The Ohio State University

Thomas Jefferson University

The Government of the United States of America As Represented by the Secretary of the Deptartment of Health and Human Services

The Wistar Institute

Other

University of Kentucky Research Foundation

Ohio State Innovation Foundation

Temple University

Fudan University

Raggio-italgene S.p.a.

Carlo M Croce

George A Calin

Stefano Volinia

Curtis C Harris

Aaron J Schetter

Ramiro Garzon

Frances Kay Huebner

Leonard Gomella

S Grant Mulholland

Jose G Moreno

Chang-Gong Liu

Rainer Fischer

Cinzia Sevignani

Xin Wei Wang

Eli Canaani

Nicola Valeri

Nozomu Yanaihara

Giandomenico Russo

Hui Li

Hilary Koprowski

Peixuan Guo

Farzin Haque

Subrata Haldar

Andrea Vecchione

Muller Fabbri

Junfang Ji

Zhao-you Tang

Hideshi Ishii

Tae Jin Lee

Yoshihide Tsujimoto

Taro Yamashita

Walter U Gerhard

Danuta Kozbor

Denis Guttridge

David E Cohn

Kimberly E Resnick

Hansjuerg Alder

Giulia Romano

Hui-chuan Sun

Francesco Trapasso

Anuradha Budhu

The presently-disclosed subject matter relates to an artificial RNA nanostructure molecule and method to treat brain tumor in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure containing a multiple branched RNA nanoparticle, a brain tumor targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanostructure composition to treat brain tumor in a subject having or at risk of having brain tumor.

RNA nanoparticles for brain tumor treatment

The present invention relates, in various embodiments, to methods of treating cachexia (e.g., cancer cachexia) in a patient. The methods comprise administering at least one compound for inhibiting, in alternative embodiments, the expression or activity of a microRNA that is present in microvesicles secreted from cancer cells in the patient (e.g., a miR-21 gene product), the expression or activity of a Toll-like receptor (e.g., TLR7, TLR8), the expression or activity of a c-Jun N-terminal kinase (JNK), the secretion of microvesicles from cancer cells, or the fusion of microvesicles from cancer cells with muscle cells or adipocytes. The present invention also relates, in certain embodiments, to pharmaceutical compositions comprising at least two compounds useful in the practice of the methods of the invention described herein.

Compositions and methods for treating cachexia

Described herein are methods for diagnosing ovarian cancer. In particular, certain microRNAs are useful to the response to chemotherapy of ovarian cancer patients.

MicroRNAs useful for treating ovarian cancer

Described herein are methods and compositions for the diagnosis, prognosis and treatment of ovarian cancer. Also described are methods of identifying anti-cancer agents.

MicroRNA signatures in human ovarian cancer

MicroRNA genes are highly associated with chromosomal features involved in the etiology of different cancers. The perturbations in the genomic structure or chromosomal architecture of a cell caused by these cancer-associated chromosomal features can affect the expression of the miR gene(s) located in close proximity to that chromosomal feature. Evaluation of miR gene expression can therefore be used to indicate the presence of a cancer-causing chromosomal lesion in a subject. As the change in miR gene expression level caused by a cancer-associated chromosomal feature may also contribute to cancerigenesis, a given cancer can be treated by restoring the level of miR gene expression to normal. microRNA expression profiling can be used to diagnose cancer and predict whether a particular cancer is associated with an adverse prognosis. The identification of specific mutations associated with genomic regions that harbor miR genes in CLL patients provides a means for diagnosing CLL and possibly other cancers.

Diagnosis and treatment of cancers with microrna located in or near cancer-associated chromosomal features

Methods and compositions for the diagnosis, prognosis and/or treatment of ovarian cancer are disclosed.

MicroRNA-based methods and compositions for the diagnosis, prognosis and treatment of ovarian cancer using a real-time PCR platform

Provided are methods and compositions for the treatment of cancers associated with overexpression of a BCL2 gene and/or gene product in a subject, and methods and compositions for the improvement of anti-cancer therapy, such as chemotherapy and radiation therapy. Also provided are methods for determining the efficacy of a cancer therapy in a subject, methods for diagnosing cancer, methods for assessing patient prognosis, and methods for inducing apoptosis of a cell.

Compositions and methods for the diagnosis and therapy of BCL2-associated cancers

The present invention provides materials and methods related to the discovery that tumor secreted miR-21 and miR-29can function by binding as ligands to receptors of the Tolllike receptor family, murine TLR7 and human TLR8, in immune cells, triggering a TLR-mediated prometastatic inflammatory response, which leads to tumor growth and metastasis. Thus, by acting as paracrine agonists of TLRs, secreted miRNAs are key regulators of the tumor microenvironment. This mechanism of action of miRNAs is important in the tumor-immune system communication, in tumor growth and spread, and in cancer treatment.

Methods and compositions related to miR-21 and miR-29a, exosome inhibition, and cancer metastasis

MicroRNA profiles transition from normal breast to ductal carcinoma in situ and transition to invasive ductal carcinoma (IDC) and methods of use thereof are described. Methods of diagnosis and prognosis using microRNA signatures to differentiate invasive from in situ carcinoma are described. Also described is the use of microRNA expression for predicting overall survival and time to metastasis.

Breast cancer biomarker signatures for invasiveness and prognosis

Methods and compositions for inhibiting tumorigenicity both in vitro and in vivo in a subject in need thereof, comprising administering an effective amount of an anti-miR-494 nucleic acid construct sufficient to target one or more tumor suppressor genes (TSGs) are described. Activation of the ERK1/2 pathway is a major determinant of diverse cellular processes and cancer development and is responsible for the transcription of several important miRNAs. Described herein is a link between the ERK1/2 pathway and BIM expression through miR-494. This ERK1/2 pathway regulates apoptosis and cell proliferation through miR-494 and mechanisms responsible for TRAIL resistance. Materials and methods related to the study and treatment of cancer are described.

Use of miR-494 to modulate TRAIL-induced apoptosis through BIM down-regulation

Described herein is the discovery that miR-21 targets and down-regulates the core mismatch repair (MMR) recognition protein complex hMSH2 and hMSH6. Anti-sense miR-21 is therefore proven as therapeutic herein. Therefore, compositions, kits, therapies and other methods, including methods of treatment/amelioration of symptoms, are disclosed herein.

Materials and methods related to MicroRNA-21, mismatch repair, and colorectal cancer

Methods for assessing a pathological condition in a subject include measuring one or more markers where a difference is indicative of acute lymphoblastic leukemia (ALL) or a predisposition to ALL, uses and compositions are disclosed.

Methods and compositions for inducing deregulation of EPHA7 and ERK phosphorylation in human acute leukemias

Methods and materials related to ovarian cancer

It is disclosed herein that miR-221 and miR-222 down-regulate PTEN and TIMP3 tumor suppressors, resulting in TRAIL resistance. The present invention provides research, diagnostic, and therapeutic tools and methods related to this discovery. Diagnostics, prognostics and treatments for human hepatocellular cancer and non-small cell lung carcinoma having a TRAIL resistance are particularly described herein.

Materials and methods useful for affecting tumor cell growth, migration and invasion

Growing community of inventors

Columbus, OH, United States of America

Carlo M Croce