Synergistische Wirkung des Farnesyltransferaseinhibitors Lonafarnib und des Kinaseinhibitors Flavopiridol auf Proliferation und Zellzyklus von Ovarialkarzinomzellen in vitro

Einer der am häufigsten zum Tode führenden malignen Tumore der Frau ist das Ovarialkarzinom. Bei der Ersttherapie ist immer noch die radikale chirurgische Resektion maßgeblich; gefolgt von einer Platin-haltigen Kombinationschemotherapie. Trotz guter initialer Therapieerfolge ist die Rezidivrate sehr...

Ausführliche Beschreibung

Gespeichert in:
1. Verfasser: Heimbach, Sandy geb. Christiani
Beteiligte: Wagner, Uwe, Prof. Dr. (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Deutsch
Veröffentlicht: Philipps-Universität Marburg 2014
Frauenheilkunde und Geburtshilfe
Ausgabe:http://dx.doi.org/10.17192/z2014.0799
Schlagworte:
Online Zugang:PDF-Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!

1. http://archiv.ub.uni-marburg.de/diss/z2003/0482


2. Marcus A.I., Zhou J., O'Brate A., Hamel E., Wong J., Nivens M., El-Naggar A., Yao T.P., Khuri F.R., Giannakakou P.: The synergistic combination of the farnesyl transferase inhibitor lonafarnib and paclitaxel enhances tubulin acetylation and requires a functional tubulin deacetylase; Cancer Res. 2005 May 1;65(9):3883-93


3. Fehrmann R.S.N., Li X.-y., van der Zee A.G.J., de Jong S., te Meerman G.J., de Vries E.G.E., Crijns A.P.G.: Profiling Studies in Ovarian Cancer: A Review; Gynecologic Oncology, The Oncologist, Vol. 12, No. 8, August 2007 , 960-966


4. Bible K.C., Lensing J.L., Nelson S.A., Lee Y.K., Reid J.M., Ames M.M., Isham C.R., Piens J., Rubin S.L., Rubin J., Kaufmann S.H., Atherton P.J., Sloan J.A., Daiss M.K., Adjei A.A., Erlichman C.: Phase 1 trial of flavopiridol combined with cisplatin or carboplatin in patients with advanced malignancies with the assessment of pharmacokinetic and pharmacodynamic end points; Clin Cancer Res. 2005 Aug 15;11(16):5935-41.


5. Dy G.K., Bruzek L.M., Croghan G.A., Mandrekar S., Erlichman C., Peethambaram P., Pitot H.C., Hanson L.J., Reid J.M., Furth A., Cheng S., Martell R.E., Kaufmann S.H., Adjei A.A..: A phase I trial of the novel farnesyl protein transferase inhibitor, BMS-214662, in combination with paclitaxel and carboplatin in patients with advanced cancer; Clin Cancer Res. 2005 Mar 1;11(5):1877-83.


6. Shapiro G.I., Supko J.G., Patterson A., Lynch C., Lucca J., Zacarola P.F., Muzikansky A., Wright JJ, Lynch TJ Jr, Rollins BJ: A Phase II Trial of the Cyclin-dependent Kinase Inhibitor Flavopiridol in Patients with Previously Untreated Stage IV Non-Small Cell Lung Cancer; Clinical Cancer Research June 2001 7; 1590


7. Niessner H., Beck D., Sinnberg T., Lasithiotakis K., Maczey E., Gogel J., Venturelli S., Berger A., Mauthe M., Toulany M., Flaherty K., Schaller M., Schadendorf D., Proikas-Cezanne T., Schittek B., Garbe C., Kulms D., Meier F.: The Farnesyl Transferase Inhibitor Lonafarnib Inhibits mTOR Signaling and Enforces Sorafenib-Induced Apoptosis in Melanoma Cells; Journal of Investigative Dermatology (2011) 131, 468–479; doi:10.1038/jid.2010.297; published online 14 October 2010


8. Perren T.J., Swart A.M., Pfisterer J., Ledermann J.A., Pujade-Lauraine E., Kristensen G., Carey M.S., Beale P., Cervantes A., Kurzeder C., du Bois A., Sehouli J., Kimmig R., Stähle A., Collinson F., Essapen S., Gourley C., Lortholary A., Selle F., Mirza M.R., Leminen A., Plante M., Stark D., Qian W., Parmar M.K.B., Oza A.M.: A Phase 3 Trial of Bevacizumab in Ovarian Cancer; N Engl J Med 2011; 365:2484- 2496 December 29, 2011 DOI: 10.1056/NEJMoa1103799


