Jin Zhang

Chinese Academy of Medical Sciences, Peping, Beijing, China

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Publications (1)2.8 Total impact

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    ABSTRACT: Chidamide (CS055/HBI-8000) is a new histone deacetylase (HDAC) inhibitor of the benzamide class currently under clinical development in cancer indications. This study reports the in vitro and in vivo antitumor characteristics of the compound. Selectivity and potency of chidamide in inhibition of HDAC isotypes were analyzed by using a panel of human recombinant HDAC proteins. Tumor cell lines either in culture or inoculated in nude mice were used for the evaluation of the compound's antitumor activity. To investigate the immune cell-mediated antitumor effect, isolated peripheral blood mononuclear cells from healthy donors were treated with chidamide, and cytotoxicity and expression of relevant surface proteins were analyzed. Microarray gene expression studies were performed on peripheral white blood cells from two T-cell lymphoma patients treated with chidamide. Chidamide was found to be a low nanomolar inhibitor of HDAC1, 2, 3, and 10, the HDAC isotypes well documented to be associated with the malignant phenotype. Significant and broad spectrum in vitro and in vivo antitumor activity, including a wide therapeutic index, was observed. Chidamide was also shown to enhance the cytotoxic effect of human peripheral mononuclear cells ex vivo on K562 target cells, accompanied by the upregulation of proteins involved in NK cell functions. Furthermore, the expression of a number of genes involved in immune cell-mediated antitumor activity was observed to be upregulated in peripheral white blood cells from two T-cell lymphoma patients who responded to chidamide administration. The results presented in this study provide evidence that chidamide has potential applicability for the treatment of a variety of tumor types, either as a single agent or in combination therapies.
    Cancer Chemotherapy and Pharmacology 11/2011; 69(4):901-9. · 2.80 Impact Factor

Publication Stats

8 Citations
2.80 Total Impact Points

Institutions

  • 2011
    • Chinese Academy of Medical Sciences
      Peping, Beijing, China