radiovictrix cultures This work was performed under the auspices

radiovictrix cultures. This work was performed under the auspices of the US Department of Energy Office of Science, Biological and Environmental Research Program, and by the University of California, Lawrence Berkeley National Laboratory under contract No. DE-AC02-05CH11231, Lawrence Livermore National Laboratory under Contract No. DE-AC52-07NA27344, and Los Alamos National Laboratory under contract No. DE-AC02-06NA25396, UT-Battelle and Oak Ridge National Laboratory under contract DE-AC05-00OR22725, as well as German Research Foundation (DFG) INST 599/1-2.
A representative genomic 16S rRNA sequence of strain Yu37-1T was compared using BLAST under default settings (e.g.

, considering only only the high-scoring segment pairs (HSPs) from the best 250 hits) with the most recent release of the Greengenes database [7] and the relative frequencies of taxa and keywords (reduced to their stem [8]) were determined, weighted by BLAST scores. The most frequently occurring genera were Deferribacter (33.4%), Alteromonas (21.3%), Magnetococcus (9.4%), Shuttleworthia (7.5%) and Geovibrio (7.3%) (61 hits in total). Regarding the single hit to sequences from members of the species, the average identity within HSPs was 99.9%, whereas the average coverage by HSPs was 96.7%. Among all other species, the one yielding the highest score was Deferribacter desulfuricans, which corresponded to an identity of 88.1% and an HSP coverage of 86.0%.

The highest-scoring environmental sequence was “type”:”entrez-nucleotide”,”attrs”:”text”:”DQ424925″,”term_id”:”89994032″,”term_text”:”DQ424925″DQ424925 (‘Enrichment and Thermophilic Mediator-Less Microbial Fuel Cell thermophilic microbial fuel cell enriched artificial wastewater clone 1B62′) [9], which showed an identity of 99.7% and an HSP coverage of 98.2%. The most frequently occurring keywords within the labels of environmental samples were ‘microbiota’ (4.1%), ‘microbi’ (4.1%), ‘intestin’ (4.0%), ‘mous’ (3.8%) and ‘compet, exploit, inflamm, salmonella, typhimurium’ (3.7%) (183 hits in total). The most frequently occurring keywords within the labels of environmental samples which yielded hits of a higher score than the highest scoring species were ‘microbi’ (8.6%), ‘thermophil’ (6.7%), ‘enrich’ (5.7%), ‘cell, fuel’ (5.3%) and ‘spring’ (3.6%) (21 hits in total), which seem to fit to the features known for C. nitroreducens.

Figure 1 shows the phylogenetic neighborhood of C. nitroreducens Yu37-1T in a 16S rRNA based Brefeldin_A tree. The two copies of the 16S rRNA gene in the genome differ by one nucleotide from each other any by up to one nucleotide from the previously published 16S rRNA sequence (“type”:”entrez-nucleotide”,”attrs”:”text”:”AB364234″,”term_id”:”194072585″,”term_text”:”AB364234″AB364234). Figure 1 Phylogenetic tree highlighting the position of C.

The current research work deals with the development

The current research work deals with the development Erlotinib cost of spectrophotometric method and its validation as per International Conference on Harmonisation (ICH) guidelines.[3] MATERIALS AND METHODS Experimental Instrument and materials Instrument used were Schimadzu 1800 double beam UV/Visible Spectrophotometer and schimadzu 1600 analytical balance. Lafutidine pure drug was obtain from Ajanta Pharmaceuticals Ltd., Mumbai, India as gift sample with 99.9% (w/w) assay value and was used without further purification. All chemicals and reagents used were of analytical grade. Methodology Preparation of standard stock solution Standard drug solution of lafutidine was prepared by dissolving 10 mg lafutidine in 5 ml methanol this solution was transferred it to 10 ml volumetric flask and volume was made up to mark with distilled water to obtain stock solution of 1 mg/ml concentration.

