Ellipsoid plots are generated in the standard way [25] and [30]: a

unit sphere is scaled by the moduli of the eigenvalues in the three primary directions, rotated into the principal axis frame of the tensor and translated to the point of the corresponding nucleus. Blue axes are drawn inside for positive eigenvalues and red axes for negative eigenvalues. Dipolar interaction tensors are not visualized – inter-nuclear DNA Damage inhibitor dipolar coupling is visually apparent from the distances and electron–nuclear dipolar coupling is contained in the hyperfine interaction. In systems with multiple electrons, the inter-electron dipolar coupling is either contained in the distances (in the individual electron spin representation) or in the zero-field splitting tensor (in the total electron spin representation). It is often the case in Magnetic Resonance simulations that electrons do not have specific Cartesian coordinates, being instead delocalized over the nuclear ensemble and manifesting themselves through hyperfine interactions. For this reason electrons are drawn separately BMN 673 molecular weight in the lower part of the central area of Fig. 3. Electron interaction ellipsoids rotate synchronously with the rest of the molecule, but the electrons themselves (visualized as translucent blobs)

do not move around the visualization window. Zero-field splitting tensors and g-tensors are visualized as ellipsoids centered on their corresponding electrons and inter-electron exchange couplings are shown as coils with the amplitude Etomidate mapped to the color. A summary of the visualization methods is given in Table 1. Visualization tab in the upper part of the main window controls the appearance and scaling of the ellipsoids as well as magnitude-color maps in the 3D view using logarithmic sliders. Visualization of individual interactions may be switched on and off using the tick boxes. NMR and EPR buttons switch the 3D view to the visualization of the corresponding interactions – shielding, shift, J-coupling,

quadrupolar coupling for the NMR mode; g-tensor, hyperfine coupling, exchange coupling, zero-field splitting for the EPR mode. The primary format for spin system data storage and retrieval is SpinXML, but the GUI can also import Gaussian 03/09 logs (*.log, *.out), Cartesian XYZ files (*.xyz, coordinates only, isotopes are guessed) and both versions of CASTEP files (*.magres). When multiple instances of the relevant tables are present in the file (e.g. multiple coordinate sections in geometry optimizations), the last section is read. For Gaussian 03/09 calculations, the detailed printing option is required in the route section of the input file. Electronic structure theory calculations often produce large quantities of small interactions (e.g.

Rats were housed during treatment at a constant room temperature, humidity, and light cycle (12:12-h light-dark) with free access to tap water and fed standard chow ad libitum. Rats were divided into two groups: control (vehicle–saline solution, im) and Daporinad in vivo those

treated with mercury chloride for 30 days (1st dose 4.6 μg/kg, subsequent dose 0.07 μg/kg/day, i.m to cover daily loss). Our group described that this treatment led to blood levels of ~ 8 ng/mL ( Wiggers et al., 2008). All experiments were conducted in compliance with the guidelines for biomedical research as stated by the Brazilian Societies of Experimental Biology, were in accordance with the National Institute of Health Guidelines for the Care and Use of Laboratory Animals and were approved by local ethics committee TGF-beta inhibitor (CEUA-EMESCAM 003/2007, 007/2007). At the end of treatment, rats (N = 22) were anesthetized with urethane (1.2 g/kg, Sigma (St Louis, MO, USA), and a polyethylene catheter (PE50) filled with heparinized saline (50 U/ml) was introduced into the carotid artery to measure arterial systolic blood pressure (SBP) and diastolic blood pressure (DBP). The carotid artery catheter was introduced into the left ventricle to measure systolic pressure (LVSP) and its

positive and negative time derivatives (dP/dt + LV and dP/dt −LV, respectively), as well as left ventricular end diastolic pressure (LVEDP). Recordings were performed over a 30-min period with a pressure transducer (TSD104A),

