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Simple Summary: In recent years, much research has focused on how exercise improves cancer prognosis and how the protein myokine, which is associated with exercise, inhibits cancer progression. However, there have been few detailed studies on oral cancer. This study is the first to show that exercise inhibits the progression of oral cancer. While other studies have shown that exercise suppresses growth, decreases the tumor formation rate, or improves survival in patients with other organ cancers, this study showed that exercise inhibits tumor formation and growth in oral cancer and prolongs survival. Furthermore, while many studies have demonstrated an indirect immune-mediated mechanism by which exercise suppresses cancer, this study suggests the additional possibility that myokines released by exercise directly affect oral cancer cells. This study has the above novelties. Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study. Just prior to transplantation, blood was collected from the mice, and the levels of myokines were measured by ELISA. Oncostatin M (OSM), a selected myokine, was added to HSC-3-M3 cells, after which the cell proliferation ability, cell cycle, and protein expression were analyzed in vitro. Tumor cell viability was lower (control: 100%, exercise: 75%), tumors were smaller (control: 26.2 mm3, exercise: 6.4 mm3), and survival was longer in the exercise group than in the control group in vivo. OSM inhibited HSC-3-M3 cell proliferation in a concentration-dependent manner in vitro. The addition of OSM increased the proportion of cells in the G0/G1 phase, decreased the proportion of cells in the G2/M phase, and increased the expression of the CDK inhibitors p21 and p27. These results indicate that exercise may directly inhibit the proliferation of HNSCC cell lines via OSM. [ABSTRACT FROM AUTHOR]

Simple Summary: The presence of cervical lymph node metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC). Therefore, the detection of metastatic lymph nodes before treatment is most important to improve patient prognosis. The purpose of this study was to combine imaging findings of cervical lymph nodes and histopathological factors of biopsy specimens associated with cervical lymph node metastasis in OSCC. Our results suggest that cervical lymph node metastasis is related to the internal echo of ultrasonography (US), rim enhancement of enhanced Computed Tomography (CT), vascular invasion, and Yamamoto–Kohama (YK) classification of biopsy specimens. We have established new diagnostic criteria combining these factors. This strategy may reduce false negative diagnoses of cervical lymph node metastasis. Purpose: To establish a diagnosis method based on imaging findings and histopathological factors associated with cervical lymph node metastasis. Methods: A total of 1587 cervical lymph nodes that were detected using imaging tools in 73 OSCC patients who underwent surgical treatment were enrolled to evaluate the association between imaging findings (long diameter, short diameter, long–short ratio, US findings (hilum and internal echo), contrast effect with enhanced CT, standardized uptake value (SUV) max and SUV average with 18F FDG-Positron Emission Tomography (PET)) and metastatic cervical lymph nodes. In 57 OSCC patients, biopsy specimens were evaluated for histopathologic factors (budding score, lymphatic invasion, vascular invasion, nerve invasion, and YK classification) and the presence of cervical lymph node metastases. Cervical lymph node metastasis was determined based on histopathological examination of the lymph nodes of patients with no metastasis observed 3 years after primary surgery. Results: In total, 22 of the 73 patients had cervical lymph node metastasis pathologically. In the comparison of the presence of metastatic lymph nodes, univariate analysis showed significant differences in cervical lymph node long and short diameter, long/short ratio, internal echo, rim enhancement, SUV max, SUV average, budding score, and vascular invasion. Multivariable analysis showed significant differences in internal echo, rim enhancement, SUV max, and budding score. Conclusions: We propose a chart diagnostic system that combines imaging and histopathological findings to improve the diagnosis of cervical lymph node metastasis. [ABSTRACT FROM AUTHOR]

This paper proposes a stiffness sensitivity analysis with principal strain application to decrease the out-of-plane vibration, which is the main source of the sound radiation of mechanical structures with thin plate parts. The sensitivity is evaluated as a differential coefficient of the target response with respect to the design variable, e.g., stiffness or mass. For suppressing the out-of-plane vibration, we pay attention to finding an appropriate location on the structure to add local stiffness. The location is decided according to stiffness sensitivity analysis results. The compliance frequency response function (FRF) is considered as the target response, and the thickness of stiffener is considered as the design variable. The validity of the proposed method is examined through numerical simulation with a finite element method (FEM) model of a thin plate. The modal principal strain distributions, stiffness sensitivity, and FRF changes by local thickening are calculated based on 4 selected natural modes. It is also examined by the experimental approach. The expected reduction of the response is attained by adding the stiffener (a thin stainless plate) to the appropriate location on the plate. [ABSTRACT FROM AUTHOR]

