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)

The serum transferrin receptor (sTfR) is a sensitive indicator of iron-deficiency erythropoiesis that is not affected by inflammation. Concentrations of this molecule are inversely correlated with body-iron stores, and increased body-iron stores are associated with an increased risk of cancer of the liver and lungs. However, an association between iron status as assessed on the basis of sTfR and prostate cancer has not been previously investigated. We measured sTfR and serum ferritin by means of an enzyme immunoassay in 27 men with newly diagnosed, untreated prostate cancer and in 72 controls. Our study population ranged in age from 38 to 78 years. The mean serum ferritin concentration in men with prostate cancer was 44.8% lower than that in men without this tumor ( P < .05). In contrast, the mean values of sTfR and sTfR/log serum ferritin were 32% and 60% higher, respectively, in men with prostate cancer than in those without this tumor ( P < .05). Differences between groups persisted after we took into account inflammation (alpha 1-acid glycoprotein > 1 g/L, C-reactive protein > 10 mg/L; P < .05). Among the entire study population and among men without inflammation, a higher percentage of subjects (29%-31%) than of controls (14%-22%) had sTfR values greater than 8 mg/L, suggestive of iron-deficiency erythropoiesis ( P < .05). The odds ratios for men with prostate cancer to have sTfR values of less than 2.9 mg/L (suggestive of increased body-iron stores) was 0, compared with 1.745 to 3.65 for the same men to have sTfR values greater than 8 mg/L. sTfR was negatively correlated with log ferritin ( r = -.422, P < .05) but did not correlate with tissue inflammation, tumor stage, or acute-phase proteins. It appears that prostate cancer is not associated with increased body-iron stores.
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PMID:Increased levels of serum transferrin receptor and serum transferrin receptor/log ferritin ratios in men with prostate cancer and the implications for body-iron stores. 1553 86

Prognosis of pancreatic cancer is still remarkably poor, even if complete resection was performed by enlarged abscission. On the other hand, carbon-ion beam therapy is giving good results in some selected carcinoma such as small cell lung cancer, prostate cancer, uterus cancer, and soft tissue/bone tumor. In this report, we discuss four patients with pancreatic cancer treated by surgical pancreatectomy combined with preoperative carbon-ion beam irradiation. All patients were irradiated with 48 GyE carbon-iron beam by HIMAC (Heavy Ion Medical Accelerator in Chiba) to the pancreatic area including lymph nodes and nerve plexus. Severe cholangitis, as the postoperative complication, had occurred in one of the patients. However, there was no complication or disorder caused by carbon-iron radiation. All four patients are alive now, but two of them developed tumor recurrence, one with hepatic metastasis and the other with peritoneal dissemination. Surgical treatment for pancreatic cancer combined with preoperative carbon-ion irradiation is expected as a promising cure, but it is necessary to examine more cases in the future to evaluate the clinical outcome of this treatment.
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PMID:[Surgical resection for pancreatic cancer combined with preoperative carbon-ion beam irradiation]. 1555 46

Lysosomes, lysosomal enzymes and oxidant processes are known to be involved in cancer processes. The prostasomes contain proteins and enzymes that would constitute pathways for the hydrolysis of proteins and peptides. However, integrated biochemical and cell biology studies are necessary to understand how lysosomal enzymes and prostasomal enzymes combined with oxidant processes could initiate cancer. Most prostate cancer is likely to be initiated in the prostate duct system. The lysosomal enzymes acid phosphatase and glucosidase and prostasomal proteins and enzymes are found in human semen and therefore have come through prostate ducts. The hypothesis presented here is that the lysosomal enzymes and prostasomes are exocytosed from prostate cells into the duct system of the prostate where their hydrolytic enzymes and oxidative processes, for example, the iron from the iron-sulfur clusters of the prostasomal dehydrogenases, damage proteins and other components of cells leading to the initiation of cancer. Risk factors for prostate cancer are known to initiate activity of lysosomal enzymes and could initiate activity of prostasomal enzymes. These risk factors include: ionizing radiation, oxidative stress, environmental toxicants and dietary components including those with high fat content. Other dietary components in fruits and vegetables protect against prostate cancer and can be hypothesized as decreasing cellular output of lysosomal or protasomal enzymes or inhibiting lysosomal and prostasomal enzymes in the duct system. Measurements of multiple lysosomal and prostasomal enzyme activities and their biochemical pathways are vital to the understanding of protectors to inhibit lysosomal or prostasomal enzyme activities that might be leading to prostate cancer. Inhibitors of lysosomal and prostasomal enzymes can be investigated in cellular and biochemical systems, and these inhibitors could be used to control these enzyme activities in vivo. In situ enzyme analyses including substrates producing fluorescent products are applicable. Screening assays could be developed to detect in vivo lysosomal and prostasomal enzyme activities in semen. Lysosomal enzyme activities may be precursors to the onset of other kinds of cancer with other similar non-invasive screening techniques possible. Present knowledge encompasses mobilization of sperm when prostasomes bind to sperm in semen. A further hypothesis of this study projects that prostasomal dehydrogenases and their NADH products initiate the formation of ATP in the sperm mitochondria which activates flagellar movement. This overall hypothesis suggests protection against prostate cancer by inhibitors of lipid peroxidation including the dietary antioxidants selenium, vitamin E and lycopene and also cysteine glutathione.
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PMID:Lysosomal and prostasomal hydrolytic enzymes and redox processes and initiation of prostate cancer. 1582 10

