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Role of NF-Kappa B in the Approach to Pancreatic Ductal Adenocarcinoma

Yıl 2015, , 565 - 577, 15.09.2015
https://doi.org/10.17827/aktd.31545

Öz

Pancreatic ductal adenocarcinoma is now one of the most common causes of cancer death worldwide. K-ras mutations are present in up to 90% of pancreatic cancer cases. The expression of mutant K-ras activates the Akt/protein kinase B pathway, resulting in the activation of the nuclear factor-kappaB (NF-kB) transcriptional factor. Based on in vitro studies, constitutive NF-kB activity plays a key role in pancreatic carcinoma. NF-kB expression does not have direct effects on the overall survival of pancreatic ductal adenocarcinoma. The correlation with the positive lymph node status suggests a role in invasive properties of the tumor. Activation of NF-kB is most likely an early event in pancreatic carcinogenesis. Due to the increased activation in pancreatic cancer, NF-kB seems to be a good target for therapeutic interventions.

Kaynakça

  • Hruban RH, Goggins M, Parsons J, Kern SE. Progression model for pancreatic cancer. Clin Cancer Res. 2000;6:2969-72.
  • Hruban RH, Wilentz RE, Kern SE. Genetic progression in the pancreatic ducts. Am J Pathol. 2000;156:1821-5
  • Hruban RH, Iacobuzio-Donahue C, Wilentz RE, Goggins M, Kern SE, Molecular pathology of pancreatic cancer. Cancer J. 2001;7:251-8.
  • Hameed M, Marrero AM, Conlon KC, Brennan MF, Klimstra DS. Expression of p53 nucleophosphoprotein in in situ pancreatic ductal adenocarcinoma: An immunohistochemical study of 100 cases. Lab Invest. 1994;70:132A.
  • Barton CM, Staddon SL, Hughes CM, Hall PA, O'Sullivan C, Kloppel G et al. Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer.Br J Cancer. 1991;64:1076-82.
  • Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53:549-54.
  • Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB et al. Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet. 1994;8:27-32.
  • Hall PA, Hughes CM, Staddon SL, Richman PI, Gullick WJ, Lemoine NR. The c-erb B-2 proto- oncogene in human pancreatic cancer. J Pathol. 1990;161:195-200.
  • Schutte M, Hruban RH, Geradts J, Maynard R, Hilgers W, Rabindran SK et al. Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res. 1997;57:3126-30.
  • Wilentz RE, Su GH, Dai JL, Sparks AB, Argani P, Sohn TA et al. Immunohistochemical labeling for dpc4 mirrors genetic status in pancreatic adenocarcinomas : a new marker of DPC4 inactivation. Am J Pathol. 2000;156:37-43.
  • Pellegata NS, Sessa F, Renault B, Bonato M, Leone BE, Solcia E et al. K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. Cancer Res. 1994;54:1556-60.
  • Kloppel G, Hruban RH, Longnecker D. Ductal adenocarcinoma of the pancreas, in Pathology and genetics of tumors of the digestive system. WHO classification of the tumors. S. Hamilton and L. Aaltonen. Editors. Lyon, IARC Press, 2000:221-30..
  • Adsay NV, Klimstra D. Benign and malignant tumors of the pancreas. In Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas (Eds. R Odze, J Goldblum, J Crawford):699-736. Philadelphia, Saunders, 2004.
  • Karin M. Nuclear factor-kappaB in cancer development and progression. Nature. 2006;441:431-6.
  • Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005;5:749-59.
  • Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006;25:6680-4.
  • Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D, Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 1995;9:2723-35.
  • Siebenlist, U, Franzoso G, Brown K. Structure, regulation and function of NF-kappa B. Annu Rev Cell Biol. 1994;10:405-55.
  • Baldwin AS Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol.1996;14:649-83.
  • Ghosh S, May MJ, Kopp EB. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225-60.
  • Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell. 2002;109: 81-96.
  • Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol. 2000;18:621-63.
  • Sen R, Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986;47:921-8.
  • Luo JL, Kamata H, Karin M. IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy. J Clin Invest. 2005;115: 2625-32.
  • Sarkar F.H, Li YW. Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy. Acta Pharmacol Sin. 2007;28:1305-15.
  • Dejardin E, Deregowski V, Chapelier M, Jacobs N, Gielen J, Merville MP et al. Regulation of NF- kappaB activity by I kappaB-related proteins in adenocarcinoma cells. Oncogene. 1999;18:2567- 77.
  • Nakshatri H, Bhat-Nakshatri P, Martin DA, Goulet Jr. RA, Sledge Jr. GW, Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol Cell Biol. 1997;17:3629-39.
  • Sovak MA, Bellas RE, Kim DW, Zanieski GJ, Rogers AE, Traish AM et al. Aberrant nuclear factor- kappaB/Rel expression and the pathogenesis of breast cancer. J Clin Invest. 1997;100:2952-60.
  • Bours V, Dejardin E, Goujon-Letawe F, Merville MP, Castronovo V, The NF-kappa B transcription factor and cancer: high expression of NF-kappa B- and I kappa B-related proteins in tumor cell lines. Biochem Pharmacol. 1994;47:145-9.
  • Sumitomo M, Tachibana M, Ozu C, Asakura H, Murai M, Hayakawa M et al. Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IkappaBalpha overexpression. Hum Gene Ther. 1999;10:37-47.
  • Sumitomo M, Tachibana M, Nakashima J, Murai M, Miyajima A, Kimura F et al. An essential role for nuclear factor kappa B in preventing TNF-alpha-induced cell death in prostate cancer cells. J Urol. 1999;161:674-9.
  • Suh J, Payvandi F, Edelstein LC, Amenta PS, Zong WX, Gelinas C et al. Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells. Prostate. 2002;52:183-200.
  • Herrmann, JL, Beham AW, Sarkiss M, Chiao PJ, Rands MT, Bruckheimer EM et al. Bcl-2 suppresses apoptosis resulting from disruption of the NF-kappa B survival pathway. Exp Cell Res. 1997;237:101-9.
  • Devalaraja MN, Wang DZ, Ballard DW, Richmond A. Elevated constitutive IkappaB kinase activity and IkappaB-alpha phosphorylation in Hs294T melanoma cells lead to increased basal MGSA/GRO-alpha transcription. Cancer Res. 1999;59:1372-7.
  • Sebens S, Arlt A, Schafer H. NF-kappaB as a molecular target in the therapy of pancreatic carcinoma. Recent Results Cancer Res. 2008;177:151-64.
  • Wang W, Abbruzzese JL, Evans DB, Larry L, Cleary KR, Chiao PJ. The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin Cancer Res. 1999;5:119-27.
  • Xiao G, Fu J. NF-KB and cancer: a paradigm of Yin-Yang. Am J Cancer Res. 2011;1:192-221.
  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C et al. Cancer statistics. Cancer J Clin. 2006;56:106-30.
  • Blackbourne LH, Jones RS, Catalano CJ, Iezzoni JC, Bourgeois FJ. Pancreatic adenocarcinoma in the pregnant patient: case report and review of the literature. Cancer. 1997;79:1776-9.
  • Luttges, J, Stigge C, Pacena M, Kloppel G. Rare ductal adenocarcinoma of the pancreas in patients younger than age 40 years. Cancer. 2004;100:173-82.
  • Pernick NL, Eldean ZS, Kabbani W, Philip PA, Shields AF, Vaitkevicius V et al. Pancreatic ductal adenocarcinoma in young patients. Modern Pathology. 2001;14:201A.
  • Evans DB, Abruzzese JL, Rich TA. Cancer of the pancreas. In Cancer: Principles and Practice of Oncology (Eds VT Devita, S Hellman, SA Rosenberg):1126-61. MA, Lippincott-Raven, 2001.
  • Brennan MF, Moccia RD, Klimstra D. Management of adenocarcinoma of the body and tail of the pancreas. Ann Surg. 1996; 223: 506-11; discussion 511-2.
  • Solcia E, Capella C, Klöppel G. Tumors of the pancreas. In Armed Forces Institute Pathology. Atlas of Tumor Pathology. Washington, DC, American Registry of Pathology, 2007.
  • Luttges J, Vogel I, Menke M, Henne-Bruns D, Kremer B, Kloppel G. The retroperitoneal resection margin and vessel involvement are important factors determining survival after pancreaticoduodenectomy for ductal adenocarcinoma of the head of the pancreas. Virchows Arch. 1998;433:237-42.
  • Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200-10.
  • Nagakawa T, Nagamori M, Futakami F, Tsukioka Y, Kayahara M, Ohta T et al. Results of extensive surgery for pancreatic carcinoma. Cancer. 1996;77:640-5.
  • Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg. 1990;211:447-58.
  • Carpelan-Holmstrom M, Nordling S, Pukkala E, Sankila R, Luttges J, Kloppel G et al. Does anyone survive pancreatic ductal adenocarcinoma? a nationwide study re-evaluating the data of the Finnish Cancer Registry. Gut. 2005;54:385-7.
  • Mimeault M, Brand RE, Sasson AA, Batra SK. Recent advances on the molecular mechanisms involved in pancreatic cancer progression and therapies. Pancreas. 2005;31:301-16.
  • Jimeno A, Hidalgo M. Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer. Mol Cancer Ther. 2006;5:787-96.
  • Maitra A, Kern SE, Hruban RH. Molecular pathogenesis of pancreatic cancer. Best Pract Res Clin Gastroenterol. 2006;20:211-26.
  • Carbone C, Melisi D. NF-KB as a target for pancreatic cancer therapy. Expert Opin Ther Targets. 2012;16:1-10.
  • Sarkar FH, Banerjee S, Li Y. Pancreatic cancer: pathogenesis, prevention and treatment. Toxicol Appl Pharmacol. 2007;224:326-36.
  • Garcea G, Neal CP, Pattenden CJ, Steward WP, Berry DP. Molecular prognostic markers in pancreatic cancer: a systematic review. Eur J Cancer. 2005;41:2213-36.
  • Mukhopadhyay T., Roth JA, Maxwell SA. Altered expression of the p50 subunit of the NF-kappa B transcription factor complex in non-small cell lung carcinoma. Oncogene. 1995;11:999-1003.
  • Motokura, T, Arnold A. PRAD1/cyclin D1 proto-oncogene: genomic organization, 5' DNA sequence, and sequence of a tumor-specific rearrangement breakpoint. Genes Chromosomes Cancer. 1993;7:89-95.
  • Visconti R, Cerutti J, Battista S, Fedele M, Trapasso F, Zeki K et al..Expression of the neoplastic phenotype by human thyroid carcinoma cell lines requires NFkappaB p65 protein expression. Oncogene. 1997;15:1987-94.
  • Cowgill SM, Muscarella P. The genetics of pancreatic cancer. Am J Surg. 2003;186:279-86.
  • Jaffee EM, Hruban RH, Canto M, Kern SE. Focus on pancreas cancer. Cancer Cell. 2002;2:25-8.
  • Ranson J. The roles of Hedgehog signalling and NF-κB activity in pancreatic cancer and opportunities for treatment cancer and opportunities for treatment. Bioscience Horizons. 2014; 7:1-10.
  • Chandler NM, Canete JJ, Callery MP. Increased expression of NF-kappa B subunits in human pancreatic cancer cells. J Surg Res. 2004;118:9-14.
  • Liptay S, Weber L, Ludwig Wagner M, Adler G, Schmid RM. Mitogenic and antiapoptotic role of constitutive NF-kappaB/Rel activity in pancreatic cancer. Int J Cancer. 2003;105:735-46.
  • Pham NA, Schwock J, Iakovlev V, Pond G, Hedley DW, Tsao MS. Immunohistochemical analysis of changes in signaling pathway activation downstream of growth factor receptors in pancreatic duct cell carcinogenesis. BMC Cancer. 2008;8:43.
  • Wu WJ, Pan CE, Liu QG, Meng KW, Yu HB, Wang YL et al. Expression of heparanase and nuclear factor kappa B in pancreatic adenocarcinoma. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27:1267-70.
  • Weichert W, Boehm M, Gekeler V, Bahra M, Langrehr J, Neuhaus P et al. High expression of RelA/p65 is associated with activation of nuclear factor-kappaB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis. Br J Cancer. 2007;97:523- 30.
  • Burris H, Storniolo AM. Assessing clinical benefit in the treatment of pancreas cancer: gemcitabine compared to 5-fluorouracil. Eur J Cancer. 1997;33:18-22.
  • Burris HA, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403-13.
  • Arlt A, Gehrz A, Muerkoster S, Vorndamm J, Kruse ML, Folsch UR et al. Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death. Oncogene. 2003;22:3243-51.
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  • Correspondence Address / Yazışma Adresi

