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Head and Neck Critical Illness: Basic and Clinical Research Implications
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Head and Neck Critical Illness: Basic and Clinical Research Implications

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (31 December 2018) | Viewed by 102902

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Hiroyuki Tomita

E-Mail Website
Guest Editor
Department of Tumor Pathology, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
Interests: pathology; tumor microenvironment; carcinogenesis; stem cell; mouse models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There are various malignant tumors in the head and neck area, including oral cavity, pharynx, sinonasal cavity, and salivary glands. Squamous cell carcinoma is the most common cancer among head and neck cancers. In salivary glands, there are many types of malignancies that can develop, such as malignant lymphoma, adenoid cystic carcinoma, adenocarcinoma, and mesenchymal tumors. In a clinical setting, imaging, such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), is very important in terms of the prediction of histological type and evaluation of the extent of invasion of adjacent structures. In basic research, there are few animal models in head and neck malignancies. In this Special Issue, we broadly discuss basic and clinical research in head and neck malignancies.

Prof. Dr. Hiroyuki Tomita
Guest Editor

Manuscript Submission Information

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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 Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Malignancy
  • Head and neck
  • Cancer
  • Imaging
  • Carcinoma

Published Papers (19 papers)

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Editorial

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2 pages, 147 KiB  
Editorial
Comment from the Editor on the Special Issue “Head and Neck Critical Illness: Basic and Clinical Research Implications”
by Hiroyuki Tomita
J. Clin. Med. 2019, 8(11), 1905; https://doi.org/10.3390/jcm8111905 - 07 Nov 2019
Viewed by 1413
Abstract
While oncogenic mutations of head and neck squamous cell carcinomas (HNSCC) in head and neck malignancies are uncommon, analysis using next-generation sequencing (NGS) technologies is growing. Further, single-cell analysis is being developed to overcome cancer cell heterogeneity and improve the poor survival of [...] Read more.
While oncogenic mutations of head and neck squamous cell carcinomas (HNSCC) in head and neck malignancies are uncommon, analysis using next-generation sequencing (NGS) technologies is growing. Further, single-cell analysis is being developed to overcome cancer cell heterogeneity and improve the poor survival of patients. However, it is important for researchers to know how to use this information to improve patients’ survival. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)

Research

Jump to: Editorial, Review, Other

12 pages, 1565 KiB  
Article
Frequent Alteration of Annexin A9 and A10 in HPV-Negative Head and Neck Squamous Cell Carcinomas: Correlation with the Histopathological Differentiation Grade
by Cecilia Salom, Saúl Álvarez-Teijeiro, M. Pilar Fernández, Reginald O. Morgan, Eva Allonca, Aitana Vallina, Corina Lorz, Lucas de Villalaín, M. Soledad Fernández-García, Juan P. Rodrigo and Juana M. García-Pedrero
J. Clin. Med. 2019, 8(2), 229; https://doi.org/10.3390/jcm8020229 - 10 Feb 2019
Cited by 12 | Viewed by 2946
Abstract
The annexin protein superfamily has been implicated in multiple physiological and pathological processes, including carcinogenesis. Altered expression of various annexins has frequently been observed and linked to the development and progression of various human malignancies. However, information is lacking on the expression and [...] Read more.
The annexin protein superfamily has been implicated in multiple physiological and pathological processes, including carcinogenesis. Altered expression of various annexins has frequently been observed and linked to the development and progression of various human malignancies. However, information is lacking on the expression and clinical significance of annexin A9 (ANXA9) and A10 (ANXA10) in head and neck squamous cell carcinomas (HNSCC). ANXA9 and ANXA10 expression was evaluated in a large cohort of 372 surgically treated HPV-negative HNSCC patients and correlated with the clinicopathologic parameters and disease outcomes. Down-regulation of ANXA9 expression was found in 42% of HNSCC tissue samples, compared to normal epithelia. ANXA9 expression in tumors was significantly associated with oropharyngeal location and histological differentiation grade (p < 0.001). In marked contrast, ANXA10 expression was absent in normal epithelium, but variably detected in the cytoplasm of cancer cells. Positive ANXA10 expression was found in 64% of tumors, and was significantly associated with differentiation grade (p < 0.001), being also more frequent in oropharyngeal tumors (p = 0.019). These results reveal that the expression of both ANXA9 and ANXA10 is frequently altered in HNSCC and associated to the tumor differentiation grade, suggesting that they could be implicated in the pathogenesis of these cancers. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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18 pages, 2800 KiB  
Article
Involvement of HPV Infection in the Release of Macrophage Migration Inhibitory Factor in Head and Neck Squamous Cell Carcinoma
by Nadège Kindt, Géraldine Descamps, Jérôme R. Lechien, Myriam Remmelink, Jean-Marie Colet, Ruddy Wattiez, Guy Berchem, Fabrice Journe and Sven Saussez
J. Clin. Med. 2019, 8(1), 75; https://doi.org/10.3390/jcm8010075 - 10 Jan 2019
Cited by 11 | Viewed by 4054
Abstract
Human papilloma virus (HPV) infection has been well-established as a risk factor in head and neck squamous cell carcinoma (HNSCC). The carcinogenic effect of HPV is mainly due to the E6 and E7 oncoproteins, which inhibit the functions of p53 and pRB, respectively. [...] Read more.
