We constructed a biologicmaterial composedoffetal ratbrain cells (neurospheres) and adult rat bone marrow stromal cells (MSCs), designated as NMCspheres Adult rats were subjected to 2 hours of middle cerebral artery occlusion (MCAo) and implanted with cultured prelabeled NMCspheres (n=6), neurospheres (n=5) or MSCs (n=6) into the ischemic penumbra at 24 hours after MCAo. Control adult rats (n=10) were subjected to MCAo alone. In vitro within the NMCspheres, MSCs rapidly fonned a process network with intact neural cells compared with a necrotic core within neurospheres alone An in vivo rat corneal assay demonstrated that NMCspheres enhanced angiogenesis compared to MSCs and neurospheres Neurological functional recovery after stroke was enhanced in rats trcated with NMCspheres, compared to rats with neurosphere or MSC treatments by day 7 and day 14 after transplantation. The NMCspheres are a new compositc material that may be employed in the treatment of stroke

The present study investigates the induction of neurogenesis, reduction of apoptosis, and promotion of basic fibroblast growth factor (bFGF) expression as possible mechanisms by which treatment of stroke with bone marrow stromal cells (MSCs) improves neurological functional recovery. Additionally, for the first time, we treated cerebral ischemia in female rats with intraveneous administration of MSCs. Female rats were subjected to 2 hr of middle cerebral artery occlusion (MCAo), followed by an injection of 3

A class of structurally simplified analogues of the naturally occurring annonaceous acetogenins were developed, amongst which some non-THF analogues showed remarkable cytotoxicities against tumor cell lines, as well as good selectivity between human tumor cells and normal cells. The synthetic routes were significantly shortened because of the removal of the chiral centers bearing the THF rings on the natural templates. This simplification also provides access to the parallel synthesis of these mimics by a ombinatorial strategy. The remaining stereogenic centers at the positions-to the ethereal links were introduced by the Chiron approach from the easily accessible chiral building blocks 6a and/or 6b, made in turn from-ascorbic acid or-mannitol, while the one in the butenolide segment was taken from-lactate. All four diastereomeric non-THF analogues 2a-2d showed remarkable activity against the HCT-8 cell line, and better differentiation was found when testing against the HT-29 cell line. It was also discovered that both the butenolide and ethylene glycol subunits play essential roles in the cytotoxicities against tumor cell lines, while the 10-substituted hydroxy group and the absolute configuration of methyl group at the butenolide moiety are less important for their activity.

(E)-2'-Deoxy-(fluoromethylene) cytidine (FMdC) is known as an inhibitor of ribonucleoside diphosphate reductase, a key enzyme in the de novo pathway of DNA synthesis. FMdC was tested as a modifier of radiation response in vitro on a human colon carcinoma cell line (WiDr), and the observed radiosensitization was confirmed on two human cervix cancer cell lines (C33-A and SiHa). Using the clonogenic assay, the effect ratio (ER) at a clinically relevant dose level of 2 Gy was 2.10 (50nM FMdC), 1.70 (30nM FMdC), and 1.71 (40nM FMdC) for the three cell lines WiDr, C33-A, and SiHa, respectively. A more detailed analysis of the importance of timing and concentration of FMdC was done on the WiDr cell line alone, yielding an increased ER (2Gy) with increasing concentration and duration of exposure to the drug, ranging from 1.0 (6h) to 1.8 (72h) at 30 nM FMdC and from 1.2 (6h) to 3.5 (24h) at 300nM. We investigated the effect of FMdC on the cellular deoxynucleotide triphosphate pool in WiDr cells and demonstrated a marked depletion of dATP and a significant rise of TTP levels. Cell cycle analysis showed early S-phase accumulation induced by FMdC alone, G2-M block induced by irradiation alone, and an increased accumulation of cells in G2-M if both modalities are used. Our data suggest that FMdC is a radiation response modifier in vitro on different cancer cell lines. The observed radiosensitization may in part be explained by alteration of the deoxynucleotide triphosphate pool, which is consistent with the effect of FMdC on ribonucleoside diphosphate reductase.