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From Molecules to Disease: Research and Clinical Advances in Pituitary...
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From Molecules to Disease: Research and Clinical Advances in Pituitary and Neuroendocrine Tumors

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 9163

Special Issue Editors

Dr. Raul M. Luque

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Guest Editor
1. Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Cordoba, Spain
2. Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Cordoba, Spain
3. Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain
Interests: cancer biology; obesity; metabolic diseases; animal models of human disease; pituitary and neuroendocrine tumors; gene expression and genomic stability machinery; diagnostic and prognostic biomarkers; therapeutic targets
Dr. Justo P. Castaño

E-Mail Website
Guest Editor
Maimonides Institute for Biomedical Research of Córdoba (IMIBIC) / Department of Cell Biology, Physiology, and Immunology, University of Córdoba / Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain
Interests: cellular and molecular endocrine oncology; pituitary and neuroendocrine tumors; pancreatic cancer; animal models of human disease; spliceosome; somatostatin; diagnostic and prognostic biomarkers; therapeutic targets

Special Issue Information

Dear Colleagues, 

Pituitary and neuroendocrine tumors (PitNETs and NETs) comprise a challenging group of neoplasms that share key cellular and molecular features engrained in their intrinsic hormone-producing cell origin. Yet, as their precise hormonal lineage, secretory nature, and bodily location can be highly diverse and variable, this group of tumors is extremely heterogeneous. This hampers our ability to identify common biomarkers and therapeutic tools to facilitate their clinical management and treatment. Owing to their relatively low incidence rate, both PitNETs and NETs have long been considered rare diseases. However, improvements in their detection and management have resulted in the increased prevalence of figures. Accordingly, rising interest has prompted current advances in research of the molecular and cellular basis of PitNETs and NETs, and the accompanying development of novel, personalized diagnostic and therapeutic tools for these tumors. Hence, emerging information is enabling scientists to establish the genetic, epigenetic, and transcriptomic landscape of PitNETs and NETs. This provides the grounds for the discovery of new actionable molecular targets from druggable gene mutations to non-coding RNA biomarkers, which could pave the way for precision medicine to conquer this field. 

This Special Issue aims to cover recent advances in the research and clinical management of PitNETs and NETs, highlighting both their unique features and common hallmarks, and offering novel research discoveries. Additionally, we are calling for updated reviews on current trends in the neuroendocrine tumor arena.

Dr. Raul M. Luque
Dr. Justo P. Castaño
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pituitary neuroendocrine tumors (PitNETs)
  • neuroendocrine tumors (NETs)
  • molecular therapeutic targets of NETs and PitNETs
  • new biomarkers of NETs and PitNETs
  • clinical management of NETs and PitNETs

Published Papers (4 papers)

