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Posts Tagged ‘Genitourinary’


Curator: Aviva Lev-Ari, PhD, RN

A new etiology for Prostate Cancer based on Integrative Genomic Analyses reveals difference in Pathomechanism between Early onset and and Non-Early onset  was reported this week in Cancer CellVolume 23, Issue 2, 159-170, 11 February 2013

Early Onset: Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer

Median age of 47: EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG

Non Early onset:

Around 65 years of age at onset:  elderly-onset PCAs displayed primarily non-androgen-associated structural rearrangement (SR) formations.

Treatment Comparison for Clinically Localized Primary Prostate Cancer Therapies

Treatment

Description

Selected Risks

Recovery

Selected Outcomes

HIFU – (high intensity focused ultrasound) Minimally invasive use of focused ultrasound waves
to ablate diseased tissue
Incontinence: 0-10% 1-3
Impotence: 8-50%4,5
Rectal Injury: <3% 4-6
Catheter worn for
approximately 2-3 weeks; can
return to normal activities
within a few days
55-95% biochemical
disease-free survival rate at 5 years; 55-98% negative biopsy1-9
Cryotherapy Minimally invasive
procedure using
controlled freeze and thaw cycles to destroy the prostate
Incontinence: 3-10% 10
Impotence: 40-100% 10
Rectal Injury: 0-3% 10
2-3 hour procedure with possible overnight stay; return to normal activities within a few days 50-92% biochemical
disease-free survival at 5 years; 87-98% negative biopsy 11,12
Radical Prostatectomy Surgery to remove
prostate, open or
laparoscopic
Incontinence: 9-20% 13
Impotence: 4-85%13
Rectal Injury:0-5%14
2-3 day hospital stay, catheter for 2-3 weeks for open surgery; shorter
hospitalization and fewer postoperative complications for laparoscopic procedure
68–98% biochemical
disease-free survival15,16
External Beam Radiation 6-8 week treatment;
external machine
concentrating radiation
beams to the prostate
Incontinence: 4-15% 17
Impotence: 41-62% 17
Rectal Injury: 15%17
Five treatments per week for 6-8 weeks, up to 2 months fatigue after full course of treatment 55–86% biochemical
disease-free survival18-19
Brachytherapy Minimally invasive implants of radiation seeds in the prostate Incontinence: 3-18% 20
Impotence: 14-82% 20
Rectal Injury: 3%21
1-2 hour procedure with
possible overnight stay
78–89% biochemical
disease-free survival22

Data presented are for clinically localized, low-high risk primary prostate cancer. The information provided in the chart is therapy and not device specific and may not include all potential risks, recovery and outcome information. For further information please see references.

The Sonablate® 500 is approved for investigational use within the U.S. and is being studied for the treatment of prostate cancer in clinical trials in the U.S. The FDA has made no decision as to the safety or efficacy of the Sonablate® 500 for the treatment of prostate cancer. Currently, the device is available for the treatment of prostate cancer outside the U.S. in more than 30 countries.

http://www.internationalhifu.com/treatment-options/treatment-comparison.html?kmas=1&kmkw=prostate%20cancer%20treatment&gclid=CJbo37P0trUCFQdU4AodWhkAxQ

http://www.internationalhifu.com/treatment-options/treatment-comparison.html?kmas=1&kmkw=prostate%20cancer%20treatment&gclid=CJbo37P0trUCFQdU4AodWhkAxQ#ixzz2KuxByzdV

Prostate Cancer and Nanotecnology

Dr. T. Barlyia summaried:

Early detection of prostate cancer increased dramatically the five-year survival of patients. “This study demonstrates for the first time that it is possible to generate medicines with both targeted and programmable properties that can concentrate the therapeutic effect directly at the site of disease, potentially revolutionizing how complex diseases such as cancer are treated”. The Phase I clinical trial is still ongoing and continued dose escalation is underway; BIND Biosciences is now planning Phase II trials, which will further investigate the treatment’s effectiveness in a larger number of patients.

