Tumour cell expansion in bladder epithelium

Bladder cancer is common in western society. The major problem of patients with superficial bladder cancer is the high recurrence rate and multifocality of these tumours. In 70 % of the patients superficial bladder cancer recurs after local resection of the tumour within 15 years. The tumour recurrences are probably caused by tumour cells that were not removed by the therapy. These residual tumour cells apparently can form secondary tumours at multiple sites in the bladder mucosa. In this respect bladder cancer is different from other carcinomas. Factors involved in the normal physiology of the bladder epithelium may also attribute to the expansion of tumour cells and the recurrence of bladder carcinomas. In order to provide better understanding of the process of bladder cancer recurrence the anatomy and histology of the urinary bladder and the carcinogenesis of bladder carcinoma are described in paragraphs 1.1 and 1.2. In paragraph 1.3 the development of tumour recurrences is described and a hypothesis is developed regarding the role of extracellular matrix components, growth factors and adhesion molecules in the development of recurrences, either by affecting the normal bladder epithelium or by affecting the bladder carcinoma cells themselves (paragraph 1.4)

Immunological basis of differences in disease resistance in the chicken

Genetic resistance to diseases is a multigenic trait governed mainly by the immune system and its interactions with many physiologic and environmental factors. In the adaptive immunity, T cell and B cell responses, the specific recognition of antigens and interactions between antigen presenting cells, T cells and B cells are crucial. It occurs through a network of mediator proteins such as the molecules of the major histocompatibility complex (MHC), T cell receptors, immunoglobulins and secreted proteins such as the cytokines and antibodies. The diversity of these proteins that mainly is due to an intrinsic polymorphism of the genes causes phenotypic variation in disease resistance. The well-known linkage of MHC polymorphism and Marek's disease resistance difference represents a classic model revealing immunological factors in resistance differences and diversity of mediator molecules. The molecular bases in any resistance variation to infectious pathogens are vaguely understood. This paper presents a review of the major immune mediators involved in resistance and susceptibility to infectious diseases and their functional mechanisms in the chicken. The genetic interaction of disease resistance with production traits and the environment is mentioned

Effect of organically and conventionally produced diets on jejunal gene expression in chickens

Using a nutrigenomics approach we studied the response of second-generation chickens at a transcriptional level to organically grown feed ingredients compared with conventionally grown feed ingredients. Both diets consisted of the same amounts of ingredients, the only difference was the production method. Gene expression was analysed in jejuni using whole genome chicken cDNA arrays. After analysis, forty-nine genes were found to be differentially regulated between chickens fed on the different diets, independent of their genetic background. Of these forty-nine genes, seven genes were involved in cholesterol biosynthesis. Genes involved in cholesterol biosynthesis were higher expressed in jejuni from organically fed birds. Other genes found to be regulated were involved in immunological processes, such as B-G protein (part of chicken major histocompatibility complex), chemokine ah221, and the immunoglobulin heavy chain. Using quantitative PCR the effect of genetic background on the differential expression of genes was studied. Differences in gene expression existed between animals fed different diets as well as between different chicken lines. This indicated that diet and genetic background influence the transcriptional response of the jejunum. This is the first time that significant differences in gene expression were shown between animals on diets with organically or conventionally produced ingredient

Kruiden verdringen antibiotica

Vanwege beperking van het antibioticagebruik vallen veehouders steeds vaker terug op kruiden, bacteriedrankjes en andere natuurlijke middelen om dieren gezond te maken én te houden. Hoewel harde medische claims niet altijd voorhanden zijn, boeken boeren soms spectaculaire resultaten met natuurlijke preparaten

Modulation of intra-epithelial expansion of human T24 bladder-carcinoma cells in murine urothelium by growth factors and extracellular-matrix components

The high recurrence rate of bladder cancer is probably due to an efficient repopulation of the bladder by residual transformed cells after resection of the tumour. However, the regenerating capacity of the normal urothelial cells is very high. To study the balance between regenerating normal urothelium and outgrowth of transformed urothelial cells, we recently developed an in vitro co-cultivation model. With this model system we studied the effects of growth factors and extracellular-matrix components on the intra-epithelial expansion of human T24 bladder-carcinoma cells in primary mouse-bladder explants. Exposure of the cultures to acidic fibroblast growth factor (aFGF) and laminin led to a dramatic increase in the number of invasive T24 cells into the primary urothelium. Epidermal growth factor (EGF) and collagen types I and IV counteracted the infiltration of individual T24 cells. EGF, aFGF, laminin and collagen types I and IV did not directly affect the migration and proliferation of T24 cells. Apparently, the efficacy of invasion of transformed urothelial cells into primary urothelium is not only dependent on the intrinsic characteristics of the transformed cells, but can be influenced to a considerable extent by exogenous components exerting their influence on the normal urothelium. The clinical relevance of this observation needs to be studied further

