Thyroid hormone profile in breast cancer patients in postmenopause

Objective: The aim of this study was to determine thyroid hormone (TH) profile in postmenopausal patients with breast cancer (BC). Subjects and methods: 12 CaM patients stages I or II, without interventions that could interfere with tumor progression were selected, as well as and a control group with 18 postmenopausal women without CaM. We measured serum anti-thyroperoxidase antibody (TPOAB), thyroid-stimulating hormone (TSH), free thyroxine (T4L), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), before and after surgery, besides immunohistochemistry for estrogen (ER) and progesterone (PR) receptors. Results: Four patients with CaM showed changes in thyroid hormone profile: two had hyperthyroidism, one hypothyroidism, and one was positive for TPO-AB. All of them positive for ER and PR.TSH levels in breast cancer patients were not different from levels found in the control group (1.89 +/- 1.56 vs. 2.86 +/- 3.12 mIU/mL), but the levels of T4L in patients with CaM were statistically higher than those of the control group (1.83 +/- 0.57 vs. 1.10 +/- 0.20 ng/dL). Conclusion: These results reinforce the need for assessment of thyroid status in CaM patients, since in the absence of E2, changes in clinical HTs can act in E2-controlled processes. Arq Bras Endocrinol Metab. 2012;56(4):238-43

DM-1, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate: a curcumin analog with a synergic effect in combination with paclitaxel in breast cancer treatment

This paper describes a new method for the preparation of sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate, DM-1, and 3-oxo-penta-1,4-dienyl-bis (2-methoxy-phenolate), DM-2. The aim of this work was to evaluate the antitumor effects of DM-1 in adjuvant chemotherapy for breast cancer treatment. Mice bearing mammary adenocarcinomas (Ehrlich ascites tumors) were treated with paclitaxel alone, DM-1 alone, and paclitaxel + DM-1. Tumor samples were used to perform cytological analysis by the Papanicolaou method and apoptosis analysis by annexin V and phosphorylated caspase 3. The paclitaxel + DM-1 group had decreased tumor areas and tumor volumes, and the frequency of metastasis was significantly reduced. This caused a decrease in cachexia, which is usually caused by the tumor. Furthermore, treatment with paclitaxel + DM-1 and DM-1 alone increased the occurrence of apoptosis up to 40% in tumor cells, which is 35% more than in the group treated with paclitaxel alone. This cell death was mainly caused through phosphorylated caspase 3 (11% increase in paclitaxel + DM-1 compared to the paclitaxel group), as confirmed by reduced malignancy criteria in the ascitic fluid. DM-1 emerges as a potential treatment for breast cancer and may act as an adjuvant in chemotherapy, enhancing antitumor drug activity with reduced side effects.

Liberação de peróxido de hidrogênio por fagócitos de glândulas mamárias bovinas hígidas e infectadas

O objetivo do presente estudo foi avaliar a capacidade de liberação de peróxido de hidrogênio (H2O2) por fagócitos oriundos de glândulas mamárias bovinas sadias e infectadas. Desse modo, 73 amostras de leite provenientes das glândulas mamárias foram classificadas em sadias e infectadas de acordo com a cultura bacteriológica e a contagem de células somáticas (CCS). Após o isolamento das células do leite, procedeu-se à contagem diferencial de leucócitos e determinação da liberação de H2O2 pela oxidação da solução de vermelho fenol. Foi observada menor liberação de H2O2 pelos fagócitos oriundos dos quartos mamários infectados, assim como houve correlação negativa entre a liberação de H2O2 por fagócitos e a CCS (r=-0,34; P=0,0025), e a porcentagem de neutrófilos (r=-0,24; P=0,04). Além disso, houve tendência de menor liberação de H2O2 pelos fagócitos estimulados por forbol 12-miristato 13-acetato nas glândulas mamárias infectadas. Entretanto, observou-se maior liberação de H2O2 pelos fagócitos em 1mL de leite nos quartos mamários infectados, ao considerar a CCS mL-1. Pode-se concluir que fagócitos de quartos mamários infectados apresentaram menor liberação de H2O2, o que indica menor capacidade microbicida. Por outro lado, observou-se maior liberação de H2O2 pelos fagócitos em 1mL de leite nos quartos infectados, fato que pode contribuir com o maior recrutamento de leucócitos para a glândula mamária e/ou a persistência do processo inflamatório.