9. Takada Y., Aggarwal B.B.: Flavopiridol Inhibits NF-κB Activation Induced by Various Carcinogens and Inflammatory Agents through Inhibition of IκBα Kinase and p65 Phosphorylation ABROGATION OF CYCLIN D1, CYCLOOXYGENASE-2, AND MATRIX METALLOPROTEASE-9; First Published on November 20, 2003, doi:10.1074/jbc.M304546200February 6, 2004 The Journal of Biological Chemistry, 279, 4750-4759


10. Takada Y., Sethi G., Sung B., Aggarwal B.B.: Flavopiridol Suppresses Tumor Necrosis Factor-Induced Activation of Activator Protein-1, c-Jun N-Terminal Kinase, p38 Mitogen-Activated Protein Kinase (MAPK), p44/p42 MAPK, and Akt, Inhibits Expression of Antiapoptotic Gene Products, and Enhances Apoptosis through Cytochrome c Release and Caspase Activation in Human Myeloid Cells " , Published online before print February 20, 2008, doi:10.1124/mol.107.041350Molecular PharmacologyMay 2008 vol. 73 no. 51549-1557


11. Luke J.J., D'Adamo D.R., Dickson M.A., Keohan M.L., Carvajal R.D., Maki R.G., de Stanchina E., Musi E., Singer S., Schwartz G.K.: The cyclin-dependent kinase inhibitor flavopiridol potentiates doxorubicin efficacy in advanced sarcomas: preclinical investigations and phase I clinical trial; Clinical Cancer Research, Published OnlineFirst February 28, 2012; doi: 10.1158/1078-0432.CCR-11-3203


12. Salzberg M., Thürlimann B., Bonnefois H., Fink D., Rochlitz C., von Moos R., Senn H.: Current Concepts of Treatment Strategies in Advanced or Recurrent Ovarian Cancer; Oncology 2005; 68, Vol. 68,No. 4-6, 293-298, (DOI: 10.1159/000086967)


13. Cimica V., Smith M.E., Zhang Z., Mathur D., Mani S., Kalpana G.V.: Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen; BMC Cancer. 2010; 10: 634, Published online 2010 November 19. doi: 10.1186/1471-2407-10-634


14. Shetty V., Hafner J., Shah P., Nickens Z., Philip R.: Investigation of ovarian cancer associated sialylation changes in N-linked glycopeptides by quantitative proteomics; Clinical Proteomics 2012, 9:10 doi:10.1186/1559-0275-9-10


15. Wang K., Hampson P., Hazeldine J., Krystof V., Strnad M., Pechan P., Janet M.: Cyclin-Dependent Kinase 9 Activity Regulates Neutrophil Spontaneous Apoptosis; PLoS One. 2012; 7(1): e30128, Published online 2012 January 19. doi: 10.1371/journal.pone.0030128


16. Karp J.E., Garrett-Mayer E.L., Estey E.H., Rudek M.A., Smith B.D., Greer J.M., Drye D.M., Mackey K., Dorcy K.S., Gore S.D., Levis M.J., McDevitt M.A., Carraway H.E., Pratz K.W., Gladstone D.E., Showell M.M., Othus M,. Doyle L.A., Wright J.J., Pagel J.M.: Randomized phase II study of two schedules of flavopiridol given as timed sequential therapy with cytosine arabinoside and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia; Published online before print June 24, 2012, doi:10.3324/haematol.2012.062539, haematol June 24, 2012haematol.2012.062539


17. Li Y., Tanaka K., Li X., Okada T., Nakamura T., Takasaki M., Yamamoto S., Oda Y., Tsuneyoshi M., Iwamoto Y.: Cyclin-dependent kinase inhibitor, flavopiridol, induces apoptosis and inhibits tumor growth in drug-resistant osteosarcoma and Ewing's family tumor cells; Int J Cancer. 2007 Sep 15;121(6):1212-8.


