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Personalized Medicine in Skull Base and Sinonasal Tumors
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Personalized Medicine in Skull Base and Sinonasal Tumors

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Personalized Therapy and Drug Delivery".

Deadline for manuscript submissions: closed (5 March 2024) | Viewed by 6215

Special Issue Editors

Dr. Davide Mattavelli

E-Mail Website
Guest Editor
Unit of Otorhinolaryngology—Head and Neck Surgery, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, ASST Spedali Civili of Brescia, University of Brescia, Brescia, Italy
Interests: head and neck surgery; skull base surgery; endonasal endoscopic surgery; sinonasal cancer; skull base tumors; oral cancer; otolaryngology
Dr. Paolo Bossi

E-Mail Website
Guest Editor
Unit of Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, ASST Spedali Civili of Brescia, University of Brescia, Brescia, Italy
Interests: cancer chemotherapy; cancer diagnostics; cancer biology; head and neck cancer; sinonasal cancer; skin cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent decades, multidisciplinary approaches and innovations in treatments (such as endoscopic surgery and heavy ion irradiation) have improved outcomes in sinonasal and skull base tumors. However, a relevant proportion of patients still bears a poor prognosis despite the intensified regimen of treatment. Tumor biology largely drives prognosis in this subset of patients, while the rarity of these tumors, together with their great histologic variety, hinders a more accurate definition of tumor profiles. Multi-omics analysis could largely improve our understanding of these diseases and provide us with biomarkers to better depict these tumors at multiple levels: diagnosis, prognostic stratification, and the prediction of response to treatment. Likewise, they can identify therapeutic targets to inspire new pharmaceutical options. In this regard, the tumor–host interplay, immune contexture, and immunotherapy are still to be investigated in sinonasal and skull base tumors, representing a new therapeutic frontier to explore.

Overall, such studies can lead to the definition of new multimodal treatment strategies, and possibly pave the way towards a more effective, less toxic, personalized therapy.

Dr. Davide Mattavelli
Dr. Paolo Bossi
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 Personalized Medicine 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.

Keywords

  • sinonasal and skull base tumors
  • genomics
  • epigenetics
  • gene profiling
  • radiomics
  • biomarkers (diagnostic, prognostic, and predictive of response to therapy)
  • target therapy
  • immune contexture
  • immunotherapy
  • toxicity

Published Papers (5 papers)

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Editorial

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4 pages, 193 KiB  
Editorial
Personalized Medicine in Skull Base and Sinonasal Tumors
by Davide Mattavelli and Paolo Bossi
J. Pers. Med. 2022, 12(12), 1983; https://doi.org/10.3390/jpm12121983 - 01 Dec 2022
Cited by 1 | Viewed by 955
Abstract
Skull base and sinonasal tumors (SBSNTs) represent a considerable challenge for clinicians in view of their rarity, anatomical complexity of the site of origin, and great histological variety [...] Full article
(This article belongs to the Special Issue Personalized Medicine in Skull Base and Sinonasal Tumors)

