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Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) have been increasingly investigated for cancer therapy and drug delivery, and they offer an advanced cell-free therapeutic option. However, their overall effects and efficacy depend on various factors, including the MSC source and cargo content. In this study, we isolated EVs from the conditioned medium of human immature dental pulp stem cells (hIDPSC-EVs) and investigated their effects on two papillary thyroid cancer (PTC) cell lines (BCPAP and TPC1). We observed efficient uptake of hIDPSC-EVs by both PTC cell lines, with a notable impact on gene regulation, particularly in the Wnt signaling pathway in BCPAP cells. However, no significant effects on cell proliferation were observed. Conversely, hIDPSC-EVs significantly reduced the invasive capacity of both PTC cell lines after 120 h of treatment. These in vitro findings suggest the therapeutic potential of hIDPSC-EVs in cancer management and emphasize the need for further research to develop novel and effective treatment strategies. Furthermore, the successful internalization of hIDPSC-EVs by PTC cell lines underscores their potential use as nanocarriers for anti-cancer agents.
Assuntos
Proliferação de Células , Polpa Dentária , Vesículas Extracelulares , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Polpa Dentária/citologia , Vesículas Extracelulares/metabolismo , Câncer Papilífero da Tireoide/terapia , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/terapia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Linhagem Celular Tumoral , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Via de Sinalização Wnt , Meios de Cultivo Condicionados/farmacologiaRESUMO
OBJECTIVE: The association between Papillary Thyroid Carcinoma (PTC) and coexistent Hashimoto's Thyroiditis (HT) was controversial. The purpose of this study was to evaluate the presence of HT exerts any influence on the aggressiveness of PTC, and to establish a nomogram for predicting the possibility of aggressiveness in PTC. METHODS: 373 consecutive PTC patients with/without coexistent HT from January 2017 to December 2020 were retrospective reviewed. Patients' clinicopathologic and sonographic characteristics were collected for univariate and multivariate analyses. A nomogram was established based on the risk factors for aggressiveness in PTC. RESULTS: Male (pâ¯=â¯0.001), tumor size >1.0â¯cm (pâ¯=â¯0.046) and lymph node metastasis (pâ¯=â¯0.018) were negatively associated with PTC coexisted with HT, while it was significantly positively associated with the frequence of multifocality (pâ¯=â¯0.010). Univariate and multivariate analyses suggested that age ≥55 years (pâ¯=â¯0.000), male (pâ¯=â¯0.027), HT (pâ¯=â¯0.017), tumor size >1.0â¯cm (pâ¯=â¯0.015), multifocality (pâ¯=â¯0.041), distance to capsular ≤0â¯cm (pâ¯=â¯0.050) and blood flow (Grade I: pâ¯=â¯0.044) were independent risk factors for predicting the aggressiveness in PTC. A nomogram according to these predictors was further developed and validated. The receiver operating characteristic curve (AUCâ¯=â¯0.734 and 0.809 for training and validation cohorts, respectively) and decision curve analyses indicated that the nomogram model was clinically useful. The calibration curve revealed that the nomogram exhibited an excellent consistency. CONCLUSIONS: In this study, the coexistent HT might play a protective role in preventing the proliferation of PTC. Dispensable aggressive treatment may be reduced in PTC by pre-operative identification of sonographic and clinical characteristics and incorporating with the predicted nomogram model.
Assuntos
Doença de Hashimoto , Nomogramas , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Ultrassonografia , Humanos , Masculino , Doença de Hashimoto/complicações , Doença de Hashimoto/diagnóstico por imagem , Doença de Hashimoto/patologia , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Adulto , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/complicações , Fatores de Risco , Idoso , Adulto Jovem , Metástase Linfática/diagnóstico por imagemRESUMO
TERT promoter mutations C228T and C250T are associated with disease aggressiveness and poor clinical outcomes in patients with papillary thyroid carcinomas. However, very little is known about the transcriptional consequences of these mutations and whether they both carry similar oncogenic potential. Here we characterized the transcriptional disturbances and clinical outcomes associated with the presence of each of these two mutations using data derived from The Cancer Genome Atlas. We observed that tumors harboring the C228T mutation (n = 27) exhibited a 16-fold increase in TERT mRNA levels (P = 5.3 × 10-42), whereas C250T tumors (n = 8) showed only a two-fold increase in expression (P = 0.034). The C228T mutation was associated with the activation of signaling pathways controlling the cell cycle, cellular division, and extracellular matrix degradation. Univariate analysis demonstrated that the C228T mutation was associated with older age at diagnosis, large tumor size, lymph node invasion, and distant metastases at diagnosis. The C228T mutation was also associated with worse progression-free interval (PFI) in comparison to WT tumors (HR = 5,04; P < 0.001). This association remained significant in a multivariate analysis (HR = 3.74, P = 0.003) adjusting for BRAF-V600E status and ATA risk group. Our data indicate that TERT promoter mutations C228T and C250T have distinct transcriptional consequences in papillary thyroid carcinoma (PTC), suggesting a greater oncogenic potential for the C228T mutation. TERT promoter mutation C228T may be a useful prognostic marker to identify patients at high risk of distant recurrence. Clinical data for the C250T mutation is still limited, with no evidence up to date to confirm its prognostic significance.
