Synthetic fragment antigen-binding (Fab) antibodies are disclosed that bind to an N-terminal activation site of BCL-2-associated X-protein (BAX) and inhibit BAX activation. Also disclosed are methods of using the Fabs for measuring inactive monomeric BAX levels, screening for small molecules that bind to an N-terminal activation site of BAX, inhibiting apoptotic cell death, and predicting the ability of a cancer therapy to promote apoptotic cell death.

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

The invention relates to cell death of cancer cells, and in particular to biomarkers that may be used to identify cancer cells that are sensitive to death receptor ligand (DRL)-induced cell death. The invention also extends to prognostic methods and kits for identifying cancer cells that are sensitive to DRL-induced cell death. The invention further extends to novel compositions and therapeutic methods using such compositions for treating cancer.

The invention disclosed herein is for an in vitro cell-based assay for predicting the conversion from mild cognitive impairment to Alzheimer's disease in a patient who has received a diagnosis of MCI. The method comprises the following steps: a) culturing human hippocampal progenitor cells in a culture medium comprising serum, obtained from said patient, during a period of proliferation of said progenitor cells; b) subsequently culturing said hippocampal progenitor cells in a culture medium comprising serum, obtained from said patient, during a period of differentiation of said progenitor cells; c) determining the level of proliferation of said cultured progenitor cells; d) determining the average cell count of said cultured progenitor cells; and e) monitoring apoptotic cell death after differentiation of the proliferated hippocampal progenitor cells, wherein the outcomes of each of (c) to (e) are applied to a statistical analysis, the result of which is predictive of conversion from MCI to AD in the patient.

Provided are suspension-based cell culture systems and media for the timely and efficient proliferation of human tumor cell clusters from a patient, and related methods of evaluating the potential responsiveness of the tumor cells and the patient to one or more therapeutic agents.

Provided herein are methods of screening a therapy for induction of ferroptosis, the method comprising: exposing a cell line to a potential therapy; measuring induction of Heme Oxygenase 1 (HMOX1) resulting from the exposing the cell line to the potential therapy; and identifying the potential therapy as passing or failing the screening of the therapy for induction of ferroptosis based on the measuring the induction of HMOX1.

Provided herein are methods of functionally linking two or more genetic loci of a genome of a cell sample, the method comprising: exposing the cell sample to a plurality of different stimuli in parallel for a period of time sufficient to elicit a transcriptional response from the cell sample directly or indirectly; performing a transcriptional run-on assay on the cell sample to yield labeled nascent RNA transcripts; isolating the labeled nascent RNA transcripts; preparing a nascent RNA library from the labeled nascent RNA transcripts; sequencing the nascent RNA library to produce sequencing reads and mapping the sequencing reads to a reference genome, wherein the sequencing reads that are mapped represent genomic locations in the cell sample where active transcription was occurring at the end of the period of time; and identifying active enhancers and correlating activity of the active enhancers with the active transcription of the cell samples.

The present invention is drawn to the use of Minaprine dihydrochloride and analogs thereof, for reducing tumor growth when administered to a patient suffering from cancer.

Methods of generating conditionally active proteins that target senescent cells and which are conditionally active in an extracellular environment of a senescent cell. The methods include discovery methods using libraries of evolved proteins and assays employing physiological concentrations of components of bodily fluids. Also disclosed are conditionally active proteins for killing or removing senescent cells, pharmaceutical compositions employing these conditionally active proteins and methods for treatment of age-related diseases, conditions or disorders using same. The conditionally active proteins may be further evolved, conjugated to other molecules, masked, reduced in activity by attaching a cleavable moiety.

Methods for inducing growth inhibition or apoptosis of Bcl-2-expressing cells and treatments of Bcl-2 expressing cancers are provided. Additionally, assays for agents that can induce apoptosis of Bcl-2 expressing cells are disclosed.