When Korean women move to California, selleck chem Enzalutamide their smoking prevalence goes from 7% in Korea to 17% in California as they approximate full acculturation (Song et al., 2004). This probably represents the effect of acculturation in California, with substantially more gender equity, interacting with the previous Korean contingencies that suppressed female smoking (Hofstetter et al., 2004). These results show that ��gender�� acts as a marker for unique social contingencies for males and females. This interaction demonstrates the power of subculture contingencies and the importance of engineering gender-specific contingencies to protect women or other ��high risk�� immigrants from the tobacco industry. One such example is a media program modeled after the ��truth�� campaign (Farrelly et al.

, 2002), to counter the industry’s luring women to smoke with promises of equality and freedom. The BEM and the tobacco industry The tobacco industry knows how to change behavior The tobacco industry has been changing cultures. Brandt (2007) summarized how the industry has employed concepts from the BEM (e.g., promoting tobacco use among women as a demonstration of gender equality) and made tobacco a central feature of Western culture, if not worldwide cultures. The industry lobbies for laws that protect it. The industry illustrates how to engineer social contingencies that define our tobacco culture. Litigation is working but not without compromise Even as the industry has come under attack through civil litigation, it has turned failures into protectionist policies.

However, as recent large-scale litigation has produced ��losses�� for the industry, there is an impression that the larger culture can exact counter-control (Gostin, 2007). However, negotiated settlements have included clever stipulations. For example, awards to the Flight Attendant Medical Research Institute (FAMRI) were provided to conduct research to prevent or control diseases linked to SHSe. This spans basic, clinical, and epidemiological science, including large centers of excellence. The FAMRI will yield discoveries that contribute to disease prevention; some studies will improve clinical treatment of tobacco-related diseases, and some will inform effective smoking cessation treatments or prevention of SHSe. However, the settlement precluded research funding for new tobacco policies, including those that might inform means of population-wide protection from SHSe.

Nevertheless, the FAMRI remains a model settlement, in contrast to the track record for the Master Settlement Agreement (MSA) between the tobacco industry and attorneys general of 46 states. The MSA is the largest dollar ��award�� from the industry (Wilson, GSK-3 1999) but provides almost no support of tobacco control interventions such as media campaigns or tobacco prevention research.

Within the word clouds, font size was not too variable, suggesting agreement in the reasons for smoking and recommendations for treatment. The word clouds, as Rapamycin clinical trial a visual display of word frequency, are a useful adjunctive tool to be interpreted within the larger meaning and context of the words (McNaught & Lam, 2010). Although Figure 2 depicts the popularity of strategies, long-term tobacco abstinence will likely be supported through a combination of approaches. Interventions delivered in health care settings offer the appeal of broad reach and integration within ongoing medical care. Yet, historically, tobacco use in the mental health setting has been normalized. A culture shift is needed. In this qualitative study, the providers interviewed were highly trained clinicians in high-performing clinical sites.

As such, the findings reflect a best-case scenario and, notably, suggest great room and receptivity for improvement. The adolescents largely viewed the mental health setting as a safe place to tackle issues with which they struggle such as smoking. To increase clinician prioritization and delivery of tobacco treatment, recent research in adult drug treatment programs supports the evidence of organizational interventions consisting of staff training, consultation, policy development, leadership support, and access to cessation medication (Guydish et al., 2012). An emphasis on tobacco treatment��s broader possible effects for enhancing sobriety and mental wellness may be particularly helpful (Prochaska, Delucchi, & Hall, 2004; Prochaska et al., 2008).

At the patient level, clinical trials research is needed to evaluate the acceptability and efficacy of tobacco cessation interventions with youth in mental health settings. FUNDING This work was supported by the National Institute on Drug Abuse (#K23 DA018691, #K05 DA016752, and #P50 DA09253) and the State of California Tobacco-Related Disease Research Program (#13KT-0152). DECLARATION OF INTERESTS The authors have no competing interests to declare related to this research. ACKNOWLEDGMENTS We acknowledge Christianne Wa for transcribing the interviews, Howard Liu for secondary coding of the interviews, and our clinical collaborators Ken Epstein, MSW, Alan Louie, MD, Celia Moreno, MD, and Susan Smiga, MD, for the opportunity to work with adolescent and young adult patients and mental health providers at their outpatient sites.

