Deconstructing neutrophil to lymphocyte ratio (NLR) in early breast cancer: lack of prognostic utility and biological correlates across tumor subtypes.

PURPOSE: The prognostic utility and biological correlates of neutrophil to lymphocyte ratio (NLR), a potential biomarker of the balance between immune response and the inflammatory status, are still uncertain in breast cancer (BC). METHODS: We analysed a cohort of 959 women with early breast cancer, mostly treated with neoadjuvant or adjuvant chemotherapy. Clinical and pathological data, survival, NLR (continuous and categorical) and stromal tumor infiltrating lymphocytes (sTIL) were evaluated. RESULTS: NLR was only weakly associated with Ki67, while no association was found for grade, histology, immunohistochemical subtype or stage. Lymphocyte infiltration of the tumor did not correlate with NLR (Rho: 0.05, p = 0.30). These results were similar in the whole group and across the different BC subtypes, with no differences in triple negative BC. Relapse free interval (RFI), breast cancer specific survival (BCSS) and overall survival (OS) changed according to pre-treatment NLR neither in the univariate nor in the multivariate Cox models (RFI: HR 0.948, p = 0.61; BCSS: HR 0.920, p = 0.57; OS: HR 0.96, p = 0.59). CONCLUSION: These results question the utility of NLR as a prognostic biomarker in early breast cancer and suggest the lack of correlation of NLR with tumor microenvironment immune response.

Cáncer neuroendocrino de mama, presentación de un caso y técnicas diagnósticas / Neuroendocrine breast cancer, case report and diagnosis

El cáncer neuroendocrino de mama es una forma poco frecuente de aparición del cáncer de mama. Se presenta como un nódulo mamario asociado generalmente a una sintomatología general; por lo que también se debe realizar el diagnóstico diferencial con metástasis de cáncer neuroendocrino primario. En este artículo, presentamos el caso clínico de una paciente con cáncer de mama neuroendocrino, el tratamiento recibido y la detección e identificación del ganglio centinela mediante la utilización del trazador Magtrace® y del detector SentiMag®. Finalmente, se realiza una breve revisión de los pocos casos publicados en la literatura. (AU)

Neuroendocrine breast cancer is a rare form of breast cancer. It appears as a breast nodule, generally associated with general symptoms; therefore, the differential diagnosis should also be made with metastases from a primary neuroendocrine form. In this article, we present the clinical case of a patient with neuroendocrine breast cancer, the treatment and the detection and identification of the sentinel node using the Magtrace® tracer and the SentiMag® detector. Finally, a brief review of the few cases published in the literature is made. (AU)

Sarcoidosis cardíaca como causa muy infrecuente de muerte súbita en pacientes jóvenes asintomáticos / Cardiac sarcoidosis as an infrequent cause of sudden death in asymptomatic young patients

La afectación cardíaca en la sarcoidosis ha sido descrita tanto en presencia de síntomas como en su ausencia. Este trabajo ayuda a comprender la sarcoidosis y su presentación clínico-morfológica. Presentamos dos pacientes jóvenes (37 y 27años), con muerte súbita, a quienes se les realizó la autopsia completa con estudio toxicológico. El hombre de 37años presentaba una sarcoidosis pulmonar generalizada, en ganglios mediastínicos y granulomas sarcoideos intramiocárdicos en el ventrículo izquierdo, que producían un espesor de pared de 14mm. Esto derivó en una miocardiopatía dilatada secundaria que debutó como muerte súbita. El segundo caso, un varón de 27años, presentaba sarcoidosis con importante afectación pulmonar y mediastínica. La presencia de granulomas en el tabique cardíaco sobre un fondo fibrótico podría ser el origen de un mecanismo arritmogénico de muerte súbita. La autopsia clásica y el examen del sistema de conducción cardíaco son cruciales en la muerte súbita.(AU)