https://pharmaceuticalintelligence.com/2013/02/07/prostate-cancer-and-nanotecnology/

BIND-014 is a programmable nanomedicine that combines a targeting ligandand a therapeutic nanoparticle.  BIND-014 contains docetaxel, a proven cancer drug which is approved in major cancer indications including breast, prostate and lung, encapsulated in FDA-approved biocompatible and biodegradable polymers. BIND-014 is targeted to prostate specific membrane antigen (PSMA), a cell surface antigen abundantly expressed on the surface of cancer cells and on new blood vessels that feed a wide array of solid tumors.  In preclinical cancer models, BIND-014 was shown to deliver up to ten-fold more docetaxel to tumors than an equivalent dose of conventional docetaxel.  The increased accumulation of docetaxel at the site of disease translated to marked improvements in antitumor activity and tolerability.  BIND-014 is currently in Phase 1 human clinical testing in cancer patients with advanced or metastatic solid tumor cancers (NCT01300533). The early development of BIND-014 was funded in part by the National Cancer Institute and the U.S. National Institutes of Standards and Technology (NIST) under its Advanced Technology Program (ATP).

State of the art in oncologic imaging of Prostate

Dr. D. Nir summarizes:

In regards to treatment choice: “active surveillance, focal therapy, radical prostatectomy, and radiation therapy represent a range of treatments with varying degrees of invasiveness for men with different disease grades and stages. Active surveillance and focal therapy, which are relatively new options, are promising but are complicated by uncertainties in risk stratification that affect treatment decision-making, as well as by uncertainties regarding the definition of appropriate outcome measures. Biopsy, which leaves the possibility of under sampling, is not sufficient to resolve these uncertainties. Novel biomarkers and modern imaging are expected to play increasingly important roles in facilitating broader acceptance of both active surveillance and focal therapy. Further research, particularly involving prospective validation, is needed to facilitate standardization and establish the roles of advanced imaging tools in routine prostate cancer management.”

My summary: Prostate cancer is a disease managed by urologists, not radiologists. This disease’s multi-choice of pathways is “craving” for tissue characterization. Nothing could fit the urologist’s work-flow better than ultrasound-based tissue characterization!

Age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. 

Early Onset:

Median age of 47: EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG,

Non Early onset:

Around 65 years of age at onset:  elderly-onset PCAs displayed primarily non-androgen-associated SRs.

Integrative Genomic Analyses Reveal an Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer

Authors

  • Genome sequencing revealed age-related genetic alterations in PCA
  • Early-onset PCAs display a specific abundance of androgen-driven rearrangements
  • These age-linked alterations coincide with activity levels of the androgen receptor
  • This is an observation of age-specific DNA alterations in a common cancer

Summary

Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with “classical” (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions includingTMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic “androgen-type” pathomechanism in EO-PCA.


Early onset prostate cancer tumors tend to have a propensity for containing balanced structural rearrangements, particularly involving genes regulated by the androgen hormone, according to a study in Cancer Cell. As part of the International Cancer Genome Project’s Early-Onset Prostate Cancer project, researchers from Germany and the UK performed whole-genome sequencing on tumor and matched normal samples from 11 individuals who were surgically treated for prostate cancer at a median age of 47 years old. The tumors were also subjected to transcriptome and methylome sequencing.

When they compared sequences from these tumors with sequences from a previously described set of samples taken from seven individuals diagnosed with prostate cancer at around 65 years of age, investigators saw a rise in gene fusion-producing structural changes in the early onset samples.

Those fusions often affected ETS family genes and other genes prone to androgen-related regulation, researchers reported. In contrast, tumors from individuals whose prostate cancer appeared later in life were more apt to contain structural rearrangements affecting genes without any androgen ties.

Follow-up tests using samples from more than 10,000 other patients seemed to support this link between age at prostate cancer diagnosis and androgen receptor rearrangement, study authors said, pointing to a distinct, androgen-driven “pathomechanism” in early-onset forms of the disease.

