Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation.

Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, has been reported to act as insulin sensitizer and exert cardiovascular actions. In this work, we hypothesized that RGZ exerts a PPARγ-dependent regulation of blood pressure through modulation of angiotensin-converting enzyme (ACE)-type 2 (ACE2)/angiotensin-(1-7)/angiotensin II type-2 receptor (AT2R) axis in an experimental model of high blood pressure. We carried on experiments in normotensive (Sham) and aortic coarctation (AoCo)-induced hypertensive male Wistar rats. Both sham and AoCo rats were treated 7 days with vehicle (V), RGZ (5 mg/kg/day), or RGZ+BADGE (120 mg/kg/day) post-coarctation. We measured blood pressure and vascular reactivity on aortic rings, as well as the expression of renin-angiotensin system (RAS) proteins. We found that RGZ treatment in AoCo group decreases blood pressure values and improves vascular response to acetylcholine, both parameters dependent on PPARγ-stimulation. RGZ lowered serum angiotensin II (AngII) but increased Ang-(1-7) levels. It also decreased 8-hydroxy-2'-deoxyguanosine (8-OH-2dG), malondialdehyde (MDA), and improved the antioxidant capacity. Regarding protein expression of RAS, RGZ decreases ACE and angiotensin II type 1 receptor (AT1R) and improved ACE2, AT2R, and Mas receptor in AoCo rats. Additionally, an in silico analysis revealed that 5'UTR regions of RAS and PPARγ share motifs with a transcriptional regulatory role. We conclude that RGZ lowers blood pressure values by increasing the expression of RAS axis proteins ACE2 and AT2R, decreasing the levels of AngII and increasing levels of Ang-(1-7) in a PPARγ-dependent manner. The in silico analysis is a valuable tool to predict the interaction between PPARγ and RAS.

Peroxisome proliferator-activated receptors (PPAR) downregulate the expression of pro-inflammatory molecules in an experimental model of myocardial infarction.

Myocardial infarction (MI) has been associated with an inflammatory response and a rise in TNF-α, interleukin (IL)-1ß, and IL-6. Peroxisome proliferator-activated receptors (PPARs) promote a decreased expression of inflammatory molecules. We aimed to study whether PPAR stimulation by clofibrate decreases inflammation and reduces infarct size in rats with MI. Male Wistar rats were randomized into 3 groups: control, MI + vehicle, and MI + clofibrate (100 mg/kg). Treatment was administered for 3 consecutive days, previous to 2 h of MI. MI induced an increase in protein expression, mRNA content, and enzymatic activity of inducible nitric oxide synthase (iNOS). Additionally, MI incited an increased expression of matrix metalloproteinase (MMP)-2 and MMP-9, intercellular adhesion molecule (ICAM)-1, and IL-6. MI also elevated the nuclear content of nuclear factor-κB (NF-κB) and decreased IκB, both in myocyte nuclei and cytosol. Clofibrate treatment prevented MI-induced changes in iNOS, MMP-2 and MMP-9, ICAM-1, IL-6, NF-κB, and IκB. Infarct size was smaller in clofibrate-treated rats compared to MI-vehicle animals. In silico analysis exhibited 3 motifs shared by genes from renin-angiotensin system, PPARα, iNOS, MMP-2 and MMP-9, ICAM-1, and VCAM-1, suggesting a cross regulation. In conclusion, PPARα-stimulation prevents overexpression of pro-inflammatory molecules and preserves viability in an experimental model of acute MI.

Expresión de catepsina D en carcinoma mamario y sus correlaciones clínicas e histopatológicas / Cathepsin D expression in breast cancer and its correlations with clinical and histopathological parameters

Antecedentes. La catepsina D es una proteasa lisosomal que se puede sobrexpresar en cáncer mamario. Varios estudios hechos en citosol de tejido tumoral demuestran que los niveles elevados de catepsina D se asocian con pronóstico desfavorable en pacientes con cáncer mamario pero en estudios realizados por inmunohistoquímica, los resultados no son concluyentes. Objetivo. Evaluar si catepsina D, medida por técnica inmunohistoquímica con un anticuerpo policlonal, puede ser considerada como factor pronóstico en el cáncer de mama. Pacientes y métodos. Se realizó en 68 muestras tumorales que correspondían a pacientes con cáncer mamario en etapas clínicas I-IV, tratadas en el Instituto Nacional de Cancerología durante los años 1985 y 1986. Resultados. Treinta y cinco de las 68 pacientes (51 por ciento) presentaron tinción positiva intensa para catepsina D, 19 (28 por ciento) tuvieron tinción leve y 14 (21 por ciento) fueron negativas. En 10 de las pacientes con tinción leve existieron artificios por defectos en la fijación del tejido. La expresión de catepsina D no tuvo valor pronóstico ni se encontró asociación de la catepsiana D con otros factores pronósticos clínicos e histopatológicos conocidos. Conclusión. La catepsina D determinada por inmunohistoquímica no tuvo valor pronóstico en el cáncer de mama

