18; 95% CI, 1 06-16 51; P = 04), poor tibia] runoff (OR, 4 42; 9

18; 95% CI, 1.06-16.51; P = .04), poor tibia] runoff (OR, 4.42; 95% CI, 1.16-16.82; P = .03), and preprocedural neutrophil count in the third tertile (OF, 10.77; 95% CI, 2.19-52.91; P = .003) were independent predictors of outcome.

Conclusions. MS-275 in vivo The results suggest that the preprocedural neutrophil count could be used in global risk factor assessment of patients with advanced PVD who are being considered for PTA. The neutrophil count may reflect the burden of atherosclerosis and tissue damage, and so could identify patients who need more aggressive intervention for advanced PVD. (J Vasc Surg 2008;48:1504-8.)”
“Low dose total-body gamma-irradiation (TBI) was reported to confer

neuroprotection against MPTP-induced dopaminergic neurotoxicity. After being pretreated with a single low dose (0.5 Gy, 2.0 Gy or 3.5 Gy) TBI, C57BL/6 mice were administered with MPTP

(75 mg/kg, four times, 2 h apart) intraperitoneally (i.p.). In the group pretreated with 2.0 Gy TBI, with lower lymphocytes number, neuroprotection was found by High Performance Liquid Chromatography (HPLC) determination of the striatal dopamine. Contrarily, in the group pretreated with 0.5 Gy TBI, with higher lymphocytes number, dopaminergic neuron toxicity was enhanced. So it was probably the decrease of lymphocytes, not the radiation hormesis that rendered the potential neuroprotection. And it was the balance between radiation injury and lymphocytopenia neuroprotection that decided the effect of low dose gamma-irradiation on MPTP-induced dopaminergic neurotoxicity. (C) 2008 Elsevier

Ireland Ltd. All rights reserved.”
“Objective:To investigate whether intermittent Thiamine-diphosphate kinase pneumatic selleck chemicals compression (IPC) augments skin blood flow through transient suspension of local vasoregulation, the veno-arteriolar response (VAR), in healthy controls and in patients with peripheral arterial disease (PAD).

Methods: Nineteen healthy, limbs and twenty-two limbs with PAD were examined. To assess VAR, skin blood flow (SBF) was measured using laser Doppler fluxmetry in the horizontal and sitting positions and was defined as percentage change with postural alteration [(horizontal SBF - sitting SBF)/horizontal SBF x 100]. On IPC application to the foot, the calf, or both, SBF was measured with laser Doppler fluxmetry, the probe being attached to the pulp of the big toe.

Results: Baseline VAR was higher in the controls 63.8 +/- 6.4% than in patients with PAD (31.7 +/- 13.4%, P = .0162). In both groups SBF was significantly higher with IPC than at rest (P < .0001). A higher percentage increase with IPC was demonstrated in the controls (242 +/- 85% to 788 +/- 318%) than in subjects with PAD, for each one of the three different IPC modes investigated (98 +/- 33% to 275 +/- 72%) with IPC was demonstrated. The SBF enhancement with IPC correlated with VAR for all three compression modes (r = 0.58, P = .002 for calf compression, r = 0.65, P < .0001 for foot compression alone, and r = 0.64, P = .


These KPT 330 patients were recruited during an acute mood episode and their mood symptoms and substance abuse were assessed longitudinally for up to 28 months. Patients with a remitted SUD showed a poorer acute treatment response, a longer time to remission of their acute mood episode, and a greater percentage of time with subthreshold but clinically significant depression and manic symptoms over follow-up compared to those without this comorbidity pattern. Subsequent substance abuse during

follow-up could not fully account for the poorer course of illness. As remitted SUDS appear to negatively predict treatment outcome, current findings have implications for both clinical trials of bipolar patients as well as clinical practice. (C) 2007 Elsevier Ireland Ltd. All rights reserved.”
“Tissue transglutaminase (TG2), a multifunctional enzyme implicated in cellular proliferation and differentiation processes, plays a modulatory role in the cell response to stressors. Herein, we used olfactory ensheathing cells (OECs), representing an unusual population of glial cells to promote axonal regeneration and to provide

