Differences in the expression of the phosphatase PTP-1B in patients with localized prostate cancer with and without adverse pathological features.

Introduction: Patients with adverse pathological features (APF) at radical prostatectomy (RP) for prostate cancer (PC) are candidates for adjuvant treatment. Clinicians lack reliable markers to predict these APF preoperatively. Protein tyrosine phosphatase 1B (PTP-1B) is involved in migration and invasion of PC, and its expression could predict presence of APF. Our aim was to compare PTP-1B expression in patients with and without APF, and to explore PTP-1B expression as an independent prognostic factor. Methods: Tissue microarrays (TMAs) were constructed using RP archival specimens for immunohistochemical staining of PTP-1B; expression was reported with a standardized score (0-9). We compared median PTP-1B score between cases with and without APF. We constructed two logistic regression models, one to identify the independence of PTP-1B score from biologically associated variables (metformin use and type 2 diabetes mellitus [T2DM]) and the second to seek independence of known risk factors (Gleason score and prostate specific antigen [PSA]). Results: A total of 73 specimens were suitable for TMA construction. Forty-four (60%) patients had APF. The median PTP-1B score was higher in those with APF: 8 (5-9) vs 5 (3-8) (p=0.026). In the logistic regression model including T2DM and metformin use, the PTP-1B score maintained statistical significance (OR 1.21, 95% CI 1.01-1.45, p=0.037). In the model including PSA and Gleason score; the PTP-1B score showed no independence (OR 1.68, 95% CI 0.97-1.41, p=0.11). The area under the curve to predict APF for the PTP-1B score was 0.65 (95% CI 0.52-0.78, p=0.03), for PSA+Gleason 0.71 (95% CI 0.59-0.82, p=0.03), and for PSA+Gleason+PTP-1B score 0.73 (95% CI 0.61-0.84, p=0.001). Discussion: Patients with APF after RP have a higher expression of PTP-1B than those without APF, even after adjusting for T2DM and metformin exposure. PTP-1B has a good accuracy for predicting APF but does not add to known prognostic factors.

Immunosenescence profile and expression of the aging biomarker (p16INK4a) in testicular cancer survivors treated with chemotherapy.

BACKGROUND: Cytotoxic chemotherapy can cure advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy. METHODS: Case-control exploratory study of TCS treated with chemotherapy (≥3 BEP cycles, disease-free ≥3 months) compared with age matched healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. CDKN2A/p16INK4a expression in T cells was measured using qPCR. The percentage of lymphocyte subpopulations and the CDKN2A/p16INK4a expression in TCS were compared with the control group using the Wilcoxon signed-rank test. RESULTS: We included 16 cases and 16 controls. The median age was 27 years (minimum 24, maximum 54) and the median time on surveillance was 26.5 months (minimum 3, maximum192). TCS had a lower percentage of total T cells and CD4+ T cells in total lymphocytes. Among the CD4+ T lymphocytes, TCS had less naïve CD4+ and increased memory CD4+ cells. Within the CD8+ T lymphocytes, TCS exhibited a decrease in the percentage of naïve cells and an increase in CD8 + CD45RA + CD57+ cells. TCS also exhibited decreased memory CD19+ B cells compared to the controls. The relative expression of CDKN2A/p16INK4a in T cells was increased in TCS (mean 1.54; 95% CI of the mean: 1.074-2.005; p = 0.048). CONCLUSION: In this exploratory study, TCS showed increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype that has been associated with immunosenescence. Further studies are warranted to define the clinical implications of these alterations in TCS.

Metformin enhances left ventricular function in patients with metabolic syndrome / La metformina mejora la función ventricular izquierda en pacientes con síndrome metabólico

Background: Metabolic syndrome foretells several cardiovascular complications, including heart failure (HF). Left ventricular (LV) dysfunction accompanies the MS. Although metformin improves LV function in diabetics with HF, there is no evidence of its effect on LV dysfunction in MS patients. We studied the effect of metformin on LV dysfunction in MS patients using tissue Doppler myocardial imaging and two-dimensional speckle tracking. Aims: To evaluate the effects of metformin on metabolic syndrome (MS) induced left ventricular dysfunction. Material and methods: Patients with MS were randomly allocated into two groups (n = 20 each) receiving, an antagonist of angiotensin 2 receptors and; statins, fibrates or both. One group received 850 mg of metformin daily. LV mass, relative wall thickness (RWT), ejection fraction, E/A and E/E' relationship, systolic tissue Doppler velocity (Sm), mean peak systolic strain (SS), and peak early diastolic strain rate (SR-LVe) echocardiographic measurements, at baseline and six months were obtained. Results: All patients had LH concentric hypertrophy or remodeling. Metformin reduced LV mass and RWT. There were LV systolic and diastolic alterations in both groups that metformin improved significantly. SR-LVe increased nearly 2-fold with metformin. Diastolic function improvement was not related to regression of hypertrophy. Conclusions: Patients with MS experienced subtle alterations of systolic and diastolic functions, which improved significantly with a small dosage of metformin over a treatment period of six months.