Background: Currently, patients with dysphagia are receiving dietary management that deviates from their original swallowing function. Objective: To evaluate the clinical significance of fibreoptic endoscopic evaluation of swallowing (FEES) and dietary intervention (DI) by multi‐professional collaboration during visit care for determining the actual oral intake status in patients with dysphagia. Methods: Five hundred and eighteen patients with dysphagia underwent FEES, focusing on the penetration‐aspiration scale, and DI. Oral intake status was categorised using the functional oral intake scale (FOIS). FOIS scores at the first visit, after FEES, and at the reassessment were compared. Results: At the first visit, 34.7% of the patients had an FOIS score of level 1 (no oral intake) and 65.3% had a score of level 2 or higher (capable of oral intake). Following FEES, 7.1% of patients had an FOIS score of level 1, and 44.4% had a score of level 2 with resumption of oral intake. At the reassessment, 489 patients (94.4%) were capable of oral ingestion (FOIS level 2 or higher). There were significant differences between the distributions of FOIS scores at the first visit and following FEES (P <.01) and between those at the first visit and at the reassessment (P <.01). Regarding tube feeding, 17 (5.9%) of 289 patients, who had received tube feeding at the first visit, were completely capable of oral intake following FEES and at the reassessment. Conclusion: Appropriate evaluation of swallowing function using FEES and DI helps to understand the definite swallowing function in patients with dysphagia. [ABSTRACT FROM AUTHOR]

Tumor eradication and esthetic and functional recovery of upper jaw defects are two of the greatest challenges in the treatment of an extensive maxillary tumor affecting the paranasal sinus. Here, we report a case of successful treatment of an advanced maxillary ameloblastoma extending to the maxillary and ethmoid sinuses and affecting the orbital floor. A 45-year-old man, who presented with a large mass in the left maxilla and a marked swelling of the cheek was referred to our department. He had a medical history of being given a diagnosis of ameloblastoma in the maxilla 13 years ago, but he had not undergone any treatment. Pre-operative radiographic examinations, CT, and MRI revealed a large tumor destroying the maxillary bone and extending into maxillary and ethmoid sinuses. The left nasal cavity was completely obstructed, and the bone of the orbital floor was lifted and deformed. After confirming the tumor as ameloblastoma, excision of the total left maxilla, palate, and orbital floor bone including the tumor extending to the nasal cavity and ethmoid sinus was carried out in joint surgery with an otolaryngologist. The surgical wound of the orbital floor and in the buccal area was covered by a forearm flap and skin graft in order to maintain a direct view of possible tumor recurrence near the skull base. Two years after the operation, there was no recurrence of the tumor. Disturbance of eyeball movement was not detected. Occlusal and speech functions were recovered using a maxillofacial prosthesis made by a prosthodontist. [ABSTRACT FROM AUTHOR]

Local electromagnetic field enhancement in resonant metamaterials is useful for efficient generation of nonlinear phenomena; however, the field enhancement is suppressed by losses of nonlinear elements in metamaterials. For overcoming this issue, we investigate the nonlinear response of an electromagnetically induced transparency-like metasurface loaded with gas as the nonlinear element. To induce nonlinearity in the gas associated with discharges, an electromagnetic wave with a modulated amplitude is incident on the metasurface. The measured waveform and spectrum of the transmitted electromagnetic wave, along with light emission from the discharge microplasma, reveal that frequency mixing can occur on the metasurface. The parameter dependence of the conversion efficiency of the frequency mixing phenomenon shows that the efficiency is determined almost entirely by the ratio of the duration of microplasma generation to the modulation period of the incident wave amplitude. This result implies that the frequency mixing is derived from a binary change in the transmittance of the metasurface caused by the generation and quenching of the microplasma. [ABSTRACT FROM AUTHOR]

