22 research outputs found
A plasma metabolomic signature discloses human breast cancer
Purpose: Metabolomics is the comprehensive global study of metabolites in
biological samples. In this retrospective pilot study we explored whether serum
metabolomic profile can discriminate the presence of human breast cancer irrespective
of the cancer subtype.
Methods: Plasma samples were analyzed from healthy women (n = 20) and
patients with breast cancer after diagnosis (n = 91) using a liquid chromatographymass
spectrometry platform. Multivariate statistics and a Random Forest (RF) classifier
were used to create a metabolomics panel for the diagnosis of human breast cancer.
Results: Metabolomics correctly distinguished between breast cancer patients
and healthy control subjects. In the RF supervised class prediction analysis comparing
breast cancer and healthy control groups, RF accurately classified 100% both samples
of the breast cancer patients and healthy controls. So, the class error for both group
in and the out-of-bag error were 0. We also found 1269 metabolites with different
concentration in plasma from healthy controls and cancer patients; and basing on
exact mass, retention time and isotopic distribution we identified 35 metabolites.
These metabolites mostly support cell growth by providing energy and building
stones for the synthesis of essential biomolecules, and function as signal transduction
molecules. The collective results of RF, significance testing, and false discovery rate
analysis identified several metabolites that were strongly associated with breast
cancer.
Conclusions: In breast cancer a metabolomics signature of cancer exists and can
be detected in patient plasma irrespectively of the breast cancer type.Spanish Ministry of Economy and Competitiveness, Institute Carlos III (FIS grant)
PI14/00328Generalitat de Catalunya
2014SGR168FEDER funds from the European Union ('Una manera de hacer Europa'
Curcumin and Health
Nowadays, there are some molecules that have shown over the years a high capacity to act against relevant pathologies such as cardiovascular disease, neurodegenerative disorders or cancer. This article provides a brief review about the origin, bioavailability and new research on curcumin and synthetized derivatives. It examines the beneficial effects on health, delving into aspects such as cancer, cardiovascular effects, metabolic syndrome, antioxidant capacity, anti-inflammatory properties, and neurological, liver and respiratory disorders. Thanks to all these activities, curcumin is positioned as an interesting nutraceutical. This is the reason why it has been subjected to several modifications in its structure and administration form that have permitted an increase in bioavailability and effectiveness against different diseases, decreasing the mortality and morbidity associated to these pathologies
Hypoxia-Inducible Factor-1 Alpha Expression Is Predictive of Pathological Complete Response in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy
Supplementary Materials
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cancers14215393/s1, Table S1: Relation between HIF-1α expression and pAKT and pMAPK; Table S2: Logistic regression model as a predictive factor of response to treatment.To demonstrate the value of hypoxia-inducible factor-1α (HIF-1α) in predicting response in patients with breast cancer receiving standard neoadjuvant chemotherapy (NAC). Methods: Ninety-five women enrolled in two prospective studies underwent biopsies for the histopathological diagnosis of breast carcinoma before receiving NAC, based on anthracyclines and taxanes. For expression of HIF-1α, EGFR, pAKT and pMAPK, tumor samples were analyzed by immunohistochemistry in tissues microarrays. Standard statistical methods (Pearson chi-square test, Fisher exact test, KruskalâWallis test, MannâWhitney test and KaplanâMeier method) were used to study the association of HIF-1α with tumor response, survival and other clinicopathologic variables/biomarkers. Results: HIF-1α expression was positive in 35 (39.7%) cases and was significantly associated to complete pathological response (pCR) (p = 0.014). HIF-1α expression was correlated positively with tumor grade (p = 0.015) and Ki-67 expression (p = 0.001) and negativity with progesterone receptors (PR) (p = 0.04) and luminal A phenotype expression (p = 0.005). No correlation was found between HIF-1α expression and EGFR, pAKT and pMAPK. In terms of survival, HIF-1α expression was associated with a significantly shorter disease-free survival (p = 0.013), being identified as an independent prognostic factor in multivariate analysis. Conclusions: Overexpression of HIF-1α is a predictor of pCR and shorter DFS; it would be valuable to confirm these results in prospective studies
Hydroxytyrosol Supplementation Modifies Plasma Levels of Tissue Inhibitor of Metallopeptidase 1 in Women with Breast Cancer
The etiology of breast cancer can be very different. Most antineoplastic drugs are not
selective against tumor cells and also affect normal cells, leading to a wide variety of adverse
reactions such as the production of free radicals by altering the redox state of the organisms.
