Body weight gain and control: beneficial effect of extra virgin olive oil versus corn oil in an experimental model of mammary cancer.

Obesity is a known risk factor for breast cancer, the most common malignancy among women worldwide. We have previously described different effects of high-fat diets on mammary experimental carcinogenesis. In this work, we analyzed the animal growth data obtained in six experimental assays, in healthy and carcinogen-induced rats undergoing different dietary interventions. The animals were fed with three experimental diets administered at different periods of development: a control low-fat diet, and two isocaloric high-fat diets (rich in corn oil or in extravirgin olive oil -EVOO-). Weekly weight throughout the development of 818 animals have been compiled and reanalyzed using adjusted mathematical models. Molecular mechanisms have been investigated: ethanolamides in small intestine, neuropeptides controlling satiety in hypothalamus, and proteins controlling lipid metabolism in adipose and mammary tissues. The results indicated that the effect of diets depended on type of lipid, timing of intervention and health status. The high corn oil diet, but not the high EVOO diet, increased body weight and mass, especially if administered from weaning, in healthy animals and in those that received a moderate dose of carcinogen. The potential protective effect of EVOO on weight maintenance may be related to anorexigenic neuropeptides such as oxytocin and lipolysis/deposition balance in adipose tissue (increasing phospho-PKA, HSL, MGL and decreasing FAS). In animals with cancer, body weight gain was related to the severity of the disease. Taken together, our results suggest that EVOO has a beneficial effect on body weight maintenance in both health and cancer.

Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin.

The aim of this study was to investigate the effects of two phenolic compounds found in extra virgin olive oil, hydroxytyrosol (HT) and luteolin (LUT), on the metabolism of breast cancer (BC) cells of different molecular subtypes. An untargeted metabolomics approach was used to characterize the metabolic responses of both triple-negative MDA-MB-231 cells and hormone-responsive MCF-7 cells to treatment with these phenols. Notably, while some effects were common across both cell types, others were dependent on the cell type, highlighting the importance of cellular metabolic phenotype. Common effects included stimulation of mitochondrial metabolism, acetate production, and formate overflow. On the other hand, glucose metabolism and lactate production were differentially modulated. HT and LUT appeared to inhibit glycolysis and promote the hexosamine biosynthetic pathway in MDA-MB-231 cells, while MCF-7 cells exhibited higher glycolytic flux when treated with phenolic compounds. Another significant difference was observed in lipid metabolism. Treated MDA-MB-231 cells displayed increased levels of neutral lipids (likely stored in cytosolic droplets), whereas treatment of MCF-7 cells with HT led to a decrease in triacylglycerols. Additionally, glutathione levels increased in MDA-MB-231 cells treated with HT or LUT, as well as in MCF-7 cells treated with LUT. In contrast, in HT-treated MCF-7 cells, glutathione levels decreased, indicating different modulation of cellular redox status. Overall, this work provides new insights into the metabolic impact of HT and LUT on different BC cell subtypes, paving the way for a better understanding of the nutritional relevance of these phenolic compounds in the context of BC prevention and management.

Extra-Virgin Olive Oil and Its Minor Compounds Influence Apoptosis in Experimental Mammary Tumors and Human Breast Cancer Cell Lines.

Breast cancer is the most common malignancy among women worldwide. Modifiable factors such as nutrition have a role in its etiology. In experimental tumors, we have observed the differential influence of high-fat diets in metabolic pathways, suggesting a different balance in proliferation/apoptosis. In this work, we analyzed the effects of a diet high in n-6 polyunsaturated fatty acids (PUFA) and a diet high in extra-virgin olive oil (EVOO) on the histopathological features and different cell death pathways in the dimethylbenz(a)anthracene-induced breast cancer model. The diet high in n-6 PUFA had a stimulating effect on the morphological aggressiveness of tumors and their proliferation, while no significant differences were found in groups fed the EVOO-enriched diet in comparison to a low-fat control group. The high-EVOO diet induced modifications in proteins involved in several cell death pathways. In vitro analysis in different human breast cancer cell lines showed an effect of EVOO minor compounds (especially hydroxytyrosol), but not of fatty acids, decreasing viability while increasing apoptosis. The results suggest an effect of dietary lipids on tumor molecular contexts that result in the modulation of different pathways, highlighting the importance of apoptosis in the interplay of survival processes and how dietary habits may have an impact on breast cancer risk.