Europium oxide (EuO) is coated on zinc (Zn) wire using the electrophoretic deposition process. The coated Zn wire is subjected to the wire explosion process (WEP) which is rapid (< 15 min), and chimie douce (soft chemical, low temperature), in nature; this results in the formation of Eu doped ZnO. The explosion chamber contains oxygen (99.9%) at atmospheric pressure. Electron micrographs indicate that the particle sizes are ∼ 80 nm. Diffractogram-based analysis suggests that the crystallite size is ~ 18-20 nm in the as-prepared doped ZnO nanoparticles. Electron paramagnetic resonance shows the presence of Zn vacancies and the cryo-photoluminescence spectrum indicates that Eu exists in the + 3 state. A combined Williamson-Hall plot and Kisielowski's model based analysis indicates that Eu is a substitutional dopant in WEP derived Eu:ZnO particles. It is estimated that this material has ∼ 0.24 at.% doping. This analysis also shows that, unlike another popular material GaN, in the case of ZnO, Eu strictly substitutes for Zn (i.e., dopant replacing a cation-anion pair does not seem possible). It may be noted that Eu in a suitable host is oftentimes reported to be an efficient luminophore. The IR spectra show a band shift from 486 cm to 493 cm; with peak shifts from 436 cm to 430 cm in Raman spectra. These too indicate the presence of Eu in the samples. However, at room temperature, only green luminescence (centered at 534 nm) is observed from the sample indicating (1) high concentrations of O anti-site defects and Zn vacancies, and (2) concomitant quenching of the luminescence at room temperature. Our results suggest that WEP is viable for synthesizing rare earth doped ceramic materials. However, obtaining efficient phosphors using this approach will likely require, (1) reduction of defect densities, and (2) appropriate passivation using post-processing. [ABSTRACT FROM AUTHOR]

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare odontogenic malignant tumor, and the origin is considered remnant odontogenic epithelium, odontogenic cyst, and rarely benign odontogenic tumors. We report an extremely rare case of PIOSCC arising from ameloblastoma. A 62-year-old man complained a large hard mass at the sublingual to the submental region. The computed tomography images revealed a large multilocular soft tissue mass extending into the bilateral molar areas with expansion of the mandible and also into the subcutaneous layer at the submental and the submandibular regions. He had received a curettage treatment of unicystic ameloblastoma in the right mandible 23 years ago. Malignant odontogenic tumor was suspected, and sectional mandibulectomy following reconstruction using a titanium plate and pedicle latissimus dorsi flap were performed. Histological examination disclosed a close correlation of intraosseous growth of squamous cell carcinoma and ameloblastoma. PIOSCC arising and dedifferentiated from long term existed ameloblastoma was mostly considered. There has been no recurrence and no metastasis for more than five years after the surgical treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Mucoepidermoid carcinoma (MEC) is the most common malignancy of all salivary neoplasms, and no effective treatment strategy for MEC has been established other than resection. In this study, we showed that Purkinje cell protein (PCP) 4/peptide (PEP) 19 and human epidermal growth factor receptor 2 (HER2) are predicted to play important roles in the pathogenesis and progression of MEC. The detection of PCP4/PEP19 and HER2 may be useful for providing more effective treatments against MEC. Mucoepidermoid carcinoma (MEC) is one of the most common malignant salivary gland carcinomas, but no effective treatment strategy has been established other than surgical resection. Purkinje cell protein (PCP) 4/peptide (PEP) 19 is a calmodulin-binding antiapoptotic peptide that is expressed and inhibits apoptosis in human breast cancer cells. Human epidermal growth factor receptor 2 (HER2) is an epidermal growth factor that has been implicated in the pathogenesis of many carcinomas, particularly breast and gastric carcinomas. In the present study, we performed immunohistochemical analyses of samples from 73 patients who underwent surgical resection for MEC of the salivary gland using antibodies against PCP4/PEP19 and HER2. PCP4/PEP19 expression was related to better prognosis, while HER2 expression was associated with worse prognosis. Patients that were PCP4/PEP19-positive and HER2-negative showed similar outcomes to PCP4/PEP19 and HER2 alone. Therefore, PCP4/PEP19 and HER2 are predicted to play important roles in the pathogenesis and progression of MEC. [ABSTRACT FROM AUTHOR]

