Abstract: The present invention relates to methods for modulating angiogenesis, comprising administering to a subject, or cells or tissue derived therefrom: (i) one or more miRNA, or precursors or variants thereof, wherein at least one of said miRNA comprises a seed region comprising the sequence UCACAGU (SEQ ID N0:37) to inhibit angiogenesis; or (ii) one or more antagonists of a miRNA, wherein said miRNA comprises a seed region comprising the sequence UCACAGU (SEQ ID N0:37) to promote or induce angiogenesis. Also provided are methods of diagnosis of conditions associated with abnormal angiogenesis, or determining predisposition thereto. Suitable pharmaceutical compositions are also provided.

Abstract: The present invention provides methods for increasing the sensitivity of a tumour to immunotherapy, chemotherapy or radiotherapy by administering an effective amount of an oligonucleotide that inhibits the binding of miR-27a, or a variant thereof, to its target mRNA. Oligonucleotides used in the invention are typically in the form of a blockmirs used as an adjunctive therapy to inhibit tumour growth, normalise and/or improve function of tumour vasculature, and/or promote immune cell infiltration of tumours.

Abstract: The present invention provides oligonucleotides that inhibit the binding of miR-27a to VE-cadherin mRNA, particularly in the form of blockmirs. The invention also provides compositions comprising such oligonucleotides and methods of use of such oligonucleotides to modulate the activity of VE-cadherin, inhibit or reduce vascular permeability, treat or prevent a vascular permeability-associated disease or condition, inhibit tumor growth, treat ischaemic injury, enhance recovery from ischaemic injury, treat surgical wounds and/or promotes post-operative recovery, and promote or induce angiogenesis.

Abstract: The present invention relates to methods for modulating angiogenesis, comprising administering to a subject, or cells or tissue derived therefrom: (i) one or more miRNA, or precursors or variants thereof, wherein at least one of said miRNA comprises a seed region comprising the sequence UCACAGU (SEQ ID NO:37) to inhibit angiogenesis; or (ii) one or more antagonists of a miRNA, wherein said miRNA comprises a seed region comprising the sequence UCACAGU (SEQ ID NO:37) to promote or induce angiogenesis. Also provided are methods of diagnosis of conditions associated with abnormal angiogenesis, or determining predisposition thereto. Suitable pharmaceutical compositions are also provided.

Abstract: The present invention relates to methods for modulating angiogenesis, comprising administering to a subject, or cells or tissue derived therefrom: (i) one or more miRNA, or precursors or variants thereof, wherein at least one of said miRNA comprises a seed region comprising the sequence UCACAGU (SEQ ID NO:37) to inhibit angiogenesis; or (ii) one or more antagonists of a miRNA, wherein said miRNA comprises a seed region comprising the sequence UCACAGU (SEQ ID NO:37) to promote or induce angiogenesis. Also provided are methods of diagnosis of conditions associated with abnormal angiogenesis, or determining predisposition thereto. Suitable pharmaceutical compositions are also provided.

Abstract: The present invention provides oligonucleotides that inhibit the binding of miR-27a to VE-cadherin mRNA, particularly in the form of blockmirs. The invention also provides compositions comprising such oligonucleotides and methods of use of such oligonucleotides to modulate the activity of VE-cadherin, inhibit or reduce vascular permeability, treat or prevent a vascular permeability-associated disease or condition, inhibit tumour growth, treat ischaemic injury, enhance recovery from ischaemic injury, treat surgical wounds and/or promotes post-operative recovery, and promote or induce angiogenesis.

Abstract: The present invention relates to methods for modulating angiogenesis, comprising administering to a subject, or cells or tissue derived therefrom: (i) one or more miRNA, or precursors or variants thereof, wherein at least one of said miRNA comprises a seed region comprising the sequence UCACAGU (SEQ ID NO:37) to inhibit angiogenesis; or (ii) one or more antagonists of a miRNA, wherein said miRNA comprises a seed region comprising the sequence UCACAGU (SEQ ID NO:37) to promote or induce angiogenesis. Also provided are methods of diagnosis of conditions associated with abnormal angiogenesis, or determining predisposition thereto. Suitable pharmaceutical compositions are also provided.

Abstract: The present invention relates generally to a sphingosine kinase variant and to derivatives, analogues, chemical equivalents and mimetics thereof exhibiting reduced catalytic activity and, more particularly, to sphingosine kinase variants which exhibit a reduced capacity to phosphorylate sphingosine to sphingosine-1-phosphate. The present invention also contemplates genetic sequences encoding said sphingosine kinase variants and derivatives, analogues and mimetics thereof. The variants of the present invention are useful in a range of therapeutic and prophylactic applications.

