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837 results on '"Nishida, Kotaro"'

5. Reversion of methionine addiction of osteosarcoma cells to methionine independence results in loss of malignancy, modulation of the epithelial-mesenchymal phenotype and alteration of histone-H3 lysine-methylation

Author

Aoki, Yusuke, Han, Qinghong, Tome, Yasunori, Yamamoto, Jun, Kubota, Yutaro, Masaki, Noriyuki, Obara, Koya, Hamada, Kazuyuki, Wang, Justin D, Inubushi, Sachiko, Bouvet, Michael, Clarke, Steven G, Nishida, Kotaro, and Hoffman, Robert M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Pediatric, Cancer, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, malignancy, methionine addiction, Hoffman effect, methionine-independent revertant, epithelial-mesenchymal phenotype, histone-methylation, osteosarcoma, Clinical sciences, Oncology and carcinogenesis
Abstract

Methionine addiction, a fundamental and general hallmark of cancer, known as the Hoffman Effect, is due to altered use of methionine for increased and aberrant transmethylation reactions. However, the linkage of methionine addiction and malignancy of cancer cells is incompletely understood. An isogenic pair of methionine-addicted parental osteosarcoma cells and their rare methionine-independent revertant cells enabled us to compare them for malignancy, their epithelial-mesenchymal phenotype, and pattern of histone-H3 lysine-methylation. Methionine-independent revertant 143B osteosarcoma cells (143B-R) were selected from methionine-addicted parental cells (143B-P) by their chronic growth in low-methionine culture medium for 4 passages, which was depleted of methionine by recombinant methioninase (rMETase). Cell-migration capacity was compared with a wound-healing assay and invasion capability was compared with a transwell assay in 143B-P and 143B-R cells in vitro. Tumor growth and metastatic potential were compared after orthotopic cell-injection into the tibia bone of nude mice in vivo. Epithelial-mesenchymal phenotypic expression and the status of H3 lysine-methylation were determined with western immunoblotting. 143B-P cells had an IC50 of 0.20 U/ml and 143B-R cells had an IC50 of 0.68 U/ml for treatment with rMETase, demonstrating that 143B-R cells had regained the ability to grow in low methionine conditions. 143B-R cells had reduced cell migration and invasion capability in vitro, formed much smaller tumors than 143B-P cells and lost metastatic potential in vivo, indicating loss of malignancy in 143B-R cells. 143B-R cells showed gain of the epithelial marker, ZO-1 and loss of mesenchymal markers, vimentin, Snail, and Slug and, an increase of histone H3K9me3 and H3K27me3 methylation and a decrease of H3K4me3, H3K36me3, and H3K79me3 methylation, along with their loss of malignancy. These results suggest that shifting the balance in histone methylases might be a way to decrease the malignant potential of cells. The present results demonstrate the rationale to target methionine addiction for improved sarcoma therapy.

Published
2022

6. Histone H3 lysine-trimethylation markers are decreased by recombinant methioninase and increased by methotrexate at concentrations which inhibit methionine-addicted osteosarcoma cell proliferation

Author

Aoki, Yusuke, Tome, Yasunori, Han, Qinghong, Yamamoto, Jun, Hamada, Kazuyuki, Masaki, Noriyuki, Bouvet, Michael, Nishida, Kotaro, and Hoffman, Robert M

Subjects
Biochemistry and Cell Biology, Biological Sciences, Cancer, Brain Disorders, Pediatric Cancer, Pediatric, Osteosarcoma, Recombinant methioninase, Methionine restriction, Methotrexate, Methylation, Histone, H3K9me3, H3K27me3, Biochemistry and cell biology
Abstract

Methionine addiction is a fundamental and general hallmark of cancer cells, which require exogenous methionine, despite their ability to synthesize normal amounts of methionine from homocysteine. In contrast, methionine-independent normal cells do not require exogenous methionine in the presence of a methionine precursor. The methionine addiction of cancer cells is due to excess transmethylation reactions. We have previously shown that histone H3 lysine marks are over-methylated in cancer cells and the over-methylation is unstable when the cancer cells are restricted of methionine. In the present study, we show that methionine-addicted osteosarcoma cells are sensitive to both methotrexate (MTX) and recombinant methioninase (rMETase), but they affect histone H3 lysine-methylation in the opposite direction. Concentrations of MTX and rMETase, which inhibit osteosarcoma cells viability to 20%, had opposing effects on the status of histone methylation of H3K9me3 and H3K27me3. rMETase significantly decreased the amount of H3K9me3 and H3K27me3. In contrast, MTX significantly increased the amount of H3K9me and H3K27me3. The results suggest that increase or decrease in these methylated histone lysine marks is associated with proliferation arrest of methionine-addicted osteosarcoma.

