Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perlecan (Pln) is a major heparan sulfate proteoglycan (HSPG) of extracellular matrices and bone marrow stroma. Pln, via glycosaminoglycans in domains I and V, acts as a co-receptor for delivery of heparin binding growth factors (HBGFs) that support cancer growth and vascularization. Specifically, glycosaminoglycans bind HBGFs and activate HBGF receptors, including those for FGF-2 and VEGF-A. The contribution of Pln to prostate cancer growth was tested using a ribozyme approach to knockdown Pln expression levels. Transfection into the androgen-independent, bone targeted prostate cancer line, C4-2B, and efficient stable knockdown of Pln was demonstrated by quantitative PCR, immunohistochemistry and immunoblotting. Three individually isolated subclones with 75-80% knockdown in Pln mRNA, protein expression and secretion into ECM were used to study in vitro growth responses to FGF-2 and VEGF-A. While cells with normal Pln levels responded to both HBGFs, knockdown cells responded poorly. All lines responded to serum growth factors and IGF-I. Anchorage-independent growth assays showed reduced colony size and cohesiveness by all Pln deficient subclones compared to parental C4-2B cells. In vivo effects of Pln knockdown were measured by inoculating knockdown and control ribozyme transfected cell lines into athymic mice. A reduced growth rate, smaller tumor size, diminished vascularization and failure to elevate serum PSA characterized mice bearing Pln knockdown C4-2B cells. Poor vascularization correlated with reduced levels of VEGF-A secreted by Pln knockdown lines. We conclude that Pln is an essential ECM component involved in growth responses of metastatic prostate cancer cells to HBGFs deposited in local and metastatic microenvironment.
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PMID:Perlecan knockdown in metastatic prostate cancer cells reduces heparin-binding growth factor responses in vitro and tumor growth in vivo. 1628 81

In this study, we screened in vitro the different capabilities of trophic factors with promising effect for enhancing selective regeneration and thus promoting specific reinnervation of target organs after peripheral nerve regeneration. We found that FGF-2 (18 kDa) was the trophic factor that exerted the most selective effect in promoting neurite outgrowth of spinal motoneurons both in terms of elongation and arborization. The mechanism underlying this effect on neuritogenesis seems related to FGF-2 enhancing the interaction between FGFR-1 and PSA-NCAM. The interaction of these two receptors is important during the early stages of neuritogenesis and pathfinding, while integrin alpha7B subunit seems to play a role during neurite stabilization.
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PMID:FGF-2 low molecular weight selectively promotes neuritogenesis of motor neurons in vitro. 2327 75

Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the "Prof. Dr. Theodor Burghele" Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life.
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PMID:The remote effects of intravitreal anti-VEGF therapy. 2792 44