SOURCE:

http://www.genomeweb.com//node/1191311?hq_e=el&hq_m=1498692&hq_l=5&hq_v=5f2bf80408

Cancer Cell, Volume 23, Issue 2, 159-170, 11 February 2013
Copyright © 2013 Elsevier Inc. All rights reserved.
10.1016/j.ccr.2013.01.002

http://www.internationalhifu.com/treatment-options/treatment-comparison.html?kmas=1&kmkw=prostate%20cancer%20treatment&gclid=CJbo37P0trUCFQdU4AodWhkAxQ#ixzz2KuxrkZbB

REFERENCES

  1. Uchida T, Ohkusa H, Nagata Y, Hyodo T, Satoh T, Irie A. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU international 2006;97:56-61.
  2. Uchida T, Ohkusa H, Yamashita H, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. International journal of urology : official journal of the Japanese Urological Association 2006;13:228-33.
  3. Muto S, Yoshii T, Saito K, Kamiyama Y, Ide H, Horie S. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Japanese journal of clinical oncology 2008;38:192-9.
  4. Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. British journal of cancer 2009;101:19-26.
  5. Inoue Y, Goto K, Hayashi T, Hayashi M. Transrectal high-intensity focused ultrasound for treatment of localized prostate cancer. International journal of urology : official journal of the Japanese Urological Association 2011;18:358-62.
  6. Uchida T, Shoji S, Nakano M, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. International journal of urology : official journal of the Japanese Urological Association 2009;16:881-6.
  7. Sumitomo M, Hayashi M, Watanabe T, et al. Efficacy of short-term androgen deprivation with high-intensity focused ultrasound in the treatment of prostate cancer in Japan. Urology 2008;72:1335-40.
  8. Sumitomo M, Asakuma J, Yoshii H, et al. Anterior perirectal fat tissue thickness is a strong predictor of recurrence after high-intensity focused ultrasound for prostate cancer. International journal of urology : official journal of the Japanese Urological Association 2010;17:776-82.
  9. Dudderidge T, Ahmed H, Emberton M. High-intensity focused ultrasound for localized prostate cancer: initial experience with a 2-year follow-up. BJU international 2009;104:1170-1; author reply 1.
  10. Shelley M, Wilt TJ, Coles B, Mason MD. Cryotherapy for localised prostate cancer. Cochrane Database Syst Rev 2007:CD005010.
  11. Cheetham P, Truesdale M, Chaudhury S, Wenske S, Hruby GW, Katz A. Long-term cancer-specific and overall survival for men followed more than 10 years after primary and salvage cryoablation of the prostate. Journal of endourology / Endourological Society 2010;24:1123-9.
  12. Jones JS, Rewcastle JC, Donnelly BJ, Lugnani FM, Pisters LL, Katz AE. Whole gland primary prostate cryoablation: initial results from the cryo on-line data registry. The Journal of urology 2008;180:554-8.
  13. Hu JC, Gu X, Lipsitz SR, et al. Comparative effectiveness of minimally invasive vs open radical prostatectomy. JAMA : the journal of the American Medical Association 2009;302:1557-64.
  14. Williams SB, Prasad SM, Weinberg AC, et al. Trends in the care of radical prostatectomy in the United States from 2003 to 2006. BJU international 2011;108:49-55.
  15. Mullins JK, Feng Z, Trock BJ, Epstein JI, Walsh PC, Loeb S. The impact of anatomical radical retropubic prostatectomy on cancer control: the 30-year anniversary. The Journal of urology 2012;188:2219-24.
  16. Loeb S, Zhu X, Schroder FH, Roobol MJ. Long-term radical prostatectomy outcomes among participants from the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam. BJU international 2012.
  17. Budaus L, Bolla M, Bossi A, et al. Functional outcomes and complications following radiation therapy for prostate cancer: a critical analysis of the literature. European urology 2012;61:112-27.
  18. Grimm P, Billiet I, Bostwick D, et al. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU international 2012;109 Suppl 1:22-9.
  19. Wilt TJ, MacDonald R, Rutks I, Shamliyan TA, Taylor BC, Kane RL. Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Annals of internal medicine 2008;148:435-48.
  20. Buckstein M, Kerns S, Forysthe K, Stone NN, Stock RG. Temporal patterns of selected late toxicities in patients treated with brachytherapy or brachytherapy plus external beam radiation for prostate adenocarcinoma. BJU international 2012.
  21. Orio PF, 3rd, Merrick GS, Galbreath RW, Butler WM, Lief J, Wallner KE. Patient-reported long-term rectal function after permanent interstitial brachytherapy for clinically localized prostate cancer. Brachytherapy 2012;11:341-7.
  22. Critz FA, Benton JB, Shrake P, Merlin ML. 25 year disease free survival rate after irradiation of prostate cancer calculated with the prostate specific antigen definition of recurrence used for radical prostatectomy. The Journal of urology 2012.

