Increased radiation sensitivity of head and neck squamous cell carcinoma with sphingosine kinase 1 inhibition

Head & Neck ◽  
2011 ◽  
Vol 33 (2) ◽  
pp. 178-188 ◽  
Author(s):  
Uttam K. Sinha ◽  
Victor J. Schorn ◽  
Christian Hochstim ◽  
Steven B. Chinn ◽  
Sutao Zhu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Sphingosine Kinase ◽  
Radiation Sensitivity ◽  
Neck Squamous Cell Carcinoma ◽  
Sphingosine Kinase 1

scholarly journals Sphingosine Kinase 1(SphK1) – A Novel Marker for Cancer Risk Assessment in Oral Premalignancy

2021 ◽  
Vol 4 (1) ◽  
pp. 51-60
Author(s):  
Bodh Bikram Karki ◽  
Debao Wu ◽  
Jun Shen
Keyword(s):  
Risk Assessment ◽  
Squamous Cell Carcinoma ◽  
Cancer Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Sphingosine Kinase ◽  
Oral Leukoplakia ◽  
Cancer Risk Assessment ◽  
Sphingosine Kinase 1

Introduction Head and neck cancer is the sixth most common cancer worldwide, resulting in approximately 550,000 diagnoses of new cases and 300,000 deaths per year globally. Overexpression of Sphingosine kinase - 1 (SphK1) is found in head and neck squamous cell carcinoma (HNSCC) from early to advanced stages and is associated with tumor progression, invasion, metastasis and poor prognosis. This study assesses the expression of sphingosine kinase - 1 (SphK1) in oral leukoplakia and oral squamous cell carcinoma (OSCC)  and suggests its role as a potential biomarker tool for cancer risk assessment in oral leukoplakia. Methods In this retrospective study, eighty-two (n = 82) archival formalin-fixed paraffin blocks consisting of 10 normal tongue mucosa (Group A), 42 cases of oral leukoplakia (Group B) and 30 cases of OSCCs (Group C) were selected and subjected to immunohistochemical staining for anti-rabbit SphK1 antibody. The three different groups were compared for the presence of Sphk1 expression. The clinicopathological parameters such as age, gender, habits, histopathology, and Sphk1 expression were analyzed and compared between the malignantly transformed leukoplakia with untransformed leukoplakia. Results Positive SphK1 expression was found in 18 out of 42 (42.9 %) cases of oral leukoplakia and 17 out of 30 (56.7 %) cases of OSCCs while there was no SphK1 expression in normal tongue mucosa. The expression of SphK1 among three different groups of tissue samples was statistically significant (P = 0.007). The correlation between the malignant transformed and untransformed leukoplakia lesion with respect to SphK1 expression was also found to be statistically significant (P= 0.007) Conclusions Positive SphK1 expression in oral leukoplakia is suggestive of an increased risk for malignant transformation which can be used as a biomarker tool. Higher SPHK1 expression in the OSCC may suggest an important role in the early stages of tumorigenesis.

scholarly journals Photodynamic Therapy as a Potent Radiosensitizer in Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1193
Author(s):  
Won Jin Cho ◽  
David Kessel ◽  
Joseph Rakowski ◽  
Brian Loughery ◽  
Abdo J. Najy ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Photodynamic Therapy ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Treatment Protocol ◽  
Radiation Sensitivity ◽  
Neck Squamous Cell Carcinoma ◽  
Autophagic Flux

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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