Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

Accuracy and reliability of pulse oximetry at different arterial carbon dioxide pressure levels.

The present study aimed to assess whether arterial carbon dioxide pressure (Pa,CO(2)) has an impact on agreement between oxygen saturation measured with pulse oximetry (Sp,O(2)) or arterial blood gas co-oximetry (Sa,O(2)). Sa,O(2) and Sp,O(2) determinations were obtained simultaneously from 846 patients under assessment for long-term home oxygen therapy in a specialised outpatient clinic. Both measurements were taken with patients seated and breathing room air. Agreement between Sa,O(2) and Sp,O(2) results was analysed by the Bland-Altman method and the Lin concordance coefficient. In addition, potential interactions of arterial oxygen tension (Pa,O(2)) or Pa,CO(2) on agreement were analysed by adjusted multivariate analysis. Upon comparison of Sa,O(2) and Sp,O(2) results, the Bland-Altman technique yielded a bias (95% confidence interval (CI)) of -1.24 (-6.86-4.38) and -1.32 (-7.78-5.15) when Pa,CO(2) >48 mmHg (6.39 kPa) or Pa,O(2) <54 mmHg (7.20 kPa), respectively. Estimate by Lin's coefficient (95% CI) in these cases was 0.88 (0.85-0.90) and 0.81 (0.77-0.85). Adjusted multivariate analysis, performed to assess the impact of pH, Pa,O(2), Pa,CO(2) and bicarbonate on bias, showed that Pa,O(2), Pa,CO(2) and their interaction terms were the most important predictors of the bias (standardised estimates of -0.54, -0.94, and 0.85, respectively). The effect of pH, although statistically significant, was small, and bicarbonate had no significant effect. Arterial carbon dioxide pressure status can contribute to impaired agreement between arterial oxygen saturation and arterial oxygen saturation measured with pulse oximetry, particularly in patients with hypercapnia.

Are the olive oil and other dietary lipids related to cancer? Experimental evidence.

There is a wealth of evidence supporting the relationship between dietary lipids and cancer, particularly those of the breast, colon and rectum and prostate. The main support comes from the international correlational studies and, especially, from experimental ones. The evidence from human analytical studies is less consistent because of several conflicting findings, probably due to methodological issues. Experimentally, it has been clearly demonstrated that quantity and type of dietary lipids as well as the particular critical phases of the carcinogenesis in which they act, are the essential factors in this relationship. Thus, whereas high dietary intake of n-6 polyunsaturated fatty acids (PUFA), primarily LA, and saturated fat has tumor-enhancing effects, long chain n-3 PUFA, CLA and GLA have inhibitory effects. Monounsaturated fatty acids (MUFA), mainly OA, present in high quantities in olive oil, seem to be protective although some inconsistent results have been reported. Bioactive compounds of virgin olive oil may also account for the protective effect of this oil, which is the main source of fat in the Mediterranean diet. Experimental studies have also provided evidence of several putative mechanisms of action of dietary lipids on cancer. Lipids can influence the hormonal status, modify cell membranes structure and function, cell signalling transduction pathways and gene expression, and modulate the function of the immune system. Although further studies are needed to evaluate and verify these mechanisms in humans, based on the multiple ways dietary lipids can act, they may have an important influence on tumorigenesis.

Are the olive oil and other dietary lipids related to cancer? Experimental evidence

There is a wealth of evidence supporting the relationship between dietary lipids and cancer, particularly those of the breast, colon and rectum and prostate. The main support comes from the international correlational studies and, especially, from experimental ones. The evidence from human analytical studies is less consistent because of several conflicting findings, probably due to methodological issues. Experimentally, it has been clearly demonstrated that quantity and type of dietary lipids as well as the particular critical phases of the carcinogenesis in which they act, are the essential factors in this relationship. Thus, whereas high dietary intake of n-6 polyunsaturated fatty acids (PUFA), primarily LA, and saturated fat has tumor-enhancing effects, long chain n-3 PUFA, CLA and GLA have inhibitory effects. Monounsaturated fatty acids (MUFA), mainly OA, present in high quantities in olive oil, seem to be protective although some inconsistent results have been reported. Bioactive compounds of virgin olive oil may also account for the protective effect of this oil, which is the main source of fat in the Mediterranean diet. Experimental studies have also provided evidence of several putative mechanisms of action of dietary lipids on cancer. Lipids can influence the hormonal status, modify cell membranes structure and function, cell signalling transduction pathways and gene expression, and modulate the function of the immune system. Although further studies are needed to evaluate and verify these mechanisms in humans, based on the multiple ways dietary lipids can act, they may have an important influence on tumorigenesis (AU)

International conference on the healthy effect of virgin olive oil.

1. Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheimer's disease, vascular dementia, cognitive decline, diabetes and cancer. 2. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. 3. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. 4. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. 5. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. 6. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. 7. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. 8. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations.

Mecanismos de activación de proto-oncogenes. Papel de la sobreexpresión génica en cáncer de mama / Proto-oncogenes activation mechanisms. Role of gene overexpression in breast cancer

Los proto-oncogenes desempeñan un papel clave en la regulación de la proliferación y diferenciación celular, junto con genes supresores, genes de reparación del ADN y genes reguladores de la apoptosis, fundamentalmente. La acumulación de sucesivas alteraciones cualitativas y/o cuantitativas de estos genes constituye la base del desarrollo del cáncer. La sobreexpresión de proto-oncogenes constituye un importante mecanismo de activación oncogénica al representar una ganancia de función y, por tanto, la estimulación de la proliferación o la supervivencia celular. La sobreexpresión génica puede estar asociada a cambios genéticos, tales como la translocación cromosómica o la amplificación génica, o a cambios epigenéticos, consistentes principalmente en alteraciones de los patrones de metilación del ADN y acetilación de las histonas. Dicha alteración es frecuente en cáncer de mama y se asocia a factores de mal pronóstico y resistencia al tratamiento. (AU)

Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells.

It has been suggested that dietary interventions may improve the effectiveness of cancer chemotherapy. We have examined the combined in vitro cytotoxicity of paclitaxel and the fatty acids gamma-linolenic acid (GLA, 18:3n-6) and oleic acid (OA, 18:1n-9) in human breast carcinoma MDA-MB-231 cells. The effect of fatty acids on paclitaxel chemosensitivity was determined by comparing IC(50) and IC(70) (50 and 70% inhibitory concentrations, respectively) obtained when the cells were exposed to IC(50) and IC(70) levels of paclitaxel alone and fatty acids were supplemented either before or during the exposure to paclitaxel. The 3-4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to determine cell growth inhibition. GLA by itself showed antiproliferative effects, and a possible GLA-paclitaxel interaction at the cellular level was assessed by the isobologram and the combination-index (CI) methods. Isobole analysis at the isoeffect levels of 50 and 70% revealed that drug interaction was predominantly synergistic when GLA and paclitaxel were added concurrently for 24 h to the cell cultures. Interaction assessment using the median-effect principle and the combination-index (CI) method showed that exposure of MDA-MB-231 cells to an equimolar combination of concurrent GLA plus paclitaxel for 24 h resulted in a moderate synergism at all effect levels, consistent with the results of the isobologram analysis. When exposure to GLA (24 h) was followed sequentially by paclitaxel (24 h) only an additive effect was observed. The GLA-mediated increase in paclitaxel chemosensitivity was only partially abolished by Vitamin E, a lipid peroxidation inhibitor, suggesting a limited influence of the oxidative status of GLA in achieving potentiation of paclitaxel toxicity. When OA (a non-peroxidisable fatty acid) was combined with paclitaxel, an enhancement of chemosensitivity was found when OA was used concurrently with paclitaxel, although less markedly than with GLA. Pretreatment of MDA-MB-231 cells with OA for 24 h prior to a 24 h paclitaxel exposure produced greater enhancement of paclitaxel sensitivity at high OA concentrations than the concurrent exposure to OA and paclitaxel. The OA-induced sensitisation to paclitaxel was not due to the cytoxicity of the fatty acid itself. When these observations were extended to three additional breast carcinoma cell lines (SK-Br3, T47D and MCF-7), simultaneous exposure to GLA and paclitaxel also resulted in synergism. GLA preincubation followed by paclitaxel resulted in additivity for all cell lines. Simultaneous exposure to paclitaxel and OA enhanced paclitaxel cytotoxicity in T47D and MCF-7 cells, but not in SK-Br3 cells, whereas preincubation with OA failed to increase paclitaxel effectiveness in all three cell lines. For comparison, the effects of other fatty acids on paclitaxel chemosensitivity were examined: GLA was the most potent at enhancing paclitaxel cytotoxicity, followed by alpha-linolenic acid (ALA; 18:3n.3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), whereas linoleic acid (LA; 18:2n-6) did not increase paclitaxel toxicity. These findings provide experimental support for the use of fatty acids as modulators of tumour cell chemosensitivity in paclitaxel-based therapy.