Influence of Olive Oil and Its Components on Breast Cancer: Molecular Mechanisms.

Breast cancer is the most frequent malignant neoplasia and a leading cause of mortality in women worldwide. The Mediterranean diet has been proposed as a healthy dietary pattern with protective effects in several chronic diseases, including breast cancer. This diet is characterized by the consumption of abundant plant foods and olive oil as the principal source of fat, which is considered one of the main components with potential antioxidant, anti-inflammatory and anticancer effects. Extra-virgin olive oil (EVOO) has several bioactive compounds, mainly including monounsaturated fatty acids, triterpenes and polyphenols, such as phenolic alcohols (e.g., hydroxytyrosol), secoiridoids (e.g., oleuropein and oleocanthal), lignans (e.g., pinoresinol) or flavonoids (e.g., luteolin). While epidemiological evidence is still limited, experimental in vivo and in vitro data have shown a protective effect of this oil and its compounds on mammary carcinogenesis. Such effects account through complex and multiple mechanisms, including changes in epigenetics, transcriptome and protein expression that modulate several signaling pathways. Molecular targets of EVOO compounds have a role in the acquisition of cancer hallmarks. Although further research is needed to elucidate their beneficial effects on human prevention and progression of the disease, evidence points to EVOO in the context of the Mediterranean diet as a heathy choice, while EVOO components may be promising adjuvants in anticancer strategies.

A high extra-virgin olive oil diet induces changes in metabolic pathways of experimental mammary tumors.

Breast cancer is the most common malignancy in women worldwide, and environmental factors, especially diet, have a role in the etiology of this disease. This work aimed to investigate the influence of high fat diets (rich in corn oil or extra virgin olive oil -EVOO-) and the timing of dietary intervention (from weaning or after induction) on tumor metabolism in a seven,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer model in rat. The effects of lipids (oils and fatty acids) have also been investigated in MCF-7 cells. The results have confirmed different effects on tumor progression depending on the type of lipid. Molecular analysis at mRNA, protein and activity level of enzymes of the main metabolic pathways have also shown differences among groups. Thus, the animals fed with the EVOO-enriched diet developed tumors with less degree of clinical and morphological malignancy and showed modified glucose and mitochondrial metabolism when compared to the animals fed with the corn oil-enriched diet. Paradoxically, no clear influence on lipid metabolism by the high fat diets was observed. Considering previous studies on proliferation and apoptosis in the same samples, the results suggest that metabolic changes have a role in the molecular context that results in the modulation of different signaling pathways. Moreover, metabolic characteristics, without the context of other pathways, may not reflect tumor malignancy. The time of dietary intervention plays also a role, suggesting the importance of metabolic plasticity and the relation with mammary gland status when the tumor is induced.

Fluorescent in situ hybridization (FISH): A useful diagnostic tool for childhood conjunctival melanoma.

INTRODUCTION: Conjunctival melanoma is extremely rare in children and has low rates of resolution. Definitive histopathological diagnosis based exclusively on microscopic findings is sometimes difficult. Thus, early diagnosis and adequate treatment are essential to improve clinical outcomes. CLINICAL CASE: We present the first case in which the fluorescent in situ hybridization (FISH) diagnostic technique was applied to a 10-year-old boy initially suspected of having amelanotic nevi in his right eye. Based on the 65% of tumor cells with 11q13 (CCND1) copy number gain and 33% with 6p25 (RREB1) gain as measured by the FISH analysis, and on supporting histopathological findings, the diagnosis of conjunctival melanoma could be made. Following a larger re-excision, adjuvant therapy with Mitomycin C (MMC), cryotherapy and an amniotic membrane graft, the patient has remained disease-free during 9 years of long-term follow-up. CASE DISCUSSION: Every ophthalmologist should remember to consider and not forget the possibility of using FISH analyses during the differential diagnosis of any suspicious conjunctival lesions. Genetic techniques, such as FISH, have led to great advances in the classification of ambiguous lesions. Evidence-based guidelines for diagnosing conjunctival melanoma in the pediatric population are needed to determine the most appropriate strategy for this age group.

