A network model for angiogenesis in ovarian cancer

BMC Bioinformatics

Volumn 16, Issue 1, 2015, Pages

  Glass, Kimberly ^a,b,c   Quackenbush, John ^a,b   Spentzos, Dimitrios ^d   Haibe Kains, Benjamin ^e   Yuan, Guo Cheng ^a,b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e PRINCESS MARGARET HOSPITAL   (Canada)

Author keywords

Angiogenesis; Cancer subtypes; Gene regulation; Network modeling; Ovarian cancer; Regulatory networks

Indexed keywords

ACTIVATION ANALYSIS; ALKYLATION; DISEASES; GENE EXPRESSION; GENES; TRANSCRIPTION;

ANGIOGENESIS; CANCER SUBTYPES; NETWORK MODELING; OVARIAN CANCERS; REGULATORY NETWORK;

COMPLEX NETWORKS;

ANTINEOPLASTIC AGENT; TRANSCRIPTION FACTOR;

EPIGENETICS; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORK; GENETICS; HUMAN; METABOLISM; NEOVASCULARIZATION (PATHOLOGY); OVARIAN NEOPLASMS; STATISTICAL ANALYSIS; STATISTICAL MODEL; VASCULARIZATION;

ANTINEOPLASTIC AGENTS; DATA INTERPRETATION, STATISTICAL; EPIGENOMICS; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE REGULATORY NETWORKS; HUMANS; MODELS, STATISTICAL; NEOVASCULARIZATION, PATHOLOGIC; OVARIAN NEOPLASMS; TRANSCRIPTION FACTORS;

EID: 84928540618     PISSN: None     EISSN: 14712105     Source Type: Journal    
DOI: 10.1186/s12859-015-0551-y     Document Type: Article

