Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy

Effects of melatonin on the ovarian response to pinealectomy or continuous light in female rats: similarity with polycystic ovary syndrome

The current study was conducted to investigate the relationship between melatonin and chronic anovulation. Adult (3-4 months old) female Wistar rats were submitted to pinealectomy: group I: pinealectomized ovariectomized melatonin-treated (N = 10); group II: pinealectomized ovariectomized placebo-treated (N = 12); group III: pinealectomized light-treated placebo-treated(N = 10) or maintained under continuous light; group IV: maintained under continuous light, ovariectomized melatonin-treated (N = 22); group V: maintained under continuous light, ovariectomized placebo-treated (N = 10); group VI: maintained under continuous light placebo-treated (N = 10). In order to assess ovarian modifications, unilateral ovariectomy was performed during the fourth month in groups I, II, IV, V and the other ovary was removed after 8 months. Ovariectomy was performed in groups III and VI only after eight months. Melatonin (200 µg/100 g body weight) dissolved in 0.02 ml absolute ethanol was injected intramuscularly daily during the last 4 months into groups I and IV. The other groups were treated with placebo (NaCl). The ovarian cysts were analyzed and their area, perimeter and maximum diameter, as well as the thickness of the ovarian capsule were measured. Daily colpocytological smears were performed throughout the study. Persistent estrous condition and ovarian cysts were observed in all groups. In pinealectomized rats the ovarian and vaginal alterations disappeared at the end of the study and in rats maintained under continuous light the vaginal and ovarian polycystic aspect was reversed only in those treated with melatonin. We conclude that melatonin may act on the ovarian response reverting chronic anovulation induced by pinealectomy or continuous light

Effects of β-adrenoceptor antagonists in the neural nitric oxide release induced by electrical field stimulation and sodium channel activators in the rabbit corpus cavernosum

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOβ-Adrenoceptor antagonists may present receptor-independent mechanisms, such as blockade of voltage-gated sodium channels. This study aimed to investigate the effects of non-selective (propranolol), and selective β1- (atenolol, metoprolol and betaxolol) and β2-adrenoceptor (ICI 118,551) antagonists in the nitric oxide (NO)-mediated rabbit corpus cavernosum relaxations induced by either electrical field stimulation (EFS) or activators of voltage-gated sodium channels. The sodium channel blockers tetrodotoxin and saxitoxin abolished the relaxations induced by EFS or sodium channel activators of binding site-2 (aconitine and veratridine), site-3 (Ts3 toxin), site-4 (Ts1 toxin) and site-5 (brevetoxin-3). The β-adrenoceptor antagonists failed to affect the relaxations induced by EFS, aconitine and veratridine. Relaxations induced by Ts3 and Ts1 toxins, as well as brevetoxin-3, were markedly reduced by prior addition of propranolol, betaxolol and ICI 118,551. During the established relaxation induced by Ts3 toxin, propranolol failed to restore the basal tone. In conclusion, β-adrenoceptor antagonists may cause an allosteric inhibition at the binding site-3, -4 and -5 of voltage-gated sodium channels, leading to blockade of neural NO release. © 2005 Elsevier B.V.β-Adrenoceptor antagonists may present receptor-independent mechanisms, such as blockade of voltage-gated sodium channels. This study aimed to investigate the effects of non-selective (propranolol), and selective β1- (atenolol, metoprolol and betaxolol) and β2-adrenoceptor (ICI 118,551) antagonists in the nitric oxide (NO)-mediated rabbit corpus cavernosum relaxations induced by either electrical field stimulation (EFS) or activators of voltage-gated sodium channels. The sodium channel blockers tetrodotoxin and saxitoxin abolished the relaxations induced by EFS or sodium channel activators of binding site-2 (aconitine and veratridine), site-3 (Ts3 toxin), site-4 (Ts1 toxin) and site-5 (brevetoxin-3). The β-adrenoceptor antagonists failed to affect the relaxations induced by EFS, aconitine and veratridine. Relaxations induced by Ts3 and Ts1 toxins, as well as brevetoxin-3, were markedly reduced by prior addition of propranolol, betaxolol and ICI 118,551. During the established relaxation induced by Ts3 toxin, propranolol failed to restore the basal tone. In conclusion, β-adrenoceptor antagonists may cause an allosteric inhibition at the binding site-3, -4 and -5 of voltage-gated sodium channels, leading to blockade of neural NO release5191-2146153FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçã