BackgroundUp-regulation of the PI3K/mTOR (phosphatidylinositol-3′ kinase/mammalian target of rapamycin) signaling is common in carcinoma. Consistently, targeting these molecules has been shown to halt the growth of many tumors. The main purpose of this study was to develop surrogate biomarkers of the antitumor activity of PI3K/mTOR inhibitors.MethodsFragments from eight tumors were collected immediately after resection in ice-cold RPMI gassed with 95% O2 :5% CO2. Viability was determined by measuring tumor cellular respiration (mitochondrial O2 consumption). The specimens were incubated at 37°C with and without 50 nM GSK2126458 (a highly potent and selective inhibitor of PI3K/mTOR) for 90 min. The tissue was then processed for histology, measurement of intracellular caspase-3 activity (using the caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin), and immunohistochemical detection of the apoptotic biomarkers caspase-3, cytochrome C, and annexin A2.ResultsGSK2126458 induced morphologic changes in four tumors (two invasive ductal carcinomas, one invasive lobular carcinoma, and one ovarian dysgerminoma), intracellular caspase-3 activity in three tumors (two invasive ductal carcinomas and one poorly differentiated signet ring adenocarcinoma of gastric origin), and immunohistochemical evidence of apoptosis in at least four tumors (three invasive ductal carcinomas and one adenocarcinoma of gastric origin). Two tumors (ovarian serous carcinoma and moderately differentiated adenocarcinoma of colorectal origin) demonstrated no treatment effect.ConclusionThese preliminary results demonstrate the feasibility of using in vitro biomarkers for detecting antitumor activities of the rapidly emerging PI3K/mTOR inhibitors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-014-0090-z) contains supplementary material, which is available to authorized users.

In operable breast cancer patients, a negative AUS+/- Bx may be a predictor of non-involvement of the NSLN.

The incidence of cardiac rupture following blunt trauma is rare, occurring in 0.3%-0.5% of all blunt trauma patients. It can be fatal at the trauma scene, and is frequently missed in the emergency room setting. The severity of a cardiac trauma is based on the mechanism and degree of the force applied. The objective of this study was to report the case of a 32-year-old male patient who was involved in a motor vehicle collision and presented to the emergency room with signs of hypovolemic shock. The patient was found to have severe chest trauma associated with massive hemothorax requiring immediate intervention. The patient had an emergent thoracotomy revealing a right atrial injury. Repair of the atrial injury reversed the state of shock. The patient was discharged after 35 days of hospitalization in good condition.