Breast cancer is the leading cause of cancer mortality in females worldwide. Studies based on gene expression profiles have identified different breast cancer molecular subtypes, such as luminal A and B cells, cancer cells that are estrogen receptor (ER) and/or progesterone receptor (PR) positive, human epidermal growth factor 2 (HER2)-enriched cells, cancer cells that exhibit an overexpression of the oncogene HER2, and triple-negative cells, cancer cells that are negative for ER, PR and HER2 expression. Immunohistochemistry is the most common type of method used for the identification of these molecular subtypes, through the identification of specific cell receptors. The present study aimed to evaluate the ER, PR and HER2 receptor expression in human breast cancer cell lines, and to classify the corresponding molecular subtype comparing two alternative methods. In the present study, a panel of human mammary carcinoma cell lines: BT-20; Hs578T; MCF-7; MCF-7/AZ; MDA-MB-231; MDA-MB-468; SKBR3; and T47D were used. Immunohistochemical and immunocytochemistry assays were used to characterize the breast cancer subtypes of these cell lines according to the expression of ER, PR and HER2 receptors. The results revealed the molecular characterization of this panel of breast cancer cell lines, using the differential expression of classical and clinically used markers in concordance with previous studies. In addition, these data are important for additional in vitro studies of these specific receptors.
Our results confirm the action of melatonin on the miR-152-3p regulation known to be involved in the progression of breast cancer.
The present review has for objective to stand out some aspects little argued of the cardiopulmonary bypass (CPB), taking in consideration physiology, physiopathology and some new technologies of perfusion. Thus, some points, sometimes philosophical, had motivated the elaboration of this revision: a) To preserve and to bring up to date the surgeon CPB knowledge, for the simple fact to even keep its pedagogical leadership on its team; b) To question if patient aged and/or diabetic, for its individual characteristics, deserved more appropriate protocols as well as adopted for children; c) One third aspect would be the questioning of the systemic inflammatory reaction caused by the exposition of the blood to CPB non-endothelized circuit surface ahead of the increasing importance of the wound surgical contact of the blood; d) In relation to the treatment of the vasoplegic syndrome, methylene blue continues being the best therapeutical option, even so, many times are not efficient because of a highly probable existence of a "therapeutical window" based in the guanylate cyclase dynamics of action (saturation and synthesis "de novo") and; finally, e) The reason of the choice of the heading standing out that, in its current patterns, the CPB would be consequence of empirism, art, or science. The final message comes with the certainty of that as much the empirism, art and science are very strong concerning CPB.Descriptors: Extracorporeal circulation. Cardiopulmonary bypass. Cardiac surgical procedures. 79MOTA, AL ET AL -Adult cardiopulmonary bypass in the twentyfirst century. Science, art or empiricism? Rev Bras Cir Cardiovasc 2008; 23(1): 78-92
At present, four main types of serotonin (5-HT) receptors have been identified in the brain (5-HT1, 5-HT2, 5-HT3, and 5-HT4). In addition, the 5-HT1 have been further subclassified. We have taken advantage of a new selective 5-HT1D receptor agonist 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide succinate, Sumatriptan, to evaluate the role of 5-HT1D receptors on GH secretion. To this end, several tests with or without sumatriptan were undertaken in normal prepubertal children. Furthermore, we assessed the effect of Sumatriptan on basal GH secretion and the GH response to GHRH in obese children. In normal children, Sumatriptan administration (3 mg, sc) resulted in an increase in basal GH levels at 30 min (7.7 +/- 1.5 micrograms/L; P < 0.05) and increased GH responses to GHRH (47.3 +/- 6.4 vs. 29.6 +/- 9.7 micrograms/L; P < 0.05). The Sumatriptan-induced increase in GH responses to GHRH was dependent on the stimulus tested. Pretreatment with Sumatriptan did not modify the GH response to clonidine or pyridostigmine, as assessed by the peak GH response and the area under the curve. In contrast, it increased the GH response to arginine. In the obese subjects, the GH response to GHRH was reduced (7.3 +/- 1.0 vs. 29.6 +/- 9.7 micrograms/L at 30 min) compared to that in control children (P < 0.05). Sumatriptan administration did not alter the basal GH value (peak GH, 1.7 +/- 0.3 micrograms/L at 30 min). However, Sumatriptan administration clearly increased the effect of GHRH, resulting in a GH peak of 14.6 +/- 3.1 micrograms/L at 30 min (P < 0.01). To assess the specificity of Sumatriptan on anterior pituitary hormone secretion, we studied its effect on TSH and PRL responses to TRH as well as LH-releasing hormone-induced LH and FSH secretion. Administration of Sumatriptan did not alter the response of any of these hormones. Our results indicate that 5-HT1D receptors have a stimulatory effect on GH secretion, possibly by inhibiting hypothalamic somatostatin release.
Background: Breast cancer is a heterogeneous disease and is the leading cause of cancer-related deaths among women. Even after diagnosis, the prognosis cannot be concluded since patients can develop resistance to therapy, which favors tumor growth, invasion and metastasis. In recent years, research has focused on identifying significant markers that can be used to determine the prognosis. Melatonin can act through G protein– coupled MT1 receptor, which controls selected protein kinases, influences the levels of transcription factor phosphorylation, specific genes expression, proliferation, angiogenesis, cell differentiation, migration, and indirectly controls the transport of glucose in cancer cells. It is known that glucose enters the cells by glucose transporters, such as GLUT1 which shows wide tissue distribution and appears to be altered in human breast carcinoma. High GLUT1 expression is associated with increased malignant potential, invasiveness and poor prognosis in some cancers including breast cancer. Objective: The aim of this study was to evaluate the expression of MT1 receptor and GLUT1 in breast tumors and correlate with molecular subtypes and prognostic characteristics. Method: Protein expression was performed by an immunohistochemical procedure with specific antibodies and positive and negative controls. Results: We found that MT1 high expression was associated with good prognosis subtype (Luminal A), while GLUT1 high expression was related to poor prognosis subtype (triple-negative). In addition, we found high expression of MT1 in ER+ and the inverse in GLUT1 expression. GLUT1 is also highly expressed in tumor ≥20mm. Conclusion: These results indicate MT1 and GLUT1 as potential targets for breast cancer subtypes and prognosis.
Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression.
Doubt about pre-operative carbohydrate supplementationWe commend Fawcett and Thomas for their review of pre-operative fasting recommendations [1] and applaud their candid acknowledgement of the mounting evidence of lack of clinical benefit for oral pre-operative carbohydrate loading (preCHO), considered an essential element of the enhanced recovery after surgery (ERAS)We wish to mount further direct challenges to the concept of preCHO, on several grounds. The subjective benefits of preCHO, namely the reduction in anxiety, distress, thirst and hunger [1][2][3], are relative to the dietary habit of the subject during the preceding weeks, as much as they are to the immediate duration of restriction of food and water. A predominantly carbohydrate-based 'standard' diet (such as has been advised by national advisory bodies for several decades) accentuates these symptoms, whereas the widespread adoption of reduced fasting times for both food and water (6 h and 2 h, respectively), reduces the impact of this acute deprivation. Indeed, preCHO has been shown to be of benefit only when compared with fasting without water, but negligible when compared with water[1]. The analogy drawn between surgical stress and exercise, with respect to lactate production and carbohydrate loading, is both false and out-dated. In the context of exercise, lactic acid is produced when
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