GROUP VI: Cu LE pre-treated at a dose of 300 mg/kg body weight and piroxicam fed group (Cu LE4). Cu LE was administered at 300 mg/kg bodyweight at the onset of the experiments and immediately after one hour, the animals were orally fed piroxicam at 30 mg/kg body weight. In another separate set of experiment, animals were divided into the following four groups to ascertain the mechanism underlying Cu LE mediated protection against piroxicam induced gastric ulcer: GROUP I: Control group

(C). Rats were allowed to drink water supplied ad libitum. GROUP II: Cu LE treated group (Cu LE200). Rats were orally administered Cu LE at 200 mg/kg body weight. GROUP III: Piroxicam treated group (Px). Rats were orally administered piroxicam at dose of 30 mg/kg body weight. The treatment was carried out immediately after 40 hours fasting. GROUP IV: Cu buy LY2109761 LE pre-treated at 200 mg/kg body piroxicam fed group (Cu LE200 + Px). Cu LE was administered at 200 mg/kg

bodyweight at the onset of the experiments and immediately after one hour, the animals were orally fed piroxicam at 30 mg/kg body weight. Each group of animals comprised of 6 rats. At the end of treatment, all Panobinostat chemical structure the animals were allowed to drink water and kept undisturbed for four hours. The animals were sacrificed by cervical dislocation following light ether anesthesia. The abdomen of each rat was surgically opened to collect the stomach for macroscopic observations, histological studies and biochemical estimations. The stomach tissue was kept in sterile plastic vial at -20 °C until further biochemical analysis. For histological studies, an appropriate portion of the fundic part of the stomach was placed immediately in formalin fixative. Prior to sacrifice blood was collected through cardiac puncture for determination of PG E2 in serum. Each set of experiment was repeated at least three times. A separate set of experiment was carried out to determine the degree of inhibition of free hydroxyl radical generation in vivo with oral administration of Cu LE at a dose of 200 mg/kg body weight. Stomach was flushed with saline and lesions in glandular portion were then exposed

and examined under a Phospholipase D1 magnifying glass. The grade of lesions was scored according to the following scale: 0, no pathology; 1, small 1–2 mm ulcers; 2, medium 3–4-mm ulcers; 4, large 5–6-mm ulcers; 8, ulcers greater than 6 mm. The sum of the total ulcer scores in each group of rats was divided by the number of animals in the group to give the mean ulcer index for that group [7]. The free mucin content in the gastric tissues was estimated by measuring the amount of alcian blue bound to mucus (Tariq et al., 2005). The glandular stomach tissues were incubated with a 1% buffered sucrose solution of alcian blue in (0.1%) sodium acetate at 37 °C for 60 min. After incubation, the tissues were washed with sucrose and centrifuged. The supernatant was extracted with MgCl2, and the amount of alcian blue was estimated spectrophotometrically at 610 nm.

Topics of the Congress will focus on various aspects of physical activity and nutrition, including psychological well-being, special groups (children, adolescents, elderly, athletes, people with disabilities), measurement issues, chronic diseases, public health, weight management, recreation, and public policy. For more information, visit www.ipanhec2011.org. Deadline for submitting material for the People and Events section is the first of the month, 3 months before the date of the issue (eg, May 1 for the August issue). Publication of an educational event is not an endorsement by the Association of the event of sponsor.

Send material to: Ryan Lipscomb, Department Editor, Journal of the American Dietetic Association, 120 S. SCH772984 purchase Riverside Plaza, Suite 2000, Chicago, IL 60606; [email protected]; 312/899-4829; or fax, 312/899-4812. Florence Labelle Thoke, April 2011, Dasatinib solubility dmso was a member of the American Dietetic Association and the California Dietetic Association. After graduating from Michigan State University with a Bachelor of Science Degree in Dietetics, she began

her career as a dietitian in Detroit at the Stouffer’s Top of the Flame Restaurant and continued with the Stouffer’s Company in Chicago, where she worked until 1986. Thoke then moved to California and continued her professional career at the Eisenhower Medical Center until her retirement. “
“The article in the June 2011 issue of the Journal on the American Dietetic Association’s 2011-2012 Board of Directors (pp 942-946) misstated information about Barbara J. Ivens. Her identification should have read: Barbara J. Ivens, MS, RD, FADA, Omaha,

