scholarly journals In vitro benzo[a]pyrene diol epoxide-induced DNA damage and chromosomal aberrations in primary lymphocytes, smoking, and risk of squamous cell carcinoma of the head and neck

2007 ◽  
Vol 121 (12) ◽  
pp. 2735-2740 ◽  
Author(s):  
Ping Xiong ◽  
Zhibin Hu ◽  
Chunying Li ◽  
Li-E Wang ◽  
Adel K. El-Naggar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Chromosomal Aberrations ◽  
Diol Epoxide

scholarly journals In vitro Benzo[a]pyrene Diol Epoxide–Induced DNA Adducts and Risk of Squamous Cell Carcinoma of Head and Neck

2007 ◽  
Vol 67 (12) ◽  
pp. 5628-5634 ◽  
Author(s):  
Donghui Li ◽  
Li-E Wang ◽  
Ping Chang ◽  
Adel K. El-Naggar ◽  
Erich M. Sturgis ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Dna Adducts ◽  
Squamous Cell ◽  
Diol Epoxide

scholarly journals The DNA Damage Response Is Differentially Involved in HPV-Positive and HPV-Negative Radioresistant Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3717
Author(s):  
Marieke Bamps ◽  
Rüveyda Dok ◽  
Sandra Nuyts
Keyword(s):  
Dna Damage ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Dna Damage Response ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Damage Response

Radioresistance is a major cause of recurrences and radiotherapy (RT) failure in head and neck squamous cell carcinoma (HNSCC). DNA damage response (DDR) is known to be important for RT response, but its role in radioresistance is not fully understood. Here, we assessed the role of DDR in the radioresistance process of HNSCC by generating radioresistant clones from both HPV-positive SCC154 and HPV-negative SCC61 cells. We show that fractionated RT decreased RT response of HPV-positive and HPV-negative radioresistant clones in vitro and in vivo. Moreover, HPV-positive and HPV-negative radioresistant clones were characterized by differential DDR response. HPV-positive radioresistant clones showed less residual double-strand break damage and increased G2/M arrest recovery after RT, indicating an acquisition of increased DDR kinetics. In contrast, HPV-negative radioresistant clones showed less micronucleated cells after RT and increased survival upon checkpoint inhibition, indicating an increased replicative capacity. Inhibiting key factors of DDR in combination with RT rescued the radioresistant phenotype of both HPV-positive and HPV-negative radioresistant clones. Altogether, our results not only highlight the importance of DDR response in the radioresistance process of HPV-positive and HPV-negative HNSCC, but also provide possibilities for new therapies for HNSCC patients in recurrent settings.

Comparison of in vivo and in vitro prostaglandin E production by squamous cell carcinoma of the head and neck

1994 ◽  
Vol 111 (3) ◽  
pp. 189-196 ◽  
Author(s):  
C SNYDERMAN ◽  
I KLAPAN ◽  
M MILANOVICH ◽  
D HEO ◽  
R WAGNER ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prostaglandin E

scholarly journals JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Jing ◽  
Dandan Liu ◽  
Qingchuan Lai ◽  
Linqi Li ◽  
Mengqian Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Gene Expression Omnibus ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
In Vivo Experiments

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.

scholarly journals Antitumor Activity of Nanoparticles Loaded with PHT-427, a Novel AKT/PDK1 Inhibitor, for the Treatment of Head and Neck Squamous Cell Carcinoma

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1242
Author(s):  
Joaquín Yanes-Díaz ◽  
Raquel Palao-Suay ◽  
María Rosa Aguilar ◽  
Juan Ignacio Riestra-Ayora ◽  
Antonio Ferruelo-Alonso ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Polymeric Nanoparticles ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Neck Squamous Cell Carcinoma ◽  
Current Standard

