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Biomedicines
Special Issues
Head and Neck Cancers: Diagnosis, Therapy, Molecular and Cellular Mechanisms
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Head and Neck Cancers: Diagnosis, Therapy, Molecular and Cellular Mechanisms

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

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 8358

Special Issue Editors

Dr. Chia-Yu Yang

E-Mail Website
Guest Editor
1. Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
2. Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
Interests: cancer biology; immunology; animal experiment; next-generation sequencing
Dr. Kai-Ping Chang

E-Mail Website
Guest Editor
1. Department of Otolaryngology—Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33302, Taiwan
2. College of Medicine, Chang Gung University, Taoyuan, Taiwan
Interests: oral cavity cancer surgery; parotid and salivary gland tumor treatment; nasopharyngeal carcinoma and skull base surgery treatment; laryngeal carcinoma and hypopharyngeal carcinoma surgical treatment

Special Issue Information

Dear Colleagues,

Head and neck cancer is the sixth most common cancer worldwide, most of which are squamous epithelial malignancies derived from the oral cavity, pharynx, larynx or sinonasal tract. It is an aggressive malignant tumor with high recurrence/metastasis rate and poor prognosis in the advanced stage. Many studies in the past have identified multiple genomic alternations and biological pathways that contributed to the pathophysiology of head and neck cancers. Surgery, radiation, chemotherapy, EGFR-targeted therapy, and immunotherapy are the contemporary management for head and neck cancers. Further breakthroughs are needed in the development of drugs, disease monitoring biomarkers, and advances in molecular mechanisms of recurrent/metastatic head and neck cancers.

This Special Issue in Biomedicines, entitled "Head and Neck Cancers: Diagnosis, Therapy, Molecular and Cellular Mechanisms", aims to publish high-quality manuscripts with an emphasis on using multi-omics approaches to investigate the biomarkers, cancer pathogenesis, or clinical insights in head and neck cancers. We welcome reviews and original articles discussing novel basic research or translational medicine with respect to the molecular and cellular mechanisms of head and neck cancers.

We look forward to your contributions.

Dr. Chia-Yu Yang
Dr. Kai-Ping Chang
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.

Published Papers (4 papers)