Pankreas Duktal Adenokarsinomuna Yaklaşımda NF-Kappa B’nin Rolü

Yıl 2015, , 565 - 577, 15.09.2015
https://doi.org/10.17827/aktd.31545

Öz

Pankreasın duktal adenokarsinomu en agresif kanser tiplerinden biridir. K-ras mutasyonu, %90’a varan oranda pankreas kanseri olgularında mevcuttur. Mutant K-ras ekspresyonu Akt/protein kinaz B yolağını aktive ederek Nükleer Faktör-Kappa B (NF-kB) transkripsiyon faktörü etkin kılar. In vitro çalışmalar ışığında, NF-kB aktivitesinin pankreas karsinomunda anahtar role sahip olduğu bildirilmektedir. Lenf bezi durumu ile NF-kB aktivitesinin korelasyonu tümörün invaziv olma özelliğini ön plana çıkartmakta olup pankreas karsinogenezinde erken aşamalarda görülmesi tedavi açılımlarının geliştirilmesi açısından hedef molekül olabileceğini düşündürmektedir.

Kaynakça

  • Hruban RH, Goggins M, Parsons J, Kern SE. Progression model for pancreatic cancer. Clin Cancer Res. 2000;6:2969-72.
  • Hruban RH, Wilentz RE, Kern SE. Genetic progression in the pancreatic ducts. Am J Pathol. 2000;156:1821-5
  • Hruban RH, Iacobuzio-Donahue C, Wilentz RE, Goggins M, Kern SE, Molecular pathology of pancreatic cancer. Cancer J. 2001;7:251-8.
  • Hameed M, Marrero AM, Conlon KC, Brennan MF, Klimstra DS. Expression of p53 nucleophosphoprotein in in situ pancreatic ductal adenocarcinoma: An immunohistochemical study of 100 cases. Lab Invest. 1994;70:132A.
  • Barton CM, Staddon SL, Hughes CM, Hall PA, O'Sullivan C, Kloppel G et al. Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer.Br J Cancer. 1991;64:1076-82.
  • Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53:549-54.
  • Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB et al. Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet. 1994;8:27-32.
  • Hall PA, Hughes CM, Staddon SL, Richman PI, Gullick WJ, Lemoine NR. The c-erb B-2 proto- oncogene in human pancreatic cancer. J Pathol. 1990;161:195-200.
  • Schutte M, Hruban RH, Geradts J, Maynard R, Hilgers W, Rabindran SK et al. Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res. 1997;57:3126-30.
  • Wilentz RE, Su GH, Dai JL, Sparks AB, Argani P, Sohn TA et al. Immunohistochemical labeling for dpc4 mirrors genetic status in pancreatic adenocarcinomas : a new marker of DPC4 inactivation. Am J Pathol. 2000;156:37-43.
  • Pellegata NS, Sessa F, Renault B, Bonato M, Leone BE, Solcia E et al. K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. Cancer Res. 1994;54:1556-60.
  • Kloppel G, Hruban RH, Longnecker D. Ductal adenocarcinoma of the pancreas, in Pathology and genetics of tumors of the digestive system. WHO classification of the tumors. S. Hamilton and L. Aaltonen. Editors. Lyon, IARC Press, 2000:221-30..
  • Adsay NV, Klimstra D. Benign and malignant tumors of the pancreas. In Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas (Eds. R Odze, J Goldblum, J Crawford):699-736. Philadelphia, Saunders, 2004.
  • Karin M. Nuclear factor-kappaB in cancer development and progression. Nature. 2006;441:431-6.
  • Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005;5:749-59.
  • Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006;25:6680-4.
  • Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D, Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 1995;9:2723-35.
  • Siebenlist, U, Franzoso G, Brown K. Structure, regulation and function of NF-kappa B. Annu Rev Cell Biol. 1994;10:405-55.
  • Baldwin AS Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol.1996;14:649-83.
  • Ghosh S, May MJ, Kopp EB. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225-60.
  • Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell. 2002;109: 81-96.
  • Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol. 2000;18:621-63.
  • Sen R, Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986;47:921-8.
  • Luo JL, Kamata H, Karin M. IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy. J Clin Invest. 2005;115: 2625-32.
