Elena Navarro-González’s research while affiliated with Hospital Universitario Virgen del Rocío and other places

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Publications (19)


Figure 4. LINC00887 knockdown impacts on TPC1 and BCPAP cell colony formation. Representative images are shown for colony formation assays of TPC1 (A) and BCPAP (B) cells. Analysis comparison of colony numbers in TPC1 (C) and BCPAP (D) cells. Data are presented as the mean ± SD based on more than three independent experiments (* p < 0.05, ** p < 0.01).
Delving into the Role of lncRNAs in Papillary Thyroid Cancer: Upregulation of LINC00887 Promotes Cell Proliferation, Growth and Invasion
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January 2024

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19 Reads

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3 Citations

International Journal of Molecular Sciences

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Carmen Muñoz-Redondo

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Angela Gavilán

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Papillary thyroid carcinoma (PTC) is the most common histological category of thyroid cancer. In recent years, there has been an increasing number of studies on lncRNAs in PTC. Long intergenic non-protein coding RNA 887 (LINC00887) is a critical oncogene in developing other cancers. LINC00887 is upregulated in PTC samples but its role in PTC is currently unclear. This study aimed to investigate the impact the disruption of LINC00887 expression has on PTC progression. We performed a CRISPR/Cas9 strategy for the truncation of LINC00887 in BCPAP and TPC1 cell lines. Functional assays showed that LINC00887 knockdown in both TPC1 and BCPAP cells reduced cell proliferation, colony formation and migration, delayed the cell cycle, and increased apoptosis. These results strengthened the role of LINC00887 in cancer and showed for the first time that this lncRNA could be a potential oncogene in PTC, acting as a tumor promoter. Modulation of the immune system may be one of the etiopathogenic mechanisms of LINC00887 in PTC, as shown by the observed influence of this lncRNA on PD-L1 expression. In addition, the biological pathways of LINC00887 identified to date, such as EMT, the Wnt/β-catenin signaling pathway or the FRMD6-Hippo signaling pathway may also be relevant regulatory mechanisms operating in PTC.

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Figure 2. Survival plots at 5 years according to whether patients received I131 treatment or not (A); the presence of nodal disease (N1) at 5 years (B); the presence of pulmonary metastases at 5 years (C); and the presence of other metastases at 10 years (D).
Bone metastases of differentiated thyroid cancer: characteristics and prognostic factors in a multicenter series

July 2023

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15 Reads

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4 Citations

European Thyroid Journal

Objective: To describe the characteristics, survival and prognostic factors of a cohort of patients with bone metastases (BM) from differentiated thyroid carcinoma (DTC). Methods: This was a multicenter retrospective observational study including patients diagnosed with BM from DTC between 1980-2021. A Cox-regression was performed to study prognostic factors for 5- and 10-year survival. Kaplan-Meier and log-rank tests were performed for survival analysis and comparison between groups. Results: Sixty-three patients were evaluated. Median follow-up from BM diagnosis was 35(15-68) months. 30(48.4%) patients presented with synchronous BM. Regarding histology, 38(60.3%) had the papillary variant. BM were multiple in 32(50.8%) patients. The most frequent location was the spine (60.3%). Other metastases were present in 77.8%, mainly pulmonary (69.8%). Concerning treatment, 54(85.9%) patients received I131, with BM uptake in 31(49.2%), and 25(39.7%) received treatment with multikinase inhibitors. Regarding complications, 34(54%) patients had skeletal-related events, 34(54%) died and 5- and 10-year overall survival was 42.4% and 20.4%, respectively. Significant prognostic factors in the multivariate analysis were the presence of lymph node involvement (HR 2.916 (95% CI 1.013-8.391);p=0.047) and treatment with I131 (HR 0.214 (95% CI 0.069-0.665);p=0.008) at 5 years, the presence of other metastases (HR 6.844. 95% CI 1.017-46.05;p=0.048) and treatment with I131 (HR 0.23 (95% CI 0.058-0.913);p=0.037) at 10 years. Conclusions: Our study reflects the management of patients with bone metastases from differentiated thyroid carcinoma in real clinical practice in several centers in southern Spain. Overall survival at 5 and 10 years was lower in patients who were not treated with I131, had nodal involvement and/or had other metastases.