Preparation of calibration curve Aliquots of 1�C5 ml portion of stock solutions were transferred to series of 100 ml volumetric flasks, and volume made up to mark with distilled water. Solutions were scanned in the range of 200�C400 nm against blank. The absorption maxima were found to be at 279 nm against blank. The calibration curve was plotted. The optical characteristics are summarized in Table 1. Table 1 Calibration curve parameter Preparation of sample solution The proposed method was applied to analyze commercially available lafutidine tablet. Ten tablets were weighed and powdered.

The amount of tablet powder equivalent to 10 mg of lafutidine was weighed accurately and transfer to 10 ml volumetric flask then 5 ml methanol was added and kept for 15 min with frequent shaking and volume was made up to mark with distilled water. The solution was then filtered through Whattman filter paper #41. This filtrate was diluted suitably with distilled water to get the solution of 10 ��g/ ml concentration. The absorbance was measured against solution blank. The drug content of the preparation was calculated using standard calibration curve. Amount of drug estimated by this method in Table 2. Table 2 Determination of accuracy by percentage recovery method RESULT AND DISCUSSION Linearity The linearity of the response of the drug was verified at 10�C50 ��g/ml concentrations. The calibration curve was obtained by plotting the absorbance versus the concentration data and was treated by linear regression analysis [Table 3].

The equation of the calibration curve for lafutidine obtained was y = 0.0100x + 0.035, the calibration curve was found to be linear in the aforementioned concentrations (the correlation coefficient (r2 ) of determination was 0.999) [Figure [Figure22 and and33]. Table 3 Validation parameters Figure 2 Calibration curve Figure 3 Overlay figure of linearity ranges of lafutidine (10�C50 ��g/ml) Precision Assay of method precision (intraday precision) was evaluated by carrying out six GSK-3 independent assays of test samples of lafutidine.

6 mm i d , 5 ��m particle size) were selected to achieve good res

6 mm i.d., 5 ��m particle size) were selected to achieve good resolution and acceptable peak symmetry. Flow rates between 0.5 and 1.2 ml/min were tried. Flow rate of 1.0 ml/min was observed to be enough to get both the drugs eluted within less than 10 min. The column temperature was set at 40��C. System suitability The retention times for LAMI, TDF, and EFV using optimum conditions were 2.76, 3.96, and 10.5 min, respectively. For three of them, the peak symmetries were <1.5 and the theoretical plates�� numbers were >2000. These values are within the acceptable range of United state pharmacopoeia definition and the chromatograms obtained under optimized chromatographic conditions. Figure 4 clearly shows the ability of the method to assess the analyte in the presence of other excipients. The results obtained are shown in Table 1. Figure 4 Chromatograms of LAMI (3 ��g/ml), TDF (3 ��g/ml), and EFV (6 ��g/ml) reference substances Table 1 System suitability parameters Method validation[36] The developed method for simultaneous estimation of LAMI, TDF, and EFV has been validated in accordance with the ICH guidelines.[11] Linearity Linearity was checked by preparing standard solutions at six different concentration levels of each of LAMI, TDF, and EFV, ranging from 1 to 6 ��g/ml for each of LAMI and TDF and from 2 to 12 ��g/ml for EFV. Triplicates of 20-��l injections were made for each concentration and were chromatographed under the chromatographic conditions mentioned above. Peak areas were plotted against the corresponding concentrations to obtain the calibration graph for each compound. The regression analysis data are given in Table 2. Table 2 Linearity data Sensitivity The sensitivity of the analytical method was evaluated by determining the limits of detection (LOD) and quantitation (LOQ). The values of LOD and LOQ for LAMI, TDF, and EFV are given in Table 2. Accuracy The accuracy of the method for assay determination was checked at three concentration levels of 80%, 100%, and 120% for LAMI, TDF, and EFV. The percentage recoveries are tabulated in Table 3. The recovery was calculated from the slope and intercept of the calibration curve of each drug. As per the ICH guideline, the % recovery must be between 98% and 102%. Table 3 Repeatability precision Precision Repeatability: System repeatability was determined by replicate applications and measurements of peak area for LAMI, TDF, and EFV. One dilution in six replicates was analyzed on the same day for repeatability and results were found within acceptable limits (RSD <2) as shown in Table 4. Table 4 Result of recovery studies with static evaluation Intermediate precision: Intermediate precision was assessed by the assay of sample sets on three different days (inter-day precision). Three dilutions in three replicates were analyzed and results were found within acceptable limits (RSD <2) as shown in Table 4.

