Publications by authors named "I Tena"

19 Publications

Corpora Amylacea in the Human Brain Exhibit Neoepitopes of a Carbohydrate Nature.

Front Immunol 2021 28;12:618193. Epub 2021 Jun 28.

Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Barcelona, Spain.

Corpora amylacea (CA) in the human brain are polyglucosan bodies that accumulate residual substances originated from aging and both neurodegenerative and infectious processes. These structures, which act as waste containers, are released from the brain to the cerebrospinal fluid, reach the cervical lymph nodes the meningeal lymphatic system and may be phagocytosed by macrophages. Recent studies indicate that CA present certain neoepitopes (NEs) that can be recognized by natural antibodies of the IgM class, and although evidence of different kinds suggests that these NEs may be formed by carbohydrate structures, their precise nature is unknown. Here, we adapted standard techniques to examine this question. We observed that the preadsorption of IgMs with specific carbohydrates has inhibitory effects on the interaction between IgMs and CA, and found that the digestion of CA proteins had no effect on this interaction. These findings point to the carbohydrate nature of the NEs located in CA. Moreover, the present study indicates that, , the binding between certain natural IgMs and certain epitopes may be disrupted by certain monosaccharides. We wonder, therefore, whether these inhibitions may also occur . Further studies should now be carried out to assess the possible effect of glycemia on the reactivity of natural IgMs and, by extension, on natural immunity.
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http://dx.doi.org/10.3389/fimmu.2021.618193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273382PMC
September 2021

Prevalence and Clinicopathological Characteristics of Moderate and High-Penetrance Genes in Non-BRCA1/2 Breast Cancer High-Risk Spanish Families.

J Pers Med 2021 Jun 12;11(6). Epub 2021 Jun 12.

Cancer Genetic Counseling Unit, Medical Oncology Department, Castellon Provincial Hospital, 12002 Castellon, Spain.

(1) Background: Over the last decade, genetic counseling clinics have moved from single-gene sequencing to multigene panel sequencing. Multiple genes related to a moderate risk of breast cancer (BC) have emerged, although many questions remain regarding the risks and clinical features associated with these genes. (2) Methods: Ninety-six BC index cases (ICs) with high-risk features for hereditary breast and ovarian cancer (HBOC) and with a previous uninformative result for were tested with a panel of 41 genes associated with BC risk. The frequency of pathogenic variants (PVs) was related to the clinical characteristics of BC. (3) Results: We detected a PV rate of 13.5% (excluding two cases each of and . Among the 95 assessed cases, 17 PVs were identified in 16 ICs, as follows: ( = 2), ( = 3), ( = 5), ( = 2), ( = 2), ( = 1), ( = 1), and ( = 1). We also identified a novel loss-of-function variant in a candidate gene for increased BC risk. There was no evidence that the clinical characteristics of BC might be related to a higher chance of identifying a PV. (4) Conclusions: In our cohort, which was enriched with families with a high number of BC cases, a high proportion of mutations in and were identified. The clinical characteristics of BC associated with moderate-risk genes were different from those related to genes.
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http://dx.doi.org/10.3390/jpm11060548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231620PMC
June 2021

Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas.

Clin Transl Oncol 2021 Oct 6;23(10):1995-2019. Epub 2021 May 6.

Endocrinology and Nutrition Department, Hospital Clinic Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.
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http://dx.doi.org/10.1007/s12094-021-02622-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390422PMC
October 2021

Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World.

Front Endocrinol (Lausanne) 2021 29;12:625312. Epub 2021 Mar 29.

Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.

Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This overexpression is a well-established finding in gastroenteropancreatic neuroendocrine tumors which has guided new medical therapies in the administration of somatostatin analogs, both "cold", particularly octreotide and lanreotide, and "hot" analogs, chelated to radiolabeled isotopes. The binding of these analogs to somatostatin receptors effectively suppresses excess hormone secretion and tumor cell proliferation, leading to stabilization, and in some cases, tumor shrinkage. Radioisotope-labeled somatostatin analogs are utilized for both tumor localization and peptide radionuclide therapy, with Ga-DOTATATE and Lu-DOTATATE respectively. Benign and malignant pheochromocytomas and paragangliomas also overexpress somatostatin receptors, irrespective of embryological origin. The pattern of somatostatin receptor overexpression is more prominent in gene mutation, which is more aggressive than other subgroups of this disease. While the Food and Drug Administration has approved the use of Ga-DOTATATE as a radiopharmaceutical for somatostatin receptor imaging, the use of its radiotherapeutic counterpart still needs approval beyond gastroenteropancreatic neuroendocrine tumors. Thus, patients with pheochromocytoma and paraganglioma, especially those with inoperable or metastatic diseases, depend on the clinical trials of somatostatin analogs. The review summarizes the advances in the utilization of somatostatin receptor for diagnostic and therapeutic approaches in the neuroendocrine tumor subset of pheochromocytoma and paraganglioma; we hope to provide a positive perspective in using these receptors as targets for treatment in this rare condition.
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http://dx.doi.org/10.3389/fendo.2021.625312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039528PMC
March 2021

Epigenetic Deregulation of Protocadherin PCDHGC3 in Pheochromocytomas/Paragangliomas Associated With SDHB Mutations.

J Clin Endocrinol Metab 2019 11;104(11):5673-5692

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota.

Context: SDHB mutations are found in an increasing number of neoplasms, most notably in paragangliomas and pheochromocytomas (PPGLs). SDHB-PPGLs are slow-growing tumors, but ∼50% of them may develop metastasis. The molecular basis of metastasis in these tumors is a long-standing and unresolved problem. Thus, a better understanding of the biology of metastasis is needed.

Objective: This study aimed to identify gene methylation changes relevant for metastatic SDHB-PPGLs.

Design: We performed genome-wide profiling of DNA methylation in diverse clinical and genetic PPGL subtypes, and validated protocadherin γ-C3 (PCDHGC3) gene promoter methylation in metastatic SDHB-PPGLs.

Results: We define an epigenetic landscape specific for metastatic SDHB-PPGLs. DNA methylation levels were found significantly higher in metastatic SDHB-PPGLs than in SDHB-PPGLs without metastases. One such change included long-range de novo methylation of the PCDHA, PCDHB, and PCDHG gene clusters. High levels of PCDHGC3 promoter methylation were validated in primary metastatic SDHB-PPGLs, it was found amplified in the corresponding metastases, and it was significantly correlated with PCDHGC3 reduced expression. Interestingly, this epigenetic alteration could be detected in primary tumors that developed metastasis several years later. We also show that PCDHGC3 down regulation engages metastasis-initiating capabilities by promoting cell proliferation, migration, and invasion.

Conclusions: Our data provide a map of the DNA methylome episignature specific to an SDHB-mutated cancer and establish PCDHGC3 as a putative suppressor gene and a potential biomarker to identify patients with SDHB-mutated cancer at high risk of metastasis who might benefit from future targeted therapies.
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http://dx.doi.org/10.1210/jc.2018-01471DOI Listing
November 2019
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