43 to 3.19, indicating increased stroke risk associated with obesity, however it was measured, even after adjustment for potential confounders. Additional adjustment for factors that may mediate the relationship, such as diabetes and hypertension, significantly attenuated the associations, suggesting that these factors may explain much of the stroke risk associated with obesity.\n\nConclusions-Degree of obesity, defined by body mass index, waist circumference, or waist-to-hip ratio, was a significant risk factor for ischemic stroke regardless of

sex or race. (Stroke. 2010;41:417-425.)”
“Background and objectives: The kidney is important not only in the genesis of blood pressure elevation, but declining renal function is also important for predicting cardiovascular risk. The primacy of the kidney in causing essential hypertension was a topic of Nutlin-3 price debate until the proof-of-principle experiment was performed, which demonstrated remission of essential hypertension in six African-American hypertensives with ESRD after they received successful kidney transplants from normotensive donors. The resolution of hypertension and hypokalemia in a patient with

Liddle’s syndrome and ESRD after subsequent successful renal transplantation also demonstrated the primacy of the kidney in a monogenic form of hypertension related to sodium epithelial channel dysfunction.\n\nDesign, setting, MK2206 participants, & measurements: A review of the available evidence linking cardiovascular disease with chronic kidney disease.\n\nResults: The cause for the inverse continuous relationship between kidney function and cardiovascular

events in patients with native kidney disease and kidney transplant recipients is unknown but may be related to traditional and nontraditional HDAC assay cardiovascular risk factors. This is an important clinical concern and requires close attention to cardiovascular risk reduction measures.\n\nConclusions: Increased cardiovascular disease in patients with chronic kidney disease is an important clinical concern. Improved biomeasures of cardiovascular risk and response to therapy are needed. Clin I Am Soc Nephrol 4 2045-2050, 2009 doi 10 2215/CJN 03050509″
“Remote Magnetic Navigation for VT Ablation. Background: This study aimed to compare acute and late outcomes of VT ablation using the magnetic navigation system (MNS) to manual techniques (MAN) in patients with (SHD) and without (NSHD) structural heart disease. Methods: Ablation data of 113 consecutive patients (43 SHD, 70 NSHD) with ventricular tachycardia treated with catheter ablation at our center were analyzed. Success rate, complications, procedure, fluoroscopy, and ablation times, and recurrence rates were systematically recorded for all patients. Results: A total of 72 patients were included in the MNS group and 41 patients were included in the MAN group. Patient age, gender, and right ventricular and left ventricular VT were equally distributed.

Fourier transform allows in-depth localization of the scatterers,

and the 3D microstructure of the sample is reconstructed by raster scanning. Simultaneously impedance spectroscopy is performed with a dielectric probe connected to an impedance analyzer to gather additional cellular information, and synchronized with FDOCT measurements.\n\nResults: CBL0137 supplier A combined IS-FDOCT system allowing an axial resolution of 5 micrometer in tissues and impedance measurements over the range 20MHz-1GHz has been developed. Alginate matrices have been characterized in terms of microstructure and impedance. Matrices seeded with adipose-derived stem cells have been monitored without the use of labeling agent.\n\nConclusions: We have developed a multimodality system that will be instrumental to non-invasively Selleck GSK1210151A monitor changes in total cell volume fraction and infer cell-specific dielectric properties in 3D structure. (Int J Artif Organs 2010; 33: 238-43)”
“In the adult central nervous system, the vasculature of the neurogenic niche regulates neural stem cell behavior by providing circulating and secreted factors. Age-related decline of neurogenesis and cognitive function is associated

with reduced blood flow and decreased numbers of neural stem cells. Therefore, restoring the functionality of the niche should counteract some of the negative effects of aging. We show that factors found in young blood induce vascular remodeling, culminating in increased neurogenesis and improved olfactory discrimination in aging mice. Further, we show that GDF11 alone can improve the cerebral vasculature and enhance neurogenesis. The identification of factors that slow the age-dependent deterioration of the neurogenic niche in mice may constitute the basis for new methods of treating age-related neurodegenerative BVD-523 order and neurovascular diseases.”
“The reductive coupling of phthalimides with ketones and aldehydes by Zn-TiCl4 in THF gave two- and four-electron reduced