References (110)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10-29.
2. Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;351(24):2519-29.
3. Bentink S, Haibe-Kains B, Risch T, Fan JB, Hirsch MS, Holton K, et al. Angiogenic mRNA and microRNA gene expression signature predicts a novel subtype of serous ovarian cancer. PLoS One. 2012;7(2):e30269.
4. Tothill RW, Tinker AV, George J, Brown R, Fox SB, Lade S, et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res. 2008;14(16):5198-208.
5. TCGA. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609-15.
6. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57-70.
7. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):1182-6.
8. Ingber DE, Folkman J. Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix. J Cell Biol. 1989;109(1):317-30.
9. Dike LE, Chen CS, Mrksich M, Tien J, Whitesides GM, Ingber DE. Geometric control of switching between growth, apoptosis, and differentiation during angiogenesis using micropatterned substrates. In Vitro Cell Dev Biol Anim. 1999;35(8):441-8.
10. Moses MA, Wiederschain D, Loughlin KR, Zurakowski D, Lamb CC, Freeman MR. Increased incidence of matrix metalloproteinases in urine of cancer patients. Cancer Res. 1998;58(7):1395-9.
11. Veikkola T, Karkkainen M, Claesson-Welsh L, Alitalo K. Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res. 2000;60(2):203-12.
12. Korpelainen EI, Alitalo K. Signaling angiogenesis and lymphangiogenesis. Curr Opin Cell Biol. 1998;10(2):159-64.
13. Ferrara N. Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int. 1999;56(3):794-814.
14. Burger RA. Overview of anti-angiogenic agents in development for ovarian cancer. Gynecol Oncol. 2011;121(1):230-8.
15. Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;25(33):5165-71.
16. Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007;25(33):5180-6.
17. Matulonis UA, Berlin S, Ivy P, Tyburski K, Krasner C, Zarwan C, et al. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clinical Oncol. 2009;27(33):5601-6.
18. Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clinical Oncol. 2012;30(17):2039-45.
19. Liu J, Matulonis UA. Anti-angiogenic agents in ovarian cancer: dawn of a new era? Curr Oncol Rep. 2011;13(6):450-8.
20. Emmert-Streib F. The chronic fatigue syndrome: a comparative pathway analysis. J Comput Biol. 2007;14(7):961-72.
21. Barabasi AL. Network medicine-from obesity to the "diseasome". N Engl J Med. 2007;357(4):404-7.
22. Silverman EK, Loscalzo J. Developing new drug treatments in the era of network medicine. Clin Pharmacol Ther. 2013;93(1):26-8.
23. Silverman EK, Loscalzo J. Network medicine approaches to the genetics of complex diseases. Discov Med. 2012;14(75):143-52.
24. Papin JA, Reed JL, Palsson BO. Hierarchical thinking in network biology: the unbiased modularization of biochemical networks. Trends Biochem Sci. 2004;29(12):641-7.
25. Nariai N, Tamada Y, Imoto S, Miyano S. Estimating gene regulatory networks and protein-protein interactions of Saccharomyces cerevisiae from multiple genome-wide data. Bioinformatics. 2005;21 Suppl 2:ii206-12.
26. Hartemink AJ, Gifford DK, Jaakkola TS, Young RA. Combining location and expression data for principled discovery of genetic regulatory network models. Pac Symp Biocomput. 2002;7:437-49.
27. Hecker M, Lambeck S, Toepfer S, van Someren E, Guthke R. Gene regulatory network inference: data integration in dynamic models-a review. Biosystems. 2009;96(1):86-103.
28. Glass K, Huttenhower C, Quackenbush J, Yuan GC. Passing messages between networks to refine predicted interactions. PLoS One. 2013;8(5), e64832.
29. McCall MN, Bolstad BM, Irizarry RA. Frozen robust multiarray analysis (fRMA). Biostatistics (Oxford, England). 2010;11(2):242-53.
30. Smedley D, Haider S, Ballester B, Holland R, London D, Thorisson G, et al. BioMart - biological queries made easy. BMC Genomics. 2009;10(1):22.
31. Ravasi T, Suzuki H, Cannistraci CV, Katayama S, Bajic VB, Tan K, et al. An atlas of combinatorial transcriptional regulation in mouse and man. Cell. 2010;140(5):744-52.
32. Aurora AB, Biyashev D, Mirochnik Y, Zaichuk TA, Sanchez-Martinez C, Renault MA, et al. NF-kappaB balances vascular regression and angiogenesis via chromatin remodeling and NFAT displacement. Blood. 2010;116(3):475-84.
33. Webb CF, Bryant J, Popowski M, Allred L, Kim D, Harriss J, et al. The ARID family transcription factor bright is required for both hematopoietic stem cell and B lineage development. Mol Cell Biol. 2011;31(5):1041-53.