methylohalidivorans DSM 14336T (pMeth_A285) as well as the RepC-8

methylohalidivorans DSM 14336T (pMeth_A285) as well as the RepC-8 type plasmid of Phaeobacter daeponensis DSM23529T (pDaep_A276). Table 6 Integrated Microbial Genome Ceritinib 1032900-25-6 (IMG) locus tags of P. caeruleus DSM 24564T genes for the initiation of replication, toxin/antitoxin modules and two representatives of type IV secretion systems (T4SS) that are required for conjugation. The locus tags are … Several strains affiliated with the Roseobacter clade show a high potential to produce secondary metabolites [51]. Pigmentation of cells is often related with secondary metabolite production [61]. We assume that the characteristic blue color of P. caeruleus is attributed to the production of the blue pigment indigoidine. In the closely related and blue-colored Phaeobacter sp.

strain Y4I indigoidine is produced via a non-ribosomal peptide synthase (NRPS)-based biosynthetic pathway encoded by the gene cluster igiBCDFE [62]. In strain Y4I indigoidine production is correlated with pleiotrophic effects, such as motility, resistance to hydrogen peroxide, surface colonization and inhibition of Vibrio fischeri. A cluster analysis revealed that the P. caeruleus plasmid pCaer_B246 contains a homologous igiBCDFE gene cluster (Caer_4407 – Caer_4412). Thus it seems likely that P. caeruleus can also produce the antimicrobial secondary metabolite indigoidine via its NRPS cluster. Therefore, indigoidine could be the pigment responsible for the blue color and P. caeruleus could have inhibitory effects on other bacteria. Mutants in either of the two LuxIR systems in Phaeobacter sp.

strain Y4I are lacking the indigoidine production, therefore, quorum sensing seems to play a role in its biosynthesis [62]. A correlation between quorum sensing and pigmentation and antimicrobial effects is already known for members of the Roseobacter clade. The LuxIR-type quorum sensing system of P. inhibens DSM 17395 (originally deposited as P. gallaeciensis DSM 17395; Buddruhs et al., unpublished) regulates N-acyl homoserine lactones production which co-occurs with the strains AV-951 dark pigmentation and antibiotic activity [63]. The P. caeruleus DSM 24564T chromosome cCaer_A3521 has a luxIR gene cluster (Caer_1365 – Caer_1371) which shows strong homology to the mentioned LuxIR-type cluster of P. inhibens DSM 17395 and strain Y4I, thus pigmentation and putative inhibitory effects could be regulated via quorum sensing. Besides these luxIR genes, five other luxIR clusters are encoded in the genome of strain DSM 24564T which could play an important role in cell-cell signaling. Recently siderophore production was shown for P. inhibens DSM 17395 [64].

Intraoperative parameters including estimated blood loss (EBL), c

Intraoperative parameters including estimated blood loss (EBL), conversion to open surgery, selleck chemicals Nilotinib and complications were collected. With respect to postoperative data, return of bowel function, resumption of oral intake, complications, length of stay (LOS), secondary interventions, and readmissions within 30 days after discharge were evaluated. 2.1. Operative Technique Initial entry into the peritoneal cavity was achieved under direct visualization using an Optiview trocar (Ethicon Endo-Surgery Inc., Cincinnati, OH, USA). An additional two or three 5 mm trocars were utilized with placement dependent on the suspected location of the perforation. Laparoscopic exploration was performed and followed by identification and isolation of the site of the colonic perforation.