In 2011, the lifetime prevalence of cigarette smoking in 8th grade was 18.4% rising to 40.0% by 12th grade (Johnston, Cilengitide O��Malley, Bachman, & Schulenberg, 2012), indicating the importance of understanding the patterns of growth in smoking across this developmental period. The present study investigated individual trajectory classes of cigarette smoking across adolescence, and examined their precursors and consequences.

assessmentcenter.net) have resulted in broad uptake of the PROMIS item banks among the behavioral research community. selleck chem Temsirolimus The PROMIS Smoking Initiative, funded through a 5-year grant by National Institute on Drug Abuse to the RAND Corporation (Principal Investigator: ME), has the goal of developing, evaluating, and making widely available a set of item banks that can form the basis for standardized assessment of smoking behavior and the biopsychosocial constructs that can be used to predict smoking outcomes. The PROMIS Smoking Initiative involves several detailed steps and procedures (see Cella et al.

, 2007 for details of the PROMIS approach) including (a) collecting all the existing scales and items that are used to assess key assessment domains (see Shadel & Shiffman, 2005), (b) reviewing items from all the scales to eliminate redundant and poorly worded items, (c) incorporating feedback from focus groups and cognitive interviews to further refine item wording and format, and (d) analyzing data from large representative samples to evaluate the psychometric properties of the items through factor analysis and item response theory calibration. The item banks that result from this initiative will be included in the larger PROMIS framework and be made widely available to the research community. Detailed descriptions of this work and results from the PROMIS Smoking Initiative will be available in future reports. Funding This research was funded by R01DA026943 from the National Institute on Drug Abuse. Declaration of Interests None declared.

Acknowledgments The authors would like to thank the PROMIS Smoking Initiative Group: Li Cai, Ronald D. Hays, and Michael Ong, University of California, Los Angeles; David Cella, Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University; Daniel McCaffrey, RAND Corporation; Raymond Niaura, American Legacy Foundation; Paul Pilkonis, University of Pittsburgh; and David Thissen, University of North Carolina at Chapel Hill.
Tobacco use is largely driven by nicotine dependence, characterized as commonly involving cycles of repeated quit attempts and relapse (Fiore et al., 2008). Traditional models of nicotine dependence treatment offer only a single short-term (i.e., 1�C12 weeks) intervention and do not include a mechanism for assisting those not interested in quitting, those not responsive to treatment, or those who relapse (Fiore et al.

, 2008). Evaluation of these interventions is commonly limited to 6- or 12-month follow-up. KanQuit was designed to provide the support systems Carfilzomib needed to address nicotine dependence as a chronic disease, using the Chronic Care Model (Ellerbeck et al., 2009). The study enrolled rural smokers from primary care practices, independent of interest in stopping smoking, and compared varying intensities of disease management (pharmacotherapy alone or with disease management and motivational counseling).

5 and 25 mg/kg/day dose, respectively. Figure 2 Treatment of T. cruzi-infected mice (104 Y strain/mice) with DB1965. trichostatin a clinical trials On the other hand, gavage administration of DB1965 and Bz resulted in 51 and 100% of decrease in parasitaemia levels, respectively (Fig. 2A). Biochemical analysis performed at 30 days post treatment showed that only minor differences could be noted between the different mice groups. Regarding ALT measurements a significant increase (p=0.02) was found when infected but untreated animals were compared to uninfected group. However, Bz (p=0.18), 12.5 (p=0.33) and 25 mg/kg (p=0.80) DB1965 did not show any statistically significant difference as compared to uninfected mice (Table 3). When urea levels were analyzed, although no major alteration (p=0.

14) was noticed among uninfected and infected but untreated mice, the administration of 12.5 mg/kg DB1965 displayed a statistical difference (p=0.03) as compared to those infected mice that did not receive any treatment (Table 3). On the other hand, neither Bz (p=0.16) and 25 mg/kg DB1965 (p=0.10) showed considerable alteration urea plasma levels as compared to those infected but untreated animals (Table 3). Table 3 Biochemical analysis of T.cruzi-infected mice treated or not by DB1965 and Benznidazole. The analysis of parasitological cure (by hemocultive and PCR) demonstrated that no cure was achieved in both Bz and DB1965 treated mice (Table 4). Also, as the ip dose of 12.5 mg/kg of the AIA achieved 100% of animal survival (Fig. 2B), this later dose was selected for the second round of assays, using 10 daily consecutive doses (at 5 dpi for 10 dpi).