products, 3-hydroxy-3-(1-hydroxyalkyl)isoindolin-1-ones and alkylideneisoindolin-1-ones, selectively by controlling the reaction conditions. Therefore, the one-pot synthesis of alkylideneisoindolin-1-ones from phthalimides was effected by this reaction. Although the alicylideneisoindolin-1ones prepared from phthalimides and aldehydes were formed as mixtures of geometric isomers in most cases, the geometric ratios could be increased by reflux in cat. PPTS/toluene. After the isomerization, the E-isomers of N-methyl substituted alkylideneisoindolin-1-ones (X = Me, R-1 = R, R-2 = H) and the Z-isomers of N-unsubstituted alkylideneisoindolin-1-ones (X = H, R-1 = H, R-2 = R) were obtained preferentially.

Overexpression of Not4 enhanced Stat92E-mediated gene responses PP2 research buy in vitro and in vivo in Drosophila. Specifically, Not4 increased Stat92E-mediated reporter gene activation in S2 cells; and in flies, Not4 overexpression resulted in an 8-fold increase in Turandot M (TotM) and in a 4-fold increase in Turandot A (TotA) stress gene activation when compared to wild-type flies. Drosophila Not4 is structurally related to human CNOT4, which was found to regulate interferon-gamma- and interleukin-4-induced STAT-mediated

gene responses in human HeLa cells. Not4 was found to coimmunoprecipitate with Stat92E but not to affect tyrosine phosphorylation of Stat92E in Drosophila cells. However, Not4 is required for binding of Stat92E to its DNA recognition

sequence in the TotM gene promoter. In summary, Not4/CNOT4 is a novel positive regulator of the JAK/STAT pathway in Drosophila and in humans.-Gronholm, J., Kaustio, M., Myllymaki, H., Kallio, J., Saarikettu, J., Kronhamn, J., Valanne, S., Silvennoinen, O., Ramet, M. Not4 enhances JAK/STAT pathway-dependent gene expression in Drosophila and in human cells. FASEB J. 26, 1239-1250 (2012). www.fasebj.org”
“During recovery from lymphopenia, the naive T-cells undergo homeostasis driven proliferation (HDP) and acquire a memory phenotype. The HDP of T-cells requires signals derived from T-cell-receptor, p56lck kinase, IL-7R and IL-15R. However, the role of other signaling molecules during HDP of CD4+ check details T-cells remains speculative. The differentiation of naive T-cells into Th1/Th2/Th17

or Treg populations during HDP is not well understood. Present report describes the spatial and signaling characteristics of HDP of CD4+ T-cells and their cytokine profiles. The HDP of CD4+ T-cells was found to occur only in specific areas (T-cell zones) of secondary lymphoid organs of lymphopenic mice. The inhibitors of MEK selleck screening library and PKC and their combination with inhibitors of PI3kinase and mTOR suppressed mitogen induced T-cell proliferation without affecting their HDP. The CD4+ T-cells taken from reconstituted lymphopenic mice showed activation of proteins involved in NF-kappa B pathway, significantly higher production of proinflammatory cytokine IL-6, and lower production of IL-4 as compared to T-cells from normal mice. Plumbagin, a known NF-kappa B blocker inhibited survival as well as HDP of CD4+ T-cells and IL-6 production in activated T-cells. Our results demonstrate the essential role of NF-kappaB during HDP of T-cells. (C) 2009 Elsevier Ltd. All rights reserved.”
“Objective: To evaluate the association of risk and age at onset (AAO) of Alzheimer disease (AD) with single-nucleotide polymorphisms (SNPs) in the chromosome 19 region including apolipoprotein E (APOE) and a repeat-length polymorphism in TOMM40 (poly-T, rs10524523).

