Comparisons, Connections & Conspiracy Theories, page-296

Mal, if that is the case you should be the first person supporting a biotech company who motis opprandi and IP is looking for a cure for Neurofibromitosis. Read up: http://grantome.com/grant/NIH/R29-NS037895-04

It might be the case your former investment in Cellmid created personal issues that may have led to financial difficulties, relationship breakdowns, depression, anxiety and you may feel that you have an axe to wield to anyone and everyone associated with the company. However the reality is, whether you like it or not we all have options and no one was holding a gun to your head when you bought, held or was forced to sell to facilitate a settlement. 

This constant negativity, and your attempt to trash the company is only keeping your wounds open and you may think this is your revenge; a point in time comes when you need to man up and accept some responsibility and move on.

You have moved on from the rat race of Sydney to a beautiful island home; it might be time you also moved on from some your grudges and attempted retributions. 

Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disorder with an incidence of 1:3500. NF1 is associated with mutations in the NF1 gene and characterized by learning impairment, abnormal growth of neural crest derivatives such as Schwann cells and melanocytes and, most prominently, develop tumors. Multiple neurofibromas are the defining feature of NF1 and they are the cause for much of the medical burden of this condition. The major cellular component of neurofibromas are Schwann cells. Schwann cells derived from neurofibromas are angiogenic and invasive as are Schwann cells from NF1-/- and +/- knockout mice indicating that tumor cells produce altered levels of growth factors. It is not known, which growth factors are upregulated as a result of NF1 deficiency. Recent work from the principal investigator's laboratory has identified a number of growth factors which are upregulated in NF1-/- Schwann cells.These studies have shown that one of these factors, midkine (MK), stimulates proliferation of systemic and brain endothelial cells and of neurofibroma derived cells. MK is able to induce tumor growth after transfection into non-tumorigenic, MK negative SW-13 cells and NIH3T3 cells. Furthermore, the principal investigator found MK expressed in Schwann cells and endothelial cells of dermal neurofibromas, and in malignant and benign peripheral nerve sheet tumors (PNST) of NF1 patients. Finally, MK is expressed in the skin of NF1 patients but is not expressed in non-NF1 skin. The principal investigator proposes experiments that will elucidate the physiological role of MK and its contribution to tumor growth. In Aim 1 he will express MK in neurofibroma-derived cell lines which have a low tumorigenic potential and express very low levels of MK and study phenotypic changes. The expression of MK will be under the control of a tetracycline-regulatable promoter that allows to regulate transfected MK in vitro and in vivo by administration of tetracycline. In Aim 2 he will use molecular targeting of MK mRNA with ribosomes to elucidate the contribution of MK to tumor growth of malignant PNST-derived cells that express high levels of MK. In Aim 3 he will study tumor formation in NF1+/- MK-/- double knockout mice. Neurofibromas will be induced in these mice by nerve transection and tumor incidence, time of onset and tumor growth rate will be evaluated. In Aim 4 he proposes to study whether MK levels can be detected in skin and/or serum samples of NF1 patients and may serve as a diagnostic indicator for NF1.