Cont.
Possible interactions of thyroid cancer-associated genes harboring candidate variants. The interactions were predicted according to the ToppGene Suite tool.
Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing

April 2023

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56 Reads

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4 Citations

International Journal of Molecular Sciences

Thyroid carcinoma (TC) can be classified as medullary (MTC) and non-medullary (NMTC). While most TCs are sporadic, familial forms of MTC and NMTC also exist (less than 1% and 3–9% of all TC cases, respectively). Germline mutations in RET are found in more than 95% of familial MTC, whereas familial NMTC shows a high degree of genetic heterogeneity. Herein, we aimed to identify susceptibility genes for familial NMTC and non-RET MTC by whole exome sequencing in 58 individuals belonging to 18 Spanish families with these carcinomas. After data analysis, 53 rare candidate segregating variants were identified in 12 of the families, 7 of them located in previously TC-associated genes. Although no common mutated genes were detected, biological processes regulating functions such as cell proliferation, differentiation, survival and adhesion were enriched. The reported functions of the identified genes together with pathogenicity and structural predictions, reinforced the candidacy of 36 of them, suggesting new loci related to TC and novel genotype–phenotype correlations. Therefore, our strategy provides clues to possible molecular mechanisms underlying familial forms of MTC and NMTC. These new molecular findings and clinical data of patients may be helpful for the early detection, development of tailored therapies and optimizing patient management.



Use of multikinase inhibitors/lenvatinib concomitant with antiresorptive therapy for bone metastases from radioiodine‐resistant differentiated thyroid cancer

July 2022

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27 Reads

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6 Citations

Bone is the second most common distant metastasis site in differentiated thyroid cancer (DTC) and is normally associated with the presence of other metastases, which are usually radioiodine‐resistant. The presence of bone metastasis (BM) determines low survival and greater morbidity due to the frequency of skeletal‐related events (SREs), which can be a serious complication of BM. There is evidence that antiresorptive therapy (AT) reduces SREs in other solid tumors, but not yet in DTC BM, for which data are scant. The same is true for systemic therapy with multikinase inhibitors (MKIs). In general, the results for MKI use are well known, although the effect on BM has rarely been evaluated. While MKIs are indicated in current clinical practice guidelines, studies evaluating the benefits and risks of concomitant treatment with MKIs and AT are lacking, and the available data come from small samples in retrospective studies. The objective of this article is to review the latest evidence for concomitant MKIs and AT. Bone is a common distant metastasis in differentiated thyroid cancer, that is associated with the presence of other metastases, low survival and high morbidity. There is evidence that antiresorptive therapy and multikinase inhibitors reduce skeletal‐related events in other solid tumors, but studies evaluating the benefits and risks of concomitant treatment are lacking in differentiated thyroid cancer. This article reviews the latest evidence.


Figure 1 ERUDIT study design and evolution timeline of the aDTC patients included according to the type of their diagnosis. Type 1: de novo metastatic with resectable locoregional disease. Type 2: de novo locoregional unresectable disease. Type 3: recurrent metastatic without resectable locoregional disease. Type 4: recurrent locoregional unresectable disease, with or without distant metastases. aDTC, advanced differentiated thyroid cancer; eDTC, early stage differentiated thyroid cancer; FSR, final study report.
Figure 2 Flow diagram of eligible patients and analysed groups with evaluable data from the initial diagnosis of differentiated thyroid cancer (DTC). The (relapse/ progression) free survival ((RP)FS) evaluation describes the time elapsed from an upfront treatment until death, relapse into advanced DTC (aDTC) in patients who were initially free of disease, or structural progression into aDTC in patients who had initial residual disease, respectively. n, number of patients with available data evaluable. ∲, from 208 total patients with evaluable outcome from first surgery to death, of which, 13 patients were excluded because of 'metastases resection' (n = 8) and 'other results' (n = 5). ∯, only 188 patients had evaluable response from the first RAI therapy to death. ∰, from 98 total patients in the cohort with initial early disease with evaluable outcome from first surgery to death or from the first RAI therapy to death, of which, 7 patients were excluded because of 'metastases resection' (n = 3) and 'other results' (n = 4). **, ATA RAI response.
Multivariate analyses for overall survival in the global study population.
Initial Clinical and Treatment Patterns of Advanced Differentiated Thyroid Cancer. ERUDIT Study

