Showing papers by "Javier A. Menendez published in 2009"
TL;DR: It is demonstrated that HER2 oncoprotein itself may represent a key cellular target involved in the anti-breast cancer actions of metformin, and the presence/absence of molecular hallmarks such as HER2 overexpression and/or p70S6K1 hyperactivation might dictate alternative responses in meetformin-based treatment of early breast cancer.
Abstract: Population studies have revealed that treatment with the anti-diabetic drug metformin significantly associates with reduced breast cancer risk. Animal studies have shown that metformin suppresses the development of mammary carcinomas in transgenic female mice carrying a HER2 oncogene, but not that of spontaneous tumors. We herein demonstrate that HER2 oncoprotein itself may represent a key cellular target involved in the anti-breast cancer actions of metformin. First, ectopical overexpression of HER2 oncogene significantly enhances metformin-induced breast cancer cell growth inhibition. Second, metformin treatment drastically down-regulates HER2 protein levels (up to 85% reduction) in a dose- and time-dependent manner. Metformin-induced inhibition of HER2 take places regardless the molecular mechanism contributing to HER2 overexpression (i.e., human HER2 cDNA exogenously driven by a viral promoter and naturally occurring endogenous HER2 gene amplification). Mechanistically, metformin-induced suppress...
247 citations
TL;DR: This is the first report showing that HER2-overexpressing breast cancer cells chronically exposed to Tzb exhibit a bona fide up-regulation of the autophagic activity that efficiently works to protect breast cancers cells from the growth-inhibitory effects of Tzb.
Abstract: Autophagy has been emerging as a novel cytoprotective mechanism to increase tumor cell survival under conditions of metabolic stress and hypoxia as well as to escape chemotherapy-induced cell death. To elucidate whether autophagy might also protect cancer cells from the growth inhibitory effects of targeted therapies, we evaluated the autophagic status of preclinical breast cancer models exhibiting auto-acquired resistance to the anti-HER2 monoclonal antibody trastuzumab (Tzb). We first examined the basal autophagic levels in Tzb-naive SKBR3 cells and in two pools of Tzb-conditioned SKBR3 cells (TzbR), which optimally grow in the presence of Tzb doses as high as 200 µg/ml Tzb. Fluorescence microscopic analyses revealed that the number of punctate LC3 structures -a hallmark of autophagy- was drastically higher in Tzb-refractory cells than in Tzb-sensitive SKBR3 parental cells. Immunoblotting analyses confirmed that the lipidation product of the autophagic conversion of LC3 was accumulated to high levels in TzbR cells. High levels of the LC3 lipidated form in Tzb-refractory cells were accompanied by decreased p62/sequestosome-1 protein expression, a phenomenon characterizing the occurrence of increased autophagic flux. Moreover, increased autophagy was actively used to survive Tzb therapy as TzbR pools were exquisitely sensitive to chemical inhibitors of autophagosomal formation/function. Knockdown of LC3 expression via siRNA similarly resulted in reduced TzbR cell proliferation and supra-additively interacted with Tzb to re-sensitize TzbR cells. Sub-groups of Tzb-naive SKBR3 parental cells accumulated LC3 punctate structures and decreased p62 expression after treatment with high-dose Tzb, likely promoting their own resistance. This is the first report showing that HER2-overexpressing breast cancer cells chronically exposed to Tzb exhibit a bona fide up-regulation of the autophagic activity that efficiently works to protect breast cancer cells from the growth-inhibitory effects of Tzb. Therapeutic targeting autophagosome formation/function might represent a novel molecular avenue to reduce the emergence of Tzb resistance in HER2-dependent breast carcinomas.
239 citations
TL;DR: The use of insulin sensitizers in parallel with forthcoming FASN inhibitors should be a valuable therapeutic approach that, in association with lifestyle interventions, would concurrently improve energy-flux status, ameliorate insulin sensitivity, and alleviate the risk of lipogenic carcinomas.
