The invention relates to systems and methods for the diagnosis, amelioration, and treatment of ischemic tissues in patients caused by and/or resulting from diminished microvascular blood flow. Patients suffering from ischemic tissue conditions can be categorized into specific subsets that are deemed to have a potential to respond to therapy. In particular, the invention includes various therapies involving stimulation of angiogenesis, vasculogenesis, arteriogenesis and/or neovascularization so as to increase perfusion of various tissues.

Methods are provided for treating a subject with prostate cancer and/or diagnosing a subject at risk for prostate cancer, which can include measuring increased expression of at least two prostate cancer-related molecules in a sample obtained from a subject, including the prostate cancer-related molecules AGR2, AGR3, CRISP3, CCL3, CEACAM5, CEACAM6, IL24, MMP9, CXCL14, CD90, POSTN, and SFRP4. The methods can include administering at therapy to a subject with prostate cancer. Methods are provided for treating a subject with intermediate- or high-risk prostate cancer, which can include measuring increased expression of MMP9 in a sample obtained from a subject compared to a control representing expression of MMP9 expected in a sample from a subject who has low-risk prostate cancer.

The invention relates to systems and methods for the diagnosis, amelioration, and treatment of ischemic tissues in patients caused by and/or resulting from diminished microvascular blood flow. Patients suffering from ischemic tissue conditions can be categorized into specific subsets that are deemed to have a potential to respond to therapy. In particular, the invention includes various therapies involving stimulation of angiogenesis, vasculogenesis, arteriogenesis and/or neovascularization so as to increase perfusion of various tissues.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more of Metalloproteinase inhibitor 1, Metalloproteinase inhibitor 2, Metalloproteinase inhibitor 4, CC motif chemokine 15, CC motif chemokine 18, CC motif chemokine 23, and/or, CC motif chemokine 24 as diagnostic and prognostic biomarker assays in renal injuries.

Described herein are method(s), kit(s), reagent(s) and the like for determining von Willebrand factor (VWF) activity in a sample in the absence of ristocetin.

Methods and compositions are provided for assessing (e.g., diagnosing), treating, and preventing diseases, especially cancer, and particular lung cancer, using lung cancer markers (LCM). Individual LCM and panels comprising multiple LCM are provided for these and other uses. Methods and compositions are also provided for determining or predicting the effectiveness of a treatment or for selecting a treatment using LCM. Methods and compositions are further provided for modulating cell function using LCM. Also provided are compositions that modulate LCM (e.g., antagonists or agonists), such as antibodies, proteins, small molecule compounds, and nucleic acid agents (e.g., RNAi and antisense agents), as well as pharmaceutical compositions thereof. Further provided are methods of screening for agents that modulate LCM, and agents identified by these screening methods.

The transmembrane metalloproteinase-disintegrin ADAM8 mediates cell adhesion and shedding of ligands, receptors, and extracellular matrix components. ADAM8 is abundantly expressed in breast tumors and derived metastases compared to normal tissue, especially in triple-negative breast cancers (TNBCs). High ADAM8 levels predicted poor patient outcome, and ADAM8 promoted an aggressive phenotype of TNBC cells in culture. Tumors derived from TNBC cells with ADAM8 knockdown failed to grow beyond a palpable size and displayed poor vascularization. Circulating tumor cells and brain metastases were also significantly reduced. ADAM8 stimulated angiogenesis through release of VEGF-A and cell migration through 1-integrin activation. Treatment with anti-ADAM8 antibody in vivo resulted in reduced primary tumor burden and reduced metastases. Furthermore, antibody treatment of established tumors profoundly decreased metastases in a resection model. ADAM8 represents a promising novel target for treatment of TNBCs, which currently lack targeted therapies and frequently progress with fatal dissemination.

A four-biomarker panel for diagnosis of chronic graft-versus-host disease (cGVHD) and methods of prognosing and/or diagnosing cGVHD using the biomarker panel are disclosed.

Methods and kits for diagnosing the presence of and prognosing the appearance of tissue remodelling-associated conditions, involving the presence of enzyme complexes in a biological sample, are disclosed. In particular, the method pertains to diagnosing the presence of or prognosing appearance of metastatic cancer by the identification of high molecular weight enzyme complexes comprising MMPs.

In a first aspect, there is provided an isolated polypeptide substrate for a disintegrin-like and metallopeptidase with thrombospondin type-1 motif, 13 (ADAMTS13) that is from 45 to 70 amino acids in length and has an amino acid sequence that is substantially similar to part of the von Willebrand factor A2 domain sequence set forth in SEQ ID NO: 2, with one or more of the following modifications: (i) the amino acid corresponding to position 1599 of SEQ ID NO: 2 is mutated from Q to K; (ii) the amino acid corresponding to position 1610 of SEQ ID NO: 2 is mutated from N to C; and (iii) the amino acids corresponding to Q1624 to R1641 of SEQ ID NO: 2 are deleted. In another aspect, there is provided an ADAMTS13 polypeptide substrate that is from 50 to 75 amino acids in length and has an amino acid sequence that is substantially similar to part of the von Willebrand factor A2 domain sequence set forth in SEQ ID NO: 2, with one or more of the following modifications: (i) the amino acid corresponding to position 1599 of SEQ ID NO: 2 is mutated from Q to K; (ii) the amino acid corresponding to position 1610 of SEQ ID NO: 2 is mutated from N to C; (iii) the amino acid corresponding to position 1629 of SEQ ID NO: 2 is mutated from G to E; and (iv) the amino acids corresponding to G1631 to R1641 of SEQ ID NO: 2 are deleted.