What the Orphan Drug Act has done lately for children with rare diseases: a 10-year analysis.

Objectives: The 1983 US Orphan Drug Act (ODA) provided incentives to stimulate treatment product development for patients with rare disease. This article highlights a decade of ODA contributions to this goal for children with RDs.

Methods: An internal US Food and Drug Administration database was the information source for orphan designations, marketing approvals, and prevalence numbers for 2000 to 2009.

The Orphan Drug Act and the development of stem cell-based products for rare diseases.

The Orphan Drug Act encourages the development of products for rare diseases and conditions. Many conditions that stand to benefit from stem cell-based products are rare diseases. We address the Orphan Drug Act in relation to the development of stem cell-based products.

RhoBTB2 (DBC2) is a mitotic E2F1 target gene with a novel role in apoptosis.

We have identified the RhoBTB2 putative tumor suppressor gene as a direct target of the E2F1 transcription factor. Overexpression of E2F1 led to up-regulation of RhoBTB2 at the level of mRNA and protein. This also occurred during the induction of E2F1 activity in the presence of cycloheximide, thus indicating that RhoBTB2 is a direct target.

E2F4 deficiency promotes drug-induced apoptosis.

E2F1 and E2F4 are known to have opposing roles in cell cycle control. In the present work, we examine the role of both E2F1 and E2F4 in apoptosis induced by three cyclin-dependent kinase inhibitors (roscovitine, BMS-387032, and flavopiridol) as well as by three established chemotherapeutic drugs (VP16, cisplatin and paclitaxel). We find that E2F4 levels are diminished following treatment with cyclin dependent kinase inhibitors (flavopiridol, roscovitine and BMS-387032) or with DNA damaging drugs (cisplatin and VP16).