In vitro models of pancreatic cancer for translational oncology research

Bibliography

• Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58(2):71-96
   PubMed Web of Science ®Google Scholar
• ACS. Cancer facts & figures 2008. Atlanta: Am Cancer Society 2008
   Google Scholar
• Carpelan-Holmstrom M, Nordling S, Pukkala E, et al. Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the finnish cancer registry. Gut 2005;54(3):385-7
   PubMed Web of Science ®Google Scholar
• Jamieson JD. Prospectives for cell and organ culture systems in the study of pancreatic carcinoma. J Surg Oncol 1975;7(2):139-41
   PubMedGoogle Scholar
• Longnecker DS, Wiebkin P, Schaeffer BK, Roebuck BD. Experimental carcinogenesis in the pancreas. Int Rev Exp Pathol 1984;26:177-229
   PubMedGoogle Scholar
• Hall PA, Lemoine NR. Rapid acinar to ductal transdifferentiation in cultured human exocrine pancreas. J Pathol 1992;166(2):97-103
   PubMed Web of Science ®Google Scholar
• Habbe N, Shi G, Meguid RA, et al. Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice. Proc Natl Acad Sci USA 2008;105(48):18913-8
   Web of Science ®Google Scholar
• Park SW, Davison JM, Rhee J, et al. Oncogenic KRAS induces progenitor cell expansion and malignant transformation in zebrafish exocrine pancreas. Gastroenterol 2008;134(7):2080-90
   PubMed Web of Science ®Google Scholar
• Murtaugh LC, Leach SD. A case of mistaken identity? Nonductal origins of pancreatic “ductal” cancers. Cancer Cell 2007;11(3):211-3
   PubMed Web of Science ®Google Scholar
• Githens S. Pancreatic duct cell cultures. Annu Rev Physiol 1994;56:419-43
   PubMed Web of Science ®Google Scholar
• Githens S. The pancreatic duct cell: proliferative capabilities, specific characteristics, metaplasia, isolation, and culture. J Pediatr Gastroenterol Nutr 1988;7(4):486-506
   PubMed Web of Science ®Google Scholar
• Bonner-Weir S, Toschi E, Inada A, et al. The pancreatic ductal epithelium serves as a potential pool of progenitor cells. Pediatr diabetes 2004;5 (Suppl 2):16-22
   Google Scholar
• Jones RT, Barrett LA, van Haaften, et al. Carcinogenesis in the pancreas. I. Long-term explant culture of human and bovine pancreatic ducts. J Natl Cancer Inst 1977;58(3):557-65
   PubMed Web of Science ®Google Scholar
• Oda D, Savard CE, Nguyen TD, et al. Culture of human main pancreatic duct epithelial cells. In Vitro Cell Dev Biol Anim 1998;34(3):211-6
   PubMed Web of Science ®Google Scholar
• Trautmann B, Schlitt HJ, Hahn EG, Lohr M. Isolation, culture, and characterization of human pancreatic duct cells. Pancreas 1993;8(2):248-54
   PubMed Web of Science ®Google Scholar
• Furukawa T, Duguid WP, Rosenberg L, et al. Long-term culture and immortalization of epithelial cells from normal adult human pancreatic ducts transfected by the E6E7 gene of human papilloma virus 16. Am J Pathol 1996;148(6):1763-70
   PubMed Web of Science ®Google Scholar
• Ouyang H, Mou L, Luk C, et al. Immortal human pancreatic duct epithelial cell lines with near normal genotype and phenotype. Am J Pathol 2000;157(5):1623-31
   PubMed Web of Science ®Google Scholar
• Lee KM, Yasuda H, Hollingsworth MA, Ouellette MM. Notch 2-positive progenitors with the intrinsic ability to give rise to pancreatic ductal cells. Lab Invest 2005;85(8):1003-12
   PubMed Web of Science ®Google Scholar
• Qian J, Niu J, Li M, et al. In vitro modeling of human pancreatic duct epithelial cell transformation defines gene expression changes induced by K-ras oncogenic activation in pancreatic carcinogenesis. Cancer Res 2005;65(12):5045-53
   PubMed Web of Science ®Google Scholar
