Massachusetts Institute of Technology

University of Massachusetts

St. Jude Children's Research Hospital

Sheldon Penman

Edward G Fey

Jeanne B Lawrence

Andre J Van Wijnen

Janet L Stein

Jane B Lian

Gary S Stein

Scott Hiebert

Shari Meyers

Lindsay Shopland

Cong-Mei Zeng

Nuclear matrix targeting peptides (NMTPs) capable of delivering a variety of therapeutic and diagnostic agents, such as transcription regulatory factors, to the nuclear matrix of a cell are disclosed.

Isolated nuclear matrix targeting peptide

Disclosed are non-histological methods for determining the presence in a sample of a preselected cell type such as a malignant or genetically defective cell, or cell nucleus debris from such cells. The methods involve determination of an intranuclear matrix protein, the mRNA encoding that protein, or matrix protein associated DNA or RNA which acts as a marker for the preselected cell type, the presence of which indicates the presence of the cell type in the test sample. The intranuclear matrix marker protein or nucleotide are detected by hybridization, immunoassay, or other known means.

Non-histological cell type determination

A biochemical procedure for identification and characterization of cells in a biopsy or sample of a body fluid. The method can be used to determine cell type, i.e. epidermal, neuronal; tissue of origin, i.e. breast tissue, liver tissue; and degree of abnormality. The procedure can also be used to make antibodies and hybridization probes to detect cell or tissue specific antigens and nuclear matrix associated nucleic acids in cellular material and body fluids. The procedure is based on the isolation and analysis of the components of a specific subcellular protein fraction referred to here as the 'nuclear matrix'. The nuclear matrix includes proteins and nuclear matrix associated DNA specific to different cell types. These proteins and nucleic acids are altered or new ones expressed as a result of viral infection, genetic defects or malignancy. The method has a number of important clinical applications in determining tissue type, tissue of origin, degree of malignancy and extent of metastasis in cancer patients; in detecting and analyzing chromosomal deficiencies or genetic defects, especially in cells obtained by amniocentesis; in identifying viral or other infections; and in measuring the extent and location of cell damage, particularly in patients with localized cell damage or autoimmune disease. The isolated nuclear matrix proteins are also useful in screening for drugs binding to and affecting the nuclear matrix.

Method for determining tissue of origin and presence and extent of

A biochemical procedure for diagnosis of three important properties of cells in a biopsy or blood sample: tumor type i.e., the tissue type that has become neoplastic; tissue of origin if the tumor has arisen from a metastasis; and degree of malignancy. The procedure can also be used to obtain antibodies which can be used to determine tissue of origin by immunostaining and to detect tumor antigens appearing in blood by radioimmunoassay. The procedure consists of isolating and analyzing components of a specific subcellular fraction referred to here as the 'nuclear matrix'. The nuclear matrix consists of proteins specific to different cell types and nuclear matrix associated DNA. The electrophoretic pattern of the proteins and restriction endonuclease digested DNA is unique and reproducible within a particular cell type and is therefore useful in diagnosing cell type. Changes in these patterns following transformation to a malignant phenotype provide additional diagnostic information.

Method for determining tissue of origin and degree of malignancy of

A composition is tested to determine whether it is a tumor promoter or a complete carcinogen by exposing a stable epithelial cell line to the composition for an incubation time period sufficient to induce morphological changes in the cell line. After the incubation time, the cells are observed by morphology changes induced by the composition, which changes are compared to that caused by a known tumor promoter or a known complete carcinogen.

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Brookline, MA, United States of America

Sheldon Penman