Marian Adamkov

Objetivos: Se conocen diferencias considerables entre el colon proximal y el distal, estas incluyen características embriológicas, anatómicas, histológicas, bioquímicas y fisiológicas. Las distinciones antes mencionadas pueden influir en el desarrollo de entidades clínico-morfológicas variables. La proteína antiapoptótica multifuncional survivina participa en la regulación del ciclo celular, las cascadas apoptóticas y estimula la angiogénesis. Material y métodos: Se evaluó inmunohistoquímicamente el patrón de expresión de la proteína antiapoptótica survivina en un panel de 243 adenomas de colon para determinar su asociación con la localización colónica. En cada sección se evaluó la compartimentación subcelular de la survivina y la intensidad de la inmunorreacción. Resultados: La survivina se expresó en 190 casos (78,2%). El análisis estadístico confirmó una correlación significativa de la compartimentación subcelular de survivina y la intensidad de la inmunorreacción con la localización de los adenomas en el colon. Conclusiones: Teniendo en cuenta las características únicas de la survivina, su patrón de expresión en los adenomas del lado proximal y las distinciones entre el colon derecho e izquierdo, suponemos que el nivel de survivina puede contribuir a un mayor fenotipo proliferativo de los adenomas proximales.

Airway remodeling (AR) consists of wall thickening and hyperreactivity. STIM (stromal interaction molecule) and Orai protein pathways mediate extracellular Ca²⁺ signals involved in AR. This study aims to define the effects on AR of the STIM-Orai antagonist SKF 96365 given by inhalation in three increasing doses in ovalbumin-induced AR. In the control group, the antiasthmatic budesonide and salbutamol were given in the same model. The airway structure was evaluated by histological and immunohistochemistry and reactivity by specific airway resistance, contraction strength of isolated airway smooth muscles, and mucociliary clearance expressed by ciliary beating frequency. The immuno-biochemical markers of chronic inflammation were evaluated by BioPlex and ELISA assays. The AR was mediated by inflammatory cytokines and growth factors. The findings show significant anti-remodeling effects of SKF 96365, which were associated with a decrease in airway hyperreactivity. The anti-remodeling effect of SKF 96365 was mediated via the suppression of IL-4, IL-5, and IL-13 synthesis, and IL-12–INF-γ–TGF-β pathway. The budesonide-related AR suppression had to do with a decrease in proinflammatory cytokines and an increase in the anti-inflammatory IL-10, with negligible influence on growth factors synthesis and mucous glands activity.

The data from in-vitro and in-vivo studies show that both peroral antidiabetic metformin (MF) and pineal hormone melatonin (MT) inhibit the growth of many cancers, including breast cancer. However, most in-vivo studies used standard-type diet with low fat content. Therefore, in this study, we evaluated the chemopreventive effect of MF and MT in an in-vivo model of breast cancer in rats on a high-fat diet (10% of total fat). Mammary carcinogenesis was induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats. Chemoprevention with MF (administered in a diet, 0.2%) and MT (administered in tap water, 20 mg/l) was induced 20 days before the carcinogen administration through the termination of the experiment (14 weeks after carcinogen administration). Tumor growth parameters were analyzed together with histopathological examination and immunohistochemical detection of KI67 (proliferation marker), caspase-3, BAX, BCL-2 (apoptosis markers), and CD24 and CD44 (cancer stem cell markers) in mammary tumor samples. The combination of chemopreventive agents decreased tumor incidence by 29%. Cumulative tumor volume was lower in all groups treated with chemoprevention. Histopathology did not show significant changes in high-grade/low-grade tumor ratio. Immunohistochemistry showed increased expression of BAX in the combination group, and caspase-3 expression increased in both MT and combination groups. MT, and particularly the MF and MT combination, inhibited DMBA-induced mammary tumor growth in rats by apoptosis stimulation in cancer cells. Our results indicate that MT supplements in patients treated with MF may have a considerable effect on the incidence of breast cancer.