Influence of Pleural Drain Insertion in Lung Function of Patients Undergoing Coronary Artery Bypass Grafting

Background and objectives: Longitudinal, prospective, randomized, blinded Trial to assess the influence of pleural drain (non-toxic PVC) site of insertion on lung function and postoperative pain of patients undergoing coronary artery bypass grafting in the first three days post-surgery and immediately after chest tube removal. Method: Thirty six patients scheduled for elective myocardial revascularization with cardiopulmonary bypass (CPB) were randomly allocated into two groups: SX group (subxiphoid) and IC group (intercostal drain). Spirometry, arterial blood gases, and pain tests were recorded. Results: Thirty one patients were selected, 16 in SX group and 15 in IC group. Postoperative (PO) spirometric values were higher in SX than in IC group (p < 0.05), showing less influence of pleural drain location on breathing. PaO2 on the second PO increased significantly in SX group compared with IC group (p < 0.0188). The intensity of pain before and after spirometry was lower in SX group than in IC group (p < 0.005). Spirometric values were significantly increased in both groups after chest tube removal. Conclusion: Drain with insertion in the subxiphoid region causes less change in lung function and discomfort, allowing better recovery of respiratory parameters.

Association between the C242T polymorphism in the p22phox gene with arterial stiffness in the Brazilian population

de Oliveira Alvim R, Lima Santos PCJ, Goncalves Dias R, Rodrigues MV, de Sa Cunha R, Mill JG, Junior WN, Krieger JE, Pereira AC. Association between the C242T polymorphism in the p22phox gene with arterial stiffness in the Brazilian population. Physiol Genomics 44: 587-592, 2012. First published April 10, 2012; doi:10.1152/physiolgenomics.00122.2011.-NADPH oxidase p22phox subunit is responsible for the production of reactive oxygen species in the vascular tissue. The C242T polymorphism in the p22phox gene has been associated with diverse coronary artery disease phenotypes, but the findings about the protective or harmful effects of the T allele are still controversial. Our main aim was to assess the effect of p22phox C242T genotypes on arterial stiffness, a predictor of late morbidity and mortality, in individuals from the general population. We randomly selected 1,178 individuals from the general population of Vitoria City, Brazil. Genotypes for the C242T polymorphism were detected by PCR-RFLP, and pulse wave velocity (PWV) values were measured with a noninvasive automatic device Complior. p22phox and TNF-alpha gene expression were quantified by real-time PCR in human arterial mammary smooth muscle cells. In both the entire and nonhypertensive groups: individuals carrying the TT genotype had higher PWV values and higher risk for increased arterial stiffness [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.27-2.92 and OR 1.78, 95% CI 1.07-2.95, respectively] compared with individuals carrying CC + CT genotypes, even after adjustment for covariates. No difference in the p22phox gene expression according C242T genotypes was observed. However, TNF-alpha gene expression was higher in cells from individual carrying the T allele, suggesting that this genetic marker is associated with functional phenotypes at the gene expression level. In conclusion, we suggest that p22phox C242T polymorphism is associated with arterial stiffness evaluated by PWV in the general population. This genetic association shed light on the understanding of the genetic modulation on vascular dysfunction mediated by NADPH oxidase.

