Journal articles on the topic 'Head and Neck Suqamous Cell Carcinoma (HNSCC)'
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1
Romanowska, Kamila, Agnieszka Sobecka, Agnieszka A. Rawłuszko-Wieczorek, Wiktoria M. Suchorska, and Wojciech Golusiński. "Head and Neck Squamous Cell Carcinoma: Epigenetic Landscape." Diagnostics 11, no. 1 (December 27, 2020): 34. http://dx.doi.org/10.3390/diagnostics11010034.
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Head and neck squamous carcinoma (HNSCC) constitutes the sixth most prevalent cancer worldwide. The molecular pathogenesis of HNSCC includes disorders in cell cycle, intercellular signaling, proliferation, squamous cell differentiation and apoptosis. In addition to the genetic mutations, changes in HNSCC are also characterized by the accumulation of epigenetic alterations such as DNA methylation, histone modifications, non-coding RNA activity and RNA methylation. In fact, some of them may promote cancer formation and progression by controlling the gene expression machinery, hence, they could be used as biomarkers in the clinical surveillance of HNSCC or as targets for therapeutic strategies. In this review, we focus on the current knowledge regarding epigenetic modifications observed in HNSCC and its predictive value for cancer development.
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Li, John Zenghong, Wei Gao, Jimmy Yu-Wai Chan, Wai-Kuen Ho, and Thian-Sze Wong. "Hypoxia in Head and Neck Squamous Cell Carcinoma." ISRN Otolaryngology 2012 (October 16, 2012): 1–8. http://dx.doi.org/10.5402/2012/708974.
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Hypoxia is a common feature in most of the solid tumors including head and neck squamous cell carcinoma (HNSCC). Hypoxia reflects the imbalance between oxygen consumption by the rapidly proliferating cancer cells and the insufficient oxygen delivery due to poor vascularization and blood supply. The hypoxic microenvironment in the HNSCC contributes to the development of aggressive carcinoma phenotype with high metastatic rate, resistance to therapeutic agents, and higher tumor recurrence rates, leading to low therapeutic efficiency and poor outcome. To overcome the therapeutic resistance due to hypoxia and improving the prognosis of the HNSCC patients, many approaches have been examined in laboratory studies and clinical trials. In this short paper, we discuss the mechanisms involved in the resistance of radiotherapy and chemotherapy in hypoxic condition. We also exploit the molecular mechanisms employed by the HNSCC cells to adapt the hypoxic condition and their tumorigenic role in head and neck, as well as the strategies to overcome hypoxia-induced therapeutic resistance.
3
Fukusumi, T., and J. A. Califano. "The NOTCH Pathway in Head and Neck Squamous Cell Carcinoma." Journal of Dental Research 97, no. 6 (February 28, 2018): 645–53. http://dx.doi.org/10.1177/0022034518760297.
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Comprehensive genomic analyses have been performed for head and neck squamous cell carcinoma (HNSCC), revealing a significant rate of NOTCH1 mutations and identifying NOTCH1 as the second most frequently mutated gene after TP53. Most NOTCH1 mutations are considered inactivating, indicating that NOTCH1 is a tumor suppressor gene. On the other hand, cohorts from Asian populations with HNSCC have shown activating NOTCH1 mutations. HNSCC with NOTCH1 mutations have a worse prognosis than the NOTCH1 wild-type tumors. Additional data on other NOTCH family members have shown that NOTCH promotes HNSCC progression. NOTCH family members, including NOTCH pathway genes, are upregulated in HNSCC compared with normal tissues, and inhibition of the NOTCH pathway decreases cell proliferation and invasion. NOTCH activity in HNSCC is therefore contextual, and NOTCH in HNSCC is considered to have a bimodal role as a tumor suppressor and an oncogene. In this review, recent understandings of NOTCH pathway genes, including NOTCH genes, in HNSCC are described. In addition, the implications of NOTCH pathway alteration for HNSCC-specific NOTCH-targeted cancer therapy are explored.
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Kakurina, G. V., E. S. Kolegova, О. V. Cheremisina, and Е. L. Choinzonov. "Molecular features of head and neck squamous cell carcinoma." Bulletin of Siberian Medicine 17, no. 3 (September 29, 2018): 61–69. http://dx.doi.org/10.20538/1682-0363-2018-3-61-69.
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Relevance.To identify new markers of early diagnosis and prognosis of head and neck squamous cell carcinoma (HNSCC) it is necessary to study the molecular features of this disease.Purpose.The aim of the study was to analyze blood serum protein spectrum in patients with HNSCC and in healthy volunteers using the methods of mass spectrometry and to evaluate the selected serum protein markers as candidates for early detection of HNSCC.Materials and Methods: The blood serum of HNSCC patients before therapy with metastases, without metastases and healthy volunteers was studied by proteomic methods. Validation of the results of proteomic analysis was carried out by ELISA in serum of 52 patients with HNSCC (T1-4N0-3M0), 10 patients with chronic hyperplastic laryngitis, dysplasia DII-DIII and 10 healthy volunteers. The statistical analysis was carried out using Statistica 6.0. Software package.Results.Blood serum proteome of HNSCC patients with metastases, without metastases and healthy volunteers are different and contain proteins of different classes. Adenylyl cyclase-associated protein 1 (CAP1) and protein phosphatase 1B (PPM1B) were selected to validate the obtained results. It was shown that the serum level of CAP1 and PPM1B differed in control and dysplasia groups and dysplasia and cancer groups (p ≤ 0,05). In patients with HNSCC (T1N0M0) the serum CAP1 and PPM1B levels were higher than in patients with dysplasia and healthy individuals (p ≤ 0,05). It was noted the positive correlation of the CAP1 level in the serum with the presence of metastases and the PPM1B level.Conclusion.Candidates for serum markers of HNSCC prognosis were identified. The difference in serum levels of CAP1 and PPM1B depending on the prevalence of primary tumors and the difference in serum level of CAP1 depending on the presence of regional metastases was shown. Determination of CAP1 level in the serum can be useful for early diagnosis and prognosis of HNSCC.
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Shah, Pooja A., Chenfei Huang, Qiuli Li, Sawad A. Kazi, Lauren A. Byers, Jing Wang, Faye M. Johnson, and Mitchell J. Frederick. "NOTCH1 Signaling in Head and Neck Squamous Cell Carcinoma." Cells 9, no. 12 (December 12, 2020): 2677. http://dx.doi.org/10.3390/cells9122677.
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Biomarker-driven targeted therapies are lacking for head and neck squamous cell carcinoma (HNSCC), which is common and lethal. Efforts to develop such therapies are hindered by a genomic landscape dominated by the loss of tumor suppressor function, including NOTCH1 that is frequently mutated in HNSCC. Clearer understanding of NOTCH1 signaling in HNSCCs is crucial to clinically targeting this pathway. Structural characterization of NOTCH1 mutations in HNSCC demonstrates that most are predicted to cause loss of function, in agreement with NOTCH1’s role as a tumor suppressor in this cancer. Experimental manipulation of NOTCH1 signaling in HNSCC cell lines harboring either mutant or wild-type NOTCH1 further supports a tumor suppressor function. Additionally, the loss of NOTCH1 signaling can drive HNSCC tumorigenesis and clinical aggressiveness. Our recent data suggest that NOTCH1 controls genes involved in early differentiation that could have different phenotypic consequences depending on the cancer’s genetic background, including acquisition of pseudo-stem cell-like properties. The presence of NOTCH1 mutations may predict response to treatment with an immune checkpoint or phosphatidylinositol 3-kinase inhibitors. The latter is being tested in a clinical trial, and if validated, it may lead to the development of the first biomarker-driven targeted therapy for HNSCC.
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Boschert, Verena, Jonas Teusch, Urs D. A. Müller-Richter, Roman C. Brands, and Stefan Hartmann. "PKM2 Modulation in Head and Neck Squamous Cell Carcinoma." International Journal of Molecular Sciences 23, no. 2 (January 11, 2022): 775. http://dx.doi.org/10.3390/ijms23020775.
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The enzyme pyruvate kinase M2 (PKM2) plays a major role in the switch of tumor cells from oxidative phosphorylation to aerobic glycolysis, one of the hallmarks of cancer. Different allosteric inhibitors or activators and several posttranslational modifications regulate its activity. Head and neck squamous cell carcinoma (HNSCC) is a common disease with a high rate of recurrence. To find out more about PKM2 and its modulation in HNSCC, we examined a panel of HNSCC cells using real-time cell metabolic analysis and Western blotting with an emphasis on phosphorylation variant Tyr105 and two reagents known to impair PKM2 activity. Our results show that in HNSCC, PKM2 is commonly phosphorylated at Tyrosine 105. Its levels depended on tyrosine kinase activity, emphasizing the importance of growth factors such as EGF (epidermal growth factor) on HNSCC metabolism. Furthermore, its correlation with the expression of CD44 indicates a role in cancer stemness. Cells generally reacted with higher glycolysis to PKM2 activator DASA-58 and lower glycolysis to PKM2 inhibitor Compound 3k, but some were more susceptible to activation and others to inhibition. Our findings emphasize the need to further investigate the role of PKM2 in HNSCC, as it could aid understanding and treatment of the disease.
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Rahman, Sadia, Sandra Kraljević Pavelić, and Elitza Markova-Car. "Circadian (De)regulation in Head and Neck Squamous Cell Carcinoma." International Journal of Molecular Sciences 20, no. 11 (May 30, 2019): 2662. http://dx.doi.org/10.3390/ijms20112662.
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Head and neck cancer encompass different malignancies that develop in and around the throat, larynx, nose, sinuses and mouth. Most head and neck cancers are squamous cell carcinomas (HNSCC) that arise in the flat squamous cells that makeup the thin layer of tissue on the surface of anatomical structures in the head and neck. Each year, HNSCC is diagnosed in more than 600,000 people worldwide, with about 50,000 new cases. HNSCC is considered extremely curable if detected early. But the problem remains in treatment of inoperable cases, residues or late stages. Circadian rhythm regulation has a big role in developing various carcinomas, and head and neck tumors are no exception. A number of studies have reported that alteration in clock gene expression is associated with several cancers, including HNSCC. Analyses on circadian clock genes and their association with HNSCC have shown that expression of PER1, PER2, PER3, CRY1, CRY2, CKIε, TIM, and BMAL1 are deregulated in HNSCC tissues. This review paper comprehensively presents data on deregulation of circadian genes in HNSCC and critically evaluates their potential diagnostics and prognostics role in this type of pathology.
