Circulating oxidative stress parameters in pre- and post-menopausal healthy women and in women suffering from breast cancer treated or not with neoadjuvant chemotherapy.

We evaluate here the redox status in pre- and post-menopausal healthy women and in women with breast cancer in order to understand the consequences of the hormonal alterations of menopause for the oxidative stress status, its modifications with breast cancer and the influence of neoadjuvant chemotherapy (NC). To that, serum oxidative stress parameters (total antioxidant capacity, lipid peroxidation and protein oxidation), non-enzyme antioxidant defenses (total glutathione, uric acid and bilirubin) and enzyme antioxidant defenses (superoxide dismutase, catalase and glutathione peroxidase activities) were measured in healthy women and in women with breast cancer divided according to their menopausal status and that received or not NC. Circulating estradiol, progesterone, FSH and LH were also analyzed. We found that menopause itself modifies the redox status of healthy women, being most of these differences also reflected in women with breast cancer. However, several changes occur as a consequence of the disease. Furthermore, NC increases oxidative damage, decreases antioxidant defenses and eliminates the differences found in menopause. We conclude that the normal redox balance is disrupted by breast cancer but is also affected by the hormonal status promoted by menopause. In fact, NC nullifies the differences found between pre- and postmenopausal women in several antioxidant defense systems.

Eficacia de la biopsia intraoperatoria del ganglio centinela mediante el método one step nucleic acid amplification para evitar la linfadenectomía axilar en mujeres con cáncer de mama tratadas previamente con quimioterapia neoadyuvante / Effectiveness of intra-operative sentinel node biopsy by one-step nucleic acid amplification to avoid axillary lymphadenectomy in women with breast cancer treated with neoadjuvant chemotherapy

Objetivos. Evaluar en pacientes con ganglios axilares clínicamente negativos de inicio, la efectividad de la biopsia selectiva del ganglio centinela (BSGC) intraoperatoria mediante el método one step nucleic acid amplification (OSNA) para detectar metástasis microscópicas o celulares tras quimioterapia neoadyuvante, y evitar la duplicidad de procedimientos quirúrgicos. Pacientes y métodos. Se evaluó la efectividad de la BSGC mediante OSNA en pacientes con cáncer de mama que previamente tenían una axila clínica y ecográficamente negativa tras quimioterapia neoadyuvante (44 pacientes) o antes de la quimioterapia neoadyuvante (33 pacientes). Resultados. La tasa de identificación del ganglio centinela (GC) fue del 100% en ambos grupos. En las pacientes con BSGC previa a la quimioterapia se detectaron 13 mujeres con ganglios positivos (11 macrometástasis y 2 micrometástasis). En las pacientes tratadas primero con quimioterapia, se detectaron 10 mujeres con GC positivos, que fueron todos macrometástasis. El valor predictivo negativo de la prueba de ultrasonidos fue del 60,6% en pacientes con BSGC previa a quimioterapia y del 77,3% en pacientes con quimioterapia y posterior BSGC. Conclusiones. La BSGC mediante el método OSNA en mujeres que presentan clínicamente ganglios linfáticos negativos tras haber recibido quimioterapia neoadyuvante predice el estado axilar con gran precisión. Permite de forma inmediata tomar decisiones sobre la indicación o no de realizar una linfadenectomía axilar, evitando así el retraso en la administración de la quimioterapia y beneficiándose las pacientes de un solo procedimiento quirúrgico(AU)

Objectives. To evaluate in patients with clinically negative axillary nodes at initial presentation, the effectiveness of sentinel lymph node biopsy (SLNB) using intraoperative the one step nucleic acid amplification (OSNA) method to detect microscopic metastases or isolated tumor cells after neoadjuvant chemotherapy. Thus, axillary dissection and duplication of surgical procedures will be avoided. Patients and methods. We evaluated in patients with breast cancer and clinically negative axilla, the effectiveness of SLNB by OSNA after neoadjuvant chemotherapy (44 patients) or prior to neoadjuvant chemotherapy (33 patients). Results. The rate of SLN identification was 100% in both groups. In patients with SLNB prior to systemic treatment, 13 women showed positive nodes (11 macrometastases and 2 micrometastases), and those with SLNB after neoadjuvant chemotherapy, positive SLNB were detected in 10 women, which were all of them macrometastases. The negative predictive value of ultrasonography was 60.6% in patients with SLNB prior to neoadjuvant therapy and 77.3% in patients with chemotherapy followed by SLNB. Conclusions. Intraoperative SLNB using OSNA in women with clinically negative axillary lymph nodes at initial presentation who received neoadjuvant chemotherapy, predicts axillary status with high accuracy. Also it allows immediately make decisions about the indication or not to perform an axillary dissection, thus avoiding delay in the administration of chemotherapy and benefit the patients for a single surgical procedure(AU)

Intracellular signaling pathways involved in the cell growth inhibition of glioma cells by melatonin.

Melatonin is an indolamine mostly produced in the pineal gland, soluble in water, and highly lipophilic, which allows it to readily cross the blood-brain barrier. Melatonin possesses antioxidant properties and its long-term administration in rodents has not been found to cause noteworthy side effects. In the present work, we found that millimolar concentrations of this indolamine reduced cell growth of C6 glioma cells by 70% after 72 hours of treatment, inhibiting cell progression from G(1) to S phase of the cell cycle. Intraperitoneal administration of 15 mg/kg body weight of melatonin to rats previously injected in the flank with C6 glioma cells reduces tumor growth by 50% 2 weeks after the implant. Inhibition of cell growth does not depend on melatonin membrane receptor activation whereas it seemingly relates to the reduction of intracellular basal free radical levels by 30%. Increase of basal redox state of the cells and constitutive activation of tyrosine kinase receptor [receptor tyrosine kinase (RTK)] pathways, including the extracellular signal-regulated kinase 1/2 (ERK1/2) and the Akt and protein kinase C (PKC) signaling pathways, contribute to the progression of the gliomas leading to the constitutive activation of the redox-dependent survival transcription factor nuclear factor kappaB (NF-kappaB). The antioxidant effect of melatonin in C6 cells is associated to inhibition of NF-kappaB and Akt, but not of ERK1/2. The antiproliferative effect of the indolamine on these cells is partially abolished when coincubated with the PKC activator 12-O-tetradecanoylphorbol-13-acetate, thus indicating that the ability of melatonin to change cellular redox state may be inactivating the pathway RTK/PKC/Akt/NF-kappaB.