Role of splice variants in the metastatic progression of prostate cancer

AS (alternative splicing) and its role in disease, especially cancer, has come to forefront in research over the last few years. Alterations in the ratio of splice variants have been widely observed in cancer. Splice variants of cancer-associated genes have functions that can alter cellular phenotype, ultimately altering metastatic potential. As metastases are the cause of approximately 90% of all human cancer deaths, it is crucial to understand how AS is dysregulated in metastatic disease. We highlight some recent studies into the relationship between altered AS of key genes and the initiation of prostate cancer metastasis. ©The Authors Journal compilation ©2012 Biochemical Society

Evaluating the Number of Stages in Development of Squamous Cell and Adenocarcinomas across Cancer Sites Using Human Population-Based Cancer Modeling

BACKGROUND: Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by clinical and molecular characteristics. We evaluated the characteristics of carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of various organs to test whether these characteristics differed between cancer subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Histotype-specific incidence rates of 14 ACs and 12 SCCs from the SEER Registry (1973-2003) were analyzed by fitting several biologically motivated models to observed age patterns. A frailty model with the Weibull baseline was applied to each age pattern to provide the best fit for the majority of cancers. For each cancer, model parameters describing the underlying mechanisms of carcinogenesis including the number of stages occurring during an individual's life and leading to cancer (m-stages) were estimated. For sensitivity analysis, the age-period-cohort model was incorporated into the carcinogenesis model to test the stability of the estimates. For the majority of studied cancers, the numbers of m-stages were similar within each group (i.e., AC and SCC). When cancers of the same organs were compared (i.e., lung, esophagus, and cervix uteri), the number of m-stages were more strongly associated with the AC/SCC subtype than with the organ: 9.79±0.09, 9.93±0.19 and 8.80±0.10 for lung, esophagus, and cervical ACs, compared to 11.41±0.10, 12.86±0.34 and 12.01±0.51 for SCCs of the respective organs (p<0.05 between subtypes). Most SCCs had more than ten m-stages while ACs had fewer than ten m-stages. The sensitivity analyses of the model parameters demonstrated the stability of the obtained estimates. CONCLUSIONS/SIGNIFICANCE: A model containing parameters capable of representing the number of stages of cancer development occurring during individual's life was applied to the large population data on incidence of ACs and SCCs. The model revealed that the number of m-stages differed by cancer subtype being more strongly associated with ACs/SCCs histotype than with organ/site

Effects of low level electromagnetic field exposure at 2.45 GHz on rat cornea.

Abstract PURPOSE: To investigate the effects of low level electromagnetic field (low level-EMF) exposure, as frequently encountered in daily life, on the normal rat cornea using histological and stereological method. METHODS: Twenty-two adult male Wistar rats were randomly divided into two groups: Study group (n = 11) and control group (n = 11). Rats in the study group were exposed to 2.45 GHz microwave (MW) radiation (11.96 \ub1 0.89 V/m), 0.25 W/kg specific absorption rate (SAR) for 2 hours each day for 21 days. The corneal thickness and the anterior epithelium corneal thickness were measured using two different methods. RESULTS: Using the histological method, the mean corneal thicknesses in the control and study group were 278.9 \ub1 54.5 \u3bcm, and 272.4 \ub1 85.6 \u3bcm, respectively. There was no statistically significant difference between the groups (p > 0.05). The anterior corneal epithelium thickness was 28.1 \ub1 4.9 \u3bcm in the control group and 31.7 \ub1 5.5 \u3bcm in the study group. There were statistically differences between the groups with regard to the thickness of anterior epithelium (p < 0.05). In the measurement made by the stereological method, the percentage of the cornea occupied by anterior corneal epithelium was 15.94% in the control group and 17.9% in the study group. Despite the fact that there was a relation between increased anterior epithelial area (AEA) and radiation exposure, no statistically significant relationship in area fraction of each compartment was found between the control and study groups. CONCLUSIONS: Results of this preliminary study show that exposure to MW radiation might cause alterations in the rat cornea

Infrared Spectroscopy with Multivariate Analysis Potentially Facilitates the Segregation of Different Types of Prostate Cell.

The prostate gland is conventionally divided into zones or regions. This morphology is of clinical significance as prostate cancer (CaP) occurs mainly in the peripheral zone (PZ). We obtained tissue sets consisting of paraffin-embedded blocks of cancer-free transition zone (TZ) and PZ and adjacent CaP from patients (n = 6) who had undergone radical retropubic prostatectomy; a seventh tissue set of snap-frozen PZ and TZ was obtained from a CaP-free gland removed after radical cystoprostatectomy. Paraffin-embedded tissue slices were sectioned (10-µm thick) and mounted on suitable windows to facilitate infrared (IR) spectra acquisition before being dewaxed and air dried; cryosections were dessicated on BaF2 windows. Spectra were collected employing synchrotron Fourier-transform infrared (FTIR) microspectroscopy in transmission mode or attenuated total reflection-FTIR (ATR) spectroscopy. Epithelial cell and stromal IR spectra were subjected to principal component analysis to determine whether wavenumber-absorbance relationships expressed as single points in "hyperspace" might on the basis of multivariate distance reveal biophysical differences between cells in situ in different tissue regions. After spectroscopic analysis, plotted clusters and their loadings curves highlighted marked variation in the spectral region containing DNA/RNA bands (1490–1000 cm–1). By interrogating the intrinsic dimensionality of IR spectra in this small cohort sample, we found that TZ epithelial cells appeared to align more closely with those of CaP while exhibiting marked structural differences compared to PZ epithelium. IR spectra of PZ stroma also suggested that these cells are structurally more different to CaP than those located in the TZ. Because the PZ exhibits a higher occurrence of CaP, other factors (e.g., hormone exposure) may modulate the growth kinetics of initiated epithelial cells in this region. The results of this pilot study surprisingly indicate that TZ epithelial cells are more likely to exhibit what may be a susceptibility-to-adenocarcinoma spectral signature. Thus, IR spectroscopy on its own may not be sufficient to identify premalignant prostate epithelial cells most likely to progress to CaP