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)

Chromogranin-A is considered a sensitive immunohistochemical tissue marker in neuroendocrine prostatic carcinoma. We report that the plasma chromogranin-A level was elevated in 48% of 25 patients with stage D2 prostate cancer, and suggest that this marker can be used to monitor the clinical course of these patients.
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PMID:Elevated plasma chromogranin-A concentrations in prostatic carcinoma. 185 31

To clarify the relationship between the neuroendocrine expression of prostatic carcinoma and prognosis, we studied immunohistochemically formalin-fixed and paraffin-embedded tissue sections from 30 cases of prostate cancer by means of neuroendocrine (NE) differentiation markers. The rate of NE positive-staining cases was 40% (12/30), and more than two kinds of NE markers were expressed in 9/12 cases. The NE markers were NSE (7 positive cases), Chromogranin-A (7), Calcitonin (2), Gastrin (2), hCG (4), S-100 Protein (2), Serotonin (3), EMA (23) and Lillie argentaffin staining (2). Follow-up of the 30 patients showed that NE negative tumors have a prognosis better than NE positive tumors (P < 0.005). Their poor prognosis is due to poor response to endocrine therapy, and the mechanism is that some neuropeptides secreted by NE cells affect the growth of tumor cells. Finally, how to improve the prognosis of the patients who have NE expression of their prostate cancer is discussed.
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PMID:[Relation between neuroendocrine expression of prostatic carcinoma and prognosis]. 803 80

Neuroendocrine (NE) cells are present in both benign and malignant human prostate. However, their function is poorly understood, mainly due to the lack of suitable experimental models. The nerve growth factor-beta (NGF-beta) promotes the rat pheochromocytoma cell line PC-12 to differentiate into neuronal like cells. We have studied the effect of NGF-beta on four human prostate cancer cell lines, LNCaP, DU-145, PC-3, and TSU-pr1. NGF-beta stimulates the growth rate in all these cell lines, but does not induce a neuronal phenotype. NE tumour markers (chromogranin A [CgA] and chromogranin B[CgB]) could not be demonstrated by immunocytochemistry (CgA and CgB), Northern blotting (CgA), or ELISA techniques (CgA), neither in control nor in NGF-beta stimulated cells. Consequently, other experimental models have to be sought in the study of NE cells in the human prostate.
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PMID:NGF-beta, NE-cells and prostatic cancer cell lines. A study of neuroendocrine expression in the human prostatic cancer cell lines DU-145, PC-3, LNCaP, and TSU-pr1 following stimulation of the nerve growth factor-beta. 956 67

Neuroendocrine (NE) cells are androgen-independent cells and secrete growth-modulating neuropeptides via a regulated secretory pathway (RSP). We studied NE differentiation after androgen withdrawal in the androgen-dependent prostate cancer xenograft PC-310. Expression patterns of chromogranin A, secretogranin III, and prohormone convertase-1 were analyzed at both protein and mRNA level to mark the kinetics of NE differentiation both in vivo and in vitro. PC-310 tumor-bearing nude mice were killed at 0, 2, 5, 7, 14, and 21 days postcastration. PC-310C cultures initiated from collagenase-treated tumor tissue could be maintained up to four passages, and androgen-deprivation experiments were performed similarly. PC-310 tumor volumes decreased by 50% in 10 days postcastration. Proliferative activity and prostate-specific antigen (PSA) serum levels decreased to zero postcastration, whereas PSA levels in PC-310C culture media first decreased and subsequently increased after 5 days. In vivo, androgen receptor (AR) expression decreased initially but returned to control level from 5 days postcastration on. CgA, secretogranin III, and secretogranin V expression increased in vivo from 5 days postcastration on. Subsequently, prohormone convertase-1 and peptidyl alpha-amidating monooxygenase as well as the vascular endothelial growth factor were expressed from 7 days postcastration on, and, finally, growth factors such as gastrin-releasing peptide and serotonin were expressed in a small part of the NE cells 21 days postcastration. The PC-310 tumors did not show colocalization of the AR on the NE cells in the tumor residues after 21 days. As in the PC-310 xenograft, NE differentiation was induced and AR expression relapsed after prolonged androgen suppression in PC-310C. For PC-310C cells, this relapse was associated with the secretion of PSA. PC-310C is the first culture of human prostatic cancer cells having the NE phenotype. The PC-310 model system is a potential androgen-dependent model for studying the role of NE cells in the progression of clinical prostate cancer. Androgen deprivation of NE-differentiated prostate cancer may induce the formation of both NE- and AR-positive dormant tumor residues, capable of actively producing NE growth factors via a RSP, possibly leading to hormone refractory disease.
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PMID:Androgen deprivation of the PC-310 [correction of prohormone convertase-310] human prostate cancer model system induces neuroendocrine differentiation. 1067 62