• Campbell PM, Lee KM, Ouellette MM, et al. Ras-driven transformation of human nestin-positive pancreatic epithelial cells. Methods Enzymol 2008;439:451-65
   PubMed Web of Science ®Google Scholar
• Bendayan M, Duhr MA, Gingras D. Studies on pancreatic acinar cells in tissue culture: basal lamina (basement membrane matrix promotes three-dimensional reorganization. Eur J Cell Biol 1986;42(1):60-7
   PubMedGoogle Scholar
• Longnecker DS, Lilja HS, French J, et al. Transplantation of azaserine-induced carcinomas of pancreas in rats. Cancer Lett 1979;7(4):197-202
   PubMed Web of Science ®Google Scholar
• Ulrich AB, Schmied BM, Standop J, et al. Pancreatic cell lines: a review. Pancreas 2002;24(2):111-20
   PubMed Web of Science ®Google Scholar
• Esni F, Miyamoto Y, Leach SD, Ghosh B. Primary explant cultures of adult and embryonic pancreas. Methods Mol Med 2005;103:259-71
   PubMedGoogle Scholar
• Hober C, Benhamou PY, Watt PC, et al. A new culture method for human pancreatic islets using a biopore membrane insert. Pancreas 1997;14(2):199-204
   PubMed Web of Science ®Google Scholar
• Kenmochi T, Miyamoto M, Une S, et al. Improved quality and yield of islets isolated from human pancreata using a two-step digestion method. Pancreas 2000;20(2):184-90
   PubMed Web of Science ®Google Scholar
• Lucas-Clerc C, Massart C, Campion JP, et al. Long-term culture of human pancreatic islets in an extracellular matrix: morphological and metabolic effects. Mol cell endocrinol 1993;94(1):9-20
   PubMed Web of Science ®Google Scholar
• Yuan S, Rosenberg L, Paraskevas S, et al. Transdifferentiation of human islets to pancreatic ductal cells in collagen matrix culture. Differ 1996;61(1):67-75
   PubMed Web of Science ®Google Scholar
• Beattie GM, Itkin-Ansari P, Cirulli V, et al. Sustained proliferation of PDX-1+ cells derived from human islets. Diabetes 1999;48(5):1013-9
   PubMed Web of Science ®Google Scholar
• Lu J, Gu YP, Xu X, et al. Adult islets cultured in collagen gel transdifferentiate into duct-like cells. World J Gastroenterol 2005;11(22):3426-30
   PubMed Web of Science ®Google Scholar
• Murray HE, Paget MB, Bailey CJ, Downing R. Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system. Diabetol 2009
   Google Scholar
• Mueller BM, Reisfeld RA. Potential of the scid mouse as a host for human tumors. Cancer Metastasis Rev 1991;10(3):193-200
   PubMed Web of Science ®Google Scholar
• Pantelouris EM. Absence of thymus in a mouse mutant. Nat 1968;217(5126):370-1
   Google Scholar
• van Weerden WM, Romijn JC. Use of nude mouse xenograft models in prostate cancer research. Prostate 2000;43(4):263-71
   PubMed Web of Science ®Google Scholar
• Ikeda Y, Ezaki M, Hayashi I, et al. Establishment and characterization of human pancreatic cancer cell lines in tissue culture and in nude mice. Jpn J Cancer Res 1990;81(10):987-93
   Google Scholar
• Rubio-Viqueira B, Jimeno A, Cusatis G, et al. An in vivo platform for translational drug development in pancreatic cancer. Clin Cancer Res 2006;12(15):4652-61
   Google Scholar
• Walter K, Eshleman J, Goggins M. Xenografting and harvesting human ductal pancreatic adenocarcinomas for DNA analysis. Methods Mol Med 2005;103:103-11
   PubMedGoogle Scholar
• Pretlow TG, Delmoro CM, Dilley GG, et al. Transplantation of human prostatic carcinoma into nude mice in Matrigel. Cancer Res 1991;51(14):3814-7
   PubMed Web of Science ®Google Scholar
• Elsasser HP, Lehr U, Agricola B, Kern HF. Establishment and characterisation of two cell lines with different grade of differentiation derived from one primary human pancreatic adenocarcinoma. Virchows Arch B Cell Pathol Incl Mol Pathol 1992;61(5):295-306
