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

Effects of acidic calcium phosphate concentration on setting reaction and tissue response to β-tricalcium phosphate granular cement

Beta-tricalcium phosphate granular cement (β-TCP GC), consisting of β-TCP granules and an acidic calcium phosphate (Ca-P) solution, shows promise in the reconstruction of bone defects as it sets to form interconnected porous structures, i.e., β-TCP granules are bridged with dicalcium phosphate dihydrate (DCPD) crystals. In this study, the effects of acidic Ca-P solution concentration (0–600 mmol/L) on the setting reaction and tissue response to β-TCP GC were investigated. The β-TCP GC set upon mixing with its liquid phase, based on the formation of DCPD crystals, which bridged β-TCP granules to one another. Diametral tensile strength of the set β-TCP GC was relatively the same, at approximately 0.6 MPa, when the Ca-P concentration was 20–600 mmol/L. Due to the setting ability, reconstruction of the rat’s calvarial bone defect using β-TCP GC with 20, 200, and 600 mmol/L Ca-P solution was much easier compared to that with β-TCP granules without setting ability. Four weeks after the reconstruction, the amount of new bone was the same, approximately 17% in both β-TCP GC and β-TCP granules groups. Cellular response to β-TCP granules and β-TCP GC using the 20 mmol/L acidic Ca-P solution was almost the same. However, β-TCP GC using the 200 and 600 mmol/L acidic Ca-P solution showed a more severe inflammatory reaction. It is concluded, therefore, that β-TCP GC, using the 20 mmol/L acidic Ca-P solution, is recommended as this concentration allows surgical techniques to be performed easily and provides good mechanical strength, and the similar cellular response to β-TCP granules

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

Histological comparison of three apatitic bone substitutes with different carbonate contents in alveolar bone defects in a beagle mandible with simultaneous implant installation

Since bone apatite is a carbonate apatite containing carbonate in an apatitic structure, carbonate content may be one of the factors governing the osteoconductivity of apatitic bone substitutes. The aim of this study was to evaluate the effects of carbonate content on the osteoconductivity of apatitic bone substitutes using three commercially available bone substitutes for the reconstruction of alveolar bone defects of a beagle mandible with simultaneous dental implant installation. NEOBONE®, Bio-Oss®, and Cytrans® that contain 0.1 mass%, 5.5 mass%, and 12.0 mass% of carbonate, respectively, were used in this study. The amount of newly formed bone in the upper portion of the alveolar bone defect of the beagle’s mandible was 0.7%, 6.6%, and 39.4% at 4 weeks after surgery and 4.7%, 39.5% and 75.2% at 12 weeks after surgery for NEOBONE®, Bio-Oss®, and Cytrans®, respectively. The results indicate that bone-to-implant contact ratio was the largest for Cytrans®. Additionally, the continuity of the alveolar ridge was restored in the case of Cytrans®, whereas the continuity of the alveolar ridge was not sufficient when using NEOBONE® and Bio-Oss®. Both Cytrans® and Bio-Oss® that has a relatively larger carbonate content in their apatitic structure was resorbed with time. We concluded that carbonate content is one of important factors governing the osteoconductivity of apatitic bone substitutes

マイクロファイバーを用いた多孔質炭酸アパタイト顆粒の開発とウサギ頭蓋骨における組織学的評価

Carbonate apatite (CO3Ap) granules are known to show good osteoconductivity and replaced to new bone. On the other hand, it is well known that a porous structure allows bone tissue to penetrate its pores, and the optimal pore size for bone ingrowth is dependent on the composition and structure of the scaffold material. Therefore, the aim of this study was to fabricate various porous CO3Ap granules through a two-step dissolution-precipitation reaction using CaSO4 as a precursor and 30-, 50-, 120-, and 205-μm diameter microfibers as porogen and to find the optimal pore size of CO3Ap. Porous CO3Ap granules were successfully fabricated with pore size 8.2-18.7% smaller than the size of the original fiber porogen. Two weeks after the reconstruction of rabbit calvarial bone defects using porous CO3Ap granules, the largest amount of mature bone was seen to be formed inside the pores of CO3Ap (120) [porous CO3Ap granules made using 120-μm microfiber] followed by CO3Ap (50) and CO3Ap (30). At 4 and 8 weeks, no statistically significant difference was observed based on the pore size, even though largest amount of mature bone was formed in case of CO3Ap (120). It is concluded, therefore, that the optimal pore size of the CO3Ap is that of CO3Ap (120), which is 85 μm

Pulse number control of electrical resistance for multi-level storage based on phase change