Gastric carcinoma: curative resection and adjuvant chemotherapy

A retrospective study of gastric adenocarcinoma treated with surgery as curative attempt was performed at the Oncology Service, in the Hospital Regional 20 de Noviembre, ISSSTE, Morbidity and mortality of the surgical procedures were evaluated, the significance of several risk factors factors and the survival impact of adjuvant chemotherapy with 5-fluorouracil (5-FU) and mitomycin C (MMC). In the period from 1975 to 1991 a total of 483 new cases were seen. In only 54 patients (11.2 por ciento) was it possible to undertake a curative resection. The patients were assigned to three groups of treatment: surgery alone (14 cases), surgery + 5-FU (19 cases), and surgery + 5-FU -MMC (21 cases). Three different types of surgical techniques are regularly performed in our service for gastric cancer treatment: Billroth II distal gastrectomy, total gastrectomy with roux-En-Y reconstruction, and esophagogastrectomy with esophagogastrostomy. Surgical morbidity and mortality was zero. Chemotherapy toxicity was transient and low, no related deaths were recorded. The prognostic factor associated significantly with survival were lymph node status and tumor penetration. The histologic differentiation as well the tumor location and type of surgery had no significance. The estimated 5-year survival of the patients treated with surgery alone was 62 per cent, while that of the patients treated with surgery plus chemotherapy was 38 per cent. These groups treated with 5-FU alone or in combination with MMC had no survival difference between them. Surgery in our institution has low morbidity and mortality. The lymph node status, as well as the tumor penetration through the gastric wall, are some of the main prognostic factors in gastric carcinoma. No improvement in survival or disease-free interval was observed when MMC was added to 5-FU. The studies aimed to demonstrate adjuvant chemotherapy effectiveness must include a group treated only with surgery and at the present time combination adjuvant chemotherapy should not be administered on a routine basis outside clinical trials

Amplificación y rearreglo in vivo del oncogen c-myc en tumores de mama humano / Entargement and read justment in vivo of the c-myc oncogene in tumors of human breast

Hemos estudiado la organozación genómica del proto-oncogen myc celular (c-myc) en 48 tumores de mama primarios de humano. Dos tipos de alteraciones (amplificación y rearreglo) se observó en 27 de los tumores estudiados (56%). El proto-oncogen c-myc, apareció amplificado de 2 a 15 veces en el DNA de 20 tumores (41%). Fragmentos relacionados a c-myc no germinal (rearreglos) de tamaño variable fueron detectados en 7 tumores de mama primarios (6 malignos, 1 benigno); 4 de estos tumores presentaron tanto arreglo como amplificación y los otros 3 presentaron únicamente rearreglo. La mayoría de los tumores analizados fueron adenocarcinomas ductal invasivo; 58% de éstos mostraron alteraciones genéticas en el locus c-myc. Aunque las alteraciones de c-myc descritas aquí no aparecen correlacionarse con el comportamiento agresivo de los tumores de mama primarios, parecen estar asociados con el desarrollo de carcinoma mamario

Alteraciones genéticas del proto-oncogen c-myc en carcinoma canalicular infiltrante de glándula mamaria y su relación con la presencia de receptores esteroideos y características microscópicas del tumor / Proto-oncogene c-myc genetic disorders in infiltrant chanalicular carcinoma of mammary gland and its relation with steroidal receptors and tumor microcopic characteristics

Se presentaron los resultados del estudio de alteraciones genéticas del proto-oncogen c-myc en 29 muestras de tumores de pacientes con carcinoma canalicular infiltrante, utilizando como referencia DNA de linfocitos de sangre periférica de las mismas pacientes. Se analizaron también las características microscópicas de los tumores estudiados y el contenido de receptores para Estradiol (E2) y Progesterona Pg) en las mismas muestras