Purpose: To study the role of the adrenomedullin system [adrenomedullin and its receptors (AMR), CLR, RAMP2, and RAMP3] in prostate cancer androgen-independent growth.Experimental Design: Androgen-dependent and -independent prostate cancer models were used to investigate the role and mechanisms of adrenomedullin in prostate cancer hormone-independent growth and tumor-associated angiogenesis and lymphangiogenesis.Results: Adrenomedullin and AMR were immunohistochemically localized in the carcinomatous epithelial compartment of prostate cancer specimens of high grade (Gleason score >7), suggesting a role of the adrenomedullin system in prostate cancer growth. We used the androgen-independent Du145 cells, for which we demonstrate that adrenomedullin stimulated cell proliferation in vitro through the cAMP/CRAF/MEK/ERK pathway. The proliferation of Du145 and PC3 cells is decreased by anti-adrenomedullin antibody (aAM), supporting the fact that adrenomedullin may function as a potent autocrine/paracrine growth factor for prostate cancer androgen-independent cells. In vivo, aAM therapy inhibits the growth of Du145 androgenindependent xenografts and interestingly of LNCaP androgen-dependent xenografts only in castrated animals, suggesting strongly that adrenomedullin might play an important role in tumor regrowth following androgen ablation. Histologic examination of aAM-treated tumors showed evidence of disruption of tumor vascularity, with depletion of vascular as well as lymphatic endothelial cells and pericytes, and increased lymphatic endothelial cell apoptosis. Importantly, aAM potently blocks tumor-associated lymphangiogenesis, but does not affect established vasculature and lymphatic vessels in normal adult mice.Conclusions: We conclude that expression of adrenomedullin upon androgen ablation in prostate cancer plays an important role in hormone-independent tumor growth and in neovascularization by supplying/amplifying signals essential for pathologic neoangiogenesis and lymphangiogenesis.

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OBJECTIVE To analyse the clinical and radiological features of metanephric adenoma (MA, a rare benign renal tumour) in nine patients, and to review previous reports. PATIENTS AND METHODS From 1992 to 2007, we identified nine patients (eight women and one man) with MA at our institution. Four patients had a radical nephrectomy and five a partial nephrectomy. Preoperative imaging was reviewed by a senior radiologist. Renal colour Doppler ultrasonography (US), abdominal computed tomography and abdominal magnetic resonance imaging were used in seven, eight and four patients, respectively. RESULTS The mean (range) age of the patients was 46.8 (19–79) years. Six tumours were discovered incidentally. Three patients were symptomatic (two with haematuria and one with polycythaemia). There was no vascular flow on colour Doppler US within the tumours. There were peripheral and/or central calcifications in six of the tumours. All the tumours were well‐circumscribed with minimal enhancement after injection with non‐ionic intravenous contrast or gadolinium. CONCLUSIONS Renal MA is a benign tumour occurring mainly in young and middle‐aged women. Polycythaemia is associated in ≈10%. Generally, MA is solid, well‐circumscribed and hypovascular, often with calcifications. Based on a combination of clinical and imaging features, it might be possible to suspect the diagnosis of MA and propose a preoperative diagnostic biopsy, a partial nephrectomy or active surveillance.

Prostate cancer is the second cause of cancer mortality in men in Western countries. To study new therapeutic approaches such as gene therapy, animal models of human prostate cancer with metastatic behavior are mandatory. We used the Nod Scid mouse strain to develop an orthotopic animal model. Two androgen-independent cell lines (PC-3 and DU 145) were used. Local tumor growth and metastases were analyzed. The tumor take rates were close to those reported in the literature. However, a high frequency of various metastatic sites has been observed (liver, lung, spleen, adrenal, kidney, lymph node, and diaphragm). It can be concluded that the Nod Scid mouse is a relevant preclinical animal model to study human prostate cancer. Metastatic sites seem more numerous in comparison to other orthotopic mice models described.