Oral Diseases: Biological and Molecular Pathogenesis

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 2392

Special Issue Editor


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Guest Editor
1. Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
2. Hard Tissue Pathology Unit, Graduate School of Oral Medicine, Matsumoto Dental University, 1780 Hirookagohara, Shiojiri, Nagano 399-0781, Japan
Interests: abnormal cornification of oral mucosa and diseases; molecular changes of odontogenic lesions; molecular pathology of soft tissue neoplasms of the oral cavity

Special Issue Information

Dear Colleagues,

The era of advanced molecular technology in the 2000s has provided us with a wealth of knowledge in all areas of disease, including the oral region. These developments may clarify the pathogenesis of oral neoplasia, oral mucous diseases and other oral diseases, and improve strategies for diagnosing or treating them. Currently, we are on the way to achieving a breakthrough for many oral diseases. There is no striking impact of single pathogenesis in most oral diseases, unlike clear cell odontogenic carcinoma harboring an EWSR1 rearrangement, and the pathogenesis of most oral diseases is multifactorial and complex. Cellular character, cell kinetics, abnormal protein distribution or genetic changes are closely related to the development of oral disease. In this Special Issue, we encourage the submission of papers highlighting new advances in the biological or molecular pathogenesis of oral diseases, with a particular focus on aspects of unique cellular alterations. Original research articles and reviews are welcome. Research areas may include, but are not limited to the following: oral squamous cell carcinoma, oral dysplasia, oral lichen planus, odontogenic neoplasms, odontogenic cysts and other inflammatory disorders of the oral cavity.

Prof. Dr. Hiromasa Hasegawa
Guest Editor

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Keywords

  • pathogenesis
  • immunohistochemical and molecular alteration
  • oral diseases

Published Papers (2 papers)

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Research

25 pages, 3128 KiB  
Article
Genomic Engineering of Oral Keratinocytes to Establish In Vitro Oral Potentially Malignant Disease Models as a Platform for Treatment Investigation
by Leon J. Wils, Marijke Buijze, Marijke Stigter-van Walsum, Arjen Brink, Britt E. van Kempen, Laura Peferoen, Elisabeth R. Brouns, Jan G. A. M. de Visscher, Erik H. van der Meij, Elisabeth Bloemena, Jos B. Poell and Ruud H. Brakenhoff
Cells 2024, 13(8), 710; https://doi.org/10.3390/cells13080710 - 19 Apr 2024
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Abstract
Precancerous cells in the oral cavity may appear as oral potentially malignant disorders, but they may also present as dysplasia without visual manifestation in tumor-adjacent tissue. As it is currently not possible to prevent the malignant transformation of these oral precancers, new treatments [...] Read more.
Precancerous cells in the oral cavity may appear as oral potentially malignant disorders, but they may also present as dysplasia without visual manifestation in tumor-adjacent tissue. As it is currently not possible to prevent the malignant transformation of these oral precancers, new treatments are urgently awaited. Here, we generated precancer culture models using a previously established method for the generation of oral keratinocyte cultures and incorporated CRISPR/Cas9 editing. The generated cell lines were used to investigate the efficacy of a set of small molecule inhibitors. Tumor-adjacent mucosa and oral leukoplakia biopsies were cultured and genetically characterized. Mutations were introduced in CDKN2A and TP53 using CRISPR/Cas9 and combined with the ectopic activation of telomerase to generate cell lines with prolonged proliferation. The method was tested in normal oral keratinocytes and tumor-adjacent biopsies and subsequently applied to a large set of oral leukoplakia biopsies. Finally, a subset of the immortalized cell lines was used to assess the efficacy of a set of small molecule inhibitors. Culturing and genomic engineering was highly efficient for normal and tumor-adjacent oral keratinocytes, but success rates in oral leukoplakia were remarkably low. Knock-out of CDKN2A in combination with either the activation of telomerase or knock-out of TP53 seemed a prerequisite for immortalization. Prolonged culturing was accompanied by additional genetic aberrations in these cultures. The generated cell lines were more sensitive than normal keratinocytes to small molecule inhibitors of previously identified targets. In conclusion, while very effective for normal keratinocytes and tumor-adjacent biopsies, the success rate of oral leukoplakia cell culturing methods was very low. Genomic engineering enabled the prolonged culturing of OL-derived keratinocytes but was associated with acquired genetic changes. Further studies are required to assess to what extent the immortalized cultures faithfully represent characteristics of the cells in vivo. Full article
(This article belongs to the Special Issue Oral Diseases: Biological and Molecular Pathogenesis)
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18 pages, 10326 KiB  
Article
Neoadjuvant Radiochemotherapy Alters the Immune and Metabolic Microenvironment in Oral Cancer—Analyses of CD68, CD163, TGF-β1, GLUT-1 and HIF-1α Expressions
by Manuel Weber, Jutta Ries, Kristina Braun, Falk Wehrhan, Luitpold Distel, Carol Geppert, Rainer Lutz, Marco Kesting and Leah Trumet
Cells 2024, 13(5), 397; https://doi.org/10.3390/cells13050397 - 25 Feb 2024
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Abstract
Background: The first-line treatment of oral squamous cell carcinoma (OSCC) involves surgical tumor resection, followed by adjuvant radio(chemo)therapy (R(C)T) in advanced cases. Neoadjuvant radio- and/or chemotherapy has failed to show improved survival in OSCC. Recently, neoadjuvant immunotherapy has shown promising therapeutic efficacy in [...] Read more.
Background: The first-line treatment of oral squamous cell carcinoma (OSCC) involves surgical tumor resection, followed by adjuvant radio(chemo)therapy (R(C)T) in advanced cases. Neoadjuvant radio- and/or chemotherapy has failed to show improved survival in OSCC. Recently, neoadjuvant immunotherapy has shown promising therapeutic efficacy in phase 2 trials. In this context, the addition of radio- and chemotherapy is being reconsidered. Therefore, a better understanding of the tumor-biologic effects of neoadjuvant RCT would be beneficial. The current study was conducted on a retrospective cohort of patients who received neoadjuvant RCT for the treatment of oral cancer. The aim of the study was to evaluate the influence of neoadjuvant RCT on the immunological tumor microenvironment (TME) and hypoxic and glucose metabolisms. Methods: A cohort of 45 OSSC tissue samples from patients were analyzed before and after RCT (total 50.4 Gy; 1.8 Gy 5× weekly; Cisplatin + 5-Fluorouracil). Immunohistochemistry for CD68, CD163, TGF-β, GLUT-1 and HIF-1α was performed using tissue microarrays and automated cell counting. Differences in expression before and after RCT and associations with histomorphological parameters (T-status, N-status) were assessed using the Mann–Whitney U test. Results: Tumor resection specimens after neoadjuvant RCT showed a significant decrease in CD68 infiltration and a significant increase in CD163 cell density. The CD68/CD163 ratio was significantly lower after RCT, indicating a shift toward M2 polarization. The GLUT-1 and HIF-1α expressions were significantly lower after RCT. Larger tumors (T3/T4) showed a lower GLUT-1 expression. Other biomarkers were not associated with the T- and N-status. Conclusions: Neoadjuvant RCT with 50.4 Gy induced a shift toward the M2 polarization of macrophages in the TME. This change in immune composition is not favorable and may be prognostically negative and counteract immunotherapeutic approaches. In addition, the decreased expressions in GLUT-1 and HIF-1α indicate reductions in the glucose metabolism and hypoxic energy metabolism in response to “high dose” neoadjuvant RCT, which may be therapeutically desirable. Full article
(This article belongs to the Special Issue Oral Diseases: Biological and Molecular Pathogenesis)
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