trophic support, as well as to assess whether the effect of some Growth Factors (GFs), NGF, bFGF or GDNF, on TG2 overexpression induced by stress conditions, such as glutamate or lipopolysaccaride (LPS). Glial Fibrillary Acidic Protein (GFAP) and vimentin were used QNZ mw as markers of astroglial differentiation and cytoskeleton component, respectively. Glutamate or LPS treatment induced a particular increase of TG2 expression. A pre-treatment of the cells with the GFs restored the levels of the protein to that of untreated ones. Our results demonstrate that the treatment of OECs with the GFs was able to restore the OECs

oxidative status as modified by stress, also counteracting TG2 overexpression. It suggests that. in OECs, TG2 modulation enough or inhibition induced by GFs might represent a therapeutic target to control the excitotoxicity and/or inflammation, which are involved in several acute and chronic brain diseases. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Most daily tasks are performed almost automatically, but occasionally it is necessary to alter a routine if something changes in the environment and the routine behavior becomes inappropriate. Such behavioral switching can occur either retroactively based on error feedback or proactively by detecting a contextual cue. Recent imaging and electrophysiological data in humans and monkeys support the view that the frontal cortical areas play executive roles in behavioral switching. The anterior cingulate cortex acts retroactively and the pre-supplementary motor area acts proactively to enable behavioral switching. The lateral prefrontal cortex reconfigures cognitive processes constituting the switched behavior.

Morphologic, histologic, and immunohistochemical analyses were pe

Morphologic, histologic, and immunohistochemical analyses were performed on arteries treated with the CaPO4 model and the conventional

CaCl2 model as the control. In vitro methods were performed using a mixture of CaCl2 and PBS to create CaPO4 crystals. CaPO4-induced apoptosis of primary cultured mouse vascular smooth muscle cells (VSMCs) was measured by DNA fragmentation enzyme-linked immunosorbent assay.

Results: The CaPO4 model produces AAA, defined as an increase of >= 50% in the diameter of the aorta, faster than in the CaCl2 model. The CaPO4 model showed significantly larger aneurysmal dilation at 7, 28, and 42 days, as reflected by a maximum diameter (measured in mm) fold-change of 1.69 +/- 0.07, 1.99 +/- 0.14, and 2.13 find more +/- 0.09 vs 1.22 +/- 0.04, 1.48 +/- 0.07, and 1.68 +/- 0.06 in a CaCl2 model, respectively (n = 6; P < .05). A semiquantitative AC220 grading analysis of elastin fiber integrity at 7 days revealed a significant increase in elastin degradation in the CaPO4 model compared with the CaCl2 model (2.7 +/- 0.2 vs 1.5 +/- 0.2;

n = 6; P < .05). A significantly higher level of apoptosis occurred in the CaPO4 model (apoptosis index at 1, 2, and 3 days postsurgery: 0.26 +/- 0.14, 0.37 +/- 0.14, and 0.33 +/- 0.08 vs 0.012 +/- 0.10, 0.15 +/- 0.02, and 0.12 +/- 0.05 in the conventional CaCl2 model; n = 3; P < .05). An enhancement of macrophage infiltration and calcification was also observed at 3 and 7 days in the CaPO4 model. CaPO4 induced approximately 3.7 times more apoptosis in VSMCs than a mixture of CaCl2 (n

= 4; P < .0001) in vitro.

