A synthetic inhibitor of histone deacetylase, MS-27-275, with marked
            <i>in vivo</i>
            antitumor activity against human tumors

Saito, Akiko; Yamashita, Takashi; Mariko, Yukiyasu; Nosaka, Yasuhito; Tsuchiya, Katsumi; Ando, Tomoyuki; Suzuki, Tateyuki; Tsuruo, Takashi; Nakanishi, Osamu

doi:10.1073/pnas.96.8.4592

Cited by 658 publications

(473 citation statements)

References 46 publications

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“…However, as a marker of mature hepatocytes, the ALB was not detected in ES-derived hepatic progenitor cells. The result showed that the ES-derived hepatic progenitor cells have some similar molecular characterizations as the previously reported hepatic progenitor/stem cells [Brill et al, 1999;Saito et al, 1999;Azuma et al, 2003;Lazaro et al, 2003;Strick-Marchand and Weiss, 2003;Zhang et al, 2003;Petkov et al, 2004].…”

Section: Identification and Characterization Of Es-derived Hepatic Prsupporting

confidence: 80%

“…Hepatic progenitor cells, which express a series of early liver lineage specific markers and are capable of differentiating into hepatocytes or bile duct epithelial cells under proper conditions, have been identified in embryonic, adult liver or bone marrow of rodents and human [Brill et al, 1999;Saito et al, 1999;Azuma et al, 2003;Lazaro et al, 2003;StrickMarchand and Weiss, 2003;Zhang et al, 2003;Petkov et al, 2004]. But none of previous articles have reported that ES cells can be directly induced to differentiate into hepatic progenitor cells in vitro.…”

mentioning

confidence: 99%

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In vitro differentiation of hepatic progenitor cells from mouse embryonic stem cells induced by sodium butyrate

Zhou

Xiang

Shao

et al. 2006

J of Cellular Biochemistry

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Recently it was shown that embryonic stem (ES) cells could differentiate into hepatocytes both in vitro and in vivo, however, prospective hepatic progenitor cells have not yet been isolated and characterized from ES cells. Here we presented a novel 4-step procedure for the differentiation of mouse ES cells into hepatic progenitor cells and then hepatocytes. The differentiated hepatocytes were identified by morphological, biochemical, and functional analyses. The hepatic progenitor cells were isolated from the cultures after the withdrawal of sodium butyrate, which was characterized by scant cytoplasm, ovoid nuclei, the ability of rapid proliferation, expression of a series of hepatic progenitor cell markers, and the potential of differentiation into hepatocytes and bile duct-like cells under the proper conditions that favor hepatocyte and bile epithelial differentiation. The differentiation of hepatocytes from hepatic progenitor cells was characterized by a number of hepatic cell markers including albumin secretion, upregulated transcription of glucose-6-phophatase and tyrosine aminotransferase, and functional phenotypes such as glycogen storage. The results from our experiments demonstrated that ES cells could differentiate into a novel bipotential hepatic progenitor cell and mature into hepatocytes with typical morphological, phenotypic and functional characteristics, which provides an useful model for the studies of key events during early liver development and a potential source of transplantable cells for cell-replacement therapies.

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Section: Identification and Characterization Of Es-derived Hepatic Prsupporting

confidence: 80%

mentioning

confidence: 99%

In vitro differentiation of hepatic progenitor cells from mouse embryonic stem cells induced by sodium butyrate

Zhou

Xiang

Shao

et al. 2006

J of Cellular Biochemistry

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“…The benzamide (e.g. MS-275 and CI-994) (Saito et al, 1999;Prakash et al, 2001) and electrophilic ketone (e.g. trifluoromethyl ketones and a-ketoamides) (Frey et al, 2002) classes of HDAC inhibitors are less potent than hydroxamates and cyclic tetrapeptides, exhibiting HDAC inhibition activity in the micromolar concentration range.…”

Section: Cellular Effects Of Hdac Inhibitorsmentioning

confidence: 99%

Modulation of cellular radiation responses by histone deacetylase inhibitors

Karagiannis

El‐Osta

2006

Oncogene

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Histone deacetylase (HDAC) inhibitors are emerging as a new class of targeted cancer chemotherapeutics. Several HDAC inhibitors are currently in clinical trials and promising anticancer effects at well-tolerated doses have been observed for both hematologic and solid cancers. HDAC inhibitors have been shown to induce cell-cycle and growth arrest, differentiation and in certain cases apoptosis in cell cultures and in vivo. However, it is known that these compounds induce varying responses in different cells and biological settings, and identifying their precise mechanisms of action is an area of great interest. Important findings are continually expanding our understanding of the cellular effects of HDAC inhibitors and recent studies will be briefly outlined in this review. In addition to their intrinsic anticancer properties, numerous studies have demonstrated that HDAC inhibitors can modulate cellular responses to other cytotoxic modalities including ionizing radiation, ultraviolet radiation and chemotherapeutic drugs. Hence, there is a growing interest in potential clinical use of HDAC inhibitors in combination with conventional cancer therapies. In this review, the interaction of HDAC inhibitors with other anticancer agents is discussed. The focus of the article is on the different mechanisms by which HDAC inhibitors enhance the sensitivity of cells to the effects of ionizing radiation.

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“…) is an orally active bioavailable histone deacetylase inhibitor [1]. In preclinical studies, MS-275 has demonstrated antitumor activity against a variety of human cancer cell lines [1,2].…”

Section: Ms-275 (3-pyridylmethyl-n-{4-[(2-amino-pyenyl0-carbamoyl]-bementioning

confidence: 99%

A liquid chromatography/tandem mass spectrometry assay to quantitate MS-275 in human plasma

Zhao¹,

Rudek²,

Mnasakanyan³

et al. 2007

Journal of Pharmaceutical and Biomedical Analysis

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A rapid, sensitive and selective method was developed and validated using LC/MS/MS for determination of MS-275 in human plasma. Sample preparation involved a single step liquid-liquid extraction by the addition of 0.2 ml of plasma with 5 ml acetonitrile/n-butyl-chloride. Separation of the compounds of interest, including the internal standard paclitaxel, was achieved on a Waters XTerra C 18 (50 x 2.1 mm i.d., 3.5 μm) analytical column using a mobile phase consisting of acetonitrileammonium acetate (pH 2.9; 2 mM)(60:40, v/v) containing 0.1% formic acid and isocratic flow at 0.15 ml/min for 3 minutes. The analytes were monitored by tandem-mass spectrometry with electrospray positive ionization. Linear calibration curves were generated over the range of 0.5 to 100 ng/ml with values for the coefficient of determination of >0.99. The values for both within day and between day precision and accuracy were well within the generally accepted criteria for analytical methods (<15%). This method was subsequently used to measure concentrations of MS-275 in cancer patients receiving an oral weekly dose of 4 mg/m.

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A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors

Cited by 658 publications

References 46 publications

In vitro differentiation of hepatic progenitor cells from mouse embryonic stem cells induced by sodium butyrate

In vitro differentiation of hepatic progenitor cells from mouse embryonic stem cells induced by sodium butyrate

Modulation of cellular radiation responses by histone deacetylase inhibitors

A liquid chromatography/tandem mass spectrometry assay to quantitate MS-275 in human plasma

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