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Infections with certain types of papillomavirus, such as the human papillomavirus 16 (HPV16), are associated with the development of preneoplastic lesions and cancers of the anogenital, and head and neck regions. Cytinus hypocistis (L.) L. extracts are composed of substances presenting antiproliferative, antioxidant, anti-inflammatory and antibacterial properties, which might be promising as new therapeuticcompounds. This study analysed the influence of topical application of an extract obtained from C. hypocistis (CH) on K14-HPV16 and FVB/n mice to evaluate its therapeutic and toxicological properties. To achieve the study goals,30 female mice, 33–37 weeks old, were divided into six groups (n=5/group): I (HPV+CH3.1); II (HPV+CH6.2); III (HPV+CH12.4); IV (FVB/n+CH12.4); V (HPV+control) and VI (FVB/n+-control). CH was applied topically to both ears for 28 days. After this period, all animals were sacrificed for samples collection. Skin lesions were classified histologically. Toxicological parameters included haematological and biochemical blood markers, and hepatic oxidative stress analysis. Transgenic animals showed a decrease in mean body weight regardless of the concentration of extract applied. The extract had no influence on physiological parameters, organ weight, or biochemical and oxidative stress parameters. Histology demonstrated the presence of proliferative epithelial lesions in the skin and oral mucosa of K14-HPV16 mice, with no association with the application of this extract. Overall, the application of CH extract had no influence on the skin lesions and was well tolerated by the animals in these concentrations.

Prostate cancer (PCa) is among the most frequent cancers worldwide. Nowadays, several therapeutic strategies are available for PCa treatment, namely chemotherapy, immunotherapy, radiotherapy, and hormonal therapy. Despite existing therapeutic approaches, in vitro and in vivo models are essential to better understand cancer development and search for more effective therapies, with a positive impact in cancer patient survival and quality of life. Among several models available, the rat model is the one most frequently used, since it shares anatomical, physiological, pathological, and behavioral features with humans. Animal models can be classified as: spontaneous, chemically-induced; hormonally-induced; implantation of cancer cell lines obtained from humans or from the same species, in the place of disease development or in a different place; and genetically-modified models. The chemically-induced models are among the most frequently used for PCa research. This manuscript provides a comprehensive overview of PCa models, presenting their application, advantages, and disadvantages, and their importance for the development of current therapies for prostate cancer.

This work aimed to understand how lifelong exercise training promotes the remodelling of the immune system and prostate signalome in a rat model of PCa. Fifty-five male Wistar rats were divided into four groups: control sedentary, control exercised, induced PCa sedentary and induced PCa exercised. Exercised animals were trained in a treadmill for 53 weeks. Pca induction consisted on the sequential administration of flutamide, N-methyl-N-nitrosourea and testosterone propionate implants. Serum concentrations of C-reactive protein (CRP) and tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) were not different among groups. Peripheral levels of γδ T cells were higher in Pca exercised group than in the PCa sedentary group (p

The growing incidence of prostate cancer has prompted a great investment in basic biology and translational studies to develop new therapies. Multiple animal models have been established to study etiological factors, cancer-preventive strategies and the molecular determinants of aggressiveness and metastases. The rat model of prostate cancer induced by chemical carcinogen N-methyl-N-nitrosourea (MNU) and testosterone exposure has become an important tool to study prostatic carcinogenesis and chemopreventive approaches. Over prolonged treatment, this model develops prostatic lesions that closely mimic those observed in human patients. By modifying the experimental conditions, different research groups have been able to induce a vast spectrum of lesions, ranging from early prostatic intraepithelial neoplasia to metastatic cancer. These carefully tuned experimental settings allowed researchers to test lifestyle interventions, and different pharmacological and chemopreventive strategies. However, this model's great flexibility requires careful planning to ensure that the experimental conditions are adequate to obtain the spectrum of lesions intended. The present review addresses such issues, highlighting the value of the rat prostate cancer model and the multiple challenges and opportunities it offers to researchers worldwide.