34. Komiyama T, Coppola JM, Larsen MJ, van Dort ME, Ross BD, Day R, et al. Inhibition of furin/proprotein convertase-catalyzed surface and intracellular processing by small molecules. J Biol Chem. 2009;284(23):15729-38.
35. Stevens TA, Meech R. BARX2 and estrogen receptor-alpha (ESR1) coordinately regulate the production of alternatively spliced ESR1 isoforms and control breast cancer cell growth and invasion. Oncogene. 2006;25(39):5426-35.
36. Gershenwald JE, Sumner W, Calderone T, Wang Z, Huang S, Bar-Eli M. Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo. Oncogene. 2001;20(26):3363-75.
37. Tanaka M, Chen Z, Bartunkova S, Yamasaki N, Izumo S. The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development. 1999;126(6):1269-80.
38. Bergwerff M, Gittenberger-de Groot AC, Wisse LJ, DeRuiter MC, Wessels A, Martin JF, et al. Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus. Virchows Archiv. 2000;436(1):12-9.
39. Roman AC, Carvajal-Gonzalez JM, Rico-Leo EM, Fernandez-Salguero PM. Dioxin receptor deficiency impairs angiogenesis by a mechanism involving VEGF-A depletion in the endothelium and transforming growth factor-beta overexpression in the stroma. J Biol Chem. 2009;284(37):25135-48.
40. Schmidlin H, Diehl SA, Nagasawa M, Scheeren FA, Schotte R, Uittenbogaart CH, et al. Spi-B inhibits human plasma cell differentiation by repressing BLIMP1 and XBP-1 expression. Blood. 2008;112(5):1804-12.
41. Tsai SJ, Hwang JM, Hsieh SC, Ying TH, Hsieh YH. Overexpression of myeloid zinc finger 1 suppresses matrix metalloproteinase-2 expression and reduces invasiveness of SiHa human cervical cancer cells. Biochem Biophys Res Commun. 2012;425(2):462-7.
42. Kawai H, Li H, Chun P, Avraham S, Avraham HK. Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells. Oncogene. 2002;21(50):7730-9.
43. Kang HJ, Yi YW, Kim HJ, Hong YB, Seong YS, Bae I. BRCA1 negatively regulates IGF-1 expression through an estrogen-responsive element-like site. Cell Death Dis. 2012;3:e336.
44. Huang KJ, Sui LH. The relevance and role of vascular endothelial growth factor C, matrix metalloproteinase-2 and E-cadherin in epithelial ovarian cancer. Med Oncol. 2012;29(1):318-23.
45. Arnaldez FI, Helman LJ. Targeting the insulin growth factor receptor 1. Hematol Oncol Clin North Am. 2012;26(3):527-42. vii-viii.
46. Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst. 2000;92(18):1472-89.
47. Davison Z, de Blacquiere GE, Westley BR, May FE. Insulin-like growth factor-dependent proliferation and survival of triple-negative breast cancer cells: implications for therapy. Neoplasia. 2011;13(6):504-15.
48. Perrotti D, Melotti P, Skorski T, Casella I, Peschle C, Calabretta B. Overexpression of the zinc finger protein MZF1 inhibits hematopoietic development from embryonic stem cells: correlation with negative regulation of CD34 and c-myb promoter activity. Mol Cell Biol. 1995;15(11):6075-87.
49. da Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44-57.
50. Gerger A, LaBonte M, Lenz HJ. Molecular predictors of response to antiangiogenesis therapies. Cancer J. 2011;17(2):134-41.
51. Murukesh N, Dive C, Jayson GC. Biomarkers of angiogenesis and their role in the development of VEGF inhibitors. Br J Cancer. 2010;102(1):8-18.
52. Yang SX, Steinberg SM, Nguyen D, Wu TD, Modrusan Z, Swain SM. Gene expression profile and angiogenic marker correlates with response to neoadjuvant bevacizumab followed by bevacizumab plus chemotherapy in breast cancer. Clin Cancer Res. 2008;14(18):5893-9.
53. Lelievre E, Lionneton F, Soncin F, Vandenbunder B. The Ets family contains transcriptional activators and repressors involved in angiogenesis. Int J Biochem Cell Biol. 2001;33(4):391-407.
54. Sato Y. Role of ETS family transcription factors in vascular development and angiogenesis. Cell Struct Funct. 2001;26(1):19-24.
55. Khatun S, Fujimoto J, Toyoki H, Tamaya T. Clinical implications of expression of ETS-1 in relation to angiogenesis in ovarian cancers. Cancer Sci. 2003;94(9):769-73.
56. Elvert G, Kappel A, Heidenreich R, Englmeier U, Lanz S, Acker T, et al. Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). J Biol Chem. 2003;278(9):7520-30.
57. Dutta D, Ray S, Vivian JL, Paul S. Activation of the VEGFR1 chromatin domain: an angiogenic signal-ETS1/HIF-2alpha regulatory axis. J Biol Chem. 2008;283(37):25404-13.
58. Beischlag TV, Taylor RT, Rose DW, Yoon D, Chen Y, Lee WH, et al. Recruitment of thyroid hormone receptor/retinoblastoma-interacting protein 230 by the aryl hydrocarbon receptor nuclear translocator is required for the transcriptional response to both dioxin and hypoxia. J Biol Chem. 2004;279(52):54620-8.