Effects of diets high in corn oil or in extra virgin olive oil on oxidative stress in an experimental model of breast cancer.

Experimental evidence highlights the importance of dietetic factors on breast cancer. In this work we aimed to analyze the effects two oils, corn oil (rich in n-6 polyunsaturated fatty acids -PUFA-) and extra virgin olive oil (EVOO), on oxidative stress in an animal model of breast carcinogenesis. Female rats were fed a low-fat control, a high-corn oil, or a high-EVOO diet from weaning or after induction with 7,12-dimethylbenz[a]anthracene at 53 days. Animals were euthanized at 36, 51, 100 and 246 days of age. We analyzed antioxidant enzymes (mRNA and activity of superoxide dismutase, glutathione peroxidase and catalase), non-enzymatic capacity (oxidized and reduced glutathione) and DNA damage (8-oxo-dG) in tumors and mammary gland at different ages. We also analyzed lipid peroxidation (isoprostanes in serum and lipofuscin in liver). Results indicated a decrease in the enzymatic antioxidant capacity and increased oxidative stress in mammary gland of healthy young animals after a short period of high-fat diets intake, followed by an adaptation to chronic dietary intervention. After induction both diets, especially the one high in n-6 PUFA, increased the oxidized glutathione. In tumors no clear effects of the high-fat diets were observed, although in the long-term lipofuscin and 8-oxo-dG suggested greater oxidative damage by effect of the n-6 PUFA-rich diet. Considering the differential effects of these diets on mammary carcinogenesis that we have previously reported, this study suggests that these high-fat diets could have an effect on oxidative stress that would lead to different signaling pathways.

A high-corn-oil diet strongly stimulates mammary carcinogenesis, while a high-extra-virgin-olive-oil diet has a weak effect, through changes in metabolism, immune system function and proliferation/apoptosis pathways.

Breast cancer is the most common malignancy in women worldwide, and dietary lipids are important environmental factors influencing its etiology. We have investigated the effects, and the mechanisms associated, of high-fat diets on 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors. Animals were fed a low-fat, a high-corn-oil (HCO) or a high-extra-virgin-olive-oil (HOO) diet from weaning or after induction. The HCO diet had a clear stimulating effect on mammary carcinogenesis, especially when dietary intervention started after induction, whereas the tumors from HOO diet groups exhibited clinical and morphological characteristics similar to those from low-fat controls. Transcriptomic and further protein and immunohistochemical analyses of tumors also indicated different modulatory effects of high-fat diets affecting relevant biological functions: metabolism, immunosurveillance and proliferation/apoptosis pathways. Thus, the results suggested different metabolic adaptations with increased glycolysis by effect of HOO diet. Moreover, leukocyte tumor infiltration and inflammation mediators showed increased cytotoxic T cells and decreased TGFß1 expression by the HOO diet, while the HCO one increased arginase expression and IL-1α plasma levels. Furthermore, the study of proteins controlling proliferation/apoptosis pathways (Sema3A, Stat5, Smad1, Casp3) suggested an increase in proliferation by the HCO diet and an increase of apoptosis by the diet rich in olive oil. In conclusion, the HCO diet clearly stimulated mammary carcinogenesis, especially in the promotion phase, and induced molecular changes suggesting increased tumor proliferation/apoptosis balance and a proinflammatory microenvironment. The HOO diet, despite being high fat, had a weaker effect on tumorigenesis probably related to metabolic adaptations, enhanced immunosurveillance and increased apoptosis.

Gene ontology analysis of transcriptome data from DMBA-induced mammary tumors of rats fed a high-corn oil and a high-extra virgin olive oil diet.

