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Viedma-Rodriguez R.,Mexican Institute of Social Insurance | Viedma-Rodriguez R.,National Autonomous University of Mexico | Baiza-Gutman L.A.,National Autonomous University of Mexico | Garcia-Carranca A.,National Autonomous University of Mexico | And 3 more authors.
International Journal of Oncology | Year: 2013

Apoptosis is controlled by the BCL-2 family of proteins, which can be divided into three different subclasses based on the conservation of BCL-2 homology domains. BIK is a founding member of the BH3-only pro-apoptotic protein family. BIK is predominantly localized in the endoplasmic reticulum (ER) and induces apoptosis through the mitochondrial pathway by mobilizing calcium from the ER to the mitochondria. In this study, we determined that suppression of the death gene Bik promotes resistance to tamoxifen (TAM) in MCF-7 breast cancer cells. We utilized small interfering (siRNA) to specifically knockdown BIK in MCF-7 cells and studied their response to tamoxifen. The levels of cell apoptosis, the potential mitochondrial membrane (△ψm), and the activation of total caspases were analyzed. Western blot analysis was used to determine the expression of some BCL-2 family proteins. Flow cytometry studies revealed an increase in apoptosis level in MCF-7 cells and a 2-fold increase in relative BIK messenger RNA (mRNA) expression at a concentration of 6.0 μM of TAM. BIK silencing, with a specific RNAi, blocked TAM-induced apoptosis in 45±6.78% of cells. Moreover, it decreased mitochondrial membrane potential (ψm) and total caspase activity, and exhibited low expression of pro-apoptotic proteins BAX, BAK, PUMA and a high expression of BCl-2 and MCL-1. The above suggests resistance to TAM, regulating the intrinsic pathway and indicate that BIK comprises an important factor in the process of apoptosis, which may exert an influence the ER pathway, which regulates mitochondrial integrity. Collectively, our results show that BIK is a central component of the programmed cell death of TAM-induced MCF-7 breast cancer cells. The silencing of BIK gene will be useful for future studies to establish the mechanisms of regulation of resistance to TAM.

Vasquez C.,University of Colima | Millan-Guerrero R.O.,Mexican Institute of Social Insurance | Trujillo-Hernandez B.,Mexican Institute of Social Insurance | Isais-Millan S.,Mexican Institute of Social Insurance | And 3 more authors.
Journal of International Medical Research | Year: 2012

Objectives: To determine among adult patients with type-2 diabetes mellitus the proportion diagnosed with diabetic polyneuropathy (DPN) by clinical evaluation and by the Hoffmann reflex (H-reflex). In addition, the predictive value of the H-reflex in the diagnosis of DPN was evaluated. Methods: Studies were carried out on 150 adult patients referred for neuropathy screening. Diagnostic criteria for DPN were at least two abnormalities in clinical neurophysiological examinations and electrophysiological testing (H-reflex and nerve conduction velocity). Logistic regression analysis was performed to identify unique contributions of study characteristics to positive versus negative outcomes. RESULTS: H-reflex was absent in 39.3% (59/150) and latency was prolonged in 43.3% (65/150) of patients. Ulnar nerve motor branch nerve conduction showed prolonged latency in 9.3% (14/150) of patients. Logistic regression analysis indicated that the H-reflex was significantly associated with positive outcomes. CONCLUSION: The H-reflex could have a predictive value in DPN, providing more quantitative information regarding diagnosis than conventional nerve conduction studies. © 2012 Field House Publishing LLP.

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