital. MTC were categorized using modified TI-RADS classification, then were classified as "malignant" (m-MTC) or "US-low-suspicious" (l-MTC). We compared the biological behavior between the two groups, and further analyzed the risk factors for the recurrence. RESULTS: A total of 78 patients were enrolled, of which 55 m-MTC (70.5%) and 23 l-MTC (29.5%) were identified. The N staging of the m-MTC was significantly higher than that of l-MTC(P = 0.000). The preoperative serum Ct level in m-MTC were significantly higher than that of l-MTC(P = 0.035). Biochemical cure were more frequent in l-MTC than that of m-MTC (P = 0.002). Disease recurrence rates were 19.7% (14 of 71). Disease recurrence was more frequent in m-MTC than that of l-MTC (P = 0.013). Disease recurrence was positively associated with extrathyroid extension (P = 0.047), N staging (P = 0.003), preoperative serum Ct level (P = 0.009) and negatively associated with biochemical cure(P = 0.000). In multivariable Cox regression analysis, extrathyroid extension and biochemical cure were independent risk factors for recurrence of MTC. CONCLUSIONS: L-MTC has a more indolent character than m-MTC. The extrathyroid extension and biochemical cure were independent risk factors for recurrence of MTC.

5.
ACS Appl Mater Interfaces ; 13(5): 6043-6052, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33525876

RESUMO

DNA methylation is a kind of a crucial epigenetic marker orchestrating gene expression, molecular function, and cellular phenotype. However, manipulating the methylation status of specific genes remains challenging. Here, a clustered regularly interspaced palindromic repeats-Cas9-based near-infrared upconversion-activated DNA methylation editing system (CNAMS) was designed for the optogenetic editing of DNA methylation. The fusion proteins of photosensitive CRY2PHR, the catalytic domain of DNMT3A or TET1, and the fusion proteins for CIBN and catalytically inactive Cas9 (dCas9) were engineered. The CNAMS could control DNA methylation editing in response to blue light, thus allowing methylation editing in a spatiotemporal manner. Furthermore, after combination with upconversion nanoparticles, the spectral sensitivity of DNA methylation editing was extended from the blue light to near-infrared (NIR) light, providing the possibility for remote DNA methylation editing. These results demonstrated a meaningful step forward toward realizing the specific editing of DNA methylation, suggesting the wide utility of our CNAMS for functional studies on epigenetic regulation and potential therapeutic strategies for related diseases.


Assuntos
Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas/genética , Edição de Genes , Técnicas Genéticas , Raios Infravermelhos , Neoplasias da Glândula Tireoide/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose/genética , Proteína 9 Associada à CRISPR/metabolismo , Sobrevivência Celular , Células Cultivadas , Metilação de DNA/genética , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Tamanho da Partícula , Propriedades de Superfície , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia
6.
Cancer Biol Med ; 18(1): 105-119, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33628588

RESUMO

Objective: The oncoprotein, hepatitis B X-interacting protein (HBXIP), has been reported to play an important role in human malignancies. However, its functions in non-small cell lung cancer (NSCLC) are poorly understood. The goal of the present study was to identify the role of HBXIP in the regulation of NSCLC development. Methods: The level of HBXIP expression in NSCLC tissue was assessed by immunohistochemical and Western blot analyses, and its relationships with clinicopathological features and outcomes were statistically evaluated. The effects of HBXIP on NSCLC cell progression were assessed through cell viability, colony formation, and flow cytometry analyses in vitro. The mechanism by which HBXIP regulated the MAPK pathway was studied by Western blot, immunofluorescence, and immunoprecipitation assays. In addition, in vivo experiments were performed to evaluate the progression of NSCLC and ERK signaling pathway activation after HBXIP knockdown. Results: HBXIP was overexpressed in human NSCLC and was correlated with the invasiveness of NSCLC. The high expression of HBXIP in NSCLC was significantly correlated with gender (P = 0.033), N stage (P = 0.002), and tumor-node-metastasis stage (P = 0.008). In vitro experiments using an NSCLC cell line revealed that HBXIP knockdown resulted in the suppression of cell proliferation and colony formation, which was consistent with the enhanced cell cycle arrest in G1 phase. The results of a mechanistic investigation suggested that binding of HBXIP to MEK1 protein promoted MAPK/ERK signaling pathway activation in NSCLC by preventing the proteasome-mediated degradation of MEK1. In addition, the results obtained using in vivo subcutaneous tumor xenografts confirmed that HBXIP deficiency decreased MEK1 protein levels and NSCLC tumor growth. Conclusions: Taken together, our results showed that the HBXIP-MEK interaction promoted oncogenesis via the MAPK/ERK pathway, which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant feature.

