Abstract: This invention relates to methods of using O-substituted fumagillol derivatives or salts thereof preferably, O-(N-chloroacetylcarbamoyl) fumagillol, O-(N-chloroacetylcarbamoyl)dihydrofumagillol or O-(N-chloracetylcarbamoyl)-6'b-hydroxyfumagillol, which have angiogenesis inhibitory activity, in the treatment and prevention of various diseases caused or advanced by abnormally hyperactive angiogenesis, especially various inflammatory diseases (rheumatism, psoriasis, etc.), diabetic retinopathy and cancer and other angiogenesis-dependent tumors, especially Kaposi's sarcoma, breast cancer, colon cancer.

Abstract: A recombinant non-glycosylated mammalian growth factor (BTC-GF) stimulates proliferation of human smooth muscle cells. Especially, the amino acid sequence of the protein deduced from the nucleotide sequence coding for human BTC-GF is as that comprising the amino acids No. 1 to No. 147 of FIG. 10 (SEQ ID NO:18) or the amino acids No. 1 to 80 of FIG. 10, (SEQ ID NO:18) and the amino acid sequence of the protein deduced from the nucleotide sequence coding for mouse BTC-GF is as that comprising the amino acids No. 1 to No. 146 of FIG. 9 (SEQ ID NO:17).

Abstract: A recombinant non-glycosylated mammalian growth factor (BTC-GF) stimulates proliferation of human smooth muscle cells. Especially, the amino acid sequence of the protein deduced from the nucleotide sequence coding for human BTC-GF is as that comprising the amino acids No. 1 to No. 147 of FIG. 10 (SEQ ID NO:5) or the amino acids No. 1 to 80 of FIG. 10 (SEQ ID NO:18), and the amino acid sequence of the protein deduced from the nucleotide sequence coding for mouse BTC-GF is as that comprising the amino acids No. 1 to No. 146 of FIG. 9 (SEQ ID NO:17).

Abstract: The application discloses methods of treating mammalian diseases characterized by undesirable angiogenesis by administering estradiol derivatives including those comprising colchicine or combretastatin A-4 structural motifs of the general formulae found below in a dosage sufficient to inhibit cell mitosis. The application discloses novel compounds used in the methods.

Abstract: This invention describes pharmaceutical compositions and methods of treating ulcerating diseases of the gastrointestinal tract in mammals with an acid-resistant fibroblast growth factor compositions. Also described is the use of acid-resistant fibroblast growth factor compositions in the treatment of various other fibroblast growth factor-responsive conditions.

Abstract: A novel growth factor (BTC-GF) was purified from the conditioned medium of pancreatic beta tumor cells initially derived from transgenic mice (RIPI-Tag2). The purification scheme included BioRex 70 chromatography, phenyl-Sepharose chromatography, TSL-GEL heparin FPLC and C4 reverse phase HPLC. The peptide also stimulated proliferation of bovine smooth muscle cells. It was not inactivated by boiling, by 10 mM dithiothreitol or by exposure to 1M acetic acid. Biological activity of BTC-GF was recovered from a single band of protein which had a molecular weight of 32,000 on SDS-PAGE.

Abstract: O-substituted fumagillol derivatives and its salts have an angiogenesis regressing activity are useful for treatment of diseases induced by abnormally stimulated neovascularization.

Abstract: A novel growth factor (BTC-CG) was purified from the conditioned medium of pancreatic beta tumor cells initially derived from transgenic mice (RIPl-Tag2). The purification scheme included BioRex 70 chromatography, phenyl-Sepharose chromatography, TSL-GEL heparin FPLC and C4 reverse phase HPLC. The peptide also stimulated proliferation of bovine smooth muscle cells. It was not inactivated by boiling, by 10 mM dithiothreitol or by exposure to IM acetic acid. Biological activity of BTC-GF was recovered from a single band of protein which had a molecular weight of 2,000 on SDS-PAGE. The Partial N-terminal amino acid sequence of this protein was determined with an ABI 470A protein sequencer as: Asp-Gly-[X]-Thr-[X]-Arg-Thr-Pro-Glu-[X]-Asn-Gly.

