American Journal of Medicine and Medical Sciences

p-ISSN: 2165-901X     e-ISSN: 2165-9036

20111(1): 7-14

doi: 10.5923/j.ajmms.20110101.02

Pro-Angiogenic Mediators as Targets for Chemotherapy of Colorectal Carcinoma

Copyright © 2011 Scientific & Academic Publishing. All Rights Reserved.

Abstract

Purpose Angiogenesis and chronic inflammation are codependent in pathogenesis of colorectal carcinoma (CRC). We aim to assess whether vascular endothelial growth factor (VEGF), nitric oxide (NO) and total lipase (TL) activity being contributors to angiogenesis, are targets for CRC chemotherapy. Methods we enrolled 60 subjects, 20 volunteers (10 males and 10 females) were assigned as control (group I). Forty CRC patients, 20 locally advanced (group II), subjected to surgery and chemotherapy (5-fluorouracil (5-FU, 425 mg/m2) plus leucovorin (LV, 20 mg/m2), IV, daily for 5 consecutive days, repeated every 3 to 5 weeks for 6 courses). The other 20 patients, were metastatic, (group III), followed up, given only adjuvant chemotherapy. Results Serum carcino embryonic antigen (CEA), cancer antigen (CA19.9), VEGF, NO concentrations and TL activity were significantly elevated in CRC compared to control and in Gp III compared to Gp II patients, but were down-regulated by chemotherapy. VEGF, NO and TL helped in diagnosis and follow up of CRC, although they were not returned to reference intervals. In conclusion, the response to chemotherapy of VEGF, NO and TL substantiates an anti-angiogenic potential in controlling CRC. AFP level was not changed in secondary metastatic hepatocellular carcinoma (HCC), seemingly, it rises only in primary HCCs

