Washington University

Duke University

Other

Steven R Patierno

Michael J Manyak

Daniel George

Jennifer Freedman

Bruce A Sullenger

Brendon Patierno

Bi-Dar Wang

Norman Lee

Bonnie Lacroix

Timothy Robinson

Qingyi Wei

Yanru Wang

Hongliang Liu

The present disclosure provides methods and compositions for the treatment of cancer. In some aspects, the present disclosure provides splice-switching oligonucleotides that downregulate AR expression and methods of using these splice-switching oligonucleotides to treat cancer, specifically castrate resistant prostate cancer.

Splice-switching oligonucleotides and methods of use

The present disclosure provides methods and compositions for the treatment of cancer. In some aspects, the present disclosure provides splice-switching oligonucleotides that downregulate AR or EGFR expression and methods of using these splice-switching oligonucleotides to treat cancer.

The present disclosure provides biomarkers for the identification of prostate cancer and methods of use. The present disclosure also provide biomarkers that can be used for determining risk of developing prostate cancer, aggressiveness of prostate cancer and survival rate for subpopulations of African American males or non-Hispanic white males.

Biomarkers for the identification of prostate cancer and methods of use

Disclosed are novel splicing variants of the genes associated with prostate cancer risk and survival, particularly splicing variants of PIK3CD, FGFR3, TSC2, RASGRP2, ITGA4, MET, NF1 and BAK1. The disclosure also relates risk assessment, detection, diagnosis, or prognosis of prostate cancer. More specifically, this disclosure relates to the detection of certain splicing variants of PIK3CD, FGFR3, TSC2, RASGRP2, ITGA4, MET, NF1 and BAK1.

Alternative splicing variants of genes associated with prostate cancer risk and survival

The present invention relates to pharmaceutical compositions, methods and kits that provide for the early diagnosis and treatment of lung cancer. More particularly, the present invention relates to pharmaceutical compositions containing uteroglobin for preventing or inhibiting metastasis of lung tumor cells and methods of using the same to prevent or inhibit metastasis of lung tumor cells. The present invention also relates to methods and kits for early diagnosis of metastatic lung cancer by assaying for uteroglobin and comparing the results against control cells. The present invention also relates to methods and kits for detection of metastatic lung cancer by assaying for the presence of an aberrant form of uteroglobin.

Pharmaceutical compositions, methods, and kits for treatment and diagnosis of lung cancer

The present invention provides a novel method for inhibiting the growth of tumor cells of epithelial origin, comprising administration of a functional uteroglobin gene in a gene therapy regime, so as to inhibit growth of the tumor cells.

Uteroglobin gene therapy for epithelial cell cancer

The invention relates to methods for determining degree of integrin-mediated maintenance of cell invasive capacity of tumors, and to methods and compositions for inhibiting or preventing metastasis of cancers. In one aspect, the invention provides a method to determine degree of integrin-mediated maintenance of cell invasive capacity of epithelial derived tumors, particularly prostatic, breast, and lung cancers. In these regards, the invention relates to determining protein or mRNA of effectors of integrin-mediated maintenance of cell invasive capacity, particularly uteroglobin protein or mRNA, or to gauge degree of integrin-mediated maintenance of cell invasive capacity of prostatic, breast, or lung tumors. The invention also relates to methods and compositions, such as uteroglobin, which specifically bind to integrin and are effectors of integrin-mediated maintenance of tumor cell invasive capacity and thus inhibit metastasis.

Methods for inhibiting metastasis

The invention relates to methods for identifying prostatic intraepithelial neoplasia, methods for determining metastatic potential of tumors, and to methods and compositions for inhibiting or preventing metastasis of cancers. In one aspect, the invention provides a method to determine metastatic potential of tumors, particularly prostatic tumors. In another aspect, the invention provides a method of identifying prostate cancer associated conditions, particularly prostatic intraepithelial neoplasia. In these regards, the invention relates to determining protein or mRNA of effectors of arachidonic acid release, particularly uteroglobin protein or mRNA, to identify intermediate conditions such as PIN or to gauge metastatic potential of prostatic tumors. The invention also relates to methods and compositions that prevent or inhibit metastasis of cancers. In this regard, the invention particularly relates to methods and compositions that inhibit arachidonic acid, those that inhibit phospholipase A . More particularly in this regard, the invention relates to uteroglobin or muteins, peptide analogs or mimetics of uteroglobin and lipocortins or muteins, peptide analogs, or mimetics of lipocortins that inhibit metastasis. Especially it relates to methods and compositions in which uteroglobins, particularly human uteroglobins, inhibit or prevent metastasis of cancer, particularly prostatic cancer.

