Pathophysiology of benign prostate enlargement and lower urinary tract symptoms: Current concepts

Benign prostatic hyperplasia cell line viability and modulation of jm-27 by doxazosin and ibuprofen

Aberrant activation of the androgen receptor (AR) plays a key role during prostate cancer (PCa) development and progression to castration-resistant prostate cancer (CR-PCa) after androgen deprivation therapy, the mainstay systemic treatment for PCa. New strategies to abrogate AR activity and biomarkers that predict aggressive tumor behavior are essential for improved therapeutic intervention. PCa tissue microarrays herein reveal that prostate-associated gene 4 (PAGE4), an X-linked cancer/testis antigen, is highly up-regulated in the epithelium of preneoplastic lesions compared with benign epithelium, but subsequently decreases with tumor progression. We show that AR signaling is attenuated in PAGE4-expressing cells both in vitro and in vivo , most likely via impaired androgen-induced AR nuclear translocation and subsequently reduced AR protein stabilization and phosphorylation at serines 81 and 213. Consistently, epithelial PAGE4 protein levels inversely correlated with AR activation status in hormone-naive and CR-PCa clinical specimens. Moreover, PAGE4 impaired the development of CR-PCa xenografts, and strong PAGE4 immunoreactivity independently predicted favorable patient survival in hormone-naive PCa. Collectively, these data suggest that dysregulation of epithelial PAGE4 modulates AR signaling, thereby promoting progression to advanced lethal PCa and highlight the potential value of PAGE4 as a prognostic and therapeutic target.

PAGE4 Positivity Is Associated with Attenuated AR Signaling and Predicts Patient Survival in Hormone-Naive Prostate Cancer

The negotiating mandate for the Doha Development Agenda is both broad and comprehensive. This paper focuses on the basic mandate given to negotiators in the area of tariffs and trade in industrial products. With respect to developed country markets the key issue is how to tackle the residual protection arising from low overall levels of protection. We have identified a number of products at the 4-digit level of the HS system where issues of peaks and escalation need to be addressed. For developing countries there are two issues – their high levels of tariffs and the limited coverage of bindings for some Members. These, however, do not preclude problems of peaks and escalation such as those that we have identified in developed country markets. Finally, for LDCs the issues are the degree of effective non-reciprocal market access granted by developed countries, and the very high levels of protection they face in developing country markets, and the role that high levels of protection are playing as industry policy instruments in their own economies.

/pdf/industrial-tariff-liberalization-and-the-doha-development-3siap9etzy.pdf

Industrial tariff liberalization and the Doha Development Agenda

Simple Summary In this review paper, we explore the role of chronic inflammation in the pathogenesis of prostatic diseases, such as chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic inflammation is a significant risk factor for these diseases, but the molecular mechanisms behind it are not yet fully understood. Previous attempts to investigate, link, and target inflammatory signaling molecules in men with these conditions have been clinically ambiguous and inconclusive. As a result, we proposed a paradigm shift in which less-explored molecules in the inflammatory signaling cascade are investigated as possible therapeutic targets for prostate diseases. In addition, we comprehensively discuss how aberrant signaling of these molecules may cause prostate cancer stemness, neuroendocrine differentiation, castration resistance, metabolic reprogramming, and immunosuppression. In conclusion, we forecast that targeting the interleukin-1 receptor-associated kinases (IRAKs) signaling pathway may provide a far more effective therapeutic or prophylactic strategy for the management of chronic inflammation-driven prostatic diseases. Abstract Chronic inflammation is now recognized as one of the major risk factors and molecular hallmarks of chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate tumorigenesis. However, the molecular mechanisms by which chronic inflammation signaling contributes to the pathogenesis of these prostate diseases are poorly understood. Previous efforts to therapeutically target the upstream (e.g., TLRs and IL1-Rs) and downstream (e.g., NF-κB subunits and cytokines) inflammatory signaling molecules in people with these conditions have been clinically ambiguous and unsatisfactory, hence fostering the recent paradigm shift towards unraveling and understanding the functional roles and clinical significance of the novel and relatively underexplored inflammatory molecules and pathways that could become potential therapeutic targets in managing prostatic diseases. In this review article, we exclusively discuss the causal and molecular drivers of prostatitis, BPH, and prostate tumorigenesis, as well as the potential impacts of microbiome dysbiosis and chronic inflammation in promoting prostate pathologies. We specifically focus on the importance of some of the underexplored druggable inflammatory molecules, by discussing how their aberrant signaling could promote prostate cancer (PCa) stemness, neuroendocrine differentiation, castration resistance, metabolic reprogramming, and immunosuppression. The potential contribution of the IL1R-TLR-IRAK-NF-κBs signaling molecules and NLR/inflammasomes in prostate pathologies, as well as the prospective benefits of selectively targeting the midstream molecules in the various inflammatory cascades, are also discussed. Though this review concentrates more on PCa, we envision that the information could be applied to other prostate diseases. In conclusion, we have underlined the molecular mechanisms and signaling pathways that may need to be targeted and/or further investigated to better understand the association between chronic inflammation and prostate diseases.

The Molecular Basis and Clinical Consequences of Chronic Inflammation in Prostatic Diseases: Prostatitis, Benign Prostatic Hyperplasia, and Prostate Cancer

Despite intense research efforts, the etiology of prostatic hyperplasia associated with both benign prostatic hyperplasia (BPH) and prostate cancer remains poorly understood. Our previous studies using array technology identified JM-27 as a transcript that is dramatically up-regulated in the prostates of patients with symptomatic BPH and in normal, adjacent prostatic regions of patients with prostate cancer. In the present study, using an extended sample set, we show a correlation between the messenger RNA and protein expression of JM-27. To investigate the possible functions of this gene, its expression in the rat prostate was examined by immunoblot analysis using a polyclonal antibody specific to human JM-27. This antibody reacts with 2 rat polypeptides of 17 kd and 27 kd in size. Whereas the 27-kd form of the JM-27 protein found in human prostate is selectively expressed in the dorsolateral lobes of the rat prostate, the 17-kd form is expressed only in the ventral lobe. Expression of both forms of this protein appears to be androgen-regulated. There is a time-dependent decrease in expression of the protein products in the ventral and dorsolateral lobes of the rat prostate after castration. Administration of exogenous testosterone in castrated animals maintains protein expression in both lobes. Androgens are believed to play a central role in prostate growth and development, and therefore, it is tempting to speculate that JM-27, an androgen-regulated gene, may be involved in prostatic growth regulation. Further studies are underway to evaluate such a function for JM-27 in prostatic diseases.

Androgen regulation of JM-27 is associated with the diseased prostate.

Androgen Regulation of JM-27 is Associated With the Diseased Prostate

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Sun Lu

Author Tools

Chat about Author

Papers

Androgen regulation of JM-27 is associated with the diseased prostate.

Androgen Regulation of JM-27 is Associated With the Diseased Prostate