Abstract: Provided herein are polymers, pH-sensitive polymers and/or linkers; conjugates comprising said polymers and/or linkers, optionally, coupled to one or more agents and/or targeting moieties; and particles (e.g., nanoparticles comprising the aforesaid polymers, linkers and/or conjugates), which can be used to enhance the delivery and/or efficacy of one or more agents in a subject.

Abstract: Agents that inhibit CX3CL1 in endothelial cells to reduce or inhibit immunosuppression mechanisms that are co-opted by cancer cells to evade host immune system, and that reduce immunosuppression in context of therapies that target VEGF-dependent signaling, and methods of use thereof.

Abstract: Agents that inhibit CX3CL1 in endothelial cells to reduce or inhibit immunosuppression mechanisms that are co-opted by cancer cells to evade host immune system, and that reduce immunosuppression in context of therapies that target VEGF-dependent signaling, and methods of use thereof.

Abstract: The present invention relates to a pharmaceutical combination which comprises (a) a phosphatidylinositol 3-kinase inhibitor or pharmaceutically acceptable salt thereof, and (b) a Her3 antagonist, for simultaneous, separate or sequential administration for the treatment of breast cancer brain metastases; a method of treating a subject having a breast cancer brain metastases comprising administration of said combination to a subject in need thereof; use of such combination for the treatment of breast cancer brain metastases; and a commercial package comprising such combination.

Abstract: The present invention relates to a pharmaceutical combination which comprises (a) a phosphatidylinositol 3-kinase inhibitor or pharmaceutically acceptable salt thereof, and (b) a Her3 antagonist, for simultaneous, separate or sequential administration for the treatment of breast cancer brain metastases; a method of treating a subject having a breast cancer brain metastases comprising administration of said combination to a subject in need thereof; use of such combination for the treatment of breast cancer brain metastases; and a commercial package comprising such combination.

Abstract: Provided herein are polymers, pH-sensitive polymers and/or linkers; conjugates comprising said polymers and/or linkers, optionally, coupled to one or more agents and/or targeting moieties; and particles (e.g., nanoparticles comprising the aforesaid polymers, linkers and/or conjugates), which can be used to enhance the delivery and/or efficacy of one or more agents in a subject.

Abstract: Nanoparticles for a selective, two stage delivery to tumors have been developed. The nanoparticles are initially sized so that they preferentially accumulate in the tumor tissue as a result of leakage through the defective vascular in the solid tumors. Once in the tumor tissue, the nanoparticles are cleaved hydrolytically and/or by enzymatic cleavage over time to release smaller nanoparticles carrying therapeutic, prophylactic or diagnostic agents into the necrotic interior of the tumors. This provides a simple, elegant and highly effective means of delivery drug selectively not just to tumors generally, but, more importantly, into the poorly vascularized necrotic interiors which drugs are normally unable to penetrate. The nanoparticles have a number of advantages: less toxicity due to selective accumulation only in the tumors; access into the poorly vascularized necrotic interiors of the tumor; and sustained release over a period of time within the tumor.

Abstract: Methods and compositions for improving the delivery and/or efficacy of a therapy (e.g., an anti-cancer, anti-fibrotic or anti-inflammatory therapy) are disclosed. The invention is based, at least in part, on the discovery that metformin, a widely prescribed anti-diabetic drug, can affect the tumor microenvironment (e.g., directly, i.e., independent of its effects on cancer cells themselves or tumor metabolism). In embodiments described herein, metformin has been shown to reduce the amount of extracellular matrix, including collagen 1 and hyaluronan, in the fibro-inflammatory tumor microenvironment in a subject (e.g., a subject with a desmoplastic tumor).

Abstract: Inhibition of CXCR4 can inhibit tumor growth and metastasis during certain therapeutic windows. Disclosed are novel methods for treating and preventing cancer in a subject related to administration of CXCR4 inhibitors during a therapeutic window following treatment with another anti-tumor therapy.

Abstract: Multistage nanostructures, e.g., for delivery of agents such as imaging agents and therapeutic agents to tumor vasculature.

Abstract: Inhibition of CXCR4 can inhibit tumor growth and metastasis during certain therapeutic windows. Disclosed are novel methods for treating and preventing cancer in a subject related to administration of CXCR4 inhibitors during a therapeutic window following treatment with another anti-tumor therapy.

Abstract: Nanoparticles for a selective, two stage delivery to tumors have been developed. The nanoparticles are initially sized so that they preferentially accumulate in the tumor tissue as a result of leakage through the defective vascular in the solid tumors. Once in the tumor tissue, the nanoparticles are cleaved hydrolytically and/or by enzymatic cleavage over time to release smaller nanoparticles carrying therapeutic, prophylactic or diagnostic agents into the necrotic interior of the tumors. This provides a simple, elegant and highly effective means of delivery drug selectively not just to tumors generally, but, more importantly, into the poorly vascularized necrotic interiors which drugs are normally unable to penetrate. The nanoparticles have a number of advantages: less toxicity due to selective accumulation only in the tumors; access into the poorly vascularized necrotic interiors of the tumor; and sustained release over a period of time within the tumor.

Abstract: Multistage nanostructures, e.g., for delivery of agents such as imaging agents and therapeutic agents to tumor vasculature.

Abstract: Inhibition of CXCR4 can inhibit tumor growth and metastasis during certain therapeutic windows. Disclosed are novel methods for treating and preventing cancer in a subject related to administration of CXCR4 inhibitors during a therapeutic window following treatment with another anti-tumor therapy.

Abstract: Methods and compositions for modulating lymphatic function, e.g., by altering NO levels, are disclosed.

Abstract: The instant invention provides methods for treating a solid tumor in a subject comprising modulating nitric oxide production in the tumor to normalize tumor vasculature and administering an anti-tumor therapy to the subject. The invention further provides methods of treating a solid tumor in a subject comprising selectively increasing cyclic guanosine monophosphate (cGMP) or cGMP dependent protein kinase G production in the tumor vasculature to an amount effective to normalize tumor vasculature and administering an anti-tumor therapy to the subject.

Abstract: Provided are nanostructures comprising a charged outer surface and an inner core comprising a cancer therapeutic agent or imaging agent, wherein the charged outer surface is selectively removable. Further provided are methods of treating subjects having cell proliferative disorders, e.g., cancer, and kits comprising the above nanostructures.

Abstract: Methods and compositions for modulating lymphatic function, e.g., by altering NO levels, are disclosed.

Abstract: In general, this invention provides methods and compositions for stabilizing, repairing, or replacing damaged or diseased tissues or organs by engineering blood vessels in such tissues or organs. In addition, the invention further provides methods and compositions for producing functional microvascular networks useful in tissue engineering.

Abstract: The invention provides methods for the treatment or prevention of obesity. The invention also provides screening methods for determining whether a compound is useful for the treatment or prevention of obesity.