Non-steroidal anti-inflammatory agent therapy for epithelial cell cancer

Uteroglobin therapy for epithelial cell cancer

The present invention relates to pharmaceutical compositions, methods and kits that provide for the early diagnosis and treatment of breast cancer. More particularly, the present invention relates to pharmaceutical compositions containing uteroglobin for preventing or inhibiting metastasis of breast tumor cells and methods of using the same to prevent or inhibit metastasis of breast tumor cells. The present invention also relates to methods and kits for early diagnosis of metastatic breast cancer by assaying for uteroglobin and comparing the results against control cells. The present invention also relates to methods and kits for detection of metastatic breast cancer by assaying for the presence of an aberrant form of uteroglobin.

Pharmaceutical compositions methods and kits for treatment and diagnosis of breast cancer

The invention relates to methods for identifying prostatic intraepithelial neoplasia, methods for determining metastatic potential of tumors, and to methods and compositions for inhibiting or preventing metastasis of cancers. In one aspect, the invention provides a method to determine metastatic potential of tumors, particularly prostatic tumors. In another aspect, the invention provides a method of identifying prostate cancer associated conditions, particularly prostatic intraepithelial neoplasia. In these regards, the invention relates to determining protein or mRNA of effectors of arachidonic acid release, particularly uteroglobin protein or mRNA, to identify intermediate conditions such as PIN or to gauge metastatic potential of prostatic tumors. The invention also relates to methods and compositions that prevent or inhibit metastasis of cancers. In this regard, the invention particularly relates to methods and compositions that inhibit arachidonic acid, those that inhibit phospholipase A.sub.2. More particularly in this regard, the invention relates to uteroglobin or muteins, peptide analogs or mimetics of uteroglobin and lipocortins or muteins, peptide analogs, or mimetics of lipocortins that inhibit metastasis. Especially it relates to methods and compositions in which uteroglobins, particularly human uteroglobins, inhibit or prevent metastasis of cancer, particularly prostatic cancer.

Kit for indentifying prostatic intraepithelial neoplasia (PIN)

The invention relates to methods for identifying prostatic intraepithelial neoplasia by determining the uteroglobin concentration in a tissue sample.

Use of uteroglobin expression as a molecular marker for prostatic

The invention relates to methods for determining metastatic potential of tumors and to methods and compositions for inhibiting or preventing metastasis of cancers. In one aspect, the invention provides a method to determine metastatic potential of tumors, particularly prostatic tumors. In this regard the invention relates to determining protein or mRNA of effectors of arachadonic acid release to gauge metastatic potential, particularly uteroglobin protein or mRNA to determine metastatic potential of prostatic tumors. The invention also relates to methods and compositions that prevent or inhibit metastasis of cancers. In this regard, the invention particularly relates to methods and compositions that inhibit arachidonic acid, those that inhibit phospholipase A.sub.2. More particularly in this regard, the invention relates to uteroglobin or muteins, peptide analogs or mimetics of uteroglobin and lipocortins or muteins, peptide analogs, or mimetics of lipocortins that inhibit metastasis. Especially it relates to methods and compositions in which uteroglobins, particularly human uteroglobins, inhibit or prevent metastasis of cancer, particularly prostatic cancer.

Determining invasiveness of prostatic adenocarcinoma

The present invention relates to methods and compositions that prevent or inhibit metastases of cancers of epithelial cell origin, especially human prostate cancers. A particular aspect of the invention relates to methods and compositions that inhibit arachidonic acid release in cells of these cancers and inhibit or prevent metastasis. In one aspect in this regard, the invention particularly relates to methods and compositions that inhibit phospholipase A.sub.2 that mediates arachidonic acid release in the cancer cells. In a further aspect, the invention relates to methods and compositions wherein uteroglobin, uteroglobin muteins, peptide analogs of uteroglobins, lipocortins, lipocortin muteins and peptide analogs of lipocortins inhibit arachidonic acid release by cancer cells. In this regard, the invention relates especially to uteroglobins, particularly human uteroglobins.

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Falls Church, VA, United States of America

Steven R Patierno