and with an interface and data collection software (MP100A, BIOPAC System, Inc., Santa Barbara, CA, USA). Heart rate (HR) was determined from intra-beat intervals. After treatment, rats (N = 14) were anesthetized with urethane (1.2 g/kg), treated with heparin (500 UI, i.p.) and euthanized by exsanguination; the heart was excised after 10 min and mounted in an isolated organ chamber and perfused according to the Langendorff technique at constant flow (10 mL/min) with Krebs–Henseleit bicarbonate buffered solution containing (in mM): 120 NaCl, 5.4 KCl, 1.25 CaCl2, 2.5 MgSO4, 1.2 Na2SO4, Interleukin-2 receptor 2.0 NaH2PO4, 20 NaHCO3, and 11 glucose (salts used were of analytical grade; Sigma, St Louis, MO, USA and Merk, Darmstat, Germany). This solution was filtered and continuously bubbled with 95% O2 and 5% CO2 (pH = 7.4) and kept between 34 and 35 °C. After mounting, the left atrium was opened and a soft distensible balloon mounted at the tip of a rigid plastic tube was inserted into the left ventricular cavity through the atrioventricular valve. To avoid liquid accumulation in the ventricular cavity, the ventricle was perforated with a puncture needle. The balloon was connected, via a Y piece, to a pressure transducer (TSD 104A) and to a syringe so that the diastolic pressure of the left ventricle could be adjusted to predetermined values by injecting water into the balloon. The resulting pressure was registered.

A recent TMS study using intentional

binding as an implicit measure of agency also suggests a contribution of the supplementary motor complex (Moore et al., 2010). But that study was designed http://www.selleckchem.com/PARP.html to test whether candidate areas were necessary for intentional binding, and could not draw strong anatomical conclusions about the precise location of the neural correlates of implicit agency. Indeed, the repetitive stimulation protocol used in such studies may have rather widespread effects in the stimulated region of cortex (Mochizuki et al., 2005), and can also produce remote effects via neural connections with the stimulated region (Stefan et al., 2008). A recent meta-analysis of studies on the neural correlates of agency as

identified in neuroimaging data has implicated the importance of parietal brain regions such as angular gyrus, TPJ and pre-SMA, but also found an association between agency and activation of the insula, dorsofrontomedian cortex and precuneus (Sperduti et al., 2011). However, this meta-analysis did not focus on low-level implicit markers of sense of agency. We therefore aimed to identify brain regions associated with the implicit sense of agency, taking intentional binding as a proxy for sense of agency. We used an interval estimation task, in which participants judged the time between a button press and a resulting tone. In one condition this tone was elicited by the participant’s active button press, in another condition the tone was learn more elicited by a passive movement of the same finger (cf. Engbert et al., 2007). In order to extract brain areas associated with the intentional binding effect we used a parametric Org 27569 approach in which we modulated each trial with its respective judgement error. Thus, trials with strong

binding effects would have large and negative values for this regressor, since underestimation of an action–effect interval corresponds to a negative judgement error. The parametric regressor in the passive condition of the interval estimation task is assumed to capture all brain activation responsible for non-specific causes of variation in time estimation, such as arousal, division of attention etc. The parametric regressor for the active condition on the other hand was assumed to identify both these non-specific factors, and additionally the agency-related changes in time perception due to intentional binding. Contrasting these two parametrically modulated conditions – one that shows the attraction of voluntary action and tone, and one that does not – offers the possibility to extract brain regions that are related to intentional binding. We used this technique to investigate the specific contributions of the SMA and the angular gyrus to sense of agency, given that these areas were repeatedly reported in previous studies of agency. Seventeen healthy students (five males; age: mean = 22.

TRCN0000107268) and YAPshRNA#5 (Clone No. TRCN0000107269). 293FT-packaging cells were cotransfected with pCMV-VSVg, pCMV-dR8.74, and the SB431542 clinical trial respective pLKO.1 plasmids using Fugene6 (Roche Applied Science, Mannheim, Germany). An empty pLKO.1 vector containing

no shRNA sequence was used as a negative “mock” control. Supernatant containing lentivirus was harvested after 48 and 72 hours and used to transduce human ccRCC cell lines. Puromycin selection of resistant ccRCC cells was performed, and cells were cultured in the presence of puromycin throughout all experiments. Determination of cell viability was performed using the 3-(4,5-dimethyl-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay Selleck BIBW2992 as previously described [12]. Briefly, 2000 cells per well were incubated in full growth media for 0, 48, or 96 hours, respectively. All experiments were set up in quadruplicates,

and results were normalized to the mean cell viability at 0 hour. CellTiter 96 Aqueous One solution (20 μl; Promega, Madison, WI) was added to each well and absorbance at 492 nm was determined using a 96-well plate reader (BMG Labtech, Offenburg, Germany) on incubation of plates at 37°C for 2 hours. Cells were seeded into six-well plates at 1000 cells per well in full growth media. Once colonies became visible, cells were fixed with 70% ethanol and stained with a 0.05% aqueous solution of crystal violet (Sigma-Aldrich, Steinheim, Germany). Colonies were counted and colony

