Abstract: Signal Transducer and Activator of Transcription (STAT) proteins have a fundamental role cell signaling, and are activated by a large number of cytokines and growth factors. One member of the STAT family, STAT3, has a critical role in oncogenesis. The present invention relates generally to disruption of the pathway of STAT3 signaling in the treatment of human cancer. STAT3 activation is shown to be present in diverse tumor cell lines and tumors, to promote oncogenesis, to inhibit apoptosis, and to reduce sensitivity to chemotherapeutic agents. Inhibition of STAT3 signaling induces apoptosis specifically in tumor cell lines, and increases sensitivity to chemotherapeutic agents. The invention relates more particularly to methods, compositions, means of administering such compositions, and means for identifying such compositions for the inhibition of STAT3 intracellular signaling in the treatment of human cancers.

Abstract: A method for facilitating a delivery of a molecule into an interior space of a cell includes the steps of introducing a molecule into a biological structure comprising a cell and applying a substantially continuous low-level electric field, in the form of non-thermal plasma (ionized gas) generated by a direct current voltage applied to an electrode, to the molecule and biological structure. The field is applied for a duration sufficient to effect a change in porosity the cell of the biological structure sufficient to facilitate an entry of a desired molecule into an interior thereof.

Abstract: A method for facilitating a delivery of a molecule into an interior space of a cell includes the steps of introducing a molecule into a biological structure comprising a cell and applying a substantially continuous low-level electric field, in the form of non-thermal plasma (ionized gas) generated by a direct current voltage applied to an electrode, to the molecule and biological structure. The field is applied for a duration sufficient to effect a change in porosity the cell of the biological structure sufficient to facilitate an entry of a desired molecule into an interior thereof.

Abstract: The electroporation system and method combine pulses having different characteristics for delivering molecules to cells in vivo. The pulses include a high-intensity pulse for inducing electroporation and a low-intensity pulse to induce electrophoretic molecule movement within an interstitial space, molecule adherence to a cell membrane, and electrophoretic movement of the molecule through the permeabilized membrane. The use of a high-intensity and a low-intensity pulse achieves improved delivery; reduction of intensity and/or duration of pulses for inducing electroporation; and decreased muscle stimulation, tissue damage, and patient discomfort.

Abstract: In accordance with the present invention is provided a novel tri-pronged electrode that produces minimal damage to deep brain or spinal cord regions. The apparatus and associated method of the present invention provides for a single insertion of a novel probe effective for both delivery of DNA and delivery of therapeutic electroporating current, thereby minimizing the potential damage to the nervous system.

Abstract: The present invention provides for a system and method whereby aspirin and acetic acid help to permeabilize cell membranes to allow exogenous molecules to gain access to the cell interior. As such, the present invention provides a low cost drug and gene delivery tool that can be applied in combination with other molecular delivery methods.

Abstract: Signal Transducer and Activator of Transcription (STAT) proteins have a fundamental role cell signaling, and are activated by a large number of cytokines and growth factors. One member of the STAT family, STAT3, has a critical role in oncogenesis. The present invention relates generally to disruption of the pathway of STAT3 signaling in the treatment of human cancer. STAT3 activation is shown to be present in diverse tumor cell lines and tumors, to promote oncogenesis, to inhibit apoptosis, and to reduce sensitivity to chemotherapeutic agents. Inhibition of STAT3 signaling induces apoptosis specifically in tumor cell lines, and increases sensitivity to chemotherapeutic agents. The invention relates more particularly to methods, compositions, means of administering such compositions, and means for identifying such compositions for the inhibition of STAT3 intracellular signaling in the treatment of human cancers.

Abstract: The present invention is a method of eliciting an antitumor effect in vivo comprising the steps of identifying a species representative of a treatment subject, identifying at least one non-coding nucleic acid sequence, introducing the at least one nucleic acid to at least one tumor in the treatment subject and applying an energy source to the at least one tumor. The energy source may comprise, but is not limited to, electrical, sonic, photonic, and microwave output.

Abstract: The present invention provides an apparatus and method that will accomplish molecular delivery and subsequent electroporation with a single apparatus without the need for separate molecule injection and placement of the electroporation applicators.

Abstract: In accordance with the present invention is provided a device and method for delivering DNA for the purpose of gene therapy to specific regions within and around the eye.

Abstract: A method for in vivo electrotherapy, or electroporation-mediated therapy, using a needle array apparatus is provided. Treatment of tumors with a combination of electroporation using the apparatus of the invention, and a chemotherapeutic agent, caused regression of tumors in vivo.

Abstract: The present invention is a device for electromanipulation of chemical species in vivo relative to a target tissue including a nonconductive, conformable array base adapted to be placed coincident to the target tissue, a plurality of electrode elements projecting from the array base towards the target tissue, the electrode elements addressable individually, an electrical source coupled to the plurality of electrodes, a control means interposed between the electrical source and the plurality of electrode elements and in circuit communication therein, the control means adapted to establish an electrical potential between at least two electrodes, and a delivery means adapted to introduce chemical species to the target tissue.

Abstract: The manipulator includes a support and at least one member affixed to and extending away from the support. The member has at least two differentially activatable electrodes. The electrodes are configured to establish a first electromagnetic field in vivo between selected electrodes sufficient to manipulate a molecule relative to a target tissue and to establish a second, typically higher, electromagnetic field sufficient to cause transient permeability of a cell membrane within the target tissue. One method of using the device is for enhancing the delivery of a molecule into a tissue site. In a related embodiment the device may be used to cause the electromigration of at least two components of a multicomponent reactive system into apposition to permit a reaction to occur at a desired target tissue site. The target tissue may comprise a tumor, organ, or wound site.

Abstract: A device for manipulating a molecule in vivo relative to a target tissue in three dimensions includes a support and at least one member affixed to and extending away from the support. The member has at least two discrete and separately activatable electrodes. The electrodes are configured to establish a first electromagnetic field between selected electrodes sufficient to manipulate a molecule relative to a target tissue. The electrodes are further configured to establish a second, typically higher-level, electromagnetic field sufficient to cause transient permeability of a cell membrane within the target tissue. A third electromagnetic field may also be applied to cause further translation of the molecule into an electropermeabilized cell and/or manipulated with respect to the tissue. Thus three-dimensional manipulation of the molecule relative to the target tissue is effected to optimize a desired positioning thereof, such as entry into a cell.