The influence of α1-antagonist on the expression pattern of TNF receptor family in primary culture of prostate epithelial cells from BPH patients

Drewa, Tomasz; Wolski, Zbigniew; Misterek, Bartosz; Dębski, Robert; Styczyński, Jan

doi:10.1038/sj.pcan.4500978

Cited by 6 publications

(9 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…44 Instead, molecular targets consistent with tumour necrosis factor (TNF)--related activity were identified. 44,45 In the mouse prostate reconstitutional model, doxazosin induced apoptosis and increased TGF-ß protein expression with no effect on cell proliferation. 14 However, in spontaneously hypertensive rats, terazosin suppressed cellular proliferation with prominent effects on prostate histology that were abolished one month following treatment discontinuation.…”

Section: Discussionmentioning

confidence: 99%

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Mitropoulos

Kyroudi-Voulgari²,

Christelli³

et al. 2009

CIM

View full text Add to dashboard Cite

Purpose: Alpha1-adrenergic receptor antagonists may not act solely on smooth muscle contractility. We evaluated the in vivo effect of the alpha1 blocker, terazosin, on the expression of basic fibroblast growth factor (bFGF) in the rat ventral prostate. Methods: Wistar rats were treated with terazosin (1.2 mg/ kg body weight, po, every second day) for 120 days. The expression of bFGF was assessed immuno-histochemically in tissue sections and by Western blotting in whole tissue preparations. Results: Terazosin treatment did not affect prostate weight or histomorphology. In the control group, epithelial and stromal cells demonstrated positive staining for the antibFGF antibody. In contrast, the same staining in terazosintreated specimens was either absent or extremely weak. An analogous difference was observed among the corresponding immunoblots. Conclusions: These findings implicate the reduction of bFGF expression by terazosin as a potential additional molecular mechanism of its action that may include alterations in peptide growth factor mediated prostate homeostasis.Drugs that block the action of sympathetic neurotransmitters on 1-adrenergic receptors ( 1-ADRs) are widely used for the treatment of patients with benign prostate hyperplasia (BPH)-related lower urinary tract symptoms. The rationale for their use stems is that they effectively relax prostate smooth muscles, 1 which represent approximately 40% of the cellular volume in hyperplastic glands. 2 The biological effects of extrinsic factors such as hormones and other endocrine-related agents on the prostate are mediated by various peptide growth factors produced by the gland and influence prostate growth, differentiation and function by promoting inter-and intracellular signaling between and within cell populations, through paracrine, autocrine and intracrine effects. 3 Data from several studies indicate that 1-ADR antagonists may not act solely on smooth muscle contractility. Intact autonomic innervation of the rat ventral prostate is necessary to maintain its structural and functional integrity. [4][5][6] Administration of the sympathomimetic phenylephrine induces ventral prostate hyperplasia associated with reduced rates of cellular apoptosis, but not with increased rates of cellular proliferation. 7 Moreover, rapid proliferation of prostatic epithelial cells has been seen in the spontaneously hypertensive rat, 8 an animal model with in-ORIGINAL RESEARCH

show abstract

Section: Discussionmentioning

confidence: 99%

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Mitropoulos

Kyroudi-Voulgari²,

Christelli³

et al. 2009

CIM

View full text Add to dashboard Cite

show abstract

“…We observe, second on the ranking of all samples, a probe for CD40 (TNFRSF5, B-cell surface antigen CD40), BX381481 with a Spearman correlation of 0.7616. Loss of CD40 expression has been previously reported in prostate cancer and it is the object of a study that attempts to establish dendritic cell gene therapies [504], [505], [506], [507], [508], [509], [510], [511], [512], [513], [514], [515], [516], [517], [518], [519], [520], [521], [522]. We will continue discussing CD40 in the following subsection in concert with other genes.…”

Section: Resultsmentioning

confidence: 99%

Cancer Biomarker Discovery: The Entropic Hallmark

Berretta

Moscato

2010

PLoS ONE

View full text Add to dashboard Cite

BackgroundIt is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods.Methodology/Principal FindingsUsing melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer.Conclusions/SignificanceWe thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-througput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases.

show abstract

“…Doxazosin is commonly used in BPH treatment and induces apoptosis among prostate stroma smooth muscle and epithelial cells [12]. In our previous study we observed decreasing number of viable cells in co-cultures of CD133 + /CD133 cells after doxazosin application [7].…”

Section: Discussionmentioning

confidence: 98%

Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients

Bajek¹,

Pokrywka²,

Wolski³

et al. 2011

cejurol4/2011

View full text Add to dashboard Cite

IntroductionInduction of apoptosis in prostatic epithelial cells by doxazosin, terazosin and prazosin has been well documented. However, the biochemical pathways of doxazosin action is still unclear. Aforementioned drugs should lead to decrease of prostate volume, although this effect was never observed in patients suffering from BPH after treatment with α1-antagonists. Probably, it is connected with cancer stem cells’ resistance on chemotherapeutic agents. The aim of this study was to compare incidence of apoptosis induced by doxazosin in progenitor and differentiated cells isolated from human prostate epithelium.Material and methodsFor this purpose tissue specimens were obtained from 10 patients suffering from BPH, the primary cultures of prostate epithelium were established and CD133 MicroBeads sorting was prepared. Both, CD133(+)/CD133(-) co-cultures and CD133(+) cells were incubated with different concentration of doxazosin for 12 h. Cell viability and apoptosis was estimated with Annexin V-FITC.Results12 h incubation of CD133(+)/CD133(-) co-cultures with doxazosin resulted in increase of apoptotic cells, while in CD133(+) cultures no changes were observed. Correlation between apoptotic cell number and doxazosin concentration in CD133(+)/ CD133(-) co-cultures group was high (R = 0.99).ConclusionDoxazosin induced apoptosis in co-cultures of progenitor and differentiated epithelial cells. However, progenitor cells were not susceptible to apoptosis, what can be a reason of treatment failure in BPH patients.

show abstract

The influence of α1-antagonist on the expression pattern of TNF receptor family in primary culture of prostate epithelial cells from BPH patients

Cited by 6 publications

References 32 publications

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Cancer Biomarker Discovery: The Entropic Hallmark

Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients

Contact Info

Product

Resources

About