NE. “
“Treatment of patients with type 2 diabetes (T2D) aims to reduce insulin oxyclozanide resistance and enhance beta-cell secretion through lifestyle modification and use of metformin, followed by the combination of other oral antidiabetic drugs (OADs). Nevertheless, due to the progressive deterioration in glycaemic control, insulin therapy is often required to achieve glycaemic goals [1]. Lowering glucose levels to the recommended HbA1c level <7.0% is associated with reduction in microvascular complications and, if achieved in a timely manner after diagnosis, may also improve macrovascular outcomes [1]. Sitagliptin, a widely used, highly selective oral dipeptidyl peptidase-4 (DPP-4) inhibitor, can be used in dual or triple therapy when glycaemic control is not attained with metformin [1] and [2]. Although DPP-4 inhibitors are weight-neutral and have a low hypoglycaemia risk, they are associated with modest glucose-lowering activity (HbA1c reduction 0.5–0.9%) [3] and [4]. In a head-to-head comparison, significantly better glycaemic control was achieved with insulin glargine versus sitagliptin, both with metformin, in insulin-naïve patients with T2D, although symptomatic hypoglycaemia was also significantly greater with this insulin-based regimen [5].

The percentage of positive cells was graded as follows: 0: negative; 1: up to 10% positive cells; 2: 11% to 50%; 3: 51% to 90%; and 4: > 90%. Staining intensity was graded as follows: 0: negative; 1: weakly positive; 2: moderately positive and 3: strongly positive [21]. All stainings were evaluated by an experienced pathologist (D.L.). Cells were cultured in a Modular Incubator Chamber (MIC-101, Billups-Rothenberg inc.),

flushed with 20 liters/minute (flow meter; RMA-23-SSV; Dwyer) with certified premixed gas composed of 1% O2 , 5% CO2 and 94% N2 (CARBAGAS, Switzerland). The O2 concentration inside the chamber was measured with an oxygen sensor (VTI-122, Disposable Polarographic Oxygen Cell; 100122, Vascular Technology). The hypoxia chamber was placed in an incubater CYC202 ic50 at 37 °C for 72 hours before RNA isolation. Total RNA was extracted from primary melanoma cell cultures using TRIzol according to manufacturer’s instructions selleck inhibitor (Invitrogen, Carlsbad, CA, USA). Total RNA was used for cDNA synthesis using Promega’s Reverse Transcription System (Promega, Madison, WI, USA) according to the supplied protocols. Gene expression was quantified using the FastStart Universal SYBR Green

Master (ROX; 04913914001, Roche Basel, Switzerland) and the Viia7 system from Applied Biosystems. The primers for DCT and RPL28 were purchased from Qiagen (Venlo, The Netherlands). Correlations between TRP-2, Melan A, Mib-1 and Hif-1α in melanoma were analyzed using Spearman’s rank correlation. TRP-2, TRP-2/Mib-1, Hif-1α and Melan A were compared between different patient groups using the Mann–Whitney test. Wilcoxon

signed ranks test was used to analyse the expression of TRP-2, Melan A and Hif-1α in matched tumor samples. Survival differences between groups were calculated by a HSP90 log rank test. The Cox-regression analysis was applied for analysis of the association between tumor TRP-2/Mib-1 expression and tumor-specific survival. p-values below 0.05 were considered as significant. IBM SPSS Statistics 20 (SPSS Inc., Chicago, IL) was used for statistical analyses. GraphPad Prism 5 was used for Boxplots and Kaplan-Meier curve. We found a correlation between expression of TRP-2 and the melanoma differentiation anitgen Melan A in primary melanomas (p = 0.0001; Spearman’s correlation coefficient 0,6) as well as in metastases (p = 0.0001; Spearman’s correlation coefficient 0,6). Importantly, there was a significant more frequent TRP-2 expression in primary melanomas compared to metastases (p = 0.009; Figure 1A). Thirty-six of 81 (44%) primary melanomas and 14 of 59 (24%) metastases showed TRP-2 expression in over 10% of melanoma cells. In 9 out of 12 matched samples a decrease in TRP-2 expression was detected in the metastases compared to the primaries; in 2 out of 12 samples an increase of TRP-2 in the metastases compared to the primaries was detected and in 1 out of 12 the expression of TRP-2 was absent in the primary as well as in the metastases.

