References Singh Et Al

Singh et al

References:

1.Pancreatic Cancer [database on the Internet]. WebMed. 2009 [cited 2010]. Available from:

2.Landis SH, Murray T, Bolden S, et al. Cancer statistics, 1998. CA Cancer J Clin. 1998;48(1):6-29.

3.Fisher WE, Berger DH. Angiogenesis and antiangiogenic strategies in pancreatic cancer. Int J Gastrointest Cancer. 2003;33(1):79-88.

4.Hruban RH, Goggins M, Parsons J, et al. Progression model for pancreatic cancer. Clin Cancer Res. 2000;6(8):2969-72.

5.Almoguera C, Shibata D, Forrester K, et al. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53(4):549-54.

6.Tada M, Omata M, Kawai S, et al. Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma. Cancer Res. 1993;53(11):2472-4.

7.Klimstra DS, Longnecker DS. K-ras mutations in pancreatic ductal proliferative lesions. Am J Pathol. 1994;145(6):1547-50.

8.Rozenblum E, Schutte M, Goggins M, et al. Tumor-suppressive pathways in pancreatic carcinoma. Cancer Res. 1997;57(9):1731-4.

9.Campbell SL, Khosravi-Far R, Rossman KL, et al. Increasing complexity of Ras signaling. Oncogene. 1998;17(11 Reviews):1395-413.

10.Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer. 2003;3(6):459-65.

11.Matsuo Y, Campbell PM, Brekken RA, et al. K-Ras promotes angiogenesis mediated by immortalized human pancreatic epithelial cells through mitogen-activated protein kinase signaling pathways. Mol Cancer Res. 2009;7(6):799-808.

12.Fleming JB, Shen GL, Holloway SE, et al. Molecular consequences of silencing mutant K-ras in pancreatic cancer cells: justification for K-ras-directed therapy. Mol Cancer Res. 2005;3(7):413-23.

13.Ji B, Tsou L, Wang H, et al. Ras activity levels control the development of pancreatic diseases. Gastroenterology. 2009;137(3):1072-82, 82 e1-6.

14.Whitcomb DC, Pogue-Geile K. Pancreatitis as a risk for pancreatic cancer. Gastroenterol Clin North Am. 2002;31(2):663-78.

15.Guerra C, Schuhmacher AJ, Canamero M, et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell. 2007;11(3):291-302.

16.Hezel AF, Kimmelman AC, Stanger BZ, et al. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 2006;20(10):1218-49.

17.Omer CA, Kohl NE. CA1A2X-competitive inhibitors of farnesyltransferase as anti-cancer agents. Trends Pharmacol Sci. 1997;18(11):437-44.

18.Van Cutsem E, van de Velde H, Karasek P, et al. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol. 2004;22(8):1430-8.

19.Singh A, Greninger P, Rhodes D, et al. A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival. Cancer Cell. 2009;15(6):489-500.

20.Scholl C, Frohling S, Dunn IF, et al. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell. 2009;137(5):821-34.

21.Lee SH, Lee SJ, Jung YS, et al. Blocking of p53-Snail binding, promoted by oncogenic K-Ras, recovers p53 expression and function. Neoplasia. 2009;11(1):22-31, 6p following

22.Schmidt RL, Park CH, Ahmed AU, et al. Inhibition of RAS-mediated transformation and tumorigenesis by targeting the downstream E3 ubiquitin ligase seven in absentia homologue. Cancer Res. 2007;67(24):11798-810.

23.Rejiba S, Wack S, Aprahamian M, et al. K-ras oncogene silencing strategy reduces tumor growth and enhances gemcitabine chemotherapy efficacy for pancreatic cancer treatment. Cancer Sci. 2007;98(7):1128-36.

24.Shi XH, Liang ZY, Ren XY, et al. Combined silencing of K-ras and Akt2 oncogenes achieves synergistic effects in inhibiting pancreatic cancer cell growth in vitro and in vivo. Cancer Gene Ther. 2009;16(3):227-36.

25.Jasinski P, Zwolak P, Terai K, et al. Novel Ras pathway inhibitor induces apoptosis and growth inhibition of K-ras-mutated cancer cells in vitro and in vivo. Transl Res. 2008;152(5):203-12.

26.Lee SH, Lee SJ, Chung JY, et al. p53, secreted by K-Ras-Snail pathway, is endocytosed by K-Ras-mutated cells; implication of target-specific drug delivery and early diagnostic marker. Oncogene. 2009;28(19):2005-14.