http://www.internationalhifu.com/treatment-options/treatment-comparison.html?kmas=1&kmkw=prostate%20cancer%20treatment&gclid=CJbo37P0trUCFQdU4AodWhkAxQ#ixzz2KuxrkZbB

Other research papers related to the management of Prostate cancer were published on this One Access Online Scientific Journal

Imaging agent to detect Prostate cancer-now a reality

Scientists use natural agents for prostate cancer bone metastasis treatment

Today’s fundamental challenge in Prostate cancer screening

ROLE OF VIRAL INFECTION IN PROSTATE CANCER

Men With Prostate Cancer More Likely to Die from Other Causes

New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests

New clinical results supports Imaging-guidance for targeted prostate biopsy

Prostate Cancer and Nanotecnology

https://pharmaceuticalintelligence.com/2013/02/07/prostate-cancer-and-nanotecnology/

State of the art in oncologic imaging of Prostate

https://pharmaceuticalintelligence.com/2013/01/28/state-of-the-art-in-oncologic-imaging-of-prostate/

Genomically Guided Treatment after CLIA Approval: to be offered by Weill Cornell Precision Medicine Institute
https://pharmaceuticalintelligence.com/2013/02/06/genomically-guided-treatment-after-clia-approval-to-be-offered-by-weill-cornell-precision-medicine-institute/

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Reported by: Dr. Venkat S. Karra, Ph.D.

 

NEW EVIDENCE FOR POLYOMAVIRUS BK ROLE IN PROSTATE CANCER

 

Prostate cancer is the leading cause of cancer morbidity and the third greatest cause of cancer death among men in developed countries.

English: Two-panel drawing shows normal male r...

English: Two-panel drawing shows normal male reproductive and urinary anatomy and benign prostatic hyperplasia (BPH). Panel on the left shows the normal prostate and flow of urine from the bladder through the urethra. Panel on the right shows an enlarged prostate pressing on the bladder and urethra, blocking the flow of urine. (Photo credit: Wikipedia)

A major question in cancer research has been whether virus infection plays a role in cancers of the genitourinary tract.

Now there seem to be a new evidence suggesting human polyomavirus BK is involved in maintaining and enhancing an environment suitable for prostate cancer growth. The research results were published in the August Journal of Virology, and the authors hope that these findings could lead to preventive and/or therapeutic prostate cancer vaccines.

(G. Sais, S. Wyler, T. Hudolin, I. Banzola, C. Mengus, L. Bubendorf, P.J. Wild, H.H. Hirsch, T. Sulser, G.C. Spagnoli, and M. Provanzano, 2012. Differential patterns of large tumor antigen-specific immune responsiveness in patients with BK polyomavirus-positive prostate cancer or benign prostatic hyperplasia. J. Virol. 86:8461-8471.)

Download a copy of the article at: http://bit.ly/asm0812b

 

 

 

 

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