A Nd:YAG (neodymium-doped yttrium aluminum garnet) laser is environmentally safe, due to the absence of any poisonous or hazardous gases, and also economical, without the need for expensive gases. We can thus expect a safe and low cost REBa2Cu3Oy (REBCO)-coated conductor fabrication process by using an Nd:YAG laser. We investigated the fabrication of YBa2Cu3Oy (YBCO) films using a PLD method with a fourth harmonic Nd:YAG laser. The YBCO films showed good superconducting properties; for example, on SrTiO3 single crystalline substrates, Tc and Jc were about 90 K and 2.5 MA/cm^2, respectively, at 77 K. In order to enhance Jc in magnetic fields, BaSnO3 was doped into YBCO films by means of a combinatorial Nd:YAG-PLD method. The combinatorial method enabled the growth and study of a library of samples ranging from pure-YBCO to BSO-doped-YBCO. We demonstrated rapid optimization of BaSnO3 content by the combinatorial method and concluded that the optimal BSO content was around 3.6 wt%. In addition, in order to enhance material yield of the Nd:YAG-PLD method, we optimized the oxygen pressure and distance between the target and substrate. On a substrate with dimensions of 10\times 10\ mm^2, the material yield of a YBCO film reached about 19.0%. These results suggest that the Nd:YAG-PLD method is promising for forming YBCO-coated conductors. [ABSTRACT FROM AUTHOR]

Simple Summary: As sarcopenia has been shown to be associated with a variety of functional impairments and increased mortality, it has become increasingly important to evaluate sarcopenia comorbidity in oral squamous cell carcinoma (OSCC). We assessed sarcopenia in patients with OSCC in a way that is feasible in daily practice and retrospectively evaluated its impact on prognosis. Patients with both low quality and low quantity of cervical muscles had a significantly worse prognosis. Assessing sarcopenia by evaluating both the quality and quantity of preoperative cervical skeletal muscle mass may be useful in optimizing the treatment of patients with OSCC without requiring additional imaging or patient burden. Accumulating evidence has shown that sarcopenia in patients with oral squamous cell carcinoma (OSCC) is at a risk of poor prognosis. There is no universal consensus on how to assess sarcopenia in patients with OSCC in daily practice. It is important to validate the usefulness of sarcopenia assessment from cervical muscles, which are frequently used in routine clinical practice in patients with OSCC. In this study, we investigated whether preoperative lumbar (L3) skeletal muscle mass and adiposity in OSCC patients were associated with cervical (C3) skeletal muscle mass and adiposity from CT measurements. We also investigated whether skeletal muscle mass and adiposity in the C3 muscles were associated with survival rates in patients with OSCC. We demonstrated that both the quality and quantity of muscle between the C3 and L3 levels were positively correlated with each other. We also demonstrated that the survival rates in patients with low sternocleidomastoid muscle mass index, high processus spinosus muscle-intramuscular adipose tissue content, and the combination of both were significantly lower than those in the controls. These results suggest that the assessment of sarcopenia from multiple neck muscles by preoperative CT measurements may be useful in predicting the prognosis of patients with OSCC. [ABSTRACT FROM AUTHOR]