Cardiac involvement in sarcoidosis has been described in both symptomatic and asymptomatic patients. The aim of this report is to further the understanding of sarcoidosis and its clinical presentation. We report the autopsy and toxicology results of two cases of sudden death in young men. A 37-year-old male had generalized sarcoidosis, in mediastinal glands and intramyocardial sarcoid granulomas in the left ventricle, which had caused a 14mm thickening of the ventricular wall and a secondary dilated myocardiopathy causing sudden death. A 27-year-old male had extensive sarcoidosis of the lungs and mediastinum. Granulomas with a fibrotic background were found in the cardiac wall which could have originated an arrhythmogenic mechanism causing sudden death. Post-mortem study including careful examination of cardiac conduction pathways are vital to ascertain the cause of sudden death.(AU)

[Cardiac sarcoidosis as an infrequent cause of sudden death in asymptomatic young patients]. / Sarcoidosis cardíaca como causa muy infrecuente de muerte súbita en pacientes jóvenes asintomáticos.

Cardiac involvement in sarcoidosis has been described in both symptomatic and asymptomatic patients. The aim of this report is to further the understanding of sarcoidosis and its clinical presentation. We report the autopsy and toxicology results of two cases of sudden death in young men. A 37-year-old male had generalized sarcoidosis, in mediastinal glands and intramyocardial sarcoid granulomas in the left ventricle, which had caused a 14mm thickening of the ventricular wall and a secondary dilated myocardiopathy causing sudden death. A 27-year-old male had extensive sarcoidosis of the lungs and mediastinum. Granulomas with a fibrotic background were found in the cardiac wall which could have originated an arrhythmogenic mechanism causing sudden death. Post-mortem study including careful examination of cardiac conduction pathways are vital to ascertain the cause of sudden death.

Clinical Meaning of Stromal Tumor Infiltrating Lymphocytes (sTIL) in Early Luminal B Breast Cancer.

Luminal breast cancer (BC) is associated with less immune activation, and the significance of stromal lymphocytic infiltration (sTIL) is more uncertain than in other BC subtypes. The aim of this study was to investigate the predictive and prognostic value of sTIL in early luminal BC. The study was performed with an observational design in a prospective cohort of 345 patients with predominantly high-risk luminal (hormone receptor positive, HER2 negative) BC and with luminal B features (n = 286), in which the presence of sTIL was analyzed with validated methods. Median sTIL infiltration was 5% (Q1-Q3 range (IQR), 0-10). We found that sTIL were associated with characteristics of higher biological and clinical aggressiveness (tumor and lymph node proliferation and stage, among others) and that the percentage of sTIL was predictive of pathologic complete response in patients treated with neoadjuvant chemotherapy (OR: 1.05, 95%CI 1.02-1.09, p < 0.001). The inclusion of sTIL (any level of lymphocytic infiltration: sTIL > 0%) in Cox regression multivariable prognostic models was associated with a shorter relapse-free interval (HR: 4.85, 95%CI 1.33-17.65, p = 0.016) and significantly improved its performance. The prognostic impact of sTIL was independent of other clinical and pathological variables and was mainly driven by its relevance in luminal B BC.

Combining Oxidative Stress Markers and Expression of Surfactant Protein A in Lungs in the Diagnosis of Seawater Drowning.

