Summary Objectives: This analysis examined the association between oral hygiene and head and neck cancer (HNC) and whether this association differed by the consumption of alcohol, betel quid, or ...cigarette and by the genetic polymorphisms of inflammation-related genes. Materials and methods: Interviews regarding dental care and oral health were conducted with 317 HNC cases and 296 controls. Genotyping was performed for 6 single nucleotide polymorphisms in IL6 , IL10 and PTGS2. Results: A positive association was observed between HNC and no regular dental visits (odds ratio (OR) = 2.86, 95% confidence interval (CI): 1.47–5.57), brushing teeth <2 times/day (OR = 1.51, 95% CI: 1.02–2.23), frequent gum bleeding (OR = 3.15, 95% CI: 1.36–7.28), and loss of >20 teeth (OR = 2.31, 95% CI: 1.05–5.07). Analysis with dental care score (range: 0–4, 4 = worst dental care), which combined regular dental visits, toothbrushing, and use of dental floss and mouthwash, showed a positive trend with HNC risk, particularly among alcohol drinkers and cigarette smokers. Multifactor dimensionality reduction analysis divided the study subjects into high- and low-risk group based on combinations of dental care score and IL6 rs1800796 genotypes. Compared to the low-risk group, the high-risk group had an OR of HNC = 2.16 (95% CI: 1.44–3.25). Conclusions: This study observed a positive association between poor oral hygiene and HNC, which appeared to differ by alcohol or cigarette consumption and the genotypes of IL6 rs1800796. Further investigations are needed to determine whether poor oral hygiene is a cause for HNC or a surrogatemarker of an unhealthy lifestyle that increases the risk of HNC.
Alcohol consumption is an established risk factor for head and neck cancer (HNC). The major carcinogen from alcohol is acetaldehyde, which may be produced by humans or by oral microorganisms through ...the metabolism of ethanol. To account for the different sources of acetaldehyde production, the current study examined the interplay between alcohol consumption, oral hygiene (as a proxy measure for the growth of oral microorganisms), and alcohol‐metabolizing genes (ADH1B and ALDH2) in the risk of HNC. We found that both the fast (*2/*2) and the slow (*1/*1 + *1/*2) ADH1B genotypes increased the risk of HNC due to alcohol consumption, and this association differed according to the slow/non‐functional ALDH2 genotypes (*1/*2 + *2/*2) or poor oral hygiene. In persons with the fast ADH1B genotype, the HNC risk associated with alcohol drinking was increased for those with the slow/non‐functional ALDH2 genotypes. For those with the slow ADH1B genotypes, oral hygiene appeared to play an important role; the highest magnitude of an increased HNC risk in alcohol drinkers occurred among those with the worst oral hygiene. This is the first study to show that the association between alcohol drinking and HNC risk may be modified by the interplay between genetic polymorphisms of ADH1B and ALDH2 and oral hygiene. Although it is important to promote abstinence from or reduction of alcohol drinking to decrease the occurrence of HNC, improving oral hygiene practices may provide additional benefit.
What's new?
Drinking alcohol increases risk of head and neck cancer, because the body metabolizes alcohol into acetaldehyde, a carcinogen. Bacteria lingering in the mouth can also perform this change, raising the question of whether oral hygiene influences cancer risk. These authors investigated the interaction between alcohol consumption, oral hygiene, and expression of alcohol metabolizing genes in relation to risk of head and neck cancer. They found that poor oral hygiene did indeed increase cancer risk among those with a genotype indicating slower alcohol metabolism, suggesting that careful teeth‐cleaning may reduce risk among those unwilling to forgo alcohol.
