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1.
Ann Surg Oncol ; 30(4): 2246-2253, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36581723

RESUMO

BACKGROUND: Active surveillance (AS) of low-risk T1a papillary thyroid carcinoma (PTC) is generally accepted as an alternative to immediate surgery. The cut-off in the size criterion for AS has recently been extended in select individuals, especially older patients. We evaluated the clinicopathological differences of T1b PTC according to age to investigate the possibility of AS in older patients. PATIENTS AND METHODS: From a cohort study of 1269 patients undergoing lobectomy for PTC, 1223 PTC patients with T1 stage disease (tumor ≤ 2 cm) were enrolled. The clinicopathological characteristics between T1a and T1b patients according to age were analyzed. RESULTS: Among the 1223 T1 cases, 918 (75.1%) were T1a (≤ 1 cm) and 305 (34.9%) T1b (> 1 and ≤ 2 cm). T1b PTC was associated with male sex, minimal extrathyroidal extension, lymphovascular invasion, occult central lymph node (LN) metastasis, and a higher number of metastatic LNs than T1a. However, in patients over 55 years of age, the clinicopathological features of the patients with T1a and T1b PTC were not significantly different except for minimal extrathyroidal extension, although many clinicopathological differences were observed in patients under 55 years of age. CONCLUSION: The clinicopathological features of patients with T1b PTC over 55 years of age are similar to those with T1a PTC and less aggressive than those with T1b PTC under 55 years of age. These findings suggest that AS may be possible in patients with T1b PTC over 55 years of age without high-risk features on preoperative examinations.


Assuntos
Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Conduta Expectante , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Metástase Linfática , Estudos Retrospectivos , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Feminino
2.
Ann Surg Oncol ; 29(4): 2550-2556, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34792697

RESUMO

BACKGROUND: The optimal extent of therapeutic lateral neck dissection (ND) in papillary thyroid carcinoma (PTC) continues to be debated. We analyzed the frequency, patterns, and predictive factors of occult level Va and Vb metastasis in clinically lateral node-positive PTC patients. METHODS: We reviewed the data of PTC patients who underwent thyroidectomy and therapeutic lateral ND from level II to V between May 2008 and August 2020. In our study, 46 patients without clinically positive metastatic lymph nodes (LNs) at level V on the preoperative evaluation were included to analyze occult metastasis at level Va and Vb, respectively. Patient demographics, including age, sex, distribution of pathologic LNs, and characteristics of the primary tumors, were reviewed. In addition, clinicopathologic factors associated with occult level Va and Vb metastasis were analyzed. RESULTS: Of the 46 patients, 14 (30.4%) patients had occult metastases at level Vb. No occult metastases were found at level Va. Clinically positive level II metastasis (p = 0.015) and simultaneous level II, III, and IV metastases (p = 0.010) in the preoperative evaluation were significantly associated with occult level Vb metastasis. Patients without LN metastasis at level IV or with three or fewer metastatic LNs in the lateral neck never had occult LN metastases at level Vb. CONCLUSIONS: Occult metastasis at level Va is rare in PTC with lateral LN metastasis. Occult metastasis at level Vb may occur in PTC patients with multilevel involvement, including level II and/or four or more lateral LN metastases.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Esvaziamento Cervical , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
3.
Int J Mol Sci ; 23(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36077112

