Brain atrophy in normal older adult links tooth loss and diet changes to future cognitive decline.

Several studies have found associations between poor oral health, particularly tooth loss and cognitive decline. However, the specific brain regions affected by tooth loss and the probable causes remain unclear. We conducted a population-based longitudinal cohort study in Nakajima, Nanao City, Japan. Between 2016 and 2018, 2454 residents aged ≥60 participated, covering 92.9% of the local age demographics. This study used comprehensive approach by combining detailed dental examinations, dietary assessments, magnetic resonance imaging (MRI) analysis, and cognitive evaluations. Tooth loss, even in cognitively normal individuals, is associated with parahippocampal gyrus atrophy and increased WMH volume, both of which are characteristics of dementia. Tooth loss was associated with altered dietary patterns, notably a reduction in plant-based food intake and an increase in fatty, processed food intake. This study highlights a possible preventative pathway where oral health may play a significant role in preventing the early neuropathological shifts associated with dementia.

Precise analysis of single small extracellular vesicles using flow cytometry.

Methods that enable specific and sensitive quantification of small extracellular vesicles (sEVs) using flow cytometry are still under development. Aggregation or adsorption of antibodies causes sub-nano sized particles or non-specific binding and largely affects the results of flow cytometric analysis of single sEVs. Comparison of control IgG and target-specific IgG is inappropriate because they have different characters. Here, we evaluate four preparation methods for flow cytometry, including ultracentrifugation, density gradient centrifugation, size exclusion chromatography (SEC), and the TIM4-affinity method by using tetraspanin-deficient sEVs. The ultracentrifugation or density gradient centrifugation preparation method has large false-positive rates for tetraspanin staining. Conversely, preparation methods using SEC or the TIM4-affinity method show specific detection of single sEVs, which elucidate the roles of sEV biogenesis regulators in the generation of sEV subpopulations. The methods are also useful for the detection of rare disease-related markers, such as PD-L1. Flow cytometric analysis using SEC or the TIM4-affinity method could accelerate research into sEV biogenesis and the development of sEV-based diagnostics and therapies.

The pattern and spread of invasion can predict late cervical lymph node metastasis in early tongue squamous cell carcinoma.

To determine the predictive indexes of late cervical lymph node metastasis in early tongue squamous cell carcinoma (TSCC). We retrospectively analyzed the cases of 25 patients with stage I/II TSCC who had undergone surgical treatment without elective neck dissection. We evaluated the relationships between clinicopathologic factors and the occurrence of late cervical lymph node metastasis. Of the 25 cases, metastasis to the cervical lymph nodes was observed in nine cases (36.0%). The clinicopathological factors associated with late cervical lymph node metastasis were the mode of invasion (MOI, p = 0.032), depth of invasion (DOI, p = 0.004), and perineural invasion (PNI, p = 0.040). A multivariate analysis revealed that only the DOI was an independent predictor of late cervical lymph node metastasis. The combination of the DOI and MOI or the PNI and MOI was significantly correlated with late cervical lymph node metastasis (p = 0.004 and p = 0.012, respectively). Our findings suggest that combinations of the MOI, DOI, and PNI could be used as an index for predicting late cervical lymph node metastasis in early TSCC.

Tumour: Fibroblast Interactions Promote Invadopodia-Mediated Migration and Invasion in Oral Squamous Cell Carcinoma.

Objectives: In the progression of cancer, interactions between cancer cells and cancer-associated fibroblasts (CAFs) play important roles. Cancer cell invasion is facilitated by filamentous actin (F-actin)-rich membrane protrusions called invadopodia, and the relationship between CAFs and invadopodia has been unclear. We used oral squamous cell carcinoma (OSCC) to investigate CAFs' effects on the formation of invadopodia, and we assessed the expressions of invadopodia markers and CAF markers ex vivo and their relationship with clinical parameters and survival. Materials and Methods: We examined the effect of culture with normal oral fibroblast (NOF)-derived and CAF-derived conditioned medium on the migration and invasion of two OSCC-derived cell lines using Transwells in the absence/presence of Matrigel. Immunoblotting and immunocytochemistry were conducted to assess the expressions of the invadopodia markers tyrosine kinase substrate 5 (Tks5) and membrane type 1 matrix metalloproteinase (MT1-MMP). We also used immunohistochemistry to examine patients with OSCC for an evaluation of the relationship between the CAF marker alpha smooth muscle actin (αSMA) and the expression of Tks5. The patients' survival was also assessed. Results: Compared to the use of culture medium alone, NOF-CM and CAF-CM both significantly increased the OSCC cells' migration and invasion (p < 0.05), and they significantly increased the expressions of both Tks5 and MT1-MMP. After the depletion of Tks5, the OSCC cells' migration and invasion abilities decreased. The expression of Tks5 and that of αSMA were correlated with poor survival, and a high expression of both markers was associated with an especially poor prognosis. Conclusions: These results indicate that the formation of invadopodia is (i) important for OSCC cells' migration and invasion and (ii) regulated by the interaction of OSCC cells and stromal fibroblasts.

