GPRC5B (G protein-coupled receptor class C group 5 member B) suppresses glucose starvation-induced apoptosis in head-and-neck squamous cell carcinoma.

G protein-coupled receptor class C group 5 member B (GPRC5B) is involved in extracellular glucose sensing, glucose metabolism, and insulin resistance. Many cancers require glucose at high concentrations to survive and grow. We have investigated the association between tumour GPRC5B expression and the prognosis for patients with cancer, including head-and-neck squamous cell carcinoma (HNSCC), using data from The Human Protein Atlas. The 5-year survival rate was significantly reduced in patients with HNSCC, gastric, pancreatic, colorectal, and breast cancers if their tumours exhibited high levels of GPRC5B expression. The role of GPRC5B in glucose metabolism was assessed using six HNSCC cell lines with varying levels of GPRC5B expression. High levels of GPRC5B expression were found to favour rapid cell growth. The viability of an HNSCC cell line with normal and transfected GPRC5B expression was also assessed and no differences were observed under standard culture conditions. However, under glucose-deficient culture conditions, GPRC5B-overexpressing cells exhibited increased viability and reduced apoptosis. The results highlight the association between high GPRC5B expression and poor 5-year survival rates in patients with various cancers, including HNSCC. Furthermore, we have demonstrated that GPRC5B supports cancer cell survival under glucose-depleted conditions and could be a target molecule for cancer therapy.

Predictors of early postoperative pneumonia after oncologic surgery with the patients receiving professional oral health care: A prospective, multicentre, cohort study.

This study was a prospective, multicentre, cohort study on 685 patients who had undergone oncologic surgery. The patients were divided into two groups according to the presence or absence of postoperative pneumonia. The two groups were compared with respect to their background, index operation, food eaten, oral condition, contents of oral care and dental treatment, laboratory data, and bacterial flora. All postoperative pneumonias occurred in six cases within four days postoperatively. The multivariable logistic regression analysis showed that preoperative serum C-reactive protein was the strongest predictor of postoperative pneumonia. In addition, decreased postoperative Candida albicans colonies was an effective predictor of postoperative pneumonia. For patients with predictors of postoperative pneumonia, perioperative strategies for its prevention should be considered in addition to professional oral health care. This study was approved by the National Hospital Organization's Central Ethics Review Board and was also approved by the directors of the participating institutions.

Antimicrobial susceptibility surveillance of bacterial isolates recovered in Japan from odontogenic infections in 2013.

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to ß-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with ß-lactamase inhibitor showed low MIC90 values.

Comparison of CD34 expression in fibrous reactive hyperplasia and healthy oral mucosa.

OBJECTIVES: Fibrous reactive hyperplasia (FRH) is a common fibrous lesion in the oral cavity. The disease characteristics of FRH, including the expression patterns of CD34, which is a well-known fibroblast marker, have not been investigated in detail. Therefore, in this study, we aimed to investigate the characteristics of FRH compared to those of the healthy mucosa, based on CD34 expression profiles. METHODS: CD34 expression was analyzed at the protein and mRNA levels using immunohistochemistry, quantitative polymerase chain reaction, and in situ hybridization (ISH). RESULTS: CD34 was not expressed in the lamina propria of the oral mucosa, but was commonly observed in submucosal fibroblasts. CD34-positive fibroblasts were commonly observed in FRH. A total of 17 out of 19 cases (89.5%) were CD34-positive. Furthermore, we identified a significant difference in the ratio of CD34-positive cells between the healthy and FRH tissues. Quantitative polymerase chain reaction showed that CD34 mRNA was expressed in all cases of FRH, and CD34 mRNA expression in FRH samples was found to be localized to spindle-shaped fibroblasts, as determined by ISH. A positive correlation was also found between the CD34 mRNA levels and the proportion of the CD34-positive cells. CONCLUSIONS: These findings suggest that the increase in collagen synthesis in CD34-positive fibroblasts in the submucosa leads to the development of FRH. To our knowledge, this is the first report confirming the mRNA expression patterns of CD34 in FRH.

C-X-C Motif Chemokine Ligand 14 is a Unique Multifunctional Regulator of Tumor Progression.