Human papilloma virus (HPV) infection has been well-established as a risk factor in head and neck squamous cell carcinoma (HNSCC). The carcinogenic effect of HPV is mainly due to the E6 and E7 oncoproteins, which inhibit the functions of p53 and pRB, respectively. These oncoproteins could also play a role in the Warburg effect, thus favoring tumor immune escape. Here, we demonstrated that the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) is expressed at higher levels in HPV-negative patients than in HPV-positive patients. However, the secretion of MIF is higher in HPV-positive human HNSCC cell lines, than in HPV-negative cell lines. In-HPV positive cells, the half inhibitory concentration (IC50) of MIF inhibitor (4-iodo-6-phenylpyrimidine (4-IPP)) is higher than that in HPV-negative cells. This result was confirmed in vitro and in vivo by the use of murine SCCVII cell lines expressing either E6 or E7, or both E6 and E7. Finally, to examine the mechanism of MIF secretion, we conducted proton nuclear magnetic resonance (1H-NMR) experiments, and observed that lactate production is increased in both the intracellular and conditioned media of HPV-positive cells. In conclusion, our data suggest that the stimulation of enzymes participating in the Warburg effect by E6 and E7 oncoproteins increases lactate production and hypoxia inducible factor 1α (HIF-1α) expression, and finally induces MIF secretion. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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14 pages, 584 KiB  
Article
Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy
by Thomas Senghore, Huei-Tzu Chien, Wen-Chang Wang, You-Xin Chen, Chi-Kuang Young, Shiang-Fu Huang and Chih-Ching Yeh
J. Clin. Med. 2019, 8(1), 33; https://doi.org/10.3390/jcm8010033 - 01 Jan 2019
Cited by 10 | Viewed by 2853
Abstract
The nucleotide excision repair (NER) pathway plays a major role in the repair of DNA damaged by exogenous agents, such as chemotherapeutic and radiotherapeutic agents. Thus, we investigated the association between key potentially functional single nucleotide polymorphisms (SNPs) in the NER pathway and [...] Read more.
The nucleotide excision repair (NER) pathway plays a major role in the repair of DNA damaged by exogenous agents, such as chemotherapeutic and radiotherapeutic agents. Thus, we investigated the association between key potentially functional single nucleotide polymorphisms (SNPs) in the NER pathway and clinical outcomes in oral squamous cell carcinoma (OSCC) patients treated with concurrent chemoradiotherapy (CCRT). Thirteen SNPs in five key NER genes were genotyped in 319 male OSCC patients using iPLEX MassARRAY. Cox proportional hazards models and Kaplan–Meier survival curves were used to estimate the risk of death or recurrence. Carriers of the XPC rs2228000 TT genotype showed a borderline significant increased risk of poor overall survival under the recessive model (hazard ratio (HR) = 1.81, 95% confidence interval (CI) = 0.99–3.29). The CC genotypes of ERCC5 rs17655 (HR = 1.54, 95% CI = 1.03–2.29) and ERCC1 rs735482 (HR = 1.65, 95% CI = 1.06–2.58) were associated with an increased risk of worse disease-free survival under the recessive model. In addition, participants carrying both the CC genotypes of ERCC5 rs17655 and ERCC1 rs735482 exhibited an enhanced susceptibility for recurrence (HR = 2.60, 95% CI = 1.11–6.09). However, no statistically significant interaction was observed between them. Our findings reveal that the ERCC5 rs17655 CC and ERCC1 rs735482 CC genotypes were associated with an increased risk of recurrence in male patients with OSCC treated with CCRT. Therefore, CCRT may not be beneficial, and alternative treatments are required for such patients. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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12 pages, 1045 KiB  
Article
Distinct Expression and Clinical Significance of Zinc Finger AN-1-Type Containing 4 in Oral Squamous Cell Carcinomas
by Julián Suárez-Canto, Faustino Julián Suárez-Sánchez, Francisco Domínguez-Iglesias, Gonzalo Hernández-Vallejo, Juana M. García-Pedrero and Juan C. De Vicente
J. Clin. Med. 2018, 7(12), 534; https://doi.org/10.3390/jcm7120534 - 10 Dec 2018
Cited by 2 | Viewed by 2424
Abstract
Zinc finger AN1-type containing 4 (ZFAND4) has emerged as a promising prognostic marker and predictor of metastasis for patients with oral squamous cell carcinoma (OSCC). However, further validation is fundamental before clinical implementation. Hence, this study evaluated the expression pattern of ZFAND4 protein [...] Read more.