Evaluation of factors related to morphological masseter muscle changes after preoperative orthodontic treatment in female patients with skeletal class III dentofacial deformities.

BACKGROUND: The purpose of the current study was to investigate factors related to morphological changes in the masseter muscle after preoperative orthodontic treatment in patients with skeletal class III dentofacial deformities for analysis of muscle changes and malocclusions. METHODS: Twenty female patients with dentofacial deformities were included in the study. Computed tomography was performed before and after preoperative orthodontic treatment, and the lengths, widths, and cross-sectional areas of the masseter muscles were measured. Changes in these parameters were evaluated, and factors related to changes in masseter muscle area after preoperative orthodontic treatment were analyzed. RESULTS: The lengths, widths, and areas of masseter muscles were significantly smaller after preoperative orthodontic treatment. Smaller masseter muscle area was significantly associated with changes in overbite and pretreatment values of SNA angle. CONCLUSIONS: Atrophy of the masseter muscle during preoperative orthodontic treatment was greater in patients with increased open bite due to improved dental compensation in patients with skeletal class III dentofacial deformities with maxillary retraction.

Evaluation of Rhythmic Masseter Muscle Activity during Sleep and Awake in Patients with Dentofacial Deformity.

Objectives: Investigate the activity of rhythmic masseter muscles activity (RMMA) during sleep in patients with dentofacial deformities. Materials and methods: Fifty patients with dentofacial deformities (16 male, 34 female) who required orthognathic surgery. An electrode was attached to the masseter muscle bilaterally, and preoperative polysomnography was performed. The frequency of RMMA onset per hour was measured on the left and the right sides. Values were classified as phasic (grinding: P-RMMA) and tonic (clenching: T-RMMA) to examine the onset of RMMA. Correlation between the RMMA index and various morphological and physical factors were determined including sleep or awake, rapid eye movement (REM), non-rapid eye movement (NREM) phases (NR1-NR4) in the sleep stage, phasic and tonic, gender, and mandibular asymmetry. Results: The RMMA index values at the time of sleep were significantly small than during awake. The values were significantly higher during the NREM sleep than during the REM sleep and were the highest in the NR1 phase. P-RMMA index was significantly higher than the T-RMMA index. The P-RMMA index was also significantly higher than the T-RMMA index for men. In patients with greater asymmetry in the RMMA index values between the left and the right side (more than 30% difference), deviation between the midpoint of the maxillary and the mandibular incisal edges (U1-L1 deviation) was significantly higher. Conclusion: RMMA in patients with dentofacial deformity was statistically higher in awake than sleep, higher in NREM sleep than REM sleep, higher in male than female on grinding, and higher in upper and lower incisor high deviation.

Automatic discrimination of Yamamoto-Kohama classification by machine learning approach for invasive pattern of oral squamous cell carcinoma using digital microscopic images: a retrospective study.

OBJECTIVE: The Yamamoto-Kohama criteria are clinically useful for determining the mode of tumor invasion, especially in Japan. However, this evaluation method is based on subjective visual findings and has led to significant differences in determinations between evaluators and facilities. In this retrospective study, we aimed to develop an automatic method of determining the mode of invasion based on the processing of digital medical images. STUDY DESIGN: Using 101 digitized photographic images of anonymized stained specimen slides, we created a classifier that allowed clinicians to introduce feature values and subjected the cases to machine learning using a random forest approach. We then compared the Yamamoto-Kohama grades (1, 2, 3, 4C, 4D) determined by a human oral and maxillofacial surgeon with those determined using the machine learning approach. RESULTS: The input of multiple test images into the newly created classifier yielded an overall F-measure value of 87% (grade 1, 93%; grade 2, 67%; grade 3, 89%; grade 4C, 83%; grade 4D, 94%). These results suggest that the output of the classifier was very similar to the judgments of the clinician. CONCLUSIONS: This system may be valuable for diagnostic support to provide an accurate determination of the mode of invasion.