(C) 2014 Elsevier B.V. All rights reserved.”
“Background and Purpose In patients with mild to moderate symptomatic carotid artery stenosis, intraplaque hemorrhage (IPH)

and a thin/ruptured fibrous cap (FC) as evaluated with MRI, and the presence of microembolic signals (MESs) as detected with transcranial Doppler, are associated with an increased risk of a (recurrent) stroke. The objective of the present study is to determine whether the prevalence of MES differs in patients with and without IPH and thin/ruptured FC, and patients with only a thin/ruptured FC without IPH. Methods In this multicenter, diagnostic cohort study, patients with recent transient Entinostat nmr ischemic attack or minor stroke in the carotid territory and an ipsilateral mild to moderate carotid artery plaque were included. IPH and FC status were dichotomously scored. Analysis of transcranial Doppler data was done blinded for the MRI results. Differences between groups were analyzed with Fisher exact test. Results A total of 113 patients were included. Transcranial Doppler measurements were feasible in 105 patients (average recording time, 219 minutes). A total of 26 MESs were detected in 8 of 105 patients. In 44 of 105 plaques IPH was present. In 92 of 105 plaques Torin 2 price FC

status was assessable, 36 of these had a thin/ruptured FC. No significant difference in the prevalence of MES between patients with and without IPH (P=0.46) or with thick versus thin/ruptured FC (P=0.48) was found. Conclusions In patients with a symptomatic mild to moderate carotid artery stenosis, IPH and FC status are not associated with MES. This suggests that RG-7388 MRI and transcranial Doppler provide different information on plaque vulnerability. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01709045.”
“A macroporous, styrene-divinylbenzene polymer with N,N-dichlorosulfonamide functional groups (SO2NCl2), containing two chlorine atoms with oxidation number +1, have been prepared through the chemical modification of a commercial

sulfonic cation exchanger (Amberlyst 15, Rohm and Haas). Obtained product was used as the heterogeneous oxidant of As(III) in aqueous solutions. The polymer’s oxidizing capacity, determined as part of the batch studies, amounted to 193.29 mg As(III) g(-1) (pH=7.7) and 206.03 mg As(III) g(-1) (pH=2.0). The suitability of the redox polymer for long-lasting operation in the aqueous environment was confirmed in the column study conducted using a solution with a concentration of 10 mg As(III) dm(-3) at a flow rate of 6 bed volumes (BV) h(-1). The concentration of As(III) in the effluent reached the value of 0.01 mg As(III) dm(-3) only after 8 weeks of continuous operation when 7930 BV of the solution had passed through the bed. (c) 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41552.

Furthermore, two additional recombinant viruses were constructed by mutating from ATG to CTG the initiation codons of gE (gEctg) or both gE and gM (gEctg + gMctg), causing lack of expression of gE or both gE and gM, respectively. A fourth mutant virus was constructed to specify the gEctg + gD Delta ct mutations. The replication properties of these viruses were compared to those of a newly constructed recombinant virus unable to express UL20 due to alteration of the two initiation codons of UL20 (UL20ctgctg). All recombinant viruses were constructed by using the double-Red, site-directed mutagenesis system implemented on the HSV-1(F) genome cloned into a bacterial artificial chromosome. The gEctg,

gEctg + gMctg, gD Delta ct, and gEctg + gD Delta ct viruses produced viral plaques on African monkey kidney cells (Vero), as well as other cells, that were on average approximately 30 to 50% smaller than selleck chemicals those produced by the wild-type virus HSV-1(F). In contrast, the UL20ctgctg virus produced very small plaques containing three to five cells, as reported previously for the Delta UL20 virus lacking the entire UL20 gene. Viral replication kinetics of intracellular and extracellular viruses

revealed that all recombinant viruses produced viral titers similar to those produced by the wild-type HSV-1(F) virus intracellularly and extracellularly at late times postinfection, with the exception Z-IETD-FMK order of the UL20ctgctg and Delta UL20 viruses, which replicated more than two-and-a-half logs less efficiently than HSV-1(F). https://www.selleckchem.com/products/epz004777.html Electron microscopy confirmed that all viruses, regardless of their different gene

