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Passarin M.G.,USSL 22 | Moretto G.,Azienda Ospedaliera Universitaria di Verona | Musso A.M.,Azienda Ospedaliera Universitaria di Verona | Ottaviani S.,Azienda Ospedaliera Universitaria di Verona | And 8 more authors.
Journal of Neuro-Oncology | Year: 2010

Leptomeningeal dissemination of low-grade gliomas is an uncommon event. A 43-year old male presented with dizziness, gait ataxia, and diplopia. A nonenhancing lesion in the right cerebellar peduncle was identified, subtotally resected, and diagnosed as a grade II astrocytoma. After one year a nodular spread in the brain and leptomeninges was diagnosed, so the patient started chemotherapy with temozolomide and liposomal cytarabine. Complete remission was achieved after 12 months of treatment and the patient is still free from the disease after a follow-up of 24 months. We suggest that this combination may be a valuable treatment option. © Springer Science+Business Media, LLC. 2009. Source

Nones K.,University of Queensland | Waddell N.,University of Queensland | Song S.,University of Queensland | Patch A.-M.,University of Queensland | And 40 more authors.
International Journal of Cancer | Year: 2014

The importance of epigenetic modifications such as DNA methylation in tumorigenesis is increasingly being appreciated. To define the genome-wide pattern of DNA methylation in pancreatic ductal adenocarcinomas (PDAC), we captured the methylation profiles of 167 untreated resected PDACs and compared them to a panel of 29 adjacent nontransformed pancreata using high-density arrays. A total of 11,634 CpG sites associated with 3,522 genes were significantly differentially methylated (DM) in PDAC and were capable of segregating PDAC from non-malignant pancreas, regardless of tumor cellularity. As expected, PDAC hypermethylation was most prevalent in the 5 region of genes (including the proximal promoter, 5UTR and CpG islands). Approximately 33% DM genes showed significant inverse correlation with mRNA expression levels. Pathway analysis revealed an enrichment of aberrantly methylated genes involved in key molecular mechanisms important to PDAC: TGF-β, WNT, integrin signaling, cell adhesion, stellate cell activation and axon guidance. Given the recent discovery that SLIT-ROBO mutations play a clinically important role in PDAC, the role of epigenetic perturbation of axon guidance was pursued in more detail. Bisulfite amplicon deep sequencing and qRT-PCR expression analyses confirmed recurrent perturbation of axon guidance pathway genes SLIT2, SLIT3, ROBO1, ROBO3, ITGA2 and MET and suggests epigenetic suppression of SLIT-ROBO signaling and up-regulation of MET and ITGA2 expression. Hypomethylation of MET and ITGA2 correlated with high gene expression, which was associated with poor survival. These data suggest that aberrant methylation plays an important role in pancreatic carcinogenesis affecting core signaling pathways with potential implications for the disease pathophysiology and therapy. What's new? Based on a large genome-wide scan of DNA methylation, this study reports that global DNA methylation patterns can robustly segregate tumor and non-malignant pancreata. Cancer methylation also affects key pathways in pancreatic carcinogenesis, including TGF-β, WNT, and axon guidance signaling. This study confirms that methylation plays an important role in the development and progression of pancreatic cancer, with implications for both ongoing research and therapeutic development. © The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC. Source

Porcaro A.B.,Azienda Ospedaliera Universitaria di Verona | Monaco C.,Azienda Ospedaliera Universitaria di Verona | Romano M.,Azienda Ospedaliera Universitaria di Verona | Petrozziello A.,Azienda Ospedaliera Universitaria di Verona | And 7 more authors.
Urologia Internationalis | Year: 2010

Objectives: To explore the significance of the pretreatment total prostate-specific antigen (PSA) to free testosterone (FT) ratio (PSA/FT) as a marker for assessing the pathologic Gleason sum (pGS) and levels of tumor extension (pT) in prostatectomy specimens. Patients and Methods: 128 of 135 consecutive patients diagnosed with prostate cancer underwent radical prostatectomy. Simultaneous pretreatment serum samples were obtained to measure serum total testosterone, FT and total PSA levels. The statistical design of the study included 2 sections: the first part trying to explore the role of the PSA/FT ratio in clustering patients with different pathologic prognostic factors, and the second to investigate the PSA/FT ratio distribution in different groups of patients according to the pathologic stage and pGS of the specimen after radical prostatectomy. Results: The average age was 65.80 (range 51.21-77.26) years, mean PSA was 8.88 (range 1.22-44.27) μg/l, mean FT was 35.32 (range 13.70-69.30) pmol/l, and the mean PSA/FT ratio was 0.27 (range 0.04-1.48). The PSA/FT ratio significantly clustered both the pT and pGS groups. Analysis of variance for the distribution of the PSA/FT ratio was significant for the pT model groups. The mean PSA/FT ratio increased as the tumor extended and grew through the prostate gland (high-stage disease). Analysis of variance for the different distributions of the PSA/FT ratio was significant for all model pGS groups. In our investigation we also found (data not shown) that a PSA/FT ratio of ≥0.40 was strongly correlated with large extensive (pT3b+pT4) and high-grade cancers (pGS8+pGS9). Conclusions: Prostate cancer patients may be classified into 3 different pathologic prognostic groups according to the PSA/FT ratio: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40), and high risk (PSA/FT >0.40 and ≤1.5). The PSA/FT ratio may be considered as the marker expressing different biology groups of prostate cancer patients, and it is strongly associated with pT and pGS. Copyright © 2010 S. Karger AG, Basel. Source

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