Abstract
Purpose: To investigate the effects of bevacizumab experimentally on adhesion formation and vascular endothelial growth factor (VEGF) expression in rats.
Materials and Methods: Rats were divided into three groups as sham, control and study groups, each group including 10 rats. In the sham group only laparotomy was performed. Post laparotomy, in both study and control groups, left lower parietal periton was abraded and serosal defects formed on caecum, ileum and right corn of uterus. Following peritoneal abrasions, we applied bevacizumab solution (1 mg/kg) to the study group intravenously, and the same volume of normal saline to the control group in the same manner. We performed relaparotomy to all groups on the 15th day to score and evaluate the adhesion formation. We also took samples from adhesion areas in all three groups for VEGF staining.
Results: Adhesion formation and VEGF staining was significantly higher in the control group than in sham and bevacizumab groups (p<0,05). Adhesion formation difference was not significant however between sham and bevacizumab groups (p=0.165).
Conclusion: Bevacizumab decreases the adhesion formation in experimentally adhesion formatted rats. There is a correlation between adhesion severity and VEGF expression.
Keywords:
Bevacizumab, VEGF expression, peritoneal adhesion, adhesion severity.
References
1Barbul A. Wound Healing. Brunicardi FC, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Pollock RE(eds), In Schwartz's Principles of Surgery 8 th. Ed. McGraw-Hill, Philadelphia 2005; pp. 223–248.
2Özçelik B, Serin S, Başbuğ M, et al. Effect of melatonin in the prevention of post-operative adhesion formation in a rat uterine horn adhesion model. Hum Reprod 2003; 18: 1703–1706.
3Müller SA, Treutner KH, Anurov M, et al. Experimental evaluation of phospholipids and icodextrin in re-formation of peritoneal adhesions. Br J Surg, 2003; 90: 1604–1607.
4Gerwins P, Skoldenberg E, Claesson-Welsh L. Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis. Crit Rev Oncol Hematol, 2000; 34: 185–194.
5Ferrara N, Gerber HP. The role of vascular endothelial growth factor in angiogenesis. Acta Haematol 2001; 10: 148–156.
6Bloch W, Huggel K, Sasaki T, et al. The angiogenesis inhibitor endostatin impairs blood vessel maturation during wound healing. FASEB J, 2000; 14: 2373–2376.
7Karayiannakis AJ, Syrigos KN, Polychronidis A, et al. Circulating VEGF levels in the serum of gastric cancer patients: correlation with pathological variables, patient survival, and tumor surgery. Ann Surg, 2002; 236: 37–42
8Nakasaki T, Wada H, Sh, Shigemori C, et al. Expression of tissue factor and VEGF is associated with angiogenesis in colorectal cancer. Am J Hematol, 2002; 69: 347–254.
9Kalofonos HP, Grivas PD. Monoclonal antibodies in the management of solid tumors. Curr Top Med Chem, 2006; 6: 1687–1705
10Laud K, Spaide RF, Freund KB, et al. Treatment of choroidal neovascularization in pathologic myopia with intravitreal bevacizumab. Retina, 2006; 26: 960–963.
11Linsky CB, Diamond MP, Cunnigham T, et al. Adhesion reduction in a rabbit uterine horn model using an absorbable barrier TC–7. J Re prod Med 1987; 32: 17–20.
12Goldman CK, Bharara S, Palmar CA, et al. Brain edema in meningiomas is associated with increased VEGF expression. Neurosurgery, 1997; 40: 1269–1277.
13Hellebrekers BWJ, Trimbos-Kemper TCM, Trimbos JBMZ, et al. Use of fibrinolytic agents in the prevention of postoperative adhesion formation. Fertil Steril, 2000; 74: 203–212.
14Holtz G. Current use of ancillary modalities for adhesion prevention. Fertil Steril, 1985; 44: 174–176.
15San Flippo JS, Cox JG, Nealon NA, et al. Comparision of corticosteroid therapy in the prevention of pelvic tissue reaction and adhesion formation. Int J Fertil, 1986; 30: 57–61.
16Şahin Y, Sağlam A. Synergistic effects of carboxymethylcellulose and low molecular weight heparin in reducing adhesion formation in the rat uterine horn model. Acta Obstet Gynecol Scand, 1994; 73: 70–73.
17Başbuğ M, Aygen E, Tayyar M, et al. Hyaluronic acid plus heparin for improved efficacy in prevent of adhesion formation in rat uterine horn model. Eur J Obst Gynecol, 1998; 78: 109–112.
18Kaya E, Sağlam A, Şahin Y. Postoperatif yapışıklıkların azaltılmasında sodyum diklofenak'ın rolü. Kadın Doğum Dergisi, 1992; 7: 264–266.
19Steinleitner A, Lambert H, Montoro L, et al. The use of calcium channel blockade for the prevention of postoperative adhesion formation. Fertil Steril, 1988; 50: 818–821.
20Blauer KL, Collins RL. The effect of intraperitoneal progesterone on postoperative adhesion formation in rabbits. Fertil Steril, 1988; 49: 144–149.
21Bedirli A, Gokahmetoglu S, Sakrak O, et al. Prevention of intraperitoneal adhesion formation using beta-glucan after ileocolic anastomosis in a rat bacterial peritonitis model. Am J Surg, 2003; 185: 339–343.
22Keckstein J, Ulrich U, Sasse V, et al. Reduction of postoperative adhesion formation after laparoscopic ovarian cystectomy. Hum Reprod, 1996; 11: 579–582.
23Zareian Z, Zareian P. Non-closure versus closure of peritoneum during cesarean section: A randomized study. Eur J Obstet Gynecol Reprod Biol, 2006; 128: 267–279.
24Gordon MS, Cunningham D. Managing patients treated with bevacizumab combination therapy. Oncology, 2005; 69: 25–33.
25Holash J, Wiegend SJ, Yancopoulos GD. New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene, 1999; 18: 5356–5362.
26Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med, 1986; 315: 1650–1659.
27Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 1989; 161: 851–858.
28Mıtchell RN. Wound Healing. Kumar V, Cotran RS, Robbins SL(eds), In Robbıns Basic Pathology 7 th ed. Philadelphia, W.B.S.C., 2003; pp: 61–78.
29Chiang SC, Cheng CH, Moulton KS, et al. TNP–470 inhibits intraabdominal adhesion formation. J Pediatr Surg, 2000; 35.189–196.
30Greene AK, Alwayn I P J, Nose V, et al. Prevention of intra-abdominal adhesions using the antiangiogenic COX–2 Inhibitor Celecoxib. Ann Surg, 2005; 242: 140–146
