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)

Bone metabolic disruption that occurs in bone metastatic prostate cancer could lead to disturbances of calcium metabolism. The prognostic role of either hypocalcemia or hypercalcemia was assessed in a consecutive series of hormone-refractory bone metastatic prostate cancer patients. Serum calcium was measured in 192 patients. The presence of hypocalcemia and hypercalcemia was related with baseline biochemical and clinical characteristics and the role of these two calcium disturbances in predicting prognosis and adverse skeletal-related events (SREs) was assessed. As compared to normocalcemic patients, hypocalcemic patients (n=51) had higher tumor load in bone (P=0.005), higher plasma chromogranin A (CgA, P=0.01), serum alkaline phosphatase (P=0.01), urinary N-telopeptide (NTX, P=0.002) and lower hemoglobin values (P=0.01), while hypercalcemic patients (n=16) had higher plasma CgA (P=0.001) and serum lactate dehydrogenase values (P=0.001), higher bone pain (P=0.003) and a lower frequency of pure osteoblastic lesions (P=0.001). Hypercalcemia was significantly associated with poor prognosis: hazard ratio (HR), 1.9 (95% confidence Interval (CI) 1.2-3.3) and higher risk to develop SREs HR, 2.5 (95% CI 1.2-5.2, P=0.01), while hypocalcemia was not associated with poor prognosis. The prognostic role of hypercalcemia was maintained in multivariate analysis after adjusting for validated prognostic parameters: HR, 2.72 (95% CI 1.1-6.8, P=0.03). These data suggest that serum calcium levels should be taken into account in the clinical decision-making process of bone metastatic prostate cancer patients. Patients with asymptomatic hypercalcemia could benefit of a strict follow-up and an immediate bisphosphonate treatment. Further prospective clinical trials are needed to confirm this finding.
Prostate Cancer Prostatic Dis 2009
PMID:Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease. 1833 1

Regenerating islet-derived family, member 4 (REG4, which encodes Reg IV) is a candidate marker for cancer and inflammatory bowel disease. We investigated the potential prognostic role of Reg IV immunostaining in clinically localized prostate cancer (PCa) after radical prostatectomy. Immunohistochemical staining of Reg IV was performed in 98 clinically localized PCa tumors obtained during curative radical prostatectomy. Intestinal and neuroendocrine differentiation was investigated by MUC2 and chromogranin A immunostaining, respectively. The prognostic significance of immunohistochemical staining for these factors on prostate-specific antigen (PSA)-associated recurrence was assessed by Kaplan-Meier analysis and a Cox regression model. Phosphorylation of the epidermal growth factor receptor (EGFR) by Reg IV was analyzed by Western blot. In total, 14 (14%) of the 98 PCa cases were positive for Reg IV staining. Reg IV positivity was observed frequently in association with MUC2 (P = 0.0182) and chromogranin A positivity (P = 0.0012). Univariate analysis revealed that Reg IV staining (P = 0.0004), chromogranin A staining (P = 0.0494), Gleason score (P < 0.0001) and preoperative PSA concentration (P = 0.0167) were significant prognostic factors for relapse-free survival. Multivariate analysis indicated that Reg IV staining (P = 0.0312), Gleason score (P = 0.0014) and preoperative PSA concentration (P = 0.0357) were independent predictors of relapse-free survival. In the LNCaP cell line, EGFR phosphorylation was induced by the addition of Reg IV-conditioned medium. These results suggest that Reg IV expression is an independent prognostic indicator of relapse after radical prostatectomy.
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PMID:Reg IV is an independent prognostic factor for relapse in patients with clinically localized prostate cancer. 1875 68

