Chemotherapy induces plasmatic antioxidant changes in pediatric patients with acute lymphoid leukemia B that correlate to disease prognosis.

Pediatric acute lymphoid leukemias (ALL) is the most common childhood cancer, and cytotoxic chemotherapy remains the primary treatment option. Chemotherapic drugs act by oxidative stress generation, but their clinical meaning is poorly understood. During the chemotherapy schedule, this study evaluated the antioxidant profile of peripheral blood samples from 34 patients diagnosed with type B-cell ALL (B-ALL). Peripheral blood samples were collected at diagnosis (D0) and during the induction, consolidation, and maintenance phases. The plasma total antioxidant capacity (TRAP) was determined using the high-sensitivity chemiluminescence technique. Antioxidant levels were higher on D0 compared to day 7 after treatment starting (D7) in the induction phase (28.68-1194.71 µM Trolox, p = 0.0178) and in the high-risk group (age > ten years and/or with white blood cell counts and/or > 50,000 white blood cells/m3 at diagnosis) concerning low-risk patients (253.79-1194.71 µM Trolox, p = 0.0314). Reduced TRAP was also detected in patients who died compared to those who survived (392.42-1194.71 µM Trolox, p = 0.0278). Patients under consolidation (56.14-352.05 µM Trolox, p=<0.0001) and maintenance (30.48-672.99 µM Trolox, p=<0.0001) showed a significant reduction in TRAP levels compared to those from the induction phase (28.68-1390.26 µM Trolox), reaching levels similar to cured patients out of treatment (64.82-437.82 µM Trolox). These findings suggest that the variation of the total antioxidant capacity in B-ALL during chemotherapy is a parameter that correlates to some predictors of disease prognosis.

Chimarrão consumption and prognostic factors in breast cancer: Correlation with antioxidants and blood caffeine levels.

Breast cancer is the second most common malignancy among women. Ilex paraguariensis A. St. Hil, known as yerba mate, is widely consumed in southern Brazil as a hot infusion drink known as chimarrão. This herb has a complex chemical composition and is rich in antioxidants, which may interfere in the course of chronic inflammatory diseases as breast cancer. This study investigated the impact of chimarrão consumption on the clinicopathological profile of women with breast cancer attended at Francisco Beltrão Cancer Hospital, Paraná, Brazil. Blood antioxidants and caffeine profiles were assessed. Decreases in reduced glutathione and metallothionein levels, and increase in catalase activity were observed among breast cancer patients that were chimarrão consumers. The levels of circulating caffeine in breast cancer patients with luminal A tumors were higher than those in patients with luminal B and HER-2 subtypes. Furthermore, overweight patients presented higher caffeine levels than the eutrophic ones. It was found positive associations between chimarrão intake and high body mass index, and chimarrão intake and menopause at diagnosis. Altogether, these findings suggest that chimarrão consumption affects the blood antioxidants of breast cancer patients, and that the caffeine present in this mixture may favor the development of tumor of good prognosis. HIGHLIGHTS: Chimarrão consumption may affect the course of chronic inflammatory diseases, as breast cancer. Chimarrão intake changed blood antioxidants in breast cancer patients who were current consumers when compared to the non-consumers ones. High levels of caffeine were detected in patients bearing luminal A tumors, suggesting a protective role.

Low Plasmatic 25-hydroxyvitamin D at Diagnosis is Associated with Axillary Invasion, Chemoresistance and Metastasis in Women with Breast Cancer.

PURPOSE: In this study, we investigated the circulating levels of 25-hydroxyvitamin D (25[OH]D) in Brazilian women with breast cancer in samples collected at diagnosis, and correlated these with clinicopathological parameters relevant to disease prognosis. METHODS: This study involved 147 women diagnosed with infiltrative ductal carcinoma whose peripheral blood samples were collected, to have 25(OH)D levels measured in plasma. RESULTS: Our findings indicated that circulating 25(OH)D levels at diagnosis were insufficient in patients with breast cancer. Further, 25(OH)D reduced plasmatic levels at diagnosis correlated significantly with poor prognosis parameters, including axillar positivity, chemoresistance and metastasis. Patients bearing triple-negative tumors also presented reduced 25(OH)D in plasma when compared to those who carried Luminal tumors. Our data suggest relevant correlations when 25(OH)D is reduced in plasma at diagnosis, such as advanced disease with axillar positivity, chemoresistance with advanced disease, early age at diagnosis with high histological grade and dead with axilla positivity. CONCLUSIONS: Altogether, our findings reinforce that 25(OH)D reduction can be a plausible marker of disease prognosis in breast cancer.

Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice.

Infection with the protozoan Trypanosoma cruzi causes Chagas disease and consequently leads to severe inflammatory heart condition; however, the mechanisms driving this inflammatory response have not been completely elucidated. Nitric oxide (NO) is a key mediator of parasite killing in T. cruzi-infected mice, and previous studies have suggested that leukotrienes (LTs) essentially regulate the NO activity in the heart. We used infected 5-lipoxygenase-deficient mice (5-LO-/-) to explore the participation of nitric oxide synthase isoforms, inducible (iNOS) and constitutive (cNOS), in heart injury, cytokine profile, and oxidative stress during the early stage of T. cruzi infection. Our evidence suggests that the cNOS of the host is involved in the resistance of 5-LO-/- mice during T. cruzi infection. iNOS inhibition generated a remarkable increase in T. cruzi infection in the blood and heart of mice, whereas cNOS inhibition reduced cardiac parasitism (amastigote nests). Furthermore, this inhibition associates with a higher IFN-γ production and lower lipid peroxidation status. These data provide a better understanding about the influence of NO-interfering therapies for the inflammatory response toward T. cruzi infection.

High-fat diet inhibits PGC-1α suppressive effect on NFκB signaling in hepatocytes.

PURPOSE: The peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) regulates the expression of genes implicated in fatty acid oxidation and oxidative phosphorylation. Its role in liver steatosis is well established, since mice with liver-specific deletion of PGC-1α exhibit lipid accumulation and high-fat diet reduces hepatic PGC-1α expression in mice. In this study, we investigated the role of PGC-1α in the inflammatory changes observed in steatohepatitis induced by high-fat diet. METHODS: C57black/6 mice were fed a high-fat diet containing 30% fat for 10 weeks. After euthanasia, liver morphology was examined by HE staining and inflammation was determined by IL-6, TNF-α, and IL-1ß quantification. Liver gene expression of PGC-1 isoforms was evaluated by real-time PCR and p65 NFκB nuclear translocation by Western blotting. HepG2 cells were treated with linoleic acid overload for 72 h to create an in vitro model of steatohepatitis. RNA interference (RNAi) was used to evaluate the involvement of PGC-1α on inflammatory mediators' production by hepatocytes. RESULTS: The high-fat diet led to a state of nonalcoholic steatohepatitis, associated with increased deposits of intra-abdominal fat, hyperglycemia and hyperlipidemia. Mice liver also exhibited increased proinflammatory cytokines' levels, decreased PGC-1α expression, and marked increase in p65 NFκB nuclear translocation. Linoleic acid treated cells also presented increased expression of proinflammatory cytokines and decreased PGC-1α expression. The knockdown of PGC-1α content caused an increase in IL-6 expression and release via enhanced IκBα phosphorylation and subsequent increase of p65 NFκB nuclear translocation. CONCLUSION: High-fat diet induces liver inflammation by inhibiting PGC-1α expression and its suppressive effect in NFκB pathway.

Sepsis induces telomere shortening: a potential mechanism responsible for delayed pathophysiological events in sepsis survivors?

Sepsis survivors suffer from additional morbidities, including higher disk of readmissions, nervous system disturbances and cognitive dysfunction, and increased mortality, even several years after the initial episode of sepsis. In many ways, the phenotype of sepsis survivors resembles the phenotype associated with accelerated aging. Since telomere shortening is a hallmark of aging, we investigated whether sepsis also leads to telomere shortening. Male balb/c mice were divided into two groups: the control group received 100 µl of normal saline intraperitoneally; the sepsis group received 15 mg/kg of bacterial lipopolysaccharide i.p. After 48 hours, animals were sacrificed to collect blood, spleen and kidney. The human component of our study utilized blood samples obtained from patients in the Trauma Department and samples collected 7 days later in those patients who developed sepsis. Telomere length was measured by quantitative PCR. Since oxidative stress is a known inducer of telomere shortening, thiobarbituric acid reactive substances and superoxide dismutase (SOD) activity were analyzed in order to evaluate oxidative stress burden. Induction of endotoxemia in mice resulted in significant telomere shortening in spleen and kidney. Blood cells from patients that progressed to sepsis also exhibited a statistically significant reduction of telomere length. Endotoxemia in mice also induced an early-onset increase in oxidative stress markers, but was not associated with a downregulation of telomerase protein expression. We conclude that endotoxemia and sepsis induce telomere shortening in various tissues and hypothesize that this may contribute to the pathogenesis of the delayed pathophysiological events in sepsis survivors.

Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer.

Chemotherapy remains the first-choice option for adjuvant therapy in breast cancer. Here, we investigated the impact of the first chemotherapic cycle of doxorubicin on the plasmatic-proteomic profiling of women diagnosed with breast cancer (n = 87). Blood samples were obtained from the same patient before and after doxorubicin infusion (1 h, 60 mg/m(2)) and processed for label-free LC-MS proteomic screening. A total of 80 proteins were downregulated after chemotherapy. In silico analysis revealed that the main biological process enrolled was inflammation and canonical pathways involving acute phase proteins. TNF-α, IL-1ß, IL-12, TGF-ß1, clusterin, and gelsolin were chosen as relevant for further validation. All selected targets presented reduced plasmatic levels after treatment. Our results indicate that doxorubicin downregulated acute phase proteins immediately after its infusion. Since such proteins are cancer promoting, its downregulation could support the effectiveness of doxorubicin along treatment.

PGC-1ß regulates HER2-overexpressing breast cancer cells proliferation by metabolic and redox pathways.

Breast cancer is a prevalent neoplastic disease among women worldwide which treatments still present several side effects and resistance. Considering that cancer cells present derangements in their energetic homeostasis, and that peroxisome proliferator-activated receptor- gamma coactivator 1 (PGC-1) is crucial for cellular metabolism and redox signaling, the main objective of this study was to investigate whether there is a relationship between PGC-1 expression, the proliferation of breast cancer cells and the mechanisms involved. We initially assessed PGC-1ß expression in complementary DNA (cDNA) from breast tumor of patients bearing luminal A, luminal B, and HER2-overexpressed and triple negative tumors. Our data showed that PGC-1ß expression is increased in patients bearing HER2-overexpressing tumors as compared to others subtypes. Using quantitative PCR and immunoblotting, we showed that breast cancer cells with HER2-amplification (SKBR-3) have greater expression of PGC-1ß as compared to a non-tumorous breast cell (MCF-10A) and higher proliferation rate. PGC-1ß expression was knocked down with short interfering RNA in HER2-overexpressing cells, and cells decreased proliferation. In these PGC-1ß-inhibited cells, we found increased citrate synthase activity and no marked changes in mitochondrial respiration. Glycolytic pathway was decreased, characterized by lower intracellular lactate levels. In addition, after PGC-1ß knockdown, SKBR-3 cells showed increased reactive oxygen species production, no changes in antioxidant activity, and decreased expression of ERRα, a modulator of metabolism. In conclusion, we show an association of HER2-overexpression and PGC-1ß. PGC-1ß knockdown impairs HER2-overexpressing cells proliferation acting on ERRα signaling, metabolism, and redox balance.

Role of leptin in the pathogenesis of breast cancer / Papel da leptina na patogênese do câncer de mama

A leptina é um pequeno polipeptídeo codificado pelo gene OB, profundamente relacionado com a massa de gordura corporal e o balanço energético. Devido aos seus diversos efeitos biológicos e transdutores de sinal regulados, múltiplas classificações biológicas tem sido atribuídas à leptina, incluindo hormônio,citocina, adipocina, fator de crescimento, e fator de desenvolvimento, dentre outros. Este cenário nos dá uma idéia do tamanho do potencial de efeitos biológicos gerados por esta molécula. A concentração de leptina no corpo é determinada pela quantidade de tecido adiposo; portanto, hiperleptinemia é um achado comum em indivíduos obesos. Além disso, níveis elevados de leptina circulante pode conferirum pior prognóstico para qualquer condição patológica. Apesar da história da leptina ter sido reportada por mais de 20 anos, sua relação com o câncer ganhou notoriedade nos últimos 10 anos, quando estudos focaram e discutiram o papel da obesidade com um forte fator de risco para o desenvolvimento de câncer.Adicionalmente, evidências crescentes apontam a leptina como mediador primordial da resposta imune, oque agrava o cenário da ocorrência de câncer na presença de obesidade. Assim, a leptina pode apresentar pelo menos duas faces na patogênese do câncer, agindo através de mecanismos imunológicos e não imunológicos.Neste trabalho, revisamos a dinâmica do eixo leptina no câncer de mama e discutimos seu papel na doença, imunopatogênese e prognóstico.