Factors related to oxygen desaturation index during sleep 7 days after bilateral sagittal splitting ramus osteotomy in patients without previous obstructive sleep apnea.

PURPOSE: The incidence of obstructive sleep apnea (OSA) immediately after surgery in patients with dentofacial deformities without previous OSA remains unknown. We aimed to perioperatively evaluate factors associated with oxygen desaturation index (ODI) during sleep, 7 days after bilateral splitting ramus osteotomy (BSSRO) in patients without previous OSA. METHODS: Fifty-one patients (15 males, 36 females) with dentofacial deformities, scheduled to undergo BSSRO, were included. Polysomnography was performed before orthognathic surgery. Perioperative OSA was evaluated with peripheral arterial tonometry on the day of surgery and 1, 2, 3, 4, and 7 days postoperatively. Rapid eye movement (REM) sleep periods and the ODI were measured. Factors associated with perioperative ODI after surgery were statistically analyzed. RESULTS: REM sleep periods were significantly decreased on the day of surgery and significantly increased at 4 and 7 days postoperatively, compared to the preoperative period. ODI increased on the day of surgery, decreased after 1 day, and increased again at 4 and 7 days postoperatively. ODI on the day of surgery was significantly increased due to increased preoperative ODI, overjet, and SN-MP angle and decreased SNA and SNB angle. ODI at 7 days postoperatively was significantly increased due to increased REM sleep periods and decreased SN-MP and gonial angle. ODI was increased in response to REM sleep periods 7 days after BSSO. CONCLUSION: Airway management in patients with dentofacial deformity should be given more attention by preoperative assessment for OSA, even in the absence of previous OSA, until 7 days postoperatively due to REM rebound.

The dipeptide prolyl-hydroxyproline promotes cellular homeostasis and lamellipodia-driven motility via active ß1-integrin in adult tendon cells.

Collagen-derived hydroxyproline (Hyp)-containing peptides have a variety of biological effects on cells. These bioactive collagen peptides are locally generated by the degradation of endogenous collagen in response to injury. However, no comprehensive study has yet explored the functional links between Hyp-containing peptides and cellular behavior. Here, we show that the dipeptide prolyl-4-hydroxyproline (Pro-Hyp) exhibits pronounced effects on mouse tendon cells. Pro-Hyp promotes differentiation/maturation of tendon cells with modulation of lineage-specific factors and induces significant chemotactic activity in vitro. In addition, Pro-Hyp has profound effects on cell proliferation, with significantly upregulated extracellular signal-regulated kinase phosphorylation and extracellular matrix production and increased type I collagen network organization. Using proteomics, we have predicted molecular transport, cellular assembly and organization, and cellular movement as potential linked-network pathways that could be altered in response to Pro-Hyp. Mechanistically, cells treated with Pro-Hyp demonstrate increased directional persistence and significantly increased directed motility and migration velocity. They are accompanied by elongated lamellipodial protrusions with increased levels of active ß1-integrin-containing focal contacts, as well as reorganization of thicker peripheral F-actin fibrils. Pro-Hyp-mediated chemotactic activity is significantly reduced (p < 0.001) in cells treated with the mitogen-activated protein kinase kinase 1/2 inhibitor PD98059 or the α5ß1-integrin antagonist ATN-161. Furthermore, ATN-161 significantly inhibits uptake of Pro-Hyp into adult tenocytes. Thus, our findings document the molecular basis of the functional benefits of the Pro-Hyp dipeptide in cellular behavior. These dynamic properties of collagen-derived Pro-Hyp dipeptide could lead the way to its application in translational medicine.

Metalloelastase-12 is involved in the temporomandibular joint inflammatory response as well as cartilage degradation by aggrecanases in STR/Ort mice.

