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Year 2013, Volume: 5 Issue: 3, 18 - 23, 01.12.2013

Abstract

Objective: The relationship between angiogenesis and hyperexpression of COX-2 in various tumors has been studied. In our study, COX-2 expression in pancreatic ductal adenocarcinoma, and micro vessel density was investigated in relation to each other and with various clinicopathological parameters. Materials and Methods: There are sixty one cases diagnosed with pancreas immunoperoxidase staining technique was applied to sections belonging to the cases, using primary polyclonal antibody developed against the CD31 protein and primary polyclonal antibody developed against the COX-2 protein. Microvessels marked with CD31 antibodies were numerically evaluated by the stereological method described by Barth and his colleagues in their studies. The relationship between COX-2 expression, microvessel density and the clinicopathological parameters were also evaluated. Evidence: COX-2 expression was shown in 73.8% of the cases. No correlation was detected between rates of COX-2 receptor staining, vessel parameters, standard prognostic parameters and survival. Conclusion: Although COX-2 expression was tracked in most cases diagnosed with pancreatic ductal adenocarcinoma, no significant association was found between COX-2 and angiogenesis, and it was thought that hyperexpression of COX-2 doesn't have an impact on prognosis, considering the clinicopathological factors

References

  • Warshaw AL, Fernandez-Del Castillo C. Pancreatic carcinoma. N Engl J Med. 1992; 326(7): 455-65.
  • Ikeda N, Adachi M, Taki T, et al. Prognostic significance of angiogenesis in human pancreatic cancer. Br J Cancer. 1999; 79(9): 1553-63.
  • Yamanaka Y, Friess H, Buchler M, et al. Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage. Cancer Res. 1993; 53(21): 5289-96.
  • Reinmuth N, Parikh AA, Ahmad SA, et al. Biology of angiogenesis in tumors of the gastrointestinal tract. Micrscopy Research and Technique 2003; 60 (2): 199-207.
  • Chen YK, Capdevila J, Haris RC. Cytochrome p450 epoxygenase metabolism of arachidonic acid inhibits apoptosis. Mol Cell Biol. 2001a; 21 (18): 6322-31.
  • Subbaramaiah K, Zakim D, Weksler BB, Dannenberg AJ. Inhibition of cyclooxygenase: A novel approach to cancer prevention. Proc Soc Biol Med. 1997; 216(2): 201-10.
  • Tessner TG, Cohn SM, Schloemann S, Stenson WF. Prostaglandins prevent decreased epithelial cell proliferation associated with dexran sodium sulfate injury in mice. Gastroenterology 1998; 115(4): 874-82.
  • Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN. Modulation of apoptosis and Bcl-2 expression by Prostaglandin E2 in human colon cancer cells. Cancer Res. 1998; 58(2): 362-6.
  • Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell. 1998; 93(5): 705-16.
  • Barth PJ, Weingartner K, Köhler HH, et al. Assessment of the vascularization in prostatic carcinoma: a morphometric investigation. Hum Pathol. 1996; 27(12): 1306-1310.
  • Cheng S-Y, Huang HJ, Nagane M, et al. Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor. Proc Natl Acad Sci USA. 1996; 93(16): 8502-7.
  • Warren RS, Yuan H, Matli MR, Gillet NA, Ferrara N. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a Mouse model of experimental liver metastasis. J Clin Invest. 1995; 95(4): 1789-97.
  • Weidner N, Semple JP, Elch WR, Folkman J. Tumor angiogenesis and metastases-correlation in invasive breast carcinoma. N Eng J Med. 1991; 324(1): 1-8.
  • Horak ER, Leek N, Lejeune S, Smith K, Stuart N, Greenall M, Stepniewska K, Harris AL. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastasis and survival in breast cancer. Lancet 1992; 340(8828): 1120-4.
  • Weidner N. Intratumor Microvessel Density as a Prognostic Factor in Cancer. Am J Pathol. 1995;147(1):9- 19.
  • Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ. Tumor angiogenesis in advanced ovarian carcinoma. Ann J Pathol. 1995; 147(1): 33-41.
  • Köhler HH, Barth PJ, Siebel A, Gerharz EW, Bittinger A. Quantitative assesment of vascular surface density in renal cell carcinomas. Br J Urol. 1996; 77(5): 650-4.
  • Macchiarini P, Fontanini G, Hardin MJ, Squartini F, Angeletti CA. Relation of neovascularition to metastasis of non-small-cell lung cancer. Lancet. 1992; 340(8812): 145-6.
  • O’Brien T, Cranston D, Fuggle S, Bicknell R, Harris AL. Two mechanisms of basic fibroblast growth factor-induced angiogenesis in bladder cancer. Cancer Res. 1997; 57 (1): 136-40.
  • Yörükoğlu K, Sağol Ö, Özkara E, et al. Comparison of microvascularization in diagnostic needle biopsies and radical prostatectomies in prostate carcinoma. Eur Urol. 1999; 35(2): 109-12.
  • Ellis LM, Takahashi Y, Fenoglio CJ, Cleary KR, Bucan CD, Evans DB. Vessel counts and vascular endotelial growth factor expression in pancreatic adenocarcinoma. Eur J Cancer. 1998; 34(2): 337-40.
  • Egawa S, Tsutsumi M, Konishi Y, et al. The role of angiogenesis in the tumor growth of Syrian hamster pancreatic cancer cell line HPD-NR. Gastroenterology. 1995; 108(5): 1526-33.
  • Kawarada Y, Ishikura H, Kishimoto T, et al. Inhibitory effects of the angiogenetic agent TNP-470 on establishment and growth of hematogenous metastasis of human pancreatic carcinoma in SCID beige mice in vivo. Pancreas. 1997; 15(3): 251-7.
  • Ohno R, Yoshinaga K, Fujita T, et al. Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma. Cancer. 2001; 91(10): 1876-81.
  • Shi H, Xu JM, Hu NZ, Xie HJ. Prognostic significance of expression of cyclooxygenase-2 and vascular endothelial growth factor in human gastric carcinoma. World J Gastroenterol. 2003; 9(7): 1421-6.
  • Uefuji K, Ichikura T, Mochizuki H. Cyclooxygenase-2 expression is related to Prostaglandin biosynthesis and angiogenesis in human gastric cancer. Clin Cancer Res. 2000; 6(1): 135-8.
  • Howe LR, Dannenberg AJ. COX-2 inhibitors for prevention of breast cancer. J Mammary Gland Biol Neoplasia. 2003; 8(1): 31-43.
  • Molina MA, Sitja-Arnau M, Lemoine MG, et al. Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res. 1999; 59(17): 4356-62.

