Browsing by Subject "Prostate carcinoma"

Now showing 1 - 4 of 4
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    Neuropeptides bombesin and calcigonin induce resistance to etoposide induced apoptosis in prostate cancer cell lines
    (Murcia : F. Hernández, 2000) Salido, M.; Vilches, J.; Lopez, A.
    Background: Neuroendocrine differentiation in prostatic carcinoma has been related to regulation of proliferation and metastatic potential and correlated with prognosis. More than 80% of prostate carcinomas initially respond to androgen ablation, but most relapse, due to the heterogeneous presence of androgendependent and independent clones. The pathways of cellular proliferation and apoptosis are inexorabily linked to minimize the ocurrence of neoplasia, and disfunction of apoptosis is proposed as a pathogenic process in malignant tumors. Androgen-dependent prostatic cancer cells undergo apoptosis after androgen deprivation, but not androgen-independent ones due to a defect in the initiation step. Anyway, they retain the basic cellular machinery to undergo apoptosis. We suggest a possible role of neuroendocrine differentiation in the onset and regulation of apoptosis in prostatic neoplasia. Methods: LNCaP, PC-3 and DU 145 prostatic cancer cell lines were induced to undergo apoptosis after treatment with etoposide alone or plus androgen ablation. We tested the role of neuropeptides bombesin and calcitonin at modulating etoposide induced apoptosis. Results: Etoposide-induced apoptosis in all cancer cell lines was achieved. In LNCaP androgen ablation was also required. Apoptosis is prevented in all three lines when bombesin was added. Calcitonin addition prevents apoptosis in PC-3, LNCaP and in an etoposide dose-dependent way in DU 145. Conclusion: Neuropeptides bombesin and calcitonin can modulate the apoptotic response of prostate cancer cells by inducing resistance to etoposide-induced apoptosis, suggesting that neuropeptides can be used as a target of therapeutical approach in prostatic carcinoma.
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    Receptor activator of nuclear factor-kB ligand -RANKL- as a novel prognostic marker in prostate carcinoma
    (Murcia : F. Hernández, 2008) Pérez-Martínez, Francisco C.; Alonso, Verónica; Sarasa, José L.; Manzarbeitia, Félix; Vela-Navarrete, Remigio; Calahorra, Francisco J.; Esbrit, Pedro
    Combined immunodetection of parathyroid hormone-related protein (PTHrP) and receptor activator of NF-kB ligand (RANKL) has shown to successfully distinguish poorly- and well-differentiated prostate carcinoma (PCa). In the present study, we aimed to assess whether immunohistochemical evaluation of these factors, and also osteoprotegerin (OPG) and Ki67, in radical prostatectomy specimens can predict biochemical recurrence. Fifty nine PCa cases undergoing radical prostatectomy between 1995 and 1998, without history of neoadjuvant hormonal therapy, were studied. Preoperative serum prostate-specific antigen (PSA), Gleason-sum score, pathologic stage, perineural invasion, seminal vesicle involvement, and positive surgical margins were assessed in these patients. Biochemical recurrence, defined by PSA > 0.4 ng/mL at 90 days or later after prostatectomy, occurred in 32/59 patients. In these patients, positivity for OPG and RANKL in the tumoral epithelium was higher than in those patients with no biochemical recurrence. Using univariate analysis, Gleason-sum score, surgical margins, and seminal vesicle involvement, as well as OPG and RANKL immunostaining (using a score value corresponding to moderate staining as cut-off) were significant predictors of biochemical recurrence (p<0.05). Using the multivariate Cox model, among the evaluated factors only RANKL expression (hazard ratio 11.6; p <0.001) was an independent prognostic indicator. Our findings suggest that immunohistochemical evaluation of RANKL in the primary tumor is a potential risk factor in PCa patients.
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    TNF-aIL-1-NF-kB transduction pathway in human cancer prostate
    (Murcia : F. Hernández, 2008) Royuela, Mar; Rodríguez-Berriguete, Gonzalo; Fraile, Benito; Paniagua, Ricardo
    TNFa exerts apoptosis throughout an intracellular transduction pathway that involves the kinase proteins TRAF-2 (integration point of apoptotic and survival signals), ASK1 (pro-apoptotic protein), MEK-4 (p38 activator and metastasis suppressor gene), JNK (stress mitogen activated protein kinase) and the transcription factor AP-1. TNFa also exerts proliferation by p38 activation, or when TRAF-2 simultaneously induces the transcription factor NF-kB by NIK. NIK and p38 may also be activated by IL-1. P38 activated several transcription factors such as Elk-1, ATF-2 and NF-kB. NIK also may activate NF-kB. The aim of the present article was to evaluate the different components of this TNFa/IL-1 transduction pathway in human prostate carcinoma (PC) in comparison with normal human prostate. In prostate cancer, pro-apoptotic TNFa/AP-1 pathway is probably inactivated by different factors such as p21 (at ASK-1 level) and bcl-2 (at JNK level), or diverted towards p38 or NIK activation. IL-1a enhances proliferation through IL-1RI that activates either NIK or p38 transduction pathway. P38 and NIK activate different transcription factors related with cell proliferation and survival such as ATF-2, Elk-1 or NF-kB. In order to search a possible target to cancer prostate treatment we proposed that inhibition of several proinflamatory cytokines such as IL-1 and TNFa might be a possible target for PC treatment, because decrease the activity of all transduction pathway members that activate transcription factors as NF-kB, Elk-1 or ATF-2.
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    Tracking prostate carcinoma micrometastasis to multiple organs using histochemical marker genes and novel cell systems
    (Murcia : F. Hernández, 2001) Culp, L.A.; Holleran, J.L.; Miller, C.J.
    Studies of human prostate carcinoma (PCA) have been hampered by only a few cell systems from already-metastatic human disease. We have developed a novel cell system by using tissue cultured CWR22R cells from a xenograft of a primary tumor from a human patient. These cells were transfected with the bacterial lacZ gene to maximize their detection during progression and metastasis in nude mice. LZ-CWR22R cells are extremely stable for lacZ expression over 25 passages and metastasize to lung, liver, and bone from the subcutis - major sites of metastasis of the human disease. A matrigel vehicle facilitated development of primary tumors and micrometastases in al1 organs. While some micrometastases developed into overt metastases, others remained as micrometastases for long periods of time, possibly providing a model of latency of metastatic disease. An experimental metastasis model (tail vein injection) also generated micrometastases in lung, liver, and bone with differing kinetics of formation and stability. Serial sections of many individual lung micrometastases within one hour of injection indicated considerable heterogeneity in cellular composition (from 1 to 19 cells/site) while liver sites at later times were comprised of only 1 or 2 cells (the size of bone sites were comparable to those of liver). By combining use of these histochemically-tagged PCA cell systems with high resolution molecular analyses (laser-capture microdissection), it will now be possible to analyze gene expression patterns characteristic of micrometastases developing in severa1 different organs.