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

Abstract: The present invention provides methods for decreasing tumor growth in a subject that rely on detecting an increase in the expression of angiopoietin-1 or a decrease in the expression of angiopoietin-2 in the tumor or in the bloodstream of the subject to detect the normalization window in tumor vasculature.

Abstract: Disclosed are new methods for treatment of angiogenesis-related disorders. Angiogenesis-related disorders are treated by administration of a Tie1 ectodomain-binding agent and a VEGF antagonist agent.

Abstract: Novel N-formyl hydroxylamine compounds and their derivatives are disclosed. These N-formyl hydroxylamine compounds inhibit peptidyl deformylase (PDF), an enzyme present in prokaryotes. The compounds are useful as antimicrobials and antibiotics. The compounds of the invention display selective inhibition of peptidyl deformylase versus other metalloproteinases such as MMPs. Methods of preparation and use of the compounds are also disclosed.

Abstract: N-[1-oxo-2-alkyl-3-(N-hydroxyformamido)-propyl]-(carbonylamino-aryl or -heteroaryl)-azacyclo4-7alkanes or thiazacyclo4-7alkanes or imidazacyclo4-7alkanes have interesting properties, e.g., in the treatment or prevention of disorders amenable to treatment by peptidyl deformylase inhibitors such as treatment of bacterial infections.

Abstract: N-[1-oxo-(optionally 2-aza)-2-alkyl-3-(carboxyl or thiol or hydroxyaminocarbonyl or N-hydroxyformamido)-propyl]-(aryl or heteroaryl)-azacyclo4-7alkanes or thiazacyclo4-7alkanes, salts or prodrugs thereof have interesting properties, e.g., in the treatment or prevention of disorders amenable to treatment by PDF inhibitors, such as treatment of bacterial infections.

Abstract: The present invention pertains to improved methods for the destruction of undesirable tissue using photodynamic therapy (PDT) and/or sonodynamic therapy (SDT). Such methods include the use of fractionated dosing of the photosensitizer or sonosensitizer to ensure that the sensitizer can be found in various compartments of the tissue and appropriate vasculature prior to the application of activating energy such as electromagnetic radiation or ultrasonic energy.

Abstract: The present invention pertains to improved methods for the destruction of undesirable tissue using photodynamic therapy (PDT). Such methods include the use of fractionated dosing of the photosensitizer to ensure that the photosensitizer(s) has sufficient time to enter various compartments of the tissue and appropriate vasculature prior to the application of activating radiation.

Abstract: Disclosed are methods for potentiating the anti-cancer properties of an anti-cancer therapy in a mammal by administering with the therapy a compound (such as relaxin or &ggr;-IFN) that has a tissue tensile modulus-reducing property, an ability to reduce the interstitial viscosity of the cancer, an ability to increase the hydraulic conductance of the cancer, or an ability to increase collagen turnover or decrease collagen formation at or near the cancer, where the therapy and the compound are administered at dosages which together are sufficient to destroy, slow, or arrest the cancer. Also disclosed is a method for treating cancer in a mammal involving the administration of relaxin and/or &ggr;-IFN peptides and an anti-cancer therapy to the mammal, where the peptides and the therapy are administered at dosages which together are sufficient to destroy, slow, or arrest the cancer.

Abstract: The invention is based on the discovery that angiogenic vessels have heterogeneous surface charge and that cationic liposomes actually target human tumor blood vessels only in irregularly shaped patches. The invention thus features methods for delivering therapeutic compounds to angiogenic vascular endothelial surfaces using a mixture, or “cocktail”, of positively charged and neutral liposomes. The new methods can be used to target multiple regions on the same tumor vessel and/or clusters of vessels within the same tumor. Liposomes with different chemical and/or physical properties (e.g., charge, stability, solubility, diameter) can be delivered simultaneously, and can target tumor vessels and other angiogenic vessels with greater efficiency compared to cationic liposomes alone.

Abstract: N-[1-oxo-(optionally 2-aza)-2-alkyl-3-(carboxyl or thiol or hydroxyaminocarbonyl or N-hydroxyformamido)-propyl]-(aryl or heteroaryl)-azacyclo4-7alkanes or thiazacyclo4-7alkanes, salts or prodrugs thereof have interesting properties, e.g., in the treatment or prevention of disorders amenable to treatment by PDF inhibitors, such as treatment of bacterial infections.

Abstract: N-[1-oxo-2-alkyl-3-(N-hydroxyformamido)-propyl]-(carbonylamino-aryl or -heteroaryl)-azacyclo4-7alkanes or thiazacyclo4-7alkanes or imidazacyclo4-7alkanes have interesting properties, e.g., in the treatment or prevention of disorders amenable to treatment by peptidyl deformylase inhibitors such as treatment of bacterial infections.

Abstract: The invention is based on the discovery that angiogenic vessels have heterogeneous surface charge and that cationic liposomes actually target human tumor blood vessels only in irregularly shaped patches. The invention thus features methods for delivering therapeutic compounds to angiogenic vascular endothelial surfaces using a mixture, or “cocktail”, of positively charged and neutral liposomes. The new methods can be used to target multiple regions on the same tumor vessel and/or clusters of vessels within the same tumor. Liposomes with different chemical and/or physical properties (e.g., charge, stability, solubility, diameter) can be delivered simultaneously, and can target tumor vessels and other angiogenic vessels with greater efficiency compared to cationic liposomes alone.