counts were normalized to the mean colony count of mock-transduced cell lines. Soft agar assays were set up in six-well plates with a bottom layer of 1% agarose (Life Technologies, Darmstadt, Germany), an intermediate layer containing 0.6% agarose and 10,000 cells per well, as well as a final layer of media only. Plates were incubated for 4 weeks at 37°C buy Verteporfin and medium was exchanged once weekly. Colonies were stained with a 0.05% aqueous solution of crystal violet (Sigma-Aldrich) and visualized by trans-UV illumination (Bio-Rad, Hercules, CA). Colonies were counted and colony counts were normalized to the mean colony count of mock-transduced cell lines. Modified Boyden chamber assays were set up in 24-well transwell plates with 8-μm pore size filters (BD Biosciences, San Jose, CA). Fifty thousand cells per well were applied and transwell migration was assessed after 48 and 72 hours of incubation at 37°C, respectively. Cells adherent at the bottom of the filter were fixed in 70% ethanol and stained with hematoxylin. Cells were counted in three randomly selected microscopic fields and means and SDs were calculated. Cells were lysed in radioimmunoprecipitation assay buffer (1% Igepal CA 630, 0.5% Na-deoxycholate, 0.

, 1992). HI-6 is available both as a dichloride or dimethanesulfonate salt. The dichloride form of HI-6 is moderately effective in vitro at reactivating GB-inhibited rat AChE (Esposito et al., 2014), whereas the dimethanesulfonate salt was shown to be superior in terms of both solubility in biocompatible vehicles and biodistribution (Kuca et al., 2007b). HI-6 historically is a potent in vitro reactivator of GD- and GF- but not GA-inhibited AChE (Lundy et al., 1992, Clement et al., 1992, Worek et al., www.selleckchem.com/products/ink128.html 2007 and Esposito et al., 2014). Some have even stated that HI-6, despite poor activity against GA, is as close to a broad-spectrum oxime as any (Soukup et al., 2013). In the

present study, HI-6 DMS at 146 μmol/kg was significantly effective in promoting survival against GA, GB, GF, and paraoxon, but did not possess as broad a spectrum of activity as did MMB4 DMS or HLö-7 DMS. At the TI dose level (245 μmol/kg) similar results were seen as compared to the equimolar treatment, except with paraoxon where the TI therapy was not effective. Obidoxime dichloride offered significant survival protection against GA, (nearly GB, p = 0.0515), VX, and each of the pesticide oxons, confirming historical data. In vitro tests showed that obidoxime was a relatively poor reactivator of rat GA/AChE and GF/AChE conjugates, was a moderate reactivator against GB, but performed

well against VX (Esposito et al., 2014). Obidoxime has exhibited ChE reactivation activity Etofibrate against the pesticides chlorpyrifos (Musilek et al., 2005), parathion, and oxydemeton-methyl Selleck Palbociclib (Thiermann et al., 1997). RS194B is a relatively new compound, the most effective among a class of uncharged N-substituted 2-hydroxyiminoacetamido alkylamine compounds tested in mice (Radić et al., 2012). However, at the equi-molar

to 2-PAM Cl level of 146 μmol/kg, a significant increase in survival was observed only against GB in the present study. However, significant survival was seen against GB and chlorpyrifos oxon at the TI dose level (281 μmol/kg). Since TMB-4 was lethal at 146 μmol/kg in atropinized guinea pigs in the present study, the treatment dose was reduced to 35 μmol/kg (20% of the IM LD50) for evaluations. TMB-4 at 35 μmol/kg significantly improved survival rates only against LD85 challenge doses of VX and paraoxon, but significant reactivation of blood AChE was observed only against VX, paraoxon, GB, and CPO. These observations are partially in agreement with those observed by others, where TMB-4 offered high reactivation of rat AChE inhibited by either GA, GB, or VX but not GF (Esposito et al., 2014). MINA was the only non-heterocyclic oxime tested in the present study. This oxime is also capable of diffusion across the BBB (Skovira et al., 2010). Here, protection by MINA alone at the equimolar dose did not reach statistical significance against all OPs tested.