mutations, efficiently produced enveloped virions within infected cells, with the exception of the UL20ctgctg and Delta UL20 viruses, which accumulated high levels of unenveloped virions in the cytoplasm. These results show that the carboxyl terminus of gD and the full-length gE, either alone or in a redundant manner, are not essential in cytoplasmic virion envelopment and egress from infected cells. Similarly, gM and gE do not function alone or in a redundant manner in cytoplasmic envelopment and virion egress, confirming previous findings.”
“Objective: To estimate the probability of live birth, adverse treatment outcome, and extremes of ovarian response at different antral follicle count (AFC) cutoff levels in a large prospective cohort of women undergoing IVF treatment.\n\nDesign: Prospective study.\n\nSetting: University-based assisted conception unit.\n\nPatient(s): A total of 1,012 consecutive subjects of all ages undergoing their first cycle of assisted reproductive techniques.\n\nIntervention(s): Transvaginal three-dimensional ultrasound assessment and venipuncture in the early follicular phase of the menstrual cycle.\n\nMain Outcome Measure(s): Live birth rate, poor ovarian response, and ovarian hyperstimulation syndrome (OHSS).

Settled pelagic phytoplankton (1 to 36%) and tychopelagic phytoplankton (5 to 10%) were also present. The settled phytoplankton were mostly present on the sediment during fall and winter. The abundance of benthic cells was directly correlated with light levels on the seafloor and sediment chlorophyll a values. Picocyanobacteria, selleck pennate diatoms and filamentous cyanobacteria dominated the sediment community (by density for all cells 0.2 to 8.0 mu m in diameter)

during summer. The presence of a viable community of microphytobenthos during hypoxia indicates that the potential for photosynthetic oxygen production exists and may influence the oxygen dynamics in the hypoxic zone.”
“Biomass bales often need to be aggregated (collected into groups and transported) to a field-edge stack or a temporary storage before utilization. Several logistics scenarios for aggregation involving equipment and aggregation strategies were modeled and evaluated.

Cumulative Euclidean distance criteria evaluated the various aggregation scenarios. Application of a single-bale loader that aggregated bales individually was considered as the “control” scenario with which others were compared. A computer simulation program developed determined bale coordinates in ideal and random layouts that evaluated aggregation scenarios. Simulation results exhibited a “diamond pattern” of bales on ideal layout and a “random pattern” emerged when bigger than = 10% variation PFTα in vitro was introduced.

Statistical analysis revealed that the effect of field shape, swath width, biomass yield, and randomness on bale layout did not affect aggregation logistics, while area and number of bales handled had significant effects. Number of bales handled in the direct method significantly influenced the efficiency. Self-loading bale picker with minimum distance path (MDP, 80%) and parallel transport of loader and truck with MDP (78%) were ranked the highest, and single-bale central grouping the lowest (29%) among 19 methods studied. The MDP was found significantly more efficient (4%-16%) than the baler path. Simplistic methods, namely a direct triple-bale loader with MDP (64%-66%), or a loader and truck handling six bales running parallel with MDP (75%-82%) were highly efficient. Great Z-IETD-FMK inhibitor savings on cumulative distances that directly influence time, fuel, and cost were realized when the number of bales handled was increased or additional equipment was utilized. Published by Elsevier Ltd.”
“The interplay between nitrogen fertilization (N), yield, nitrous oxide emissions (N2O), and diesel fuel utilization associated with harvest and transport logistics of biomass crops remains poorly understood. In this research, we show that intensification (in terms of N) of bioenergy cropping to maximize yield supports not only minimized land use but also maximized logistics efficiency in terms of diesel use.

Rat mesenchymal stem cells (rMSCs) were seeded on the decellularized bone/bone marrows and cultured for 21 days. The adhesion of rMSCs on or into decellularized bone/bone marrows was confirmed and proliferated over time in culture. The osteogenic differentiation effect of decellularized bone/bone marrows on rMSCs MI-503 in the presence

or absence of dexamethasone was investigated. Decellularized bone/bone marrows without dexamethasone significantly increased alkaline phosphatase (ALP) activity, indicating promoted osteogenic differentiation of rMSCs. In an animal study, when decellularized bone/bone marrows were implanted into the rat subcutaneous, no immune reaction occurred and clusters of the hematopoietic cells could be observed, suggesting the decellularized bone/bone marrows can provide a microenvironment in vivo. (C) 2011 Elsevier Ltd. All rights reserved.”
“Higher throughput thermodynamic

