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Current Opinion in Hematology Mar 1995The search for, and discovery of, a physiologic model in which the developmentally regulated switch from fetal to adult globin gene expression could be prevented has... (Review)
Review
The search for, and discovery of, a physiologic model in which the developmentally regulated switch from fetal to adult globin gene expression could be prevented has resulted in the development of a new class of therapeutic agents, consisting of simple fatty acids, such as butyric acid, for the treatment of the beta-hemoglobinopathies. Butyrate and related drugs stimulate fetal (gamma-) globin gene expression in erythroid cells cultured from patients, and in chicken, ovine, and primate animal models. The butyrates are perhaps the first class of drugs designed to transcriptionally activate specific genes--in this particular case, to reactivate the developmentally silenced fetal globin genes. Phase I-II clinical trials resulting from this basic research have been initiated on a small scale during the past 3 years. Analysis of two butyrate-derived therapeutic agents, one delivered intravenously and one orally, has shown initial efficacy in stimulating fetal hemoglobin expression in 50% to 85% of patients. Correction of the anemia from the beta-hemoglobinopathy has followed induction of fetal globin, and has been adequate to eliminate the need for erythrocyte transfusions in some patients with beta-thalassemia. These compounds have been relatively safe and without generalized cytotoxicity in patients, but drug tolerance develops in some patients after prolonged therapy. Third-generation, small two- to five-carbon butyrate derivatives are in development. The molecular basis for butyrate action is being defined. Binding of putative regulatory proteins to a specific region of the gamma-globin promoter is altered in vivo in patients receiving butyrate therapy. Further analysis of the mode of action may contribute to development of other therapeutic agents designed to regulate gene transcription.
Topics: Anemia, Sickle Cell; Butyrates; Butyric Acid; Forecasting; Gene Expression Regulation; Globins; Humans; beta-Thalassemia
PubMed: 9371980
DOI: 10.1097/00062752-199502020-00002 -
The Proceedings of the Nutrition Society Nov 1996
Review
Topics: Apoptosis; Butyrates; Butyric Acid; Cell Differentiation; Colon; Energy Metabolism; Humans; Tumor Cells, Cultured
PubMed: 9004335
DOI: 10.1079/pns19960090 -
Journal of Oleo Science Oct 2019Lipase is a potential biocatalyst and can be exploited for various applications such as food, pharmaceutical, oleochemistry, organic chemistry, biofuels and in detergent...
Lipase is a potential biocatalyst and can be exploited for various applications such as food, pharmaceutical, oleochemistry, organic chemistry, biofuels and in detergent industries. In the present study, lipase from Aspergillus fumigatus was purified to homogeneity by SDS and Native PAGE and evaluated as biocatalyst for the synthesis of methyl butyrate which is a flavor ester. A purification fold of 6.96 was achieved by using Octyl Sepharose column chromatography. Methyl butyrate was synthesized by trans-esterification of vinyl butyrate with methanol, in a medium containing n-hexane as a solvent. The molar ratio of 2:2 (vinyl butyrate:methanol) was found to be optimum for the synthesis of methyl butyrate. The yield of methyl butyrate was maximum when reactants were incubated for 16 h at an incubation temperature of 40°C. The maximum yield (86%) of ester was obtained with 30 µg/ml of purified lipase.
Topics: Aspergillus fumigatus; Biocatalysis; Butyrates; Lipase
PubMed: 31511470
DOI: 10.5650/jos.ess19125 -
Neurogastroenterology and Motility Jan 2021
Topics: Butyrates; Butyric Acid; Colitis; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases; Microbiota
PubMed: 33222317
DOI: 10.1111/nmo.14038 -
Clinical Cancer Research : An Official... Jul 2002Pivaloyloxymethyl butyrate (AN-9), an acyloxyalkyl ester prodrug of butyric acid (BA), has demonstrated greater potency than BA at inducing malignant cell... (Clinical Trial)
Clinical Trial Review
Pivaloyloxymethyl butyrate (AN-9), an acyloxyalkyl ester prodrug of butyric acid (BA), has demonstrated greater potency than BA at inducing malignant cell differentiation and tumor growth inhibition and has demonstrated more favorable toxicological, pharmacological, and pharmaceutical properties than BA in preclinical studies. The principal objective of this study was to determine the feasibility of administering AN-9 as a 6-h i.v. infusion daily for 5 days every 3 weeks in patients with advanced solid malignancies. The study also sought to determine the principal toxicities and maximum tolerated dose of AN-9 on this intermittent schedule, as well as the effects of AN-9 on fetal hemoglobin production, a parameter indicative of RBC differentiation. None of the 28 patients treated with 85 total courses of AN-9 at dosages ranging from 0.047 to 3.3 g/m(2)/day every 3 weeks experienced dose limiting toxicity. Mild to moderate nausea, vomiting, hepatic transaminase elevation, hyperglycemia, fever, fatigue, anorexia, injection site reaction, diarrhea, and visual complaints were observed. Dose escalation of AN-9 was limited by the maximum feasible volume of its intralipid formulation vehicle that could be administered safely on this schedule, resulting in a maximum deliverable dose of 3.3 g/m(2)/day. There was no consistent increase in fetal hemoglobin with AN-9 treatment. A partial response was observed in a previously untreated patient with metastatic non-small cell lung cancer. Additional disease-directed clinical evaluations of AN-9 are necessary to establish the breadth of its antitumor activity and to assess its role as an effective differentiating agent.
