Pulmonary carcinoma associated with cystic airspaces in two dogs.

Malignant pulmonary neoplasia associated with cystic airspaces is a well-recognised disease entity in humans. Two elderly dogs, previously diagnosed with a solitary emphysematous bulla, presented with non-specific clinical signs. At presentation, pulmonary auscultation was unremarkable. In both cases, thoracic CT demonstrated the transformation of the cystic airspace lesions characterised by a progressive increase of the solid component and reduction of the air component. Cytological evaluation and subsequent surgical excision followed by histopathology confirmed pulmonary carcinoma in both cases. These two cases represent the first demonstration of possible malignant transformation of pulmonary cystic airspace in dogs. Veterinarians should consider neoplastic transformation as a differential diagnosis in cases of cystic airspaces, particularly cases with features including thickening or irregularity of the wall, associated soft-tissue nodules or solid and non-solid tissue intermixed within clusters of multiple cystic airspaces. Ongoing monitoring of cystic airspace lesions through diagnostic imaging is recommended.

Factors influencing local control in patients undergoing breast conservation surgery for ductal carcinoma in situ.

BACKGROUND: The aim of our study was to assess various predictors for local recurrence (LR) in patients undergoing breast conservation surgery (BCS) for ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: An audit was performed of 582 consecutive patients with DCIS between Jan 1975 to June 2008. In patients undergoing BCS, local guidelines reported a margin of ≥10 mm during the above period. Guideline with regard to margin of excision changes soon after this period. We retrospectively analysed clinical and pathological risk factors for local recurrence in patients undergoing BCS. Statistical analysis was carried out using SPSS version 19, and a cox regression model for multivariate analysis of local recurrence was used. RESULTS: Overall 239 women had BCS for DCIS during the above period. The actuarial 5-year recurrence rate was 9.6%. The overall LR rate was 17% (40/239. LR was more common in patients ≤50 years: (10/31 patients, 32%) compared to patients > 50 years (30/208, 14%, P = 0.02). Forty three per cent of patients (6/14) with <5 mm margin developed LR which was significantly higher compared to patients with 5-9 mm margin (12%, 3/25) and with ≥10 mm margin (14%, 27/188, P = 0.01). On multivariate analysis age ≤50 years, <5 mm pathological margin were independent prognostic factors for local recurrence. CONCLUSION: Our study shows that younger age (≤50 years) and a margin < 5 mm are poor prognostic factors for LR in patients undergoing breast conservation surgery for DCIS.

Upregulation of miR-21 by Ras in vivo and its role in tumor growth.

miR-21 is a microRNA (miRNA) frequently overexpressed in human cancers. Here we show that miR-21 is upregulated both in vitro and in vivo by oncogenic Ras, thus linking this miRNA to one of the most frequently activated oncogenes in human cancers. Ras regulation of miR-21 occurs with a delayed kinetic and requires at least two Ras downstream pathways. A screen of human thyroid cancers and non-small-cell lung cancers for the expression of miR-21 reveals that it is overexpressed mainly in anaplastic thyroid carcinomas, the most aggressive form of thyroid cancer, whereas in lung its overexpression appears to be inversely correlated with tumor progression. We also show that a LNA directed against miR-21 slows down tumor growth in mice. Consistently, a search for mRNAs downregulated by miR-21 shows an enrichment for mRNAs encoding cell cycle checkpoints regulators, suggesting an important role for miR-21 in oncogenic Ras-induced cell proliferation.

Inhibition of orotidine 5'-monophosphate decarboxylase and its therapeutic potential.

Orotidine 5'-monophosphate decarboxylase (ODCase) is among the most proficient enzymes, and catalyzes the decarboxylation of OMP to UMP. An overview of ODCase and various proposals for its catalytic mechanism of decarboxylation are briefly presented here. A number of inhibitors of ODCase and new developments in the X-ray structures of ODCases from different species are discussed in the context of their therapeutic potential against cancer and infectious diseases. Latest discoveries in the inhibition of ODCase, for example using the novel C6 substitutions on the uridine, open new doors for drug discovery targeting parasitic diseases such as malaria.