Abstract: Background: An emerging paradigm supports the notion that deregulation of fatty acid synthase (FASN)-catalyzed de novo FA biogenesis could play a central role in the pathogenesis of metabolic diseases sharing the hallmark of insulin-resistance.
Content: We reviewed pharmacological and genetic alterations of FASN activity that have been shown to significantly influence energy expenditure rates, fat mass, insulin sensitivity, and cancer risk. This new paradigm proposes that insulin-resistant conditions such as obesity, type 2 diabetes, and cancer arise from a common FASN-driven “lipogenic state”. An important question then is whether the development or the progression of insulin-related metabolic disorders can be prevented or reversed by the modulation of FASN status. If we accept the paradigm of FASN dysfunction as a previously unrecognized link between insulin resistance, type 2 diabetes, and cancer, the use of insulin sensitizers in parallel with forthcoming FASN inhibitors should be a valuable therapeutic approach that, in association with lifestyle interventions, would concurrently improve energy-flux status, ameliorate insulin sensitivity, and alleviate the risk of lipogenic carcinomas.
Conclusions: Although the picture is currently incomplete and researchers in the field have plenty of work ahead, the latest clinical and experimental evidence that we discuss illuminates a functional and drug-modifiable link that connects FASN-driven endogenous FA biosynthesis, insulin action, and glucose homeostasis in the natural history of insulin-resistant pathologies.
165 citations
TL;DR: The phenolic fraction and other polar compounds of the Hibiscus sabdariffa were separated and identified by HPLC with diode array detection coupled to electrospray TOF and IT tandem MS in order to obtain molecular formula and exact mass.
Abstract: The phenolic fraction and other polar compounds of the Hibiscus sabdariffa were separated and identified by HPLC with diode array detection coupled to electrospray TOF and IT tandem MS (DAD-HPLC-ESI-TOF-MS and IT-MS). The H. sabdariffa aqueous extract was filtered and directly injected into the LC system. The analysis of the compounds was carried out by RP HPLC coupled to DAD and TOF-MS in order to obtain molecular formula and exact mass. Posterior analyses with IT-MS were performed and the fragmentation pattern and confirmation of the structures were achieved. The H. sabdariffa samples were successfully analyzed in positive and negative ionization modes with two optimized linear gradients. In positive mode, the two most representative anthocyanins and other compounds were identified whereas the phenolic fraction, hydroxycitric acid and its lactone were identified using the negative ionization mode.
99 citations
TL;DR: A primordial mitotic role for the α catalytic AMPK subunit in the eukaryotic evolutionary process as it may ensure, at the cell level, an exquisite coordination between sensing of energy resources and the fundamental biological process of genome division.
Abstract: The metabolic rheostat AMP-activated protein kinase (AMPK) is unexpectedly required for proper cell division and faithful chromosomal segregation during mitosis. Although it is conceptually attractive to assume that AMPK-interpreted microenvironmental bioenergetics may strictly engage cell’s energy status, cell grow, and cell division to avoid that energy stresses trigger cell death, the ultimate framework of AMPK activity towards chromosomal and cytoskeletal mitotic regulation is a question that remains unanswered. We herein reveal that the active form of the α-catalytic AMPK subunit (P-AMPKαThr172) -but not its total form (AMPKα)- transiently associates with several mitotic structures including centrosomes, spindle poles, the central spindle midzone and the midbody throughout all of the mitotic stages and cytokinesis in human cancer-derived epithelial cells. At prophase, P-AMPKαThr172 associates with the two asters of microtubules that begin to nucleate from mature centrosomes. The overlapping localiz...
94 citations
TL;DR: It is suggested that molecular co-evolution of the energy-sensing cytokinetic tumor suppressor AMPK within the chronic biophysical constraints of the tumor microenvironment may inherently promote a continuous generation of structural and numerical changes in chromosomes favoring generation of nascent tumor cells and/or tumor-initiating cells over tumor cell death.