Abstract: Cells in a matrix or in the matrix in a vessel are grown to form a multicellular aggregate. Pressure is exerted on the growing cells by the matrix or the matrix together with the vessel due to growing cellular mass displacing the matrix. A value representing pressure exerted on the cells is calculated and the pressure is modulated to control growth of the multicellular aggregate, or to produce a multicellular aggregate of a pre-selected size or a pre-selected size and shape. Matrices include agarose, alginate and collagen gels, and the pressure exerted on the cells can be non-isotropic. The cells may be tumor cells, or liver, pancreatic, brain, skin, bone or muscle cells, and cell growth can be in vitro or in vivo. When collagen forms the matrix, the matrix may contain glycosaminoglycan.

Abstract: A combinatorial chemical library of compounds structurally related to the moenomycin class of antibiotics has the formula wherein D is a donor mono- or disaccharide, A is an acceptor monosaccharide, and P-R is a lipophosphoglycerate mimetic group. Members of the library have a glycosidic linkage between the anomeric carbon of D and the C2 carbon of A, and the D-A moiety is in turn covalently linked through the anomeric carbon of A to the P-R group. Members of the library exhibit their greatest structural diversity in terms of substitutions occurring at the C3 position of the A residue, substitutions at the C2 position of the D residue, and different P-R groups used in assembling the compounds. Members of the library are preferably synthesized by solid phase techniques involving stepwise coupling of the respective units to a support, functionalizing the A and/or D saccharides either before or after immobilizing them on the support, and cleaving the assembled compounds from the support.

Abstract: A combinatorial chemical library of compounds structurally related to the moenomycin class of antibiotics has the formula wherein D is a donor mono- or disaccharide, A is an acceptor monosaccharide, and P—R is a lipophosphoglycerate mimetic group. Members of the library have a glycosidic linkage between the anomeric carbon of D and the C2 carbon of A, and the D—A moiety is in turn covalently linked through the anomeric carbon of A to the P—R group. Members of the library exhibit their greatest structural diversity in terms of substitutions occurring at the C3 position of the A residue, substitutions at the C2 position of the D residue, and different P—R groups used in assembling the compounds.

Abstract: A combinatorial chemical library of compounds structurally related to the moenomycin class of antibiotics has the formula ##STR1## wherein D is a donor mono- or disaccharide, A is an acceptor monosaccharide, and P-R is a lipophosphoglycerate mimetic group. Members of the library have a glycosidic linkage between the anomeric carbon of D and the C2 carbon of A, and the D-A moiety is in turn covalently linked through the anomeric carbon of A to the P-R group. Members of the library exhibit their greatest structural diversity in terms of substitutions occurring at the C3 position of the A residue, substitutions at the C2 position of the D residue, and different P-R groups used in assembling the compounds. Members of the library are preferably synthesized by solid phase techniques involving stepwise coupling of the respective units to a support, functionalizing the A and/or D saccharides either before or after immobilizing them on the support, and cleaving the assembled compounds from the support.

Abstract: A method of treating a condition involving vascular adhesion of cytotoxic white cells by (a) identifying an animal suspected of having a condition involving vascular adhesion of cytotoxic white cells and (b) administering to the animal an amount of bFGF sufficient to decrease cell surface expression of ICAM-I or VCAM-I on endothelial cells, thereby reducing adhesion of cytotoxic white cells to vascular endothelium.

Abstract: Compounds which bind to selectin receptors and thus may modulate the course of inflammation, cancer and related processes by intervening with cell-cell adhesion events. Further, such compounds can be used for identification and analysis of such receptors. In this regard the invention is directed to compounds of formula (I). ##STR1## wherein R.sup.1 is independently H, alkyl, aryl, an aryl alkyl, alkenyl or one or more additional saccharide residues; R.sup.2 =H or OH provided that when R.sup.2 is H, R.sup.3 is OH; R.sup.3 =H or OH provided that when R.sup.3 is H, R.sup.2 is OH; X=H, SO.sub.3.sup.- or PO.sub.4.sup.- ; Y is independently H, OH, OR.sup.4 or NHCOR.sup.4, wherein R.sup.4 is alkyl, and Z is an organic acid residue. .alpha.-L-Fucose residue can be modified or replaced with suitable bioisosters or a different saccharide residue such as D-mannose. Modification of L-fucose may include replacement of each or all of the hydroxyl groups with H or OR' wherein R' can be methyl, ethyl or allyl groups.

Abstract: The invention provides a method of enhancing the amount of a pharmaceutical composition delivered to a target tissue site in a mammal, by creating a transient differential between tile hydrostatic pressure in the target site and a region near the target tissue site whereby the composition is transported toward the site. An apparatus for performing the method is provided. In one form that apparatus includes a pharmaceutical reservoir, pump, and an agent reservoir and pump.