Abstract: A catheter system adapted for navigating, guiding and implanting a catheter or a plurality of catheters in a spatially-defined implantation within the tissue of a patient is provided. The system can include a tissue navigation system and a probe to inform the navigation system to guide emplacement of the catheters within a target tissue. The probe can provide images, such as fiberoptic visual images, or ultrasound images, or can provide radiolocation data, to guide the catheter emplacement. The catheters supply a pressurized liquid including a bioactive agent, such as can be used in the treatment of cancer, for example 123I- or 125I-IUDR. The system and methods provided can be used in the treatment of locally advanced tumors, such as cancers of the brain, head or neck, esophagus, prostate, ovary, liver, pancreas, bladder or rectum.

Abstract: A method is provided for treatment of disorders involving hyperproliferative cells, such as malignancies, advanced stage solid tumors like glioblastoma multiforme, and non-malignant hyperproliferative pathological conditions such as adult macular degeneration. A short range, unselective cell killing radiotherapeutic substance is administered, optionally in a spatially defined volume of tissue, optionally in combination with a mitogenic agent that stimulates or induces DNA biosynthesis. In this way, the percentage of hyperproliferative that are susceptible to killing by the radiotherapeutic agent is increased. Cancer stem cells can be induced to enter S phase with the mitogenic agent, then killed with the radiotherapeutic agent.

Abstract: Methods are provided for the local radiotherapy of cancers such as locally invasive, advanced stage solid tumors, and normal tissues penetrated by processes of cancerous tissue, through administration of Auger-electron emitting radionucleoside analogs using high-flow microinfusion techniques (“convection-enhanced delivery”). Direct infusion under pressure, at flow rates in excess of at least about 0.5 microliters/min of the radionucleosides provides for their mass transport through tissue to a much higher degree than could be achieved by passive, unpressurized diffusion.

Abstract: A catheter array system adapted for implanting a plurality of catheters within the tissue of a patient in a spatially defined array, comprising a plurality of catheters, a catheter guide template adapted to guide the implantation of catheters, and a liquid supply system including a pressurizer and a manifold, is provided. A method of treatment of a malcondition in a patient comprises implantation of a spatially definted array of catheters using the system is also provided. The bioactive agent can be a radiotherapeutic agent, a chemotherapeutic agent, a protein, an antibody, an oligonucleotide-based therapeutic agent such as siRNA, or a combination of agents. A preferred radiotherapeutic agent is 123I- or 125I-IUDR, for example in the treatment of locally advanced tumors, such as glioblastoma multiforme.

Abstract: A method is provided for treatment of disorders involving hyperproliferative cells, such as malignancies, advanced stage solid tumors like glioblastoma multiforme, and non-malignant hyperproliferative pathological conditions such as adult macular degeneration. A short range, unselective cell killing radiotherapeutic substance is administered, optionally in a spatially defined volume of tissue, optionally in combination with a mitogenic agent that stimulates or induces DNA biosynthesis. In this way, the percentage of hyperproliferative that are susceptible to killing by the radiotherapeutic agent is increased. Cancer stem cells can be induced to enter S phase with the mitogenic agent, then killed with the radiotherapeutic agent.

Abstract: A catheter system adapted for navigating, guiding and implanting a catheter or a plurality of catheters in a spatially-defined implantation within the tissue of a patient is provided. The system can include a tissue navigation system and a probe to inform the navigation system to guide emplacement of the catheters within a target tissue. The probe can provide images, such as fiberoptic visual images, or ultrasound images, or can provide radiolocation data, to guide the catheter emplacement. The catheters supply a pressurized liquid including a bioactive agent, such as can be used in the treatment of cancer, for example 123I- or 125I-IUDR. The system and methods provided can be used in the treatment of locally advanced tumors, such as cancers of the brain, head or neck, esophagus, prostate, ovary, liver, pancreas, bladder or rectum.

Abstract: A filament comprising a biocompatible material and a bioactive agent, adapted for implantation within the tissue of a patient wherein the bioactive agent is released over a period of time, is provided. An array of a plurality of the filaments implanted within the tissue of a patient, an array assembler, and a matrix comprising a plurality of filaments and a base adapted for implantation within the tissue of a patient, are further provided. A method for treatment of a malcondition in a patient comprises implantation of a filament, an array of filaments, or a matrix. The bioactive agent can be a chemotherapeutic agent or a radiotherapeutic agent. A radiotherapeutic agent is 123I- or 125I-IUDR, for example in treatment of an advanced stage localized brain tumor such as glioblastoma multiforme.

Abstract: The present invention relates to an octreotide sustained release delivery system for treatment of diseases relating to somatotropin and/or somatostatin. The sustained release delivery system of the invention includes a flowable composition containing an octreotide compound, and an implant containing the octreotide compound. The flowable composition may be injected into tissue whereupon it coagulates to become the solid or gel, monolithic implant. The flowable composition includes a biodegradable, thermoplastic polymer, an organic liquid and an octreotide compound.

Abstract: The present invention provides bioerodible, water-soluble pharmaceutical carriers for ocular (e.g., transconjunctival or transcorneal) delivery of pharmaceuticals for either systemic or local therapy.

Abstract: Novel methods and drug products for treating superficial bladder cancer (SBC) are disclosed, which involve parenteral administration of low doses of a type 1 interferon. The doses used are subtherapeutic for other solid tumors. Use of the novel methods and products in combination with other therapies for SBC is also described.

Abstract: A macromolecular delivery method that utilizes a series of peptides with unique and versatile nuclear targeting properties has been developed, where the peptides are derived from the COOH terminal domain (CTD) of the largest subunit of RNA polymerase II and include heptapeptide units similar or identical to the following consensus sequence: Tyrosine--Serine--Proline--Threonine--Serine--Proline--Serine (YSPTSPS).sub.x (SEQ ID NO. 1). When expressed in vivo, the CTD peptides are phosphorylated and they accumulate in discrete compartments within the nucleus. The CTD peptides concentrate indicator molecules in discrete subnuclear compartments where pre-mRNA molecules are synthesized and spliced. The length and composition of the CTD peptides can be manipulated to obtain different intranuclear partitioning properties. The CTD peptides are functional in the nuclei of S. cerevisiae, S. pombe, nematodes, insects, plants, and all vertebrates.

Abstract: Antibodies to the large subunit of DNA-dependent RNA polymerase II (Pol II LS) and methods of use thereof, including use as research tools and for the diagnosis of proliferative diseases such as cancer and the screening of anti-cancer therapies, and a method for delivering molecules to predetermined sites in the nucleus of a cell using a molecule containing the C-terminal domain of the Pol II LS protein. The anti-Pol II LS antibodies are highly specific for phosphorylated Pol II LS and bind to the C-terminal domain of the Pol II LS molecule in a phosphorylation-dependent manner.

Abstract: Genetically engineered endothelial cells which exhibit enhanced cell migration and enhanced urokinase-type plasminogen activator (u-PA) activity are provided. The cells are modified by incorporation of the coding sequence for the c-src gene so that the cells express elevated levels of the tyrosine kinase protein, pp60.sup.c-src. The C-src gene is a naturally occurring gene which appears to be present in all animal species and is highly conserved. Because of their enhanced migration rates, the modified cells can be used to efficiently seed denuded segments of vessels or natural or synthetic grafts prior to implantation. Because of their enhanced u-PA activity, the cells can reduce the probability of thrombus formation at sites of vessel damage, such as that produced during such surgical procedures as coronary angioplasty and vessel reconstruction with grafts, stents, or the like.