Abstract: The AMP-activated protein kinase (AMPK) system, an evolutionary conserved low-energy checkpoint, functions as a canonical suppressor of cell proliferation. Proliferating cells, however, should also ensure a proper spatio-temporal bond between AMPK-sensed cell's metabolic status and cell division. A crucial linkage between cell proliferation and AMPK-interpreted cell bioenergetics appears to take place during the M-phase of the cell cycle. A recent description of a physical interplay between the active form the alpha-catalytic AMPK subunit with essential mitotic regulators in the centrosome and midbody has provided direct evidence that tumor-suppressive properties for AMPK closely relate to its ability to exquisitely coordinate sensing of energy resources and the fundamental biological process of genome division during mitosis and cytokinesis. Based on recent findings in our laboratory observing abortive cytokinesis followed by nuclear shape reorganization, mitotic catastrophe, polyploidization events, and cell giantism in p53-null cancer cells pharmacologically manipulated to exhibit sustained activation of AMPK, we now propose that AMPK is a novel and biologically significant participant with a tumor suppressive activity in the mitotic/cytokinetic phase of the cell cycle. In this scenario, molecular co-evolution of the energy-sensing cytokinetic tumor suppressor AMPK within the chronic biophysical constraints of the tumor microenvironment may inherently promote a continuous generation of structural and numerical changes in chromosomes favoring generation of nascent tumor cells and/or tumor-initiating cells over tumor cell death.
70 citations
TL;DR: Lapatinib-refractory models recently developed at the bench and the survival pathways discovered are reviewed and the unexpected ability of the anti-type II diabetes drug metformin to inactivate mTOR and decrease p70S6K1 activity further reveals that this biguanide, generally considered non-toxic and remarkably inexpensive, might be considered for new combinatorial lapatinIB-based protocols in HER2-overexpressing breast cancer patients.
Abstract: The small molecule HER2 tyrosine kinase inhibitor (TKI) lapatinib (Tykerb®) is approved for the therapy of patients with HER2-positive breast carcinomas who have progressed on trastuzumab (Herceptin®). Unfortunately, the efficacy of this HER2 TKI is limited by both primary (inherent) and acquired resistance, the latter typically occurring within 12 months of starting therapy. One of the key factors limiting our understanding of the mechanisms involved in lapatinib resistance is the lack of published preclinical models. We herein review lapatinib-refractory models recently developed at the bench and the survival pathways discovered. As hyperactivation of the pharmacologically targetable PI3K/mTOR/p70S6K1 axis appears to be central to the occurrence of lapatinib resistance, preclinical data showing enhanced antitumour effects when combining lapatinib with mTOR inhibitors (e.g., rapamycin analogues and NVP-BEZ235) highlight the importance of translational work to yield clinically useful regimens capable of delaying or treating lapatinib resistance. The unexpected ability of the anti-type II diabetes drug metformin to inactivate mTOR and decrease p70S6K1 activity further reveals that this biguanide, generally considered non-toxic and remarkably inexpensive, might be considered for new combinatorial lapatinib-based protocols in HER2-overexpressing breast cancer patients.
65 citations
TL;DR: It is revealed that, at doses that lead to activation of the AMP-activated protein kinase (AMPK), metformin not only down-regulates genes coding for ribosomal proteins but unexpectedly suppresses numerous mitosis-related gene families including kinesins, tubulins, histones, auroras and polo-like kinases.