Published
2021

13. A new era in the management of spinal metastasis

Author

Morimoto, Tadatsugu, primary, Toda, Yu, additional, Hakozaki, Michiyuki, additional, Paholpak, Permsak, additional, Watanabe, Kazuyuki, additional, Kato, Kinshi, additional, Tsukamoto, Masatsugu, additional, Hirata, Hirohito, additional, Kaneuchi, Yoichi, additional, Tome, Yasunori, additional, Nagamine, Satomi, additional, Nishida, Kotaro, additional, Katsuya, Hiroo, additional, Matsumoto, Yoshihiro, additional, Otani, Koji, additional, Mawatari, Masaaki, additional, and Nikaido, Takuya, additional

Published
2024
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21. Functional impact of integrin α5β1 on the homeostasis of intervertebral discs: a study of mechanotransduction pathways using a novel dynamic loading organ culture system

Author

Kurakawa, Takuto, Kakutani, Kenichiro, Morita, Yusuke, Kato, Yuki, Yurube, Takashi, Hirata, Hiroaki, Miyazaki, Shingo, Terashima, Yoshiki, Maeno, Koichiro, Takada, Toru, Doita, Minoru, Kurosaka, Masahiro, Inoue, Nozomu, Masuda, Koichi, and Nishida, Kotaro

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Biotechnology, Animals, Cell Count, Homeostasis, Immunohistochemistry, Integrin alpha5beta1, Intervertebral Disc, Intervertebral Disc Degeneration, Matrix Metalloproteinase 3, Mechanotransduction, Cellular, Oligopeptides, Organ Culture Techniques, Rats, Real-Time Polymerase Chain Reaction, Stress, Mechanical, Intervertebral disc degeneration, Organ culture, Mechanical load, Compression, Mechanoreceptor, Integrin, Neurosciences, Orthopedics, Clinical sciences, Allied health and rehabilitation science
Abstract

Background contextIntervertebral disc (IVD) degeneration, a major cause of low back pain, is considered to be induced by daily mechanical loading. Mechanical stress is widely known to affect cell survival and extracellular matrix metabolism in many cell types. Although the involvement of integrin α5β1 transmembrane mechanoreceptor in IVD degeneration has been reported, the precise function of integrin α5β1 remains obscure.PurposeTo reflect IVD tissue response to mechanical stress using a dynamic loading organ culture system and elucidate the functional impact of integrin α5β1 on the pathomechanism of IVD degeneration.Study designAn ex vivo study using a dynamic loading organ culture system.MethodsNinety-six rat IVD explants were examined. Intervertebral discs were subjected to 1.3 MPa, 1.0 Hz dynamic compressive load in the presence or absence of an Arg-Gly-Asp (RGD) peptide with affinity to the fibronectin binding-site of integrin α5β1. Cell viability and histomorphology were assessed. The localization of integrin α5β1 in the IVD was assessed by immunohistochemistry. Gene expression levels of IVD cells were evaluated using real-time reverse transcription-polymerase chain reaction.ResultsIn the nucleus pulposus (NP), cell density and viability were reduced by dynamic compressive load. Histologic degenerative alterations, mainly seen in the NP, were the morphologic changes of NP cells. In both NP and annulus fibrosus (AF), immunohistochemistry revealed localization of integrin α5β1 and that the messenger-RNA expression of integrin α5β1 was increased by dynamic load. Dynamic load induced a catabolic effect, the stimulation of matrix metalloproteinase-3 and -13 gene expressions by NP and AF cells. The RGD peptide partially blocked the histologic alterations and the catabolic effect.ConclusionsThe dynamic loading organ culture system simulated cellular responses to mechanical loading of the IVD. Our results suggest that IVD cells recognize the mechanical stress through RGD integrins, particularly the α5β1 subtype that is highly expressed in NP and AF cells. Further experiments using this system will provide information about pathomechanisms of IVD degeneration through the mechanotransduction pathways.

