Head and Neck Cancer Recurrence and Mortality in Nonselective Cyclooxygenase Inhibitor Users

Gillespie, M. Boyd; Moody, Marcus W.; Lee, Fu‐Shing; Poole, Lynn; Hornig, Joshua D.; Lathers, Deanne; Young, Matthew R.; Day, Terry A.

doi:10.1001/archotol.133.1.28

Cited by 14 publications

(17 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a few clinical trials, administration of celecoxib as an adjuvant therapy has been associated with significant response rates (22, 31, 32). One retrospective study looking at the relationship between the use of non-selective cyclooxygenase inhibitors and overall survival in HNSCC patients found that median survival was increased among COX inhibitor users, although the regimen/type of COX inhibitor use was not controlled for in this study (21). A critical gap remains in our knowledge of how COX inhibition impacts on the T cell responses in HNSCC patients.…”

Section: Discussionmentioning

confidence: 79%

“…In several murine and hamster models of head and neck cancer, administration of the COX-2 inhibitor celecoxib decreased expression of vascular endothelial growth factor (VEGF) and survivin, increased tumor cell apoptosis and decreased tumor growth (18–20). A few studies have shown clinical responses resulting from COX inhibition in HNSCC patients (21, 22). In a model of lung carcinoma, inhibition of COX-2 resulted in increased antitumor reactivity by shifting the cytokine balance of resident immune cells toward a more proinflammatory, Th1-like phenotype, as characterized by increased IL-12 production and decreased IL-10 production (23).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Indomethacin Treatment of Mice with Premalignant Oral Lesions Sustains Cytokine Production and Slows Progression to Cancer

Johnson

Young

2016

Front. Immunol.

View full text Add to dashboard Cite

Current treatment options for head and neck squamous cell carcinoma (HNSCC) patients are often ineffective due to tumor-localized and systemic immunosuppression. Using the 4-NQO mouse model of oral carcinogenesis, this study showed that premalignant oral lesion cells produce higher levels of the immune modulator, PGE2, compared to HNSCC cells. Inhibiting prostaglandin production of premalignant lesion cells with the pan-cyclooxygenase inhibitor indomethacin stimulated their induction of spleen cell cytokine production. In contrast, inhibiting HNSCC prostaglandin production did not stimulate their induction of spleen cell cytokine production. Treatment of mice bearing premalignant oral lesions with indomethacin slowed progression of premalignant oral lesions to HNSCC. Flow cytometric analysis of T cells in the regional lymph nodes of lesion-bearing mice receiving indomethacin treatment showed an increase in lymph node cellularity and in the absolute number of CD8+ T cells expressing IFN-γ compared to levels in lesion-bearing mice receiving diluent control treatment. The cytokine-stimulatory effect of indomethacin treatment was not localized to regional lymph nodes but was also seen in the spleen of mice with premalignant oral lesions. Together, these data suggest that inhibiting prostaglandin production at the premalignant lesion stage boosts immune capability and improves clinical outcomes.

show abstract

Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Indomethacin Treatment of Mice with Premalignant Oral Lesions Sustains Cytokine Production and Slows Progression to Cancer

Johnson

Young

2016

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…However, clinical trials have been unable to show efficacy of celecoxib (a specific COX-2 inhibitor) [80] and Ketorolac (COX-1 and -2 inhibitor) [81] in inhibiting oral leukoplakia and oral premaligant lesions, respectively. Non-steroidal anti-inflammatory drugs (NSAIDs), a known PGE 2 inhibitor, had no effect on HNSCC recurrence or survival when compared to non-users in a retrospective case-control study [82]. Thus, COX-2 therapies may be most effective when used with other therapies.…”

Section: Sphk1 Influence In Head and Neck Cancermentioning

confidence: 99%

The Impact of Sphingosine Kinase-1 in Head and Neck Cancer

et al. 2013

View full text Add to dashboard Cite

Head and neck squamous cell carcinoma (HNSCC) has a high reoccurrence rate and an extremely low survival rate. There is limited availability of effective therapies to reduce the rate of recurrence, resulting in high morbidity and mortality of advanced cases. Late presentation, delay in detection of lesions, and a high rate of metastasis make HNSCC a devastating disease. This review offers insight into the role of sphingosine kinase-1 (SphK1), a key enzyme in sphingolipid metabolism, in HNSCC. Sphingolipids not only play a structural role in cellular membranes, but also modulate cell signal transduction pathways to influence biological outcomes such as senescence, differentiation, apoptosis, migration, proliferation, and angiogenesis. SphK1 is a critical regulator of the delicate balance between proliferation and apoptosis. The highest expression of SphK1 is found in the advanced stage of disease, and there is a positive correlation between SphK1 expression and recurrent tumors. On the other hand, silencing SphK1 reduces HNSCC tumor growth and sensitizes tumors to radiation-induced death. Thus, SphK1 plays an important and influential role in determining HNSCC proliferation and metastasis. We discuss roles of SphK1 and other sphingolipids in HNSCC development and therapeutic strategies against HNSCC.

show abstract

“…Twenty-one studies (two on all cancer sites, five on breast cancer, eight on colorectal cancer (CRC), one on head and neck cancer, one on pancreas cancer and four on prostate cancer) were identified that studied anti-inflammatory medications and cancer recurrence and cancer-specific mortality ( Table 4) [72,75,101,[115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132]. The drugs evaluated in the studies included all antiinflammatory drugs (i.e., aspirin, ibuprofen and COX inhibitors) and acetaminophen.…”

Section: Current Literaturementioning

confidence: 99%

Commonly used diabetes and cardiovascular medications and cancer recurrence and cancer-specific mortality: a review of the literature

Boudreau

Park

et al. 2014

Expert Opinion on Drug Safety

View full text Add to dashboard Cite

Metformin and aspirin were associated with a reduced risk of cancer recurrence and cancer-specific mortality. The evidence for statins and antihypertensive medications on cancer survival was inconsistent. There were few studies to suggest that any of the medication classes of interest were associated with negative effects on cancer survival. Methodological shortcomings within observational studies, such as confounding, distinguishing between use of medications pre-cancer versus post-cancer diagnosis/treatment, misclassification of exposures/outcomes, informative censoring and competing risks, must be considered. New observational studies addressing these limitations are essential. Some clinical trials are underway to further investigate the beneficial effects of these drugs and completed trials have confirmed results demonstrated in observational studies.

show abstract

Head and Neck Cancer Recurrence and Mortality in Nonselective Cyclooxygenase Inhibitor Users

Cited by 14 publications

References 15 publications

Indomethacin Treatment of Mice with Premalignant Oral Lesions Sustains Cytokine Production and Slows Progression to Cancer

Indomethacin Treatment of Mice with Premalignant Oral Lesions Sustains Cytokine Production and Slows Progression to Cancer

The Impact of Sphingosine Kinase-1 in Head and Neck Cancer

Commonly used diabetes and cardiovascular medications and cancer recurrence and cancer-specific mortality: a review of the literature

Contact Info

Product

Resources

About