Aftab Ahmad ANJUM, Muhammad AZEEM, Muti-ur-Rehman KHAN, Gulbeena SALEEM, Waqas AHMAD, Ubaid-ur-Rehman ZIA, Fahad AKRAM

Assessment of tumor-induced pain and C-reactive protein levels in dogs with canine transmissible venereal tumors

The aim of this study was to determine the impact of tumor volume on generalized behavior, pain perception, and serumC-reactive protein (CRP) in dogs with canine transmissible venereal tumors (CTVTs). Pain scoring was performed using theGlasgow Composite Measure Pain Scale Short-Form. Cytomorphology of the tumors was studied through fine-needle aspiration andhistopathology. Molecular identification of CTVTs was carried out using PCR assays based on LINE-1/c-myc. Hematological profilesincluding complete blood count and CRP were analyzed using an automatic hematology analyzer and immunoturbidimetric assays,respectively. Chi-square and regression analysis statistics were used for data analysis. Results of the study revealed a statisticallysignificant (R2 = 0.798) impact of tumor volume on pain scores in corresponding individuals. Hematological parameters and serumCRP values were observed in normal ranges and did not reveal any significant association with tumor volume. All of the samples werefound positive for LINE-1/c-myc molecular rearrangement, revealing a 552-bp PCR product. On the basis of cytology tumors weredifferentiated into plasmacytoid, lymphocytoid, and mixed types. No significant association could be observed among cytological typesand sex of the individuals. It may be concluded that increasing tumor size may result in localized pain and mild behavioral alterations inaffected dogs. However, hematology profiles and serum CRP levels are independent of the localized tumor proliferation.