Zinc finger AN1-type containing 4 (ZFAND4) has emerged as a promising prognostic marker and predictor of metastasis for patients with oral squamous cell carcinoma (OSCC). However, further validation is fundamental before clinical implementation. Hence, this study evaluated the expression pattern of ZFAND4 protein expression by immunohistochemistry using an independent cohort of 125 patients with OSCC, and correlations with the clinicopathologic parameters and disease outcome. Remarkably, ZFAND4 expression, while negligible in normal epithelium, exhibited two distinct expression patterns in tumors that did not overlap. A gross granular staining was characteristic of the undifferentiated cells at the invasive front of tumors, whereas the most differentiated cells located at the center of the tumor nests showed diffuse non-granular staining. ZFAND4 staining was higher in undifferentiated than in differentiated areas of tumors. High ZFAND4 expression in differentiated cells was significantly associated to well-differentiated (p = 0.04) and non-recurrent tumors (p = 0.04), whereas ZFAND4 expression in undifferentiated cells correlated with tumor location (p = 0.005). No correlations between the ZFAND4 expression and patient survival were found. These data question the clinical relevance of ZFAND4 expression as a prognostic biomarker in OSCC, and also reveal distinct ZFAND4 expression patterns depending on the differentiation areas of tumors that should be evaluated separately. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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14 pages, 1554 KiB  
Article
The Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Head and Neck Cancer Patients Treated with Radiotherapy
by Yeona Cho, Jun Won Kim, Hong In Yoon, Chang Geol Lee, Ki Chang Keum and Ik Jae Lee
J. Clin. Med. 2018, 7(12), 512; https://doi.org/10.3390/jcm7120512 - 03 Dec 2018
Cited by 35 | Viewed by 3656
Abstract
Background: To investigate the prognostic value of pre-treatment neutrophil/lymphocyte ratio (NLR) in patients treated with definitive radiotherapy (RT) for head and neck cancer. Methods: We retrospectively analyzed 621 patients who received definitive RT for nasopharyngeal, oropharyngeal, hypopharyngeal, and laryngeal cancer. An NLR cut-off [...] Read more.
Background: To investigate the prognostic value of pre-treatment neutrophil/lymphocyte ratio (NLR) in patients treated with definitive radiotherapy (RT) for head and neck cancer. Methods: We retrospectively analyzed 621 patients who received definitive RT for nasopharyngeal, oropharyngeal, hypopharyngeal, and laryngeal cancer. An NLR cut-off value of 2.7 was identified using a receiver operating characteristic curve analysis, with overall survival (OS) as an endpoint. Results: The 5-year progression-free survival (PFS) and OS for all patients were 62.3% and 72.1%, respectively. The patients with a high NLR (68%) had a significantly lower 5-year PFS and OS than their counterparts with a low NLR (32%) (PFS: 39.2% vs. 75.8%, p < 0.001; OS: 50.9% vs. 83.8%, p < 0.001). In a subgroup analysis according to primary site, a high NLR also correlated with a lower PFS and OS, except in oropharyngeal cancer, where a high NLR only exhibited a trend towards lower survival. In a multivariate analysis, a high NLR remained an independent prognostic factor for PFS and OS. Conclusion: Head and neck cancer tends to be more aggressive in patients with a high NLR, leading to a poorer outcome after RT. The optimal therapeutic approaches for these patients should be reevaluated, given the unfavorable prognosis. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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14 pages, 2358 KiB  
Article
Distinctive Expression and Amplification of Genes at 11q13 in Relation to HPV Status with Impact on Survival in Head and Neck Cancer Patients
by Francisco Hermida-Prado, Sofía T. Menéndez, Pablo Albornoz-Afanasiev, Rocío Granda-Diaz, Saúl Álvarez-Teijeiro, M. Ángeles Villaronga, Eva Allonca, Laura Alonso-Durán, Xavier León, Laia Alemany, Marisa Mena, Nagore Del-Rio-Ibisate, Aurora Astudillo, René Rodríguez, Juan P. Rodrigo and Juana M. García-Pedrero
J. Clin. Med. 2018, 7(12), 501; https://doi.org/10.3390/jcm7120501 - 01 Dec 2018
Cited by 16 | Viewed by 3338
Abstract
Clear differences have been established between head and neck squamous cell carcinomas (HNSCC) depending on human papillomavirus (HPV) infection status. This study specifically investigated the status of the CTTN, CCND1 and ANO1 genes mapping at the 11q13 amplicon in relation to the [...] Read more.