59. Fritz WA, Lin TM, Peterson RE. The aryl hydrocarbon receptor (AhR) inhibits vanadate-induced vascular endothelial growth factor (VEGF) production in TRAMP prostates. Carcinogenesis. 2008;29(5):1077-82.
60. Scheuermann TH, Tomchick DR, Machius M, Guo Y, Bruick RK, Gardner KH. Artificial ligand binding within the HIF2alpha PAS-B domain of the HIF2 transcription factor. Proc Natl Acad Sci U S A. 2009;106(2):450-5.
61. Hao N, Whitelaw ML, Shearwin KE, Dodd IB, Chapman-Smith A. Identification of residues in the N-terminal PAS domains important for dimerization of Arnt and AhR. Nucleic Acids Res. 2011;39(9):3695-709.
62. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003;4(2):249-64.
63. Dai M, Wang P, Boyd AD, Kostov G, Athey B, Jones EG, et al. Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res. 2005;33(20):e175.
64. Brun YF, Varma R, Hector SM, Pendyala L, Tummala R, Greco WR. Simultaneous modeling of concentration-effect and time-course patterns in gene expression data from microarrays. Cancer Genomics Proteomics. 2008;5(1):43-53.
65. Li D, Williams JI, Pietras RJ. Squalamine and cisplatin block angiogenesis and growth of human ovarian cancer cells with or without HER-2 gene overexpression. Oncogene. 2002;21(18):2805-14.
66. Card PB, Erbel PJ, Gardner KH. Structural basis of ARNT PAS-B dimerization: use of a common beta-sheet interface for hetero- and homodimerization. J Mol Biol. 2005;353(3):664-77.
67. 1x0o: http://www.rcsb.org/pdb/explore.do?structureId=1x0o .
68. Cardoso R, Love R, Nilsson CL, Bergqvist S, Nowlin D, Yan J, et al. Identification of Cys255 in HIF-1alpha as a novel site for development of covalent inhibitors of HIF-1alpha/ARNT PasB domain protein-protein interaction. Protein Sci. 2012;21(12):1885-96.
69. Mimura I, Nangaku M, Kanki Y, Tsutsumi S, Inoue T, Kohro T, et al. Dynamic change of chromatin conformation in response to hypoxia enhances the expression of GLUT3 (SLC2A3) by cooperative interaction of hypoxia-inducible factor 1 and KDM3A. Mol Cell Biol. 2012;32(15):3018-32.
70. Storti P, Bolzoni M, Donofrio G, Airoldi I, Guasco D, Toscani D, et al. Hypoxia-inducible factor (HIF)-1alpha suppression in myeloma cells blocks tumoral growth in vivo inhibiting angiogenesis and bone destruction. Leukemia. 2013;27(8):1697-706.
71. Safe S. Molecular biology of the Ah receptor and its role in carcinogenesis. Toxicol Lett. 2001;120(1-3):1-7.
72. Fritz WA, Lin TM, Safe S, Moore RW, Peterson RE. The selective aryl hydrocarbon receptor modulator 6-methyl-1,3,8-trichlorodibenzofuran inhibits prostate tumor metastasis in TRAMP mice. Biochem Pharmacol. 2009;77(7):1151-60.
73. Ishimura R, Kawakami T, Ohsako S, Tohyama C. Dioxin-induced toxicity on vascular remodeling of the placenta. Biochem Pharmacol. 2009;77(4):660-9.
74. Bertazzi A, Pesatori AC, Consonni D, Tironi A, Landi MT, Zocchetti C. Cancer incidence in a population accidentally exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin. Epidemiology. 1993;4(5):398-406.
75. Carlson EA, McCulloch C, Koganti A, Goodwin SB, Sutter TR, Silkworth JB. Divergent transcriptomic responses to aryl hydrocarbon receptor agonists between rat and human primary hepatocytes. Toxicol Sci. 2009;112(1):257-72.
76. Fracchiolla NS, Todoerti K, Bertazzi PA, Servida F, Corradini P, Carniti C, et al. Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects. Toxicology. 2011;283(1):18-23.
77. Privalov PL, Jelesarov I, Read CM, Dragan AI, Crane-Robinson C. The energetics of HMG box interactions with DNA: thermodynamics of the DNA binding of the HMG box from mouse sox-5. J Mol Biol. 1999;294(4):997-1013.
78. Prokhortchouk E, Defossez PA. The cell biology of DNA methylation in mammals. Biochim Biophys Acta. 2008;1783(11):2167-73.
79. Hellebrekers DM, Griffioen AW, van Engeland M. Dual targeting of epigenetic therapy in cancer. Biochim Biophys Acta. 2007;1775(1):76-91.
80. Yoo CB, Jones PA. Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov. 2006;5(1):37-50.
81. Matsumura N, Huang Z, Mori S, Baba T, Fujii S, Konishi I, et al. Epigenetic suppression of the TGF-beta pathway revealed by transcriptome profiling in ovarian cancer. Genome Res. 2011;21(1):74-82.
82. Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006;313(5795):1929-35.
83. Evidente A, Kireev AS, Jenkins AR, Romero AE, Steelant WF, Van Slambrouck S, et al. Biological evaluation of structurally diverse amaryllidaceae alkaloids and their synthetic derivatives: discovery of novel leads for anticancer drug design. Planta Med. 2009;75(5):501-7.