Assuntos
Mutação , Regiões Promotoras Genéticas , Telomerase , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Telomerase/genética , Humanos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Prognóstico , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Adulto , IdosoRESUMO
Background: Papillary thyroid carcinoma has become increasingly prevalent over the years. Avoiding unnecessary treatments and the risk of complications is essential, as well as understanding the mechanisms of tumor progression and the conditions that indicate a worse prognosis. Assessment of the tumor microenvironment can allow us understand how the immune system organizes itself to contain neoplastic progression. Methods: We compared characteristics related to the lymphocytic subpopulations in the thyroid tumor microenvironment and lymph nodes in two groups, with and without lymph node metastatic involvement. Results: Of the 400 cases followed up at a thyroid cancer reference service, 32 were selected, of which, 13 cases did not present lymph node metastasis (N0 group) and 19 had lymph node involvement (N1 group). Clinical data were collected, and immunohistochemical reactions were performed for markers CD4, CD8, FoxP3, CD25, and CD20 in lymph nodes and peritumoral infiltrate. We found that the N1 group had larger tumor sizes, higher risk staging, higher frequency of extrathyroidal extension, shorter disease-free times, and higher expression of CD4+ T lymphocytes in lymph nodes; however, there was no difference in the expression of other markers or in the pattern of lymphocyte distribution in the lymph node. Conclusion: In cervical lymph nodes, the higher frequency of CD4+ T lymphocytes is related to the presence of metastasis. However, there were no differences in lymphocytic subpopulations in the thyroid tumor microenvironment. The absence of changes in unaffected lymph nodes could not predict any tumor behavior.
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In solid tumors, hypereosinophilia is a rare phenomenon and is mainly associated with mucin-secreting carcinomas. Thyroid tumors associated with neutrophilia and/or eosinophilia have been described exclusively in patients with anaplastic thyroid cancer. Eosinophilia associated with papillary thyroid cancer is extremely rare and there are very few cases currently described. It has been suggested that three cytokines, namely interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte-macrophage colony-stimulating factor (GM-CSF), may act as a peptide potential eosinophilic. To date, only three patients with differentiated thyroid cancer associated with eosinophilia have been reported, two of the papillary type and one of the medullary type. A 48-year-old patient consulted in 2022 due to bilateral cervical lymphadenopathy of 3 years' duration associated with wasting syndrome and hypereosinophilia. PET CT was requested, which showed hypermetabolic focus in the right thyroid lobe and lymph node, lung, bone, and liver metastases; Thyroid ultrasound showing a nodule of high suspicion of malignancy and a conglomerate of lymphadenopathy in the right lobe with positive needle wash for thyroglobulin. Hypereosinophilia was evaluated with initial leukocytosis values of GB 30,310/mm3 (10,608/mm3 of eosinophils) to maximum values of GB 77,090/mm3 (eosinophils 20,814/mm3). It was interpreted as paraneoplastic syndrome and corticosteroid therapy was started at immunosuppressive doses without response. Our observations presented in this article are in line with most studies reflecting that paraneoplastic hypereosinophilia is characterized by more advanced disease and poor prognosis.