Any bowel spillage was aspirated, and the area was irrigated. The necrotic edges of the perforation were debrided, and colorrhaphy was performed with interrupted 3-0 Vicryl (Ethicon Inc., Somerville, NJ, USA) suture in a single layer technique. An air insufflation test was performed in all cases to confirm the integrity of the repair. 3. Results Five female patients presented with acute iatrogenic colonic perforation, which occurred during screening colonoscopy. The mean age, mean BMI, and median ASA of the patients were 71.4 �� 9.7 years (range: 58�C83 years), 26.4 �� 3.4kg/m2 (range: 21.3�C30.9kg/m2), and 2 (range: 2-3), respectively (Table 1). Three perforations were secondary to mechanical trauma and recognized during the colonoscopy, while two perforations occurred due to thermal injury and were identified within 24 hours of the colonoscopy.

The perforations were located in the sigmoid (n = 4) and cecum (n = 1). While in 3 cases the time interval between perforation and surgery was 3-4 hours, in 2 cases surgery was performed following 18 and 20 hours of perforation. Table 1 Preoperative and intraoperative parameters. All procedures were successfully performed using pure laparoscopic technique. There was no significant blood loss (range: 0�C50mL) or intraoperative complications during the procedures, and none required conversion to open surgery. Surgical resection and diversion were not required for any of the perforations. Mean resumption of oral intake and return of bowel function, as evidenced by passage of flatus, were 1.4 �� 0.5 and 1.6 �� 0.9 days, respectively (range: 1-2 days).

The average length of hospital stay (LOS) was 3.8 �� 0.8 days (range: 3�C5 days). There were no postoperative complications, and none of the patients required readmission or Cilengitide secondary operative intervention (Table 2). Table 2 Postoperative outcomes. 4. Discussion Although complications during colonoscopy are uncommon, colonic perforation represents a potentially life-threatening event that may result in peritonitis, sepsis, and multiorgan failure, thus demanding prompt diagnosis and intervention [1].

This can lead to ripping of the tissue or the suture This can be

This can lead to ripping of the tissue or the suture. This can be a significant problem early on, although the improvement in visualization is such that the surgeon rapidly learns visual clues to compensate for his lack Sunitinib FLT3 of feedback. Despite this, RAS still requires careful handling of tissues by the surgeon. 5.2. Equipment Size and Weight Increased physical space requirements in the operating room are needed to accommodate the large and heavy equipment. Additional time and personnel are needed to set it up, along with specialized training for OR staff. 5.3. Cost of the Device Initial installation cost ranges from 1.5 to 2.5 million dollars (US) depending on the model, along with an approximately 100,000 dollars annual maintenance fee and 2000 dollars per instrument (each instrument has a ten use lifespan); the da Vinci robotic system is one of the most expensive operating tools available, making it impractical for many institutions.

5.4. New Technology and Unproven Benefit Stronger studies are needed to assess the real cost-benefit of this technology compared to other techniques. 6. Surgical Set-Up The description below applies to the TORS procedures, although not all procedures in the head and neck region use this approach. (Other approaches are commented on in each procedure description.) Transoral Robotic Surgery (TORS) is defined as surgery performed via the oral cavity that uses a minimum of three robotic arms and allows bimanual manipulation of tissues [21]. It was first developed by Weinstein and O’Malley, who have assessed the feasibility of this technique using the da Vinci Robotic System [13, 22�C27].