Clear differences have been established between head and neck squamous cell carcinomas (HNSCC) depending on human papillomavirus (HPV) infection status. This study specifically investigated the status of the CTTN, CCND1 and ANO1 genes mapping at the 11q13 amplicon in relation to the HPV status in HNSCC patients. CTTN, CCND1 and ANO1 protein expression and gene amplification were respectively analyzed by immunohistochemistry and real-time PCR in a homogeneous cohort of 392 surgically treated HNSCC patients. The results were further confirmed using an independent cohort of 279 HNSCC patients from The Cancer Genome Atlas (TCGA). The impact on patient survival was also evaluated. CTTN, CCND1 and ANO1 gene amplification and protein expression were frequent in HPV-negative tumors, while absent or rare in HPV-positive tumors. Using an independent validation cohort of 279 HNSCC patients, we consistently found that these three genes were frequently co-amplified (28%) and overexpressed (39–46%) in HPV-negative tumors, whereas almost absent in HPV-positive tumors. Remarkably, these alterations (in particular CTTN and ANO1 overexpression) were associated with poor prognosis. Taken together, the distinctive expression and amplification of these genes could cooperatively contribute to the differences in prognosis and clinical outcome between HPV-positive and HPV-negative tumors. These findings could serve as the basis to design more personalized therapeutic strategies for HNSCC patients. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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12 pages, 2401 KiB  
Article
Nox4 Overexpression as a Poor Prognostic Factor in Patients with Oral Tongue Squamous Cell Carcinoma Receiving Surgical Resection
by Yen-Hao Chen, Chih-Yen Chien, Fu-Min Fang, Tai-Lin Huang, Yan-Ye Su, Sheng-Dean Luo, Chao-Cheng Huang, Wei-Che Lin and Shau-Hsuan Li
J. Clin. Med. 2018, 7(12), 497; https://doi.org/10.3390/jcm7120497 - 01 Dec 2018
Cited by 7 | Viewed by 2556
Abstract
Background: Nox4 has been reported to promote tumor progression of various types of cancer through many different pathways. The current study was designed to evaluate the prognostic significance of Nox4 in patients with oral tongue squamous cell carcinoma (OTSCC) receiving surgical resection. Methods: [...] Read more.
Background: Nox4 has been reported to promote tumor progression of various types of cancer through many different pathways. The current study was designed to evaluate the prognostic significance of Nox4 in patients with oral tongue squamous cell carcinoma (OTSCC) receiving surgical resection. Methods: We retrospectively analyzed the 161 patients with OTSCC treated with surgical resection, including 81 patients with high expression of Nox4 and 80 patients with low expression of Nox4. Two OTSCC cell lines, SAS and SCC4, were used to investigate the proliferation activity. Results: The univariate and multivariable analyses showed that negative nodal metastasis and low expression of Nox4 were significantly associated with superior disease-free survival (DFS) and overall survival (OS). Western blotting analysis indicated that Nox4 was highly expressed in these two OTSCC cell lines and knockdown of Nox4 was successful by transfecting with Nox4 shRNA. In addition, these cell lines were also treated with a Nox4 inhibitor (GKT-137831) and the results showed GKT-137831 could inhibit the proliferation of OTSCC tumor cells in a dose-dependent manner. Conclusion: Our study suggests that Nox4 plays an important role in disease progression of OTSCC and Nox4 overexpression is a poor prognostic factor for patients with OTSCC who received surgical resection. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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19 pages, 2970 KiB  
Article
Map1lc3b and Sqstm1 Modulated Autophagy for Tumorigenesis and Prognosis in Certain Subsites of Oral Squamous Cell Carcinoma
by Pei-Feng Liu, Hsueh-Wei Chang, Jin-Shiung Cheng, Huai-Pao Lee, Ching-Yu Yen, Wei-Lun Tsai, Jiin-Tsuey Cheng, Yi-Jing Li, Wei-Chieh Huang, Cheng-Hsin Lee, Luo-Pin Ger and Chih-Wen Shu
J. Clin. Med. 2018, 7(12), 478; https://doi.org/10.3390/jcm7120478 - 24 Nov 2018
Cited by 26 | Viewed by 3725
Abstract
Oral squamous cell carcinoma (OSCC) is one of the most common cancer types worldwide and can be divided into three major subsites: buccal mucosal SCC (BMSCC), tongue SCC (TSCC), and lip SCC (LSCC). The autophagy marker microtubule-associated protein light chain 3B (MAP1LC3B) and [...] Read more.