Abstract: Prompted by the ever-growing scientific rationale for examining the antidiabetic drug metformin as a potential antitumor agent in breast cancer disease, we recently tested the hypothesis that the assessment of metformin-induced global changes in gene expression –as identified using 44K (double density) Agilent’s whole human genome arrays- could reveal gene-expression signatures that would allow proper selection of breast cancer patients who should be considered for metformin-based clinical trials. Using Database for Annotation, Visualization and Integrated Discovery bioinformatics (DAVID) resources we herein reveal that, at doses that lead to activation of the AMP-activated protein kinase (AMPK), metformin not only down-regulates genes coding for ribosomal proteins (i.e. protein and macromolecule biosynthesis) but unexpectedly suppresses numerous mitosis-related gene families including kinesins, tubulins, histones, auroras and polo-like kinases. This is, to our knowledge, the first genome-scale evidence ...
56 citations
TL;DR: The fragmentation pathway of oleuropein aglycon was successfully elucidated and all possible transformations among isomers of olurope in agly Con were suggested.
Abstract: In this work, rapid-resolution liquid chromatography (RRLC) coupled to electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) and ion trap multiple mass spectrometry (IT-MS(n)) has been applied to separate and characterize eleven isomers of oleuropein aglycon in fourteen Spanish extra-virgin olive oils. After the extra-virgin olive oil sample had been dissolved in hexane and cleaned up by a diol-bonded phase solid-phase extraction (SPE) cartridge, the eluting extract was resolved in methanol and analyzed on an Angilent 1200 system with a 4.6 x 150 mm, 1.8 microm Zorbax Eclipse plus C18 column. Mass spectrometry was carried out on a Bruker Daltonics microTOF mass spectrometer and a Bruker Daltonics ion trap mass spectrometer. The characterization of isomers of oleuropein aglycon was based on accurate mass data and the isotope function of characteristic fragment ions in the studied compounds by TOF-MS, and the fragment ions were further confirmed by IT-MS(n). The fragmentation pathway of oleuropein aglycon was successfully elucidated and all possible transformations among isomers of oleuropein aglycon were suggested.
51 citations
TL;DR: A definitive elucidation of phospho-AMPKalpha(Thr172) in coordinating the chromosomal and cytoskeletal events of mitosis might radically amend the current perception of other AMPK-related diseases such as obesity, cardiac hypertrophy or accelerated aging syndromes.
Abstract: When interrogating the activation status of AMP-activated protein kinase-measured as AMPKalpha(Thr172) phosphorylation-in tissue sections of human carcinomas and in cultured human cancer cells, the spatiotemporal dynamics of AMPK activity during the G(1)/S-to-M-phase transition strikingly resembles that of well-characterized "chromosomal passenger" proteins such as Aurora B, INCENP or Histone H3. The mitotic kinase behavior of the active form of AMPK may represent a candidate molecular link through which energy status directly influences tumorigenesis. A definitive elucidation of phospho-AMPKalpha(Thr172) in coordinating the chromosomal and cytoskeletal events of mitosis might radically amend our current perception of other AMPK-related diseases such as obesity, cardiac hypertrophy or accelerated aging syndromes.
47 citations
TL;DR: Rapid-resolution liquid chromatography coupled with electrospray time-of-flight mass spectrometry (ESI-TOF-MS and ESI-IT-MS) has been applied to separate and characterize the phenolic compounds in five Spanish extra virgin olive oils.
Abstract: Rapid-resolution liquid chromatography (RRLC) coupled with electrospray time-of-flight mass spectrometry (ESI-TOF-MS) and electrospray ion-trap multiple mass spectrometry (ESI-IT-MS(n)) has been applied to separate and characterize the phenolic compounds in five Spanish extra virgin olive oils. The phenolic compounds were characterized on the basis of accurate mass data according to studies by TOF-MS, and the fragmentation ions were further confirmed by IT-MS(n) whenever possible. Eight compounds, hydroxytyrosol (m/z 153), tyrosol (m/z 137), deacetoxy oleuropein aglycon (m/z 319), luteolin (m/z 285), pinoresinol (m/z 357), acetoxypinoresinol (m/z 415), apigenin (m/z 269), and deacetoxy ligstroside aglycon (m/z 303), all normally found in olive oil, were characterized in all five samples. Nevertheless, 30 uncommon phenolic compounds, including 10 ligstroside aglycon isomers (m/z 361) and two methyl oleuropein aglycon isomers (m/z 391), were also characterized in some of the five samples, and their fragmentation pathways were successfully elucidated.