Currently, new treatments are required to supplement the current standard of care for head and neck squamous cell carcinoma (HNSCC). The phosphatidylinositol3-kinase (PI3K) signaling pathway is commonly altered and activated in HNSCC. PHT-427 is a dual PI3K-mammalian target of the AKT/PDK1 inhibitor; however, to the best of our knowledge, the effect of the PHT-427 inhibitor on HNSCC has not been investigated. This study aims to evaluate the antitumoral effect of PHT-427-loaded polymeric nanoparticles based on α-tocopheryl succinate (α-TOS). The in vitro activity of PHT-427 was tested in hypopharynx carcinoma squamous cells (FaDu) to measure the cell viability, PI3KCA/AKT/PDK1 gene expression, and PI3KCA/AKT/PDK1 levels. Apoptosis, epidermal growth factor receptor (EGFR), and reactive oxygen species (ROS) were also measured. The presence of PHT-427 significantly enhances its antiproliferative and proapoptotic activity by inactivating the PI3K/AKT/PDK1 pathway. Nanoparticles (NPs) effectively suppress AKT/PDK1 expression. Additionally, NPs loaded with PHT-427 produce high oxidative stress levels that induce apoptosis. In conclusion, these results are promising in the use of this nanoformulation as a PHT-427 delivery system for effective HNSCC treatment.

scholarly journals The circ_0032822 Promotes the Proliferation of Head and Neck Squamous Cell Carcinoma Cells Through miR-141/EF3 Signaling Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuajia Zhang ◽  
Jiahui Han ◽  
Jing Fu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Tumor Tissues ◽  
Mechanistic Analysis ◽  
Repressive Effect ◽  
Signaling Axis

Head and neck squamous cell carcinoma (HNSCC) refers to an epithelial malignant tumor that originates in the head and neck, and over 600,000 new cases are reported every year, However, the overall prognosis is still poor due to local recurrence and distant metastasis after surgery. The circ_0032822 has been reported upregulated in human oral squamous cell carcinoma; however, the detailed function or mechanism remains unknown. In this study, we confirmed the upregulation of circ_0032822 in HNSCC tumor tissues. Functionally, the overexpression of circ_0032822 significantly promoted the proliferation of HNSCC cell lines along with the S phase arrest and reduced apoptosis, while downregulation of circ_0032822 has the opposite effect in vitro. Mechanistic analysis showed that circ_0032822 acted as a competing endogenous RNA of miR-141 to diminish the repressive effect of miR-141 on its target E2F3. In conclusion, we demonstrated that circ_0032822 functions as a tumor oncogene in HNSCC and that its function is regulated via the miR-141/E2F3 axis.

(S,R)3-(4-Hydroxyphenyl)-4,5-Dihydro-5-Isoxazole Acetic Acid Methyl Ester Inhibits Epithelial-to-Mesenchymal Transition through TGF-β/Smad4 Axis in Nasopharyngeal Carcinoma

2021 ◽  
Vol 21 ◽  
Author(s):  
Qibing Chen ◽  
Yan Wang ◽  
Fen Li ◽  
Xiang Cheng ◽  
Yu Xiao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Nasopharyngeal Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Immunofluorescence Assay ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background: Macrophage migration inhibitory factor (MIF), originally reported as an inflammation regulating molecule, is elevated in various cancer cells, which may promote carcinogenesis. Meanwhile, ISO-1 is a potent small molecular inhibitor of MIF, which has not been investigated in nasopharyngeal carcinoma (NPC); hence the impact of ISO-1 on NPC cells remains to be illustrated. Objective: This study intended to explore the biological function of ISO-1 in NPC cells in vitro and prove a possibility of ISO-1 being a novel agent in NPC treatments. Methods: Gene expression of MIF in Head and Neck squamous cell carcinoma were obtained from The Cancer Genome Atlas (TCGA) database. Nasal pharyngeal tissues were collected from adult patients undergoing nasopharyngeal biopsy for MIF level detection. Proliferation of NPC cell lines 5-8B and 6-10B was studied using Cell Counting Kit-8 (CCK-8) assay and plate-colony-formation assay, apoptosis was determined by flow cytometry and TUNEL staining, migration and invasion capacities were measured by wound-healing assay and transwell assay, all to explore the function of ISO-1 in NPC cells in vitro. Epithelial-to-mesenchymal transition (EMT) level of NPC cells was determined by Western blot analysis and immunofluorescence assay. Results: Transcript level of MIF was significantly higher in head and neck squamous cell carcinoma. Protein MIF was overexpressed in human NPC tissues compared to non-cancerous ones, and its expression could be compromised by ISO-1 in vitro. 100μM ISO-1 significantly hindered NPC cells migration and invasion capacities in vitro but acted relatively poorly on proliferation and apoptosis. Immunofluorescence assay and Western blotting implied a down-regulated EMT level through TGF-β/Smad4 axis in ISO-1 treated NPC cells compared to the vehicle. Conclusion: This study indicated that MIF antagonist ISO-1 holds impact on NPC progression by influencing the migration and invasion of NPC cells ISO-1 inhibits the EMT process of NPC cells through TGF-β/Smad4 axis, supporting that prudent application of ISO-1 may be a potential adjuvant treatment for NPC.