Implementation of a critical care pathway (CCP) for acute coronary syndrome (ACS) has been shown to improve early compliance to guideline-directed therapies and reduce early mortality. Nevertheless ...its long-term impact on the compliance with medications or clinical outcomes remains unknown. Between 2004 and 2015, 2023 consecutive patients were admitted to our coronary care unit with ACS. We retrospectively compared the outcomes of 628 versus 1059 patients (mean age 66.1 ± 13.3 years, 74% male) managed before and after full implementation of a CCP. Compared with standard care, implementation of the CCP significantly increased coronary revascularization and long-term compliance with guideline-directed medical therapy (both P < 0.01). After a mean follow-up of 66.5 ± 44.0 months, 46.7% and 22.2% patients admitted before and after implementation of the CCP, respectively, died. Kaplan-Meier analyses showed that patients managed by CCP had better overall survival (P = 0.03) than those managed with standard care. After adjustment for clinical covariates and coronary anatomy, CCP remained independently predictive of better survival from all-cause mortality hazard ratio (HR): 0.75, 95%confidence intervals (CI): 0.62-0.92, P < 0.01. Stepwise multivariate cox regression model showed that both revascularization (HR: 0.55, 95%CI: 0.45-0.68, P < 0.01) and compliance to statin (HR: 0.70, 95%CI: 0.58-0.85, P < 0.01) were accountable for the improved outcome.
Abstract The success of using glycolytic inhibitors for cancer treatment depends on studying the individual role of frequently deregulated glycolytic genes in cancer. This report aims to study the ...prognostic implication, and determine the cellular role and action mechanism of glycolytic ENO1 overexpression in head and neck cancer. The relationship of ENO1 mRNA expression in 44-pair clinical specimens with patient clinicopathologic characteristics was analysed by semi-quantitative RT-PCR, Kaplan–Meier survival curve and Cox model analyses. Following ectopic ENO1 expression or knockdown, we studied the proliferative, migratory, invasive, colony-forming and tumourigenic abilities of ENO1 -genetically altered cells. DNA microarray analysis was used to identify downstream targets responsible for the ENO1 action in the cells. The expression of ENO1 mRNA was increased in 68% of tumour (T) specimens when compared to their normal (N) counterparts, and positively associated with clinical progression ( p < 0.05). High ENO1 expression (T/N ⩾ 2) was frequently observed in the patients with large primary tumours, late clinical stages or advanced neck metastasis. Moreover, high ENO1 patients had significantly poorer clinical outcomes than low expressers (T/N < 2). Ectopic ENO1 expression stimulated cell transformation, invasion and tongue tumour formation. ENO1 knockdown abrogated the stimulation. Suppression of ENO1 -induced proinflammatory CCL20 chemokine expression significantly attenuated its stimulatory effects on cell transformation and invasion. A concordant expression of ENO1 and CCL20 was validated both in ENO1 -expresing cells and in clinical specimens. Together, we demonstrate a prognostic role of ENO1 overexpression in head and neck cancer and ENO1 -mediated promotion of cell transformation and invasion partly via induced CCL20 expression.
J Oral Pathol Med (2010) 39: 342–348
Background: Oral squamous cell carcinoma (OSCC) is one of the most malignant neoplasms worldwide, and the molecular mechanism of oral tumorigenesis is still ...unclear. Fatty‐acid‐binding protein 5 (FABP5) was found in our previous study to be upregulated in oral squamous cell carcinomas by proteomic analysis. The implications of FABP5 overexpression in oral cancer progression have not yet been elucidated.
Materials and methods: In this study, the recombinant adeno‐associated virus vectors were used to deliver and increase the expression of FABP5 in human OSCC cell lines. U6 promoter‐driven short‐hairpin RNA (shRNA)‐triggered RNA interference was used to block FABP5 gene expression. Transwell Matrigel invasion assay, MTS cell proliferation assay, reverse transcription‐polymerase chain reaction, Western blot, and gelatin zymography analysis were used to investigate the effects of FABP5 on cell invasion, growth, and matrix metalloproteinase (MMP) production.
Results: Overexpression of FABP5 in oral cancer cells increased cell proliferation and invasiveness by increasing the expression of MMP‐9. Silencing FABP5 with shRNA significantly suppressed cell proliferation, MMP‐9 activities, and invasiveness.
