Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Target Concepts:
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Query: UMLS:C0376358 (
prostate cancer
)
59,338
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Protein phosphatase 1 nuclear-targeting subunit (PNUTS) is ubiquitously expressed and associates with PTEN and
protein phosphatase
1 (PP1) to control its activity. The role of PNUTS overexpression has hardly been studied in cancer. In this study, we used immunohistochemistry to quantitate PNUTS expression on a tissue microarray containing 17,747 clinical
prostate cancer
specimens. As compared to normal prostate epithelium, PNUTS expression was often higher in cancer. Among 12,235 interpretable tumors, PNUTS staining was negative in 21%, weak in 34%, moderate in 35%, and strong in 10% of cases. High PNUTS expression was associated with higher tumor stage, classical and quantitative Gleason grade, nodal stage, surgical margin, Ki67 labeling index, and early biochemical recurrence (
p
< 0.0001 each). PNUTS expression proved to be a moderate prognostic parameter with a maximal univariable Cox proportional hazard for PSA recurrence-free survival of 2.21 compared with 5.91 for Gleason grading. It was independent from established prognostic parameters in multivariable analysis. Comparison with molecular data available from earlier studies using the same TMA identified associations between high PNUTS expression and elevated androgen receptor expression (
p
< 0.0001), presence of
TMPRSS2:ER
G fusion (
p
< 0.0001), and 8 of 11 chromosomal deletions (3p13, 5q21, 8p21, 10q23, 12p13, 13q14, 16q24, and 17p13;
p
< 0.05 each). Particularly strong associations with PTEN and 12p13 deletions (
p
< 0.0001 each) may indicate a functional relationship, which has already been established for PNUTS and PTEN. PNUTS had no additional role on outcome in PTEN-deleted cancers. In conclusion, the results of our study identify high PNUTS protein levels as a predictor of poor prognosis possibly linked to increased levels of genomic instability. PNUTS measurement, either alone or in combination, might be of clinical utility in prostate cancers.
...
PMID:Upregulation of Phosphatase 1 Nuclear-Targeting Subunit (PNUTS) Is an Independent Predictor of Poor Prognosis in Prostate Cancer. 3237 72
Prostate cancer
patients are often treated with radiotherapy. MnTE-2-PyP, a superoxide dismutase (SOD) mimic, is a known radioprotector of normal tissues. Our recent work demonstrated that MnTE-2-PyP also inhibits
prostate cancer
progression with radiotherapy; however, the mechanisms remain unclear. In this study, we identified that MnTE-2-PyP-induced intracellular H
2
O
2
levels are critical in inhibiting the growth of PC3 and LNCaP cells, but the increased H
2
O
2
levels affected the two cancer cells differently. In PC3 cells, many proteins were thiol oxidized with MnTE-2-PyP treatment, including Ser/Thr
protein phosphatase
1 beta catalytic subunit (PP1CB). This resulted in reduced PP1CB activity; however, overall cell cycle progression was not altered, so this is not the main mechanism of PC3 cell growth inhibition. High H
2
O
2
levels by MnTE-2-PyP treatment induced nuclear fragmentation, which could be synergistically enhanced with radiotherapy. In LNCaP cells, thiol oxidation by MnTE-2-PyP treatment was not observed previously and, similarly to PC3 cells, there was no effect of MnTE-2-PyP treatment on cell cycle progression. However, in LNCaP cells, MnTE-2-PyP caused an increase in low RNA population and sub-G
1
population of cells, which indicates that MnTE-2-PyP treatment may cause cellular quiescence or direct cancer cell death. The protein oxidative modifications and mitotic catastrophes caused by MnTE-2-PyP may be the major contributors to cell growth inhibition in PC3 cells, while in LNCaP cells, tumor cell quiescence or cell death appears to be major factors in MnTE-2-PyP-induced growth inhibition.
...
PMID:MnTE-2-PyP Suppresses Prostate Cancer Cell Growth via H
2
O
2
Production. 3251 86
Dioscin possesses antioxidant effects and has anticancer ability in many solid tumors including
prostate cancer
(PCa). Nevertheless, its effect and mechanism of anti-PCa action remain unclear. The tyrosine
protein phosphatase
SHP1, which contains an oxidation-sensitive domain, has been confirmed as a target for multicancer treatment. Further studies are needed to determine whether dioscin inhibits PCa through SHP1. We performed
in vitro
studies using androgen-sensitive (LNCaP) and androgen-independent (LNCaP -C81) cells to investigate the anticancer effects and possible mechanisms of dioscin after administering interleukin-6 (IL-6) and dihydrotestosterone (DHT). Our results show that dioscin inhibited cell growth and invasion by increasing SHP1 phosphorylation [p-SHP1 (Y536)] and inhibiting the subsequent P38 mitogen-activated protein kinase signaling pathway. Further
in vivo
studies confirmed that dioscin promoted caspase-3 and Bad-related cell apoptosis in these two cell lines. Our research suggests that the anticancer effects of dioscin on PCa may occur through SHP1. Dioscin may be useful to treat androgen-sensitive and independent PCa in the future.
...
PMID:Dioscin Promotes Prostate Cancer Cell Apoptosis and Inhibits Cell Invasion by Increasing SHP1 Phosphorylation and Suppressing the Subsequent MAPK Signaling Pathway. 3279 45
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