A method for monitoring fetal and/or preterm infant development and a method to promote normal growth & development of preterm infants, especially in regards to each preterm infant's collective set of immature organs. Monitoring development is accomplished by using VEGF 121 as a biomarker in bodily fluid levels, to determine whether appropriate angiogenic activity is occurring to allow preterm infant or fetal development to proceed normally. The promotion of preterm infant normal development is accomplished by administering to a preterm infant human chorionic gonadotropin (hCG) and/or Luteinizing hormone (LH) and/or Luteinizing hormone releasing hormone (LHRH) in physiological amounts at appropriate intervals to raise and maintain the activation level of the patient's combined hCG/LH receptor activity, or VEGF 121 level, to a level that is normally present in fetuses of the equivalent developmental (gestational) age. By promoting normal development, we prevent onset or progression of disorders associated with premature organs rather than treat disorders associated with the premature organs after they occur.

The present application is directed to the use of a VEGF-C inhibitor, a VEGFR-2 inhibitor and/or a VEGFR-3 inhibitor as a prophylactic or therapeutic for the treatment of eye disorders such as a maculopathy and pathogenic ocular neovascularization. The application is also directed to the use of a VEGF-C measurement from a biological sample from a mammalian subject as a predictive marker, a selected marker, a responsive marker or a tracking marker for a disease or condition selected from the group consisting of a maculopathy and pathogenic ocular neovascularization.

The invention includes, in part, methods and compounds for diagnosing diseases and conditions characterized by altered threonyl-tRNA synthetase (TARS) activity, which include, but are not limited to diseases and conditions in which angiogenesis is altered. In some embodiments of the invention, a level of a TARS molecule is determined and compared to a control level of TARS to assess onset, progression, and/or regression of a disease or condition associated with altered TARS activity.

Methods and compositions are provided for the identification of a molecular diagnostic test for cancer. The test identifies cancer subtypes that are responsive to anti-angiogenesis therapeutics and enables classification of a patient within this subtype. The present invention can be used to determine whether patients with cancer are clinically responsive or non-responsive to a therapeutic regimen prior to administration of any anti-angiogenic agent. This test may be used in different cancer types and with different drugs that directly or indirectly affect angiogenesis or angiogenesis signalling. In addition, the present invention may be used as a prognostic indicator for certain cancer types. In particular, the present invention is directed to the use of certain combinations of predictive markers, wherein the expression of the predictive markers correlates with responsiveness or non-responsiveness to a therapeutic regimen.

This present invention relates to compounds (e.g., TM4SF1 binding proteins, e.g., anti-TM4SF1 antibodies) that specifically bind to a polypeptide at an epitope including an amino acid sequence of SEQ ID NO: 1. In particular, the compounds of the invention are capable of being internalized into a TM4SF1-expressing cell (e.g., a tumor cell or an angiogenic vasculature endothelial cell) following binding to the epitope of including the amino acid sequence of SEQ ID NO: 1. The invention also provides methods of treating a subject having a disorder associated with pathological angiogenesis with the compounds of the invention.

The invention includes, in part, methods and compounds for treating diseases and conditions characterized by elevated threonyl-tRNA synthetase (TARS) activity, which include, but are not limited to diseases and conditions in which angiogenesis is elevated as compared to normal. In some embodiments of the invention, a level of a TARS molecule is determined and compared to a control level of TARS to assess a treatment for a disease or condition characterized by elevated TARS activity.

A method of assessing a possibility of cancerization including culturing a cell structure including normal cells and having a vascular network structure in a presence of a biological specimen from a subject, and assessing a possibility of cancerization in the subject based on a state of vessels in the cell structure after the culturing. The biological specimen is a body fluid specimen from the subject, a cell extract of cells from the subject, or a culture supernatant of cells from the subject, and the possibility of cancerization is assessed as high in the subject when a number of cells forming the vessels in the cell structure is larger than a number of cells cultured in an absence of the body fluid specimen, or when the vascular network structure in the cell structure extends.

Methods for detecting angiopoietin-2 (Angpt-2) and/or thrombospondin-2 (Tsp-2) in a sample involve obtaining or having obtained a blood or plasma sample from a subject; and detecting or Angpt-2 and Tsp-2 in the sample. Detecting can involve performing an assay to determine whether the sample includes Angpt-2 and/or Tsp-2 or elevated levels of Angpt-2 and/or Tsp-2. Elevated levels are indicative of acute heart failure.

The disclosure concerns a method for measuring and reporting vascularity in a biological tissue sample. The method generally includes: within a digital image of a tissue section, (i) identifying endothelial cells, lymphatic cells, or a combination thereof; (ii) mapping one or more proximity regions, each of the proximity regions defining an area between detected vessels and a first distance outwardly therefrom; and (iii) calculating one or more of: a vessel proximity score or a hypoxia score, wherein the vessel proximity score relates a composition of objects within the proximity regions, and wherein the hypoxia score relates a composition of tissue within or outside of the proximity regions, respectively.

The invention includes, in part, methods and compounds for diagnosing diseases and conditions characterized by altered threonyl-tRNA synthetase (TARS) activity, which include, but are not limited to diseases and conditions in which angiogenesis is altered. In some embodiments of the invention, a level of a TARS molecule is determined and compared to a control level of TARS to assess onset, progression, and/or regression of a disease or condition associated with altered TARS activity.