July 2022

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93 Reads

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3 Citations

European Thyroid Journal

Background. Up to 30% of differentiated thyroid cancer (DTC) will develop advanced-stage disease (aDTC) with reduced overall survival (OS). Objective. To characterize initial diagnosis of aDTC, its therapeutic management, and prognosis in Spain and Portugal. Methods. Multicentre, longitudinal, retrospective study of adult patients diagnosed with aDTC in Iberian Peninsula between Jan’2007 and Dec’2012. Analyses of baseline characteristics and results to initial treatments, relapse- or progression-free survival [(RP)FS] from first DTC diagnosis, OS, and prognostic factors impacting the evolution of advanced disease were evaluated. Results. 213 patients (median age 63 years; 57% female) were eligible from 23 hospitals. Advanced disease presented at first diagnosis (de novo aDTC) in 54% of patients, while 46% had relapsed from early disease (recurrent/progressive eDTC). At initial stage, most patients received surgery (98%) and/or RAI (89%), with no differences seen between median OS (95%CI) [10.4(7.3 - 15.3) years], and median disease-specific-survival (95%CI) [11.1(8.7 - 16.2) years; log-rank test p=0.4737]. Age at diagnosis <55 years was associated with lower risk of death (Wald chi-square [Wc-s] p<0.0001), while poor response to RAI to a higher risk of death ([Wc-s] p<0.05). In the eDTC cohort, median (RP)FS (95%CI) was of 1.7(1.0-2.0) years after RAI, with R0/R1 surgeries being the only common significant favourable factor for longer (RP)FS and time to aDTC ([Wc-s] p<0.05). Conclusion. Identification of early treatment-dependent prognostic factors for an unfavourable course of advanced disease, is possible. An intensified therapeutic attitude may reverse this trend and should be considered in poor-performing patients. Prospective studies are required to confirm these findings.



Thyroid disorders associated with immune control point inhibitors

October 2021

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11 Reads

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3 Citations

Endocrinología Diabetes y Nutrición (English ed )

Introduction Immune checkpoint inhibitors (ICPI) have improved progression-free survival in several solid tumors. Side effects are related to overstimulation of the immune system. Thyroid dysfunction (TD) is the most common endocrine immune-related adverse event of ICPI. Objective To describe the clinical presentation and the course of TD in cancer patients treated with ICPI referred to an endocrinology outpatient clinic. Material and methods This was a descriptive, retrospective and multicenter study of patients with TD associated with ICPI in six Spanish hospitals. Results 120 patients (50.8% women), mean age 60 ± 12 years were included. The initial TD was hypothyroidism in 49% of patients and hyperthyroidism in 51%, with an average of 76 (41–140) and 43 (26–82) days respectively between the onset of ICPI and the analytical alteration. Significantly, the earlier the first analytical determination was, the greater the prevalence of hyperthyroidism. A turnover was observed in 80% of subjects during follow-up, mostly from hyperthyroidism to hypothyroidism. Twenty-one percent received double ICPI therapy. The most frequent form of presentation in monotherapy was hypothyroidism (57%), and in double therapy it was hyperthyroidism (77%) (p = 0.002). Patients under double therapy showed thyroid alterations earlier than those in the monotherapy group (p = 0.001). After a follow-up of 205 (112–360) days, half of the patients continued under levothyroxine treatment. Conclusions Hypothyroidism and hyperthyroidism present in a similar proportion in cancer patients undergoing ICPI therapy. Our results suggest that transitory hyperthyroidism may not be detected in a relevant number of cases. In addition, TD in double therapy presents earlier. This should be taken into account in the follow-up protocols of these patients.