Alteraciones frecuentes en la expresión del oncogén PCPH en sistemas experimentales de cáncer de mama / Frequent alterations in the expression of the PCPH oncogene in experimental models of breast cancer

No disponible

El oncogén HER2 como ejemplo del progreso diagnóstico y terapéutico en cáncer de mama / The HER2 oncogene as an example of diagnostic and therapeutic progress in breast cancer

La amplificación del oncogén HER2 fue descrita en humanos en 1985; detectándose en el 20-30 por ciento de cánceres de mama. En 1987 se describió el valor pronóstico de la amplificación en cáncer de mama, y más tarde de la sobreexpresión del RNAm y de la proteína. Dos de las aplicaciones clínicas actuales del oncogén HER2 son el valor pronóstico y el valor predictivo de la sobreexpresión del gen en cáncer de mama. Una tercera aplicación de la oncoproteína HER2 es su papel como diana terapéutica para los nuevos tratamientos que están dirigidos contra la proteína HER2.En la actualidad existe el consenso de que la expresión de HER2 en carcinomas de mama tiene un valor pronóstico adverso, aunque en general es de menor importancia que el valor pronóstico que confieren indicadores clásicos como el tamaño tumoral o el número de ganglios axilares afectados.Respecto al valor predictivo de HER2, todos los estudios clínicos realizados, salvo uno, han mostrado que existe una asociación entre la expresión de HER2 y la eficacia de los tratamientos hormonales. La diferencia entre la respuesta clínica al tamoxifeno u otros tratamientos endocrinos es, en general, muy marcada, y en varios de los estudios clínicos la eficacia de la hormonoterapia en las pacientes con sobreexpresión de HER2 es de la mitad o menos de la mitad que en las pacientes sin sobreexpresión de HER2. Las investigaciones realizadas en cáncer de mama primario o metastásico sugieren que HER2 puede tener valor predictivo de resistencia a la quimioterapia. La asociación de HER2 con la resistencia a la quimioterapia es especialmente notable en tres estudios que se han realizado en pacientes con cáncer avanzado de mama, en las que se ha evaluado la expresión del dominio extracelular de HER2 en el suero, y que han mostrado que la eficacia de la quimioterapia puede verse reducida a menos de la mitad en los casos HER2 positivos. Aunque en este momento no se pueden efectuar recomendaciones terapéuticas definitivas basadas en los datos de los que se disponen, sí debe recomendarse la participación de las pacientes con sobreexpresión de HER2 en ensayos clínicos que investiguen el uso de los tratamientos estándar con o sin la adición de tratamientos dirigidos contra HER2, como el anticuerpo monoclonal Herceptin (AU)

Dietary polyunsaturated n-6 lipids effects on the growth and fatty acid composition of rat mammary tumors.

The aim of this study was to analyze the effects of a polyunsaturated n-6 high-fat diet on rat DMBA-induced breast cancer at different stages of the carcinogenesis and to investigate if changes in the tumor fatty acid composition are one of the mechanisms by which dietary lipids could exert their effects. 14 fatty acids were evaluated in 6 lipid fractions. The results firstly showed that this high-fat diet stimulated the malignant mammary tumor growth, mainly all in the promotion group. The tumor lipid analysis indicated: 1) that each lipid fraction presented distinct major fatty acids (>5%) which were not the most abundant in the diet, except in the case of the triacylglicerides, suggesting the different resistance to dietary fatty acid modification of the tumor lipid fractions; 2) a higher arachidonic acid content in the fractions with less linoleic acid, above all in phospholipids, particularly in the phosphatidylethanolamine, indicating a different efficiency of conversion; 3) the three most abundant fatty acids in the dietary lipid (18:2n-6, 18:1n-9 and 16:0) were those which essentially displayed the differences between groups; thus, the high-fat diet changed the tumor lipid profile, increasing the 18:2n-6 relative content and decreasing that of the 18:1n-9; differences were significant in phosphatidylcholine, free fatty acids and triacylglycerides. Any change was obtained in the phosphatidylinositol. The greatest number of differences was found in the promotion group. Taken as a whole, our results suggest the different roles of lipid fractions in breast cancer cells and an association between cancer malignancy and the content of linoleic and oleic acids.

An improved protocol to increase sensitivity of Southern blot using dig-labelled DNA probes.

