The Prostate. Supplement最新文献

{"title":"Presence of chromogranins and regulation of their synthesis and processing in a neuroendocrine prostate tumor cell line.","authors":"R Ischia,&nbsp;Z Culig,&nbsp;U Eder,&nbsp;G Bartsch,&nbsp;H Winkler,&nbsp;R Fischer-Colbrie,&nbsp;H Klocker","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Small-cell carcinoma and carcinoid tumors of the prostate display a neuroendocrine phenotype. To some extent, adenocarcinomas of the prostate also express neuroendocrine properties. Prostatic neuroendocrine tumors do not respond to androgen ablation therapy. The regulation of synthesis of chromogranins and their processing into neuropeptides have not yet been studied in neuroendocrine cells of the prostate. We used CRL-5813 cells which were derived from a metastasis from small-cell prostate cancer for studies on steroid receptor expression and chromogranin processing.</p><p><strong>Methods: </strong>The expression of steroid receptor mRNA in CRL-5813 cells was examined by polymerase chain reaction. The synthesis and secretion of chromogranin- and secretogranin II-derived peptides were investigated by radioimmunoassays and high-performance liquid chromatography in untreated cells and in cells treated with the protein kinase A activator forskolin or basic fibroblast growth factor (bFGF).</p><p><strong>Results: </strong>cDNA fragments for alpha-estrogen receptor and androgen receptor but not for beta-estrogen receptor, progesterone receptor, and glucocorticoid receptor were amplified from CRL-5813 cells. These cells were found to contain typical markers of large dense-core vesicles, i.e., chromogranins A and B and secretogranin II. Forskolin significantly stimulated the synthesis and secretion of the chromogranin B-derived peptide PE-11 and the secretogranin II-derived secretoneurin. bFGF significantly induced PE-11 protein levels in cell extracts. CONCLUSIONS. Our results demonstrate the expression of typical large dense-core vesicle proteins, i.e., chromogranins, in a small-cell prostate cancer cell line and their upregulation by a protein kinase A activator and, in part, by bFGF.</p>","PeriodicalId":77436,"journal":{"name":"The Prostate. Supplement","volume":"8 ","pages":"80-7"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20607110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of neuroendocrine differentiation in prostate cancer by interleukin-1 and -2.","authors":"M Diaz,&nbsp;M Abdul,&nbsp;N Hoosein","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Neuroendocrine differentiation in prostate cancer has received much attention recently because it has been found to be associated with androgen independence and shortened patient survival in some studies. We have investigated the effect of the cytokines interleukin-1 (IL-1), IL-2, and IL-6 on the expression of the neuroendocrine marker chromogranin A in human prostate cancer cell lines. Chromogranin A was measured by fluorescence-immunoassay, as well as by immunoblotting. We find that IL-1beta and IL-6 increase the cellular content and chromogranin A secretion by LNCaP and DU-145 cells. By contrast, IL-2 decreases the cellular and secreted chromogranin A levels in the two cell lines. Our results suggest that these proinflammatory cytokines can influence neuroendocrine differentiation in prostate cancer and be involved in disease progression.</p>","PeriodicalId":77436,"journal":{"name":"The Prostate. Supplement","volume":"8 ","pages":"32-6"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20607778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostate innervation.","authors":"K T McVary,&nbsp;K E McKenna,&nbsp;C Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The growth of the prostate gland has been considered to be controlled exclusively by endocrine means. The abundance of alpha adrenergic and muscarinic receptors and nerve fibers suggests that the autonomic nervous system may in fact play a role in the growth maturation and secretory functions of the prostate. The predominant adrenergic input to the prostate is from short adrenergic neurons, while cholinergic nerves are closely related to the glandular epithelium, presumably affecting a secretory function. The prostate has a high density of alpha-1 and beta-2 adrenergic receptors, and the presence of these receptors, as well as their regulation by androgens, suggests and supports the direct mitogenic effect of catecholamines on prostate growth. The activated signal transduction pathways in these neural systems also appear to modulate prostatic function and growth. Denervation of the prostate results in a loss of functional