RESUMO

Various enzymes in the one-carbon metabolic pathway are closely related to the development of tumors, and they can all be potential targets for cancer therapy. Serine hydroxymethyltransferase2 (SHMT2), a key metabolic enzyme, is very important for the proliferation and growth of cancer cells. However, the function and mechanism of SHMT2 in head and neck cancer (HNC) are not clear. An analysis of The Cancer Genome Atlas (TCGA) data showed that the expression of SHMT2 was higher in tumor tissue than in normal tissue, and its expression was significantly associated with male sex, aggressive histological grade, lymph node metastasis, distant metastasis, advanced TNM stage, and lymphovascular invasion in HNC. SHMT2 knockdown in FADU and SNU1041 cell lines significantly inhibited cell proliferation, colony formation, migration, and invasion. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using TCGA data revealed that SHMT2 was closely related to cancer stem cell regulation and maintenance. Furthermore, we found that silencing SHMT2 inhibited the expression of stemness markers and tumor spheroid formation compared with a control group. On the contrary, stemness markers were significantly increased after SHMT2 overexpression in HEP-2 cells. Interestingly, we found that knocking down SHMT2 reduced the expression of genes related to the Notch and Wnt pathways. Finally, silencing SHMT2 significantly reduced tumor growth and decreased stemness markers in a xenograft model. Taken together, our study suggests that targeting SHMT2 may play an important role in inhibiting HNC progression.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço , Proliferação de Células/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Células-Tronco Neoplásicas/metabolismo , Serina/metabolismo
4.
Int J Mol Sci ; 23(15)2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35897746

RESUMO

Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling.


Assuntos
Tendão do Calcâneo , Material Particulado , Tendão do Calcâneo/metabolismo , Animais , Fenômenos Biomecânicos , Metilação de DNA , Material Particulado/toxicidade , RNA/metabolismo , Ratos , Ratos Sprague-Dawley , Análise de Sequência de RNA
5.
Int J Mol Sci ; 22(20)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34681812

RESUMO

Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-ß (TGF-ß) superfamily, has been reported to be overexpressed in different kinds of cancer types. However, the function and mechanism of GDF15 in head and neck cancer (HNC) remains unclear. The Cancer Genome Atlas (TCGA) data show that the expression of GDF15 is significantly associated with tumor AJCC stage, lymph vascular invasion and tumor grade in HNC. In this study, we confirmed that knockdown of GDF15 attenuated: cell proliferation, migration and invasion via regulation of EMT through a canonical pathway; SMAD2/3 and noncanonical pathways; PI3K/AKT and MEK/ERK in HNC cell lines. Furthermore, we found that early growth response 1 (EGR1) was a transcription factor of GDF15. Interestingly, we also demonstrated that GDF15 could regulate the expression of EGR1, which meant a positive feedback loop occurred between these two factors. Moreover, combined inhibition of both GDF15 and EGR1 in a HNC mouse xenograft model showed significantly decreased tumor volume compared to inhibition of EGR1 or GDF15 alone. Our study showed that the GDF15-EGR1 signaling axis may be a good target in HNC patients.


Assuntos
Proteína 1 de Resposta de Crescimento Precoce/genética , Fator 15 de Diferenciação de Crescimento/genética , Neoplasias de Cabeça e Pescoço/patologia , Animais , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Proteína 1 de Resposta de Crescimento Precoce/fisiologia , Transição Epitelial-Mesenquimal/genética , Retroalimentação Fisiológica/fisiologia , Regulação Neoplásica da Expressão Gênica , Fator 15 de Diferenciação de Crescimento/fisiologia , Células HaCaT , Neoplasias de Cabeça e Pescoço/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/genética , Células Tumorais Cultivadas
6.
FASEB J ; 33(3): 4097-4106, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30548079

