8551 Assessment of oxidative stress in tumors cells and histologically normal mucosa from head and neck squamous cell carcinoma patients

Abstract Objectives Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) and interferon-induced transmembrane protein 3 (IFITM3) are commonly induced by type I interferon. The study aims to investigate the expression and clinical significance of IFIT1 and IFITM3 in head and neck squamous cell carcinoma (HNSCC). Methods Immunohistochemistry was applied on tissue microarray to reveal IFIT1 and IFITM3 expression in 275 HNSCC, 69 dysplasia, and 42 normal mucosa samples. The clinicopathologic features associated with IFIT1 and IFITM3 expression in HNSCC patients were analyzed. Results IFIT1 and IFITM3 were highly expressed in HNSCC tissues. High expression of IFIT1 and IFITM3 predicts a negative prognosis for patients (P < .01). IFIT1 and IFITM3 expression was associated with programmed cell death ligand 1, B7-H4, V-domain Ig suppressor of T-cell activation, indoleamine 2,3-dioxygenase, and macrophage marker immunoreactivity. Conclusions IFIT1 and IFITM3 were overexpressed in HNSCC and indicated poor prognoses for patients with HNSCC. IFIT1 and IFITM3 expression was correlated with several immune checkpoint molecules and tumor-associated macrophage markers.

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Abstract PO-094: Glutaminase inhibition increases ionizing radiation induced oxidative stress and DNA damage in head and neck squamous cell carcinoma models

10.1158/1557-3265.radsci21-po-094 ◽

2021 ◽

Author(s):

Christina A. Wicker ◽

Brian G. Hunt ◽

Sarah Palackdharry ◽

William R. Elaban ◽

Trisha M. Wise-Draper ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Squamous Cell Carcinoma ◽

Ionizing Radiation ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Radiation Induced

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Acquisition of Cisplatin Resistance Shifts Head and Neck Squamous Cell Carcinoma Metabolism toward Neutralization of Oxidative Stress

Cancers ◽

10.3390/cancers12061670 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1670 ◽

Cited By ~ 1

Author(s):

Wangjie Yu ◽

Yunyun Chen ◽

Nagireddy Putluri ◽

Cristian Coarfa ◽

Matthew J. Robertson ◽

...

Keyword(s):

Oxidative Stress ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Cisplatin Resistance ◽

Integrated Approach ◽

Metabolic Reprogramming ◽

Neck Squamous Cell Carcinoma ◽

Cross Resistance

Background: Cisplatin (CDDP) is commonly utilized in the treatment of advanced solid tumors including head and neck squamous cell carcinoma (HNSCC). Cisplatin response remains highly variable among individual tumors and development of cisplatin resistance is common. We hypothesized that development of cisplatin resistance is partially driven by metabolic reprogramming. Methods: Using a pre-clinical HNSCC model and an integrated approach to steady state metabolomics, metabolic flux and gene expression data we characterized the interaction between cisplatin resistance and metabolic reprogramming. Results: Cisplatin toxicity in HNSCC was driven by generation of intra-cellular oxidative stress. This was validated by demonstrating that acquisition of cisplatin resistance generates cross-resistance to ferroptosis agonists despite the fact that cisplatin itself does not trigger ferroptosis. Acquisition of cisplatin resistance dysregulated the expression of genes involved in amino acid, fatty acid metabolism and central carbon catabolic pathways, enhanced glucose catabolism and serine synthesis. Acute cisplatin exposure increased intra-tumoral levels of S-methyl-5-thiadenosine (MTA) precursors and metabotoxins indicative of generalized oxidative stress. Conclusions: Acquisition of cisplatin resistance is linked to metabolic recovery from oxidative stress. Although this portends poor effectiveness for directed metabolic targeting, it supports the potential for biomarker development of cisplatin effectiveness using an integrated approach.

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