Molecular Mechanisms and Pathophysiology of Oral Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: 31 January 2025 | Viewed by 3657

Special Issue Editor


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Guest Editor
Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Japan
Interests: histopathology; biomaterials; tumor microenvironment; regenerative medicine; material science
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Special Issue Information

Dear Colleagues,

Surgical resection is the first-line treatment for oral cancer; however, the quality of life of patients after surgical resection is significantly reduced. In recent years, molecular targeted drugs as well as immune checkpoint inhibitors have been developed for the treatment of oral cancer and have shown some efficacy against advanced oral cancer, but their effect is still not sufficient. In addition, the existence of the tumor microenvironment, consisting of tumor cells and tumor stroma, a heterogeneous cell population composed of various cell types, hinders our understanding of oral cancer progression and makes the development of oral cancer treatments difficult. In order to establish new therapeutic strategies, there is an urgent need to elucidate the molecular mechanisms and pathophysiology of oral cancer progression and metastasis, focusing on the tumor microenvironment. 

This Special Issue focuses on how the interaction between cancer cells and their microenvironment regulates the progression of oral cancer and contributes to the development, progression, and metastasis of oral cancer. This Special Issue solicits high-quality original papers and comprehensive review articles.

Dr. Kiyofumi Takabatake
Guest Editor

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Keywords

  • oral cancer
  • oral squamous cell carcinoma
  • tumor microenvironment
  • tumor stroma
  • molecular mechanism
  • signaling pathways

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Published Papers (2 papers)

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Research

12 pages, 5962 KiB  
Article
Efficacy of Cisplatin–CXCR4 Antagonist Combination Therapy in Oral Cancer
by Saori Yoshida, Hotaka Kawai, Yamin Soe, Htoo Shwe Eain, Sho Sanou, Kiyofumi Takabatake, Yohei Takeshita, Miki Hisatomi, Hitoshi Nagatsuka, Junichi Asaumi and Yoshinobu Yanagi
Cancers 2024, 16(13), 2326; https://doi.org/10.3390/cancers16132326 - 25 Jun 2024
Cited by 2 | Viewed by 1287
Abstract
Cisplatin is a platinum-based compound that is widely used for treating inoperable oral squamous cell carcinoma (OSCC) in Japan; however, resistance to cisplatin presents a challenge and innovative approaches are required. We aimed to investigate the therapeutic potential of targeting the chemokine receptor [...] Read more.
Cisplatin is a platinum-based compound that is widely used for treating inoperable oral squamous cell carcinoma (OSCC) in Japan; however, resistance to cisplatin presents a challenge and innovative approaches are required. We aimed to investigate the therapeutic potential of targeting the chemokine receptor CXCR4, which is involved in angiogenesis and tumor progression, using the CXCR4 inhibitor AMD3100, in combination with cisplatin. AMD3100 induced necrosis and bleeding in OSCC xenografts by inhibiting angiogenesis. We investigated the combined ability of AMD3100 plus cisplatin to enhance the antitumor effect in cisplatin-resistant OSCC. An MTS assay identified HSC-2 cells as cisplatin-resistant cells in vitro. Mice treated with the cisplatin-AMD combination exhibited the most significant reduction in tumor volume, accompanied by extensive hemorrhage and necrosis. Histological examination indicated thin and short tumor vessels in the AMD and cisplatin–AMD groups. These results indicated that cisplatin and AMD3100 had synergistic antitumor effects, highlighting their potential for vascular therapy of refractory OSCC. Antitumor vascular therapy using cisplatin combined with a CXCR4 inhibitor provides a novel strategy for addressing cisplatin-resistant OSCC. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Oral Cancer)
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13 pages, 1609 KiB  
Article
Three-Dimensional Spheroid Configurations and Cellular Metabolic Properties of Oral Squamous Carcinomas Are Possible Pharmacological and Pathological Indicators
by Sho Miyamoto, Nami Nishikiori, Tatsuya Sato, Megumi Watanabe, Araya Umetsu, Yuri Tsugeno, Fumihito Hikage, Takashi Sasaya, Hirotaka Kato, Kazuhiro Ogi, Masato Furuhashi, Hiroshi Ohguro and Akihiro Miyazaki
Cancers 2023, 15(10), 2793; https://doi.org/10.3390/cancers15102793 - 17 May 2023
Cited by 5 | Viewed by 1801
Abstract
The objective of the current study was to elucidate the clinicopathological significance and appearance of in vitro three-dimension (3D) spheroid models of oral malignant tumors that were prepared from four pathologically different squamous cell carcinoma (OSCC; low-grade; SSYP and MO-1000, intermediate-grade; LEM2) and [...] Read more.
The objective of the current study was to elucidate the clinicopathological significance and appearance of in vitro three-dimension (3D) spheroid models of oral malignant tumors that were prepared from four pathologically different squamous cell carcinoma (OSCC; low-grade; SSYP and MO-1000, intermediate-grade; LEM2) and oral adenosquamous carcinoma (OASC; high-grade; Mesimo) obtained from patients with different malignant stages. To characterize the biological significance of these cell lines themselves, two-dimensional (2D) cultured cells were subjected to cellular metabolic analysis by a Seahorse bioanalyzer alongside the measurement of the cytotoxicity of cisplatin (CDDP). The appearance of their 3D spheroids was then observed by phase contrast microscopy, and both 2D and 3D cultured cells were subject to trypsin digestion and qPCR analysis of factors related to oncogenic signaling and other related analyses. ATP-linked respiration and proton leaking were significantly different among the four cell lines, and the malignant stages of these cultures were significantly associated with increased ATP-linked respiration and decreased proton leakage. Alternatively, the appearances of these 3D spheroids were also significantly diverse among them, and their differences increased in the order of LEM2, MO-1000, SSYP, and Mesimo. Interestingly, these orders were exactly the same in that the efficacies of CDDP-induced cytotoxicity increased in the same order. qPCR analysis indicated that the levels of expression of oncogenic signaling-related factors varied among these four cell lines, and the values for fibronectin and a key regulator of mitochondrial biogenesis, PGC-1α, were prominently elevated in cultures of the worst malignant Mesimo cells. In addition, although 0.25% trypsin-induced destruction was comparable among all four 2D cultured cells, the values for the 3D spheroids were also substantially varied among these cultures. The findings reported herein indicate that cellular metabolic functions and 3D spheroid architectures may be valuable and useful indicators for estimating the pathological and drug-sensitive aspects of OSCC and OASC malignancies. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Oral Cancer)
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