The sample of 277 patients was predominantly made up of males (56.7%), presented a mean age of 51.3 years (standard

deviation [SD]: 7.7), and a mean duration of chronic HCV diagnosis of 6.4 years (SD: 3.7). Thirty-four www.selleckchem.com/products/obeticholic-acid.html percent of the patients had been infected through blood transfusion, and of those who acquired HCV sharing syringes, 69% did so to use vitamin complex injections. Almost 75% of the sample had acquired genotype 1 HCV, and 81.5% had been treated with pegylated IFN-α. The most common co-occurring diseases were systemic arterial hypertension (32.1%), diabetes mellitus (17%), and hepatic cirrhosis (15.9%). Table 1 summarizes the characteristics of the individuals who met criteria for a major depressive episode during the course of IFN-α therapy. The level of fibrosis revealed by the hepatic biopsy was the only variable associated with the diagnosis of IFN-α-related depression (p = 0.03). Regarding psychiatric features, MINI indicated that 21.3% of

the sample met criteria for a major depressive episode during the course of IFN-α therapy, 10.1% met criteria for lifetime major depressive episode with no relation to IFN-α exposure, and 4.7% of the patients were depressed at the time of the evaluation. The mean current scores of BAY 80-6946 order BDI and HADS were, respectively, 11.2 ± 10.0, and 11.4 ± 7.7. Approximately 18% of the patients referred to a current or past psychiatric treatment, 17.7% fulfilled criteria for lifetime anxiety disorder, and 35.7% for lifetime substance abuse or dependence. Table 2 summarizes the data concerning the psychiatric disorders detected, personal and family psychiatric history, and the psychometric measures in the groups of individuals with and without IFN-α-related depression. Current major depression and/or current anxiety disorder was significantly associated with IFN-α-related depression (p < 0.005). However, lifetime major depression non-related to IFN-α and lifetime substance use disorders showed no association with IFN-α-related depression

(p > 0.05). The current anxiety disorders associated with the diagnosis of IFN-α-related depression were generalized anxiety disorder (GAD) (p = 0.03), and specific phobia (p = 0.003). The only past anxiety disorder with a statistically significant correlation was panic disorder (p = 0.04) although only 2 patients presented Rebamipide with this diagnosis. The observed genotype frequencies for the rs3824259; rs10089084 and rs35099072 SNPs were demonstrated in Hardy–Weinberg Equilibrium in our sample (p > 0.05). Based on the genotypic data of the 35 AIMs, for the sample as a whole, the STRUCTURE 2.1 program estimated the mean ancestry proportions of the individuals to be: 53.5 ± 19.3% European, 29.1 ± 18.8% West-African, and 17.3 ± 10.9% Native American. The ancestry proportions did not differ between groups of patients with and without IFN-α-related depression (p > 0.05).

Very little demographic information was provided about the people (physicians, nurses, pharmacists, and so forth) who received the interventions and in most studies it is not clear how many prescribers were involved. The studies ranged in size from 21 to 7000; approximately 19,300 people with dementia were included in total (information not provided in all studies). Descriptions of the interventions used in the studies are shown in Table 3. We grouped studies according to intervention type using

4 categories: educational programs (n = 11 studies), in-reach services (n = 2 studies), medication review (n = 4 studies), and multicomponent interventions (n = 5 studies). The EPOC Data Collection Checklist includes BMS-354825 cell line a taxonomy of intervention components grouped under 4 headings: professional, organizational, structural, and regulatory.16 The interventions within studies of educational programs14, 18, 19, 20,

23, 24, 25, 29, 30, 31 and 32 consisted mainly of professional components, such as educational meetings, distribution of educational materials, and educational outreach. In-reach services21 and 26 contained mainly organizational and structural components. Studies containing the most variety were those in the medication review22, 33, 34 and 35 Cyclopamine molecular weight and multicomponent intervention groups27, 28, 36, 37, 38 and 39 incorporating educational, organizational, structural, and

regulatory interventions. In many cases, there was insufficient information provided in the article to replicate the intervention in another setting. Using the EPOC Data Collection Checklist classification, the number of intervention components per study ranged from 1 to 7; most studies consisted of 3. The most frequently oxyclozanide used intervention component was educational outreach (14 studies), and this was evident across all 4 types of intervention. Educational outreach was defined as the use of a trained person who met with providers in their practice settings to give information with the intent of changing the provider’s practice. Assessment of the quality of each included study is shown in Table 4. The global assessment of just over a third of the studies was moderate or strong. The main areas of weakness were in the collection of primary outcome data and in the reporting of withdrawals and dropouts. In most of the studies, the outcome assessor was aware of the intervention status of participants and the study participants (prescribers) were aware of the research question. Although data on prescribing rates were taken from patient and pharmacy records in many cases, the data-collection process was performed by one individual with no procedure for checking accuracy. Furthermore, the data-collection tool was often not described, precluding judgment on the validity of the measure.