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Research

9 pages, 14977 KiB  
Article
Sex Hormone Receptor Expression in Craniopharyngiomas and Association with Tumor Aggressiveness Characteristics
by Antonio Martínez-Ortega, Álvaro Flores-Martinez, Eva Venegas-Moreno, Elena Dios, Diego Del Can, Eloy Rivas, Ariel Kaen, Eugenio Cárdenas Ruiz-Valdepeñas, Elena Fajardo, Florinda Roldán, Natividad González-Rivera, Rosario Oliva, José Ignacio Fernández-Peña, Alfonso Soto-Moreno and David A. Cano
J. Clin. Med. 2022, 11(1), 281; https://doi.org/10.3390/jcm11010281 - 5 Jan 2022
Cited by 1 | Viewed by 1947
Abstract
Craniopharyngiomas (CPs) are rare tumors of the sellar and suprasellar regions of embryonic origin. The primary treatment for CPs is surgery but it is often unsuccessful. Although CPs are considered benign tumors, they display a relatively high recurrence rate that might compromise quality [...] Read more.
Craniopharyngiomas (CPs) are rare tumors of the sellar and suprasellar regions of embryonic origin. The primary treatment for CPs is surgery but it is often unsuccessful. Although CPs are considered benign tumors, they display a relatively high recurrence rate that might compromise quality of life. Previous studies have reported that CPs express sex hormone receptors, including estrogen and progesterone receptors. Here, we systematically analyzed estrogen receptor α (ERα) and progesterone receptor (PR) expression by immunohistochemistry in a well-characterized series of patients with CP (n = 41) and analyzed their potential association with tumor aggressiveness features. A substantial proportion of CPs displayed a marked expression of PR. However, most CPs expressed low levels of ERα. No major association between PR and ERα expression and clinical aggressiveness features was observed in CPs. Additionally, in our series, β-catenin accumulation was not related to tumor recurrence. Full article
(This article belongs to the Special Issue From Molecules to Disease: Research and Clinical Advances in Pituitary and Neuroendocrine Tumors)
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12 pages, 1621 KiB  
Article
Invasive and Noninvasive Nonfunctioning Gonadotroph Pituitary Tumors Differ in DNA Methylation Level of LINE-1 Repetitive Elements
by Natalia Rusetska, Paulina Kober, Sylwia Katarzyna Król, Joanna Boresowicz, Maria Maksymowicz, Jacek Kunicki, Wiesław Bonicki and Mateusz Bujko
J. Clin. Med. 2021, 10(4), 560; https://doi.org/10.3390/jcm10040560 - 3 Feb 2021
Cited by 3 | Viewed by 1736
Abstract
Purpose: Epigenetic dysregulation plays a role in pituitary tumor pathogenesis. Some differences in DNA methylation were observed between invasive and noninvasive nonfunctioning gonadotroph tumors. This study sought to determine the role of DNA methylation changes in repetitive LINE-1 elements in nonfunctioning gonadotroph pituitary [...] Read more.
Purpose: Epigenetic dysregulation plays a role in pituitary tumor pathogenesis. Some differences in DNA methylation were observed between invasive and noninvasive nonfunctioning gonadotroph tumors. This study sought to determine the role of DNA methylation changes in repetitive LINE-1 elements in nonfunctioning gonadotroph pituitary tumors. Methods: We investigated LINE-1 methylation levels in 80 tumors and normal pituitary glands with bisulfite-pyrosequencing. Expression of two LINE-1 open reading frames (L1-ORF1 and L1-ORF2) was analyzed with qRT-PCR in tumor samples and mouse gonadotroph pituitary cells treated with DNA methyltransferase inhibitor. Immunohistochemical staining against L1-ORF1p was also performed in normal pituitary glands and tumors. Results: Hypomethylation of LINE-1 was observed in pituitary tumors. Tumors characterized by invasive growth revealed lower LINE-1 methylation level than noninvasive ones. LINE-1 methylation correlated with overall DNA methylation assessed with HM450K arrays and negatively correlated with L1-ORF1 and L1-ORF2 expression. Treatment of αT3-1 gonadotroph cells with 5-Azacytidine clearly increased the level of L1-ORF1 and L1-ORF2 mRNA; however, its effect on LβT2 cells was less pronounced. Immunoreactivity against L1-ORF1p was higher in tumors than normal tissue. No difference in L1-ORF1p expression was observed in invasive and noninvasive tumors. Conclusion: Hypomethylation of LINE-1 is related to invasive growth and influences transcriptional activity of transposable elements. Full article
