Abstract: Systems and methods for detection and localization of a foreign body object in a region are provided. In embodiments, a system can a processor and one or more computer-readable storage media storing instructions which, when executed on the processor, cause the processor to perform a method for forming a trained model using a plurality of training images and a plurality of training boundary data sets. The systems and methods further apply the trained model to process an image and generate a boundary data set. In embodiments, the image can be an ultrasound image, and the boundary data set can correspond to a bounding box enclosing the foreign body object.

Abstract: A drug delivery device comprising: a first layer comprising a first coaxially electrospun nanofiber membrane; a second layer comprising a second coaxially electrospun nanofiber membrane; a first therapeutic agent integrated into the first coaxially electrospun nanofiber membrane; and a second therapeutic agent integrated into the second coaxially electrospun nanofiber membrane. The second therapeutic agent is different from the first therapeutic agent.

Abstract: The presently disclosed subject matter provides methods, compositions, and kits for the treatment of cancer using a combination treatment comprising a locally administered chemotherapy and an immunotherapeutic agent. The presently disclosed subject matter also provides methods of promoting the combination treatment and instructing a patient to receive the combination treatment are also provided, as well immunotherapeutic, non-immunosuppressive compositions comprising the combination treatment, and methods of using the immunotherapeutic, non-immunosuppressive compositions for treating cancer.

Abstract: The present invention relates to the field of cancer. More specifically, the present invention provides compositions and methods utilizing Meteorin-like (METRNL), C-X-C Motif Chemokine Receptor 6 (CXCR6) and/or endogenous C-X-C Motif Ligand 16 (CXCL16) as immune-oncology targets. Accordingly, in one aspect, the present invention provides compositions and methods directed to the knockout of METRNL, CXCR6 and/or CXCL16 expression in a cell. In particular embodiments, the cell is a T cell. In a specific embodiment, the present invention provides an engineered T-cell comprising disruption in the METRNL, CXCR6 and/or CXCL16 gene sequence. In another embodiment, an engineered T-cell comprises (a) at least one chimeric antigen receptor (CAR); and (b) at least one genomic disruption of METRNL, CXCR6 and/or CXCL16. In certain embodiments, the genomic disruption is performed using a CRSIPR endonuclease system.

Abstract: The presently disclosed subject matter provides methods, compositions, and kits for the treatment of cancer using a combination treatment comprising a locally administered chemotherapy and an immunotherapeutic agent. The presently disclosed subject matter also provides methods of promoting the combination treatment and instructing a patient to receive the combination treatment are also provided, as well immunotherapeutic, non-immunosuppressive compositions comprising the combination treatment, and methods of using the immunotherapeutic, non-immunosuppressive compositions for treating cancer.

Abstract: A marker for imaging includes a bio-dissolvable material and a contrast agent configured to provide contrast during an imaging procedure. A method can include forming a marker for imaging from a bio-dissolvable material and impregnating the bio-dissolvable material with a contrast agent. A method can include implanting a bio-dissolvable marker for imaging into a patient.

Abstract: The presently disclosed subject matter provides methods, compositions, and kits for the treatment of cancer using a combination treatment comprising a locally administered chemotherapy and an immunotherapeutic agent. The presently disclosed subject matter also provides methods of promoting the combination treatment and instructing a patient to receive the combination treatment are also provided, as well immunotherapeutic, non-immunosuppressive compositions comprising the combination treatment, and methods of using the immunotherapeutic, non-immunosuppressive compositions for treating cancer.

Abstract: The presently disclosed subject matter provides methods, compositions, and kits for the treatment of cancer using a combination treatment comprising a locally administered chemotherapy and an immunotherapeutic agent. The presently disclosed subject matter also provides methods of promoting the combination treatment and instructing a patient to receive the combination treatment are also provided, as well immunotherapeutic, non-immunosuppressive compositions comprising the combination treatment, and methods of using the immunotherapeutic, non-immunosuppressive compositions for treating cancer.

Abstract: An embodiment in accordance with the present invention provides a transducer design for minimally invasive focused ultrasound (MIFU). The present invention allows flexible control of a focused ultrasound wave using mechanical and electrical control. The transducer array is implemented on a flexible substrate that can be mechanically controlled through two or more physical configurations. As with conventional electronic “steering,” the transducer elements can be controlled electronically to provide adjustable focus of the ultrasound. The combination of mechanical and electronic control provides the device a very flexible method for delivering focused ultrasound. The invention also includes a design that allows integration of ultrasound and endoscopic image guidance. The ultrasound guidance includes anatomical visualization and functional imaging (e.g. blood flow and coagulation of vasculature). The ultrasound imaging transducer is used for thermometry within the region of interest for treatment.

Abstract: Local delivery formulations of the antineoplastic and microbicide agent acriflavine, and methods of making and using thereof are significantly more efficacious at increasing the median survival of subjects with proliferative disease than systemic administrations of acriflavine. The local delivery formulations of acriflavine show a dose-dependent increase in the median survival of subjects. The local delivery forms provide the increased efficacy without the toxicity associated with systemic administration of the agent.

Abstract: Local delivery formulations of the antineoplastic and microbicide agent acriflavine, and methods of making and using thereof are significantly more efficacious at increasing the median survival of subjects with proliferative disease than systemic administrations of acriflavine. The local delivery formulations of acriflavine show a dose-dependent increase in the median survival of subjects. The local delivery forms provide the increased efficacy without the toxicity associated with systemic administration of the agent.

Abstract: A marker for imaging includes a bio-dissolvable material and a contrast agent configured to provide contrast during an imaging procedure. A method can include forming a marker for imaging from a bio-dissolvable material and impregnating the bio-dissolvable material with a contrast agent. A method can include implanting a bio-dissolvable marker for imaging into a patient.