26,26,26,27,27,27-Hexafluoro-1,25-dihydroxyvitamin D[sub 3] (ST-630) is a newly developed agent to maintain the levels of calcium and phosphorus in blood. Herein, we investigated the effect of this compound on the expression of vitamin-D-responsive genes in vitamin-D-deficient mice. ST-630 was more effective than 1,25-dihydroxyvitamin D[sub 3] [1,25(OH)[sub 2] D[sub 3] ] with respect to the induction of Cyp24 and calbindin-D[sub 9k] mRNAs in the kidney and in the small intestine. Moreover, the increase in mRNA levels of vitamin-D-responsive genes induced by ST-630 lasted longer than that induced by 1,25(OH)[sub 2] D[sub 3] . These results indicate that ST-630 was more effective in inducing Cyp24 and calbindin-D[sub 9k] gene expression than 1,25(OH)[sub 2] D[sub 3] when both compounds were injected into vitamin-D-deficient mice. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral squamous cell carcinoma (OSCC) has the highest mortality rate among all head and neck cancers. To date, the impact of preoperative malnutrition and sarcopenia on survival in OSCC patients remains controversial. The aim of our study was to investigate the effects of preoperative nutritional status and abnormalities in body composition on the mortality of OSCC patients. The disease-specific survival (DSS) rate among patients with a high intramuscular adipose tissue content (IMAC) and a low psoas muscle mass index was significantly lower than that in controls. Multivariate analysis revealed that a low preoperative Prognostic Nutritional Index (PNI) and high IMAC were independent risk factors. We demonstrated that preoperative malnutrition and abnormal body composition, such as abnormal preoperative skeletal muscle quality, are associated with DSS in OSCC patients. Our study suggests that the evaluation of preoperative malnutrition and skeletal muscle quality would be useful for predicting mortality in patients with OSCC. The impact of preoperative malnutrition and sarcopenia on survival in oral squamous cell carcinoma (OSCC) patients remains controversial. We investigated the effects of the preoperative nutritional status and abnormalities in body composition on the mortality of OSCC patients. A retrospective study involving 103 patients with OSCC was conducted. Disease-specific survival (DSS) according to the preoperative psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) was evaluated. Univariate and multivariate analyses were performed to determine the predictive performance of the covariates with respect to DSS. The DSS rate in patients with high IMAC and low PMI was significantly lower than that in controls. Multivariate analysis revealed that a low preoperative Prognostic Nutritional Index (PNI) and high IMAC were independent risk factors. We demonstrated that preoperative malnutrition and abnormal body composition, such as preoperative skeletal muscle quality, are associated with DSS in OSCC patients. Our study suggests that the evaluation of preoperative malnutrition and skeletal muscle quality would be useful for predicting mortality in patients with OSCC. [ABSTRACT FROM AUTHOR]

A novel three component gel is obtained from the reaction of succinic acid, Cu(NO3)2, and 1,4-diaza-bicyclo[2.2.2]octane (DABCO) in various organic solvents. The presence of the three components is essential for gelation in the solvents. [ABSTRACT FROM AUTHOR]

Introduction: The most effective method of assessing sarcopenia has yet to be determined, whether by single muscle or by whole muscle segmentation. The purpose of this study was to compare the prognostic value of these two methods using computed tomography (CT) images in patients with oral squamous cell carcinoma (OSCC)., Materials and Methods: Sex- and age-adjusted Cox proportional hazards models were employed for each parameter of sarcopenia related to overall survival, disease-free survival, and disease-specific survival. Harrell's concordance index was calculated for each model to assess discriminatory power., Results: In this study including 165 patients, a significant correlation was found between the CT-based assessment of individual muscles and their cross-sectional area. Single muscle assessments showed slightly higher discriminatory power in survival outcomes compared to whole muscle assessments, but the difference was not statistically significant, as indicated by overlapping confidence intervals for the C-index between assessments. To further validate our measurements, we classified patients into two groups based on intramuscular adipose tissue content (P-IMAC) of the spinous process muscle. Analysis showed that the higher the P-IMAC value, the poorer the survival outcome., Conclusion: Our findings indicate a slight advantage of single-muscle over whole-muscle assessment in prognostic evaluation, but the difference between the two methods is not conclusive. Both assessment methods provide valuable prognostic information for patients with OSCC, and further studies involving larger, independent cohorts are needed to clarify the potential advantage of one method over the other in the prognostic assessment of sarcopenia in OSCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Takayama, Yoshimura, Suzuki, Hirano, Tezuka, Ishida, Ishihata, Amitani, Amitani, Nakamura, Imamura, Inui and Nakamura.)