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Nair, Sindhu, James A. Bonner, and Markus Bredel. "EGFR Mutations in Head and Neck Squamous Cell Carcinoma." International Journal of Molecular Sciences 23, no. 7 (March 30, 2022): 3818. http://dx.doi.org/10.3390/ijms23073818.
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EGFR is a prototypical receptor tyrosine kinase that is overexpressed in multiple cancers including head and neck squamous cell carcinoma (HNSCC). The standard of care for HNSCC remains largely unchanged despite decades of research. While EGFR blockade is an attractive target in HNSCC patients and anti-EGFR strategies including monoclonal antibodies and kinase inhibitors have shown some clinical benefit, efficacy is often due to the eventual development of resistance. In this review, we discuss how the acquisition of mutations in various domains of the EGFR gene not only alter drug binding dynamics giving rise to resistance, but also how mutations can impact radiation response and overall survival in HNSCC patients. A better understanding of the EGFR mutational landscape and its dynamic effects on treatment resistance hold the potential to better stratify patients for targeted therapies in order to maximize therapeutic benefits.
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Mazumder, Tarikul, Sayantan Nath, Nibendu Nath, and Munish Kumar. "Head and Neck Squamous Cell Carcinoma: Prognosis using molecular approach." Open Life Sciences 9, no. 6 (June 1, 2014): 593–613. http://dx.doi.org/10.2478/s11535-014-0292-3.
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AbstractHead and neck squamous cell carcinoma (HNSCC) is the fifth most prevalent cancer worldwide. Apart from various known clinicopathogical factors, it is still a major concern as many genetic and epigenetic alterations bring about the possibility of this deadly disease. The aim of this review is to explore the possible role of DNA repair pathways and the polymorphic status of DNA repair genes (XPA, XPC, XPD, XRCC1 and XRCC3) in the onset of HNSCC, along with sequence variations in genes such as Glutathione S-transferases (GSTT1, M1 and P1) that are significantly associated with HNSCC risk. We also focus on the p53 gene mutation induced by various etiological agents and threat factors with its implications towards HNSCC, and emphasise the current therapeutic interventions in treating HNSCC.
10
Bais, M. V. "Impact of Epigenetic Regulation on Head and Neck Squamous Cell Carcinoma." Journal of Dental Research 98, no. 3 (January 7, 2019): 268–76. http://dx.doi.org/10.1177/0022034518816947.
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The most common type of head and neck cancer, head and neck squamous cell carcinoma (HNSCC), can develop therapeutic resistance that complicates its treatment. The 5-y survival rate for HNSCC remains at ~50%, and improving these outcomes requires a better understanding of the pathogenesis of HNSCC. Studies of HNSCC using in vitro, ex vivo, and in vivo approaches provide a novel conceptual framework based on epigenetic mechanisms for developing future clinical applications. Normal oral tissues are influenced by environmental factors that induce pathological changes affecting the network of epigenetic enzymes and signaling pathways to induce HNSCC growth and metastasis. Although various epigenetic regulator families, such as DNA methyltransferases, ten-eleven translocation proteins, histone acetyltransferases, histone deacetylases, BET bromodomain proteins, protein arginine methyltransferases, histone lysine methyltransferases, and histone lysine demethylases, have a role in diverse cancers, specific members have a function in HNSCC. Recently, lysine-specific demethylases have been identified as a potential, attractive, and novel target of HNSCC. Lysine-specific demethylase 1 (LSD1) expression is inappropriately upregulated in HNSCC and an orthotopic HNSCC mouse model. LSD1 can demethylate lysine at specific histone positions to repress gene expression or stimulate transcription, indicating a dual and context-dependent role in transcriptional regulation. Our study showed that LSD1 promotes HNSCC growth and metastasis. Pharmacological attenuation of LSD1 inhibits orthotopic and patient-derived HNSCC xenograft growth-specific target genes and signaling pathways. This review provides recent evidence demonstrating the function of epigenetic regulator enzymes in HNSCC progression, including potential therapeutic applications for such enzymes in combination and immunotherapy.
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Wang, Lei, Wenjing Pang, Kun Zhou, Lei Li, Feng Wang, Wei Cao, and Xiangjun Meng. "Risk Factors for Esophageal Squamous Cell Carcinoma in Patients with Head and Neck Squamous Cell Carcinoma." Journal of Oncology 2022 (August 27, 2022): 1–6. http://dx.doi.org/10.1155/2022/5227771.
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Background. Esophageal squamous cell carcinoma (ESCC) is a common second primary neoplasia in patients with a history of head and neck squamous cell carcinoma (HNSCC). The aim of this study was to provide further information and novel insights into the risk factors for ESCC in patients with HNSCC. Methods. We retrospectively analyzed 98 HNSCC patients diagnosed from 2007 to 2017, 30 HNSCC patients suffering from ESCC, who had undergone endoscopic examination because of positive imaging examinations or symptoms, and 68 HNSCC patients who had no ESCC occurrence for at least six years post-HNSCC diagnosis. Associated clinicopathological data and lifestyle information of the ESCC group and the without ESCC group were collected, and a case-control study of risk factors was analyzed between the two groups. Results. The majority (83.4%) of the cases with HNSCC esophageal cancers were male patients over 50 years. We established that 93.75% (30/32) of the ESCC occurred within six years after HNSCC diagnosis. HNSCC location, stage, and radiotherapy history had no significant association with the development of ESCC. High Ki67 labeling index (Ki67 LI) (>46) patients tended to be 3.1 times (95% CI = 1.3–7.6) more likely to develop ESCC compared to low Ki67 LI (≤45) patients ( P < 0.05 ). Drinkers with alcohol flushing response were at a 3.3 times higher risk to have ESCC (95% CI = 1.0–10.4) than drinkers without flush response ( P < 0.05 ). Conclusions. HNSCC patients, especially drinkers with an alcohol flushing response, as well as those with high Ki67 LI of HNSCC tissue, were more likely to develop ESCC.
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Isaacsson Velho, Pedro Henrique, Gilberto Castro, and Christine H. Chung. "Targeting the PI3K Pathway in Head and Neck Squamous Cell Carcinoma." American Society of Clinical Oncology Educational Book, no. 35 (May 2015): 123–28. http://dx.doi.org/10.14694/edbook_am.2015.35.123.
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Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosal epithelia in the head and neck region. The most common risk factors are tobacco use, alcohol consumption, and HPV infection, particularly in the oropharynx. The HPV-positive HNSCC is biologically and clinically distinct from the HPV-negative HNSCC; however, deregulations within the phosphatidylinositol 3-kinase (PI3K) pathway are frequent in both HPV-positive and HPV-negative HNSCC as it is the most frequently altered oncogenic pathway with a gain-of-function in HNSCC. This article reviews the basic biology and clinical data from the trials involving anticancer agents targeting the PI3K pathway in HNSCC. It also discusses the difficulties of translating the preclinical data to tangible clinical efficacy of these agents in patients with HNSCC even when there is significant preclinical data suggesting the PI3K pathway is a promising therapeutic target in HNSCC. We conclude that additional studies to determine appropriate patient selection for the activation of PI3K pathway and to develop targeted agents either as a monotherapy or combination therapy with favorable toxicity profiles are required before a broader clinical application.
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Major, Aidan G., Luke P. Pitty, and Camile S. Farah. "Cancer Stem Cell Markers in Head and Neck Squamous Cell Carcinoma." Stem Cells International 2013 (2013): 1–13. http://dx.doi.org/10.1155/2013/319489.
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Head and neck squamous cell carcinoma (HNSCC) is one of the world’s top ten most common cancers. Current survival rates are poor with only 50% of patients expected to survive five years after diagnosis. The poor survival rate of HNSCC is partly attributable to the tendency for diagnosis at the late stage of the disease. One of the reasons for treatment failure is thought to be related to the presence of a subpopulation of cells within the tumour called cancer stem cells (CSCs). CSCs display stem cell-like characteristics that impart resistance to conventional treatment modalities and promote tumour initiation, progression, and metastasis. Specific markers for this population have been investigated in the hope of developing a deeper understanding of their role in the pathogenesis of HNSCC and elucidating novel therapeutic strategies.
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Ingruber, Julia, Dragana Savic, Teresa Bernadette Steinbichler, Susanne Sprung, Felix Fleischer, Rudolf Glueckert, Gabriele Schweigl, Ira-Ida Skvortsova, Herbert Riechelmann, and József Dudás. "KLF4, Slug and EMT in Head and Neck Squamous Cell Carcinoma." Cells 10, no. 3 (March 3, 2021): 539. http://dx.doi.org/10.3390/cells10030539.
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Epithelial to mesenchymal transition (EMT) is clinically relevant in head and neck squamous cell carcinoma (HNSCC). We hypothesized that EMT-transcription factors (EMT-TFs) and an anti-EMT factor, Krüppel-like-factor-4 (KLF4) regulate EMT in HNSCC. Ten control mucosa and 37 HNSCC tissue samples and three HNSCC cell lines were included for investigation of EMT-TFs, KLF4 and vimentin at mRNA and protein levels. Slug gene expression was significantly higher, whereas, KLF4 gene expression was significantly lower in HNSCC than in normal mucosa. In the majority of HNSCC samples, there was a significant negative correlation between KLF4 and Slug gene expression. Slug gene expression was significantly higher in human papilloma virus (HPV) negative HNSCC, and in tumor samples with irregular p53 gene sequence. Transforming-growth-factor-beta-1 (TGF- β1) contributed to downregulation of KLF4 and upregulation of Slug. Two possible regulatory pathways could be suggested: (1) EMT-factors induced pathway, where TGF-β1 induced Slug together with vimentin, and KLF4 was down regulated at the same time; (2) p53 mutations contributed to upregulation and stabilization of Slug, where also KLF4 could co-exist with EMT-TFs.