RESUMO

The use of nonthermal atmospheric plasma (NTP) in the biomedical field has recently expanded into cell death induction in cancer, infection prevention, inflammation treatment, and wound-healing enhancement. NTP has been demonstrated to enhance skin and muscle regeneration, but its effects on tissue regeneration, following deep tissue or muscle damage, remains underinvestigated. In this study, we determined the effects of NTP on muscle differentiation and the mechanisms of NTP's contribution to differentiation and regeneration. NTP treatment enhanced cell differentiation in primary normal human skeletal muscle myoblast cells and increased the relative expression of mRNA levels of MyoD which is one of the earliest markers of myogenic commitment, and myogenin, which are important transcription factors required for myogenic differentiation. Furthermore, NTP treatment induced increases in the levels of myosin heavy chain, a differentiated muscle-specific protein, and in myotube formation of myoblasts. We observed that signal transducer and activator of transcription 3 (STAT3) activation induced by NTP treatment affects the myogenic differentiation. In addition, STAT3 phosphorylation was also enhanced by NTP treatment in injured animal muscle. These findings indicate that NTP could enhance musculoskeletal differentiation by acting as an external stimulus for myoblast differentiation, suggesting its treatment potential in promoting regeneration of damaged muscle.-Park, J. K., Kim, Y. S., Kang, S. U., Lee, Y. S., Won, H.-R., Kim, C.-H. Nonthermal atmospheric plasma enhances myoblast differentiation by eliciting STAT3 phosphorylation.


Assuntos
Diferenciação Celular/fisiologia , Mioblastos Esqueléticos/metabolismo , Mioblastos Esqueléticos/fisiologia , Fosforilação/fisiologia , Plasma/metabolismo , Fator de Transcrição STAT3/metabolismo , Adolescente , Animais , Linhagem Celular , Humanos , Masculino , Desenvolvimento Muscular/fisiologia , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/fisiologia , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Proteína MyoD/metabolismo , Miogenina/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia
7.
Int J Mol Sci ; 21(18)2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32927894

RESUMO

Particulate matter (PM) is an environmental exposure factor that adversely affects human health. PM is a risk factor for various diseases. However, the mechanism by which PM affects the vocal folds (VF) has not yet been evaluated. Thus, we investigated the cytotoxic effects of PM on human vocal fold fibroblasts (hVFF) and the underlying signaling pathways. hVFF were isolated from human VF. The effect of PM on hVFF, and the underlying mechanism, were analyzed using Western blot, quantitative real-time polymerase chain reaction, and flow cytometry. In addition, a histological evaluation was performed in animal experiments. Cell proliferation decreased after the PM treatment. PM increased the expression of interleukin (IL)-6 and IL-1ß. The generation of reactive oxygen species (ROS) in PM-treated hVFF and subsequent activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways were confirmed. Furthermore, PM increased the expression of fibrosis-related markers and induced the accumulation of collagen in the extracellular matrix. As a result, PM exposure significantly enhances the inflammatory response on VF through the ROS-mediated activation of the MAPK and NF-κB signaling pathways. In addition, PM promotes differentiation into myofibroblasts and induces fibrosis. These results suggest that PM triggers an inflammatory reaction through ROS production and causes VF fibrosis.


Assuntos
Doenças da Laringe/induzido quimicamente , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Material Particulado/efeitos adversos , Prega Vocal/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fibrose , Humanos , Doenças da Laringe/metabolismo , Doenças da Laringe/patologia , Miofibroblastos , Cultura Primária de Células , Espécies Reativas de Oxigênio/metabolismo , Prega Vocal/metabolismo , Prega Vocal/patologia
8.
BMC Nephrol ; 20(1): 414, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730449

RESUMO

BACKGROUND: Secondary hyperparathyroidism is a common complication in patients with chronic kidney disease that requires vigilant treatment due to its high mortality rate. Pharmacologic therapy is recommended as an initial treatment; if there is no response, a total parathyroidectomy is performed. In some cases, surgery is accompanied by auto-transplantation of parathyroid tissue. CASE PRESENTATION: The patient was diagnosed with chronic kidney disease and received a kidney transplant. However, due to rejection of the transplanted kidney, medical nephrectomy was carried out and routine hemodialysis was initiated and observed. At this time, secondary hyperparathyroidism with elevated parathyroid hormone and hyperphosphatemia developed and pharmacologic treatment was applied. However, there was no response to pharmacologic treatment; therefore, total parathyroidectomy with auto-transplantation was performed. Eight years after surgery, a growing mass was observed in the transplantation site, accompanied by an elevation of parathyroid hormone. A complete resection of the mass was performed, and the patient was diagnosed with parathyroid carcinoma. Additional adjuvant radiation therapy was ordered, and the patient is being monitored. CONCLUSIONS: This is a rare but remarkable case of parathyroid carcinoma arising from auto-transplanted parathyroid tissue after total parathyroidectomy in a patient with secondary hyperparathyroidism. We suggest caution should be taken when choosing to auto- transplant parathyroid tissue and that careful postoperative observation should be performed.