(This article belongs to the Special Issue From Molecules to Disease: Research and Clinical Advances in Pituitary and Neuroendocrine Tumors)
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13 pages, 964 KiB  
Article
Quantitative Analysis of Somatostatin and Dopamine Receptors Gene Expression Levels in Non-functioning Pituitary Tumors and Association with Clinical and Molecular Aggressiveness Features
by Álvaro Flores-Martinez, Eva Venegas-Moreno, Elena Dios, Pablo Remón-Ruiz, Noelia Gros-Herguido, M. Carmen Vázquez-Borrego, Ainara Madrazo-Atutxa, Miguel A. Japón, Ariel Kaen, Eugenio Cárdenas-Valdepeñas, Florinda Roldán, Justo P. Castaño, Raúl M. Luque, David A. Cano and Alfonso Soto-Moreno
J. Clin. Med. 2020, 9(9), 3052; https://doi.org/10.3390/jcm9093052 - 22 Sep 2020
Cited by 9 | Viewed by 2442
Abstract
The primary treatment for non-functioning pituitary tumors (NFPTs) is surgery, but it is often unsuccessful. Previous studies have reported that NFPTs express receptors for somatostatin (SST1-5) and dopamine (DRDs) providing a rationale for the use of dopamine agonists and somatostatin analogues. [...] Read more.
The primary treatment for non-functioning pituitary tumors (NFPTs) is surgery, but it is often unsuccessful. Previous studies have reported that NFPTs express receptors for somatostatin (SST1-5) and dopamine (DRDs) providing a rationale for the use of dopamine agonists and somatostatin analogues. Here, we systematically assessed SST1-5 and DRDs expression by real-time quantitative PCR (RT-qPCR) in a large group of patients with NFPTs (n = 113) and analyzed their potential association with clinical and molecular aggressiveness features. SST1-5 expression was also evaluated by immunohistochemistry. SST3 was the predominant SST subtype detected, followed by SST2, SST5, and SST1. DRD2 was the dominant DRD subtype, followed by DRD4, DRD5, and DRD1. A substantial proportion of NFPTs displayed marked expression of SST2 and SST5. No major association between SSTs and DRDs expression and clinical and molecular aggressiveness features was observed in NFPTs. Full article
(This article belongs to the Special Issue From Molecules to Disease: Research and Clinical Advances in Pituitary and Neuroendocrine Tumors)
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12 pages, 1390 KiB  
Article
Differential Expression of MicroRNAs in Silent and Functioning Corticotroph Tumors
by Araceli García-Martínez, Antonio C. Fuentes-Fayos, Carmen Fajardo, Cristina Lamas, Rosa Cámara, Beatriz López-Muñoz, Ignacio Aranda, Raúl M. Luque and Antonio Picó
J. Clin. Med. 2020, 9(6), 1838; https://doi.org/10.3390/jcm9061838 - 12 Jun 2020
Cited by 6 | Viewed by 2262
Abstract
The potential role of miRNAs in the silencing mechanisms of pituitary neuroendocrine tumors (PitNETs) has not been addressed. The aim of the present study was to evaluate the expression levels and the potential associated role of some miRNAs, pathways, and transcription factors in [...] Read more.
The potential role of miRNAs in the silencing mechanisms of pituitary neuroendocrine tumors (PitNETs) has not been addressed. The aim of the present study was to evaluate the expression levels and the potential associated role of some miRNAs, pathways, and transcription factors in the silencing mechanisms of corticotroph tumors (CTs). Accordingly, the expression of miR-375, miR-383, miR-488, miR-200a and miR-103; of PKA, MAP3K8, MEK, MAPK3, NGFIB, NURR1, PITX1, and STAT3 were analyzed via qRT-PCR in 23 silent and 24 functioning CTs. miR-200a and miR-103 showed significantly higher expression in silent than in functioning CTs, even after eliminating the bias of tumor size, therefore enabling the differentiation between the two variants. Additionally, miR-383 correlated negatively with TBX19 in silent CTs, a transcription factor related with the processing of POMC that can participate in the silencing mechanisms of CTs. Finally, the gene expression levels of miR-488, miR-200a, and miR-103 were significantly higher in macroadenomas (functioning and silent) than in microadenomas. The evidence from this study indicates that miRNAs could be involved in the pathophysiology of CTs. The translational implications of these findings suggest that pharmacological treatments specifically targeting these miRNAs could become a promising therapeutic option for these patients. Full article
(This article belongs to the Special Issue From Molecules to Disease: Research and Clinical Advances in Pituitary and Neuroendocrine Tumors)
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