Specialty Services Guide | Page 7

Neoplasia Index The Neoplasia Index (NI) is a dual-biomarker algorithm that combines the dysregulated proliferation marker TK and the systemic inflammatory marker CRP (dogs) or Hpt (cats). TK is involved in the synthesis of DNA precursors and is only expressed in S-G2 cells (ie, cell division). TK levels have been shown in numerous studies, both in humans as well as animals, to correlate to the proliferative activity of tumor disease. Le ak ag e Tumor Cell Cytoplasm TK1 dT (TK2) ATP dTMP ADP Nucleus DNA-synthesis Others elevated APP Cancer elevated TK overlap elevated NI Trauma The Acute Phase Response CRP/Hpt are major acute phase proteins produced, mainly in the liver, in response to inflammation and the release of cytokines. Serum APP levels correlate to both the severity and duration of the inflammatory stimuli. Inflammation Infection INFLAMMATION Fibrinogen Liver Haptoglobin Serum amyloid protein C-reactive protein These two independent variables – thymidine kinase & acute phase proteins – combine two distinct hallmarks of neoplasia: rapid, dysregulated cell division & systemic inflammation. The algorithm developed to integrate the dual biomarkers, produces the resultant Neoplasia Index. NI is useful in a wide variety of cancers(1-9): • Lymphoma • Carcinoma • Sarcoma • Hemangiosarcoma • Histiocytic sarcoma • Osteosarcoma • Mast cell tumor (grade II and III) • Others 1. Nakamura N, Momoi Y, Watari T, Yoshino T, Tsujimoto H, Hasegawa A. Plasma thymidine kinase activity in dogs with lymphoma and leukemia. Journal Veterinary Medical Science. 1997, 59(10): 957-960 2. von Euler H, Einarsson R, Olsson U, Lagerstedt AS, Eriksson S. Serum thymidine kinase activity in dogs with malignant lymphoma: a potent marker for prognosis and monitoring the disease. Journal Veterinary Internal Medicine 2004, 18: 696-702 3. Madewell, BR. Editorial: Serum thymidine kinase activity: an alternative to histologic markers of cellular proliferation in canine lymphoma. Journal of Veterinary Internal Medicine, 2004, 18: 595–596. 4. von Euler HP, Ohrvik AB, Eriksson SK. A non-radiometric method for measuring serum thymidine kinase activity in malignant lymphoma in dogs. Research Veterinary Science 2006, 80: 17-24 5. von Euler HP, Rivera P, Aronsson AC, Bengtsson C, Hansson LO, Eriksson SK. Monitoring therapy in canine malignant lymphoma and leukemia with serum thymidine kinase 1 activity - evaluation of a new, fully automated non-radiometric assay", 2008. International Journal of Oncology. 2009, 34:505-510 6. Thamm DH, Kamstock DA, Sharp CR, Johnson SI, Mazzaferro E, Herold LV, Barnes SM, Winkler K, Selting KA. Elevated serum thymidine kinase activity in canine splenic hemangiosarcoma. Veterinary and Comparative Oncology. 2011, doi: 10.1111/j.1476-5829.2011.00298.x 7. Selting KA, Sharp CR, Ringold R, Kouse J. Serum thymidine kinase 1 and C-reactive protein as biomarkers for screening clinically healthy dogs for occult disease. Veterinary and Comparative Oncology. 2013, doi: 10.1111/vco.12052 8. Selting KA, Ringold, R. Use of thymidine kinase type 1 and C-reactive protein to detect cancer in dogs. Veterinary Cancer Society Abstract 2013. 9. Taylor SS, Dodkin S, Papasouliotis K, Evans H, Graham PA, Belshaw Z, Westberg S, von Euler HP. Serum thymidine kinase activity in clinically healthy and diseased cats: a potential biomarker for lymphoma. Journal of Feline Medicine and Surgery. 2013, doi: 10.1177/1098612X12463928 7