Abstract

Objectives: The pathways involved in the carcinogenesis of bladder urothelial carcinoma have been well established and are used for the development of new diagnostic and prognostic markers for the disease. The main genetic pathway for the development of low-grade pTa urothelial carcinomas is related to FGFR3 mutation. MicroRNAs have been related to processes involved in carcinogenesis in many organs, and miR-100 was recently shown to target FGFR3 messenger RNA. Our aim was to study the profile of expression of miR-100 and FGFR3 in low-grade, pTa bladder urothelial carcinoma.
Methods and Materials: Using qRT-PCR, we studied the expression of miR-100 and FGFR3 in 30 patients who had undergone transurethral resection of low-grade, pTa bladder urothelial carcinoma.
Results and Conclusion: There was under-expression of miR-100 and over-expression of FGFR3 in 100% of the specimens. Under-expression of miR-100 might be an alternative pathway for low-grade pTa urothelial bladder carcinogenesis and the identification of this molecular alteration may constitute a new diagnostic and prognostic marker for the disease.

Oxidatively induced DNA damage is caused by endogenous and exogenous sources in living organisms. Many resulting DNA lesions are mutagenic and lead to mutations commonly found in cancer. Repairs mechanisms exist to repair this type of DNA damage. Unrepaired and accumulated DNA lesions may lead to carcinogenesis and other disease processes. Defects in DNA repair are associated with cancer. Oxidatively induced DNA lesions accumulate in cancerous tissues, possibly contributing to genomic instability and metastatic potential. Recent evidence suggests that some tumors may even possess increased DNA repair capacity, leading to therapy resistance. DNA repair inhibitors are being developed to target the repair pathways and increase the efficacy of cancer therapy. Oxidatively induced DNA lesions and DNA repair proteins are potential biomarkers for early detection, cancer risk assessment, prognosis and monitoring the therapy. Overall, accumulated evidence suggests that oxidatively induced DNA damage and its repair are important factors in carcinogenesis, and deserve more research to understand and fight cancer.

Ovarian cancer is a very aggressive disease that is mostly asymptomatic at early onset. Approximately 85% of patients are diagnosed at late-stage disease, which greatly compromises full recovery. Standard detection methods include measurement of the ovarian cancer biomarker CA-125. However, CA-125 is associated with false positive diagnosis and is largely limited to late-stage disease. As a result, there is a great need to discover new biomarkers and develop novel detection and imaging methods for ovarian cancer. Patients with ovarian cancer often respond to initial chemotherapy but most will succumb to recurrent disease. Such poor prognosis is associated with a drug resistant subpopulation of cancer cells with stem-like properties known as cancer stem cells (CSC). Traditional chemotherapy fails to target CSC, and it is widely accepted that this process leads to the recurrence of more aggressive tumors. Therefore, it is essential to discover new ovarian CSC biomarkers and develop therapies that specifically target this subpopulation. Bacteriophage (phage) display technology allows identification of high affinity peptides by screening of peptide libraries against cellular targets. The large amount of unique peptides in a library facilitates high throughput selections both in vivo and in vitro. Here we discuss how phage display can be utilized to discover novel peptides with high binding affinity for normal ovarian cancer cells and ovarian CSC. Such peptides may be radiolabeled and employed in SPECT and PET imaging as well as in therapeutic settings. Further, both phage and phage display derived peptides can be employed in identification of targeted antigens and novel ovarian cancer biomarkers using mass spectrometry analysis. Such biomarkers may be utilized in diagnosis and in identification and selection of ovarian cancer subpopulations.

MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression post-transcriptionally. They bind to complementary sequences on target mRNA and typically down regulate expression or increase the rate of degradation; however, the roles of miRNA are still evolving and some miRNA have been shown to increase specific gene translation. miRNA holds a unique position among RNA for use as a biomarker due to its unique stability. Unlike mRNA, miRNA has been shown to be remarkably stable in a variety of tissues and body fluids. This greatly facilitates the use of miRNAs as clinical biomarkers of disease and injury since sample handling and processing is much less problematic when compared to mRNA. miRNA expression profiles have been extensively investigated for distinguishing cancerous vs. non-cancerous tissue. Taking this approach one step further, profiles of miRNA in cell-free body fluids have also been able to distinguish patients with different types of cancer and even provide prognostic information about disease outcome. The rationale behind this approach is that cancerous masses release miRNA into the systemic circulation and changes in the pattern and amount of miRNA can be used to detect the type of cancer. A recent extension of this approach is using miRNA in cell-free body fluids to detect organ injury. Several studies have shown increased serum levels of specific miRNA after myocardial or hepatocellular injury. Since some miRNA exhibit tissue specific expression, it is possible that miRNA profiles could be used to not only identify gross organ injury but also distinguish between different types of organ injury (e.g., heart vs. liver). This article will provide an overview of the role of miRNA in the cell, review the literature on using miRNA profiles to identify organ injury, and highlight the potential use of miRNA for assessing drug-induced liver injury. It should be noted that at the time of this writing, none of the profiles have been qualified for clinical use by the FDA.

The objective of the study was to develop a model for the diagnosis of prion diseases in live animals, using magnetic resonance imaging (MRI). Hamsters experimentally infected with the 263K strain of scrapie were imaged periodically during the course of prion infection. Changes in the brain, particularly the hippocampus, were observed during the first quarter of the incubation period. These changes included an increase in T2 relaxation time and apparent diffusion coefficient (ADC), indicative of an increase in the water content of tissues. These changes were apparent well before the appearance of clinical symptoms, and did not correlate with the typical histological changes characteristic of prion disease, (vacuolation, accumulation of PrP protein, gliosis) suggesting that the changes are caused by a progressive accumulation of fluid. This oedema may be a novel early marker of prion disease, and could play a role in pathogenesis.