Cellular and Pathogenesis Mechanisms in Oral Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 28 February 2025 | Viewed by 7905

Special Issue Editor


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Guest Editor
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Interests: oral squamous cell carcinoma; head and neck cancer; oral oncology; biomarkers; prognostic markers; oral epithelial dysplasia; oral cancer
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Special Issue Information

Dear Colleagues,

Oral cancer is a multi-step process in which multiple genetic events occur that alter the normal function of oncogenes and tumor suppressor genes. Despite advances in surgical techniques, radiation therapy, chemotherapy protocols and other treatment modalities, long-term survival rates for oral cancer patients have been unsatisfactory for several decades. Furthermore, although most oral cancers arise from oral epithelial dysplasia, a premalignant lesion, useful markers for its early detection are still lacking.

Therefore, this Special Issue aims to provide a "research update" on understanding the molecular regulation of the various pathways associated with oral cancer, allowing for more accurate diagnosis and prognostic evaluation, thereby paving the way for new approaches to treatment and prevention.

Dr. Jun-Ichi Tanuma
Guest Editor

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Keywords

  • oral carcinogenesis
  • oral cancer model
  • OSCC
  • oral cytology
  • biomarkers
  • targeted therapies
  • precision medicine
  • bioinformatics

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Published Papers (4 papers)