Topics: Adult; Aged; Antineoplastic Agents; Butyrates; Cell Differentiation; Drug Administration Schedule; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms; Prodrugs; Safety
PubMed: 12114414
DOI: No ID Found -
The New England Journal of Medicine Nov 1995
Topics: Butyrates; Butyric Acid; Hemoglobinopathies; Humans
PubMed: 7566012
DOI: 10.1056/NEJM199511093331913 -
Gastroenterology Mar 1997
Topics: Animals; Apoptosis; Butyrates; Butyric Acid; Cell Survival; Colon; Guinea Pigs; Intestinal Mucosa
PubMed: 9041270
DOI: 10.1053/gast.1997.v112.agast971036 -
Leukemia & Lymphoma Jul 2001n-Butyric acid and its "polymorphic" derivatives have been largely but somehow "blindly" studied in oncology and in red cell diseases with consistent results through... (Review)
Review
n-Butyric acid and its "polymorphic" derivatives have been largely but somehow "blindly" studied in oncology and in red cell diseases with consistent results through decades indicating a strong maturative effect determined by enhancement of gene transcription. Although these effects have been observed mainly in vitro, the relative absence of systemic toxicity of butyrates render these compounds appealing as specific therapeutic agents. More interestingly, their specific mechanism of action, i.e. inhibition of histone deacetylase and de-repression of transcription represents at present an unique tool for diseases such as acute leukemias which are characterised by a disregulation of co-repressors and co-activators of gene transcription. More insight into specificity and modalities of action of different butyrate derivatives may be a guarantee for excellent tailored antileukemic therapy in the future.
Topics: Antineoplastic Agents; Butyrates; Enzyme Inhibitors; Hematologic Neoplasms; Histone Deacetylases; Humans; Leukemia; Neoplasms; Transcription, Genetic
PubMed: 11699392
DOI: 10.3109/10428190109064584 -
Gut Microbes 2024The gut microbiota and Short-chain fatty acids (SCFAs) can influence the progression of diseases, yet the role of these factors on gastric cancer (GC) remains uncertain....
The gut microbiota and Short-chain fatty acids (SCFAs) can influence the progression of diseases, yet the role of these factors on gastric cancer (GC) remains uncertain. In this work, the analysis of the gut microbiota composition and SCFA content in the blood and feces of both healthy individuals and GC patients indicated that significant reductions in the abundance of intestinal bacteria involved in SCFA production were observed in GC patients compared with the controls. ABX mice transplanted with fecal microbiota from GC patients developed more tumors during the induction of GC and had lower levels of butyric acid. Supplementation of butyrate during the induction of gastric cancer along with H. pylori and N-methyl-N-nitrosourea (MNU) in WT in GPR109Amice resulted in fewer tumors and more IFN-γ CD8 T cells, but this effect was significantly weakened after knockout of GPR109A. Furthermore, In vitro GC cells and co-cultured CD8 T cells or CAR-Claudin 18.2 CD8 T cells, as well as in vivo tumor-bearing studies, have indicated that butyrate enhanced the killing function of CD8 T cells or CAR-Claudin 18.2 CD8 T cells against GC cells through G protein-coupled receptor 109A (GPR109A) and homologous domain protein homologous box (HOPX). Together, these data highlighted that the restoration of gut microbial butyrate enhanced CD8 T cell cytotoxicity via GPR109A/HOPX, thus inhibiting GC carcinogenesis, which suggests a novel theoretical foundation for GC management against GC.
Topics: Humans; Mice; Animals; Butyrates; Gastrointestinal Microbiome; CD8-Positive T-Lymphocytes; Stomach Neoplasms; Fatty Acids, Volatile; Butyric Acid; Claudins
PubMed: 38319728
DOI: 10.1080/19490976.2024.2307542 -
European Journal of Cancer Prevention :... Oct 1995
Review
Topics: Adenoma; Apoptosis; Butyrates; Butyric Acid; Carcinoma; Cell Survival; Colonic Neoplasms; Dose-Response Relationship, Drug; Humans; Rectal Neoplasms; Tumor Cells, Cultured
PubMed: 7496324
DOI: 10.1097/00008469-199510000-00005