measurements can provide value in structure-based drug see more discovery during fragment screening, hit validation, and lead optimization Enthalpy can be used to detect and characterize ligand binding, and changes that affect the interaction of protein and ligand can sometimes be detected more readily from changes in the enthalpy of binding than from the corresponding free-energy changes or from protein-ligand structures Newer higher throughput calorimeters are being incorporated into the drug discovery process Improvements in titration calorimeters come from extensions of a mature technology and face limitations Galardin chemical structure in scaling Conversely, array calorimetry, an emerging technology, shows promise for substantial improvements in throughput and material utilization but improved sensitivity is needed”
“Aquaporin-1 (AQP-1), the universal water channel, is responsible for rapid response of cell volume to changes in plasma tonicity. In the membrane of the red cell the concentration of the protein is tightly controlled. Here, we show that AQP-1 is partially lost during in vitro maturation of mouse reticulocytes and that it is associated with exosomes, released throughout this process. AQP-1 in young reticulocytes localizes to the plasma membrane and also

in endosomal compartments and exosomes, formed both in vitro and in vivo. During maturation a part of the total pool of AQP-1 is differentially sorted and released via the exosomal pathway. A proteasome inhibitor, MG132, suppresses secretion of AQP-1, implying that ubiquitination is a sorting signal for its release. We further show that modulation of medium tonicity in vitro regulates the secretion of AQP-1, thus showing that extracellular osmotic conditions can drive sorting of selected proteins by the exosomal pathway. These results lead us to suggest that AQP-1 sorting into exosomes may be the mechanism by which the reticulocyte adapts to environmental changes during its maturation. (Blood. 2009;114:3928-3934)”
“JS-2 is a novel gene located at 5p15.

\n\nMethods: Data on infection control policies, structural characteristics, and MDRO

rates were collected through a 2010 survey of California infection control departments. Bivariate and multivariable Poisson and negative binomial regressions were conducted.\n\nResults: One hundred eighty hospitals provided data (response rate, 54%). Targeted MRSA screening upon admission was reported by the majority of hospitals (87%). The majority of hospitals implemented contact precautions for confirmed MDRO and C difficile patients; presumptive isolation/contact precautions for patients with pending screens were less frequently implemented. Few infection control policies were associated with Selleck BMS345541 lower MDRO rates. Hospitals with a certified infection control director had AZD0530 molecular weight significantly lower rates of MRSA bloodstream infections (P < .05).\n\nConclusion: Although most California hospitals are involved in activities to decrease MDRO, there is variation in specific activities utilized with the most focus placed on MRSA. This study

highlights the importance of certification and its significant impact on infection rates. Additional research is needed to confirm these findings. Copyright (C) 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.”
“Turfgrass systems represent one major group of intensively managed ecosystems and a potential carbon (C) sink. Turfgrass management practices critically influence C inputs to soil, soil microbial dynamics, C59 Wnt cost and in turn soil C and nitrogen (N) balance. However, how management practices influence soil organic C and microbial dynamics in turfgrass systems is not well understood. We investigated the effect of management duration and intensities on soil microbial biomass, microbial

activities and soil organic C contents in two golf courses dominated by Bermuda grass near Raleigh, NC, USA. In Hope Valley, two fairways were studied under the same management scheme but for a huge difference in duration (10 vs. 80 years). Whereas, in Treyburn, rough, fairway, and tee areas that were constructed in the same year but received different N and water inputs, and with different cutting frequencies were examined. Results showed conversion of a pine forest to turfgrass course reduced soil microbial biomass, microbial activities and soil organic C. Long term turfgrass planting accumulated soil organic C and N at rates of 71.9 and 10.6 g m(-2) y(-1) over 80 years. Moderate management intensity resulted in highest soil organic C and microbial biomass C.