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Research

14 pages, 1139 KiB  
Article
Prediction of Histological Grade of Oral Squamous Cell Carcinoma Using Machine Learning Models Applied to 18F-FDG-PET Radiomics
by Yutaka Nikkuni, Hideyoshi Nishiyama and Takafumi Hayashi
Biomedicines 2024, 12(7), 1411; https://doi.org/10.3390/biomedicines12071411 - 25 Jun 2024
Viewed by 1155
Abstract
The histological grade of oral squamous cell carcinoma affects the prognosis. In the present study, we performed a radiomics analysis to extract features from 18F-FDG PET image data, created machine learning models from the features, and verified the accuracy of the prediction [...] Read more.
The histological grade of oral squamous cell carcinoma affects the prognosis. In the present study, we performed a radiomics analysis to extract features from 18F-FDG PET image data, created machine learning models from the features, and verified the accuracy of the prediction of the histological grade of oral squamous cell carcinoma. The subjects were 191 patients in whom an 18F-FDG-PET examination was performed preoperatively and a histopathological grade was confirmed after surgery, and their tumor sizes were sufficient for a radiomics analysis. These patients were split in a 70%/30% ratio for use as training data and testing data, respectively. We extracted 2993 radiomics features from the PET images of each patient. Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Naïve Bayes (NB), and K-Nearest Neighbor (KNN) machine learning models were created. The areas under the curve obtained from receiver operating characteristic curves for the prediction of the histological grade of oral squamous cell carcinoma were 0.72, 0.71, 0.84, 0.74, and 0.73 for LR, SVM, RF, NB, and KNN, respectively. We confirmed that a PET radiomics analysis is useful for the preoperative prediction of the histological grade of oral squamous cell carcinoma. Full article
(This article belongs to the Special Issue Cellular and Pathogenesis Mechanisms in Oral Cancer)
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22 pages, 6199 KiB  
Article
Rapamycin Induces Phenotypic Alterations in Oral Cancer Cells That May Facilitate Antitumor T Cell Responses
by Amirmoezz Yonesi, Kei Tomihara, Danki Takatsuka, Hidetake Tachinami, Manabu Yamazaki, Amir Reza Younesi Jadidi, Mayu Takaichi, Shuichi Imaue, Kumiko Fujiwara, Shin-Ichi Yamada, Jun-Ichi Tanuma and Makoto Noguchi
Biomedicines 2024, 12(5), 1078; https://doi.org/10.3390/biomedicines12051078 - 13 May 2024
Cited by 2 | Viewed by 1477
Abstract
Objectives: In this study, we investigated the antitumor immunomodulatory effects of rapamycin in oral cancer. Study Design: We examined the proliferation, apoptosis, and migration of cancer cells and investigated the cell surface expression levels of immune accessory molecules and T cell immune responses [...] Read more.
Objectives: In this study, we investigated the antitumor immunomodulatory effects of rapamycin in oral cancer. Study Design: We examined the proliferation, apoptosis, and migration of cancer cells and investigated the cell surface expression levels of immune accessory molecules and T cell immune responses in vitro. We investigated the effect of in vivo administration of rapamycin on immune cell distribution and T cell immune responses in oral tumor-bearing mice. Results: Rapamycin treatment significantly inhibited OSCC cell proliferation and migration, increased apoptotic cell death, and upregulated cell surface expression of several immune accessory and adhesion molecules, including CD40, CD83, PD-L1, PD-L2, MHC class I, P-selectin, and VCAM-1. These cancer cells augmented T cell proliferation. In vivo rapamycin administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T cells, CD8+ T cells, and dendritic cells (DCs); decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor cells and regulatory T cells; enhanced DC maturation and upregulated the surface expression of CD40, CD86, and ICAM-1. Conclusions: Our results suggest that the therapeutic effect of mTOR inhibition in oral cancer can cause direct antitumor and immunomodulatory effects. Full article
(This article belongs to the Special Issue Cellular and Pathogenesis Mechanisms in Oral Cancer)
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11 pages, 1694 KiB  
Article
Cetuximab–Toxin Conjugate and NPe6 with Light Enhanced Cytotoxic Effects in Head and Neck Squamous Cell Carcinoma In Vitro
by Noriko Komatsu, Azuma Kosai, Mikako Kuroda, Takao Hamakubo and Takahiro Abe
Biomedicines 2024, 12(5), 973; https://doi.org/10.3390/biomedicines12050973 - 29 Apr 2024
Cited by 2 | Viewed by 1510
Abstract
Background: Photodynamic therapy (PDT) is a cancer-targeted treatment that uses a photosensitizer (PS) and irradiation of a specific wavelength to exert cytotoxic effects. To enhance the antitumor effect against head and neck squamous cell carcinoma (HNSCC), we developed a new phototherapy, intelligent targeted [...] Read more.
Background: Photodynamic therapy (PDT) is a cancer-targeted treatment that uses a photosensitizer (PS) and irradiation of a specific wavelength to exert cytotoxic effects. To enhance the antitumor effect against head and neck squamous cell carcinoma (HNSCC), we developed a new phototherapy, intelligent targeted antibody phototherapy (iTAP). This treatment uses a combination of immunotoxin (IT) and a PS for PDT and light irradiation. In our prior study, we demonstrated that an immunotoxin (IT) consisting of an anti-ROBO1 antibody conjugated to saporin, when used in combination with the photosensitizer (PS) disulfonated aluminum phthalocyanine (AlPcS2a) and irradiated with light at the appropriate wavelength, resulted in increased cytotoxicity against head and neck squamous cell carcinoma (HNSCC) cells. ROBO1 is a receptor known to be involved in the progression of cancer. In this study, we newly investigate the iTAP targeting epidermal growth factor receptor (EGFR) which is widely used as a therapeutic target for HNSCC. Methods: We checked the expression of EGFR in HNSCC cell lines, SAS, HO-1-u-1, Sa3, and HSQ-89. We analyzed the cytotoxicity of saporin-conjugated anti-EGFR antibody (cetuximab) (IT-Cmab), mono-L-aspartyl chlorin e6 (NPe6, talaporfin sodium), and light (664 nm) irradiation (i.e., iTAP) in SAS, HO-1-u-1, Sa3, and HSQ-89 cells. Results: EGFR was expressed highly in Sa3, moderately in HO-1-u-1, SAS, and nearly not in HSQ-89. Cmab alone or IT-Cmab alone did not show cytotoxic effects in Sa3, HO-1-u-1, and HSQ-89 cells, which have moderate or low expression levels of EGFR protein. However, the iTAP method enhanced the cytotoxicity of IT-Cmab by the photodynamic effect in Sa3 and HO-1-u-1 cells, which have moderate levels of EGFR expression. Conclusion: Our study is the first to report on the iTAP method using IT-Cmab and NPe6 for HNSCC. The cytotoxic effects are enhanced in cell lines with moderate levels of EGFR protein expression, but not in nonexpressing cell lines, which is expected to expand the range of therapeutic windows and potentially reduce complications. Full article
(This article belongs to the Special Issue Cellular and Pathogenesis Mechanisms in Oral Cancer)
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15 pages, 3731 KiB  
Article
Comparing the Diagnostic Accuracy of Ultrasonography, CT, MRI, and PET/CT in Cervical Lymph Node Metastasis of Oral Squamous Cell Carcinoma
by Masaki Takamura, Yutaka Nikkuni, Takafumi Hayashi, Kouji Katsura, Hideyoshi Nishiyama, Manabu Yamazaki, Satoshi Maruyama and Jun-ichi Tanuma
Biomedicines 2023, 11(12), 3119; https://doi.org/10.3390/biomedicines11123119 - 22 Nov 2023
Viewed by 2627
Abstract
(1) Background: In oral cancer staging, ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) with positron emission tomography/computed tomography (PET/CT) are routinely used in clinical practice. The present study is a retrospective examination of the diagnostic accuracy of cervical [...] Read more.
(1) Background: In oral cancer staging, ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) with positron emission tomography/computed tomography (PET/CT) are routinely used in clinical practice. The present study is a retrospective examination of the diagnostic accuracy of cervical lymph node metastasis using US, CT, MRI, and PET/CT, with histopathological diagnosis as a reference, to compare the different diagnostic imaging modalities. (2) Methods: The participants included 16 patients with oral squamous cell carcinoma who underwent US-, CT-, MRI-, and PET/CT-based preoperative diagnostic imaging and simultaneous primary lesion resection and neck dissection, including 82 level regions and 424 lymph nodes. We compared the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of each imaging modality based on the imaging results and the pathology results of metastasis. (3) Results: Of the four diagnostic imaging modalities, PET/CT exhibited the highest sensitivity but the lowest specificity and accuracy. US, CT, and MRI had high specificities. Comparing each level region and lymph node showed that differences were observed in PET/CT. (4) Conclusions: PET/CT to diagnose lymph node metastasis requires a comprehensive evaluation because it produces more false positives than other diagnostic imaging modalities. Using US, CT, and MRI, which have excellent spatial resolution, improves diagnostic accuracy at the lymph node level. Full article
(This article belongs to the Special Issue Cellular and Pathogenesis Mechanisms in Oral Cancer)
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