Breast cancer is the most common malignancy in women worldwide, and dietary lipids are important environmental factors influencing its etiology. In this work we present data in relation to the transcriptional effects of two high-fat diets, one high in corn oil (HCO) and one high in extra-virgin olive oil (HOO), administered from weaning or after induction, on 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. Raw data were deposited at ArrayExpress under accession number E-MTAB-3541. We compared the gene expression profiles of the mammary tumors from the high-fat diet groups with those from the control group, finding different effects of diets depending on timing and type of dietary intervention. Lists of differentially expressed genes were analyzed to find overrepresented categories of biological significance. Here we provide information about the cell functions categories overrepresented in significantly modulated genes by effect of the high-fat diets. Further investigations of such functions are described in "A high corn oil diet strongly stimulates mammary carcinogenesis, while a high extra virgin olive oil diet has a weak effect, through changes in metabolism, immune system function, and proliferation/apoptosis pathways" (Escrich et al., in press) [1].

The Dietary Antioxidant Piceatannol Inhibits Adipogenesis of Human Adipose Mesenchymal Stem Cells and Limits Glucose Transport and Lipogenic Activities in Adipocytes.

Phenolic compounds are among the most investigated herbal remedies, as is especially the case for resveratrol. Many reports have shown its anti-aging properties and the ability to reduce obesity and diabetes induced by high-fat diet in mice. However, such beneficial effects hardly translate from animal models to humans. The scientific community has therefore tested whether other plant phenolic compounds may surpass the effects of resveratrol. In this regard, it has been reported that piceatannol reproduces in rodents the anti-obesity actions of its parent polyphenol. However, the capacity of piceatannol to inhibit adipocyte differentiation in humans has not been characterized so far. Here, we investigated whether piceatannol was antiadipogenic and antilipogenic in human preadipocytes. Human mesenchymal stem cells (hMSC), isolated from adipose tissues of lean and obese individuals, were differentiated into mature adipocytes with or without piceatannol, and their functions were explored. Fifty µM of piceatannol deeply limited synthesis/accumulation of lipids in both murine and hMSC-derived adipocytes. Interestingly, this phenomenon occurred irrespective of being added at the earlier or later stages of adipocyte differentiation. Moreover, piceatannol lowered glucose transport into adipocytes and decreased the expression of key elements of the lipogenic pathway (PPARγ, FAS, and GLUT4). Thus, the confirmation of the antiadipogenic properties of piceatanol in vitro warrants the realization of clinical studies for the application of this compound in the treatment of the metabolic complications associated with obesity.

Use of negative pressure wound therapy after infection and flap dehiscence in radical vulvectomy: A case report.

INTRODUCTION: Vulvar cancer has a lower incidence in high income countries, but is rising, in part, due to the high life expectancy in these societies. Radical vulvectomy is still the standard treatment in initial stages. Wound dehiscence contitututes one of the most common postoperative complications. PRESENTATION OF CASE: A 76year old patient with a squamous cell carcinoma of the vulva, FIGO staged, IIIb is presented. Radical vulvectomy and bilateral inguinal lymph node dissection with lotus petal flaps reconstruction are performed as the first treatment. Wound infection and dehiscence of lotus petal flaps was seen postoperatively. Initial management consisted in antibiotics administration and removing necrotic tissue from surgical wound. After this initial treatment, negative wound pressure therapy was applied for 37days with good results. DISCUSSION: Wound dehiscence in radical vulvectomy remains the most frequent complication in the treatment of vulvar cancer. The treatment of this complications is still challenging for most gynecologic oncologist surgeons. CONCLUSION: The utilization of the negative wound pressure therapy could contribute to reduce hospitalization and the direct and indirect costs of these complications.

Treatment and follow-up in an asymptomatic malignant struma ovarii: A case report.

