A case-control study of post-operative endophthalmitis diagnosed at a Spanish hospital over a 13-year-period.

A retrospective case-control study of patients who had undergone cataract extraction at a Spanish hospital over a 13-year period was conducted to identify the risk factors for developing post-operative endophthalmitis (POE). During the study period, the type of antibiotic prophylaxis was changed from subconjunctival gentamicin to the addition of both vancomycin and gentamicin to the irrigating solution. The overall incidence of POE was 0·19% (35 cases/18 287 operations). For the period prior to the change in antibiotic prophylaxis, the incidence rate of POE was 3·4 cases/1000 operations while in the latter period the incidence rate decreased to 0·34 cases/1000 operations. All patients who presented a virulent microorganism had a final visual acuity worse than 20/200. The only significant risk factor identified was the type of prophylaxis used (odds ratio 1·97, 95% confidence interval 0·94-4·14, P = 0·07). There were no significant differences between cases and controls although choice of surgeon approached significance.

Activating two-dimensional semiconductors for photocatalysis: a cross-dimensional strategy.

The emerging two-dimensional (2D) semiconductors substantially extend materials bases for versatile applications such as semiconductor photocatalysis demanding semiconductive matrices and large surface areas. The dimensionality, while endowing 2D semiconductors the unique properties to host photocatalytic functionality of pollutant removal and hydrogen evolution, hurdles the activation paths to form heterogenous photocatalysts where the photochemical processes are normally superior over these on the mono-compositional counterparts. In this perspective, we present a cross-dimensional strategy to employ thenD (n= 0-2) clusters or nanomaterials as activation partners to boost the photocatalytic activities of the 2D semiconductors. The formation principles of heterogenous photocatalysts are illustrated specifically for the 2D matrices, followed by selection criteria of them among the vast 2D database. The computer investigations are illustrated in the density functional theory route and machine learning benefitted from the vast samples in the 2D library. Synthetic realizations and characterizations of the 2D heterogenous systems are introduced with an emphasis on chemical methods and advanced techniques to understand materials and mechanistic studies. The perspective outlooks cross-dimensional activation strategies of the 2D materials for other applications such as CO2removal, and materials matrices in other dimensions which may inspire incoming research within these fields.

[Gallstone disease post-radical gastrectomy for gastric adenocarcinoma at the National Institute of Neoplastic Diseases, January 1990 to December 2000]. / Litiasis vesícular post- gastrectomía radical por adenocarcinoma gástrico en el Instituto Nacional de Enfermedades Neoplásicas, enero 1990 a diciembre del 2000.

SUBJECT: To determinate the frecuency and the time of development of the gallbladder stones in gastrectomy post-operated patients with stomach adenocarcinoma at The National Cancer Institute in Lima, Peru. METHODS: In an observational, descriptive and retrospective case series design, 148 patiens' files who underwent gastrectomy for stomach adenocarcinoma in the National Cancer Institue of Lima during 1990 and 2000, have been reviewed looking for the development of gallbladder stones. RESULTS: A total de 148 patients were involved in this study. 29 of them (19.6%) develop gallbladder stones during the (x years of) follow up vs 119 (80.9%) . The mean age ot the 29 patients with gallbladder stones were 59.9 years ans 18 of them were female and 11 male.\The mean time of develop gallbladder stones was 3.1 years.According to the type of surgery, 14 patient wiht gallbladder stones underwent to subtotal gastrectomy and 15 to total gastrectomy. CONCLUSIONS: The frecuency of gallbladder stones post gastrectomy in this study was 19.6%. The mean time of the develop and diagnosis of litiasis was 3.1 years.To perform the colecistectomy at the same time of the gastrectomy could be an important decision in patients with high risk of gallstones and gallbladder cancer.We need furthermore studies to have conclusions about the risk factors.

Characterisation and tribological investigation on thermally processed nanostructured Fe-based and Cu-based cermet materials.

The feasibility of achieving a nanostructured material after different thermal processing of nanosized powders is presented. The thermal processing was done by either atmospheric plasma spraying, laser sintering, or extrusion followed by hot isostatic pressing. The structural characterisation of such thermally processed nanostructured Fe-based and Cu-based metallic or Al2O3 reinforced cermets, confirmed the retention of a nanostructure after each of these thermal processes. Hardness measurements confirmed an increased hardness as expected in the case that nanostructuring is achieved. The role of grain boundaries and second phase particles on the retention of the nanostructure after thermal processing is discussed. Finally, the possible benefit of nanostructuring on the friction and wear behaviour of materials in sliding tests against corundum in ambient air is reported and discussed.

