Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor metastasis is an important clinical problem, contributing to the majority of cancer-related deaths. The recent discovery of metastasis suppressor genes, such as N-myc downstream-regulated gene-1 (Ndrg-1), has introduced a novel approach to treating cancer and preventing metastasis. Ndrg-1 has been identified as a protein involved in the differentiation of epithelial cells. In addition, Ndrg-1 expression can be regulated by androgens and is involved in the pathology of the disease, Hereditary Motor and Sensory Neuropathy-Lom (HMSNL). However, one of the most well documented links between Ndrg-1 and pathophysiology is its association with inhibition of tumor metastasis. The expression of Ndrg-1 was found to be significantly downregulated in a variety of different neoplasms including breast, colon and prostate cancer. Furthermore, Ndrg-1 expression was shown to be negatively correlated with tumor metastasis. Studies in vitro and in vivo have demonstrated a significant reduction in the metastatic ability of cells overexpressing Ndrg-1. The ability of these cells to invade was also compromised. The Gleason grade of prostate and breast cancers was found to correlate with Ndrg-1 expression, with more advanced and poorly differentiated tumors having lower Ndrg-1 levels. Recently, Ndrg-1 expression was demonstrated to be regulated by cellular iron levels and induced by iron chelators. These latter compounds were recently identified as potential anticancer agents as they selectively prevent cancer cell proliferation and lead to apoptosis. The discovery that iron chelators also increase Ndrg-1 expression further augments their antitumor activity and provides a novel strategy for the treatment of cancer and its metastasis.
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PMID:The metastasis suppressor, Ndrg-1: a new ally in the fight against cancer. 1692 Jul 33

Endorectal MRI, now a fast and reliable examination, is an essential part of the local work-up for prostate cancer, regardless of the treatment envisioned. MRI spectroscopy, an actively maturing technique, makes it possible to combine anatomical and metabolic information that can be used for detection, staging, and posttreatment follow-up of prostate cancer. In patients with repeated negative biopsies, spectroscopy and dynamic gadolinium injection will be able to detect atypical cancer sites that escape routine biopsies. MRI of lymph nodes with ultrasmall superparamagnetic iron oxide (USPIO) injection will improve diagnostic performance in the detection of lymph node metastases. In the planning of conservative treatment, MRI and especially spectroscopic MRI will increasingly replace computed tomography. Finally, endorectal MRI of the prostate, spectroscopy, and dynamic injection will show local recurrences.
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PMID:[MRI of prostate cancer]. 1755 16

Urokinase-type plasminogen activator (uPA) on prostate cancer cell surfaces mediates pericellular proteolysis and destruction of extracellular matrix barriers to tumor invasion and metastasis. Increased expression of tumor-associated uPA leads to enhanced tumor dissemination and poor cancer outcomes in men with prostate cancer. Expression of uPA is regulated in part by the oxidant-sensitive transcription factor, NF-kappa B (NF-kappaB), which is activated by intracellular reactive oxygen intermediates (ROI). This study examined the effect of iron on the production of ROI, activation of NF-kappaB and expression of uPA in the human prostate cancer cell line, PC-3. Treatment of PC-3 cells with iron in the form of ferric nitrilotriacetate (FeNTA) in the absence of added transferrin resulted in a dose-dependent increase in cellular ferritin content in both the presence and absence of neutralizing antibody to the transferrin receptor. Cellular uptake of iron resulted in stimulation of intracellular ROI production, and increases in uPA mRNA, antigen, and activity. Concurrent treatment with the iron chelator, desferrioxamine (DFO) abrogated these effects, and treatment with DFO alone inhibited constitutive uPA production. Finally, we observed nuclear translocation, and therefore activation of NF-kappaB in response to iron exposure. We conclude that iron enters PC-3 cells via a non-transferrin dependent pathway and increases uPA expression. Our data indicate that one mechanism by which iron may stimulate uPA production is through the generation of intracellular ROI and activation of NF-kappaB-mediated signaling pathways.
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PMID:Iron stimulates urokinase plasminogen activator expression and activates NF-kappa B in human prostate cancer cells. 1757 74