Stem cells in embryonic skin development

The skin is a complex stratified organ which acts not only as a permeability barrier and defense against external agents, but also has essential thermoregulatory, sensory and metabolic functions. Due to its high versatility and activity, the skin undergoes continuous self-renewal to repair damaged tissue and replace old cells. Consequently, the skin is a reservoir for adult stem cells of different embryonic origins. Skin stem cell populations reside in the adult hair follicle, sebaceous gland, dermis and epidermis. However, the origin of most of the stem cell populations found in the adult epidermis is still unknown. Far more unknown is the embryonic origin of other stem cells that populate the other layers of this tissue. In this review we attempt to clarify the emergence, structure, markers and embryonic development of diverse populations of stem cells from the epidermis, dermis and related appendages such as the sebaceous gland and hair follicle.

E-cadherin in canine mast cell tumors: Decreased expression and altered subcellular localization in Grade 3 tumors

Mast cell tumors (MCTs) are the most frequent round cell tumors in dogs and comprise approximately 21% of all canine cutaneous tumors. MCTs are highly invasive and metastatic corresponding to the histological grade. E-cadherin is an adhesion molecule expressed in epithelial cells and although it is an epithelial cellular marker, studies have shown expression of E-cadherin in canine round cell tumors. To better characterize the expression pattern of E-cadherin in several different histological grades of MCTs in dogs, the expression and localization of the adhesion molecule was investigated using immunohistochemistry. For this purpose, 18 cutaneous MCTs were classified into three histological grades, 1, 2 or 3. Clinical history and follow-up data were available for all of the dogs. Cytoplasmic and nuclear expressions of E-cadherin in all three types of tumors were verified by immunostaining using two different antibodies. There was decreased E-cadherin expression in the more aggressive MCTs (Grade 3), suggesting an association between E-cadherin and tumor aggressiveness. Additionally, the loss of E-cadherin expression in either the cytoplasm or nucleus in more aggressive and undifferentiated tumor types confirmed the importance of cellular adhesion in tumor behavior. (C) 2012 Published by Elsevier Ltd.

Characterization of PAR1 and FGFR1 expression in invasive breast carcinomas: Prognostic significance

Breast cancer is the most common cause of cancer mortality among women worldwide. Among the several factors associated with breast cancer development, angiogenesis plays an essential role and has currently emerged as a potential diagnostic, prognostic and therapeutic target. Protease-activated receptor 1 (PAR1) and fibroblast growth factor receptor 1 (FGFR1) have important activities in tumor angiogenesis and progression. The aim of this study was to investigate the prognostic significance of these two receptors, hypothesising significant correlations between receptor expression in tumor angiogenesis and clinicopathological parameters customarily used in breast cancer prognosis and prediction. Formalin-fixed and paraffin-embedded samples of ductal invasive breast carcinomas were used to analyze the expression of PAR1 and FGFR1, in the tumor cells as well as in the tumor stroma, and further determine intratumoral microvessel density (iMVD) to quantify intratumoral angiogenesis. Correlations between PAR1 and FGFR1 expression in tumor cells and stroma, iMVD and several clinicopathological parameters and molecular markers used in breast cancer diagnosis have been addressed. The correlation between PAR1 and FGFR1 suggests an association of the two receptors with a more aggressive breast cancer phenotype and, consequently, a potential role during tumor progression. The results reported in the present study also emphasize the importance of microenvironmental factors in tumor progression, while precluding the positive association between iMVD and breast cancer aggressiveness.

Toll-like receptor 3: implications for proinflammatory microenvironment in human breast cancer

