Computer Directed Photodynamic Therapy of Prostate Ca

Summary

Principal Investigator: Jerzy Jankun
Abstract: DESCRIPTION (Verbatim from Applicant's Abstract): The objective of the proposal is to provide a critical body of knowledge with the ultimate goal of transferring photodynamic therapy (PDT) to the clinical arena for the treatment of prostate cancer. The widespread use of PSA test as an adjunct to digital rectal examination has led to an increase in the diagnosis of prostate cancer in its early stages. Treatment of organ confined prostatic cancer includes radical prostatectomy, radiotherapy, brachytherapy and cryosurgical ablation. Results from all these are favorable at least in terms of short outcomes. Still, with Tic disease, 30 percent of patients will have biochemical failure within 5 years of treatment. Clearly novel methods of prostate cancer treatment are needed. We want to utilize PDT as a novel approach to the treatment of prostatic cancer. PDT for prostate cancer depends on the sequestration of a PDT drug within the glandular tissue of the prostate. The photosensitizer is subsequently activated by high-energy light producing cytotoxic substances, which in turn destroy cancerous tissue. Since prostate cancer is a multi-focal disease, PDT must ablate the prostate completely. Complete ablation will depend on quantification of tissue sensitivity to a photosensitizer, precise placement of light sources in the prostate and delivery of a therapeutic light dose to the entire gland. The prostate is irregular in shape, so transurethral light delivery cannot be used for the treatment of the majority of prostate cancers. Additionally, most cancers are located in the peripheral zone of the prostate, an area unlikely to be reached by transurethrally launched light. Sources of light and their spatial distribution must be tailored to each patient. More uniform light distribution can be achieved by interstitial light irradiation. In this case, the light is delivered by diffusers placed within the substance of the prostate parallel to the urethra at a distance optimized to deliver adequate levels of light and to create the desired photodynamic effect. To achieve uniform light distribution throughout the prostate we are developing a computer program that can determine treatment effects by calculating the distribution of light energy depending on the number of light sources placed in the prostate, their position in the gland, the dimension of the prostate, and the tissue attenuation coefficient.
Funding Period: 2001-03-02 - 2007-02-28
more information: NIH RePORT

Top Publications

  1. ncbi In vivo and in vitro effect of baicalein on human prostate cancer cells
    Ranko Miocinovic
    Urology Research Center, Department of Urology, Medical College of Ohio, Toledo, OH 43614, USA
    Int J Oncol 26:241-6. 2005
  2. ncbi PAI-1 induces cell detachment, downregulates nucleophosmin (B23) and fortilin (TCTP) in LnCAP prostate cancer cells
    Jerzy Jankun
    Urology Research Center, University of Toledo, Health Science Campus, Toledo, OH 43614 5807, USA
    Int J Mol Med 20:11-20. 2007
  3. ncbi Nutraceutical inhibitors of urokinase: potential applications in prostate cancer prevention and treatment
    Jerzy Jankun
    Urology Research Center, Medical University of Ohio, Department of Urology, Toledo, OH 43614 5807, USA
    Oncol Rep 16:341-6. 2006
  4. ncbi Effect of crystal freezing and small-molecule binding on internal cavity size in a large protein: X-ray and docking studies of lipoxygenase at ambient and low temperature at 2.0 A resolution
    E Skrzypczak-Jankun
    Urology Research Center, Medical University of Ohio, Toledo, OH 43614, USA
    Acta Crystallogr D Biol Crystallogr 62:766-75. 2006
  5. ncbi Synthetic curcuminoids modulate the arachidonic acid metabolism of human platelet 12-lipoxygenase and reduce sprout formation of human endothelial cells
    Jerzy Jankun
    Urology Research Center, Medical University of Ohio, 3065 Arlington, Toledo, OH 43614 5807, USA
    Mol Cancer Ther 5:1371-82. 2006
  6. ncbi Development and characterization of multi-sensory fluence rate probes
    Natalie Pomerleau-Dalcourt
    Department of Medical Biophysics, University of Toronto, Toronto, Canada
    Phys Med Biol 51:1929-40. 2006
  7. ncbi Vascular endothelial growth factor production in human prostate cancer cells is stimulated by overexpression of platelet 12-lipoxygenase
    N Patrick McCabe
    Urology Research Center, Medical University of Ohio at Toledo, Toledo, Ohio OH 43699 0008, USA
    Prostate 66:779-87. 2006
  8. ncbi Plasminogen activator inhibitor-1 is locked in active conformation and polymerizes upon binding ligands neutralizing its activity
    Jerzy Jankun
    Urology Research Center, Medical University of Ohio, Toledo, 43614, USA
    Int J Mol Med 17:437-47. 2006
  9. ncbi Aspirin blocks binding of photosensitizer SnET2 into human serum albumin: implications for photodynamic therapy
    E Skrzypczak-Jankun
    Urology Research Center, Department of Urology, Medical College of Ohio, Toledo, OH 43614, USA
    Int J Mol Med 15:777-83. 2005
  10. ncbi Highly stable plasminogen activator inhibitor type one (VLHL PAI-1) protects fibrin clots from tissue plasminogen activator-mediated fibrinolysis
    Jerzy Jankun
    Urology Research Center, Health Science Campus, University of Toledo, Toledo, OH 43614 5807, USA
    Int J Mol Med 20:683-7. 2007

Scientific Experts

  • Jerzy Jankun
  • E Skrzypczak Jankun
  • E Skrzypczak-Jankun
  • N Patrick McCabe
  • Natalie Pomerleau-Dalcourt
  • O Y Borbulevych
  • Steven H Selman
  • Ranko Miocinovic
  • Lothar Lilge
  • V Petricek
  • M I Zavodszky
  • M R Baranski
  • K Padmanabhan
  • Rick W Keck
  • J Aniola
  • M Niedre
  • L Lilge
  • A Melillo
  • S H Selman
  • R Keck
  • James A Hampton
  • M Soriano-Garcia

Detail Information

Publications10

  1. ncbi In vivo and in vitro effect of baicalein on human prostate cancer cells
    Ranko Miocinovic
    Urology Research Center, Department of Urology, Medical College of Ohio, Toledo, OH 43614, USA
    Int J Oncol 26:241-6. 2005
    ..01) when compared to the control. This is the first study demonstrating an in vivo growth inhibitory effect of orally administered baicalein on human prostate tumors in mice...
  2. ncbi PAI-1 induces cell detachment, downregulates nucleophosmin (B23) and fortilin (TCTP) in LnCAP prostate cancer cells
    Jerzy Jankun
    Urology Research Center, University of Toledo, Health Science Campus, Toledo, OH 43614 5807, USA
    Int J Mol Med 20:11-20. 2007
    ..We hope that by exploring PAI-1's structure and function we might be able to understand and separate the different effects of PAI-1 on cancer cells and develop more effective therapeutic strategies in cancer treatment...
  3. ncbi Nutraceutical inhibitors of urokinase: potential applications in prostate cancer prevention and treatment
    Jerzy Jankun
    Urology Research Center, Medical University of Ohio, Department of Urology, Toledo, OH 43614 5807, USA
    Oncol Rep 16:341-6. 2006
    ..If true, a proper diet rich in uPA-inhibiting nutraceuticals might support the prevention of prostrate cancer and be a supportive tool in prostate cancer treatment...
  4. ncbi Effect of crystal freezing and small-molecule binding on internal cavity size in a large protein: X-ray and docking studies of lipoxygenase at ambient and low temperature at 2.0 A resolution
    E Skrzypczak-Jankun
    Urology Research Center, Medical University of Ohio, Toledo, OH 43614, USA
    Acta Crystallogr D Biol Crystallogr 62:766-75. 2006
    ....
  5. ncbi Synthetic curcuminoids modulate the arachidonic acid metabolism of human platelet 12-lipoxygenase and reduce sprout formation of human endothelial cells
    Jerzy Jankun
    Urology Research Center, Medical University of Ohio, 3065 Arlington, Toledo, OH 43614 5807, USA
    Mol Cancer Ther 5:1371-82. 2006
    ..This universal event for all tested lipoxygenase inhibitors suggests that the inhibition of sprout formation was most likely due to the inhibition of human P-12-LOX but not other cancer-related pathways...
  6. ncbi Development and characterization of multi-sensory fluence rate probes
    Natalie Pomerleau-Dalcourt
    Department of Medical Biophysics, University of Toronto, Toronto, Canada
    Phys Med Biol 51:1929-40. 2006
    ..Three-fluorophore MSPs permitted three simultaneous measurements of the fluence rate gradient in a tissue-like phantom, with an average accuracy of 6.7%. No appreciable photodegradation or cross-talk was observed...
  7. ncbi Vascular endothelial growth factor production in human prostate cancer cells is stimulated by overexpression of platelet 12-lipoxygenase
    N Patrick McCabe
    Urology Research Center, Medical University of Ohio at Toledo, Toledo, Ohio OH 43699 0008, USA
    Prostate 66:779-87. 2006
    ..The mechanisms underlying the role of P12-LOX in angiogenesis remain unclear...
  8. ncbi Plasminogen activator inhibitor-1 is locked in active conformation and polymerizes upon binding ligands neutralizing its activity
    Jerzy Jankun
    Urology Research Center, Medical University of Ohio, Toledo, 43614, USA
    Int J Mol Med 17:437-47. 2006
    ..The polymerization of PAI-1 reduces PAI-1 activity by encapsulating the critical RCL fragment inside the formed PAI-1/PAI-1 polymers...
  9. ncbi Aspirin blocks binding of photosensitizer SnET2 into human serum albumin: implications for photodynamic therapy
    E Skrzypczak-Jankun
    Urology Research Center, Department of Urology, Medical College of Ohio, Toledo, OH 43614, USA
    Int J Mol Med 15:777-83. 2005
    ..This observation could be exploited to improve photo-efficiency of SnET2 by finding drugs that could compete with the photosensitizer for binding into Sudlow Site I of HSA...
  10. ncbi Highly stable plasminogen activator inhibitor type one (VLHL PAI-1) protects fibrin clots from tissue plasminogen activator-mediated fibrinolysis
    Jerzy Jankun
    Urology Research Center, Health Science Campus, University of Toledo, Toledo, OH 43614 5807, USA
    Int J Mol Med 20:683-7. 2007
    ....