Oral and oro-pharyngeal squamous cell carcinomas (OSCC) exhibit surface breach, and recent studies have demonstrated bacterial contamination of primary and metastatic OSCC. Increasing concentrations of inflammatory products, such as interleukin (IL)-6 and vascular endothelial growth factor (VEGF), correlate with, and contribute to, cancer progression, but their regulation in OSCC is poorly understood. We hypothesized that monocyte-lineage cells and bacterial contamination may contribute important inflammatory products that can support OSCC progression. We found that relative to non-specific chronic mucositis, oral carcinoma-in-situ/superficially-invasive OSCC contained more monocyte-lineage cells. In vitro, we used lipopolysaccharide (LPS) to model bacterial contamination, and evaluated the effects of oral and oropharyngeal (O)SCC-monocyte interactions and of LPS on OSCC cells and on the production of IL-6 and VEGF. OSCC cell lines varied in constitutive cytokine and chemokine production, and OSCC-monocyte interactions in the absence of LPS stimulated IL-6 and VEGF occasionally, while LPS-OSCC-monocyte interactions were always strongly stimulatory. Importantly, LPS independently stimulated some OSCC lines to secrete monocyte-dendritic cell chemoattractants CCL2 and/or CCL20, as well as IL-6 and/or VEGF. While very little constitutive Y705-STAT3 phosphorylation (pY705-STAT3) was detectable in HNSCC lines, IL-6 rapidly induced pY705-STAT3 in OSCC lines that produced little IL-6 constitutively. Supernatants from LPS-OSCC-monocyte co-cultures always rapidly and strongly activated STAT3, which was partly due to IL-6. We conclude that monocytes and microbial contamination have the potential to contribute to OSCC progression, as STAT3 activation in OSCC cells depends on soluble factors, which are consistently available through LPS-OSCC-monocyte interactions.
Dry mouth is common in elderly patients. However, the use of saliva substitute has been limited due to its inedibility. This study investigated the efficacy of oral moisturizing jelly (OMJ), a novel edible saliva substitute. A pre-post design was conducted in 118 elderly patients diagnosed with hypertension and/or diabetes mellitus. After using OMJ, signs and symptoms of dry mouth were compared with baseline data. The properties of saliva were compared between the OMJ use and non-use periods. The use of OMJ for 2 weeks significantly reduced symptoms of dry mouth, while the use for 1 month reduced the signs of xerostomia, prevented the decline of salivary pH(s) and improved buffering capacities. OMJ was equally effective in patients taking 1 to 2 and 3 to 7 medications. Furthermore, 65% of patients preferred OMJ over a commercial product. OMJ could be new edible saliva substitute for elderly patients suffering from dry mouth. Clinicaltrials.gov ID: NCT02317172.
The aim of this study is to investigate the effect of an edible saliva substitute, oral moisturizing jelly (OMJ), and a topical saliva gel (GC) on dry mouth, swallowing ability, and nutritional status in post-radiotherapy head and neck cancer patients. Methods Sixty-two post-radiation head and neck cancer patients with xerostomia completed a blinded randomized controlled trial. They were advised to swallow OMJ (n = 31) or apply GC orally (n = 31) for 2 months. Outcome measures were assessed at baseline, 1, and 2 months, including subjective and objective dry mouth (Challcombe) scores, subjective swallowing problem scores (EAT-10), water swallowing time, clinical nutritional status (PG-SGA), body weight, and dietary intake. Results After 1 and 2 months of interventions, subjective and objective dry mouth scores, subjective swallowing problem scores, swallowing times, and clinical nutritional status in both groups were significantly improved (p < 0.0001). Compared to GC, OMJ group had higher percent improvement in all outcome measures (p < 0.001) except swallowing time and clinical nutritional status. Interestingly, subjective dry mouth scores were significantly correlated with subjective swallowing problem scores (r = 0.5321, p < 0.0001). Conclusions Continuous uses of saliva substitutes (OMJ or GC) for at least a month improved signs and symptoms of dry mouth and enhanced swallowing ability. An edible saliva substitute was superior to a topical saliva gel for alleviating dry mouth and swallow problems. These lead to improved clinical nutritional status. Thus, palliation of dry mouth may be critical to support nutrition of post-radiotherapy head and neck cancer patients. Clinical trial registry Clinicaltrials.gov NCT03035825 Keywords Dysphagia. Xerostomia. Saliva substitute. Nutritional status. Head and neck cancer. Radiation therapy Abbreviations BIA Bioelectrical impedance assessment BMI Body mass index EAT-10 Eating Assessment Tool OMJ Oral moisturizing jelly PG-SGA Patient Generate-Subjective Global Assessment WST Water swallowing test Electronic supplementary material The online version of this article (
Objectives To evaluate (a) oral colonization of Candida species, especially for non‐albicans Candida species (NACS), in xerostomic postradiotherapy head and neck cancer patients and (b) risk factors affecting their colonization. Materials and methods Subjective and objective dry mouth scores, stimulated salivary flow rates, pH and buffering capacity were measured in 72 xerostomic postradiotherapy head and neck cancer patients. Candida counts and species identification were performed using oral rinse samples cultured in Candida Chromagar, followed by polymerase chain reaction and API 20C AUX system. Results Candida colonization was observed in 87.5% of subjects, with 80.6% and 48.6% of study population colonized by C. albicans and NACS, respectively. NACS was associated with high objective dry mouth scores, denture use, and females (p = .006, .009, and .036, respectively). In addition, Candida glabrata was detected more in females (p = .018) and denture wearers (p = .026), while Candida tropicalis was associated with high objective dry mouth scores (p = .022) and females (p = .027). Quantity of Candida colonization correlated positively with objective dry mouth scores (r = 0.599, p < .001) and negatively with salivary flow rates (r = −0.258, p = .041) and pH (r = −0.290, p = .022). Conclusion NACS colonization was common in xerostomic head and neck cancer patients. Increased signs of dry mouth, female and dental prostheses may promote NACS colonization.
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