Do oral biofilms influence the wear and corrosion behavior of titanium?

The main aim of this work was to study the simultaneous wear-corrosion of titanium (Ti) in the presence of biofilms composed of Streptococcus mutans and Candida albicans. Both organisms were separately grown in specific growth media, and then mixed in a medium supplemented with a high sucrose concentration. Corrosion and tribocorrosion tests were performed after 48 h and 216 h of biofilm growth. Electrochemical corrosion tests indicated a decrease in the corrosion resistance of Ti in the presence of the biofilms although the TiO(2) film presented the characteristics of a compact oxide film. While the open circuit potential of Ti indicated a tendency to corrosion in the presence of the biofilms, tribocorrosion tests revealed a low friction on biofilm covered Ti. The properties of the biofilms were similar to those of the lubricant agents used to decrease the wear rate of materials. However, the pH-lowering promoted by microbial species, can lead to corrosion of Ti-based oral rehabilitation systems.

A search for differential polypeptide synthesis throughout the cell cycle of HeLa cells.

The polypeptides synthesized during the cell cycle of HeLa cells were analyzed by means of two-dimensional gel electrophoresis followed by fluorography under conditions in which the position of 700 polypeptides (acidic and basic) could be reproducibly assessed. Mitotic cells obtained by mechanical detachment and synchronized cells in other stages of the cell cycle were labeled with [35S]methionine for 30-min pulses or for long terms starting at the beginning of each phase. Visual comparison of the polypeptide maps obtained in the different stages of the cell cycle showed that these were strikingly similar, and there was no indication that the synthesis of any of the detected polypeptides was confined to only one of the cell cycle phases. Quantitation of 99 abundant polypeptides (acidic and basic) in pulse-labeled and long-term labeled cells revealed that the relative amount (i.e., the rate of synthesis) of most polypeptides, including total actin, alpha-actinin, 6 abundant basic nonhistone proteins, and 13 major acidic proteins present in Triton cytoskeletons, remains constant throughout the cell cycle. Among the few variable polypeptides (markers), we have identified alpha- and beta-tubulin (increase in M), the subunit of the 100-A filament protein "fibroblast type" (decreases in M), and a 36,000 mol wt acidic cytoarchitectural protein that increases in S. A few other unidentified polypeptides have also been found to vary in M and in M and G2, but no marker was found in G1.

Monoclonal antibody specific for human nuclear proteins IEF 8Z30 and 8Z31 accumulates in the nucleus a few hours after cytoplasmic microinjection of cells expressing these proteins.

A monoclonal antibody (mAB 1C4C10) that reacts specifically with human nuclear proteins IEF 8Z30 and 8Z31 (charge variants; HeLa protein catalogue number; Bravo, R., and J. E. Celis, 1982, Clin. Chem., 28:766-781) has been microinjected into the cytoplasm of cultured cells that either express (primates) or lack these proteins (at least having similar molecular weights and pIs; other species), and its cellular localization has been determined by indirect immunofluorescence. Nuclear localization (nucleolar and nucleoplasmic) of the antibody was observed only in cells expressing these antigens, suggesting that a determinant present in IEF 8Z30 and 8Z31 is required for cytoplasm-nuclear translocation. Nuclear migration was not inhibited by cycloheximide, implying that these proteins may shuttle between nucleus and cytoplasm. The results assumed to support the signal rather than the free diffusion model are further supported by microinjection experiments using antibodies (proliferating cell nuclear antigen/cyclin, DNA) that react with nuclear components but do not recognize cytoplasmic antigens. Furthermore, they raise the possibility that some nonnuclear proteins may be transported to the nucleus by interacting with proteins harboring nuclear location signals.

Comparative two-dimensional gel analysis and microsequencing identifies gelsolin as one of the most prominent downregulated markers of transformed human fibroblast and epithelial cells.

A systematic comparison of the protein synthesis patterns of cultured normal and transformed human fibroblasts and epithelial cells, using two-dimensional gel protein analysis combined with computerized imaging and data acquisition, identified a 90-kD protein (SSP 5714) as one of the most striking downregulated markers typical of the transformed state. Using the information stored in the comprehensive human cellular protein database, we found this protein strongly expressed in several fetal tissues and one of them, epidermis, served as a source for preparative two-dimensional gel electrophoresis. Partial amino acid sequences were generated from peptides obtained by in situ digestion of the electroblotted protein. These sequences identified the marker protein as gelsolin, a finding that was confirmed by two-dimensional immunoblotting of human MRC-5 fibroblast proteins using specific antibodies and by coelectrophoresis with purified human gelsolin. These results suggest that an important regulatory protein of the microfilament system may play a role in defining the phenotype of transformed human fibroblast and epithelial cells in culture.

Proteins IEF (isoelectric focusing) 31 and IEF 46 are keratin-type components of the intermediate-sized filaments: keratins of various human cultured epithelial cells.

Mouse polyclonal antibodies have been raised against two human proteins (IEF [isoelectric focusing] 31, Mr = 50,000; IEF 46, Mr = 43,500) that have previously been shown to be present in HeLa cytoskeletons enriched in intermediate-sized filaments. Immunoprecipitation studies show that both proteins share common antigenic determinants with each other and with the putative human keratins IEF 36 and 44, also present in HeLa cytoskeletons. Indirect immunofluorescence studies showed that both antibodies revealed similar filamentous networks in various cultured epithelial cells of human origin. These included AMA (transformed amnion), HeLa (cervical carcinoma), normal amnion cells, Fl-amnion (transformed amnion), WISH-amnion (transformed amnion), Chang liver (liver), and Detroid-98 (sternal marrow). Human cells that did not react with both antibodies included skin fibroblasts, lung fibroblasts (WI-38), SV40-transformed lung fibroblasts, Molt 4 (leukemia), lymphocytes, and monocytes. These results were in complete agreement with the presence or absence of both proteins in two-dimensional gels of the different cell types. Exposure of AMA cells to demecolcine (24 h; 10 micrograms/ml) caused the total collapse of vimentin filaments but, as seen by indirect immunofluorescence, caused only a partial redistribution of the IEF 31 and 46 filaments. These results are taken to suggest that both proteins are components of the intermediate-sized filaments of the "keratin" type. The antibodies could be clearly differentiated by staining human bladder carcinoma EJ 19 cells, as only the IEF 46 antibody stained a filamentous network in these cells The occurrence of keratins IEF 31, 36, 44, and 46 in different cultured human epithelial cells has been studied using two-dimensional gel electrophoresis.

Phosphorylation of keratin and vimentin polypeptides in normal and transformed mitotic human epithelial amnion cells: behavior of keratin and vimentin filaments during mitosis.

Analysis by means of two-dimensional gel electrophoresis (IEF) of [32P]orthophosphate-labeled proteins from mitotic and interphase transformed amnion cells (AMA) has shown that keratins IEF 31 (Mr = 50,000; Hela protein catalogue number), 36 (Mr = 48,500), 44 (Mr = 44,000), 46 (Mr = 43,500), as well as vimentin (IEF 26; Mr = 54,000) are phosphorylated above their interphase level during mitosis. Similar studies of normal human amnion epithelial cells (AF type) confirmed the above observations except in the case of keratin IEF 44 whose relative proportion was too low to be analyzed. Immunofluorescent staining of methanol/acetone-treated mitotic transformed amnion cells with a mouse polyclonal antibody elicited against human keratin IEF 31 showed a dotted staining (with a fibrillar background) in all of the cells in late anaphase/early telophase (characteristic "domino" pattern) and in a sizeable proportion of the cells in other stages of mitosis. Normal mitotic amnion cells on the other hand showed a fine fibrillar staining of keratins at all stages of mitosis. Similar immunofluorescent staining of normal and transformed mitotic cells with vimentin antibodies revealed a fibrillar distribution of vimentin in both cell types. Taken together the results indicate that the transformed amnion cells may contain a factor(s) that modulates the organization of keratin filaments during mitosis. This putative factor(s), however, is most likely not a protein kinase as transformed amnion cells and amnion keratins are modified to similar extents. It is suggested that in general the preferential phosphorylation of intermediate-sized filament proteins during mitosis may play a role in modulating the various proposed associations of these filaments with organelles and other cellular structures.

Self-assembly from milli- to nanoscales: methods and applications.