Table 4 Cure assessment of DB1965 combined or not with benznidazole (Bz) in murine model of acute T. cruzi-infection1. The data showed that quite similar parasitaemia control was reached using Bz (99.8%) and DB1965 (97%) (Fig. 2C). Although both DB1965 and Bz were effective in protecting against animal mortality, resulting in about 90 and 100% of survival, respectively (Fig. 2D), neither were able to produce parasitological cure of the animals (Table 4). Because some reversible side effects like hyperactivity was noted for the DB1965 group at the end of the treatment (after the 7th day of DB1965 administration), and aiming to find an alternative scheme of therapy using this highly active AIA, a combined treatment of DB1965 (5 mg/kg/day) and Bz (50 mg/kg/day) was next employed, under a scheme of 20 daily consecutive doses. Our data showed that all Dacomitinib treated mice (treated with each compound alone and with Bz+DB1965) presented 100% of survival (Fig. 2F). These treated mice also displayed a suppression of the parasitaemia at the peak day exhibiting 100, 100 and 84% of decrease after Bz, Bz+DB1965 and DB1965 administration (Fig. 2E).

Videos were SB203580 cost considered positive if they mentioned or portrayed smoking in a favorable light, by showing smoking as fun, desirable, pleasurable, sexy, and/or socially advantageous. Videos were considered neutral if smoking was unimportant to the video and neither portrayed it positively or negatively. ENDS videos were considered positive smoking videos. Videos were further sorted by genre after identifying recurrent themes. Genres identified were how to quit monologues, professionally produced antismoking commercials, homemade appearing antismoking videos, comedy, e-cigarettes, smoking fetish, cigarette commercials, magic tricks, music, popular media and movie clips, poetry, satire, smoking while shooting guns and/or lighting fireworks, and videos making fun of smoking laws.

Definitions were developed for each genre to assure consistency in assessment. The videos were also sorted by whether they contained a cigarette brand reference, and if so, the brand was recorded. A video was considered to have a brand reference if a brand name was either visually apparent or if the name was verbalized in the video. Results The number of hits retrieved by both search terms and by relevance and view count increased from May to July by an average of 11% (Table 1). Of 59 videos that met inclusion criteria in the May 2009 sample, 10 (16.95%) contained negative smoking messages. Together these 10 videos had been viewed a total of 1,791,975 times, accounting for 6.4% of total views of all May-sampled videos. Forty-eight videos contained positive smoking messages, comprising 81.

36% of the sample. Collectively, these 48 videos had been viewed 24,572,388 times, accounting for 87.72% of total views. One video contained a neutral message and had been viewed 1,649,513 times, accounting for 5.89% of total views. Table 1. Total YouTube hits for the search terms ��cigarettes�� and ��smoking cigarettes�� The July sample (n = 65) was similar, with 10 videos (15.38%) featuring negative smoking videos. These videos had been viewed collectively 1,009,971 times, accounting for 3.68% of total views. Fifty-three videos (81.54%) portrayed smoking positively, and these videos had been viewed 25,123,202 times, accounting for 91.49% of total views. Two videos contained a neutral message and had been viewed 1,326,435 times, accounting for 4.83% of total views.

Twenty-seven videos appeared in both May and July samples. Thirty-eight videos (58%) were new to the July sample, while 32 videos in the May sample no longer appeared in the July sample. Of videos featuring Anacetrapib antismoking content, professionally produced tobacco control videos were the most popular and were viewed the most often, followed by homemade negative imagery (Table 2). The professionally produced videos were high-impact videos that graphically showed the disease effects of smoking (MisterTrimble, 2006; ZerlinTV, 2007).

Results MyD88 Silencing ABT-888 and Cancer Cell Viability In Vitro To investigate the role for MyD88 in the maintenance of transformation of Ras-dependent tumor cells, we performed siRNA experiments targeting MyD88 in colon cancer cell lines bearing activating mutations in the Ras oncogene and a functional p53 (6,7). As shown in Figure 1A, MyD88 silencing (controls in Supplementary Figure 1A, available online) induces apoptosis in all four colon cancer cell lines (all RNA interference extinction controls are found in the Supplementary Material, available online). To investigate a possible implication of p53 in the apoptosis observed upon MyD88 silencing, we used the isogenic HCT116 colon cancer cell lines (p53+/+ and p53�C/�C) (8).

