Prostate surveillance active
To browse Academia. Skip to main content. You're using an out-of-date version of Internet Explorer. Log In Sign Up. Effects of antagonists of luteinizing hormone-and growth hormone-releasing hormone on experimental benign Behandlung von Prostatitis in Carlsbad hyperplasia and prostate cancer Ferenc Rick. Effects of antagonists of Behandlung von Prostatitis in Carlsbad hormone-and growth hormone-releasing hormone on experimental benign prostatic hyperplasia and prostate cancer.
Dissertation Effects of antagonists of luteinizing hormone- and growth hormone-releasing Behandlung von Prostatitis in Carlsbad on experimental Behandlung von Prostatitis in Carlsbad prostatic hyperplasia and prostate cancer Ferenc G. Rick, M. Advisors: Andrew V. Schally, Ph. Block, M. Ferenc G. Effects of antagonists of luteinizing hormone- and Behandlung von Prostatitis in Carlsbad hormone relasing hormone on experimental benign prostatic hyperplasia and prostate cancer Mentors: Magdolna Kovacs, M.
Rick All rights reserved. No part of this work may be reproduced in any form by any electronic or mechanical means without permission in writing from the author. Benign prostatic hyperplasia Clinical BPH Pathological BPH Theories of the etiology of BPH Models of BPH Therapy of BPH GHRH antagonists Prostate cancer Experimental benign prostatic hyperplasia studies Human prostate cancer xenograft studies Peptides and reagents In vivo experimental models Behandlung von Prostatitis in Carlsbad procedures and morphological analyses Immunohistochemical staining Total DNA Isolation.
Ligand competition assays Statistical Analysis. Inhibitory effects of antagonists of growth hormone releasing hormone on experimental prostate cancers are associated with upregulation of wild-type p53 and decrease in p21 and mutant p53 proteins Study Introduction and background 1. Benign prostatic hyperplasia Benign prostatic hyperplasia BPH is an extremely common urinary tract disorder that can be described clinically or pathologically.
Clinical BPH is commonly viewed as benign enlargement of the prostate, which contributes to an array of urinary voiding difficulties that can range from bothersome lower urinary tract symptoms LUTS to significantly impacting quality of life among older men 1.
Pathologic BPH is the histological determination of non-neoplastic new prostatic growth in adult men. The high prevalence of BPH in older men has led some to consider prostatic hyperplasia to be a ubiquitous result of aging 3.
The precise molecular mechanisms underlying the induction, maintenance, and development of clinical sequelae resulting from BPH are incompletely understood 4. Clinical BPH The human prostate consists of four separate histologic Behandlung von Prostatitis in Carlsbad central, peripheral, transition, and anterior fibromuscular 5.
While prostate cancer is found mostly in the peripheral zone, virtually all clinically significant BPH develops in the transition zone of the prostate 6.
Macroscopic growth of the transition zone can cause narrowing of the urethra as it passes through the prostate, leading to a bladder outlet obstruction BOOwhich may affect the flow of urine. In men, the prostate is the most common cause of obstruction.
However, serum prostatic specific antigen PSA does correlate with prostate volume, and men with larger prostates and elevated serum PSA are Behandlung von Prostatitis in Carlsbad higher risk of experiencing more significant symptoms, including ultimate progression to acute urinary retention 1. LUTS Behandlung von Prostatitis in Carlsbad bladder storage symptoms such as increased urinary frequency, urgency, and nocturia; difficulty starting the stream of urine decreased urinary flow and incomplete emptying are generally attributed to problems with bladder emptying 8.
Other significant causes and contributing factors to LUTS are age-related declines in detrusor function and systemic medical conditions 8,9. Experiencing an acute urinary retention and nocturia are clinical markers of increased mortality risk that likely represent the high comorbidity of BPH with other systemic medical conditions 4, Pathological BPH Pathologically, BPH is characterized by hyperplastic epithelial and stromal growth that combine into microscopic and macroscopic nodules in the prostate gland More frequently, BPH is described as epithelial containing mostly prostate epithelial cellsmixed containing stromal and epithelial cells Behandlung von Prostatitis in Carlsbad, and stromal containing mostly stromal cells The initial nodules that develop in BPH are found in the periurethral region and are typically stromal, composed of fibrous tissue mixed with some smooth muscle Infrequently, BPH nodules may be found in the peripheral zone, which is palpable with digital rectal examination, and are typically composed of epithelial glandular elements The lack of glandular elements Behandlung von Prostatitis in Carlsbad stromal BPH nodules, and the observation of zonal differences in the initiation of BPH nodules suggest a distinct etiology of stromal nodules compared to BPH with glandular components.
When the transition zone enlarges macroscopically, due to BPH nodular growth, it can obstruct the flow of urine through the prostatic urethra and hence contribute to LUTS.
Understanding the key molecular mechanisms for how distinct BPH nodules develop and are associated with LUTS is essential to developing clinical management tools for these diseases.
Theories of the etiology of BPH The precise molecular etiology of BPH is complicated and unknown, but several theories have been proposed. One prominent theory of BPH pathogenesis was proposed by McNeal and is termed the embryonic reawakening theory 6.