Antecedentes: El síndrome metabólico (SM) predice varias complicaciones cardiovasculares, como la insuficiencia cardiaca (IC). La disfunción ventricular izquierda (DVI) acompaña al síndrome metabólico. Aunque la metformina mejora la función del ventrículo izquierdo en pacientes diabéticos con insuficiencia cardiaca, no hay evidencia de su efecto sobre la disfunción ventricular izquierda en pacientes con síndrome metabólico. Se estudió el efecto de la metformina sobre la disfunción ventricular izquierda en pacientes con síndrome metabólico utilizando imágenes Doppler de tejido miocárdico y rastreo de manchas bidimensional. Objetivos: Evaluar los efectos de la metformina sobre la disfunción ventricular izquierda inducida por el SM. Material y métodos: Los pacientes con SM fueron asignados al azar en dos grupos (n = 20 cada uno) que recibieron, un antagonista de la angiotensina 2 y receptores; estatinas, fibratos o ambos. Un grupo recibió 850 mg de metformina diaria. La masa del VI, el espesor relativo de la pared (ERP), fracción de eyección, E/A y relación E/E', la velocidad Doppler tisular sistólica (Sm), el promedio de pico de tensión sistólica (SS), y la velocidad de deformación diastólica precoz pico (VDDPP) se obtuvieron por mediciones ecocardiográficas al inicio del estudio y a los seis meses. Resultados: Todos los pacientes presentaban hipertrofia concéntrica o remodelado. La metformina reduce la masa del VI y el ERP. Había alteraciones del ventrículo izquierdo sistólica y diastólica, alteraciones en ambos grupos que la metformina mejoró significativamente. VDDPP aumentó casi al doble con metformina. La mejoría de la función diastólica no se relacionó con regresión de la hipertrofia. Conclusiones: Los pacientes con SM experimentaron alteraciones sutiles de las funciones sistólica y diastólica, lo que mejoró significativamente con una pequeña dosis de metformina en un periodo de tratamiento de seis meses.

Atherosclerotic risk in middle-aged women with rheumatoid arthritis / Riesgo aterosclerótico en mujeres de mediana edad con artritis reumatoide

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease, with progressive joint destruction, leading to disability. In half of patients, mortality is associated to coronary events, caused by classical risk factors (RF) and/or the inflammatory process. Objectives: To explore the relevance of systemic inflammatory milieu in RA without the burden of traditional RF. Methods: Women with RA and free of traditional RF (n = 30) were compared against healthy women (n = 31). Body mass index, blood pressure, glycemia, serum creatinine, total cholesterol (TC), high density lipoprotein (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG) and oxidized LDL (oxLDL), erythrocyte sedimentation rate, high-sensitivity C reactive protein (hsCRP), lipid quotients for assessing risk (TC/HDLc, LDLc/HDLc, oxLDL/non HDL cholesterol, TG/HDLc), and ultrasonographic carotid intima media thickness (IMT) were estimated or measured. Results: hsCRP and oxLDL were significantly higher in RA patients. IMT values were among normality, but thickness was slightly increased in left carotid, suggesting early atherosclerotic changes. In RA patients inflammation is associated to a higher concentration of oxLDL. No atherosclerosis was proven but a slight greater thickness in left carotid foretells the development of the disease. Conclusions: In RA patients without vascular RF, a special follow up must be implemented to halt atherosclerosis development.

Antecedentes: La artritis reumatoide (AR) es una enfermedad inflamatoria crónica, con destrucción progresiva de las articulaciones, que lleva a la discapacidad. En la mitad de lospacientes, la mortalidad se asocia con eventos coronarios, causados por factores de riesgo (FR) clásicos y/o el proceso inflamatorio. Objetivo: Explorar la relevancia del medio inflamatorio sistémico en la AR sin la carga de FR tradicionales. Métodos: Las mujeres con AR, sin los FR tradicionales (n = 30) fueron comparados contra mujeres sanas (n = 31). El índice de masa corporal, presión arterial, glucemia, creatinina sérica, colesterol total (CT), lipoproteínas de alta densidad (HDL-c), colesterol de lipoproteínas de baja densidad (LDL-c), triglicéridos (TG) y LDL oxidada (LDLox), velocidad de sedimentación de los eritrocitos, proteína C reactiva de alta sensibilidad (PCR-us), cocientes de lípidos para la evaluación de riesgos (TC/HDLc, LDLc/HDLc, colesterol LDLox/noHDL, TG/HDLc), y el espesor ultrasonográfico de la capa íntima-media carotídea (IMT), fueron estimados o medidos. Resultados: hsCRP y LDLox fueron significativamente mayores en los pacientes con AR. Los valores de IMT estaban dentro de la normalidad, pero el espesor se incrementó ligeramente en la carótida izquierda, lo que sugiere cambios ateroscleróticos tempranos. En los pacientes con AR la inflamación está asociada con una mayor concentración de oxLDL. No se comprobó aterosclerosis pero un espesor ligeramente mayor en la carótida izquierda, los hace propensos a desarrollar la enfermedad. Conclusiones: En los pacientes con AR sin FR vascular, un seguimiento especial debe ser implementado para frenar el desarrollo de la aterosclerosis.