BACKGROUND AND OBJECTIVES: The diagnosis of seawater drowning (SWD) remains one of the most complex and contentious. It is one of the leading causes of unintentional death around the world. In most cases, the forensic pathologist must reach an accurate diagnosis from the autopsy findings and a series of complementary tests such as histopathological, biological, and chemical studies. Despite the lung being the most affected organ in death by submersion, there are few studies on this type of death's impact on this organ. The aim was to investigate human lung cadavers of forensic cases due to different causes of death, the concentration of the oxidative stress markers malondialdehyde (MDA) and γ-glutamyl-l-cysteinyl glycine (GSH), and the relationship with the expression of surfactant protein A (SP-A) to try to discriminate SWD from other types of causes of death. MATERIALS AND METHODS: A total of 93 forensic autopsy cases were analyzed. Deaths were classified into three major groups based on the scene, cause of death, and autopsy findings (external foam, frothy fluid in airways, overlapping medial edges of the lungs): (a) drowning in seawater (n = 35), (b) other asphyxia (n = 33), such as hangings (n = 23), suffocations (n = 6), and strangulation (n = 4), and (c) other causes (n = 25), such as multiple suffocations. Oxidative stress markers (MDA and GSH) and the immunohistochemical expression of SP-A were determined in both lungs. RESULTS: MDA levels were statistically higher in both lungs in cases of SWD than in other causes of death (p = 0.023). Similarly, significantly higher levels of GSH were observed in SWD compared to the rest of the deaths (p = 0.002), which was more significant in the right lung. Higher immunohistochemical expression of SP-A was obtained in the cases of SWD than in the other causes of death, with higher levels in both lungs. The correlation analysis between the levels of oxidative stress (MDA and GSH) in the lung tissue and the expression level of SP-A showed positive and significant results in SWD, both in the alveolar membrane and the alveolar space. CONCLUSIONS: Determining the levels of MDA and GSH in lung tissue and the expression level of SP-A can be of great importance in diagnosing SWD and the circumstances of death. A better understanding of the physiology of submersion is essential for its possible repercussions in adopting measures in the approach to patients who have survived a submersion process. It is also necessary for forensic pathology to correctly interpret the events that lead to submersion.

Metástasis parotídea de carcinoma de células claras renal con presencia simultánea de pseudoaneurisma arterial. Caso clínico y revisión de la literatura / Parotid metastasis of clear cell renal carcinoma with simultaneous presence of arterial pseudoaneurysm. Case report and review of literature

Las metástasis en glándula parótida son muy poco frecuentes. Presentamos el caso de una mujer de 73 años cuyos antecedentes oncológicos principales a destacar son carcinoma ductal infiltrante de mama tratado con mastectomía y linfadenectomía axilar y, posteriormente, carcinoma de células renales de célula clara bilaterales metacrónicos tratados con nefrectomía radical. Desde entonces la mujer se encuentra en diálisis. Presenta tumoración en parótida de 4 cm, que radiológicamente es catalogada como pseudoaneurisma arterial intraparotídeo. Tras la extirpación de la parótida, seis años después de la última nefrectomía, en el estudio anatomopatológico se observa, junto a vasos dilatados, lesión neoplásica compatible morfológica e inmunohistoquímicamente con metástasis de carcinoma de células renales de célula clara. Se ha realizado una profunda revisión de la literatura encontrando menos de 60 casos descritos de metástasis parotídea de carcinoma de células renales de célula clara. Analizándolos observamos metástasis en otros lugares en el 61 % de los mismos, principalmente pulmonares, óseas y en glándulas adrenales, existiendo mayor porcentaje de segundas metástasis (70 %) cuando hay sincronía entre carcinoma renal y metástasis parotídea. En conclusión, presentamos un caso inusual de metástasis tardía de carcinoma renal de célula clara en parótida, y el primero, según nuestro conocimiento, que se diagnostica como hallazgo incidental en la extirpación de un aneurisma intraparotídeo. (AU)

Parotid gland metastases are very rare. We present the case of a 73-year-old woman whose main oncological history to highlight is infiltrating ductal carcinoma of the breast treated with mastectomy and axillary lymphadenectomy and after that. metachronous bilateral clear cell renal cell carcinoma treated with radical nephrectomy. Since then, the woman has been on dialysis. It presents a 4 cm parotid tumor, which is radiologically classified as an intraparotid arterial pseudoaneurysm. After extirpation of the parotid gland, six years after the last nephrectomy, in the pathological study, together with dilated vessels, a neoplastic lesion compatible morphologically and immunohistochemically with metastasis of clear cell renal cell carcinoma is observed. A thorough review of the literature has been carried out, finding less than 60 reported cases of parotid metastasis from clear cell renal cell carcinoma. Analyzing them, we observed metastases in other places in 61 % of them, mainly lung, bone and adrenal glands, with a higher percentage of second metastases (70 %) when there was a synchrony between renal carcinoma and parotid metastasis. In conclusion, we have presented an unusual case of late metastasis of clear cell renal carcinoma in the parotid, and the first –to our knowledge–, which is diagnosed as an incidental finding in the removal of an intraparotid aneurysm. (AU)

Study of the Effect of Photobiomodulation on a Skin Repair Model in SKH-1 Mice.

