Refine
Document Type
- Article (1)
- Part of Periodical (1)
Language
- English (2)
Has Fulltext
- yes (2)
Is part of the Bibliography
- no (2)
Keywords
- Acute lymphoblastic leukemia (1)
- Aronia (1)
- Cancer chemotherapy (1)
- Cancer treatment (1)
- DNA (1)
- Flow cytometry (1)
- Integrins (1)
- Leukemias (1)
- Mouse models (1)
- Multiple sclerosis (1)
- Rosaceae (1)
- hybridity (1)
- morphology (1)
Institute
- Medizin (1)
We recently demonstrated the effectiveness of blocking CD49d with anti-functional antibodies or small molecule inhibitors as a rational targeted approach to the treatment of acute leukemia in combination with chemotherapy. Antisense oligonucleotide promises to be no less specific than antibodies and inhibitors, but more interesting for pharmacokinetics and pharmacodynamics. We addressed this using the published CD49d antisense drug ATL1102. In vitro, we incubated/nucleofected the ALL cell line Kasumi-2 with ATL1102. In vivo, immunodeficient hosts were engrafted with primary ALL cells and treated with ATL1102. Changes in expression of CD49d mRNA and CD49d protein, and of cooperating gene products, including ß1 integrin and CXCR4, as well as survival in the mouse experiments were quantified. We observed dose-dependent down-regulation of CD49d mRNA and protein levels and its partner integrin ß1 cell surface protein level and, up-regulation of CXCR4 surface expression. The suppression was more pronounced after nucleofection than after incubation, where down-regulation was significant only at the higher doses. In vivo effects of ATL1102 were not sufficient to translate into “clinical” benefit in the leukemia model. In summary, antisense oligonucleotides are successful tools for specifically modulating gene expression but sufficient delivery to down-regulate CD49d in vivo may be difficult to achieve.
Aronia Medik. (chokeberry, Rosaceae) is a genus of woody shrubs with two or three North American species. Species boundaries and relationships between species of Aronia are frequently under question. The only European species in the genus, A. mitschurinii A.K.Skvortsov & Maitul., is suggested to be an inter-generic hybrid. In order to clarify the relationships between species of Aronia, we performed several morphometric and molecular analyses and found that the molecular and morphological diversity within data on American Aronia is low, and species boundaries are mostly not clearly expressed. Whereas morphology is able to separate American species from A. mitschurinii, there is no support for such discrimination from the molecular data; our analyses did not reveal evidence of A. mitschurinii hybrid origin. We believe that higher-resolution markers are needed to resolve species boundaries and putative hybridization events.