Keywords: Angiogenesis, Chemotherapy, CRC, Metastasis, NO, Total lipase, VEGF

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Reference

[1]  W. Khafagy, EI-Ghazaly, M, El-Shobaky, MT and Khafagy, M Colorectal Cancer in Egypt – Does it Differ?. Semin Oncol 32 (2000) 3-10
[2]  H. T. Lynch, and A. de la Chapelle, Hereditary colorectal cancer. N Engl J Med 348 (2003) 919-32
[3]  R. J. Mitchell, D. Brewster, H. Campbell, M. E. Porteous, A. H. Wyllie, C. C. Bird, and M. G. Dunlop, Accuracy of reporting of family history of colorectal cancer. Gut 53 (2004) 291-5
[4]  D. A. Lieberman, S. Prindiville, D. G. Weiss, and W. Willett, Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals. Jama 290 (2003) 2959-67
[5]  A. Russo, S. Franceschi, C. La Vecchia, L. Dal Maso, M. Montella, E. Conti, A. Giacosa, F. Falcini, and E. Negri, Body size and colorectal-cancer risk. Int J Cancer 78 (1998) 161-5
[6]  C. A. Doubeni, T. S. Field, D. S. Buist, E. J. Korner, C. Bigelow, L. Lamerato, L. Herrinton, V. P. Quinn, G. Hart, M. C. Hornbrook, J. H. Gurwitz, and E. H. Wagner, Racial differences in tumor stage and survival for colorectal cancer in an insured population. Cancer 109 (2007) 612-20
[7]  A. Rullier, and C. Laurent, [Recommendations for clinical practice. Therapeutic choices for rectal cancer. What quality criteria are important for surgical excision of rectal cancer?]. Gastroenterol Clin Biol 31 Spec No 1 (2007) 1S34-51, 1S91-5
[8]  M. Vermaas, F. T. Ferenschild, C. Verhoef, J. J. Nuyttens, A. W. Marinelli, T. Wiggers, W. J. Kirkels, A. M. Eggermont, and J. H. de Wilt, Total pelvic exenteration for primary locally advanced and locally recurrent rectal cancer. Eur J Surg Oncol 33 (2007) 452-8
[9]  W. Zhang, M. Gordon, and H. J. Lenz, Novel approaches to treatment of advanced colorectal cancer with anti-EGFR monoclonal antibodies. Ann Med 38 (2006) 545-51
[10]  W. S. Liao, A. R. Conn, and J. M. Taylor, Changes in rat alpha 1-fetoprotein and albumin mRNA levels during fetal and neonatal development. J Biol Chem 255 (1980) 10036-9
[11]  M. F. Yuen, C. C. Cheng, I. J. Lauder, S. K. Lam, C. G. Ooi, and C. L. Lai, Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience. Hepatology 31 (2000) 330-5
[12]  Y. H. Ding, X. D. Luan, J. Li, J.A. Rafols, M. Guthinkonda, F. G. Diaz, and Y. Ding, Exercise-induced overexpression of angiogenic factors and reduction of ischemia/reperfusion injury in stroke. Curr Neurovasc Res 1 (2004) 411-20
[13]  R. M. Kraus, H. W. Stallings, 3rd, R. C. Yeager, and T. P. Gavin, Circulating plasma VEGF response to exercise in sedentary and endurance-trained men. J Appl Physiol 96 (2004) 1445-50
[14]  J. Folkman, Tumor angiogenesis: therapeutic implications. N Engl J Med 285 (1971) 1182-6
[15]  C. J. Wray, H. L. Rilo, and S. A. Ahmad, Colon cancer angiogenesis and antiangiogenic therapy. Expert Opin Investig Drugs 13 (2004) 631-41
[16]  B. M. Prior, H.T. Yang, and R.L. Terjung, What makes vessels grow with exercise training? J Appl Physiol 97 (2004) 1119-28
[17]  Y. H. Kim, K. J. Woo, J. H. Lim, S. Kim, T. J. Lee, E. M. Jung, J. M. Lee, J. W. Park, and T. K. Kwon, 8-Hydroxyquinoline inhibits iNOS expression and nitric oxide production by down-regulating LPS-induced activity of NF-kappaB and C/EBPbeta in Raw 264.7 cells. Biochem Biophys Res Commun 329 (2005) 591-7
[18]  L. J. Hofseth, S. Saito, S. P. Hussain, M. G. Espey, K. M. Miranda, Y. Araki, C. Jhappan, Y. Higashimoto, P. He, S. P. Linke, M. M. Quezado, I. Zurer, V. Rotter, D. A. Wink, E. Appella, and C. C. Harris, Nitric oxide-induced cellular stress and p53 activation in chronic inflammation. Proc Natl Acad Sci U S A 100 (2003) 143-8