We observed that MyD88 silencing (controls in Supplementary Figure 1B, available online) induces substantially higher apoptosis levels in HCT116 p53+/+ compared to HCT116 p53�C/�C cells (Figure 1B). To ascertain that the difference in MyD88 knockdown-mediated apoptosis in these two lines is exclusively due to their p53 status, we knocked down MyD88 and p53, either separately or simultaneously, in HCT116 p53+/+ but also in LS513 cell lines. We observed that simultaneous extinction of MyD88 and p53 (controls in Supplementary Figure 1C, available online) completely reversed the apoptosis caused by MyD88 silencing in both cell lines, thereby confirming that this apoptosis is strictly dependent on p53 (Figure 1C). Figure 1. Effect of MyD88 silencing p53-dependent apoptosis. A) Apoptosis of colon cancer cell lines upon MyD88 silencing by small interfering RNA (siRNA).

B) Apoptosis of HCT116 p53+/+ or p53�C/�C cell lines upon MyD88 silencing by siRNA. C) Apoptosis … Moreover, an overexpression of p53 and p21 proteins was observed in HCT116 p53+/+ upon MyD88 silencing (Figure 1D). The stabilization of p53 and the overexpression of p21 are well-known signatures of the activation of the p53 pathway (7). Furthermore, to rule out the possibility that the observed apoptosis is dependent on the MyD88 siRNA sequence used and off-target effects, we performed MyD88 silencing experiments using a second siRNA sequence targeting MyD88, and obtained similar results to those obtained with the first siRNA sequence (Supplementary Figure 1D, available online). MyD88 Silencing and Tumor Growth In Vivo We then investigated the in vivo relevance of our in vitro observations.

In order to avoid potential hurdles generally associated with systemic injection of siRNA into mice, we generated by viral transduction HCT116 p53+/+ or GSK-3 p53�C/�C cell lines stably expressing a doxycycline-inducible nonsilencing shRNA (shNS) or MyD88 shRNA (shMyD88). First, the four resulting HCT116 cell lines were tested for apoptosis induction upon doxycycline treatment.

5%. Using these adherence cut points, sensitivity was comparable across measures (see Table 4); however, pill count specificity (80% specificity, 95% CI = 30.0�C99.0) sellekchem was markedly greater than that of 3-day recall and VAS (60% specificity, 95% CI = 17.0�C93.0 for both measures). The probability that adherence��plasma varenicline levels greater than or equal to 2.0 ng/ml��was correctly identified across measures (i.e., positive predictive value) was high and ranged from 0.96 to 0.98, whereas the probability that pill count or self-report indicating nonadherence��plasma varenicline levels less than 2.0 ng/ml��was accurate (i.e., negative predictive value) was lower, ranging from 0.33 to 0.55. Table 4.

Optimum Adherence Cutpoints and Related Sensitivity, Specificity, PPV, and NPV of Pill Count, 3-Day Recall, and Visual Analogue Scale for Detecting Adherence When Compared With Plasma Varenicline Concentrationa Figure 1. Area under the receiver operating characteristic curve for pill count, 3-day recall, and VAS. Discussion In this study, we found significant concordance among the varenicline adherence self-report measures, pill count, and plasma varenicline concentration. Of the pill count and two commonly used self-report adherence measures (3-day recall and VAS), pill count had the strongest association with plasma varenicline concentration, the largest area under the ROC curve, and also demonstrated the best combined sensitivity and specificity. Specifically, among participants categorized as adherent by their plasma varenicline concentration, pill count correctly classified them 88% of the time (sensitivity).

While 3-day recall and VAS also demonstrated high sensitivity, the specificity of pill count was greater. Specifically, for participants categorized as non adherent by their plasma varenicline concentration, pill count correctly classify them 80% of the time compared with only 60% of the time with 3-day recall and VAS (specificity). Across all measures, the probability that a result indicating adherence would meet the threshold of 2.0 ng/ml for varenicline plasma adherence was uniformly high (positive predictive value). However, given the high rate of adherence in our sample, the probability that participants categorized as nonadherent on pill count, 3-day recall, or VAS had varenicline plasma concentrations of less than 2.

0 ng/ml was lower (ranging from 33% for VAS to 50% for 3-day recall; negative predictive value). Few studies have examined pill count as a method for assessing adherence to smoking cessation pharmacotherapy, although it has been used widely across other health domains and could be reasonably Batimastat incorporated into tobacco dependence treatment (Bangsberg et al., 2001; Kalichman et al., 2007, 2008; van Onzenoort et al., 2009).

