論文 - 古橋　眞人

非透析症例におけるHIF-PH阻害薬のeGFR保持効果の検討

相神 智宏, 石郷 友之, 宮尾 舞, 野々山 雅俊, 山下 智久, 小山 雅之, 藤居 賢, 矢野 俊之, 古橋 眞人, 福土 将秀

日本腎臓病薬物療法学会誌 ( 日本腎臓病薬物療法学会 )  12 ( 特別号 ) S200 - S200  2023年10月

心臓血管外科における未来医療を目指して:予測医学・シミュレーションを用いたPrecision medicine Random survival forest法を用いた機械学習による術後予後予測の有用性に関する検討 生存時間解析における古典的Cox比例ハザードモデルとの比較と課題

保坂 到, 田中 希尚, 秋山 幸功, 佐藤 亮太, 森 和真, 小川 俊史, 梅津 新矢, 遠藤 圭佑, 三上 拓真, 佐藤 達也, 梅田 璃子, 宇塚 武司, 古橋 眞人, 川原田 修義

日本胸部外科学会定期学術集会 ( (一社)日本胸部外科学会 )  76回   CSY3 - 4  2023年10月

心臓血管外科における未来医療を目指して:予測医学・シミュレーションを用いたPrecision medicine Random survival forest法を用いた機械学習による術後予後予測の有用性に関する検討 生存時間解析における古典的Cox比例ハザードモデルとの比較と課題

保坂 到, 田中 希尚, 秋山 幸功, 佐藤 亮太, 森 和真, 小川 俊史, 梅津 新矢, 遠藤 圭佑, 三上 拓真, 佐藤 達也, 梅田 璃子, 宇塚 武司, 古橋 眞人, 川原田 修義

日本胸部外科学会定期学術集会 ( (一社)日本胸部外科学会 )  76回   CSY3 - 4  2023年10月

TGF-β2 Induces Epithelial-Mesenchymal Transitions in 2D Planer and 3D Spheroids of the Human Corneal Stroma Fibroblasts in Different Manners.

Araya Umetsu, Yosuke Ida, Tatsuya Sato, Masato Furuhashi, Hiroshi Ohguro, Megumi Watanabe

Biomedicines   11 ( 9 )  2023年09月  [国際誌]

　概要を見る

To examine the epithelial-mesenchymal transition (EMT) that is induced on the human corneal stroma, two- and three-dimensional (2D and 3D) cultures of human corneal stroma fibroblasts (HCSFs) were used. In this study, HCSF 2D monolayers and 3D spheroids were characterized by (1) scanning electron microscopy (SEM), (2) trans-endothelial electrical resistance (TEER) measurements and fluorescein isothiocyanate (FITC)-dextran permeability, (3) cellular metabolic measurements, (4) the physical properties of 3D HCSF spheroids, and (5) the extracellular matrix (ECM) molecule gene expressions, including collagen (COL) 1, 4 and 6, and fibronectin (FN), a tissue inhibitor of metalloproteinase (TIMP) 1-4, matrix metalloproteinase (MMP) 2, 3, 9 and 14, and several endoplasmic reticulum (ER) stress-related factors. In the 2D HCSFs, TGF-β2 concentration-dependently generated (1) a considerable increase in ECM deposits revealed by SEM, (2) an increase in TEER values and a decrease in FITC-dextran permeability, (3) increases in both mitochondrial and glycolytic functions, and a substantial upregulation of COL1, COL4, FN, αSMA, TIMP1, TIMP, and most ER stress-related genes and the downregulation of COL6 and MMP3. In the case of 3D spheroids, TGF-β2 induced the downsizing and stiffening of 3D spheroids and the upregulation of COL6, MMP14, and most ER stress-related genes. These findings suggest that TGF-β2 significantly induced a number of EMT-associated biological events including planar proliferation, cellular metabolic functions, and the production of ECM molecules in the 2D cultured HCSF cells, but these effects were significantly less pronounced in the case of 3D HCSF spheroids.