Assuntos
Autoenxertos , Glândulas Paratireoides , Neoplasias das Paratireoides , Paratireoidectomia , Complicações Pós-Operatórias , Insuficiência Renal Crônica , Transplante Autólogo/efeitos adversos , Adulto , Autoenxertos/patologia , Autoenxertos/cirurgia , Rejeição de Enxerto/cirurgia , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Nefrectomia/efeitos adversos , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/patologia , Glândulas Paratireoides/transplante , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/etiologia , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/radioterapia , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia/efeitos adversos , Paratireoidectomia/métodos , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/radioterapia , Complicações Pós-Operatórias/cirurgia , Radioterapia Adjuvante , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/cirurgia , Transplante Autólogo/métodos , Resultado do Tratamento
11.
J Clin Med ; 13(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38337356

RESUMO

BACKGROUND: Despite its rarity and limited documentation, therapeutic neck dissection (ND) for cervical lymph node (LN) metastases from distant primary sites is increasingly practiced, potentially enhancing survival rates. However, the optimal ND extent remains unclear. This study aimed to determine the safety of excluding upper neck levels from ND. METHODS: We retrospectively analyzed 25 patients who underwent ND for cervical LN metastases from remote primary tumors between 2015 and 2021 (12 with primary lung tumors, four with ovary, three with mammary gland, three with esophagus, two with thymus, and one with colon). RESULTS: Assessing clinical characteristics and occult metastasis rates, we observed LN metastases predominantly at levels III and IV. Occult metastases occurred in 14 out of 25 patients, primarily at neck levels III and IV (55.0% and 50.0%, respectively). The five-year disease-specific survival rate for all patients was 44.3%. While no statistically significant impact of occult metastasis on prognosis was confirmed, an association between the postoperative LN ratio and poor prognosis was revealed. CONCLUSIONS: Our findings suggest that prophylactic NDs at levels I, II, and Va may not be essential for managing cervical LN metastases from remote primary malignancies. This could lead to a more tailored and less invasive therapeutic strategy.