However, there is also evidence that the prion diseases, such as Creuzfeld-Jacob’s disease and Alzheimer’s, are associated with copper deficiency [14], [15] and [16]. Thus it is important that the reaction between Cu and EGCG is understood as fully as possible, especially if

the chemistry of EGCG mirrors that of GA where precipitation of copper complexes U0126 research buy occurs at physiological pH values. Although both GA and EGCG belong to the same family of polyphenols, there are important differences in their structures. The structure of GA is simple and consists of a carboxyl group attached to a pyrogallol entity (Fig. 1a). The structure of EGCG is more complex with two pyrogallol groups in the molecular structure (one on ring B and one on ring D (Fig. 1b), and one resorcinol group on ring A, but no free carboxyl group. Therefore the principal objective

of the present investigation was to determine the extent to which the reactions of GA and EGCG with transition metal ions such as Cu(II) follow similar or different pathways, and to gain information on the complex formation of these polyphenols with Cu(II). For example, the formation of di- or polymeric species involving Cu(II) and Alectinib order the carboxylate group was proposed by Ferreira Severino et al. [9] for the identity of the “EPR silent” species in the reaction of Cu(II) with GA, but since there is no free carboxyl group in EGCG, a similar reaction would not be expected with that polyphenol. In the previous report of the reactions between Cu(II) and GA, EPR spectra were only obtained from fluid solutions, since the objective of that investigation was simply to distinguish between the relative importance of redox, complexation and polymerisation reactions at different pH values. No anisotropic (rigid limit) spectral parameters were reported, although these could provide additional information on the Cu coordination environment in the mononuclear complexes. Furthermore, the Cu(II) spectra all showed the presence of linewidth anisotropy as a result of incomplete averaging of the anisotropic spectral parameters through molecular motion, but these were

not analysed in detail apart from the derivation of approximate Adenosine triphosphate values for the isotropic g-values and hyperfine coupling constants. However, if the anisotropic values from the rigid limit spectra are available, it is possible to analyse the fluid solution spectral lineshapes to produce rotational correlation times that are related to the molecular masses of the complexes. In the present paper we report the results of a comprehensive EPR spectroscopic investigation of the EGCG/Cu(II) system along with additional measurements on the GA/Cu(II) reaction to extend those reported by Ferreira Severino et al. [9]. Spectra were recorded with fluid and frozen solutions at X-band (~ 9 GHz) and S-band (~ 3 GHz) frequencies for samples with a wide range of pH values and Cu:polyphenol ratios.

Although, as a type III interferon that shares signaling pathways with type I interferons, 24 it most likely protects via a direct mechanism on the hepatocyte, possibly inhibiting HCV replication like the related molecule IFN-λ1 25 or rendering cells less susceptible to infection. 26 Additionally, IFN-λ2 does not appear to directly affect NK cells. 27 Therefore, there is a biologic rationale for the separation of these 2 genetic effects. One model for resistance to, or resolution of, HCV

infection is that possession of multiple independent protective factors may synergize to provide protection against chronic infection so that individuals with more protective factors have a greater chance of resolution of HCV infection. Our data do not support this hypothesis. Instead, we propose that KIR:HLA and IL28B define 2 genetically distinct subpopulations of individuals CH5424802 concentration who are relatively protected against chronic HCV infection. Future genetic studies of resolution of HCV infection should stratify for these genotypes to take this heterogeneity into account. The authors thank Dr Bernard North for statistical advice. “
“Evidence from

a meta-analysis of longitudinal studies among adults indicated an association between whole grain (WG) intake and reduced risk of type 2 diabetes, cardiovascular disease, and overweight [1]. Whole grain intake among school-aged children (third-sixth grades) and female adolescents was associated with lower body mass index z-scores and lower risk of overweight in young adulthood, respectively STA-9090 price [2] and [3]. The protective health benefits of WG have been attributed to numerous components including total dietary fiber and bioactive compounds