and structural integrity of the gland. The effects of sympathectomy and parasympathectomy support the conclusion that the dichotomy of function in prostatic autonomic innervation has a fundamental regulatory purpose. The majority of the afferent innervation to the ventral prostate is localized to sensory nerves from the L5 and L6 segments. There is some smaller degree of innervation from T13-L2. There is evidence of extensive bilateral innervation of pelvic viscera. Despite the importance of afferent sensory feedback in regulating the control of prostate growth, its effect is of a smaller magnitude than that observed with androgens. Regardless of the specific control mechanisms suggested by neural involvement in the growth differentiation and secretory function of the prostate, the presence of innervation appears to be consistent and reproducible, and holds great potential for increasing our understanding of pathologic influences in prostate disease.</p>","PeriodicalId":77436,"journal":{"name":"The Prostate. Supplement","volume":"8 ","pages":"2-13"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20607819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of neuroendocrine differentiation in clinically localized prostatic carcinoma.","authors":"P A Abrahamsson,&nbsp;A T Cockett,&nbsp;P A di Sant'Agnese","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Several recent studies have focused attention on neuroendocrine differentiation (NED) in prostatic carcinoma (PC). Clinical studies have shown PC with NED to behave aggressively and to be associated with poor prognosis. To evaluate NED as an independent prognostic factor, we conducted a retrospective study of 87 patients with clinically localized PC who underwent radical prostatectomy. The presence of neuroendocrine tumor cells was confirmed by positive immunostaining for serotonin, chromogranin A, and neuron-specific enolase. The correlation between NED and disease progression was assessed. Progression of cancer was demonstrated in 35 (40%) of the patients. The presence of NED was confirmed in 60 (69%) of cases, and of these patients 26 (43%) manifested evidence of disease progression. Disease progression was also manifest in nine (33%) of the 27 patients without evidence of NED. Thus, in the setting of clinically localized carcinoma of the prostate, NED does not appear to be a statistically significant independent prognostic factor.</p>","PeriodicalId":77436,"journal":{"name":"The Prostate. Supplement","volume":"8 ","pages":"37-42"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20607779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroendocrine differentiation in prostatic carcinoma: an update.","authors":"P A di Sant'Agnese","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Neuroendocrine differentiation in prostatic carcinoma may be related to the growth and prognosis of prostate cancer, especially androgen-insensitive tumors.</p><p><strong>Materials and methods: </strong>This update reviews new investigations relating to neuroendocrine differentiation of prostatic carcinoma building on two previous review articles. All relevant publications are systematically reviewed.</p><p><strong>Results: </strong>New developments include the detection of bombesin, calcitonin and serotonin receptors, as well as a clearer delineation of the role that neuroendocrine products play in the growth, invasiveness, and motility of prostate cancer. Prognostic studies are still somewhat contradictory, but those studies and studies related to serum/plasma levels of neuroendocrine products in prostate cancer suggest that neuroendocrine differentiation may be more important in androgen-independent tumors and metastatic tumors than in hormone-sensitive and locally recurrent tumors. New cell line xenograft and transgenic mouse models for neuroendocrine prostatic carcinoma are described and will provide the basis for further investigations into the role played by neuroendocrine differentiation in prostatic carcinoma.</p><p><strong>Conclusions: </strong>Neuroendocrine differentiation in prostatic carcinoma is of great potential significance but needs to be better defined before its significance can be accurately assessed.</p>","PeriodicalId":77436,"journal":{"name":"The Prostate. Supplement","volume":"8 ","pages":"74-9"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20607783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptors for BPH growth factors are located in some neuroendocrine cells.","authors":"M Iwamura,&nbsp;K Koshiba,&nbsp;A T Cockett","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Prostatic neuroendocrine (NE) cells play an important role in the growth and differentiation of the prostate. We are still unable to characterize the exact mechanisms which lead to interactions between the epithelial cell and the NE cell. We offer several interactions generated by the NE cells, and speculate on some actions of selected NE cells.