12.
Surgery ; 175(4): 1049-1054, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38281855

RESUMO

BACKGROUND: The clinicopathological impact of chronic lymphocytic thyroiditis on patients with papillary thyroid carcinoma patients is still controversial. This study aimed to evaluate the clinicopathologic differences and risk factors for central lymph node metastasis based on the presence of coexistent chronic lymphocytic thyroiditis in patients with low- to intermediate-risk papillary thyroid carcinoma. METHODS: The medical records of 1,022 patients with low- to intermediate-risk papillary thyroid carcinoma who underwent lobectomy and central neck dissection between June 2020 and March 2022 were reviewed. Differences in clinicopathological factors were analyzed in patients with papillary thyroid carcinoma with or without chronic lymphocytic thyroiditis. Furthermore, risk factors for central lymph node metastasis in patients with low- to intermediate-risk papillary thyroid carcinoma with or without chronic lymphocytic thyroiditis were evaluated. RESULTS: Among the 1,022 patients with low to intermediate-risk papillary thyroid carcinoma, 102 (10.0%) had coexisting chronic lymphocytic thyroiditis. Female sex (odds ratio = 3.536, P = .001, 95% confidence interval 1.781-8.069), a multifocal tumor (odds ratio = 2.162, P = .001, 95% confidence interval 1.358-3.395), and angiolymphatic invasion (odds ratio = 0.365, P < .001, 95% confidence interval 0.203-0.625) were independent factors associated with patients who had coexisting chronic lymphocytic thyroiditis compared to those without chronic lymphocytic thyroiditis. There were 358 (35%) patients who had central lymph node metastasis. Multivariate analysis showed that younger age (odds ratio = 0.667, P = .013, 95% confidence interval 0.482-0.555), male sex (odds ratio = 0.549, P < .001, 95% confidence interval 0.402-0.751), tumor size >1 cm (odds ratio = 1.454, P = .022, 95% confidence interval 1.053-2.003), extrathyroidal extension (odds ratio = 1.874, P < .001, 95% confidence interval 1.414-2.486), and angiolymphatic invasion (odds ratio = 3.094, P < .001, 95% confidence interval 2.339-4.101) were risk factors for central lymph node metastasis. Angiolymphatic invasion (odds ratio = 11.184, P < .001, 95% confidence interval 3.277-46.199) was identified as the sole independent risk factor for central lymph node metastasis in patients with papillary thyroid carcinoma with coexisting chronic lymphocytic thyroiditis. CONCLUSION: Our data suggest that patients with low to intermediate-risk papillary thyroid carcinoma with coexistent chronic lymphocytic thyroiditis exhibit different clinical features than patients with papillary thyroid carcinoma without chronic lymphocytic thyroiditis. Additionally, the presence of chronic lymphocytic thyroiditis may be considered a potential factor against central lymph node metastasis.


Assuntos
Carcinoma Papilar , Carcinoma , Doença de Hashimoto , Neoplasias da Glândula Tireoide , Humanos , Masculino , Feminino , Câncer Papilífero da Tireoide/complicações , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Doença de Hashimoto/complicações , Doença de Hashimoto/cirurgia , Doença de Hashimoto/patologia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Metástase Linfática/patologia , Carcinoma/complicações , Carcinoma/cirurgia , Carcinoma/patologia , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Tireoidectomia , Estudos Retrospectivos , Fatores de Risco , Linfonodos/patologia
13.
Eur Thyroid J ; 13(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38484463

RESUMO

Objective: Active surveillance (AS) is generally accepted as an alternative to immediate surgery for papillary thyroid carcinoma (PTC) measuring ≤1.0 cm (cT1a) without risk factors. This study investigated the clinicopathologic characteristics of PTCs measuring ≤2.0 cm without cervical lymph node metastasis (cT1N0) by tumor size group to assess the feasibility of AS for PTCs between 1.0 cm and 1.5 cm (cT1b≤1.5). Design: This study enrolled clinically T1N0 patients with preoperative ultrasonography information (n= 935) from a cohort of 1259 patients who underwent lobectomy and were finally diagnosed with PTC from June 2020 to March 2022. Results: The cT1b≤1.5 group (n = 171; 18.3 %) exhibited more lymphatic invasion and occult central lymph node (LN) metastasis with a higher metastatic LN ratio than the cT1a group (n = 719; 76.9 %). However, among patients aged 55 years or older, there were no significant differences in occult central LN metastasis and metastatic LN ratio between the cT1a, cT1b≤1.5, and cT1b>1.5 groups. Multivariate regression analyses revealed that occult central LN metastasis was associated with age, sex, tumor size, extrathyroidal extension, and lymphatic invasion in patients under 55, while in those aged 55 or older, it was associated only with age and lymphatic invasion. Conclusion: For PTC patients aged 55 years or older with cT1b≤1.5, AS could be a viable option due to the absence of a significant relationship between tumor size and occult central LN.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Estudos de Viabilidade , Conduta Expectante , Carcinoma Papilar/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Ultrassonografia
14.
Nat Commun ; 15(1): 1163, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331894

RESUMO

The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.