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Ho, Alan L., Irene Brana, Robert Haddad, Jessica Bauman, Keith Bible, Sjoukje Oosting, Deborah J. Wong, et al. "Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations." Journal of Clinical Oncology 39, no. 17 (June 10, 2021): 1856–64. http://dx.doi.org/10.1200/jco.20.02903.
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PURPOSE Mutations in the HRAS (m HRAS) proto-oncogene occur in 4%-8% of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Tipifarnib is a farnesyltransferase inhibitor that disrupts HRAS function. We evaluated the efficacy of tipifarnib in patients with R/M m HRAS HNSCC. METHODS We enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for m HRAS malignancies; one additional patient was treated on an expanded access program. After an ad hoc analysis of the first 16 patients with HNSCC with m HRAS variant allele frequency (VAF) data, enrollment was limited to those with a m HRAS VAF of ≥ 20% (high VAF). The primary end point was objective response rate. Secondary end points included assessing safety and tolerability. Patients received tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles. RESULTS Of the 22 patients with HNSCC with high VAF, 20 were evaluable for response at the time of data cutoff. Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7). The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anemia (37%) and lymphopenia (13%). CONCLUSION Tipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with HRAS mutations for whom limited therapeutic options exist ( NCT02383927 ).
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Charap, Andrew J., Tomohiro Enokida, Rachel Brody, John Sfakianos, Brett Miles, Nina Bhardwaj, and Amir Horowitz. "Landscape of natural killer cell activity in head and neck squamous cell carcinoma." Journal for ImmunoTherapy of Cancer 8, no. 2 (December 2020): e001523. http://dx.doi.org/10.1136/jitc-2020-001523.
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Head and neck squamous cell carcinoma (HNSCC) encompasses a set of cancers arising from the epithelia of the upper aerodigestive tract, accounting for a significant burden of disease worldwide due to the disease’s mortality, morbidity, and predilection for recurrence. Prognosis of HNSCC in the recurrent and/or metastatic (R/M-HNSCC) setting is especially poor and effective treatment options increasingly rely on modulating T-cell antitumor responses. Still, immunotherapy response rates are generally low, prompting the exploration of novel strategies that incorporate other effector cells within the tumor microenvironment. Within the last decade, important advances have been made leveraging the powerful innate antitumor function of natural killer (NK) cells to treat solid tumors, including head and neck squamous cell carcinoma. NK cells are hybrid innate-adaptive effector cells capable of directly eliminating tumor cells in addition to initiating adaptive antitumor immune responses. In the setting of HNSCC, NK cells are important for tumor surveillance and control, and NK cell infiltration has repeatedly been associated with a favorable prognosis. Yet, HNSCC-infiltrating NK cells are susceptible to an array of immune evasion strategies employed by tumors that must be overcome to fully realize the antitumor potential of NK cells. We believe that a conceptual framework informed by the basic biological understanding of the mechanisms underlying NK cell activation can improve treatment of HNSCC, in part by selecting for patients most likely to respond to NK cell-based immunotherapy. Herein, we review the activity of NK cells in HNSCC, paying special attention to the role of environmental and genetic determinants of NK cell antitumor function. Moreover, we explore the evidence that NK cells are a crucial determinant of the efficacy of both established and emerging treatments for HNSCC.
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Qi, Zongtai, Yating Liu, Michael Mints, Riley Mullins, Reilly Sample, Travis Law, Thomas Barrett, et al. "Single-Cell Deconvolution of Head and Neck Squamous Cell Carcinoma." Cancers 13, no. 6 (March 11, 2021): 1230. http://dx.doi.org/10.3390/cancers13061230.
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Complexities in cell-type composition have rightfully led to skepticism and caution in the interpretation of bulk transcriptomic analyses. Recent studies have shown that deconvolution algorithms can be utilized to computationally estimate cell-type proportions from the gene expression data of bulk blood samples, but their performance when applied to tumor tissues, including those from head and neck, remains poorly characterized. Here, we use single-cell data (~6000 single cells) collected from 21 head and neck squamous cell carcinoma (HNSCC) samples to generate cell-type-specific gene expression signatures. We leverage bulk RNA-seq data from >500 HNSCC samples profiled by The Cancer Genome Atlas (TCGA), and using single-cell data as a reference, apply two newly developed deconvolution algorithms (CIBERSORTx and MuSiC) to the bulk transcriptome data to quantitatively estimate cell-type proportions for each tumor in TCGA. We show that these two algorithms produce similar estimates of constituent/major cell-type proportions and that a high T-cell fraction correlates with improved survival. By further characterizing T-cell subpopulations, we identify that regulatory T-cells (Tregs) were the major contributor to this improved survival. Lastly, we assessed gene expression, specifically in the Treg population, and found that TNFRSF4 (Tumor Necrosis Factor Receptor Superfamily Member 4) was differentially expressed in the core Treg subpopulation. Moreover, higher TNFRSF4 expression was associated with greater survival, suggesting that TNFRSF4 could play a key role in mechanisms underlying the contribution of Treg in HNSCC outcomes.
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Zhou, Xin, and Xiaoshen Wang. "Radioimmunotherapy in HPV-Associated Head and Neck Squamous Cell Carcinoma." Biomedicines 10, no. 8 (August 17, 2022): 1990. http://dx.doi.org/10.3390/biomedicines10081990.
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HPV-associated head and neck squamous cell carcinoma (HNSCC) is a cancer entity with unique biological and clinical characteristics that requires more personalized treatment strategies. As the backbone of conventional therapeutics, radiation is now harnessed to synergize with immunotherapy in multiple malignancies. Accumulating preclinical and clinical data have suggested the potential of radioimmunotherapy in eliciting local and systemic anti-tumor response via direct killing of tumor cells and immunogenic cell death. However, this effect remains uncertain in HPV-associated HNSCC. Owing to its intrinsic radiosensitivity and distinct tumor microenvironment, HPV-associated HNSCC may represent a good candidate for radioimmunotherapy. In this review, we provide a detailed illustration of the biology, the genomic features, and immune landscapes of HPV-associated HNSCC that support the synergism between radiation and immune agents. The interaction between radiotherapy and immunotherapy is described. We also highlight the present evidence as well as ongoing trials using different combination strategies in the recurrent/metastatic or definitive settings. In addition, we have summarized the challenges and outlook for future trial design, with special emphasis on radiotherapy optimization and novel therapeutic options to incorporate.
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Xie, Jing, Quan Li, Xi Ding, and Yunyun Gao. "Targeting mTOR by CZ415 Inhibits Head and Neck Squamous Cell Carcinoma Cells." Cellular Physiology and Biochemistry 46, no. 2 (2018): 676–86. http://dx.doi.org/10.1159/000488724.
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Background/Aims: mTOR is an important therapeutic target for human head and neck squamous cell carcinoma (HNSCC). The current study tested the anti-HNSCC cell activity by a mTOR kinase inhibitor CZ415. Methods: HNSCC cells were treated with CZ415. Cell death was tested by lactate dehydrogenase (LDH) assay and MTT assay. Cell proliferation was tested by BrdU ELISA assay and [H3] thymidine incorporation assay, with apoptosis assayed by the TUNEL staining. A Western blotting assay was applied to test autophagy-associated proteins, mTOR and signalings. The nude mice xenograft model was established to study CZ415-mediated anti-tumor activity. Results: In established (SCC-9, SQ20B and A253 lines) and primary human HNSCC cells, CZ415 efficiently inhibited cell survival and proliferation. CZ415 blocked mTORC1/2 activation and inhibited ERK in HNSCC cells. CZ415 provoked feedback autophagy activation. Conversely, autophagy inhibitors (3-methyladenine and chloroquine) or Beclin-1 shRNA sensitized CZ415-induced HNSCC cell death. In vivo, CZ415 gavage inhibited SCC-9 tumor growth in nude mice, showing higher efficiency against Beclin-1-silenced tumors. Conclusion: CZ415 inhibits HNSCC cell growth in vitro and in vivo. Inhibition of autophagy can further sensitize CZ415 against HNSCC cells.
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Dudás, József, Anna Riml, Raphaela Tuertscher, Christian Pritz, Teresa Steinbichler, Volker Schartinger, Susanne Sprung, et al. "Brain-Derived Neurotrophin and TrkB in Head and Neck Squamous Cell Carcinoma." International Journal of Molecular Sciences 20, no. 2 (January 11, 2019): 272. http://dx.doi.org/10.3390/ijms20020272.
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We hypothesized that in head and neck squamous cell carcinoma (HNSCC), the neurotrophin brain-derived neurotrophic factor (BDNF) and its high affinity receptor TrkB regulate tumor cell survival, invasion, and therapy resistance. We used in situ hybridization for BDNF and immunohistochemistry (IHC) for TrkB in 131 HNSCC samples. Brain-derived neurotrophic factor was highly expressed in normal mucosa in HNSCC tissue and in cell lines, whereas only 42.74% of HNSCC tissue was TrkB+. One fourth of HNSCC cases was human papilloma virus (HPV)− positive, but the TrkB IHC frequency was not different in HPV-positive (HPV+) and negative cases. The UPCI-SCC090 cells expressed constitutive levels of TrkB. Transforming-growth-factor-β1 (1 ng/mL TGF-β1) induced TrkB in a subpopulation of SCC-25 cells. A single 10-µg/mL mitomycin C treatment in UPCI-SCC090 cells induced apoptosis and BDNF did not rescue them. The SCC-25 cells were resistant to the MMC treatment, and their growth decreased after TGF-β1 treatment, but was restored by BDNF if it followed TGF-β1. Taken together, BDNF might be ineffective in HPV+ HNSCC patients. In HPV− HNSCC patients, tumor cells did not die after chemotherapeutic challenge and BDNF with TGF-β1 could improve tumor cell survival and contribute to worse patient prognosis.
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Veigas, Florencia, Yamil D. Mahmoud, Joaquin Merlo, Adriana Rinflerch, Gabriel Adrian Rabinovich, and María Romina Girotti. "Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma." Cancers 13, no. 5 (March 1, 2021): 1018. http://dx.doi.org/10.3390/cancers13051018.
