The Johns Hopkins University

Other

Cell Genesys, Inc.

Biosante Pharmaceuticals, Inc.

William G Nelson

Srinivasan Yegnasubramanian

Xiaohui S Lin

Margo R Roberts

Dale Ando

James G McArthur

Zachery Reichert

Traci J Speed

Ju-Fay Chang

Jonathan Simons

William B Isaacs

Ajay Vaghasia

Philipp Nuhn

Angelo M DeMarzo

Paul O Ts'o

Alan W Partin

G Steven Bova

Paul R Weber

Michael Christoph Haffner

Alcides Chaux

Randy Alberg

Julia C Tchou

Jila Bakker

Wen-Hsiang Lee

Srinivasan Nasubramanian

Stephen A Lesko

Martin Aryee

Zheng-Pin Wang

The disclosure generally relates to compositions and methods for the treatment of cancer. In some aspects, disclosed herein are methods for the induction of synthetic lethality with epigenetic therapy (ISLET) using a combination of at least one epigenetic compound and at least one chemotherapeutic agent. Also disclosed herein are screening methods for identifying compounds that induce killing of cancer cells when combined with at least one epigenetic compound. Further disclosed herein are methods of potentiating a therapeutic effect of a chemotherapeutic agent against a cancer, comprising administering to a subject having the cancer an epigenetic compound in an amount effective to potentiate the therapeutic effect of the chemotherapeutic agent against the cancer.

Induction of synthetic lethality with epigenetic therapy

The present invention provides methods for discovering agents that are effective in reversing epigenetic silencing by inhibiting the interaction of methyl-binding (MBD) proteins with methylated genomic DNA. Also provided are methods for reactivating silenced genes having CpG island hypermethylation along with methods for treatment and prevention of diseases, such as cancer and sickle cell anemia, by administering an agent that modulates methyl-binding domain (MBD) protein-mediated transcriptional repression, thereby increasing gene transcription to prevent or treat disease. Additionally, compounds identified by the present invention useful for treatment and prevention of diseases, such as cancer and sickle cell anemia, are provided.

Agents for reversing epigenetic silencing of genes

The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions useful for assessing prostate cancer. In a specific embodiment, present inventors have developed and applied a new technology and associated computation methods enabling simultaneous genome-scale analysis of genetic (copy number) and epigenetic (total methylation (TM) and allele-specific methylation (ASM) alternation, This method, called MBD-SNP, features affinity enrichment or methylated genomic DNA fragments using a methyl-binding domain polypeptide.

DNA methylation markers for metastatic prostate cancer

The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions useful for diagnosing or predicting cancer in a patient. In one embodiment, a method for identifying a patient as having cancer comprises the steps of (a) providing a formalin-fixed, paraffin-embedded or fresh frozen sample of patient tissue; (b) steaming the sample in antigen retrieval buffer; (c) incubating the sample in hydrochloric acid (HCl); (d) incubating the sample with an affinity reagent specific for 5hmC under conditions to form a complex between the affinity reagent and 5-hydroxymethylcytosine (5hmC) present in the sample; (e) detecting the complexes formed between 5hmC and the affinity reagent with secondary detection reagents; (f) quantifying 5hmC levels; and (g) identifying the patient as having cancer if the 5hmC levels in the sample are reduced as compared to a control.

5-hydroxymethylcytosine in human cancer

An ice making machine includes a heat pipe that extends between a freezer compartment and a refrigerator compartment. The heat pipe has a first end in the freezer compartment and a second end in the refrigerator compartment. A heat exchanger is located in the freezer compartment and is in contact with the first end of the heat pipe. A heat block is located in the refrigerator compartment and is in contact with the second end of the heat pipe. A removable ice cube tray is mounted on the heat block with a surface in contact with the heat block such that when the removable ice cube tray is filled with water, ice forms from the surface of the removable ice cube tray in contact with the block.

Clear ice making machine

The present invention provides methods and kits useful for enriching, identifying and quantifying methylated DNA3 particularly hypermethylated CpG islands by digesting a sample with a methylation-sensitive restriction endonuclease and capturing methylated restriction fragments with a methyl-binding capture reagent. The methods of the invention may be used in the detection of cancer, particularly detection of prostate cancer.

Compare-MS: method rapid, sensitive and accurate detection of DNA methylation

The present invention provides novel, isolated, tumor-associated antigens, and methods for identifying such antigens in a biological sample, and of screening for the presence of such an antigen in a biological specimen, wherein the tumor antigen identified reacts with serum from a subject treated with a vaccine comprising a cytokine and proliferation-incompetent tumor cells which express the tumor-associated antigen. Also provided are kits for carrying out the methods of the invention.

Cancer-associated antigens and methods of their identification and use

A carbonator tank includes a liquid inlet, a gas inlet and a liquid outlet. A liquid level sensor includes a liquid level sensing portion extending along and within the interior of the carbonator and provides for determining a full and minimal liquid level therein. The level sensor includes an outer contact portion for connection to an electronic control and the contact portion is integral with the liquid inlet. Additionally, the level sensor includes a deflection plate extending from the liquid level sensing portion in a direction there from that is transverse to the direction of flow of liquid into the carbonator interior through the liquid inlet. The liquid then flows into the carbonator interior and contacts the deflection plate and is deflected thereby so that such liquid flow does not disrupt the operation of the level sensing portion of the level sensor.

Semi-frozen food product carbonator

Provided are methods and compositions useful for the diagnosis, prognosis and treatment of hepatic cellular proliferative disorders. The methods include the modulation or analysis of hypemethylated glutathione-S-transferase nuleic acid sequence in hepatic samples and biological fluids.

Methods of diagnosing and treating hepatic cell proliferative disorders

A method for enriching cancer cells such as prostate cancer cells in a bodily fluid sample is disclosed comprising (a) obtaining the sample comprising cancer cells and non-rare cells; (b) subjecting the sample to multiple density gradient separation comprising a first density gradient and a second density gradient, wherein the second density gradient is greater than the first density gradient, and producing a first fluid comprising an increased concentration of cancer cells of a first density, and a second fluid comprising an increased concentration of cancer cells of a second density, wherein the second density is greater than the first density; wherein subjecting the sample to multiple density gradient separation includes producing a plasma layer, a first interface layer, a first gradient layer, a second interface layer, a second gradient layer, and a cell pellet; wherein producing the first fluid includes combining the first interface layer and the first gradient layer and forming a first suspension; and wherein producing the second fluid includes combining the second interface layer and the second gradient layer and forming a second suspension; (c) subjecting said second fluid comprising the second suspension to a binding agent that binds non-rare cells; and (d) removing the bound non-rare cells from the second fluid to provide a second fluid enriched with the greater density cancer cells.

Method of enriching rare cells

Growing community of inventors

Towson, MD, United States of America

William G Nelson