Oral squamous cell carcinoma (OSCC) is one of the most common cancer types worldwide and can be divided into three major subsites: buccal mucosal SCC (BMSCC), tongue SCC (TSCC), and lip SCC (LSCC). The autophagy marker microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1(SQSTM1) are widely used proteins to evaluate autophagy in tumor tissues. However, the role of MAP1LC3B and SQSTM1 in OSCC is not fully understood, particularly in certain subsites. With a tissue microarray comprised of 498 OSCC patients, including 181 BMSCC, 244 TSCC, and 73 LSCC patients, we found that the expression levels of MAP1LC3B and cytoplasmic SQSTM1 were elevated in the tumor tissues of three subsites compared with those in adjacent normal tissues. MAP1LC3B was associated with a poor prognosis only in TSCC. SQSTM1 was associated with poor differentiation in three subsites, while the association with lymph node invasion was only observed in BMSCC. Interestingly, MAP1LC3B was positively correlated with SQSTM1 in the tumor tissues of BMSCC, whereas it showed no correlation with SQSTM1 in adjacent normal tissue. The coexpression of higher MAP1LC3B and SQSTM1 demonstrated a significantly worse disease-specific survival (DSS) and disease-free survival (DFS) in patients with BMSCC and LSCC, but not TSCC. The knockdown of MAP1LC3B and SQSTM1 reduced autophagy, cell proliferation, invasion and tumorspheres of BMSCC cells. Additionally, silencing both MAP1LC3B and SQSTM1 enhanced the cytotoxic effects of paclitaxel in the tumorspheres of BMSCC cells. Taken together, MAP1LC3B and SQSTM1 might modulate autophagy to facilitate tumorigenesis and chemoresistance in OSCC, particularly in BMSCC. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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11 pages, 692 KiB  
Article
High Risk of Deep Neck Infection in Patients with Type 1 Diabetes Mellitus: A Nationwide Population-Based Cohort Study
by Geng-He Chang, Meng-Chang Ding, Yao-Hsu Yang, Yung-Hsiang Lin, Chia-Yen Liu, Meng-Hung Lin, Ching-Yuan Wu, Cheng-Ming Hsu and Ming-Shao Tsai
J. Clin. Med. 2018, 7(11), 385; https://doi.org/10.3390/jcm7110385 - 25 Oct 2018
Cited by 20 | Viewed by 3665
Abstract
Objective: To investigate the risk of deep neck infection (DNI) in patients with type 1 diabetes mellitus (T1DM). Methods: The database of the Registry for Catastrophic Illness Patients, affiliated to the Taiwan National Health Insurance Research Database, was used to conduct a retrospective [...] Read more.
Objective: To investigate the risk of deep neck infection (DNI) in patients with type 1 diabetes mellitus (T1DM). Methods: The database of the Registry for Catastrophic Illness Patients, affiliated to the Taiwan National Health Insurance Research Database, was used to conduct a retrospective cohort study. In total, 5741 patients with T1DM and 22,964 matched patients without diabetes mellitus (DM) were enrolled between 2000 and 2010. The patients were followed up until death or the end of the study period (31 December 2013). The primary outcome was the occurrence of DNI. Results: Patients with T1DM exhibited a significantly higher cumulative incidence of DNI than did those without DM (p < 0.001). The Cox proportional hazards model showed that T1DM was significantly associated with a higher incidence of DNI (adjusted hazard ratio, 10.71; 95% confidence interval, 6.02–19.05; p < 0.001). The sensitivity test and subgroup analysis revealed a stable effect of T1DM on DNI risk. The therapeutic methods (surgical or nonsurgical) did not differ significantly between the T1DM and non-DM cohorts. Patients with T1DM required significantly longer hospitalization for DNI than did those without DM (9.0 ± 6.2 vs. 4.1 ± 2.0 days, p < 0.001). Furthermore, the patients with T1DM were predisposed to DNI at a younger age than were those without DM. Conclusions: T1DM is an independent risk factor for DNI and is associated with a 10-fold increase in DNI risk. The patients with T1DM require longer hospitalizations for DNI and are younger than those without DM. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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17 pages, 2325 KiB  
Article
PG-Priming Enhances Doxorubicin Influx to Trigger Necrotic and Autophagic Cell Death in Oral Squamous Cell Carcinoma
by Shian-Ren Lin and Ching-Feng Weng
J. Clin. Med. 2018, 7(10), 375; https://doi.org/10.3390/jcm7100375 - 21 Oct 2018
Cited by 17 | Viewed by 4053
Abstract
Synergistic effects between natural compounds and chemotherapy drugs are believed to have fewer side effects with equivalent efficacy. However, the synergistic potential of prodigiosin (PG) with doxorubicin (Dox) chemotherapy is still unknown. This study explores the synergistic mechanism of PG and Dox against [...] Read more.
Synergistic effects between natural compounds and chemotherapy drugs are believed to have fewer side effects with equivalent efficacy. However, the synergistic potential of prodigiosin (PG) with doxorubicin (Dox) chemotherapy is still unknown. This study explores the synergistic mechanism of PG and Dox against oral squamous cell carcinoma (OSCC) cells. Three OSCC cell lines were treated with different PG/Dox combinatory schemes for cytotoxicity tests and were further investigated for cell death characteristics by cell cycle flow cytometry and autophagy/apoptosis marker labelling. When OSCC cells were pretreated with PG, the cytotoxicity of the subsequent Dox-treatment was 30% higher than Dox alone. The cytotoxic efficacy of PG-pretreated was found better than those of PG plus Dox co-treatment and Dox-pretreatment. Increase of Sub-G1 phase and caspase-3/LC-3 levels without poly (ADP-ribose) polymeras (PARP) elevation indicated both autophagy and necrosis occurred in OSCC cells. Dox flux after PG-priming was further evaluated by rhodamine-123 accumulation and Dox transporters analysis to elucidate the PG-priming effect. PG-priming autophagy enhanced Dox accumulation according to the increase of rhodamine-123 accumulation without the alterations of Dox transporters. Additionally, the cause of PG-triggered autophagy was determined by co-treatment with endoplasmic reticulum (ER) stress or AMP-activated protein kinase (AMPK) inhibitor. PG-induced autophagy was not related to nutrient deprivation and ER stress was proved by co-treatment with specific inhibitor. Taken together, PG-priming autophagy could sensitize OSCC cells by promoting Dox influx without regulation of Dox transporter. The PG-priming might be a promising adjuvant approach for the chemotherapy of OSCC. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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15 pages, 1217 KiB  
Article
Predictive Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio in Head and Neck Squamous Cell Carcinoma
by Miao-Fen Chen, Ming-Shao Tsai, Wen-Cheng Chen and Ping-Tsung Chen
J. Clin. Med. 2018, 7(10), 294; https://doi.org/10.3390/jcm7100294 - 20 Sep 2018
Cited by 22 | Viewed by 3322
Abstract
This study assessed the significance of the neutrophil-to-lymphocyte ratio (NLR) in head and neck squamous cell carcinoma (HNSCC), and the relationships of the NLR with the aldehyde dehydrogenase 1 (ALDH1) level in tumors and the proportion of myeloid-derived suppressor cells (MDSCs) in the [...] Read more.