To minimize obstruction and maximize the communication between the surgeon and his/her assistants in TORS surgery, the surgeon’s cart should be located at the end of the operating room, allowing free space to maneuver the surgical cart that is placed on the right side of the patient, opposite to the surgeon. The support staff and instrument carts are located on the side of the patient, opposite the surgeon as well. The anesthesia machine and anesthesiologist are at the patient’s foot (Figure 1). Anesthesia induction is usually done without moving the patient; this technique is described in detail by Chi et al. [28]. According to Chi et al., this method of organization slightly complicates the induction, but vastly simplifies setup for procedure, saving 15�C20 minutes per case.

Performing the induction across from the anesthesia unit does not require the disconnection/reconnection of IV lines, monitor devices, or the anesthesia circuit, avoiding entanglement with the robotic equipment. Next, with the patient in supine position, the airway is secured via standard endotracheal intubation and the tube is appropriately Drug_discovery secured. Safety goggles and a molded dental guard are used to protect the patient.

Moreover, the involvement of the jejunum alone is uncommon and it

Moreover, the involvement of the jejunum alone is uncommon and it is more difficult to investigate because of its tendency to stay non distended[3]. The clinical importance of the SB CD phenotype is the impact that a diffuse SB disease is expected to have on a child��s growth and development. Moreover, patients with SB CD are more likely to experience complications, including intestinal obstruction and less commonly fistulization[4,5]. Thus, objective evaluation of the SB is essential in differentiating CD from other enteropathies and in directing the management of the patients with inflammatory bowel disease (IBD)[6,7]. The morphological evaluation of the SB, useful in the diagnosis and management of CD, has long been made only with conventional radiology.

In the last decade there has been a progressive improvement of cross-sectional imaging [ultrasonography (US), computed tomography (CT), and magnetic resonance (MR)] that has significantly changed the way to diagnose and treat the patients[8,9]. Indeed, their accuracy in detecting mucosal alterations and transmural and perienteric inflammations, has led to a new disease staging, a detection of asymptomatic disease and a better assessment of response to therapy[10]. For these reasons modern cross-sectional imaging have replaced the traditional fluoroscopy-based for visualization of the SB. In the ��Porto criteria�� small-bowel follow-through (SBFT) was the recommended imaging modality in children[11]. However, concerns about the proven increased risk of high radiation exposure in pediatric patients mandates the use of alternative techniques when possible[12-14].

In the European Crohn��s and Colitis Organization (ECCO) guidelines[14] it is stated that MR and CT enterography or enteroclysis are the imaging modalities with the highest diagnostic accuracy. Moreover in the pediatric section of the ECCO guidelines[15,16] dynamic contrast-enhanced MRI is considered the best imaging to show most of the CD��s lesions without exposure Brefeldin_A to ionizing radiation. In the same way the Appropriateness Criteria of the American College of Radiology[17] point out that, in the pediatric patients, MR enterography may have sensitivity and specificity similar to CT enterography and avoids radiation risks. Ultimately the same accuracy, the choice of examination depends on several variables, such as institutional preferences and resources (US, CT, or MR scan), age and compliance of the patient, the eventually acute presentation, and finally radiologist expertise. In this article we discuss all the methods commonly used for imaging the small bowel in paediatric patients with Crohn��s disease analyzing the advantages and disadvantages of each modality, with particular emphasis on MR imaging.

Patients with primary SI-NETs were collected after surgery with a

Patients with primary SI-NETs were collected after surgery with a curative intent. Serum and plasma samples were obtained and analyzed from 66 lung carcinoid patients: 52 TC (named TLC) and 14 AC (named ALC). The median ages of the patients were SI-NET 63 years (range, 27�C82) and TLC & ALC 59 years (range, 13�C81). Moreover, 50 serum samples from healthy volunteers were collected at the Uppsala contain University Hospital and used as negative controls. Clinicians at the Uppsala University Hospital, Neuroendocrine Center of Excellence, Uppsala, Sweden and at the European Institute of Oncology, Milan, Italy that follow the SI-NET and lung carcinoid patients have never identified PNS and neurological symptoms.