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and nonprostatic solid tumor neovasculature and is a target for anticancer imaging and therapeutic agents. PSMA acts as a glutamate carboxypeptidase (GCPII) on small molecule substrates, including folate, the anticancer drug methotrexate, and the neuropeptide N-acetyl-l-aspartyl-l-glutamate. Here we present the 3.5-A crystal structure of the PSMA ectodomain, which reveals a homodimer with structural similarity to transferrin receptor, a receptor for iron-loaded transferrin that lacks protease activity. Unlike transferrin receptor, the protease domain of PSMA contains a binuclear zinc site, catalytic residues, and a proposed substrate-binding arginine patch. Elucidation of the PSMA structure combined with docking studies and a proposed catalytic mechanism provides insight into the recognition of inhibitors and the natural substrate N-acetyl-l-aspartyl-l-glutamate. The PSMA structure will facilitate development of chemotherapeutics, cancer-imaging agents, and agents for treatment of neurological disorders.
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PMID:Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase. 1583 26

Computed tomography (CT) imaging is the standard method for the assessment of lymph node metastases in renal cell and testicular cancer. In bladder cancer and prostate cancer the results of CT are not convincing due to a large number of false-negative findings and the prognostic relevance of undetected metastases. For both entities recent studies revealed that MR lymphography using iron oxide particles allows the detection of small metastatic lymph nodes. For penile cancer reliable results for imaging of lymph node metastases do not exist. PET imaging using [(18)F]-fluorodeoxyglucose (FDG) is the modality of choice in therapy control of seminomas but has no defined value in other urological malignancies. PET with [(11)C] choline and [(11)C] acetate offers great potential in staging and restaging of prostate cancer. Further investigations are necessary to determine the role of these new methods.
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PMID:[Value of imaging for lymph node metastases from renal cell, bladder, prostate, penile, and testicular cancers]. 1590 89

We have developed a novel water-dispersible oleic acid (OA)-Pluronic-coated iron oxide magnetic nanoparticle formulation that can be loaded easily with high doses of water-insoluble anticancer agents. Drug partitions into the OA shell surrounding iron oxide nanoparticles, and the Pluronic that anchors at the OA-water interface confers aqueous dispersity to the formulation. Neither the formulation components nor the drug loading affected the magnetic properties of the core iron oxide nanoparticles. Sustained release of the incorporated drug is observed over 2 weeks under in vitro conditions. The nanoparticles further demonstrated sustained intracellular drug retention relative to drug in solution and a dose-dependent antiproliferative effect in breast and prostate cancer cell lines. This nanoparticle formulation can be used as a universal drug carrier system for systemic administration of water-insoluble drugs while simultaneously allowing magnetic targeting and/or imaging.
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PMID:Iron oxide nanoparticles for sustained delivery of anticancer agents. 1593 80

Hereditary hemochromatosis (HH), the most common genetic disease in northern Europeans, is an autosomal recessive disorder of iron metabolism. The association between hepatocellular carcinoma and HFE homozygosity is well documented, but recently HFE hetero- and homozygosity has also been linked to nonhepatocellular malignancies, including female breast cancer. We hypothesized that C282Y and H63D mutations in the HFE gene could contribute to male breast cancer (MBC) and prostate cancer (PC) susceptibility at the population level in Finland. We screened the 2 major HFE mutations, H63D and C282Y, from 116 MBC cases diagnosed in Finland between 1967 and 1996, 843 consecutive unselected PC cases diagnosed at the Pirkanmaa Hospital District between 1999 and 2001 and 480 anonymous blood donor controls by minisequencing. Our results indicate that the frequencies of the HFE mutations do not significantly differ between MBC and PC patients and the population-based controls. No significantly altered risks for MBC or PC among carriers of the 2 variants were observed. However, HFE mutations were seen twice as often among carriers of a common BRCA2 mutation 9346(-2)A-->G compared with the rest of the MBC cases, indicating that HFE may be an MBC risk modifier gene among BRCA2 mutation carriers. In conclusion, our results indicate a minor role for the HFE mutations C282Y and H63D in the causation of MBC and PC, but carriers of both BRCA2 9346(-2)A-->G and an HFE mutation may be at an increased risk.
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PMID:Hemochromatosis gene mutations among Finnish male breast and prostate cancer patients. 1600 28

