The disclosure provides methods of treating a tumor/cancer by administering naltrexone or an analogue thereof, followed by a recovery phase, and then administering a small molecule signaling inhibitor such as PI3-kinase inhibitors, AKT inhibitors, taxanes, antimetabolites, alkylating agents and/or cell cycle inhibitors. The disclosure also provides diagnostic methods for assessing a therapeutic response to the methods of treatment.

An object of the present invention is to provide novel apoptosis inhibitors and therapeutic agents for inner ear hearing impairment. As a pharmaceutical agent for this purpose, biguanide compounds represented by the following structural formula (I) or a rapamycin derivative represented by the following structural formula (II) as an active ingredient is provided:

##STR00001##

wherein R.sup.1 to R.sup.7 are each independently selected from a hydrogen atom, a halogen atom, or a C.sup.1-6 alkyl group, a C.sub.3-8 cycloalkyl group, a C.sub.6-10 aryl group, a 5- or 6-membered heteroaryl group, or a 5- or 6-membered non-aromatic heterocyclic group, each of which may have a substituent selected from a halogen atom, a cyano group, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group, a C.sub.1-6 alkoxy carbonyl group, a C.sub.3-8 cycloalkyl group, a C.sub.2-6 alkenyl group, a C.sub.2-6 alkynyl group, and a phenyl group;

##STR00002##

wherein R.sub.1 is a C.sub.1-6 alkyl or a C.sub.3-6 alkynyl, R.sub.2 is H, CH2-OH or CH.sub.2CH.sub.2OH, and X is O, (H, H) or (H, OH).

Provided herein are methods and compositions related to a retinoid receptor-selective pathway. As described herein, this pathway can be targeted to manipulate a tumor microenviroment. For example, the methods and compositions described herein can be used to induce apoptosis in a cancer cell. Further, the compositions described herein, including Sulindac and analogs thereof, can be used to target this pathway for the treatment or prevention of cancer in human patients.

Provided herein are methods and assays for isolating and culturing seborrheic keratosis cells ex vivo. Also provided herein are screening assays using cultured seborrheic keratosis cells and methods for treating seborrheic keratosis in a subject.

The present invention relates to a method for detecting apoptosis using a phosphatidylinositol phosphate-binding material, a method for screening anticancer agents, a method for screening apoptosis-inhibiting materials, and a method for inhibiting phagocytosis.

Disclosed herein are antibodies having binding specificity to the amino acid sequences Ala Ser Ser Gly Leu Thr Val Glu Val Asp (SEQ ID NO:1) and Thr Val Glu Val Asp (SEQ ID NO:14), and methods of detecting cell death in a sample, comprising contacting the sample with a first antibody specific for a C-terminal amino acid sequence Ala Ser Ser Gly Leu Thr Val Glu Val Asp (SEQ ID NO:1) or Thr Val Glu Val Asp (SEQ ID NO:14) of a CK18 protein fragment having a C-terminal amino acid sequence of Val Glu Val Asp (SEQ ID NO:2) and a second antibody that specifically binds an epitope that is present in both full-length CK18 and the CK18 protein fragment, and that does not overlap with SEQ ID NO:1 or SEQ ID NO:14, under conditions such that the CK1 8 protein fragment present in the sample specifically binds to the first antibody and the second antibody, wherein one of the antibodies is bound to a solid support and the other antibody is bound to a detection moiety capable of producing a signal; optionally removing any unbound or excess material; and detecting the signal from the detection moiety, wherein the signal is positively correlated with the presence of the CK18 protein fragment in the sample.

The invention described herein features infrared fluorescent protease reporters (iProteases) and methods of use thereof. The iProteases can be used in in vivo and in vitro assays to detect protease activity and disease states associated with protease activity. In a still further embodiment, the present invention provides a kit comprising any of the above described polynucleotides. In a further aspect, the present invention provides a method of in vivo optical imaging. In a still further embodiment, the in vivo imaging is performed in a living animal. In a further aspect, the present invention provides a method of detecting protease activity, the method comprising expressing a polypeptide according to any of those described above in a cell.

The present invention provides methods of determining cell sensitivity to a therapeutic agent.

The present invention provides methods, compositions and kits for the characterization of cellular pathways in cells containing genetic alterations.

A method for predicting a subject's response to a TUSC2 therapy is provided. In particular, a subject's response is predicted based on the proportion of cancers cells that are apoptotic. Also provided is a method of treating a subject previously predicted to have a favorable response with a TUSC2 therapy. Methods for treating cancer by administration of a TUSC2 therapeutic in conjunction with an EGFR inhibitor and/or a protein kinase inhibitor are also disclosed. Kits and reagents for use in TUSC2 therapy are provided.