The use of methods for nonradioactive labelling of nucleic acids has increased in recent years because they avoid disadvantages associated with radioisotopes. The most frequently used label is digoxigenin (DIG). The greatest problem of nonradioactive methods is their high nonspecific background mainly caused by the multistep detection. A diffuse background can mask the specific signal; furthermore nonspecific signals can make it difficult to interpret the result. In this study we have attempted to identify elements which could generate background. We have also determined the probe and antibody concentrations by which the higher sensitivity is obtained.

Ha-ras in normal and tumoral tissues: structure, function and regulation.

The c-Ha-ras1 gene belongs to an eucaryotic ubiquitous gene family which codes important molecules involved in the transduction of mitogenic signals and of cellular differentiation. The c-Ha-ras1 estructure, in four coding exons and a non-coding 5'exon, is highly preserved throughout evolution. This gene, which generates a 1.4 Kb transcript, is expressed in practically all the cell lineages with a tissue-specific pattern. The coded protein, of 189 amino acids and 21 kDa, is a small protein that binds guanine nucleotides (GTP/GDP), is associated with the plasma membrane and possesses low intrinsic GTPase activity. p21ras functions as a molecular switch active when GTP is bound to it and inactive in the GDP-bound form. Its activity is very tightly controlled in the cell by various positive and negative control mechanisms. The ras gene family is the most frequently involved in the development of human and animal tumors. Qualitative (point mutations) and quantitative (over expression) mechanisms of oncogenic activation have been described. The possible relation between determined human Ha-ras1 alleles and the predisposition to cancer has been suggested as well.

Experimental diets for the study of lipid influence on the induced mammary carcinoma in rats: II--Suitability of the diets.

We have previously reported one method for obtention of experimental diets for the study of the effects of dietary lipids on the rat breast carcinoma. The purpose of this second part of the study was to develop a quality control system for demonstrating the suitability of these diets. This system is essentially based on the animals' growth control, their period clinical examination as well as the anatomopathological postmortem study of the animals submitted to such diets. Two groups of weaning rats, control (C) and hyperlipidic (HL), were submitted to a low-fat diet (N3) or a high-fat polyunsaturated--corn oil--diet (HL20) respectively. At 53 days of age all animals were induced with 5mg of dimethylbenz (a) anthracene. Experiments were ended when animals reached a mean age of 214 days. The results show: 1) a normal ponderal evolution of the animals in the two experimental groups with respect to two series of the same strain fed with a standard diet, and 2) the homogeneity of growth determined by the coefficient of variance study. On the other hand, neither the weekly clinical examination nor the anatomopathological post-mortem studies revealed any pathology that could be specifically attributed to nutritional imbalance. These results confirm the suitability of both diets for rat growth. Their use in the study of the effects of dietary lipids on the mammary carcinoma would satisfy the initial aim of guaranteeing the specificity of the results.

Experimental diets for the study of lipid influence on the induced mammary carcinoma in rats: I--Diet definition.

There is a considerable variation in the diets used in studies on the influence of dietary fat on rat mammary cancer. In view of the fact that diet is the most remarkable factor in these studies, the aim of this work was to define two experimental diets, one of them normal (N3) and another hyperlipidic (HL20), both allowing the normal growth of the rat and neither of them containing factors that could unspecifically affect mammary carcinogenesis. Semisynthetic diets were selected instead of natural ones. A normal diet (3% corn oil, 18% casein, 67.9% dextrose) and a hyperlipidic diet (20% corn oil, 23% casein, 45.9% dextrose) were defined for the rat. Both diets also contain 5% cellulose, 5.9% salt mix and 0.24% vitamin mix. In order to avoid the influence of the above mentioned unspecific factors, the control of specificity and quality of nutrients is proposed as an essential measure. Moreover, it is also necessary to adopt measures to avoid the presence of fatty acid metabolites, including the calculation of the necessary vitamin E, selenium and sulfur amino acid and the determination of factors potentially able to stimulate or inhibit carcinogenesis such as phenolic antioxidants, retinoids or the trans isomer of fatty acids. On the other had, casein, dextrose, choline and folic acid contents were modified in order to equilibrate the lipid increase experimentally introduced in the HL20 diet or to ensure the normal maintenance of the animals' metabolism. The method used is based on the concept of quality assurance.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of an androgenic derivative on the development of chemically-induced mammary carcinogenesis in the rat.