7.
Biomark Med ; 14(18): 1683-1692, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33346697

RESUMO

Background: The clinical value of antithyroglobulin antibodies (TgAb) as a tumor marker for differentiated thyroid cancer (DTC) is still controversial. Materials & methods: We studied 110 TgAb positive DTC patients who underwent total thyroidectomy and 131I therapies. Multivariate logistic regression was conducted to analyze the association between prognostic factors and disease outcomes. Results & conclusion: Pre-ablation TgAb levels and the changes of TgAb in 6-12 months after the first 131I therapy were risk factors for disease outcome in patients younger than 55, while extrathyroid extension was a risk factor in patients older than 55. The median TgAb half-life was 7.7 months and the median time for TgAb positivity to become negative was 15.8 months. The dynamics of TgAb within the first year after remnant ablation could predict disease outcome for DTC patients.

8.
PeerJ ; 8: e9675, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194342

RESUMO

Objective: To explore the relationship between body mass index (BMI) and clinicopathological characteristics in patients with papillary thyroid carcinoma (PTC). Methods: The clinical data of 1,579 patients with PTC, admitted to our hospital from May 2016 to March 2017, were retrospectively analyzed. According to the different BMI of patients, it can be divided into underweight recombination (BMI < 18.5 kg/m), normal body recombination (18.5 ≤ BMI < 24.0 kg/m2), overweight recombination (24.0 ≤ BMI < 28.0 kg/m2) and obesity group (BMI ≥ 28.0 kg/m2). The clinicopathological characteristics of PTC in patients with different BMIs group were compared. Results: In our study, the risk for extrathyroidal extension (ETE), advanced T stage (T III/IV), and advanced tumor-node-metastasis stage (TNM III/IV) in the overweight group were higher, with OR (odds ratio) = 1.99(1.41-2.81), OR = 2.01(1.43-2.84), OR = 2.94(1.42-6.07), respectively, relative to the normal weight group. The risk for ETE and T III/IV stage in the obese group were higher, with OR = 1.82(1.23-2.71) and OR = 1.82(1.23-2.70), respectively, relative to the normal weight group. Conclusion: BMI is associated with the invasiveness of PTC. There is a higher risk for ETE and TNM III/IV stage among patients with PTC in the overweight group and for ETE among patients with PTC in the obese group.

9.
J Cancer Res Ther ; 16(5): 960-966, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004735

RESUMO

As a treatment option for cancer, thermal ablation has satisfactory effects on many types of solid tumors (such as liver and renal cancers). However, its clinical applications for the treatment of thyroid nodules and metastatic cervical lymph nodes are still under debate both in China and abroad. In 2015, the "Zhejiang Expert consensus on thermal ablation for thyroid benign nodules, microcarcinoma, and metastatic cervical lymph nodes (2015 edition)," was released by the Thyroid Cancer Committee of Zhejiang Anti-Cancer Association, China. To further standardize the application of thermal ablation for thyroid tumors, the Thyroid Tumor Ablation Experts Group of Chinese Medical Doctor Association has organized many seminars and finally produced a consensus to formulate the "Expert consensus workshop report: Guidelines for thermal ablation of thyroid tumors (2019 edition)."

10.
Cell Death Dis ; 11(10): 839, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037185

RESUMO

Polyamine biosynthesis is an essential metabolic pathway for cell growth and differentiation in non-small-cell lung cancer (NSCLC). Fragile-site associated tumour suppressor (FATS) is a novel gene involved in cancer. The results of our previous study showed that FATS-mediated polyubiquitination of p53 promotes the activation of p53 in response to DNA damage; however, little is known about the role of FATS in metabolic reprogramming in NSCLC. In the present study, FATS was observed to be significantly downregulated in NSCLC tissues compared with paired adjacent normal tissues and was associated with the survival of NSCLC patients. We further showed that the presence of the tumour suppressor FATS in NSCLC cells led to apoptosis by inducing pro-death autophagy. In addition, FATS was shown to function as a suppressor of polyamine biosynthesis by inhibiting ornithine decarboxylase (ODC) at the protein and mRNA levels, which was partially dependent on oestrogen receptor (ER). Furthermore, FATS was observed to bind to ERß and translocate to the cytosol, leading to ODC degradation. The findings of our study demonstrate that FATS plays important roles in polyamine metabolism in NSCLC and provides a new perspective for NSCLC progression.