Temporomandibular joint dysfunction (TMJD) is characterised by clinical symptoms involving both the masticatory muscles and the temporomandibular joint (TMJ). Disc internal derangement and osteoarthritis (OA) are the most common forms of TMJD. Currently, the molecular process associated with degenerative changes in the TMJ is unclear. Our previous study showed that elastin-digested peptides act on human TMJ synovial cells and lead to upregulation of interleukin-6 (IL-6) and metalloelastase-12 (MMP-12; an elastin-degrading enzyme) in vitro. However, there is limited information regarding the involvement of elastin-degradation by MMP-12 in the processes of inflammatory responses and cartilage degradation in vivo. STR/Ort mice were used as a model of TMJ OA in the present study. Significant articular cartilage degeneration was observed starting at 20 weeks of age in the STR/Ort mice and this progressed gradually until 40 weeks, compared with the age-matched CBA mice. Immunostaining analysis showed that MMP-12 and IL-6 were expressed in the chondrocytes in the superficial zones of the cartilage. Immunostaining also showed that aggrecanases [a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5] were expressed in the chondrocytes in the superficial zones of the cartilage. These findings suggest that an inflammatory and degradative process was initiated in the TMJ. Harmful mechanical stimuli, particularly pressure, may cause damage to the elastin fibres in the most elastin-rich superficial layer of the articular cartilage. Elastin-digested peptides are then generated as endogenous warning signals and they initiate a pro-inflammatory cascade. This leads to upregulation of pro-inflammatory mediators, such as IL-6 and MMP-12, which further trigger tissue damage resulting in elevated levels of elastin-digested peptides. IL-6 increases expression of the aggrecanases ADAMTS-4 and ADAMTS-5, following cartilage degradation. This leads to the establishment of a positive feedback loop and may result in chronic inflammation and cartilage degradation of the TMJ in vivo.

Comparison of Postoperative Stability Between BSSRO and Le Fort 1 Osteotomy with BSSRO in Skeletal Class III Malocclusion with Severe Open Bite.

INTRODUCTION: We aimed to investigate postoperative stability after orthognathic surgery in patients with skeletal class III malocclusion with severe open bite by comparison between bilateral sagittal splitting osteotomy (BSSRO) and BSSRO with Le Fort 1 osteotomy. MATERIALS AND METHODS: Seventeen patients with skeletal class III malocclusion with severe open bite who were needed more than 6 degree counterclockwise rotation of distal segment by only BSSRO in preoperative cephalometric prediction. The subjects were divided into group A, where 9 patients were treated by BSSRO, and group B, where 8 patients were treated by BSSRO with Le Fort 1 osteotomy. Patient's characteristics of age, gender, preoperative over jet (OJ) and over bite (OB) were not found to be significantly different between the two groups. Counterclockwise rotation of distal segment in preoperative cephalometric prediction by only BSSRO was not found to be significantly different between group A of 7.6 (6-10.6) degree and group B of 9 (6-13) degree. The amount of rotation was reduced to 5.4 (3-10) degree by bimaxillary surgery using BSSRO and Le Fort 1 osteotomy in group B. OJ and OB were measured as occlusal stability factor. Distance between ANS-to-PNS plane and the edge of upper incisor (NF-U1Ed), and distance between Menton and edge of lower incisor (Me-L1Ed) were measured as skeletal stability factor using cephalometric analysis. These lengths were measured at pre-surgery (T0), 2 weeks after surgery (T1) and 1 year after surgery (T2), and these differences between the two groups were statistically analyzed. RESULTS: OJ and OB kept a good relation at any experimental periods. The change of Me-L1Ed was significantly larger in group A (1.21 mm at T0-T1, 1.02 mm at T0-T2) than in group B (0.14 mm at T0-T1, 0.16 mm at T0-T2). The change of NF-U1Ed was not significantly different between group A (1.07 mm at T0-T1, 0.57 mm at T0-T2) and group B (0.51 mm at T0-T1, - 0.05 mm at T0-T2). CONCLUSION: In case with more than 6 degree counterclockwise rotation of distal segment, skeletal stability was better after bimaxillary surgery than only BSSRO; however, OJ and OB kept a good relation.

Comparison of Maximum Mouth Opening Following Mandibular Bilateral Sagittal Splitting Ramus osteotomies in Class III Females Using Two Different Osteosynthesis Methods.

