Immunology and mammary cancer development: addressing the role of mast cells

Background: Mammary cancer is one of the most frequent cancers worldwide. Mast cells are among the cells of tumor microenvironment and have been associated with increased angiogenesis and poor prognosis. Despite this, the role of mast cells on mammary cancer is not fully elucidated. In this way, this work studied the role of mast cells in a rat model of mammary cancer chemically-induced. Materials and Methods: All experiments were performed in accordance with the Portuguese and European legislation on the protection of animals used for scientific purposes. The experiments were approved by the Portuguese (no.008961) and University (CE_12-2013) Ethics Committees. Thirty- four female Sprague-Dawley rats were randomly divided into five experimental groups. At seven weeks of age, mammary tumors’ development was induced in animals from groups I, II, III (n = 10+10+10) by a single intraperitoneal injection of the carcinogen N-methyl-N-nitrosourea (MNU). Groups II and IV (n = 2) were treated with ketotifen in drinking water (1 mg/kg/day, 7 days/week) immediately after the MNU ad- ministration for 18 weeks, while the group III received the ketotifen after the development of the first mammary tumor. Groups I and V (n = 2) received only water. Animals were sacrificed at 25 weeks of age by an overdose of ketamine and xylazine, followed by an exsanguination by cardiac puncture. Mammary tumors were collected and immersed in formalin for posterior analysis. Tumors’ vascularization, proliferation and apoptosis were also assessed by immunohistochemistry (Vascular Endothelial Growth Factor (VEGF)-A, Ki-67, and caspase-3 and caspase-9). Results: Animals from groups IV and V did not develop any mammary tumor. Twenty-one animals (six animals from group I, eight animals from group II and seven animals from group III) developed a total of 58 mammary tumors, mainly classified as papillary non-invasive carcinomas. Tumors’ vascularization was similar among groups (P > 0.05). Mammary tumors from group II exhibited the lowest prolif- eration (P < 0.05) and apoptotic indexes. Conclusions: The mainly positive effect of the ketotifen administration seems to be the reduction of tumor prolifera- tion when the drug was administered before mammary tumor development

Thiol modifier effects of diphenyl diselenides: insight from experiment and DFT calculations

A combination of spectroscopic, chromatographic and computational approaches was employed to investigate the reaction of several diselenides of formula (R-PhSe)(2) (R = CH3O, CH3, H, Cl, CF3) with a thiolate nucleophile, leading to the breaking of the selenium-selenium (Se-Se) bond. This process has fundamental importance in biological environments and provides a rationale to analyze the so-called thiol modifier effect of diselenides, which may be exploited in pharmacology and toxicology. Our data suggest that withdrawing substituents favor the reaction, effectively making the reaction energy more negative, but strong electron-withdrawing groups also prompt structural modification on the starting reactant, increasing the reaction barrier. Thus, the nature (electron rich or electron poor) of the diselenides can play an essential role in the reactivity and biological activity of these molecules

The influence of physical exercise on oestrogen and androgen receptor expression in a chemically and hormonally-induced rat model of prostate cancer

Background: Oestrogen (ER) and androgen (AR) recep- tors play an important role in normal prostate development and are also implied in prostate cancer (PCa) development. Several studies suggested that physical activity may decrease the risk of PCa development and also changes sexual hor- mones and their receptors. This study aimed to evaluate the effects of physical exercise on ERα and AR expression in a rat model of chemically and hormonally-induced PCa. Materials and Methods: Fifty-five male Wistar Unilever rats of 12 weeks of age were randomly divided into four groups: control sedentary (n = 10), control exercised (n = 10), induced sedentary (n = 15) and induced exercised (n = 20). Animals from exercised groups started the exercise training in a treadmill (Treadmill Control LE 8710, Harvard Apparatus, USA), at the age of 8 weeks, for 35 weeks (5 days/week). The protocol for PCa induction started at 12 weeks of age and consisted of sequential administration of flutamide (50 mg/kg, TCI Chemicals), testosterone propion- ate (100 mg/kg, TCI Chemicals) and N-methyl-N-nitrosourea (30 mg/kg, Isopac®, Sigma Chemical Co.), followed by sub- cutaneous implants of crystalline testosterone. Animals were sacrificed at 61 weeks of age and a complete necropsy was performed. All experiments were approved by DGAV (no. 021326). Antibodies for Erα (1:500, clone 6F11, Novocastra) and AR (clone PG21, Merck Millipore) were used for the immunohistochemical study. The staining extension was evaluated in normal prostate tissue and in dorsolateral pros- tate lesions (hyperplasia, dysplasia, prostatic intraepithelial neoplasia (PIN) and microinvasive carcinoma) and assessed to five levels (0%, 75%), con- sidering the extension of immunopositive tissue. Data was analysed with SPSS 25.Results: The normal prostate tissue and dorsolateral prostate lesions of animals from all groups were immunopositive for Erα and AR. However, the groups showed high immunoposi- tivity for AR and low positivity for Erα ( 0.05). The malignant lesions (PIN and microinvasive carcinoma) showed lower AR expression when compared with normal prostate tissue in all groups. Conclusions: As expected, the AR expression was lower in malignant lesions. Inversely to that reported in other studies, the exercise training did not modify the ERα and AR expres- sion, which may be related to the duration and type of exer- cise performed

Enhancement of affective processing induced by bifrontal transcranial direct current stimulation in patients with major depression

ObjectiveOur aim was to evaluate whether one single section of transcranial direct current stimulation (tDCS), a neuromodulatory technique that noninvasively modifies cortical excitability, could induce acute changes in the negative attentional bias in patients with major depression. Subjects and MethodsRandomized, double-blind, sham-controlled, parallel design enrolling 24 age-, gender-matched, drug-free, depressed subjects. Anode and cathode were placed over the left and right dorsolateral prefrontal cortex. We performed a word Emotional Stroop Task collecting the response times (RTs) for positive-, negative-, and neutral-related words. The emotional Stroop effect for negative vs. neutral and vs. positive words was used as the measure of attentional bias. ResultsAt baseline, RTs were significantly slower for negative vs. positive words. We found that active but not sham tDCS significantly modified the negative attentional bias, abolishing slower RT for negative words. ConclusionActive but not sham tDCS significantly modified the negative attentional bias. These findings add evidence that a single tDCS session transiently induces potent changes in affective processing, which might be one of the mechanisms of tDCS underlying mood changes

Noncommutative cosmological models coupled to a perfect fluid and a cosmological constant

In this work we carry out a noncommutative analysis of several Friedmann-Robert-Walker models, coupled to different types of perfect fluids and in the presence of a cosmological constant. The classical field equations are modified, by the introduction of a shift operator, in order to introduce noncommutativity in these models. We notice that the noncommutative versions of these models show several relevant differences with respect to the correspondent commutative ones.Comment: 27 pages. 7 figures. JHEP style.arXiv admin note: substantial text overlap with arXiv:1104.481