This favours the depletion of oxygen and ultimately the development of anoxic conditions in large areas of the central Baltic Sea despite the relatively low biomass production in the surface water. The respective annual inputs of dissolved inorganic nitrogen (DIN =nitrate+ammonia) and PO4 into the Baltic Sea in 1995 amounted to 990 000 t-N yr−1 (7.1 × 1010 mol-N yr−1) and 40 000 t-P yr−1 (1.3 × 109 mol- P yr−1) (HELCOM 2001). Whereas PO4 is mainly transported by

river water, the DIN input includes about 20% atmospheric deposition. The input data correspond to a molar N/P ratio of 55, which is much higher than the ratio of the DIN and PO4 inventories of the central Baltic Sea, which have values of less than 10 (Nausch et al. 2008). This shift in the N/P ratio can only be explained by intense denitrification, which probably occurs largely in coastal areas directly affected by riverine nutrient inputs. GSK126 ic50 The low N/P ratios have far-reaching consequences for the plankton succession during the productive period. The molar NO3/PO4

ratios in the winter surface water of the Baltic Proper vary interannually between 6 and 9 (HELCOM, 2001) and are thus about 50% smaller than the Redfield N/P ratio of 16 (Redfield et al. 1963), which characterizes nutrient uptake Antidiabetic Compound Library chemical structure during primary production. As a consequence, the spring plankton bloom is limited by the availability of NO3 and further net production based on the PO4 excess is sustained by nitrogen fixing cyanobacteria. The net biomass production fuelled by nitrogen fixation may be as large as or even exceed the spring bloom production (Schneider et al. 2009) and thus contributes substantially to oxygen depletion and hydrogen sulphide formation in the deep water of the central basins. In a steady state PO4 sources are balanced by burial of phosphorus in the sediments, which thus constitute a PO4 sink. The PO4 concentrations in the water HSP90 column are governed by the efficiency with which P-containing particles are recycled.

These particles consist mainly of organic carbon (POC) generated by biological production and thus contain organic phosphorus (POP). During mineralization of POP, PO4 is released and again becomes available for production. Mineralization occurs to some degree already in the surface water and fuels the regenerated production. The POC fraction removed from the surface by particle sinking is mineralized mainly at the immediate sediment surface (Schneider et al. 2010) and after some delay in deeper sediment layers. Under anoxic conditions mineralization occurs as a result of sulphate reduction, the mineralization products being CO2, NH3 and PO4. The release of PO4 from the sediment surface is frequently regarded as a PO4 source and compared with riverine PO4 input. However, this is a misleading view since the released PO4 originates from riverine input and does not constitute an independent term in the mass balance.

Therefore, this led to many the patients with polysomy 17 but non-HER2 cluster amplification losing the opportunity to receive targeted treatment. When we reevaluated the 48 cases that were HER2-non-amplified and polysomy 17-accompanied, we found that 16 and six cases could be defined as HER2-amplified and HER2-equivocal, respectively. Compared to other cases, polysomy 17 was much more common in IHC 2+

cases, which agrees the findings of others [27], [28] and [30]. selleck chemical Subsequently, there was a significant increase in the number of HER2-amplified and HER2-equivocal cases. Importantly, the majority of IHC 2+ cases, i.e., cases where there was an increase from 34 to 43 patients, were responsive to the targeted therapy, followed by the IHC 3+ cases; the reevaluation also improved the prospects for the IHC 0/1+ cases. In addition to the 16 cases redefined as HER2-amplified, redefining the six cases as HER2-equivocal means that these patients may be able to receive targeted treatment. In our series, polysomy 17 was defined as CEP17/nucleus ratio > 1.86 [27], [28], [29], [30] and [31],