Tumor necrosis factor alpha induces increased reactive oxygen species (ROS) generation in different experimental models. However, the nature of this phenomenon is still unknown. We hypothesized that TNF-induced ROS formation is due to JNK-regulated ferritin degradation and an increase in labile iron pool (LIP). We used as a model human prostate cancer cells, DU145. TNF treatment induced ROS formation, which was reduced to the control level in cells pretreated with desferrioxamine, an iron chelator. TNF induced a drop in light chain of the ferritin level, as judged by immunoblotting and an increase in LIP, evaluated by calcein fluorescence. Moreover, we observed that the JNK inhibitor SP600125 abolished TNF-induced changes in LIP, which suggests that JNK kinases are involved in this process. To explore which one of the JNK kinases is responsible for these effects, DU145 cells were transiently transfected with plasmids encoding inactive mutants of JNK1 or JNK2. The cells expressing inactive JNK1 mutant, but not cells expressing JNK2 mutant or possessing an empty vector, were completely resistant to TNF-induced ROS generation, ferritin degradation, and an increase in LIP. These data suggest that TNF-induced ROS formation is mediated by JNK1, which regulates ferritin degradation and thus the level of highly reactive iron.
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PMID:Tumor necrosis factor-alpha-induced reactive oxygen species formation is mediated by JNK1-dependent ferritin degradation and elevation of labile iron pool. 1760 35

Antibody-conjugated iron oxide nanoparticles offer a specific and sensitive tool to enhance magnetic resonance (MR) images of both local and metastatic cancer. Prostate-specific membrane antigen (PSMA) is predominantly expressed on the neovasculature of solid tumors and on the surface of prostate cells, with enhanced expression following androgen deprivation therapy. Biotinylated anti-PSMA antibody was conjugated to streptavidin-labeled iron oxide nanoparticles and used in MR imaging and confocal laser scanning microscopic imaging studies using LNCaP prostate cancer cells. Labeled iron oxide nanoparticles are internalized by receptor-mediated endocytosis, which involves the formation of clathrin-coated vesicles. Endocytosed particles are not targeted to the Golgi apparatus for recycling but instead accumulate within lysosomes. In T(1)-weighted MR images, the signal enhancement owing to the magnetic particles was greater for cells with magnetic particles bound to the cell surface than for cells that internalized the particles. However, the location of the particles (surface vs internal) did not significantly alter their effect on T(2)-weighted images. Our findings indicate that targeting prostate cancer cells using PSMA offers a specific and sensitive technique for enhancing MR images.
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PMID:Targeting and cellular trafficking of magnetic nanoparticles for prostate cancer imaging. 1771 83

We have previously shown that doxorubicin sensitizes prostate cancer cells to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL). Sensitization correlated with decreased expression of the antiapoptotic cellular FLICE-like inhibitor protein (cFLIP(S)). The decrease in cFLIP(S) could not be explained by transcriptional regulation or increased degradation, leading us to focus on translational mechanisms. In this study, we found that doxorubicin caused strong and sustained phosphorylation of elongation factor 2 (EF-2), which interferes with protein elongation. Phosphorylation of EF-2 appeared to occur in a kinase-independent manner. Treatment with hydrogen peroxide recapitulated the events observed after doxorubicin treatment. In addition, cells treated with hydrogen peroxide expressed less X-linked inhibitor of apoptosis protein (XIAP) and survivin which, like cFLIP(S), are short-half-life proteins with an antiapoptotic function while expression levels of DR5, caspases-8, -9, -3, and Bax are maintained. The doxorubicin-mediated decrease in cFLIP(S) and XIAP and the TRAIL-induced apoptosis were prevented by pretreatment with an iron chelator, indicating that expression of these proteins was affected by free radical generation upon interaction of iron with doxorubicin. In conclusion, our data suggest that free radicals can affect the phosphorylation of EF-2 resulting in a net loss of short-half-life proteins such as cFLIP(S) and XIAP, leaving a cell more vulnerable to apoptotic stimuli.
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PMID:Doxorubicin generates a proapoptotic phenotype by phosphorylation of elongation factor 2. 1789 44