in bran and germ such as vitamins, minerals, trace elements, polyphenols, alkylresorcinols, and Erythromycin carotenoids [4], [5], [6] and [7]. US Dietary Guideline recommendations indicate that at least half of all grains be consumed as WGs [8], which typically includes at least 3 ounce equivalents (oz eq)/d for adults and 1.5 to 4 oz eq/d for children/adolescents, depending on age, sex, and energy needs [8]. However, US National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 data showed that only 1.5% to 4.3% of children/adolescents, 4.8% of adults aged 19 to 50 years, and 6.6% of adults aged 51+ years consumed at least 3 WG oz eq/d [9] and [10]. Most children/adolescents and adults also do not consume the recommended grams/day of total dietary fiber [11]. Adequate Intake (AI) values of 19 to 25 g/d were established for children aged 1 to 8 years, 31 to 38 g/d for boys aged 9 to 18 years, 26 g/d for girls aged 9 to 13 years, and 21 to 38 g/d for women and men 19 years or older from Dietary Reference Intakes [12]. Based on data from NHANES 2003 to 2006, less than 3% of children/adolescents had a usual fiber intake that was greater than the AI [11].

It is not known if vocal communication in the common marmoset is an innate or learned behavior, but it remains possible that some kind of plasticity is involved as vocalizations change gradually throughout development (Pistorio et al., 2006). It will be interesting to investigate correlations between gene expression changes during development and behaviors such as vocal communication. Moreover, it is not known if marmosets have the ability to read. It has been reported that with training, the baboon (Papio papio) can discriminate words and non-words ( Grainger, Dufau, Montant, Ziegler, & Fagot, 2012). Thus, by drawing parallels, it could be speculated that monkeys have the origin

or precursor of the neural circuit underlying reading ability in humans. Our findings may therefore be useful for understanding the neural mechanisms of speech and reading ability. An association between phonological buffer deficits related to Raf inhibitor SLI, and SNPs in the ROBO1 gene has been reported ( Bates et al., 2011), suggesting there may be a correlation between dyslexia and SLI ( Bishop & Snowling, 2004). ROBO1 regulates midline crossing of major nerve

tracts, a fundamental property of the mammalian central nervous system. From studying a dyslexic patient with a weak expression haplotype for ROBO1, it is known that ROBO1 expression levels are important for normal crossing of the auditory CT99021 pathway ( Lamminmaki, Massinen, Nopola-Hemmi, Kere, & Hari, 2012). Our data also demonstrate that ROBO1

is expressed in layers II, III, and V, layers that project to the contralateral side ( Table 2). In addition, SNPs in the KIAA0319 gene are associated with SLI ( Rice, Smith, & Gayan, 2009), and associations between reading-related measures and CNTNAP2 and CMIP variants in SLI families have been reported ( Newbury et al., 2011). CNTNAP2 is also associated with non-word repetition in dyslexia patients ( Peter et al., 2011), and FOXP2 genetic variants with dyslexia-specific brain activations ( Wilcke et al., 2012). By contrast, DCDC2 variants are only associated with dyslexia ( Newbury et al., 2011). Thus, overlapping expression patterns of CNTNAP2, CMIP, PFKL ROBO1, and KIAA0319 (but not DCDC2) are consistent with the overlapping symptoms caused by variants of these genes, and the published association study ( Newbury et al., 2011), and further our understanding of the molecular basis underlying language impairments. Nevertheless, it is difficult to draw specific conclusions about where and how genetic variants of human speech- and reading-related genes influence the brain and behavior. To do this, it will be necessary for future studies to artificially manipulate gene expression in different brain regions and determine the effects of these modifications on language-related behaviors. A recent study developed a transgenic common marmoset (Sasaki et al., 2009).

planci; (3) assess possible flow-on effects of injected COTS on fish, corals, and other echinoderms; (4) compare the efficacy of bile and dry acid solutions in field conditions; and (5) monitor immediate flow-on effects on fish that approach or bite injected selleck A. planci in the field and assess the health of coral species in close proximity to injected sea stars. The

study was conducted at Lizard Island (14°40′S, 145°27′E), northern GBR, Australia. A total of 220 sea stars, ranging in size from 30 to 42 cm diameter were collected from back reef environments at Lizard Island. Specimens were immediately transported to the Lizard Island Research Station and kept in large holding tanks (2.7 m × 1.6 m × 0.5 m) with constant flow of ambient seawater (mean temperature = 26 °C, salinity = 33 ppt, pH = 8.3).

