Abstract: The present application provides methods and systems for detecting and quantifying chromosomal instability from histology images with machine-learning. Also described herein are methods for selecting treatments for a medical disease, by determining a chromosomal instability metric from histology images. The disclosed methods and systems may also be used to investigate disease progression and prognosis.

Abstract: The invention provides for an isolated nucleic acid encoding Mda-5 (melanoma differentiation associated gene-5) and an isolated Mda-5 polypeptide. The invention further provides a vector comprising the nucleic acid encoding Mda-5, as well as a host cell comprising the vector. The invention provides an antibody which specifically binds to an Mda-5 polypeptide. The invention further provides a method for determining whether a compound is an inducer of Mda-5 gene expression and assays to determine whether a compound modifies the enzymatic activity of the Mda-5 polypeptide.

Abstract: The present invention relates to methods of treating a cancer in a subject comprising generating within one or more cancer cells of a subject an effective amount of MDA-7 and an effective amount of one or more free radicals. The present invention further relates to methods of inhibiting proliferation or promoting death in a cancer cell of a subject comprising generating within one or more cancer cells of a subject an effective amount of MDA-7 and an effective amount of one or more free radicals. Generation of an effective amount of MDA-7 can occur by administering to the cancer cell an effective amount of an mda-7 nucleic acid, MDA-7 protein, functional equivalents of either of these molecules, by upregulation of the endogenous mda-7 gene, or by stabilization of the mda-7 mRNA.

Abstract: The present invention relates to the discoveries that apoptotic effects of the melanoma differentiation associated gene mda-7 (also known as interleukin-24, “IL-24”) on malignant cells occur via the p38 MAPK pathway and members of the Growth Arrest and DNA Damage (“GADD”) gene family but are substantially independent of the JAK/STAT pathway. Accordingly, the invention provides for methods for identifying apoptosis-modulating agents using assay methods which determine the ability of a test agent to increase or decrease expression of constituents of the mda-7 apoptosis pathway, preferably in a JAK/STAT substantially independent manner. Such agents may be small molecules or may be fragments, variants and/or derivatives of native MDA-7.

Abstract: The present invention relates to mda-5 nucleic acids, MDA-5 proteins, the mda-5 promoter, and related molecules, and the use of each of these elements in protecting against or limiting viral infection, controlling cell proliferation, and promoting apoptosis. It is based upon the discovery that, contrary to earlier hypotheses based on the amino acid sequence of MDA-5, the protein is not a defective ATPase but rather exhibits ATPase activity. This supports the role of MDA-5 as a RNA helicase protein and consequently its use in promoting RNA degradation, for example in the context of antiviral defense, limitation of cell proliferation, or induction of apoptosis.

Abstract: A vector having the Protein Translation Peptide Elongation Factor-1&agr; (EF-1&agr;) promoter and nucleic acids encoding a reverse tetracycline-controlled activator is provided, wherein the expression of the activator is under the control of the EF-1&agr; promoter. In addition, a method of generating a reverse tetracycline-controlled transactivator expression system for inducible tetracycline-regulated gene expression is provided that consists of: (a) isolation of a DNA fragment encoding the reverse tetracycline-controlled transactivator, (b) isolation of a DNA fragment containing the EF-1&agr; promoter, (c) subcloning of these DNA fragments into a plasmid or other suitable vector to create a vector in which the reverse tetracycline-controlled transactivator is operably linked to the EF-1&agr; promoter.

Abstract: The present invention provides a vector comprising Protein Translation Peptide Elongation Factor-1 &agr; promoter and nucleic acids encoding reverse tetracycline controlled transactivator, wherein the expression of said transactivator is under the control of Protein Translation Peptide Elongation Factor-1 &agr; promoter.