This study assessed the significance of the neutrophil-to-lymphocyte ratio (NLR) in head and neck squamous cell carcinoma (HNSCC), and the relationships of the NLR with the aldehyde dehydrogenase 1 (ALDH1) level in tumors and the proportion of myeloid-derived suppressor cells (MDSCs) in the peripheral circulation. In total, 227 HNSCC patients who had received curative treatment at our hospital were enrolled into the present study. The NLR of each HNSCC patient before treatment was calculated. The associations of NLR with various clinicopathological parameters and prognoses were then examined. In addition, correlations between the proportion of MDSCs and level of ALDH1 with the NLR were assessed. Our data revealed that an elevated NLR was significantly correlated with the risk of developing locoregional recurrence and with a reduced overall survival in HNSCC patients. Multivariate analyses revealed that the NLR pretreatment and surgical resection were significantly correlated with the rate of treatment failure and the overall survival rate in HNSCC patients. Furthermore, the levels of ALDH1 in tumors and MDSCs in the peripheral circulation were significantly correlated with the prognosis of HNSCC, and the NLR was positively correlated with MDSC levels in the circulation and ALDH1 staining intensity in tumor specimens. In conclusion, the NLR has power in predicting the expression of ALDH1 in tumors, the circulating level of MDSCs, and the prognosis in HNSCC. We suggest that the NLR is an important biomarker that can assist the clinician and patient in making informed decisions regarding treatment options for HNSCC patients. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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10 pages, 2398 KiB  
Article
The Role of Diffusion-Weighted Magnetic Resonance Imaging in the Differentiation of Head and Neck Masses
by Lutfi Kanmaz and Erdal Karavas
J. Clin. Med. 2018, 7(6), 130; https://doi.org/10.3390/jcm7060130 - 29 May 2018
Cited by 11 | Viewed by 5626
Abstract
The purpose of this study was to evaluate the value of diffusion-weighted MRI (DW-MRI) in differentiating benign and malignant head and neck masses by comparing their apparent diffusion coefficient (ADC) values. The study included 32 patients with a neck mass >1 cm in [...] Read more.
The purpose of this study was to evaluate the value of diffusion-weighted MRI (DW-MRI) in differentiating benign and malignant head and neck masses by comparing their apparent diffusion coefficient (ADC) values. The study included 32 patients with a neck mass >1 cm in diameter who were examined with echo planar DW-MRI. Two different diffusion gradients (b values of b = 0 and b = 1000 s/mm2) were applied. DWI and ADC maps of 32 neck masses in 32 patients were obtained. Mean ADC values of benign and malignant neck lesions were measured and compared statistically. A total of 15 (46.9%) malignant masses and 17 (53.1%) benign masses were determined. Of all the neck masses, the ADC value of cystic masses was the highest and that of lymphomas was the lowest. The mean ADC values of benign and malignant neck masses were 1.57 × 10−3 mm2/s and 0.90 × 10−3 mm2/s, respectively. The difference between mean ADC values of benign and malignant neck masses was significant (p < 0.01). Diffusion-weighted MRI with ADC measurements can be useful in the differential diagnosis of neck masses. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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7 pages, 510 KiB  
Article
Canaloplasty in Corticosteroid-Induced Glaucoma. Preliminary Results
by Paolo Brusini, Claudia Tosoni and Marco Zeppieri
J. Clin. Med. 2018, 7(2), 31; https://doi.org/10.3390/jcm7020031 - 11 Feb 2018
Cited by 8 | Viewed by 3707
Abstract
Purpose: to present the mid-term results of canaloplasty in a small cohort of corticosteroid glaucoma patients. Material and Methods: Nine eyes from seven patients with various types of corticosteroid glaucoma in maximum medical therapy underwent canaloplasty. Patients underwent complete ophthalmic examination every six [...] Read more.