CYP17 is a steroidogenic enzyme located in the zona fasciculata and zona reticularis of the adrenal cortex and gonad tissues and which has dual functions - hydroxylation and as a lyase. The first activity gives hydroxylation of pregnenolone and progesterone at the C(17) position to generate 17alpha-hydroxypregnenolone and 17alpha-hydroxyprogesterone, while the second enzymic activity cleaves the C(17)-C(20) bond of 17alpha-hydroxypregnenolone and 17alpha-hydroxyprogesterone to form dehydroepiandro-sterone and androstenedione respectively. The modulation of these two activities occurs through cytochrome b(5). Association of cytochrome b(5) and CYP17 is thought to be based primarily on electrostatic interactions in which the negatively charged residues pair up with positively charged residues on the proximal surface of the CYP17 molecule. Non-specific interactions of the hydrophobic membrane regions of cytochrome b(5) and CYP17 are also thought to play a crucial role in the association of these two haemoproteins. Although cytochrome b(5) is known to stimulate CYP activity by contributing the second electron in the catalytic cycle, in the case of CYP17, the mechanism of cleavage stimulation proceeds via an allosteric mode. It is hypothesised that cytochrome b(5) promotes the cleavage by aligning the iron-oxygen complex attack onto the C(20) rather than the C(17) atom of the steroid substrate molecule. Thus, further understanding of the mechanism of modulation by cytochrome b(5) of the hydroxylase and lyase activities should shed new insights on developing therapeutic targets in CYP17-linked biochemical processes such as adrenarche, polycystic ovary syndrome and prostate cancer.
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PMID:Cytochrome b(5) modulation of 17{alpha} hydroxylase and 17-20 lyase (CYP17) activities in steroidogenesis. 1629 74

It has been suggested that iron overload may be carcinogenic. In the present study, we evaluated the effect of plasma and prostate carotenoid concentration on oxidative DNA damage in 12-week-old Wistar rats treated with intraperitoneal (ip) ferric nitrilotriacetate (Fe-NTA) (10 mg Fe/kg). Plasma beta-carotene and lycopene concentrations were measured as a function of time after ip injection of carotenoids (10 mg kg(-1) day(-1) beta-carotene or lycopene) in rats. The highest total plasma concentration was reached 3 and 6 h after ip injection of lycopene or beta-carotene, respectively. After 5 days of carotenoid treatment, lycopene and beta-carotene were present in the 0.10-0.51 nmol/g wet tissue range in the prostate. Using a sensitive method to detected 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) by HPLC/EC, the level of 8-oxodGuo in rat prostate DNA was significantly higher (6.3 +/- 0.6 residues/10(6) dGuo) 3 h after Fe-NTA injection compared with control rats (1.7 +/- 0.3 residues/10(6) dGuo). Rats supplemented with lycopene or beta-carotene for 5 days prior to Fe-NTA treatment showed a reduction of about 70% in 8-oxodGuo levels to almost control levels. Compared with control rats, the prostate of Fe-NTA-treated animals showed a 78% increase in malondialdehyde accumulation. Lycopene or beta-carotene pre-treatment almost completely prevented lipid damage. Epidemiological studies have suggested a lower risk of prostate cancer in men reporting a higher consumption of tomato products. However, before associating this effect with tomato sauce constituents, more information is required. The results described here may contribute to the understanding of the protective effects of carotenoids against iron-induced oxidative stress.
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PMID:Lycopene and beta-carotene protect in vivo iron-induced oxidative stress damage in rat prostate. 1647 Mar 7

We have shown previously that generation of reactive oxygen species (ROS) is a critical event in G(2)-M phase cell cycle arrest caused by diallyl trisulfide (DATS), which is a highly promising anticancer constituent of processed garlic. Using DU145 and PC-3 human prostate cancer cells as a model, we now report a novel mechanism involving c-Jun NH(2)-terminal kinase (JNK) signaling axis, which is known for its role in regulation of cell survival and apoptosis, in DATS-induced ROS production. The DATS-induced ROS generation, G(2)-M phase cell cycle arrest and degradation, and hyperphosphorylation of Cdc25C were significantly attenuated in the presence of EUK134, a combined mimetic of superoxide dismutase and catalase. Interestingly, the DATS-induced ROS generation and G(2)-M phase cell cycle arrest were also inhibited significantly in the presence of desferrioxamine, an iron chelator, but this protection was not observed with iron-saturated desferrioxamine. DATS treatment caused a marked increase in the level of labile iron that was accompanied by degradation of light chain of iron storage protein ferritin. Interestingly, DATS-mediated degradation of ferritin, increase in labile iron pool, ROS generation, and/or cell cycle arrest were significantly attenuated by ectopic expression of a catalytically inactive mutant of JNK kinase 2 and RNA interference of stress-activated protein kinase/extracellular signal-regulated kinase 1 (SEK1), upstream kinases in JNK signal transduction pathway. In conclusion, the present study provides experimental evidence to indicate existence of a novel pathway involving JNK signaling axis in regulation of DATS-induced ROS generation.
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PMID:c-Jun NH(2)-terminal kinase signaling axis regulates diallyl trisulfide-induced generation of reactive oxygen species and cell cycle arrest in human prostate cancer cells. 1670 65


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