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Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors usually diagnosed at an advanced stage and characterized by a poor prognosis. The main risk factors associated with its development include tobacco and alcohol consumption and Human Papillomavirus (HPV) infections. The immune system has a significant role in the oncogenesis and evolution of this cancer type. Notably, the immunosuppressive tumor microenvironment triggers immune escape through several mechanisms. The improved understanding of the antitumor immune response in solid tumors and the role of the immune checkpoint molecules and other immune regulators have led to the development of novel therapeutic strategies that revolutionized the clinical management of HNSCC. However, the limited overall response rate to immunotherapy urges identifying predictive biomarkers of response and resistance to treatment. Here, we review the role of the immune system and immune checkpoint pathways in HNSCC, the most relevant clinical findings linked to immunotherapeutic strategies and predictive biomarkers of response and future treatment perspectives.
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Cho, Won Jin, David Kessel, Joseph Rakowski, Brian Loughery, Abdo J. Najy, Tri Pham, Seongho Kim, et al. "Photodynamic Therapy as a Potent Radiosensitizer in Head and Neck Squamous Cell Carcinoma." Cancers 13, no. 6 (March 10, 2021): 1193. http://dx.doi.org/10.3390/cancers13061193.
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Despite recent advances in therapeutic modalities such as radiochemotherapy, the long-term prognosis for patients with advanced head and neck squamous cell carcinoma (HNSCC), especially nonviral HNSCC, remains very poor, while survival of patients with human papillomavirus (HPV)-associated HNSCC is greatly improved after radiotherapy. The goal of this study is to develop a mechanism-based treatment protocol for high-risk patients with HPV-negative HNSCC. To achieve our goal, we have investigated molecular mechanisms underlying differential radiation sensitivity between HPV-positive and -negative HNSCC cells. Here, we found that autophagy is associated with radioresistance in HPV-negative HNSCC, whereas apoptosis is associated with radiation sensitive HPV-positive HNSCC. Interestingly, we found that photodynamic therapy (PDT) directed at the endoplasmic reticulum (ER)/mitochondria initially induces paraptosis followed by apoptosis. This led to a substantial increase in radiation responsiveness in HPV-negative HNSCC, while the same PDT treatment had a minimal effect on HPV-positive cells. Here, we provide evidence that the autophagic adaptor p62 mediates signal relay for the induction of apoptosis, promoting ionizing radiation (XRT)-induced cell death in HPV-negative HNSCC. This work proposes that ER/mitochondria-targeted PDT can serve as a radiosensitizer in intrinsically radioresistant HNSCC that exhibits an increased autophagic flux.
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Stukan, A. I., V. A. Porhanov, V. N. Bodnya, O. Yu Chuhraj, Y. M. Makarova, and I. S. Elizbaryan. "Molecular and genetic profile of head and neck squamous cell carcinoma." Medical Herald of the South of Russia 9, no. 3 (October 1, 2018): 50–57. http://dx.doi.org/10.21886/2219-8075-2018-9-3-50-57.
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To determine the molecular pathways of head and neck squamous cell carcinoma (HNSCC) tumorogenesis there are held a great amount of investigations. New therapeutic models for HNSCC are discussed considering genetic and biochemical specifications and taking in account significant scientific strategies. Dividing HNSCC into 2 large groups in accordance to human papilloma virus (HPV) association with different survival rates is a great achievement of the last decades in carcinogenesis researching and treatment of HNSCC. It is well known that chemical carcinogens are the main cause of HPV-negative tumors development. HPV-positive HNSCC is associated with E6 and E7 HPV proteins. The results of whole exome sequencing of HNSCC are of the great interest. Molecular expression profile of Rb-E2F/p53 were diff erent in HPV-positive and HPV-negative tumors. The phosphorylated pRb and p16 proteins analysis showed low pRb and high p16 levels in HPV-positive tumors in contrast to HPV-negative samples due to the HPV E7 ability to degrade Rb. P16 expression was higher in HPV-positive tumors, so it is immunohystochemical marker of HPV-positive status. The p53 expression pattern is determined also to identify its mechanism of degradation in HPV-positive tumors. Due to carcinogenic HPV ability by inactivation of cell cycle regulators р53 and pRb with the help of E6 and E7 oncoproteins, mutations of TP 53 shouldn’t play leading role in HPV-induced tomorogenity. Nevertheless, there are controversial data concerning HPV-positive tumors that part of them gain p53-mutations at the same time having integrated HPV-genome. The p53 expression in HPV-positive samples was the same as if in the absence of HPV.
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Zhang, Yaoting, Sultan Kadasah, Jiaheng Xie, and Dongsheng Gu. "Head and Neck Squamous Cell Carcinoma: NT5E Could Be a Prognostic Biomarker." Applied Bionics and Biomechanics 2022 (April 25, 2022): 1–14. http://dx.doi.org/10.1155/2022/3051907.
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Head and neck squamous cell carcinoma (HNSCC) is a type of tumour with a relatively poor prognosis. In recent years, immune checkpoint inhibitors, such as CTLA-4 and PD-1/PDL-1 inhibitors, have improved the treatment status of advanced tumours. However, the emergence of drug resistance has brought difficulties to clinical treatment, and new immune checkpoint research is imminent. The hypoxia-adenosine pathway, in which CD73 encoded by the NT5E gene is a key enzyme for adenosine production, has been identified as an immune checkpoint of great potential. Therefore, NT5E may play an important role in HNSCC. We performed a detailed bioinformatics analysis of NT5E in HNSCC, and the results showed that the overexpression of NT5E in HNSCC was associated with poor prognosis. Our further investigation of the coexpression pattern of HNSCC could provide a reference for drug resistance and immunotherapy studies.
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Zhang, Yaoting, Sultan Kadasah, Jiaheng Xie, and Dongsheng Gu. "Head and Neck Squamous Cell Carcinoma: NT5E Could Be a Prognostic Biomarker." Applied Bionics and Biomechanics 2022 (April 25, 2022): 1–14. http://dx.doi.org/10.1155/2022/3051907.
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Head and neck squamous cell carcinoma (HNSCC) is a type of tumour with a relatively poor prognosis. In recent years, immune checkpoint inhibitors, such as CTLA-4 and PD-1/PDL-1 inhibitors, have improved the treatment status of advanced tumours. However, the emergence of drug resistance has brought difficulties to clinical treatment, and new immune checkpoint research is imminent. The hypoxia-adenosine pathway, in which CD73 encoded by the NT5E gene is a key enzyme for adenosine production, has been identified as an immune checkpoint of great potential. Therefore, NT5E may play an important role in HNSCC. We performed a detailed bioinformatics analysis of NT5E in HNSCC, and the results showed that the overexpression of NT5E in HNSCC was associated with poor prognosis. Our further investigation of the coexpression pattern of HNSCC could provide a reference for drug resistance and immunotherapy studies.
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Huang, Chao-Cheng, Ching-Mei Chen, and Chih-Yen Chien. "S145 – RAP1 Expression in Squamous Cell Carcinoma of Head and Neck." Otolaryngology–Head and Neck Surgery 139, no. 2_suppl (August 2008): P125. http://dx.doi.org/10.1016/j.otohns.2008.05.318.
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Objectives Rap1 has been shown to be activated in response to various growth factors, cytokines, and chemokines that act on receptor tyrosine kinases (RTKs) or G-protein-coupled receptors, and implicated in a wide range of biochemical pathways in all eukaryotic cells through a number of distinct effectors. This study was aimed to investigate the role of RAP1 in the tumorigenesis of squamous cell carcinoma of head and neck (HNSCC). Methods Immunohistochemical analysis was performed to study RAP1, CK 10, and E-cadherin expressions on the paraffin-embedded tissue of 198 HNSCCs. The relationship between RAP1 expression and the clinical prognosis was also investigated. Results RAP1 expression was readily detected in the normal epithelium and the well-differentiated HNSCC, whereas its expression turned to be weak or undetectable in the poorly differentiated HNSCC (p < 0.001). When RAP1 expression was decreased, the expressions of CK 10 (differentiation marker) and E-cadherin protein were also down regulated. In addition, patients with high RAP1 expression had significantly longer median survival than patients with low RAP1 expression (median = 51.21 vs. 13.14 months, p <0.001) by survival analysis based on the Kaplan-Meier method. Conclusions RAP1 expression may be related to cell differentiation in HNSCC. In addition, RAP1 could be a useful biomarker for tumor progression and survival of HNSCC.
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Wicker, Christina Ann, Samuel Thompson, Poornima Dubey, and Vinita Takiar. "Abstract 6062: Radiosensitizing head and neck squamous cell carcinoma using isothiocyanates." Cancer Research 82, no. 12_Supplement (June 15, 2022): 6062. http://dx.doi.org/10.1158/1538-7445.am2022-6062.
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Abstract Head and neck cancer kills over 400,000 people each year with the majority of cases being head and neck squamous cell carcinoma (HNSCC). Despite major advances in cancer treatment, radiation resistance contributes to increased morbidity and mortality of patients with HNSCC. Few FDA-approved radiosensitizers exist for the treatment of HNSCC and the majority are associated with severe adverse effects. Therefore, there is a clear need to examine novel treatment combinations to improve radiosensitivity and HNSCC outcomes. Isothiocyanates enhance response to cytokines, chemotherapy, and radiation in other in vitro and in vivo cancer models, including pancreatic and breast cancer. Isothiocyanates are antioxidants found in cruciferous vegetables such as watercress and broccoli. Phenethyl isothiocyanate (PEITC) was well tolerated by patients in chemopreventative clinical trials and was thus selected for this study. We hypothesize that PEITC radiosensitizes HNSCC cells through increasing DNA damage, apoptosis and reactive oxygen species (ROS). Non-human papilloma virus or P16 negative HNSCC are associated with increased radioresistance and as such human HNSCC cell lines HN5 and CAL27 were selected. Combination of PEITC and photon radiation (XRT) decreased cell survival by half as compared to cells treated with PEITC or XRT alone for both HN5 and CAL27 cells as determined by clonogenic assay (n≥3). PEITC enhanced XRT-induced apoptosis in HN5 and CAL27 cells as indicated by increased cleavage of effector caspases 3 and 7, which was reversed upon treatment with pan-caspase inhibitor, QVD-OPH. Preliminary comet assays identified that combination of PEITC with XRT significantly increased Tail DNA % relative to vehicle (p<0.001), PEITC alone (p<0.0001), or XRT alone (p<0.0001) in HN5 cells. Preliminary data in CAL27 cells identified significantly increased signal of y-H2Ax in cells treated with both PEITC and XRT was 2.2 fold higher than XRT alone (p<0.001) and 12.1 fold higher than PEITC alone (p<0.001) in CAL27 cells. PEITC increased XRT-induced ROS generation in CAL27 cells relative to independent treatment as determined by 2′,7′ dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Taken together, these results support that PEITC synergistically enhances HNSCC cell response to XRT. The results of this study warrant further investigation into the potential of PEITC to improve radiation efficacy in pre-clinical HNSCC models with the long-term goal of testing this well-tolerated compound in clinical trials. Citation Format: Christina Ann Wicker, Samuel Thompson, Poornima Dubey, Vinita Takiar. Radiosensitizing head and neck squamous cell carcinoma using isothiocyanates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6062.