</p><p><strong>Methods: </strong>We used thin sections of prostatic tissue made from 20 radical prostatectomies. Our team used validated rabbit polyclonal antibodies which were raised against human EGFR and C-erb B-2, using the streptavidin-peroxidase conjugate method.</p><p><strong>Results: </strong>A strong immunoreactivity was noted with both antibodies in the cytosol of some NE cells. These cells had a dendritic appearance, and they were located in the acini and ducts of small-to-moderate-sized prostatic glands. Double immunostaining revealed the colocalization of both antigens with chromogranin A (CgA), a polypeptide that is expressed by NE cells. Of interest was the finding that EGFR and C-erb B-2 were colocalized as well as independently expressed by separate populations of NE cells.</p><p><strong>Conclusions: </strong>We conclude that NE cells may be regulated by the HER protein family, probably in a ligand-specific fashion. This is a revised report which identifies a pathway regulating NE cells, and their interactions with epithelial cells.</p>","PeriodicalId":77436,"journal":{"name":"The Prostate. Supplement","volume":"8 ","pages":"14-7"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20607820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroendocrine cells in benign and malignant prostate tissue: morphogenesis, proliferation, and androgen receptor status.","authors":"H Bonkhoff","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>The presence of neuroendocrine (NE) differentiation in benign and neoplastic prostate tissue has attracted increasing attention in contemporary prostate cancer research.</p><p><strong>Methods: </strong>The present review focuses on the proliferation and androgen receptor (AR) status of NE phenotypes and their morphogenetic origin in benign and malignant prostate tissue.</p><p><strong>Results: </strong>Recent data have documented phenotype relation between NE cells and other cell lineages in benign and malignant prostate tissue indicating their common origin. NE cell types (as defined by the most commonly used endocrine marker, chromogranin A) do not show evidence of cell proliferation and consistently lack the nuclear AR in both benign and malignant conditions.</p><p><strong>Conclusions: </strong>Prostatic NE cells most likely derive from local stem cells and represent terminally differentiated and androgen-insensitive cell populations in benign prostate tissue. The frequent occurrence of NE differentiation in prostatic adenocarcinoma obviously reflects the differentiation repertoire of its stem cells. Neoplastic NE cells devoid of nuclear AR constitute an androgen-insensitive cell population in prostate cancer. Furthermore, the absence of proliferation activity may endow NE tumor cells with relative resistance toward cytotoxic drugs and radiation therapy.</p>","PeriodicalId":77436,"journal":{"name":"The Prostate. Supplement","volume":"8 ","pages":"18-22"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20607776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroendocrine differentiation and the bombesin/gastrin-releasing peptide family of neuropeptides in the progression of human prostate cancer.","authors":"A G Aprikian,&nbsp;K Han,&nbsp;L Guy,&nbsp;F Landry,&nbsp;L R Begin,&nbsp;S Chevalier","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77436,"journal":{"name":"The Prostate. Supplement","volume":"8 ","pages":"52-61"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20607781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostate innervation.","authors":"K. McVary, K. Mckenna, Chung Lee","doi":"10.1002/(sici)1097-0045(1998)8+<2::aid-pros2>3.3.co;2-v","DOIUrl":"https://doi.org/10.1002/(sici)1097-0045(1998)8+<2::aid-pros2>3.3.co;2-v","url":null,"abstract":"The growth of the prostate gland has been considered to be controlled exclusively by endocrine means. The abundance of alpha adrenergic and muscarinic receptors and nerve fibers suggests that the autonomic nervous system may in fact play a role in the growth maturation and secretory functions of the prostate. The predominant adrenergic input to the prostate is from short adrenergic neurons, while cholinergic nerves are closely related to the glandular epithelium, presumably affecting a secretory function. The prostate has a high