Research Development Foundation

The University of Texas System

New Chapter Inc.

Research Development Corporation

Universidad Autonoma De Nuevo León

Universidad Autonoma De Nievo Leon

Bharat B Aggarwal

Robert A Newman

Paul Schulick

Thomas Newmark

Kapil Mehta

Bryant G Darnay

William J Kohr

Michael G Rosenblum

Razelle Kurzrock

Lan Li

Sujay Singh

Cristina Rodriguez-Padilla

Michael E Hogan

Robert F Rando

Dezider Grunberger

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 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.

The inventive subject matter relates to methods for modulating an eicosanoid metabolic process in cells of an animal in need thereof, which comprises administering to the animal an amount of the inventive compositions effective for regulating the activity of an eicosanoid oxygenase. In particular, the inventive subject matter relates to methods for modulating arachidonic acid metabolism by administering an amount of the inventive compositions effective for regulating the activity of lipoxygenases and cyclooxygenases.

Methods for modulating eicosanoid metabolism

The inventive subject matter relates to methods for modulating an eicosanoid metabolic process in cells of an animal in need thereof, which comprises administering to the animal an amount of the inventive compositions effective for regulating the activity of an eicosanoid oxygenase. In particular, the inventive subject matter relates to methods for modulating arachadonic acid metabolism by administering an amount of the inventive compositions effective for regulating the activity of lipoxygenases and cyclooxygenases.

The present invention provides a method of reducing or inhibiting osteoclast development induced by the receptor for activation of nuclear factor kappa B ligand (RANKL), comprising the step of contacting said osteoclast, or a precursor of the osteoclast, with a pharmacologically effective dose of compounds such as diferuloylmethane, guggulsterone, 1'-Acetoxychavicol or analogues thereof.

Osteoclastogenesis inhibitors and uses thereof

The present invention provides cell permeable NF-&#x3ba;B inhibitors consist of a polypeptide derived from the p65 subunit of NF-&#x3ba;B and a protein transduction domain derived from antennapedia third helix sequence. The inhibitor suppressed NF-&#x3ba;B activation induced by TNF, LPS, IL-1, okadaic acid, PMA, HOand cigarette smoke condensate. NF-&#x3ba;B-regulated reporter gene expression induced by TNF, TNFR1, TRADD, TRAF2, NIK, IKK and p65 was suppressed by the inhibitor. The inhibitor enhanced TNF- and chemotherapeutic agent-induced apoptosis. Overall these results demonstrate a NF-&#x3ba;B inhibitor that can selectively inhibit NF-&#x3ba;B activation induced by various inflammatory stimuli, downregulate NF-&#x3ba;B mediated gene expression and upregulate apoptosis.

Selective inhibitors of nuclear factor-&#x3ba;B activation and uses thereof

The present invention is directed to the applications of a novel cytokine, named THANK, for TNF homologue that activates apoptosis, NF-&#x3ba;B and c-jun N-terminal kinase. Such applications include using THANK inhibitors to inhibit the activation of NF-&#x3ba;B and to treat a pathological condition caused by the activation of NF-&#x3ba;B. Also provided is a method of inhibiting growth of a wide variety of tumor cells by administering THANK protein.

Uses of THANK, a TNF homologue that activates apoptosis

All multiple myeloma cell lines examined showed constitutively active I&#x3ba;B kinase (IKK), I&#x3ba;B&#x3b1; phosphorylation and constitutively active NF-&#x3ba;B. Curcumin, a chemopreventive agent, suppressed constitutive I&#x3ba;B&#x3b1; phosphorylation through inhibition of IKK activity and downregulated NF-&#x3ba;B. Curcumin also downregulated expression of NF-&#x3ba;B-regulated gene products such as I&#x3ba;B&#x3b1;, Bcl-2, Bcl-x, cyclin D1 and interleukin-6. Consequently, curcumin suppressed multiple myeloma cell proliferation and arrested cells at the G1/S phase of the cell cycle. Curcumin also induced apoptosis and chemosensitivity to vincristine. Overall, results presented herein provide a molecular basis for the treatment of multiple myeloma patients with this pharmacologically safe agent.

Treatment of human multiple myeloma by curcumin

The present invention provides methods of inhibiting metastasis of a tumor and methods of treating a tumor using a combination of an inhibitor of the activation of nuclear factor NF-&#x3ba;B and a cancer chemotherapeutic agent. In one embodiment of the present invention, combination of curcumin and paclitaxel (taxol) can be used to treat and inhibit metastasis of breast tumor.

Synergistic effects of nuclear transcription factor NF-&#x3ba;B inhibitors and anti-neoplastic agents

The present invention provides a RANK (receptor activator of NF-&#x3ba;B) inhibitor consisted of a TRAF-6 (TNF receptor-associated factor-6) binding domain attached to a leader sequence. The peptide inhibitor inhibits RANKL (RANK ligand)-mediated osteoclast differentiation, thus indicating that targeted disruption of interaction between RANK and TRAF6 may prove useful as a therapeutic for metabolic bone disorders, leukemia, arthritis, and metastatic cancer of the bone.

Inhibitors of receptor activator of NF-&#x3ba;B and uses thereof

The present invention provides methods for the therapeutic application of TRANK, a novel cytokine. TRANK is secreted by cells and activates NF-&kgr;B, c-Jun N-terminal kinase (JNK) and downstream gene products. Provided is a method of inhibiting NF-&kgr;B activation in an individual in need of such treatment, comprising the step of administering an effective dose of an anti-TRANK antibody to said individual.

Uses of trank, a novel secretory cytokine

The present invention is directed to the applications of a novel cytokine, named THANK, for TNF homologue that activates apoptosis, NF-&kgr;B and c-jun N-terminal kinase. Such applications include using THANK inhibitors to inhibit the activation of NF-&kgr;B and to treat a pathological condition caused by the activation of NF-&kgr;B. Also provided is a method of inhibiting growth of a wide variety of tumor cells by administering THANK protein.

This invention relates to substantially purified gelonin, toxic fragments thereof, the DNA sequences encoding gelonin and use of the DNA for producing, by recombinant technology, gelonin, toxic fragments thereof and fusion proteins. More specifically, the invention relates to the primary amino acid sequence of gelonin, and of the DNA encoding said gelonin and the production of synthetic gelonin and toxic fragments thereof.

Protein sequence of the plant toxin gelonin

The present invention provides a novel human cytokine termed Oncoinhibin. The protein Oncoinhibin is secreted by human erythroblastoid cells, has a molecular weight of approximately 28 kDa and exerts diverse neoplastic activity. The present invention also provides a method for treating neoplastic cells using human Oncoinhibin and a pharmaceutical composition comprised essentially of Oncoinhibin.

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Houston, TX, United States of America

Bharat B Aggarwal