Reagents and antibodies Maxisorp strips (NunC, Roskilde, Denmark), GST-PNMA2 recombinant protein (Abnova, Taipei, Taiwan); 3,3��,5,5-tetramethylbenzidine (TMB) + substrate (Dako, Glostrup, Denmark), Peroxidase with dakocytomation peroxidase block (Dako), Dakocytomation envision? system labeled polymer-HRP anti-rabbit kit and 3-3��-diaminobenzidine (Dako), Mayer’s hematoxylin (Histolab Product AB, Gothenburg, Sweden), Graded alcohol (Kemetyl, Vestby, Norway), Xylen (Solveco, Rosersberg, Sweden), Pertex? (Histolab, Gothenburg, Sweden), Tris-Glycine blotting buffer (Amresco, Solon, OH), Western blotting (WB) reagent and Lumi-Light WB substrate (Roche, Basel, Switzerland), EasyTag Methionine-L-35S, NEG709A005MC (PerkinElmer, Waltham, MA), Full-length cDNA clone for human PNMA2, ID6580976 (BioScience Geneservice, Cambridge, UK), TnT? SP6 Quick Coupled Transcription/Translation System (Promega, Madison, WI), Protein G-Sepharose beads (GE Healthcare, Little Chalfont, Buckinghamshire, UK), Peroxidase (HRP)-conjugated rabbit anti human IgG (anti-IgG) (Dako), rabbit polyclonal antibody anti-PNMA2 (Atlas Antibodies, Stockholm, Sweden), monoclonal mouse anti-GST, sc-138, polyclonal goat anti-human Ma2, sc-68099, HRP-donkey anti-goat, sc-2020, (Santa Cruz Biotechnology, Santa Cruz, CA), HRP-goat anti-rabbit, P0448, (Dako) and Ravo PNS-Blot, (Ravo Diagnostika GmbH, Freiburg, Germany).

Indirect ELISA We set up a novel indirect ELISA to detect Ma2 autoantibody levels in sera and plasma of NET patients and healthy volunteers. The standard curves to screen both serum and plasma samples were constructed by serial dilutions 1100, 1200, 1400, 1800, 11,600, 13,200 and 16,400 using the serum and the plasma from the same patient with primary SI-NET, expressing anti-Ma2 used as reference.

Two controls were used to evaluate individual runs. One was from a patient with primary SI-NET, expressing high titer of anti-Ma2 and the other one was from a healthy donor expressing low titer of anti-Ma2. GST-PNMA2 recombinant protein (Abnova, Taiwan), diluted in the coating buffer Dacomitinib (15 mM Na2CO3, 35 mM NaHCO3, pH 9.

Declaration of Interests None declared

Declaration of Interests None declared.
Despite better an overall decrease in the rates of smoking, a significant proportion of children in the United States remain exposed to secondhand smoke (SHS). Like active smoking, SHS remains a class-based health risk since exposure among low-income children in urban areas ranges from 30% to 79% (Cornelius, Goldschmidt, & Dempsey, 2003) and varies inversely with family income and parental education (Marano, Schober, Brody, & Zhang, 2009; Soliman, Pollack, & Warner, 2004). While there have been general trends in the United States in reduced tobacco use over the past decade, smoking among adults from lower socioeconomic groups remains prevalent and has changed less than other groups (CDC, 2010).

A group of vulnerable children persists, despite national trends of reduced smoking prevalence in adults (Singh, Siahpush, & Kogan, 2010). Therefore, SHS-related morbidities in children could be considered a health risk disparity. We report on relationships observed between parental report of their child��s SHS exposure with a biological marker of long-term SHS exposure (hair nicotine levels) in two age groups of children (ages 2�C5 or 9�C14 years) from low-income families. This datum was obtained as part of a larger study on SHS exposure and markers of cardiovascular risk in children. These two age groups were of interest because of the high SHS exposure of the younger children based on our previous work (Groner et al., 2004) and the ability of the older group to cooperate with additional cardiovascular testing as part of the larger study.