DOI PubMed

Circulating level of β-aminoisobutyric acid (BAIBA), a novel myokine-like molecule, is inversely associated with fat mass in patients with heart failure

Satoshi Katano, Toshiyuki Yano, Hidemichi Kouzu, Ryohei Nagaoka, Ryo Numazawa, Kotaro Yamano, Yusuke Fujisawa, Katsuhiko Ohori, Nobutaka Nagano, Takefumi Fujito, Ryo Nishikawa, Wataru Ohwada, Masaki Katayose, Tatsuya Sato, Atsushi Kuno, Masato Furuhashi

Heart and Vessels ( Springer Science and Business Media LLC )   2023年09月

DOI

Fatty Liver Indexを用いて高血圧発症を予測する機械学習モデルの構築

田中 希尚, 秋山 幸功, 佐藤 亮太, 保坂 到, 三上 拓真, 遠藤 圭佑, 梅津 新矢, 小川 俊史, 森 和真, 佐藤 達也, 塙 なぎさ, 古橋 眞人

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 )  45回   391 - 391  2023年09月

心不全患者におけるレニン-アンジオテンシン系活性化は骨格筋量の低下と関連する

沼澤 瞭, 片野 唆敏, 矢野 俊之, 長岡 凌平, 神津 英至, 大堀 克彦, 藤澤 佑輔, 山埜 光太郎, 長南 新太, 小山 雅之, 橋本 暁佳, 古橋 眞人

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 )  45回   398 - 398  2023年09月

Calculated Small Dense Low-Density Lipoprotein Cholesterol Level is A Predominant Predictor for New Onset of Ischemic Heart Disease.

Masafumi Inyaku, Marenao Tanaka, Tatsuya Sato, Keisuke Endo, Kazuma Mori, Itaru Hosaka, Takuma Mikami, Araya Umetsu, Hirofumi Ohnishi, Yukinori Akiyama, Nagisa Hanawa, Masato Furuhashi

Journal of atherosclerosis and thrombosis    2023年08月  [国内誌]

　概要を見る

AIM: A high level of directly measured small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for ischemic heart disease (IHD). However, it remains unclear whether estimated sdLDL-C level is a predictor for IHD. We investigated the associations of new onset of IHD with levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), LDL-C and calculated sdLDL-C by Sampson's equation. METHODS: After exclusion of subjects with IHD or those with TG ≥ 800 mg/dL, a total of 18,176 subjects (men/women: 11,712/6,464, mean age: 46 years) were recruited among 28,990 Japanese individuals who received annual health checkups. RESULTS: During the 10-year follow-up period, 456 men (3.9%) and 121 women (1.9%) newly developed IHD. Multivariable Cox proportional hazard analyses after adjustment of age, sex, obesity, smoking habit, family history of IHD, estimated glomerular filtration rate, hypertension and diabetes mellitus at baseline showed that the hazard ratio (HR) (1.38 [95% confidence interval: 1.03-1.85]) for new onset of IHD in subjects with the 4th quartile (Q4) of sdLDL-C (≥ 42 mg/dL) was significantly higher than that in subjects with the 1st quartile (Q1) (≤ 24 mg/dL) as the reference, though the adjusted HRs in subjects with Q2-Q4 of TC, HDL-C, non-HDL-C, LDL-C and TG were comparable with those in subjects with Q1 of the respective lipid fractions. The adjusted HR with a restricted cubic spline increased with a higher level of calculated sdLDL-C as a continuous value at baseline. CONCLUSIONS: sdLDL-C level calculated by Sampson's equation is a predominant predictor for the development of IHD in a general Japanese population.

DOI PubMed

Physical Properties and Cellular Metabolic Characteristics of 3D Spheroids Are Possible Definitive Indices for the Biological Nature of Cancer-Associated Fibroblasts.

Nami Nishikiori, Kohichi Takada, Tatsuya Sato, Sho Miyamoto, Megumi Watanabe, Yui Hirakawa, Shohei Sekiguchi, Masato Furuhashi, Akira Yorozu, Kenichi Takano, Akihiro Miyazaki, Hiromu Suzuki, Hiroshi Ohguro

Cells   12 ( 17 )  2023年08月  [国際誌]