27.Lu X, Xu T, Qian J, et al. Detecting K-ras and p53 gene mutation from stool and pancreatic juice for diagnosis of early pancreatic cancer. Chin Med J (Engl). 2002;115(11):1632-6.

28.Berthelemy P, Bouisson M, Escourrou J, et al. Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancreatic cancer. Ann Intern Med. 1995;123(3):188-91.

29.Boadas J, Mora J, Urgell E, et al. Clinical usefulness of K-ras gene mutation detection and cytology in pancreatic juice in the diagnosis and screening of pancreatic cancer. Eur J Gastroenterol Hepatol. 2001;13(10):1153-9.

30.Olsen CC, Schefter TE, Chen H, et al. Results of a phase I trial of 12 patients with locally advanced pancreatic carcinoma combining gefitinib, paclitaxel, and 3-dimensional conformal radiation: report of toxicity and evaluation of circulating K-ras as a potential biomarker of response to therapy. Am J Clin Oncol. 2009;32(2):115-21.

31.Serrano J, Goebel SU, Peghini PL, et al. Alterations in the p16INK4a/CDKN2A tumor suppressor gene in gastrinomas. J Clin Endocrinol Metab. 2000;85(11):4146-56.

32.Sherr CJ. Parsing Ink4a/Arf: "pure" p16-null mice. Cell. 2001;106(5):531-4.

33.Goldstein AM, Fraser MC, Struewing JP, et al. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N Engl J Med. 1995;333(15):970-4.

34.Whelan AJ, Bartsch D, Goodfellow PJ. Brief report: a familial syndrome of pancreatic cancer and melanoma with a mutation in the CDKN2 tumor-suppressor gene. N Engl J Med. 1995;333(15):975-7.

35.Goldstein AM, Struewing JP, Chidambaram A, et al. Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations. J Natl Cancer Inst. 2000;92(12):1006-10.

36.Lynch HT, Brand RE, Hogg D, et al. Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: the familial atypical mole melanoma-pancreatic carcinoma syndrome. Cancer. 2002;94(1):84-96.

37.de Snoo FA, Bishop DT, Bergman W, et al. Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma families. Clin Cancer Res. 2008;14(21):7151-7.

38.Chen J, Li D, Wei C, et al. Aurora-A and p16 polymorphisms contribute to an earlier age at diagnosis of pancreatic cancer in Caucasians. Clin Cancer Res. 2007;13(10):3100-4.

39.Hustinx SR, Leoni LM, Yeo CJ, et al. Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion. Mod Pathol. 2005;18(7):959-63.

40.Gerdes B, Ramaswamy A, Kersting M, et al. p16(INK4a) alterations in chronic pancreatitis-indicator for high-risk lesions for pancreatic cancer. Surgery. 2001;129(4):490-7.

41.Fukushima N, Sato N, Ueki T, et al. Aberrant methylation of preproenkephalin and p16 genes in pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma. Am J Pathol. 2002;160(5):1573-81.

42.Ohtsubo K, Watanabe H, Yamaguchi Y, et al. Abnormalities of tumor suppressor gene p16 in pancreatic carcinoma: immunohistochemical and genetic findings compared with clinicopathological parameters. J Gastroenterol. 2003;38(7):663-71.

43.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 U S A. 2006;103(15):5947-52.

44.Tsiambas E, Karameris A, Gourgiotis S, et al. Simultaneous deregulation of p16 and cyclin D1 genes in pancreatic ductal adenocarcinoma: a combined immunohistochemistry and image analysis study based on tissue microarrays. J BUON. 2007;12(2):261-7.

45.Salek C, Benesova L, Zavoral M, et al. Evaluation of clinical relevance of examining K-ras, p16 and p53 mutations along with allelic losses at 9p and 18q in EUS-guided fine needle aspiration samples of patients with chronic pancreatitis and pancreatic cancer. World J Gastroenterol. 2007;13(27):3714-20.

46.Bian Y, Matsubayashi H, Li CP, et al. Detecting low-abundance p16 and p53 mutations in pancreatic juice using a novel assay: heteroduplex analysis of limiting dilution PCRs. Cancer Biol Ther. 2006;5(10):1392-9.

