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19 results on '"Nakashima, Makoto"'

2. Targeting Excessive EZH1 and EZH2 Activities for Abnormal Histone Methylation and Transcription Network in Malignant Lymphomas

Author

Yamagishi, Makoto, Hori, Makoto, Fujikawa, Dai, Ohsugi, Takeo, Honma, Daisuke, Adachi, Nobuaki, Katano, Harutaka, Hishima, Tsunekazu, Kobayashi, Seiichiro, Nakano, Kazumi, Nakashima, Makoto, Iwanaga, Masako, Utsunomiya, Atae, Tanaka, Yuetsu, Okada, Seiji, Tsukasaki, Kunihiro, Tobinai, Kensei, Araki, Kazushi, Watanabe, Toshiki, Uchimaru, Kaoru, Yamagishi, Makoto, Hori, Makoto, Fujikawa, Dai, Ohsugi, Takeo, Honma, Daisuke, Adachi, Nobuaki, Katano, Harutaka, Hishima, Tsunekazu, Kobayashi, Seiichiro, Nakano, Kazumi, Nakashima, Makoto, Iwanaga, Masako, Utsunomiya, Atae, Tanaka, Yuetsu, Okada, Seiji, Tsukasaki, Kunihiro, Tobinai, Kensei, Araki, Kazushi, Watanabe, Toshiki, and Uchimaru, Kaoru

Abstract

type:Article, Although global H3K27me3 reprogramming is a hallmark of cancer, no effective therapeutic strategy for H3K27me3-high malignancies harboring EZH2^ has yet been established. We explore epigenome and transcriptome in EZH2^ and EZH2^ aggressive lymphomas and show that mutual interference and compensatory function of co-expressed EZH1 and EZH2 rearrange their own genome-wide distribution, thereby establishing restricted chromatin and gene expression signatures. Direct comparison of leading compounds introduces potency and a mechanism of action of the EZH1/2 dual inhibitor (valemetostat). The synthetic lethality is observed in all lymphoma models and primary adult T cell leukemia-lymphoma (ATL) cells. Opposing actions of EZH1/2-polycomb and SWI/SNF complexes are required for facultative heterochromatin formation. Inactivation of chromatin-associated genes (ARID1A, SMARCA4/BRG1, SMARCB1/SNF5, KDM6A/UTX, BAP1, KMT2D/MLL2) and oncovirus infection (HTLV-1, EBV) trigger EZH1/2 perturbation and H3K27me3 deposition. Our study provides the mechanism-based rationale for chemical dual targeting of EZH1/2 in cancer epigenome.

Published
2020

3. Targeting Excessive EZH1 and EZH2 Activities for Abnormal Histone Methylation and Transcription Network in Malignant Lymphomas

Author

Yamagishi, Makoto, Hori, Makoto, Fujikawa, Dai, Ohsugi, Takeo, Honma, Daisuke, Adachi, Nobuaki, Katano, Harutaka, Hishima, Tsunekazu, Kobayashi, Seiichiro, Nakano, Kazumi, Nakashima, Makoto, Iwanaga, Masako, Utsunomiya, Atae, Tanaka, Yuetsu, Okada, Seiji, Tsukasaki, Kunihiro, Tobinai, Kensei, Araki, Kazushi, Watanabe, Toshiki, Uchimaru, Kaoru, Yamagishi, Makoto, Hori, Makoto, Fujikawa, Dai, Ohsugi, Takeo, Honma, Daisuke, Adachi, Nobuaki, Katano, Harutaka, Hishima, Tsunekazu, Kobayashi, Seiichiro, Nakano, Kazumi, Nakashima, Makoto, Iwanaga, Masako, Utsunomiya, Atae, Tanaka, Yuetsu, Okada, Seiji, Tsukasaki, Kunihiro, Tobinai, Kensei, Araki, Kazushi, Watanabe, Toshiki, and Uchimaru, Kaoru

Abstract

Although global H3K27me3 reprogramming is a hallmark of cancer, no effective therapeutic strategy for H3K27me3-high malignancies harboring EZH2(WT/WT) has yet been established. We explore epigenome and transcriptome in EZH2(WT/WT) and EZH2(WT/Mu) aggressive lymphomas and show that mutual interference and compensatory function of co-expressed EZH1 and EZH2 rearrange their own genome-wide distribution, thereby establishing restricted chromatin and gene expression signatures. Direct comparison of leading compounds introduces potency and a mechanism of action of the EZH1/2 dual inhibitor (valemetostat). The synthetic lethality is observed in all lymphoma models and primary adult T cell leukemia-lymphoma (ATL) cells. Opposing actions of EZH1/2-polycomb and SWI/SNF complexes are required for facultative heterochromatin formation. Inactivation of chromatin-associated genes (ARID1A, SMARCA4/BRG1, SMARCB1/SNF5, KDM6A/UTX, BAP1, KMT2D/MLL2) and oncovirus infection (HTLV-1, EBV) trigger EZH1/2 perturbation and H3K27me3 deposition. Our study provides the mechanism-based rationale for chemical dual targeting of EZH1/2 in cancer epigenome.

Published
2019

8. Almost sure central limit theorem for branching random walks in random environment

Author

Nakashima, Makoto and Nakashima, Makoto

Abstract

We consider the branching random walks in d-dimensional integer lattice with time–space i.i.d. offspring distributions. Then the normalization of the total population is a nonnegative martingale and it almost surely converges to a certain random variable. When d≥3 and the fluctuation of environment satisfies a certain uniform square integrability then it is nondegenerate and we prove a central limit theorem for the density of the population in terms of almost sure convergence.

Published
2011
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19. The Experimental Study on Lung Transplantation

Author

Tsuji, Yasukuni, Tomita, Masao, Kawashima, Nozomu, Shigematsu, Sazuku, Miura, Toshio, Hamasaki, Akira, Nakashima, Makoto, Fukuda, Masaharu, Tsuji, Yasukuni, Tomita, Masao, Kawashima, Nozomu, Shigematsu, Sazuku, Miura, Toshio, Hamasaki, Akira, Nakashima, Makoto, and Fukuda, Masaharu

Abstract

Previous studies in the laboratory have been shown that homografts of the lung in canine can survive extended period of time, if methotrexate is given to the recipient animal, Several homografts survive more than a month. A series of fifty unrelated mongrel pairs have been subjected to, homotransplantation of the left lung. In each case the donor lung was stored in vitro 2 to 12 hours before placement in the recipient animal. The lung was perfusated with 5% dextrose, 3.6% PVP and plasma at 4°C by infusion pump and was ventilated with room air by respirator. It has been eluciated by histologic and electromicroscopic study including autopsy and survival rate that the safety storage period had been within 4 to 6 hours to prevent a fine change on donor lung due to storages., Acta medica Nagasakiensia. 1964, 9(1-2), p.22-28

Published
1964

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