　概要を見る

The current study's objective was to elucidate some currently unknown biological indicators to evaluate the biological nature of cancer-associated fibroblasts (CAFs). For this purpose, four different CAFs, CAFS1, CAFS2, SCC17F and MO-1000, were established using surgical specimens from oral squamous cell carcinomas (OSCC) with different clinical malignant stages (CAFS1 and CAFS2, T2N0M0, stage II; SCC17F and MO-1000, T4aN2bM0, stage IVA). Fibroblasts unrelated to cancer (non-CAFs) were also prepared and used as controls. Initially, confirmation that these four fibroblasts were indeed CAFs was obtained by their mRNA expression using positive and negative markers for the CAF or fibroblasts. To elucidate possible unknown biological indicators, these fibroblasts were subjected to a cellular metabolic analysis by a Seahorse bioanalyzer, in conjugation with 3D spheroid cultures of the cells and co-cultures with a pancreas ductal carcinoma cell line, MIA PaCa-2. The mitochondrial and glycolytic functions of human orbital fibroblasts (HOF) were nearly identical to those of Graves'-disease-related HOF (GOF). In contrast, the characteristics of the metabolic functions of these four CAFs were different from those of human conjunctival fibroblasts (HconF), a representative non-CAF. It is particularly noteworthy that CAFS1 and CAFS2 showed markedly reduced ratios for the rate of oxygen consumption to the extracellular acidification rate, suggesting that glycolysis was enhanced compared to mitochondrial respiration. Similarly, the physical aspects, their appearance and stiffness, of their 3D spheroids and fibroblasts that were induced effects based on the cellular metabolic functions of MIA PaCa-2 were also different between CAFs and non-CAFs, and their levels for CAFS1 or SCC17F were similar to those for CAFS2 or MO-1000 cells, respectively. The findings reported herein indicate that cellular metabolic functions and the physical characteristics of these types of 3D spheroids may be valuable and useful indicators for estimating potential biological diversity among various CAFs.

DOI PubMed

Development and validation of osteoporosis risk assessment score, ORAS, in heart failure patients: comparison with the Osteoporosis Self-Assessment Tool for Asians (OSTA)

Ryo Numazawa, Satoshi Katano, Toshiyuki Yano, Masayuki Koyama, Ryohei Nagaoka, Yusuke Fujisawa, Kotaro Yamano, Suguru Honma, Katsuhiko Ohori, Hidemichi Kouzu, Masaki Katayose, Masato Furuhashi, Kazufumi Tsuchihashi, Akiyoshi Hashimoto

European Journal of Cardiovascular Nursing ( Oxford University Press (OUP) )   2023年08月

　概要を見る

Abstract Aim Osteoporosis is prevalent and is associated with poor prognosis in heart failure (HF) patients. However, bone mineral density (BMD) measurement by a dual-energy X-ray absorptiometry (DEXA) scan is not always available in a daily clinical setting and large-scale population-based studies. Methods A single-center, cross-sectional observational study was conducted with 387 patients (median age: 77 years [interquartile range: 68 to 83 years]; 37% women). BMDs were measured by DEXA scans, and osteoporosis was diagnosed as ≤ -2.5 standard deviation of the BMDs in healthy young adults. Osteoporosis risk assessment score (ORAS) was developed using significant predictors from a logistic regression model for osteoporosis and was subsequently validated. Results Osteoporosis was found in 103 (27%) of the 387 HF patients. Multivariate logistic regression analyses yielded the ORAS based on sex, BMI, handgrip strength, and anti-coagulant therapy utilization. The C-index of ORAS in the developmental set (0.796, 95% confidence interval: 0.747 to 0.845) was similar to the bootstrap validation of the prediction model (0.784), and tended to be higher than that of the Osteoporosis Self-Assessment Tool for Asians (OSTA). A nomogram of ORAS, established on the basis of the final logistic regression model, demonstrated 100% sensitivity at the lowest score (35 points), with an optimal cutoff point of 127 points, yielding 85% sensitivity and 62% specificity. Conclusions ORAS exhibits superior predictive performance to OSTA in predicting osteoporosis in HF patients, establishing itself as a valuable tool for early detection in both daily clinical practice and large-scale population-based studies.

DOI

An increase in calculated small dense low-density lipoprotein cholesterol predicts new onset of hypertension in a Japanese cohort.