Influenza is an extremely contagious respiratory disease, which predominantly affects the upper respiratory tract. There are four types of influenza virus, and pigs and chickens are considered two key reservoirs of this virus. Equine influenza (EI) virus was first identified in horses in 1956, in Prague. The influenza A viruses responsible for EI are H7N7 and H3N8. Outbreaks of EI are characterized by their visible and rapid spread, and it has been possible to isolate and characterize H3N8 outbreaks in several countries. The clinical diagnosis of this disease is based on the clinical signs presented by the infected animals, which can be confirmed by performing complementary diagnostic tests. In the diagnosis of EI, in the field, rapid antigen detection tests can be used for a first approach. Treatment is based on the management of the disease and rest for the animal. Regarding the prognosis, it will depend on several factors, such as the animal's vaccination status. One of the important points in this disease is its prevention, which can be done through vaccination. In addition to decreasing the severity of clinical signs and morbidity during outbreaks, vaccination ensures immunity for the animals, reducing the economic impact of this disease.

Prostate cancer (PCa) is one of the most common cancers in men, with a huge impact on their health. The use of Castanea sativa Mill. flowers (CFs) in beverages has been reported, through ancestral claims, as having health benefits. In vitro research has evidenced the properties of CFs, such as antitumor and antioxidant activities. This study aimed to evaluate the effects of CF extract in an animal model of PCa. Forty male Wistar Unilever rats were randomly assigned to four groups: control, induced, control + CF, and induced + CF groups. Animals from the induced groups were exposed to a multistep protocol for PCa induction. The CF extract, rich in trigalloyl-HHDP-glucoside and obtained via decoction, was administered to the CF groups in drinking water (3 mg per animal per day) for 49 weeks. Animals were sacrificed at 61 weeks of age. Regarding the effects of CFs on dorsolateral prostate tumorigenesis, no significant differences were observed between the induced and induced + CF groups. However, animals exposed to the CF extract showed fewer inflammation areas on the dorsolateral prostate lobe than those not exposed to CF. Moreover, the CF extract alleviated the hepatic oxidative stress associated with the multistep protocol, resulting in lower levels of lipid peroxidation. These results suggest that CF extract has antioxidant and anti-inflammatory properties. This journal is. This work was supported by European Investment Funds by FEDER/COMPETE/POCI - Operational Competitiveness and Internationalization and National Funds by FCT - Portuguese Foundation for Science and Technology, under the projects UIDB/04033/2020 (CITAB), UIDB/00690/2020 (CIMO), UIDB/50006/2020 (LAQV), UIDB/CVT/00772/2020 (CECAV), and UIDP/00616/2020 (CQ-VR), the project RUNawayPCa (POCI-01-0145- FEDER-016728 and PTDC/DTP-DES/6077/2014), and PhD fellowship SFRH/BD/136747/2018. L. Barros also acknowledges national funding by FCT, P.I., through the institutional scientific employment program-contract for her contract. The Interreg Program received financial support from the Project IBERPHENOL, Project Number 0377_IBERPHENOL_6_E, cofinanced by the European Regional Development Fund (ERDF) through POCTEP 2014-2020. info:eu-repo/semantics/publishedVersion

Aim: This work intended to improve the knowledge of the rat model of prostate cancer (PCa) by ultrasonographic monitoring. Materials and Methods: Male Wistar rats were divided into control (n=8) and PCa (n=14) groups. PCa development was induced in the PCa group through the sequential administration of the anti-androgenic drug flutamide, testosterone propionate and the carcinogenic N-methyl-N-nitrosourea. The prostate was evaluated by ultrasonography at five timepoints along 49 weeks of the experimental protocol. Ventral prostate lobes were observed in all ultrasonographic examinations. Results: The ventral prostate area of the control group increased gradually between the first and the last ultrasonographic examination. The ventral prostate area of PCa groups decreased due to flutamide administration and increased after androgen and carcinogen administration. The area of the dorsal prostate lobe increased between the fourth and the fifth ultrasonographic examination. In the last ultrasonographic examination, hypoechoic and anechoic lesions were observed in the PCa group. Conclusion: To our knowledge, this is the first study presenting a follow-up of rat prostatic dimensions by ultrasonography. Ultrasonography is a feasible approach for prostate cancer monitoring in experimental models. published

Objectives This study aimed to evaluate the impact of long-term exercise training on the vascularization of rat mammary tumors. Methods Female rats were divided into 4 groups: N-methyl-N-nitrosourea (MNU) treated sedentary, MNU treated exercised, control sedentary, and control exercised. Tumor development was induced in the MNU groups by MNU administration. Exercised groups were trained for 35 weeks. Tumor vascularization was evaluated by pulsed Doppler and contrast-enhanced ultrasonography. Results The pulsatility and resistive indices were slightly higher in the MNU sedentary group (P > .05). Mammary tumors mainly had centripetal and heterogeneous enhancement of the contrast, clear margins, and the presence of penetrating vessels. The MNU exercised group had a lower arrival time and time to peak and higher peak intensity, wash-in, and wash-out (P > .05). The area under the curve was similar between groups (P > .05). Conclusions The contrast-enhanced ultrasonographic study did not detect differences in mammary tumor vascularization between MNU sedentary and MNU exercised groups previously detected by power Doppler imaging, B-flow imaging, and immunohistochemistry.

