P38 MAPK expression and activation predicts failure of response to CHOP in patients with Diffuse Large B-Cell Lymphoma

The p38 MAPK is constitutively activated in B-NHL cell lines and regulates chemoresistance. Accordingly, we hypothesized that activated p38 MAPK may be associated with the in vivo unresponsiveness to chemotherapy in B-NHL patients.Tissue microarrays generated from eighty untreated patients with Diffused Large B Cell Lymphoma (DLBCL) were examined by immunohistochemistry for the expression of p38 and phospho p38 (p-p38) MAPK. In addition, both Bcl-2 and NF-κB expressions were determined. Kaplan Meier analysis was assessed.Tumor tissues expressed p38 MAPK (82 %) and p-p38 MAPK (30 %). Both p38 and p-p38 MAPK expressions correlated with the high score performance status. A significant correlation was found between the expression p-p38 and poor response to CHOP. The five year median follow-up FFS was 81 % for p38(-) and 34 % for p38(+) and for OS was 83 % for p38(-) and 47 % for p38(+). The p-p38(+) tissues expressed Bcl-2 and 90 % of p-p38(-) where Bcl-2(-). The coexpression of p-p38 and Bcl-2 correlated with pool EFS and OS. There was no correlation between the expression of p-p38 and the expression of NF-κB.The findings revealed, for the first time, that a subset of patients with DLBCL and whose tumors expressed high p-p38 MAPK responded poorly to CHOP therapy and had poor EFS and OS. The expression of p38, p-p38, Bcl2 and the ABC subtype are significant risk factors both p38 and p-p38 expressions remain independent prognostic factors

Serum human chorionic gonadotropin is associated with angiogenesis in germ cell testicular tumors

<p>Abstract</p> <p>Background</p> <p>Germ cell testicular tumors have survival rate that diminishes with high tumor marker levels, such as human chorionic gonadotropin (hCG). hCG may regulate vascular neoformation through vascular endothelial growth factor (VEGF). Our purpose was to determine the relationship between hCG serum levels, angiogenesis, and VEGF expression in germ cell testicular tumors.</p> <p>Methods</p> <p>We conducted a retrospective study of 101 patients. Serum levels of hCG, alpha-fetoprotein (AFP), and lactate dehydrogenase were measured prior to surgery. Vascular density (VD) and VEGF tissue expression were determined by immunohistochemistry and underwent double-blind analysis.</p> <p>Results</p> <p>Histologically, 46% were seminomas and 54%, non-seminomas. Median follow-up was 43 ± 27 months. Relapse was present in 7.5% and mortality in 11.5%. Factors associated with high VD included non-seminoma type (<it>p </it>= 0.016), AFP ≥ 14.7 ng/mL (<it>p </it>= 0.0001), and hCG ≥ 25 mIU/mL (<it>p </it>= 0.0001). In multivariate analysis, the only significant VD-associated factor was hCG level (<it>p </it>= 0.04). When hCG levels were stratified, concentrations ≥ 25 mIU/mL were related with increased neovascularization (<it>p </it>< 0.0001). VEGF expression was not associated with VD or hCG serum levels.</p> <p>Conclusion</p> <p>This is the first study that relates increased serum hCG levels with vascularization in testicular germ cell tumors. Hence, its expression might play a role in tumor angiogenesis, independent of VEGF expression, and may explain its association with poor prognosis. hCG might represent a molecular target for therapy.</p

Potencial productivo y dinamica de tallos de dos brachiarias a edades de rebrote en otoño: Productive potential and stem dynamics of two brachiarias species at regrowth ages in autumn