金沢大学大学院医学系研究科量子医療技術学Phase change nonvolatile memory devices composed of SeSbTe chalcogenide semiconductor thin film were fabricated. The resistivity of the SeSbTe system was investigated to apply to multi-level data storage. The chalcogenide semiconductor acts as a programmable resistor that has a large dynamic range. The resistance of the chalcogenide semiconductor can be set to intermediate resistances between the amorphous and crystalline states using electric pulses of a specified power, and it can be controlled by repetition of the electric pulses. The size of the memory cell used in this work is 200 nm thick with a contact area of 1 µm diameter. The resistance of the chalcogenide semiconductor gradually varies from 41 kΩ to 840 Ω within octal steps. The resistance of the chalcogenide semiconductor decreases with increasing number of applied pulses. The step-down characteristic of the resistance can be explained as the crystalline region of the active phase change region increases with increasing number of applied pulses. The extent of crystallization was also estimated by the overall resistivity of the active region of the memory cell

Current status and future development of carbonate apatite as a bone substitute

A main inorganic component of human bone is not hydroxyapatite but carbonate apatite (CQ3Ap). Hydroxyapatite is not resorbed in the body but C03Ap can be resorbed and replaced with bone. We have succeeded in fabricating low crystalline CQ3Ap without sintering by dissolution-precipitation reaction using calcium hydroxide as a precursor. C03Ap showed excellent biocompatibility and faster bone formation compared to other bone substitutes (anorganic bovine bone and hydroxyapatite) in rabbit femur and dog mandible. Clinical study on effectiveness and safety of C03Ap granules in sinus floor augmentation was successfully concluded in 2016. CQ3Ap granules were approved by Japanese government in 2017, and marketed in 2018 as Cytrans® Granules. This comprehensive review explains the clinical cases of sinus lift and alveolar ridge augmentation of Cytrans® and its recommended clinical usage. Furthermore, we have succeeded in developing porous C03Ap and showed it was useful for reconstruction of mandibular bone defect in rabbit model and also aim to use it as a scaffold for bone regenerative medicine.ヒトの骨の無機主成分はハイドロキシアパタイトではなく，炭酸アパタイト (CO3Ap) である．ハイドロキシアパタイトは体内で吸収されないが，CO3Apは吸収されて骨と置換する．われわれは水酸化カルシウムを前駆物質として，焼結操作を用いずに溶解析出反応によって低結晶性の炭酸アパタイトを人工合成することに成功した．炭酸アパタイ卜顆粒は，ウサギ大腿骨とイヌ顎骨における実験で，他の骨補填材よりも骨が速く形成すること，優れた生体親和性を示すことを明らかにした．2016年に上顎洞底挙上術での臨床治験を成功裏に終え，2017年に炭酸アパタイト顆粒は薬事承認され，2018年からサイトランス® グラニュールとして市販された本総説では，サイトランス® による上顎洞底挙上症例と歯槽堤造成術症例を紹介すると共に，その臨床的推奨使用法を説明した．さらに，著者らは多孔質の炭酸アパタイトの作製に成功し，炭酸アパタイト多孔体がウサギの下顎骨欠損モデルにおいて骨再建に有用であることを示した．現在，炭酸アパタイト多孔体の骨再生医療用スキャフォールドヘの応用を目指している

Reconstruction of rabbit mandibular bone defects using carbonate apatite honeycomb blocks with an interconnected porous structure

Carbonate apatite (CO3Ap) granules are useful as a bone substitute because they can be remodeled to new natural bone in a manner that conforms to the bone remodeling process. However, reconstructing large bone defects using CO3Ap granules is difficult because of their granular shape. Therefore, we fabricated CO3Ap honeycomb blocks (HCBs) with continuous unidirectional pores. We aimed to elucidate the tissue response and availability of CO3Ap HCBs in the reconstruction of rabbit mandibular bone defects after marginal mandibulectomy. The percentages of the remaining CO3Ap area and calcified bone area (newly formed bone) were estimated from the histological images. CO3Ap area was 49.1 ± 4.9%, 30.3 ± 3.5%, and 25.5 ± 8.8%, whereas newly formed bone area was 3.0 ± 0.6%, 24.3 ± 3.3%, and 34.7 ± 4.8% at 4, 8, and 12 weeks, respectively, after implantation. Thus, CO3Ap HCBs were gradually resorbed and replaced by new bone. The newly formed bone penetrated most of the pores in the CO3Ap HCBs at 12 weeks after implantation. By contrast, the granulation tissue scarcely invaded the CO3Ap HCBs. Some osteoclasts invaded the wall of CO3Ap HCBs, making resorption pits. Furthermore, many osteoblasts were found on the newly formed bone, indicating ongoing bone remodeling. Blood vessels were also formed inside most of the pores in the CO3Ap HCBs. These findings suggest that CO3Ap HCBs have good osteoconductivity and can be used for the reconstruction of large mandibular bone defects

Nonvolatile SRAM based on Phase Change

金沢大学大学院自然科学研究科電子情報科学金沢大学工学