Search Results - (Author, Cooperation:C. Miething)

2012-06-23

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Animals ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Gene Deletion ; Gene Regulatory Networks ; Genetic Testing ; Humans ; Lymphoma, B-Cell/*genetics/physiopathology ; Lysine/*analogs & derivatives/chemistry ; Mice ; Mice, Inbred C57BL ; Polyamines/*chemistry ; RNA, Small Interfering/genetics/metabolism ; Reproducibility of Results ; Tumor Suppressor Proteins/*genetics

2014-05-09

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Animals ; Chemokines/metabolism ; Gene Knockdown Techniques ; Leukemia/*enzymology/genetics/*physiopathology ; Mice, Transgenic ; PTEN Phosphohydrolase/*genetics/*metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; RNA Interference ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Tumor Microenvironment/*physiology

1365-3083

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The human interleukin(IL)-18 is a key regulator of interferon(IFN)-γ production and T-cell differentiation. Here we report the complete genomic structure and characterization of the 5′untranslated promoter region of the human IL-18 gene. The gene is composed of six exons and five introns, spanning approximately 19.5kb. Promoter activity of the 5′-flanking region was investigated with a luciferase reporter gene assay. Transient transfection studies demonstrate a constitutive expression of the IL-18 gene in monocytic U937 and THP-1 cells. For this constitutive expression at least 92 base pairs of the promoter region are essential as shown by consecutive 5′ promoter deletions in both cell types. DNA protein binding experiments revealed specific binding of activated signal transducer and activator of transcription factor-5 (STAT5) but not of STAT3 to three consensus sequences upstream in the promoter region. Cotransfection of STAT5 resulted in increased induction of the IL-18 promoter in the U937 and THP-1 cells.

Electronic Resource

1569-8041

acute myeloid leukemia ; AML ; bcl-2 ; prognosis ; quantitative PCR ; RT-PCR

Springer Online Journal Archives 1860-2000

Medicine

Abstract Background: The bcl-2 oncoprotein is suggested to be directly involved in the emergence of drug resistance by disrupting or delaying the apoptotic program and promoting tumor survival. Patients and methods: In order to define the clinical relevance of the bcl-2 mRNA expression in acute myeloid leukemia (AML) and its correlation to therapy outcome and prognosis, we analyzed 219 AML bone marrow (BM) samples, including 119 patients with de novo AML at presentation, 37 with AML following myelodysplastic syndrome (MDS), as well as 42 BM samples of AML in relapse and 21 in complete remission (CR) using RT-PCR. For performing quantitative measurements of bcl-2 mRNA, we developed a quantitative RT-PCR. Results: Bcl-2 mRNA was detectable in 133 of 156 (84%) patients at diagnosis and 40 of 42 (95%) at relapse. AML patients with high bcl-2 mRNA expression achieved lower CR rates than those with no or low expression. Concerning the long-term outcome, the overall (OS) and disease-free survival (DFS) was significantly worse in AML patients with high expression levels of bcl-2 mRNA. The three-year OS for all newly diagnosed AML patients was 49% and 10% (P = 0.028), respectively, and 71% and 15% (P = 0.0004) for patients 〈60 years. Comparable significant differences were observed for the DFS. In AML following MDS and patients 〉60 years, the bcl-2 expression was not associated with remission rate or survival. Conclusions: The expression of bcl-2 mRNA may serve as a prognostic factor predicting remission outcome and long-term prognosis in AML.

Electronic Resource