All sea stars were left to acclimatize for 3 days. Weak or injured individuals were discarded. Two types of bile derivatives were used for tank experiments to determine which solution to use in transmission experiments and field tests: (1) Oxgall (Difco®), which is a purified and dehydrated form of fresh bovine bile, and (2) Bile Salts No. 3 (Oxoid®), which is a refined fraction of bile acid salts widely used as a selective inhibitory agent in culture media. Two stock solutions at different concentrations were prepared for each bile derivative: (1) Oxgall at 6 g l−1 and 12 g l−1, and Bile Salts No. 3 at 4 g l−1 Selleck Ixazomib and 8 g l−1. Four g l−1 of Bile Salts No. 3 and 6 g l−1 of Oxgall were the minimum concentrations of each substance known to induce 100% mortality based on previous tank experiments conducted in the Philippines, albeit with much smaller sea stars (ca. 15–22 cm diameter) (Rivera-Posada et al., 2013). Due to the larger size of COTS used in this study and a marked delay in the time to death (>40 h), higher concentrations (8 g l−1 Bile Salts No. 3 and 12 g l−1 of Oxgall) were also tested. To prepare the solutions, the aforementioned amounts were added to 1 L of distilled water in a flask

and stirred at room temperature until the powder was completely dissolved. The flasks were covered in aluminum foil and stored at room temperature before use. To prepare an 8 g l−1 solution of Bile Salts No. 3 for field application, 4 L of distilled water was added to the 5-l plastic next bottle, which attaches to the injection gun. Bile Salts No. 3 powder (32 g) was then poured into the bottle through a dry funnel. Appropriate eye protection and safety masks were used to handle the dry powder, following manufacturer’s safety instructions. The cap was screwed on the bottle and then shaken vigorously for 30 s until the powder is dissolved. It is possible to use tap water or fresh seawater instead of distilled water, but any naturally occurring bacteria in the water could break down bile and make it less potent. Lead weights were also placed inside the bladders to prevent floating when contents are spent. A total of 50 A.

“
“Paolo Bonanni, MD: Paolo Bonanni is Full Professor of Hygiene in the Faculty of Medicine at the University of Florence, Italy. He is also Director of the University’s postgraduate

course on ‘Vaccines and Vaccination Strategies’ which was established in 2001 and has since BMS354825 been undertaken by over 500 Italian MDs. Professor Bonanni graduated in medicine and surgery in 1985 and gained two specialisations in hygiene and preventive medicine at the University of Genoa, Italy. From 1992 to 2000 he was Associate Professor in the Faculty of Medicine at the University of Florence. His

scientific activity has covered the epidemiology and prevention of infectious diseases, particularly selleck chemical viral hepatitis, diphtheria, tetanus, pertussis, influenza, measles, rubella, varicella and, most recently, bacterial invasive diseases and HPV, including clinical trials and economic evaluation of vaccination strategies. Professor Bonanni has been a member of the National Vaccination Commission of the Italian Ministry of Health, and he acts as an expert consultant for the European Centre for Disease Prevention and Control (ECDC). He

is standing advisor for the Viral Hepatitis Prevention Board (VHPB), an international independent committee of experts in viral hepatitis prevention. Professor Bonanni has received several grants from the Italian Ministry Coproporphyrinogen III oxidase of Education, University and Research for projects relating to vaccine-preventable infections and was responsible for a research unit in three EU-funded projects: ANTRES (antibiotic resistance in Latin America), EURO-HEPNET (feasibility of an EU network for surveillance of vaccine-preventable hepatitis) and VACSATC (vaccine safety, attitudes and training). Professor Bonanni has authored or co-authored 200 scientific papers published in international and national journals. Figure options Download full-size image Download as PowerPoint slide Wen-Fang Cheng, MD, PhD: Wen-Fang Cheng is a Professor at the Graduate Institute of Oncology at the National Taiwan University College of Medicine, and Gynaecologic Oncologist at the Department of Obstetrics and Gynecology, National Taiwan University Hospital.

