Axl/Gas6/NFκB signalling in schwannoma pathological proliferation, adhesion and survival.

TAM family receptor tyrosine kinases comprising Tyro3 (Sky), Axl, and Mer are overexpressed in some cancers, correlate with multidrug resistance and contribute to tumourigenesis by regulating invasion, angiogenesis, cell survival and tumour growth. Mutations in the gene coding for a tumour suppressor merlin cause development of multiple tumours of the nervous system such as schwannomas, meningiomas and ependymomas occurring spontaneously or as part of a hereditary disease neurofibromatosis type 2. The benign character of merlin-deficient tumours makes them less responsive to chemotherapy. We previously showed that, amongst other growth factor receptors, TAM family receptors (Tyro3, Axl and Mer) are significantly overexpressed in schwannoma tissues. As Axl is negatively regulated by merlin and positively regulated by E3 ubiquitin ligase CRL4DCAF1, previously shown to be a key regulator in schwannoma growth we hypothesized that Axl is a good target to study in merlin-deficient tumours. Moreover, Axl positively regulates the oncogene Yes-associated protein, which is known to be under merlin regulation in schwannoma and is involved in increased proliferation of merlin-deficient meningioma and mesothelioma. Here, we demonstrated strong overexpression and activation of Axl receptor as well as its ligand Gas6 in human schwannoma primary cells compared to normal Schwann cells. We show that Gas6 is mitogenic and increases schwannoma cell-matrix adhesion and survival acting via Axl in schwannoma cells. Stimulation of the Gas6/Axl signalling pathway recruits Src, focal adhesion kinase (FAK) and NFκB. We showed that NFκB mediates Gas6/Axl-mediated overexpression of survivin, cyclin D1 and FAK, leading to enhanced survival, cell-matrix adhesion and proliferation of schwannoma. We conclude that Axl/FAK/Src/NFκB pathway is relevant in merlin-deficient tumours and is a potential therapeutic target for schwannoma and other merlin-deficient tumours

Serum proinflammatory cytokine response in patients with advanced liver tumors following selective internal radiation therapy (SIRT) with 90Yttrium microspheres.

NRC publication: Ye

Endoscopic endonasal transsphenoidal surgery: A mentoring surgical model

Background:  We report the experience of endoscopic endonasal transsphenoidal surgery (EETS) for resection of pituitary region tumours at Wellington, the central regional referral centre for neurosurgery in New Zealand, and discuss the collaborative mentoring surgical model that enhanced the learning experience. Method:  Between January 2007 and June 2009, a total of 47 operations on 46 patients were performed and reviewed retrospectively. All patients had perioperative clinical assessment, hormonal profile and magnetic resonance imaging studies for residual/recurrent disease. The collaborative model utilized two neurosurgeons with experience in the microsurgical resection of pituitary tumours: an endoscopic skull base fellowship trained rhinologist and an endoscopic skull base rhinologist with more experience who visited twice a year from Adelaide, Australia. Results:  The pathology results included: 30 non-functioning pituitary adenomas, 10 secreting pituitary adenomas, 3 meningiomas, 1 chordoma, 1 anterior skull base adenocarcinoma and 1 clival prostate metastasis. Complete tumour resection was intended and achieved in 38 cases. All 10 patients with secreting adenomas achieved improvement of hormonal profile. Nineteen out of 27 cases demonstrated improvement of vision. Perioperative complications included one epistaxis, three cerebrospinal fluid fistulae, one delayed chronic subdural haematoma and one persistent diabetes insipidus. Conclusion:  Our results highlight the value of a collaborative mentoring surgical model for a single centre adopting the endoscopic transsphenoidal technique and demonstrate that excellent EETS outcomes can be achieved in a smaller endoscopic skull base unit in Australasia during the learning phase.Joseph Y. M. Yang, Ingrid De Ruiter, Andrew Parker, Peter J. Wormald, Simon Robinson and Agadha Wickremeseker

oceanic corpo-graphies, refugee bodies and the making and unmaking of waters

This essay considers the challenges that the gendered and raced transnational subaltern refugee subject poses to the order of ‘the liberal state’ and ‘the liberal subject’, and argues that the latter are bound up in complex ways with entrenched understandings of the ocean as elementally distinct from land. This distinction, constituted by the freedom of the sea-going individualist liberal subject, invariably raced as white and gendered as male, to range across the waves in search of new worlds to conquer, is one that is continually reproduced both in popular culture's contemporary sea romances, and in the spatial and legal demarcations of the nation and its limits. In the diverse forms of traffic flowing from south to north, the historical oceanic mobility of this unfettered liberal subject (always shadowed and weighted down by its invisible freight of non-white bodies) now meets the transversal movements of the contemporary transnational subaltern as complex subject. Through the narratives of two refugees to Australia, the article traces the possibilities of an embodied refugee poetics for inscribing new geographies across the global borderlands