Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of reg...Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of registered deaths in 2012 was 12,852. The Renin-Angiotensin System (RAS) is known for its role in arterial hypertension and in other cardiovascular diseases. Angiotensin-Converting Enzyme 2 (ACE2) is the key to Ang-(1-7) formation, and counterbalances the ACE1/AngII/AGTR1 axis actions. RAS components have complex interactions with different tissues and their actions are not restricted to the cardiovascular system. Recently, the RAS has been associated with different types of cancers and in particular with gynecological cancers. Objectives: Our aim is to investigate possible associations between allelic distribution of two genetic polymorphisms in the AGTR2 receptor with ACEs 1 and 2 plasma levels among women with breast cancer. Patients and Methods: Patients with breast cancer were genotyped for two polymorphisms of the AGTR2 (T1247G and A5235G). Genotyping assays (TaqMan) were performed with genomic DNA extracted from blood cells. ACEs plasma level measurements were conducted in women from the breast-cancer group (N = 53). ACEs were measured in the plasma of these patients using ELISA kits. Results: SNPs genotype distribution is correlated with ACEs plasma levels. ACEs plasma levels are also correlated with clinical variables and ACE2 high levels are associated with better prognostics. Conclusions: Changes in circulating levels of ECA1/AngII ECA2/ Ang-(1-7) determine the magnitude of the inflammatory response that an individual can trigger and the variation in ACE 1 and 2 plasma level measurements in the blood of breast cancer patients suggests an association with the process of mammary carcinogenesis. Thus, the RAS may be associated with the process of mammary carcinogenesis by both genotypic variations of RAS components and by circulating levels of ACEs.展开更多
Introduction: Polycystic ovarian syndrome (PCOS) is undoubtedly the commonest androgen disorder in woman’s fertile period and certainly one of the most prevalent causes of anovulation. The syndrome has an estimated p...Introduction: Polycystic ovarian syndrome (PCOS) is undoubtedly the commonest androgen disorder in woman’s fertile period and certainly one of the most prevalent causes of anovulation. The syndrome has an estimated prevalence of 4% - 10% among women of childbearing age. Previously, our group demonstrated the effect of gonadal white adipose tissue transplantation from wild-type lean and fertile female mice to isogenic obese anovulatory ob/ob mice. These complex metabolic interrelationships between obesity and PCOS have yet to be fully understood. The aim of this study was to evaluate the effect of gonadal white adipose tissue (WAT) transplantation from the wild-type lean and fertile female mice to isogenic obese, anovulatory mice (Lep ob/Lep ob) on the expression of glycolysis- and TCA cycle-related genes and obtain a general view of the glucose metabolism in the brain of these animals. Methods: Fifteen ob/ob mice ranging from 2 to 3 months of age were divided into 3 experimental groups: control normal weight (n = 5), obese control (n = 5) and obese 7 days leptin treated (n = 5). The whole brains of the mice were processed for RNA extraction. The samples from each group were used to perform PCR assays using an array plate containing 84 primers to study the glucose metabolism-related genes. Results: The glycolysis- and TCA cycle-related genes were significantly downregulated. The most significantly affected genes were as follows: for glycolysis (fold regulation with p < 0.05):Pgm1,Bpgm,Aldob, andEno3 (119, 45, 18, and 28 times less, respectively);and for the TCA cycle (fold regulation with p < 0.05):Cs,Idh3b, andMdh2 (84, 27, and 37 times less, respectively).Conclusion: The seven-day leptin treated mice show a decrease in the glucose metabolism. These results confirm the ability of the adipose tissue-derived hormone leptin to regulate early crucial genes that are related to glycolysis mechanisms and to the TCA cycle. This hormone seems to revert early the central physiological conditions that are associated with PCOS;however, the morphological alterations can only be observed within a 45-day treatment.展开更多
文摘Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of registered deaths in 2012 was 12,852. The Renin-Angiotensin System (RAS) is known for its role in arterial hypertension and in other cardiovascular diseases. Angiotensin-Converting Enzyme 2 (ACE2) is the key to Ang-(1-7) formation, and counterbalances the ACE1/AngII/AGTR1 axis actions. RAS components have complex interactions with different tissues and their actions are not restricted to the cardiovascular system. Recently, the RAS has been associated with different types of cancers and in particular with gynecological cancers. Objectives: Our aim is to investigate possible associations between allelic distribution of two genetic polymorphisms in the AGTR2 receptor with ACEs 1 and 2 plasma levels among women with breast cancer. Patients and Methods: Patients with breast cancer were genotyped for two polymorphisms of the AGTR2 (T1247G and A5235G). Genotyping assays (TaqMan) were performed with genomic DNA extracted from blood cells. ACEs plasma level measurements were conducted in women from the breast-cancer group (N = 53). ACEs were measured in the plasma of these patients using ELISA kits. Results: SNPs genotype distribution is correlated with ACEs plasma levels. ACEs plasma levels are also correlated with clinical variables and ACE2 high levels are associated with better prognostics. Conclusions: Changes in circulating levels of ECA1/AngII ECA2/ Ang-(1-7) determine the magnitude of the inflammatory response that an individual can trigger and the variation in ACE 1 and 2 plasma level measurements in the blood of breast cancer patients suggests an association with the process of mammary carcinogenesis. Thus, the RAS may be associated with the process of mammary carcinogenesis by both genotypic variations of RAS components and by circulating levels of ACEs.
文摘Introduction: Polycystic ovarian syndrome (PCOS) is undoubtedly the commonest androgen disorder in woman’s fertile period and certainly one of the most prevalent causes of anovulation. The syndrome has an estimated prevalence of 4% - 10% among women of childbearing age. Previously, our group demonstrated the effect of gonadal white adipose tissue transplantation from wild-type lean and fertile female mice to isogenic obese anovulatory ob/ob mice. These complex metabolic interrelationships between obesity and PCOS have yet to be fully understood. The aim of this study was to evaluate the effect of gonadal white adipose tissue (WAT) transplantation from the wild-type lean and fertile female mice to isogenic obese, anovulatory mice (Lep ob/Lep ob) on the expression of glycolysis- and TCA cycle-related genes and obtain a general view of the glucose metabolism in the brain of these animals. Methods: Fifteen ob/ob mice ranging from 2 to 3 months of age were divided into 3 experimental groups: control normal weight (n = 5), obese control (n = 5) and obese 7 days leptin treated (n = 5). The whole brains of the mice were processed for RNA extraction. The samples from each group were used to perform PCR assays using an array plate containing 84 primers to study the glucose metabolism-related genes. Results: The glycolysis- and TCA cycle-related genes were significantly downregulated. The most significantly affected genes were as follows: for glycolysis (fold regulation with p < 0.05):Pgm1,Bpgm,Aldob, andEno3 (119, 45, 18, and 28 times less, respectively);and for the TCA cycle (fold regulation with p < 0.05):Cs,Idh3b, andMdh2 (84, 27, and 37 times less, respectively).Conclusion: The seven-day leptin treated mice show a decrease in the glucose metabolism. These results confirm the ability of the adipose tissue-derived hormone leptin to regulate early crucial genes that are related to glycolysis mechanisms and to the TCA cycle. This hormone seems to revert early the central physiological conditions that are associated with PCOS;however, the morphological alterations can only be observed within a 45-day treatment.