Pankreas Adenokarsinomunda Anjiogenetik Aktivite ve Cox-2 Ekspresyonunun Prognostik Önemi

Year 2013, Volume: 5 Issue: 3, 18 - 23, 01.12.2013

Abstract

Amaç: Çeşitli tümörlerde anjiogenez ve siklooksijenaz 2 (COX-2)’nin artmış ekspresyonu arasındaki ilişki çalışılmıştır. Bizim çalışmamızda pankreas duktal adenokarsinomunda COX-2 ekspresyonu ve mikrodamar dansitesinin birbirleri ile ve çeşitli klinikopatolojik parametreler ile ilişkisi araştırılmıştır. Gereç ve Yöntem: Bu çalışmada pankreas adenokarsinomu tanısı almış 61 olgu yer almaktadır. Olgulara ait kesitlere CD31 proteinine karşı geliştirilmiş primer poliklonal antikor ve COX-2 proteinine karşı geliştirilmiş primer poliklonal antikor kullanılarak, streptavidin-biotinimmunperoksidaz yöntemiyle boyama uygulandı. CD31 antikoru ile işaretlenen mikrodamarlar Barth ve arkadaşlarının çalışmalarında tanımladıkları stereolojik yöntem ile sayısal olarak değerlendirildi. COX-2 ekspresyonu, mikrodamar yoğunluğu ve klinikopatolojik parametreler arasındaki ilişki değerlendirildi. Bulgular: Olguların %73.8’inde COX-2 ekspresyonu gösterilmiştir. Çalışmamızda COX-2 reseptör boyanma oranları ve damar parametreleri ve standart prognostik parametrelerin sağ kalım ile ilişkisi saptanmamıştır. Sonuç: Pankreas duktal adenokarsinom tanısı almış olgularımızın çoğunda COX-2 ekspresyonu izlense de COX-2 ile anjiogenez arasında anlamlı bir ilişki saptanmamıştır ve klinikopatolojik faktörler değerlendirildiğinde COX-2’nin aşırı ekspresyonunun prognoza etkisi olmadığı düşünülmüştür