It is recommended that the patient be clinically assessed for surgical complications before source delivery. Immediate postoperative complications, such as hemorrhage, seroma,

wound breakdown, dehiscence, or infection, may delay loading of radiation and necessitate repeat treatment planning. Typically, 5 days is allowed to elapse for wound healing before treatment starts depending on the extent and location selleck chemicals llc of the surgery and the relationship of the implant to the wound closure. 192Ir source loading (LDR or HDR) has been described in the literature between postoperative Day 2–4 (33) and Day 5–8 (7). MSKCC found decreased toxicity with loading Day 5 or more (34). The surgical wound and implant catheters should be kept as clean and dry as possible. This objective may be accomplished

by the application of sterile dressing between cleansings. The patient should avoid showering, bathing, or wetting the implant catheters except during wound care. Antibiotic ointment may be applied sparingly at the catheter entrance and exit sites. Catheter removal should be in as clean a fashion as possible. In the removal of double leader implants, the catheters should be sterile prepared on the side that will be cut at the skin surface. The skin Panobinostat chemical structure should then be depressed slightly so the catheter can be cut in a way to avoid pulling the external aspect of the catheter through the wound. Dose rate is an important consideration in BT. Interstitial catheter BT for STS has used LDR iridium wires or seeds in ribbons that are loaded manually in the catheters. A randomized study (7) and a number of prospective and retrospective Phospholipase D1 reports have evaluated LDR BT either as monotherapy or in combination with EBRT [9], [22], [35], [36], [37], [38], [39], [40], [41], [42] and [43]. LC after LDR monotherapy is reported between 66% and 96% and LDR BT and EBRT between 78 and 100%. The complication

rates are also comparable with reoperation rates of 10–12% for monotherapy and 2.3–13.8% for BT and EBRT (Table 1). Alekhteyar et al. (9) evaluated 105 patients who underwent WLE followed by LDR BT vs. LDR BT and EBRT. They did not find a significant difference in 2-year LC between the cohorts (90% vs. 82%) but a trend for improved LC in patients with positive margins who had BT and EBRT compared with BT alone (90% vs. 59%, p = 0.08). There was no difference in wound complication rate (26% vs. 38%). Laskar et al. (44) reported 50 pediatric patients who underwent WLE and then either BT or BT and EBRT. They found LC to be comparable (78% vs. 84%, p = 0.89). Andrews et al. (22) reported on 86 patients treated with EBRT alone (61 patients) or in combination with BT (25 patients). The decision to use BT was based on a perceived risk of microscopically positive margins. There was no difference in 5-year overall survival (OS) (82% vs. 72%, p = 0.

Similarly, gene expression studies of clinical samples have also defined molecularly defined subgroups within a number

of tumour types [26, 27 and 28•]. It is entirely plausible that these molecularly defined subgroups will exhibit different biological characteristics including drug response and therefore any screen that utilises cancer cell lines must be of sufficient scale to capture both the tissue-type and genetic diversity of human cancers. Only in this way will it be possible to accurately model the effect of cancer mutations on drug response. One of the first systematic efforts to use cancer cell lines to identify biomarkers of drug sensitivity was the NCI-60 panel at the National Cancer Institute in 1990 [29••] (http://dtp.nci.nih.gov/branches/btb/ivclsp.html). Although these 60 cell lines have now been screened against many thousands of chemical agents, it has become increasingly this website clear that much larger numbers of cell lines are required to capture the genetic diversity of human cancer. It is now clear from next-generation sequencing studies that cancers are remarkably

heterogeneous and many cancer genes are present in only a fraction of any tumour type. It is therefore likely that hundreds of cancer cell lines would be required to capture this landscape of cancer gene mutations. To address this need, a Wellcome Trust Sanger Institute and Massachusetts General Hospital collaboration was established in 2009 to screen Lapatinib purchase >1000 cancer cell lines against 400 cancer drugs and to make that data publicly accessible (pharmacologic profiles of 142 cancer drugs screened across 668 cell lines are currently available) (http://www.cancerrxgene.org/) (Figure 1). A similar initiative funded by the pharmaceutical company Novartis at the Broad Institute has profiled 24 cancer drugs across 504 cell lines (http://www.broadinstitute.org/ccle/home). A key element of both endeavours is the detailed genomic, epigenetic Gefitinib cost and transcriptomic characterisation that has been made possible for these cancer cell

lines by advances in next-generation sequencing, such that multi-dimensional signatures of drug response can be derived from such screens and that could be used to stratify patients for clinical trial recruitment or treatment in the clinic. Landmark papers by both these groups recently demonstrated the power of these large screens to identify both novel and previously documented biomarkers of drug response in a completely unbiased fashion [18•• and 30••]. It is now feasible to consider profiling all new experimental oncology compounds in such screens in order to develop hypotheses as to mechanisms of activity as well as insights into patient subgroups that may be most likely to respond to treatment in the clinic.