Conclusion: Our study provides the first evidence that FABP5 expression modulated MMP‐9 production and the invasive behavior of oral cancer cells and suggests that FABP5 may provide novel targets for therapeutic intervention.
Poor oral hygiene is an established risk factor of head and neck cancer (HNC); however, its role in the survival of HNC patients is unclear. This study evaluated the association between oral hygiene ...habits, including regular dental visits, frequency of tooth brushing, and use of dental floss, and the overall survival (OS) of HNC patients using interview data collected from 740 HNC patients. In addition, the interactions between oral hygiene and the polymorphisms of TLR2 and TLR4 on the OS of HNC patients were assessed. The analysis indicated that poor oral hygiene was significantly associated with poorer OS of HNC patients (hazard ratio (HR) = 1.38, 95% confidence interval (CI): 1.03‐1.86). This association was modified by a single nucleotide polymorphism, rs11536889, of TLR4. A significant association between poor oral hygiene and worse survival of HNC was observed among those with the CG or CC genotype (HR = 2.32, 95% CI: 1.41‐3.82) but not among those with the GG genotype (HR = 0.95, 95% CI: 0.65‐1.40). Our results suggested that poor oral hygiene is not only a risk factor but may also be a prognostic factor of HNC.
Poor oral hygiene was associated with a worse survival of head and neck cancer. TLR4 affected the survival of head and neck cancer due to poor oral hygiene. Poor oral hygiene is both a risk and a prognostic factor of head and neck cancer
Although alcohol is an established risk factor of head and neck cancer (HNC), insufficiencies exist in the literature in several aspects. We analyzed detailed alcohol consumption data (amount and ...type of alcoholic beverage) of 811 HNC patients and 940 controls to evaluate the association between alcohol and HNC by HNC sites and by genotypes of ADH1B and ALDH2. Alcohol was associated with an increased HNC risk in a dose-response relationship, with the highest risk observed for hypopharyngeal cancer, followed by oropharyngeal and laryngeal cancers. Liquor showed a stronger positive association with HNC than beer and wine. The highest HNC risk occurred in individuals with the slow ADH1B and slow/non-functional ALDH2 genotype combination. In our study population, 21.8% of HNCs, 55.7% of oropharyngeal cancers, and 89.1% of hypopharyngeal cancers could be attributed to alcohol. Alcohol accounted for 47.3% of HNCs among individuals with the slow ADH1B and slow/non-functional ALDH2 genotype combination. The HNC risk associated with alcohol became comparable to that of never/occasional drinkers after ten or more years of cessation from regular alcohol drinking. In conclusion, alcohol use is associated with an increased HNC risk, particularly for individuals with slow ethanol metabolism. HNC incidence may be reduced by alcohol cessation.
Galectin-1 (Gal-1) is a β-galactose-binding lectin; its expression level has been reported to correlate with tumor progression.
Gal-1 is highly expressed in the invasive front of primary tumors and ...in the cancer cells of metastatic lesions in the lymph
nodes of patients with oral squamous cell carcinoma. However, the molecular mechanism of Gal-1 in tumor metastasis is not
completely clear. We found that increased Gal-1 expression is closely associated with its high levels of invasion in lung
adenocarcinoma and oral squamous cell carcinoma cell lines. Knocking down Gal-1 with small interfering RNA in highly invasive
cancer cells reduced their invasion levels. Moreover, the invasion ability of poorly invasive cancer cells was significantly
increased after Gal-1 overexpression of Gal-1. Mechanism studies revealed that Gal-1 promoted tumor invasion mainly by up-regulating
matrix metalloproteinase (MMP)-9 and MMP-2 and by reorganizing actin cytoskeleton. Gal-1 enhanced the activation of Cdc42,
a small GTPase and member of the Rho family, thus increasing the number and length of filopodia on tumor cells. Furthermore,
Gal-1-overexpressing cells had higher metastatic abilities in tail vein metastasis assays in vivo . We conclude that Gal-1 is involved in tumor invasion and metastasis by increasing MMP expression and reorganizing cytoskeletons
in oral cancers and lung adenocarcinoma. (Mol Cancer Res 2009;7(3):311–8)
Background
Oral squamous cell carcinoma (OSCC) is a common human malignancy and is usually preceded by the oral precancerous lesions. Oral submucous fibrosis (OSF) is one of the oral precancerous ...lesions with high incidence of malignant transformation. In addition to cancer cells, cancer‐associated fibroblasts in the tumor microenvironment are correlated with cancer progression, but the role of fibroblasts from OSF in tumorigenesis and progression is still unknown. Growth‐regulated oncogene‐α (GRO‐α), a member of CXC chemokine family, is related to tumorigenesis in several cancers. In this study, we would like to explore the role of GRO‐α from OSF‐associated fibroblasts in oral cancer progression.
