RESUMEN
Breast cancer (BC) is a heterogenous disease with multiple pathways implicated in its development, progression, and drug resistance. Autophagy, a cellular process responsible for self-digestion of damaged organelles, had been recognized as eminent player in cancer progression and chemotherapeutic resistance. The haploinsufficiency of Beclin 1 (BECN1), autophagy protein, is believed to contribute to cancer pathogenesis and progression. In our study, we investigated the expression of BECN1 in a BC female Egyptian patient cohort, as well as its prognostic role through evaluating its association with disease free survival (DFS) after 2 years follow up and association of tumor clinicopathological features. Twenty frozen female BC tissue samples and 17 adjacent normal tissue were included and examined for the expression levels of BECN1. Although the tumor tissues showed lower expression 0.73 (0-8.95) than their corresponding normal tissues 1.02 (0.04-19.59), it was not statistically significant, p: 0.463. BECN1 expression was not associated with stage, nodal metastasis or tumor size, p:0.435, 0.541, 0.296, respectively. However, statistically significant negative correlation was found between grade and BECN1 mRNA expression in the studied cases, p:0.028. BECN1 expression had no statistically significant association with DFS, P = 0.944. However, we observed that triple negative (TNBC) cases had significantly lower DFS rate than luminal BC patients, p: 0.022, with mean DFS 19.0 months, while luminal BC patients had mean DFS of 23.41 months. Our study highlights the potential role of BECN1 in BC pathogenesis, showing that BECN1 expression correlates with poorer differentiation of BC, indicating its probable link with disease aggressiveness. DFS two years follow up showed that TNBC subtype remains associated with less favorable prognosis.
Asunto(s)
Beclina-1 , Neoplasias de la Mama , Clasificación del Tumor , ARN Mensajero , Humanos , Femenino , Beclina-1/genética , Beclina-1/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Persona de Mediana Edad , Adulto , ARN Mensajero/genética , ARN Mensajero/metabolismo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Supervivencia sin Enfermedad , Biomarcadores de Tumor/genética , Anciano , EgiptoRESUMEN
Acute myocardial infarction (AMI) is an instant death of cardiomyocytes that ends in a large mortality worldwide. Thus, there is a great interest to come up with novel protective approaches for AMI to mount cardiomyocyte survival, enhance postinfarcted cardiac function, and countermand the process of cardiac remodeling. Spermidine has vital roles in vast cellular processes under pathophysiological circumstances. This study aims to enhance our comprehension of the role of autophagy as a possible protective sequel of spermidine supplementation on postinfarction ventricular dysfunction in a rat model of AMI induced by isoproterenol (ISO). Thirty male rats were divided into three groups (control, AMI, and spermidine + AMI). AMI was induced by subcutaneous ISO injections for two consecutive days. Rats were pretreated with spermidine by intraperitoneal injection before induction of AMI. Electrocardiogram (ECG) was recorded in all rats 24 h after the second dose of ISO. Rats were sacrificed after ECG recording, and samples were taken for biochemical assessments. Spermidine intake before induction of AMI in rats significantly attenuated cardiac dysfunction where cardiac enzymes are decreased, and ECG changes induced by ISO are reversed in cardiomyocytes. Spermidine affects the autophagic flux of autophagy-related protein expression (LC3-II, TFEP, and p62). Furthermore, it increased the total antioxidant capacity.