BACKGROUND: Limitation of mouth opening is a common complaint following orthognathic surgery. OBJECTIVES: This investigation reports on the progress of maximum incisal opening following orthognathic surgery and compares the impact of two different osteosynthesis methods on mouth opening in female patients with Class III dentofacial deformities. METHODS: Forty cases of skeletal class III malocclusion were divided into twenty cases treated using the conventional single miniplate osteosynthesis method (P1) and twenty cases using the additional L-shaped miniplate osteosynthesis method (P2). No significant differences in pre-operative clinical status were detected between the P1 and P2 group, and all patients were managed with elastics in the post-operative period. Independent mouth opening exercises were initiated seven days after surgery, and inter-incisal distance was measured as maximum mouth opening (MMO) at 1 week, 2 weeks, and 1, 2, 3, 6 months. Statistical analysis was performed in order to analyse differences in MMO between the P1 and P2 groups (Prism 7 GraphPad software, San Diego, CA). Values of P < .05 were considered to be significant. RESULTS: MMO significantly increased from 2 weeks after surgery in both groups. The MMO of P2 was significantly larger than that of P1 in all experimental periods after surgery. MMO was statistically improved in P2 at 2 months after surgery, while MMO in P1 was significantly smaller than the pre-operative MMO, even at 6 months post-operative. A minimum MMO of 40 mm was achieved by all patients. CONCLUSION: L-shaped miniplate osteosynthesis was more useful for early limitation of mandibular opening improvement than conventional single miniplate osteosynthesis.

Relationship between pharyngeal airway depth and ventilation condition in mandibular setback surgery: A computational fluid dynamics study.

OBJECTIVES: This study aimed to determine the anteroposterior depth (APD) of the pharyngeal airway (PA) where post-operative PA obstruction was predicted, using computer fluid dynamics (CFD), in order to prevent obstructive sleep apnoea after mandibular setback surgery. SETTINGS AND SAMPLE POPULATION: Nineteen skeletal Class III patients (8 men; mean age, 26.7 years) who required mandibular setback surgery had computed tomography images taken before and 6 months after surgery. METHODS: The APD of each site of the four cross-sectional reference planes (retropalatal airway [RA], second cervical vertebral airway, oropharyngeal airway and third cervical vertebral airway) were measured. The Maximum negative pressure (Pmax) of the PA was measured at inspiration using CFD, based on a three-dimensional PA model. Intersite differences were determined using analysis of variance and the Friedman test with Bonferroni correction. The relationship between APD and Pmax was evaluated by Spearman correlation coefficients and non-linear regression analysis. RESULTS: The smallest PA site was the RA. Pmax was significantly correlated with the APD of the RA (rs  = .628, P < .001). The relationship between Pmax and the APD-RA was fitted to a curve, which showed an inversely proportional relationship of Pmax to the square of the APD-RA. Pmax substantially increased even with a slight reduction of the APD-RA. In particular, when the APD-RA was 7 mm or less, Pmax increased greatly, suggesting that PA obstruction was more likely to occur. CONCLUSIONS: The results of this study suggest that APD-RA is a useful predictor of good PA ventilation after surgery.

Caveolin-1 Expression at Metastatic Lymph Nodes Predicts Unfavorable Outcome in Patients with Oral Squamous Cell Carcinoma.

We evaluated the clinical and prognostic value of the protein expression of caveolin-1 (CAV1) and p16 at the primary site and metastatic lymph nodes of oral squamous cell carcinoma (OSCC). Primary site specimens from 80 OSCC cases were randomly selected and lymph node specimens from 15 preserved metastatic lymph nodes from among those patients were selected for examination. We evaluated the CAV1 and p16 expression at both the primary site and metastatic lymph nodes, and analyzed the patients' clinicopathological data in relation to CAV1 and p16 expression. Our analysis revealed significant positive correlations between CAV1 expression at the primary site and pathological metastasis, cell differentiation, and mode of invasion (p = 0.019, p = 0.002, p = 0.015, respectively), but p16 expression was not associated with any clinicopathological factors. Patients with high CAV1 expression at the primary sites showed significantly worse prognoses than those with low or negative CAV1 expression (p = 0.002), and multivariate analysis showed that the T classification and CAV1 expression were independent OSCC prognostic factors. CAV1 expression was also present in the metastatic lymph nodes of the OSCC cases with particularly poor differentiation and high invasive grade, and patients with CAV1-positive metastatic lymph nodes showed significantly worse prognoses than those with CAV1-negative metastatic lymph nodes (p = 0.018). CAV1 may activate metastaticity and the invasive capacity of OSCC cells. CAV1 expression, particularly at metastatic lymph nodes, predicts a worse outcome for OSCC, suggesting that CAV1 could be used as a prognostic marker for OSCC.

