Abstract Background This work presents relative survival estimates regarding urinary tract tumours among adult patients (age ⩾ 15 years) diagnosed in Europe. It reports on survival estimates of cases ...diagnosed in 2000–2007, and on survival time trends from 1999–2001 to 2005–2007. Methods Data on 677,340 adult urinary tract tumour patients, (429,154 cases of invasive and non-invasive bladder and 248,186 cases of invasive kidney cancers) diagnosed between 2000 and 2007 were provided by 86 population-based cancer registries from 29 European countries. The complete approach was used to estimate survival in 2000–2007; the period approach was used to estimate survival over time. Results The age-standardised 5-year relative survival for patients with kidney tumours diagnosed in Europe during 2000–2007 was 60%. The best prognosis was observed in Southern and Central Europe and prognosis improved in all regions along the time period. For invasive and non-invasive patients with bladder tumours combined the age-standardised 5-year relative survival in Europe was 68%. The best prognosis was observed in Southern and Northern Europe. However, in Scotland and The Netherlands the relative survival was significantly lower, although the survival estimates for these two countries were based on invasive tumours only. Conclusions Differences in registration practices affect comparisons of survival values between European countries, especially in patients with urinary bladder cancers. The between-country variation in survival is influenced by the varying use of diagnostic investigation in urinary tract tumours. Further data on stage at diagnosis can help to elucidate the influence of diagnostic intensity or early diagnosis on the survival patterns.
Urinary bladder cancer can be treated by intravesical application of therapeutic agents, but the specific targeting of cancer urothelial cells and the endocytotic pathways of the agents are not ...known. During carcinogenesis, the superficial urothelial cells exhibit changes in sugar residues on the apical plasma membranes. This can be exploited for selective targeting from the luminal side of the bladder. Here we show that the plant lectins Jacalin (from
Artocarpus integrifolia
), ACA (from
Amaranthus caudatus
) and DSA (from
Datura stramonium
) selectively bind to the apical plasma membrane of low- (RT4) and high-grade (T24) cancer urothelial cells in vitro and urothelial tumours ex vivo. The amount of lectin binding was significantly different between RT4 and T24 cells. Endocytosis of lectins was observed only in cancer urothelial cells and not in normal urothelial cells. Transmission electron microscopy analysis showed macropinosomes, endosome-like vesicles and multivesicular bodies filled with lectins in RT4 and T24 cells and also in cells of urothelial tumours ex vivo. Endocytosis of Jacalin and ACA in cancer cells was decreased in vitro after addition of inhibitor of macropinocytosis 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and increased after stimulation of macropinocytosis with epidermal growth factor (EGF). Clathrin, caveolin and flotillin did not colocalise with lectins. These results confirm that the predominant mechanism of lectin endocytosis in cancer urothelial cells is macropinocytosis. Therefore, we propose that lectins in combination with conjugated therapeutic agents are promising tools for improved intravesical therapy by targeting cancer cells.
To develop an advanced diagnostic method for urinary bladder tumour grading. A novel soft computing modelling methodology based on the augmentation of fuzzy cognitive maps (FCMs) with the ...unsupervised active Hebbian learning (AHL) algorithm is applied.
One hundred and twenty-eight cases of urinary bladder cancer were retrieved from the archives of the Department of Histopathology, University Hospital of Patras, Greece. All tumours had been characterized according to the classical World Health Organization (WHO) grading system. To design the FCM model for tumour grading, three experts histopathologists defined the main histopathological features (concepts) and their impact on grade characterization. The resulted FCM model consisted of nine concepts. Eight concepts represented the main histopathological features for tumour grading. The ninth concept represented the tumour grade. To increase the classification ability of the FCM model, the AHL algorithm was applied to adjust the weights of the FCM.
The proposed FCM grading model achieved a classification accuracy of 72.5%, 74.42% and 95.55% for tumours of grades I, II and III, respectively.
An advanced computerized method to support tumour grade diagnosis decision was proposed and developed. The novelty of the method is based on employing the soft computing method of FCMs to represent specialized knowledge on histopathology and on augmenting FCMs ability using an unsupervised learning algorithm, the AHL. The proposed method performs with reasonably high accuracy compared to other existing methods and at the same time meets the physicians’ requirements for transparency and explicability.