Malabsorption syndrome in broilers

Malabsorption syndrome (MAS) is a multifactorial disease that causes intestinal disorders in broilers due to infection of the gastrointestinal tract with different infectious agents. The exact aetiology is unknown, although several viruses are isolated from MAS affected chickens. None of these isolated infectious agents alone inducted the malabsorption syndrome. MAS in broilers is characterised by poor growth and lesions in the Gl-tract, mainly in the small intestine. Experimentally, MAS can be induced in one-day old broilers by oral inoculation of homogenates obtained from digestive tract tissues of MAS affected broilers. Susceptibility to the MAS syndrome differs between broiler lines. The susceptibility to MAS is correlated with the severity of the lesions, apoptosis and heterophil infiltration of the jejunum. Susceptibility to MAS is also related to the frequency of CD4 and CDS positive T-cells in the intestinal villus and the mRNA expression level of different cytokines in control and in MAS induced broilers. With the use of micro-arrays differences in gene expression levels between broiler lines that differ in MAS susceptibility were observed. From these experiments genes that are immune and food absorption related were identified. If some of these genes or the T-cell population in the gut and the other MAS susceptible related parameters could predict or prevent MAS susceptibility in broilers needs to be further investigated but can be interestingly for breeding programmes

Long-lasting effects of Early-life Antibiotic Treatment and routine Animal Handling on Gut Microbiota Composition and Immune System in Pigs

Background In intensive pig husbandry systems, antibiotics are frequently administrated during early life stages to prevent respiratory and gastro-intestinal tract infections, often in combination with stressful handlings. The immediate effects of these treatments on microbial colonization and immune development have been described recently. Here we studied whether the early life administration of antibiotics has long-lasting effects on the pig’s intestinal microbial community and on gut functionality. Methodology/Principal Findings To investigate the long-lasting effect of early-life treatment, piglets were divided into three different groups receiving the following treatments: 1) no antibiotics and no stress, 2) antibiotics and no stress, and 3) antibiotics and stress. All treatments were applied at day four after birth. Sampling of jejunal content for community scale microbiota analysis, and jejunal and ileal tissue for genome-wide transcription profiling, was performed at day 55 (~8 weeks) and day 176 (~25 weeks) after birth. Antibiotic treatment in combination with or without exposure to stress was found to have long-lasting effects on host intestinal gene expression involved in a multitude of processes, including immune related processes. Conclusions/Significance The results obtained in this study indicate that early life (day 4 after birth) perturbations have long-lasting effects on the gut system, both in gene expression (day 55) as well as on microbiota composition (day 176). At day 55 high variance was observed in the microbiota data, but no significant differences between treatment groups, which is most probably due to the newly acquired microbiota during and right after weaning (day 28). Based on the observed difference in gene expression at day 55, it is hypothesized that due to the difference in immune programming during early life, the systems respond differently to the post-weaning newly acquired microbiota. As a consequence, the gut systems of the treatment groups develop into different homeostasis

An in vitro model of urothelial regeneration: Effects of growth factors and extracellular matrix proteins

Although the cellular turnover of resting urothelium is very low, its regenerative capacity is known to be outstanding. In organotypic mouse urothelial cultures closely mimicking the differentiation and multilayering of normal urothelium, we examined the cell biological mechanisms underlying urothelial regeneration and the specific role of growth factors and several extracellular matrix (ECM) components. Exposure to epidermal growth factor (EGF) and acidic fibroblast growth factor (aFGF) and culture on laminin resulted in enhanced expansion of the urothelium. Microscopy and assessment of proliferative activity revealed that enhanced urothelial expansion due to EGF could be attributed to increased proliferative activity and an increase in cell numbers, whereas aFGF-stimulated expansion must be considered the consequence of increased cellularity and migration. Laminin-enhanced urothelial expansion was shown to be the result of spreading of the entire urothelial organotypic culture. This was associated with a considerable decrease in the number of cell layers. A synergistic effect of growth factors and laminin was not found. This organotypic urothelial cell culture model seems to be very useful in studying strategies to improve urothelial regeneration