Focal Adhesion Kinase (FAK) Overexpression and Phosphorylation in Oral Squamous Cell Carcinoma and their Clinicopathological Significance.

Focal adhesion kinase (FAK) is involved in progression of various cancers, and FAK overexpression has been associated with cancer invasion and metastasis. However, the involvement of FAK expression in the clinicopathological malignancy of oral squamous cell carcinoma (OSCC) remains unknown. In addition, there is no consensus regarding the role of p16 expression in OSCC. In this study, the immunohistochemically measured expression of FAK, phosphorylated FAK (FAKpY397) and p16 expressions and their associations with clinicopathological features and 5-year survival rates were examined in surgical samples from 70 patients with primary OSCC. FAK and FAKpY397 were expressed at high levels in 42 cases (60.0%) and 34 cases (48.6%), respectively, and 9 cases (12.9%) were positive for p16. FAK expression was significantly correlated with local recurrence, subsequent metastasis, and the mode of invasion. FAKpY397 expression was significantly correlated with both N classification and the mode of invasion. p16 expression was significantly correlated with clinical stage only. Patients having high expression of FAK, FAKpY397, or both showed significantly worse prognosis, but p16 expression showed no significant relation to prognosis. The results suggested that overexpression and phosphorylation of FAK in OSCC may affect cancer progression, such as local invasion and lymph node metastasis, and thereby contribute to life prognosis.

Factors related to patients' nutritional state after orthognathic surgery.

PURPOSE: The purpose of this study was to evaluate patients' nutritional state after orthognathic surgery. METHODS: The subjects were 40 female patients with dentofacial deformity aged 17-33 years who were undergoing bilateral sagittal splitting ramus osteotomy. Twenty patients were treated with intermaxillary fixation, and 20 patients were treated without intermaxillary fixation. Age and body mass index (kg/m2) were assessed as physical factors, operation time, blood loss, and amount of mandibular movement with or without intermaxillary fixation were assessed as operation stress factors, and the following laboratory data, total protein, serum albumin, total cholesterol, total lymphocytes, and cholinesterase were assessed as nutritional state factors at 1 and 2 weeks after surgery. Statistical analysis was performed for body weight loss and relationship between body weight loss and examination factors. RESULTS: Body weight significantly decreased 2.3% at 1 week and 3.9% at 2 weeks after surgery rather than preoperation. All laboratory data except total lymphocyte were decreased at 1 week after surgery and still remained significantly decreased at 2 weeks after surgery. There was a statistically significant relationship between body weight loss at 1 week after surgery and operation time. CONCLUSIONS: These results indicate that long operation time caused body weight loss in orthognathic surgery.

Selectively high efficacy of eribulin against high-grade invasive recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have a poor prognosis. Over the past decade, a major development in the first-line treatment of R/M SCCHN was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy. Currently, a promising novel treatment option in R/M SCCHN has emerged, termed immune checkpoint inhibitors. However, only a few patients presenting with R/M SCCHN have exhibited meaningful tumor regression with these agents. Therefore, novel agents are required to order improve the overall survival of patients with R/M SCCHN. Recently, we demonstrated that R/M SCCHN cells are highly sensitive to eribulin. In the present study, the effects of eribulin, paclitaxel and vinblastine were investigated in R/M SCCHN (OLC-01 and OSC-19) and locally advanced SCCHN (OSC-20) cells. Tumour-inhibitory activities of eribulin against R/M SCCHN were evaluated in orthotopic xenograft models. The data revealed that eribulin has sub-nM growth inhibitory activities in vitro against OLC-01 cells, and that it is more potent than paclitaxel and vinblastine. The reduced expression of Tubulin Beta 3 Class III (TUBB3) following treatment was correlated with a high sensitivity to eribulin. Histological analysis of OLC-01 cells in NOD-SCID mice demonstrated that they had a higher invasiveness in the tissue around the alveolar cancer when compared with the histology of OSC-19 cells, which has been reported in our previous study. Treatment with eribulin revealed marked inhibitory activities in vivo at 0.125 mg/kg against OLC-01 cells orthotopic xenografts. In conclusion, the results highlight the existence of invasive-type heterogeneity in R/M SCCHN with respect to eribulin sensitivity. Eribulin is already an approved clinical agent; therefore, the continued investigation of its preclinical antitumor attributes may contribute significantly to the future process of identifying novel uses of eribulin against R/M SCCHN.