Conclusions: The CaPO4 model accelerates aneurysm formation with the enhancement of apoptosis, macrophage infiltration, and calcium deposition. This modified model, with its rapid and robust dilation, can be used as a new model for AAAs. (J Vasc Surg 2012;56:455-61.)”
“Neural progenitors/stem cells (NSCs) exist in neonatal mouse subventricular zone (SVZ). To explore the differentiation of the NSCs in neonatal mouse SVZ and the distribution of the progeny cells derived from these NSCs in early adulthood, the enhanced green fluorescent protein (EGFP) plasmid was transferred into the NSCs in the lateral ventricle of newborn mice (P0) by in-vivo electroporation RVX-208 to trace these cells and their progeny cells. Thirty days after electroporation, histological sections of mouse brain were prepared for immunofluorescence with cell-specific antibodies to identify the type(s) of cells that were marked by EGFP. The results showed that EGFP-positive cells were distributed mainly in the olfactory bulb (OB), cortex, and SVZ, and double labeled with NeuN (neuron marker) in OB, glial fibrillary acidic protein (GFAP) (astrocyte marker) in the cortex, and Blbp and GFAP (astrocyte marker) in SVZ. However, there was no-EGFP-positive cell in the hippocampus.

0-T magnetic field compared to digital subtraction angiography (D

0-T magnetic field compared to digital subtraction angiography (DSA) as the reference standard for the diagnosis of brain arteriovenous malformation (bAVM).

Nineteen patients with 19 angiographically confirmed untreated bAVM were investigated with both DSA and TR-CE-MRA for the initial diagnosis. Examinations were compared by two independent readers.

Interobserver agreement and intermodality agreement with respect to nidus size, arterial feeders, and venous drainage were determined using the K statistic test. Also, the quality of the TR-CE-MRA images was evaluated.

Seventeen of the 19 bAVM (89.5%) Evofosfamide detected with DSA were diagnosed with TR-CE-MRA. Interobserver agreement for TR-CE-MRA was good for nidus size, venous drainage, and arterial feeders (K = 0.75, 95% CI 0.50-1.00; K = 0.77, 95% CI 0.54-1.00; and K = 0.80, 95% CI 0.59-1.00 respectively). Intermodality agreement was good for nidus size and venous drainage (K = 0.75, 95% CI 0.49-1.00 and K = 0.77, 95% CI 0.54-1.00, respectively) and moderate for arterial feeders (K = 0.44, 95% CI 0.17-0.70).

TR-CE-MRA at 3.0 T has

a good sensitivity for bAVM detection and good agreement with DSA for determining Blasticidin S ic50 nidus size and the type of venous drainage, suggesting that TR-CE-MRA is potentially a reliable tool for the diagnosis and assessment of bAVMs. However, it still suffers from low spatial resolution and vessel superposition, making differentiation of the arterial feeders of the nidus difficult at times.”
“Lymph node

metastasis (LNM) is recognized as an important factor involved in the tumor malignancy progression. Our previous study has indicated tetracosactide that the hepatocarcinoma cell line with 75% of LNM (Hca-F)-cell-induced neoplasia and the hepatocarcinoma cell line with 25% of LNM-induced neoplasia are accompanied with high (75%) and low (25%) incidences of LNM. In the current study, 62 and 54 protein spots were observed up-regulated and down-regulated in Hca-F cell relative to the hepatocarcinoma cell line with 25% of LNM by 2-D DIGE. Totally, 113 unique proteins were identified by HPLC-nano ESI-MS/MS analysis. The expression levels of Annexin A7, Ulch3, and ER protein 29 were validated by Western blotting analyses. The abnormally regulated proteins were categorized and annotated by protein analysis through evolutionary relationships analysis with the aid of the database for annotation, visualization and integrated discovery tool. Seventeen gene candidates concordantly expressed both at mRNA and protein levels. By making a challenge, we detected expression levels of Annexin A7 in primary gastric cancer (GC) and primary GC cancer tissues with LNMs by immunohistochemisty. Higher ratio of positive and strong expressions Annexin A7 in GC might correlate with the tumor progression. The repression of Annexin A7 inhibits the mobility and invasion abilities of Hca-F cell, increases the apoptosis rate of Hca-F cell.