References

  • Warshaw AL, Fernandez-Del Castillo C. Pancreatic carcinoma. N Engl J Med. 1992; 326(7): 455-65.
  • Ikeda N, Adachi M, Taki T, et al. Prognostic significance of angiogenesis in human pancreatic cancer. Br J Cancer. 1999; 79(9): 1553-63.
  • Yamanaka Y, Friess H, Buchler M, et al. Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage. Cancer Res. 1993; 53(21): 5289-96.
  • Reinmuth N, Parikh AA, Ahmad SA, et al. Biology of angiogenesis in tumors of the gastrointestinal tract. Micrscopy Research and Technique 2003; 60 (2): 199-207.
  • Chen YK, Capdevila J, Haris RC. Cytochrome p450 epoxygenase metabolism of arachidonic acid inhibits apoptosis. Mol Cell Biol. 2001a; 21 (18): 6322-31.
  • Subbaramaiah K, Zakim D, Weksler BB, Dannenberg AJ. Inhibition of cyclooxygenase: A novel approach to cancer prevention. Proc Soc Biol Med. 1997; 216(2): 201-10.
  • Tessner TG, Cohn SM, Schloemann S, Stenson WF. Prostaglandins prevent decreased epithelial cell proliferation associated with dexran sodium sulfate injury in mice. Gastroenterology 1998; 115(4): 874-82.
  • Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN. Modulation of apoptosis and Bcl-2 expression by Prostaglandin E2 in human colon cancer cells. Cancer Res. 1998; 58(2): 362-6.
  • Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell. 1998; 93(5): 705-16.
  • Barth PJ, Weingartner K, Köhler HH, et al. Assessment of the vascularization in prostatic carcinoma: a morphometric investigation. Hum Pathol. 1996; 27(12): 1306-1310.
  • Cheng S-Y, Huang HJ, Nagane M, et al. Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor. Proc Natl Acad Sci USA. 1996; 93(16): 8502-7.
  • Warren RS, Yuan H, Matli MR, Gillet NA, Ferrara N. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a Mouse model of experimental liver metastasis. J Clin Invest. 1995; 95(4): 1789-97.
  • Weidner N, Semple JP, Elch WR, Folkman J. Tumor angiogenesis and metastases-correlation in invasive breast carcinoma. N Eng J Med. 1991; 324(1): 1-8.
  • Horak ER, Leek N, Lejeune S, Smith K, Stuart N, Greenall M, Stepniewska K, Harris AL. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastasis and survival in breast cancer. Lancet 1992; 340(8828): 1120-4.
  • Weidner N. Intratumor Microvessel Density as a Prognostic Factor in Cancer. Am J Pathol. 1995;147(1):9- 19.
  • Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ. Tumor angiogenesis in advanced ovarian carcinoma. Ann J Pathol. 1995; 147(1): 33-41.
  • Köhler HH, Barth PJ, Siebel A, Gerharz EW, Bittinger A. Quantitative assesment of vascular surface density in renal cell carcinomas. Br J Urol. 1996; 77(5): 650-4.
  • Macchiarini P, Fontanini G, Hardin MJ, Squartini F, Angeletti CA. Relation of neovascularition to metastasis of non-small-cell lung cancer. Lancet. 1992; 340(8812): 145-6.
  • O’Brien T, Cranston D, Fuggle S, Bicknell R, Harris AL. Two mechanisms of basic fibroblast growth factor-induced angiogenesis in bladder cancer. Cancer Res. 1997; 57 (1): 136-40.
  • Yörükoğlu K, Sağol Ö, Özkara E, et al. Comparison of microvascularization in diagnostic needle biopsies and radical prostatectomies in prostate carcinoma. Eur Urol. 1999; 35(2): 109-12.
  • Ellis LM, Takahashi Y, Fenoglio CJ, Cleary KR, Bucan CD, Evans DB. Vessel counts and vascular endotelial growth factor expression in pancreatic adenocarcinoma. Eur J Cancer. 1998; 34(2): 337-40.
  • Egawa S, Tsutsumi M, Konishi Y, et al. The role of angiogenesis in the tumor growth of Syrian hamster pancreatic cancer cell line HPD-NR. Gastroenterology. 1995; 108(5): 1526-33.
  • Kawarada Y, Ishikura H, Kishimoto T, et al. Inhibitory effects of the angiogenetic agent TNP-470 on establishment and growth of hematogenous metastasis of human pancreatic carcinoma in SCID beige mice in vivo. Pancreas. 1997; 15(3): 251-7.
  • Ohno R, Yoshinaga K, Fujita T, et al. Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma. Cancer. 2001; 91(10): 1876-81.
  • Shi H, Xu JM, Hu NZ, Xie HJ. Prognostic significance of expression of cyclooxygenase-2 and vascular endothelial growth factor in human gastric carcinoma. World J Gastroenterol. 2003; 9(7): 1421-6.
  • Uefuji K, Ichikura T, Mochizuki H. Cyclooxygenase-2 expression is related to Prostaglandin biosynthesis and angiogenesis in human gastric cancer. Clin Cancer Res. 2000; 6(1): 135-8.
  • Howe LR, Dannenberg AJ. COX-2 inhibitors for prevention of breast cancer. J Mammary Gland Biol Neoplasia. 2003; 8(1): 31-43.
  • Molina MA, Sitja-Arnau M, Lemoine MG, et al. Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res. 1999; 59(17): 4356-62.
There are 28 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Paksoy S This is me