La estacionalidad y la frecuencia de cosecha tienen un efecto en la tasa de rebrote en los pastos y pueden disminuir el porcentaje de senescencia y descomposición del forraje, por lo tanto, influyen en el rendimiento, en la calidad y la persistencia de la pradera. El objetivo fue evaluar el potencial productivo y dinámica de tallos de los ecotipos Insurgente (Brachiaria brizantha Hochst. Stapf Cv. Insurgente) y Mulato (Brachiaria hibrido Cv. Mulato II) en tres periodos de corte (21, 42, y 63 días) en Otoño. En el Campus Tuxpan de la Facultad de Ciencias Agropecuarias y Ambientales, de Iguala, Gro. Las variables evaluadas fueron: rendimiento de forraje (kg MS ha-1), producción de componentes morfológicos (HOJA Y TALLO), relación hoja tallo (H:T), densidad poblacional (DPT), tasa de aparición de tallos (TAT), tasa de muerte de tallos (TMT), tasa de sobrevivencia de tallos (TST) e índice de estabilidad de tallos (IET), Se utilizó un diseño de bloques completamente al azar con arreglo bifactorial (Factor 1: Brachiarias, Factor 2: periodos de corte). Los datos se analizaron con el procedimiento ANOVA del paquete estadístico SAS® versión 9.2 para Windows®. La comparación de medias se realizó con la prueba de “t” de “Student” (P&lt;0.05). La producción total de materia seca (4392.7 Kg MS ha-1), la de hoja (3084.8 Kg MS ha-1), la tasa de crecimiento (209.17 Kg MS ha-1) y la relación hoja tallo (4.2943 Kg MS kg-1) fueron afectados por los periodos de corte (P &lt;0001) y por los ecotipos, el Mulato presentó los valores más altos. La mayor producción de hoja, tallo y total de materia seca se presentó en el tercer periodo de corte y de igual forma la tasa de crecimiento. En la dinámica de tallos los ecotipos no presentaron diferencias, los periodos de corte si afectaron a la TAT (81.87 tallos m2) y al IET (1.79), en los que el periodo de corte 1 presento los valores más altos. &nbsp

Enfermedades crónicas

Adherencia al tratamiento farmacol&oacute;gico y relaci&oacute;n con el control metab&oacute;lico en pacientes con DM2Aluminio en pacientes con terapia de reemplazo renal cr&oacute;nico con hemodi&aacute;lisis en Bogot&aacute;, ColombiaAmputaci&oacute;n de extremidades inferiores: &iquest;est&aacute;n aumentando las tasas?Consumo de edulcorantes artificiales en j&oacute;venes universitariosC&oacute;mo crecen ni&ntilde;os normales de 2 a&ntilde;os que son sobrepeso a los 7 a&ntilde;osDiagn&oacute;stico con enfoque territorial de salud cardiovascular en la Regi&oacute;n MetropolitanaEfecto a corto plazo de una intervenci&oacute;n con ejercicio f&iacute;sico, en ni&ntilde;os con sobrepesoEfectos de la cirug&iacute;a bari&aacute;trica en pacientes con s&iacute;ndrome metab&oacute;lico e IMC &lt; 35 KG/M2Encuesta mundial de tabaquismo en estudiantes de profesiones de saludEnfermedades cr&oacute;nicas no transmisibles: Consecuencias sociales-sanitarias de comunidades rurales en ChileEpidemiolog&iacute;a de las muertes hospitalarias por patolog&iacute;as relacionadas a muerte encef&aacute;lica, Chile 2003-2007Estado nutricional y conductas alimentarias en adolescentes de 4&ordm; medio de la Regi&oacute;n de CoquimboEstudio de calidad de vida en una muestra del plan piloto para hepatitis CEvaluaci&oacute;n del proceso asistencial y de resultados de salud del GES de diabetes mellitus 2Factores de riesgo cardiovascular en poblaci&oacute;n universitaria de la Facsal, universidad de Tarapac&aacute;Implicancias psicosociales en la g&eacute;nesis, evoluci&oacute;n y tratamiento de pacientes con hipertensi&oacute;n arterial esencialInfarto agudo al miocardio (IAM): Realidad en el Hospital de Puerto Natales, 2009-2010Introducci&oacute;n de nuevas TIC y mejor&iacute;a de la asistencia a un programa de saludNi&ntilde;os obesos atendidos en el Cesfam de Puerto Natales y su entorno familiarPerfil de la mortalidad por c&aacute;ncer de cuello uterino en R&iacute;o de JaneiroPerfil del paciente primo-consultante del Programa de Salud Cardiovascular, Consultorio Cordillera Andina, Los AndesPrevalencia de automedicaci&oacute;n en mujeres beneficiarias del Hospital Comunitario de Til-TiPrevalencia de caries en poblaci&oacute;n preescolar y su relaci&oacute;n con malnutrici&oacute;n por excesoPrevalencia de retinopat&iacute;a diab&eacute;tica en comunas dependientes del Servicio de Salud Metropolitano Occidente (SSMOC)Problemas de adherencia farmacol&oacute;gica antihipertensiva en poblaci&oacute;n mapuche: Un estudio cualitativoRol biol&oacute;gico de los antioxidantes innatos en pacientes portadores de VIH/SidaSobrepeso en empleados de un restaurante de una universidad p&uacute;blica del estado de S&atilde;o Paul