47.Jeong J, Park YN, Park JS, et al. Clinical significance of p16 protein expression loss and aberrant p53 protein expression in pancreatic cancer. Yonsei Med J. 2005;46(4):519-25.

48.Klump B, Hsieh CJ, Nehls O, et al. Methylation status of p14ARF and p16INK4a as detected in pancreatic secretions. Br J Cancer. 2003;88(2):217-22.

49.Talar-Wojnarowska R, Gasiorowska A, Smolarz B, et al. Usefulness of p16 and K-ras mutation in pancreatic adenocarcinoma and chronic pancreatitis differential diagnosis. J Physiol Pharmacol. 2004;55 Suppl 2:129-38.

50.Halloran CM, Ghaneh P, Shore S, et al. 5-Fluorouracil or gemcitabine combined with adenoviral-mediated reintroduction of p16INK4A greatly enhanced cytotoxicity in Panc-1 pancreatic adenocarcinoma cells. J Gene Med. 2004;6(5):514-25.

51.Schulz P, Scholz A, Rexin A, et al. Inducible re-expression of p16 in an orthotopic mouse model of pancreatic cancer inhibits lymphangiogenesis and lymphatic metastasis. Br J Cancer. 2008;99(1):110-7.

52.Spillare EA, Okamoto A, Hagiwara K, et al. Suppression of growth in vitro and tumorigenicity in vivo of human carcinoma cell lines by transfected p16INK4. Mol Carcinog. 1996;16(1):53-60.

53.Rocco JW, Li D, Liggett WH, Jr., et al. p16INK4A adenovirus-mediated gene therapy for human head and neck squamous cell cancer. Clin Cancer Res. 1998;4(7):1697-704.

54.Chen F, Li Y, Lu Z, et al. Adenovirus-mediated Ink4a/ARF gene transfer significantly suppressed the growth of pancreatic carcinoma cells. Cancer Biol Ther. 2005;4(12):1348-54.

55.Hosotani R, Miyamoto Y, Fujimoto K, et al. Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in mice. Clin Cancer Res. 2002;8(4):1271-6.

56.Vousden KH. Switching from life to death: the Miz-ing link between Myc and p53. Cancer Cell. 2002;2(5):351-2.

57.Seoane J, Le HV, Massague J. Myc suppression of the p21(Cip1) Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature. 2002;419(6908):729-34.

58.Haupt Y, Maya R, Kazaz A, et al. Mdm2 promotes the rapid degradation of p53. Nature. 1997;387(6630):296-9.

59.Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 1997;420(1):25-7.

60.Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature. 1997;387(6630):299-303.

61.Midgley CA, Lane DP. p53 protein stability in tumour cells is not determined by mutation but is dependent on Mdm2 binding. Oncogene. 1997;15(10):1179-89.

62.Issaeva N, Friedler A, Bozko P, et al. Rescue of mutants of the tumor suppressor p53 in cancer cells by a designed peptide. Proc Natl Acad Sci U S A. 2003;100(23):13303-7.

63.Selivanova G, Wiman KG. Reactivation of mutant p53: molecular mechanisms and therapeutic potential. Oncogene. 2007;26(15):2243-54.

64.Shieh SY, Ikeda M, Taya Y, et al. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell. 1997;91(3):325-34.

65.Scarpa A, Capelli P, Mukai K, et al. Pancreatic adenocarcinomas frequently show p53 gene mutations. Am J Pathol. 1993;142(5):1534-43.

66.Hainaut P, Hollstein M. p53 and human cancer: the first ten thousand mutations. Adv Cancer Res. 2000;77:81-137.

67.Nio Y, Dong M, Uegaki K, et al. Comparative significance of p53 and WAF/1-p21 expression on the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma of the pancreas. Pancreas. 1999;18(2):117-26.

68.Jinfeng M, Kimura W, Sakurai F, et al. Prognostic role of angiogenesis and its correlations with thymidine phosphorylase and p53 expression in ductal adenocarcinoma of the pancreas. Hepatogastroenterology. 2007;54(78):1635-40.

69.Hermanova M, Karasek P, Nenutil R, et al. Clinicopathological correlations of cyclooxygenase-2, MDM2, and p53 expressions in surgically resectable pancreatic invasive ductal adenocarcinoma. Pancreas. 2009;38(5):565-71.