Regenerating islet-derived family, member 4 (Reg IV) is a candidate marker for cancer and inflammatory bowel disease and is associated with neuroendocrine and intestinal differentiation. We have reported that 14% of prostate cancer (PCa) cases are positive for Reg IV by immunohistochemistry. In the present study, we performed immunohistochemical analysis of Reg IV in other major urological cancers, including 101 renal cell carcinoma (RCC), and 95 urothelial carcinoma (UC) of urinary bladder by immunohistochemistry. We also investigated neuroendocrine differentiation by chromogranin A and synaptophysin staining along with intestinal differentiation by MUC2 staining. Immunohistochemical analysis of Reg IV revealed no expression of Reg IV in RCC, and only one case (1%) of UC expressed Reg IV. Neither neuroendocrine nor intestinal differentiation was found in RCC. Among 95 UC cases, neuroendocrine differentiation was detected in 13 cases (14%), and intestinal differentiation was observed in 33 cases (35%). In one Reg IV-positive UC case, MUC2 staining was observed. Since Reg IV expression was frequently found in PCa, we also measured Reg IV levels in sera from patients with PCa by enzyme-linked immunosorbent assay. The serum Reg IV concentration in PCa patients (n=38, mean +/- SE, 1.69+/-0.16 ng/ml) was significantly higher than that in control individuals (n=40, 1.28+/-0.11 ng/ml, P=0.0199, Mann-Whitney U test). The sensitivity and specificity for detection of PCa were 34% (13/38) and 90% (36/40), respectively. These results suggest that among major urologic cancers, Reg IV is expressed frequently in PCa, and that serum Reg IV represents a novel biomarker for PCa.
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PMID:Immunohistochemical analysis of Reg IV in urogenital organs: Frequent expression of Reg IV in prostate cancer and potential utility as serum tumor marker. 1908 48

Finasteride has been recognized as a drug suitable for the chemoprevention of prostate cancer (PC) by reducing intracellular dihydrotestosterone (DHT) levels. The Prostate Cancer Prevention Trial (PCPT) database on continuous finasteride treatment of almost 19 thousands patients indicated the reduction in cancer prevalence by about 25% . However, in this same study more than a twofold increase in high grade aggressive prostate tumors was recorded when compared to controls thus arising serious doubts upon the real benefits of the protocol. Here, our investigation was performed three years on a continuous versus intermittent (six month treatment followed by 6 months resting period) finasteride treatment in 125 BPH patients (pts) each. The overall PC prevalence in both finasteride-treated groups was lower that in untreated controls and thus being in accordance with the PCPT data. However, continuous therapy gave significantly higher incidence in Gleason score (GS)>6 carcinomas compared to intermitted therapy and controls (44.5%, 25% and 18.2% of total acquired PC, respectively). In addition, the acquired elevated chromogranin A (CgA) values were also more than doubled in pts treated continuously compared to the other two groups (13.6%, 5.6% and 6.4%, respectively). Acquired PC GS>6 recorded in pts with a raise in CgA was higher in continuously treated pts (50%) than in the other two studied groups (20% and 25%, respectively). In pts with the retained normal CgA concentration highest PC incidence was found in controls (5.1%) and lower prevalence was recorded in continuously (2.8%) and intermittently treated pts (2.5%) while the respective PC GS>6 incidence was lower in controls than in treated pts. Seemingly, finasteride treatment reduces PC prevalence in pts free of NED but elevates the number of aggressive carcinomas in CgA-positive pts only if continuous treatment is applied. In conclusion, current chemoprevention protocols need to be carefully reconsidered prior to the selection between continuous and discontinued finasteride treatment.
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PMID:Continuous finasteride therapy for benign prostate hypertrophy upgrades both neuroendorcine differentiation and aggressive prostate cancer. 1944 7