Cancer is a leading cause of death and disease worldwide, with a tremendous financial impact. Thus, the development of cost-effective novel approaches for suppressing tumor growth and progression is essential. In an attempt to identify the mechanisms responsible for tumor suppression, we screened for molecules downregulated in a cancer progression model and found that the chemokine CXCL14, also called BRAK, was the most significantly downregulated. Increasing the production of CXCL14 protein by transfecting tumor cells with a CXCL14 expression vector and transplanting the cells into the back skin of immunodeficient mice suppressed tumor cell growth compared with that of parental tumor cells, suggesting that CXCL14 suppressed tumor growth in vivo. However, some studies have reported that over-expression of CXCL14, especially in stromal cells, stimulated the progression of tumor formation. Transgenic mice expressing 10-fold more CXCL14 protein than wild-type C57BL/6 mice showed reduced rates of chemical carcinogenesis, transplanted tumor growth, and metastasis without apparent side effects. CXCL14 also acts as an antimicrobial molecule. In this review, we highlight recent studies involving the identification and characterization of CXCL14 in cancer progression and discuss the reasons for the context-dependent effects of CXCL14 on tumor formation.

The Candida species that are important for the development of atrophic glossitis in xerostomia patients.

BACKGROUND: The purpose of this study was to clarify the species of Candida that are important for the development of atrophic glossitis in xerostomia patients. METHODS: A total of 231 patients with subjective dry mouth were enrolled in the present study. Logistic regression analysis was performed to clarify the contribution of each Candida species and other variables to the development of atrophic glossitis. The dependent variable was the absence/presence of atrophic glossitis. The Candida colony-forming units (CFU) of C. albicans, C. glabrata, C. tropicalis, and C. krusei, as well as age, gender, resting (RSFR) and stimulated (SSFR) whole salivary flow rate, and denture-wearing status, were treated as explanatory variables. RESULTS: Logistic regression analysis showed that two factors were closely associated with the presence of atrophic glossitis: an increase in C. albicans CFU and a decrease in the SSFR. CONCLUSIONS: C. albicans, but not non-albicans Candida, was associated with atrophic glossitis in xerostomia patients who had no systemic predisposing factors, indicating that C. albicans remains a treatment target for Candida-related atrophic glossitis.

[Determination of the Effect of Aprepitant and Fosaprepitant for Nausea in Patients with Oral Cancer Receiving Combination Chemotherapy with TPF].

The objective of this study was to determine the effect of aprepitant(from days 1 to 3, po)and fosaprepitant(day 1, iv) for nausea in patients with oral cancer receiving combination chemotherapy with docetaxel, nedaplatin, or cisplatin(divided doses for 5 days), and 5-fluorouracil(TPF).The incidence rate of nausea in the aprepitant group was 60%(6/10), and that in the fosaprepitant group was 90%(9/10).The incidence rate of continuous nausea for more than 2 days was significantly lower in the aprepitant group than in the fosaprepitant group(40%[4/10]vs 90%[9/10], p=0.02; c 2 test).In addition, the mean area under the curve of the chronological changes in the grade of nausea tended to be lower in the aprepitant group than in the fosaprepitant group.In both groups, 3 cases(30%)of vomiting were observed.However, the incidence of continued daily vomiting tended to be lower in the aprepitant group than in the fosaprepitant group.These results suggest that aprepitant is more effective than fosaprepitant for nausea induced by TPF.

A new oral care gel to prevent aspiration during oral care.

AIM: Although oral care is important in the prevention of aspiration pneumonia, the different institutions and practitioners employ various oral care methods, some of which are associated with the risk of aspiration. We have developed a new gel with the physical properties needed for waterless oral care. In the present study, we evaluated and investigated the properties and effectiveness of this gel. METHODS: The physical properties of the trial gel and commercial moisturizing gels were compared using a VAS scale. The effects of plaque elimination were evaluated in healthy volunteers. Brushing was carried out by a dental hygienist using the gel and water. The number of throat suctions performed during brushing was also counted, and the difference was evaluated. RESULTS: In the evaluation of physical characteristics, trial Gel B showed a significantly higher rating than the other gels. In plaque elimination, the rate of decrease in a modified PCR was significantly greater with the gel trial. Suctioning was also performed significantly fewer times with the trial gel. CONCLUSIONS: Good results were obtained with the newly developed trial Gel B with regard to the physical properties and the sensory evaluations. Its effectiveness was also confirmed in plaque elimination and in the evaluated risk of aspiration. The use of Gel B may have the potential to decrease the risk of aspiration during oral care and reduce the occurrence of aspiration pneumonia.