Abstract: The present invention relates generally to a method of modulating cellular transendothelial migration and to agents useful for same. More particularly, the present invention relates to a method of modulating leukocyte extravasation by modulating an endothelial cell intracellular ERK (extracellular regulated kinase)-dependent signalling mechanism. The method of the present invention is useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by aberrant, unwanted or otherwise inappropriate transendothelial cells migration, in particular, inflammatory conditions which are characterised by inappropriate leukocyte and, in particular, neutrophil transendothelial migration.

Abstract: The present invention relates generally to novel protein molecules and to derivatives, analogues, chemical equivalents and mimetics thereof capable of modulating cellular activity and, in particular, modulating cellular activity via the modulation of signal transduction. More particularly, the present invention relates to human sphingosine kinase and to derivatives, analogues, chemical equivalents and mimetics thereof. The present invention also contemplates genetic sequences encoding said protein molecules and derivatives, analogues, chemical equivalents and mimetics thereof. The molecules of the present invention are useful in a range of therapeutic, prophylactic and diagnostic applications.

Abstract: The invention relates to detection of sphingosine kinase activity and sphingosine kinase agonist or antagonist activity.

Abstract: The present invention relates generally to a method of modulating endothelial cell functional characteristics and to agents useful for same. More particularly, the present invention relates to a method of modulating vascular endothelial cell pro-inflammatory and angiogenic phenotypes by modulating the functional levels of intracellular sphingosine kinase. The method of the present invention is useful, inter alia, in relation to the treatment and/or prophylaxis of conditions which are characterised by inadequate endothelial cell functioning and may include conditions such as vascular engraftment, organ transplantation or wound healing or conditions which are characterised by an aberrant endothelial cell inflammatory or angiogenic phenotype. Further, the method of the present invention facilitates the development of agents, such as functionally manipulated endothelial cell populations, for a range of therapeutic and/or prophylactic uses.

Abstract: The present invention relates generally to a method of modulating endothelial cell activity and to agents useful for same. More particularly, the present invention relates to a method of modulating intercellular vascular endothelial permeability by modulating an intracellular protein kinase C-dependent signalling mechanism. The method for the present invention is useful, inter alia, in the treatment and/or prophylaxis of a condition charicterised by aberrant, unwanted or otherwise inappropriate endothelial cell activity, in particular, conditions characterised by a loss of vascular intergrity.

Abstract: An isolated nucleic acid molecule comprising the sequence set forth in one of SEQ ID Numbers: 1 to 20.

Abstract: The present invention relates generally to a method of modulating cytokine-mediated cellular activity and to agents useful for same. More particularly, the present invention contemplates a method of modulating tumor necrosis factor-mediated cellular activity by modulating an intracellular sphingosine kinase-dependent signalling mechanism. The method of the present invention is useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by aberrant, unwanted or otherwise inappropriate cytokine-mediated cellular activity The present invention is further directed to methods for identifying and/or designing agents capable of modulating the subject sphingosine kinase-dependent signalling mechanism.

Abstract: The present invention relates generally to a method of modulating cellular activity and agents useful for same. More particularly, the present invention contemplates a method of modulating endothelial cell activity and even more particularly endothelial cell adhesion molecule expression. Most particularly, the present invention provides a method of treating coronary heart disease by preventing or reducing endothelial cell adhesion molecule expression.

Abstract: A method of modulating the growth of a cell, such as a neoplastic or malignant cell from the colon, stomach, lung, brain, bone, esophagus, pancreas, breast, ovary or uterus includes contacting the cell with an agent for a time and under conditions sufficient to modulate the functional activity of sphingosine kinase in which down-regulation of the functional activity of the sphingosine kinase down-regulates growth of the cells and up-regulation of the functional activity of this sphingosine kinase up-regulates the growth of the cell. The down-regulation can reduce the functional activity of this sphingosine kinase to an oncogenic ineffective level.

Abstract: The present invention relates generally to a method of modulating the growth of cells and, more particularly, to a method of down-regulating the growth of neoplastic cells. The present invention is useful, inter alia, in the therapeutic and/or prophylactic treatment of cancers such as, but not limited to, solid cancers such as cancers of the colon, stomach, lung, brain, bone, oesophagus, pancreas, breast, ovary or uterus.

Abstract: A screening method for identifying a therapeutic candidate for a coronary heart disease or an inflammatory condition is disclosed. The screening method tests for the presence or absence of an effect by a putative therapeutic agent on a component of a sphingosine kinase signaling pathway.

Abstract: The present invention relates generally to a method of modulating cellular activity and agents useful for same. More particularly, the present invention contemplates a method of modulating endothelial cell activity and even more particularly endothelial cell adhesion molecule expression. Most particularly, the present invention provides a method of treating coronary heart disease by preventing or reducing endothelial cell adhesion molecule expression.