TL;DR: Whether serum FASN (sFASN) could associate with circulating HER2 extracellular domain (HER2 ECD) in the blood of metastatic breast cancer patients and if quantitative determination of FASn molecules in blood could become a rapid and accurate non-invasive test to monitor disease progression and survival in HER2-overexpressing MBC undergoing Her2-targeted therapies is investigated.
Abstract: Clinicopathological assessment of the functional relationship between the HER2 oncogene and tumor-associated fatty acid synthase (FASN) is largely precluded because immunohistochemical and/or mRNA studies should be performed in biopsies from breast cancer patients. We here sought to determine whether serum FASN (sFASN) could associate with circulating HER2 extracellular domain (HER2 ECD) in the blood of metastatic breast cancer (MBC) patients. Concentrations of serum FASN and HER2 ECD were measured with ELISA in sera retrospectively obtained from 201 patients with metastatic breast cancer (MBC) and 31 healthy subjects. Mechanistical in vitro studies were performed using pharmacological inhibitors of HER2 and FASN as well as cultured cancer cells engineered to overexpress HER2 and FASN human genes. When the upper limit of normal sFASN was defined as the mean + 2SD of the control group, sFASN was elevated above this cut-off (12 ng/ml) in 70 MBC patients (35%). Eighty-nine MBC patients (44%) had elevated levels of HER2 ECD (HER2 ECD cut-off = 15 ng/ml). HER2 ECD-positive MBC patients slightly increased their sFASN levels compared with HER2 ECD-negative MBC patients. sFASN-positive MBC patients had significantly increased levels of HER2 ECD when compared with sFASN-negative MBC patients (mean HER2 ECD=34 ng/ml, 95% CI 26-41 ng/ml and 18 ng/ml -95% CI 15-21 ng/ml, respectively; p=0.002). Sixty percent of sFASN-positive patients concurrently exhibited high levels of HER2 ECD whereas 64% of sFASN-negative patients were negative for circulating HER2 ECD. In vitro studies revealed that BC cells bearing HER2 gene-amplification released higher levels of extracellular FASN than HER2-negative BC cells. Trastuzumab-induced blockade of HER2 ECD shedding failed to prevent FASN release and retrovirally-induced HER2 overexpression in MCF-7 cells did not increase extracellular FASN. Of note, pharmacological inhibition of FASN activity significantly decreased HER2 ECD levels in the supernatant of HER2-overexpressing BC cells while transient overexpression of FASN gene in HBL100 cells promoted FASN protein release and concomitantly increased HER2 ECD shedding into the extracellular milieu. Subsequent studies should explore if quantitative determination of FASN molecules in blood could become a rapid and accurate non-invasive test to monitor disease progression and survival in HER2-overexpressing MBC undergoing HER2-targeted therapies.
TL;DR: 2‐D‐HPLC‐CE‐MS provides enough resolving power to separate hundreds of compounds from highly complex samples, such as olive oil and in vitro studies of its anti‐carcinogenic capacity are concluded.
Abstract: A 2-D-HPLC/CE method was developed to separate and characterize more in depth the phenolic fraction of olive oil samples. The method involves the use of semi-preparative HPLC (C18 column 250x10 mm, 5 microm) as a first dimension of separation to isolate phenolic fractions from commercial extra-virgin olive oils and CE coupled to TOF-MS (CE-TOF-MS) as a second dimension, to analyze the composition of the isolated fractions. Using this method, a large number of compounds were tentatively identified, some of them by first time, based on the information concerning high mass accuracy and the isotopic pattern provided by TOF-MS analyzer together with the chemical knowledge and the behavior of the compounds in HPLC and CE. From these results it can be concluded that 2-D-HPLC-CE-MS provides enough resolving power to separate hundreds of compounds from highly complex samples, such as olive oil. Furthermore, in this paper, the isolated phenolic fractions have been used for two specific applications: quantification of some components of extra-virgin olive oil samples in terms of pure fractions, and in vitro studies of its anti-carcinogenic capacity.