? Fields which have string values in XML are converted to properties in OWL. Example: The field Name which has a string value type becomes a datatype property hasName ? Ambiguous labels are unified. Example: The field Results is used in several different contexts, that is why we rename it to TreatmentResults, in the treatment www.selleckchem.com/products/Roscovitine.html group; ? Wherever possible, object type properties are introduced instead of datatype ones �C thus string values are replaced by named concepts. Example: In ToxML schema the field Sex is defined as a simple type of type string, which would be converted to property in direct conversion, but in OWL we introduce a new class Sex, thus creating an object property has Sex instead of a datatype one. ? Mapping to Organ ontology and study type classifications can be applied.

OpenToxipedia has been developed using the SMW. It was created manually by experts in the fields of in silico and experimental toxicology on the basis of known regulatory documents, glossaries, dictionaries and some primary publications. All registered members are welcome to add new entries, suggest definitions and edit the existing resource at http://www.opentoxipedia.org. OpenToxipedia is curated by toxicology experts within the OT community. The SMW was chosen for OpenToxipedia representation for the following main reasons: it enables automatic processing of the wiki knowledgebase and it gives a possibility for data transfer between RDF and SMW through SPARQL. SMW will facilitate the automatic data exchange between OpenToxipedia, the ontologies and OpenTox web services using RDF data.

The SMW is a collaborative system, supports versioning, RDF export, tools to lock pages by a curator (fixing a validated vocabulary) and the possibility to add annotation without changing the ontology or RDF information. Results and discussion Sub-ontology projects developed within the OpenTox project Up to now, six ontologies have been made available through the OT Collaborative Prot��g�� Server: ? Toxicological Endpoint ontology; ? Organs system and Effects ontology; ? ToxML ontology; ? OpenTox ontology, representing components of OpenTox web services, framework and Algorithm types; ? ToxLink (ToxCast [39] assays ontology); ? OpenToxipedia: SMW toxicology knowledge resource.

Toxicological Endpoint ontology The OT Toxicological Endpoint ontology contains five toxicity study types: carcinogenicity, in vitro bacterial mutagenicity, in vivo micronucleus mutagenicity, repeated dose toxicity (e.g., chronic, sub-chronic or sub-acute study types) and aquatic toxicity (see Figure Figure22). Figure 2 OpenTox toxicological ontology structure The purpose of Cilengitide this ontology is to enable the attributes of toxicological dataset entries to be associated with ontology concepts. The OT framework exposes REST web services, corresponding to common OT components.

In the liver, cortisol is converted to its inactive metabolite cortisone by the enzyme 11�� – hidroxysteroid dehydrogenase. After diffusion across the cell membrane, cortisol binds to glucocorticoid receptor and translocates into the nucleus those of the cell[37] where its effects are exerted (increased vascular tonus and cardiac output, protein catabolism, lipolysis, hyperglycemia, and decreased cytokine production)[38]. These effects of cortisol are beneficial in critical illness, and several studies have shown that corticosteroid therapy is beneficial in patients with severe sepsis or septic shock[12-14,39,40]. As adrenal glands do not store cortisol, this must urgently be synthesized from its precursor, cholesterol, under any conditions of stress.

In cirrhotic patients there is a low substrate (HDL cholesterol) for the synthesis of cortisol, favoring AI in conditions of stress[26]. PATHOGENESIS Mechanisms leading to AI in liver cirrhosis remain largely unknown, although some hypotheses such as endotoxemia, decreased levels of apolipoprotein A-1, HDL cholesterol and LDL cholesterol, increased levels of proinflammatory mediators, structural damage to the adrenal gland due to infarction or hemorrhage, bacterial translocation of enteric organisms, ��exhaustion�� of the adrenal cortex, and glucocorticoid resistance have been suggested[12,41-49]. Many (if not all) of these pathophysiologic mechanisms are also involved in the genesis of AI in critically ill patients with sepsis[50-56]. As we have mentioned, cholesterol is the main source of steroidogenic substrate in the adrenal gland[26,57].

