Structure and stability of Con(pyridine)m − clusters: Absence of metal inserted structures

A synergistic approach combining the experimental photoelectron spectroscopy and theoretical electronic structure studies is used to probe the geometrical structure and the spin magnetic moment of Con(pyridine)−m clusters. It is predicted that the ground state of Co(pyridine)− is a structure where the Co atom is inserted in a CH bond. However, the insertion is marked by a barrier of 0.33eV that is not overcome under the existing experimental conditions resulting in the formation of a structure where Co occupies a site above the pyridine plane. For Co2(pyridine)−, a ground-state structure is predicted in which the Co2 diametric moiety is inserted in one of the CH bonds, but again because of a barrier, the structure which matches the photoelectron spectrum is a higher-energy isomer in which the Co2 moiety is bonded directly to nitrogen on the pyridine ring. In all cases, the Co sites have finite magnetic moments suggesting that the complexes may provide ways of making cluster-based magnetic materials

Reversal of Stathmin-Mediated Microtubule Destabilization Sensitizes Retinoblastoma Cells to A Low Dose of Antimicrotubule Agents: A Novel Synergistic Therapeutic Intervention

PURPOSE. To explore the possibility of stathmin as an effective therapeutic target and to evaluate the synergistic combination of stathmin RNAi and the antimicrotubule agents paclitaxel and vincristine to retinoblastoma Y79 cells. METHODS. RNAi-mediated specific inhibition of stathmin expression in Y79 cells was shown by real-time quantitative RT-PCR (RT-Q-PCR), its effect on cell proliferation by MTT assay, cell invasion using matrigel, microtubule polymerization by immunohistochemistry, apoptosis, cell cycle analysis by flow cytometry analysis, and the changes in FOXM1 protein expression were studied by Western blot. The effect of combination treatment of stathmin siRNA and paclitaxel/ vincristine was studied by assessing cell viability and apoptosis. RESULTS. Short interfering RNA-mediated transient stathmin downregulation resulted in a marked inhibition of retinoblastoma cell proliferation and cell invasion in vitro. Stathmin inhibition promoted Y79 cells to G2/M phase, and ultimately there were increased apoptotic events as evidenced by higher caspase-3 activation and cleaved poly-(ADP-ribose) polymerase expression. Cells transfected with stathmin siRNA showed long and bundled microtubule polymers and sensitized the Y79 cells significantly to paclitaxel and vincristine. CONCLUSIONS. Stathmin may be a pivotal determinant for retinoblastoma tumorigenesis and chemosensitivity. Strategies to inhibit stathmin will help to enhance the cytotoxic effect of paclitaxel while reducing toxicity (or side effects) to normal cells caused by high doses. (Invest Ophthalmol Vis Sci. 2011; 52:5441-5448

Hemodialysis Removes Uremic Toxins That Alter the Biological Actions of Endothelial Cells

Chronic kidney disease is linked to systemic inflammation and to an increased risk of ischemic heart disease and atherosclerosis. Endothelial dysfunction associates with hypertension and vascular disease in the presence of chronic kidney disease but the mechanisms that regulate the activation of the endothelium at the early stages of the disease, before systemic inflammation is established remain obscure. In the present study we investigated the effect of serum derived from patients with chronic kidney disease either before or after hemodialysis on the activation of human endothelial cells in vitro, as an attempt to define the overall effect of uremic toxins at the early stages of endothelial dysfunction. Our results argue that uremic toxins alter the biological actions of endothelial cells and the remodelling of the extracellular matrix before signs of systemic inflammatory responses are observed. This study further elucidates the early events of endothelial dysfunction during toxic uremia conditions allowing more complete understanding of the molecular events as well as their sequence during progressive renal failure

Stem cell markers: ABCG2 and MCM2 expression in retinoblastoma

BACKGOUND/AIM: The authors studied the expression of cancer stem cell surface marker, ABCG2, and neural stem cell marker, MCM2, in retinoblastoma and correlated clinicopathologically. METHODS: Among 39 retinoblastomas, 18 tumours were not subjected to preoperative/postoperative chemotherapy, 15 tumours underwent postoperative chemotherapy, and six tumours had preoperative chemotherapy. There were 20 tumours with no invasion and 19 tumours with invasion of choroid/optic nerve. ABCG2 and MCM2 expression was studied by immunohistochemistry. RESULTS: ABCG2 was positive in six of six and MCM2 was positive in five of six tumours that had recurred in the orbit or metastasised. ABCG2 was positive in 15/19 tumours with invasion. MCM2 was positive in 16/19 tumours with invasion. Invasive tumours showed higher expression of ABCG2 (p<0.01) and MCM2 (p<0.01) proteins. There was no correlation with differentiation and laterality of the tumours. Non‐neoplastic retina was positive for ABCG2 and MCM2. CONCLUSION: ABCG2 and MCM2 were expressed more in invasive tumours. Further studies are needed to understand the significance of ABCG2 and MCM2 expression in retinoblastoma

Bromelain-Induced Apoptosis in GI-101A Breast Cancer Cells

Bromelain is a proteolytic enzyme extracted from the stems and the immature fruits of pineapple that was found to be antitumorigenic in different in vitro models. Bromelain has been reported to promote apoptosis, particularly in breast cancer cells, with the up-regulation of c-Jun N-terminal kinase and p38 kinase. Our study was designed to determine if bromelain could induce apoptosis in GI-101A breast cancer cells. GI-101A cells were treated with increasing concentrations of bromelain for 24 hours. The effect of bromelain for inducing cell death via activation of the apoptosis mechanism in GI-101A cells was further determined by using caspase-9 and caspase-3 assays along with the M30-Apoptosense assay to measure cytokeratin 18 (CK18) levels in the cytoplasm of the cultured cancer cells. A dose-dependent increase in the activities of caspase-9 and caspase-3 coinciding with elevation of CK18 levels was found in bromelain-treated cells compared with control cells. Furthermore, the apoptosis induction by bromelain was confirmed by DNA fragmentation analysis and 4,6\u27-diamino-2-phenylindole dihydrochloride fluorescence staining of the nucleus. Our results indicate an increase in apoptosis-related cell death in breast cancer cells with increasing concentrations of bromelain