Marenao Tanaka, Tatsuya Sato, Keisuke Endo, Masafumi Inyaku, Kazuma Mori, Itaru Hosaka, Takuma Mikami, Yukinori Akiyama, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi

Hypertension research : official journal of the Japanese Society of Hypertension    2023年08月  [国際誌]

　概要を見る

A disorder of lipid metabolism is involved in cardiovascular diseases including hypertension. A high level of small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for atherosclerotic cardiovascular disease. However, the association between sdLDL-C and hypertension has not been fully investigated. We investigated the associations between the development of hypertension during a 10-year period and levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), and LDL-C and sdLDL-C calculated by using the Sampson equations in 28,990 Japanese subjects who received annual health examinations. After exclusion of subjects with missing data, those with hypertension, and those with TG ≥ 800 mg/dL at baseline, a total of 15,177 subjects (men/women: 9374/5803, mean age: 46 years) were recruited. During the 10-year period, 2379 men (25.4%) and 724 women (12.5%) had new onset of hypertension. Multivariable Cox proportional hazard model analyses showed that levels of HDL-C, non-HDL-C, TG and sdLDL-C, but not levels of TC and LDL-C, were independent risk factors for the development of hypertension after adjustment of age, sex, family history of hypertension, systolic blood pressure, obesity, current smoking habit, alcohol drinking habit, estimated glomerular filtration rate, diagnosis of diabetes mellitus and use of lipid-lowering drugs and that the adjusted risk of sdLDL-C (per 1-standard deviation) was highest (hazard ratio [95% confidence interval: 1.09 [1.05-1.13]). The addition of sdLDL-C to traditional risk factors for hypertension significantly improved the discriminatory capability, which was better than that of other lipid fractions. In conclusion, a high level of calculated sdLDL-C predicts the development of hypertension.

DOI PubMed

Coexistence of Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Kidney Disease Is a More Potent Risk Factor for Ischemic Heart Disease.

Daisuke Miyamori, Marenao Tanaka, Tatsuya Sato, Keisuke Endo, Kazuma Mori, Takuma Mikami, Itaru Hosaka, Nagisa Hanawa, Hirofumi Ohnishi, Masato Furuhashi

Journal of the American Heart Association   12 ( 14 ) e030269  2023年07月  [国際誌]

　概要を見る

Background Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as fatty liver with overweight/obesity, type 2 diabetes, or metabolic abnormalities, is a newly proposed disease. However, it remains unclear whether the coexistence of MAFLD and chronic kidney disease (CKD) is a more potent risk factor for ischemic heart disease (IHD). Methods and Results We investigated the risk of the combination of MAFLD and CKD for development of IHD during a 10-year follow-up period in 28 990 Japanese subjects who received annual health examinations. After exclusion of subjects without data for abdominal ultrasonography or with the presence of IHD at baseline, a total of 14 141 subjects (men/women: 9195/4946; mean age, 48 years) were recruited. During the 10-year period (mean, 6.9 years), 479 subjects (men/women, 397/82) had new onset of IHD. Kaplan-Meier survival curves showed significant differences in rates of the cumulative incidence of IHD in subjects with and those without MAFLD (n=4581) and CKD (n=990; stages 1/2/3/4-5, 198/398/375/19). Multivariable Cox proportional hazard model analyses showed that coexistence of MAFLD and CKD, but not MAFLD or CKD alone, was an independent predictor for development of IHD after adjustment for age, sex, current smoking habit, family history of IHD, overweight/obesity, diabetes, hypertension, and dyslipidemia (hazard ratio, 1.51 [95% CI, 1.02-2.22]). The addition of the combination of MAFLD and CKD to traditional risk factors for IHD significantly improved the discriminatory capability. Conclusions The coexistence of MAFLD and CKD predicts new onset of IHD better than does MAFLD or CKD alone.

DOI PubMed

Prostanoid FP and EP2 Receptor Agonists Induce Epithelial and Subepithelial Fibrogenetic Changes in Human Conjunctival Fibroblasts in Different Manners.

