Abstract: A rodent mammary window for intravital microscopy of orthotopic breast cancer and the related method of use in rodents to provide a useful model to investigate the cellular behavior of implanted tumor cells in an orthotopic environment and to observe the earliest events during angiogenesis. The mammary window is surgically secured in the mammary gland of the rodent on top of implanted tumor fragments or cells that have been implanted into the nipple sinus of the mammary gland. Periodically the rodent is secured to a microscopy platform with a restrainer plate mounted on top of the abdomen of the rodent such that a central aperture in the restrainer plate is aligned with the mammary window and selective aspects of tumor growth are observed by intravital microscopy including microvascular function and angiogenesis in the orthotopic site.

Abstract: Methods and compositions useful for detecting an in vivo blood pool, monitoring the distribution of a compound of interest to a desired site in an organism by magnetic resonance imaging, monitoring the accumulation of a compound of interest at a desired site in vivo by magnetic resonance imaging, and monitoring the release of liposomal contents to an external stimulus at a desired site in vivo by magnetic resonance imaging are disclosed. Some compositions comprise envirosensitive or non-sensitive liposomes. Contrast agents, such as manganese-based compounds, are also disclosed.

Abstract: A chamber for in vivo delivery of an active agent, the chamber including a housing having at least two porous surfaces, the at least two porous surfaces disposed on substantially opposite sides of the housing from each other; an internal void space within the housing; and a matrix composition comprising an active agent, the matrix composition disposed within the internal void space. Therapeutic and screening methods employing the chamber are also disclosed, including methods for in vivo screening of angiogenesis and/or tumor growth modulating agents.

Abstract: A method for controlling in vivo heat-inducible gene expression for provision of therapeutic polypeptide. The method includes the steps of: (a) providing a construct comprising a polynucleotide encoding a therapeutic polypeptide, wherein the polynucleotide is operatively linked to a heat-inducible promoter; (b) administering the construct to a warm-blooded vertebrate at a site at or near the tumor; and (c) applying heat to the site at or near the tumor to express the therapeutic polypeptide, whereby anti-tumor activity is observed.

Abstract: Patients with pathologic conditions involving constriction or proliferation of smooth muscle or disease associated with cysteine containing proteins, or who are at risk for such, are administered a therapeutically effective amount of a nitric oxide (NO) donor which is insufficient to acutely lower mean arterial blood pressure or pulmonary artery pressure by more than 10%. In one subgenus, NO donor is administered to modify red blood cell membrane receptors to prevent red blood cells from causing vasoconstriction. A related method which allows increased dosage of NO donor without acutely lowering mean arterial blood pressure comprises administering the NO donor into an artery of the patient. In another method, patients having a cardiovascular syndrome, or who are at risk for such, are administered a therapeutically effective amount of thiol which does not acutely affect blood pressure to a significant degree.

Abstract: Imaging agents for magnetic resonance imaging are disclosed. Methods of monitoring angiogenesis and the growth and remission of tumor tissue are also disclosed. Methods of monitoring blood clot formation and dissolution are additionally disclosed. Methods of monitoring wound healing are further disclosed. A kit for obtaining an image of a biological structure is further disclosed.

Abstract: The present invention is directed to the use of an inhibitor of NO activity, such as a nitric oxide scavenger or an NO synthase inhibitor, as as an adjunct to treatment of inappropriate tissue vascularization disorders.

Abstract: The present invention is directed to the use of an inhibitor of NO activity, such as a nitric oxide scavenger or an NO synthase inhibitor, as an antitumor therapy to reduce tumor blood flow and oxygenation. The invention is also directed to administration of a nitric oxide scavenger or a nitric oxide synthase inhibitor to enhance the effectiveness of tumor therapy with hypoxic or acidic chemotherapeutic agents or hyperthermia. The invention is also directed to the administration of a nitric oxide synthase substrate to a subject previously administered a nitric oxide synthase inhibitor, in order to selectively inhibit tumor perfusion. In a specific example, administration of cell free hemoglobin, a nitric oxide scavenger, in conjunction with mitomycin C, a hypoxic cytotoxin, results in a significant delay in tumor growth of a human tumor xenograft in a mouse compared to mitomycin C alone.

Abstract: The present invention is directed to administration of a nitric oxide scavenger or a nitric oxide synthase inhibitor to enhance the effectiveness of tumor therapy with hypoxic or acidic chemotherapeutic agents or hyperthermia. In a specific example, administration of cell free hemoglobin, a nitric oxide scavenger, in conjunction with mitomycin C, a hypoxic cytotoxin, results in a significant delay in tumor growth of a human tumor xenograft in a mouse compared to mitomycin C alone.

Abstract: The present invention is directed to the use of an inhibitor of NO activity, such as a nitric oxide scavenger or an NO synthase inhibitor, as an antitumor therapy to reduce tumor blood flow and oxygenation. The invention is also directed to administration of a nitric oxide scavenger or a nitric oxide synthase inhibitor to enhance the effectiveness of tumor therapy with hypoxic or acidic chemotherapeutic agents or hyperthermia. The invention is also directed to the administration of a nitric oxide synthase substrate to a subject previously administered a nitric oxide synthase inhibitor, in order to selectively inhibit tumor perfusion. In a specific example, administration of cell free hemoglobin, a nitric oxide scavenger, in conjunction with mitomycin C, a hypoxic cytotoxin, results in a significant delay in tumor growth of a human tumor xenograft in a mouse compared to mitomycin C alone.

Abstract: An automated temperature scanning system for monitoring hyperthermia treatment has a linear drive assembly operatively connected to a non-rotational extended-length screw shaft which is linearly translated by a stepper motor. A first tube having a thermometric probe concentrically positioned therein is fixedly secured to the linear drive assembly so as to be motivated thereby. A second tube is secured at one end to an interstitial catheter and is adapted to be at least partially slidably received within the first tube so that linear movement of the first tube toward the second tube slidably moves the thermometric probe within the second tube and an interstitial catheter associated therewith. A computer is electrically connected to the stepper motor to control the movement of the thermometric probe utilizing real time data generated thereby.