Leptin is a small polypeptide codified by the Obese Gene (OB), deeply related with the body fat massand energetic balance. Due to its diverse biological effects and downstream signal transducers, multipleclassifications have been attributed to leptin, as hormone, cytokine, adypokine, growth factor, anddevelopmental factor, among others. This scenario gives us an idea of the size of the potential biological effects generated by this molecule. The concentration of leptin in the body is determined by the amountof adipose tissue; the refore, hyperleptinemia is a common finding in obese individuals. In addition, highlevels of circulating leptin may confer a poor prognosis for any pathological condition. Although leptin history has been reported for more than 20 years, its relationship with cancer has gained notoriety in the past ten years, where studies focused on discussing the issue of obesity as a strong risk factor for cancer developing. Further, growing evidences have pointed leptin as a pivotal mediator of immune response, which aggravates the scenario of cancer occurrence in the presence of obesity. Therefore, leptin can present at least two faces in the pathogenesis of breast cancer, acting by immune and non-immune mechanisms. In this paper we review the dynamic of the leptin axis in breast cancer and further discussits role in disease, immunopathogenesis and prognosis.

Redox-driven events in the human immunodeficiency virus type 1 (HIV-1) infection and their clinical implications.

Oxidative stress is a condition characterized by the imbalance between the production of reactive species (RS) or free radicals and their neutralization by the antioxidant defenses, leading to the accumulation of RS and their derived metabolites, with changes in the redox status of the cell. These RS can act on biological components and induce the oxidative and nitrosative reactions on lipids, proteins, and DNA. In this context, a wide variety of chronic diseases present oxidative stress as a part of the pathogenesis, including the human immunodeficiency virus type 1 (HIV-1) infection. The relationship between oxidative stress and HIV-1 infection lies in the fact that the RS species are important components of the innate immune response, and their derived metabolites and reactions participate in several events of the adaptative immune response. On the other hand, studies have shown specific roles for oxidative-driven events in both the host immunity and the virus biology. Undoubtedly, the occurrence of oxidative stress in HIV-1-infected patients has been implicated in disease progression, as well as in developing other secondary disorders, such as cardiovascular diseases, insulin resistance, and metabolic syndrome. This review aims to characterize the redox-driven events in the HIV-1 infection and their clinical implications in the disease features.

Breast cancer in Brazil: epidemiology and treatment challenges.

Notwithstanding the advances in tumor research, diagnosis, and treatment, breast cancer is still a challenge worldwide. This global burden of disease has been associated with population aging and the persistence of cancer-related behaviors. The number of women diagnosed with breast cancer has been estimated as increasing, especially in middle-income countries such as Brazil. Estimates from the Instituto Nacional de Câncer (INCA) point to breast cancer as the major malignant neoplasia in Brazilian women and the main cause of death from cancer in the country. This fact has been associated with increased life expectancy, urbanization, and cancer-related behaviors. Given this scenario, it is clear that there is a need for identifying and discussing which factors have substantially contributed to this growing number of cases in Brazil, including access to treatment, prevention and early diagnosis, weaknesses of the local health policy, and intrinsic genetic peculiarities of the Brazilian population. This review aims to address the role of such factors.

Post-translational modifications disclose a dual role for redox stress in cardiovascular pathophysiology.