Prostate adenocarcinomas (PAC) consist mainly of tumour cells of luminal immunophenotype and scattered neuroendocrine (NE) cells. NE cells are defined by chromogranin A (CgA) immunoreactivity. T he aim of this study is the evaluation of CgA serum levels in monitoring prostate cancer (PC) patients under complete androgen deprivation (CAD) in comparison with the prostate specific antigen (PSA) as a prognostic marker of androgen resistance and bone metastases. Ninety-two patients with newly diagnosed PAC and 30 healthy blood donors serving as the control group were enrolled in the study. Serum CgA and PSA values were measured. All patients had locally advanced or metastatic disease and received CAD treatment. In the group of PAC patients bone scanning with 925MBq (99m)Tc-MDP revealed the presence of bone metastatic lesions in 50 patients (29 with more than 3 lesions and 21 with less than 3 lesions). The other 42 patients had no bone metastases. The patients and the control group were re-evaluated after 1 year. Our results showed that serum CgA positively correlated with multiple bone metastases and higher Gleason score, serum levels of CgA and PSA. Levels of PSA were significantly higher in patients with PAC and bone metastases compared with those with no bone metastases (P<0.001). In patients with multiple bone metastases and Gleason Score >7 elevated serum levels of CgA higher than those of PSA were found. In conclusion, serum CgA levels is a valuable marker for predicting the presence of multiple bone metastases in PAC patients. Combined with PSA, CgA can predict disease progression in patients with advanced PAC under CAND treatment and is correlated with poor prognosis.
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PMID:The prognostic value of serum chromogranin A and prostate specific antigen in prostate cancer patients for progression to the hormone resistance state. 1993 34

The treatment of advanced prostate cancer (CaP) with androgen deprivation therapy inevitably renders the tumours castration resistant and incurable. Under these conditions, neuroendocrine differentiation (NED) of CaP cells occurs and neuropeptides released by neuroendocrine cells facilitate tumour progression. Pharmacological strategies aiming to prevent or delay NED during androgen ablation could, therefore, increase the effectiveness of the therapy. Mechanisms and pathways inducing NED in CaP are poorly understood and data are often discordant. In the present study, we used several CaP cell lines (androgen-responsive: LNCaP, PC3-AR, 22RV1 and -irresponsive: DU145 and PC3) to evaluate NED after androgen deprivation or treatment with epidermal growth factor (EGF). NED was determined by neuron-specific enolase and chromogranin A expression and by the occurrence of morphological changes in the cells. Androgen-deprivation conditions induced NED in LNCaP and PC3-AR, but not in 22Rv1, PC3 and DU145 cells. LNCaP and PC3-AR cells also became resistant to thapsigargin-induced apoptosis. In all the AR-positive cell lines, androgen deprivation caused a decrease in androgen receptor expression indicating that it is downregulated irrespective of NED induction. Treatment with EGF induced NED in DU145 cells and the EGF receptor inhibitor gefinitib prevented the process. On the contrary, no effect of EGF was demonstrated in LNCaP or 22Rv1 cells. CaP cell lines did not respond univocally to treatments inducing NED, suggesting that studies on this topic should be performed in a wide spectrum of cell models which can be more indicative of the tumour variability in vivo.
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PMID:Androgen-responsive and -unresponsive prostate cancer cell lines respond differently to stimuli inducing neuroendocrine differentiation. 2008 46

Prostate cancer is one of the most frequently diagnosed cancer in men. Treatment by radical prostatectomy, radiotherapy and anti-androgen drugs is successful in patients with localized cancer. However, prolonged androgen deprivation often leads to hormone refractory condition, associated with disease relapse. ErbB1 and ErbB2 activity has been correlated with androgen-independence. We determined the effects of GW2974, a dual inhibitor of ErbB-1 and ErbB-2 tyrosine kinase activity, on growth, NSE, chromogranin A and osteopontin cytosol content in the androgen-independent prostate cancer cell line PC-3. We found that PC-3 cell growth was inhibited by GW2974, whereas NSE and chromogranin A cell contents were stimulated and osteopontin cytosol level was not affected. The present data may have clinical implications for the treatment of advanced prostate cancer.
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PMID:Effects of the ErbB1/ErbB2 kinase inhibitor GW2974 on androgen-independent prostate cancer PC-3 cell line growth and NSE, chromogranin A and osteopontin content. 2051 64

