INHIBITION OF IFN-γ PRODUCTION BY SOLUBLE FACTORS DERIVED FROM ORAL CANCER CELLS

The streptococcal antitumor agent OK-432 is commonly used as an immunopotentiator for immunotherapy in various types of malignant tumors including oral cancer. It has been demonstrated that OK-432 elicits an antitumor effect by stimulating immunocompetent cells, thereby inducing multiple cytokines including interferon (IFN)-γ, interleukin (IL)-2 and IL-12. Serum concentrations of IFN-γ in patients with oral cancer were examined 24 h after administration of OK-432. Serum concentrations of IFN-γ in patients with advanced cancer were significantly lower than those in patients with early cancer. These results suggested that some soluble factors produced by cancer cells may inhibit IFN-γ production with OK-432. Thus, in the present study, an in vitro simulation model was established for the immune status of patients with oral cancer by adding conditioned medium (CM) derived from oral cancer cell lines into a culture of peripheral blood mononuclear cells (PBMCs) derived from a healthy volunteer. We investigated whether soluble factors derived from oral cancer cells affected IFN-γ production from PBMCs following stimulation with OK-432. PBMCs stimulated with OK-432 produced a large amount of IFN-γ; however, both IFN-γ production and cytotoxic activity from PBMCs induced by OK-432 were inhibited by the addition of CM in a dose-dependent manner. In order to examine these inhibitory effects against IFN-γ production, the contribution of inhibitory cytokines such as IL-4, IL-6, IL-10, transforming growth factor-β and vascular endothelial growth factor was investigated. However, neutralization of these inhibitory cytokines did not recover IFN-γ production inhibited by CM. These results indicated that unknown molecules may inhibit IFN-γ production from PBMCs following stimulation with OK-432

CSC MARKERS IN OSCC AND THEIR ASSOCIATION WITH CLINICAL FACTORS

Cancer stem cells (CSCs) exhibit self-replication, self-differentiation, drug resistance and immune evasion activities. In recent years CSCs have become increasingly important for the treatment of malignant tumors. CSCs express specific markers, including cluster of differentiation (CD)44, CD44 variant 9 (CD44v9), ATP-binding cassette sub-family G member 2 (ABCG2), CD24, B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) and aldehyde dehydrogenase 1 (ALDH1). However, the prognostic value of their expression in patients with oral squamous cell carcinoma (OSCC) are not well known. The present study evaluated these markers in stage I and II patients with OSCC and examined the association between T classification, histological differentiation, classification of invasion mode, lymph node metastasis and disease-free survival rate. Tissue specimens were obtained from 70 patients with stage I or II OSCC following either surgery or biopsy. Immunohistochemistry was performed and positive staining was defiend as 10% positive cells. CD44 and CD44v9 expressions were strongly detected in all OSCC tissues compared with normal epithelial cells. A total of 22 (31.4%) cases expressed ABCG2 and there was a significant association between ABCG2 expression and invasion. A total of 41 cases (59.0%) expressed CD24 and there was a significant association between CD24 expression and invasion. A total of 33 cases (47.1%) expressed BMI-1 and there was a significant association between BMI-1 expression and the disease-free survival rate. A total of 18 cases (25.7%) expressed ALDH1. Although there was no association between ALDH1 expression and T classification, there were significant associations between ALDH1 expression and histological differentiation, invasion mode, metastasis and the disease-free survival rate. Multivariate analysis revealed that ALDH1 expression was the only prognostic factor for disease-free survival rate. The results of the present study suggest that the positivity of ALDH1 detected in patients with OSCC correlates with the number of cells undergoing epithelial mesenchymal transition and metastasis. These findings indicated that the expression of ALDH1 may be an effective prognostic marker indicating the survival of patients with stage I and II OSCC

Prevalence and Imaging Characteristics of Palatine Tonsilloliths Detected by CT in 2,873 Consecutive Patients

Tonsilloliths are calcified structures that develop in tonsillar crypts. They are commonly detected in daily clinical practice. The prevalence of tonsilloliths was 16 to 24% in previous reports, but it is inconsistent with clinical experience. The aim of this study is to clarify the prevalence, number, and size distribution of tonsilloliths using computed tomography (CT) in a relatively large number of patients. Materials and Methods. We retrospectively reviewed the scans of 2,873 patients referred for CT examinations with regard to tonsilloliths. Results. Palatine tonsilloliths were found in 1,145 out of 2,873 patients (39.9%). The prevalence of tonsilloliths increased with age, and most commonly in patients of ages 50–69. The prevalence in the 30s and younger was statistically lower than in the 40s and older (P < 0.05). The number of tonsilloliths per palatine tonsil ranged from one to 18. The size of the tonsilloliths ranged from 1 to 10 mm. For the patients with multiple CT examinations, the number of tonsilloliths increased in 51 (3.9%) and decreased in 84 (6.5%) of the tonsils. Conclusions. As palatine tonsilloliths are common conditions, screenings for tonsilloliths during the diagnosis of soft tissue calcifications should be included in routine diagnostic imaging