Although some of the redox changes that occur in biological components may result in deleterious events, this process has recently been tackled as a modulatory event. Advances in our understanding regarding the role of some oxidative/nitrosative reactions revealed that proteins can be structurally and functionally modified by chemical reactions, an epigenetic event known as post-translational modification (PTM). PTMs can function as an "on-off switch" for signaling cascades, and are dependent on the specific generation of redox components such as reactive oxygen species (ROS) and nitric oxide (NO). NO-driven modifications regulate a wide range of cellular processes and have been highlighted as an epigenetic event that protects proteins from proteolytic degradation. On the other hand, ROS-driven modifications are implicated in cell damage in a number of pathological conditions, especially in the cardiovascular system. Therefore, while mitochondrial uncoupling yields the massive production of ROS in the heart, some cellular redox-sensitive pathways trigger PTMs that may play a cardioprotective role. In this review, we present an overview of the oxidative/nitrosative milieu in cardiac pathologies and address the role of the main redox-driven PTMs as epigenetic events in cardioprotection, as well as its regulatory function in cardiomyocyte signaling. Improved understanding of the role of these PTMs in cardiovascular disease can help direct some approaches for future clinical research regarding health risk assessment, as well as inform strategies for disease treatment and prevention.

Mecanismos de proliferação celular dependentes da atividade do coativador - 1 de receptor ativado por proliferadores de peroxissoma gama (PGC-1) / Mechanisms of cellular proliferation dependent on peroxisome proliferator-activated receptor-gamma coactivator 1 (PGC-1)

Apesar dos avanços no tratamento dos diferentes subtipos moleculares do câncer de mama, diversos efeitos colaterais e resistência ao tratamento são observados. Nesse contexto, a busca por novos marcadores moleculares ainda é necessária. A família do coativador - 1 do receptor ativado por proliferadores de peroxissoma gama-1 (PGC-1) exerce funções cruciais no metabolismo energético celular e alguns trabalhos na literatura mostram alterações de PGC-1 no desenvolvimento do câncer. Contudo, mecanismos envolvidos na proliferação celular do carcinoma de mama permanecem desconhecidos. O objetivo geral foi determinar os mecanismos pelos quais PGC-1 controla a proliferação de células tumorais de mama, com foco em vias metabólicas e de sinalização redox. Para alcançar os objetivos, foi determinada a expressão de PGC-1alfa e beta em células tumorais de mama dos subtipos moleculares luminal (MCF-7), HER2- superexpresso (SKBR3) e triplo negativo (MDAMB231) em relação a uma linhagem de mama não tumoral (MCF-10A). Foi encontrada maior expressão gênica e proteica de PGC-1beta na superexpressão de HER2, e maior taxa de crescimento para essa linhagem. Para investigar se PGC-1beta pode estar envolvido na proliferação dessas células, utilizamos sequências específicas de RNA de interferência para o knockdown de PGC-1beta nas células SKBR3. Após o tratamento houve diminuição de proliferação celular. Assim, investigamos os prováveis mecanismos pelos quais PGC-1beta diminui a proliferação celular. Nossos resultados mostram que o knockdown de PGC-1beta não influenciou a expressão de ciclinas (B, C, D e E) e não houve diferença na quantidade de DNA mitocondrial, fator de transcrição mitocondrial A (TFAM), fator de respiração nuclear (NRF) 1 e 2. Em seguida, mostramos que o knockdown de PGC-1beta diminuiu a produção de lactato intracelular e aumentou a atividade da enzima citrato sintase, e houve tendência a maior taxa de respiração celular. Detectamos maiores...

Despite a marked improvement in treatments for all breast cancer subtypes, several side-effects and resistance to therapy are noticed. In this context, the searching for new molecular targets for breast cancer treatment is still a challenge. Peroxisome proliferator-activated receptor- gamma coactivator 1 (PGC-1) is the main regulator of cell energy homeostasis and studies in the literature show alterations regarding PGC-1 in cancer development. However, mechanisms involved in cellular proliferation of breast cancer remain unknown. We aimed to determine the mechanisms by which PGC-1beta controls breast cancer cell proliferation, focusing on metabolic and redox signaling. To reach this goal, we determined PGC-1alfa and beta expression in breast cancer cell lines as luminal (MCF-7), HER2-overexpressed (SKBR3) and triple- negative (MDAMB231) as compared to a non-tumoral breast cell line (MCF-10A). We found increased gene and protein expression of PGC-1beta in HER2- overexpressed cells and increased cellular proliferation. To investigate whether PGC-1beta could be involved in the proliferation of those cells, we used specific sequences of silencing interfering RNA for knockdown of PGC-1beta in SKBR3 cells. After treatment we observed a decrease in cellular proliferation. Thus, we next investigated the probable mechanisms by which PGC-1beta could decrease cellular proliferation. Our results showed that knockdown of PGC-1beta did not influence on cyclin expression (B, C, D and E), mitochondrial DNA number, mitochondrial transcription factor - A (TFAM), nuclear receptor factor (NRF) 1 and 2 expression. We showed that knockdown of PGC-1beta induced a decrease intracellular lactate production, increase in citrate synthase activity and a trend to increase cellular respiration rate. Thereby, we detected greater amounts of reactive oxygen species (ROS) after knockdown of PGC-1beta, and no alterations was found for nitrite and nitrate levels. No alterations regarding...