The present work describes a rare case of a spontaneous high-grade carcinoma in a seven-week-old Sprague-Dawley female rat that had been included in the control group of an assay of mammary carcinogenesis. The mass was detected at 50days of age, it grown quickly and the animal was humanely sacrificed eight days later. The tumor was located in the left cervical region, in the vicinity of the left submandibular and sublingual glands. It was soft and reddish and had several dens with a bloody content. The tumor was PAS negative and exhibited immunostaining for ER-α. The histopathologic and immunohistochemical data are suggestive of a high-grade carcinoma from mammary gland. It was the first report of a spontaneous mammary tumor in such a young rat.

Chemically-induced mammary tumors in rats by the carcinogens 1-methyl-1-nitrosourea- (MNU) and 7,12-dimethylbenz[a]anthracene (DMBA) are the most widely used models for studies related with human breast cancer. This study aimed to evaluate the immunoexpression of the prognostic factors estrogen receptor α (ERα), progesterone receptor (PR) and Ki-67, in MNU and DMBA-induced rat mammary tumors, in order to know the model that best suits to woman breast cancer. Twenty-eight MNU-induced and 16 DMBA-induced mammary tumors in virgin female Sprague-Dawley rats were analyzed. The expression of the prognostic markers ERα, PR and Ki-67 proliferation index (Ki-67 PI) was assessed by immunohistochemistry. Mitotic activity index (MAI) was also evaluated. More than one histological pattern was identified in each mammary tumor. Carcinomas constituted the lesions most frequently induced by both carcinogens: 33 MNU-induced carcinomas and 23 DMBA-induced carcinomas. All MNU and DMBA-induced mammary carcinomas were ER+/PR+, with a higher expression of ERα when compared with PR. Tumors' weight, the expression of ERα, PR, Ki-67 PI and MAI were higher in MNU-induced mammary carcinomas when compared with the DMBA-induced ones. Statistically significant differences between groups were observed for ERα, PR and MAI (p

Mammary cancer is one of the most common cancers, victimizing more than half a million of women worldwide every year. Despite all the studies in this field, the current therapeutic approaches are not effective and have several devastating effects for patients. In this way, the need to better understand the mammary cancer biopathology and find effective therapies led to the development of several rodent models over years. With this review, the authors intended to provide the readers with an overview of the rat models used to study mammary carcinogenesis, with a special emphasis on chemically-induced models.

Histamine is a biogenic amine, synthetized and released by mast cells, which acts as a vasodilator in several pathologic processes, namely in allergies and conjunctivitis. Its role on cancer is not fully understood. High levels of histamine have been associated with a bivalent behavior in regulation of several tumors (i.e. cervical, ovarian, vaginal, uterine, vulvar, colorectal cancer, and melanoma), promoting or inhibiting their growth. Histamine receptors (H1, H2, H3 and H4) are present in a vast group of cells, including tumor cells, making them sensitive to histamine variations. In this work, we review the role of mast cells and histamine on cancer development and the possibility of use antihistamines in the clinical management of this disease.

The rat has been frequently used as a model to study several human diseases, including cancer. In many research protocols using cancer models, researchers find it difficult to perform several of the most commonly used techniques and to compare their results. Although the protocols for the study of carcinogenesis are based on the macroscopic and microscopic anatomy of organs, few studies focus on the use of imaging. The use of imaging modalities to monitor the development of cancer avoids the need for intermediate sacrifice to assess the status of induced lesions, thus reducing the number of animals used in experiments. Our work intends to provide a complete and systematic overview of rat prostate anatomy and imaging, facilitating the monitoring of prostate cancer development through different imaging modalities, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI).

Colorectal cancer is one of the most common gastrointestinal malignancies in humans, affecting approximately 1.8 million people worldwide. This disease has a major social impact and high treatment costs. Animal models allow us to understand and follow the colon cancer progression; thus, in vivo studies are essential to improve and discover new ways of prevention and treatment. Dietary natural products have been under investigation for better and natural prevention, envisioning to show their potential. This manuscript intends to provide the readers a review of rodent colorectal cancer models available in the literature, highlighting their advantages and disadvantages, as well as their potential in the evaluation of several drugs and natural compounds’ effects on colorectal cancer.

