University of Texas System

Other

Research Development Foundation

Signpath Pharma, Inc.

Aronex Pharmaceuticals, Inc.

Kapil Mehta

Gabriel Lopez-Berestein

Razelle Kurzrock

Lan Li

Bharat B Aggarwal

Bharat Bhushan Aggarawal

Roman Perez-Soler

Lawrence Helson

Ramaswamy Chandrashekar

Evan M Hersh

Reeta Mehta

Rudolph L Juliano

Roy L Hopfer

Victor Fainstein

Jansina Fok

Michael G Rosenblum

Anil K Sood

Brian E Gilbert

Shuxing Zhang

Robert P Lenk

Ranjani Parthasarathy

Alan C Hayman

Robert Lenk

Anupam Kumar

Amit Verma

Alan C Hayman, Deceased

Sushovan Guha

The present invention provides a compositions and methods for the treatment of cancer, including pancreatic cancer, breast cancer and melanoma, in a human patient. The methods and compositions of the present invention employ curcumin or a curcumin analog encapsulated in a colloidal drug delivery system, preferably a liposomal drug delivery system. Suitable colloidal drug delivery systems also include nanoparticles, nanocapsules, microparticles or block copolymer micelles. The colloidal drug delivery system encapsulating curcumin or a curcumin analog is administered parenterally in a pharmaceutically acceptable carrier.

Liposomal curcumin for treatment of cancer

The present invention provides compositions and methods for the treatment of a human patient. The methods and compositions of the present invention include composition for the efficient loading of curcumin, comprising: an amount of a curcuminoid:liposome complex effective to load curcumin into the liposome, wherein the curcuminoids has between 2 to 9 weight percent of the total composition and the curcuminoids are natural or synthetic.

Liposomal curcumin for treatment of diseases

The present invention provides a compositions and methods for the treatment of cancer, including pancreatic cancer, breast cancer and melanoma, in a human patient. The methods and compositions of the present invention employ curcumin or a curcumin analogue encapsulated in a colloidal drug delivery system, preferably a liposomal drug delivery system. Suitable colloidal drug delivery systems also include nanoparticles, nanocapsules, microparticles or block copolymer micelles. The colloidal drug delivery system encapsulating curcumin or a curcumin analogue is administered parenterally in a pharmaceutically acceptable carrier.

Methods and compounds for treating cancer, dmg resistance and/or metastasis are described herein. These methods and compounds can inhibit the expression of aberrant TG2 expression and/or inhibit the binding of GTP to TG2, and thereby prevent the induction of epithelial to mesenchymal transition of cancer cells, and a stem cell-like phenotype.

TG2 inhibitors and uses thereof

A method for treating cancer comprising inhibiting transglutaminase activity is provided. Suitable cancer types for which the methods of the present disclosure can be used to treat include, but are not limited to, pancreatic, breast, and ovarian cancers and melanoma. The inhibition of transglutaminase activity may be performed by one or more techniques, including, but not limited to, downregulating transglutaminase expression, inhibiting TG2 translation, or blocking TG2 enzymatic activity, such as with a small molecule inhibitor or intracellular antibody (intrabody).

Methods for treating cancer targeting transglutaminase

The present invention is directed to the use of agents that induce high levels of cell surface molecules to provide targets for immunotoxins directed against the same cell surface molecules. A specific example is given in which all-trans-retinoic acid (RA) is used to induce high levels of CD38 cell surface antigen expression in several myeloid and lymphoid leukemia cells. CD38 was then used as target for delivering plant toxin (gelonin) to leukemia cells. Treatment of leukemia cells with RA induced high levels of CD38 in those cells that otherwise had low CD38 expression. The RA-induced leukemia cells then became exquisitely sensitive to an immunotoxin constructed from an anti-CD38 monoclonal antibody conjugated to the plant toxin gelonin.

