Johns Hopkins University

Duke University

University of Illinois

Vanquish Oncology, Inc.

Institute of Organic Chemistry and Biochemistry Ascr, V.v.i.

Gregory J Riggins

Bert Vogelstein

Kenneth W Kinzler

Nickolas Papadopoulos

Darell D Bigner

Victor E Velculescu

Hai Yan

Sian Jones

Rebecca J Leary

Xiaosong Zhang

Avadhut D Joshi

Paul Joseph Hergenrother

Mark J Gilbert

Chien-Tsun Kuan

Timothy M Fan

D Williams Parsons

Rachel C Botham

Jimmy Cheng-Ho Lin

Giovanni Parmigiani

Philipp Angenendt

Rachel Karchin

Michael K Handley

Theodore Michael Tarasow

Janete Cerruti

Renyuan Bai

Verena Staedtke

Barbara S Slusher

Pavel Majer

Meng Li

Rana Rais

Shibin Zhou

Andrej Jancarik

Lukas Tenora

Tomas Tichy

Jan Vavra

William T Loging

Anita Lal

Theodore M Tarasow

Michael J Handley

Tara Williamson

Janete Cerutti

Donald Williams Parsons

Ren-Yuan Bai

Williams Parsons

Kenneth Kinzler

Compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other cancer therapies that achieve the same or similar therapeutic effect.

Procaspase combination therapy for glioblastoma

The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds.

Prodrugs of mebendazole and methods for their use in treating a disease, disorder, or disorder, including cancer, are disclosed.

Mebendazole prodrugs with enhanced solubility and oral bioavailability

This document provides methods and materials for preventing cytokine release syndrome (CRS). For example, methods and materials for using one or more catecholamine inhibitors to prevent a mammal from developing CRS are provided.

Preventing cytokine release syndrome

Mebendazole is an antiparasitic drug with over 40 years of safe use. Recently mebendazole was repurposed for glioblastoma therapy. Three polymorphs of mebendazole exist, but the relative polymorph content for existing drugs varies, and the therapeutic anti-cancer relevance of the different polymorphs was unknown. As an oral drug mebendazole polymorph C is a superior form, and it reaches the brain and brain tumors in effective concentrations. Efficacy is further improved by combining mebendazole with a P-glycoprotein inhibitor. Mebendazole may also be used for therapy of other cancers, as well as a chemo-preventative agent.

Mebendazole polymorph for treatment and prevention of tumors

We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.

Genetic alterations in isocitrate dehydrogenase and other genes in malignant glioma

We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in gliblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.

Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high density microarrays and sequenced all known protein-coding genes and miRNA genes using Sanger sequencing. We found that, on average, each tumor had 11 gene alterations, markedly fewer than in common adult cancers. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone H3K4 trimethylase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis.

Medulloblastoma genes as targets for diagnosis and therapeutics

This invention relates, e.g., to a method for detecting the presence of lymph node metastases in a subject having papillary thyroid carcinoma (PTC), comprising measuring in a sample from the subject the amount of expression (e.g., the amount of protein, or the amount of mRNA encoding the protein) of one or more of the following proteins: (a) LIMD2, and/or (b) PTPRC, and/or (c) LTB, and/or (d) CD48, and/or (e) ABCC3, wherein a significant amount of over-expression of one or more of protein(s) (a)-(e), compared to the baseline value, indicates that lymph node metastases are likely to be present in the subject.

Protein markers for the detection of thyroid cancer metastasis

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Baltimore, MD, United States of America

Gregory J Riggins