70.Salek C, Minarikova P, Benesova L, et al. Mutation status of K-ras, p53 and allelic losses at 9p and 18q are not prognostic markers in patients with pancreatic cancer. Anticancer Res. 2009;29(5):1803-10.

71.Petty RD, Cree IA, Sutherland LA, et al. Expression of the p53 tumour suppressor gene product is a determinant of chemosensitivity. Biochem Biophys Res Commun. 1994;199(1):264-70.

72.Fan S, Smith ML, Rivet DJ, 2nd, et al. Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and pentoxifylline. Cancer Res. 1995;55(8):1649-54.

73.Mueller H, Eppenberger U. The dual role of mutant p53 protein in chemosensitivity of human cancers. Anticancer Res. 1996;16(6B):3845-8.

74.Sigal A, Rotter V. Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome. Cancer Res. 2000;60(24):6788-93.

75.Morton JP, Timpson P, Karim SA, et al. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci U S A. 2010;107(1):246-51.

76.Yan W, Liu G, Scoumanne A, et al. Suppression of inhibitor of differentiation 2, a target of mutant p53, is required for gain-of-function mutations. Cancer Res. 2008;68(16):6789-96.

77.Li Y, Prives C. Are interactions with p63 and p73 involved in mutant p53 gain of oncogenic function? Oncogene. 2007;26(15):2220-5.

78.Zhou R, Shanas R, Nelson MA, et al. Increased expression of the heterogeneous nuclear ribonucleoprotein K in pancreatic cancer and its association with the mutant p53. Int J Cancer. 2010;126(2):395-404.

79.Taghavi MH, Davoodi J. Restoration of p53 functions suppresses tumor growth of pancreatic cells with different p53 status. Cancer Biother Radiopharm. 2007;22(3):322-32.

80.Singh PK, Behrens ME, Eggers JP, et al. Phosphorylation of MUC1 by Met modulates interaction with p53 and MMP1 expression. J Biol Chem. 2008;283(40):26985-95.

81.Hermanova M, Trna J, Nenutil R, et al. Expression of COX-2 is associated with accumulation of p53 in pancreatic cancer: analysis of COX-2 and p53 expression in premalignant and malignant ductal pancreatic lesions. Eur J Gastroenterol Hepatol. 2008;20(8):732-9.

82.Sui X, Shin S, Zhang R, et al. Hdm2 is regulated by K-Ras and mediates p53-independent functions in pancreatic cancer cells. Oncogene. 2009;28(5):709-20.

83.Morton JP, Klimstra DS, Mongeau ME, et al. Trp53 deletion stimulates the formation of metastatic pancreatic tumors. Am J Pathol. 2008;172(4):1081-7.

84.Kang R, Tang D, Schapiro NE, et al. The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ. 2010;17(4):666-76.

85.Ji Q, Hao X, Zhang M, et al. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS One. 2009;4(8):e6816.

86.Chang TC, Wentzel EA, Kent OA, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26(5):745-52.

87.Deramaudt TB, Takaoka M, Upadhyay R, et al. N-cadherin and keratinocyte growth factor receptor mediate the functional interplay between Ki-RASG12V and p53V143A in promoting pancreatic cell migration, invasion, and tissue architecture disruption. Mol Cell Biol. 2006;26(11):4185-200.

88.Lancaster J, Wooster R, Mangion J, et al. BRCA2 mutations in primary breast and ovarian cancers. Nature Genet 1996;13:238-40.

89.Edwards S, Kote-Jarai Z, Meitz J, et al. Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. J Hum Genet. 2003;72 1-12.

90.Lawniczak M, Gawin A, Bialek A, et al. Is there any relationship between BRCA1 gene mutation and pancreatic cancer development? Pol Arch Med Wewn. 2008;118(11):645-9.

91.Al-Sukhni W, Rothenmund H, Borgida AE, et al. Germline BRCA1 mutations predispose to pancreatic adenocarcinoma. Hum Genet. 2008;124(3):271-8.

92.Rajan JV, Wang M, Marquis ST, et al. Brca2 is coordinately regulated with Brca1 during proliferation and differentiation in mammary epithelial cells. Proc Natl Acad Sci U S A. 1996;93(23):13078-83.

93.Milner J, Ponder B, Hughes-Davies L, et al. Transcriptional activation functions in BRCA2. Nature. 1997;386(6627):772-3.

94.Daniels MJ, Wang Y, Lee M, et al. Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2. Science. 2004;306(5697):876-9.

