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Contains fulltext : 292890.pdf (Publisher’s version ) (Open Access) Despite advances in transplant medicine, prevalence of complications after hematopoietic stem cell transplantation (HSCT) remains high. The impact of pre-HSCT oral health factors on the incidence and severity of complications post-HSCT is poorly understood. The aim of this prospective, observational study was to analyze oral health in patients planned for HSCT. Patients ≥18 years requiring HSCT were included from five sites between 2011-2018. General health, oral findings and patient-reported symptoms were registered in 272 patients. Oral symptoms around disease onset were reported by 43 patients (15.9%) and 153 patients (58.8%) reported oral complications during previous chemotherapy. One third of patients experienced oral symptoms at the oral examination before conditioning regimen and HSCT. In total, 124 (46.1%) patients had dental caries, 63 (29.0%) had ≥one tooth with deep periodontal pockets, 147 (75.0%) had ≥one tooth with bleeding on probing. Apical periodontitis was observed in almost 1/4 and partially impacted teeth in 17 (6.3%) patients. Oral mucosal lesions were observed in 84 patients (30.9%). A total of 45 (17.4%) of 259 patients had at least one acute issue to be managed prior to HSCT. In conclusion, oral symptoms and manifestations of oral disease were prevalent in patients planned for HSCT. The extent of oral and acute dental diseases calls for general oral screening of patients pre-HSCT.

OBJECTIVES: This study evaluates the impact of systemic medications and polypharmacy on unstimulated (UWS) and chewing-stimulated whole saliva (SWS) flow rates in patients with xerostomia.MATERIAL AND METHODS: This cross-sectional multicenter study is based on data of patients referred to five oral medicine outpatient practices in Europe and USA from January 2000 and April 2014. Relevant demographic, social, medical history and current medications were collected.RESULTS: The study included 1144 patients, 972 (85%) females, with a mean (SD) age of 59 (14.1) years. In unmatched patients, the UWS flow rate was lower in patients taking a medication (vs. not taking a medication) from the following drug categories: opioid analgesics, anticonvulsants, antidepressants, antihypertensives, benzodiazepines, corticosteroids, diuretics, disease-modifying antirheumatic drugs (DMARDs) and hormones. There was a greater negative effect on SWS flow rate in patients taking (vs. not taking) anticonvulsants, antidepressants, benzodiazepines, corticosteroids, and DMARDs. In matched patients, both UWS (0.22 vs. 0.19 ml/min; p = 0.03) and SWS (0.97 vs. 0.85 ml/min; p = .017) flow rates were higher in patients on non-opioid analgesics (vs. not taking). The UWS flow rate was lower in patients taking antidepressants (vs. not taking) (0.16 vs. 0.22 ml/min p = .002) and higher (and within normal range) in patients taking sex hormones (vs. not taking) (0.25 vs. 0.16 ml/min; p = .005). On the other hand, SWS was lower in patients taking corticosteroid (vs. not taking) (0.76 vs. 1.07 ml/min; p = .002), and in patients taking DMARDs (vs. not taking) (0.71 vs. 0.98 ml/min; p = .021). Finally, differences in medians of both UWS and SWS were statistically significant in patients taking 1 or more than 1 opioid analgesic (vs. not taking, p ≤ .0001 and p = .031, respectively), 1 or more than 1 anticonvulsants (vs. not taking, p = .008 and p = .007), 1 or more than 1 antidepressants (vs. not taking, p CONCLUSIONS: A greater negative impact on UWS and SWS flow rates was seen in patients taking more than one medication from the same drug class. Intake of antidepressants, corticosteroids and DMARDs is associated with lower whole saliva flow rates.CLINICAL RELEVANCE: Salivary flow rate can be modified by some specific medications, mostly by polypharmacy.

To establish and test a clinician-reported outcome measure of oral lichen planus (OLP): OLP Investigator global assessment (IGA).OLP IGA scale was tested with retrospective data from clinical practice and a phase II clinical trial. A comparison of the OLP IGA score with patient-reported outcomes was completed.Clinical Practice: The mean (SD) OLP IGA score (0-4) in 107 OLP patients was 1.8 (1.0) with correlation of 0.25-0.48 (p value 0.01 -0.0001) with symptom scores. There was a significant increase in OLP symptoms based on OLP IGA score.The mean (SD) OLP IGA score in 137 research participants was 2.5 (1.2) with correlation of 0.43-0.52 (all p values0.0001) with symptoms scores. There was a significant increase in OLP symptoms based on OLP IGA score. Forty-seven (35%) participants in the phase 2 study had an improvement in the OLP IGA score of ≥2. There were significant improvements in all symptoms scores in relation to the change in IGA score.The OLP IGA is designed to assess changes in symptomatic OLP lesions and is appropriate for use across the full range of symptomatic OLP severity and represents a scale with utility in clinical practice and clinical trials.