Several studies reported a significant decrease in the level of serum HDL in cirrhotic patients which was related to the severity of the disease[12,26,47]. Furthermore, increased levels of circulating endotoxin (lipopolysaccharide) and TNF-�� inhibit cortisol synthesis, limiting the delivery of HDL cholesterol to the adrenal gland[58-60]. In addition to this, TNF-��, IL-1 and IL-6 decrease hepatocyte synthesis of apolipoprotein A-1[58], the major component of HDL cholesterol. The lack of substrate for steroidogenesis will eventually lead to the so-called ��adrenal exhaustion syndrome��[42] which contributes to AI in cirrhotic patients. Besides low levels of serum total cholesterol, HDL-cholesterol and LDL-cholesterol, other factors may play a definite role in the pathogenesis Brefeldin_A of AI in patients with liver cirrhosis. Thus, coagulopathy (frequent in liver cirrhosis) may cause adrenal hemorrhage and infarction leading to structural damage of the adrenal gland[5], resulting in AI. Systemic inflammation is common in cirrhotic patients[61]. Bacterial translocation of enteric organisms has been demonstrated in patients with advanced liver cirrhosis[41,62].

Primers selleckbio were designed for hK1: Forward 5��-GGGTCGCCACAACTTGTTTG-3�� and Reverse 5��-GCTGTAGTCCTCGTCTGCTT-3�� B1R: Forward 5��-CTTCCCTCAAAATGCTACGGC-3�� and Reverse 5��-TCTGCCACGTTCAGTTGCC-3�� B2R: Forward 5��-GTCTGTTCGTGAGGACTCCG-3�� and Reverse 5��-CTGGGCAAAGGTCCCGTTAAG-3�� ACE: Forward 5��-AACGAAACCCACTTTGATGC-3�� and Reverse 5��-TCAGCCTCATCAGTCACCAG-3�� HMK: Forward 5��-TGGGGCCATGAAAAACAAAG-3�� and Reverse 5��-CTTGGCTAGGGAAGGGATGG-3�� LMK: Forward 5��-CCAGCATCTGAGAGGGAGGT-3�� and Reverse 5��-GCAGAATGGGTAGGGCTGAA-3��. BrdU cell proliferation assay Gastrointestinal stromal tumour cells were seeded in 96-well plates (5000 cells per well) and incubated with BrdU for 24h in normal medium or in the presence of 0.5, 0.05 or 0.005�� of specific hK1 inhibitors VA999154 or VA999024, kindly provided by Vantia Ltd.

(Chilworth, UK) BrdU incorporation was determined following the manufacturer’s protocol (Roche, Melwin, UK). GIST invasion assay The invasion capacity of GIST882 and GIST48 cells was measured by seeding 5 �� 104 cells on top of an 8��m filter coated with Matrigel (BD, 1:100). Medium containing 5% FBS was used as a stimulus. hK1 inhibitors VA999154 and VA999024 were added at a concentration of 0.5�� as described above. After 24h, the filters were mounted with DAPI to recognise the nuclei of migrated cells. Cell number was calculated by averaging the counts of five microscopic fields (photographed at �� 20). Endothelial cell migration assay The migratory response of ECs to GIST was assessed in a transwell array (Corning, Corning, NY, USA).

Briefly, 3 �� 105 GIST882 cells were plated on the bottom chamber of the migration system. Human umbilical vein ECs (HUVECs) were preincubated with B1R or B2R antagonists (Lys-des-Arg9Leu8-BK, LdL-BK or Icatibant, IC, respectively, 2 �� 10?7M) or PBS (vehicle), plated on top of the insert (50000 cell per insert) and then left to migrate overnight in the presence or absence of B1R or B2R antagonists. Migrated HUVECs were counted as described for the invasion assay and the percentage of migrated cells was calculated on the number of plated cells. Matrigel angiogenesis assay HUVECs pretreated for 30min with the hK1 inhibitor kallistatin (1��, R&D) (Wolf et al, 1999), the serine protease inhibitor Aprotinin (50Uml?1, Bayer, FRG) or vehicle were plated on growth factor-reduced Matrigel (BD Biosciences, Erembodegem, Belgium) in the presence of GIST882-conditioned medium or unconditioned medium (as a control).

Total tube length Batimastat and average tube thickness were measured on photographs captured at 24h and analysed using ImagePro Plus software (Media Cybernetics, Bethesda, MD, USA). FACS analysis Cells were incubated with rabbit polyclonal antibodies for B1R and B2R (1:100, Sigma), followed by FITC-labelled antirabbit secondary antibodies (Sigma) and analysed in a FACScalibur (BD Biosciences) flow cytometer. Controls were stained with isotype control.