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15 pages, 23363 KiB  
Article
The Chemokine CCL4 Stimulates Angiopoietin-2 Expression and Angiogenesis via the MEK/ERK/STAT3 Pathway in Oral Squamous Cell Carcinoma
by Chien-Chi Lu, Hsiao-Chi Tsai, Dong-Ying Yang, Shih-Wei Wang, Ming-Hsui Tsai, Chun-Hung Hua, Kwei-Jing Chen, Michael Yuan-Chien Chen, Ming-Yu Lien and Chih-Hsin Tang
Biomedicines 2022, 10(7), 1612; https://doi.org/10.3390/biomedicines10071612 - 06 Jul 2022
Cited by 5 | Viewed by 2163
Abstract
Oral squamous cell carcinoma (OSCC) is a common malignant tumor with a poor prognosis and is a major public health burden in Taiwan. Angiogenesis, the formation of new blood vessels, promotes tumor proliferation, maintenance, and metastasis. Angiopoietin 2 (Angpt2), a mitogen with a [...] Read more.
Oral squamous cell carcinoma (OSCC) is a common malignant tumor with a poor prognosis and is a major public health burden in Taiwan. Angiogenesis, the formation of new blood vessels, promotes tumor proliferation, maintenance, and metastasis. Angiopoietin 2 (Angpt2), a mitogen with a strong angiogenic effect, is highly specific to endothelial cells and a key player in angiogenesis. The inflammatory chemokine (C-C motif) ligand 4 (CCL4) is also important in the pathogenesis and progression of cancer. In this study, an analysis of records from The Cancer Genome Atlas (TCGA) database found higher CCL4 expression in oral cancer tissue than in normal healthy tissue. CCL4 treatment of oral cancer cells upregulated Angpt2 expression and stimulated mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase 1/2 (ERK), and signal transducer and activator of transcription 3 (STAT3) phosphorylation. Transfection of oral cancer cells with MEK, ERK, and STAT3 inhibitors and their small interfering RNAs inhibited CCL4-induced promotion of Angpt2 expression and angiogenesis. In a mouse model of OSCC, CCL4-treated cells promoted neovascularization in implanted Matrigel plugs, whereas inhibiting CCL4 expression suppressed Angpt2 expression and angiogenesis. CCL4 shows promise as a new molecular therapeutic target for inhibiting angiogenesis and metastasis in OSCC. Full article
(This article belongs to the Special Issue Head and Neck Cancers: Diagnosis, Therapy, Molecular and Cellular Mechanisms)
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14 pages, 1608 KiB  
Article
Serum Levels of Stromal Cell-Derived Factor-1α and Vascular Endothelial Growth Factor Predict Clinical Outcomes in Head and Neck Squamous Cell Carcinoma Patients Receiving TPF Induction Chemotherapy
by Yen-Hao Chen, Chih-Yen Chien, Yu-Ming Wang and Shau-Hsuan Li
Biomedicines 2022, 10(4), 803; https://doi.org/10.3390/biomedicines10040803 - 29 Mar 2022
Cited by 2 | Viewed by 1468
Abstract
Chemokines, such as stromal cell-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF), are associated with clinical outcomes in several cancer types. This study aimed to investigate the role of SDF-1α and VEGF in the prognosis of patients with head and neck squamous [...] Read more.
Chemokines, such as stromal cell-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF), are associated with clinical outcomes in several cancer types. This study aimed to investigate the role of SDF-1α and VEGF in the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) who underwent TPF induction chemotherapy (docetaxel, cisplatin, and 5-fluorouracil). A total of 77 HNSCC patients were enrolled and circulating SDF-1α and VEGF values were examined at two time points for each patient, including pre-TPF treatment (treatment-naïve) and post-TPF treatment but before chemoradiotherapy. The median progression-free survival (PFS) and overall survival (OS) were 18.1 and 32.9 months, respectively. Decreased SDF-1α and VEGF levels after TPF treatment, post-TPF SDF-1α < 1500 pg/mL and VEGF value < 150 pg/mL were independent prognostic factors for better PFS and OS in univariate and multivariate analyses. A combination of SDF-1α and VEGF values may predict clinical outcomes significantly. Our study confirmed the role of SDF-1α and VEGF in the disease progression of HNSCC, and that decreased SDF-1α and VEGF after TPF treatment and lower post-TPF SDF-1α and VEGF values were associated with better prognosis in HNSCC patients who received induction chemotherapy with TPF followed by chemoradiotherapy. Full article
(This article belongs to the Special Issue Head and Neck Cancers: Diagnosis, Therapy, Molecular and Cellular Mechanisms)
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20 pages, 3176 KiB  
Article
Prognosis Value of Immunoregulatory Molecules in Oral Cancer Microenvironment: An Immunohistochemical Study
by Juan Francisco Peña-Cardelles, José Juan Pozo-Kreilinger, Giovanna Roncador, Jesús Esteban-Hernández, José Ernesto Moro-Rodríguez, Ana Sastre-Perona, Beatriz Castelo-Fernández and José Luis Cebrián-Carretero
Biomedicines 2022, 10(3), 710; https://doi.org/10.3390/biomedicines10030710 - 19 Mar 2022
Cited by 1 | Viewed by 1996
Abstract
Objectives: To evaluate the relationship of the immune-checkpoint PD-1/PD-L1 with the clinical evolution of OSCC; to assess survival in OSCC based on the characteristics of TME and histologic risk score; to evaluate the clinical and histopathological relationship of OSCC with immunological TME. Material [...] Read more.
Objectives: To evaluate the relationship of the immune-checkpoint PD-1/PD-L1 with the clinical evolution of OSCC; to assess survival in OSCC based on the characteristics of TME and histologic risk score; to evaluate the clinical and histopathological relationship of OSCC with immunological TME. Material and Methods: A retrospective study was carried out on 65 samples from patients with OSCC on the floor of the mouth or tongue. Clinicopathological variables and the expression of the biomarkers PD-1, PD-L1, FoxP3, CD4, CD8, CSF1R, and p16 were recorded. The relationship of the clinical and histological variables with the expression of the biomarkers and survival was studied. Results: The univariate and multivariate analysis indicated that positive PD-1 expression was an independent protective factor for survival (overall, disease-free, disease-specific survival) and that high PD-L1 also improved survival. Poorly differentiated histological grades and metastasis were associated with a worse prognosis. Conclusions: PD-1 is a protective survival factor that is maintained independently of PD-L1 expression. High values of PD-L1 expression also improve survival. Higher expression of PD-1 is observed in smaller tumors, and higher expression of PD-L1 is more likely in women. No relationship between the tumor microenvironment and histologic risk score was found to influence the survival patterns studied in the OSCC. There is no evidence of a relationship between the histopathological features and the studied markers, although the positive PD-1 and PD-L1 cases have a lower risk of a high WPOI score, and positive PD-1 expression was associated with a lower DOI. Full article
(This article belongs to the Special Issue Head and Neck Cancers: Diagnosis, Therapy, Molecular and Cellular Mechanisms)
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14 pages, 1066 KiB  
Systematic Review
Prognostic and Predictive Biomarkers in Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy—A Systematic Review
by Daniel H. Schanne, Alexander Koch, Olgun Elicin, Roland Giger, Michaela Medová, Yitzhak Zimmer and Daniel M. Aebersold
Biomedicines 2022, 10(12), 3288; https://doi.org/10.3390/biomedicines10123288 - 19 Dec 2022
Cited by 2 | Viewed by 1918
Abstract
Background: Radiotherapy is a mainstay in head and neck squamous cell carcinoma (HNSCC) treatment but is mostly applied without stratification by molecular diagnostics. Development of reliable biomarkers may have the potential to improve radiotherapy (RT) efficacy and reduce toxicity. We conducted a [...] Read more.
Background: Radiotherapy is a mainstay in head and neck squamous cell carcinoma (HNSCC) treatment but is mostly applied without stratification by molecular diagnostics. Development of reliable biomarkers may have the potential to improve radiotherapy (RT) efficacy and reduce toxicity. We conducted a systematic review to summarize the field of biomarkers in HNSCC treated by RT. Methods: Pubmed and EMBASE were searched independently by two researchers following pre-defined inclusion and exclusion criteria. Z curves were generated to investigate publication bias. OncoKB was used for identification of druggable targets. Results: 134 manuscripts remained for data extraction. 12% of tumors were AJCC/UICC stage I–II and 82% were stage III–IV. The most common biomarkers were proteins (39%), DNA (14%) and mRNA (9%). Limiting analysis to prospective data and statistically significant results, we found three potentially druggable targets: ERCC2, PTCH1 and EGFR. Regarding data quality, AJCC/UICC stage was missing in 32% of manuscripts. 73% of studies were retrospective and only 7% were based on prospective randomized trials. Z-curves indicated the presence of publication bias. Conclusion: An abundance of potential biomarkers in HNSCC is available but data quality is limited by retrospective collection, lack of validation and publication bias. Improved study design and reporting quality might accelerate successful development of personalized treatments in HNSCC. Full article
(This article belongs to the Special Issue Head and Neck Cancers: Diagnosis, Therapy, Molecular and Cellular Mechanisms)
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