INTRODUCTION: Struma ovarii is a rare ovarian tumor, representing 0.5-1% of all ovarian tumors and 2-5% of ovarian teratomas. It is defined as an ovarian teratoma composed mostly of thyroid tissue. The symptoms are nonspecific, and the imaging studies can help in characterize the mass; however, the definitive diagnosis is usually given by the Pathologist. Classically, the treatment is the surgical resection of the ovarian mass, however there is no consensus regarding the follow-up. PRESENTATION OF CASE: An asymptomatic malignant struma ovarii in a 43 year-old patient is presented. The diagnosis was postoperatively following a laparoscopic adnexectomy due to an apparently benign ovarian teratoma. The histopathology results revealed a mature ovarian cystic teratoma with papillary carcinoma with immunohistochemical characteristics suggesting a thyroid origin. Seeing that there was no thyroid affectation or metastatic disease, we decided a conservative management. A yearly follow-up with CT scan and tumor markers was performed. The endocrinologist also performed annual controls with thyroid ultrasound and serum tests. The patient has remained asymptomatic during these last four years. DISCUSSION: There is little evidence in literature on the conservative management in cases with evidence of malignancy. If fertility preservation is desired, an unilateral oophorectomy could be performed, along with levels of serum thyroglobulin as a marker of relapse. Other authors claim for aggressive ovarian cancer surgery followed by a total thyroidectomy. There is still no established management for struma ovarii patients and the choice for a conservative or radical approach depends only on the professional decision.

Diets high in corn oil or extra-virgin olive oil differentially modify the gene expression profile of the mammary gland and influence experimental breast cancer susceptibility.

PURPOSE: Nutritional factors, especially dietary lipids, may have a role in the etiology of breast cancer. We aimed to analyze the effects of high-fat diets on the susceptibility of the mammary gland to experimental malignant transformation. METHODS: Female Sprague-Dawley rats were fed a low-fat, high-corn-oil, or high-extra-virgin olive oil (EVOO) diet from weaning or from induction. Animals were induced with 7,12-dimethylbenz[a]anthracene at 53 days and euthanized at 36, 51, 100 and 246 days. Gene expression profiles of mammary glands were determined by microarrays. Further molecular analyses were performed by real-time PCR, TUNEL and immunohistochemistry. Carcinogenesis parameters were determined at 105 and 246 days. RESULTS: High-corn-oil diet increased body weight and mass when administered from weaning. The EVOO diet did not modify these parameters and increased the hepatic expression of UCP2, suggesting a decrease in intake/expenditure balance. Both diets differentially modified the gene expression profile of the mammary gland, especially after short dietary intervention. Corn oil down-regulated the expression of genes related to immune system and apoptosis, whereas EVOO modified the expression of metabolism genes. Further analysis suggested an increase in proliferation and lower apoptosis in the mammary glands by effect of the high-corn-oil diet, which may be one of the mechanisms of its clear stimulating effect on carcinogenesis. CONCLUSIONS: The high-corn-oil diet strongly stimulates mammary tumorigenesis in association with modifications in the expression profile and an increased proliferation/apoptosis balance of the mammary gland.

The Role of Dietary Extra Virgin Olive Oil and Corn Oil on the Alteration of Epigenetic Patterns in the Rat DMBA-Induced Breast Cancer Model.

Disruption of epigenetic patterns is a major change occurring in all types of cancers. Such alterations are characterized by global DNA hypomethylation, gene-promoter hypermethylation and aberrant histone modifications, and may be modified by environment. Nutritional factors, and especially dietary lipids, have a role in the etiology of breast cancer. Thus, we aimed to analyze the influence of different high fat diets on DNA methylation and histone modifications in the rat dimethylbenz(a)anthracene (DMBA)-induced breast cancer model. Female Sprague-Dawley rats were fed a low-fat, a high corn-oil or a high extra-virgin olive oil (EVOO) diet from weaning or from induction with DMBA. In mammary glands and tumors we analyzed global and gene specific (RASSF1A, TIMP3) DNA methylation by LUMA and bisulfite pyrosequencing assays, respectively. We also determined gene expression and enzymatic activity of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) and evaluated changes in histone modifications (H3K4me2, H3K27me3, H4K20me3 and H4K16ac) by western-blot. Our results showed variations along time in the global DNA methylation of the mammary gland displaying decreases at puberty and with aging. The olive oil-enriched diet, on the one hand, increased the levels of global DNA methylation in mammary gland and tumor, and on the other, changed histone modifications patterns. The corn oil-enriched diet increased DNA methyltransferase activity in both tissues, resulting in an increase in the promoter methylation of the tumor suppressor genes RASSF1A and TIMP3. These results suggest a differential effect of the high fat diets on epigenetic patterns with a relevant role in the neoplastic transformation, which could be one of the mechanisms of their differential promoter effect, clearly stimulating for the high corn-oil diet and with a weaker influence for the high EVOO diet, on breast cancer progression.