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Kemal, Yasemin, Ozgur Kemal, Mehmet Kefeli, Ayse Bel, Nilgun Sahin, Sinan Atmaca, Mehmet Koyuncu, and Idris Yucel. "Human papillomavirus detection in head and neck squamous cell carcinoma in Turkey." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e17538-e17538. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e17538.
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e17538 Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide. In Turkey, 5538 new cases and 2340 deaths from head and neck cancer are estimated to occur every year. Tobacco and alcohol are the most important etiological risk factors but in the past three decads tobacco usage is decreased and Human Papilloma Virus (HPV) has changed HNSCC epidemiology. Many new reports suggests that almost 25% of all cases of HNSCC are related to HPV. But its prevelans shows a wide variation among different populations.Today in Turkey HPV positivity in HNSCC is currently not known and this retrospective study aimed to to evaluate the HPV infection in our HNSCC patients. Methods: We included 125 HNSCC patients diagnosed and treated in our hospital beween January 2010 and December 2016. Oral cavity, oropharyngeal, laryngeal and hypopharyngeal cancers were included. Nasopharyngeal and salivary gland cancers were exculuded. Head and neck cancer tissue samples fixed using 10% Neutral Buffered Formalin and embedded blocks were used. From an initial evaluation of 125 patients records 77 of the paients blocks could be adequate for the HPV testing. Detection and genotyping of HPV genotypes were done using a polymerase chain reaction (PCR) protocol. Results: PCR amplification was succesful in 61 of 77 patients. Among the 61 HNSCC patients only 3 patients were HPV positive(4.9 %). HPV 16 subtype was detected in one patient who was 70 years old male, stage III laryngeal cancer with a smoking history. The subtypes detected in other two patients were different from 16 and 18. One of these patients was 42 years old nonsmoker female stage IVa hypopharyngeal cancer and the other one was 56 years old smoker male with stage II oropharyngeal cancer. Conclusions: In Turkey, this is the first study that evaluated HPV positivity in HNSCC. Our results suggest a low prevelance of HPV in Turkish HNSCC patients; large scale population based studies are needed to confirm our findings.
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Nasib, Bushra, Maria Tasneem Khattak, Raazia Mahmood, Shahid Hasnain, Sahibzadi Fatima Tariq, and Masroor Hassan. "Expression of P16 in Head and Neck Squamous Cell Carcinoma." Pakistan Journal of Medical and Health Sciences 16, no. 1 (January 30, 2022): 1072–76. http://dx.doi.org/10.53350/pjmhs221611072.
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Introduction: Head and neck squamous cell carcinoma (HNSCC) is a malignant neoplasm that arises in the oral cavity, nasal cavity, paranasal sinuses, oropharynx, nasopharnx, and larynx. Among various prognostic markers in HNSCC, demonstration of p16 protein expression is of great importance. Objective: To determine the frequency of p16 expression in head and neck squamous cell carcinoma by Immuno-histochemistry (IHC) in patients reporting at Rehman Medical Institute. Methodology: This was descriptive, cross sectional study piloted at the Department of Histopathology, Rehman Medical Institute (RMI) for a period of six months from 10/March/2016 to 10/September/2016. This study was carried out on a total of 103 patients diagnosed with head and neck squamous cell carcinoma. On Formalin Fixed Parafin embedded blocks of already diagnosed OSCC cases, IHC staining was done by using p16 (monoclonal) antibody on FFPE blocks of OSCC. Statistical analysis of the data was done by using the software SPSS version 20. Results: p16 was positive in 95 cases (92.2%) and negative in 8 cases (7.8%). Chi-square test was performed between p16 and site of biopsy, a significant relation was observed with P-value 0.023 (<0.05). Of all the positive cases, p16 was positive in 51 cases (53.7%) of oral cavity SCC, 17 cases (17.9%) of pharyngeal SCC, 23 cases (24.2 %) of laryngeal SCC and 4 cases (4.2%) of nasal cavity SCC. Conclusion: High expression of p16 was observed in HNSCC cases with correlation to various sites of Head and Neck. Keywords: HNSCC, p16; Prognosis, Cancer
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Monroe, Marcus M., Eric C. Anderson, Daniel R. Clayburgh, and Melissa H. Wong. "Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma." Journal of Oncology 2011 (2011): 1–8. http://dx.doi.org/10.1155/2011/762780.
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Accumulating evidence suggests that self-renewal and differentiation capabilities reside only in a subpopulation of tumor cells, termed cancer stem cells (CSCs), whereas the remaining tumor cell population lacks the ability to initiate tumor development or support continued tumor growth. In head and neck squamous cell carcinoma (HNSCC), as with other malignancies, cancer stem cells have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In this paper we summarize the current knowledge of the role of CSCs in HNSCC and discuss the therapeutic implications and future directions of this field.
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Yousaf, Sabeeh, Sajjad Ali Shahid, and Obaid Hayat. "SQUAMOUS CELL CARCINOMA." Professional Medical Journal 25, no. 12 (December 8, 2018): 1840–47. http://dx.doi.org/10.29309/tpmj/18.4785.
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Background: Head and Neck Squamous cell carcinoma is the sixth most common cancer globally with increasing frequency in developing countries. Despite huge advancement in surgery, radiotherapy and chemotherapy there is a little changed in the overall survival rate for patient with HNSCC over the past few decades. Due to its late diagnosis and lack of availability of reliable biomarker for this disease, its incidence is still on rise. Aims &Objectives: This study was aimed to study the expression of miR-21 in the tumor genesis of HNSCC. The objective of the study is to analyze the expression profile of miR-21 in HNSCC, to study the miRNA expression profile of miR-21 between control and tumor samples, to study the expression profile of miR-21 benign tumors and different categories of HNSCC Tumors on the basis of Histological Differentiation, gender-based Comparison of Benign and Malignant HNSCC Tumors, age-based Comparison of Benign and Malignant HNSCC Tumors, tumor Sitebased Comparison of Benign and Malignant HNSCC Tumors. Study Design: Case-control study. Study Setting: The University of Lahore. Period: June -2014 June -2105. Materials & Methods: In this research, 43 Formalin-fixed paraffin embedded (FFPE) tissue samples (31 malignant HNSCC samples and 12 benign tumors from the same region) of both genders and aged 15-80 years were included in this study. 31 cases were malignant tumors were further consisted of 14 well-, 11 moderately- and 6 poorly differentiated tumors. Total RNA was extracted using PureLink FFPE RNA Isolation Kit and Two-Step RT-PCR was performed. TaqMan primer/ probe sets were used for the target miRNA- 221, while RNUB6 was the normalization control.By calculating __Ct and fold change difference according to Livak method. late onset disease the Relative quantification was done to determine the level of expression of miRNA-221. Tumor site did not show any effect on miR-21 expression levels. Results: Our results showed that the malignant samples have higher expression level of miR-21 then benign control samples. Significantly higher expression was observed in moderately and poorly categories of HNSCC. Gender-based expression showed that females had higher level of expression, while it was found that its expression is high in late onset disease. Tumor site did not show any effect on miR-21 expression levels. Conclusion: Our miRNA expression profile provides a potential strategy for finding new head and neck squamous cell carcinoma (HNSCC) molecular targets. miR-21 could be regarded as potential diagnostic marker in HNSCC.
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Chang, Hyun, Yun-Gyoo Lee, Yoon Ho Ko, Jang Ho Cho, Jong-Kwon Choi, Keon Uk Park, Eun Joo Kang, et al. "Prognostic Value of CD200R1 mRNA Expression in Head and Neck Squamous Cell Carcinoma." Cancers 12, no. 7 (July 3, 2020): 1777. http://dx.doi.org/10.3390/cancers12071777.
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Immune system dysfunction is associated with head and neck squamous cell carcinoma (HNSCC) development and progression and immune checkpoint inhibitors have demonstrated substantial survival benefits in platinum-refractory HNSCC; therefore, we examined the prognostic value of immune-related gene (IRG) expression in HNSCC. We analyzed the expression of 82 IRGs in 71 patients with HNSCC enrolled in a feasibility study for a prospective HNSCC biomarker-driven umbrella trial (Korean Cancer Study Group TRIUMPH study, NCT03292250). CD200R1 was identified as an independent prognostic factor and validated in GEO and TCGA database. CD2000R1 mRNA expression was found to be an independent favorable prognostic factor in patients with HNSCC. Moreover, CD200R1 was found to affect genes and pathways associated with the immune response, while seven differentially expressed genes (CD8A, DOK2, CX3CR1, TYROBP, CXCL9, CD300LF, IFNG) were associated with CD200R1 expression. Samples with higher CD200R1 expression displayed higher tumor-infiltrating immune cell counts both in silico and in histological analysis. These findings will help in the development of more accurate prognostic tools and suggest CD200R1 modulation as a HNSCC immunotherapy.