Published
2015

23. Risk Factor for Poor Patient Satisfaction After Lumbar Spine Surgery in Elderly Patients Aged Over 80 years

Author

Hikata, Tomohiro, Ishii, Ken, Matsumoto, Morio, Kobayashi, Kazuyoshi, Imagama, Shiro, Ando, Kei, Ishiguro, Naoki, Yamashita, Masaomi, Seki, Shoji, Terai, Hidetomi, Suzuki, Akinobu, Tamai, Koji, Aramomi, Masaaki, Ishikawa, Tetsuhiro, Kimura, Atsushi, Inoue, Hirokazu, Inoue, Gen, Miyagi, Masayuki, Saito, Wataru, Yamada, Kei, Hongo, Michio, Endo, Kenji, Suzuki, Hidekazu, Nakano, Atsushi, Watanabe, Kazuyuki, Ohya, Junichi, Chikuda, Hirotaka, Aoki, Yasuchika, Shimizu, Masayuki, Futatsugi, Toshimasa, Mukaiyama, Keijiro, Hasegawa, Masaichi, Kiyasu, Katsuhito, Iizuka, Haku, Kobayashi, Ryoichi, Iizuka, Yoichi, Nishida, Kotaro, Kakutani, Kenichiro, Nakajima, Hideaki, Murakami, Hideki, Demura, Satoru, Kato, Satoshi, Yoshioka, Katsuhito, Namikawa, Takashi, Watanabe, Kei, Nakanishi, Kazuyoshi, Nakagawa, Yukihiro, Yoshimoto, Mitsunori, Fujiwara, Hiroyasu, Nishida, Norihiro, Imajo, Yasuaki, Yamazaki, Masashi, Abe, Tetsuya, Fujii, Kengo, Kaito, Takashi, Eguchi, Yawara, Furuya, Takeo, Orita, Sumihisa, and Ohtori, Seiji

Published
2020
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29. Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study

Author

Otomo, Nao, primary, Khanshour, Anas M., additional, Koido, Masaru, additional, Takeda, Kazuki, additional, Momozawa, Yukihide, additional, Kubo, Michiaki, additional, Kamatani, Yoichiro, additional, Herring, John A., additional, Ogura, Yoji, additional, Takahashi, Yohei, additional, Minami, Shohei, additional, Uno, Koki, additional, Kawakami, Noriaki, additional, Ito, Manabu, additional, Sato, Tatsuya, additional, Watanabe, Kei, additional, Kaito, Takashi, additional, Yanagida, Haruhisa, additional, Taneichi, Hiroshi, additional, Harimaya, Katsumi, additional, Taniguchi, Yuki, additional, Shigematsu, Hideki, additional, Iida, Takahiro, additional, Demura, Satoru, additional, Sugawara, Ryo, additional, Fujita, Nobuyuki, additional, Yagi, Mitsuru, additional, Okada, Eijiro, additional, Hosogane, Naobumi, additional, Kono, Katsuki, additional, Nakamura, Masaya, additional, Chiba, Kazuhiro, additional, Kotani, Toshiaki, additional, Sakuma, Tsuyoshi, additional, Akazawa, Tsutomu, additional, Suzuki, Teppei, additional, Nishida, Kotaro, additional, Kakutani, Kenichiro, additional, Tsuji, Taichi, additional, Sudo, Hideki, additional, Iwata, Akira, additional, Inami, Satoshi, additional, Wise, Carol A., additional, Kochi, Yuta, additional, Matsumoto, Morio, additional, Ikegawa, Shiro, additional, Watanabe, Kota, additional, and Terao, Chikashi, additional

Published
2023
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38. Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese

Author

Kou, Ikuyo, Otomo, Nao, Takeda, Kazuki, Momozawa, Yukihide, Lu, Hsing-Fang, Kubo, Michiaki, Kamatani, Yoichiro, Ogura, Yoji, Takahashi, Yohei, Nakajima, Masahiro, Minami, Shohei, Uno, Koki, Kawakami, Noriaki, Ito, Manabu, Yonezawa, Ikuho, Watanabe, Kei, Kaito, Takashi, Yanagida, Haruhisa, Taneichi, Hiroshi, Harimaya, Katsumi, Taniguchi, Yuki, Shigematsu, Hideki, Iida, Takahiro, Demura, Satoru, Sugawara, Ryo, Fujita, Nobuyuki, Yagi, Mitsuru, Okada, Eijiro, Hosogane, Naobumi, Kono, Katsuki, Nakamura, Masaya, Chiba, Kazuhiro, Kotani, Toshiaki, Sakuma, Tsuyoshi, Akazawa, Tsutomu, Suzuki, Teppei, Nishida, Kotaro, Kakutani, Kenichiro, Tsuji, Taichi, Sudo, Hideki, Iwata, Akira, Sato, Tatsuya, Inami, Satoshi, Matsumoto, Morio, Terao, Chikashi, Watanabe, Kota, and Ikegawa, Shiro

Published
2019
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45. Reversion of methionine addiction of osteosarcoma cells to methionine independence results in loss of malignancy, modulation of the epithelial-mesenchymal phenotype and alteration of histone-H3 lysine-methylation

Author

Aoki, Yusuke, primary, Han, Qinghong, additional, Tome, Yasunori, additional, Yamamoto, Jun, additional, Kubota, Yutaro, additional, Masaki, Noriyuki, additional, Obara, Koya, additional, Hamada, Kazuyuki, additional, Wang, Justin D., additional, Inubushi, Sachiko, additional, Bouvet, Michael, additional, Clarke, Steven G., additional, Nishida, Kotaro, additional, and Hoffman, Robert M., additional

Published
2022
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49. Quality of life and cost-utility of surgical treatment for patients with spinal metastases: prospective cohort study

Author

Miyazaki, Shingo, Kakutani, Kenichiro, Sakai, Yoshitada, Ejima, Yasuo, Maeno, Koichiro, Takada, Toru, Yurube, Takashi, Terashima, Yoshiki, Ito, Masaaki, Kakiuchi, Yuji, Takeoka, Yoshiki, Hara, Hitomi, Kawamoto, Teruya, Sakashita, Akihiro, Okada, Takuya, Kiyota, Naomi, Kizawa, Yoshiyuki, Sasaki, Ryohei, Akisue, Toshihiro, Minami, Hironobu, Kuroda, Ryosuke, and Nishida, Kotaro

Published
2017
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50. Wide excision alone for elderly patients aged > 70 years old with soft tissue sarcomas

Author

Aoki, Yusuke, Tome, Yasunori, Oshiro, Hiromichi, Katsuki, Ryo, Tamaki, Tomoko, Wada, Naoki, Karube, Kennosuke, and Nishida, Kotaro

Subjects
wide excision, overall survival, soft tissue sarcoma, elderly
Abstract

The purpose of the present study was to clarify clinical outcomes of elderly patients with soft tissue sarcoma who underwent surgery neither with neoadjuvant nor adjuvant chemotherapy. The median follow-up period was 46.3 (range 6.7–99.0) months. All patients underwent surgical resections. R0 margins were achieved in 24 cases (92.3%) and R1 margins in 2 cases (7.7%). The 1-, 2-, and 5-year sarcoma-specific survival (SSS) rates were 92.3%, 88.5%, and 83.8%, respectively. Multivariate analysis showed no significant risk factors for SSS. No significant relationship of histological grades and local recurrences (P = .56) or distant metastases (P = .54) was shown. In the current study, we observed a comparable survival ratio, despite no neoadjuvant or adjuvant chemotherapies performed. Tumor resections with adequate margins might, at least in part, have contributed to the decent survival ratio regardless of histological grade. Twenty-six consecutive patients aged ≥ 70 years, who underwent surgical resections of soft tissue sarcoma between January 2013 and December 2019, were included. SSS were analyzed by the Kaplan–Meier method, and the relationships between SSS and clinical parameters were evaluated by Cox proportional hazards analysis.

Published
2022

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