Breast cancer is the most common malignancy in women worldwide. Several studies have suggested that exercise training may decrease the risk of breast cancer development. This study aimed to evaluate the effects of long-term exercise training on mammary tumorigenesis in an animal model of mammary cancer. Fifty female Sprague-Dawley rats were randomly divided into four groups: MNU sedentary, MNU exercised, control sedentary and control exercised. Animals from MNU groups received an intraperitoneal administration of N-methyl-N-nitrosourea (MNU). Animals were exercised on a treadmill during 35 weeks. When animals were killed, blood samples were collected to determine the hematocrit and to perform the biochemical analysis. Mammary tumors were collected and histologically evaluated; the expression of ERs α and β was evaluated in tumor sections by immunohistochemistry. All survived animals from both MNU groups developed mammary tumors. The number of mammary tumors (p > 0.05) and lesions (p = 0.056) was lower in MNU exercised than in MNU sedentary animals. MNU exercised animals showed lower number of malignant lesions than MNU sedentary animals (p = 0.020). C-reactive protein serum concentration was lower in exercised animals; however, the levels of 17-β estradiol were higher in exercised animals. Tumors from exercised animals exhibited higher expression of ER α than tumors from sedentary animals (p

The analysis of metals in different tissues of raptors has been an important tool for assessing metal pollution. Several studies using a range of sentinel raptor species have been carried out in Portugal and Spain since the 1980s to identify the adverse effects in the animals themselves and on their populations, to identify the contamination of the food chain, to determine the levels of environmental contamination and to estimate human health risks. The aim of this work is to provide synthesized information of the studies carried out in Portugal and Spain in the direct biomonitoring of metals and metalloids using raptors, through a systematic search of the published literature. The information is summarized taking into account specific issues, such as monitored raptor species, sampling periods, monitored areas, type of samples, analytical techniques used in the determination of the metals and metalloids, the analysed metals and metalloids, and overall analysis of the concentrations obtained. There is a striking difference between the number of studies performed in Portugal and Spain, and most of them have been carried out in Spain. The eagle owl, black kite, and common buzzard were the species from which the greatest number of individuals have been analysed. Among the most analyzed biological samples, the blood and liver samples were used to measure the concentrations of all studied metals, while bone was mainly collected to evaluate chronic exposure to lead and feathers to evaluate exposure to mercury during feather growth. Atomic absorption spectrometry has been the most frequently performed technique to determine the majority of metals and arsenic. In general, the concentrations of metals detected in raptor samples from Portugal and Spain are low and insufficient to produce toxic side effects. Only lead, in certain cases, can be related with toxic side effects. However, particular attention should be given to mercury due to its high toxicity, its transport from an aquatic environment to the adjacent terrestrial food web, and because the mercury toxicity threshold has yet to be established for raptors. This work confirms the need for further biomonitoring studies of metals with raptors, especially in Portugal; the establishing of national programs to conduct long-term studies; and creating a network between Portugal and Spain to study environmental contamination using raptors.

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This work aimed to evaluate the effects on renal tissue integrity after hydroxyethyl starch (HES) 130/0.4 and Ringer’s lactate (RL) administration in pigs under general anesthesia after acute bleeding. A total of 30 mL/kg of blood were passively removed from the femoral artery in two groups of Large White pigs, under total intravenous anesthesia with propofol and remifentanil. After bleeding, Group 1 (n =11) received RL solution (25 mL/kg) and Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg). Additionally, Group 3 (n = 6) was not submitted to bleeding or volume replacement. Pigs were euthanized and kidneys were processed for histopathological and immunohistochemical analyses. Minimal to moderate glomerular, tubular, and interstitial changes, as well as papillary necrosis, were observed in all experimental groups. Pre-apoptosis and apoptosis indicators were higher in pigs that received HES 130/0.4, indicating a higher renal insult. Both HES 130/0.4 and RL administration may cause renal injury, although renal injury may be more significant in pigs receiving HES 13/0.4. Results also suggest that total intravenous anesthesia with propofol and remifentanil may cause renal injury, and this effect can be dose related. info:eu-repo/semantics/publishedVersion

