No effect of stem cell mobilization with GM-CSF on infarct size and left ventricular function in experimental acute myocardial infarction

Objectives:. To evaluate the effect of bone marrowpluripotent stem cell mobilization with granulocyte-monocyte colony stimulating factor (GMCSF) on infarct size and left ventricular function, in the setting of acute myocardial infarction, with a protocol easily applicable in clinical practice. Methods:. Ten pigs underwent left thoracotomy and left anterior descending coronary artery occlusion for 1 h, followed by reperfusion. After 50 min of arterial occlusion, the animals were randomly divided between treatment with placebo (Group 1) and subcutaneous GM-CSF (Group 2). The thoracotomy was closed and the animals recovered. In Group 2, GM-CSF, 20 mug/kg, was administered daily, 5 days/week, for 3 weeks. Echocardiograms were obtained at 5 and 28 days after acute myocardial infarction. At 30 days, infarct size, expressed as a percentage of the whole left ventricular mass, was measured. Results:. The white blood cell count increased from 13000 +/- 3338/mul to 28700 +/- 4916/mul (p = 0.001) in the GM-CSF-treated group. Infarct size was 7.8 +/- 6.1% in Group 1 vs 7.5 +/- 7.7% in Group 2 (ns). Similarly, no significant difference was observed between the 2 study groups in any of the echocardiographic measurements made at 28 days. Conclusions:. Subcutaneous GMCSF administered during the early post acute myocardial infarction period neither decreased infarct size nor improved left ventricular function. Other protocols for mobilization of stem cells and their concentration in the injured area should be developed to combine efficacy and clinical applicability

Expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin in localized prostate cancer

Objective: To explore the correlation between the expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin in prostate cancer (PCa) and its clinicopathological data including tumor grade and clinical stage. Methods: The expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin was examined in 157 cases of PCa and adjacent normal prostatic tissue by immunohistochemical assay, and the correlation with clinicopathological features was analyzed. Results: Expressions of α5-integrin, α7-integrin, and Ε-cadherin in PCa were lower than those in normal prostatic tissues (P<0.05). N-cadherin expression was higher in cancer prostatic tissue than in normal prostatic tissues (P<0.05). The reduced expression of α5-integrin, α7-integrin, and Ε-cadherin was related to Gleason score, pathological stage, lymph node metastasis, and prostate-specific antigen level, but it was not associated with positive surgical margins and patient age. The increased expression of N-cadherin was related to Gleason score, pathological stage, lymph node metastasis, and prostate-specific antigen level, but not to age and positive surgical margins. The expression of E-cadherin was highly negatively correlated with that of N-cadherin and also positively correlated with that of α5-integrin and α7-integrin. Conclusion: The reduced expression of α5-integrin, α7-integrin, and Ε-cadherin and abnormal expression of N-cadherin play an important role in the occurrence and development of PCa. The results indicate that these have potential values in the diagnosis and are predictable indices in the proliferation of PCa. © 2016 Elsevier Inc

. Inclusion of Quercetin in Gold Nanoparticles Decorated with Supramolecular Hosts Amplifies Its Tumor Targeting Properties

Despite the anticancer potential of natural products (NPs), their limited bioavailability necessitates laborious derivatization or covalent conjugation to delivery vehicles. To unleash their potential we developed a nanohybrid delivery platform with noncovalently tunable surface. Initially, the active compound was encapsulated in a macrocycle, p-sulphonatocalix[4]arene, enabling a 62,000-fold aqueous solubility amplification as also a 2.9-fold enhancement in its cytotoxicity with respect to the parent compound in SW-620 colon cancer cells. A pH stimuli responsive behavior was recorded for this formulate, where a programmable release of quercetin from the macrocycle was monitored in acidic environment. Then, a nanoparticle gold core was decorated with calixarene hosts to accommodate non-covalently NPs. The loaded nanocarrier with the NP quercetin dramatically enhanced the cytotoxicity (>50 fold) of the parent NP in colon cancer and altered its cell membrane transport mode. In vivo experiments in a mouse 4T1 tumor model showed a reduction of tumor volume in mice treated with quercetin-loaded nanoparticles without apparent toxic effects. Further analysis of the tumor-derived RNA highlighted that treatment with quercetinloaded nanoparticles altered the expression of 27 genes related to apoptosis