Background and objective: Laser applied at low power (400-1100 nm), currently named photobiomodulation (PBM), is a noninvasive therapy to speed up wound healing. The purpose of this study was whether two different laser PBM delivery protocols would impact the skin wound healing in a mouse model. Materials and methods: A total of 24 SKH-1 mice were divided into three groups: Group 1 (control: untreated ulcers), Group 2 (a single postsurgical laser application), and Group 3 (laser each other day for 10 days; total five applications). Laser parameters were 940 nm, 0.4 W, 10 mm spot size, 0.008 J/cm2, 300 sec/wound. Each animal received two skin wounds which were photographed on days 0, 5, and 10 to determine wound closure (ImageJ). Half of the animals in each group were sacrificed on day 5 and the other half on day 10. Samples were routinely processed for histological analysis (re-epithelization, angiogenesis, granulation tissue formation, inflammation, and collagen deposition). Results: The closure of the wounds at the end of the experiment in the animals photobiostimulated each other day was more advanced than in the controls and in those treated only once, in both the macroscopic and microscopic studies. Angiogenesis was higher in both treated groups than in the control in the first study time (day 5). However, inflammation, maturation of the granulation tissue, and collagen deposition only improved when the laser was applied each other day. Conclusions: In our study, with the parameters used, PBM improved the healing of skin wounds when applied every other day and not in a single dose.

Disposition of Dietary Polyphenols in Breast Cancer Patients' Tumors, and Their Associated Anticancer Activity: The Particular Case of Curcumin.

SCOPE: Some polyphenol-derived metabolites reach human breast cancer (BC) tissues at concentrations that induce cell senescence. However, this is unknown for isoflavones, curcuminoids, and lignans. Here, their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly-diagnosed BC patients and the tissue-occurring metabolites' anticancer activity are evaluated. METHODS AND RESULTS: Patients (n = 26) consumed 3 capsules/day (turmeric, red clover, and flaxseed extracts plus resveratrol; 296.4 mg phenolics/capsule) from biopsy-confirmed diagnosis to surgery (5 ± 2 days) or did not consume capsules (n = 13). NT and MT, blood, and urine are analyzed by UPLC-QTOF-MS using targeted metabolomics. Anticancer activity was tested in MCF-7 and MDA-MB-231 BC cells. Mainly phase-II metabolites were detected (108, 84, 49, and 47 in urine, plasma, NT, and MT, respectively). Total metabolite concentrations reached 10.7 ± 11.1 and 2.5 ± 2.4 µmol L-1 in NT and MT, respectively. Free curcumin, but not its glucuronide, was detected in the tissues (1.1 ± 1.8 and 0.2 ± 0.2 µmol L-1 in NT and MT, respectively). Breast tissue-occurring metabolites' antiproliferation was mainly exerted in p53-wild-type MCF-7 cells by curcuminoids through cell cycle arrest, senescence, and apoptosis induction via p53/p21 induction, while isoflavone-derived metabolites exerted estrogenic-like activity. CONCLUSION: Curcuminoids could be coadjuvants that might help fight BC upon regular consumption.

Cytologic and histologic features of COVID-19 post-vaccination lymphadenopathy.

In this study, we present six cases of axillary or supraclavicular lymphadenopathies in the days following to the Pfizer-BioNTech vaccine's first dose and its study for fine-needle aspiration cytology (two patients), biopsy with a gross needle (two patients), and the evolution of two other patients. Cytological smears and histological sections reveal reactive nodes, predominantly T, CD8, and the presence of atypia with striking mitosis. Differential diagnosis with viral lymphadenopathies and lymphoma is important, so the clinical correlation, in a vaccination context, sudden appearance, and progressive decrease in days of the adenopathy, is essential. In this article, we have studied the cytohistological manifestations of post-Pfizer-BioNTech vaccination lymphadenopathy and discussed its differential diagnosis.

Chemopreventive effect of pomegranate and cocoa extracts on ultraviolet radiation-induced photocarcinogenesis in SKH-1 mice.