18. Mayer F., Mueller S., Malenke E., Kuczyk M., Hartmann J.T., Bokemeyer C.: Induction of apoptosis by flavopiridol unrelated to cell cycle arrest in germ cell tumour derived cell lines; Invest New Drugs. 2005


19. Harousseau J.L..: Farnesyltransferase inihibitors in hematologic malignancies; Blood Rev. 2007


20. Schlumbrecht M.P., Xie S.S., Shipley G.L., Urbauer D.L., Broaddus R.R.: Molecular Clustering Based on ERα and EIG121 Predicts Survival in High-Grade Serous Carcinoma of the Ovary/Peritoneum; Mod Pathol. 2011 March ; 24(3): pages 453–462 [111-113]


21. Aklilu M., Kindler H.L., Donehower R.C., Mani S., Vokes E.E.: Phase II study of flavopiridol in patients with advanced colorectal cancer; Ann Oncol. 2003 Aug;14(8):1270-3


22. Lee H.Y., Moon H., Chun K.H., Chang Y.S., Hassan K., Ji L., Lotan R., Khuri F.R., Hong W.K.: Effects of insulin-like growth factor binding protein-3 and farnesyltransferase inhibitor SCH66336 on Akt expression and apoptosis in non-small-cell lung cancer cells; J Natl Cancer Inst. 2004 Oct 20;96(20):1536-48.


23. Rahal R., Amon A.: Mitotic CDKs control the metaphase-anaphase transition and trigger spindle elongation; Genes Dev. 2008 Jun 1;22(11):1534-48


24. Ozols R.F.: Treatment goals on ovarian cancer; International Journal of Gynecological Cancer, Volume 15, Supplement 1, May 2005 , 3-11


25. Du Bois A., Pfisterer J.: Future Options for first-line therapy options of advanced ovarian cancer; Int J Gynecol Cancer. 2005 May-Jun;15 Suppl 1:42-50.


26. Schafer-Hales K., Iaconelli J., Snyder J.P., Prussia A., Nettles J.H., El-Naggar A., Khuri F.R., Giannakakou P., Marcus A.I.: Farnesyl transferase inhibitors impair chromosomal maintenance in cell lines and human tumors by compromising CENP-E and CENP-F function; Mol Cancer Ther. 2007


27. Glass T.L., Liu T.J., Yung W.K.: Inhibition of cell growth in human glioblastoma cell lines by farnesyltransferase inhibitor SCH66336; Neuro Oncol. 2000 Jul;2(3):151-8.


28. Pérez-Roger I., Ivorra C., Díez A., Cortés M.J., Poch E., Sanz-González S.M., Andrés V.: Inhibition of cellular proliferation by drug targeting of cyclin-dependent kinases; Curr Pharm Biotechnol. 2000


29. Burger R.A., Brady M.F., Bookman M.A., Fleming G.F., Monk B.J., Huang H., Mannel R.S., Homesley H.D., Fowler J., Greer B.E., Boente M., Birrer M.J., Liang S.X.: Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer; N Engl J Med 2011;365:2473-83.


30. Berek J., Taylor P., McGuire W., Smith L.M., Schultes B., Nicodemus C.F.: Oregovomab Maintenance Monoimmunotherapy Does Not Improve Outcomes in Advanced Ovarian Cancer; Journal of Clinical Onocoloy 2009, January 20, vol. 27no. 3: 418-425


31. Pfisterer J., Weber B., Reuss A., Kimmig R., du Bois A., Wagner U., Bourgeois H., Meier W., Costa S., Blohmer J.U., Lortholary A., Olbricht S., Stähle A., Jackisch C., Hardy-Bessard A.C., Möbus V., Quaas J., Richter B., Schröder W., Geay J.F., Lück H.J., Kuhn W., Meden H., Nitz U., Pujade-Lauraine E.; AGO- OVAR; GINECO: Randomized phase III trial of topotecan following carboplatin and paclitaxel in first- line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO; J Natl Cancer Inst. 2006 Aug 2;98(15):1036-45


32. Adjei A.A., Davis J.N., Erlichman C., Svingen P.A., Kaufmann S.H.: Comparison of potential markers of farnesyltransferase inhibition; Clin Cancer Res. 2000 Jun;6(6):2318-25.


33. Kim J.C., Saha D., Cao Q., Choy H.: Enhancement of radiation effects by combined docetaxel and flavopiridol treatment in lung cancer cells; Radiotherapy and Oncology, Volume 71, Issue 2, 1 May 2004, Pages 213–221


34. Nahta R., Trent S., Yang C., Schmidt E.V.: Epidermal growth factor receptor expression is a candidate target of the synergistic combination of trastuzumab and flavopiridol in breast cancer; Cancer Res. 2003


35. Raju U., Nakata E., Mason K.A., Ang K.K., Milas L.: Flavopiridol, a cyclin-dependent kinase inhibitor, enhances radiosensitivity of ovarian carcinoma cells; Cancer Res. 2003 Jun 15;63(12):3263-7


36. Shapiro G.I., Koestner D.A., Matranga C.B., Rollins B.J.: Flavopiridol Induces Cell Cycle Arrest and p53-independent Apoptosis in Non-Small Cell Lung Cancer Cell Lines, Clinical Cancer Research, October 1999 5; 2925


37. Demidenko Z.N., Blagosklonny M.V.: Flavopiridol induces p53 via initial inhibition of Mdm2 and p21 and, independently of p53, sensitizes apoptosis-reluctant cells to tumor necrosis factor; Cancer Res. 2004 May 15;64(10):3653-60.