a significant increase of plasma Glu and a significant reduction

a significant increase of plasma Glu and a significant reduction of plasma GABA/Glu ratio were observed The ratio returned to the control level at week 6 even though concentrations of GABA and Glu were still distant from normal After the Bonferroni correction, partial correlation analyses showed that plasma GABA and GABA/Glu ratio were positively correlated with the close of risperidone and plasma concentration of 9-hydroxyrisperidone The reduction of

plasma GABA/Glu ratio was positively correlated with the improvement of activation symptom cluster.

Conclusions: The elevated plasma Selleckchem PND-1186 GABA/Glu ratio reinforces the Idea of an abnormal GABA-Glu interaction in schizophrenia The ratio may be a good peripheral

state-like marker in schizophrenia research (C) 2010 Elsevier Inc All rights reserved”
“Introduction Some studies have found that antidepressants increase serum brain-derived neurotrophic factor (BDNF) levels in patients with major depression and the expression KPT-8602 purchase of BDNF mRNA in limbic structures of rats

Objectives. This study addressed whether the SSRI escitalopram increases serum BDNF levels in subjects with PTSD and whether BDNF levels are associated with treatment response

Methods Medically Calpain healthy male subjects (N= 16) with chronic PTSD completed a 12 week open-label trial of flexible dose (5-20 mg/day) escitalopram monotherapy BDNF levels were obtained at baseline, and at weeks 4,8 and 12

Results PTSD symptoms significantly declined over the course of the 12 week escitalopram treatment Despite a substantial improvement

in PTSD symptoms, there was virtually no change in BDNF levels over time Nevertheless, mean BDNF levels across the trial were strongly correlated with the slope of PTSD symptoms over the 12 weeks (r = 0 58. p = 0.018). Lower mean BDNF was associated with a greater decrease in PTSD symptoms over the course of the trial

Conclusions PTSD subjects with low BDNF levels demonstrated the largest treatment response from an agent with putative neurotrophic effects (C) 2010 Elsevier Inc All rights reseived”

Diabetes is a risk factor for dementia. It is unknown whether higher glucose levels increase the risk of dementia in people without diabetes.


We used 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2067 participants without dementia to examine the relationship between glucose levels and the risk of dementia.

In developing Countries, direct anterior fracture fixation is rep

In developing Countries, direct anterior fracture fixation is replacing posterior fusion in many cases. Recently, it has been demonstrated that patient age does not influence the Outcome in terms Of fusion after odontoid screw fixation. There is considerable disagreement about correct

treatment in the case of remote fractures. in the literature, there have been no studies considering the feasibility and results of anterior screw fixation in elderly patients with remote Type II axis fractures.

METHODS: From 1989 to 2005, we observed 9 patients over the age of 65 years with isolated Type II remote fractures of the dens. TPX-0005 clinical trial All fractures were considered to be inveterate, as the traumatic events had occurred 6 to 12 months earlier. All fractures were treated with anterior infibulation of the dens with single 3.5-mm cannulated screws.

RESULTS: A bony fusion was radiologically documented in 7 patients (77%) 4 to 16 months after the intervention. In 1 patient, a fibrous union was observed. The neurological status remained unchanged in all patients, and no patients showed any neurological impairment at the time of follow-up.

CONCLUSION: According to Our preliminary study, the technique appears to be feasible for remote axis fractures within 12 months of trauma, and it seems to be safe for elderly patients. Further data from additional studies are needed.”
“Purpose: Routine radiological evaluation in children with urinary tract infections includes ultrasound.

Additional dimercaptosuccinic acid scintigraphy in this setting is a common but not routine practice to determine whether there is parenchymal injury. Because dimercapto-succinic selleck acid scintigraphy involves further time, expense and radiation, we determined whether ultrasound findings could substitute for dimercapto-succinic acid scintigraphy. Therefore, in children with urinary tract infections we researched the RANTES incidence of discordant findings between dimercapto-succinic acid scintigraphy and normal ultrasound.