Signs and symptoms representative of a systemic condition can manifest in the oral cavity and orofacial region. Such conditions may be previously diagnosed, or the orofacial manifestation may be the presenting sign of an acute or chronic systemic condition not previously diagnosed. Pathologic processes in the mouth, jaws, and contiguous structures could have a direct and indirect impact on the patient's overall systemic condition. Moreover, systemic conditions may result in compromised function of the orofacial region or impact patients' oral health profile. This article reviews selected systemic conditions that present or impact on the oral cavity and orofacial region.

OBJECTIVE: To examine effects of Radiation therapy (RT) for Head and Neck Cancer (HNC) on periodontal disease and relationships to caries. METHODS: Multicenter prospective observational cohort study conducted in patients undergoing RT for HNC. Assessments conducted by calibrated examiners at the pre-RT (baseline) visit (n=533), the 12-month visit (n=414), and the 24-month visit (n=365). RESULTS: Average whole mouth mean(SE) distance from the cemento-enamel junction to the gingival margin (CEJ-GM) decreased significantly from 0.43(0.04) mm at baseline to 0.24(0.04) mm at 12 months, and 0.11(0.04) mm at 24 months (p-values ≤0.001). Whole mouth mean(SE) percentage of sites with CEJ-GM distance of less than 0 mm increased significantly from 23.3%(1.0%) at baseline, to 28.5%(1.0%) at 12 months, and 30.5%(1.1%) at 24 months (p-values ≤0.02). Higher mean radiation dose to the mandible was associated with greater increase in percentage of mandibular sites with CEJ-GM distance of less than 0 mm (p=0.003). Both mean CEJ-GM distance and percentage of sites with CEJ-GM distance less than 0 mm were strongly associated with whole mouth mean proportion of decayed, missing, and filled surfaces, as well as proportion of decayed or filled facial/buccal surfaces specifically, (p-values

Haematopoietic stem cell transplantation (HSCT) preceded by a conditioning regimen is an established treatment option for many haematological diseases. Decreased salivary flow rates after HSCT may increase caries risk. We aim to estimate the extent to which caries lesions develop or progress in adult HSCT recipients and assess its association with salivary flow rates. A multi-centre prospective observational study was conducted in which patients receiving HSCT were followed up for 18 months. We included 116 patients (median age 56 years, 43% female) from two medical centres in the Netherlands. Unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected, and full caries charts were made before HSCT and 3, 6, 12, and 18 months post-HSCT. Caries was scored according to the ICDAS criteria by trained dentist-examiners. New dentine lesions or lesion progression into dentine (ICDAS ≥4 or cavitated root lesions) occurred in 32% of patients over 18 months. The median number of affected surfaces was 2 (range: 1–12) per patient with caries progression. The influence of hyposalivation of unstimulated saliva (p < 0.001), while hyposalivation of SWS at baseline and hyposalivation of UWS were not. We conclude that caries progression is a common oral complication in patients after HSCT, and stimulated hyposalivation shortly after treatment is a significant risk indicator for caries progression.

BackgroundOral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa. Currently there is no approved treatment for OLP. We report on the efficacy and safety of a novel mucoadhesive clobetasol patch (Rivelin®-CLO) for the treatment of OLP.MethodsPatients with confirmed OLP and measurable symptomatic ulcer(s) participated in a randomized, double-blind, placebo-controlled, multicenter clinical trial testing a novel mucoadhesive clobetasol patch (Rivelin®-CLO) in OLP across Europe, Canada, and the United States. Patients were randomized to placebo (nonmedicated), 1, 5, 20 µg Clobetasol/patch, twice daily, for 4 weeks. The primary endpoint was change in total ulcer area compared to baseline. Secondary endpoints included improvement from baseline in pain, disease activity, and quality of life.ResultsData were analyzed and expressed as mean [SD]. One hundred thirty-eight patients were included in the study; 99 females and 39 males, mean age was 61.1 [11.6] years. Statistical analyses revealed that treatment with 20-μg Rivelin®-CLO patches demonstrated significant improvement with ulcer area (p = 0.047), symptom severity (p = 0.001), disease activity (p = 0.022), pain (p = 0.012), and quality of life (p = 0.003) as compared with placebo. Improvement in OLP symptoms from beginning to the end of the study was reported as very much better (best rating) in the 20-µg group (25/32) patients compared to the placebo group (11/30), (p = 0.012). Adverse events were mild/moderate. Candidiasis incidence was low (2%).ConclusionsRivelin®-CLO patches were superior to placebo demonstrating statistically significant, clinically relevant efficacy in objective and subjective improvement and, with a favorable safety profile.