Assuntos
Multiômica , Neoplasias da Glândula Tireoide , Humanos , Glicina Hidroximetiltransferase/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Redes e Vias Metabólicas/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo
15.
Eur Thyroid J ; 12(6)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37992297

RESUMO

Objective: Active surveillance (AS) has been suggested as a management option for low-risk papillary thyroid microcarcinoma (PTMC). However, the currently proposed selection criteria for AS application do not consider various clinical factors. The purpose of this study was to analyze clinical factors related to recurrence that could be confirmed preoperatively in patients who underwent surgery for PTMC and to identify factors worth considering when deciding whether to apply AS. Materials and methods: Data were collected from patients with PTMC who underwent surgical treatment at Chungnam National University Hospital. A retrospective cohort was established according to the presence or absence of recurrence during the follow-up period. In total, 2717 patients were enrolled, of whom 60 experienced recurrence. Various clinical factors that could be identified before surgery were analyzed. Results: The relationship between various clinical factors that could be confirmed preoperatively and recurrence was confirmed through Cox regression analysis and Kaplan-Meier curve analysis. BRAF mutation and the tall cell variant were significantly more common in patients with recurrence. In patients aged 55 years or older, the risk of recurrence was lower than in younger patients, while the recurrence-free survival (RFS) rate was higher. Conclusion: When choosing between surgical treatment or AS in PTMC patients, additional consideration of the patient's clinical factors, such as age and BRAF mutation status, may be required in addition to the existing criteria.


Assuntos
Proteínas Proto-Oncogênicas B-raf , Neoplasias da Glândula Tireoide , Humanos , Estudos Retrospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Conduta Expectante , Neoplasias da Glândula Tireoide/cirurgia
16.
Sci Rep ; 13(1): 2000, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737651

RESUMO

Oral squamous cell carcinoma (OSCC) has high recurrence and mortality rates despite advances in diagnosis and treatment. Therefore, it is necessary to identify new biomarkers for early detection, efficient monitoring, and prognosis prediction. Since microRNA (miRNA) is stable and detectable in serum, it has been reported to inform the diagnosis and monitor disease progression through liquid biopsy. In this study, a circulating specific miRNA panel in OSCC patients was developed, and its usefulness as a dynamic monitor was validated. Small RNAs were extracted from the serum of OSCC patients (n = 4) and normal controls (n = 6) and profiled using next-generation sequencing. NGS identified 42 differentially expressed miRNAs (DEmiRNAs) in serum between patients with OSCC and healthy controls, with threefold differences (p < 0.05). Combining the 42 DEmiRNAs and The Cancer Genome Atlas (TCGA) databases OSCC cohort, 9 overlapping DEmiRNAs were screened out. Finally, 4 significantly up-regulated miRNAs (miR-92a-3p, miR-92b-3p, miR-320c and miR-629-5p) were identified from OSCC patients via validation in the Chungnam National University Hospital cohort. Application of the specific miRNA panel for distinguishing OSCC patients from healthy controls produced specificity and sensitivity of 97.8 and 74%, respectively. In addition, the serum levels of these 4 miRNAs significantly decreased after complete surgical resection and increased after recurrence. We suggest that circulating 4-miRNA panel might be promising non-invasive predictors for diagnosing and monitoring the progression of patients with OSCC.


Assuntos
MicroRNA Circulante , MicroRNAs , Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Biomarcadores Tumorais/genética , MicroRNA Circulante/genética , Perfilação da Expressão Gênica , MicroRNAs/genética , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
17.
Clin Exp Otorhinolaryngol ; 16(2): 184-197, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36822197