84. Antoun MD, Mendoza NT, Rios YR, Proctor GR, Wickramaratne DB, Pezzuto JM, et al. Cytotoxicity of Hymenocallis expansa alkaloids. J Nat Prod. 1993;56(8):1423-5.
85. Liao N, Ao M, Zhang P, Yu L. Extracts of Lycoris aurea induce apoptosis in murine sarcoma S180 cells. Molecules. 2012;17(4):3723-35.
86. Brown C, Fezoui M, Selig WM, Schwartz CE, Ellis JL. Antitussive activity of sigma-1 receptor agonists in the guinea-pig. Br J Pharmacol. 2004;141(2):233-40.
87. Do W, Herrera C, Mighty J, Shumskaya M, Redenti SM, Sauane M. Sigma 1 Receptor plays a prominent role in IL-24-induced cancer-specific apoptosis. Biochem Biophys Res Commun. 2013;439(2):215-20.
88. Bobek V, Kovarik J. Antitumor and antimetastatic effect of warfarin and heparins. Biomed Pharmacother. 2004;58(4):213-9.
89. Gerotziafas GT, Papageorgiou C, Hatmi M, Samama MM, Elalamy I. Clinical studies with anticoagulants to improve survival in cancer patients. Pathophysiol Haemost Thromb. 2008;36(3-4):204-11.
90. Ahn KS, Sethi G, Jain AK, Jaiswal AK, Aggarwal BB. Genetic deletion of NAD(P)H:quinone oxidoreductase 1 abrogates activation of nuclear factor-kappaB, IkappaBalpha kinase, c-Jun N-terminal kinase, Akt, p38, and p44/42 mitogen-activated protein kinases and potentiates apoptosis. J Biol Chem. 2006;281(29):19798-808.
91. Dai F, Chen Y, Song Y, Huang L, Zhai D, Dong Y, et al. A natural small molecule harmine inhibits angiogenesis and suppresses tumour growth through activation of p53 in endothelial cells. PLoS One. 2012;7(12):e52162.
92. Zhang H, Sun K, Ding J, Xu H, Zhu L, Zhang K, et al. Harmine induces apoptosis and inhibits tumor cell proliferation, migration and invasion through down-regulation of cyclooxygenase-2 expression in gastric cancer. Phytomedicine. 2014;21(3):348-55.
93. El Gendy MA, El-Kadi AO. Harman induces CYP1A1 enzyme through an aryl hydrocarbon receptor mechanism. Toxicol Appl Pharmacol. 2010;249(1):55-64.
94. El Gendy MA, Soshilov AA, Denison MS, El-Kadi AO. Transcriptional and posttranslational inhibition of dioxin-mediated induction of CYP1A1 by harmine and harmol. Toxicol Lett. 2012;208(1):51-61.
95. Kumaran GC, Jayson GC, Clamp AR. Antiangiogenic drugs in ovarian cancer. Br J Cancer. 2009;100(1):1-7.
96. Spannuth WA, Sood AK, Coleman RL. Angiogenesis as a strategic target for ovarian cancer therapy. Nat Clin Pract Oncol. 2008;5(4):194-204.
97. Teoh D, Secord AA. Antiangiogenic agents in combination with chemotherapy for the treatment of epithelial ovarian cancer. Int J Gynecol Cancer. 2012;22(3):348-59.
98. O'Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997;88(2):277-85.
99. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473-83.
100. Moreno Garcia V, Basu B, Molife LR, Kaye SB. Combining antiangiogenics to overcome resistance: rationale and clinical experience. Clin Cancer Res. 2012;18(14):3750-61.
101. Collinson F, Hutchinson M, Craven RA, Cairns DA, Zougman A, Wind TC, et al. Predicting response to bevacizumab in ovarian cancer: a panel of potential biomarkers informing treatment selection. Clin Cancer Res. 2013;19(18):5227-39.
102. Madsen CV, Steffensen KD, Olsen DA, Waldstrom M, Smerdel M, Adimi P, et al. Serial measurements of serum PDGF-AA, PDGF-BB, FGF2, and VEGF in multiresistant ovarian cancer patients treated with bevacizumab. J Ovarian Res. 2012;5(1):23.
103. Horowitz NS, Penson RT, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, et al. Safety, Efficacy, and Biomarker Exploration in a Phase II Study of Bevacizumab, Oxaliplatin, and Gemcitabine in Recurrent Mullerian Carcinoma. Clin Ovarian Cancer Gynecol Malign. 2011;4(1):26-33.
104. Sessa C, Guibal A, Del Conte G, Ruegg C. Biomarkers of angiogenesis for the development of antiangiogenic therapies in oncology: tools or decorations? Nat Clin Pract Oncol. 2008;5(7):378-91.
105. Glass K: PANDA Implementation ( http://sourceforge.net/projects/panda-net/ ). 2013.
106. Fraley C, Raftery AE. Model-Based Clustering, Discriminant Analysis, and Density Estimation. J Am Stat Assoc. 2002;97(458):611-31.
107. Stormo GD. DNA binding sites: representation and discovery. Bioinformatics. 2000;16(1):16-23.
108. Wasserman WW, Sandelin A. Applied bioinformatics for the identification of regulatory elements. Nat Rev Genet. 2004;5(4):276-87.
109. Xu J, Shao Z, Glass K, Bauer DE, Pinello L, Van Handel B, et al. Combinatorial assembly of developmental stage-specific enhancers controls gene expression programs during human erythropoiesis. Dev Cell. 2012;23(4):796-811.
110. Oron AP, Jiang Z, Gentleman R. Gene set enrichment analysis using linear models and diagnostics. Bioinformatics. 2008;24(22):2586-91.