and we believe that CEP17 represents find more chromosome 17, but the question of whether CEP17 copy number actually reflects the condition of polysomy 17 remained. In view of this, determining HER2 amplification status may partly depend on whether CEP17 copy number is taken into account. Indeed, 54.2% of the cases harboring CEP17 did not have HER2 gene amplification. Importantly, the majority of these cases had a borderline IHC score (2+), and >75% of patients who were IHC 2+ were HER2-negative by FISH. Therefore, these cases were not responsive to anti-HER2 targeted therapy and did not fit the category of HER2-amplified breast carcinoma. Another interesting issue of clinical relevance is whether polysomy 17 is associated with clinical behavior similar to that of HER2-amplified tumors. Many previous studies suggest

that independently of HER2 amplification status, the presence of CEP17 alterations identifies a subset of breast cancer with more aggressive biological Dapagliflozin and clinical behaviors that may not respond to conventional therapy [30], [33], [34] and [35]. In a recent study, Bartlett et al. showed that the presence of polysomy 17, as established by CEP17 FISH, was predictive of response to anthracyclines [36]. Therefore, it is important to assess chromosome 17 copy number to investigate its possible implication in the clinical management of patients with invasive primary breast cancer. Indeed, a recently published study suggested that the presence of CEP17 alterations could identify a more aggressive subset of breast cancers that are non-responsive to conventional therapy independently of HER2 amplification status [37]. However, other researchers believe that polysomy 17 without HER2 amplification do not predict response to lapatinib in metastatic breast cancer [38].

With the aim of targeting prostate cancer (PCa), a PtIV prodrug (for CDDP) has been encapsulated into aptamer (Apt)-targeted poly

(d,l-lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles (NPs) forming a Pt-PLGA-b-PEG-Apt-NP conjugate (40) engineered to target the prostate-specific membrane antigen (PSMA). These nanoparticles demonstrated enhanced in vivo pharmacokinetics (PK), biodistribution, tolerability and efficacy. The maximum tolerated dose (MTD) for Pt-PLGA-b-PEG-NP was 40 mg/kg while that of CDDP and the prodrug alone was 20 mg/kg. The Pt in 40 remained in systemic circulation one hour post-administration [ 41••], longer than for cisplatin itself. Since the androgen receptor (AR) is upregulated in breast, Obeticholic Acid datasheet ovarian and prostate tumour cells, Huxley et al. have designed multiple androgenic steroidal ligands with various nitrogen-containing heterocyclic rings conjugated to either cis-platin or trans-platin (41 and 42, Figure 3d) as platinum drug delivery vectors. These [PtII(NH3)2Cl(steroid)] conjugates were 2–12-fold more cytotoxic than the non-steroidal complexes, but with a similar activity range as CDDP. Interestingly, the cis-complex conjugates displayed two to threefold higher activity than their trans analogues. Conjugation to lipophilic testosterone appears to help the cationic complexes through the cell membrane [ 42]. Many proliferating cells have a high

demand for cobalamin selleck compound (Cbl, coenzyme vitamin B12) making it an attractive carrier. Enzymatic reduction of complexes of the type B12-CN-PtII (Figure 3g) releases PtII diammine complexes. Complex 43 was the most active but still with an IC50 ca. 27-fold

higher than free CDDP; conjugates 44 and 45 were ca. 180-fold less active than free cisplatin towards A2780 ovarian and MCF-7 breast cancer cell lines. The reduced cytotoxicity was attributed to a low receptor-mediated response [43]. Nowotnik et al. have reviewed the nano-polymer, ProLindac™ (46), consisting of the active Pt(R,R-dach)2+ fragment of oxaliplatin bound to hydroxypropylmethacryl-amide (HMPA). Release of the active platinum pharamacophore clonidine was ca. seven-times greater at pH 5.4 in comparison to pH 7.4 after 24 hours. The superior activity of ProLindac™ over oxaliplatin was shown in both human and mouse xenograft models, while the cytotoxicity profile of 46 was similar to oxaliplatin [ 2•• and 44]. Release of nitric oxide (NO) from prodrugs is usually activated by glutathione reductase in tumour cells resulting in growth inhibition of cancerous tissues. Duan et al. have synthesised both hydrophilic poly(acrylic)-cis-[Pt(NH3)2(carboxylate)2] (47 and 48) and hydrophobic NO-donating (49) prodrugs ( Figure 3h) combining NO prodrug therapy with Pt based-therapy. The extended life-times of both prodrugs suggest potential future use in combination therapy.