Research

Jump to: Editorial

14 pages, 8246 KiB  
Article
Sox2 and βIII-Tubulin as Biomarkers of Drug Resistance in Poorly Differentiated Sinonasal Carcinomas
by Luis López, Laura Fernández-Vañes, Virginia N. Cabal, Rocío García-Marín, Laura Suárez-Fernández, Helena Codina-Martínez, Sara L. Lorenzo-Guerra, Blanca Vivanco, Verónica Blanco-Lorenzo, José L. Llorente, Fernando López and Mario A. Hermsen
J. Pers. Med. 2023, 13(10), 1504; https://doi.org/10.3390/jpm13101504 - 18 Oct 2023
Cited by 2 | Viewed by 1185
Abstract
Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and βIII-tubulin as biomarkers that [...] Read more.
Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and βIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors. The cohort included 57 cases of PDCs: 36 sinonasal undifferentiated carcinoma (SNUC) cases, 13 olfactory neuroblastoma (ONB) cases, and 8 sinonasal neuroendocrine carcinoma (SNEC) cases. Clinical follow-up data were available for 26 of these cases. Sox2 expression was detected using immunohistochemistry in 6 (75%) SNEC cases, 19 (53%) SNUC cases, and 6 (46%) ONB cases. The absence of Sox2 staining correlated with a higher rate of recurrence (p = 0.015), especially distant recurrence. The majority of cases showed βIII-tubulin expression, with strong positivity in 85%, 75%, and 64% of SNEC, ONB, and SNUC cases, respectively. Tumors with stronger βIII-tubulin expression demonstrated longer disease-free survival than those with no expression or low expression (p = 0.049). Sox2 and βIII-tubulin expression is common in poorly differentiated sinonasal tumors and has prognostic and therapeutic utility. Full article
(This article belongs to the Special Issue Personalized Medicine in Skull Base and Sinonasal Tumors)
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9 pages, 4242 KiB  
Communication
Expression, Prognostic Value and Correlation with HPV Status of Hypoxia-Induced Markers in Sinonasal Squamous Cell Carcinoma
by Alessandro Vinciguerra, Vincent Bedarida, Charlotte Pronier, Sophie El Zein, Michel Wassef, Sarah Atallah, Florian Chatelet, Joffrey Molher, Philippe Manivet, Philippe Herman, Homa Adle-Biassette and Benjamin Verillaud
J. Pers. Med. 2023, 13(5), 767; https://doi.org/10.3390/jpm13050767 - 29 Apr 2023
Viewed by 1152
Abstract
(1) Background: In head and neck squamous cell carcinoma, tumor hypoxia has been associated with radio/chemoresistance and poor prognosis, whereas human papillomavirus (HPV)-positive status has a positive impact on treatment response and survival outcomes. The aim of this study was to evaluate the [...] Read more.
(1) Background: In head and neck squamous cell carcinoma, tumor hypoxia has been associated with radio/chemoresistance and poor prognosis, whereas human papillomavirus (HPV)-positive status has a positive impact on treatment response and survival outcomes. The aim of this study was to evaluate the expression and the potential prognostic value of hypoxia-induced endogenous markers in patients treated for squamous cell carcinoma of the nasal cavity and paranasal sinuses (SNSCC), and their correlation with HPV status. (2) Methods: In this monocentric study, patients treated in a curative intent for a SNSCC were screened retrospectively. Protein expression of CA-IX, GLUT-1, VEGF, VEGF-R1, and HIF-1α was determined by immunohistochemical staining, scored, and then correlated with overall survival (OS) and locoregional recurrence free survival (LRRFS). HPV status was assessed and correlated with hypoxic markers. (3) Results: 40 patients were included. A strong expression of CA-IX, GLUT-1, VEGF, and VEGF-R1 was detected in 30%, 32.5%, 50%, and 37.5% of cases, respectively. HIF-1α was detected in 27.5% of cases. High CA-IX expression was associated in univariate analysis with poor OS (p = 0.035), but there was no significant association between GLUT-1, VEGF, VEGF-R1, and HIF-1α expression, and OS/LRRFS. There was no correlation found between HPV status and hypoxia-induced endogenous markers (all p > 0.05). (4) Conclusions: This study provides data on the expression of hypoxia-induced endogenous markers in patients treated for SNSCC and underlines the potential role of CA-IX as a prognostic biomarker for SNSCC. Full article
(This article belongs to the Special Issue Personalized Medicine in Skull Base and Sinonasal Tumors)
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14 pages, 5351 KiB  
Article
The Prognostic Role of the Immune Microenvironment in Sinonasal Intestinal-Type Adenocarcinoma: A Computer-Assisted Image Analysis of CD3+ and CD8+ Tumor-Infiltrating Lymphocytes
by Marco Ferrari, Lara Alessandrini, Enrico Savietto, Diego Cazzador, Gloria Schiavo, Stefano Taboni, Andrea L. C. Carobbio, Leonardo Calvanese, Giacomo Contro, Piergiorgio Gaudioso, Enzo Emanuelli, Marta Sbaraglia, Elisabetta Zanoletti, Gino Marioni, Angelo P. Dei Tos and Piero Nicolai