En los tumores sólidos la hipereosinofilia es un fenómeno raro y se asocia principalmente con carcinomas secretores de mucina. Los tumores tiroideos asociados a neutrofilia y/o eosinofilia se han descrito exclusivamente en pacientes con cáncer anaplásico de tiroides. La eosinofilia asociada con cáncer papilar de tiroides es extremadamente rara y se encuentran muy pocos casos descriptos actualmente. Se ha sugerido que tres citocinas, a saber, la interleucina-3 (IL-3), la interleucina-5 (IL-5) y el factor estimulante de colonias de granulocitos y macrófagos (GM-CSF), pueden actuar como un péptido eosinofílico potencial. Hasta el momento solo se han reportado tres pacientes con cáncer diferenciado de tiroides asociados a eosinofilia, dos de tipo papilar y uno de tipo medular. Paciente de 48 años consultó en el año 2022 por adenopatías cervicales bilaterales de 3 años de evolución asociado a síndrome consuntivo e hipereosinofilia. Se solicitó PET CT que evidenció foco hipermetabólico en lóbulo tiroideo derecho y metástasis ganglionares, pulmonares, óseas y hepáticas; ecografía tiroidea que evidencia en lóbulo derecho nódulo de alta sospecha de malignidad y conglomerado de adenopatías con lavado de aguja positivo para tiroglobulina. Evaluada la hipereosinofilia con valores iniciales de leucocitosis de GB 30310/mm3 (10608/mm3 de eosinófilos) hasta valores máximos de GB 77090/mm3 (eosinófilos 20814/mm3) se interpretó como síndrome paraneoplásico y se inició corticoterapia en dosis inmunosupresoras sin respuesta. Nuestras observaciones presentadas en este artículo están en línea con la mayoría de los estudios que reflejan que la hipereosinofilia paraneoplásica se caracteriza por una enfermedad más avanzada y un mal pronóstico.
Assuntos
Síndromes Paraneoplásicas , Neoplasias da Glândula Tireoide , Humanos , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia , Síndromes Paraneoplásicas/etiologia , Síndrome Hipereosinofílica/complicações , Masculino , Feminino , Carcinoma Papilar/complicações , Eosinofilia/complicaçõesRESUMO
BACKGROUND: Salivary gland cystadenoma (SGCA) is a rare benign tumor that predominantly occurs in the parotid gland. SGCAs affecting the minor salivary glands are uncommon and often resemble, clinically and histopathologically, other salivary gland lesions. METHODS: This study aimed to describe a series of four cases of SGCA affecting intraoral sites and performed a literature review of well-reported SGCA published in the English-language literature. RESULTS: SGCA cases included in this series were diagnosed in the buccal mucosa, lip, and hard palate of female patients aged between 19 and 78 years. All cases underwent excisional biopsy and were histologically characterized by a multicystic growth with variable degrees of capsule formation and were lined by several types of epithelium, including some cell types that are infrequently reported in SGCA. In some cases, a small collection of lymphocytes was observed adjacent to cystic formations. All SGCA were positive for periodic acid-Schiff, and immunohistochemical reactions were positive for CK7 and p63. The follow-up time ranged widely from 3 to 53 months, and to date, no recurrence has been observed. CONCLUSION: The literature review revealed a total of 33 published studies accounting for 55 SGCA cases.
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Cistadenoma , Neoplasias das Glândulas Salivares , Humanos , Feminino , Neoplasias das Glândulas Salivares/patologia , Adulto , Pessoa de Meia-Idade , Cistadenoma/patologia , Idoso , Adulto JovemRESUMO
BACKGROUND: In previous studies, we demonstrated the downregulation of several miRNAs from the DLK1-DIO3 genomic region in papillary thyroid carcinoma (PTC). Due to the large number of miRNAs within this region, the individual contribution of these molecules to PTC development and progression remains unclear. OBJECTIVE: In this study, we aimed to clarify the contribution of DLK1-DIO3-derived miRNAs to PTC. METHODS: We used different computational approaches and in vitro resources to assess the biological processes and signaling pathways potentially modulated by these miRNAs. RESULTS: Our analysis suggests that, out of more than 100 mature miRNAs originated from the DLK1-DIO3 region, a set of 12 miRNAs accounts for most of the impact on PTC development and progression, cooperating to modulate distinct cancer-relevant biological processes, such as cell migration, extracellular matrix remodeling, and signal transduction. The restoration of the expression of one of these miRNAs (miR-485-5p) in a BRAFT199A-positive PTC cell line impaired proliferation and migration, suppressing the expression of GAB2 and RAC1, validated miR-485-5p targets. CONCLUSIONS: Overall, our results shed light on the role of the DLK1-DIO3 region, which harbors promising tumor suppressor miRNAs in thyroid cancer, and open prospects for the functional exploration of these miRNAs as therapeutic targets for PTC.