Publication Date December 1, 2013
Published in Issue Year 2013 Volume: 5 Issue: 3

Cite

APA S, P. (2013). Pankreas Adenokarsinomunda Anjiogenetik Aktivite ve Cox-2 Ekspresyonunun Prognostik Önemi. Konuralp Medical Journal, 5(3), 18-23.
AMA S P. Pankreas Adenokarsinomunda Anjiogenetik Aktivite ve Cox-2 Ekspresyonunun Prognostik Önemi. Konuralp Medical Journal. December 2013;5(3):18-23.
Chicago S, Paksoy. “Pankreas Adenokarsinomunda Anjiogenetik Aktivite Ve Cox-2 Ekspresyonunun Prognostik Önemi”. Konuralp Medical Journal 5, no. 3 (December 2013): 18-23.
EndNote S P (December 1, 2013) Pankreas Adenokarsinomunda Anjiogenetik Aktivite ve Cox-2 Ekspresyonunun Prognostik Önemi. Konuralp Medical Journal 5 3 18–23.
IEEE P. S, “Pankreas Adenokarsinomunda Anjiogenetik Aktivite ve Cox-2 Ekspresyonunun Prognostik Önemi”, Konuralp Medical Journal, vol. 5, no. 3, pp. 18–23, 2013.
ISNAD S, Paksoy. “Pankreas Adenokarsinomunda Anjiogenetik Aktivite Ve Cox-2 Ekspresyonunun Prognostik Önemi”. Konuralp Medical Journal 5/3 (December 2013), 18-23.
JAMA S P. Pankreas Adenokarsinomunda Anjiogenetik Aktivite ve Cox-2 Ekspresyonunun Prognostik Önemi. Konuralp Medical Journal. 2013;5:18–23.
MLA S, Paksoy. “Pankreas Adenokarsinomunda Anjiogenetik Aktivite Ve Cox-2 Ekspresyonunun Prognostik Önemi”. Konuralp Medical Journal, vol. 5, no. 3, 2013, pp. 18-23.
Vancouver S P. Pankreas Adenokarsinomunda Anjiogenetik Aktivite ve Cox-2 Ekspresyonunun Prognostik Önemi. Konuralp Medical Journal. 2013;5(3):18-23.