\n\nForty young athletes with the indication of ACL reconstruction with patellar tendon grafts were randomly

assigned to group A (n = 20 patients, control group) or group B (n = 20 patients, PRP group). The autologous PRP gel was applied to both the patellar and tendon bone plug harvest site and stabilized by the peritenon suture. At 12-month follow-up, all patients underwent clinical examination and VAS and VISA questionnaires, respectively, evaluating the average daily pain of the knee and the pain NVP-AUY922 during particular activities involving the knee, were filled. MRI at the same time point was also performed.\n\nVISA scores were significantly higher in the patients treated with PRP (84.5 +/- A 11.8 and 97.8 +/- A 2.5 for group A and for group B; P = 0.041), whereas no significant

difference in postoperative VAS scores between the two groups was observed (1 +/- A 1.4 and 0.6 +/- A 0.9 for group A and group B, n.s.). In 85% of PRP group patients, the tibial and patellar bone defect was satisfactorily filled by new bony tissue (> 70% of bone gap filled), whereas this percentage was just of HSP990 order 60% in control group patients, but this difference was not statistically significant.\n\nThe study shows the usefulness of PRP in reducing subjective pain at the donor-site level after ACL reconstruction with BPTB. However, this approach deserves further investigations to confirm PRP efficacy and to elucidate its mechanism of action.\n\nProspective randomized controlled study, buy SBC-115076 Level I.”
“This study compared reactive agility between higher-standard (n = 14) and lower-standard

(n = 14) Australian footballers using a reactive agility test incorporating a life-size video image of another player changing direction, including and excluding a feint. Mean agility time in the feint trials was 34% (509+/-243 ms; p<0.001; effect size 3.06) longer than non-feint trials. In higher-standard players, agility time was shorter than for lower-standard players in both feint (114+/-140 ms; p = 0.18; effect size 0.52; likely beneficial) and non-feint (32+/-44 ms; p = 0.22; effect size 0.47; possibly beneficial) trials. Additionally, the inclusion of a feint resulted in movement time increasing over three times more in the lower-standard group (197+/-91 ms; p = 0.001; effect size 1.07; almost certainly detrimental) than the higher-standard group (62+/-86 ms; p = 0.23; effect size 0.66; likely detrimental). There were weak correlations between the feint and non-feint trials (r = -0.13-0.14; p>0.05), suggesting that reactive agility involving a feint is a unique skill.

TxB(2) increased in the RAL versus PI/NNRTI arm (+0.09 versus -0.02;P = 0.06). Baseline PGI-M was lower in the RAL arm (P = 0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho = 0.45;P = 0.04) and TxB 2 (rho = 0.44;P = 0.005) changes, with a trend seen for PGE-M (rho = 0.41;P = 0.07). In an adjusted model, age bigger than = 50 years (P = 8) was associated with increased PGE-M (P = 0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing

PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age ( bigger than = 50) Protein Tyrosine Kinase inhibitor was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require Wee1 inhibitor further study.”
“The mammalian nasal cavity is

characterized by a unique anatomy with complex internal features. The evolution of turbinals was correlated with endothermic and macrosmatic adaptations in therapsids and in early mammals, which is still apparent in their twofold function (warming and moistening of air, olfaction). Fossil evidence for the transformation from the nonmammalian to the mammalian nasal cavity pattern has been poor and inadequate. Ossification of the cartilaginous nasal capsule and turbinals seems to be a feature that occurred only very late in synapsid evolution but delicate ethmoidal

bones are rarely preserved. Here we provide the first mu CT investigation of the nasal cavity of the advanced non-mammaliaform cynodont Brasilitherium riograndensis from the Late Triassic of Southern find more Brazil, a member of the sister-group of mammaliaforms, in order to elucidate a critical anatomical transition in early mammalian evolution. Brasilitherium riograndensis already had at least partially ossified turbinals as remnants of the nasoturbinal and the first ethmoturbinal are preserved. The posterior nasal septum is partly ossified and contributes to a mesethmoid. The nasal cavity is posteriorly expanded and forms a distinctive pars posterior (ethmoidal recess) that is ventrally separated from the nasopharyngeal duct by a distinct lamina terminalis. Thus, our observations clearly demonstrate that principal features of the mammalian nasal cavity were already present in the sister-group of mammaliaforms. Anat Rec, 297:2018-2030, 2014. (c) 2014 Wiley Periodicals, Inc.”
“Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent. Recombinant human TRAIL has been evaluated in clinical trials, however, various malignant tumors are resistant to TRAIL. Parthenolide (PT) has recently been demonstrated as a highly effective anticancer agent and has been suggested to be used for combination therapy with other anticancer agents.