METHODS AND COMPOSITIONS TO DETECT THE LEVEL OF LYSOSOMAL EXOCYTOSIS ACTIVITY AND METHODS OF USE

摘要

Methods are provided for the prognosis, diagnosis and treatment of various pathological states, including cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. The methods provided herein are based on the discovery that various proteins with a high level of sialylation are shown herein to be associated with disease states, such as, cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. Such methods provide a lysosomal exocytosis activity profile comprising one or more values representing lysosomal exocytosis activity. Also provided herein, is the discovery that low lysosomal sialidase activity is associated with various pathological states. Thus, the methods also provide a lysosomal sialidase activity profile, comprising one or more values representing lysosomal sialidase activity. A lysosomal sialidase activity profile is one example of a lysosomal exocytosis activity profile. As such, the level of lysosomal exocytosis activity and/or lysosomal sialidase activity is predictive of a diagnosis and/or prognosis of cancer, chemotherapy resistance or dementia associated with Alzheimer's disease.

主权项

1. A method of determining the prognosis for a subject with cancer, comprising the steps of
a) providing a subject profile comprising a lysosomal sialidase activity profile comprising two or more values from different lysosomal sialidase activity markers, a NEU1 substrate sialylation activity profile or a NEU1 level activity profile from a tumor sample from said subject; b) providing a corresponding reference profile comprising a lysosomal sialidase activity profile comprising two or more values from different lysosomal sialidase activity markers, a NEU1 substrate sialylation activity profile or a NEU1 level activity profile from a control sample, wherein the subject profile and the reference profile comprise one or more values representing lysosomal sialidase activity, NEU1 substrate sialylation activity or NEU1 level activity; and c) comparing said subject and said reference lysosomal sialidase activity profiles to thereby determine the prognosis for said subject with cancer, wherein a lower lysosomal sialidase activity, a higher NEU1 substrate sialylation activity or a higher NEU1 level activity of said subject as compared to the lysosomal sialidase activity, NEU1 substrate sialylation activity or NEU1 level activity of said reference results in a prediction of an invasive cancer for said subject.