The Penn State Research Foundation

Isis Pharmaceuticals, Inc.

Research, Incorporated

Other

Novartis Ag

Siemens Healthcare Diagnostics Gmbh

Allan Lipton

Lois Mary Witters

C Frank Bennett

Walter P Carney

Jonathan Green

Peter J Hamer

Nancy Kepner

Suhail M Ali

Thomas J Jennings

Kim Leitzel

The present invention describes clinically and medically important methods of monitoring the outcome of a cancer patient who is suffering from disease or who is undergoing treatment or therapy for his or her disease. More specifically, the invention provides a method of monitoring the progression of disease or cancer treatment effectiveness in a cancer patient by measuring the level of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR) in a sample taken from the cancer patient, preferably, before treatment, at the start of treatment, and at various time intervals during treatment, wherein a decrease in the level of the ECD of the EGFR in the cancer patient compared with the level of the ECD of the EGFR in normal control individuals serves as an indicator of cancer advancement or progression and/or a lack of treatment effectiveness for the patient. As another aspect of determining disease outcome and survival, the invention further provides assessing both EGFR and HER-2/neu levels, in combination, in a patient sample. A finding of decreased levels of EGFR concomitantly with elevated or increased levels of HER-2/neu relative to control levels indicates poor outcome and short time to progression.

Assays for cancer patient monitoring based on levels of epidermal growth factor receptor (EGFR) extracellular domain (ECD) analyte, alone or in combination with other analytes, in body fluid samples

A pharmaceutical composition for treatment of malignancies, in particular a malignant disease which is associated with the development of bone metastases or excessive bone resorption, comprises in combination a bisphosphonates, COX-2 inhibitor and/or a taxol or derivative thereof for simultaneous, sequential or separate use. Also provided is a method of treating a patient suffering from a malignant disease comprising administering to the patient an effective amount of a bisphosphonates, an effective amount of a COX-2 inhibitor and/or and effective amount of a taxol or derivative thereof.

Pharmaceutical composition for use for the treatment of malignancies comprising in combination a bisphosphonates, a cox-2 inhibitor and a taxol

Compounds, compositions and methods are provided for inhibiting the expression of human EGFR. The compositions comprise oligonucleotides complementary to mRNA targeted to nucleic acids encoding EGFR. Methods of using these oligonucleotides for inhibition of EGFR expression and for treatment of diseases such as cancers associated with overexpression of EGFR are provided.

Oligonucleotide inhibition of epidermal growth factor receptor expression

Compounds, compositions and methods are provided for inhibiting the expression of human HER-2 (also known as c-neu, ErbB-2 and HER-2/neu). The compositions comprise antisense oligonucleoptides targeted to nucleic acids encoding HER-2. Methods of using these oligonucleotides for inhibition of HER-2 expression and for treatment of diseases such as cancers associated with overexpression of HER-2 are provided. Methods of inhibiting other growth factor receptors using antisense oligonucleotides targeted to nucleic acids encoding HER-2 are also provided.

Antisense oligonucleotide modulation of human HER-2 expression

A proteinaceous factor substantially purified from mammalian spinal cord which has mitogenic activity, a molecular weight of about 11,000, a pI of 9.6 and which is heat and acid labile, is useful for the promotion of growth of cells.

Mitogenic spinal cord growth factor

A purified cell growth factor is produced which comprises a substantially purified glycoproteinaceous factor from platelets which has mitogenic activity toward transformed cells, a molecular weight of 3,000-5,000 daltons and a pI of 7.8-8.3. The growth factor is stable to treatment with 4M guanidine hydrochloride, and is heat labile when treated at 100.degree. C. for 5 minutes.

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Hershey, PA, United States of America

Allan Lipton