734 EAST MEETS WEST: THE MUSHROOM EXTRACT PSK ENHANCES DOCETAXEL THERAPY FOR CASTRATE RESISTANT PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011734 EAST MEETS WEST: THE MUSHROOM EXTRACT PSK ENHANCES DOCETAXEL THERAPY FOR CASTRATE RESISTANT PROSTATE CANCER Joel Slaton, Michael Verneris, Haling Lu, and Cynthia Wenner Joel SlatonJoel Slaton Minneapolis, MN More articles by this author , Michael VernerisMichael Verneris Minneapolis, MN More articles by this author , Haling LuHaling Lu Seattle, WA More articles by this author , and Cynthia WennerCynthia Wenner Kenmore, WA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1703AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Polysaccharide Krestin (PSK), an extract of the mushroom Trametes versicolor and a known immunomodulator, has proven to enhance survival in randomized clinical trials in Asia.when combined with chemotherapy in patients with breast, colon and stomach cancer. The role of PSK in prostate cancer has not previously been investigated due to the lack of effective chemotherapy. However, with the demonstration of improved survival in patients with castrate resistant prostate cancer (CPRC) with the use of docetaxel, there is now an opportunity to investigate the effect of adding PSK to docetaxel in CRPC. METHODS C57BL/6 mice bearing established orthotopic CRPC PC3-LN4 tumors (100 mg) were randomized to four groups for treatment with a) saline b) docetaxel 5mg/kg ip every other day, c) PSk 300 mg/kg po and d) docetaxel plus PSK Mice were treated were 12 days and then sacrificed the following day 14. Mice were weighed daily. At time of sacrifice, blood and organs were collected for evidence of toxicity. Tumors and lymph nodes were weighed and preserved in either nitrogen or formalin and analyzed for immunomodulatory changes. Spleens were assessed for NK cell activity. RESULTS A combination of docetaxel and PSK resulted in the greatest tumor inhibition (399+62 mg) compared to saline ((826 +82 mg), PSK (780+75 mg), and docetaxel (528+ 62 mg) alone. Combination therapy resulted in the highest level of apoptosis (determined by TUNEL) and greatest inhibition of proliferation (determined by Ki67). Simultaneously, combination therapy resulted in a 25% higher total white count and a 10% higher animal weight. Treatment with PSK, a known inhibitor of toll-like receptor 4 (TLR4) resulted in a complete inhibition of expression of interferon gamma within the tumors and upregulation of T-regulatory cell. NK cell activity and CD4 count was higher in the mice treated with combination therapy compared to controls and docetaxel treated group. CONCLUSIONS Combination therapy with docetaxel and the mushroom extract PSK has superior antitumor and immunoprotective activity compared to docetaxel alone. This data served as the basis for a recently NIH-funded Phase I clinical trial combining PSK and docetaxel in CPRC patients which will soon be open for accrual. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e295 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joel Slaton Minneapolis, MN More articles by this author Michael Verneris Minneapolis, MN More articles by this author Haling Lu Seattle, WA More articles by this author Cynthia Wenner Kenmore, WA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...