University of South Florida

H. Lee Moffitt Cancer Center and Research Institute, Inc.

University of California

Arizona State University

Yale University

William S Dalton

Lori Hazlehurst

Anne E Cress

Mark L McLaughlin

Timothy J Yeatman

Priyesh Jain

Jason S Damiano

Said M Sebti

Kit S Lam

Richard M Heller

Andrew D Hamilton

Richard Jove

Mark Jeffrey Jaroszeski

Richard A Gilbert

Hua Yu

Qing Chen

Mark Mclaughlin

Integrin interaction inhibitors using a beta-turn promoter are described herein. These peptides are useful in treating cancer, such as multiple myeloma, by administering a therapeutically effective amount of the integrin interaction inhibitor. Data show that integrin interaction inhibitors act synergistically or additively interact with anti-proliferative agents such as doxorubicin, SAHA, arsenic trioxide, and etoposide.

Integrin interaction inhibitors for the treatment of cancer

Signal Transducer and Activator of Transcription (STAT) proteins have a fundamental role cell signaling, and are activated by a large number of cytokines and growth factors. One member of the STAT family, STAT3, has a critical role in oncogenesis. The present invention relates generally to disruption of the pathway of STAT3 signaling in the treatment of human cancer. STAT3 activation is shown to be present in diverse tumor cell lines and tumors, to promote oncogenesis, to inhibit apoptosis, and to reduce sensitivity to chemotherapeutic agents. Inhibition of STAT3 signaling induces apoptosis specifically in tumor cell lines, and increases sensitivity to chemotherapeutic agents. The invention relates more particularly to methods, compositions, means of administering such compositions, and means for identifying such compositions for the inhibition of STAT3 intracellular signaling in the treatment of human cancers.

Inhibition of STAT3 signal transduction for human cancer therapy

The subject invention pertains to materials and methods for treating oncological disorders. The subject invention also pertains to materials and methods for preventing or reducing the development by cancer cells of resistance to an anticancer therapy, such as chemotherapy, radiotherapy and/or immunotherapy. In one embodiment, a patient is treated with an agent that inhibits cholesterol synthesis or that prevents or reduces the increase in cholesterol synthesis observed in therapy-resistant cancer cells. In another embodiment, a patient is treated with an agent that increases the expression, activity, or amount of a Bim protein in a cell. In another embodiment, a patient is treated with an agent to inhibit or reduce cancer cell adhesion to extracellular matrices or stromal cells. In another embodiment, a patient is treated with an agent to inhibit expression of a gene of function of a protein of the FANC/BRCA pathway. In a further embodiment, a patient is treated with an agent to prevent or reduce the DNA crosslink repair function of a cell.

Materials and methods for treating oncological disorders

Systems and methods are provided including a system for managing patient data. The system includes a computing system including a processing unit and a storage. The processing unit executes one or more programs for managing patient data. Managing patient data includes enrolling patients in a centralized care network including presenting each patient with an electronic enrollment interface, assigning each patient a patient identifier, and receiving an electronic consent to collect data. Managing patient data further includes providing patient data to the centralized care network including patient data relating to disease progression, clinical trials and treatments rendered.

Front end

Computers, computer program products, and methods for identifying a plurality of subjects for a clinical trial are provided. A candidate set of molecular profiles in a stored plurality of molecular profiles are identified. Each such profile has measurements for a discriminating set of cellular constituents that match the measurements of corresponding cellular constituents in a responder set of biological samples, thereby identifying the plurality of subjects for the trial from those subjects from which the candidate set of molecular profiles were derived. Each respective molecular profile in the stored plurality of profiles has measurements of a plurality of cellular constituents from a respective biological sample in a plurality of samples obtained from a first plurality of subjects. The discriminating set of cellular constituents is identified from those cellular constituents in the plurality of cellular constituents whose measurement values discriminates between the responder and nonresponder sets of biological samples.

Computer systems and methods for selecting subjects for clinical trials

The invention provides a computer network comprising a first computer and one or more second computers that are in electronic communication with each other. The first computer is associated with a first health care facility and has instructions for retrieving, over a network, one or more data structures for a patient enrolled in a health care program. The one or more data structures for the patient collectively comprise (i) a patient identifier, (ii) a molecular profile from a biological specimen obtained from the patient at the first health care facility; and (iii) a clinical characterization of the patient that was made at the first health care facility. The first computer has instructions for retrieving, over the network connection, one or a plurality of treatment regimens that are deemed suitable for the patient based upon the molecular profile and the clinical characterization of the patient. The one or more second computers are at one or more locations other than the first health care facility and have one or more data structures for each patient in a plurality of patients enrolled in the health care program.

Computer systems and methods for providing health care

Systems and methods including a computer network are provided. The computer network includes a plurality of affiliate computing systems, each affiliate computing system including a processing unit and storage, the processing unit executing one or more programs for supporting care of a patient. The computer network includes a centralized care network including a central health care computing system, the central health care computing system being coupled to each affiliate computing system by way of a network and including a processing unit and storage, the processing unit executing one or more programs for managing patient records stored in the storage.

Value network

The present invention concerns fragments and variants of the HYD1 peptide; polynucleotides encoding the peptides; host cells genetically modified with the polynucleotides; vectors comprising the polynucleotides; compositions containing these peptides, polynucleotides, vectors, or host cells; and methods of using the peptides, polynucleotides, vectors, and host cells as inhibitors of aberrant cell growth in vitro or in vivo, e.g., as anti-cancer agents for treatment of cancer, such as myeloma. The present invention further includes a method of increasing the efficacy of chemotherapy and radiation therapy, comprising administering an agent that binds &#x3b2;1 integrin to a patient in need thereof. In one embodiment, the &#x3b2;1 integrin binding agent is the HYD1 peptide, or a functional fragment or variant thereof. In another aspect, the invention pertains to a composition (an adhesion trap) comprising a substrate (also referred to as a surface or support) with a HYD1 peptide, or fragment or variant thereof, immobilized to the substrate, and a method of removing circulating tumor cells (CTC) from blood by contacting a subject's blood with the immobilized peptide. Another aspect of the invention concerns a method of identifying modulators of peptide binding. Another aspect of the invention concerns a method for detecting CTC.

HYD1 peptides as anti-cancer agents

Peptides and methods of their use for inhibiting drug and radiation-therapy resistance in cancerous cells in which efficacy of chemotherapy and/or radiotherapy of a patient is enhanced by administration of an effective amount of a peptide that inhibits cell adhesion mediated drug resistance (CAM-DR). Preferably, the peptide comprises D-amino acids having the sequence:kmviywkag (RZ-3)or is a variant or modified version thereof. The peptide is preferably administered to the patient prior to chemotherapy and/or radiation therapy. Inhibition of cell adhesion mediated drug resistance (CAM-DR) by RZ-3 in multiple myeloma cells is disclosed.

Growing community of inventors

Temple Terrace, FL, United States of America

William S Dalton