Dietary extra-virgin olive oil and corn oil differentially modulate the mRNA expression of xenobiotic-metabolizing enzymes in the liver and in the mammary gland in a rat chemically induced breast cancer model.

High extra-virgin olive oil (EVOO) and corn oil diets differentially modulate experimental mammary carcinogenesis. We have investigated their influence on the initiation stage through the modulation of the expression of xenobiotic-metabolizing enzymes (XMEs) in the liver and the mammary gland. Female Sprague-Dawley rats were fed a low-fat (LF), high corn oil (HCO), or high EVOO (HOO) diet from weaning and gavaged with 7,12-dimethylbenz(a)anthracene (DMBA). The HCO diet increased the mRNA levels of the phase I enzymes CYP1A1, CYP1A2 and, to a lesser extent, CYP1B1, in the liver. The Aryl hydrocarbon receptor (AhR) seemed to be involved in this upregulated CYP1 expression. However, a slight trend toward an increase in the mRNA levels of the phase II enzymes GSTP1 and NQO1 was observed with the HOO diet. At least in the case of GSTP1, this effect was linked to an increased Nrf2 transactivation activity. This different regulation of the XMEs expression led, in the case of the HCO diet, to a balance between the production of active carcinogenic compounds and their inactivation tilted toward phase I, which would stimulate DMBA-induced cancer initiation, whereas the HOO diet was associated with a slower phase I metabolism accompanied by a faster phase II detoxification, thus reducing the output of the active compounds to the target tissues. In the mammary gland, the differential effects of diets may be conditioned by the state of cell differentiation, sexual maturity, and hormone metabolism.

Ontogeny of the major xenobiotic-metabolizing enzymes expression and the dietary lipids modulatory effect in the rat dimethylbenz(a)anthracene-induced breast cancer model.

Breast cancer is the most common malignancy in women worldwide. Environmental factors such as xenobiotic exposure and lifestyle and nutrition play a key role in its etiology. This study was designed to evaluate the age-related changes in the expression of major xenobiotic-metabolizing enzymes (XMEs) in the rat liver and the mammary gland in the dimethylbenz(a)anthracene-induced breast cancer model. The influence of dietary lipids on the ontogeny of XMEs was also evaluated. mRNA and protein levels of phase I (CYP1A1, CYP1A2, and CYP1B1) and phase II (NAD(P)H:quinone acceptor oxidoreductase 1 and GSTP1) enzymes were analyzed, as well as their regulation by AhR and Nrf2, respectively. Results showed differences in the phase I enzymes expression, whereas little changes were obtained in phase II. High corn oil and olive oil diets differentially influenced the expression of age-related changes, suggesting that the different susceptibility to xenobiotic exposure depending upon the age may be modulated by dietary factors.

Study of neuron survival on polypyrrole-embedded single-walled carbon nanotube substrates for long-term growth conditions.

Cultures of primary embryonic rat brain hippocampus neurons with supporting glia cells were carried out on different substrates containing polypyrrole (PPy) and/or single-walled carbon nanotubes (SWCNTs). Neuron adhesion, neurites and dendrites branching elongation, and development of neuron networks on substrates were followed by phase-contrast optical microscopy and quantified to state cell survival and proliferation. Suspensions of as-grown and purified SWCNTs were sprayed on a glass coverslips and PPy/SWCNTs were deposited by potentiodynamic electrochemical deposition. Cell neurotoxicity revealed by neuron death was very high for purified SWCNTs substrates in good agreement with [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) test showing lower viability on SWCNTs containing substrates compared with PPy-substrates and control samples probably due to the metal content and the carboxylic groups introduced during the purification. It is interesting to highlight that neurons grown on PPy-substrates adhere developing neurites and branching dendrites earlier even than on control cultures. On subsequent days the neurons are able to adapt to nanotube substrates developing neuron networks for 14-day cultures with similar patterns of complexity for control, PPy and PPy/SWCNT substrates. PPy/SWCNT substrates show a lower impedance value at frequencies under 1 Hz. We have come to the conclusion that glia cells and PPy added to the culture medium and substrates respectively, improve in some degree nanotube biocompatibility, cell adhesion and hence cell viability.