OBJECTIVES: Salivary hypofunction and xerostomia, are common side effects of radiotherapy, negatively impacting quality of life. The OraRad study presents results on the longitudinal impact of radiotherapy on salivary flow and patient-reported outcomes. PATIENTS AND METHODS: Prospective, multicenter cohort study of 572 patients receiving curative-intent head and neck radiotherapy (RT). Stimulated salivary flow (SSF) rate and patient-reported outcomes were measured prior to RT and at 6- and 18-months post-RT. Linear mixed effects models examined the relationship between RT dose and change in salivary flow, and change in patient-reported outcomes. RESULTS: 544 patients had baseline salivary flow measurement, with median (IQR) stimulated flow rate of 0.975 (0.648, 1.417) g/min. Average RT dose to parotid glands was associated with change in salivary flow post-RT (p < 0.001). Diminished flow to 37% of pre-RT level was observed at 6 months (median: 0.358, IQR: 0.188 to 0.640 g/min, n=481) with partial recovery to 59% of pre-RT at 18 months (median: 0.575, IQR: 0.338 to 0.884 g/min, n=422). Significant improvement in patient-reported swallowing, senses (taste and smell), mouth opening, dry mouth, and sticky saliva (p-values < 0.03) were observed between 6 and 18 months post-RT. Changes in swallowing, mouth opening, dry mouth, and sticky saliva were significantly associated with changes in salivary flow from baseline (p-values < 0.04). CONCLUSION: Salivary flow and patient-reported outcomes decreased as a result of RT, but demonstrated partial recovery during follow-up. Continued efforts are needed to improve post-RT salivary function to support quality of life.

BACKGROUND Patients with head and neck cancer (HNC) treated with radiation therapy (RT) are at risk for jaw osteoradionecrosis (ORN), which is largely characterized by the presence of exposed necrotic bone. This report describes the incidence and clinical course of and risk factors for exposed intraoral bone in the multicenter Observational Study of Dental Outcomes in Head and Neck Cancer Patients (OraRad) cohort. METHODS Participants were evaluated before RT and at 6, 12, 18, and 24 months after RT. Exposed bone was characterized by location, sequestrum formation, and other associated features. The radiation dose to the affected area was determined, and the history of treatment for exposed bone was recorded. RESULTS The study enrolled 572 participants; 35 (6.1%) were diagnosed with incident exposed bone at 6 (47% of reports), 12 (24%), 18 (20%), and 24 months (8%), with 60% being sequestrum and with 7 cases (20%) persisting for >6 months. The average maximum RT dose to the affected area of exposed bone was 5456 cGy (SD, 1768 cGy); the most frequent associated primary RT sites were the oropharynx (42.9%) and oral cavity (31.4%), and 76% of episodes occurred in the mandible. The diagnosis of ORN was confirmed in 18 participants for an incidence rate of 3.1% (18 of 572). Risk factors included pre-RT extractions (P = .008), a higher RT dose (P = .039), and tobacco use (P = .048). CONCLUSIONS The 2-year incidence of exposed bone in the OraRad cohort was 6.1%; the incidence of confirmed ORN was 3.1%. Exposed bone after RT for HNC is relatively uncommon and, in most cases, is a short-term complication, not a recurring or persistent one.

Sjögren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.