TL;DR: Results reveal for the first time that PP-mTOR(Ser2481) may be unexpectedly involved in the terminal stages of cytokinesis.
TL;DR: Immunoblotting procedures using a battery of anti-FASN antibodies and ELISA-based analyses revealed that extracellular FASN dramatically augmented in a dose- and time-dependent manner, suggesting that FASn release might represent a previously unrecognized mechanism through which AMPK monitor and restores cellular energy state in response to increasing AMP/ATP ratios.
TL;DR: Investigation of the spatio-temporal sub-cellular distribution of the Serine 2481-autophosphorylated form of mTOR during the G(1)/S-to-M-phase transition observed that mitotic cells notably accumulated a distinct pattern of nuclear and cytoplasmic immunolabelings of PP-mTOR(Ser2481).
Abstract: The prognostic abilities of breast cancer gene expression signatures are due mostly to the detection of proliferation activity. One of the strongest, yet simple and well-reproducible proliferation-associated prognostic factors is the mitotic activity index (MAI). However: a) counting mitotic figures is regarded by many histopathologists as cumbersome and time-consuming, and b) most available immunohistochemical markers are much weaker predictors than the MAI. We have investigated the spatio-temporal sub-cellular distribution of the Serine 2481-autophosphorylated form of mTOR (PP-mTOR(Ser2481)) during the G(1)/S-to-M-phase transition both in cultured cancer cells and in cancer tissue specimens. Using a high-resolution, automated confocal high-content imaging system, we observed that mitotic cells notably accumulated a distinct pattern of nuclear and cytoplasmic immunolabelings of PP-mTOR(Ser2481). Parallel experiments examining site-specific phosphorylation (i.e., Serine 10 and Serine 28) of the G(2)/M marker Histone H3 (PP-H3) revealed that PP-H3(Ser10/Ser28) staining efficiently detected mitotic cells from prophase until the beginning of anaphase, but not during late anaphase, telophase and cytokinesis. PP-mTOR(Ser2481) staining associated near and between separating chromosomes not only during early mitotic stages but also to the midzone and to midbody at ana/telophase through cytokinesis. We then evaluated the usefulness of PP-mTOR(Ser2481) immunostaining for improving the efficiency of mitotic counting using. Anti-PP-mTOR(Ser2481)-labeled mitotic figures (MFs) were easily seen and permitted a quick identification of mitotic hotspots in formalin-fixed cancer tissues, even at low magnification. Importantly, average mitotic counts were significantly higher when using PP-mTOR(Ser2481) staining than with the hematoxylin and eosin (H&E) protocol in breast cancer core biopsies. Mitotic count based on PP-mTOR(Ser2481) immunostaining increased tumor grade by one grade in 2 of 9 breast carcinomas. These findings warrant forthcoming studies to confirm both the accuracy and the prognostic value of PP-mTOR(Ser2481) as a novel high-contrast immunohistochemical mitosis marker in larger populations of human breast carcinomas.
TL;DR: Adult white men with the Ile 1483 variant of the FASn gene seem protected from developing central obesity through decreased adipose tissue FASN activity.