  • Sarkar F.H, Li YW. Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy. Acta Pharmacol Sin. 2007;28:1305-15.
  • Dejardin E, Deregowski V, Chapelier M, Jacobs N, Gielen J, Merville MP et al. Regulation of NF- kappaB activity by I kappaB-related proteins in adenocarcinoma cells. Oncogene. 1999;18:2567- 77.
  • Nakshatri H, Bhat-Nakshatri P, Martin DA, Goulet Jr. RA, Sledge Jr. GW, Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol Cell Biol. 1997;17:3629-39.
  • Sovak MA, Bellas RE, Kim DW, Zanieski GJ, Rogers AE, Traish AM et al. Aberrant nuclear factor- kappaB/Rel expression and the pathogenesis of breast cancer. J Clin Invest. 1997;100:2952-60.
  • Bours V, Dejardin E, Goujon-Letawe F, Merville MP, Castronovo V, The NF-kappa B transcription factor and cancer: high expression of NF-kappa B- and I kappa B-related proteins in tumor cell lines. Biochem Pharmacol. 1994;47:145-9.
  • Sumitomo M, Tachibana M, Ozu C, Asakura H, Murai M, Hayakawa M et al. Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IkappaBalpha overexpression. Hum Gene Ther. 1999;10:37-47.
  • Sumitomo M, Tachibana M, Nakashima J, Murai M, Miyajima A, Kimura F et al. An essential role for nuclear factor kappa B in preventing TNF-alpha-induced cell death in prostate cancer cells. J Urol. 1999;161:674-9.
  • Suh J, Payvandi F, Edelstein LC, Amenta PS, Zong WX, Gelinas C et al. Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells. Prostate. 2002;52:183-200.
  • Herrmann, JL, Beham AW, Sarkiss M, Chiao PJ, Rands MT, Bruckheimer EM et al. Bcl-2 suppresses apoptosis resulting from disruption of the NF-kappa B survival pathway. Exp Cell Res. 1997;237:101-9.
  • Devalaraja MN, Wang DZ, Ballard DW, Richmond A. Elevated constitutive IkappaB kinase activity and IkappaB-alpha phosphorylation in Hs294T melanoma cells lead to increased basal MGSA/GRO-alpha transcription. Cancer Res. 1999;59:1372-7.
  • Sebens S, Arlt A, Schafer H. NF-kappaB as a molecular target in the therapy of pancreatic carcinoma. Recent Results Cancer Res. 2008;177:151-64.
  • Wang W, Abbruzzese JL, Evans DB, Larry L, Cleary KR, Chiao PJ. The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin Cancer Res. 1999;5:119-27.
  • Xiao G, Fu J. NF-KB and cancer: a paradigm of Yin-Yang. Am J Cancer Res. 2011;1:192-221.
  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C et al. Cancer statistics. Cancer J Clin. 2006;56:106-30.
  • Blackbourne LH, Jones RS, Catalano CJ, Iezzoni JC, Bourgeois FJ. Pancreatic adenocarcinoma in the pregnant patient: case report and review of the literature. Cancer. 1997;79:1776-9.
  • Luttges, J, Stigge C, Pacena M, Kloppel G. Rare ductal adenocarcinoma of the pancreas in patients younger than age 40 years. Cancer. 2004;100:173-82.
  • Pernick NL, Eldean ZS, Kabbani W, Philip PA, Shields AF, Vaitkevicius V et al. Pancreatic ductal adenocarcinoma in young patients. Modern Pathology. 2001;14:201A.
  • Evans DB, Abruzzese JL, Rich TA. Cancer of the pancreas. In Cancer: Principles and Practice of Oncology (Eds VT Devita, S Hellman, SA Rosenberg):1126-61. MA, Lippincott-Raven, 2001.
  • Brennan MF, Moccia RD, Klimstra D. Management of adenocarcinoma of the body and tail of the pancreas. Ann Surg. 1996; 223: 506-11; discussion 511-2.
  • Solcia E, Capella C, Klöppel G. Tumors of the pancreas. In Armed Forces Institute Pathology. Atlas of Tumor Pathology. Washington, DC, American Registry of Pathology, 2007.
  • Luttges J, Vogel I, Menke M, Henne-Bruns D, Kremer B, Kloppel G. The retroperitoneal resection margin and vessel involvement are important factors determining survival after pancreaticoduodenectomy for ductal adenocarcinoma of the head of the pancreas. Virchows Arch. 1998;433:237-42.
  • Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200-10.
  • Nagakawa T, Nagamori M, Futakami F, Tsukioka Y, Kayahara M, Ohta T et al. Results of extensive surgery for pancreatic carcinoma. Cancer. 1996;77:640-5.
  • Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg. 1990;211:447-58.