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Merkley, Mark A., Paul M. Weinberger, Lana L. Jackson, Robert H. Podolsky, Jeffrey R. Lee, and William S. Dynan. "2D-DIGE proteomic characterization of head and neck squamous cell carcinoma." Otolaryngology–Head and Neck Surgery 141, no. 5 (November 2009): 626–32. http://dx.doi.org/10.1016/j.otohns.2009.08.011.
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Objective: Identify proteins that are differentially expressed between head and neck squamous cell cancer (HNSCC) and patient-matched normal adjacent tissue, and validate findings in a separate patient cohort. Study Design: Cross-sectional study of surgical specimens. Setting: Tertiary care academic medical center. Subjects and Methods: Laser capture microdissection and two-dimensional difference gel electrophoresis were used previously to establish proteomic profiles for tumor and normal adjacent tissue from 14 patients. Here, significance analysis of microarray was used to rank candidate biomarkers. Spots meeting statistical and biological criteria of significance were analyzed by liquid chromatography and tandem mass spectrometry to obtain protein identifications. The expression pattern of the highest-ranked candidate biomarker (cornulin) was validated in a larger, independent patient cohort (n = 68) by immunohistochemical staining of a tissue microarray. Results: Of 732 spots, 117 (15.9%) met criteria for significance. Identities were obtained for 39 spots, representing 17 different proteins. Four proteins were novel in the context of HNSCC: glutathione synthetase, which was upregulated; and cornulin (squamous epithelial heat shock protein 53), guanylate binding protein 6, and heat shock 70 kDa protein 5 (glucose-regulated protein, 78 kDa), which were downregulated. Cornulin functions in the stress response in normal squamous epithelium, and reduced expression has been proposed as a marker of susceptibility to laryngopharyngeal reflux and other stressors. Loss of cornulin expression was confirmed in an independent HNSCC patient cohort ( P < 0.001). Conclusions: Downregulation of cornulin is a prominent feature of the molecular signature of HNSCC identified by comparative proteomics. Cornulin may represent a link between HNSCC and other pathologies arising in stratified squamous epithelium.
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Cristina, Valerie, Ruth Gabriela Herrera-Gómez, Petr Szturz, Vittoria Espeli, and Marco Siano. "Immunotherapies and Future Combination Strategies for Head and Neck Squamous Cell Carcinoma." International Journal of Molecular Sciences 20, no. 21 (October 30, 2019): 5399. http://dx.doi.org/10.3390/ijms20215399.
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Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage and has a dismal prognosis. Nearly 10 years after the approval of cetuximab, anti-PD1/PD-L1 checkpoint inhibitors are the first drugs that have shown any survival benefit for the treatment on platinum-refractory recurrent/metastatic (R/M) HNSCC. Furthermore, checkpoint inhibitors are better tolerated than chemotherapy. The state of the art in the treatment of R/M HNSCC is changing, thanks to improved results for checkpoint inhibitors. Results for these treatments are also awaited in curative settings and for locally advanced HNSCC. Unfortunately, the response rate of immunotherapy is low. Therefore, the identification of predictive biomarkers of response and resistance to anti-PD1/PD-L1 is a key point for better selecting patients that would benefit the most from immunotherapy. Furthermore, the combination of checkpoint inhibitors with various agents is being currently evaluated to improve the response rate, prolong response duration, and even increase the chances for a cure. In this review, we summarize the most important results regarding immune targeting agents for HNSCC, predictive biomarkers for resistance to immune therapies, and future perspectives.
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John, Keziah, Jennifer Wu, Bing-Wei Lee, and Camile S. Farah. "MicroRNAs in Head and Neck Cancer." International Journal of Dentistry 2013 (2013): 1–12. http://dx.doi.org/10.1155/2013/650218.
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microRNAs (miRs) are small noncoding single-stranded RNAs, about 19–25 nucleotides long. They have been shown to be capable of altering mRNA expression; thus some are oncogenic or tumour suppressive in nature and are regulated by cellular and epigenetic factors. The molecular pathogenic pathway of many cancers has been modified since the discovery of miRs. Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer in the world, has recently been associated with infection by the human papillomavirus (HPV). miR expression profiles are altered in the transition from dysplasia to carcinoma, with some changes being specific to the underlying risk factor. This difference is particularly significant in HPV-positive HNSCC where host miRs are modulated by the virus, creating a different profile to HPV-negative HNSCC. Saliva, as an easily collected proximal biofluid containing numerous miRs, presents an attractive noninvasive diagnostic tool in detecting HNSCC and determining prognosis. Furthermore, miRs may play a role in the analysis of surgical margins for residual tumour extension and in the development of novel miR-based therapeutic targets and agents.
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Jimenez, Lizandra, Sangeeta K. Jayakar, Thomas J. Ow, and Jeffrey E. Segall. "Mechanisms of Invasion in Head and Neck Cancer." Archives of Pathology & Laboratory Medicine 139, no. 11 (June 5, 2015): 1334–48. http://dx.doi.org/10.5858/arpa.2014-0498-ra.
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Context The highly invasive properties demonstrated by head and neck squamous cell carcinoma (HNSCC) are often associated with locoregional recurrence and lymph node metastasis in patients and is a key factor leading to an expected 5-year survival rate of approximately 50% for patients with advanced disease. It is important to understand the features and mediators of HNSCC invasion so that new treatment approaches can be developed. Objectives To provide an overview of the characteristics, mediators, and mechanisms of HNSCC invasion. Data Sources A literature review of peer-reviewed articles in PubMed on HNSCC invasion. Conclusions Histologic features of HNSCC tumors can help predict prognosis and influence clinical treatment decisions. Cell surface receptors, signaling pathways, proteases, invadopodia function, epithelial-mesenchymal transition, microRNAs, and tumor microenvironment are all involved in the regulation of the invasive behavior of HNSCC cells. Identifying effective HNSCC invasion inhibitors has the potential to improve outcomes for patients by reducing the rate of spread and increasing responsiveness to chemoradiation.
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Suzuki, Shinsuke, Satoshi Toyoma, Yohei Kawasaki, and Takechiyo Yamada. "Irradiated fibroblasts increase interleukin-6 expression and induce migration of head and neck squamous cell carcinoma." PLOS ONE 17, no. 1 (January 28, 2022): e0262549. http://dx.doi.org/10.1371/journal.pone.0262549.
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Background Cytotoxic effects of radiation play an important role in the treatment of head and neck cancer. However, irradiation is known to lead to the migration of various cancer cells, including those of head and neck cancer. Recently, fibroblasts in the cancer microenvironment have been reported to be involved in this mechanism. Nevertheless, the mechanism underlying migration of head and neck cancer cells remains unclear. Herein, we aimed to elucidate this migration mechanism induced by irradiation in terms of the interaction of head and neck cancer cells with fibroblasts. Methods We used the head and neck squamous cell carcinoma (HNSCC) cell lines SAS and FaDu as well as fibroblast cell lines. These cells were irradiated and their viability was compared. In fibroblasts, changes in interleukin-6 (IL-6) secretion caused by irradiation were measured by enzyme-linked immunosorbent assay (ELISA). The cell migration ability of cancer cells was evaluated via a migration assay using a semipermeable membrane. HNSCC cells were cocultured with irradiated and nonirradiated fibroblasts, and their migration ability under each condition was compared. We also examined the effect of IL-6 on the migration of HNSCC cells. Furthermore, to investigate the effect of fibroblast-derived IL-6 on the migration ability of HNSCC cells, we conducted a coculture study using IL-6 neutralizing antibody. Results Irradiation reduced the survival of HNSCC cells, whereas fibroblasts were resistant to irradiation. Irradiation also increased IL-6 secretion by fibroblasts. Migration of HNSCC cells was enhanced by coculture with fibroblasts and further enhanced by coculture with irradiated fibroblasts. We also confirmed that the migration of HNSCC cells was induced by IL-6. The enhanced migration of cancer cells caused by coculturing with fibroblasts was canceled by the IL-6 neutralizing antibody. Conclusion These results show that fibroblasts survive irradiation and induce the migration ability of HNSCC cells through increased secretion of IL-6.
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Nakagawa, Takuya, Tomoya Kurokawa, Masato Mima, Sakiko Imamoto, Harue Mizokami, Satoru Kondo, Yoshitaka Okamoto, Kiyoshi Misawa, Toyoyuki Hanazawa, and Atsushi Kaneda. "DNA Methylation and HPV-Associated Head and Neck Cancer." Microorganisms 9, no. 4 (April 10, 2021): 801. http://dx.doi.org/10.3390/microorganisms9040801.
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Head and neck squamous cell carcinoma (HNSCC), especially oropharyngeal squamous cell carcinoma (OPSCC), has recently been found to be significantly associated with human papillomavirus (HPV) infection. The incidence of OPSCC has been increasing and surpassed the number of cervical cancer cases in the United States. Although HPV-associated OPSCC has a relatively better prognosis than HPV-negative cancer, approximately 20% of HPV-associated HNSCC patients show a poor prognosis or therapeutic response, and the molecular mechanism behind this outcome in the intermediate-risk group is yet to be elucidated. These biological differences between HPV-associated HNSCC and HPV-negative HNSCC are partly explained by the differences in mutation patterns. However, recent reports have revealed that epigenetic dysregulation, such as dysregulated DNA methylation, is a strikingly common pathological feature of human malignancy. Notably, viral infections can induce aberrant DNA methylation, leading to carcinogenesis, and HPV-associated HNSCC cases tend to harbor a higher amount of aberrantly methylated DNA than HPV-negative HNSCC cases. Furthermore, recent comprehensive genome-wide DNA-methylation analyses with large cohorts have revealed that a sub-group of HPV-associated HNSCC correlates with increased DNA methylation. Accordingly, in this review, we provide an overview of the relationship between DNA methylation and HPV-associated HNSCC.
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Shin, Eunbie, and Joon Kim. "The potential role of YAP in head and neck squamous cell carcinoma." Experimental & Molecular Medicine 52, no. 8 (August 2020): 1264–74. http://dx.doi.org/10.1038/s12276-020-00492-9.
