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Articles by D Lacombe
Total Records ( 2 ) for D Lacombe
  C. N Sternberg , H Dumez , H Van Poppel , I Skoneczna , A Sella , G Daugaard , T Gil , J Graham , P Carpentier , F Calabro , L Collette , D Lacombe and for the EORTC Genitourinary Tract Cancer Group
 

Background: This randomized, phase II study assessed the activity of oblimersen sodium, a Bcl-2 antisense oligonucleotide, administered before docetaxel (Taxotere) to patients with castration-resistant prostate cancer.

Patients and methods: Chemotherapy-naive patients with prostate-specific antigen (PSA) progression and testosterone ≤0.5 ng/ml received docetaxel 75 mg/m2 on day 1 or oblimersen 7 mg/kg/day continuous i.v. infusion on days 1–7 with docetaxel 75 mg/m2 on day 5 every 3 weeks for ≤12 cycles. Primary end points were confirmed PSA response (Bubley criteria) and major toxic events.

Results: Confirmed PSA response was observed in 46% and 37% of 57 and 54 patients treated with docetaxel and docetaxel–oblimersen, respectively. Partial response (RECIST) was achieved in 18% and 24%, respectively. Oblimersen added to docetaxel was associated with an increase in the incidence of grade ≥3 fatigue, mucositis, and thrombocytopenia. Major toxic events were reported in 22.8% and 40.7% of patients with docetaxel and docetaxel–oblimersen, respectively.

Conclusions: The primary end points of the study were not met: a rate of confirmed PSA response >30% and a major toxic event rate <45% were not observed with docetaxel–oblimersen.

  A Carre , G Szinnai , M Castanet , S Sura Trueba , E Tron , I Broutin L`Hermite , P Barat , C Goizet , D Lacombe , M. L Moutard , C Raybaud , C Raynaud Ravni , S Romana , H Ythier , J Leger and M. Polak
 

Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain–lung–thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC). The objectives of the present study were (i) detection of NKX2-1 mutations in patients with CH associated with pneumopathy and/or BHC, (ii) functional analysis of new mutations in vitro and (iii) description of the phenotypic spectrum of brain–lung–thyroid syndrome. We identified three new heterozygous missense mutations (L176V, P202L, Q210P), a splice site mutation (376-2A->G), and one deletion of NKX2-1 at 14q13. Functional analysis of the three missense mutations revealed loss of transactivation capacity on the human thyroglobulin enhancer/promoter. Interestingly, we showed that deficient transcriptional activity of NKX2-1-P202L was completely rescued by cotransfected PAX8-WT, whereas the synergistic effect was abolished by L176V and Q210P. The clinical spectrum of 6 own and 40 published patients with NKX2-1 mutations ranged from the complete triad of brain–lung–thyroid syndrome (50%), brain and thyroid disease (30%), to isolated BHC (13%). Thyroid morphology was normal (55%) and compensated hypothyroidism occurred in 61%. Lung disease occurred in 54% of patients (IRDS at term 76%; recurrent pulmonary infections 24%). On follow-up, 20% developed severe chronic interstitial lung disease, and 16% died. In conclusion, we describe five new NKX2.1 mutations with, for the first time, complete rescue by PAX8 of the deficient transactivating capacity in one case. Additionally, our review shows that the majority of affected patients display neurological and/or thyroidal problems and that, although less frequent, lung disease is responsible for a considerable mortality.

 
 
 
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