Oxidative stress, redox signaling and cancer chemoresistance: putting together the pieces of the puzzle.

Chemotherapy continues to be the main treatment option for cancer. Although systemic chemotherapy can efficiently eradicate cancer cells, a significant proportion of patients carry tumors that present a chemoresistant phenotype, resulting in disease progression, cancer relapse, and reduced survival. It has also become clear that the effect of most chemotherapeutic drugs is associated with their capacity to generate reactive species (RS) that bind to specific structures within the cancer cell and promote cell death. Due to repeated exposure to chemotherapeutic agents, the redox homeostasis of cancer cells is continuously disturbed, which can result in changes to the cell's ability to cope with excessive RS levels through the production of protective molecules. It is thought that the imbalance resulting from this process-- oxidative stress--is toxic to cancer cells. Paradoxically, the metabolites produced during oxidative stress can favor the survival of some cancer subpopulations, which present specific gene signatures that confer a chemoresistant phenotype on these clones. Despite the huge amount of information generated by currently available technologies, we cannot predict whether this resistance will arise during chemotherapy and we still do not fully understand the mechanism by which it arises. In this review, we discuss the main findings regarding the role of oxidative stress signaling in cancer chemotherapy and the key redox molecules and pathways that lead to the development of chemoresistance.

Mapping oxidative changes in breast cancer: understanding the basic to reach the clinics.

Since long, oxidative stress-driven modifications in breast cancer were faced as detrimental cellular events that cause obligatory cell damage. Recent studies show that the products generated during redox reactions are able to modulate pivotal processes regarding breast cancer survival, proposing a new way of looking at the events linked to oxidative stress. Therefore, it is necessary to understand the basis of oxidative stress generation in breast cancer by reviewing the two most important events that perpetuate the malignant transformation: mitochondrial dysfunction and DNA damage/misguided repair. In this context, the present review addresses the main events related with redox events reported in breast cancer studies, highlighting the impact of the oxidative environment on DNA damage and the role of the mitochondria as a determinant of oxidative modifications. In addition, we further discuss the main stand-out findings concerning the modulatory role of the metabolites derived from redox stresses, with a special focus on the oxidative changes detected in the breast cancer microenvironment and its systemic impact.

Screening of circulating TGF-ß levels and its clinicopathological significance in human breast cancer.

BACKGROUND: Transforming growth factor beta-1 (TGF-ß1) participation in breast cancer development and metastasis is well-established, however, the clinical meaning of its circulating levels in women with breast cancer is poorly understood. AIM: To characterize the levels of TGF-ß1 in plasma from women with breast cancer and to associate them with the main clinical factors associated with disease prognosis. PATIENTS AND METHODS: TGF-ß1 levels were measured by Enzyme-linked immunoassay (ELISA). Clinicopathological data were also assessed. RESULTS: Women bearing triple-negative tumors presented significantly reduced levels of this cytokine when compared to the other subtypes (p=0.0338). Patients with metastases exhibited lower levels of TGF-ß1 than the non-metastatic cohort (p=0.0442). Patients with early-onset disease had the highest plasma TGF-ß1 levels (p=0.0036). Doxorubicin chemotherapy induced a reduction in TGF-ß1 level, promptly after drug infusion (p=0.0494). Patients with TGF-ß1 levels lower than 20 pg/ml exhibited a tendency to have a reduced overall survival in a 40-month follow-up. CONCLUSION: Lower levels of circulating TGF-ß1 are associated with a poor disease prognosis.