Non-melanoma skin cancer (NMSC) has a high and increasing incidence all over the world. Solar radiation is the main aetiology for humans. Although most research into photocarcinogenesis uses UVB as a source of radiation, UVA is also carcinogenic in long term. Pomegranate (PGE) and cocoa (CE) extracts have been used for medicinal purposes for time immemorial. Recently, it has been claimed that some of their properties may be an effective preventative measure against photocarcinogenesis and photoaging, but to date in vivo models have not been tested using RUVA, the objective of the present work. A lower incidence of lesions was observed in SKH-1 mice treated with PGE (p<0.001), and lower incidence of invasive squamous carcinoma in both treatment groups (p<0.001 for PGE and p<0.05 for CE); the PGE group also showed a lower level of cell proliferation than the control group (p<0.001). Significantly greater p53 alteration was observed in the control group than the treatment groups (p<0.001 for PGE and p = 0.05 for CE). No significant differences were found in relation to TIMP-1 and MMP-9. Taken together, the results suggest that oral feeding of PGE and CE to SKH-1 mice affords substantial protection against the adverse effects of RUVA, especially PGE.

Nurse's A-Phase-Silicocarnotite Ceramic-Bone Tissue Interaction in a Rabbit Tibia Defect Model.

Calcium phosphate materials are widely used as bone substitutes due to their bioactive and biodegradable properties. Also, the presence of silicon in their composition seems to improve the bioactivity of the implant and promote bone tissue repair. The aim of this study was to develop a novel ceramic scaffold by partial solid-state sintering method with a composition lying in the field of the Nurse's A-phase-silicocarnotite, in the tricalcium phosphate-dicalcium silicate (TCP-C2S) binary system. Also, we evaluated its osteogenic and osteoconductive properties after being implanted into tibia defects in New Zealand rabbits. X-ray, microcomputer tomography, and histomorphometry studies demonstrated that this porous ceramic is highly biocompatible and it has excellent osteointegration. The material was being progressively reabsorbed throughout the study and there was no unspecified local or systemic inflammatory response observed. These results suggest that ceramic imitates the physicochemical characteristics of bone substitutes used in bone reconstruction.

Metabolic Profiling of Dietary Polyphenols and Methylxanthines in Normal and Malignant Mammary Tissues from Breast Cancer Patients.

SCOPE: Dietary polyphenols may protect against breast cancer. However, it is unknown whether polyphenols reach human malignant breast tumors in molecular forms and(or) at concentrations likely to act against cancer. METHODS AND RESULTS: Ninteen breast cancer patients consumed three capsules daily from biopsy-confirmed diagnosis to surgery (6 ± 2 days). The capsules contained pomegranate, orange, lemon, olive, cocoa, and grapeseed extracts plus resveratrol, providing 37 different phenolics (473.7 mg), theobromine and caffeine (19.7 mg). A total of 101 metabolites are identified in urine, 69 in plasma, 39 in normal (NT), and 33 in malignant (MT) tissues by UPLC-ESI-QTOF-MS. Eight control patients did not consume extracts. Phenolic-derived metabolites in MT and NT are mainly glucuronidated and(or) sulfated. Some representative metabolites detected in MT (median and range, pmol g-1 ) are urolithin-A-3-O-glucuronide (26.2; 3.2-66.5), 2,5-dihydroxybenzoic acid (40.2; 27.7-52.2), resveratrol-3-O-sulfate (86.4; 7.8-224.4), dihydroresveratrol-3-O-glucuronide (109.9; 10.3-229.4), and theobromine (715.0; 153.9-3,216). Metabolites, as detected in breast tissues, do not exert antiproliferative or estrogenic/antiestrogenic activities in MCF-7 breast cancer cells. CONCLUSION: This is the first study that describes the metabolic profiling of dietary phenolics and methylxanthines in MT and NT comprehensively. Although phase-II conjugation might hamper a direct anticancer activity, long-term tumor-senescent chemoprevention cannot be discarded.

[Relationship between anogenital distance and prognosis of prostate cancer.] / Relación entre distancia anogenital y pronóstico del cáncer de próstata.