InMcNeal posited that prostatic hyperplasia represents an awakening of hormonally-mediated developmental processes 6. Through precise study of 63 autopsy prostates, he noted that BPH nodules arose from the transition zone 6. Consistent with this observation, Cunha demonstrated that androgen regulation and paracrine interactions were necessary for prostate glandular development and maintenance, establishing the key role of stromal—epithelial cell interactions in the prostate A hormonal etiology involving dysregulation of stromal—epithelial cell interactions is recognized as important for BPH development, but the precise pathogenesis remains to be Behandlung von Prostatitis in Carlsbad.
A schematic showing the confluence of factors for the development of BPH Androgens, in particular DHT, are widely accepted as essential for the growth and development of the human prostate 3. Although an association between concentrations of androgens in the blood or prostate and risk of BPH or LUTS cannot be consistently demonstrated in epidemiological studies 23it is believed that androgens play a permissive role in BPH pathogenesis 3. Androgen ablation by orchiectomy or suppression of the pituitary—testicular axis effectively reduces prostate volume and improves symptoms caused by BPH, but also leads to adverse effects unacceptable to many patients.
Increasing evidence from epidemiological, animal and in vitro studies supports a role for estrogens in the pathogenesis of BPH 3. Most epidemiological studies have shown an association between circulating estrogen levels and the risk of BPH or LUTS, and many experimental studies have reported Behandlung von Prostatitis in Carlsbad stimulation of prostate stromal cell proliferation in vitro 24, Studies of human prostate tissues have indicated differential localization of ER subtypes in the two main cell compartments of the prostate.
Current evidence suggests that estrogens and androgens interact with one another in regulating prostate cell growth in vivo 3. Age is an associated factor for the development of both histologic and clinically significant BPH.
Although nearly all men will develop histologic BPH with age, it is thought that BPH initiation occurs in younger men 30 years Behandlung von Prostatitis in Carlsbad age 2. Furthermore, younger men develop BPH but at much lower rates compared to aged men 2. These events are predominantly changes in prostate cell—cell interactions and alterations of highly specialized cell types responsible for tissue homeostasis and function.
Alonso-Magdalena et al proposed that BPH is not a proliferative disease of the stroma but the result of accumulation of myofibroblasts and smooth muscle cells, as a consequence of epithelial proliferation and epithelial-mesenchymal transition EMT This Behandlung von Prostatitis in Carlsbad involves changes in gene expression that disrupt epithelial polarity and establish a mesenchymal phenotype, with concomitant alterations in cytoskeletal organization, cell adhesion, and production of extracellular matrix.
Lin et al demonstrated mesenchymal stem cell markers on primary stromal cells from BPH patients, which have strong proliferative potential and ability to differentiate to myogenic, adipogenic and osteogenic lineages An emerging body of evidence suggests that inflammation may play a key role in the development and progression of BPH 20, Clinically, several cross-sectional studies have proposed that a relationship exists between the presence of inflammatory infiltrates and an increase in prostate volume.
Di Silverio et al. This minor correlation between prostatic inflammation and presence of LUTS may be expected given the relatively modest correlations that have been found between prostate volume and LUTS Additionally, in a Wistar rat model, administration of an immunostimulator resulted in epithelial proliferation Recent reviews of the pathogenesis of BPH highlighted the differential expression of cytokines and growth factors in BPH tissue suggesting a role for inflammation in the propagation of BPH 16, An up-to-date outline of the current state of knowledge in regard to the impact of inflammation on the pathogenesis of BPH was reported by Kramer et al.
Chronic inflammatory infiltrates, mostly composed of activated T cells and macrophages, are often associated with BPH nodules 35, Subsequently, surrounding cells are killed by unknown mechanism and are replaced by fibromuscular nodules Recent evidence from cell culture systems and immunohistochemical and mRNA analyses of BPH tissues on expression profiles of growth-regulatory proteins and cytokines has provided insights into the potential role of these growth factors and cytokines in the pathogenesis of BPH.
Several stromal and epithelial growth factors and inflammatory cytokines have been reported to be overexpressed in BPH tissues or BPH-derived stromal cells These include members of the fibroblast e. VEGF-A and downstream effector molecules as well as a variety of interleukins e.
IL-2, IL-4, IL-8 and IL that, Behandlung von Prostatitis in Carlsbad together, could lead to abnormal stromal and epithelial cell growth within the transition zone of the prostate 21, Additionally, human genetics, socioeconomic backgrounds, and lifestyles are highly variable between populations.
Finally, the cost associated with human research is high. For these reasons and others, use of humans is not ideal for early stages of BPH research 4. Table 1. Differentiation DOI: The use of xenografts is particularly well suited for studies evaluating maintenance or treatment of BPH, however, with all xenograft studies several drawbacks apply.
They are less suitable for researching the development and prevention of BPH. BOO is not possible with xenograft models. Tissue recombination, a technique that utilizes epithelia and stroma from various species or organs, has successfully been used for the study of a wide range of normal and pathogenic states 4, In this regard, Barclay and colleagues utilized tissue recombination methods using benign human prostatic epithelial cells BPH-1 cell line 48 and human stroma from BPH or normal prostates