95.Sharan SK, Morimatsu M, Albrecht U, et al. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature. 1997;386(6627):804-10.

96.Xia F, Taghian DG, DeFrank JS, et al. Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining. Proc Natl Acad Sci U S A. 2001;98(15):8644-9.

97.Yang H, Li Q, Fan J, et al. The BRCA2 homologue Brh2 nucleates RAD51 filament formation at a dsDNA-ssDNA junction. Nature. 2005;433(7026):653-7.

98.Chen J, Silver DP, Walpita D, et al. Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. Mol Cell. 1998;2(3):317-28.

99.Hiripi E, Lorenzo Bermejo J, Li X, et al. Familial association of pancreatic cancer with other malignancies in Swedish families. Br J Cancer. 2009;101(10):1792-7.

100.Shi C, Hruban RH, Klein AP. Familial pancreatic cancer. Arch Pathol Lab Med. 2009;133(3):365-74.

101.Stracci F, D'Alo D, Cassetti T, et al. Incidence of multiple primary malignancies in women diagnosed with breast cancer. Eur J Gynaecol Oncol. 2009;30(6):661-3.

102.Bartsch DK, Langer P, Habbe N, et al. Clinical and genetic analysis of 18 pancreatic carcinoma/melanoma-prone families. Clin Genet. 2009.

103.van der Heijden MS, Yeo CJ, Hruban RH, et al. Fanconi anemia gene mutations in young-onset pancreatic cancer. Cancer Res. 2003;63(10):2585-8.

104.Couch FJ, Johnson MR, Rabe K, et al. Germ line Fanconi anemia complementation group C mutations and pancreatic cancer. Cancer Res. 2005;65(2):383-6.

105.Dagan E, Shochat T. Quality of life in asymptomatic BRCA1/2 mutation carriers. Prev Med. 2009;48(2):193-6.

106.Ferrone CR, Levine DA, Tang LH, et al. BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. J Clin Oncol. 2009;27(3):433-8.

107.Chalasani P, Kurtin S, Dragovich T. Response to a third-line mitomycin C (MMC)-based chemotherapy in a patient with metastatic pancreatic adenocarcinoma carrying germline BRCA2 mutation. JOP. 2008;9(3):305-8.

108.James E, Waldron-Lynch MG, Saif MW. Prolonged survival in a patient with BRCA2 associated metastatic pancreatic cancer after exposure to camptothecin: a case report and review of literature. Anticancer Drugs. 2009;20(7):634-8.

109.Edwards SL, Brough R, Lord CJ, et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008;451(7182):1111-5.

110.Sakai W, Swisher EM, Karlan BY, et al. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature. 2008;451(7182):1116-20.

111.Liu F, Pouponnot C, Massague J. Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-inducible transcriptional complexes. Genes Dev. 1997;11(23):3157-67.

112.Nakao A, Afrakhte M, Moren A, et al. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature. 1997;389(6651):631-5.

113.Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature. 1997;390(6659):465-71.

114.Robson CN, Gnanapragasam V, Byrne RL, et al. Transforming growth factor-beta1 up-regulates p15, p21 and p27 and blocks cell cycling in G1 in human prostate epithelium. J Endocrinol. 1999;160(2):257-66.

115.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.

116.van Heek T, Rader AE, Offerhaus GJ, et al. K-ras, p53, and DPC4 (MAD4) alterations in fine-needle aspirates of the pancreas: a molecular panel correlates with and supplements cytologic diagnosis. Am J Clin Pathol. 2002;117(5):755-65.

117.Hahn SA, Schutte M, Hoque AT, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 1996;271(5247):350-3.

118.Schutte M, Hruban RH, Hedrick L, et al. DPC4 gene in various tumor types. Cancer Res. 1996;56(11):2527-30.

119.Hruban RH, Goggins M, Kern SE. Molecular genetics and related developments in pancreatic cancer. Curr Opin Gastroenterol. 1999;15(5):404-9.

120.Iacobuzio-Donahue CA, Fu B, Yachida S, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009;27(11):1806-13.

121.Chow JY, Dong H, Quach KT, et al. TGF-beta mediates PTEN suppression and cell motility through calcium-dependent PKC-alpha activation in pancreatic cancer cells. Am J Physiol Gastrointest Liver Physiol. 2008;294(4):G899-905.

