Methods and assays for determining the activation level of the plasma kallikrein (pKal) system and the uses thereof for assessing the activity of pKal modulators on the pKal system.

The present teachings are generally directed to sensors that employ antibody- and/or aptamer-functionalized graphene layer (or graphene flakes and/or graphdiyne layer) for detecting a prostate-specific biomarker in a sample. A graphene layer can be deposited on a underlying substrate and functionalized with an antibody and/or aptamer that specifically binds with an analyte of interest (e.g., a prostate-specific biomarker). A sample under investigation can be introduced onto the functionalized graphene layer. The interaction of the analyte of interest, if present in the sample, with the functionalized graphene layer can mediate a change in at least one electrical property of the graphene layer, e.g., their DC electrical resistance. An analyzer can detect such a change and analyze it to determine whether the analyte is present in the sample. In some embodiments, calibration methods can be employed to quantify the analyte present in the sample.

The present disclosure provides methods of evaluating a subject, e.g., a subject at risk for or suffering from a pKal-mediated or bradykinin-mediated disorder, based on values (e.g., percentages) of intact and/or cleaved kininogen in a sample of the subject. Provided methods permit analysis of patients with plasma kallikrein-mediated angioedema (KMA), or other diseases mediated by pKal useful in the evaluation and treatment. Such methods can involve the use of a detection agent that preferentially binds cleaved kininogen or intact kininogen.

Described here are techniques for identifying risk of primary graft dysfunction (PGD) of a subject. The disclosed method can include collecting serum of the subject, measuring a level of a PGD marker from the serum, wherein the PGD marker comprises plasma kallikrein (KLKB1), providing a PGD risk value that is quantified based on the level of the PGD marker using an adaptive Monte Carlo cross-validation (MCCV) model, and identifying the risk of PGD based on the PGD risk value.

Methods for detecting a prostate cancer in a subject comprise detecting a marker selected from an endosomal associated marker and/or a lysosomal associated marker from the subject.

The present application provides an agent comprising or consisting of a binding moiety with specificity for a kallikrein protein (for example, PSA or hK2) for use in the treatment of prostate cancer, and a method for the treatment of prostate cancer in a patient, the method comprising the step of administering a therapeutically effective amount of an agent comprising or consisting of a binding moiety with specificity for a kallikrein protein to the patient.

Aspects of the disclosure relate to improved methods for predicting whether a prostate tissue biopsy obtained from a subject will contain detectable prostate cancer.

[Problem] To provide a method for detecting high-risk prostate cancer, for the purpose of providing useful information, such as necessity of biopsy, to a test-positive patient in a PSA test. [Solution] The method for detecting high-risk prostate cancer according to the present invention comprises reacting a PSA contained in a sample composed of urine collected from a human body which is suspected to be suffering from prostate cancer with (1) a fucose α1.fwdarw.6 affinitive lectin which has a characteristic property that the lectin has affinity expressed by a binding constant of 1.0×10.sup.4 M.sup.−1 or more (at 25° C.) for an α1.fwdarw.6 fucose sugar chain No. 405. The fucose α1.fwdarw.6 affinitive lectin is preferably (2) a fucose α1.fwdarw.6 specific lectin which has a characteristic property that the lectin has a binding constant of 1.0×10.sup.4 M.sup.−1 or less (at 25° C.) for a sugar chain No. 003 that does not contain α1.fwdarw.6 fucose and a glycolipid-type sugar chain No. 909 that does not contain α1.fwdarw.6 fucose.

This invention relates to therapeutic compounds which are inhibitors of serine proteases, to pharmaceutical compositions thereof and to their use in the treatment of the human or animal body. More specifically, the present invention relates to a method for the treatment, diagnosis or prognosis of skin diseases comprising the administration to a subject in need thereof of a therapeutically effective amount of a Serine protease inhibitor.

The present disclosure provides a biosensor having improved sensitivity. The present disclosure also provides a base material for manufacturing a sensor for analyzing a detection object, said base material comprising a molecularly imprinted polymer having: a molecularly imprinted recess in which a target of the detection object is received; and a group for binding a specific bondable molecule to the target, said group being provided inside the molecularly imprinted recess. The base material is characterized in that the group for binding the specific bondable molecule is a group suited for a small substance, and/or is characterized in that the molecularly imprinted recess has a shape or structure suited for a small substance.