[19]  D. A. Wink, K. S. Kasprzak, C. M. Maragos, R. K. Elespuru, M. Misra, T. M. Dunams, T. A. Cebula, W. H. Koch, A. W. Andrews, J. S. Allen, and et al., DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254 (1991) 1001-3
[20]  D. C. Jenkins, I. G. Charles, L. L. Thomsen, D. W. Moss, L. S. Holmes, S. A. Baylis, P. Rhodes, K. Westmore, P. C. Emson, and S. Moncada, Roles of nitric oxide in tumor growth. Proc Natl Acad Sci U S A 92 (1995) 4392-6
[21]  S. Ambs, W. G. Merriam, M. O. Ogunfusika, W. P. Bennett, N. Ishibe, S. P. Hussain, E. E. Tzeng, D. A. Geller, T. R. Billiar, and C. C. Harris, p53 and vascular endothelial growth factor regulate tumor growth of NOS2-expressing human carcinoma cells. Nat Med 4 (1998) 1371-6
[22]  S. Ambs, M. O. Ogunfusika, W. G. Merriam, W. P. Bennett, T. R. Billiar, and C. C. Harris, Up-regulation of inducible nitric oxide synthase expression in cancer-prone p53 knockout mice. Proc Natl Acad Sci U S A 95 (1998) 8823-8
[23]  J. Li, T. R. Billiar, R. V. Talanian, and Y. M. Kim, Nitric oxide reversibly inhibits seven members of the caspase family via S-nitrosylation. Biochem Biophys Res Commun 240 (1997) 419-24
[24]  M. E. Lowe, The triglyceride lipases of the pancreas. J Lipid Res 43 (2002) 2007-16
[25]  M. Takahashi, Y. Hiyama, M. Yokoyama, S. Yu, Y. Hu, K. Melford, A. Bensadoun, and I. J. Goldberg, In vivo arterial lipoprotein lipase expression augments inflammatory responses and impairs vascular dilatation. Arterioscler Thromb Vasc Biol 28 (2008) 455-62
[26]  C. W. Hendrickse, S. Radley, I. A. Donovan, M. R. Keighley, and J. P. Neoptolemos, Activities of phospholipase A2 and diacylglycerol lipase are increased in human colorectal cancer. Br J Surg 82 (1995) 475-8
[27]  C. Wittekind, C. C. Compton, F. L. Greene, and L. H. Sobin, TNM residual tumor classification revisited. Cancer 94 (2002) 2511-6
[28]  M. J. O'Connell, J. A. Mailliard, M. J. Kahn, J. S. Macdonald, D. G. Haller, R. J. Mayer, and H. S. Wieand, Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol 15 (1997) 246-50
[29]  D. E. DuBois D, A formula to estimate the approximate surface area if height and weight be known. Arch Intern Medicine. 17 (1916) 863-71
[30]  Y. Wang, J. Moss, and R. Thisted, Predictors of body surface area. J Clin Anesth 4 (1992) 4-10
[31]  J. Lin, and H. Ju, Electrochemical and chemiluminescent immunosensors for tumor markers. Biosens Bioelectron 20 (2005) 1461-70
[32]  K. Lee, Kim, KI and Lee, KP, Development of Enzyme Immuno Assay Kit for Alpha Feto protein. Korean J. Immunol 19 (1997) 455-461
[33]  S. L. Sheng, S. H. Bao, G. Huang, and L. M. Wang, Development of time-resolved immunofluorometric assays for vascular endothelial growth factor and application on plasma of patients with gastric tumours. Clin Exp Immunol 151 (2008) 459-66
[34]  K. Miranda, Espey, MG and Wink, DA A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5 (2001) 62-71
[35]  B. Graca, C. Lunet, A. S. Coelho, G. Monteiro, P. Freire, A. Speidel, and L. Carvalho, [Angiogenesis and cancer: from biopathology to therapy]. Acta Med Port 17 (2004) 76-93
[36]  W. G. Hu, J. W. Li, B. Feng, M. Beveridge, F. Yue, A. G. Lu, J. J. Ma, M. L. Wang, Y. Guo, X. L. Jin, and M. H. Zheng, Vascular endothelial growth factors C and D represent novel prognostic markers in colorectal carcinoma using quantitative image analysis. Eur Surg Res 39 (2007) 229-38
[37]  N. H. Fernando, and H. I. Hurwitz, Targeted therapy of colorectal cancer: clinical experience with bevacizumab. Oncologist 9 Suppl 1 (2004) 11-8
[38]  F. F. Kabbinavar, J. Schulz, M. McCleod, T. Patel, J. T. Hamm, J. R. Hecht, R. Mass, B. Perrou, B. Nelson, and W. F. Novotny, Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 23 (2005) 3697-705