Background: Better prognostic biomarkers for oral squamous cell carcinoma (OSCC) must be developed, particularly within the realm of clinically and frequently administered tests, to advise appropriate clinical therapy and follow-up. In this study, we retrospectively investigated which of the several inflammation-nutrition indicators might predict the prognosis of patients with OSCC. Methods:   The preoperative neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), CRP-albumin ratio (CAR), Glasgow prognostic score (GPS), modified GPS (mGPS), prognostic nutritional index (PNI), controlling nutrition status (CONUT), and modified CONUT (mCONUT) were retrospectively evaluated using blood samples collected 1-5 days before surgery. To estimate the effect on the prognosis of tumor progression, the mean values of the markers between stages I/II and III/IV were used for subgroup analysis. The multivariate Cox proportional hazards model included all independent variables significantly associated with survival in the univariate analysis to determine the independent variables. Results: A total of 112 patients (69 males and 43 females) with primary OSCC who underwent surgical treatment at our hospital were included. There were statistically significant differences in the mean values of monocytes, platelets, and albumin between stages I/II and III/IV. According to the multivariate Cox proportional hazards regression, a low PNI was associated with shorter overall survival (OS) and disease-free survival (DFS); women were associated with shorter DFS. Conclusion: The pretreatment PNI had excellent predictive value for the 5-year OS and DFS of patients with OSCC. Future large-scale prospective studies with a high sample size are needed to verify our findings in OSCC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yoshimura, Suzuki, Takayama, Higashi, Hirano, Tezuka, Ishida, Ishihata, Amitani, Amitani, Nishi, Nakamura, Imamura, Nozoe, Inui and Nakamura.)

Background: School refusal occurs in about 1-2% of young people. Anxiety and depression are considered to be the most common emotional difficulties for children who do not attend school. However, at present, no definitive treatment has been established for school refusal, although interventions such as cognitive behavioral therapy have been used. This paper reports a protocol for a cluster-randomized controlled trial of a mindfulness yoga intervention for children with school refusal., Methods: This study is a multicenter, exploratory, open cluster-randomized controlled trial. This study will recruit children aged 10-15 years with school refusal. After a 2-week baseline, participants for each cluster will be randomly assigned to one of two groups: with or without mindfulness yoga for 4 weeks. Mindfulness yoga will be created for schoolchildren for this protocol and distributed to the participants on DVD. The primary outcome is anxiety among children with school refusal using the Spence Children's Anxiety Scale-Children., Discussion: For this study, we developed a mindfulness yoga program and protocol, and examine whether mindfulness yoga can improve anxiety in children with school refusal. Our mindfulness yoga program was developed based on the opinions of children of the same age, and is a program that children can continue to do every day without getting bored. In this way, we believe that we can contribute to the smooth implementation of support to reduce the anxiety of children with school refusal, and to the reduction of the number of children who refuse to go to school., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Amitani, Amitani, Owaki, Monuki, Adachi, Kawazu, Fukumoto, Suzuki, Yoshimura, Mizuma, Nishida, Watanabe, Hirose, Funakoshi, Ota, Murotani and Asakawa.)

Mucoepidermoid carcinoma (MEC) is one of the most common malignant salivary gland carcinomas, but no effective treatment strategy has been established other than surgical resection. Purkinje cell protein (PCP) 4/peptide (PEP) 19 is a calmodulin-binding antiapoptotic peptide that is expressed and inhibits apoptosis in human breast cancer cells. Human epidermal growth factor receptor 2 (HER2) is an epidermal growth factor that has been implicated in the pathogenesis of many carcinomas, particularly breast and gastric carcinomas. In the present study, we performed immunohistochemical analyses of samples from 73 patients who underwent surgical resection for MEC of the salivary gland using antibodies against PCP4/PEP19 and HER2. PCP4/PEP19 expression was related to better prognosis, while HER2 expression was associated with worse prognosis. Patients that were PCP4/PEP19-positive and HER2-negative showed similar outcomes to PCP4/PEP19 and HER2 alone. Therefore, PCP4/PEP19 and HER2 are predicted to play important roles in the pathogenesis and progression of MEC.

Objective Ameloblastoma is a representative odontogenic tumor comprising several characteristic invasive forms, and its pathophysiology has not been sufficiently elucidated. A stable animal experimental model using immortalized cell lines is crucial to explain the factors causing differences among the subtypes of ameloblastoma, but this model has not yet been disclosed. In this study, a novel animal experimental model has been established, using immortalized human ameloblastoma-derived cell lines. Methodology Ameloblastoma cells suspended in Matrigel were subcutaneously transplanted into the heads of immunodeficient mice. Two immortalized human ameloblastoma cell lines were used: AM-1 cells derived from the plexiform type and AM-3 cells derived from the follicular type. The tissues were evaluated histologically 30, 60, and 90 days after transplantation. Results Tumor masses formed in all transplanted mice. In addition, the tumors formed in each group transplanted with different ameloblastoma cells were histologically distinct: the tumors in the group transplanted with AM-1 cells were similar to the plexiform type, and those in the group transplanted with AM-3-cells were similar to the follicular type. Conclusions A novel, stable animal experimental model of ameloblastoma was established using two cell lines derived from different subtypes of the tumor. This model can help clarify its pathophysiology and hasten the development of new ameloblastoma treatment strategies.

