Erythroid Progenitor Proliferation is Stimulated by Phenoxyacetic and Phenylalkyl Acids

Torkelson, Steven; White, Brian; Faller, Douglas V.; Phipps, Krista M; Pantazis, Cooley G.; Perrine, Susan P.

doi:10.1006/bcmd.1996.0022

Cited by 21 publications

(30 citation statements)

References 3 publications

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“…Valproic acid and phenylbutyrate induce Hb F in vivo when given by mouth (Collins et al, 1994(Collins et al, , 1995Dover et al, 1994). Hb F induction by propionate was demonstrated in transgenic mice and baboons (Liakopoulou et al, 1995) and by phenyl acetic and phenylalkyl acids in cultures and in primates (Torkelson et al, 1996).…”

Section: Short-chain Fatty Acidsmentioning

confidence: 99%

Understanding mechanisms of γ‐globin gene regulation to develop strategies for pharmacological fetal hemoglobin induction

Pace

Zein

2006

Developmental Dynamics

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The developmental regulation of ␥-globin gene expression has shaped research efforts to establish therapeutic modalities for individuals affected with sickle cell disease (SCD). Fetal hemoglobin (Hb F) synthesis is high at birth, followed by a decline to adult levels by 10 months of age. The expression of ␥-globin is controlled by a developmentally regulated transcriptional program that is recapitulated during normal erythropoiesis in the adult bone marrow. It is known that naturally occurring mutations in the ␥-gene promoters cause persistent Hb F synthesis after birth, which ameliorates symptoms in SCD by inhibiting hemoglobin S polymerization and vaso-occlusion. Several pharmacological agents have been identified over the past 2 decades that reactivate ␥-gene transcription through different cellular systems. We will review the progress made in our understanding of molecular mechanisms that control ␥-globin expression and insights gained from Hb F-inducing agents that act through signal transduction pathways.

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Section: Short-chain Fatty Acidsmentioning

confidence: 99%

Understanding mechanisms of γ‐globin gene regulation to develop strategies for pharmacological fetal hemoglobin induction

Pace

Zein

2006

Developmental Dynamics

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Section: Task 8: Use In Vitro Data To Modify and Re-assess The Phase mentioning

confidence: 99%

“…We had already determined that a number of these new compounds are efficient at inducing EBV-TK mRNA ( Fig. 4.3; see Torkelson, 1996 andBoosalis, 1998, for the structure/pharmacokinetics of these new oral agents). We found that induction of TK (Fig.…”

Section: Is Ebv-tk Gene Induction By Butyrate Dependent Upon Activatimentioning

confidence: 99%

“…A number of these compounds are efficient at inducing EBV-TK mRNA (Fig. 4.3; see Torkelson, et al, 1996;and Boosalis, et al, 1997, for the structure/pharmacokinetics of these oral agents).Isobutyramide, in particular has been studied in parallel with Arginine Butyrate in the extended induction and time course studies (Tasks 2 and 3), and also in cytotoxicity testing with GCV in the tumor cell lines (Task 4). Isobutyramide appears as efficient as Arginine Butyrate in induction of TK transcript.…”

mentioning

confidence: 99%

“…11.1). In addition, we have developed more than 50 short-chain fatty acid derivatives which we tested for induction of globin genes [see Torkelson, 1996, Boosalis, 1997. We have investigated this series of derivatives of short-chain fatty acids to determine: 1) what types of functional groups which could be substituted for a carbon and retain gene-inducing actions; and then, 2) what substitutions onto these types of structures prolong the half-life of the compound in vivo.…”

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confidence: 99%

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Virus-Targeted Therapeutic for Breast Cancer