Materials and Methods: A retrospective review of children with a history of urinary tract infections who had normal ultrasound and dimercapto-succinic acid scintigraphy within 6 weeks of each other was performed through a chart review. Children with pyelonephritis within 4 months of the radiological tests were excluded. Dimercapto-succinic acid scintigraphy was considered abnormal if there was less than 40% differential function, global atrophy or focal defects.

Results: From January 2005 to December 2006, 100 children met inclusion criteria. Median patient age was 4.5 years (range 4 months to 19 years) and 84% were female. Of the 100 children 74 (74%) demonstrated vesicoureteral reflux and 18 (18%) showed abnormal dimercapto-succinic acid scintigraphy despite normal ultrasound. Children with vesicoureteral reflux showed an increased incidence of abnormal dimercapto-succinic acid scintigraphy compared to those without vesicoureteral reflux (20.

89) Further analyses showed that the 4-variable MDRD equation ha

89). Further analyses showed that the 4-variable MDRD equation had higher NPV (64%) but lower PPV (89%) than the Autophagy activator other tests (NPV 40-49%, PPV 92-100%), for identifying patients whose combined clearance was <15 ml/min.

Conclusion: The 4-variable MDRD formula is currently the best available prediction equation for GFR, but will nevertheless over estimate residual renal function when

this is significantly impaired in up to 36% cases. Collection of 24 h urine samples may still have a role in the assessment of patients with stages 4 and 5 CKD.”
“Machado-Joseph disease, also called spinocerebellar ataxia type 3 (MJD/SCA3), is a hereditary and neurodegenerative movement disorder caused by ataxin-3 Vadimezan with a pathological polyglutamine stretch (mutant ataxin-3). Seven transgenic mouse models expressing full-length human mutant ataxin-3 throughout the brain have been generated and are compared in this review. They vary in the corresponding transgenic

DNA constructs with differences that include the encoded human ataxin-3 isoform(s), number of polyglutamine(s), and the promoter driving transgene expression. The behaviors/signs evaluated in most models are body weight, balance/coordination, locomotor activity, gait, limb position, and age at death. The pathology analyzed includes presence of neuronal intranuclear inclusions, and qualitative evidence of neurodegeneration. On the basis of striking similarities PJ34 HCl in age-range of detection and number of behavior/sign abnormalities and pathology, all but 1 mouse model could be readily sorted into groups with high, intermediate, and low severity of phenotype. Stereological analysis of neurodegeneration was performed in the same brain regions in 2 mouse models; the corresponding results are consistent with the classification of the mouse models.”
“Objectives: This is a report to update our experience with repairs of the ascending and transverse arch, with an emphasis on the protective measures, including retrograde cerebral perfusion and blood flow and neurologic monitoring.

Methods: Retrospective data were collected from January 1991 to

February 2010, and analysis was conducted on 1193 patients who had aneurysms involving the ascending aorta and arch.

Results: The 30-day mortality rate was 9.3%, but with a normal glomerular filtration rate, the mortality rate was 3%. In univariate analysis of the risk factors for death, the factors were advancing age of greater than 72 years (mortality, 14.8%; P = .002), the presence of coronary artery disease (mortality, 13.5%; P = .02), aortic pathology of acute dissection (mortality, 13.9%; P = .004), the emergency nature of the operation (mortality, 16.1%; P = .0001), and renal function in the lowest 3 quartiles of glomerular filtration rate (mortality, 6.9%, 10%, and 18.3%; P = .03, .0005, and .0001, respectively, with decreasing glomerular filtration rate).