11.
Biosci Rep ; 40(10)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33015713

RESUMO

BACKGROUND: Papillary thyroid cancer (PTC) is a very common malignant disease with high morbidity. We needed some pretreatment indicators to help us predict prognosis and guide treatment. We conducted a study about some pretreatment prognostic indicators. METHODS: This clinical study recruited 705 postoperative PTC patients (211 males, 494 females). Clinical data before radioactive iodine (RAI) treatment were collected. Patients' response to therapy were classified into two categories: 'Good Prognosis Group' (GPG) and 'Poor Prognosis Group' (PPG), according to '2015 American Thyroid Association Guidelines'. Differences of indicators between different prognosis groups were compared. Odds ratios (ORs) were calculated by univariate/multiple binary logistic regression models. Difference of body mass index (BMI) changes before and after RAI treatment between different prognosis groups was also compared. RESULTS: A total of 546 (77.45%) belonged to GPG, and 159 (22.55%) belonged to PPG. Platelet (PLT), neutrophil (NEUT), PLT subgroups, and combination of red blood cell distribution width (RDW) and BMI (COR-BMI) were different between two prognosis groups. The significance of the difference between the two groups of BMI disappeared after the Bonferroni correction. PLT and PLT subgroups had detrimental effects on the risk of PPG; T stage had a positive effect on the risk of PPG. PLT subgroup showed a detrimental effect on the risk of PPG when we included additional covariates. CONCLUSIONS: We found that lower pretreatment PLT levels may indicate a poor prognosis for PTC. The relationship between platelet-derived growth factor (PDGF) and radiation sensitivity may be the key to this association.

12.
Cancer Biol Med ; 17(3): 543-554, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32944389

RESUMO

Active surveillance (AS) can be considered as a treatment strategy for low risk papillary thyroid microcarcinoma (PTMC), with the absence of clinically apparent lymph nodes, extrathyroidal extensions, and distant metastasis. After reviewing the reports on AS of low risk PTMCs worldwide, we introduced AS, and discussed the selection criteria for active surveillance candidates based on different guidelines and the follow-up schedules. Moreover, the requirement of cytological diagnosis, progression evaluation methods, necessity of thyrotropin suppression, and medical costs were issues that both clinicians and patients considered. The usefulness of AS for low risk PTMC patients depended on accurate and confidential evaluation of patient risk. Clinicians may adopt measures like dynamic monitoring, risk stratification, and making personal follow-up schedules to minimize these potential risks. By appropriately selecting PTMC patients, AS can be an effective alternative treatment to immediate surgery.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32936899

RESUMO

CONTEXT: Multiple mechanisms play roles in restricting the ability of T-cells to recognize and eliminate tumor cells. OBJECTIVE: To identify immune escape mechanisms involved in papillary thyroid carcinoma (PTC) to optimize immunotherapy. SETTING AND DESIGN: iTRAQ analysis was conducted to identify proteins differentially expressed in PTC samples with or without BRAFV600E mutation. Molecular mechanisms regulating tumor cell evasion were investigated by in vitro modulations of BRAF/MAPK and related pathways. The pathological significance of identified tumor-specific major histocompatibility complex class II (tsMHCII) molecules in mediating tumor cell immune escape and targeted immune therapy was further evaluated in a transgenic mouse model of spontaneous thyroid cancer. RESULTS: Proteomic analysis showed that tsMHCII level was significantly lower in BRAFV600E-associated PTCs and negatively correlated with BRAF mutation status. Constitutive activation of BRAF decreased tsMHCII surface expression on tumor cells, which inhibited activation of CD4+ T-cells and led to immune escape. Pathway analysis indicated that the TGF-ß1/SMAD3-mediated repression of tsMHCII, which could be reversed by BRAF inhibition (BRAFi). Targeting this pathway with a combined therapy of BRAF inhibitor PLX4032 and anti-PD-1 antibody efficiently blocked tumor growth by increasing CD4+ T-cell infiltration in a transgenic PTC mouse model. CONCLUSIONS: Our results suggest that BRAFV600E mutation in PTC impairs the expression of tsMHCII through the TGF-ß1/SMAD3 pathway to enhance immune escape. Combined treatment with PLX4032 and anti-PD-1 antibody promotes recognition and elimination of PTC by the immune system in a pre-clinical mouse model, and therefore offers an effective therapeutic strategy for patients with advanced PTC.