Lingual tonsillolith on PR and CT

Objectives: Lingual tonsilloliths are not as well-known to radiologists than palatine tonsilloliths, although they might be common in clinical practice. The aim of this investigation was to clarify the prevalence and imaging characteristics of lingual tonsilloliths using panoramic radiographs and CT images. Methods: This study included 2244 patients without pathology at the base of tongue who had undergone panoramic radiography and CT of the maxillofacial region. The size, number and position of lingual tonsilloliths relative to the mandible and tongue were evaluated. Results: Lingual tonsilloliths were observed in 33 (1.5%) and 108 (4.8%) of all patients on panoramic radiographs and CT images, respectively. The prevalence was higher in patients aged ≥40 years than in those aged < 40 years (χ2, p < 0.01). They appeared as small, round- or rod-shaped calcified bodies, and they always located closely anterior (1–17 mm) to the anterior border of oropharyngeal airway on panoramic radiographs. Lingual tonsilloliths were superimposed over the surrounding soft tissue inferior to the body of the mandible, posteroinferior to the angle of the mandible and posterior to the mandible in 16 (48.5%), 15 (45.5%) and 1 (3.0%) individual, respectively. A significant correlation was observed between the detectability on panoramic radiographs and size (Spearman’s r = 0.961, p < 0.01) of tonsilloliths, as revealed by CT images. Conclusion: Lingual tonsilloliths commonly appear on CT. They also appear on panoramic radiography and may superimpose the surrounding soft tissue of the mandible. Although lingual tonsilloliths may resemble other pathological calcifications including submandibular sialoliths and lingual osseous cholistoma, they can be differentiated by carefully observing panoramic radiographs. When clinicians detect calcified bodies near the base of tongue, lingual tonsilloliths should be included in the differential diagnoses

CT imaging of nasopharyngeal and eustachian tube tonsilloliths

Objectives: Nasopharyngeal tonsilloliths (NT) and eustachian tube tonsilloliths (ET) are not as well-known to radiologists as palatine and lingual tonsilloliths. The aim of this investigation was to determine the prevalence and imaging characteristics of NT and ET using CT and panoramic radiographs. Methods: We retrospectively assessed the scans of 2244 patients who underwent consecutive CT and panoramic radiographs of the maxillofacial region. The prevalence, size, number, and position of NT and ET were analysed. Results: NT and ET were detected in 14 (0.6%) and 6 (0.3%) of 2244 patients on CT, respectively, but they were undetectable on panoramic radiographs. No significant difference was found in the prevalence with respect to sex. Although there was also no significant difference in the prevalence among age groups, tonsilloliths were most commonly noted in patients over 40 years old; they appeared as small and round calcified bodies, ranging from 1 to 3 mm in diameter. All NT were found 0 to 3 mm beneath the nasopharyngeal mucosal surface. Conclusions: The prevalence of NT and ET on CT was lower than that of palatine and lingual tonsilloliths. However, since they are encountered more frequently than clinically significant calcifying diseases such as retropharyngeal calcific tendinitis, clinicians should be able to correctly diagnose NT and ET based on their anatomical features

Measurement of the zygomatic bone and pilot hole technique for safer installation of zygomaticus implants

The zygomaticus implant (Brånemark system, Nobel Biocare, Gotebörg, Sweden) was developed for patients with severe bone resorption of the posterior maxilla, which may eliminate or minimize the need for bone grafting. Although the zygomaticus implant has had a remarkable success rate in a difficult patient population, the method requires an advanced surgical technique and carries increased risk of complications, such as the perforation of the orbital floor or infratemporal fossa. Although it is important to have a detailed understanding of the anatomy of the zygomatic bone when performing the installation, there have been few anatomic studies on the zygomatic bone for installation of zygomaticus implants. In this study, we measured the height and thickness of the zygomatic bone for the installation. The thickness at a 90-degree angle point, where the upper margin of the zygomatic arch and the temporal margin of the frontal process of the zygomatic bone intersect and where the apex of the implant penetrates, according to the original method, was 1.8 ± 0.4 mm, which gradually increased inferiorly and anteriorly. In conclusion, the penetration point of the apex of the zygomaticus implant should be located more inferoanterior to the 90-degree angle point, as the thickness of the 90-degree angle point is thinner than the diameter of the implant. Based on these results, we have proposed a newer and safer installation method for the zygomaticus implant using a drill guide, which can be easily made