In contrast, vection occurred in only one direction (opposite to

In contrast, vection occurred in only one direction (opposite to background motion) and developed later than VEPRs. The different time course and in-congruency between direction of VEPRs and direction of vection suggests that perceptual and postural responses H 89 solubility dmso are not causally related. However, since vection did increase VEPR magnitude in the direction of background motion, we postulate that VEPRs might be mediated by two different mechanisms: (1) a

short latency system, driven by transient visual stimuli and sensitive to visual geometry (parallax-no parallax), responsible for automatic postural sway adjustments and (2) a longer latency, vection-enhanced postural mechanism, related to the conscious perception of self-motion during longer duration (locomotor, vehicular) body displacements. (C) 2008 Published by Elsevier Ireland Ltd.”
“In previous work, we developed an 8-state nonlinear

dynamic model of the acute inflammatory response, including activated phagocytic cells, pro- and anti-inflammatory cytokines, and tissue damage, and calibrated it to data on cytokines from endotoxemic rats. In the interest of parsimony, the present work employed parametric sensitivity and local identifiability, analysis to establish a core set of parameters predominantly responsible for variability in model solutions. Parameter optimization, facilitated by varying only those parameters belonging to this core set, was used to identify NSC23766 an ensemble of parameter vectors, each representing an acceptable local optimum in terms of fit to experimental data. Individual models within this ensemble, characterized by their different parameter values, showed similar cytokine but diverse tissue damage behavior. A cluster analysis of the ensemble of models Masitinib (AB1010) showed the existence of a continuum of acceptable models, characterized by compensatory mechanisms and parameter changes. We calculated the direct correlations between the core set of model parameters and identified three mechanisms responsible for the conversion

of the diverse damage time courses to similar cytokine behavior in these models. Given that tissue damage level could be an indicator of the likelihood of mortality, our findings suggest that similar cytokine dynamics could be associated with very different mortality outcomes, depending on the balance of certain inflammatory elements. Published by Elsevier Ltd.”
“We examined the involvement of oxidative stress in neuronal cell death induced by taxol, a microtubule-stabilizing anti-cancer drug and investigated whether NADPH oxidase plays a role in taxol-induced neuronal cell death in mouse cortical cultures. Cell death was assessed by measuring lactate dehydrogenase in the bathing media after 24-h exposure to taxol. Taxol (30-1000 nM) induced the concentration-dependent neuronal death with apoptotic features.

In this study,

we describe the humanization of WO-2 using

In this study,

we describe the humanization of WO-2 using complementary determining region loop grafting onto the human germline gene and the determination of the three-dimensional structure by X-ray crystallography. This humanized QNZ purchase version retains a high affinity for the A beta peptide and therefore is a potential candidate for passive immunotherapy of Alzheimer’s disease.”
“Urinary exosomes have received considerable attention as a potential biomarker source for the diagnosis of renal diseases. Notwithstanding, their use in protein biomarker research is hampered by the lack of efficient methods for vesicle isolation, lysis, and protein quantification. Here we report an improved ultracentrifugation-based method that facilitates the solubilization and removal of major impurities associated with urinary exosomes. A double-cushion sucrose/D2O

centrifugation step was used after a two-step differential centrifugation to separate exosomes from the heavier vesicles. After the removal of uromodulin, 378 and 79 unique proteins were identified, respectively, in low- and high-density fractions. Comparison of our data with two previously published data sets helped to define proteins commonly found in urinary exosomes. Lysis, protein extraction, and in-solution digestion INK1197 mouse of exosomes were then optimized for MudPIT application. More than a hundred exosomal proteins were quantified by four-plex iTRAQ analysis of single and pooled samples from two different age groups. For healthy men, six proteins (TSN1, PODXL, IDHC, PPAP, ACBP, and ANXA5) showed significant expression differences between exosome pools of those aged 25-50 and 50-70 years old. Thus, exosomes isolated by our method provide the basis for the development of robust quantitative methods for protein biomarker research.”
“The inositol monophosphatase (IMPase) enzyme from the hyperthermophilic