[39]  J. Y. Wang, C. Y. Lu, K. S. Chu, C. J. Ma, D. C. Wu, H. L. Tsai, F. J. Yu, and J. S. Hsieh, Prognostic significance of pre- and postoperative serum carcinoembryonic antigen levels in patients with colorectal cancer. Eur Surg Res 39 (2007) 245-50
[40]  M. J. Duffy, Clinical uses of tumor markers: a critical review. Crit Rev Clin Lab Sci 38 (2001) 225-62
[41]  M. Grotowski, M. Maruszynski, and W. Piechota, [Usefulness of preoperative assay CEA and CA 19-9 in colorectal cancer patients]. Pol Merkur Lekarski 11 (2001) 476-9
[42]  R. C. Bast, Jr., P. Ravdin, D. F. Hayes, S. Bates, H. Fritsche, Jr., J. M. Jessup, N. Kemeny, G. Y. Locker, R. G. Mennel, and M. R. Somerfield, 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19 (2001) 1865-78
[43]  M. J. Duffy, A. van Dalen, C. Haglund, L. Hansson, R. Klapdor, R. Lamerz, O. Nilsson, C. Sturgeon, and O. Topolcan, Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. Eur J Cancer 39 (2003) 718-27
[44]  W. S. Wang, J. K. Lin, T. J. Chiou, J. H. Liu, F. S. Fan, C. C. Yen, T. C. Lin, J. K. Jiang, S. H. Yang, H. S. Wang, and P. M. Chen, CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer. Hepatogastroenterology 49 (2002) 160-4
[45]  D. Gholam, S. Giacchetti, C. Brezault-Bonnet, M. Bouchahda, D. Hauteville, R. Adam, B. Ducot, O. Ghemard, F. Kustlinger, C. Jasmin, and F. Levi, Chronomodulated irinotecan, oxaliplatin, and leucovorin-modulated 5-Fluorouracil as ambulatory salvage therapy in patients with irinotecan- and oxaliplatin-resistant metastatic colorectal cancer. Oncologist 11 (2006) 1072-80
[46]  H. Michiko, Kenjiro, K, Kenji, K , Osamu, J, Masami, I , Shoichi, H, Takanobu, Y, Takeo, T and Seiji, G Hepatic Metastases from Alpha-Fetoprotein Producing Colorectal Cancer That Responded Remarkably to Transcatheter Arterial Chemo-embolization. Japanese Journal of Cancer and Chemotherapy 29 (2002) 2366-2369
[47]  V. Hanrahan, M. J. Currie, S. P. Gunningham, H. R. Morrin, P. A. Scott, B. A. Robinson, and S. B. Fox, The angiogenic switch for vascular endothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, and VEGF-D in the adenoma-carcinoma sequence during colorectal cancer progression. J Pathol 200 (2003) 183-94
[48]  R. E. Frank, T. J. Saclarides, S. Leurgans, N. J. Speziale, E. A. Drab, and D. B. Rubin, Tumor angiogenesis as a predictor of recurrence and survival in patients with node-negative colon cancer. Ann Surg 222 (1995) 695-9
[49]  G. Galizia, E. Lieto, F. Ferraraccio, M. Orditura, F. De Vita, P. Castellano, V. Imperatore, C. Romano, F. Ciardiello, B. Agostini, and C. Pignatelli, Determination of molecular marker expression can predict clinical outcome in colon carcinomas. Clin Cancer Res 10 (2004) 3490-9
[50]  J. C. Lee, N. H. Chow, S. T. Wang, and S. M. Huang, Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients. Eur J Cancer 36 (2000) 748-53
[51]  P. Mysliwiec, Z. Piotrowski, B. Zalewski, A. Kuklinski, and K. Pawlak, Plasma VEGF-A and its soluble receptor R1 correlate with the clinical stage of colorectal cancer. Rocz Akad Med Bialymst 49 Suppl 1 (2004) 85-7
[52]  F. Kabbinavar, H. I. Hurwitz, L. Fehrenbacher, N. J. Meropol, W. F. Novotny, G. Lieberman, S. Griffing, and E. Bergsland, Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21 (2003) 60-5
[53]  M. P. Morelli, A. M. Brown, T. M. Pitts, J. J. Tentler, F. Ciardiello, A. Ryan, J. M. Jurgensmeier, and S. G. Eckhardt, Targeting vascular endothelial growth factor receptor-1 and -3 with cediranib (AZD2171): effects on migration and invasion of gastrointestinal cancer cell lines. Mol Cancer Ther 8 (2009) 2546-58
[54]  A. Ooyama, T. Oka, H. Y. Zhao, M. Yamamoto, S. Akiyama, and M. Fukushima, Anti-angiogenic effect of 5-Fluorouracil-based drugs against human colon cancer xenografts. Cancer Lett 267 (2008) 26-36
[55]  P. Albertsson, B. Lennernas, and K. Norrby, Low-dose continuous 5-fluorouracil infusion stimulates VEGF-A-mediated angiogenesis. Acta Oncol 48 (2009) 418-25