The design and fabrication techniques for microelectromechanical systems (MEMS) and nanodevices are progressing rapidly. However, due to material and process flow incompatibilities in the fabrication of sensors, actuators and electronic circuitry, a final packaging step is often necessary to integrate all components of a heterogeneous microsystem on a common substrate. Robotic pick-and-place, although accurate and reliable at larger scales, is a serial process that downscales unfavorably due to stiction problems, fragility and sheer number of components. Self-assembly, on the other hand, is parallel and can be used for device sizes ranging from millimeters to nanometers. In this review, the state-of-the-art in methods and applications for self-assembly is reviewed. Methods for assembling three-dimensional (3D) MEMS structures out of two-dimensional (2D) ones are described. The use of capillary forces for folding 2D plates into 3D structures, as well as assembling parts onto a common substrate or aggregating parts to each other into 2D or 3D structures, is discussed. Shape matching and guided assembly by magnetic forces and electric fields are also reviewed. Finally, colloidal self-assembly and DNA-based self-assembly, mainly used at the nanoscale, are surveyed, and aspects of theoretical modeling of stochastic assembly processes are discussed.

In situ modification of activated carbons developed from a native invasive wood on removal of trace toxic metals from wastewater.

Activated carbons were developed by phosphoric acid activation of sawdust from Prosopis ruscifolia wood, an indigenous invasive species of degraded lands, at moderate conditions (acid/precursor ratio=2, 450 degrees C, 0.5h). For in situ modification of their characteristics, either a self-generated atmosphere or flowing air was used. The activated carbons developed in the self-generated atmosphere showed higher BET surface area (2281m2/g) and total pore volume (1.7cm3/g) than those obtained under flowing air (1638m2/g and 1.3cm3/g). Conversely, the latter possessed a higher total amount of surface acidic/polar oxygen groups (2.2meq/g) than the former (1.5meq/g). To evaluate their metal sorption capability, adsorption isotherms of Cu(II) ion from model solutions were determined and properly described by the Langmuir model. Maximum sorption capacity (Xm) for the air-derived carbons (Xm=0.44mmol/g) almost duplicated the value for those obtained in the self-generated atmosphere (Xm=0.24mmol/g), pointing to a predominant effect of the surface functionalities on metal sequestering behaviour. The air-derived carbons also demonstrated a superior effectiveness in removing Cd(II) ions as determined from additional assays in equilibrium conditions. Accordingly, effective phosphoric acid-activated carbons from Prosopis wood for toxic metals removal from wastewater may be developed by in situ modification of their characteristics operating under flowing air.

Tay bridge and extracellular-regulated kinase activity are required for motoneuron function in the Drosophila neural system.

Extracellular regulated kinase (Erk) activity is required during neural development for the specification of cell fates in neuroblasts and neuronal lineages, and also regulates several aspects of the activity and survival of mature neurons. The activation of Erk is regulated at multiple levels by kinases and phosphatases that alter its phosphorylation state and by other proteins that regulate its subcellular localization. Here, we find that tay bridge (tay), a negative regulator of Erk in Drosophila imaginal discs, is required in the motoneurons to regulate the number and size of neuromuscular synapses in these cells. The expression of Tay is maximal in motoneurons with low levels of activated ERK, suggesting that Tay modulates the activity of Erk in these cells. We also found that loss of tay expression and increased Erk activity specifically in the motoneurons cause a reversible decrease in walking speed. Impaired motoneurons activity may be caused by alterations in the functionality and number of synaptic boutons developing at the neuromuscular junction in tay mutants.

Building a network for multicenter, prospective research of central nervous system infections in South America: Process and lessons learned.

Multicenter collaborative networks are essential for advancing research and improving clinical care for a variety of conditions. Research networks are particularly important for central nervous system infections, which remain difficult to study due to their sporadic occurrence and requirement for collection and testing of cerebrospinal fluid. Establishment of long-term research networks in resource-limited areas also facilitates diagnostic capacity building, surveillance for emerging pathogens, and provision of appropriate treatment where needed. We review our experience developing a research network for encephalitis among twelve hospitals in five Peruvian cities since 2009. We provide practical suggestions to aid other groups interested in advancing research on central nervous system infections in resource-limited areas.

Neurological disturbances, premature lethality, and central myelination deficiency in transgenic mice overexpressing the homeo domain transcription factor Oct-6.