Studies regarding the functions of the bovine papillomavirus (BPV) E5 oncoprotein in vivo are lacking and no E5-mediated mechanism underlying epithelial carcinogenesis is known. We have shown that ...BPV-2 DNA is present in the majority of naturally occurring urinary bladder tumours of cattle and that E5 is expressed in the cancer cells. Here we show that the interaction between the platelet-derived growth factor (PDGF) beta receptor and BPV E5, described in vitro in cultured cells, takes place in vivo in bovine urinary bladder cancers. In these cancers, E5 and PDGF beta receptor colocalize, as shown by confocal microscopy, and physically interact, as shown by coimmunoprecipitation. Furthermore, the PDGF beta receptor associated with E5 is highly phosphorylated, suggesting the functional activation of the receptor upon E5 interaction. Our results demonstrate, for the first time, that E5-PDGF beta receptor interaction occurs during the natural history of bovine urinary bladder tumours, suggesting an important role for E5 in carcinogenesis. Finally, the system provides a suitable animal model of papillomavirus-associated cancer to test therapeutic vaccination against E5. Successful bladder tumour regression would provide a valuable model for therapeutic vaccination against papillomavirus-associated tumours.
Bovine papillomavirus types 1 or 2 (BPV-1/2) are involved in the aetiopathogenesis of bovine urinary bladder cancer. BPV-1/2 E5 activates the platelet-derived growth factor β receptor (PDGFβR). The ...aim of this study was to analyse the Ras/mitogen-activated protein kinase (MAPK) pathway in relation to activation of PDGFβR in natural bovine urinary bladder carcinomas. Co-immunoprecipitation and Western blot analysis demonstrated that recruitment of growth factor receptor bound protein 2 (GRB-2) and Sos-1 to the activated PDGFβR was increased in carcinomas compared to normal tissues. Higher grade bovine urinary bladder carcinomas were associated with activation of Ras, but not with activation of downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (Mek 1/2) or extracellular signal-regulated kinase (Erk 1/2).
Summary
This study was conducted with the objectives of detecting bovine papillomavirus type 2 (BPV‐2) in urine samples and urinary bladder lesions in bovines using polymerase chain reaction (PCR) ...and real‐time PCR‐based molecular diagnostic tests, and quantifying BPV‐2 in urinary bladder lesions especially in enzootic bovine haematuria (EBH)‐affected animals. BPV‐2 viral DNA was detected in urine samples (50%) and urinary bladder tissue (68.6%). Cloning and sequencing results showed a close homology with other Indian BPV‐2 sequences. Quantitative real‐time PCR (SYBR Green assay) showed that the BPV‐2 load was low and similar irrespective of inflammatory or neoplastic lesions in the bladder. It was concluded that BPV‐2 DNA is frequently present in urine and urinary bladder lesions in cows in an EBH endemic region and virus load was low in urinary bladder lesions.
In cattle, bracken fern toxicity is characterized by the presence of haematuria and tumours of the urinary bladder of both epithelial and mesenchymal origin. This syndrome is known as chronic ...enzootic hematuria (CEH) and is also present in Romania. From January 2006 to April 2007, 90 urinary bladders from slaughtered cows originating from hill-mountain area of Neamt county (Romania), where CEH is endemic, were collected. All samples were histologically examined and Bovine papillomavirus type 2 (BPV-2) DNA was detected by polymerase chain reaction (PCR) analysis in 68% of the analyzed tumours samples. BPV-2 positive urinary bladder tumours were also immunohistochemically analysed for the expression of the major viral oncoprotein E5. We found the expression of E5 intracytoplasmically with a typical juxtanuclear pattern. E5 expression was not observed in normal mucosa, suggesting a causal role for this protein in the neoplastic process.
This is the first report of BPV-2 infection in Eastern European country, confirming the role of BPV-2 in naturally occurring bovine urothelial carcinogenesis.
