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Disease
Symptom
Drug
Enzyme
Compound
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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)
The expression of the
adenosine deaminase
complexing protein (ADCP) was investigated by immunohistochemistry in the normal and hyperplastic human prostate, in 30 prostatic adenocarcinomas, and in seven human prostatic adenocarcinoma cell lines grown as xenografts in athymic nude mice. In the normal and hyperplastic prostate, ADCP was localized exclusively in the apical membrane and the apical cytoplasm of the glandular epithelial cells. In prostatic adenocarcinomas, four distinct ADCP expression patterns were observed: diffuse cytoplasmic, membranous, both cytoplasmic and membranous, and no ADCP expression. The expression patterns were compared with the presence of metastases. We found an inverse correlation between membranous ADCP immunoreactivity and metastatic propensity. Exclusively membranous ADCP immunoreactivity occurred only in non-metastatic tumours. In contrast, the metastatic tumours showed no or diffuse cytoplasmic ADCP immunoreactivity. This suggests that immunohistochemical detection of ADCP might predict the biological behaviour of
prostatic cancer
. However, the occurrence of membranous ADCP immunoreactivity in the xenograft of a cell line (PC-EW), derived from a prostatic carcinoma metastasis, indicates that not only the tendency to metastasize modulates ADCP expression.
...
PMID:Adenosine deaminase complexing protein (ADCP) expression and metastatic potential in prostatic adenocarcinomas. 169 38
Binding of plasminogen (Pg) to cell-surface receptors colocalized with plasminogen activators promotes Pg activation and enables cells to utilize the proteolytic activity of plasmin (Pm). Proteolysis by Pm is necessary in several physiological and pathological processes requiring extracellular matrix degradation including cell migration, tumor cell invasion and metastasis. The binding of Pg to cell-surface receptors is regulated by two major structural features: L-lysine binding sites (LBS) and negatively charged sialic acid residues located on its carbohydrate chains. Pg uses its LBS to bind to a wide spectrum of cell-surface receptors whereas binding through its sialic acid residues is limited only to receptor proteins containing cationic pockets or lectin-like modules. In this review, we discuss both mechanisms, including the identification of DPP IV as a Pg receptor and the possible physiological role of Pg/Pm in complex with DPP IV and
adenosine deaminase
(
ADA
) and /or the Na+/H+ exchanger isoform NHE-3 in
prostate cancer
.
...
PMID:Dipeptidyl peptidase IV (DPP IV/CD26) is a cell-surface plasminogen receptor. 1798 53
The relation between adenine nucleotides and cancer has already been described in literature. Considering that the enzymes ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and
adenosine deaminase
(
ADA
) act together to control nucleotide levels, we aimed to investigate the role of these enzymes in
prostate cancer
(PCa). E-NPP and
ADA
activities were determined in serum and platelets of PCa patients and controls. We also verified the influence of the Gleason score, bone metastasis and treatment in the enzyme activities. Platelets and serum E-NPP activity increased, whereas
ADA
activity in serum decreased in PCa patients. In addition, Gleason score, metastasis and treatment influenced E-NPP and
ADA
activities. We may propose that E-NPP and
ADA
are involved in the development of PCa. Moreover, E-NPP and
ADA
activities are modified in PCa patients with distinct Gleason score, with bone metastasis, as well as in patients under treatment.
...
PMID:Ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities in prostate cancer patients: influence of Gleason score, treatment and bone metastasis. 2343 54
Prostate cancer
antigen 3 (PCA3) is the most specific
prostate cancer
biomarker but its function remains unknown. Here we identify PRUNE2, a target protein-coding gene variant, which harbors the PCA3 locus, thereby classifying PCA3 as an antisense intronic long noncoding (lnc)RNA. We show that PCA3 controls PRUNE2 levels via a unique regulatory mechanism involving formation of a PRUNE2/PCA3 double-stranded RNA that undergoes
adenosine deaminase
acting on RNA (ADAR)-dependent adenosine-to-inosine RNA editing. PRUNE2 expression or silencing in
prostate cancer
cells decreased and increased cell proliferation, respectively. Moreover, PRUNE2 and PCA3 elicited opposite effects on tumor growth in immunodeficient tumor-bearing mice. Coregulation and RNA editing of PRUNE2 and PCA3 were confirmed in human
prostate cancer
specimens, supporting the medical relevance of our findings. These results establish PCA3 as a dominant-negative oncogene and PRUNE2 as an unrecognized tumor suppressor gene in human
prostate cancer
, and their regulatory axis represents a unique molecular target for diagnostic and therapeutic intervention.
...
PMID:PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3. 2608 Apr 35
Aberrant ligand-independent G protein-coupled receptor constitutive activity has been implicated in the pathophysiology of a number of cancers. The adenosine A2B receptor (A2BAR) is dynamically upregulated under pathologic conditions associated with a hypoxic microenvironment, including solid tumors. This, in turn, may amplify ligand-independent A2BAR signal transduction. The contribution of A2BAR constitutive activity to disease progression is currently unknown yet of fundamental importance, as the preferred therapeutic modality for drugs designed to reduce A2BAR constitutive activity would be inverse agonism as opposed to neutral antagonism. The current study investigated A2BAR constitutive activity in a heterologous expression system and a native 22Rv1 human
prostate cancer
cell line exposed to hypoxic conditions (2% O2). The A2BAR inverse agonists, ZM241385 [4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol] or PSB-603 (8-(4-(4-(4-chlorophenyl)piperazide-1-sulfonyl)phenyl)-1-propylxanthine), mediated a concentration-dependent decrease in baseline cAMP levels in both cellular systems. Proliferation of multiple
prostate cancer
cell lines was also attenuated in the presence of PSB-603. Importantly, both the decrease in baseline cAMP accumulation and the reduction of proliferation were not influenced by the addition of
adenosine deaminase
, demonstrating that these effects are not dependent on stimulation of A2BARs by the endogenous agonist adenosine. Our study is the first to reveal that wild-type human A2BARs have high constitutive activity in both model and native cells. Furthermore, our findings demonstrate that this ligand-independent A2BAR constitutive activity is sufficient to promote
prostate cancer
cell proliferation in vitro. More broadly, A2BAR constitutive activity may have wider, currently unappreciated implications in pathologic conditions associated with a hypoxic microenvironment.
...
PMID:Ligand-Independent Adenosine A2B Receptor Constitutive Activity as a Promoter of Prostate Cancer Cell Proliferation. 2679 3