Strategies to prevent tumour burden-induced cardiac remodelling that might progress to heart failure are necessary to improve patients' health outcomes and tolerability to cancer therapies. Exercise has been suggested as a measure to prevent cardiac damage; however, its effectiveness on regulating cardiac remodelling secondary to cancer was never addressed. Using an animal model of mammary tumorigenesis, we studied the impact of 35weeks of endurance training on heart, focusing on the signalling pathways modulated by pro-inflammatory and wasting cytokines. The cardiac fibrosis and myofiber disorganization induced by tumour burden was paralleled by the increase of myostatin and TWEAK with the activation of signalling pathways involving Smad-3, NF-κB, TRAF-6 and atrogin-1. The activation of Akt/mTOR was observed in heart from rats with tumours, for which contributed the extracellular matrix. Endurance training prevented the increase of serum and cardiac TWEAK promoted by cancer, as well as the activation of NF-κB, TRAF6, atrogin-1 and p70S6K in heart. Data highlight the impact of exercise in the modulation of signalling pathways activated by wasting cytokines and the resulting outcomes on heart adaptation. Future studies focused on the cellular pathways underlying cardiac remodelling will assist in the development of exercise programs targeting cancer-related cardiac alterations.

Trihalomethanes (THMs) are disinfection byproducts found in chlorinated water, and are associated with several different kinds of cancer in human populations and experimental animal models. Metabolism of THMs proceeds through enzymes such as GSTT1 and CYP2E1 and gives rise to reactive intermediates, which form the basis for their toxic activities. The aim of this study was to assess the mitochondrial dysfunction caused by THMs at low levels, and the resulting hepatic histological and biochemical changes in the mouse. Male ICR mice were administered with two THMs: dibromochloromethane (DBCM) and bromodichloromethane (BDCM); once daily, by gavage, to a total of four administrations. Animals were sacrificed four weeks after DBCM and BDCM administrations. Blood biochemistry was performed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), albumin (Alb), total protein (TP), creatinine, and urea. Animals exposed to DBCM and BDCM showed elevated ALT and TB levels (p < 0.05) as compared with controls. Histological analysis confirmed the presence of vacuolar degenerescence and a multifocal necrotizing hepatitis in 33% of animals (n = 2). Mitochondrial analysis showed that THMs reduced mitochondrial bioenergetic activity (succinate dehydrogenase (SQR), cytochrome c oxidase (COX), and ATP synthase) and increased oxidative stress (glutathione S-transferase (GST)) in hepatic tissues (p < 0.05). These results add detail to the current understanding of the mechanisms underlying THM-induced toxicity, supporting the role of mitochondrial dysfunction and oxidative stress in liver toxicity caused by DBCM and BDCM. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1009-1016, 2016.

Background/Aim: This study aimed to evaluate the utility of several biological parameters for the prediction of tumor development and animal welfare in a rat model of urinary bladder cancer. Materials and Methods: The control group (n=9) received tap water while the test group (n=12) received the carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water. A score sheet with biological variables was used to monitor animals’ welfare. Body weight, food and drink consumption and rectal temperature were measured weekly. Blood and urine samples were collected. Results: Animals from the control group exhibited a slightly higher body weight and body weight gain. The final urine volume was higher in BBN group (p

Limiting cancer-induced cardiac damage has become an increasingly important issue to improve survival rates and quality of life. Exercise training has been shown to reduce cardiovascular complications in several diseases; however, its therapeutic role against cardiovascular consequences of cancer is in its infancy. In order to add new insights on the potential therapeutic effect of exercise training on cancer-related cardiac dysfunction, we used an animal model of urothelial carcinoma submitted to 13 weeks of treadmill exercise after 20 weeks of exposure to the carcinogenic N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Data showed that 13 weeks of treadmill exercise reverted cancer-induced cardiomyocytes atrophy and fibrosis, improved cardiac oxidative capacity given by citrate synthase activity and MnSOD content, and increased the levels of the mitochondrial biogenesis markers PGC-1α and mtTFA. Moreover, exercise training reverted cancer-induced decrease of cardiac c-kit levels suggesting enhanced regenerative ability of heart. These cardiac adaptations to exercise were related to a lower incidence of malignant urothelial lesions and less signs of inflammation. Taken together, data from the present study support the beneficial effect of exercise training when started after cancer diagnosis, envisioning the improvement of the cardiovascular function.

