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Biotech / Medical : TITAN PHARMACEUTICAL (TTP) -- Ignore unavailable to you. Want to Upgrade?

To: Miljenko Zuanic who wrote (285)	6/16/2004 1:04:17 AM
From: biofreak	Respond to of 362

Blood. 2002 Nov 1;100(9):3319-24. Related Articles, Links The histone deacetylase inhibitor AN-9 has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines. Batova A, Shao LE, Diccianni MB, Yu AL, Tanaka T, Rephaeli A, Nudelman A, Yu J. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Medical Center, University of California-San Diego, 200 West Arbor Drive, San Diego, CA 92103-8447, USA. The novel prodrug of butyric acid, pivaloyloxymethyl butyrate (AN-9), a histone deacetylase inhibitor, shows great promise as an effective and relatively nontoxic anticancer agent for solid malignancies. However, little is known about its effects on hematopoietic malignancies. In this study, we show that 21 primary samples of acute leukemia were sensitive to the antiproliferative effects of AN-9, with a 50% inhibitory concentration (IC(50)) of 45.8 +/- 4.1 microM. In colony-forming assays, primary T-cell acute lymphoblastic leukemia (T-ALL) cells were 3-fold more sensitive to AN-9 than the normal hematopoietic progenitors, erythroid burst-forming units and granulocyte/monocyte colony-forming units. AN-9 induced apoptosis in the T-ALL cell line CEM. A common problem with cancer is chemoresistance, which is often typical of relapsed cancers. Remarkably, a T-ALL sample at diagnosis and an acute myeloid leukemia sample at relapse that were resistant to doxorubicin in vitro were sensitive to AN-9, with an IC(50) of 50 microM for both samples. More strikingly, samples from 2 infants with t(4;11) ALL obtained at diagnosis and relapse each were the most sensitive to AN-9, with IC(50) values of 25 microM and 17 microM, respectively. Furthermore, a doxorubicin-resistant clone of HL60, HL60/ADR, obtained by the transfection of the MDR-1 gene, was equally sensitive to AN-9 cytotoxicity as the parental cells. AN-9 induced the expression of p21 in an infant leukemia sample with 11q23 rearrangement, but not in T- or B-precursor ALL. Collectively, our results suggest that AN-9 is a selective agent for hematopoietic malignancies that can circumvent the mechanisms of chemoresistance limiting most conventional chemotherapy. PMID: 12384433 [PubMed - indexed for MEDLINE] -------------------------------------------------------------------------------- Summary Brief Abstract Citation ASN.1 MEDLINE XML UI List LinkOut Related Articles Cited in Books CancerChrom Links Domain Links 3D Domain Links GEO DataSet Links Gene Links Genome Links GEO Profile Links HomoloGene Links Nucleotide Links OMIM Links PMC Links Cited in PMC PopSet Links Protein Links SNP Links Structure Links UniSTS Links Show: 5 10 20 50 100 200 500 Sort Author Journal Pub Date Text File Clipboard E-mail Order Write to the Help Desk NCBI \| NLM \| NIH Department