Purpose: to present the mid-term results of canaloplasty in a small cohort of corticosteroid glaucoma patients. Material and Methods: Nine eyes from seven patients with various types of corticosteroid glaucoma in maximum medical therapy underwent canaloplasty. Patients underwent complete ophthalmic examination every six months. Success was defined as: post-operative intraocular pressure (IOP) ≤ 21 mmHg and ≤ 16 mmHg without (“complete success”), and with/without medical treatment (“qualified success”). The IOP reduction had to be ≥ 20. The number of medications before and after surgery was considered. The follow-up mean period was 32.7 ± 20.8 months (range 14–72 months). Results: The pre-operative mean IOP was 30.7 ± 7.2 mmHg (range: 24–45). The mean IOP at 6 and 12-month follow-up was 13.1 ± 2.6 mmHg, and 13.7 ± 1.9 mmHg, respectively. Qualified and complete success at 6 and 12 months was 100% for both of the two definitions. The number of medications used preoperatively and at the 12-month follow-up was 4.3 ± 0.7, and 0.2 ± 1.0, respectively. No serious complication was observed. Conclusions: The mid-term results of canaloplasty in patients with corticosteroid-induced glaucoma appear to be very promising. Canaloplasty should be considered as a possible alternative to filtering surgery in this form of glaucoma, when medical therapy is not sufficient to maintain the IOP within reasonable limits. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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1083 KiB  
Communication
The Impact of the Brain-Derived Neurotrophic Factor Gene on Trauma and Spatial Processing
by Jessica K. Miller, Siné McDougall, Sarah Thomas and Jan Wiener
J. Clin. Med. 2017, 6(12), 108; https://doi.org/10.3390/jcm6120108 - 27 Nov 2017
Cited by 13 | Viewed by 6237
Abstract
The influence of genes and the environment on the development of Post-Traumatic Stress Disorder (PTSD) continues to motivate neuropsychological research, with one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF) gene, given its impact on the integrity of the hippocampal memory system. Research [...] Read more.
The influence of genes and the environment on the development of Post-Traumatic Stress Disorder (PTSD) continues to motivate neuropsychological research, with one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF) gene, given its impact on the integrity of the hippocampal memory system. Research into human navigation also considers the BDNF gene in relation to hippocampal dependent spatial processing. This speculative paper brings together trauma and spatial processing for the first time and presents exploratory research into their interactions with BDNF. We propose that quantifying the impact of BDNF on trauma and spatial processing is critical and may well explain individual differences in clinical trauma treatment outcomes and in navigation performance. Research has already shown that the BDNF gene influences PTSD severity and prevalence as well as navigation behaviour. However, more data are required to demonstrate the precise hippocampal dependent processing mechanisms behind these influences in different populations and environmental conditions. This paper provides insight from recent studies and calls for further research into the relationship between allocentric processing, trauma processing and BDNF. We argue that research into these neural mechanisms could transform PTSD clinical practice and professional support for individuals in trauma-exposing occupations such as emergency response, law enforcement and the military. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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Review

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11 pages, 1098 KiB  
Review
A Review of HPV-Related Head and Neck Cancer
by Kazuhiro Kobayashi, Kenji Hisamatsu, Natsuko Suzui, Akira Hara, Hiroyuki Tomita and Tatsuhiko Miyazaki
J. Clin. Med. 2018, 7(9), 241; https://doi.org/10.3390/jcm7090241 - 27 Aug 2018
Cited by 190 | Viewed by 15130
Abstract
Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper aerodigestive tract. Tobacco and alcohol use have been reported to be associated with HNSCC. Infection with high-risk human papillomaviruses (HPVs) has recently been implicated in the pathogenesis of [...] Read more.
Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper aerodigestive tract. Tobacco and alcohol use have been reported to be associated with HNSCC. Infection with high-risk human papillomaviruses (HPVs) has recently been implicated in the pathogenesis of HNSCCs. It is now widely accepted that high-risk HPV is a cause of almost all cervical cancers as well as some forms of HNSCCs. HPV-related HNSCCs are increasing. HPV-related HNSCCs and HPV-unrelated HNSCCs differ with respect to the molecular mechanisms underlying their oncogenic processes. HPV-related HNSCCs are known to have a better prognosis response to treatment as compared with HPV-unrelated HNSCCs. Therefore, in recent years, it has been required to accurately discriminate between HPV-related and HPV-unrelated HNSCCs. To diagnose the HPV-related HNSCCs, various methods including P16 immunohistochemistry, FISH, and genetic analyses of the HPV gene from histopathological and liquid biopsy specimens have been employed. Based on the results of the differential diagnosis, various treatments employing EGFR TKI and low-dose radiation have been employed. Here, we review the involvement of the HPV virus in HNSCCs as well as the molecular mechanism of carcinogenesis, classification, prognosis, diagnostic procedures, and therapy of the disease. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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15 pages, 297 KiB  
Review
The Role of Procalcitonin in the Diagnosis of Meningitis: A Literature Review
by Dimitrios Velissaris, Martina Pintea, Nikolaos Pantzaris, Eirini Spatha, Vassilios Karamouzos, Charalampos Pierrakos and Menelaos Karanikolas
J. Clin. Med. 2018, 7(6), 148; https://doi.org/10.3390/jcm7060148 - 11 Jun 2018
Cited by 26 | Viewed by 7432
Abstract
Objective: To review the current published literature on the use of procalcitonin as a diagnostic and prognostic marker in adult patients with meningitis. Methods: We conducted a PubMed search to identify all relevant publications regarding the diagnostic and prognostic value of serum procalcitonin [...] Read more.