The Purkinje cell protein 4/peptide 19 (PCP4/PEP19) is a novel breast cancer cell expressing peptide, originally found in the neural cells as an anti-apoptotic factor, could inhibit cell apoptosis and enhance cell migration and invasion in human breast cancer cell lines. The expression of PCP4/PEP19 is induced by estrogens in estrogen receptor-positive (ER + ) MCF-7 cells but also highly expressed in ER - SK-BR-3 cells. In this study, we investigated the effects of PCP4/PEP19 on aromatase gene expression in MCF-7 and SK-BR-3 human breast cancer cells. In SK-BR-3 cells but not in MCF-7 cells, PCP4/PEP19 knockdown by siRNA silencing decreased the aromatase expression in gene transcriptional level. When PCP4/PEP19 was overexpressed by CMV promoter-driven PCP4/PEP19 expressing plasmid transfection, aromatase gene transcription increased in SK-BR-3 cells. This aromatase gene transcription is mainly mediated through promoter region PI.1, which is usually active in the placental tissue but not in the breast cancer tissue. These results indicate a new function of PCP4/PEP19 that would enhance aromatase gene upregulation to supply estrogens in heterogeneous cancer microenvironment., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6-negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.

Purkinje cell protein (PCP) 4/peptide (PEP) 19 is expressed in Purkinje cells where it has a calmodulin-binding, anti-apoptotic function. We recently demonstrated that PCP4/PEP19 is expressed and inhibit apoptosis in human breast cancer cell lines. In the present study we investigated the role of PCP4/PEP19 in cell morphology, adhesion, migration, and invasion in MCF-7 and T47D human breast cancer cell lines. Knockdown of PCP4/PEP19 reduced the formation of filopodia-like cytoplasmic structures and vinculin expression, and enhanced E-cadherin expression. Activities of migration, invasion, and cell adhesion were also decreased after the knockdown of PCP4/PEP19 in MCF-7 and T47D cells. These results suggested that PCP4/PEP19 promotes cancer cell adhesion, migration, and invasion and that PCP4/PEP19 may be a potential target for therapeutic agents in breast cancer treatment which act by inhibiting epithelial-mesenchymal transition and enhancing apoptotic cell death., Competing Interests: The authors declare no conflicts of interest

The PCP4/PEP19 is a calmodulin-binding anti-apoptotic peptide in neural cells but its potential role in human cancer has largely been unknown. We investigated the expression of PCP4/PEP19 in human breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 cells, and found that estrogen receptor (ER)-positive MCF-7 and ER-negative SK-BR-3 cells expressed PCP4/PEP19. In the MCF-7 cells, cell proliferation was estrogen-dependent, and PCP4/PEP19 expression was induced by estrogen. In both cell lines, PCP4/PEP19 knockdown induced apoptosis and slightly decreased Akt phosphorylation. Knockdown of calcium/calmodulin-dependent protein kinase kinase 1 (CaMKK1), resulting in decreased phospho-Akt(Thr308), enhanced apoptosis in SK-BR-3 but not in MCF-7 cells. CaMKK2 knockdown moderately decreased phospho-Akt(Thr308) and increased apoptosis in MCF-7 cells but not in SK-BR-3 cells. These data indicated that PCP4/PEP19 regulates apoptosis but exact mechanism is still unknown. PCP4/PEP19 can therefore potentially serve as independent oncotarget for therapy of PCP4/PEP19-positive breast cancers irrespective of ER expression.