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Abstract The transcriptional cofactor YAP and its inhibitory regulators, Hippo kinases and adapter proteins, constitute an evolutionarily conserved signaling pathway that controls organ size and cell fate. The activity of the Hippo-YAP pathway is determined by a variety of intracellular and intercellular cues, such as cell polarity, junctions, density, mechanical stress, energy status, and growth factor signaling. Recent studies have demonstrated that YAP can induce the expression of a set of genes that allow cancer cells to gain a survival advantage and aggressive behavior. Comprehensive genomic studies have revealed frequent focal amplifications of the YAP locus in human carcinomas, including head and neck squamous cell carcinoma (HNSCC). Moreover, FAT1, which encodes an upstream component of Hippo signaling, is one of the most commonly altered genes in HNSCC. In this review, we discuss the causes and functional consequences of YAP dysregulation in HNSCC. We also address interactions between YAP and other oncogenic drivers of HNSCC.
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Zhang, Hongbo, Xiteng Yin, Xinyu Zhang, Meng Zhou, Wenguang Xu, Zheng Wei, Chuanhui Song, Shengwei Han, and Wei Han. "HSP90AB1 Promotes the Proliferation, Migration, and Glycolysis of Head and Neck Squamous Cell Carcinoma." Technology in Cancer Research & Treatment 21 (January 2022): 153303382211182. http://dx.doi.org/10.1177/15330338221118202.
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Background: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. Heat shock protein 90 alpha family class B member 1 (HSP90AB1) is highly expressed in a variety of cancers and is associated with poor prognosis, however, its role in HNSCC is still poorly understood. This study aimed to explore the function HSP90AB1 played in HNSCC progression. Methods: The expression level of HSP90AB1 in HNSCC was analyzed by bioinformatics analysis and western blotting, and its relationship with clinicopathological parameters was analyzed by bioinformatics analysis and immunohistochemistry. Three stable HSP90AB1 knockdown HNSCC cell lines were constructed by lentiviral transfection. The effect of HSP90AB1 knockdown on the proliferation and migration of HNSCC cells was tested by CCK-8 assay, EdU incorporation assay, colony formation assay, nude mouse xenograft models, transwell migration assay, wound healing assay, and western blotting. The effect of HSP90AB1 knockdown on glycolysis in HNSCC cells was assessed by quantitative real-time PCR and related assay kits. Finally, the levels of Akt and phospho-Akt (Ser473) proteins after HSP90AB1 knockdown were detected by western blotting. Results: HSP90AB1 was highly expressed in HNSCC and associated with T grade, lymph node metastasis, and prognosis. Knockdown of HSP90AB1 inhibited the proliferation, migration, and glycolysis of HNSCC, and reduced the level of phospho-Akt. Conclusion: HSP90AB1 functions as an oncogene in HNSCC, and has the potential to become a prognostic factor and therapeutic target.
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Li, Cheng, Zeng-hong Wu, and Kun Yuan. "Autophagy-Related Signature for Head and Neck Squamous Cell Carcinoma." Disease Markers 2020 (October 19, 2020): 1–13. http://dx.doi.org/10.1155/2020/8899337.
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Background. Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in the world, with low survival and poor quality of life. Autophagy-associated genes (ATGs) have been reported to be involved in the initiation and progression of malignancies. Here, we aimed to investigate the association between autophagy-associated genes and the outcomes in HNSCC patients. Methods. We obtained ATGs with prognostic values by analyzing the datasets from The Cancer Genome Atlas (TCGA) and Human Autophagy Database (HADb). The enrichment functions of autophagy differential genes were analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The Kaplan-Meier method was applied to the survival curve analysis. A prognostic autophagy-related gene signature was established, and its independence was verified. Results. We acquired a total of 529 samples and 232 ATGs; further, we identified 45 genes associated with prognosis and built a prognosis autophagy signature based on risk score of 15 genes. Patients were divided into two groups based on risk scores. The Kaplan-Meier curve illustrated that the survival rate of the high-risk group was significantly lower than that of the low-risk group in both the training group and validation group. The ROC curve revealed that the risk score had the highest AUC value in the 3rd and 5th years, reaching 0.703 and 0.724, which are higher than other risk factors such as gender, age, and TNM stage. The nomogram further confirmed its weight in the prognosis of HNSCC patients. Through KEGG and GO enrichment analyses, we observed that ATGs were involved in the tumorigenesis and invasion of tumor by various mediating pathways. We gained 3 hub genes (MAP1LC3B, FADD, and LAMP1) and further analyzed the survival curves, mutations, differential expressions, and their roles in tumors on the online websites. Conclusion. We identified a novel autophagy-related signature that may provide promising biomarker genes for the treatment and prognosis of HNSCC. We need to validate its prognostic value by applying it to the clinic.
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Schnoell, Julia, Isabella Stanisz, Bernhard J. Jank, Victoria Stanek, Rainer Schmid, Markus Brunner, Gregor Heiduschka, and Ulana Kotowski. "Zerumbone acts as a radiosensitizer in head and neck squamous cell carcinoma." Investigational New Drugs 40, no. 2 (October 6, 2021): 224–31. http://dx.doi.org/10.1007/s10637-021-01190-7.
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SummaryIntroduction. Zerumbone is a phytochemical compound of the ginger plant Zingiber zerumbet with cytotoxic effects in various cancer cell lines. To date, zerumbone has shown an antiproliferative effect in oral squamous cell carcinoma cells lines. However, the effect of combination with radiation or cisplatin in head and neck squamous cell carcinoma (HNSCC) is unclear. The aim of this study was to investigate the effect of zerumbone alone, and in combination with irradiation and cisplatin on HNSCC cell lines. Methods. The three HNSCC cell lines SCC25, Cal27 and FaDu were treated with zerumbone, radiation and/or cisplatin. Cell viability and clonogenic assays were performed. The interaction between zerumbone and radiation or cisplatin was evaluated using the combination index. Apoptosis was measured by flow cytometry and cell migration was assessed using a wound healing assay. Results. Treatment with zerumbone resulted in a dose dependent induction of cytotoxicity and apoptosis in all three cell lines. The combination with cisplatin revealed a synergistic to additive effect in Cal27. The clonogenic assay showed a significant radiosensitizing effect in all three cell lines. The wound healing assay showed a reduction of cell migration in Cal27. Conclusion. The natural compound zerumbone shows a cytotoxic and proapoptotic effect on HNSCC cell lines. Furthermore, zerumbone enhances the radiation effect in all three cell lines and thus may be a suitable candidate for combination therapy in HNSCC.
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Agresta, Laura, Maria Lehn, Kristin Lampe, Rachel Cantrell, Cassandra Hennies, Sara Szabo, Trisha Wise-Draper, Laura Conforti, Kasper Hoebe, and Edith M. Janssen. "CD244 represents a new therapeutic target in head and neck squamous cell carcinoma." Journal for ImmunoTherapy of Cancer 8, no. 1 (March 2020): e000245. http://dx.doi.org/10.1136/jitc-2019-000245.
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BackgroundDeveloping novel strategies to overcome the immunosuppressive tumor microenvironment is a critically important area of cancer therapy research. Here, we assess the therapeutic potential of CD244 (2B4/signaling lymphocyte activation molecule family 4), an immunoregulatory receptor found on a variety of immune cells, including exhausted CD8+T cells, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs).MethodsUsing de-identified human tumor and blood samples from patients with head and neck squamous cell carcinoma (HNSCC) and HNSCC models in WT and CD244-/-mice, we assessed the therapeutic potential of CD244 using flow cytometry, RT-PCR, Luminex immunoassays and histopathological analyses.ResultsCompared with healthy tissues, tumor infiltrating CD8+T cells from HNSCC patients and a HNSCC mouse model showed significant increased expression of CD244 expression that correlated with PD1 expression. Moreover, CD244 was increased on intratumoral DC and MDSC and high CD244 expression correlated with PD-L1 expression and increased spontaneous expression of immune-suppressive mediators. In addition, CD244 activation inhibited production of proinflammatory cytokines in human DC in vitro. Importantly, CD244-/-mice showed significantly impaired tumor growth of HNSCC and interventional treatment of WT mice with anti-CD244 monoclonal antibody significantly impaired the growth of established HNSCC tumors and increased tumor-infiltrating CD8+T cells.ConclusionsTogether these data suggest that CD244 contributes to the overall immune-suppressive environment and therefore has potential as a new immunotherapy target in the treatment of malignancies.
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Li, Zhexuan, Changhan Chen, Juncheng Wang, Ming Wei, Guancheng Liu, Yuexiang Qin, Li She, et al. "Overexpressed PLAU and its potential prognostic value in head and neck squamous cell carcinoma." PeerJ 9 (January 15, 2021): e10746. http://dx.doi.org/10.7717/peerj.10746.
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Background Metastasis is a major event for survival and prognosis in patients with head and neck squamous cell carcinomas (HNSCC). A primary cause of metastasis is the proteolytic degradation of the extracellular matrix (ECM). The plasminogen activator urokinase (PLAU) is involved in the transformation of plasminogen to plasmin leading to hydrolyzation of ECM-related proteins. However, the role of PLAU expression in HNSCC is unclear and the worth being investigated. Methods PLAU expression profiles and clinical parameters from multiple HNSCC datasets were used to investigate the relationship of PLAU expression and HNSCC survival. GO and PPI network were established on PLAU-related downstream molecular. The stroma score was deconvoluted for analysis of PLAU’s association with the immune environment. ROC analysis was applied to show the performance of PLAU in predicting HNSCC prognosis. Results PLAU mRNA was significantly elevated, as opposed to its methylation, in HNSCC tumor samples over normal specimens (all p < 0.01). Univariate and multivariate cox analysis showed PLAU could be an independent indicator for HNSCC prognosis. Combining with neck lymph node status, the AUC of PLAU in predicting 5-years overall survival reached to 0.862. GO enrichment analysis showed the major biological process (extracellular matrix organization and the P13K-Akt signaling pathway) may involve to the possible mechanism of PLAU’s function on HNSCC prognosis. Furthermore, PLAU expression was positively correlated with stroma cell score, M1 type macrophages, and negatively associated with CD4 + T cell, Tregs cell, and follicular helper T cell. Conclusions PLAU might be an independent biomarker for predicting outcomes of HNSCC patients. The elevated expression of PLAU was associated with HPV positivity and neck node status. The PI3K-Akt pathway and aberrant proportions of immune cells might underly the mechanism of PLAU’s oncogene role in HNSCC.