Under many circumstances, the host constituents that are found in the tumor microenvironment support a malignancy network and provide the cancer cells with advantages in proliferation, invasiveness and metastasis establishment at remote organs. It is known that Toll like receptors (TLRs) are expressed not only on immune cells but also on cancer cells and it has suggested a deleterious role for TLR3 in inflammatory disease. Hypothesizing that altered IFN gamma signaling may be a key mechanism of immune dysfunction common to cancer as well CXCR4 is overexpressed among breast cancer patients, the mRNA expression of TLR3, CXCR4 and IFN gamma in breast cancer tumor tissues was investigated. No statistically significant differences in the expression of CXCR4 mRNA, IFN gamma and TLR3 between healthy and tumor tissues was observed, however, it was verified a positive correlation between mRNA relative expression of TLR3 and CXCR4 (p < 0.001), and mRNA relative expression of TLR3 was significantly increased in breast cancer tumor tissue when compared to healthy mammary gland tissue among patients expressing high IFN gamma (p = 0.001). Since the tumor microenvironment plays important roles in cancer initiation, growth, progression, invasion and metastasis, it is possible to propose that an overexpression of IFN gamma mRNA due to the pro-inflammatory microenvironment can lead to an up-regulation of CXCR4 mRNA and consequently to an increased TLR3 mRNA expression even among nodal negative patients. In the future, a comprehensive study of TLR3, CXCR4 and IFN gamma axis in primary breast tumors and corresponding healthy tissues will be crucial to further understanding of the cancer network.

Bromocriptine Treatment for Inappropriate Lactation in Mares: A Case Report

Transient mammary gland development and lactation can occur eventually in weanling foals, yearlings, and adult mares without previous or recent history of pregnancy. The etiology of this condition has not been well documented, and there is limited information on the occurrence, frequency of episodes, composition, and treatment of galactorrhea secretion. This article reports a case of Brazilian Sport Horse mare, aged 10 years, with persistent lactation during 5 months. The treatment consisted of bromocriptine 0.04 mg/kg, b.i.d., orally, for 10 days, associated with hydrotherapy for 20 minutes, twice daily. After 20 days of the treatment onset, the mare was reevaluated, and a significant decrease in the volume of the udder and the amount of secretion produced was noted, and its aspect was clearer (serous) and consisted of more fluid compared with the one collected before treatment. No other clinical alterations or associated diseases were identified. Based on these findings, we suggest the diagnosis of idiopathic inappropriate lactation. Although there is no information about pharmacokinetics and description of the oral bromocriptine use in horses, being a therapeutic option for inappropriate lactation treatment in mares, it was effective at the recommended dosage. (C) 2012 Elsevier Inc. All rights reserved.

Cu(GlyGlyHis) effects on MCF7 cells: Copper uptake, reactive oxygen species generation and membrane topography changes

Elevated levels of copper have been detected in various types of human cancer cells, such as breast cancer cells, and a number of mechanisms have been proposed to explain the action and influence of copper on tumor progress. In this work, we found that stimulating the proliferation of mammary epithelial MCF7 cells with the high-redox-potential copper complex Cu (GlyGlyHis) is associated with the copper-induced intracellular generation of reactive oxygen species (ROS) that induces lipid peroxidation and causes increased roughness of external cell membranes, which leads to the formation of larger cell domes. The results presented herein provide new insights into the molecular link between copper and the proliferation of breast cancer cells and, consequently, into the mechanism by which changes in redox balance and ROS accumulation regulates cell membrane roughness. (C) 2012 Elsevier Inc. All rights reserved.

Transcriptional effects of 1,25 dihydroxyvitamin D3 physiological and supra-physiological concentrations in breast cancer organotypic culture