Abstract: The presently disclosed subject matter provides methods, compositions, and kits for the treatment of cancer using a combination treatment comprising a locally administered chemotherapy and an immunotherapeutic agent. The presently disclosed subject matter also provides methods of promoting the combination treatment and instructing a patient to receive the combination treatment are also provided, as well immunotherapeutic, non-immunosuppressive compositions comprising the combination treatment, and methods of using the immunotherapeutic, non-immunosuppressive compositions for treating cancer.

Abstract: The additive effect of combined intracranial carmustine (“BCNU”) with intracranial temozolomide (“TMZ”), and particularly in combination with radiation (“XRT”), in the treatment of two rat intracranial glioma models, the 9L gliosarcoma and the F98 glioma, demonstrates that local delivery of both drugs, especially in combination with radiation, is far more effective than delivery of either drug alone or one systemically and one locally, either with or without radiation. The triple therapy showed a significant improvement in survival when compared to controls (p=0.0004), local BCNU (p=0.0043), oral TMZ (p=0.0026), local TMZ (p=0.0105), and the combinations of either BCNU and XRT (p=0.0378) or oral TMZ and local BCNU (p=0.0154).

Abstract: The additive effect of combined intracranial carmustine (“BCNU”) with intracranial temozolomide (“TMZ”), and particularly in combination with radiation (“XRT”), in the treatment of two rat intracranial glioma models, the 9L gliosarcoma and the F98 glioma, demonstrates that local delivery of both drugs, especially in combination with radiation, is far more effective than delivery of either drug alone or one systemically and one locally, either with or without radiation. The triple therapy showed a significant improvement in survival when compared to controls (p=0.0004), local BCNU (p=0.0043), oral TMZ (p=0.0026), local TMZ (p=0.0105), and the combinations of either BCNU and XRT (p=0.0378) or oral TMZ and local BCNU (p=0.0154).

Abstract: Localized delivery of 1,25 D3 directly to a target area using biodegradable polymeric matrices maximizes the efficacy of this drug while minimizing systemic exposure and toxicity. Anticalcemic analogs of 1,25 D3 have also been incorporated into controlled release polymer formulations to achieve efficacious intracranial concentrations of 1,25 D3 analogs for the treatment of intracranial tumors as well as neurodegenerative disorders such as Alzheimer's disease as well as to maximize the efficacy of these analogs in the treatment of systemic malignancies. The therapeutic efficacy of these formulations was demonstrated through a variety of studies in vitro and in vivo. Hybrid analogs of 1,25 D3 were incorporated into biodegradable polymer wafers composed of a polyanhydride copolymer of 1,3-bis(p-carboxyphenoxy)propane (CPP) and sebacic acid (SA) in a 20:80 molar ratio.

Abstract: Localized delivery of 1,25 D3 directly to a target area using biodegradable polymeric matrices maximizes the efficacy of this drug while minimizing systemic exposure and toxicity. Anticalcemic analogs of 1,25 D3 have also been incorporated into controlled release polymer formulations to achieve efficacious intracranial concentrations of 1,25 D3 analogs for the treatment of intracranial tumors as well as neurodegenerative disorders such as Alzheimer's disease as well as to maximize the efficacy of these analogs in the treatment of systemic malignancies. The therapeutic efficacy of these formulations was demonstrated through a variety of studies in vitro and in vivo. Hybrid analogs of 1,25 D3 were incorporated into biodegradable polymer wafers composed of a polyanhydride copolymer of 1,3-bis(p-carboxyphenoxy)propane (CPP) and sebacic acid (SA) in a 20:80 molar ratio.

Abstract: Pharmaceutical compositions for delivering an effective dose of an angiogenesis inhibitor consisting of a tetracycline or tetracycline such as minocycline. The effective dosage for inhibition of angiogenesis based on in vitro testing is between one and 500 micromolar. The compositions are delivered topically, locally or systemically using implants or injection. The composition is extremely selective for growth of endothelial cells, inhibiting growth, but is not cytotoxic at the effective dosages.

Abstract: Localized delivery of 1,25 D3 directly to a target area using biodegradable polymeric matrices maximizes the efficacy of this drug while minimizing systemic exposure and toxicity. Anticalcemic analogs of 1,25 D3 have also been incorporated into controlled release polymer formulations to achieve efficacious intracranial concentrations of 1,25 D3 analogs for the treatment of intracranial tumors as well as neurodegenerative disorders such as Alzheimer's disease as well as to maximize the efficacy of these analogs in the treatment of systemic malignancies. The therapeutic efficacy of these formulations was demonstrated through a variety of studies in vitro and in vivo. Hybrid analogs of 1,25 D3 were incorporated into biodegradable polymer wafers composed of a polyanhydride copolymer of 1,3-bis(p-carboxyphenoxy)propane (CPP) and sebacic acid (SA) in a 20:80 molar ratio. In addition to providing improved treatments for malignancies and neurodegenerative disorders.

Abstract: A method and devices for localized delivery of a chemotherapeutic agent to solid tumors, wherein the agent does not cross the blood-brain barrier and is characterized by poor bioavailability and/or short half-lives in vivo, are described. The devices consist of reservoirs which release drug over an extended period while at the same time preserving the bioactivity and bioavailability of the agent. In the most preferred embodiment, the device consists of biodegradable polymeric matrixes, although reservoirs can also be formulated from non-biodegradable polymers or reservoirs connected to implanted infusion pumps. The devices are implanted within or immediately adjacent the tumors to be treated or the site where they have been surgically removed.