[Determination of the Appropriate Timing of Aprepitant Administration for Nausea in Patients with Head and Neck Cancer Receiving Combination Chemotherapy with Docetaxel, Nedaplatin（Divided Doses for 5 Days), and 5-fluorouracil].

The objective of this study was to determine the appropriate timing of aprepitant administration in patients with oral cancer by comparing the antiemetic effect of aprepitant administered on the first day (first-day group) and third day (third-day group) of combination chemotherapy with docetaxel, nedaplatin (divided doses for 5 days), and 5-fluorouracil. 1. In both groups, very few cases of vomiting were observed. Therefore, we could not compare the incidence of vomiting. 2. The mean highest grade of nausea in the third-day group was significantly higher than that in the first-day group (2.33±0.71 vs 0.78±0.22, p=0.002; U-test). 3. In addition, the mean area under the curve of the chronological changes in the grade of nausea in the third-day group was significantly higher than that in the first-day group (13.44±9.58 vs 3.11±3.59, p=0.019; U-test). 4. The incidence of nausea of grade 2 or higher in the first-day group was significantly lower than that in the third-day group (11.1% [1/9] vs 88.9% [8/9], p<0.001; c 2 test). These results indicate that initiation of aprepitant administration on the first day of combination chemotherapy with docetaxel, nedaplatin, and 5-fluorouracil successfully prevented the development of nausea in patients with oral cancer.

Evaluation of postextraction bleeding incidence to compare patients receiving and not receiving warfarin therapy: a cross-sectional, multicentre, observational study.

OBJECTIVES: We investigated incidence and risk factors for postextraction bleeding in patients receiving warfarin and those not receiving anticoagulation therapy. DESIGN: Cross-sectional, multicentre, observational study. SETTING: 26 hospitals where an oral surgeon is available. PARTICIPANTS: Data on 2817 teeth (from 496 patients receiving warfarin, 2321 patients not receiving warfarin; mean age (SD): 62.2 (17.6)) extracted between 1 November 2008 and 31 March 2010, were collected. Warfarin-receiving patients were eligible when prothrombin time-international normalised ratio (PT-INR) measured within 7 days prior to the extraction was less than 3.0. INTERVENTIONS: Simple dental extraction was performed, and incidence of postextraction bleeding and comorbidities were recorded. PRIMARY AND SECONDARY OUTCOME MEASURES: Postextraction bleeding not controlled by basic haemostasis procedure was clinically significant. RESULTS: Bleeding events were reported for 35 (7.1%) and 49 (2.1%) teeth, of which 18 (3.6%) and 9 (0.4%) teeth were considered clinically significant, in warfarin and non-warfarin groups, respectively, the difference between which was 3.24% (CI 1.58% to 4.90%). The incidence rates by patients were 2.77% and 0.39%, in warfarin and non-warfarin groups, respectively (incidence difference 2.38%, CI 0.65% to 4/10%). Univariate analyses showed that age (OR 0.197, p=0.001), PT-INR (OR 3.635, p=0.003), mandibular foramen conduction anaesthesia (OR 4.854, p=0.050) and formation of abnormal granulation tissue in extraction socket (OR 2.900, p=0.031) significantly correlate with bleeding incidence. Multivariate analysis revealed that age (OR 0.126, p=0.001), antiplatelet drugs (OR 0.100, p=0.049), PT-INR (OR 7.797, p=0.001) and history of acute inflammation at extraction site (OR 3.722, p=0.037) were significant risk factors for postextraction bleeding. CONCLUSIONS: Our results suggest that there is slight but significant increase in the incidences of postextraction bleeding in patients receiving warfarin. Although absolute incidence was low in both groups, the bleeding risk is not negligible.

Digestive symptoms as side effects of combination chemotherapy of docetaxel, nedaplatin and 5-fluorouracil for head and neck cancer.

