Abstract:
Methods of assessing cytolysis of cancer cells, including providing a cell-substrate impedance monitoring device operably connected to an impedance analyzer, wherein the device comprises a well for receiving cells and an electrode array at a base of the well; adding target cells characterized as cancer cells to the well; adding effector cells to the well to form a test well, wherein the effector cells are immune cells obtained or derived from a same patient as the target cells; monitoring cell-substrate impedance of the test well before and after adding the effector cells and optionally deriving an impedance-based parameter from the impedance; and determining effectiveness of effector cell killing of the target cells by comparing the impedance or impedance based parameter over time.
Abstract:
A system for monitoring impedance of excitable cells in vitro, which includes a device for monitoring cell-substrate impedance at 20 millisecond resolution, which includes a nonconductive substrate with one or more electrode arrays fabricated in one or more wells, wherein cell attachment on the substrate can result in a detectable change in impedance between electrodes within each electrode array; an impedance analyzer capable of impedance measurement at 20 millisecond time resolution; electronic circuitry that can engage said device and selectively connect said two or more electrode arrays of said device to said impedance analyzer; and a software program that controls said electronic circuitry and records and analyzes data obtained from said impedance analyzer.
Abstract:
Methods for identifying compounds that modulate cellular responses stimulated by IgE, which include providing an impedance-based system that monitors cell-substrate impedance of cells on a substrate; introducing cells to the substrate of the system; adding at least one test compound and IgE to the cells, wherein the at least one test compound is suspected of modulating cell responses stimulated by the IgE; adding an antigen to the cells; monitoring the cell-substrate impedance of cells on the substrate; and analyzing the cell-substrate impedance to evaluate whether the at least one test compound alters a cellular response to stimulation with the IgE.
Abstract:
Methods of identifying whether a biologically active agent affects an oncogene addicted pathway within a cancer cell, by introducing a biologically active agent suspected of affecting an oncogene addicted pathway to a first well and a negative control to a second well, and introducing a stimulating agent that stimulates the oncogene addicted pathway to both wells; monitoring cell-substrate impedance of the two wells and optionally determining cell indices from impedance values; generating an impedance based curve for each of the two wells from the impedance values or from the cell indices; comparing the impedance-based curves to determine a degree of similarity; and if significantly different concluding the biologically active agent affects the oncogene addicted pathway within the cancer cells.
Abstract:
The present invention relates to certain pyrrolopyrimidine derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for the treatment of tumors and related diseases related to the dysregulation of kinase (such as EGFR (including HER), Alk, PDGFR, but not limited to) pathways.
Abstract:
A method of performing an assay of a response of two or more cell types to a test compound, including: providing a device for monitoring cell-substrate impedance, adding at least two different cell types to the device; adding at least one test compound to form at least two test compound wells; providing at least two control wells; monitoring impedance of the at least two test compound wells and of the at least two control wells at three or more time points after adding the at least one test compound; and analyzing measured impedance from the at least two test compound wells and from the at least two control wells at the three or more time points to obtain information on the response of the different cell types to the at least one test compound.
Abstract:
Use of cell-substrate impedance based methods for screening for agonists of G-Protein Coupled Receptors (GPCRs) or inhibitors of a Receptor Tyrosine Kinases (RTKs), identifying compounds that affect GPCR or RTK pathways, validating molecular targets involved in a GPCR or RTK signaling pathways, monitoring dose-dependent functional activation of GPCR or RTK; determining desensitization of a GPCR and identifying a compound capable of affecting RTK activity in cancer cell proliferation.
Abstract:
A method of performing an assay of a response of two or more cell types to a test compound, including: providing a device for monitoring cell-substrate impedance, adding at least two different cell types to the device; adding at least one test compound to form at least two test compound wells; providing at least two control wells; monitoring impedance of the at least two test compound wells and of the at least two control wells at three or more time points after adding the at least one test compound; and analyzing measured impedance from the at least two test compound wells and from the at least two control wells at the three or more time points to obtain information on the response of the different cell types to the at least one test compound.
Abstract:
Methods for identifying compounds that modulate cellular responses stimulated by IgE, which include providing an impedance-based system that monitors cell-substrate impedance of cells on a substrate; introducing cells to the substrate of the system; adding at least one test compound and IgE to the cells, wherein the at least one test compound is suspected of modulating cell responses stimulated by the IgE; adding an antigen to the cells; monitoring the cell-substrate impedance of cells on the substrate; and analyzing the cell-substrate impedance to evaluate whether the at least one test compound alters a cellular response to stimulation with the IgE.
Abstract:
Methods for identifying compounds that modulate cellular responses stimulated by IgE, which include providing an impedance-based system that monitors cell-substrate impedance of cells on a substrate; introducing cells to the substrate of the system; adding at least one test compound and IgE to the cells, wherein the at least one test compound is suspected of modulating cell responses stimulated by the IgE; adding an antigen to the cells; monitoring the cell-substrate impedance of cells on the substrate; and analyzing the cell-substrate impedance to evaluate whether the at least one test compound alters a cellular response to stimulation with the IgE.