PURPOSE To provide evidence-based recommendations for prevention and management of salivary gland hypofunction and xerostomia induced by nonsurgical cancer therapies. METHODS Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials published between January 2009 and June 2020. The guideline also incorporated two previous systematic reviews conducted by MASCC/ISOO, which included studies published from 1990 through 2008. RESULTS A total of 58 publications were identified: 46 addressed preventive interventions and 12 addressed therapeutic interventions. A majority of the evidence focused on the setting of radiation therapy for head and neck cancer. For the prevention of salivary gland hypofunction and/or xerostomia in patients with head and neck cancer, there is high-quality evidence for tissue-sparing radiation modalities. Evidence is weaker or insufficient for other interventions. For the management of salivary gland hypofunction and/or xerostomia, intermediate-quality evidence supports the use of topical mucosal lubricants, saliva substitutes, and agents that stimulate the salivary reflex. RECOMMENDATIONS For patients who receive radiation therapy for head and neck cancer, tissue-sparing radiation modalities should be used when possible to reduce the risk of salivary gland hypofunction and xerostomia. Other risk-reducing interventions that may be offered during radiation therapy for head and neck cancer include bethanechol and acupuncture. For patients who develop salivary gland hypofunction and/or xerostomia, interventions include topical mucosal lubricants, saliva substitutes, and sugar-free lozenges or chewing gum. For patients with head and neck cancer, oral pilocarpine and oral cevimeline, acupuncture, or transcutaneous electrostimulation may be offered after radiation therapy. Additional information can be found at www.asco.org/supportive-care-guidelines .

PURPOSE: Patients with head and neck cancer are at risk of long-term dental complications. Proper dental assessment pre- and post-treatment can improve outcomes but is logistically challenging. We surveyed oncologists to better understand their perspectives surrounding dental care in this unique population. METHODS: We surveyed oncologists at institutions associated with an ongoing national study of oral health after treatment of head and neck cancer. Seventeen questions were used to assess provider characteristics, patterns of practice, patterns of referral, barriers to referral, and willingness to apply fluoride varnish in the oncology clinic. RESULTS: Ninety-seven oncologists were invited from six institutions, of whom 40 (41%) responded. Surgeons represented 45% of the sample, followed by radiation oncologists (40%) and medical oncologists (15%). Both generalists and subspecialists were included. All practiced in a metropolitan area with an academic dental practice, and many felt that this improved access to care. Despite this, most oncologists thought that financial factors were a significant barrier to obtaining timely dental care. Most oncologists performed a dental assessment during visits. Oncologists felt qualified to identify the most significant complications of treatment, such as exposed bone, but felt underqualified to identify early changes in need of intervention. When asked if the oncology clinic could apply fluoride varnish during follow-ups, most stated that this seemed feasible but would require education and financial support. CONCLUSION: Oncologists often perform limited dental evaluations during their routine visits. Given the challenges associated with access to proper dental care for this population, these oncology visits may provide a window for preventative intervention.

Background Acinar progenitor cells within salivary glands have decreased regenerative capacity and exhibit shorter telomeres in primary Sjogren's syndrome (pSS) patients. We investigated whether DNA of saliva, PBMCs, and labial salivary gland (LSG) biopsy tissue have shorter telomeres in pSS compared to controls. mRNA expression of genes associated with pSS pathogenesis (ETS1, LEF1, and MMP9), telomere DNA damage response (ATM), senescence (CDKN2A), telomerase inhibition (IFN-y, TGFβ1), and the shelterin complex (TPP1, POT1) were assessed in LSG tissue by qRT-PCR to examine potential defects in telomere maintenance. Methods Relative telomere length in DNA of saliva, PBMCs, and LSGs from non-pSS sicca and pSS patients was measured using qPCR. Saliva DNA telomere length was further compared to healthy controls. Expression of genes affecting telomere maintenance was analyzed in LSGs using qRT-PCR. Results Primary Sjogren's syndrome patients have shorter telomeres in saliva DNA (n = 21) than healthy controls (n = 27) (P = .0035). ATM mRNA expression was higher in pSS LSG tissue (n = 16) vs non-pSS sicca patients (n = 13) (P = .0283) and strongly correlated with LEF1, TPP1, and POT1 (P 0.6). Conclusions Patients with pSS exhibited significant telomere erosion in saliva DNA. Overexpression of ATM in LSGs could represent a compensatory response to telomere shortening. The role of LEF1 in telomere erosion remains to be elucidated.

