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Biomedicines
Special Issues
Molecular Mechanisms and Treatment of Thymic Epithelial Tumors
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Molecular Mechanisms and Treatment of Thymic Epithelial Tumors

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 4111

Special Issue Editors

Dr. Georgia Levidou

E-Mail Website
Guest Editor
Department of Pathology, Paracelsus Medical University, 90419 Nuremberg, Germany
Interests: cancer; biomarkers; molecular biology; immunohistochemistry; precision medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Stamatios E. Theocharis

E-Mail Website
Guest Editor
First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Goudi, Athens, Greece
Interests: apoptosis; metabolism; cytopathology; pathology; molecular pathology; immunohistochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Thymic epithelial tumors (TETs) represent a heterogeneous group of epithelial-derived neoplasms with diverse clinical behavior and underlying molecular biology. Their classification has long been discussed among pathologists due to uncertainty in the identification of neoplastic epithelial cells in the background of thymocytes, and to their rare occurrence. They are broadly classified into thymomas and thymic carcinomas, based mainly on the relative proportion of the neoplastic epithelial cells to the non-neoplastic lymphoid component. Owing to their rare nature, the molecular classification of TETs has only recently begun to be explored.

Currently, early-stage thymic epithelial tumors are treated with surgical resection. For patients with advanced-stage or incomplete resected tumors, there is a necessity for adjuvant therapy, now consisting of platinum-based chemotherapy. The difficulties in TET treatment derive from their still largely unknown biology and pathogenetic mechanisms, and from the rarity of expert centers and lack of standardized treatments. A framework of expert multidisciplinary teams and of international networks is necessary in order to progress in our understanding and better deal with these rare tumors.

We hereby invite contributions to this Special Issue of Biomedicines  describing novel molecular alterations underlying the pathobiology of TETs, possibly influencing epithelial cell growth and survival. In addition, manuscripts discussing developments in diagnostics or therapeutics for TET are also encouraged. We invite researchers and clinicians to submit original research articles and comprehensive review articles on the topic highlighted in this Special Issue of Biomedicines.

Dr. Georgia Levidou
Prof. Dr. Stamatios E. Theocharis
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. Biomedicines is an international peer-reviewed open access monthly 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.

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Published Papers (2 papers)

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15 pages, 1662 KiB  
Article
Searching for Novel Biomarkers in Thymic Epithelial Tumors: Immunohistochemical Evaluation of Hippo Pathway Components in a Cohort of Thymic Epithelial Tumors
by Kostas Palamaris, Georgia Levidou, Katerina Kordali, Christos Masaoutis, Dimitra Rontogianni and Stamatios Theocharis
Biomedicines 2023, 11(7), 1876; https://doi.org/10.3390/biomedicines11071876 - 1 Jul 2023
Cited by 2 | Viewed by 1236
Abstract
Given the pivotal role of the Hippo pathway in different facets of tumorigenesis, which has been vigorously established in multiple heterogenous malignancies, we attempted to evaluate its potential utility as a prognostic–predictive biomarker in thymic epithelial tumors (TETs). For this purpose, we performed [...] Read more.
Given the pivotal role of the Hippo pathway in different facets of tumorigenesis, which has been vigorously established in multiple heterogenous malignancies, we attempted to evaluate its potential utility as a prognostic–predictive biomarker in thymic epithelial tumors (TETs). For this purpose, we performed a comprehensive immunohistochemical analysis of four Hippo cascade components (YAP, TAZ, TEAD4 and LATS1) in a sizeable cohort of TETs and attempted to identify possible correlations of their H-score with various clinicopathological parameters. TAZ and TEAD4 displayed both cytoplasmic and nuclear immunoreactivity in almost equal frequency, with their cytoplasmic H-score being strongly associated with more aggressive high-grade tumors (type B3, thymic carcinoma) and more advanced pathological stages. On the other hand, a primarily nuclear staining pattern was encountered in both YAP and LATS1, with the YAP nuclear H-score being higher in more indolent (type A) and earlier stage tumors. Interestingly, none of the four examined factors displayed any statistically significant correlation with patient overall (OS) or disease-free survival (DFS). In summary, our results provide some initial insight into the expression profile of these core Hippo pathway components in thymic neoplasms and point towards some clear associations with tumor characteristics, which are of paramount translational-clinical research with profound implications in therapeutic targeting of this pathway in the context of precision medicine. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Thymic Epithelial Tumors)
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19 pages, 514 KiB  
Systematic Review
Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review
by Apostolos C. Agrafiotis, Mariana Brandão, Thierry Berghmans, Valérie Durieux and Christiane Jungels
Biomedicines 2023, 11(10), 2722; https://doi.org/10.3390/biomedicines11102722 - 8 Oct 2023
Cited by 3 | Viewed by 2195
Abstract
Background: Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are reserved for unresectable and metastatic tumors. The development of new treatments, such as immune checkpoint inhibitors (ICI) and targeted [...] Read more.
Background: Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are reserved for unresectable and metastatic tumors. The development of new treatments, such as immune checkpoint inhibitors (ICI) and targeted therapies, with promising results in other types of solid tumors, has led to the investigation of their potential efficacy in TET. The study of tumor microenvironments (TME) is another field of investigation that has gained the interest of researchers. Taking into account the complex structure of the thymus and its function in the development of immunity, researchers have focused on TME elements that could predict ICI efficacy. Materials and Methods: The primary objective of this systematic review was to investigate the efficacy of ICI in TET. Secondary objectives included the toxicity of ICI, the efficacy of targeted therapies in TET, and the evaluation of the elements of TME that may be predictive factors of ICI efficacy. A literature search was conducted in February 2023 using the Ovid Medline and SciVerse Scopus databases. Results: 2944 abstracts were retrieved, of which 31 were retained for the systematic review. Five phase II and one retrospective study assessed ICI efficacy. The overall response rate (ORR) varied from 0% to 34%. Median progression-free survival (PFS) ranged from 3.8 to 8.6 months, being lower in thymic carcinoma (TC) (3.8–4.2 months). Median overall survival (OS) ranged from 14.1 to 35.4 months. Treatment-related adverse events occurred in 6.6% to 27.3% of patients. Sixteen studies assessed targeted therapies. The most active molecule was lenvatinib, with 38% ORR in patients with TC while no activity was detected for imatinib, erlotinib plus bevacizumab, and saracatinib. Ten studies assessed TME elements that could predict ICI efficacy. Four studies focused on the tumor-infiltrating immune cells suggesting improved outcomes in patients with TC and high tumor-infiltrating lymphocyte densities. Another study showed that CD8+, CD20+, and CD204+ tumor-infiltrating immune cells in cancer stroma might be prognostic biomarkers in TC. Another study identified the immune-related long non-coding RNAs as a predictor of response to ICI. Tumor mutational burden was identified as a predictive factor of ICI efficacy in one study. Conclusions: Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Thymic Epithelial Tumors)
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