Objective: To review the current published literature on the use of procalcitonin as a diagnostic and prognostic marker in adult patients with meningitis. Methods: We conducted a PubMed search to identify all relevant publications regarding the diagnostic and prognostic value of serum procalcitonin in patients with a known or suspected central nervous system infection. We also reviewed the bibliographies of all identified manuscripts in an attempt to identify additional relevant references. Results: A significant body of evidence suggests that serum procalcitonin has a promising role and can be a useful biomarker in the assessment of patients with meningitis. Conclusions: Our literature review suggests that data on the role of Cerebrospinal Fluid (CSF) procalcitonin are limited, whereas serum procalcitonin (S–PCT) is probably a useful tool in the evaluation of patients with a known or suspected central nervous system infection and can help distinguish between bacterial and viral meningitis. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
4262 KiB  
Review
Imaging Characteristics of Malignant Sinonasal Tumors
by Masaya Kawaguchi, Hiroki Kato, Hiroyuki Tomita, Keisuke Mizuta, Mitsuhiro Aoki, Akira Hara and Masayuki Matsuo
J. Clin. Med. 2017, 6(12), 116; https://doi.org/10.3390/jcm6120116 - 06 Dec 2017
Cited by 71 | Viewed by 16736
Abstract
Malignancies of the nasal cavity and paranasal sinuses account for 1% of all malignancies and 3% of malignancies of the upper aerodigestive tract. In the sinonasal tract, nearly half of all malignancies arise in the nasal cavity, whereas most of the remaining malignancies [...] Read more.
Malignancies of the nasal cavity and paranasal sinuses account for 1% of all malignancies and 3% of malignancies of the upper aerodigestive tract. In the sinonasal tract, nearly half of all malignancies arise in the nasal cavity, whereas most of the remaining malignancies arise in the maxillary or ethmoid sinus. Squamous cell carcinoma is the most common histological subtype of malignant tumors occurring in this area, followed by other epithelial carcinomas, lymphomas, and malignant soft tissue tumors. Although many of these tumors present with nonspecific symptoms, each tumor exhibits characteristic imaging features. Although complex anatomy and various normal variants of the sinonasal tract cause difficulty in identifying the origin and extension of large sinonasal tumors, the invasion of vital structures such as the brain, optic nerves, and internal carotid artery affects patients’ prognosis. Thus, diagnostic imaging plays a key role in predicting the histological subtype and in evaluating a tumor extension into adjacent structures. This article describes the computed tomography and magnetic resonance imaging findings for malignant sinonasal tumors. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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Other

2676 KiB  
Case Report
Acute Encephalitis in an Adult with Diffuse Large B-Cell Lymphoma with Secondary Involvement of the Central Nervous System: Infectious or Non-Infectious Etiology?
by Surinder S. Moonga, Kenneth Liang and Burke A. Cunha
J. Clin. Med. 2017, 6(12), 117; https://doi.org/10.3390/jcm6120117 - 07 Dec 2017
Cited by 1 | Viewed by 9174
Abstract
Both infectious and non-infectious etiologies of acute encephalitis have been described, as well as their specific presentations, diagnostic tests, and therapies. Classic findings of acute encephalitis include altered mental status, fever, and new lesions on neuroimaging or electroencephalogram (EEG). We report an interesting [...] Read more.
Both infectious and non-infectious etiologies of acute encephalitis have been described, as well as their specific presentations, diagnostic tests, and therapies. Classic findings of acute encephalitis include altered mental status, fever, and new lesions on neuroimaging or electroencephalogram (EEG). We report an interesting case of a 61-year-old male with a history of diffuse large B-cell lymphoma with secondary involvement of the central nervous system (SCNS-DLBCL). He presented with acute encephalitis: altered mental status, fever, leukocytosis, neuropsychiatric symptoms, multiple unchanged brain lesions on computed tomography scan of the head, and EEG showed mild to moderate diffuse slowing with low-moderate polymorphic delta and theta activity. With such a wide range of symptoms, the differential diagnosis included paraneoplastic and autoimmune encephalitis. Infectious and autoimmune/paraneoplastic encephalitis in patients with SCNS-DLBCL are not well documented in the literature, hence diagnosis and therapy becomes challenging. This case report describes the patient’s unique presentation of acute encephalitis. Full article
(This article belongs to the Special Issue Head and Neck Critical Illness: Basic and Clinical Research Implications)
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