In vitro assessment of the role of DpC in the treatment of head and neck squamous cell carcinoma

AbstractHead and neck squamous cell carcinoma (HNSCC), an aggressive malignancy, is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery, conventional cytotoxic chemotherapy, and irradiation. Increasing studies have supported the synergistic role of the tumor microenvironment (TME) in cancer advancement. The immune system, in particular, plays a key role in surveillance against the initiation, development, and progression of HNSCC. The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation, or expression of immunosuppressive mediators, provides the foundation for the development of advanced therapies. Furthermore, the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis, proliferation, and metastasis. This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME, with a focus on reviewing immunological principles related to HNSCC, as cancer immunosurveillance and immune escape, including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.

Download Full-text

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

Cancer Cell International ◽

10.1186/s12935-021-02060-1 ◽

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.

Download Full-text

Role of cytokines in head and neck squamous cell carcinoma

Expert Review of Anticancer Therapy ◽

10.1586/14737140.6.9.1195 ◽

2006 ◽

Vol 6 (9) ◽

pp. 1195-1203 ◽

Cited By ~ 31

Author(s):

Ralph Pries ◽

Stefan Nitsch ◽

Barbara Wollenberg

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma

Download Full-text

HOXB7 acts as an oncogenic biomarker in head and neck squamous cell carcinoma

Cancer Cell International ◽

10.1186/s12935-021-02093-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiang Wu ◽

Jin Li ◽

Tingyuan Yan ◽

Xueping Ke ◽

Xin Li ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Expression Pattern ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Clinicopathological Parameters ◽

Migration And Invasion ◽

Connectivity Map

Abstract Background The homeobox gene Homeobox B7 (HOXB7) is overexpressed across a range of cancers and promotes tumorigenesis through varying effects on proliferation, survival, migration and invasion. However, its expression pattern and oncogenic role of HOXB7 in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Here, we aimed to explore the expression pattern of HOXB7, its clinical significance as well as functional roles in HNSCC. Methods HOXB7 mRNA expression in HNSCC was determined by data mining and analyses from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The protein abundance of HOXB7 was measured by immunohistochemistry in 119 primary HNSCC samples and associations between its expression and clinicopathological parameters and patient survival were evaluated. The pro-tumorigenic roles of HOXB7 in HNSCC were further delineated in vitro by loss-of-function assay. And a xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Connectivity Map (CMap) analysis was performed to identify bioactive small molecules which might be potential inhibitors for HOXB7. Results Bioinformatics analyses showed that HOXB7 mRNA was significantly overexpressed in 8 independent HNSCC datasets from TCGA and GEO databases. HOXB7 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with high pathological grade, advanced clinical stage, cervical node metastasis (P = 0.0195, 0.0152, 0.0300) and reduced overall and disease-free survival (P = 0.0014, 0.0007). Univariate and multivariate Cox regression analyses further revealed HOXB7 as an independent prognostic factor for patients’ overall survival. Moreover, HOXB7 knockdown significantly inhibited cell proliferation, migration and invasion and induced cell apoptosis in HNSCC cells, and resulted in compromised tumour growth in vivo. Furthermore, CMap (Connectivity map) analysis has identified three potential bioactive small molecule inhibitors (NU-1025, thiamine, vinburnine) for HOXB7 targeted therapy in HNSCC. Conclusions Our findings revealed that overexpression of HOXB7 was associates with tumour aggressiveness and unfavourable prognosis by serving a novel prognostic biomarker in HNSCC. Moreover, HOXB7 might be involved in the development and progression of HNSCC as an oncogene, and thereby might be a potential therapeutic target for HNSCC.

Download Full-text

Role of E-cadherin and cyclin D1 as predictive markers of aggression and clonal expansion in head and neck squamous cell carcinoma

Journal of the Korean Association of Oral and Maxillofacial Surgeons ◽

10.5125/jkaoms.2018.44.4.182 ◽

2018 ◽

Vol 44 (4) ◽

pp. 182 ◽

Cited By ~ 1

Author(s):

Khushdeep Shergill ◽

Arijit Sen ◽

Hari Janardanan Pillai

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cyclin D1 ◽

Head And Neck ◽

Squamous Cell ◽

Clonal Expansion ◽

Predictive Markers ◽

Neck Squamous Cell Carcinoma ◽

E Cadherin

Download Full-text

The Evolving Role of Neck Dissection in the Era of Organ Preservation Therapy for Head and Neck Squamous Cell Carcinoma

Current Clinical Oncology - Squamous Cell Head and Neck Cancer ◽

10.1007/978-1-59259-938-7_4 ◽

2007 ◽

pp. 59-68

Author(s):

Tung T. Trang ◽

Pierre Lavertu

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Neck Dissection ◽

Squamous Cell ◽

Organ Preservation ◽

Neck Squamous Cell Carcinoma

Download Full-text

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

Pharmaceutics ◽

10.3390/pharmaceutics13081242 ◽

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.

Download Full-text

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

Frontiers in Oncology ◽

10.3389/fonc.2021.662496 ◽

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.

Download Full-text