Abstract: Methods for stabilizing fibroblast growth factor (FGF) in heat, acid and/or proteolytic environments are provided. Such methods comprise combining or otherwise complexing FGF with a salt of sucrose octasulfate (SOS) and in particular with the aluminum (sucralfate) or potassium salts thereof. The present invention also provides FGF-stable compositions comprising SOS and FGF. Such compositions can be used in the treatment of FGF-responsive diseases including the treatment of wounds and ulcerative conditions of the gastrointestinal tract. The present invention also provides various diagnostic protocols employing SOS as well as diagnostic kits with SOS as a component thereof. Finally, the present invention provides methods of purifying FGF with SOS.

Abstract: This invention describes pharmaceutical compositions and methods of treating ulcerating diseases of the gastrointestinal tract in mammals with an acid-resistant fibroblast growth factor compositions. Also described is the use of acid-resistant fibroblast growth factor compositions in the treatment of various other fibroblast growth factor-responsive conditions.

Abstract: Anigiogenesis is controlled by administering to a mammal an effective amount of an inhibitor of arylsulfatase. Preferably, the arylsulfatase inhibitor is administered in a pharmaceutically acceptable vehicle in combination with an angiostatic steroid and (optionally) heparin (by which term we include all forms and fragments of heparin having the desired angiostatic activity). Hydrocortisone is one specifically preferred steroid. The preferred arylsulfatase inhibitor is a carboxylic acid ester or a sulfuric acid ester of a benzylic alcohol, most preferably the esters defined more particularly below. The arylsulfatase inhibitor is preferably administered locally to the tissue experiencing undesired angiogenesis. Arylsulfatase inhibitor and an angiostatic steroid are included in a pharmaceutically acceptable vehicle, preferably also with heparin, to yield an angiostatic thereapeutic composition.

Abstract: Pathological or otherwise undesirable cell or tissue growth in mammals, including humans, is inhibited by administering thereto a composition exemplified by (1) a water-soluble cyclodextrin sulfate salt, together with (2) a growth-inhibiting organic compound. The growth-inhibiting compound (2) may be a steroid having no inhibiting effect in the absence of (1), or an organic compound which may be an active growth inhibitor, the action of which is potentiated by (1). The invention provides a method for inhibiting angiogenesis and controlling the growth of tumors as well as treating other diseases and pathological conditions associated with undesired cell or tissue growth, including angiogenesis.

Abstract: Angiogenesis in mammals is inhibited by administration of the active agents (1) heparin or a heparin fragment which is a hexasaccharide or larger or analogous compounds and (2) a steroid having 17.alpha.- and 21-hydroxy groups, 3- and 20-one groups, and in the 16-position hydrogen hydroxy or a methyl group, and non-toxic physiologically acceptable carboxylates, acetals, ketals and phosphates thereof.

Abstract: Angiogenesis in mammals is inhibited by administration of the active agents (1) heparin or a heparin fragment which is a hexasaccharide or larger or analogous compounds and (2) a steroid having 17.alpha.- and 21-hydroxy groups, 3- and 20-one groups, and in the 16-position hydrogen hydroxy or a methyl group, and non-toxic physiologically acceptable carboxylates, acetals, ketals and phosphates thereof.

Abstract: The level of heparin in a blood sample is measured by measuring the clotting time of two aliquots of the blood sample, using standard clotting assays, with one of the aliquots being firstly treated with a heparin-degrading compound, such as heparinase. The difference in clotting times is a direct measure of the heparin concentration in the sample.

Abstract: Delivery systems manufactured in the form of polymeric compositions for the controlled delivery of macromolecules to environments of use are disclosed. The systems are characterized as two-phase compositions comprising a phase formed of an insoluble polymeric matrix having limited water sorptivity containing in admixture therein an interpenetrating phase formed of a particulate hydrophilic water swellable, biologically active macromolecular material.

Abstract: Process for the production of human TAF in vitro comprising growing the human medulloblastoma cell line TE-671 in agitated, liquid suspension of nutrient culture medium at about 35.degree.-38.degree. C. for a sufficient time to elaborate TAF and recovering the resulting TAF from the cells or cell product.

Abstract: Delivery systems manufactured in the form of polymeric compositions for the controlled delivery of macromolecules to environments of use are disclosed. The systems are characterized as two-phase compositions comprising a phase formed of an insoluble polymeric matrix having limited water sorptivity containing in admixture therein an interpenetrating phase formed of a particulate hydrophilic water swellable, biologically active macromolecular material.