   PubMedGoogle Scholar
• Kobari M, Hisano H, Matsuno S, et al. Establishment of six human pancreatic cancer cell lines and their sensitivities to anti-tumor drugs. Tohoku J Exp Med 1986;150(3):231-48
   Google Scholar
• Bleday R, Tzanakakis GN, Schwalke MA, et al. Epidermal growth factor stimulation and metastatic rate in human pancreatic carcinoma cell lines. J Surg Res 1990;49(3):276-9
   PubMed Web of Science ®Google Scholar
• Silberberg JM, Gordon S, Zucker S. Identification of tissue factor in two human pancreatic cancer cell lines. Cancer Res 1989;49(19):5443-7
   PubMed Web of Science ®Google Scholar
• Kyriazis AP, McCombs WB 3rd, Sandberg AA, et al. Establishment and characterization of human pancreatic adenocarcinoma cell line SW-1990 in tissue culture and the nude mouse. Cancer Res 1983;43(9):4393-401
   PubMed Web of Science ®Google Scholar
• Chang BK, Gutman R, Chou TC. Schedule-dependent interaction of alpha-difluoromethylornithine and cis-diamminedichloroplatinum(II) against human and hamster pancreatic cancer cell lines. Cancer Res 1987;47(9):2247-50
   PubMed Web of Science ®Google Scholar
• Elsasser HP, MacDonald R, Dienst M, Kern HF. Characterization of a transglutaminase expressed in human pancreatic adenocarcinoma cells. Eur J Cell Biol 1993;61(2):321-8
   PubMed Web of Science ®Google Scholar
• Suwa H, Yoshimura T, Yamaguchi N, et al. K-ras and p53 alterations in genomic DNA and transcripts of human pancreatic adenocarcinoma cell lines. Jpn J Cancer Res 1994;85(10):1005-14
   PubMedGoogle Scholar
• Lieber M, Mazzetta J, Nelson-Rees W, et al. Establishment of a continuous tumor-cell line (panc-1) from a human carcinoma of the exocrine pancreas. Int J Cancer 1975;15(5):741-7
   PubMed Web of Science ®Google Scholar
• Jaffee EM, Schutte M, Gossett J, et al. Development and characterization of a cytokine-secreting pancreatic adenocarcinoma vaccine from primary tumors for use in clinical trials. Cancer J Sci Am 1998;4(3):194-203
   PubMed Web of Science ®Google Scholar
• Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Sci 2008;321(5897):1801-6
   Web of Science ®Google Scholar
• Moore PS, Sipos B, Orlandini S, et al. Genetic profile of 22 pancreatic carcinoma cell lines. Analysis of K-ras, p53, p16 and DPC4/Smad4. Virchows Arch 2001;439(6):798-802
   PubMed Web of Science ®Google Scholar
• Feldmann G, Maitra A. Molecular genetics of pancreatic ductal adenocarcinomas and recent implications for translational efforts. J Mol Diagn 2008;10(2):111-22
   PubMed Web of Science ®Google Scholar
• Grippo PJ, Sandgren EP. Modeling pancreatic cancer in animals to address specific hypotheses. Methods Mol Med 2005;103:217-43
   PubMedGoogle Scholar
• Sasai K, Romer JT, Lee Y, et al. Shh pathway activity is down-regulated in cultured medulloblastoma cells: implications for preclinical studies. Cancer Res 2006;66(8):4215-22
   PubMed Web of Science ®Google Scholar
• Romer JT, Kimura H, Magdaleno S, et al. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/-)p53(-/-) mice. Cancer Cell 2004;6(3):229-40
   PubMed Web of Science ®Google Scholar
• Maitra A, Hruban RH. Pancreatic cancer. Annual rev of pathol 2008;3:157-88
   PubMed Web of Science ®Google Scholar
• Mahadeven D, Von Hoff DD. Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther 2007;6(4):1186-97
   PubMed Web of Science ®Google Scholar
• Kleeff J, Beckhove P, Esposito I, et al. Pancreatic cancer microenvironment. Int J Cancer 2007;121(4):699-705
   PubMed Web of Science ®Google Scholar