Methods Recruitment Participants were recruited via convenience sampling through recruiting in Nationwide Children��s Hospital (NCH, Columbus, OH) Primary Care Network and via advertising in the NCH internal hospital E-mail system. The Network serves low-income, urban children in Columbus, OH. The inclusion criteria were healthy children in two age groups (between 2 and 5 years and between 9 and 14 years), both exposed and unexposed to SHS by parental report. The exclusion criteria were presence of one or more of the following: active smoker (referring to child or teen), acute febrile illness or other active infections, congenital heart disease, diabetes (Type 1 or 2) (elevated fasting glucose [>100 mg/dl]), concurrent daily anti-inflammatory prescription or nonprescription medications, and not having enough hair for hair sampling.

The project was approved by the NCH IRB; informed consent was obtained by parents and written assent by youth over 9 years old. SHS Exposure Assessment The presence and extent of SHS exposure were assessed by both by questionnaire and by hair sampling for nicotine determination. A ��smoker�� was defined as an individual who has smoked at least 1 cigarette/day during the Anacetrapib previous 7 days.

Bisphosphonates, which are specifically internalised into osteocl

Bisphosphonates, which are specifically internalised into osteoclasts (Sato et al, 1991), lead to inhibition of cell function because of changes following website in the cytoskeleton and loss of the ruffled border (Carano et al, 1990), as well as apoptosis (Hughes et al, 1995). Third-generation, nitrogen-containing BPs, such as zoledronic acid (ZOL) (Green et al, 1994), inhibit farnesyldiphosphate (FPP) synthase, an enzyme involved in the mevalonate pathway (Luckman et al, 1998; Benford et al, 1999), preventing post-translational events of prenylation of small GTP-binding proteins such as p21ras, Rab, Rho, Rac and cdc42 (Luckman et al, 1998), which are required for a variety of biological functions including signal transduction and cell adhesion.

In addition to the potent antiresorptive effects of nitrogen-containing BPs, recent reports have also shown that these compounds induce antiproliferative and apoptotic effects in multiple myeloma cells in vitro (Shipman et al, 1997; Aparicio et al, 1998), may synergise with chemotherapeutic or biological agents (Tassone et al, 2000, 2002), and may offer clinical benefits (Dhodapkar et al, 1998; Berenson et al, 1998). A direct effect induced by BPs has also been demonstrated on tumour cells of nonhaematopoietic origin. Bisphosphonates induce inhibition of adhesion of breast and prostate cancer cells to bone matrix (Van Der et al, 1996; Boissier et al, 1997). In a mouse model of breast cancer, BPs inhibited the progression and the development of bone metastasis (Sasaki et al, 1995).

Other studies have also suggested that BPs may interfere with the growth and survival of metastatic cancer cells in bone (Pelger et al, 1998). More recently, a variety of studies have focused on the direct effect of BPs on growth and survival of cancer cells from solid tumours. ZOL induces a significant reduction of cell viability, increases apoptotic cell death and downregulation of bcl-2 protein, p21ras delocalisation from the cell membrane and proteolytic cleavage of PARP, indicating direct antitumour effects on human breast cancer cells (Senaratne et al, 2000; Senaratne et al, 2002). In prostate cancer cells, ZOL has shown a remarkable inhibitory effect on cell proliferation by induction of cell death and/or cytostasis in vitro (Lee et al, 2001).

In this scenario, since there have been no studies addressing the possibility Brefeldin_A of a direct effect of BPs on growth and survival of human PC cells, we studied the activity of the most potent BP, ZOL, on a panel of different human PC cell lines (BxPC-3, CFPAC-1 and PANC-1). We have additionally studied whether the nitrogen-containing ZOL might induce effects on the p21ras/raf1/MEK1/ERK and on the pkB/Akt pathways, and if apoptosis should be related to caspase-9/-3 and PARP cleavage/activation in these cancer cells.