Potentiation of anti-CD38-Immunotoxin cytotoxicity

The present invention relates to parasitic nematode transglutaminase proteins; to parasitic nematode transglutaminase nucleic acid molecules, including those that encode such transglutaminase proteins; to antibodies raised against such transglutaminase proteins; and to compounds that inhibit parasitic nematode transglutaminase activity. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitory compounds. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies and/or inhibitory compounds as well as the use of such therapeutic compositions to protect animals from diseases caused by parasitic nematodes.

Parasitic nematode transglutaminase proteins and uses thereof

To optimize the delivery of all-trans retinoic acid to lung tissue, the potential of vehiculating this drug in liposomes and delivering it via aerosol was determined. Liposomes provide a means to prevent local irritation of lung tissue, reduce pulmonary toxicity, prolong therapeutic levels, and generate high drug concentrations at the tumor sites. Therefore, the delivery of ATRA to the lung tissue in mice was accomplished by nebulization of L-ATRA. The liposomes in the aerosol were uniform, stable, and retained the drug well. The drug was effectively delivered at high concentrations to the lungs of mice and was retained at least up to 96 h after a single exposure to L-ATRA aerosols. The aerosol-delivered ATRA was biologically active as demonstrated by its ability to induce the expression of tissue-type transglutaminase. Aerosol delivery of L-ATRA offers an effective way to deliver high levels of ATRA to the lung without apparent pulmonary toxic effects.

Liposomal aerosols for delivery of chemotherapeutic retinoids to the lungs

The present invention relates to parasitic nematode transglutaminase proteins; to parasitic nematode transglutaminase nucleic acid molecules, including those that encode such transglutaminase proteins; to antibodies raised against such transglutaminase proteins; and to compounds that inhibit parasitic nematode transglutaminase activity. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitory compounds. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies and/or inhibitory compounds as well as the use of such therapeutic compositions to protect animals from diseases caused by parasitic nematodes. This invention also relates to the surprising discovery that parasitic nematode transglutaminase proteins have protein disulfide isomerase activity. Accordingly, this invention relates further to inhibitors of the protein disulfide isomerase activity of said transglutaminases.

A reduced-toxicity formulation of carotenoids is disclosed which is stable in an aqueous environment. The formulation includes a carotenoid, lipid arrier particles (such as liposomes), and an intercalation promoter agent (such as a triglyceride), which causes the carotenoid to be substantially uniformly distributed with the lipid in the lipid carrier particles. The molar ratio of carotenoid to lipid is greater than about 1:10. Also disclosed is a method of inhibiting the growth of cancer cells, which comprises administering to a living subject a therapeutically effective amount of a composition as described above.

Formulation and use of carotenoids in treatment of cancer

A reduced-toxicity formulation of carotenoids is disclosed which is stable in an aqueous environment. The formulation includes a carotenoid, lipid carrier particles (such as liposomes), and an intercalation promoter agent (such as a triglyceride), which causes the carotenoid to be substantially uniformly distributed with the lipid in the lipid carrier particles. The molar ratio of carotenoid to lipid is greater than about 1:10. Also disclosed is a method of inhibiting the growth of cancer cells, which comprises administering to a living subject a therapeutically effective amount of a composition as described above.

A novel method of inhibiting production of two important mediators of cellular function, tumor necrosis factor and nitric oxide, and treating a pathophysiological state characterized by an undesirable production or level of tumor necrosis factor or nitric acid. The methods of the present invention employ retinoic acid compounds. The most preferred retinoic acid is all-trans-retinoic acid.

Inhibition of nitric oxide production by retinoic acid

A method is disclosed for treatment of disseminated fungal infection in a mammal comprising the administration of a fungicidally effective amount of Amphotericin B encapsulated in a substantially sterol-free liposome to the infected mammal. Also provided is an agent for treatment of disseminated fungal infection in a mammal comprising Amphotericin B encapsulated in a liposome which consists essentially of lipids other than sterols.

Growing community of inventors

Bellaire, TX, United States of America

Kapil Mehta