To determine whether a 2,700-year-old tumor can be reliably diagnosed using microscopic and proteomic techniques and whether such prostate carcinomas show the same morphological pattern at the micro-level as modern-day carcinomas, this case was investigated. A 40-50-year-old Scythian king who lived during the Iron Age in the steppe of Southern Siberia (Russia) suffered from macroscopically visible osteoblastic and osteoclastic lesions throughout his entire skeleton. Macro-morphological (macroscopy, endoscopy, radiology) and micro-morphological techniques (histology, scanning-electron microscopy) as well as proteomic techniques (1-D- and 2-D-electrophoresis, Western blot) were applied. The results of the morphological and biochemical investigation proved that this mature male suffered for many years from and probably died of a carcinoma of the prostate. The diagnosis mainly rests on the results of the microscopic examination of the lesions and the positive evidence of PSA, which is an important marker for the diagnosis of prostate cancer. It is remarkable that, in this ancient case, the morphological pattern at the microlevel is the same as in recent cases. The loss of the spongy bone substance (red bone marrow) provoked chronic anemia during the final months of the life of this king. The proteomic techniques applied are new for the investigation of recent and ancient macerated bones. Sensitive and reliable biochemical markers (PSA) are an important precondition to detect such tumors in recent and ancient materials. Currently, this is the oldest known case of prostate cancer diagnosed reliably by morphological and biochemical techniques.
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PMID:Oldest known case of metastasizing prostate carcinoma diagnosed in the skeleton of a 2,700-year-old Scythian king from Arzhan (Siberia, Russia). 1791 81

Molecular imaging of the body involves new techniques to image cellular biochemical processes, which results in studies with high sensitivity, specificity, and signal-to-background. The most prevalently used molecular imaging technique in body imaging is currently fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET). FDG PET has become the method of choice for the staging and restaging of many of the most common cancers, including lymphoma, lung cancer, breast cancer, and colorectal cancer. FDG PET has also become extremely valuable in monitoring the response to therapeutic drugs in many cancers. New PET agents, such as fluorothymidine and acetate, have also shown promise in the evaluation of response to therapy and in the staging of prostate cancer. Magnetic resonance (MR) spectroscopy has shown promise in the evaluation of prostate cancer. Breast cancer evaluation benefits from advances in spectroscopic imaging and contrast-enhanced kinetic evaluation of vascular permeability, which is altered in neoplastic processes because of release of angiogenic factors. Superparamagnetic iron oxide (SPIO) particles represent the first of an expanding line of MR contrast agents that target specific cellular processes. SPIO particles have also been used in the evaluation of the cirrhotic liver and at MR lymphangiography.
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PMID:Molecular imaging techniques in body imaging. 1794 Feb 97

Androgen deprivation therapy (ADT) is a commonly used treatment for metastatic prostate cancer. A 78-year-old patient with metastatic prostate cancer had transfusion-dependent anemia develop while on ADT. The patient also had hereditary hemorrhagic telangiectasia (HHT), with chronic gastrointestinal blood loss. Blood transfusions were required every 3 weeks for 4 months to keep hemoglobin levels above 8 g/dL, despite discontinuation of ADT. The anemia, which had been well managed with iron therapy before ADT, was worsened by the loss of bone marrow-stimulating testosterone effects. The case highlights testosterone's important role in erythrocyte production. Practitioners should monitor hemoglobin levels in patients undergoing ADT.
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PMID:Transfusion-dependent anemia after initiation of androgen deprivation therapy for metastatic prostate cancer. 1799 72

A siderophore conjugate was designed as a potential PSMA inhibitor and diagnostic agent for prostate cancer. A semi-rigid spacer was incorporated to avoid competitive participation of iron binding by the enzyme inhibitor relative to the siderophore component. Biological test results showed that, even with the extended scaffold, this compound is a potent PSMA inhibitor with an IC50 of 4 nM. This siderophore conjugate may be useful for detection of prostate-derived cancer cells by magnetic resonance imaging (MRI).
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PMID:Design and synthesis of a siderophore conjugate as a potent PSMA inhibitor and potential diagnostic agent for prostate cancer. 1806 Jul 94


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