OBJECTIVE: Anogenital distance (AGD), the distance from the centre of the anus to the genitals, is a sexually dimorphic phenotype in mammals. Several experimental studies have demonstrated that AGD is a biomarker of prenatal androgen exposure during the masculinisation period of development. The objective of this study was to assess the relationship between AGD (as an indirect marker of prenatal hormonal environment) and severity of the surgical specimen and prostate cancer (PCa) prognosis. METHODS: We conducted a cross-sectional study with a total of 119 PCa patients with confirmed biopsy of the tumour. Every participant underwent a physical examination where two variants of the AGD were assessed, a) from the anus to the cephalad insertion of the penis (AGDAP) and b) to the posterior base of the scrotum (AGDAS). To assess the association between both AGD and severity and PCa prognosis multiple logistic regression analysis was used. RESULTS: Longer AGDAS was significantly associated with biochemical recurrence and affected margins of the surgical specimen (OR: 2.5; IC 95%:1.2-5.5, and 2.8; IC 95%: 1.1-7.5, respectively). CONCLUSIONS: Our findings suggest that a higher prenatal androgen exposure, resulting in a longer AGD, is associated with worse prognosis of PCa.

Relación entre distancia anogenital y pronóstico del cáncer de próstata / Relationship between anogenital distance and prognosis of prostate cancer

OBJETIVO: La distancia anogenital (DAG) es un marcador de desarrollo genital que presenta un dimorfismo sexual en mamíferos. Diversos estudios experimentales han demostrado que la DAG al nacimiento refleja la exposición androgénica a la que el feto ha estado expuesto durante su desarrollo intrauterino. El objetivo de nuestro estudio fue analizar la asociación entre la DAG (como marcador indirecto del ambiente hormonal intrauterino) y la severidad en la pieza quirúrgica y el pronóstico del cáncer de próstata (CaP). MÉTODOS: Se trata de un estudio transversal que incluyó 119 pacientes intervenidos de CaP y con confirmación histológica por biopsia. A cada paciente se le realizó una exploración física y se midieron dos variantes de DAG; a) medida desde la inserción posterior del pene en el abdomen bajo al borde superior del ano (DAGAP) y b) medida desde la base posterior del escroto al borde superior del ano (DAGAS). La asociación entre ambas DAG y los indicadores de severidad y pronóstico postquirúrgicos de CaP se realizaron mediante análisis de regresión logística múltiple. RESULTADOS: La DAGAS se asoció significativamente con la recidiva bioquímica y márgenes afectados en la pieza quirúrgica (OR: 2,5; IC 95%: 1,2-5,5, y 2,8; IC 95%: 1,1-7,5, respectivamente). CONCLUSIÓN: Nuestros resultados sugieren que una mayor exposición androgénica prenatal, reflejado en una DAG alargada, estaría asociada con un peor pronóstico del CaP

OBJECTIVE: Anogenital distance (AGD), the distance from the centre of the anus to the genitals, is a sexually dimorphic phenotype in mammals. Several experimental studies have demonstrated that AGD is a biomarker of prenatal androgen exposure during the masculinisation period of development. The objective of this study was to assess the relationship between AGD (as an indirect marker of prenatal hormonal environment) and severity of the surgical specimen and prostate cancer (PCa) prognosis. METHODS: We conducted a cross-sectional study with a total of 119 PCa patients with confirmed biopsy of the tumour. Every participant underwent a physical examination where two variants of the AGD were assessed, a) from the anus to the cephalad insertion of the penis (AGDAP) and b) to the posterior base of the scrotum (AGDAS). To assess the association between both AGD and severity and PCa prognosis multiple logistic regression analysis was used. RESULTS: Longer AGDAS was significantly associated with biochemical recurrence and affected margins of the surgical specimen (OR: 2.5; IC 95%:1.2-5.5, and 2.8; IC 95%: 1.1-7.5, respectively). CONCLUSIONS: Our findings suggest that a higher prenatal androgen exposure, resulting in a longer AGD, is associated with worse prognosis of PCa

Consumption of pomegranate decreases plasma lipopolysaccharide-binding protein levels, a marker of metabolic endotoxemia, in patients with newly diagnosed colorectal cancer: a randomized controlled clinical trial.