• Tlsty TD, Coussens LM. Tumor stroma and regulation of cancer development. Annual rev of pathol 2006;1:119-50
   PubMed Web of Science ®Google Scholar
• Qiu W, Hu M, Sridhar A, et al. No evidence of clonal somatic genetic alterations in cancer-associated fibroblasts from human breast and ovarian carcinomas. Nat Genet 2008;40(5):650-5
   PubMed Web of Science ®Google Scholar
• Kurose K, Gilley K, Matsumoto S, et al. Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nat Genet 2002;32(3):355-7
   Web of Science ®Google Scholar
• Macintosh CA, Stower M, Reid N, Maitland NJ. Precise microdissection of human prostate cancers reveals genotypic heterogeneity. Cancer Res 1998;58(1):23-8
   PubMed Web of Science ®Google Scholar
• Moinfar F, Man YG, Arnould L, et al. Concurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: implications for tumorigenesis. Cancer Res 2000;60(9):2562-6
   PubMed Web of Science ®Google Scholar
• Weber F, Shen L, Fukino K, et al. Total-genome analysis of BRCA1/2-related invasive carcinomas of the breast identifies tumor stroma as potential landscaper for neoplastic initiation. Am J Hum Genet 2006;78(6):961-72
   PubMed Web of Science ®Google Scholar
• Fukino K, Shen L, Matsumoto S, et al. Combined total genome loss of heterozygosity scan of breast cancer stroma and epithelium reveals multiplicity of stromal targets. Cancer Res 2004;64(20):7231-6
   PubMed Web of Science ®Google Scholar
• Fukino K, Shen L, Patocs A, et al. Genomic instability within tumor stroma and clinicopathological characteristics of sporadic primary invasive breast carcinoma. Jama 2007;297(19):2103-11
   Web of Science ®Google Scholar
• Tuhkanen H, Anttila M, Kosma VM, et al. Frequent gene dosage alterations in stromal cells of epithelial ovarian carcinomas. Int J Cancer 2006;119(6):1345-53
   Web of Science ®Google Scholar
• Lohr M, Schmidt C, Ringel J, et al. Transforming growth factor-beta1 induces desmoplasia in an experimental model of human pancreatic carcinoma. Cancer Res 2001;61(2):550-5
   PubMed Web of Science ®Google Scholar
• Shek FW, Benyon RC, Walker FM, et al. Expression of transforming growth factor-beta 1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis. Am J Pathol 2002;160(5):1787-98
   PubMed Web of Science ®Google Scholar
• Sato N, Maehara N, Goggins M. Gene expression profiling of tumor-stromal interactions between pancreatic cancer cells and stromal fibroblasts. Cancer Res 2004;64(19):6950-6
   PubMed Web of Science ®Google Scholar
• Omary MB, Lugea A, Lowe AW, Pandol SJ. The pancreatic stellate cell: a star on the rise in pancreatic diseases. J Clin Invest 2007;117(1):50-9
   PubMed Web of Science ®Google Scholar
• Schneiderhan W, Diaz F, Fundel M, et al. Pancreatic stellate cells are an important source of MMP-2 in human pancreatic cancer and accelerate tumor progression in a murine xenograft model and CAM assay. J Cell Sci 2007;120(Pt 3):512-9
   Web of Science ®Google Scholar
• Erkan M, Kleeff J, Gorbachevski A, et al. Periostin creates a tumor-supportive microenvironment in the pancreas by sustaining fibrogenic stellate cell activity. Gastroenterol 2007;132(4):1447-64
   PubMed Web of Science ®Google Scholar
• Masamune A, Kikuta K, Watanabe T, et al. Fibrinogen induces cytokine and collagen production in pancreatic stellate cells. Gut 2008
   Google Scholar
• Vonlaufen A, Phillips PA, Xu Z, et al. Pancreatic stellate cells and pancreatic cancer cells: an unholy alliance. Cancer Res 2008;68(19):7707-10
   PubMed Web of Science ®Google Scholar
