Urokinase Plasminogen Activator System in Benign Prostatic Hyperplasia
Information source: Queen's University
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: BPH
Intervention: transurethral resection of the prostate (Procedure)
Phase: N/A
Status: Active, not recruiting
Sponsored by: Queen's University Official(s) and/or principal investigator(s):
J. Curtis Nickel, MD FRCSC, Principal Investigator, Affiliation: Queen's Universtiy
Summary
We hypothesize that the absolute or relative serum or urine levels of the urokinase
plasminogen activator system, including uPA, uPAR and PAI-1,2 (inhibitors of the uPAR/uPA
complex), are associated with inflammation in prostatic tissue.
Clinical Details
Official title: Urokinase Plasminogen Activator System in Benign Prostatic Hyperplasia: A Possible Marker of Progression and Response to Medical Therapy
Study design: Case-Only, Prospective
Detailed description:
Histological inflammation in patients with Benign Prostatic Hyperplasia (BPH) appears to
predict clinical progression and ultimate long-term response to various medical therapies,
including finasteride. Discovery of a urine or serum marker of prostate inflammation will be
an invaluable clinical tool to predict a man's risk of BPH progression and the efficacy of
various medical therapies to reduce that risk.
Specific Aim:
We plan to determine if urokinase plasminogen activators (and/or other inflammatory markers)
in serum, urine and tissue of patients can predict prostatic inflammation
Background:
Benign Prostatic Hyperplasia (BPH) and Inflammation
BPH is a common disorder of the prostate causing significant lower urinary tract symptoms and
negatively affects the quality of life in a substantial proportion of men in North America.
According to the National Institutes of Health (NIH), BPH affects more than 50% of men over
age 60 and as many as 90% of men over the age of 70. Although there are numerous genetic and
epigenetic changes associated with the progression of normal prostatic glandular formation to
BPH, as early as 1994 our group suggested that the presence of prostatic inflammation could
be associated with pathogenesis and progression of both histological and clinical BPH. We
have demonstrated that histological prostate inflammation is very common in patients with BPH
as well as patients who are both symptomatic and not symptomatic. Our local research group
spearheaded an international consensus classification system for prostatic inflammation that
we have subsequently employed in our ongoing study of over 8,000 men undergoing 3 serial
biopsies over a 4 year period of time. The MTOPS BPH study data base subanalyses of the more
than 1,000 men who underwent baseline biopsies strongly suggested that prostatic inflammation
appears to be the strongest and most robust predictor of symptomatic progression as well as
response to drug therapy. An analyses T-cell phenotypes, cytokine expression patterns and
cellular cross talk in BPH tissues of 101 BPH patients and prostatic cell cultures showed
that chronic inflammation triggers histological and clinical progression. The search for
urine or serum biomarkers of prostatic inflammation is highly relevant to better target
therapies for men with this common condition.
Urokinase Plasminogen Activator System
Proteolytic enzymes are required to mediate inflammatory cell infiltration in tissues, a
process highly regulated by the cell surface-specific receptor (uPAR) a binding partner for
the urokinase-type plasminogen activator (uPA). Numerous previous clinical investigations
have indicated that serum levels of the plasminogen activation system are an effective marker
of inflammation in several disease processes including CNS inflammation, asthma, metabolic
syndrome and pre-eclampsia. Very little data is available regarding the plasma levels of
soluble uPAR in benign prostatic diseases, although one previous report suggested higher
average levels of soluble uPAR in patients with lower urinary tract symptoms. Theses authors
reported a wide variation of uPAR in BPH patients with some having greatly elevated levels
while others had undetectable levels. However, the author's did not have pathological
confirmation of their findings and could not quantify the level of inflammation in the
prostatic tissue. We hypothesize that the absolute or relative serum levels of the urokinase
plasminogen activator system, including uPA, uPAR and PAI-1,2 (inhibitors of the uPAR/uPA
complex), are associated with inflammation in prostatic tissue.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Male.
Criteria:
Inclusion Criteria:
- scheduled for transurethral resection of the prostate
Exclusion Criteria:
- unable to give consent
Locations and Contacts
Centre for Advanced Urological Research, Kingston, Ontario K7L 3J7, Canada
Additional Information
Related publications: Nickel JC. Prostatic inflammation in benign prostatic hyperplasia - the third component? Can J Urol. 1994 Jan;1(1):1-4. Nickel JC, Downey J, Young I, Boag S. Asymptomatic inflammation and/or infection in benign prostatic hyperplasia. BJU Int. 1999 Dec;84(9):976-81. Nickel JC, True LD, Krieger JN, Berger RE, Boag AH, Young ID. Consensus development of a histopathological classification system for chronic prostatic inflammation. BJU Int. 2001 Jun;87(9):797-805. Review. McCabe NP, Angwafo FF 3rd, Zaher A, Selman SH, Kouinche A, Jankun J. Expression of soluble urokinase plasminogen activator receptor may be related to outcome in prostate cancer patients. Oncol Rep. 2000 Jul-Aug;7(4):879-82. McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr, Dixon CM, Kusek JW, Lepor H, McVary KT, Nyberg LM Jr, Clarke HS, Crawford ED, Diokno A, Foley JP, Foster HE, Jacobs SC, Kaplan SA, Kreder KJ, Lieber MM, Lucia MS, Miller GJ, Menon M, Milam DF, Ramsdell JW, Schenkman NS, Slawin KM, Smith JA; Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003 Dec 18;349(25):2387-98. Thompson IN, Goodman PJ, Tangen CM, Lucia MS, Miller CJ, Ford LC, et al. The influence of finsteride in the development of prostate cancer. New England Journal of Medicine, 2003; 349:211-220.
Starting date: November 2006
Ending date: June 2008
Last updated: April 22, 2008
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