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Weng, Junquan, Haidong Fan, Huijuan Liu, Su Tang, and Yuyan Zheng. "YTHDC1 Promotes Stemness Maintenance and Malignant Progression in Head and Neck Squamous Cell Carcinoma." Stem Cells International 2022 (November 12, 2022): 1–13. http://dx.doi.org/10.1155/2022/7494354.
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Background. YTH domain containing 1 (YTHDC1), an N6-methyladenosine (m6A) modification reading protein, plays a key role in regulating RNA translation and degradation. However, the role of YTHDC1 in head and neck squamous cell carcinoma (HNSCC) cancer stem cells remains largely unknown. This study is aimed at investigating the role of YTHDC1 in HNSCC and exploring its role in regulating cancer stem cells. Methods. RNA sequencing was used to detect differentially expressed genes (DEGs) between SCC9 spheres and SCC9 cells and to uncover molecular pathways and target molecules associated with CSCs. We detected YTHDC1 expression in The Cancer Genome Atlas (TCGA) database data and clinical samples. Subsequently, YTHDC1 gene suppression assays were performed in HNSCC cell lines to investigate the effect of YTHDC1 on tumor cell stemness maintenance, proliferation, and migration capacity. To further confirm the role of YTHDC1 in regulating cancer stem cells in HNSCC, we analyzed online HNSCC single-cell transcriptomic data to investigate YTHDC1 expression patterns at the single-cell level and the correlation of these levels with the expression of stem cell markers. Results. YTHDC1 expression levels were significantly upregulated in SCC9 spheres, and YTHDC1 was aberrantly expressed in HNSCC tumor tissues. The increased YTHDC1 expression was closely correlated with the clinical characteristics of HNSCC patients. YTHDC1 regulates the malignant phenotype of HNSCC in both in vivo and in vitro studies. Further single-cell transcriptomic data analysis revealed that YTHDC1 positively correlated with malignant epithelial cell stemness capacity at the single-cell level, and that YTHDC1 was involved in regulating stemness maintenance in HNSCC. Conclusions. These findings suggest that YTHDC1 may serve as a biomarker for stem maintenance and malignant progression in HNSCC, providing new insights into the treatment of cancer.
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He, Jingyu, Simin Ouyang, Yilong Zhao, Yuqi Liu, Yaolong Liu, Bing Zhou, Qiwen Man, Bing Liu, and Tianfu Wu. "Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma." Biomolecules 13, no. 2 (February 6, 2023): 303. http://dx.doi.org/10.3390/biom13020303.
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Background: The CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tissue. Methods: We analyzed expression profiles of CAV1 and CAV2 in HNSCC and in normal tissues via data from The Cancer Genome Altas. Prognostic significance was examined by Kaplan–Meier survival curve obtained from the Xena browser together with Cox regression analysis. Co-expressed genes were uploaded to GeneMANIA and applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, showing interaction networks. Signaling pathways of CAV1 and CAV2 in HNSCC were analyzed by Gene Set Enrichment Analysis to elucidate potential regulatory mechanisms. Gene–drug interaction network was explored via Comparative Toxicogenomics Database. Immunohistochemistry was performed to verify theoretical results. Results: Compared with normal tissues, expression levels of CAV1 and CAV2 were remarkably higher in HNSCC (p < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, p = 0.027; CAV2: HR: 1.408, p = 0.002). Co-expressed genes (PXN, ITGA3, TES, and MET) were identified and analyzed by FunRich with CAV1 and CAV2, revealing a significant correlation with focal adhesion (p < 0.001), which has a vital influence on cancer progression. GSEA also showed cellular protein catabolic process (ES = 0.42) and proteasome complex (ES = 0.72), which is a key degradation system for proteins involved in oxidatively damaging and cell cycle and transcription, closely correlated with high expression of CAV2 in HNSCC. More importantly, we found the relationship between different immune cell infiltration degrees in the immune micro-environment in HNSCC and expression levels of CAV1/CAV2 (p < 0.0001). Gene–drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC (p < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes (p < 0.05). Conclusions: The results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis.
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Scher, Richard L., Wilfred Saito, Richard K. Dodge, William J. Richtsmeier, and Robert L. Fine. "Fenretinide-Induced Apoptosis of Human Head and Neck Squamous Carcinoma Cell Lines." Otolaryngology–Head and Neck Surgery 118, no. 4 (April 1998): 464–71. http://dx.doi.org/10.1177/019459989811800406.
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BACKGROUND: Squamous cell carcinoma of the head and neck (HNSCC) has a high incidence of recurrence and associated second primary malignancy. The retinoid 13- cis-retinoic acid has been shown to be effective as both a chemopreventive and chemotherapeutic agent for HNSCC, but often with treatment-limiting toxicity. The synthetic retinoid fenretinide (N-(4-hydroxyphenyl)retinamide) (HPR) has significant antiproliferative activity against a number of animal and human malignancies and has been used in clinical trials as a chemopreventive agent in patients with breast and prostate cancer and oral leukoplakia. HPR has been shown to have a toxicity profile lower than that for other retinoids used in clinical trials. PURPOSE: The aim of this study was to investigate the effect of HPR on the growth of HNSCC cell lines in vitro. METHODS: Four HNSCC cell lines (JHU-011-SCC, JHU-020-SCC, JHU-022-SCC, and FaDu) were treated with a range of concentrations of HPR for various times. After HPR exposure, cell viability was determined by tetrazolium dye (MTT) colorimetric assay, comparing cell survival with that of untreated control cells. HPR-induced apoptosis was determined by flow-cytometric deoxyribonucleic acid cell-cycle analysis, ultrastructural analysis with electron microscopy, and deoxyribonucleic acid fragmentation detected by gel electrophoresis. RESULTS: HPR caused significant growth inhibition in three of the four HNSCC cell lines in a dose- and time-dependent fashion. In two cell lines (JHU-011-SCC, JHU-020-SCC) a significant antiproliferative effect was achieved between 1 and 2.5 μ mol/L HPR after 72 hours of treatment. By deoxyribonucleic acid cell-cycle analysis, electron microscopy, and gel electrophoresis, HPR was shown to induce apoptosis in the JHU-011-SCC and JHU-020-SCC cell lines, but not in the FaDu cell line, which was insensitive to the growth inhibitory effect of HPR. CONCLUSIONS: This study has demonstrated that HPR reduces cell viability in HNSCC cells in vitro at clinically relevant doses, with the growth inhibition occurring through the induction of apoptosis.
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Porcheri, Cristina, and Thimios A. Mitsiadis. "New Scenarios in Pharmacological Treatments of Head and Neck Squamous Cell Carcinomas." Cancers 13, no. 21 (November 3, 2021): 5515. http://dx.doi.org/10.3390/cancers13215515.
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Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent types of cancer with a lethal outcome in half of the diagnosed cases. Mostly, HNSCC develops in the oral cavity, and its development is associated with tobacco and areca nut/betel quid usage, alcohol consumption, and HPV infection. Oral squamous cell carcinoma, as other head and neck cancers, presents a high degree of intratumor heterogeneity, which makes their treatment difficult, and directly correlates with drug resistance. Since the classical treatments for HNSCC oftentimes do not resolve the clinical picture, there is great need for novel therapeutic approaches, models for drug testing, and new drug delivery systems.
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Hsieh, Yi-Ta, Yi-Fen Chen, Shu-Chun Lin, Kuo-Wei Chang, and Wan-Chun Li. "Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis." International Journal of Molecular Sciences 20, no. 16 (August 14, 2019): 3960. http://dx.doi.org/10.3390/ijms20163960.
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Considering the great energy and biomass demand for cell survival, cancer cells exhibit unique metabolic signatures compared to normal cells. Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent neoplasms worldwide. Recent findings have shown that environmental challenges, as well as intrinsic metabolic manipulations, could modulate HNSCC experimentally and serve as clinic prognostic indicators, suggesting that a better understanding of dynamic metabolic changes during HNSCC development could be of great benefit for developing adjuvant anti-cancer schemes other than conventional therapies. However, the following questions are still poorly understood: (i) how does metabolic reprogramming occur during HNSCC development? (ii) how does the tumorous milieu contribute to HNSCC tumourigenesis? and (iii) at the molecular level, how do various metabolic cues interact with each other to control the oncogenicity and therapeutic sensitivity of HNSCC? In this review article, the regulatory roles of different metabolic pathways in HNSCC and its microenvironment in controlling the malignancy are therefore discussed in the hope of providing a systemic overview regarding what we knew and how cancer metabolism could be translated for the development of anti-cancer therapeutic reagents.
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Zhao, Hongyu, Fengxu Wang, Xuehai Wang, Xinyuan Zhao, and Jinfeng Ji. "HPV-Related Prognostic Signature Predicts Survival in Head and Neck Squamous Cell Carcinoma." Journal of Oncology 2022 (November 15, 2022): 1–10. http://dx.doi.org/10.1155/2022/7357566.
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Background. Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, worldwide. Considering the role of human papilloma virus (HPV) in tumor development and sensitivity to treatment of HNSCC, we aimed to explore the prognostic classification ability of HPV-related signatures in head and neck cancer. Methods. HPV-related signatures were screened out based on Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. HPV-related signatures with prognostic value were identified through univariate Cox regression analysis and a risk signature was established by least absolute shrinkage and selection operator (LASSO). Further, we developed a nomogram by integrating independent prognostic factors. Results. A total of 55 HPV-associated signatures were differentially expressed and ten of them were associated with prognosis of HNSCC patients. The prognostic signature based on CDKN2A, CELSR3, DMRTA2, SERPINE1, TJP3, FADD, and IGF2BP2 expression was constructed. Univariate and multivariate regression analyses demonstrated that the novel prognostic signature was an independent prognostic factor of HNSCC. The nomogram integrating the prognostic signature and other independent prognostic factors was developed. Conclusion. In summary, the prognostic signature of the HPV-related signatures might serve as an important prognostic biomarker for patients with HNSCC.