density of alpha-1 and beta-2 adrenergic receptors, and the presence of these receptors, as well as their regulation by androgens, suggests and supports the direct mitogenic effect of catecholamines on prostate growth. The activated signal transduction pathways in these neural systems also appear to modulate prostatic function and growth. Denervation of the prostate results in a loss of functional and structural integrity of the gland. The effects of sympathectomy and parasympathectomy support the conclusion that the dichotomy of function in prostatic autonomic innervation has a fundamental regulatory purpose. The majority of the afferent innervation to the ventral prostate is localized to sensory nerves from the L5 and L6 segments. There is some smaller degree of innervation from T13-L2. There is evidence of extensive bilateral innervation of pelvic viscera. Despite the importance of afferent sensory feedback in regulating the control of prostate growth, its effect is of a smaller magnitude than that observed with androgens. Regardless of the specific control mechanisms suggested by neural involvement in the growth differentiation and secretory function of the prostate, the presence of innervation appears to be consistent and reproducible, and holds great potential for increasing our understanding of pathologic influences in prostate disease.","PeriodicalId":77436,"journal":{"name":"The Prostate. Supplement","volume":"01 2","pages":"2-13"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50623058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation and clinical value of neuroendocrine differentiation in human prostatic tumors.","authors":"O Cussenot,&nbsp;J M Villette,&nbsp;B Cochand-Priollet,&nbsp;P Berthon","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer, like other solid tumors, is a rather heterogeneous entity. More than 50% of all malignant prostatic tumors contain neuroendocrine-like cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, which represent only 1-2% of all prostatic malignancies. Several investigators have reported that histopathologic determination of neuroendocrine differentiation in prostate carcinomas may have prognostic implications, while others have not confirmed these results. However, on the basis of experimental data, neuroendocrine-like cells appear to be involved in the emergence of androgen-independent cells and could be a target for new prostate cancer therapeutic strategies.</p><p><strong>Methods: </strong>The literature on the neuroendocrine phenotype of prostatic carcinoma is reviewed. This review summarizes most of the accumulated experimental and clinical data on the neuroendocrine phenotype in prostate cancer. We analyze the putative functions of neuroendocrine-like cells in prostate cancer progression and discuss the place of neuroendocrine phenotype biomarkers as diagnostic and prognostic factors in prostate cancer.</p><p><strong>Results: </strong>The fact that focal, patchy and heterogeneous clusters of neuroendocrine-like cells are frequently identified in organ-confined prostatic carcinoma probably accounts for the various evaluations of the predictive value of neuroendocrine histological patterns for the clinical outcome at this stage of the disease. The amount of neuroendocrine cells required to produce a detectable elevation in plasma chromogranin A has not yet been determined, but it is correlated with the number of chromogranin A-positive neuroendocrine (NE) cells. Despite the obvious current limitations of the application of neuropeptides as a serological test, this overview will try to more accurately define the possible roles of specific neuropeptides as prostatic cancer markers in diagnostic and monitoring protocols. The plasma chromogranin A level, in comparison with neuron-specific enolase (NSE), chromogranin B (CBG), pancreastatin, or secretogranin levels, appears to be the most useful neuroendocrine marker for determination of neuroendocrine differentiation of advanced prostatic adenocarcinoma.</p><p><strong>Conclusions: </strong>Future studies on neuroendocrine should confirm whether neuroendocrine biomarkers, especially the chromogranin family of peptides, can be used as prognostic markers during the course of prostate cancer or for the selection of patients suitable for evaluation of new antineoplastic drugs known to be active against specific and aggressive subpopulations of tumor cells.</p>","PeriodicalId":77436,"journal":{"name":"The Prostate. Supplement","volume":"8 ","pages":"43-51"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20607780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}