ctDNA Is Useful to Detect Mutations at Codon 641 of Exon 16 of EZH2, a Biomarker for Relapse in Patients with Diffuse Large B-Cell Lymphoma

(1) Background: The epigenetic regulator EZH2 is a subunit of the polycomb repressive complex 2 (PRC2), and methylates H3K27, resulting in transcriptional silencing. It has a critical role in lymphocyte differentiation within the lymph node. Therefore, mutations at this level are implicated in lymphomagenesis. In fact, the mutation at the Y641 amino acid in the EZH2 gene is mutated in up to 40% of B-cell lymphomas. (2) Methods: We compared the presence of exon 16 EZH2 mutations in tumor samples and ctDNA in a prospective trial. These mutations were determined by Sanger sequencing and ddPCR. (3) Results: One hundred and thirty-eight cases were included. Ninety-eight were germinal center, and twenty had EZH2 mutations. Mean follow-up (IQR 25&ndash;75) was 23 (7&ndash;42) months. The tumor samples were considered the standard of reference. Considering the results of the mutation in ctDNA by Sanger sequencing, the sensibility (Se) and specificity (Sp) were 52% and 99%, respectively. After adding the droplet digital PCR (ddPCR) analysis, the Se and Sp increased to 95% and 100%, respectively. After bivariate analysis, only the presence of double-hit lymphoma (p = 0.04) or EZH2 mutations were associated with relapse. The median Progression free survival (PFS) (95% interval confidence) was 27.7 (95% IC: 14&ndash;40) vs. 44.1 (95% IC: 40&ndash;47.6) months for the mutated vs. wild-type (wt) patients. (4) Conclusions: The ctDNA is useful for analyzing EZH2 mutations, which have an impact on PFS

Quantitative Imaging Parameters of Contrast-Enhanced Micro-Computed Tomography Correlate with Angiogenesis and Necrosis in a Subcutaneous C6 Glioma Model

The aim of this work was to systematically obtain quantitative imaging parameters with static and dynamic contrast-enhanced (CE) X-ray imaging techniques and to evaluate their correlation with histological biomarkers of angiogenesis in a subcutaneous C6 glioma model. Enhancement (E), iodine concentration (CI), and relative blood volume (rBV) were quantified from single- and dual-energy (SE and DE, respectively) micro-computed tomography (micro-CT) images, while rBV and volume transfer constant (Ktrans) were quantified from dynamic contrast-enhanced (DCE) planar images. CI and rBV allowed a better discernment of tumor regions from muscle than E in SE and DE images, while no significant differences were found for rBV and Ktrans in DCE images. An agreement was found in rBV for muscle quantified with the different imaging protocols, and in CI and E quantified with SE and DE protocols. Significant strong correlations (Pearson r &gt; 0.7, p &lt; 0.05) were found between a set of imaging parameters in SE images and histological biomarkers: E and CI in tumor periphery were associated with microvessel density (MVD) and necrosis, E and CI in the complete tumor with MVD, and rBV in the tumor periphery with MVD. In conclusion, quantitative imaging parameters obtained in SE micro-CT images could be used to characterize angiogenesis and necrosis in the subcutaneous C6 glioma model