Androgen receptors (ARs) are probably of importance during all phases of prostate cancer (PC) growth, but their role in bone metastases is largely unexplored. Bone metastases were therefore collected from hormone-naive (n=11), short-term castrated (n=7) and castration-resistant PC (CRPC, n=44) patients by biopsy (n=4) or at surgery to alleviate symptoms from metastases complications (metastasis surgery, n=58), and immunostained for nuclear ARs, Ki67, active caspase-3, prostate-specific antigen (PSA) and chromogranin A, and results were related to serum PSA, treatments and outcome. Nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected in metastases within a few days after surgical castration. In CRPC patients, nuclear AR staining of metastases was increased when compared to short-term castrated patients. The nuclear AR staining score was related to tumour cell proliferation, but it was not associated with other downstream effects of AR activation such as apoptosis and PSA staining, and it was only marginally related to the presence of neuroendocrine tumour cells. Serum PSA at metastasis surgery, although related to outcome, was not associated with AR staining, markers of metastasis growth or PSA staining in metastases. High nuclear AR immunostaining was associated with a particularly poor prognosis after metastasis surgery in CRPC patients, suggesting that such men may benefit from the potent AR blockers now tested in clinical trials.
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PMID:Nuclear androgen receptor staining in bone metastases is related to a poor outcome in prostate cancer patients. 2068 81

Valproic Acid (VPA) is a histone deacetylase inhibitor that holds promise for cancer therapy. Here, we investigate whether VPA treatment induces neuroendocrine differentiation of Prostate Cancer (PCa). A tissue microarray of VPA-treated and untreated tumor xenografts and cell lines of human PCa (LNCaP, C4-2, DU145, and PC-3) were generated and were analyzed by immunohistochemical analysis (IHC) for NE markers chromogranin A (CgA), synaptophysin, and NCAM (neural cell adhesion molecule). Western blot analysis for CgA was performed to confirm the results of the TMA. IHC analysis did not reveal any induction of CgA, synaptophysin, or NCAM in any xenograft after VPA treatment in vivo. In vitro, VPA treatment induced little synaptophysin expression in C4-2 and PC-3 cells and NCAM expression in LNCaP and PC-3 cells. In the case of CgA, VPA treatment decreased its expression in vitro in a dose-dependent manner, as determined by western blot analysis. Thus our data demonstrates that VPA does not induce NE differentiation of PCa cells in the physiologically relevant in vivo setting.
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PMID:Does valproic acid induce neuroendocrine differentiation in prostate cancer? 2098 Dec 53

Although interracial differences of prostate cancer progression are well recognized, their underlying molecular and cellular mechanisms remain obscure. We compared the histopathologic, immunohistochemical, and molecular characteristics of unselected prostate cancer tissues obtained from U.S., Chinese, and Japanese men. Histopathologic analyses indicated that 74.4% of the prostate cancers in Chinese men were poorly differentiated, compared with 28.6% and 32.8% of the prostate cancers in U.S. and Japanese men, respectively. These differences cannot be attributed to patient age, clinical stage of disease, or methods of tissue sampling. The high proportion of poorly differentiated prostate cancer tissues in the Chinese group was not related to the patients' access to medical service or to geographic background within China. Significantly higher levels of tumor angiogenesis (2- to 4-fold), serotonin (2- to 20-fold), and bombesin (7- to 16-fold), but not chromogranin A, were found in the tissue specimens obtained from Chinese prostate cancer patients compared with those from U.S. and Japanese patients. We also observed marked interracial differences in p53 protein accumulation. The protein was present in 90.2% of Chinese specimens; 17.4% of specimens from U.S. whites; 7.1% of specimens from Japanese men; and 3.7% of specimens from U.S. blacks. Results from multivariate logistic regression analysis demonstrated that p53 protein accumulation, angiogenesis, and serotonin expression in the normal stroma area correlate independently with Chinese versus non-Chinese patient populations.
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PMID:Comparative studies of prostate cancers among United States, Chinese, and Japanese patients: characterization of histopathology, tumor angiogenesis, neuroendocrine factors, and p53 protein accumulations. 2122 92


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