Publications (3)5.82 Total impact
Article: Pre-clinical validation of early molecular markers of sensitivity to aromatase inhibitors in a mouse model of post-menopausal hormone-sensitive breast cancer.[show abstract] [hide abstract]
ABSTRACT: Changes in breast cancer cell biology following hormonal treatment have been claimed as promising predictor markers of clinical benefit even outperforming clinical response. From previous work we selected 10 genes showing both a well known regulation by oestrogen and a high level of early transcriptional regulation following therapy with aromatase inhibitors. Here we use an animal breast cancer model to explore the feasibility of the determination of their expression in minimally invasive samples and to further assess the magnitude of their regulation by letrozole. ANIMAL AND METHODS: Aromatase inhibitor sensitive breast cancer tumours were grown in athymic mice under supplement with androstenedione. Following initial tumour growth animals were assigned to a control group or to receive letrozole at two different dosages. Fine needle aspirates were obtained at the moment of treatment assignation and one week later. Expression of the following genes at both time points was determined: Ki-67, Cyclin D1, pS2, Trefoil Factor 3, PDZ domain containing 1, Ubiquitin-conjugating enzyme E2C, Stanniocalcin 2, Topoisomerase 2 alfa, MAN1A1 and FAS. Fine needles aspirates were found to be a feasible and reproducible technique for RNA extraction. Trefoil Factor 3, pS2, Cyclin D1 and Stanniocalcin 2 were significantly downregulated by letrozole. Among them pS2 appears to be most sensitive to aromatase inhibitor treatment even differentiating sub-optimal from optimal letrozole dosage. We present pre-clinical evidence to justify the exploration in clinical trials of pS2, Trefoil factor 3, Cyclin D1 and Stanniocalcin as dynamic markers of oestrogen-driven pathway activation.Breast Cancer Research and Treatment 07/2008; 109(3):463-70. · 4.43 Impact Factor
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ABSTRACT: The number of clinical trials in cancer patients has experienced an important growth during last years. However, it is difficult to find data showing this activity in Spanish Hospitals. This study analyses the clinical trials data bases between 1996 and 2002 in a cancer center. We perform a descriptive analysis of data from: selection of protocols, origin of proposals, sponsors, investigators, studies performed and published; demographic data about patients and phase of the studies in which they have been included. Evaluation was undertaken with a standardised protocol review assessment. 337 proposals of clinical trials were evaluated during 1996-2002, with a decreasing acceptance index (62.5% to 39.18%, respectively), the number of proposals has grown from 16 in 1996 to 74 in 2002. The general recruitment index was 6.64%. Between 1995-2002, 1479 patients were registered; only 5% were older than 75 years. Pharmaceutical Companies sponsored the majority of the studies, although Co-operative Groups promote an important number of studies, especially in Haematology and Radiotherapy. Thirteen studies performed between 1996-1998 had been published, and 3 more are accepted for publication (69.5%). The number of patients included in clinical trials is limited and older patients are not well represented in them.Medicina Clínica 03/2004; 122(6):212-5. · 1.38 Impact Factor
Revista Española de Geriatría y Gerontología 45(3):121-2.