scholarly journals Influence of Tea Consumption on the Development of Second Esophageal Neoplasm in Patients with Head and Neck Cancer

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 387 ◽  
Author(s):  
Yao-Kuang Wang ◽  
Wei-Chung Chen ◽  
Ying-Ho Lai ◽  
Yi-Hsun Chen ◽  
Ming-Tsang Wu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Esophageal Neoplasm ◽  
In Vitro Studies ◽  
High Grade Dysplasia ◽  
High Grade ◽  
Tea Consumption

Alcohol is an important risk factor for the development of second esophageal squamous-cell carcinoma (ESCC) in head and neck squamous-cell carcinoma (HNSCC) patients. However, the influence of tea consumption is uncertain. We prospectively performed endoscopic screening in incident HNSCC patients to identify synchronous esophageal neoplasm. In total, 987 patients enrolled between October 2008 and December 2017 and were analyzed. In vitro studies were conducted to investigate the effect of epigallocatechin gallate (EGCG) on the betel alkaloid, arecoline-stimulated carcinogenesis in two ESCC cell lines. There were 151 patients (15.3%) diagnosed to have synchronous esophageal neoplasm, including 88 low-grade dysplasia, 30 high-grade dysplasia and 33 squamous-cell carcinoma (SCC). Tea consumption was associated with a significantly lower risk of having esophageal high-grade dysplasia or SCC in HNSCC patients, especially those who were betel nut chewers, alcohol drinkers or cigarette smokers (all adjusted odds ratio were 0.5; p-values: 0.045, 0.045 and 0.049 respectively). In vitro studies indicated that EGCG suppressed arecoline-induced ESCC cell proliferation and colony formation through the inhibition of the Akt and ERK1/2 pathway in a reactive oxygen species-independent manner. In conclusion, tea consumption may protect against the development of second esophageal neoplasms among HNSCC patients, especially those who regularly consume betel nuts, alcohol and cigarettes.

scholarly journals Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 286
Author(s):  
Yen Vo-Hoang ◽  
Sergio Paiva ◽  
Leilei He ◽  
Sébastien Estaran ◽  
Yong Teng
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Critical Role ◽  
In Vitro Cytotoxicity ◽  
Neck Squamous Cell Carcinoma ◽  
Protein Levels ◽  
Design And Synthesis

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related deaths and calls for new druggable targets. We have previously highlighted the critical role of ADP-ribosylation factor-1 (Arf1) activation in HNSCC. In the present study, we address the question whether targeting Arf1 could be proposed as a valuable strategy against HNSCC. Methods: We rationally designed and synthesized constrained ATC-based (4-amino-(methyl)-1,3-thiazole-5-carboxylic acid) γ-dipeptides to block Arf1 activation. We evaluated the effects of these γ-dipeptides in HNSCC cells: The cell viability was determined in 2D and 3D cell cultures after 72 h treatment and Arf1 protein levels and activity were assessed by GGA3 pull-down and Western blotting assays. Results: Targeting Arf1 offers a valuable strategy to counter HNSCC. Our new Arf1-targeting compounds revealed a strong in vitro cytotoxicity against HNSCC cells, through inhibiting Arf1 activation and its downstream pathways. Conclusions: Arf1-targeting γ-dipeptides developed in this study may represent a promising targeted therapeutic to improve managing the HNSCC disease.

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