Gene/Protein
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Enzyme
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Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P06889 (
Mol
)
630,302
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The effect of vasoactive intestinal peptide (VIP) on cyclooxygenase-2 (COX-2) expression was analyzed in human prostate non-neoplastic (RWPE-1) as well as cancer androgen-dependent (LNCaP) and independent (PC3) cells. The three cell lines expressed VIP mRNA and VIP peptide, as measured by RT-PCR and immunochemistry, which supports an autocrine/paracrine action of VIP in the prostate gland. VIP levels were progressively higher from non-neoplastic to androgen-dependent and independent cells. Real-time RT-PCR and Western-blotting showed that VIP stimulated both COX-2 mRNA and protein expression in a faster manner as
prostate cancer stage
progressed (i.e. RWPE1<LNCaP<PC3 cells). Furthermore, VIP induced higher levels of COX-2 protein expression in cancer cells as compared with non-neoplastic cells. The anti-inflammatory agent curcumin blocked VIP-induced COX-2 expression in all cell lines studied supporting the involvement of nuclear factor-kappaB (NFkappaB) in such a response. In fact, VIP increased the translocation of the NFkappaB p50 subunit to the nucleus and the binding of the active form to its target gene promoter, as measured by Western-blotting and ELISA, respectively. VIP provoked faster responses according to the most aggressive status in cancer progression (androgen-independent situation). These results together with the existence of two NFkappaB sites in the COX-2 gene promoter together suggest that COX-2 may be a target for VIP in prostate cancer progression. On the other hand, VIP could be a proinflammatory cytokine acting through the NFkappaB/COX-2 system.
Mol
Cell Endocrinol 2007 May 30
PMID:Vasoactive intestinal peptide induces cyclooxygenase-2 expression through nuclear factor-kappaB in human prostate cell lines Differential time-dependent responses in cancer progression. 1743 57
Protein tyrosine kinase 7 (PTK7) has been studied in various tumors, but its role in prostate cancer remains unknown. This study is aimed to investigate the prognostic and predictive significance of PTK7 in patients with prostate cancer. PTK7 expression was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis in 20 pairs of benign prostatic hyperplasia specimens and prostate cancer specimens. Then, we examined the immunohistochemical expression of PTK7 in 180 prostate cancer specimens and evaluated its clinical significances. Elevated PTK7 expression was significantly associated with lymph node metastases, seminal vesicle invasion,
prostate cancer stage
, the higher preoperative prostate-specific antigen, the higher Gleason score, angiolymphatic invasion, and biochemical recurrence. The results revealed that the overexpression of PTK7 in prostate cancer was an independent prognostic factor for poor overall survival and biochemical recurrence-free survival. The present data provide evidence that PTK7 predicts lymph node metastasis and poor overall survival and biochemical recurrence-free survival, highlighting its potential function as a therapeutic target for prostate cancer.
Int J
Mol
Sci 2014 Jul 01
PMID:Protein tyrosine kinase 7 (PTK7) as a predictor of lymph node metastases and a novel prognostic biomarker in patients with prostate cancer. 2498 51
Diagnostic studies of accuracy targeting sensitivity and specificity are commonly done in a paired design in which all modalities are applied in each patient, whereas cost-effectiveness and cost-utility analyses are usually assessed either directly alongside to or indirectly by means of stochastic modeling based on larger randomized controlled trials (RCTs). However the conduct of RCTs is hampered in an environment such as ours, in which technology is rapidly evolving. As such, there is a relatively limited number of RCTs. Therefore, we investigated as to which extent paired diagnostic studies of accuracy can be also used to shed light on economic implications when considering a new diagnostic test. We propose a simple decision tree model-based cost-utility analysis of a diagnostic test when compared to the current standard procedure and exemplify this approach with published data from lymph node staging of prostate cancer. Average procedure costs were taken from the Danish Diagnosis Related Groups Tariff in 2013 and life expectancy was estimated for an ideal 60 year old patient based on
prostate cancer stage
and prostatectomy or radiation and chemotherapy. Quality-adjusted life-years (QALYs) were deduced from the literature, and an incremental cost-effectiveness ratio (ICER) was used to compare lymph node dissection with respective histopathological examination (reference standard) and (18)F-fluoromethylcholine positron emission tomography/computed tomography (FCH-PET/CT). Lower bounds of sensitivity and specificity of FCH-PET/CT were established at which the replacement of the reference standard by FCH-PET/CT comes with a trade-off between worse effectiveness and lower costs. Compared to the reference standard in a diagnostic accuracy study, any imperfections in accuracy of a diagnostic test imply that replacing the reference standard generates a loss in effectiveness and utility. We conclude that diagnostic studies of accuracy can be put to a more extensive use, over and above a mere indication of sensitivity and specificity of an imaging test, and that health economic considerations should be undertaken when planning a prospective diagnostic accuracy study. These endeavors will prove especially fruitful when comparing several imaging techniques with one another, or the same imaging technique using different tracers, with an independent reference standard for the evaluation of results.
Am J Nucl Med
Mol
Imaging 2015
PMID:Added value of cost-utility analysis in simple diagnostic studies of accuracy: (18)F-fluoromethylcholine PET/CT in prostate cancer staging. 2597 39