Background/aim Intense pulsed light (IPL) has been extensively applied in the field of dermatology and aesthetics; however, the long-term consequences of its use are poorly unknown, and to the best of our knowledge there is no study on the effect of IPL in neoplastic lesions. In order to better understand the molecular mechanisms underlying IPL application in the skin, we used an animal model of carcinogenesis obtained by chemical induction with 12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). Materials and methods Institute of Cancer Research (ICR) mice were administered DMBA and/or TPA and treated with IPL. Skin was evaluated by histopathology and 2DE-blot-MS/MS analysis. Results Our data evidenced an inflammatory response and a metabolic remodeling of skin towards a glycolytic phenotype after chronic exposure to IPL, which was accomplished by increased oxidative stress and susceptibility to apoptosis. These alterations induced by IPL were more notorious in the DMBA sensitized skin. Keratins and metabolic proteins seem to be the more susceptible to oxidative modifications that might result in loss of function, contributing for the histological changes observed in treated skin. Conclusion Data highlight the deleterious impact of IPL on skin phenotype, which justifies the need for more experimental studies in order to increase our understanding of the IPL long-term safety.

Background/Aim: The effects of mast cells on carcinogenesis is not yet fully understood. This work aimed to disclose the role of mast cells in mammary carcinogenesis in a rat model. Materials and Methods: Mammary tumors were induced by the administration of N-methyl-N-nitrosourea (MNU) in three groups of rats. Animals from one group were treated with ketotifen immediately after MNU administration, and animals from another only received ketotifen after the development of the first mammary tumor. The biochemical profile was determined. Mammary tumors were evaluated by histopathology and immunohistochemistry. Results: Animals from ketotifen-treated groups developed fewer mammary tumors, higher number of mammary lesions and had lower histamine levels when compared to non-treated animals. Animals treated with ketotifen immediately after MNU exhibited the lowest proliferative and apoptotic indexes. Conclusion: The mainly positive effect of the inhibition of mast cell degranulation seems to be the reduction of tumor proliferation when the mast cell degranulation was inhibited before tumor development.

The high prevalence of end-stage renal disease emphasizes the failure to provide therapies to effectively prevent and/or reverse renal fibrosis. Therefore, the aim of this study was to evaluate the effect of long-term treatment with chaethomellic acid A (CAA), which selectively blocks Ha-Ras farnesylation, on renal mass reduction-induced renal fibrosis. Male Wistar rats were sham-operated (SO) or subjected to 5/6 renal mass reduction (RMR). One week after surgery, rats were placed in four experimental groups: SO:SO rats without treatment (n = 13); SO + CAA: SO rats treated with CAA (n = 13); RMR:RMR rats without treatment (n = 14); and RMR + CAA:RMR rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 μg/kg three times a week for six months. Renal fibrosis was evaluated by two-dimensional ultrasonography and histopathological analysis. The kidneys of the RMR animals treated with CAA showed a significantly decrease in the medullary echogenicity (p < 0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (p < 0.001) in the RMR + CAA group when compared with the RMR group. There were no significant differences in interstitial fibrosis, interstitial inflammation and tubular dilatation scores between the RMR + CAA and RMR groups. These data suggest that CAA can be a potential future drug to attenuate the progression of chronic kidney disease. This work is supported by : European Investment Funds by FEDER/COMPETE/POCI– Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013; and by European Investment Funds by FEDER/COMPETE/POCI– Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-016728 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project PTDC/DTP-DES/6077/2014. info:eu-repo/semantics/publishedVersion

Exercise training is thought to play a protective role against cancer development and metastasis, either by reducing hormonal stimulation of hormone-dependent cancers or by reducing the permeability of vascular walls towards invading metastatic cells. The purpose of this work was to evaluate the role of long-term exercise training in the development and metastasis of breast cancer, in an immune-competent 1-methyl-1-nitrosourea (MNU) induced rat model. A single MNU dose was administered to Sprague-Dawley rats at 50 days of age and the rats were subjected to exercise training on a treadmill at 20 m/min, 60 min/day, 5 days/week for 35 weeks. Exercised animals developed slightly less (2.30 ± 1.42) tumours per animal than sedentary animals (2.55 ± 1.44) and did not develop any metastasis, while two pulmonary metastases were observed in the sedentary group. All primary neoplasms and their metastases were positive for oestrogen (ER) α and progesterone (PR) receptors, indicating high hormonal sensitivity. Interestingly, exercise training increased circulating oestrogen levels, thus suggesting that the mechanism might involve either or both of a protective hormone-independent effect and modulation of tumoural vascularization.