14.
Cancer Control ; 27(3): 1073274820945984, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32779493

RESUMO

BACKGROUND: We studied the clinical characteristics, diagnosis, treatment, and prognosis of secondary tumors of the thyroid (STTs) and analyzed this rare phenomenon based on our clinical experience. METHODS: We reviewed 16 000 malignant thyroid tumors diagnosed at 2 medical centers in China from 1978 to 2018, including 55 patients with STTs. RESULTS: The most frequent primary tumor sites included lung (21.8%), gastrointestinal (18.2%), breast (14.5%), and kidney (12.7%). The median age at STT diagnosis was 56 years. The time from diagnosis of primary tumor to metastases to the thyroid ranged from 0 to 108 months, with the longest interval being for renal cell carcinoma (RCC; mean: 49 months). There were 22 cases of single metastatic foci and 33 cases of multiple metastatic foci. At the time of STT diagnosis, 42 patients had multiple organ metastases and 13 patients had only thyroid metastases. Thyroid function was examined in 50 patients, including 23 with Hashimoto's thyroiditis. Metastases were diagnosed histologically and confirmed by negative immunohistochemistry for thyroid markers. Twenty-one patients were treated with resection, including total thyroidectomy in 14 and unilateral lobectomy in 7. Thirty-four patients were treated without resection, but 2 were treated with tracheotomy. The median survival time of all patients with metastasis was 10 months (range: 1-96 months). Patients with primary RCC had the best prognosis (median survival time: 52 months), followed by patients with breast cancer (33 months). Patients who underwent thyroid surgery had a better prognosis than patients without thyroid surgery. Patients with single metastatic foci or single organ metastases had a better prognosis than patients with multiple metastatic foci or multiple organ metastases. CONCLUSIONS: Metastasis to the thyroid is a rare clinical phenomenon, and sometimes a diagnosis of STT is difficult; so, we need to pay more attention to it. While prognosis appears to be related to surgery or some characteristics of metastatic spread, these data suggest it is more complex. Tumor biology is king; in fact, prognosis was mainly related to the biological behavior of the primary tumor. We cannot only opt for surgery; thus, case selection is important, and the treatment strategy for STT patients should be determined individually according to their specific biological behaviors.

15.
Med Sci Monit ; 26: e927007, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798214

RESUMO

BACKGROUND The number of studies on deep learning in artificial intelligence (AI)-assisted diagnosis of thyroid nodules is increasing. However, it is difficult to explain what the models actually learn in artificial intelligence-assisted medical research. Our aim is to investigate the visual interpretability of the computer-assisted diagnosis of malignant and benign thyroid nodules using ultrasound images. MATERIAL AND METHODS We designed and implemented 2 experiments to test whether our proposed model learned to interpret the ultrasound features used by ultrasound experts to diagnose thyroid nodules. First, in an anteroposterior/transverse (A/T) ratio experiment, multiple models were trained by changing the A/T ratio of the original nodules, and their classification, accuracy, sensitivity, and specificity were tested. Second, in a visualization experiment, class activation mapping used global average pooling and a fully connected layer to visualize the neural network to show the most important features. We also examined the importance of data preprocessing. RESULTS The A/T ratio experiment showed that after changing the A/T ratio of the nodules, the accuracy of the neural network model was reduced by 9.24-30.45%, indicating that our neural network model learned the A/T ratio information of the nodules. The visual experiment results showed that the nodule margins had a strong influence on the prediction of the neural network. CONCLUSIONS This study was an active exploration of interpretability in the deep learning classification of thyroid nodules. It demonstrated the neural network-visualized model focused on irregular nodule margins and the A/T ratio to classify thyroid nodules.

