Other

The United States of America As Represented by the Department of Health

Johns Hopkins University

The United States of America, As Represented by the Secretary, Department of Health and Human Services

The United States of America As Represented by the Secretary of

James L Mulshine

Melvyn S Tockman

Marti Jett

John D Minna

John K Frost

John Weinstein

Melvin S Tockman

Prabodh K Gupta

The present invention provides a method for treating and preventing an epithelial cell-derived cancer in a subject in need thereof, comprising administering to the subject an amount of a 5-lipoxygenase inhibitor and PPAR ligand or derivatives thereof, effective to treat or prevent the epithelial cell-derived cancer. Also encompassed by the invention are inhibitors of enzymes that metabolize arachidonic acid.

Use of lipoxygenase inhibitors and PPAR ligands as anti-cancer therapeutic and intervention agents

The present invention is a purified and isolated epithelial protein, peptide and variants thereof whose increased presence in an epithelial cell is indicative of precancer. One epithelial protein which is an early detection marker for lung cancer was purified from two human lung cancer cell lines, NCI-H720 and NCI-H157. Using a six-step procedure, the epithelial protein was purified using a Western blot detection system under both non-reducing and reducing conditions. Purification steps included anion exchange chromatography, preparative isoelectric focusing, polymer-based C HPLC and analytic C HPLC. After an approximately 25,000 fold purification the immunostaining protein was >90% pure as judged by Coomassie blue staining after reducing SDS-PAGE. The primary epithelial protein shares some sequence homology with the heterogeneous nuclear ribonucleoprotein (hnRNP) A2. A minor co-purifying epithelial protein shares some sequence homology with the splice variant hnRNP-B1. Molecular analysis of primary normal bronchial epithelial cell cultures demonstrated low levels of epithelial protein expression, consistent with immunohistochemical staining of clinical samples, and an increased level of expression in most lung cancer cells. The epithelial protein is a marker of epithelial transformation in lung, breast, bone, ovary, prostate, kidney, melanoma and myeloma and may be casual in the process of carcinogenesis. Methods are provided for monitoring the expression of the epithelial protein, peptides and variants using molecular and immunological techniques as a screen for precancer and cancer in mammals.

Methods for diagnosing cancer or precancer based upon hnRNP protein expression

The present invention is a purified and isolated epithelial protein, peptide and variants thereof whose increased presence in an epithelial cell is indicative of precancer. One epithelial protein which is an early detection marked for lung cancer was purified from two human lung cancer cell lines, NCI-H720 and NCI-H157. Using a six-step procedure, the epithelial protein was purified using a Western blot detection system under both non-reducing and reducing conditions. Purification steps included anion exchange chromatography, preparative isoelectric focusing, polymer-based C,HPLC and analytic C,HPLC. After an approximately 25,000 fold purification the immunostaining protein was >90% pure as judged by coomassie blue staining after reducing SDS-PAGE. The primary epithelial protein share some sequence homology with the heterogeneous nuclear ribonucleoprotein (hnRNP) A2. A minor co-purifying epithelial protein shares some sequence homology with the splice variant hnRNP-B1. Molecular analysis of primary normal bronchial epithelial cell cultures demonstrated a low level the epithelial protein expression, consistent with immunohistochemical staining of clinical samples, and an increased level of expression in most lung cancer cells. The epithelial protein is a marker of epithelial transformation in lung, breast, bone, ovary, prostate, kidney, melanoma and myeloma and may be casual in the process of carcinogenesis. Methods are provided for monitoring the expression of the epithelial protein, peptides and variants using molecular and immunological techniques as a screen for precancer and cancer in mammals. A method of computerized diagnoses of cancer and precancer is provided which detects levels of hnRNP messenger RNA.

Epithelial protein and DNA thereof for use in early cancer detection

Use of lipoxygenase inhibitors as anti-cancer therapeutic and

The present invention is a purified and isolated epithelial protein, peptide and variants thereof whose increased presence in an epithelial cell is at indicative of precancer. One epithelial protein which is an early detection marked for lung cancer was purified from two human lung cancer cell lines, NCI-H720 and NCI-H157. Using a six-step procedure, the epithelial protein was purified using a Western blot detection system under both non-reducing and reducing conditions. Purification steps included anion exchange chromatography, preparative isoelectric focusing, polymer-based C.sub.18 HPLC and analytic C.sub.4 HPLC. After an approximately 25,000 fold purification the immunostaining protein was &gt;90% pure as judged by coomassie blue staining after reducing SDS-PAGE. The primary epithelial protein share some sequence homology with the heterogeneous nuclear ribonucleoprotein (hnRNP) A2. A minor co-purifying epithelial protein shares some sequence homology with the splice variant hnRNP-B1. Molecular analysis of primary normal bronchial epithelial cell cultures demonstrated a low level the epithelial protein expression, consistent with immunohistochemical staining of clinical samples, and an increased level of expression in most lung cancer cells. The epithelial protein is a marker of epithelial transformation in lung, breast, bone, ovary, prostate, kidney, melanoma and myeloma and may be casual in the process of carcinogenesis. Methods are provided for monitoring the expression of the epithelial protein, peptides and variants using molecular and immunological techniques as a screen for precancer and cancer in mammals.

The present invention relates to a method for early detection of lung cancer. The method comprises obtaining samples from the body, especially respiratory tract material including sputum or bronchial fluid or any other pulmonary tissue or thoracic cells or regional lymph nodes, and assaying the samples with monoclonal antibodies for the presence of antigens whose enhanced presence correlates with the development of lung cancer. The method of the present invention permits identification of lung cancer up to two years prior to the development of clinical lung cancer, and thus enables early treatment of the lung cancer.

Method for early detection of lung cancer

The invention provides a method of delivering therapeutic or diagnostic reagents to the lymphatic system. In the preferred method the delivery is accomplished by use of a fiberoptic endoscope equipped with an aspiration cytology needle. The method provides an especially useful means of delivering labeled monoclonal antibodies.

Treatment or diagnosis by endoscopic administration into the lymphatics

Monoclonal antibodies 703D4 and 704A1 detect human non-small cell lung cancer (non-SCLC) and distinguish non-SCLC from all other types of lung cancer and normal tissue cells. These two antibodies may be utilized in kit form to distinguish non-SCLC from other forms of lung cancer. These monoclonal antibodies bind to S.sup.35 methionine-incorporating protein doublets under reduced and unreduced conditions. The determinants bound by these antibodies on the 31 kiladalton protein are independent of each other as determined in radiolabelled competition assays.

Growing community of inventors

Bethesda, MD, United States of America

James L Mulshine