Methods
We isolated primary culture fibroblasts of normal, precancerous, and tumor tissues from patients with OSCC accompanied with OSF. A cytokine array was used to screen cytokine secretions in the conditioned media of the fibroblasts. A wound healing migration assay, WST‐1 cell proliferation assay, rhodamine‐phalloidin staining, and soft agar colony formation assay were used to investigate the effects of GRO‐α on a dysplastic oral keratinocyte cell line (DOK) cell migration, growth, and anchorage‐independent growth.
Results
GRO‐α was identified to be increased in conditioned media of OSF‐associated fibroblasts. GRO‐α promotes DOK cells proliferation, migration, and anchorage‐independent growth through enhancing the EGFR/ERK signaling pathway, F‐actin rearrangement, and stemness properties, respectively. Moreover, GRO‐α neutralizing antibodies downregulated the conditioned medium‐induced cell proliferation and migration of DOK.
Conclusion
GRO‐α from OSF‐associated fibroblasts paracrinally promotes oral malignant transformation and significantly contributes to OSCC development.
ObjectivesThe effect of subclinical leaflet thrombosis, characterised by hypoattenuated leaflet thickening (HALT), on the valve haemodynamic function and durability of the bioprosthetic valve, is not ...yet determined. We determined the impact of HALT on valve haemodynamics after transcatheter aortic valve replacement (TAVR) and the predictors of haemodynamic structural valve deterioration (SVD).MethodsThe Anticoagulation vs Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization after Transcatheter Aortic Valve Replacement(ADAPT-TAVR) trial is a multicenter, randomised trial that compared edoxaban and dual antiplatelet therapy in patients who had undergone successful TAVR. The presence of HALT was evaluated by four-dimensional CT at 6 months and serial echocardiography performed at baseline, immediately post-TAVR and after 6 months. SVD was defined as at least one of the following: (1) mean transprosthetic gradient ≥20 mm Hg, (2) change in the mean gradient ≥10 mm Hg from baseline, or (3) new or increase in intraprosthetic aortic regurgitation of at least ≥1 grade, resulting in moderate or greater regurgitation.ResultsAt 6 months, HALT was found in 30 of 211 (14.2%) patients. The presence of HALT did not significantly affect aortic valve mean gradients (with vs without HALT; 14.0±4.8 mm Hg vs 13.7±5.5 mm Hg; p=0.74) at 6 months. SVD was reported in 30 of 206 patients (14.6%) at 6-month follow-up echocardiography. Older age (OR: 1.138; 95% CI: 1.019 to 1.293; p=0.033), use of aortic valve size ≤23 mm (OR: 6.254; 95% CI: 2.230 to 20.569; p=0.001) and mean post-TAVR pressure gradient (OR: 1.233; 95% CI: 1.123 to 1.371; p<0.001) were independent predictors of haemodynamic SVD; however, the presence of HALT was not identified as a predictor of SVD.ConclusionsIn patients who had undergone successful TAVR, aortic valve haemodynamic status was not influenced by the presence of HALT. Although HALT was not a predictor of haemodynamic SVD at 6 months, it warrants further longer-term follow-up to evaluate the effect on long-term valve durability.Trial registration numberNCT03284827 (https://www.clinicaltrials.gov).
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