Memorial Sloan Kettering Cancer Center

Cornell University

Sloan-kettering Institute for Cancer Research

University of Missouri

Howard Scher

Ulrich B Wiesner

Michelle S Bradbury

Kai Ma

Michael Overholtzer

David A Scheinberg

Francis M Sirotnak

William G Bornmann

Martin Fleisher

Daniel C Danila

Ephraim Vidal

Christopher Borella

Samuel J Danishefsky

Philip O Livingston

Govindaswami Ragupathi

Carlos Cordon-Cardo

Andrew C Koff

Thomas P Quinn

Barney Yoo

In Jong Kim

Wolfgang Weber

Susan Slovin

Karim Touijer

Daniel Danila

Described herein is a method of induced cell death via ferroptosis by nanoparticle ingestion. Moreover, the present disclosure describes the administration of high concentrations of ultrasmall nanoparticles at multiple times over the course of treatment in combination with a nutrient-depleted environment, thereby modulating cellular metabolic pathways to induce cell death by the mechanism ferroptosis. Ferroptosis involves iron, reactive oxygen species, and a synchronous mode of cell death execution.

Methods of treatment using ultrasmall nanoparticles to induce cell death of nutrient-deprived cancer cells via ferroptosis

Described herein are novel conjugates containing an inhibitor (e.g., a PSMA inhibitor, e.g., a gastrin-releasing peptide receptor inhibitor) and metal chelator that are covalently attached to a macromolecule (e.g., a nanoparticle, a polymer, a protein). Such conjugates exhibit distinct properties over the free, unbound inhibitor/chelator construct.

Inhibitor-functionalized ultrasmall nanoparticles and methods thereof

The invention relates to a method for the Cell Type specific labeling with Amino acid Precursors (CTAP). In particular, the disclosed method permits the incorporation of stable isotope-labeled amino acids into the proteome of a vertebrate cell that has been engineered to express an exogenous enzyme that enables the cell to produce an essential amino acid from its amino acid substrate. The method employs stable isotope-labeled amino acid substrate/precursors from which essential amino acids bearing the label are generated. The labeled amino acids generated by the transgenic cell not only supports growth but specifically labels proteins of the transgenic cell. Furthermore, the use of different populations of cells expressing different exogenous amino acid-producing enzymes permits differential labeling of the proteomes of the individual cell populations in multicellular environments.

Genes associated with dasatinib sensitivity

Using an RT-PCR platform, detection of gene transcripts highly expressed in prostate tissue and expressed in peripheral blood mononuclear cells (PBMC) from patients with mCRPC can provide a more reliable and robust prediction of poor overall survival than that of CTC enumeration in mCRPC. Disclosed is the identification of five genes, KLK3, KLK2, HOXB13, GHRL2 and FOXA1, the detection of two (2) or more transcripts of which predicts overall poor survival. The test is performed on blood samples that have been collected in collection tubes that stabilize intracellular RNA, require minimal on-site processing and can be easily stored and shipped for subsequent extraction of total RNA from whole blood for RT-PCR.

Gene expression profile associated with prostate cancer

This invention provides a method for determining the aggressiveness of a prostate carcinoma comprising: (a) obtaining a sample of the prostate carcinoma; and (b) detecting the presence of p27 protein in the prostate carcinoma, the absence of p27 indicating that the prostate carcinoma is aggressive. This invention also provides a method for diagnosing a beign prostate hyperplasia comprising: (a) obtaining an appropriate sample of the hyperplasia; and (b) detecting the presence of the p27 RNA, a decrease of the p27 RNA indicating that the hyperplasia is beign. This invention provides various uses of p27 in prostate cancer. Finally, this invention also provides different marker for prostate cancer.

Markers for prostate cancer

The present invention provides methods for the asymmetric synthesis of (S,S,R)-(&#x2212;)-actinonin and its analogs and the compounds thereby synthesized having a structural formula:where Ris an optionally substituted or halogenated alkyl, aryl, heteroalkyl or heteroaryl amine, said Rfurther comprising a cyclic or bicyclic structure; Ris methyl, CHCH, (CH)CH, C(CH), phenyl, 3,4-dichlorophenyl, biphenyl, benzyl, 4-hydroxybenzyl, piperidine, N-Boc-4-piperidine, CH-(N-Boc-4-piperidine), 4-tetrahydropyran, CH-4-tetrahydropyran, 3-methyl indolyl, 2-naphthyl, 3-pyridyl, 4-pyridyl, 3-thienyl; Ris Ror Calkyl, Ris Calkyl; and Ris NH, OH, NHOH, NHOCH, N(CH)OH, N(CH)OCH, NHCHCH, NH(CHCH), NHCH(2,4-(OCH3)Ph, NHCH(4-NO)Ph, NHN(CH), proline, or 2-hydroxymethyl pyrrolidine. Additionally, a method for the treatment of a neoplastic disease or for the inhibition of tumor cell growth each comprising the step of administering to an individual in need of such treatment a pharmacologically effective dose of the compounds of the present invention are provided.

Asymmetric synthesis of (S,S,R)-(-)-actinonin and its analogs and uses therefor

Synthesis of glycoconjugates of the globo-H epitope and uses thereof

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Tenafly, NJ, United States of America

Howard Scher