Disease relevance of FOXJ2

• PURPOSE: We have previously demonstrated high locoregional control rates in patients with poor-prognosis head and neck cancer using fluorouracil (5-FU), hydroxyurea (HU), and concomitant radiotherapy (RT) (FHX) [1].
• During FHX, 81% of patients had grade 3 or 4 mucositis [2].
• In the trial reported here, we added paclitaxel to the FHX base and used hyperfractionated RT to determine the maximum-tolerated dose (MTD), toxicities, and response rate in a poor-prognosis group of patients [1].

High impact information on FOXJ2

• PATIENTS AND METHODS: Three cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU), leucovorin, and interferon alfa-2b (PFL-IFN) were followed by optional surgery, and seven or eight cycles of 5-FU, hydroxyurea, and concurrent radiation for 5 days (FHX) for a total radiation dose of 65 to 75 Gy [3].
• In study 2, G-CSF was added on days 6 to 13 at 5 micrograms/kg/d. RESULTS: Acute and cumulative myelosuppression limited the feasibility of adding cisplatin to FHX without G-CSF [4].
• Polymerase chain reaction-assisted site selection experiments showed that FHX bound DNA with a dual sequence specificity [5].
• In transfection assays, FHX was capable of activating transcription from promoters containing FHX sites of either type [5].
• Although the AB domain shows the strongest transactivation capacity, all three domains are required for full FOXJ2 transcriptional activity [6].

Chemical compound and disease context of FOXJ2

• PURPOSE: We previously demonstrated high locoregional control rates in patients with poor-prognosis head and neck cancer using fluorouracil (5-FU), hydroxyurea (HU), and concomitant radiotherapy (FHX) [4].
• 13 Cis-retinoic acid was added to treatment regimen for chemoprevention and a systematic prophylaxis of mucositis was administered to all patients during FHX [7].

Biological context of FOXJ2

• FOXJ2 is a fork head transcriptional activator, the expression of which starts very early in embryonic development and it is distributed widely in the adult [6].
• We found that FHX, a recently characterized human fork-head transcriptional activator, may show such a mechanism for balancing its activity by expressing two differently sized isoforms, FHX.S and FHX.L, encoded by a single gene located on human chromosome 12 [8].

Associations of FOXJ2 with chemical compounds

• Although FOXJ2 can be phosphorylated in two serine residues, this post-translational modification did not appear to be essential for transactivation [6].
• Furthermore, a fourth region rich in proline and glutamine residues and with no intrinsic transactivation function, the P/Q domain, appears to play an important role in the FOXJ2-mediated transactivation mechanism [6].
• The treatment plan consisted of 3 cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU), l-leucovorin and interferon alpha2b (PFL-IFN) followed by 7 cycles of 5-FU, hydroxyurea and concomitant radiation for 5 days (FHX) for a total radiation dose of 70 Gy [7].

Analytical, diagnostic and therapeutic context of FOXJ2

• When followed by limited surgery and FHX, resultant local and distant disease control, organ preservation, and overall 5-year survival are very promising in high-risk stage IV patients [2].
• Clinical and/or pathological (37% of all patients had post-treatment biopsy with or without neck dissection) CR after FHX was 100% [9].

References