  • Carpelan-Holmstrom M, Nordling S, Pukkala E, Sankila R, Luttges J, Kloppel G et al. Does anyone survive pancreatic ductal adenocarcinoma? a nationwide study re-evaluating the data of the Finnish Cancer Registry. Gut. 2005;54:385-7.
  • Mimeault M, Brand RE, Sasson AA, Batra SK. Recent advances on the molecular mechanisms involved in pancreatic cancer progression and therapies. Pancreas. 2005;31:301-16.
  • Jimeno A, Hidalgo M. Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer. Mol Cancer Ther. 2006;5:787-96.
  • Maitra A, Kern SE, Hruban RH. Molecular pathogenesis of pancreatic cancer. Best Pract Res Clin Gastroenterol. 2006;20:211-26.
  • Carbone C, Melisi D. NF-KB as a target for pancreatic cancer therapy. Expert Opin Ther Targets. 2012;16:1-10.
  • Sarkar FH, Banerjee S, Li Y. Pancreatic cancer: pathogenesis, prevention and treatment. Toxicol Appl Pharmacol. 2007;224:326-36.
  • Garcea G, Neal CP, Pattenden CJ, Steward WP, Berry DP. Molecular prognostic markers in pancreatic cancer: a systematic review. Eur J Cancer. 2005;41:2213-36.
  • Mukhopadhyay T., Roth JA, Maxwell SA. Altered expression of the p50 subunit of the NF-kappa B transcription factor complex in non-small cell lung carcinoma. Oncogene. 1995;11:999-1003.
  • Motokura, T, Arnold A. PRAD1/cyclin D1 proto-oncogene: genomic organization, 5' DNA sequence, and sequence of a tumor-specific rearrangement breakpoint. Genes Chromosomes Cancer. 1993;7:89-95.
  • Visconti R, Cerutti J, Battista S, Fedele M, Trapasso F, Zeki K et al..Expression of the neoplastic phenotype by human thyroid carcinoma cell lines requires NFkappaB p65 protein expression. Oncogene. 1997;15:1987-94.
  • Cowgill SM, Muscarella P. The genetics of pancreatic cancer. Am J Surg. 2003;186:279-86.
  • Jaffee EM, Hruban RH, Canto M, Kern SE. Focus on pancreas cancer. Cancer Cell. 2002;2:25-8.
  • Ranson J. The roles of Hedgehog signalling and NF-κB activity in pancreatic cancer and opportunities for treatment cancer and opportunities for treatment. Bioscience Horizons. 2014; 7:1-10.
  • Chandler NM, Canete JJ, Callery MP. Increased expression of NF-kappa B subunits in human pancreatic cancer cells. J Surg Res. 2004;118:9-14.
  • Liptay S, Weber L, Ludwig Wagner M, Adler G, Schmid RM. Mitogenic and antiapoptotic role of constitutive NF-kappaB/Rel activity in pancreatic cancer. Int J Cancer. 2003;105:735-46.
  • Pham NA, Schwock J, Iakovlev V, Pond G, Hedley DW, Tsao MS. Immunohistochemical analysis of changes in signaling pathway activation downstream of growth factor receptors in pancreatic duct cell carcinogenesis. BMC Cancer. 2008;8:43.
  • Wu WJ, Pan CE, Liu QG, Meng KW, Yu HB, Wang YL et al. Expression of heparanase and nuclear factor kappa B in pancreatic adenocarcinoma. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27:1267-70.
  • Weichert W, Boehm M, Gekeler V, Bahra M, Langrehr J, Neuhaus P et al. High expression of RelA/p65 is associated with activation of nuclear factor-kappaB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis. Br J Cancer. 2007;97:523- 30.
  • Burris H, Storniolo AM. Assessing clinical benefit in the treatment of pancreas cancer: gemcitabine compared to 5-fluorouracil. Eur J Cancer. 1997;33:18-22.
  • Burris HA, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403-13.
  • Arlt A, Gehrz A, Muerkoster S, Vorndamm J, Kruse ML, Folsch UR et al. Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death. Oncogene. 2003;22:3243-51.
  • Li L, Braiteh FS, Kurzrock R. Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. Cancer. 2005;104:1322-31.
  • Correspondence Address / Yazışma Adresi
Toplam 71 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Derleme
Yazarlar

Deniz Tuncel

Yayımlanma Tarihi 15 Eylül 2015
Yayımlandığı Sayı Yıl 2015

Kaynak Göster

AMA Tuncel D. Role of NF-Kappa B in the Approach to Pancreatic Ductal Adenocarcinoma. aktd. Eylül 2015;24(4):565-577. doi:10.17827/aktd.31545