The influence of Bone Morphogenic Protein-2 on the consolidation phase in a distraction osteogenesis model.

We asked whether locally applied recombinant-Bone Morphogenic Protein-2 (rh-BMP-2) with an absorbable Type I collagen sponge (ACS) carrier could enhance the consolidation phase in a callotasis model. We performed unilateral transverse osteotomy of the tibia in 21 immature male rabbits. After a latency period of 7 days, a 3-weeks distraction was begun at a rate of 0.5mm/12h. At the end of the distraction period (Day 28) animals were randomly divided into three groups and underwent a second surgical procedure: 6 rabbits in Group I (Control group; the callus was exposed and nothing was added), 6 rabbits in Group II (ACS group; receiving the absorbable collagen sponge soaked with saline) and 9 rabbits in Group III (rh-BMP-2/ACS group; receiving the ACS soaked with 100μg/kg of rh-BMP-2, Inductos(®), Medtronic). Starting at Day 28 we assessed quantitative and qualitative radiographic parameters as well as densitometric parameters every two weeks (Days 28, 42, 56, 70 and 84). Animals were sacrificed after 8 weeks of consolidation (Day 84). Qualitative radiographic evaluation revealed hypertrophic calluses in the Group III animals. The rh-BMP-2/ACS also influenced the development of the cortex of the calluses as shown by the modified radiographic patterns in Group III when compared to Groups I and II. Densitometric analysis revealed the bone mineral content (BMC) was significantly higher in the rh-BMP-2/ACS treated animals (Group III).

An European Organisation for Research and Treatment of Cancer phase I study of lapatinib and docetaxel as neoadjuvant treatment for Human Epidermal Growth Factor Receptor 2 (HER2) positive locally-advanced/inflammatory or large operable breast cancer.

BACKGROUND: Lapatinib is an effective anti-HER2 therapy in advanced breast cancer and docetaxel is one of the most active agents in breast cancer. Combining these agents in pre-treated patients with metastatic disease had previously proved challenging, so the primary objective of this study aimed to determine the maximum tolerated dose (MTD) in treatment-naive patients, by identifying acute dose-limiting toxicities (DLT) during cycle 1 in the first part of a phases 1-2 neoadjuvant European Organisation for Research and Treatment of Cancer (EORTC) trial. PATIENTS AND METHODS: Patients with large operable or locally-advanced HER2 positive breast cancer were treated with continuous lapatinib, and docetaxel every 21days for 4 cycles. Dose levels (DLs) were: 1000/75, 1250/75, 1000/85, 1250/85, 1000/100 and 1250/100 (mg/day)/(mg/m(2)). RESULTS: Twenty-one patients were included. Two DLTs occurred at dose level 5 (1000/100); one grade 4 neutropenia ⩾7days and one febrile neutropenia. A further 3 patients were therefore treated at the same dose with prophylactic granulocyte-colony stimulating factor (G-CSF), and 3 patients at dose level 6. No further DLTs were observed. CONCLUSIONS: Our recommended dose for phase II is lapatinib 1000mg/day and docetaxel 100mg/m(2) with G-CSF in HER2 positive non-metastatic breast cancer. The dose of lapatinib should have been 1250mg/day but we were mindful of the high rate of treatment discontinuation in GeparQuinto with lapatinib 1250mg/day combined with docetaxel. No grade 3-4 diarrhoea was observed. Pharmacodynamics analysis suggests that concomitant medications altering P-glycoprotein activity (in addition to lapatinib) can modify toxicity, including non-haematological toxicities. This needs verification in larger trials, where it may contribute to understanding the sources of variability in clinical toxicity and treatment discontinuation.

Audit report on Wave 2 of the Phase II Strategic Sourcing Initiative implemented by the Department of Administrative Services

Audit report on Wave 2 of the Phase II Strategic Sourcing Initiative implemented by the Department of Administrative Services

Colombes, 17/2/20, France contre Pays de Galles [phase de jeu du match de rugby remporté par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58044

Colombes, 17/2/20, match France contre Pays de Galles [rugby, phase de jeu de la rencontre gagnée par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58046

Colombes, 17/2/20, France contre Pays de Galles [phase de jeu du match de rugby remporté par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58050

Colombes, 17/2/20, France contre Pays de Galles [phase de jeu du match de rugby remporté par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58054

Colombes, 17/2/20, match France contre Pays de Galles [rugby, phase de jeu de la rencontre gagnée par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58055

Colombes, 17/2/20, match France contre Pays de Galles [rugby, phase de jeu de la rencontre gagnée par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58056

Colombes, 17/2/20, match France contre Pays de Galles [rugby, phase de jeu de la rencontre gagnée par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58059

Colombes, 17/2/20, match France contre Pays de Galles [rugby, phase de jeu de la rencontre gagnée par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58060

Colombes, 17/2/20, match France contre Pays de Galles [rugby, phase de jeu de la rencontre gagnée par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58061

Colombes, 17/2/20, match France contre Pays de Galles [rugby, phase de jeu de la rencontre gagnée par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58062

Colombes, 17/2/20, match France contre Pays de Galles [rugby, phase de jeu de la rencontre gagnée par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58063

Colombes, 17/2/20, match France contre Pays de Galles [rugby, phase de jeu de la rencontre gagnée par Galles 6 à 5] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58065