Methods for inhibition of cell proliferation, synergistic transcription modules and uses thereof
OwnerAntonio Iavarone, Andrea Califanoinventors
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Abstract
The invention provides for methods for treating nervous system cancers in a subject. The invention further provides methods for treating nervous system tumor cell invasion, migration, proliferation, and angiogenesis associated with nervous system tumors.
Claims45
A method for treating nervous system cancer in a subject in need thereof comprising administering to the subject a compound that inhibits a MGES protein.
A method for decreasing MGES protein activity in a subject having a nervous system cancer, the method comprising administering to the subject a compound that inhibits a MGES protein.
A method for inhibiting a MGES protein comprising contacting said protein with an effective amount of a compound selected from the group consisting of etoposide, 5-fluorouracil, Clostridium difficile Toxin B,
- and pharmaceutically acceptable salts thereof.
A method for detecting the presence of or a predisposition to a nervous system cancer in a human subject, the method comprising:
- (a) obtaining a biological sample from a subject;
- and
- (b) detecting whether or not there is an alteration in the expression of a Mesenchymal-Gene-Expression-Signature (MGES) gene in the subject as compared to a subject not afflicted with a nervous system cancer.
A method for inhibiting proliferation of a nervous system tumor cell or for promoting differentiation of a nervous system tumor cell, the method comprising decreasing the expression of a Mesenchymal-Gene-Expression-Signature (MGES) molecule in a nervous system tumor cell, thereby inhibiting proliferation or promoting differentiation.
A method for inhibiting angiogenesis in a nervous system tumor, the method comprising decreasing the expression of a Mesenchymal-Gene-Expression-Signature (MGES) molecule in a nervous system tumor cell, thereby inhibiting angiogenesis.
A method for treating a nervous system tumor in a subject, the method comprising administering to a nervous system tumor cell in the subject an effective amount of a composition that decreases the expression of a Mesenchymal-Gene-Expression-Signature (MGES) molecule in a nervous system tumor cell, thereby treating nervous system tumor in the subject.
A method for identifying a compound that binds to a Mesenchymal-Gene-Expression-Signature (MGES) protein, the method comprising:
- a) providing an electronic library of test compounds;
- b) providing atomic coordinates for at least 20 amino acid residues for the binding pocket of the MGES protein, wherein the coordinates have a root mean square deviation therefrom, with respect to at least 50% of Cα atoms, of not greater than about 5 Å, in a computer readable format;
- c) converting the atomic coordinates into electrical signals readable by a computer processor to generate a three dimensional model of the MGES protein;
- d) performing a data processing method, wherein electronic test compounds from the library are superimposed upon the three dimensional model of the MGES protein;
- and
- e) determining which test compound fits into the binding pocket of the three dimensional model of the MGES protein,
- thereby identifying which compound binds to the Mesenchymal-Gene-Expression-Signature (MGES) protein.
A method for decreasing MGES gene expression in a subject having a nervous system cancer, the method comprising:
- a) administering to the subject an effective amount of a composition comprising a MGES inhibitor compound,
- thereby decreasing MGES expression in the subject.
A diagnostic kit for determining whether a sample from a subject exhibits increased or decreased expression of at least 2 or more MGES genes, the kit comprising nucleic acid primers that specifically hybridize to an MGES gene, wherein the primer will prime a polymerase reaction only when a nucleic acid sequence comprising any one of SEQ ID NOS:
- 232, 234, 236, 238, 240, 242, or 244 is present.
Dependencies are inferred from the claim text.