Regulation of P450 oxidoreductase by gonadotropins in rat ovary and its effect on estrogen production

<p>Abstract</p> <p>Background</p> <p>P450 oxidoreductase (POR) catalyzes electron transfer to microsomal P450 enzymes. Its deficiency causes Antley-Bixler syndrome (ABS), and about half the patients with ABS have ambiguous genitalia and/or impaired steroidogenesis. POR mRNA expression is up-regulated when mesenchymal stem cells (MSCs) differentiate into steroidogenic cells, suggesting that the regulation of POR gene expression is important for steroidogenesis. In this context we examined the regulation of POR expression in ovarian granulosa cells by gonadotropins, and its possible role in steroidogenesis.</p> <p>Methods</p> <p>Changes in gene expression in MSCs during differentiation into steroidogenic cells were examined by DNA microarray analysis. Changes in mRNA and protein expression of POR in the rat ovary or in granulosa cells induced by gonadotropin treatment were examined by reverse transcription-polymerase chain reaction and western blotting. Effects of transient expression of wild-type or mutant (R457H or V492E) POR proteins on the production of estrone in COS-7 cells were examined in vitro. Effects of POR knockdown were also examined in estrogen producing cell-line, KGN cells.</p> <p>Results</p> <p>POR mRNA was induced in MSCs following transduction with the SF-1 retrovirus, and was further increased by cAMP treatment. Expression of POR mRNA, as well as Cyp19 mRNA, in the rat ovary were induced by equine chorionic gonadotropin and human chorionic gonadotropin. POR mRNA and protein were also induced by follicle stimulating hormone in primary cultured rat granulosa cells, and the induction pattern was similar to that for aromatase. Transient expression of POR in COS-7 cells, which expressed a constant amount of aromatase protein, greatly increased the rate of conversion of androstenedione to estrone, in a dose-dependent manner. The expression of mutant POR proteins (R457H or V492E), such as those found in ABS patients, had much less effect on aromatase activity than expression of wild-type POR proteins. Knockdown of endogenous POR protein in KGN human granulosa cells led to reduced estrone production, indicating that endogenous POR affected aromatase activity.</p> <p>Conclusion</p> <p>We demonstrated that the expression of POR, together with that of aromatase, was regulated by gonadotropins, and that its induction could up-regulate aromatase activity in the ovary, resulting in a coordinated increase in estrogen production.</p

Prevalence and imaging characteristics of palatine tonsilloliths evaluated on 2244 pairs of panoramic radiographs and CT images

Objectives: Palatine tonsilloliths incidentally detected on diagnostic imaging should be differentiated from pathologic calcifications to enable correct diagnosis and treatment. The aim of this study is to clarify the prevalence and imaging characteristics of palatine tonsilloliths on panoramic radiographs. Materials and Methods: We retrospectively reviewed 2,244 individuals who underwent pairs of consecutive panoramic radiography and computed tomography (CT) of the head and neck region. The imaging characteristics of palatine tonsilloliths on panoramic radiography were compared with the findings from CT, which was considered the gold standard. Results: Tonsilloliths were detected in 300 (13.4%) and 914 (40.7%) of the 2,244 individuals on panoramic radiographs and CT, respectively. On panoramic radiographs, tonsilloliths were superimposed over the ramus of the mandible at the level coincident with and inferior to the soft palate in 176 (7.8%) and 90 (4.0%) individuals, respectively. Tonsilloliths were also superimposed over the surrounding soft tissue inferior to the body of the mandible, postero-inferior to the angle of the mandible, and posterior to the ramus of the mandible in 33 (1.5%), 26 (1.2%), and 28 (1.3%) individuals, respectively. A significant correlation was observed between the detectability on panoramic radiographs and the size (Spearman r=1.000) and number (Spearman r=0.991) of tonsilloliths, as revealed by CT images. Conclusions: The present results suggest that tonsilloliths are commonly detected on panoramic radiographs. Furthermore, they can be superimposed on both the mandible and the surrounding soft tissue. Clinical Relevance: Clinicians should include tonsilloliths among the differential diagnoses when calcified bodies are detected on panoramic radiographs