122.Zhao S, Venkatasubbarao K, Lazor JW, et al. Inhibition of STAT3 Tyr705 phosphorylation by Smad4 suppresses transforming growth factor beta-mediated invasion and metastasis in pancreatic cancer cells. Cancer Res. 2008;68(11):4221-8.

123.Xu X, Ehdaie B, Ohara N, et al. Synergistic action of Smad4 and Pten in suppressing pancreatic ductal adenocarcinoma formation in mice. Oncogene. 2010;29(5):674-86.

124.Bardeesy N, Cheng KH, Berger JH, et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev. 2006;20(22):3130-46.

125.Hua Z, Zhang YC, Hu XM, et al. Loss of DPC4 expression and its correlation with clinicopathological parameters in pancreatic carcinoma. World J Gastroenterol. 2003;9(12):2764-7.

126.Blackford A, Serrano OK, Wolfgang CL, et al. SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clin Cancer Res. 2009;15(14):4674-9.

127.Ali S, Cohen C, Little JV, et al. The utility of SMAD4 as a diagnostic immunohistochemical marker for pancreatic adenocarcinoma, and its expression in other solid tumors. Diagn Cytopathol. 2007;35(10):644-8.

128.Yasutome M, Gunn J, Korc M. Restoration of Smad4 in BxPC3 pancreatic cancer cells attenuates proliferation without altering angiogenesis. Clin Exp Metastasis. 2005;22(6):461-73.

129.Shen W, Tao GQ, Li DC, et al. Inhibition of pancreatic carcinoma cell growth in vitro by DPC4 gene transfection. World J Gastroenterol. 2008;14(40):6254-60.

130.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.

131.Wang H, Stephens B, Von Hoff DD, et al. Identification and characterization of a novel anticancer agent with selectivity against deleted in pancreatic cancer locus 4 (DPC4)-deficient pancreatic and colon cancer cells. Pancreas. 2009;38(5):551-7.

132.Harper JW, Adami GR, Wei N, et al. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993;75(4):805-16.

133.Chen J, Killary AM, Sen S, et al. Polymorphisms of p21 and p27 jointly contribute to an earlier age at diagnosis of pancreatic cancer. Cancer Lett. 2008;272(1):32-9.

134.Chen J, Amos CI, Merriman KW, et al. Genetic variants of p21 and p27 and pancreatic cancer risk in non-Hispanic Whites: a case-control study. Pancreas. 2010;39(1):1-4.

135.Ahrendt SA, Brown HM, Komorowski RA, et al. p21WAF1 expression is associated with improved survival after adjuvant chemoradiation for pancreatic cancer. Surgery. 2000;128(4):520-30.

136.Li X, Hui A, Takayama T, et al. Altered p21(WAF1/CIP1) expression is associated with poor prognosis in extrahepatic bile duct carcinoma. Cancer Lett. 2000;154(1):85-91.

137.Nio Y, Dong M, Iguchi C, et al. Expression of Bcl-2 and p53 protein in resectable invasive ductal carcinoma of the pancreas: effects on clinical outcome and efficacy of adjuvant chemotherapy. J Surg Oncol. 2001;76(3):188-96.

138.Cheng F, McLaughlin PJ, Verderame MF, et al. The OGF-OGFr axis utilizes the p21 pathway to restrict progression of human pancreatic cancer. Mol Cancer. 2008;7:5.

139.Jia D, Sun Y, Konieczny SF. Mist1 regulates pancreatic acinar cell proliferation through p21 CIP1/WAF1. Gastroenterology. 2008;135(5):1687-97.

140.Lee SO, Chintharlapalli S, Liu S, et al. p21 expression is induced by activation of nuclear nerve growth factor-induced Balpha (Nur77) in pancreatic cancer cells. Mol Cancer Res. 2009;7(7):1169-78.

141.Wang H, Song X, Logsdon C, et al. Proteasome-mediated degradation and functions of hematopoietic progenitor kinase 1 in pancreatic cancer. Cancer Res. 2009;69(3):1063-70.

142.Yang Y, Tian X, Xie X, et al. Expression and regulation of hedgehog signaling pathway in pancreatic cancer. Langenbecks Arch Surg. 2009.

143.Lu CD, Morita S, Ishibashi T, et al. Loss of p27Kip1 expression independently predicts poor prognosis for patients with resectable pancreatic adenocarcinoma. Cancer. 1999;85(6):1250-60.