The deleterious effects of head and neck radiation on bone, with osteoradionecrosis (ORN) as the major disabling side effect of head and neck cancer treatment, are difficult to prevent and hard to treat. This review focuses on the current state of the science regarding the pathobiology, clinical impact, and management of ORN. With regard to the pathobiology underlying ORN, it is not yet confirmed whether the current radiation schedules by 3-dimensional conformal radiotherapy and intensity modified radiotherapy result in an unchanged, decreased, or increased risk of developing ORN when compared with conventional radiation treatment, the main risk factor being the total radiation dose delivered on any clinically significant surface of the mandible.With regard to the prevention of ORN, a thorough, early pre-irradiation dental assessment is still considered the first step to reduce the hazard of developing ORN post-radiotherapy, and hyperbaric oxygen (HBO) treatment reduces the risk of developing ORN in case of dental surgery in an irradiated field.With regard to the treatment of ORN, the focus is bidirectional: elimination of the necrotic bone and improving the vascularity of the normal tissues that were included in the radiation portal. The cure rate of limited ORN by conservative therapy is approximately 50%, and the cure rate of surgical approaches when conservative therapy has failed is approximately 40%.Whether it is effective to support conservative or surgical treatment with HBO as an adjuvant is not set. HBO treatment is shown to increase the vascularity of hard and soft tissues and has been reported to be beneficial in selected cases. However, in randomized clinical trials comparing the preventive effect of HBO on developing ORN with, eg, antibiotic coverage in patients needing dental surgery, the preventive effect of HBO was not shown to surpass that of a more conservative approach.More recently, pharmacologic management was introduced in the treatment of ORN with success, but its efficacy has to be confirmed in randomized clinical trials. The major problem of performing well-designed randomized clinical trials in ORN is having access to large numbers of patients with well-defined, comparable cases of ORN. Because many institutions will not have large numbers of such ORN cases, national and international scientific societies must be approached to join multicenter trials. Fortunately, the interest of funding organizations and the number researchers with an interest in healthy aging is growing. Research aimed at prevention and reduction of the morbidity of cancer treatment fits well within these programs.

Objective. The objective of this study was to assess the performance and reproducibility of the two currently used ocular surface staining scores in the assessment of keratoconjunctivitis sicca in Sjögren syndrome (SS) research classification. Methods. In a multidisciplinary clinic for the evaluation of sicca, we performed all tests for the American European Consensus Group (AECG) and the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, including the van Bijsterveld score (vBS) and the Ocular Staining Score (OSS), in 994 participants with SS or with non-SS sicca. We analyzed the concordance between the scores, the diagnostic accuracy and correlation with clinical variables, and interrater and intrasubject reproducibility. Results. A total of 308 (31.1%) participants had a discordant vBS and OSS that was due to extra corneal staining points in the OSS. The presence of one or more of the additional points was highly predictive of SS classification (odds ratio = 3.66; P = 1.65 × 10e-20) and was associated with abnormal results of all measures of autoimmunity and glandular dysfunction. Receiver operating characteristic curves showed optimal cutoff values of four for the vBS (sensitivity = 0.62; specificity = 0.71; Youden’s J = 0.33) and five for the OSS (sensitivity = 0.56; specificity = 0.75; Youden’s J = 0.31). Notably, there was very poor consistency in interobserver mean scores and distributions (P < 0.0001) and in intrasubject scores after a median of 5.5 years (35% changed status of the ocular criterion). Conclusion. Ocular surface staining scores are useful for SS research classification; however, they are subject to significant interrater and intrasubject variability, which could result in changes in classification in 5%−10% of all subjects. These results highlight the need for objective and reproducible markers of disease that have thus far remained elusive for SS.

Objective A novel Oral Lichen Planus Symptom Severity Measure was developed as a clinical outcome assessment of the daily symptom experience of patients with oral lichen planus. Methods A literature review and expert input were followed by open-ended concept elicitation interviews with 17 adults with oral lichen planus in the United States and Ireland. Item content was generated, and the interviews continued until input saturation was reached. The final electronic version of the measure was cognitively debriefed in 6 US patients and subsequently translated and linguistically validated in Germany and Denmark. Results Concept elicitation interviews demonstrated content validity and saturation in identifying symptoms and daily activities that generate symptoms in patients with oral lichen planus. The content and electronic daily diary format demonstrated content validity during cognitive debriefing interviews. Linguistic validation of the 7-item Oral Lichen Planus Symptom Severity Measure in Germany and Denmark confirmed the content validity of the German and Danish versions. Conclusions Qualitative research methods generated evidence that the 7-item Oral Lichen Planus Symptom Severity Measure version 1.0 is a well-defined assessment tool to characterize the severity, specificity and variations of symptoms in patients with oral lichen planus.