In a number of studies the important role of neuroendocrine structures during the development of aggressive prostate cancer has been reported. We have recorded serum Chromogranin A and PSA values (CIS biointernational, France) in responders and nonresponders to both hormone therapy (Mab) and chemohormonal treatment (Estracyt) using (BPH) subjects as controls. In BPH patients (12 subjects) the mean CgA serotest value (+/- SD) was 23.3 + 13.9 ng/ml (range 7.2-55.9). In responders (24) and nonresponders (14) to Mab, respective values were 39.5 + 18.3 (7.6-78.4) and 214.8 + 250.3 (9.9-1084.3), while in responders (19) and nonresponders (12) to Estracyt, the mean CgA level was 47.6 +/- 22.7 (4.4-101.2) and 366.7 +/- 291.4 (82.0-925.7). In all patients osseous metastates were detected. Statistical P-values were > 0.05 in the correlation between both responders to hormonal therapy and Estracyt (P = 0.194) and nonresponders to these two therapies (P = 0.179). All other recorded P-values were < 0.01. In some nonresponders to Estracyt (3/12) the normal total PSA value together with %FPSA well below 20 indicated contribution of anaplastic tumor. Cessation of Estracyt therapy in 4/14 responders caused the sharp elevation of CgA serotest level. Accordingly, Estracyt may control the activity of CgA positive structure(s). In accordance with these preliminary data, we advocate the CgA serotest assessment in candidates for hormonal therapy as well as during follow-up of pharmacological treatment.
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PMID:Serum chromogranin A in monitoring metastatic prostate cancer patients. 1069 37

This study evaluated perioperative and postoperative variations in serum CgA levels induced by radical retropubic prostatectomy (RRP) and their relationship with serum PSA levels in prostate cancer patients. Thirty consecutive patients with clinically localized adenocarcinoma of the prostate undergoing RRP were prospectively analyzed. Serum levels of CgA and total PSA were analyzed in each case preoperatively (time 0), at removal of the prostate (time 1), 1 h after the end of RRP (time 2) and then at regular postoperative intervals till 12 weeks (time 14). During the postoperative period no adjuvant therapies were performed and none of the 30 cases showed biochemical (PSA > 0.2 ng/mL) and/or clinical progression. Mean preoperative serum levels of CgA were 57 +/- 14 ng/mL. Immediately after the surgical removal of the prostate gland (time 1), in all 30 cases there was a significant (time 0-time 1: p = .001) increase in serum PSA, but a nonsignificant modification in serum CgA levels (60 +/- 15 ng/mL). After time 1, serum PSA levels progressively decreased to below the detection limit of 0.2 ng/mL. On the contrary, at time 2, serum CgA levels were postoperatively increased (time 2 = 145 +/- 47) and they remained significantly higher than preoperative values (time 0) till the 21-day postoperative interval (time 11). Moreover, at the last control (time 14) mean and median CgA levels were very similar to those shown preoperatively (time 14: 58 +/- 18 ng/mL). In patients with untreated clinically localized adenocarcinoma of the prostate submitted to RRP, surgical and postoperative stress, more than surgical manipulation of the prostate gland, could produce a significant increase in serum CgA levels maintained for a longer period when compared to the increase in serum PSA levels.
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PMID:Variation of chromogranin A serum levels after radical retropubic prostatectomy for prostate adenocarcinoma. 1264 77

In this pilot study, the predictive value of Octreotide scintigraphy (Octreoscan) and/or Chromogranin-A (CgA) was investigated in patients with hormone-refractory prostate cancer treated with Octreotide acetate. In total, 20 patients with progressive disease and bone metastases entered the trial. At baseline Octreoscan, CgA, PSA, alkaline phosphates (ALP) and two self-administered questionnaires (EORTC QLQ C-30 (v3) and brief pain index) were performed and a diary of the pharmaceutical was started. The treatment consisted of Octreotide (Sandostatin LAR) acetate 30 mg intramuscular injection every month. The blood samples and questionnaires were repeated every month until 3 months. Clinical responder was defined as a patient with increased global health score more than 10 units and stable or decreased pain score without an increase in analgesic. In all, 17 patients were treated per protocol, and four were assessed as clinical responders. Six patients developed a reduction in ALP (median -26%, range -5 to -78%). All patients increased in PSA. At baseline, three patients had a negative Octreoscan and the patients with positive lesions, demonstrated uptake of low intensity. At baseline the CgA was elevated above the normal range in 15 of the patients, and during treatment five patients decreased their CgA to the normal range. Neither baseline Octreoscan nor CgA could identify the clinical reponders. A minority of patients improves their health-related quality of life. The decrease and normalization of CgA levels in five patients during therapy indicates therapeutic activity but Octreoscan and CgA could not identify clinical responders.
Prostate Cancer Prostatic Dis 2006
PMID:Octreotide scintigraphy and Chromogranin A do not predict clinical response in patients with octreotide acetate-treated hormone-refractory prostate cancer. 1623 Oct 13