RESUMO

OBJECTIVES: The mitochondrial ribosomal protein L14 (MRPL14) is encoded by a nuclear gene and participates in mitochondrial protein translation. In this study, we aimed to investigate the role of MRPL14 in thyroid cancer. METHODS: We investigated the association between MRPL14 expression and clinicopathological features using The Cancer Genome Atlas (TCGA) and Chungnam National University Hospital (CNUH) databases. Functional studies of MRPL14, including proliferation, migration, invasion, mitochondrial oxidative phosphorylation and reactive oxygen species (ROS) production, were performed in papillary thyroid cancer (PTC) cell lines (B-CPAP and KTC-1). RESULTS: Based on the TCGA dataset, PTC tissues lost mitochondrial integrity and showed dysregulated expression of overall mitoribosomal proteins (MRPs) compared with normal thyroid tissues. Of 78 MRPs, MRPL14 was highly expressed in thyroid cancer tissues. MRPL14 overexpression was significantly associated with advanced tumor stage, extrathyroidal extension, and lymph node metastasis. MRPL14 increased cell proliferation of thyroid cancer and promoted cell migration via epithelial-mesenchymal transition-related proteins. Moreover, MRPL14 knockdown reduced the expression of oxidative phosphorylation complex IV (MTCO1) and increased the accumulation of ROS. Cotreatment with a ROS scavenger restored cell proliferation and migration, which had been reduced by MRPL14 knockdown, implying that ROS functions as a key regulator of the oncogenic effects of MRPL14 in thyroid cancer cells. CONCLUSION: Our findings indicate that MRPL14 may promote cell growth, migration, and invasion by modulating ROS in thyroid cancer cells.

18.
Endocrinology ; 164(4)2023 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-36791033

RESUMO

The thyroid gland plays a critical role in the maintenance of whole-body metabolism. However, aging frequently impairs homeostatic maintenance by thyroid hormones due to increased prevalence of subclinical hypothyroidism associated with mitochondrial dysfunction, inflammation, and fibrosis. To understand the specific aging-related changes of endocrine function in thyroid epithelial cells, we performed single-cell RNA sequencing (RNA-seq) of 54 726 cells derived from pathologically normal thyroid tissues from 7 patients who underwent thyroidectomy. Thyroid endocrine epithelial cells were clustered into 5 distinct subpopulations, and a subset of cells was found to be particularly vulnerable with aging, showing functional deterioration associated with the expression of metallothionein (MT) and major histocompatibility complex class II genes. We further validated that increased expression of MT family genes are highly correlated with thyroid gland aging in bulk RNAseq datasets. This study provides evidence that aging induces specific transcriptomic changes across multiple cell populations in the human thyroid gland.


Assuntos
Envelhecimento , Hipotireoidismo , Humanos , Envelhecimento/genética , Envelhecimento/metabolismo , Hipotireoidismo/genética , Hormônios Tireóideos , Análise de Célula Única
19.
Clin Exp Otorhinolaryngol ; 16(1): 1-19, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36634669

RESUMO

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.

20.
J Clin Med ; 11(3)2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35160200

RESUMO

We investigated whether a fibrinogen-thrombin collagen sponge patch reduces postoperative complications of parotid gland surgery. This single-blinded, randomized controlled study included 165 patients who underwent parotid surgery for benign tumors (2018-2019) at a tertiary center. Primary outcomes were postoperative drain amount, days until drain removal, and discharge. Patients were scheduled for follow-up at 1 and 4 weeks, and 3 months after surgery. Complications including surgical site infection, pain, seroma, sialocele, salivary fistula, facial nerve palsy, Frey's syndrome with subjective symptoms, and facial asymmetry were analyzed. After identifying confounding variables, multivariate approaches were used. Histologic analysis was performed in a mouse model of salivary gland surgery. In total, 162 patients (77, fibrinogen-thrombin collagen patch group; 85, controls) were included, with no significant between-group differences other than resected tissue. Among postoperative total drain amount and days until drain removal and discharge, the only postoperative total drain was significantly lower in the patch group than in the control group in the adjusted model. Additionally, although validation through robust trials with longer follow-up is needed, we found the potential benefit of the fibrinogen patch on Frey's syndrome and facial asymmetry. In conclusion, fibrinogen-thrombin-impregnated collagen patches in parotidectomy can reduce postoperative drainage and improve outcomes.

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