Detection of sentinel lymph node using contrast-enhanced agent, Sonazoid™, and evaluation of its metastasis with superb microvascular imaging in oral and oropharyngeal cancers: a preliminary clinical study.

BACKGROUND: In sentinel lymph node (SLN) biopsy for head and neck cancers, the radioisotope method has been the gold standard. However, this method has several problems, such as unavoidable radiation exposure and requirements of expensive equipment. AIMS/OBJECTIVES: To overcome these problems, we evaluated the contrast-enhanced ultrasonography (CEUS)-guided SLN-detection method, and predicted the SLN metastatic status using novel ultrasound technology, superb microvascular imaging (SMI). METHODS: Ten patients (6 with oral and 4 with oropharyngeal cancers) without neck lymph node metastasis were enrolled in this study. Ultrasound contrast agent, Sonazoid™, was infiltrated into the mucosa at the primary site to observe the lymphatic ducts and SLNs in the neck field. The detected SLNs were examined for blood flow using SMI to categorize the SLNs metastases-positive or negative. RESULTS: SLNs were successfully detected in 8 out of 10 cases. In 7 out of the 8 cases, in whom SLNs were successfully detected, the metastatic status of SLNs was correctly diagnosed with SMI. CONCLUSIONS AND SIGNIFICANCE: Although more clinical data are needed based on a larger cohort, establishing the CEUS-guided SLN-detection and criteria for the accurate diagnosis of SLN-metastases using SMI would be valuable as an alternative to radioisotope method, in oral and oropharyngeal cancers.

Clinicopathological Significance of the ET Axis in Human Oral Squamous Cell Carcinoma.

The interaction between cancer cells and the surrounding microenvironment in malignant tumor tissue is known to be closely associated with cancer cell invasion and proliferation. Endothelin (ET) present in the microenvironment surrounding tumors has been reported to play a role in cancer cell invasion and proliferation by binding to receptors on the cell membrane of cancer cells. Here, we immunohistologically detected the expression of ET-1 and its receptor ETAR in oral squamous cell carcinoma (OSCC) and evaluated the association between the expression of each as well as their co-expression (ET-axis expression) and clinicopathological factors. A significant difference was observed between the invasion pattern as a parameter of cancer cell malignancy and the expressions of ET-1 and ETAR. The survival rates were significantly lower among the patients who were strongly positive for ET-1 and the ETAR-positive patients compared to negative patients. There was also a significant difference between ET-axis expression and the degree of histological differentiation and mode of invasion, and the survival rate of the positive cases was significantly lower than that of the negative cases. Our findings suggested that ET-axis assessments are important for assessing the malignancy of cancer cells and predicting the prognoses of OSCC patients.

Tooth loss-related dietary patterns and cognitive impairment in an elderly Japanese population: The Nakajima study.

Although several studies have demonstrated a potential correlation of dietary patterns with cognitive function, the relationship between tooth loss and dietary patterns and cognitive function have not been identified. In this cross-sectional study, we used a reduced rank regression (RRR) analysis, a technique used previously to observe dietary patterns based on the intakes of nutrients or levels of biomarkers associated with the condition of interest, to identify tooth loss-related dietary patterns and investigate the associations of such patterns with cognitive impairment in 334 community-dwelling Japanese subjects aged ≥ 60 years. According to Pearson correlation coefficients, the intakes of six nutrients (ash content, sodium, zinc, vitamin B1, α- and ß-carotene) correlated significantly with the number of remaining teeth. Using RRR analysis, we extracted four dietary patterns in our subject population that explained 86.67% of the total variation in the intakes of these six nutrients. Particularly, dietary pattern 1 (DP1) accounted for 52.2% of the total variation. Food groups with factor loadings of ≥ 0.2 included pickled green leafy vegetables, lettuce/cabbage, green leaves vegetables, cabbage, carrots/squash; by contrast, rice had a factor loading of <-0.2. In a multivariate regression analysis, the adjusted odds ratios regarding the prevalence of cognitive impairment for the lowest, middle and highest tertiles of the DP1 score were 1.00 (reference), 1.224 (95% confidence interval [CI]: 0.611-2.453) and 0.427 (95% CI: 0.191-0.954), respectively. To our knowledge, this is the first report to show that tooth loss-related dietary patterns are associated with a high prevalence of cognitive impairment. These results may motivate changes in dental treatment and the dietary behaviours and thereby lower the risk of cognitive impairment.