Wayne State University

Biomide Investment Limited Partnership

Vanderbilt University

Radiation Oncology Center Research and Development Corporation

Kenneth V Honn

Carl R Johnson

John D Taylor

Lawrence J Marnett

Yung-Fa Chen

Katsu-ichi Shimoji

Daniel A Walz

Mohanathasan Chelladurai

Mohit Trikha

Friedel Seuter

Eike Moller

Wolf-Dieter Busse

Gilles Gorins

James M Onoda

Dean G Tang

Soan Cheng

tr-&agr;IIb, a soluble, truncated integrin found to be exclusively expressed in tumor cells is provided. An additional truncated integrin, tr-&bgr;3, has also been found to be exclusively expressed in tumor cells. Diagnostic compositions including nucleic acid probes and antibodies and methods for detecting the presence of tr-&agr;IIb and tr-&bgr;3 to identify the presence of tumor cells in a sample are also provided.

Antibodies specific for soluble truncated integrins

tr-.alpha.llb, a soluble, truncated integrin found to be exclusively expressed in tumor cells is provided. An additional truncated integrin, tr-.beta.3, has also been found to be exclusively expressed in tumor cells. Diagnostic compositions including nucleic acid probes and antibodies and methods for detecting the presence of tr-.alpha.llb and tr-.beta.3 to identify the presence of tumor cells in a sample are also provided.

Nucleic acid encoding truncated integrins

A method and test kit for determining tumor cell apoptosis by inhibition of 12-lipoxygenase is described. A method for selectively inducing tumor cell apoptosis by inhibiting 12-lipoxygenase is also described. The preferred compounds are selected from the group consisting of a cyclic hydroxamic acid; and an aryl aliphatic acid; nordihydro guaiaretic acid (NDGA) and N-benzyl-N-hydroxy-5-phenylpentanamide (BHPP).

Method for induction of tumor cell apoptosis with chemical inhibitors

Thromboembolic complications have been documented in cancer patients and mismatched organ transplant recipients. Procoagulants have been implicated in these processes and may play an additional role in tumor metastases. Two proteins displaying procoagulant activity, with molecular weights of 35,000 and 28,000 daltons, were isolated from human ovarian carcinoma extracts. The amino terminal sequence of the first 12 amino acids of the 35,000 dalton protein was determined to be IKEEHVIIQAEF. This sequence displays 100% homology to the major histocompatibility (MHC) antigen HLA-DR which exists as an heterodimer composed of a 35 kDa and 28 kDa protein. The procoagulant activity was further purified through immunoaffinity column chromatography involving a monoclonal antibody to HLA-DR. The immunoaffinity purified protein enhanced thrombin generation in recalcified normal plasma approximately 20-fold. HLA-DR procoagulant activity was completely abrogated by the addition of Staphylcoccal aureus enterotoxin A (SEA).

Method for measuring blood procoagulant activity of human leukocyte

A method of testing for the presence of tumor cells which are metastatic based upon the presence of Human Leukocyte Antigen (HLA) is described. In the test a protein which selectively binds the HLA is used to determine the presence of excess HLA which is a characteristic of the tumor cells. The preferred protein is a bacterial enterotoxin, preferably the enterotoxin A (SEA) produced by Staphylococcus aureus.

Method for testing for the presence of metastatic tumor cells

This invention is related to a cyclic hydroxamic acid of the formula: ##STR1## wherein R.sup.1 is C.sub.1-24 alkyl and R.sup.2 is benzyl.

Cyclic hydroxamic acids

Novel aryl aliphatic acids or derivatives thereof of the general formula

Aryl aliphatic acids

Novel cyclic hydroxamic acids of the general formula: ##STR1## wherein ring A is 5- or 6-membered; R.sup.1, R.sup.2 and R.sup.3 each, ipendently, is hydrogen, C1-24 alkyl, C2-24 alkenyl or a group of the formula: ##STR2## wherein R.sup.4, R.sup.5, R.sup.7 and R.sup.8 each, independently is hydrogen,

Compositions and a method for inhibiting tumor cell induced platelet aggregation are described. Platelet aggregation by tumor cells is part of the metastatic cascade which is interrupted according to the present invention. The compounds include a mixture of at least two members of the group including a calcium channel blocker, a prostacyclin, a thromboxane synthase inhibitor and a phosphodiesterase inhibitor. All of the compounds utilized have an affect on calcium ion which controls platelet aggregation.

Method and compositions for inhibition of tumor cell induced platelet

A method for the treatment of malignant tumors by co-administering a platinum coordination compound and a dihydropyridine class calcium channel blocker compound is described. The compounds are administered over a period of several days in at least two separate dosages of each compound so as to produce regression of the tumor in vitro and in vivo and inhibition of metastasis of the tumor in vivo.

Method and composition for the treatment of tumors by administering a

A therapeutic method for reducing metastasis is disclosed. The method involves administering a therapeutically effective amount of 3-methyl-1-[2-(2-naphthyloxy)-ethyl]-2-pyrazolin-5-one or a pharmaceutically acceptable salt.

Method for treating human tumor cell metastasis

Novel nitrone substituted 4-aryl dihydropyridines of the formula: ##STR1## are described along with a process for their preparation. The compounds exhibit calcium channel blocker and antimetastatic acitivity.

4-(nitrone aryl) dihydropyridines

The use of calcium channel blocker compounds as antitumor and antimetastatic agents in mammals in vivo and in standard laboratory experimets with tumor cells in vitro is described. In particular the use of nimodipine (Bay e 9736) or nifedipine (Bay a 1040) and structurally related compounds as described.

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Grosse Pointe Woods, MI, United States of America

Kenneth V Honn