Yuri Tsugeno, Tatsuya Sato, Megumi Watanabe, Masato Furuhashi, Hiroshi Ohguro

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics   39 ( 6 ) 404 - 414  2023年07月  [国際誌]

　概要を見る

Purpose: To examine the effects of prostanoid FP and EP2 receptor agonists, PGF2α and Omidenepag (OMD), respectively, on the transforming growth factor beta (TGF-β2) induced conjunctival fibrogenesis. Methods: Two-dimension (2D) and three-dimension (3D) cultures of these fibroblasts were subjected to following analyses: (1) planar proliferation evaluated by transendothelial electron resistance (TEER) measurements, (2) real-time metabolic analyses, (3) subepithelial proliferation evaluated by 3D spheroid' size and stiffness measurements, and (4) the mRNA expression of extracellular matrix (ECM) molecules and their modulators. Results: TGF-β2 induced increase in the planar proliferation was significantly decreased or enhanced by PGF2α or OMD, respectively. The proportion of oxygen consumption required to drive ATP synthesis compared with that driving proton leakage was increased by PGF2α and OMD independently with TGF-β2. In contrast, maximal mitochondrial respiration was decreased by PGF2α and OMD, and the OMD-induced effect was further enhanced by the presence of TGF-β2. In addition, the TGF-β2 dependent increase in the glycolytic capacity was cancelled by PGF2α and/or OMD. Alternatively, subepithelial proliferation, as evidenced by the stiffness of the 3D spheroids, was substantially increased by both PGF2α and OMD, and these were differently modulated by TGF-β2. The expression of several related factors as above fluctuated among the conditions for both 2D and 3D and TGF-β2 untreated or treated cultures. Conclusion: The present findings indicate that the prostanoid FP or the EP2 receptor agonist may solely and differently induce the planar and subepithelial proliferation of HconF cells and these were also modulated by TGF-β2.

DOI PubMed

TGF-β Isoforms Affect the Planar and Subepithelial Fibrogenesis of Human Conjunctival Fibroblasts in Different Manners

Megumi Watanabe, Yuri Tsugeno, Tatsuya Sato, Araya Umetsu, Nami Nishikiori, Masato Furuhashi, Hiroshi Ohguro

Biomedicines    2023年07月  [査読有り]

DOI

mTOR Inhibitors Modulate the Physical Properties of 3D Spheroids Derived from H9c2 Cells

Megumi Watanabe, Toshiyuki Yano, Tatsuya Sato, Araya Umetsu, Megumi Higashide, Masato Furuhashi, Hiroshi Ohguro

International Journal of Molecular Sciences    2023年07月  [査読有り]

DOI

Simultaneous Effects of a Selective EP2 Agonist, Omidenepag, and a Rho-Associated Coiled-Coil Containing Protein Kinase Inhibitor, Ripasudil, on Human Orbital Fibroblasts.

Fumihito Hikage, Megumi Watanabe, Tatsuya Sato, Araya Umetsu, Yuri Tsugeno, Masato Furuhashi, Hiroshi Ohguro

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics    2023年06月  [国際誌]

　概要を見る

Purpose: To assess the combined effects of omidenepag (OMD), a selective EP2 agonist, and ripasudil (Rip), an inhibitor of rho-associated coiled-coil containing protein kinases, on the human orbital adipose tissue, two-dimensional (2D) or three-dimensional (3D) cultures of human orbital fibroblasts (HOFs) were employed. Methods: Cellular metabolic functions (2D), physical (3D), lipid staining (3D), and quantitative polymerase chain reaction for adipogenesis-related genes, PPARγ and AP2, and extracellular matrix (ECM) molecules, including collagen (COL)1, 4, and 6, and fibronectin (FN) (3D) were evaluated in the presence of OMD (100 nM) and/or Rip (10 μM). Results: Real-time metabolic analyses revealed that the adipogenic differentiation (DIF+) with OMD significantly shifted an energetic state toward energetic, whereas DIF+ with Rip significantly shifted that toward quiescent. In the case of both drugs upon DIF+, the metabolic effect of OMD was predominant. DIF+ induced enlargement and stiffed 3D spheroid with increased lipid staining and mRNA expression of adipogenesis-related genes, COL4 and COL6, and decreased the expression of COL1. In the presence of OMD and/or Rip to DIF+, (1) the sizes were further increased by Rip and the stiffness was significantly decreased by OMD or Rip and (2) COL4 or AP2 expression was substantially increased by OMD or Rip, respectively. Conclusion: The results presented herein indicate that the metabolic effects of OMD and Rip exerted opposing effects and the effects of OMD toward Ap2 and ECM expressions were distinct from those of Rip, but the effects of OMD toward the physical aspects and adipogenesis of the 3D cultured HOFs were similar to the effects of Rip.