Faller¹

1999

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188), Washington, DC 20503. AGENCY USE ONLY (Leave blank)2. REPORT DATE August 1999 REPORT TYPE AND DATES COVEREDFinal (15 Jul 96-14 Jul 99) TITLE AND SUBTITLEVirus-Targeted Therapeutic for Breast Cancer 6. AUTHOR(S) Douglas V. Faller, Ph.D. FUNDING NUMBERS DAMD17-96-C-6082 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)Boston University School of Medicine Boston, Massachusetts 02118 E*Mail: dfaller@bu.edu PERFORMING ORGANIZATION REPORT NUMBER SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES)Commander ABSTRACT (Maximum 200We have developed small molecules to alter the transcriptional response of viral genes for the treatment of human breast cancer. We have previously successfully used these compounds as therapeutic agents for gene regulation in humans. The transcriptional activity of certain viral genes, including the EpsteinBarr virus (EBV) Thymidine Kinase (TK) gene, is enhanced by these drugs. This work has led to the development of a virus-directed strategy for treating lymphoid malignancies associated with EBV. Exposure to Arginine Butyrate induces the latent TK gene in EBV-infected cells, resulting in susceptibility to ganciclovir. The presence of the Epstein-Barr virus in breast carcinomas of varying histology is strikingly high, raising the possibility of a therapeutic strategy for EBV(+) breast cancers. Our approach initially involves investigation of EBV sequences in breast cancer cell lines and specimens, determination of whether treatment with Arginine Butyrate will induce the viral thymidine kinase gene, and determination in vitro of whether the induction of the TK gene and gene product makes the breast cancer cells now susceptible to ganciclovir. We have initiated a clinical trial of an EBV-based strategy for treating cancers, including breast cancer, and shown safety and efficacy in early studies. Where copyrighted material is quoted, permission has been obtained to use such material. SUBJECT TERMS BreastWhere material from documents designated for limited distribution is quoted, permission has been obtained to use the material.Citations of commercial organizations and trade names in this report do not constitute an official Department of Army endorsement or approval of the products or services of these organizations.In conducting research using animals, the investigator(s) adhered to the "Guide for the Care and Use of Laboratory Anima...

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In vitro effect on human leukemic K562 cells of co-administration of liposome-associated retinoids and cytosine arabinoside (ara-C)

et al. 1999

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The administration of retinoids has been demonstrated to be of potential utility in the therapy of a wide spectrum of neoplastic pathologies due to the ability to induce differentiation in a large variety of primary tumor cells as well as in vitro cultured cell lines. Moreover, a number of compounds, including hemin, cytosine arabinoside, and 5-azacytidine are able to induce erythroid differentiation of the erythroleukemic cell line K562. In this paper we determined whether a combined treatment of K562 cells with suboptimal concentrations of cytosine arabinoside and retinoids containing liposomes lead to a full expression of differentiated functions. Liposomes were prepared by reverse phase evaporation technique followed by extrusion through polycarbonate filters. Cell growth kinetics studies and intracellular detection of hemoglobin by benzidine staining were performed. The results obtained showed that the combined treatment with liposomes containing retinoids and sub-optimal concentration of ara-C is an effective strategy to induce K562 cell differentiation, minimizing at the same time toxic effects. Control experiments aimed to determine possible selection of subpopulations of K562 cells suggest that the observed results are not related to toxicity and/or potential selection of induced cells. In conclusion, liposomally delivered retinoids could be proposed for differentiation therapy as an effective strategy in the treatment and management of malignancy. In addition, the finding that liposomally delivered retinoids increase the capacity of cytosine arabinoside to induce erythroid differentiation, could be of interest in studies aimed at the development of treatment able to reactivate fetal globin genes in beta-thalassemia patients.

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Erythroid Progenitor Proliferation is Stimulated by Phenoxyacetic and Phenylalkyl Acids

Cited by 21 publications

References 3 publications

Understanding mechanisms of γ‐globin gene regulation to develop strategies for pharmacological fetal hemoglobin induction

Understanding mechanisms of γ‐globin gene regulation to develop strategies for pharmacological fetal hemoglobin induction

Virus-Targeted Therapeutic for Breast Cancer

In vitro effect on human leukemic K562 cells of co-administration of liposome-associated retinoids and cytosine arabinoside (ara-C)

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