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Matteo Fassan,
Domenico D'Arca,
Juraj Letko,
Andrea Vecchione,
Marina P Gardiman,
Peter McCue, Bernadette Wildemore,
Massimo Rugge,
Dolores Shupp-Byrne,
Leonard G Gomella,
Andrea Morrione,
Renato V Iozzo,
Raffaele Baffa
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ABSTRACT: MITOSTATIN, a novel putative tumor suppressor gene induced by decorin overexpression, is expressed in most normal human tissues but is markedly down-regulated in advanced stages of mammary and bladder carcinomas. Mitostatin negatively affects cell growth, induces cell death and regulates the expression and activation levels of Hsp27. In this study, we demonstrated that ectopic expression of Mitostatin in PC3, DU145, and LNCaP prostate cancer cells not only induced a significant reduction in cell growth, but also inhibited migration and invasion. Moreover, Mitostatin inhibited colony formation in soft-agar of PC3 and LNCaP cells as well as tumorigenicity of LNCaP cells in nude mice. Conversely, targeting endogenous Mitostatin by siRNA and anti-sense strategies in PC3 and DU145 prostate cancer cells enhanced the malignant phenotype in both cell lines. In agreement of these anti-oncogenic roles, we discovered that Mitostatin was absent in ∼35% (n = 124) of prostate tumor samples and its overall reduction was associated with advanced cancer stages. Collectively, our findings indicate that MITOSTATIN may acts as a tumor suppressor gene in prostate cancer and provide a novel cellular and molecular mechanism to be further exploited and deciphered in our understanding of prostate cancer progression.
PLoS ONE 01/2011; 6(5):e19771. · 4.09 Impact Factor
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Domenico D'Arca,
James LeNoir, Bernadette Wildemore,
Fedra Gottardo,
Emma Bragantini,
Dolores Shupp-Byrne,
Nicola Zanesi,
Matteo Fassan,
Carlo M Croce,
Leonard G Gomella,
Raffaele Baffa
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ABSTRACT: Aberrant or increased expression of cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of many diseases, including cancer. However, the exact mechanism by which COX-2 may influence tumorigenesis has yet to be described. To investigate the chemopreventive role of a COX-2 inhibitor, rofecoxib, in the development of urinary bladder cancer, we studied the effect of this drug in heterozygous and nullizygous fragile histidine triad (FHIT) gene-deficient mice in a chemically induced carcinogenesis model.
Two-hundred eight mice consisting of 50 FHIT +/+, 63 FHIT +/- and 95 FHIT -/-, were divided into five treatment groups and followed up for 15 weeks. Mice were treated with freshly prepared solution of 0.1% or 0.01% N-butyl-N-(-4-hydroxybutyl)-nitrosamine (BBN) in their drinking water and rofecoxib was administered in mouse chow at 150 parts per million concentration. Mice were sacrificed, and accurate histological analysis of the bladder was performed.
Rofecoxib treatment significantly reduced the incidence of preneoplastic lesions/bladder tumors (P = 0.016). Comparing the incidence of neoplastic lesions in mice treated with rofecoxib and BBN (22/56, 39.3%) and mice treated only with BBN (32/57, 56.1%), a protective role of rofecoxib on the BBN tumor induction has been observed (P = 0.024). A similar result (P = 0.002) has been reached observing the incidence of mild and moderate dysplasia in mice treated with a lower concentration of BBN (8/16, 50.0% vs. 20/24, 83.3%).Moreover, as previously observed, a significant increase in neoplastic lesions in the FHIT +/- and FHIT -/- vs. FHIT +/+ mice after BBN treatment has been observed (P = 0.003).
These findings suggest that rofecoxib provides a therapeutic defense against bladder carcinogenesis in our model and confirmed that the FHIT knock-out mouse is a suitable system to study in vivo bladder carcinogenesis.
Urologic Oncology 05/2009; 28(2):189-94. · 3.22 Impact Factor
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ABSTRACT: We describe the case of a 33-year-old African-American male who presented with multiple deep venous thromboses of the upper and lower extremities. Hypercoagulable workup was unrevealing. A chest x-ray showed bilateral hilar lymph node enlargement. Mediastinoscopy with hilar lymph node biopsy was performed. Lymph node histopathologic examination showed noncaseating granulomas. Lymph node tissue culture and special stains were negative for mycobacterial or fungal infection. This is an unusual case of multiple deep venous thromboses and sarcoidosis. The subject of sarcoidosis and venous thrombosis is discussed.
Southern Medical Journal 10/2006; 99(9):998-9. · 0.83 Impact Factor
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ABSTRACT: A case of a cavitary lung lesion in the right middle lobe of a 34-year-old woman who presented with hemoptysis is presented. The patient had a 2-year history of Wegener granulomatosis that had been treated with cyclophosphamide and corticosteroids. Although the patient gradually achieved remission of her disease, she developed new pulmonary symptoms and a cavitary lesion in her right lung. Further workup revealed elevated C- and P-ANCA titers. Following partial resection of her right lung, she was found to have an aspergilloma and no evidence of active Wegener granulomatosis. Pulmonary aspergillosis was felt to be the cause of both the hemoptysis and the cavitary lesion. We postulate that C-ANCA and P-ANCA were falsely positive in this case. Although rare, false positive C-ANCA and P-ANCA have been reported in pulmonary fungal infections.
Southern Medical Journal 08/2006; 99(7):753-6. · 0.83 Impact Factor
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ABSTRACT: We report a case of pulmonary blastomycosis appearing as metastatic laryngeal squamous cell carcinoma. Pulmonary blastomycosis was discovered as right lower lobe subpleural activity consistent with metastatic disease on a positron emission tomographic (PET) scan following total laryngectomy and bilateral neck dissection for locally invasive laryngeal squamous cell carcinoma. A computed tomographic (CT) scan of the chest showed a right lower lobe, subpleural pulmonary nodule. CT-guided fine-needle aspiration of the nodule revealed broad-based budding yeast consistent with blastomycosis. To our knowledge, this is the first case of a PET-positive pulmonary blastomycosis lesion mimicking pulmonary malignancy reported in the literature.
MedGenMed: Medscape general medicine 02/2006; 8(1):31.