• Manapov F, Muller P, Rychly J. Translocation of p21(Cip1/WAF1) from the nucleus to the cytoplasm correlates with pancreatic myofibroblast to fibroblast cell conversion. Gut 2005;54(6):814-22
   PubMed Web of Science ®Google Scholar
• Jiang HB, Xu M, Wang XP. Pancreatic stellate cells promote proliferation and invasiveness of human pancreatic cancer cells via galectin-3. World J Gastroenterol 2008;14(13):2023-8
   PubMed Web of Science ®Google Scholar
• Kanno A, Satoh K, Masamune A, et al. Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells. Int J Cancer 2008;122(12):2707-18
   PubMed Web of Science ®Google Scholar
• Bellahcene A, Castronovo V, Ogbureke KU, et al. Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer. Nat Rev Cancer 2008;8(3):212-26
   PubMed Web of Science ®Google Scholar
• Pantel K, Brakenhoff RH. Dissecting the metastatic cascade. Nat Rev Cancer 2004;4(6):448-56
   PubMed Web of Science ®Google Scholar
• Lyons AB, Parish CR. Determination of lymphocyte division by flow cytometry. J Immunol Methods 1994;171(1):131-7
   PubMed Web of Science ®Google Scholar
• Nolte T, Kaufmann W, Schorsch F, et al. Standardized assessment of cell proliferation: the approach of the RITA-CEPA working group. Exp Toxicol Pathol 2005;57(2):91-103
   PubMed Web of Science ®Google Scholar
• Heatwole VM. TUNEL assay for apoptotic cells. Methods Mol Biol 1999;115:141-8
   PubMedGoogle Scholar
• Aitken RJ, De luliis GN. Value of DNA integrity assays for fertility evaluation. Soc Reprod Fertil Suppl 2007;65:81-92
   PubMedGoogle Scholar
• Albini A, Iwamoto Y, Kleinman HK, et al. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 1987;47(12):3239-45
   PubMed Web of Science ®Google Scholar
• Lee J, Cuddihy MJ, Kotov NA. Three-dimensional cell culture matrices: state of the art. Tissue Eng Part B Rev 2008;14(1):61-86
   PubMed Web of Science ®Google Scholar
• Staton CA, Stribbling SM, Tazzyman S, et al. Current methods for assaying angiogenesis in vitro and in vivo. Int J Exp Pathol 2004;85(5):233-48
   PubMed Web of Science ®Google Scholar
• Caldwell JS. Cancer cell-based genomic and small molecule screens. Adv Cancer Res 2007;96:145-73
   PubMed Web of Science ®Google Scholar
• Kaelin WG Jr. The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer 2005;5(9):689-98
   PubMed Web of Science ®Google Scholar
• Hartwell LH, Szankasi P, Roberts CJ, et al. Integrating genetic approaches into the discovery of anticancer drugs. Sci 1997;278(5340):1064-8
   Web of Science ®Google Scholar
• Wang H, Han H, Von Hoff DD. Identification of an agent selectively targeting DPC4 (Deleted in Pancreatic Cancer Locus 4)-deficient pancreatic cancer cells. Cancer Res 2006;66(19):9722-30
   PubMed Web of Science ®Google Scholar
• Romer J, Curran T. Targeting medulloblastoma: small-molecule inhibitors of the Sonic Hedgehog pathway as potential cancer therapeutics. Cancer Res 2005;65(12):4975-8
   PubMed Web of Science ®Google Scholar
• Jones S, Chen WD, Parmigiani G, et al. Comparative lesion sequencing provides insights into tumor evolution. Proc Natl Acad Sci USA 2008;105(11):4283-8
   PubMed Web of Science ®Google Scholar
• Hansel DE, Kern SE, Hruban RH. Molecular pathogenesis of pancreatic cancer. Annu Rev Genomics Hum Genet 2003;4:237-56
   PubMed Web of Science ®Google Scholar
• Yamano M, Fujii H, Takagaki T, et al. Genetic progression and divergence in pancreatic carcinoma. Am J Pathol 2000;156(6):2123-33
   PubMed Web of Science ®Google Scholar
• van Heek NT, Meeker AK, Kern SE, et al. Telomere shortening is nearly universal in pancreatic intraepithelial neoplasia. Am J Pathol 2002;161(5):1541-7
   PubMed Web of Science ®Google Scholar
