Biomedical subjects

Alexandre Bozec

Publications and source records attributed to Alexandre Bozec.

3 recordsLinked to original sources

PubMed2006

[Parathyroid carcinoma].

Parathyroid carcinoma is a rare disease accounting for 1 to 5% of parathyroid neoplasms. This malignant tumour must be suspected when a severe primary hyperparathyroidism occurs with high hypercalcemia and elevated parathormon levels. At this time, a cervical mass is often palpable. Both head and neck ultrasonography and 99mTc-sestamibi scintigraphy are the best preoperative imaging tests to suspect and localize the tumour. Surgical approach with simultaneous tumorectomy and hemithyroidectomy, completed by selective neck dissection (level VI) is the treatment of choice. An elective lateral neck dissection should be performed if necessary. Tumour control should be monitored by regular measurement of calcium and parathormon levels. Local recurrence or metastasis risk is 30 to 70% and the 5 year overall survival about 50 to 80%. In case of recurrence, aggressive surgical management should be applied and adjuvant radiation therapy may be discussed.

Humans↗

PubMed2006

Epidermal growth factor receptor/angiogenesis dual targeting: preclinical experience.

PURPOSE OF REVIEW: This review aims to critically examine the preclinical background regarding the combination of drugs targeting the epidermal growth factor receptor and anti-angiogenic compounds. RECENT FINDINGS: There are studies exploring the anti-tumor efficacy of dual inhibitors, such as the compound ZD6474, which combines in the same molecule an anti-tyrosine kinase activity against the epidermal growth factor receptor and the vascular endothelial growth factor receptor. In addition, several studies have investigated the anti-tumor effects of combinations of an anti-epidermal growth factor receptor agent and a vascular endothelial growth factor receptor inhibitor. In general, in these studies, supra-additive anti-tumor efficacy was apparent when combining anti-epidermal growth factor receptor and anti-angiogenic treatments. Beneficial effects were also observed when combining this dual targeted therapy with either conventional chemotherapy or irradiation. SUMMARY: Early clinical trials combining the anti-epidermal growth factor receptor drug erlotinib (Tarceva) and the anti-angiogenic agent bevacizumab (Avastin) show acceptable toxicity and promising anti-tumor activity (lung cancer), which need to be confirmed in randomized trials.

Angiogenesis Inhibitors↗

PubMed2005

Response of endothelial cells to a dual tyrosine kinase receptor inhibition combined with irradiation.

Recent studies suggest the possibility of a direct antiangiogenic effect of anti-epidermal growth factor receptor (EGFR) drugs due to the presence of EGFR on endothelial cells. The aim of this study was to analyze the direct effect on endothelial cells of associating EGFR targeting, vascular endothelial growth factor receptor (VEGFR)-2 targeting, and irradiation. We examined both the cytotoxic effects and the effect on molecular markers resulting from the combined action of gefitinib (Iressa; anti-EGFR), ZM317450 [VEGFR tyrosine kinase inhibitor (VTKI); anti-VEGFR-2], and irradiation (radiation therapy) on HMME7 cells, an immortalized microvascular endothelial cell of human origin. The presence of a functional EGFR pathway sensitive to gefitinib was shown in HMME7 cells (gefitinib-induced decrease in phospho-EGFR, phospho-p42/p44, and phospho-Akt). The stimulation of VEGFR-2 pathway led to an increase in Akt phosphorylation that was inhibited by VTKI. Of note, a post-radiation therapy induction of phospho-p42/p44 was observed on HMME7 cells, and this effect was inhibited by a pretreatment with gefitinib. Based on combination indexes (Chou and Talalay analyses), the associations gefitinib-radiation therapy, VTKI-radiation therapy, VTKI-gefitinib, and gefitinib-VTKI-radiation therapy were found to be additive, slightly synergistic, and markedly synergistic, respectively, for the cytotoxicity on HMME7 cells. Among molecular explanatory factors that were examined, the combination gefitinib-radiation therapy totally abolishes DNA-dependent protein kinase expression, and gefitinib attenuates the radiation therapy-induced enhancement of ERCC1 and augments the VTKI-induced CD95 enhancement. The existence of a radiation therapy-dependent neoangiogenesis may be related to the induction of EGFR pathway in endothelial cells, a phenomenon that can be attenuated by anti-EGFR drugs like gefitinib. In complement to the direct antitumor effects of radiation therapy and anti-EGFR drugs, a strong antiangiogenic effect may be obtained with therapeutic strategies combining radiation therapy with EGFR and VEGFR-2 targeting agents.

Blotting, Western↗