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1633 TARGETING THE NEURAL MICROENVIRONMENT IN PROSTATE CANCER: A NEOADJUVANT BOTOX CLINICAL TRIAL

2012; Lippincott Williams & Wilkins; Volume: 187; Issue: 4S Linguagem: Inglês

10.1016/j.juro.2012.02.1450

1527-3792

Gustavo Ayala, Diego Florentin, Jason Au, Yi Ding, Dandan He, Chad J. Creighton, Anna Frolov, Olga Dakhova, Yiqun Zhang, Christopher P. Smith, Dov Kadmon, Brian J. Miles, Michael Ittmann, David R. Rowley,

Ubiquitin and proteasome pathways

You have accessJournal of UrologyProstate Cancer: Localized VIII1 Apr 20121633 TARGETING THE NEURAL MICROENVIRONMENT IN PROSTATE CANCER: A NEOADJUVANT BOTOX CLINICAL TRIAL Gustavo Ayala, Diego Florentin, Jason K. Au, Yi Ding, Dandan He, Chad J. Creighton, Anna Frolov, Olga Dakhova, Yiqun Zhang, Christopher Smith, Dov Kadmon, Brian Miles, Michael Ittmann, and David Rowley Gustavo AyalaGustavo Ayala Houston, TX More articles by this author , Diego FlorentinDiego Florentin Houston, TX More articles by this author , Jason K. AuJason K. Au Houston, TX More articles by this author , Yi DingYi Ding Houston, TX More articles by this author , Dandan HeDandan He Houston, TX More articles by this author , Chad J. CreightonChad J. Creighton Houston, TX More articles by this author , Anna FrolovAnna Frolov Houston, TX More articles by this author , Olga DakhovaOlga Dakhova Houston, TX More articles by this author , Yiqun ZhangYiqun Zhang Houston, TX More articles by this author , Christopher SmithChristopher Smith Houston, TX More articles by this author , Dov KadmonDov Kadmon Houston, TX More articles by this author , Brian MilesBrian Miles Houston, TX More articles by this author , Michael IttmannMichael Ittmann Houston, TX More articles by this author , and David RowleyDavid Rowley Houston, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1450AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Nerve-cancer interaction provides a survival advantage for prostate cancer through perineural invasion, neurogenesis, and regulation of epithelial homeostasis. Physical and chemical (Botox) denervation affect tumor growth in vivo, using similar mechanisms. As clinical translation and proof-of-concept study, we next evaluated tissues from three patients enrolled in a Phase I clinical trial to assess the effects of Botox injections on specific endpoints of prostate tumor biology. METHODS Patients with bilateral Gleason 6-7 tumors received unilateral Botox injections (100 U in a 2.0-ml volume) into one lobe and a vehicle control injection into the contralateral lobe. Radical prostatectomy was performed 4 weeks later and biological endpoints studied in the pathologic specimen. RESULTS Examination of tissues revealed a general atrophic effect in prostate cancer cells obtained from Botox-injected lobes. Vehicle control lobes exhibited a typical Gleason 6-7 histopathology. We also identified extensive degenerative features, as evidenced by reduced cytoplasm and pyknotic nuclei, compared to features in saline-injected cancer tissues. TUNEL studies revealed a significant increase in the apoptotic ratio in the botox side than saline injected tumor. No significant changes were observed in the proliferation index, measured by Ki67. Microvessel density was increased in the tumor of 1 patients, no changes were observed in 2 patients. Nerve density was significantly decreased in the tumor of 1 patient and a trend toward decrease in another. These data suggest that Botox has an atrophic effect on the nerves, without affecting the tumor vasculature in human prostate cancer. The gene profile of the Botox treated tumors had extensive similarities with those of prostate cancer arising in patients with spinal cord injury, confirming that the effect is due mainly to denervation. CONCLUSIONS Together, previous experimental tumor study, preliminary Phase I Clinical trial study, and gene expression analysis of prostate tumors from patients with spinal cord injuries suggest that the nerve-cancer cell interaction is a key and critical element in prostate cancer cell survival and tumorigenicity. Targeting the neural microenvironment is becoming a necessity. Botox, as a chemical denervation agent, has effects on human prostate cancer. The Botox strategy could be easily translated to an active surveillance cohort. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e660 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gustavo Ayala Houston, TX More articles by this author Diego Florentin Houston, TX More articles by this author Jason K. Au Houston, TX More articles by this author Yi Ding Houston, TX More articles by this author Dandan He Houston, TX More articles by this author Chad J. Creighton Houston, TX More articles by this author Anna Frolov Houston, TX More articles by this author Olga Dakhova Houston, TX More articles by this author Yiqun Zhang Houston, TX More articles by this author Christopher Smith Houston, TX More articles by this author Dov Kadmon Houston, TX More articles by this author Brian Miles Houston, TX More articles by this author Michael Ittmann Houston, TX More articles by this author David Rowley Houston, TX More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...