DOI PubMed

Impact of Radar Chart-Based Information Sharing in a Multidisciplinary Team on In-Hospital Outcomes and Prognosis in Older Patients With Heart Failure

Satoshi Katano, Toshiyuki Yano, Ryo Numazawa, Ryohei Nagaoka, Kotaro Yamano, Yusuke Fujisawa, Suguru Honma, Ayako Watanabe, Katsuhiko Ohori, Hidemichi Kouzu, Takefumi Fujito, Tomoyuki Ishigo, Hayato Kunihara, Hiroya Fujisaki, Masaki Katayose, Akiyoshi Hashimoto, Masato Furuhashi

Circulation Reports ( Japanese Circulation Society )   2023年06月

DOI

Independent Association Between Use of Proton Pump Inhibitors and Muscle Wasting in Patients with Heart Failure: A Single-Center, Ambispective, Observational Study

Katsuhiko Ohori, Toshiyuki Yano, Satoshi Katano, Ryohei Nagaoka, Ryo Numazawa, Kotaro Yamano, Yusuke Fujisawa, Hidemichi Kouzu, Masayuki Koyama, Nobutaka Nagano, Takefumi Fujito, Ryo Nishikawa, Wataru Ohwada, Masato Furuhashi

Drugs & Aging ( Springer Science and Business Media LLC )   2023年06月

DOI

性教育を身近な指導に パンフレットを用いるメリットと課題

米川 葵, 渡辺 絢子, 中島 直美, 宮越 郁子, 石郷 友之, 加藤 貴志, 片野 唆敏, 小山 雅之, 矢野 俊之, 橋本 暁佳, 古橋 眞人

日本肺高血圧・肺循環学会学術集会抄録集 ( 日本肺高血圧・肺循環学会 )  8回   153 - 153  2023年06月

Three-Dimensional Spheroid Configurations and Cellular Metabolic Properties of Oral Squamous Carcinomas Are Possible Pharmacological and Pathological Indicators.

Sho Miyamoto, Nami Nishikiori, Tatsuya Sato, Megumi Watanabe, Araya Umetsu, Yuri Tsugeno, Fumihito Hikage, Takashi Sasaya, Hirotaka Kato, Kazuhiro Ogi, Masato Furuhashi, Hiroshi Ohguro, Akihiro Miyazaki

Cancers   15 ( 10 )  2023年05月  [国際誌]

　概要を見る

The objective of the current study was to elucidate the clinicopathological significance and appearance of in vitro three-dimension (3D) spheroid models of oral malignant tumors that were prepared from four pathologically different squamous cell carcinoma (OSCC; low-grade; SSYP and MO-1000, intermediate-grade; LEM2) and oral adenosquamous carcinoma (OASC; high-grade; Mesimo) obtained from patients with different malignant stages. To characterize the biological significance of these cell lines themselves, two-dimensional (2D) cultured cells were subjected to cellular metabolic analysis by a Seahorse bioanalyzer alongside the measurement of the cytotoxicity of cisplatin (CDDP). The appearance of their 3D spheroids was then observed by phase contrast microscopy, and both 2D and 3D cultured cells were subject to trypsin digestion and qPCR analysis of factors related to oncogenic signaling and other related analyses. ATP-linked respiration and proton leaking were significantly different among the four cell lines, and the malignant stages of these cultures were significantly associated with increased ATP-linked respiration and decreased proton leakage. Alternatively, the appearances of these 3D spheroids were also significantly diverse among them, and their differences increased in the order of LEM2, MO-1000, SSYP, and Mesimo. Interestingly, these orders were exactly the same in that the efficacies of CDDP-induced cytotoxicity increased in the same order. qPCR analysis indicated that the levels of expression of oncogenic signaling-related factors varied among these four cell lines, and the values for fibronectin and a key regulator of mitochondrial biogenesis, PGC-1α, were prominently elevated in cultures of the worst malignant Mesimo cells. In addition, although 0.25% trypsin-induced destruction was comparable among all four 2D cultured cells, the values for the 3D spheroids were also substantially varied among these cultures. The findings reported herein indicate that cellular metabolic functions and 3D spheroid architectures may be valuable and useful indicators for estimating the pathological and drug-sensitive aspects of OSCC and OASC malignancies.

DOI PubMed