Abstract: The Val1483Ile polymorphism in the human fatty acid synthase (FASN) gene is located within the interdomain region of the FASN close to the two dynamic active centers of the FASN enzyme and putatively affects FASN action. We aimed to evaluate the association of this polymorphism with obesity phenotypes, insulin sensitivity, and adipose tissue FASN activity in adult white subjects. The polymorphism was evaluated in association with metabolic variables in two independent studies: in a case-control study of 457 men (229 with normal glucose tolerance (NGT) and 228 with altered glucose tolerance (AGT)); and in 600 population-based NGT subjects (274 men and 326 women). Adipose tissue FASN activity was analyzed using the method of Nepokroeff. The Ile variant was associated with a lower waist-to-hip ratio (WHR) and a lower increase in weight over a 7-year period in NGT men. In a subset of 147 men, carriers of the Ile variant showed significantly increased insulin sensitivity. BMI (P < 0.001), WHR (P = 0.03), and Val1483Ile (P = 0.03), contributed independently to 37% of insulin sensitivity variance. In men from the population-based study, the Ile variant was associated with a lower BMI, WHR, fasting glucose, and systolic blood pressure compared with carriers of the Val variant. In agreement with these results, the adipose tissue FASN activity was significantly lower in subjects with the Ile variant (P = 0.01). In summary, adult white men with the Ile 1483 variant of the FASN gene seem protected from developing central obesity through decreased adipose tissue FASN activity.
TL;DR: Serum FASN concentrations are increased in patients with chronic liver impairment, and are associated with specific histological alterations and biochemical markers of portal inflammation, which suggest that FASn measurement may contribute significantly to the evaluation of these patients.
Abstract: Background: Fatty acid synthase (FASN) is an enzyme synthesized by the liver and plays an important role in lipogenesis. The present study aimed to assess whether serum FASN concentrations are altered in patients with chronic liver disease, and to investigate whether its measurement may be a useful tool in the clinical evaluation of this derangement. Methods: We investigated 93 patients with chronic liver disease (14 minimal change disease, 79 steatohepatitis) and 100 control subjects. Serum FASN concentrations were measured using ELISA. Results: Patients had a significant increase in serum FASN concentration (p<0.001), which was specifically associated with the hepatic Knodell sub-index III of portal inflammation (p=0.019). In addition, serum FASN concentrations were significantly correlated with the circulating levels of the monocyte chemoattractant protein-1 (MCP-1) (Spearman p=0.375; p<0.001) and type III procollagen-N-peptide (P-III-P) (Spearman p=0.297; p<0.001). Conclusions: Serum FASN concentrations are increased in patients with chronic liver impairment, and are associated with specific histological alterations and biochemical markers of portal inflammation. These data suggest that FASN measurement may contribute significantly to the evaluation of these patients. .
Patent•
04 Mar 2009
TL;DR: The use of polyphenol compounds present in extra virgin olive oil for the treatment of cancer, as well as pharmaceutical compositions containing same and to the use thereof in the production of drugs is discussed in this article.
Abstract: The invention relates to the use of polyphenol compounds present in extra virgin olive oil for the treatment of cancer, as well as to pharmaceutical compositions containing same and to the use thereof in the production of drugs.
Patent•
04 Mar 2009
TL;DR: The presente invencion se refiere al uso de compuestos polifenoles presentes en el aceite de oliva virgen extra for el tratamiento del cancer, asi como a composiciones farmaceuticas que los comprenden and al use of las mismas in la fabricación de medicamentos.
Abstract: La presente invencion se refiere al uso de compuestos polifenoles presentes en el aceite de oliva virgen extra para el tratamiento del cancer, asi como a composiciones farmaceuticas que los comprenden y al uso de las mismas en la fabricacion de medicamentos.
Patent•
04 Mar 2009
TL;DR: In this article, a presente invention concerne l'utilisation de composes polyphenoliques d'huile d'olive vierge extra dans le traitement du cancer, ainsi que des compositions pharmaceutiques comprenant lesdits composes.
Abstract: La presente invention concerne l'utilisation de composes polyphenoliques d'huile d'olive vierge extra dans le traitement du cancer, ainsi que des compositions pharmaceutiques comprenant lesdits composes et l'utilisation desdites compositions dans la fabrication de medicaments.