AIM: To describe changes in blood and urine analytes in a large group of cattle exposed to chronic bracken fern toxicity, in order to identify parameters of potential diagnostic value.
METHODS: The ...study was conducted on two livestock farms on which bovine enzootic haematuria (BEH) was known to occur; Farm A grazed a local breed of cows and Farm B grazed Friesians. Group A1 comprised 66 cows from Farm A, Group B 54 cows from Farm B, and Group A2 13 heifers from Farm A. Ten healthy cows were used as controls. A complete physical examination was performed (Group A1), and blood (all groups) and urine (Groups A1 and B) samples were collected. Necropsies and histopathology were undertaken on four cows.
RESULTS: Anaemia, leucopenia, monocytosis, thrombocytopenia, hypergammaglobulinaemia, microhaematuria and proteinuria were detected. Multivariate statistical analyses established three phases of the disease of increasing severity; an initial phase, characterised by an extremely high monocytosis and otherwise normal parameters; an intermediate phase, characterised by monocytosis and moderate changes to other analytes; and a final phase, characterised by normal levels of monocytes and many changes to other analytes.
CONCLUSIONS AND CLINICAL RELEVANCE: Monocytosis, detected in 31% of the younger animals, could represent an initial response to consumption of bracken fern and might be useful as an early haematological marker of BEH.
Systemic alkalosis has been postulated to enhance tumorigenesis, whereas systemic acidosis has been implicated to exert a favourable influence on tumour control and regression. In the present study ...the urinary pH was influenced by feeding acid-forming or base-forming diets, and the effect of alkaline or acid urine on the early and late progression phase of urinary bladder carcinogenicity was investigated in male Wistar rats. Bladder lesions were initiated by
N-butyl-
N-(4-hydroxybutyl) nitrosamine (0.05% BBN in the drinking water during 4 weeks) and promoted by sodium bicarbonate (3.4% NaHCO
3 in the diet during 15 or 25 weeks). After short- (15 week) and more long-term (25 week) promotion with NaHCO
3, groups of 20 rats were fed a diet containing the acidifying salt ammoniumchloride (2.1% NH
4Cl) or the control diet. All surviving rats were killed after a total study duration of 52 weeks. Additional control groups were, after initiation, fed diets containing NaHCO
3 and killed after 15 wk or 25 wk of promotion, or at the end of the study. In rats fed diets with added salts, water intake and the amount of urine produced were increased and the urinary density was decreased compared to rats fed control diet. During NaHCO
3 feeding, urinary pH and sodium concentration were increased. During NH
4Cl feeding, urinary pH was decreased and urinary chloride and calcium concentrations were increased. Initiation by BBN followed by treatment with NaHCO
3 caused a high incidence of papillary/nodular hyperplasia, papillomas and carcinomas of the bladder epithelium. These lesions progressed with time or longer duration of NaHCO
3 promotion. A tumour protective effect of urinary acidification by NH
4Cl was not found. In fact, both acidification and prolonged alkalinization tended to aggravate the malignancy of bladder carcinomas.
The correlation between stereological estimate of mean nuclear volume and DNA-content was studied in 55 human urinary bladder tumours. The DNA-content was determined by flow cytometry on isolated ...nuclei stained with ethidium bromide. Trout erythrocytes were used as a biological internal standard providing an accurate determination of the DNA-histogram. An unbiased estimate of the mean nuclear volume (vv) was obtained after standard formaline fixation, paraffin-embedding, sectioning and hematoxylin-eosin staining using the equation vv = pi/3.l3(0). Here l0 is the length of an intercept measured in a random direction through a test point, which hit a nucleus. A highly significant correlation was found between vv and mean DNA-content of nuclei (2p = 0.0004). A highly significant correlation was also found between vv and the highest DNA-content present in tumours having cell populations with different DNA content (2p = 0.0016). The mean nuclear volume and the DNA-content also correlated well with the pathologic grade. Although significant the correlations were far from perfect, which indicates that DNA content and mean nuclear volume may provide partly independent biological information. The methods provide objective, unbiased and reproducible data which may improve the possibility of grading and predicting the disease course of human urinary bladder tumours.
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