Pit, Oct, Unc (POU) homeo domain transcription factors have been implicated in various developmental processes, including cell division, differentiation, specification, and survival of specific cell types. Although expression of the transcription factor Oct-6 in oligodendroglia is confined to the promyelin stage and is downregulated at the myelin stage of development, the effect of Oct-6 overexpression on oligodendrocyte development has not been established. Here we show that transgenic animals overexpressing Oct-6 at late oligodendrocyte development develop a severe neurologic syndrome characterized by action tremors, recurrent seizures, and premature death. Axons in the central nervous system of Oct-6 transgenics were hypomyelinated, hypermyelinated, or dysmyelinated, and ultrastructural analyses suggested that myelin formation was premature. The vulnerability of developing oligodendroglia to Oct-6 deregulation provides evidence that the POU factor may play a direct role in myelin disease pathogenesis in the mammalian CNS.

EF-hands at atomic resolution: the structure of human psoriasin (S100A7) solved by MAD phasing.

BACKGROUND: The S100 family consists of small acidic proteins, belonging to the EF-hand class of calcium-binding proteins. They are primarily regulatory proteins, involved in cell growth, cell structure regulation and signal transduction. Psoriasin (S100A7) is an 11.7 kDa protein that is highly upregulated in the epidermis of patients suffering from the chronic skin disease psoriasis. Although its exact function is not known, psoriasin is believed to participate in the biochemical response which follows transient changes in the cellular Ca2+ concentration. RESULTS: The three-dimensional structure of holmium-substituted psoriasin has been determined by multiple anomalous wavelength dispersion (MAD) phasing and refined to atomic resolution (1.05 A). The structure represents the most accurately determined structure of a calcium-binding protein. Although the overall structure of psoriasin is similar to those of other S100 proteins, several important differences exist, mainly in the N-terminal EF-hand motif that contains a distorted loop and lacks a crucial calcium-binding residue. It is these minor differences that may account for the different specificities among members of this family. CONCLUSIONS: The structure of human psoriasin reveals that this protein, in contrast to other S100 proteins with known structure, is not likely to strongly bind more than one calcium ion per monomer. The present study contradicts the idea that calcium binding induces large changes in conformation, as suggested by previously determined structures of apo forms of S100 proteins. The substitution of Ca2+ ions in EF-hands by lanthanide ions may provide a general vehicle for structure determination of S100 proteins by means of MAD phasing.

Proteome profiling of bladder squamous cell carcinomas: identification of markers that define their degree of differentiation.

One hundred fifty fresh bladder tumors were analyzed blindly by two-dimensional PAGE in combination with proteome identification techniques (microsequencing and mass spectrometry) and immunofluorescence of cryostat sections. Of these, six showed protein expression patterns corresponding to squamous cell carcinomas (SCCs). All tumors were already invasive at the time of presentation, and in most cases, the histopathological grade could not be determined with certainty. The more differentiated of the tumors included SCC 589-1, a lesion showing extensive keratinization, and 536-1, a pure SCC that resembled normal skin growing invasively into the muscle. Both tumors expressed keratins 5, 6, 10, 14, 16, 17, and 20, as well as the differentiation-associated proteins psoriasin, psoriasis-associated fatty acid-binding protein (PA-FABP), and galectin 7. SCC 589-1, however, exhibited higher levels of keratin 10, PA-FABP, and galectin 7 and, in addition, expressed keratins 13, 15, and 19, which were not detected in the pure SCC. Involucrin, glutathione S-transferase pi, stratifin (14-3-3 sigma), and the SCC antigen 1, on the other hand, were less abundant in SCC 589-1. In comparison, less-differentiated tumors did not express keratin 10 and were characterized by a decreased expression of keratin 14, psoriasin, PA-FABP, galectin 7, and stratifin (14-3-3 sigma). Indeed, two of these lesions (553-1 and 651-1) could be readily lined up in order of decreasing degree of differentiation based on the expression of these markers. The degree of differentiation of the other two SCCs could not be assessed with certainty because they may represent special cases (SCC 646-1, solid tumor; SCC 485-1, special differentiation pattern). All six SCCs externalized psoriasin to the urine, supporting the contention that this protein, alone or in combination with other polypeptides, may represent a useful marker for the early detection of these lesions.

Proteomics and immunohistochemistry define some of the steps involved in the squamous differentiation of the bladder transitional epithelium: a novel strategy for identifying metaplastic lesions.