Therefore, the objective of this study was to elucidate if hydroxytyrosol (HT) (an antioxidant present
in extra virgin olive oil) has a chemomodulatory effect when combined with the chemotherapeutic
drugs epirubicin and cyclophosphamide followed by taxanes in breast cancer patients. Changes in
plasma levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1
(TIMP-1) throughout the chemotherapy treatment were studied. Both molecules are involved in cell
proliferation, apoptosis, neoangiogenesis, and metastasis in breast cancer patients. Women with
breast cancer were divided into two groups: a group of patients receiving a dietary supplement of
HT and a control group of patients receiving placebo. The results showed that the plasma levels of
TIMP-1 in the group of patients receiving HT were significantly lower than those levels found in
the control group after the epirubicin-cyclophosphamide chemotherapy.This research was funded by Junta de AndalucĂa, Spain, Servicio Andaluz de Salud: Subvenciones para
la financiacion de la Investigación, Desarrollo, e Innovación Biomédica en Ciencias de la Salud en Biomedicina,
Grant number PI-0695-2012
Differences reported in the lifespan and aging of male Wistar rats maintained on diets containing fat with different fatty acid profiles (virgin olive, sunflower or fish oils) are not reflected by histopathological lesions found at death in central nervous and endocrine systems
The present study was designed to examine if dietary fat sources that have shown differences in lifespan and if
some aging-related aspects can modulate the range of histopathologic changes in central nervous and endocrine
systems that occur during the lifespan of Wistar rats. Moreover, it was attempted to gain insight into the relationship
between longevity and the development of the different pathological changes, as well as possible
interaction with diet. In order to achieve this, male Wistar rats were randomly assigned to three experimental
groups fed semisynthetic and isoenergetic diets from weaning until death with different dietary fat sources,
namely virgin olive, sunflower, or fish oil. An individual follow-up until death of each animal was performed.
Incidence, severity, and burden of specific or group (i.e., neoplastic or non-neoplastic proliferative and nonproliferative)
of lesions was calculated along with individualâs disease and individual organ lesion burden.
Most of the histopathological lesions found have been described in previous studies. Neoplasms, and in particular
pituitary adenomas followed by brain tumors, were the most prevalent lesions found in the rats and the main
cause of death involving both systems. Incidence of brain lesions was associated with age-at-death. Assayed
dietary fats did not present differential effects on pathological changes occurring in endocrine and central
nervous systems throughout rat lifespan.Spanish Government AGL2008-01057Government of Andalusia AGR83
A Diet Rich in Saturated Fat and Cholesterol Aggravates the Effect of Bacterial Lipopolysaccharide on Alveolar Bone Loss in a Rabbit Model of Periodontal Disease
MarĂa D. Navarro-Hortal is a FPU fellow from the Spanish Ministry of EducaciĂłn y FormaciĂłn
Profesional. The research group was partially supported by the Visiting Scholar Program from the University of
Granada. The authors acknowledge Nutraceutical Translations for English language editing of this manuscript.Increasing evidence connects periodontitis with a variety of systemic diseases, including
metabolic syndrome, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). The proposal of
this study was to evaluate the role of diets rich in saturated fat and cholesterol in some aspects of
periodontal diseases in a lipopolysaccharide (LPS)-induced model of periodontal disease in rabbits and
to assess the influence of a periodontal intervention on hyperlipidemia, atherosclerosis, and NAFLD
progression to non-alcoholic steatohepatitis. Male rabbits were maintained on a commercial standard
diet or a diet rich in saturated fat (3% lard w/w) and cholesterol (1.3% w/w) (HFD) for 40 days. Half of
the rabbits on each diet were treated 2 days per week with intragingival injections of LPS from
Porphyromonas gingivalis. Morphometric analyses revealed that LPS induced higher alveolar bone loss
(ABL) around the first premolar in animals receiving standard diets, which was exacerbated by the
HFD diet. A higher score of acinar inflammation in the liver and higher blood levels of triglycerides
and phospholipids were found in HFD-fed rabbits receiving LPS. These results suggest that certain
dietary habits can exacerbate some aspects of periodontitis and that bad periodontal health can
contribute to dyslipidemia and promote NAFLD progression, but only under certain conditions.Ministry of Education, Culture and Sport (Spain)Spanish GovernmentTraslados Temporales FPU (University of Kings College of London
Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q10 Addition
During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil as unique fat source, supplemented or not with coenzyme Q10 (CoQ10), to evaluate the potential of adding this molecule to the n-3 polyunsaturated fatty acid (n-3 PUFA)-based diet for bone mineral density (BMD) preservation. BMD was evaluated in the femur. Serum osteocalcin, osteopontin, receptor activator of nuclear factor-ÎșB ligand, ostroprotegerin, parathyroid hormone, urinary F2-isoprostanes, and lymphocytes DNA strand breaks were also measured. BMD was lower in aged rats fed a diet without CoQ10 respect than their younger counterparts, whereas older animals receiving CoQ10 showed the highest BMD. F2-isoprostanes and DNA strand breaks showed that oxidative stress was higher during aging. Supplementation with CoQ10 prevented oxidative damage to lipid and DNA, in young and old animals, respectively. Reduced oxidative stress associated to CoQ10 supplementation of this n-3 PUFA-rich diet might explain the higher BMD found in aged rats in this group of animals.This work was supported by the Spanish Ministry of Education and Science (AGL2008-01057) and the Autonomous Government of Andalusia (AGR832). A.V.-L. is recipient of a grant for doctors from University of Granadaâs own plan
Heart Histopathology and Mitochondrial Ultrastructure in Aged Rats Fed for 24 Months on Different Unsaturated Fats (Virgin Olive Oil, Sunflower Oil or Fish Oil) and Affected by Different Longevity
Diet plays a decisive role in heart physiology, with lipids having especial importance
in pathology prevention and development. This study aimed to investigate how dietary lipids
varying in lipid profile (virgin olive oil, sunflower oil or fish oil) affected the heart of rats during
aging. Heart histopathology, mitochondrial morphometry, and oxidative status were assessed.