Background Vitamin D transcriptional effects were linked to tumor growth control, however, the hormone targets were determined in cell cultures exposed to supra physiological concentrations of 1,25(OH)2D3 (50-100nM). Our aim was to evaluate the transcriptional effects of 1,25(OH)2D3 in a more physiological model of breast cancer, consisting of fresh tumor slices exposed to 1,25(OH)2D3 at concentrations that can be attained in vivo. Methods Tumor samples from post-menopausal breast cancer patients were sliced and cultured for 24 hours with or without 1,25(OH)2D3 0.5nM or 100nM. Gene expression was analyzed by microarray (SAM paired analysis, FDR≤0.1) or RT-qPCR (p≤0.05, Friedman/Wilcoxon test). Expression of candidate genes was then evaluated in mammary epithelial/breast cancer lineages and cancer associated fibroblasts (CAFs), exposed or not to 1,25(OH)2D3 0.5nM, using RT-qPCR, western blot or immunocytochemistry. Results 1,25(OH)2D3 0.5nM or 100nM effects were evaluated in five tumor samples by microarray and seven and 136 genes, respectively, were up-regulated. There was an enrichment of genes containing transcription factor binding sites for the vitamin D receptor (VDR) in samples exposed to 1,25(OH)2D3 near physiological concentration. Genes up-modulated by both 1,25(OH)2D3 concentrations were CYP24A1, DPP4, CA2, EFTUD1, TKTL1, KCNK3. Expression of candidate genes was subsequently evaluated in another 16 samples by RT-qPCR and up-regulation of CYP24A1, DPP4 and CA2 by 1,25(OH)2D3 was confirmed. To evaluate whether the transcripitonal targets of 1,25(OH)2D3 0.5nM were restricted to the epithelial or stromal compartments, gene expression was examined in HB4A, C5.4, SKBR3, MDA-MB231, MCF-7 lineages and CAFs, using RT-qPCR. In epithelial cells, there was a clear induction of CYP24A1, CA2, CD14 and IL1RL1. In fibroblasts, in addition to CYP24A1 induction, there was a trend towards up-regulation of CA2, IL1RL1, and DPP4. A higher protein expression of CD14 in epithelial cells and CA2 and DPP4 in CAFs exposed to 1,25(OH)2D3 0.5nM was detected. Conclusions In breast cancer specimens a short period of 1,25(OH)2D3 exposure at near physiological concentration modestly activates the hormone transcriptional pathway. Induction of CYP24A1, CA2, DPP4, IL1RL1 expression appears to reflect 1,25(OH)2D3 effects in epithelial as well as stromal cells, however, induction of CD14 expression is likely restricted to the epithelial compartment.

Effect of somatic cell count and mastitis pathogens on milk composition in Gyr cows

Abstract Background Gyr cows are well adapted to tropical conditions, resistant to some tropical diseases and have satisfactory milk production. However, Gyr dairy herds have a high prevalence of subclinical mastitis, which negatively affects their milk yield and composition. The objectives of this study were (i) to evaluate the effects of seasonality, mammary quarter location (rear x front), mastitis-causing pathogen species, and somatic cell count (SCC) on milk composition in Gyr cows with mammary quarters as the experimental units and (ii) to evaluate the effects of seasonality and somatic cell count (SCC) on milk composition in Gyr cows with cows as the experimental units. A total of 221 lactating Gyr cows from three commercial dairy farms were selected for this study. Individual foremilk quarter samples and composite milk samples were collected once a month over one year from all lactating cows for analysis of SCC, milk composition, and bacteriological culture. Results Subclinical mastitis reduced lactose, nonfat solids and total solids content, but no difference was found in the protein and fat content between infected and uninfected quarters. Seasonality influenced milk composition both in mammary quarters and composite milk samples. Nevertheless, there was no effect of mammary quarter position on milk composition. Mastitis-causing pathogens affected protein, lactose, nonfat solids, and total solids content, but not milk fat content. Somatic cell count levels affected milk composition in both mammary quarters and composite samples of milk. Conclusions Intramammary infections in Gyr cows alter milk composition; however, the degree of change depends on the mastitis-causing pathogen. Somatic cell count is negatively associated with reduced lactose and nonfat solids content in milk. Seasonality significantly affects milk composition, in which the concentration of lactose, fat, protein, nonfat solids and total solids differs between dry and wet seasons in Gyr cows.