Prostate cancer is one of the most frequent tumors in men. The neuroendocrine differentiation in prostate cancer has become more widely recognized and has attracted considerable attention as a potentially new finding with major diagnostic, prognostic and therapeutic implications. We investigated the role of the serum concentrations of CgA in a group of 57 patients with prostate cancer and in 61 elderly subjects with benign prostate hyperplasia (BPH). Neuron-specific enolase (NSE) is the most frequently employed marker to detect neuroendocrine features. Serum prostate-specific antigen (PSA), CgA and NSE levels were determined. Comparing prostate cancer group versus BPH group, the CgA level difference was 63.00 ng/ml (p<0.0001) and the PSA level difference was 50.86 mcg/ml (p<0.0001). Between prostate cancer group and control group the CgA level difference was 94.3 ng/ml (p<0.0001), the PSA level difference was 52.91 mcg/ml (p<0.0001), and the NSE level difference was 1.34 microg/l (p<0.0001). Patients with higher CgA levels had poorer prognosis and survival, compared to those with lower CgA levels. These results support the concept that serum CgA level determination before treatment is a potential prognostic factor for prostate cancer.
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PMID:The chromogranin-A (CgA) in prostate cancer. 1628 Jan 80

Most of the conventional adenocarcinomas of the prostate display focal neuroendocrine (NE) differentiation at diagnosis, usually revealed by immunohistochemistry as solitary or clusters of cells, in the context of predominantly exocrine tumors. Even though the biological and clinical significance of NE differentiation in prostate cancer is still to be elucidated, NE phenotype is emerging as an important factor in the prognosis, evolution and progression of prostate cancer. It seems to be particularly relevant in facilitating prostate cancer progression during the ordinary androgen-suppression therapy (LHRH-analogs +/- anti-androgens). Several mechanisms have been identified: NE cells are androgen receptor negative, therefore they survive to androgen deprivation; NE cells produce peptides, hormones and growth factors which could stimulate proliferation [chromogranin (A-CgA), PTHrp, bombesin, etc.], inhibit apoptosis (Survivin) and stimulate neoangiogenesis [vascular endothelial GF (VEGF)] of the neighbouring exocrine prostate cancer cells. NE differentiation appears to be a dynamic phenomenon. The NE phenotype expression increases during androgen-deprivation therapy and results more elevated in hormone refractory than in hormone sensitive disease. Pre-clinical and clinical studies demonstrated a direct stimulation of NE differentiation by androgen-suppression therapy, resulting in a dramatic increase in the number of cells expressing NE markers. CgA appears to be the most sensitive marker and is most frequently used for detecting NE phenotype either at the tissue level or in the general circulation. Elevated plasma CgA levels are frequently observed in hormone-refractory disease and correlate with poor prognosis. Even in hormone refractory disease, NE differentiation is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.
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PMID:The neuroendocrine phenotype in prostate cancer: basic and clinical aspects. 1662 64

SSeCKS, a Src-suppressed protein kinase C substrate with metastasis suppressor activity, is the rodent orthologue of human gravin/AKAP12, a scaffolding protein for protein kinase A and protein kinase C. We show here that the tetracycline-regulated reexpression of SSeCKS in MatLyLu (MLL) prostate cancer cells suppressed formation of macroscopic lung metastases in both spontaneous and experimental models of in vivo metastasis while having minimal inhibitory effects on the growth of primary-site s.c. tumors. SSeCKS decreased angiogenesis in vitro and in vivo by suppressing vascular endothelial growth factor (VEGF) expression in MLL tumor cells as well as in stromal cells. The forced reexpression of VEGF(165) and VEGF(121) isoforms was sufficient to reverse aspects of SSeCKS metastasis-suppressor activity in both the experimental and spontaneous models. SSeCKS reexpression in MLL cells resulted in the down-regulation of proangiogenic genes, such as osteopontin, tenascin C, KGF, angiopoietin, HIF-1alpha, and PDGFRbeta, and the up-regulation of antiangiogenic genes, such as vasostatin and collagen 18a1, a precursor of endostatin. These results suggest that SSeCKS suppresses formation of metastatic lesions by inhibiting VEGF expression and by inducing soluble antiangiogenic factors.
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PMID:SSeCKS metastasis-suppressing activity in MatLyLu prostate cancer cells correlates with vascular endothelial growth factor inhibition. 1674 Jun 95


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