Treatment of an aneurysmal bone cyst in a young dog: A case report

BACKGROUND: An aneurysmal bone cyst (ABC) is a rare benign lytic lesion affecting the medullary canal of long bones. It has been widely reported in human medicine, but rarely described in domestic animals. OBJECTIVE: To report the surgical treatment and long term follow‐up of a dog affected by ABC. METHODS: An 8‐month‐old, intact female Weimaraner was presented with lameness affecting the left front limb and progressive swelling of the mid‐distal radius. Survey radiographs revealed a mid‐distal diaphyseal radial lesion. Fine needle aspirates, biopsy, CT scan and histopathology results supported the diagnosis of ABC. Treatment consisted of partial corticotomy of the affected radius, filling of the cystic cavity with demineralised bone matrix and autologous bone graft and stabilisation using lag screws and a neutralisation plate. RESULTS: The long‐term follow‐up, at 36 post‐operative months, showed no recurrence of the cyst and bone modelling. Comparing preoperative radiographs with those at 36 months, bone modelling reduced the radial area by 23.3% in the craniocaudal radiographic view and 30% in the mediolateral projection. CONCLUSIONS: This treatment was sucessful in the case here described, with a 3 years follow‐up

Investigating a Prognostic Factor for Canine Hepatocellular Carcinoma: Analysis of Different Histological Grading Systems and the Role of PIVKA-II

SIMPLE SUMMARY: PIVKA-II is an aberrant form of vitamin K that is increased in human coagulation disfunctions and in some neoplastic diseases. In veterinary medicine, PIVKA-II concentrations can be useful to identify patients with coagulative disorders in plasma and tissues, but its role as marker for hepatocellular carcinoma has not been investigated previously. In this study we characterized ed the expression of PIVKA-II in canine hepatocellular carcinomas in relation with the prognosis and some histological grading systems with the aim of finding useful prognostic factors for this canine tumour. ABSTRACT: Background: Hepatocellular carcinoma (HCC) in dogs is uncommon and often associated with a good prognosis, although some cases prove to be aggressive. In human oncology HCC is often very aggressive and diagnostic methods and prognostic factors are widely used to predict its biological behaviour. These include the expression of PIVKA-II. Methods: in order to identify a prognostic factor for canine HCC, we applied different methods of histological grading and investigated PIVKA-II expression in 22 HCC of dogs treated surgically and followed clinically for at least 2 years. Results: Nineteen patients analysed have passed the observation period without tumour recurrence, while 3 died following the development of metastases. PIVKA-II was positive in 15/22 cases without correlation with prognosis or tumoural grading even if a trend of PIVKA-II negativity in low WHO grades as well as increased number of PIVKA-II positive cases in higher WHO grades weres observed. Conclusions: This work showed that, PIVKA-II cannot be considered either as a marker of malignancy or as a prognostic marker for canine HCC. The poor prognosis depends usually on the clinical presentation. Thus prognostic parameters in canine HCC able to predict its aggressive behaviour through histological examination are still missing. The most promising method, limited to our study, seems to be the WHO histological grading

DIAPH3 Governs the Cellular Transition to the Amoeboid Tumour Phenotype

Therapies for most malignancies are generally ineffective once metastasis occurs. While tumour cells migrate through tissues using diverse strategies, the signalling networks controlling such behaviours in human tumours are poorly understood. Here we define a role for the Diaphanous-related formin-3 (DIAPH3) as a non-canonical regulator of metastasis that restrains conversion to amoeboid cell behaviour in multiple cancer types. The DIAPH3 locus is close to RB1, within a narrow consensus region of deletion on chromosome 13q in prostate, breast and hepatocellular carcinomas. DIAPH3 silencing in human carcinoma cells destabilized microtubules and induced defective endocytic trafficking, endosomal accumulation of EGFR, and hyperactivation of EGFR/MEK/ERK signalling. Silencing also evoked amoeboid properties, increased invasion and promoted metastasis in mice. In human tumours, DIAPH3 down-regulation was associated with aggressive or metastatic disease. DIAPH3-silenced cells were sensitive to MEK inhibition, but showed reduced sensitivity to EGFR inhibition. These findings have implications for understanding mechanisms of metastasis, and suggest that identifying patients with chromosomal deletions at DIAPH3 may have prognostic value

The conformational state of hERG1 channels determines integrin association, downstream signaling, and cancer progression

Ion channels regulate cell proliferation, differentiation, and migration in normal and neoplastic cells through cell-cell and cell-extracellular matrix (ECM) transmembrane receptors called integrins. K+ flux through the human ether-\ue0-gogo- related gene 1 (hERG1) channel shapes action potential firing in excitable cells such as cardiomyocytes. Its abundance is often aberrantly high in tumors, where it modulates integrin-mediated signaling. We found that hERG1 interacted with the \u3b21 integrin subunit at the plasma membrane of human cancer cells. This interaction was not detected in cardiomyocytes because of the presence of the hERG1 auxiliary subunit KCNE1 (potassium voltage-gated channel subfamily E regulatory subunit 1), which blocked the \u3b21 integrin-hERG1 interaction. Although open hERG1 channels did not interact as strongly with \u3b21 integrins as did closed channels, current flow through hERG1 channelswas necessary to activate the integrin-dependent phosphorylation of Tyr397 in focal adhesion kinase (FAK) in both normal and cancer cells. In immunodeficient mice, proliferation was inhibited in breast cancer cells expressing forms of hERG1 with impaired K+ flow, whereas metastasis of breast cancer cells was reduced when the hERG1/\u3b21 integrin interaction was disrupted. We conclude that the interaction of \u3b21 integrins with hERG1 channels in cancer cells stimulated distinct signaling pathways that depended on the conformational state of hERG1 and affected different aspects of tumor progression