Urothelial cancer gene regulatory networks inferred from large-scale RNAseq, Bead and Oligo gene expression data.

Background: Urothelial pathogenesis is a complex process driven by an underlying network of interconnected genes. The identification of novel genomic target regions and gene targets that drive urothelial carcinogenesis is crucial in order to improve our current limited understanding of urothelial cancer (UC) on the molecular level. The inference of genome-wide gene regulatory networks (GRN) from large-scale gene expression data provides a promising approach for a detailed investigation of the underlying network structure associated to urothelial carcinogenesis.

Collectives of diagnostic biomarkers identify high-risk subpopulations of hematuria patients: exploiting heterogeneity in large-scale biomarker data.

Background: Ineffective risk stratification can delay diagnosis of serious disease in patients with hematuria. We applied a systems biology approach to analyze clinical, demographic and biomarker measurements (n = 29) collected from 157 hematuric patients: 80 urothelial cancer (UC) and 77 controls with confounding pathologies.

Methods: On the basis of biomarkers, we conducted agglomerative hierarchical clustering to identify patient and biomarker clusters.

Standardization of diagnostic biomarker concentrations in urine: the hematuria caveat.

Sensitive and specific urinary biomarkers can improve patient outcomes in many diseases through informing early diagnosis. Unfortunately, to date, the accuracy and translation of diagnostic urinary biomarkers into clinical practice has been disappointing. We believe this may be due to inappropriate standardization of diagnostic urinary biomarkers.

SurfaceSlide: a multitouch digital pathology platform.

Background: Digital pathology provides a digital environment for the management and interpretation of pathological images and associated data. It is becoming increasing popular to use modern computer based tools and applications in pathological education, tissue based research and clinical diagnosis. Uptake of this new technology is stymied by its single user orientation and its prerequisite and cumbersome combination of mouse and keyboard for navigation and annotation.

The impact of biomarkers in multivariate algorithms for bladder cancer diagnosis in patients with hematuria.

Background: We appraised 23 biomarkers previously associated with urothelial cancer in a case-control study. Our aim was to determine whether single biomarkers and/or multivariate algorithms significantly improved on the predictive power of an algorithm based on demographics for prediction of urothelial cancer in patients presenting with hematuria.

Methods: Twenty-two biomarkers in urine and carcinoembryonic antigen (CEA) in serum were evaluated using enzyme-linked immunosorbent assays (ELISAs) and biochip array technology in 2 patient cohorts: 80 patients with urothelial cancer, and 77 controls with confounding pathologies.

Longitudinal grey-matter and glutamatergic losses in first-episode schizophrenia.

Background: Progressive volumetric changes in the brains of people with schizophrenia have been attributed to a number of factors.

Aims: To determine whether glutamatergic changes in patients with schizophrenia correlated with grey-matter losses during the first years of illness.

Method: Left anterior cingulate and thalamic glutamatergic metabolite levels and grey-matter volumes were examined in 16 patients with first-episode schizophrenia before and after 10 months and 30 months of antipsychotic treatment and in 16 healthy participants on two occasions 30 months apart.

Targeting death receptors in bladder, prostate and renal cancer.

Purpose: We describe key components of normal and aberrant death receptor pathways, the association of these abnormalities with tumorigenesis in bladder, prostate and renal cancer, and their potential application in novel therapeutic strategies targeted toward patients with cancer.

Materials And Methods: A MEDLINE literature search of the key words death receptors, TRAIL (tumor necrosis factor related apoptosis inducing ligand), FAS, bladder, prostate, renal and cancer was done to obtain information for review. A brief overview of the TRAIL and FAS death receptor pathways, and their relationship to apoptosis is described.

Apoptosis and chemotherapy for bladder cancer.

Purpose: We discuss the role of apoptosis, that is gene directed self-destruction of a cell, in the response of bladder transitional cell carcinoma cells to chemotherapy.

Materials And Methods: A directed MEDLINE literature search of apoptosis, bladder cancer and chemotherapy was performed to extract relevant information for review. The characteristics of apoptotic cells were defined and the methods in common use to detect these traits is described.

Antisense oligonucleotides in the treatment of bladder cancer.

This review examines the role that antisense oligonucleotides play in the treatment of superficial and muscle-invasive bladder cancer. The unique environment of the urinary bladder allows intravesical instillation of antisense oligonucleotides, and researchers have already demonstrated uptake of antisense oligonucleotides in models of bladder cancer. Second, proof of principle has been established by demonstrating downregulation of the antisense target mRNA and protein.

Ethylene diamine tetraacetic acid-induced colonic crypt cell proliferation in rats.

Aim: To investigate the effect of ethylene diamine tetraacetic acid (EDTA) on proliferation of rat colonic cells.

Methods: EDTA was administered into Wistar rats, carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in rats was studied with immunohistochemistry.

Results: Marked regional differences in cell proliferation were found in all groups.

Oligoclonality in bladder cancer: the implication for molecular therapies.

Purpose: There is conflicting evidence in the published literature regarding the clonal or oligoclonal origin of bladder cancer.

Materials And Methods: A MEDLINE search of articles on the clonality, genetic, epigenetic and tumor microenvironment of bladder cancer cells was done. Laboratory and clinical studies were included and relevant articles were selected if tumor cell clonality was part of the study.

The need to embrace molecular profiling of tumor cells in prostate and bladder cancer.

Purpose: Current treatment strategies for urological cancer are still based on empirical formulae as opposed to treatment tailored for each cancer patient. To individualize treatment, the multiple molecular abnormalities within tumor cell populations needs to be mapped out. The aim of this article is to explain molecular profiling (MP) and its associated techniques so that the process is not purely seen as a research tool but as a future adjunctive measure in patient diagnosis and treatment.

Variability of cell proliferation in the proximal and distal colon of normal rats and rats with dimethylhydrazine induced carcinogenesis.

Aim: To investigate the patterns of cell proliferation in proximal and distal colons in normal rats and rats with 1,2-dimethylhydrazine (DMH) induced carcinogenesis using the thymidine analogue bromodeoxyuridine.

Methods: Colonic crypt cell proliferation was immunohistochemically detected using the anti-bromodeoxyuridine Bu20a monoclonal antibody.

Results: Marked regional differences were found in both groups.