Method of diagnosing neoplastic conditions

Abstract

The present invention relates generally to a method for detecting an aberrant cell, and more particularly an apoptotic cell, in a subject or in a biological sample from said subject, and agents useful for same. The presence of the aberrant cell or group of aberrant cells provides an indication of a particular disease or condition or a propensity for development of a disease or condition. More particularly, the present invention contemplates a method for detecting an apoptotic cell by detecting the presence of extranuclear nuclear molecules, in particular La, or a relative increase in extranuclear nuclear molecule levels. The present invention further provides a method for diagnosing or monitoring conditions characterised by aberrant, unwanted or otherwise inappropriate cellular apoptosis in a subject or in a biological sample from said subject by screening for up-regulation of extranuclear nuclear molecule levels in a cell or group of cells. The present invention provides diagnostic agents useful for detecting these molecules. Such diagnostic agents include immunointeractive molecules, such as antibodies.

1 . A method for diagnosing or monitoring a condition characterised by aberrant, unwanted or otherwise inappropriate cellular apoptosis in a subject, said method comprising contacting cells or cell extracts from said subject or a biological sample from said subject with a nuclear molecule-binding effective amount of an interactive molecule directed to said nuclear molecule or an antigenic determinant or epitope thereof and then quantitatively or qualitatively detecting nuclear molecule-immunointeractive molecule complex formation wherein the non-nuclear localisation of said complex is indicative of cellular apoptosis. 
     
     
         2 . The method according to  claim 1 , wherein said nuclear molecule is Ro52, Ro60, La-SS/B, gelsolin, α-fodrin, fibrillarin, U1 small nuclear ribonuclear protein (U1 snRNP), heteronuclear ribonucleoproteins (hnRNP), lamin B, Poly(ADP-Ribose) Polymerase (PARP), Proliferating Cell Nuclear Antigen (PCNA), SC-35 splicing factor, Smith (Sm) antigen. 
     
     
         3 . The method according to  claim 2 , wherein said nuclear molecule is La. 
     
     
         4 . The method according to  claim 1 , wherein said non-nuclear localisation is cytoplasmic or associated with apoptotic bodies. 
     
     
         5 . The method according to  claim 2 , wherein said interactive molecule is a immunointeractive molecule. 
     
     
         6 . The method according to  claim 5 , wherein said immunointeractive molecule is an antibody. 
     
     
         7 . The method according to  claim 6 , wherein said antibody is a monoclonal antibody. 
     
     
         8 . The method according to  claim 1 , wherein said apoptotic cell is an apoptotic cardiac cell, neural cell or lymphoid cell. 
     
     
         9 . The method according to  claim 1 , wherein said condition is infarction of cardiac muscle or brain tissue. autoimmune and other inflammatory diseases, viral diseases such as AIDS, neurogenerative diseases such as Alzheimer's disease or Parkinson's disease, acute solid organ or bone marrow transplant rejection, chemotherapy- or radiation-induced tissue damage (‘mucositis’) or neoplasms such as tumours. 
     
     
         10 . The method according to  claim 9 , wherein said condition is a central nervous system tumours, retinoblastoma, neuroblastoma or other paediatric tumours, head and neck cancers, breast and prostrate cancers, lung cancer, kidney cancers, oesophagogastric cancers, hepatocellular carcinoma, pancreaticobiliary neoplasias, colorectal cancer, cervical and anal cancers, uterine and other reproductive tract cancers, urinary tract cancers, germ cell tumours, ovarian cancer, carcinomas of unknown primary, human immunodeficiency associated malignancies, lymphomas, leukemias, malignant melanomas, sarcomas, endocrine tumours, mesothelioma and other pleural tumours, neuroendocrine tumours and carcinoid tumours. 
     
     
         11 . The method according to  claim 10 , wherein said head and neck cancer is a squamous cell cancer, said lung cancer is a small or non-small lung cell cancer, said kidney cancer is a renal cell adenocarcinoma, said pancreatic reoplasma is an adenocarinoma islet cell tumour, said germ cell tumour is testicular cancer or ovarian cancer, and said ovarian cancer is an ovarian epithelial cancer, said human immunodeficiency associated malignancies is kaposis sarcoma and said endocrine tumour is a tumour of the thyroid gland.