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1. Setthawongsin C, Techangamsuwan S, Tangkawattana S, Rungsipipat A. Cell-based polymerase chain reaction for canine transmissible venereal tumor (CTVT) diagnosis. J Vet Med Sci 2016; 78: 1167-1173.
2. Pye RJ, Pemberton D, Tovar C, Tubio JM, Dun KA, Fox S, Darby J, Hayes D, Knowles GW, Kreiss A. A second transmissible cancer in Tasmanian devils. P Natl Acad Sci USA 2016; 113: 374-379.
3. Ganguly B, Das U, Das AK. Canine transmissible venereal tumour: a review. Veterinary comp oncol 2016; 14: 1-12.
4. Das U, Das AK. Review of canine transmissible venereal sarcoma. Vet Res Comm 2000; 24: 545-556.
5. Javanbakht J, Pedram B, Taheriyan M, Khadivar F, Hosseini S, Abdi F, Hosseini E, Moloudizargari M, Aghajanshakeri SH, Javaherypour S. Canine transmissible venereal tumor and seminoma: a cytohistopathology and chemotherapy study of tumors in the growth phase and during regression after chemotherapy. Tumor Biol 2014; 35: 5493-5500.
6. Chun JM, Kwon HJ, Sohn J, Kim SG, Park JY, Bae HI, Yun YK, Hwang YJ. Prognostic factors after early recurrence in patients who underwent curative resection for hepatocellular carcinoma. J Surg Oncol 2011; 103: 148-151.
7. Gakis G, Todenhöfer T, Renninger M, Schilling D, Sievert KD, Schwentner C, Stenzl A. Development of a new outcome prediction model in carcinoma invading the bladder based on preoperative serum C‐reactive protein and standard pathological risk factors: the TNR‐C score. BJU Int 2011; 108: 1800-1805.
8. Nozoe T, Saeki H, Sugimachi K. Significance of preoperative elevation of serum C-reactive protein as an indicator of prognosis in esophageal carcinoma. Am J Surg 2001; 182: 197- 201.
9. McMillan D, Canna K, McArdle C. Systemic inflammatory response predicts survival following curative resection of colorectal cancer. Br J Surg 2003; 90: 215-219.
10. Ueno H, Okada S, Okusaka T, Ikeda M. Prognostic factors in patients with metastatic pancreatic adenocarcinoma receiving systemic chemotherapy. Oncology 2000; 59: 296-301.
11. Scott H, McMillan D, Forrest L, Brown D, McArdle C, Milroy R. The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer. Br J Cancer 2002; 87: 264-267.
12. Pierce BL, Ballard-Barbash R, Bernstein L, Baumgartner RN, Neuhouser ML, Wener MH, Baumgartner KB, Gilliland FD, Sorensen BE, McTiernan A. Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol 2009; 27: 3437-3444.
13. Prins RC, Rademacher BL, Mongoue-Tchokote S, Alumkal JJ, Graff JN, Eilers KM, Beer TM. C-reactive protein as an adverse prognostic marker for men with castration-resistant prostate cancer (CRPC): confirmatory results. Urol Oncol 2012; 30: 33- 37.
14. Reid J, Nolan A, Hughes J, Lascelles D, Pawson P, Scott E. Development of the short-form Glasgow Composite Measure Pain Scale (CMPS-SF) and derivation of an analgesic intervention score. Anim Welfare 2007; 16 (Suppl. 1): 97-104.
15. Awan F, Ali M, Ijaz M, Khan S. Comparison of different therapeutic protocols in the management of canine transmissible venereal tumour: review of 30 cases. Glob Vet 2014; 12: 499-503.
16 Thrall MA, Weiser G, Allison R, Campbell TW. Veterinary Hematology and Clinical Chemistry. New York, NY, USA: John Wiley & Sons; 2012.
17. Chiang HC, Liao ATC, Jan TR, Wang YS, Lei HJ, Tsai MH, Chen MF, Lee CY, Lin YC, Chu RM et al. Gene-expression profiling to identify genes related to spontaneous tumor regression in a canine cancer model. Vet Immunol Immunop 2013; 151: 207-216.
18. Latimer KS. Duncan and Prasse’s Veterinary Laboratory Medicine: Clinical Pathology. New York, NY, USA: John Wiley & Sons; 2011.
19. Hellyer P, Rodan I, Brunt J, Downing R, Hagedorn JE, Robertson SA. AAHA/AAFP pain management guidelines for dogs and cats. J Feline Med Surg 2007; 9: 466-480.
20. Bancroft JD, Gamble M. Theory and Practice of Histological Techniques. New York, NY, USA: Elsevier Health Sciences; 2008.
21. Liao KW, Lin ZY, Pao HN, Kam SY, Wang FI, Chu RM. Identification of canine transmissible venereal tumor cells using in situ polymerase chain reaction and the stable sequence of the long interspersed nuclear element. J Vet Diagn Invest 2003; 15: 399-406.
22. GraphPad Software, Inc. Prism G Version 7.0 a for Mac OS X. La Jolla, CA, USA: GraphPad; 2016.
23. Araujo DCC, Antonioli T, Costa TS, de Carvalho JRG, Laguna AGV, Ramadinha RHR, Fernandes JI. Occurrence and location of transmissible venereal tumors in dogs seen at the Universidade Federal Rural do Rio de Janeiro Veterinary Hospital: Oncology Sector between 2010 and 2014. Braz J Vet Med 2017; 38: 277-280.
24. Ulcar I, Celeska I, Ilievska K, Atanaskova E, Nikolovski G, Trojacanec P. Cytological diagnostic of canine transmissible venereal tumor-case report. Mac Vet Rev 2012; 35: 91-96.
25. Murchison E. Clonally transmissible cancers in dogs and Tasmanian devils. Oncogene 2008; 27: S19-S30.
26. Rasmussen LJH, Schultz M, Gaardsting A, Ladelund S, Garred P, Iversen K, Eugen‐Olsen J, Helms M, David KP, Kjær A et al. Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer. Int J Cancer 2017; 141: 191-199.
27. Infante M, Allavena P, Garlanda C, Nebuloni M, Morenghi E, Rahal D, Roncalli M, Cavuto S, Pesce S, Monari M. Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients. Int J Cancer 2016; 138: 983-991.
28. Storm L, Christensen IJ, Jensenius JC, Nielsen HJ, Thiel S. Evaluation of complement proteins as screening markers for colorectal cancer. Cancer Immunol Immunother 2015; 64: 41- 50.
29. Andreasen EB, Nielsen OL, Tranholm M, Knudsen T, Kristensen AT. Expression of tissue factor in canine mammary tumours and correlation with grade, stage and markers of haemostasis and inflammation. Vet Comp Oncol 2016; 14: 191-201.
30. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012; 489: 519-525.
31. Craig SM, Fry JK, Rodrigues Hoffmann A, Manino P, Heilmann RM, Suchodolski JS, Steiner JM, Hottinger HA, Hunter SL, Lidbury JA. Serum C-reactive protein and S100A12 concentrations in dogs with hepatic disease. J Small Anim Pract 2016; 57: 459-464.
32. Hillström A, Hagman R, Tvedten H, Kjelgaard‐Hansen M. Validation of a commercially available automated canine‐ specific immunoturbidimetric method for measuring canine C‐reactive protein. Vet Clin Pathol 2014; 43: 235-243.
33. Fang HY, Huang XY, Chien HT, Chang JTC, Liao CT, Huang JJ, Wei FC, Wang HM, Chen IH, Kang CJ. Refining the role of preoperative C‐reactive protein by neutrophil/lymphocyte ratio in oral cavity squamous cell carcinoma. Laryngoscope 2013; 123: 2690-2699.