New targets for therapy in breast cancer: Mammalian target of rapamycin (mTOR) antagonists

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biologic functions such as transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In breast cancer this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. There is evidence suggesting that Akt promotes breast cancer cell survival and resistance to chemotherapy, trastuzumab, and tamoxifen. Rapamycin is a specific mTOR antagonist that targets this pathway and blocks the downstream signaling elements, resulting in cell cycle arrest in the G(1 )phase. Targeting the Akt/PI3K pathway with mTOR antagonists may increase the therapeutic efficacy of breast cancer therapy

Oncogenic Stress Induced by Acute Hyper-Activation of Bcr-Abl Leads to Cell Death upon Induction of Excessive Aerobic Glycolysis

In response to deregulated oncogene activation, mammalian cells activate disposal programs such as programmed cell death. To investigate the mechanisms behind this oncogenic stress response we used Bcr-Abl over-expressing cells cultivated in presence of imatinib. Imatinib deprivation led to rapid induction of Bcr-Abl activity and over-stimulation of PI3K/Akt-, Ras/MAPK-, and JAK/STAT pathways. This resulted in a delayed necrosis-like cell death starting not before 48 hours after imatinib withdrawal. Cell death was preceded by enhanced glycolysis, glutaminolysis, and amino acid metabolism leading to elevated ATP and protein levels. This enhanced metabolism could be linked to induction of cell death as inhibition of glycolysis or glutaminolysis was sufficient to sustain cell viability. Therefore, these data provide first evidence that metabolic changes induced by Bcr-Abl hyper-activation are important mediators of oncogenic stress-induced cell death

Salivary lipid peroxidation in patients with oral lichen planus

Background: Oral Lichen Planus (OLP) is an inflammatory condition with unknown etiology. Reactive oxygen species (ROS) and free radicals may play an important role in the pathogenesis of this disease. Objective: The aim of this study was to compare salivary lipid peroxidation in patients with oral lichen planus with healthy subjects. Methods: This case-control study was conducted in Zahedan School of Dentistry during 2014-15. Unstimulated saliva samples were collected from 30 patients with OLP and 30 age and gender-matched healthy controls and were transferred to the laboratory. Salivary lipid peroxidation products were measured using TBARS (thiobarbituric acid reactive substance) method. Data were analyzed using Mann-Whitney U test. Findings: Salivary lipid peroxidation in patients with OLP was significantly higher than healthy controls (1.57±0.63 μM vs. 1.2±0.77μM). Mean Salivary lipid peroxidation in women with OLP was significantly higher than healthy women (1.67±0.67 μM vs. 1.16±0.82 μM). Conclusion: With regards to the results, it seems that lipid peroxidation in patients with OLP is higher than healthy subjects