J. Pers. Med. 2023, 13(5), 726; https://doi.org/10.3390/jpm13050726 - 25 Apr 2023
Viewed by 1139
Abstract
The prognostic value of conventional histopathological parameters in the sinonasal intestinal-type adenocarcinoma (ITAC) has been debated and novel variables should be investigated. Increasing evidence demonstrated that the evolution of cancer is strongly dependent upon the complex interactions within tumor microenvironment. The aim of [...] Read more.
The prognostic value of conventional histopathological parameters in the sinonasal intestinal-type adenocarcinoma (ITAC) has been debated and novel variables should be investigated. Increasing evidence demonstrated that the evolution of cancer is strongly dependent upon the complex interactions within tumor microenvironment. The aim of this retrospective study was to assess the features of immune microenvironment in terms of CD3+ and CD8+ cells in a series of ITAC and explore their prognostic role, as well as their relations with clinicopathological variables. A computer-assisted image analysis of CD3+ and CD8+ tumor-infiltrating lymphocytes (TIL) density was conducted on surgical specimens of 51 patients with ITAC that underwent a curative treatment including surgery. ITAC displays variable TIL density, which is associated with OS. In a univariate model, the density of CD3+ TIL was significantly related to OS (p = 0.012), whereas the association with CD8+ TIL density resulted in being non-significant (p = 0.056). Patients with intermediate CD3+ TIL density were associated with the best outcome, whereas 5-year OS was the lowest for intermediate CD8+ TIL density. CD3+ TIL density maintained a significant association with OS in the multivariable analysis. TIL density was not significantly related to demographic and clinicopathological variables. CD3+ TIL density was independently associated with OS in a non-linear fashion and patients with intermediate CD3+ TIL density had the best outcome. Though based on a preliminary analysis on a relatively small series of patients, this finding makes TIL density a potential independent prognostic factor of ITAC. Full article
(This article belongs to the Special Issue Personalized Medicine in Skull Base and Sinonasal Tumors)
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12 pages, 25159 KiB  
Article
Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell Line
by Francesca Pagani, Magdalena Gryzik, Elena Somenza, Manuela Cominelli, Piera Balzarini, Alberto Schreiber, Davide Mattavelli, Piero Nicolai, Francesco Doglietto and Pietro Luigi Poliani
J. Pers. Med. 2023, 13(3), 425; https://doi.org/10.3390/jpm13030425 - 27 Feb 2023
Cited by 1 | Viewed by 1149
Abstract
Chordomas are rare primary malignant tumours of notochordal origin usually arising along the axial skeleton with particular predilection of the skull base and sacrococcygeal region. Albeit usually slow-growing, chordomas can be aggressive mostly depending on their invasive behaviour and according to different histotypes [...] Read more.
Chordomas are rare primary malignant tumours of notochordal origin usually arising along the axial skeleton with particular predilection of the skull base and sacrococcygeal region. Albeit usually slow-growing, chordomas can be aggressive mostly depending on their invasive behaviour and according to different histotypes and molecular alterations, including TBXT duplication and SMARCB1 homozygous deletion. Partial or complete PTEN deficiency has also been observed. PTEN is a negative regulator of the Akt/mTOR pathway and hyperactivation of Akt/mTOR in cells lacking PTEN expression contributes to cell proliferation and invasiveness. This pathway is targeted by mTOR inhibitors and the availability of in vitro models of chordoma cells will aid in further investigating this issue. However, isolation and maintenance of chordoma cell lines are challenging and PTEN-deleted chordoma cell lines are exceedingly rare. Hereby, we established and characterized a novel human PTEN-deleted chordoma cell line (CH3) from a primary skull base chordoma. Cells exhibited morphological and molecular features of the parent tumour, including PTEN loss and expression of Brachyury and EMA. Moreover, we investigated the activation of the mTOR pathway and cell response to mTOR inhibitors. CH3 cells were sensitive to Rapamycin treatment suggesting that mTOR inhibitors may represent a valuable option for patients suffering from PTEN-deleted chordomas. Full article
(This article belongs to the Special Issue Personalized Medicine in Skull Base and Sinonasal Tumors)
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