BACKGROUND: The study was performed to determine the frequency of digestive symptoms in combination therapy of docetaxel, nedaplatin and 5-fluorouracil for head and neck cancer. METHODS: Frequencies of digestive symptoms were retrospectively investigated in 91 patients. Data for 203 treatment courses were evaluated using the JCOG/JSCO National Cancer Institute-Common Terminology Criteria for Adverse Events(v 4.0 in Japanese). RESULTS: The percentages of patients with nausea, vomiting, stomatitis, constipation, and diarrhea in the first course were 74%, 16%, 42%, 42%, and 13%, respectively. Nausea, vomiting and constipation started mostly on day 2 or 3 and peaked between day 5 and 7. Diarrhea and stomatitis began later and peaked between day 8 and 11. Nausea showed the highest frequencies, and in the late phase(day 6 to 14)of chemotherapy rather than the acute phase(day 1 to 5). Stratified analysis based on the occurrence of nausea and vomiting in previous course showed no significant influence in the frequency of nausea.And then, another stratified analyses showed higher frequency of vomiting and diarrhea in females, nausea in patients aged B65 years old. CONCLUSION: Nausea occurred at an unexpectedly high frequency in the late phase of chemotherapy with docetaxel, nedaplatin and 5-fluorouracil.

Relationship between hyposalivation and acute respiratory infection in dental outpatients.

BACKGROUND: Hyposalivation may affect respiratory disease because the mouth serves as the entrance to the respiratory apparatus, as well as to the digestive tract. Patients with acute respiratory infection generally have a favorable prognosis and a short natural course. However, in cases in which the host has lowered resistance, such as in elderly patients, the infection may develop into pneumonia. OBJECTIVES: A prospective study was performed to examine the relationship between hyposalivation, which is common in elderly patients, and acute respiratory infection, which tends to become severe in elderly patients. METHODS: The subjects were 323 male and female patients ≥40 years old who lived in Utsunomiya City and surrounding areas and regularly visited the Department of Dentistry and Oral Surgery, Tochigi National Hospital. A 6-month follow-up survey was performed to examine development of acute respiratory infection. Age, sex, and known risk factors were also investigated. Hyposalivation was defined as a saliva production (saliva secretion rate) of ≤0.6 ml/min. Multivariate analysis adjusted for age and sex was performed to examine potential risk factors associated with the development of acute respiratory infection. RESULTS: Data were analyzed for 278 subjects who completed the follow-up survey. The incidence of acute respiratory infection was 60.4%, while hyposalivation was present in 96 subjects (35.5%). Multivariate analysis showed that the incidence of acute respiratory infection was higher in subjects with hyposalivation than in those without hyposalivation (adjusted odds ratio 1.761, p = 0.048). CONCLUSION: The results of this study suggest that hyposalivation may be a risk factor for acute respiratory infection. This also suggests that improvement of hyposalivation might prevent acute respiratory infection.

[Phase I/II clinical trial of induction chemotherapy with nedaplatin (CDGP), docetaxel (DOC) and 5-fluorouracil (5-FU) for squamous cell carcinoma of head and neck].

In a phase I study, we determined the maximum tolerated dose (MTD) and the recommended dose (RD) of nedaplatin (CDGP) in combination chemotherapy with Docetaxel (DOC) and 5-fluorouracil (5-FU) for treatment of carcinoma of the head and neck. Then, in a phase II study, we examined the efficacy and safety of the RD of chemotherapy. Fresh patients with squamous cell carcinoma of the head and neck were enrolled in the study. The dosage of chemotherapy was as follows: DOC 60 mg/m(2) on day 1 by infusion over 2 hours; CDGP 20-30 mg/m(2)/day on day 1 to 5 by infusion over 1 hour, and 5-FU 600 mg/m(2)/day on day 1 to 5 by 5 days continuous infusion. For CDGP, an initial dose level was set at 20 mg/m(2), and 3 patients were enrolled for each level of dose escalation. The DLT was defined here as grade 4 neutropenia or grade> or =3 non-hematotoxic reactions. The dose at which DLT was observed in overall 33% cases was taken as MTD. The RD for phase II study was estimated to be DOC 60 mg/m(2), CDGP 20 mg/m(2)/day, 5-FU 600 mg/m(2)/day. Forty patients were enrolled in the phase II study. DLT of neutropenia was noted in 2 of 38 cases. DLT of non-hematotoxic reactions was found in less than 33% of the cases; 17 cases showed CR, and 12 cases showed PR. The response rate was 76.3%. The overall response rate in histological assessment was 55.3%. The combination chemotherapy with Low-Divided Dose of CDGP, DOC and 5-FU was suggested to be safe and effective.