scholarly journals MiR-21 is a Predictor for Chemoradioresistance and a Novel Therapeutic Target in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Hajime Ishinaga ◽  
Yoshinaga Okugawa ◽  
Bo Hou ◽  
Feng He ◽  
Chengzeng Yin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Predictive Biomarker ◽  
Neck Squamous Cell Carcinoma ◽  
Potential Target ◽  
Programmed Cell Death 4 ◽  
Induced Apoptosis

Abstract ObjectiveThis study aimed to clarify whether circulating miR-21 represents a predictive biomarker in patients with head and neck squamous cell carcinoma (HNSCC) undergoing chemoradiotherapy, and to investigate the effect of miR-21 inhibitor for chemoradiation in human SCC cells.MethodsPlasma samples were obtained from 22 patients with HNSCC and 25 non-cancer volunteers. Plasma miR-21 expression was measured using real-time quantitative reverse transcription polymerase chain reaction. The effects of miR-21 inhibitor in human SCC cells were investigated by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blot analysis.ResultsPlasma miR-21 expression was higher in HNSCC patients than in control patients (p< 0.001). Seven patients with recurrence showed significantly higher plasma miR-21 than the 15 patients without recurrence. Moreover, miR-21 inhibition significantly enhanced cisplatin- or radiation-induced apoptosis. Western blot analysis suggested the programmed cell death 4 (PDCD4) protein as a potential target of miR-21 in relation to apoptosis. Adding miR-21 inhibition to radiation or cisplatin treatment provided clear and potent suppression of tumor cell proliferation.ConclusionThis study provides new insights into the role of miR-21 as a predictive biomarker for HNSCC treated with chemoradiotherapy, and suggests a potential target to improve the effects of chemoradiotherapy against HNSCC.

scholarly journals De-Escalating Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1787
Author(s):  
Panagiota Economopoulou ◽  
Ioannis Kotsantis ◽  
Amanda Psyrri
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Young Patients ◽  
Treatment Strategies ◽  
Predictive Biomarker ◽  
Current Data ◽  
Neck Squamous Cell Carcinoma ◽  
Hpv Status

HPV-related head and neck squamous cell carcinoma (HNSCC) has emerged as a diverse clinical and biological disease entity, mainly in young patients with oropharyngeal tumors who are nonsmokers and nondrinkers. Indeed, during the past few years, the pendulum has shifted towards a new epidemiological reality, the “HPV pandemic”, where the majority of oropharyngeal squamous cell carcinomas (OPSCCs) are attributed to HPV. The oncogenic potential of the virus is associated to its capacity of integrating oncogenes E6 and E7 into the host cell, leading to the inactivation of several tumor suppressor genes, such as Rb. HPV status can affect prognosis in OPSCC, but its role as a predictive biomarker remains to be elucidated. Given the favorable prognosis associated with HPV-positive disease, the concept of de-escalation treatment strategies has been developed with the primary intent being the reduction of treatment-related long-term toxicities. In this review, we aim to depict current data regarding treatment de-escalation in HPV-associated OPSCC and discuss ongoing clinical trials.

scholarly journals The role of acetyl-coA carboxylase2 in head and neck squamous cell carcinoma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7037 ◽  
Author(s):  
Kun Li ◽  
Chengcheng Zhang ◽  
Lei Chen ◽  
Pingping Wang ◽  
Yang Fang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Intracellular Lipid ◽  
Acetyl Coa ◽  
Fadu Cells

Background Acetyl-CoA carboxylase (ACC) plays an important role in the metabolism of various cancer cells, but its role in head and neck squamous cell carcinoma (HNSCC) is uncertain. Therefore, in the present study, we explored the role of ACC2 in HNSCC. Methods Western blot and immunohistochemistry assays were used to determine ACC2 protein expression levels in laryngocarcinoma and adjacent normal tissues derived from patients with laryngocarcinoma. ACC2 expression was knocked down in the hypopharyngeal cancer cell line FaDu to determine its effect on apoptosis. Lipid oil red staining was used to test the change of intracellular lipid. Results The results showed that the ACC2 protein was highly expressed in laryngocarcinoma and that the ACC2 expression level was positively associated with the clinical cancer stage and negatively associated with the degree of laryngocarcinoma cell differentiation. Kaplan–Meier analyses indicated that compared with patients having low levels of ACC2, those with high ACC2 levels had a decreased 5-year survival rate. The results of western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays showed that knockdown of ACC2 accelerated apoptosis in FaDu cells. Furthermore, knockdown of ACC2 significantly reduced the intracellular lipid levels in FaDu cells. Conclusion These findings suggest that ACC2 may be an important prognostic marker for patients with HNSCC and that ACC2 may be a potential target in the treatment of HNSCC.

Quantification of a panel of prognostic markers gives a novel method for predicting radiosensitivity in head and neck squamous cell carcinoma cell lines

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6082-6082
Author(s):  
K. B. Roberg ◽  
L. Farnebo ◽  
L. Norberg-Spaak
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Protein Expression ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Novel Method

6082 Background: The present study was undertaken to evaluate the possibility of using the expression of a panel of proteins involved in apoptosis and/or growth control as predictive markers for radiotherapy response. Methods: Nine head and neck squamous cell carcinoma (HNSCC) cell lines were selected to represent different parts of the spectrum of in vitro radiosensitivity. These cell lines have an intrinsic radiosensitivity (IR) between 1.4 and 2.6 measured with a 96 well plate clonogenic assay. Results: Fourteen proteins e.g. Bcl-2, Bcl-XL, Bax, Bad, Bak, Puma, survivin, COX-2, Hsp70, MDM2, p53, EGFR, cyklin D1 and SMAD4 were investigated in above mentioned cell lines and in normal oral keratinocytes (NOK). Each protein was quantified using Western blot analyse and the relative densiometric value from each blot was adjusted for actin and standardized to NOK. The correlation between each protein and IR was analyzed but none significant correlation was found. When combine different proteins, EGFR, Survivin, Bcl-2, Bak, Hsp70 and Smad4 together show the highest significant correlation to the IR. As Western blot is a semi quantitative method we decided that a division into groups depending on the level of protein expression would give a more realistic description of the prognostic value of the detected changes The protein expression was classified into four groups (0–4 point; no, small, middle or large changes compared to NOK) and each p53 mutation got one point. We named this grouping Number of Negative Points (NNP). The NNP for all 15 factors together show a significant correlations to IR, R=0.826 and P= 0.006. A multivariate statistical calculation was carried out to select the combination of factors that had the strongest correlation to IR and the best combination was EGFR, survivin and p53 mutations, R=0.935 and P<0.001. Conclusions: Our results show that it is only possible to predict the IR of tumor cells if combinations of prognostic factors can be analysed. Taken together, we here present a novel method that gives the possibility to combine different prognostic factors and which also enhances the chance to predict the radiosensitivity of HNSCC cells. No significant financial relationships to disclose.

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