• Luttges J, Galehdari H, Brocker V, et al. Allelic loss is often the first hit in the biallelic inactivation of the p53 and DPC4 genes during pancreatic carcinogenesis. Am J Pathol 2001;158(5):1677-83
   PubMed Web of Science ®Google Scholar
• Wood LD, Parsons DW, Jones S, et al. The genomic landscapes of human breast and colorectal cancers. Sci 2007;318(5853):1108-13
   Web of Science ®Google Scholar
• Hingorani SR, Petricoin EF, Maitra A, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 2003;4(6):437-50
   PubMed Web of Science ®Google Scholar
• Bardeesy N, Sharpless NE. RAS unplugged: negative feedback and oncogene-induced senescence. Cancer Cell 2006;10(6):451-3
   PubMed Web of Science ®Google Scholar
• Hingorani SR, Wang L, Multani AS, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005;7(5):469-83
   PubMed Web of Science ®Google Scholar
• Bardeesy N, Aguirre AJ, Chu GC, et al. Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc Natl Acad Sci USA 2006;103(15):5947-52
   PubMed Web of Science ®Google Scholar
• Aguirre AJ, Bardeesy N, Sinha M, et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev 2003;17(24):3112-26
   PubMed Web of Science ®Google Scholar
• Feldmann G, Habbe N, Dhara S, et al. Hedgehog inhibition prolongs survival in a genetically engineered mouse model of pancreatic cancer. Gut 2008;57(10):1420-30
   PubMed Web of Science ®Google Scholar
• Ijichi H, Chytil A, Gorska AE, et al. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Genes Dev 2006;20(22):3147-60
   PubMed Web of Science ®Google Scholar
• Hahn WC, Weinberg RA. Rules for making human tumor cells. N Engl J Med 2002;347(20):1593-603
   PubMed Web of Science ®Google Scholar
• Renan MJ. How many mutations are required for tumorigenesis? Implications from human cancer data. Mol Carcinog 1993;7(3):139-46
   PubMed Web of Science ®Google Scholar
• Campbell PM, Groehler AL, Lee KM, et al. K-Ras promotes growth transformation and invasion of immortalized human pancreatic cells by Raf and phosphatidylinositol 3-kinase signaling. Cancer Res 2007;67(5):2098-106
   PubMed Web of Science ®Google Scholar
• Lee KM, Nguyen C, Ulrich AB, et al. Immortalization with telomerase of the Nestin-positive cells of the human pancreas. Biochem Biophys Res Commun 2003;301(4):1038-44
   PubMed Web of Science ®Google Scholar
• Hahn WC, Counter CM, Lundberg AS, et al. Creation of human tumour cells with defined genetic elements. Nat 1999;400(6743):464-8
   Google Scholar
• Counter CM, Hahn WC, Wei W, et al. Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization. Proc Natl Acad Sci USA 1998;95(25):14723-8
   PubMed Web of Science ®Google Scholar
• Feldmann G, Beaty R, Hruban RH, Maitra A. Molecular genetics of pancreatic intraepithelial neoplasia. J Hepatobiliary Pancreat Surg 2007;14(3):224-32
   PubMedGoogle Scholar
• Feldmann G, Maitra A. Molecular pathology of precursor lesions of pancreatic cancer: pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm (MCN) In: Neoptolemos J, Abbruzzese J, Buchler M, Urrutia R, editors. Handbook of Pancreatic Cancer. New York: Springer 2009. In press
   Google Scholar
• Mao J, Ligon KL, Rakhlin EY, et al. A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Cancer Res 2006;66(20):10171-8
   PubMed Web of Science ®Google Scholar
• Izeradjene K, Combs C, Best M, et al. Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell 2007;11(3):229-43
   PubMed Web of Science ®Google Scholar
• Siveke JT, Einwachter H, Sipos B, et al. Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN. Cancer Cell 2007;12(3):266-79