[56]  S. S. Mirvish, Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC. Cancer Lett 93 (1995) 17-48
[57]  E. E. Mannick, L. E. Bravo, G. Zarama, J. L. Realpe, X. J. Zhang, B. Ruiz, E. T. Fontham, R. Mera, M. J. Miller, and P. Correa, Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants. Cancer Res 56 (1996) 3238-43
[58]  P. L. Majano, C. Garcia-Monzon, M. Lopez-Cabrera, E. Lara-Pezzi, E. Fernandez-Ruiz, C. Garcia-Iglesias, M. J. Borque, and R. Moreno-Otero, Inducible nitric oxide synthase expression in chronic viral hepatitis. Evidence for a virus-induced gene upregulation. J Clin Invest 101 (1998) 1343-52
[59]  M. Jaiswal, N. F. LaRusso, R. A. Shapiro, T. R. Billiar, and G. J. Gores, Nitric oxide-mediated inhibition of DNA repair potentiates oxidative DNA damage in cholangiocytes. Gastroenterology 120 (2001) 190-9
[60]  Singer, II, D. W. Kawka, S. Scott, J. R. Weidner, R. A. Mumford, T. E. Riehl, and W. F. Stenson, Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease. Gastroenterology 111 (1996) 871-85
[61]  G. Montrucchio, E. Lupia, A. de Martino, E. Battaglia, M. Arese, A. Tizzani, F. Bussolino, and G. Camussi, Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha. Am J Pathol 151 (1997) 557-63
[62]  P. Lejeune, P. Lagadec, N. Onier, D. Pinard, H. Ohshima, and J. F. Jeannin, Nitric oxide involvement in tumor-induced immunosuppression. J Immunol 152 (1994) 5077-83
[63]  O. Fantappie, E. Masini, I. Sardi, L. Raimondi, D. Bani, M. Solazzo, A. Vannacci, and R. Mazzanti, The MDR phenotype is associated with the expression of COX-2 and iNOS in a human hepatocellular carcinoma cell line. Hepatology 35 (2002) 843-52
[64]  X. P. Hao, T. G. Pretlow, J. S. Rao, and T. P. Pretlow, Inducible nitric oxide synthase (iNOS) is expressed similarly in multiple aberrant crypt foci and colorectal tumors from the same patients. Cancer Res 61 (2001) 419-22
[65]  A. Franchi, O. Gallo, M. Paglierani, I. Sardi, L. Magnelli, E. Masini, and M. Santucci, Inducible nitric oxide synthase expression in laryngeal neoplasia: correlation with angiogenesis. Head Neck 24 (2002) 16-23
[66]  S. Mocellin, V. Bronte, and D. Nitti, Nitric oxide, a double edged sword in cancer biology: searching for therapeutic opportunities. Med Res Rev 27 (2007) 317-52
[67]  K. M. Ropponen, J. K. Kellokoski, P. K. Lipponen, M. J. Eskelinen, L. Alanne, E. M. Alhava, and V. M. Kosma, Expression of inducible nitric oxide synthase in colorectal cancer and its association with prognosis. Scand J Gastroenterol 35 (2000) 1204-11
[68]  J. G. Donnelly, D. S. Ooi, B. F. Burns, and R. Goel, Chronic increased serum lipase without evidence of pancreatitis: tumor-derived lipase? Clin Chem 42 (1996) 462-4
[69]  M. Munoz-Perez, D. Sarrion-Pelous, J. Jimenez-Jimenez, P. Martinez-Montiel, and M. Gallego-Valdes, Chronic increased serum lipase in a patient with suspected pancreatic adenocarcinoma. Clin Chem 43 (1997) 191-3
[70]  R. S. Kota, C. V. Ramana, F. A. Tenorio, R. I. Enelow, and J. C. Rutledge, Differential effects of lipoprotein lipase on tumor necrosis factor-alpha and interferon-gamma-mediated gene expression in human endothelial cells. J Biol Chem 280 (2005) 31076-84
[71]  H. Nguyen, C. V. Ramana, J. Bayes, and G. R. Stark, Roles of phosphatidylinositol 3-kinase in interferon-gamma- dependent phosphorylation of STAT1 on serine 727 and activation of gene expression. J Biol Chem 276 (2001) 33361-8
[72]  G. R. Stark, I. M. Kerr, B. R. Williams, R. H. Silverman, and R. D. Schreiber, How cells respond to interferons. Annu Rev Biochem 67 (1998) 227-64.
[73]  M. Sherman, K. M. Peltekian, and C. Lee, Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology 22 (1995) 432-8