Years of Research Come to Fruition With Launch of Oral Cancer Prevention Trial

Nelson, Nancy J.

doi:10.1093/jnci/djj044

Cited by 3 publications

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“…Celecoxib is a nonsteroidal anti‐inflammatory drug (NSAID) that helps to control inflammation by inhibiting COX‐2 activity without appreciable effect on COX‐1 enzyme activity. In the last decade, numerous studies reported that celecoxib reduces the risk for a variety of human cancers, including HNSCC in experimental systems, via COX‐2–dependent and COX‐2–independent pathways 7, 18–21. Celecoxib is more potent and less toxic than traditional NSAIDs in inhibiting COX‐2.…”

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confidence: 99%

Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivovia cyclooxygenase‐2 and apoptotic pathways

Hao

Xie²,

Korotcov

et al. 2009

Intl Journal of Cancer

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Overexpression of cyclooxygenase‐2 (COX‐2) in oral mucosa has been associated with increased risk of head and neck squamous cell carcinoma (HNSCC). Celecoxib is a nonsteroidal anti‐inflammatory drug, which inhibits COX‐2 but not COX‐1. This selective COX‐2 inhibitor holds promise as a cancer preventive agent. Concerns about cardiotoxicity of celecoxib, limits its use in long‐term chemoprevention and therapy. Salvianolic acid B (Sal‐B) is a leading bioactive component of Salvia miltiorrhiza Bge, which is used for treating neoplastic and chronic inflammatory diseases in China. The purpose of this study was to investigate the mechanisms by which Sal‐B inhibits HNSCC growth. Sal‐B was isolated from S. miltiorrhiza Bge by solvent extraction followed by 2 chromatographic steps. Pharmacological activity of Sal‐B was assessed in HNSCC and other cell lines by estimating COX‐2 expression, cell viability and caspase‐dependent apoptosis. Sal‐B inhibited growth of HNSCC JHU‐022 and JHU‐013 cells with IC50 of 18 and 50 μM, respectively. Nude mice with HNSCC solid tumor xenografts were treated with Sal‐B (80 mg/kg/day) or celecoxib (5 mg/kg/day) for 25 days to investigate in vivo effects of the COX‐2 inhibitors. Tumor volumes in Sal‐B treated group were significantly lower than those in celecoxib treated or untreated control groups (p < 0.05). Sal‐B inhibited COX‐2 expression in cultured HNSCC cells and in HNSCC cells isolated from tumor xenografts. Sal‐B also caused dose‐dependent inhibition of prostaglandin E2 synthesis, either with or without lipopolysaccharide stimulation. Taken together, Sal‐B shows promise as a COX‐2 targeted anticancer agent for HNSCC prevention and treatment. © 2008 Wiley‐Liss, Inc.

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confidence: 99%

Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivovia cyclooxygenase‐2 and apoptotic pathways

Hao

Xie²,

Korotcov

et al. 2009

Intl Journal of Cancer

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“…The incidence of oral cancer is increasing in many countries, and the lack of efficient therapy and the considerable associated morbidity and mortality make chemoprevention attractive (Goodin and Shiff, 2004;Wang, 2005), particularly since this might be targeted to high-risk individuals with leukoplakia or other precursor lesions (Nelson, 2006). NSAIDs have shown promise as chemopreventive agents for oral cancer in experimental studies (Goodin and Shiff, 2004), but the available epidemiologic data including the present analysis do not support a major protective effect of NSAIDs against oral cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Epidemiologic studies have also consistently pointed to inverse associations between NSAID use and cancers of the stomach and oesophagus, whereas the results are mixed for other cancer sites (Gonzalez-Perez et al, 2003). Studies of animal models and human cancer cell lines have indicated that the potential chemopreventive effect of NSAIDs might extend to oral cancer (Goodin and Shiff, 2004;Wang, 2005), and this year a large phase III prevention trial of COX-2 inhibitors in patients with premalignant oral lesions (leukoplakia) is scheduled to be launched (Nelson, 2006). Interestingly, only a few epidemiological studies have provided data on the relationship between NSAID use and oral cancer, and the data are conflicting (Thun et al, 1993;Bosetti et al, 2003;Sørensen et al, 2003).…”

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confidence: 99%

Use of nonsteroidal anti-inflammatory drugs and risk of oral cancer: a cohort study