38. Newcomb E.W.: Flavopiridol: pleiotropic biological effects enhance its anti-cancer activity; Anticancer Drugs. 2004 Jun;15(5):411-9


39. Wagner U., du Bois A., Pfisterer J., Huober J., Loibl S., Lück H.-J., Sehouli J., Gropp M., Stähle A., Schmalfeldt B., Meier W., Jackisch C.: Gefitinib in combination with tamoxifen in patients with ovariancancer refractory or resistant to platinum–taxane based therapy—A phase II trial of the AGO OvarianCancer Study Group (AGO-OVAR 2.6); Gynecologic Oncology, Volume 105, Issue 1, April 2007: 132–137


40. Grant S., Dent P.: Gene profiling and the cyclin-dependent kinase inhibitor flavopiridol: what's in a name?; Mol Cancer Ther. 2004 Jul;3(7):861-72.


41. Ghosal A., Chowdhury S.K., Tong W., Hapangama N., Yuan Y., Su A.D., Zbaida S.: Identification of human liver cytochrome P450 enzymes responsible for the metabolism of lonafarnib (Sarasar); Drug Metab Dispos. 2006 Apr;34(4):628-35. Epub 2006 Jan 27


42. Li Y., Bhuiyan M., Alhasan S., Senderowicz A.M., Sarkar F.H.: Induction of apoptosis and inhibition of c- erbB-2 in breast cancer cells by flavopiridol; Clin Cancer Res. 2000 Jan;6(1):223-9.


43. Ohta T., Ohmichi M., Hayasaka T., Mabuchi S., Saitoh M., Kawagoe J., Takahashi K., Igarashi H., Du B, Doshida M., Mirei I.G., Motoyama T., Tasaka K., Kurachi H.: Inhibition of Phosphatidylinositol 3-Kinase Increases Efficacy of Cisplatin in in Vivo Ovarian Cancer Models " , Endocrinology April 1, 2006 vol. 147 no. 4 1761-1769


44. Bardin A., Hoffmann P., Boulle N., Katsaros D., Vignon F., Pujol P., Lazennec G.: Involvement of estrogen receptor beta in ovarian carcinogenesis; Cancer Res. 2004 Aug 15;64(16):5861-9.


45. Aktivierung in Pankreaskarzinomzelllinien unter Normoxie und Hypoxie: Kinase-Inhibitoren als Anti- HIF-1 Tumortherapie beim Pankreaskarzinom; Chirurgisches Forum 2006, Volume 35, Springer Berlin Heidelberg, 147-9


46. Koza B.(Dipl.MTA): Apoptosedetektion mittels Annexin V – Markierung; mailto:100736.427@compuserve.comhttp://www.med4you.at/laborbefunde/techniken/durchflusszytometr ie/lbef_annexin.htm


47. Ready N.E., Lipton A., Zhu Y., Statkevich P., Frank E., Curtis D., Bukowski R.M.: Phase I study of the farnesyltransferase inhibitor lonafarnib with weekly paclitaxel in patients with solid tumors; Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):576-83


48. Mabuchi S., Altomare D.A., Cheung M., Zhang L., Poulikakos P.I., Hensley H.H., Schilder R.J., Ozols R.F., Testa J.R.: RAD001 Inhibits Human Ovarian Cancer Cell Proliferation, Enhances Cisplatin-Induced Apoptosis, and Prolongs Survival in an Ovarian Cancer Model; Clinical Cancer Research 2007 July 15; 13 (14), 4261-4270 [6, 12]


49. Omerovic J., Hammond D.E., Clague M.J., Prior I.A.: Ras isoform abundance and signalling in human cancer cell lines; Oncogene. 2008 Apr 24;27(19):2754-62. Epub 2007 Nov 12.


50. Nahta R., Iglehart J.D., Kempkes B., Schmidt E.V.: Rate-limiting effects of Cyclin D1 in transformation by ErbB2 predicts synergy between herceptin and flavopiridol; Cancer Res. 2002 Apr 15;62(8):2267-71.