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OBJECTIVE: The aim of the study was to create two consensus nomograms for predicting Overall Survival (OS) and Cancer-Specific Survival (CSS) in adults with papillary Renal Cell Carcinoma (pRCC). METHODS: Using the Surveillance, Epidemiology, and End Results databases, a retrospective analysis of 1,074 adults with pRCC from 2004 to 2015 was performed. These patients were then randomly divided into two independent cohorts with a ratio of 7:3 (training cohort: 752; validation cohort: 322). In a retrospective analysis of 752 patients from the training cohort, independent prognostic variables affecting OS and CSS were found. R software was used to create prognostic nomograms based on the findings of Cox regression analysis. The performance of the nomograms was assessed using the Concordance Index (C-index), the Area Under Curve (AUC), a calibration curve, and Decision Curve Analysis (DCA). Data from the 107 postoperative pRCC patients at the Affiliated Hospital of Xuzhou Medical University were used for external validation of the nomogram. RESULTS: For OS and CSS, the C-indices and AUCs of the training cohort and the validation cohort indicated that the model had excellent discrimination. The DCA demonstrated that the model was clinically applicable, and the calibration curves in the internal and external validations showed that the model's accuracy was high. CONCLUSION: The authors developed and validated a prognostic nomogram that accurately predicted the 3-, 5-, and 8-year OS and CSS of adults with pRCC. Clinicians can use this knowledge to direct the clinical management and counseling of patients with pRCC.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Nomogramas , Humanos , Masculino , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Prognóstico , Adulto , Idoso , Reprodutibilidade dos Testes , Estadiamento de Neoplasias , Programa de SEERRESUMO
Objective: After initial treatment, up to 30% of patients with papillary thyroid cancer (PTC) have incomplete response, mainly cervical lymph node (LN) disease. Previous studies have suggested that active surveillance (AS) is a possible option for these patients. Our aim was to report the results of AS in patients with PTC and cervical LN disease. Materials and methods: In this retrospective observational study, we included adult patients treated and followed for PTC, who presented with cervical LN disease and were managed with AS. Growth was defined as an increase ≥ 3mm in either diameter. Results: We included 32 patients: 27 (84.4%) women, age of 39 ± 14 years, all initially treated with total thyroidectomy, and 22 (69%) with therapeutic neck dissection. Cervical LN disease was diagnosed 1 year (0.3-12.6) after initial management, with a diameter of 9.0 mm (6.0-19.0). After a median AS of 4.3 years (0.6-14.1), 4 (12.5%) patients had LNgrowth: 2 (50%) of whom were surgically removed, 1 (25%) was effectively treated with radiotherapy, and 1 (25%) had a scheduled surgery. Tg increase was the only predictive factor of LN growth evaluated as both the delta Tg (p < 0.0366) and percentage of Tg change (p < 0.0140). None of the included patients died, had local complications due to LN growth or salvage therapy, or developed distant metastases during follow-up. Conclusion: In selected patients with PTC and suspicious cervical LNs diagnosed after initial treatment, AS is a feasible and safe strategy as it allows effective identification and treatment of the minority of patients who progress.
Assuntos
Linfonodos , Metástase Linfática , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Tireoidectomia , Conduta Expectante , Humanos , Feminino , Masculino , Adulto , Estudos Retrospectivos , Tireoidectomia/métodos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Linfonodos/patologia , Estudos de Viabilidade , Pescoço/cirurgia , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Esvaziamento Cervical/métodos , Adulto JovemRESUMO
PURPOSE: Cervical lymph nodes (LN) represent the most common site of recurrence in differentiated thyroid cancer (DTC), frequently requiring repeated interventions that contribute to increase morbidity to a usually indolent disease. Data on active surveillance (AS) of nodal metastasis are limited. Therefore, we performed a systematic review and meta-analysis to evaluate AS in nodal metastasis of DTC patients. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched up to July 2023 for studies including DTC patients with metastatic LN who were followed up with AS. The primary outcome was disease progression, according to the study's definition. Additional outcomes were LN enlargement ≥3 mm, occurrence of new cervical metastasis, and conversion from AS to surgical treatment. RESULTS: The search identified 375 studies and seven were included, comprising 486 patients with metastatic nodal DTC. Most were female (69.5%) and had papillary thyroid cancer (99.8%). The mean AS follow-up ranged from 28-86 months. Following each study's definition of progression, the pooled incidence was 28% [95% confidence interval (CI), 20-37%]. The pooled incidence of LN growth ≥ 3 mm was 21% [95% CI, 17-25%] and the emergence of new LN sites was 19% [95% CI, 14-25%]. Combining growth of 3 mm and the emergence of new LN criteria, we found an incidence of 26% [95% CI, 20-33%]. The incidence of neck dissection during AS was 18% [95% CI, 12-26%]. CONCLUSIONS: AS seems to be a suitable strategy for selected DTC patients with small nodal disease, avoiding or postponing surgical reintervention. PROSPERO REGISTRATION: CRD42023438293.