16.
Med Sci Monit ; 26: e926096, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32555130

RESUMO

BACKGROUND Thyroid nodules are extremely common and typically diagnosed with ultrasound whether benign or malignant. Imaging diagnosis assisted by Artificial Intelligence has attracted much attention in recent years. The aim of our study was to build an ensemble deep learning classification model to accurately differentiate benign and malignant thyroid nodules. MATERIAL AND METHODS Based on current advanced methods of image segmentation and classification algorithms, we proposed an ensemble deep learning classification model for thyroid nodules (EDLC-TN) after precise localization. We compared diagnostic performance with four other state-of-the-art deep learning algorithms and three ultrasound radiologists according to ACR TI-RADS criteria. Finally, we demonstrated the general applicability of EDLC-TN for diagnosing thyroid cancer using ultrasound images from multi medical centers. RESULTS The method proposed in this paper has been trained and tested on a thyroid ultrasound image dataset containing 26 541 images and the accuracy of this method could reach 98.51%. EDLC-TN demonstrated the highest value for area under the curve, sensitivity, specificity, and accuracy among five state-of-the-art algorithms. Combining EDLC-TN with models and radiologists could improve diagnostic accuracy. EDLC-TN achieved excellent diagnostic performance when applied to ultrasound images from another independent hospital. CONCLUSIONS Based on ensemble deep learning, the proposed approach in this paper is superior to other similar existing methods of thyroid classification, as well as ultrasound radiologists. Moreover, our network represents a generalized platform that potentially can be applied to medical images from multiple medical centers.

17.
Updates Surg ; 72(3): 871-884, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32342347

RESUMO

Papillary thyroid cancer is a very common endocrine malignancy. The 8th American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system introduced major changes. We conducted this retrospective cohort analysis to assess the benefits of radioactive iodine (RAI) according to different stratification of patients. The source of the data was the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. From 2006 to 2015, patients with papillary thyroid cancer were included in our study. The interactions between different variables and RAI treatment were tested by multivariate Cox regression models to compare the survival differences according to RAI treatment between the patients assessed with the 7th and 8th edition of the AJCC/TNM staging system. The results of the interaction analysis and group comparisons indicated that the effects of RAI treatment on patients staged with the 7th and 8th editions were similar. Patients with early Stage, early T stage, N0 and subtotal or near total thyroidectomy benefited greatly from RAI treatment. Patients with Stage III according to the 8th edition benefited less from RAI than patients with Stage III according to the 7th edition. Patients with T1a benefited from RAI but benefited less than patients with other T stages. Patients with T3a benefited more from RAI than those with T3b. According to the 8th edition, Stage III/IV more accurately differentiates patients with advanced stage disease. These patients benefitted less from RAI treatment, which may be due to the relatively weaker iodine uptake by tumor cells. T1a patients benefitted less than patients with other T stages. The difference in RAI benefit between patients with T3a and T3b is a novel finding in our study.


Assuntos
Radioisótopos do Iodo/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Câncer Papilífero da Tireoide/mortalidade , Câncer Papilífero da Tireoide/radioterapia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/radioterapia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
18.
Aging (Albany NY) ; 12(7): 5733-5750, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32240105

RESUMO

Thyroid cancer (THCA) is a heterogeneous disease with multiple clinical outcomes Immune cells regulate its progression. Three immunomolecular subtypes (C1, C2, C3) were identified in gene expression data sets from TCGA and GEO databases. Among them, subtype C3 had highest frequency of BRAF mutations, lowest frequency of RAS mutations, highest mutation load and shorter progression-free survival. Functional enrichment analysis for the genes revealed that C1 was up-regulated in the ERK cascade pathway, C2 was up-regulated in cell migration and proliferation pathways, while C3 was enriched in body fluid, protein regulation and response to steroid hormones functions. Notably, the three molecular subtypes exhibit differences in immune microenvironments as shown by timer database and analysis of immune expression signatures. The abundance of B_cell, CD4_Tcell, Neutrophil, Macrophage and Dendritic cells in C2 subtype were lower than in C1 and C3 subtypes Leukocyte fraction, proliferation macrophage regulation, lymphocyte infiltration, IFN gamma response and TGF beta response scores were significantly higher in C3 compared with C1 and C2 subtypes. Unlike C3 subtype, it was observed that C1 and C2 subtypes were significantly negatively correlated with most immune checkpoint genes in two different cohorts. The characteristic genes were differentially expressed between cancer cells, adjacent tissues, and metastatic tissues in different cohorts. In summary, THCA can be subclassified into three molecular subtypes with distinct histological types, genetic and transcriptional phenotypes, all of which have potential clinical implications.