To elucidate long-term sequelae of radiation therapy (RT) in head and neck cancer (HNC) patients, a multicenter, prospective study, Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients (OraRad), was established with tooth failure as its primary outcome. We report tooth failure and associated risk factors.Demographics and cancer and dental disease characteristics were documented in 572 HNC patients at baseline and 6, 12, 18, and 24 months after RT. Eligible patients were aged 18 or older, diagnosed with HNC, and receiving RT to treat HNC. Tooth failure during follow-up was defined as losing a tooth or having a tooth deemed hopeless. Analyses of time to first tooth-failure event and number of teeth that failed used Kaplan-Meier estimators, Cox regression, and generalized linear models.At 2 years, the estimated fraction of tooth failure was 17.8% (95% confidence interval, 14.3%-21.3%). The number of teeth that failed was higher for those with fewer teeth at baseline (P.0001), greater reduction in salivary flow rate (P = .013), and noncompliance with daily oral hygiene (P = .03). Patients with dental caries at baseline had a higher risk of tooth failure with decreased salivary flow. Patients who were oral-hygiene noncompliant at baseline but compliant at all follow-up visits had the fewest teeth that failed; greatest tooth failure occurred in participants who were noncompliant at baseline and follow-up.Despite pre-RT dental management, substantial tooth failure occurs within 2 years after RT for HNC. Identified factors may help to predict or reduce risk of post-RT tooth failure.

The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1×/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3×/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (≥2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p p p

Xerostomia (subjective complaint of dry mouth) is commonly associated with salivary gland hypofunction. Molecular mechanisms associated with xerostomia pathobiology are poorly understood, thus hampering drug development. Our objectives were to (i) use text-mining tools to investigate xerostomia and dry mouth concepts, (ii) identify associated molecular interactions involving genes as candidate drug targets, and (iii) determine how drugs currently used in clinical trials may impact these genes and associated pathways. PubMed and PubMed Central were used to identify search terms associated with xerostomia and/or dry mouth. Search terms were queried in pubmed2ensembl. Protein–protein interaction (PPI) networks were determined using the gene/protein network visualization program search tool for recurring instances of neighboring genes (STRING). A similar program, Cytoscape, was used to determine PPIs of overlapping gene sets. The drug–gene interaction database (DGIdb) and the clinicaltrials.gov database were used to identify potential drug targets from the xerostomia/dry mouth PPI gene set. We identified 64 search terms in common between xerostomia and dry mouth. STRING confirmed PPIs between identified genes (CL = 0.90). Cytoscape analysis determined 58 shared genes, with cytokine–cytokine receptor interaction representing the most significant pathway (p = 1.29 × 10−23) found in the Kyoto encyclopedia of genes and genomes (KEGG). Fifty-four genes in common had drug interactions, per DGIdb analysis. Eighteen drugs, targeting the xerostomia/dry mouth PPI network, have been evaluated for xerostomia, head and neck cancer oral complications, and Sjögren’s Syndrome. The PPI network genes IL6R, EGFR, NFKB1, MPO, and TNFSF13B constitute a possible biomarker signature of xerostomia. Validation of the candidate biomarkers is necessary to better stratify patients at the genetic and molecular levels to facilitate drug development or to monitor response to treatment.

Primary Sj&ouml, gren&rsquo, s Syndrome (pSS) is an autoimmune disease mainly affecting salivary and lacrimal glands. Previous pSS studies have relied on primary cell culture models or cancer cell lines with limited relevance to the disease. Our objective was to generate and characterize immortalized salivary gland epithelial cells (iSGECs) derived from labial salivary gland (LSG) biopsies of pSS patients (focus score &gt, 1) and non-Sj&ouml, s Syndrome (nSS) xerostomic (i.e., sicca) female patients. To characterize iSGECs (n = 3), mRNA expression of specific epithelial and acinar cell markers was quantified by qRT-PCR. Protein expression of characterization markers was determined by immunocytochemistry and Western blot. Secretion of &alpha, amylase by iSGECs was confirmed through colorimetric activity assay. Spheroid formation and associated alterations in expression markers were determined using matrigel-coated cell culture plates. Consistent mRNA and protein expressions of both epithelial and pro-acinar cell markers were observed in all three iSGEC lines. When cultured on matrigel medium, iSGECs formed spheroids, secreted &alpha, amylase after &beta, adrenergic stimulation, and expressed multiple acinar cell markers at late passages. One iSGEC line retained adequate cell morphology without a loss of SV40Lt expression and proliferation potential after over 100 passages. In conclusion, our established iSGEC lines represent a viable model for salivary research due to their passaging capacity and maintenance of pro-acinar cell characteristics.