   PubMed Web of Science ®Google Scholar
• Hahn H, Wicking C, Zaphiropoulous PG, et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 1996;85(6):841-51
   PubMed Web of Science ®Google Scholar
• Berman DM, Karhadkar SS, Hallahan AR, et al. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science 2002;297(5586):1559-61
   PubMed Web of Science ®Google Scholar
• Kimura H, Stephen D, Joyner A, Curran T. Gli1 is important for medulloblastoma formation in Ptc1+/-mice. Oncogene 2005;24(25):4026-36
   PubMed Web of Science ®Google Scholar
• Berman DM, Karhadkar SS, Maitra A, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nat 2003;425(6960):846-51
   Google Scholar
• Watkins DN, Berman DM, Burkholder SG, et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nat 2003;422(6929):313-7
   Google Scholar
• Rubin LL, de Sauvage FJ. Targeting the Hedgehog pathway in cancer. Nat Rev Drug Discov 2006;5(12):1026-33
   PubMed Web of Science ®Google Scholar
• Thayer SP, Di Magliano MP, Heiser PW, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nat 2003;425(6960):851-6
   Google Scholar
• Binns W, James LF, Shupe JL, Everett G. A congenital cyclopian-type malformation in lambs induced by maternal ingestion of a range plant, veratrum californicum. Am J Vet Res 1963;24:1164-75
   PubMed Web of Science ®Google Scholar
• Keeler RF, Binns W. Teratogenic compounds of Veratrum californicum (Durand). V. Comparison of cyclopian effects of steroidal alkaloids from the plant and structurally related compounds from other sources. Teratol 1968;1(1):5-10
   PubMedGoogle Scholar
• Williams JA, Guicherit OM, Zaharian BI, et al. Identification of a small molecule inhibitor of the hedgehog signaling pathway: effects on basal cell carcinoma-like lesions. Proc Natl Acad Sci USA 2003;100(8):4616-21
   PubMed Web of Science ®Google Scholar
• Taylor FR, Wen D, Garber EA, et al. Enhanced potency of human Sonic hedgehog by hydrophobic modification. Biochem 2001;40(14):4359-71
   Web of Science ®Google Scholar
• Gabay L, Lowell S, Rubin LL, Anderson DJ. Deregulation of dorsoventral patterning by FGF confers trilineage differentiation capacity on CNS stem cells in vitro. Neuron 2003;40(3):485-99
   PubMed Web of Science ®Google Scholar
• Taipale J, Chen JK, Cooper MK, et al. Effects of oncogenic mutations in smoothened and patched can be reversed by cyclopamine. Nat 2000;406(6799):1005-9
   Google Scholar
• Pepinsky RB, Zeng C, Wen D, et al. Identification of a palmitic acid-modified form of human Sonic hedgehog. J Biol Chem 1998;273(22):14037-45
   PubMed Web of Science ®Google Scholar
• Available from: www.clinicaltrials.gov
   Google Scholar
• Hotz HG, Reber HA, Hotz B, et al. Angiogenesis inhibitor TNP-470 reduces human pancreatic cancer growth. J Gastrointest Surg 2001;5(2):131-8
   PubMed Web of Science ®Google Scholar
• Kawarada Y, Ishikura H, Kishimoto T, et al. Inhibitory effects of the antiangiogenic 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
   PubMed Web of Science ®Google Scholar
• Kato H, Ishikura H, Kawarada Y, et al. Anti-angiogenic treatment for peritoneal dissemination of pancreas adenocarcinoma: a study using TNP-470. Jpn J Cancer Res 2001;92(1):67-73
   PubMedGoogle Scholar
• Solorzano CC, Baker CH, Bruns CJ, et al. Inhibition of growth and metastasis of human pancreatic cancer growing in nude mice by PTK 787/ZK222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. Cancer Biother Radiopharm 2001;16(5):359-70
   PubMed Web of Science ®Google Scholar