19.
Front Oncol ; 10: 217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219060

RESUMO

Background: Patients with metastatic radioiodine-refractory papillary thyroid carcinoma (PTC) have limited treatment options and a poor prognosis. There is an urgent need to develop new drugs targeting PTC for clinical application. Apatinib, a novel small-molecule tyrosine kinase inhibitor (TKI), is highly selective for vascular endothelial growth factor receptor-2 (VEGFR2) and exhibits antitumor effects in a variety of solid tumors. Although apatinib has been shown to be safe and efficacious in radioiodine-refractory differentiated thyroid cancer, the mechanism underlying its antitumor effect is unclear. In this report, we explored the effects of apatinib on PTC in vitro and in vivo. Methods: VEGFR2 expression levels were evaluated by immunohistochemistry (IHC), qPCR, and western blotting (WB). The effects of apatinib on cell viability, colony formation, and migration in the Transwell assay were assessed in vitro, and its effect on tumor growth rate was assessed in vivo. In addition, the levels of proteins in signaling pathways were determined by WB. Finally, the autophagy level was assessed by WB, immunofluorescence (IF), and transmission electron microscopy. Results: We found that high VEGFR2 expression is associated with tumor size, T stage, and lymph node metastasis in patients with PTC and that apatinib inhibits PTC cell growth, promotes apoptosis, and induces cell cycle arrest through the PI3K/Akt/mTOR signaling pathway. Moreover, apatinib induces autophagy, and pharmacological inhibition of autophagy or small interfering RNA (siRNA)-mediated targeting of autophagy-associated gene 5 (ATG5) can further increase PTC cell apoptosis. Conclusion: Our data suggest that apatinib can induce apoptosis and autophagy via the PI3K/Akt/mTOR signaling pathway for the treatment of PTC and that autophagy is a potential novel target for future therapy in resistant PTC.

20.
Thyroid ; 30(9): 1245-1253, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32075524

RESUMO

Background: Thyroid cancer is the most common endocrine tumor with an increasing incidence. Limited treatment options are available for patients with advanced or recurrent metastatic disease, resulting in a poor prognosis. Surufatinib targets multiple kinases (vascular endothelial growth factor receptors, fibroblast growth factor receptor-1, and colony-stimulating factor-1 receptor) involved in tumor angiogenesis and tumor immune evasion. Surufatinib has demonstrated promising antitumor activity in various advanced solid tumors. This study aimed to determine the objective response rate (ORR) of surufatinib in patients with locally advanced or distant metastatic differentiated thyroid cancer (DTC) or medullary thyroid cancer (MTC). Methods: This Phase II open-label study by Simon's two-stage design was conducted at 10 sites across China. Patients with radioiodine (RAI)-refractory DTC with locally advanced disease or distant metastasis (DTC1 group); patients who received limited initial surgery and then developed locally advanced unresectable recurrences and were not considered candidates for RAI therapy due to residual normal thyroid tissue (DTC2 group); or patients with MTC with locally advanced disease or distant metastasis (MTC group) were enrolled. A total of 59 patients were enrolled (26 in DTC1, 6 in DTC2, and 27 in MTC) and received 300 mg surufatinib daily in 28-day cycles. The primary endpoint was ORR as determined by the investigators. Results: Overall ORR was 23.2% [95% confidence interval, CI 12.98-36.42]: 21.7% in the DTC1 cohort, 33.3% in the DTC2 cohort, and 22.2% in the MTC cohort. Forty-nine patients achieved disease control (87.5% [CI 75.93-94.82]): 87.0% in the DTC1 cohort, 83.3% in the DTC2 cohort, and 88.9% in the MTC cohort. Median time to response was 59.0 days, and 59.0, 85.5, and 59.0 days in the DTC1, DTC2, and MTC cohorts. Overall median progression-free survival was 11.1 months [CI 5.98-16.69]; 11.1 months in DTC1 and MTC cohorts, while the DTC2 cohort had not reached the median at the data cutoff. The most common treatment-emergent adverse events grade ≥3 were hypertension (20.3%), proteinuria (11.9%), and then elevated blood pressure, hypertriglyceridemia, and pulmonary inflammation (5.1% each). Conclusions: Surufatinib demonstrated promising efficacy with a tolerable and manageable safety profile for patients with locally advanced or metastatic MTC, RAI-refractory DTC, or locally advanced unresectable recurrences unable to receive RAI.

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