Olive oil and other dietary lipids in breast cancer.

Breast cancer is the most frequent malignant neoplasia among women worldwide. In addition to genetic and endocrine factors, the environment, and specifically nutritional factors, plays a key role in its aetiology. Epidemiological and in particular experimental studies have shown the link between dietary fat and breast cancer. Abundant data have attributed a potentially chemopreventive effect for extra-virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, which is associated with low incidence and mortality rates from chronic diseases such as breast cancer. We have demonstrated the differential modulatory effect of dietary lipids on mammary carcinogenesis, mainly in studies developed in an experimental model. Thus, diets high in n-6 polyunsaturated fatty acids (PUFA) have a clear stimulating influence, whereas EVOO diets mainly have a negative modulatory effect on breast cancer development. The specific mechanisms involved are not fully understood, but nowadays, it is widely accepted that they are numerous and complex. Our group has contributed to improving the knowledge of these mechanisms by demonstrating the influence of dietary lipids on the structure and function of cell membranes, the modulation of cell-signalling transduction pathways, the regulation of gene expression and growth and sexual maturity.

Olive oil, an essential component of the Mediterranean diet, and breast cancer.

OBJECTIVE: The Mediterranean diet has been related to a lower risk of some chronic diseases, including cancer. We aim to gain insight into the effects of the main source of fat of this diet on breast cancer, the most common type of malignancy in women. DESIGN: Data from sixteen experimental series analysing the effects of dietary lipids on mammary carcinogenesis in an animal model, in the context of the international literature on the Mediterranean diet, olive oil and breast cancer risk. SETTING: Experimental and human data on the effects of olive oil and Mediterranean diet on breast cancer. SUBJECTS: An animal model of induced breast cancer and other human and experimental studies in the literature. RESULTS: Diets rich in extra virgin olive oil (EVOO) exert a negative modulatory effect on experimental breast cancer to a weak promoting effect, much lower than that obtained with a high-corn oil diet. EVOO confers to the mammary adenocarcinomas a clinical behaviour and morphological features compatible with low tumour aggressiveness. This differential effect, in relation to other dietary lipids, may be related to a lower effect on body weight and sexual maturation. In addition, EVOO induced different molecular changes in tumours, such as in the composition of cell membranes, activity of signalling proteins and gene expression. All these modifications could induce lower proliferation, higher apoptosis and lower DNA damage. These results, together with the favourable effect of olive oil reported in the literature when it is consumed in moderate quantities, suggest a beneficial influence of EVOO on breast cancer risk. CONCLUSIONS: Consumption of EVOO in moderate quantities and throughout the lifetime appears to be a healthy choice and may favourably influence breast cancer risk.

Diets high in corn oil or extra-virgin olive oil provided from weaning advance sexual maturation and differentially modify susceptibility to mammary carcinogenesis in female rats.

Based on the importance of early-life events in breast cancer risk, we have investigated the effects of high-fat diets on maturation, mammary gland development, and its susceptibility to transformation. Female Sprague-Dawley rats were fed a lowfat (LF), high corn oil (HCO), or high extra-virgin olive oil (HOO) diet from weaning and gavaged with 7,12-dimethylbenz[a]anthracene. Body weight and mass increased in the HCO group compared to the LF group. The vaginal opening was advanced in both high-fat groups, especially in the HCO group. This HCO group also had increased body weight around puberty, more corpora lutea at post-puberty, and tended to have higher kisspeptin levels in the hypothalamus. Both high-fat diets induced subtle modifications in the morphology of the mammary gland, with no changes on ß-casein or hormone receptors expression in the gland. The HCO diet had a clearly stimulating effect of carcinogenesis, inducing the earliest appearance of tumors and the highest tumor incidence and yield, whereas the HOO diet seemed to have a weak enhancing effect, increasing tumor yield. Our data suggest a strong influence of the HCO diet in sexual maturation and mammary cancer risk, while rats fed the HOO diet were more similar to the controls.