• Bruns CJ, Shrader M, Harbison MT, et al. Effect of the vascular endothelial growth factor receptor-2 antibody DC101 plus gemcitabine on growth, metastasis and angiogenesis of human pancreatic cancer growing orthotopically in nude mice. Int J Cancer 2002;102(2):101-8
   PubMed Web of Science ®Google Scholar
• Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285(21):1182-6
   PubMed Web of Science ®Google Scholar
• Burris H 3rd, Rocha-Lima C. New therapeutic directions for advanced pancreatic cancer: targeting the epidermal growth factor and vascular endothelial growth factor pathways. oncologist 2008;13(3):289-98
   PubMed Web of Science ®Google Scholar
• van Es JH, Clevers H. Notch and Wnt inhibitors as potential new drugs for intestinal neoplastic disease. Trends Mol Med 2005;11(11):496-502
   PubMed Web of Science ®Google Scholar
• Kopan R, Goate A. A common enzyme connects notch signaling and Alzheimer's disease. Genes Dev 2000;14(22):2799-806
   PubMed Web of Science ®Google Scholar
• van Es JH, van Gijn ME, Riccio O, et al. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nat 2005;435(7044):959-63
   Google Scholar
• Mullendore M, Koorstra JB, Li Y, et al. Ligand-dependent Notch signaling is involved in tumor initiation and tumor maintenance in pancreatic cancer. Clin Cancer Res 2009. In press
   PubMedGoogle Scholar
• Dihlmann S, von Knebel Doeberitz M. Wnt/beta-catenin-pathway as a molecular target for future anti-cancer therapeutics. Int J Cancer 2005;113(4):515-24
   PubMed Web of Science ®Google Scholar
• Lepourcelet M, Chen YN, France DS, et al. Small-molecule antagonists of the oncogenic Tcf/beta-catenin protein complex. Cancer Cell 2004;5(1):91-102
   PubMed Web of Science ®Google Scholar
• Lahn M, Kloeker S, Berry BS. TGF-beta inhibitors for the treatment of cancer. Expert Opin Investig Drugs 2005;14(6):629-43
   PubMed Web of Science ®Google Scholar
• Jimeno A, Tan AC, Coffa J, et al. Coordinated epidermal growth factor receptor pathway gene overexpression predicts epidermal growth factor receptor inhibitor sensitivity in pancreatic cancer. Cancer Res 2008;68(8):2841-9
   PubMed Web of Science ®Google Scholar
• Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007;25(15):1960-6
   PubMed Web of Science ®Google Scholar
• Laurent-Puig P, Taieb J. Lessons from tarceva in pancreatic cancer: where are we now, and how should future trials be designed in pancreatic cancer? Curr Opin Oncol 2008;20(4):454-8
   PubMed Web of Science ®Google Scholar
• Ng R, Chen EX. Sorafenib (BAY 43-9006): review of clinical development. Curr Clin Pharmacol 2006;1(3):223-8
   PubMedGoogle Scholar
• Wilhelm SM, Adnane L, Newell P, et al. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther 2008;7(10):3129-40
   PubMed Web of Science ®Google Scholar
• Cheng GZ, Park S, Shu S, et al. Advances of AKT pathway in human oncogenesis and as a target for anti-cancer drug discovery. Curr Cancer Drug Targets 2008;8(1):2-6
   PubMed Web of Science ®Google Scholar
• Mita M, Sankhala K, Abdel-Karim I, et al. Deforolimus (AP23573) a novel mTOR inhibitor in clinical development. Expert Opin Investig Drugs 2008;17(12):1947-54
   PubMed Web of Science ®Google Scholar
• Rini BI. Temsirolimus, an inhibitor of mammalian target of rapamycin. Clin Cancer Res 2008;14(5):1286-90
   PubMed Web of Science ®Google Scholar
• Asano T, Yao Y, Zhu J, et al. The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferation. Biochem Biophys Res Commun 2005;331(1):295-302
   PubMed Web of Science ®Google Scholar
• Wolpin BM, Hezel AF, Abrams T, et al. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol 2009;27(2):193-8
   PubMed Web of Science ®Google Scholar