Here, we present a novel strategy for dissecting some of the steps involved in the squamous differentiation of the bladder urothelium leading to squamous cell carcinomas (SCCs). First, we used proteomic technologies and databases (http://biobase.dk/cgi-bin/celis) to reveal proteins that were expressed specifically by fresh normal urothelium and three SCCs showing no urothelial components. Thereafter, antibodies against some of the differentially expressed proteins as well as a few known keratinocyte markers were used to stain serial cryostat sections (immunowalking) of biopsies obtained from bladder cystectomies of two of the SCC-bearing patients (884-1 and 864-1). Because bladder cancer is a field disease, we surmised that the urothelium of these patients may exhibit a spectrum of abnormalities ranging from early metaplastic stages to invasive disease. Immunohistochemical analysis revealed three types of non-keratinizing metaplastic lesions (types 1-3) that did not express keratins 7, 8, 18, and 20 (expressed by normal urothelium) and could be distinguished based on their staining with keratin 19 antibodies. Type 1 lesions showed staining of all cell layers in the epithelium (with differences in the staining intensity of the basal compartment), whereas type 2 lesions exhibited mainly basal cell staining. Type 3 lesions did not stain with keratin 19 antibodies. In cystectomy 884-1, type 3 lesions exhibited the same immunophenotype as the SCC and may be regarded as precursors to the tumor. Basal cells in these lesions did not express keratin 13, suggesting that the tumor, which was also keratin 13 negative, may have arisen from the expansion of these cells. Similar results were observed with cystectomy 864-1, which showed carcinoma in situ of the SCC type. SCC 864-1 exhibited both keratin 19-negative and -positive cells, implying that the tumor arose from the expansion of the basal cell compartment of type 2 and 3 lesions. Besides providing with a novel strategy for revealing metaplastic lesions, our studies have shown that it is feasible to apply powerful proteomic technologies to the analysis of complex biological samples under conditions that are as close as possible to the in vivo situation.

Loss of adipocyte-type fatty acid binding protein and other protein biomarkers is associated with progression of human bladder transitional cell carcinomas.

Multifocal recurrent papillary tumors provide a unique model system to study the molecular mechanisms underlying the steps involved in transitional cell carcinoma progression and offer a valuable source of material to search for biomarkers that may form the basis for diagnosis, prognosis, and treatment. We have examined the protein expression profiles of normal bladder urothelium and of 63 transitional cell carcinomas of various histopathological grades and T stages using high-resolution, two-dimensional gel electrophoresis, microsequencing, mass spectrometry, and a two-dimensional gel protein database approach for polypeptide identification (http://biobase.dk/cgi-bin/celis). In general, the results revealed a striking similarity between the overall qualitative expression patterns of papillary tumors of all grades, as well as of papillary and solid tumors of grade III. With few exceptions, tumors of grades I-III expressed, albeit at different levels, all of the keratins (7, 8, 13, 17, 18, 19, and 20) found in the normal urothelium. Grade IV tumors lacked or expressed reduced levels of keratin 13 but most resembled low-grade tumors. One invasive grade IV tumor, however, expressed a fibroblast-like protein phenotype. Four proteins that were expressed by normal urothelium and were lost at various stages of progression were identified as glutathione S-transferase mu, prostaglandin dehydrogenase (PGDH), a fatty acid binding protein with homology to the adipocyte isoform (A-FABP), and keratin 13. The percentage of tumors expressing A-FABP was very high in low-grade lesions but decreased drastically (P = 0.0006) in grade III and IV neoplasms. In addition, low-grade tumors contained more A-FABP than their high-grade counterparts. The stage of the disease was also statistically (P = 0.0269) related to the presence or absence of A-FABP in grade III tumors. Similar analysis of glutathione S-transferase mu and PGDH showed a statistically significant decrease of these proteins in high-grade (grades III and IV) tumors (P = 0.0026 and P = 0.0044, respectively). Only PGDH showed a suggestive correlation (P = 0.0775) with the stage of the disease in grade III tumors. Keratin 13 showed a drastic decrease in grade IV tumors. In addition to identifying biomarkers that may have prognostic value, our studies have suggested that A-FABP is an important component of the pathway(s) leading to bladder cancer development.

Excellent translational research in oncology: A journey towards novel and more effective anti-cancer therapies.

Comprehensive Cancer Centres (CCCs) serve as critical drivers for improving cancer survival. In Europe, we have developed an Excellence Designation System (EDS) consisting of criteria to assess "excellence" of CCCs in translational research (bench to bedside and back), with the expectation that many European CCCs will aspire to this status.