Therefore the amount of formazan produced is proportional to the number of living mitochondria

s resulted in an overall decrease in PCa metastasis and death. Unfortunately, the application of PSA screening has also led to over-detection and overtreatment as PSA is neither cancer specific nor a surrogate for the biologic behavior of PCa. Elevations in PSA levels can reflect a cancer presence but can also be present as a result of infection, chronic inflammation or benign prostatic hyperplasia . BPH has been shown to exist in greater than 70% of men over the age of 70 but is not Prostate Cancer Exosomes Contain Survivin considered to be a precursor of prostate cancer though they frequently coexist. It is therefore necessary to continue to screen for biomarkers that are cancer-specific and that are detectable early in the course of the disease. The processes of both cell survival and cell death have involved highly regulated signaling pathways that are currently the subject of intense investigation. It is known that regulation of apoptosis has a central role in the development of prostate cancer and its progression to an androgen-independent state, which is due, in part to up regulation of antiapoptotic genes after androgen deprivation. Several lines of evidence suggest that one of the main events associated with progression after therapeutic failure is increased resistance to apoptosis, mainly due to the up regulation of antiapoptotic genes, including Bcl-2, Bcl-XL, Mcl-1, and Survivin. Survivin, an inhibitor-of-apoptosis protein family member, is associated with PCa development, progression, and drug resistance. Recent evidence indicates that the overexpression of Survivin in PCa tumors is associated with poor prognosis and increased tumor recurrence. In contrast, it has also been shown that knockdown of survivin expression by siRNAs enhances the chemosensitivity of prostate cancer cells, reducing tumorigenicity. Traditionally, Survivin has been viewed as a cytoplasmic or nuclear protein. Recently, Survivin has been also shown to exist extracellularly, contained in small membrane bound vesicles known as exosomes. Exosomes are present in serum and urine and contain a wide range of proteins and RNAs and represent their tissue of origin making them a possible source or pool of novel PCa biomarkers. Consistent with Survivin’s association with unfavorable clinicopathological parameters, extracellular trafficking of Survivin throughout the tumor microenvironment could be responsible for augmenting the aggressive status of a tumor while prohibiting or minimizing therapeutic results. We have recently shown that exosome-bound Survivin protein can be secreted by cancer cells and be taken up by surrounding cells, producing a field effect that confers a general stress-survival phenotype. Our present study was designed to investigate the existence of exosomal Survivin in the plasma of PCa patients with a variety of PCa presentations and to compare its exosomal expression levels to those found in control volunteers with no diagnosis of cancer and to patients diagnosed with benign prostatic hyperplasia or BPH. For the past 25 years the Gleason grading system has been used to help Debio 1347 evaluate the prognosis of men with prostate cancer. Together with other parameters, prostate cancer has been staged as a means to predict prognosis and guide therapy. Extracellular Survivin was found highly expressed in the plasma exosomes of PCa patients exhibiting Gleason scores of 6 and 9, and in patients who had relapsed on chemotherapy. However, there were no signi