archaeon Methanocaldococcus Inositol monophosphatase 1 jannaschii requires Mg(2+) for activity and binds three to four ions tightly in the absence of ligands: K(D) = 0.8 mu M for one ion with a K(D) of 38 mu M for the other Mg(2+) ions. However, the enzyme requires 5-10 mM Mg(2+) for optimum catalysis, suggesting substrate alters the metal ion affinity. In crystal structures of this archaeal IMPase with products, one of the three metal ions is coordinated by only one protein contact, Asp38. The importance of this and three other acidic residues in a mobile loop that approaches the active site was probed with mutational studies. Only D38A exhibited an increased kinetic K(D) for Mg(2+); D26A, E39A, and E41A showed no significant change in the Mg(2+) requirement for optimal activity. D38A also showed an increased K(m), but little effect on k(cat). This behavior is consistent with this side chain coordinating the third metal ion in the substrate complex, but with sufficient flexibility in the loop such that other acidic residues could position the Mg(2+) in the active site in the absence of Asp38.

Zolendronic acid shows its anticancer activity via apoptosis and

Zolendronic acid shows its anticancer activity via apoptosis and autophagy. These findings can potentially contribute to the beneficial use of zolendronic

acid for prostate cancer treatment.”
“The expression and function of nicotinic receptor subunits (nAChRs) in the inner ear before the onset of hearing is not well understood. We investigated the mRNA expression of the alpha 9 and alpha 10 nAChR subunits in sensory hair cells of the embryonic and postnatal rat inner ear. We mapped their spatial and temporal expression in cochlear and vestibular hair cells using qPCR, [35S] labeled cRNA in situ hybridization, and alpha-bungarotoxin (alpha-Bgt) to label the presumptive membrane-bound receptor on cochlear hair cells. The results suggest that (1) the mRNA expression of the alpha 9 subunit precedes expression of the alpha 10 subunit in both cochlear and vestibular hair cells, (2) the mRNA expression of both the alpha 9 and alpha buy AZD6244 10 subunits occurs earlier in the vestibular system than in the cochlea, (3) the mRNA expression of both subunits is required for the assembled receptor complexes, and (4) the presumptive assembled receptor, at least in the cochlea, is associated

with synapse formation and the onset of function. CB-839 solubility dmso (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose: Prostate cancer cell proliferation is inhibited by 1a,25-dihydroxyvitamin D-3. Survivin is a member of the inhibitors of apoptosis protein family. Several studies indicate that survivin

down-regulation sensitizes human tumor cells of different histological origins to conventional chemotherapeutic drugs. Cyclin-dependent kinase 3 We assessed the effect of survivin gene expression on the proliferation of prostate cancer cells in vitro and in vivo. We also examined the antitumor sensitization effect of survivin inhibition in 1a,25-dihydroxyvitamin D-3 treatment for prostate cancer cells.

Materials and Methods: We knocked down gene expression levels of survivin using siRNA against survivin in vitro and in vivo. We then assessed survivin expression in 1a,25-dihydroxyvitamin D-3 treatment and examined the antitumor sensitization effect of survivin inhibition using siRNA in 1a,25-dihydroxyvitamin D-3 treatment of hormone resistant prostate cancer cells.

Results: In vitro and in vivo siRNA against survivin significantly inhibited cell and tumor growth compared with control siRNA. In LNCaP and PC3 cells 1a,25-dihydroxyvitamin D-3 decreased survivin gene expression and inhibited cell proliferation. However, survivin gene expression and cell proliferation were not inhibited in DU145 cells but after siRNA transfection against survivin DU145 cell proliferation was inhibited by 1a,25-dihydroxyvitamin D-3.

Conclusions: Findings suggest that survivin has a significant association with prostate cancer cell proliferation and an essential role in 1a,25-dihydroxyvitamin D-3 induced prostate cancer cell growth inhibition.