Early-life environmental variation affects intestinal microbiota and immune development in new-born piglets

Background - Early-life environmental variation affects gut microbial colonization and immune competence development; however, the timin Early-life environmental variation affects gut microbial colonization and immune competence development; however, the timing and additional specifics of these processes are unknown. The impact of early-life environmental variations, as experienced under real life circumstances, on gut microbial colonization and immune development has not been studied extensively so far. We designed a study to investigate environmental variation, experienced early after birth, to gut microbial colonization and intestinal immune development. Methodology/Principal Findings - To investigate effects of early-life environmental changes, the piglets of 16 piglet litters were divided into 3 groups per litter and experimentally treated on day 4 after birth. During the course of the experiment, the piglets were kept with their mother sow. Group 1 was not treated, group 2 was treated with an antibiotic, and group 3 was treated with an antibiotic and simultaneously exposed to several routine, but stressful management procedures, including docking, clipping and weighing. Thereafter, treatment effects were measured at day 8 after birth in 16 piglets per treatment group by community-scale analysis of gut microbiota and genome-wide intestinal transcriptome profiling. We observed that the applied antibiotic treatment affected the composition and diversity of gut microbiota and reduced the expression of a large number of immune-related processes. The effect of management procedures on top of the use of an antibiotic was limited. Conclusions/Significance - We provide direct evidence that different early-life conditions, specifically focusing on antibiotic treatment and exposure to stress, affect gut microbial colonization and intestinal immune development. This reinforces the notion that the early phase of life is critical for intestinal immune development, also under regular production circumstances. g and additional specifics of these processes are unknown. The impact of early-life environmental variations, as experienced under real life circumstances, on gut microbial colonization and immune development has not been studied extensively so far. We designed a study to investigate environmental variation, experienced early after birth, to gut microbial colonization and intestinal immune development. Methodology/Principal Findings To investigate effects of early-life environmental changes, the piglets of 16 piglet litters were divided into 3 groups per litter and experimentally treated on day 4 after birth. During the course of the experiment, the piglets were kept with their mother sow. Group 1 was not treated, group 2 was treated with an antibiotic, and group 3 was treated with an antibiotic and simultaneously exposed to several routine, but stressful management procedures, including docking, clipping and weighing. Thereafter, treatment effects were measured at day 8 after birth in 16 piglets per treatment group by community-scale analysis of gut microbiota and genome-wide intestinal transcriptome profiling. We observed that the applied antibiotic treatment affected the composition and diversity of gut microbiota and reduced the expression of a large number of immune-related processes. The effect of management procedures on top of the use of an antibiotic was limited. Conclusions/Significance We provide direct evidence that different early-life conditions, specifically focusing on antibiotic treatment and exposure to stress, affect gut microbial colonization and intestinal immune development. This reinforces the notion that the early phase of life is critical for intestinal immune development, also under regular production circumstances. Figure

Hyperplasia of epithelium adjacent to transitional cell carcinoma can be induced by growth factors through paracrine pathways

Hyperplasia of transitional cell epithelium adjacent to human transitional cell carcinomas (TCC) is a common finding in pathology. This hyperplasia may be a precancerous aberration. Alternatively, it has been suggested that the hyperplasia is due to paracrine action of tumour-derived growth factors. In this study we tested the latter hypothesis using the mouse tumorigenic TCC cell line NUC-1. Transplantation of NUC-1 tumour cells into the urinary bladder submucosa of syngeneic mice in vivo induced hyperplasia of normal adjacent urothelium in all tested mice. Implantation of normal mouse bladder mucosa did not induce urothelial hyperplasia. In vitro, conditioned medium of NUC-1 cells induced the proliferation of the mouse urothelial cell line g/G, which closely resembles normal urothelial cells. This induction was inhibited by transforming growth factor β1 (TGFβ1). Similarly, TGFβ1 inhibited the fibroblast growth factor-1 (FGF-1) and FGF-2 induced proliferation of g/G cells. Chemico-physical examination, bioassays with conditioned media, and RNA analysis of NUC-1 cells revealed that these cells secreted a growth factor with FGF-like properties. These results indicate that epithelial hyperplasia surrounding carcinomas is not necessarily a precancerous aberration, but may result from direct paracrine action of tumour-derived growth factors