Alteraciones tiroideas asociadas con los inhibidores de los puntos de control inmunitario

October 2020

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20 Reads

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1 Citation

Endocrinología Diabetes y Nutrición

Resumen Introducción Los inhibidores de los puntos de control inmunitario (IPCI) han conseguido elevados porcentajes de respuesta en diversas neoplasias. Los efectos secundarios se relacionan con la hiperestimulación del sistema inmune y los que afectan a la glándula tiroides se encuentran entre los más frecuentes. Objetivo Describir la presentación clínica y evolución de la disfunción tiroidea (DT) en pacientes oncológicos en tratamiento con IPCI remitidos a las consultas de endocrinología. Material y métodos Estudio descriptivo, retrospectivo y multicéntrico de pacientes con DT asociada a IPCI en seis centros hospitalarios españoles. Resultados Se incluyeron 120 pacientes (50,8% mujeres), edad 60 ± 12 años. La DT inicial fue el hipotiroidismo en el 49% de los pacientes y el hipertiroidismo en el 51%, con una media de 76 (41-140) y 43 (26-82) días, respectivamente entre el inicio de IPCI y la alteración hormonal. El diagnóstico de hipertiroidismo estaba significativamente asociado a una evaluación analítica más temprana. En un 80% se observó un viraje durante el seguimiento, en la mayoría de hipertiroidismo a hipotiroidismo. El 21,7% recibió doble terapia con IPCI. La forma de presentación más frecuente en monoterapia fue el hipotiroidismo (57%), y en doble terapia fue el hipertiroidismo (77%) (p = 0,002). Los pacientes en doble terapia presentaron alteraciones tiroideas significativamente más tempranas que los del grupo en monoterapia. Tras un seguimiento de 205 (112-360) días, el 50% de los pacientes continuaba en tratamiento con levotiroxina. Conclusiones El hipotiroidismo y el hipertiroidismo se presentan en una proporción similar en la DT asociada a IPCI, aunque es posible que el hipertiroidismo transitorio no sea detectado en un gran número de casos. La DT en la doble terapia es más precoz, hecho que debiera tenerse en cuenta en los protocolos de seguimiento de estos pacientes.


Citations (11)


... Thyroid cancers are classified into differentiated thyroid cancer (DTC), progressively dedifferentiated DTC, poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC) according to their histopathological differentiation [59][60][61]. PTC is one of the differentiated cancers [32,64,65]. Moreover, the level of TG expression in thyroid cells correlates with their degree of differentiation [57,[59][60][61]. ...

Reference:

Environmental Exposure to Bisphenol A Enhances Invasiveness in Papillary Thyroid Cancer
Delving into the Role of lncRNAs in Papillary Thyroid Cancer: Upregulation of LINC00887 Promotes Cell Proliferation, Growth and Invasion

International Journal of Molecular Sciences

... Tumors classified as T3 or T4, denoting either larger size or invasion into adjacent tissues, are associated with less favorable outcomes in DTC. The significance of lymph node involvement and the presence of metastases on the 5-and 10-year survival rates of DTC patients were notably emphasized by Piñar et al. [18] Moreover, Kim et al [19] identified clinical staging as a pivotal factor influencing recurrence in patients with locally advanced DTC. The challenges in achieving comprehensive surgical removal and the potential reduced effectiveness of postoperative adjuvant therapy in cases with localized lymph node involvement or distant metastases often culminate in a classification of advanced or moderately advanced DTC, indicative of a poorer prognosis. ...

Bone metastases of differentiated thyroid cancer: characteristics and prognostic factors in a multicenter series

European Thyroid Journal

... According to the current literature, three variants in the CCDC134 gene (c.2 T > C, c.414C > T, and c.217delC) have been reported to cause OI [6][7][8], autism spectrum disorder [9], and thyroid cancer [10]. The c.492G > C variant is the fourth pathogenic variant to be found in this gene. ...

Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing

International Journal of Molecular Sciences

... Differentiated thyroid carcinoma (DTC) is a neoplasm with a 5year survival of over 98%. Bone metastases (BM) are present in 2-13% of patients (1) and are more common in follicular carcinomas (7-28%) (2). The prognosis worsens in patients who present BM, with survivals described in observational studies of 42-61% and 20-27% at 5 and 10 years, respectively (3)(4)(5). ...

Use of multikinase inhibitors/lenvatinib concomitant with antiresorptive therapy for bone metastases from radioiodine‐resistant differentiated thyroid cancer

... Therefore, health care professionals should conduct prospective interventions based on the specific manifestations of the disease to alleviate the burden of symptoms on patients and improve their prognosis. Patients who have already experienced multiple symptoms or symptom clusters should be referred to high-volume centers with the availability of an extended multidisciplinary team to receive tailored treatment [33,34]. There were still some limitations in this study, such as the inclusion of only 115 patients from one hospital by convenience sampling, which limited the representativeness of the sample. ...

Initial Clinical and Treatment Patterns of Advanced Differentiated Thyroid Cancer. ERUDIT Study

European Thyroid Journal

... The most common ir thyroid disorder was hypothyroidism (57%) in the monotherapy group, as opposed to hyperthyroidism (77%) in the combination group (p = 0.002). The onset of an ir thyroid disorder was significantly accelerated by a combination treatment compared to a monotherapy (p = 0.001) [60]. ...

Thyroid disorders associated with immune control point inhibitors
  • Citing Article
  • October 2021

Endocrinología Diabetes y Nutrición (English ed )

... The management of benign euthyroid goiters is challenging for both clinicians and endocrinologists (1)(2)(3). There is no clear cut universally accepted method in management of goiters (2,4,5). ...

Multinodular goiter in children: treatment controversies
  • Citing Article
  • January 2017

... However, Pedro's findings suggest that FDG detects hypermetabolic lesions related to CEA levels but is not correlated with Ctn, whereas 68Ga-DOTANOC is more closely associated with Ctn levels but not with CEA (104). Ana et al (105). reported that DOPA is superior to FDG in detecting and localizing lesions in patients with recurrent MTC, especially in those with negative results on other imaging modalities and with Ctn ≥150 pg/ mL or CEA ≥5 ng/mL. ...

Diagnostic utility of PET/CT with (18)F-DOPA and (18)F-FDG in persistent or recurrent medullary thyroid carcinoma: the importance of calcitonin and carcinoembryonic antigen cutoff

European Journal of Nuclear Medicine and Molecular Imaging

... Both 18 F-FDA and 18 F-DOPA have been shown to be superior to MIBG imaging for PHEO/PGL (62,63), with reported sensitivity as high as 100%. There is superior detection of lesions in those with hereditary neuroendocrine tumors, the SDHB mutation, von Hippel-Lindau syndrome-related, and head and neck PGLs (64)(65)(66). Limited data exist for these tracers in neuroblastoma. In a small study, sensitivity and specificity of approximately 90% were reported in stage III/IV neuroblastoma patients (67), with visualization of more disease sites and better assessment of response than with 123 I-MIBG (68). ...

[(123)I-MIBG, (18)F-DOPA and (18)F-FDG in a patient with MEN2 syndrome and recurrent pheochromocytoma.]
  • Citing Article
  • February 2013

... 11 There has been considerable research evaluating the value of FDG PET/CT in the follow-up of differentiated thyroid cancer in the past. [12][13][14][15][16] The objective of this study was to evaluate the prognostic value of follow-up FDG PET/CT on overall survival (OS) of patients with DTC and to estimate the added value of FDG PET/CT for clinical assessment at the time of the scan during follow-up. ...

Value of the negative PET-FDG in the middle term follow-up of differentiated thyroid cancer in patients with negative I-131-Na scan and elevated thyroglobulin serum levels
  • Citing Article
  • November 2012