Viabilidade celular, fagocitose e espraiamento de fagócitos mononucleares, e liberação de peróxido de hidrogênio por leucócitos de glândulas mamárias bovinas sadias e infectadas

O presente estudo objetivou avaliar a viabilidade celular, a capacidade de fagocitose e espraiamento pelos fagócitos mononucleares, e a liberação de peróxido de hidrogênio (H2O2) por leucócitos oriundos de glândulas mamárias bovinas sadias e infectadas. Deste modo, 94 amostras foram divididas de acordo com os resultados da cultura bacteriológica e da contagem de células somáticas (CCS). O presente estudo não encontrou diferenças na viabilidade celular, e nos índices de fagocitose e espraiamento entre os diferentes grupos. No entanto, a liberação de H2O2 oriundos dos quartos mamários infectados, infectados por Streptococcus spp. ou Corynebacterium spp. foi menor do que nas amostras de leite provenientes dos quartos mamários sadios. Ao estimar a concentração de H2O2 mL-1 leite observou-se que as amostras de quartos mamários positivos no exame bacteriológico, infectados por Staphylococcus spp. e negativos no exame bacteriológico com alta celularidade foram maiores que aquelas provenientes de quartos mamários sadios. Observou-se também correlação positiva entre a CCS e a viabilidade celular e os índices de fagocitose e espraiamento; e correlação negativa entre a liberação de H2O2 e a CCS e a viabilidade celular. Conclui-se que a CCS, assim como a sua viabilidade e função, são conceitos intimamente relacionados com a saúde da glândula mamária.

Carcinoma de células escamosas em glândula mamária de gata doméstica

Background: In the feline species, 80% to 93% of neoplasias in the mammary gland are malignant, being the majority carcinomas. Among them, there is the mammary squamous cell carcinoma, which amounts to a very rare neoplasm in the domestic cat, with considerable potential for malignancy. This study aimed to report a case of squamous cell mammary carcinoma in the feline species. Case: A female cat, mixed breed, ten years old, presented history of skin lesion. The cat had been spayed two years before, but with previous administration of contraceptives. At the physical examination, it was observed ulcer between the caudal abdominal mammary glands. The occurrence of skin or mammary neoplasia was conceived. The following complementary tests were requested: complete blood count, serum biochemical profi le (renal and hepatic), chest radiographs, abdominal ultrasound, and incisional biopsy of the ulcerated region periphery, followed by classic histopathology. The lesion histopathology was compatible with squamous cell carcinoma of the mammary gland. Due to such a diagnosis, bilateral mastectomy was recommended. The material obtained during the surgical procedure was sent for anatomopathological analysis. Microscopically, surgical margins infi ltration and a regional lymph node were verifi ed. The owner was advised of the need for complementary therapies and medical monitoring of the cat. However, there was no return. It is noteworthy that the animal’s physical and laboratory examinations showed no neoplasia in other regions, being the squamous cell carcinoma of the mammary gland considered primary. Discussion: The malignant mammary neoplasia genesis in feline species, in general, seems to be related to steroid hormones. The ovariectomized females are less likely to develop the disease when compared to intact cats, but there is no protective effect of surgery on those spayed after two years of age regarding the appearance of the neoplasia. Thus, at the time the reported patient was ovariectomized, this effect no longer occurred. The synthetic progestins regularly used to prevent estrus increase by three times the risk of breast carcinomas onset. In humans, there is no clear defi nition of the etiology and pathogenesis of mammary squamous cell carcinoma. However, it has been suggested its association with extreme forms of squamous metaplasia present in pre-existing mammary adenocarcinoma, besides cysts, chronic infl ammations, abscesses and mammary gland adenofi bromas. In a hypothetical way, this etiology could also be related to the feline mammary carcinoma, although, for the case at issue, the exogenous and endogenous hormonal infl uence should not be excluded. It has been reported that mammary squamous cell carcinomas in cats are classifi ed in grades II and III (ie, moderately and poorly differentiated, respectively). Thus, they are considered tumors with more unfavorable prognosis. However, the monitoring of the clinical course, in order to evaluate possible recurrence of the neoplasia and metastases to distant sites, was not possible as the animal under discussion did not return. The squamous cell carcinoma is the most common skin tumor in feline species, despite the primary location in the mammary gland. It is, therefore, important to differentiate squamous cell carcinoma originated in the breast from histological types derived from skin. The description of this special and rare feline mammary carcinoma is important due to its particular characteristics and potential for malignancy.