Typical histopathological features associated with aging, such as valvular lesions, endomyocardical
hyperplasia, or papillary muscle calcification, were found at a low extent in all the experimental
groups. The most relevant finding was that inflammation registered by fish oil group was lower
compared to the other treatments. At the ultrastructural level, heart mitochondrial area, perimeter,
and aspect ratio were higher in fish oil-fed rats than in those fed on sunflower oil. Concerning
oxidative stress markers, there were differences only in coenzyme Q levels and catalase activity,
lower in sunflower oil-fed animals compared with those fed on fish oil. In summary, dietary intake
for a long period on dietary fats with different fatty acids profile led to differences in some aspects
associated with the aging process at the heart. Fish oil seems to be the fat most protective of heart
during aging.This research was supported by R + D grants from the Spanish Ministry of Education and
Science [AGL2008-01057] and the Government of Andalusia [AGR832]
Treatment of Idiopathic Membranous Nephropathy (IMN)
We present a 59-year-old patient with type 2 diabetes mellitus and massive nephrotic syndrome (anasarca) and biochemical syndrome. The renal biopsy showed a membranous nephropathy (MN). In the blood analysis the patient presented antibodies against M-type phospholipase A2 receptor (anti-PLA2R) positive at a very high titer. Given the existence of idiopathic membranous nephropathy (IMN), treatment was started with a modified Ponticelli regimen, with no response, requiring periodic ultrafiltration sessions. Rituximab induces nephrotic syndrome (NS) remission in two-thirds of patients with IMN, even after other treatments have failed. We proposed treatment with rituximab based on published evidence. In IMN, the presence of M-type anti-receptor antibodies of A2 phospholipase is considered highly specific to idiopathic forms, but the presence of such antibodies has not been shown to be associated with a particular clinical profile. Assessing circulating anti-PLA2R autoantibodies and proteinuria may help in monitoring disease activity and guiding personalized rituximab therapy in nephrotic patients with IMN
Subtipado molecular del cĂĄncer de mama masculino con PAM50: CorrelaciĂłn con el subtipaje inmunohistoquĂmico y estudio de supervivencia.
IntroducciĂłn: El cĂĄncer de mama masculino es una enfermedad rara aĂșn poco conocida, que principalmente corresponde a subtipo luminal usando la clasificaciĂłn molecular subrogada a inmunohistoquĂmica. En este estudio, se evalĂșa por primera vez la correlaciĂłn entre los subtipos moleculares basados en un panel inmunohistoquĂmico de seis marcadores y el obtenido mediante la firma PAM50 en el cĂĄncer de mama masculino, asĂ como la evoluciĂłn clĂnica de los diferentes subtipos encontrados.
Material y mĂ©todos: Se recogieron 67 muestras quirĂșrgicas de cĂĄncer de mama masculino invasivo de cuatro diferentes Servicios de AnatomĂa PatolĂłgica. La tinciĂłn inmunohistoquĂmica se realizĂł sobre tissue-microarrays, con un panel de seis marcadores (RE, RP, Her2, Ki67, CK 5-6 y EGFR). Los subtipos de PAM50 se determinaron mediante nCounter Analysis System. Se estudiĂł la asociaciĂłn entre los subtipos obtenidos mediante inmunohistoquĂmica y los determinados por PAM50, asĂ como la supervivencia global y la supervivencia libre de enfermedad en los diferentes subtipos de cada clasificaciĂłn.
Resultados: La distribuciĂłn de los subtipos moleculares tumorales segĂșn PAM50 fue: 60% luminal B, 30% luminal A y 10% Her2-enriched. SĂłlo uno de los tumores Her2-enriched tambiĂ©n fue detectado por inmunohistoquĂmica y tratado con trastuzumab. No se obtuvo ningĂșn tumor de subtipo basal-like. Utilizando la clasificaciĂłn inmunohistoquĂmica, 51% de los tumores fueron luminal B, 43% luminal A, 3,5% triple negativo y 1,5% Her2-positivo. Las caracterĂsticas clĂnico-patolĂłgicas no difirieron significativamente entre los subtipos inmunohistoquĂmicos y PAM50. Se observĂł una supervivencia global menor en los tumores Her2-enriched comparados con los luminales.
ConclusiĂłn: El cĂĄncer de mama masculino es principalmente una enfermedad genĂłmica luminal con un predominio del subtipo luminal B. AdemĂĄs, se observaron casos de pacientes Her2-negativos por inmunohistoquĂmica, pero de perfil Her2-enriched por PAM50, con peor evoluciĂłn clĂnica comparado con el subtipo luminal, que podrĂan haberse beneficiado de terapia anti-Her2.Universidad de MĂĄlaga. Campus de Excelencia Internacional AndalucĂa Tech