Smoking as a risk factor for the development of breast cancer

INTRODUCTION: Smoking is considered a public health problem and in many cases is responsible for the development of lung diseases and cancer. One of the mechanisms by which tobacco can induce cancer is through the generation of free radicals, establishing an oxidative stress status in smokers. With increasing smoking among women, much evidence in the literature has shown a relation between smoking and breast cancer development. OBJECTIVE: The aim of this review was to analyze the available studies in literature that demonstrate the association between smoking and the risk of breast cancer development. METHODS: We performed a review from the literature based on the search results in PubMed and Scielo. The selected works were composed by current articles according to their relevance and human application. RESULTS: The literature revealed several published studies linking smoking to oxidative stress through the action of free radicals that are generated by toxic compounds found in cigarettes. There are few studies relating smoking with breast cancer, which is a relatively more recent research line, where the vast majority of works includes epidemiological and controversial studies. CONCLUSIONS: The selected works show that, although controversial, smoking is considered a risk factor for developing breast cancer.

Aspects related to oxidative stress-mediated toxicity of doxorubicin during chemotherapy treatment

OBJECTIVE: This study aimed to describe the main toxic effects mediated by oxidative stress associated with treatment with doxorubicin in scientific research articles available in the literature. MATERIAL AND METHODS: This study employed a descriptive review methodology applied to the literature. For the theoretical scientific background, we used the electronic PubMed search engines. CONCLUSION: The toxicity of chemotherapy treatment with doxorubicin causes damage in various organs of patients who are in uninterrupted treatment with this antineoplastic agent. Anthracycline-induced cardiotoxicity has been investigated to a great degree and is especially indicated as the principal side effect. Therefore, care needs to be given to other damage caused by this medication as important as myocardial toxicity, such as renal, pulmonary and liver toxicity, among others. There is a need for further studies to prevent or even encounter a way to control the damage caused by these toxicities in various tissues.

Trypanosoma cruzi: effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on levels of cytokines, nitric oxide and iNOS expression in cardiac tissue in the acute phase of infection in mice.

Leukotrienes are important mediators of inflammatory responses. In this study, we investigated the effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on levels of cytokines, nitric oxide (NO) and iNOS expression in cardiac tissue of mice infected with Trypanosoma cruzi, the agent of Chagas' disease. NO is a key mediator of parasite killing in mice experimentally infected with T. cruzi, and previous studies have suggested that leukotrienes, such as LTB(4), induces NO synthesis in T. cruzi-infected macrophages and plays a relevant role in the killing of parasite in a NO-dependent manner. We therefore investigated whether leukotrienes would have a similar role in vivo in controlling the parasite burden by regulating NO activity. We have made the striking observation that absence of 5-LO-derived leukotrienes results in increased NO and IL-6 production in the plasma with a concomitant decrease in the expression of iNOS in the cardiac tissue on day 12 after T. cruzi infection. These findings indicate that endogenous leukotrienes are important regulators of NO activity in the heart and therefore influence the cardiac parasite burden without exerting a direct action on IL-6 production in the acute phase of infection with T. cruzi.

Breast cancer and oxidative stress in chemotherapy

Objective: This revision characterizes the biomarkers used for analysis of the development of oxidative stress produced during breast cancer chemotherapy. Materials and methods: A search of articles indexed in digital databases (Lilacs, Bireme, PubMed, Scielo and digital libraries), along with publications printed as books, periodicals and articles not available online, in the period from 1979 to 2009. Conclusion: Reactive oxygen and nitrogen species are produced, principally, during aerobic metabolism; however, its synthesis can be exacerbated or antioxidant defense reduced or more usually, both conditions can occurr in many pathophysiologic situations, leading to a net reactive species yelded. This unbalance is defined as oxidative stress. Stress biomarkers can be defined as predictive indicators able to detect in vivo oxidative damage and can be subdivided into antioxidant and pro-oxidants. To verify the antioxidant system, it is possible to analyze the superoxide dismutase enzymes, catalase and glutathione, along with vitamins A, E, C and glutathione among others. The analysis of pro-oxidants can be made through the verification of protein nitration and oxidation, heat shock proteins, lipoperoxidation, formation of aldehydes for malondialdehyde tests, 4-hydroxynonenal, oxidized LDL and isoprostanes or for chemiluminescent techniques. Advances in cancer detection through the identification of potential biomarkers consist of a promising strategy for the prevention and early identification of this pathology.