The effects of an androgenic derivative--danazol--on the development of dimethylbenz(a)anthracene (DMBA)-rat mammary carcinogenesis were studied. Animals in the treated group received danazol (10-12 mg/kg/day) during 169 days, starting 5 days after DMBA induction. As compared with tumours in control animals, those treated with danazol appear later and are significantly smaller. Moreover, this treatment reduced the incidence of animals affected by mammary cancer and the average number of malignant tumours in each animal. In the same way, the incidence of animals with missing nodules was significantly higher in the group treated with danazol. It is concluded that danazol has an inhibitory effect on experimental mammary tumours. This effect seems to be greater the earlier the treatment is started and the longer time it is applied.

Study of the ability of proton nuclear magnetic resonance spectroscopy of human plasma to differentiate between controls and breast cancer patients.

Water-suppressed proton nuclear magnetic resonance spectroscopy of plasma had been proposed as a technique for detecting malignant tumors although its general diagnostic value is widely contested. To assess its diagnostic value in screening for breast cancer, we collected and analyzed 108 plasma samples from healthy women and women with breast disorders, mainly adenocarcinomas. No significant differences were found between controls and patients when average methylene-methyl linewidths were compared. Significant differences, however, were observed when methylene linewidths were compared. Unfortunately, the marked overlapping of both groups greatly reduced the possible diagnostic value of the technique. Among the various biochemical parameters analyzed for each plasma sample--triglyceride, total cholesterol and HDL cholesterol concentration, altered levels of carcinoembryonic antigen, phosphohexose isomerase, 5'-nucleotidase and phosphatase alkaline in patient samples, and estrogen and progesterone receptors of tumors--only triglyceride concentrations presented a clear inverse linear correlation with methylene linewidths.

Amine oxidase activities in rat breast cancer induced experimentally with 7,12-dimethylbenz(alpha)anthracene.

The activities and distribution of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) in solid breast tumour induced in the rat by treatment with 7,12-dimethylbenz(alpha)anthracene (DMBA) were studied. The mammary tumours were classified according to anatomopathological criteria into: the benign fibroadenoma (FAD) and the malignant adenocarcinoma (ADC) and infiltrant adenocarcinoma (I-ADC). The proportions of total MAO (15%) and SSAO activities (85%) did not change with malignancy. However, an increasing degree of malignancy was associated with an increase in MAO-A activity and a decrease in MAO-B and SSAO activities. Kinetic constants were calculated for SSAO and for each MAO form separately, using specific substrates. The Km values did not change significantly with the degree of malignancy, but Vmax values for MAO-A increased whereas Vmax for SSAO and MAO-B diminished with malignancy. The dependence of SSAO activity on protein concentration indicated the presence of endogenous reversible inhibitory material in extracts from the more malign tumours. This inhibitor was associated with the microsomal fraction and was not removed by dialysis. It was also present in detergent-solubilized extracts, suggesting that the phenomenon might be due to an association of the enzyme itself producing an inactive species.

Effects of an androgenic derivative on pre-established mammary tumours chemically induced in the rat.

The effects were studied of an androgenic derivative--danazol--administered at doses of 10-12 mg kg-1 day-1 during 97 days to rats with dimethylbenz[a] anthracene-induced mammary tumours. Our main observations were as follows. (a) Danazol did not influence ovarian function at the end of the assay. (b) The treatment with danazol reduced the incidence (P less than 0.05), number of tumours (P less than 0.05) and volume of malignant mammary tumours; on the other hand, the values of these parameters for benign tumours and those of doubtful expression were similar in both experimental groups. (c) Such differential action of Danazol seems to be due to the different incidence and/or content of receptors of both types of tumours. (d) The latter results lead to a hypothesis for the mechanism of action of danazol based on its behaviour at different levels.

Hormone-dependence of experimental mammary tumours.

The effect of hormones on mammary tumours induced experimentally in animals are revised. It is stated that the effect on tumoural induction and/or growth may depend on their concentration and on the moment, in relation to animal exposure to the carcinogen, in which they are administered. The presently known action mechanisms are also indicated, bringing out the importance of the increased level of differentiation which high estrogen doses induce, as well as some effects of progesterone and pregnancy in the protection against experimental cancer and its promoters. The efficacy of therapeutic ablative operations--ovariectomy, hypophysectomy and adrenalectomy--and additive ones--antihormones--in tumor regression, is shown. Finally the molecular bases of hormonedependence of experimental mammary tumours is established, while trying to provide an integrated concept between: hormones, receptor, growth factors, oncogens and experimental carcinogenesis.