CYP3A4, the major form of cytochrome P450 (P450) expressed in the adult human liver, is involved in the metabolism of approximately 50% of commonly prescribed drugs. Several genetic polymorphisms in CYP3A4 are known to affect its catalytic activity and to contribute in part to interindividual differences in the pharmacokinetics and pharmacodynamics of CYP3A4 substrate drugs. In this study, catalytic activities of the two alleles found in East Asians, CYP3A4*16 (T185S) and CYP3A4*18 (L293P), were assessed using the following seven substrates: midazolam, carbamazepine, atorvastatin, paclitaxel, docetaxel, irinotecan, and terfenadine. The holoprotein levels of CYP3A4.16 and CYP3A4.18 were significantly higher and lower, respectively, than that of CYP3A4.1 when expressed in Sf21 insect cell microsomes together with human NADPH-P450 reductase. CYP3A4.16 exhibited intrinsic clearances (V(max)/K(m)) that were lowered considerably (by 84-60%) for metabolism of midazolam, carbamazepine, atorvastatin, paclitaxel, and irinotecan compared with CYP3A4.1 due to increased K(m) with or without decreased V(max) values, whereas no apparent decrease in intrinsic clearance was observed for docetaxel. On the other hand, K(m) values for CYP3A4.18 were comparable to those for CYP3A4.1 for all substrates except terfenadine; but V(max) values were lower for midazolam, paclitaxel, docetaxel, and irinotecan, resulting in partially reduced intrinsic clearance values (by 34-52%). These results demonstrated that the impacts of both alleles on CYP3A4 catalytic activities depend on the substrates used. Thus, to evaluate the influences of both alleles on the pharmacokinetics of CYP3A4-metabolized drugs and their drug-drug interactions, substrate drug-dependent characteristics should be considered for each drug.

MKC-963, (R)-1-(1-cyclohexylethylamino)-4-phenylphthalazine, a potent inhibitor of platelet aggregation, was synthesized and used in clinical trials in the 1990s. In the process of clinical study, it was found that urinary excretion ratios for 6beta-hydroxycortisol and free cortisol increased significantly in parallel with decreases in the plasma concentrations of MKC-963 after repeated oral administration of the compound to healthy volunteers. These findings suggested that MKC-963 caused autoinduction (defined as the ability of a drug to induce enzymes that enhance its own metabolism, resulting in dispositional tolerance) in humans, and clinical studies using the compound were stopped. This experience prompted us to reevaluate the effects of this compound on CYP3A4 using primary human hepatocytes and cDNA-expressed human cytochrome P450 (P450) enzymes to determine whether the autoinduction of MKC-963 metabolism in humans could have been predicted if these in vitro systems had been used for the evaluation of MKC-963 in the preclinical study. The results of in vitro study showed that MKC-963 increased CYP3A4 mRNA expression level and activity of testosterone 6beta-hydroxylation to extents similar to those observed with rifampicin in primary human hepatocytes. In addition, approximately 90% of the MKC-963 metabolism in human liver microsomes was estimated to be attributable to CYP3A4. These in vitro findings are in good agreement with the results of clinical study, suggesting that studies using human hepatocytes and cDNA-expressed human P450s are useful for assessing the autoinductive nature of compounds under development before starting clinical studies.

In vehicle systems occupational drivers might expose themselves to vibration for a long time. This may cause illness of the spine such as chronic lumbago or low back pain. Therefore, it is necessary to evaluate the influence of vibration to the spinal column and to make up appropriate guidelines or counter plans. In ISO2631-1 or ISO2631-5 assessment of vibration effects to human in the view of adverse-health effect was already presented. However, it is necessary to carry out further research to understand the effect of vibration to human body to examine their validity and to prepare for the future revision. This paper shows the detail measurement of human response to vibration, and the modelling of the seated human body for the assessment of the vibration risk. The vibration transmissibilities from the seat surface to the spinal column and to the head are measured during the exposure to vertical excitation. The modal paramters of seated subject are extracted in order to understand the dominant natural modes. For the evaluation of adverse-health effect the multi-body modelling of the spinal column is introduced. A simplified model having 10 DOFs is counstructed so that the transmissibilities of the model fit to those of experiment. The transient response analysis is illustrated when a half-sine input is applied. The relative displacements of vertebrae are evaluated, which can be a basis for the assessment of vibration risk. It is suggested that the multi-body dynamic model is used to evaluate the vibration effect to the spinal column for seated subjects.