51. Tallarida R.J., Stone D.J. Jr., McCary J.D., Raffa R.B.: Response surface analysis of synergism between morphine and clonidine; J Pharmacol Exp Ther. 1999 Apr;289(1):8-13


52. Stakleff K.S., Sloan T., Blanco D., Marcanthony S., Booth T.D., Bishayee A.: Resveratrol Exerts Differential Effects in Vitro and in Vivo against Ovarian Cancer Cells; Asian Pac J Cancer Prev. 2012;13(4):1333-40


53. Behbakht K., Qamar L., Aldridge C.S., Coletta R.D., Davidson S.A., Thorburn A., Ford H.L.: Six1 Overexpression in Ovarian Carcinoma Causes Resistance to TRAIL-Mediated Apoptosis and Is Associated with Poor Survival; Cancer Res. 2007 Apr 1;67(7):3036-42.


54. Adjei A.A., Davis J.N., Bruzek L.M., Erlichman C., Kaufmann S.H.: Synergy of the protein farnesyltransferase inhibitor SCH66336 and cisplatin in human cancer cell lines; Clin Cancer Res. 2001 May;7(5):1438-45


55. Green M.R.: Targeting Targeted Therapy; N Engl J Med. 2004 May 20;350(21):2191-3. Epub 2004 Apr 29.


56. Ebenezer D., Sun S.Y., Waller E.K., Chen J., Khuri F.R., Lonial S.: The combination of the farnesyl transferase inhibitor lonafarnib and the proteasome inhibitor bortezomib induces synergistic apoptosis in human myeloma cells that is associated with down-regulation of p-AKT; Blood. 2005 Dec 15;106(13):4322-9. Epub 2005 Aug 23.


57. Basso A.D., Mirza A., Liu G., Long B.J., Bishop W.R., Kirschmeier P.: The Farnesyl Transferase Inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb Farnelysation and mTOR Signaling; J Biol Chem. 2005 Sep 2;280(35):31101-8. Epub 2005 Jul 8.


58. Tallarida R.J.: The interaction index: a measure of drug synergism; Pain 98 (2002): 163-168


59. Lü X., Burgan W.E., Cerra M.A., Chuang E.Y., Tsai M.H., Tofilon P.J., Camphausen K.: Transcriptional signature of flavopiridol-induced tumor cell death; Mol Cancer Ther. 2004 Jul;3(7):861-72.


60. Shah M.A., Smyth E.C., Shibata S., Yong W., Tang L.H., Janjigian Y.Y., Kelsen D.P., Schwartz G.K.: A multicenter random assignment phase II study of irinotecan and flavopiridol versus irinotecan alone for patients with p53 wild-type gastric adenocarcinoma (NCI 8060); J Clin Oncol 30, 2012 (suppl; abstr e14586)


61. Garg A.K., Buchholz T.A., Aggarwal B.B.: Chemosensitization and Radiosensitization of Tumors by Plant Polyphenols, ANTIOXIDANTS & REDOX SIGNALING Volume 7, Numbers 11 & 12, 2005


62. Peterson Y.K., Kelly P., Weinbaum C.A., Casey P.J.: A novel protein geranylgeranyltransferase-I inhibitor with high potency, selectivity, and cellular activity; J Biol Chem. 2006 May 5;281(18):12445-50. Epub 2006 Mar 3


63. O'Meara S.J., Kinsella B.T.: The effect of the farnesyl protein transferase inhibitor SCH66336 on isoprenylation and signalling by the prostacyclin receptor; Biochem J. 2005 Feb 15;386(Pt 1):177-89.


64. Kryštof V., Baumli S., Fürst R.: Perspective of Cyclin-dependent kinase 9 (CDK9) as a Drug Target; Current Pharmaceutical Design, 2012 July; 18(20): 2883–2890.


65. Tagliaferri P., Ventura M., Baudi F., Cucinotto I., Arbitrio M. Di Martino MT, Tassone P.: BRCA1/2 genetic background-based therapeutic tailoring of human ovarian cancer: hope or reality?; J Ovarian Res. 2009; 2: 14.


66. Taylor S.A., Marrinan C.H., Liu G., Nale L., Bishop W.R., Kirschmeier P., Liu M., Long B.J.: Combining the farnesyltransferase inhibitor lonafarnib with paclitaxel results in enhanced growth inhibitory effects on human ovarian cancer models in vitro and in vivo; Gynecol Oncol. 2008 Apr;109(1):97-106. Epub 2008 Jan 31