et al. 2006

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Epidemiologic data regarding the chemopreventive potential of nonsteroidal anti-inflammatory drugs (NSAIDs) against oral cancer are sparse. We found a relative risk for oral cancer of 1.2 (95% CI, 1.0 -1.6) among 169 589 Danish NSAID users (X2 prescriptions), with no apparent trends in subgroups. Our study provided no clear evidence that NSAIDs may protect against oral cancer. There is substantial experimental and epidemiological evidence that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protect against colorectal adenomas and cancer (Baron, 2003;Ulrich et al, 2006). Epidemiologic studies have also consistently pointed to inverse associations between NSAID use and cancers of the stomach and oesophagus, whereas the results are mixed for other cancer sites (Gonzalez-Perez et al, 2003). Studies of animal models and human cancer cell lines have indicated that the potential chemopreventive effect of NSAIDs might extend to oral cancer (Goodin and Shiff, 2004;Wang, 2005), and this year a large phase III prevention trial of COX-2 inhibitors in patients with premalignant oral lesions (leukoplakia) is scheduled to be launched (Nelson, 2006). Interestingly, only a few epidemiological studies have provided data on the relationship between NSAID use and oral cancer, and the data are conflicting (Thun et al, 1993;Bosetti et al, 2003;Sørensen et al, 2003). This paucity of epidemiologic data prompted us to examine the incidence of oral cancer in a large cohort of NSAID users in Denmark. MATERIALS AND METHODSThe study was carried out within the population of North Jutland County, Denmark (population approximately 490 000 inhabitants), during the study period 1 January 1991 to 31 December 2002. From the files of the Danish Civil Registration System, established in 1968(Frank, 2000, we identified all individuals in the county who were 16 years or older during the study period and resident in the county on 1 January 1991. We then excluded all individuals with a history of cancer (except nonmelanoma skin cancer) before study entry (1991 or age 16 years) by linkage to the Danish Cancer Registry, which has had accurate and almost complete nationwide ascertainment of cancer cases since 1943 (Storm et al, 1997). The final study population comprised 442 654 individuals.The Danish National Health Service provides tax-supported health care for all inhabitants and refunds part of patient expenditures on a wide range of prescribed drugs, including nonaspirin NSAIDs. In Denmark, non-aspirin NSAID can be obtained only by prescription, except for low doses of ibuprofen which account for approximately 14% of the total use (Sørensen et al, 2003). All health-related services are registered to individual patients by use of a civil registry number assigned to all Danish citizens, which encodes gender and date of birth. In North Jutland County, pharmacy data are transferred to a research prescription database, which was initiated in 1989 and covered all pharmacies by 1991 (Gaist et al, 1997). The database holds key information on ...

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“…The incidence of oral cancer is increasing in many countries ( Jemal et al , 2010 ; Chaturvedi et al , 2013 ) and the lack of efficient therapy and the considerable associated morbidity and mortality make chemoprevention a realistic possibility ( Jemal, 2012 ), particularly since this might be targeted to high-risk individuals with leukoplakia or other precursor lesions ( Nelson, 2006 ). NSAIDs have shown promise as chemopreventive agents for oral cancer in experimental studies ( Goodin and Shiff, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Aspirin and non-steroidal anti-inflammatory drug use and the risk of upper aerodigestive tract cancer

2014

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Background:Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesics and preventative agents for vascular events. It is unclear whether their long-term use affects cancer risk. Data on the chemopreventative role of these drugs on the risk of the upper aerodigestive tract cancer (UADT) are insufficient and mostly refer to oesophageal cancer. The aim of this study was to investigate the effect of aspirin and other NSAIDs on the risk of UADT cancers.Methods:A nested case–control study using the Primary Care Clinical Informatics Unit (PCCIU) database. Conditional logistics regression was used for data analysis.Results:There were 2392 cases of UADT cancer diagnosed between 1996 and 2010 and 7165 age-, gender- and medical practice-matched controls from 131 general medical practices. Mean age of cases was 66 years (s.d. 12) and most were male (63%). Aspirin was prescribed in a quarter of cases and controls, COX-2 inhibitors in 4% of cases and 5% of controls and other NSAIDs in 33% of cases and 36% of controls. Aspirin prescription was associated with a nonsignificant risk reduction of cancer of UADT (adjusted OR=0.9, 95% CI=0.8, 1.0), head and neck (HN; adjusted OR=0.9, 95% CI=0.7, 1.1) or the oesophagus (adjusted OR=0.8, 95% CI=0.7, 1.0). Similar results were found for COX-2 inhibitors prescription. Prescription of other NSAIDs was associated with significantly reduced risk of cancer of UADT (adjusted OR=0.8, 95% CI=0.7, 0.9), HN (adjusted OR=0.8, 95% CI=0.7, 0.9) and the oesophagus (adjusted OR=0.8, 95% CI=0.7, 0.9). An increased volume of aspirin prescriptions was associated with a significant risk reduction (test for trend P<0.001).Conclusions:The decreased risk of cancer of the UADT associated with the use of non-COX-2 inhibitors, NSAIDs and long-term aspirin therapy warrants further exploration of the benefits vs risks of the use of these agents.

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Years of Research Come to Fruition With Launch of Oral Cancer Prevention Trial

Cited by 3 publications

References 0 publications

Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivovia cyclooxygenase‐2 and apoptotic pathways

Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivovia cyclooxygenase‐2 and apoptotic pathways

Use of nonsteroidal anti-inflammatory drugs and risk of oral cancer: a cohort study

Aspirin and non-steroidal anti-inflammatory drug use and the risk of upper aerodigestive tract cancer

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