Gut microbiota dysbiosis alters the intestinal barrier function, increases plasma lipopolysaccharide (LPS) levels, which promotes endotoxemia, and contributes to the onset and development of colorectal cancer (CRC). We report here for the first time the reduction of plasma LPS-binding protein (LBP) levels, a marker of endotoxemia, after pomegranate consumption in newly diagnosed CRC patients.

Relación entre ratio digital 2D: 4D y severidad preoperatoria del cáncer de próstata / Relationship between Digit Ratio (2D:4D) and Preoperative Severity of Prostate Cancer

El cociente entre la longitud del segundo y cuarto dedo (2D:4D) de la mano es un rasgo de dimorfismo sexual, presentando los hombres una ratio menor que las mujeres.1 Varios estudios de cohortes2,3 y un metaanálisis,4 han mostrado que la diferencia de género en la ratio de los dedos se asocia con la exposición de andrógenos prenatales. El cociente 2D:4D está inversamente relacionado a la exposición intrauterina de testosterona (T) y directamente relacionado a la de estradiol.2 Existe evidencia que afirma que la ratio 2D:4D podría ser un marcador válido para los niveles hormonales del adulto (T y estrógeno),3 aunque ese dato es controvertido.4Por esa razón, el cociente 2D:4D seha utilizado como un biomarcador no invasivo y retrospectivo para la exposición prenatal de andrógenos, y se ha correlacionado con una amplia gama de enfermedades como el autismo,5 así como la cognición visoespacial y la orientación sexual.6

The quotient between the length of the second and fourth finger (2D:4D) hand is a trait of sexual dimorphism, featuring the men a lower ratio than women.1 Several studies of the cohorts2,3 and a meta-analysis,4 have shown that the difference between The gender ratio of the fingers is associated with the exposure of prenatal androgens. The quotient 2D:4D is inversely related to intrauterine testosterone (T) exposure and directly related to that of estradiol.2 There is evidence which states that the 2D:4D ratio could be a valid marker for adult hormone levels (T and estrogen),3 although that data is controversial.4 For that reason, the 2D:4D quotient has been used as a noninvasive and retrospective biomarker for prenatal exposure to androgens, and it has been correlated with a wide range of diseases such as autism,5 as well as such as visuospatial cognition and sexual orientation.6

Angiosarcoma primario de mama. A propósito de un caso / Primary breast angiosarcoma. A case report

No disponible

Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial.

The clinical evidence of dietary polyphenols as colorectal cancer (CRC) chemopreventive compounds is very weak. Verification in humans of tissue-specific molecular regulation by the intake of polyphenols requires complex clinical trials that allow for the procurement of sufficient pre- and postsupplementation tissue samples. Ellagitannins (ETs), ellagic acid (EA) and their gut microbiota-derived metabolites, the urolithins, modify gene expression in colon normal and cancer cultured cells. We conducted here the first clinical trial with 35 CRC patients daily supplemented with 900 mg of an ET-containing pomegranate extract (PE) and evaluated the expression of various CRC-related genes in normal and cancerous colon tissues before (biopsies) and after (surgical specimens) 5-35 days of supplementation. Tissues were also obtained from 10 control patients (no supplementation) that confirmed a large, gene- and tissue-specific interindividual variability and impact of the experimental protocol on gene expression, with some genes induced (MYC, CD44, CDKN1A, CTNNB1), some repressed (CASP3) and others not affected (KRAS). Despite these issues, the consumption of the PE was significantly associated with a counterbalance effect in the expression of CD44, CTNNB1, CDKN1A, EGFR and TYMs, suggesting that the intake of this PE modulated the impact of the protocol on gene expression in a gene- and tissue-specific manner. These effects were not associated with the individuals' capacity to produce specific urolithins (i.e., metabotypes) or the levels of urolithins and EA in the colon tissues and did not reproduce in vitro effects evidencing the difficulty of demonstrating in vivo the in vitro results.