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Nachweis und Charakterisierung disseminierter und zirkulierender Tumorzellen beim Ovarialkarzinom zur Etablierung und Optimierung neuer zielgerichteter Therapiestrategien

DDer Nachweis disseminierter Tumorzellen im Knochenmark und Blut von Mammakarzinompatientinnen ist mit einer schlechten Prognose assoziiert. Auch beim Ovarialkarzinom werden persistierende, disseminierte Tumorzellen im Knochenmark mittlerweile als möglicher Ausgangspunkt für ein Rezidiv und eine hämatogene Metastasierung verstanden. Der Nachweis ihres tumorigenen Potentials ist jedoch bis dato nicht direkt nachgewiesen worden. Unser Ziel ist, disseminierte und zirkulierende Tumorzellen und ihre korrespondierenden Primärtumoren von Ovarialkarzinompatientinnen mittels Phänotypisierung zu charakterisieren und tumorigene Eigenschaften von Tumorzellen mit diesem Phänotyp funktionell zu evaluieren. Die Korrelation des Phänotyps von DTZ und ZTZ mit klinischen Verlaufsdaten soll ermöglichen, Profile zu erstellen, die mit einer Tumorzellpersistenz bzw. Metastasierung assoziiert sind. Schwerpunkt hierfür sind Metastasierungs-, Stammzell- und Apoptosemarker. Da die zytotoxische Systemtherapie sowie ein radikales „Tumordebulking“ zur Vermeidung eines Rezidivs nicht ausreichen, sind die Integration von neuen Therapiekonzepten wie z.B. Antikörpertherapien basierend auf dem Expressionsprofil persistierender Tumorzellen ein wichtiger Ansatzpunkt.

 

Publikationsliste seit 2009

 

Erstautor (Originalarbeiten)

IF

 

2011

 

1.

C* Lengerke, T* Fehm, R Kurth, H Neubauer, V Scheble, F Muller, F Schneider, K Petersen, D Wallwiener, L Kanz, F Fend, S Perner, PM Bareiss, A Staebler: Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma.

BMC Cancer  11:42, 2011 epub * shared authorship

 

2,740

 

2010

 

2.

T Fehm, V Müller, B Aktas, W Janni,  A Schneeweiss, E Stickeler, O Ortmann, C Löhberg, E Solomayer, B Rack, S Riethdorf, C Klein, C Schindlbeck, S Kasimir-Bauer, D Wallwiener, K Pantel: HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial.

Breast Cancer Res Treat 124(2):403-12, 2010

4,859

 

 

2009

 

3.

T Fehm, O Hoffmann, B Aktas, S Becker, E F Solomayer, D Wallwiener, R Kimmig, S Kasimir-Bauer: Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells.

Breast Cancer Research 11(4):R59, 2009 epub

 

5,326

 

 

Letztautor

 

 

 

IF

 

 

 

 

2012

 

1.

S Kasimir-Bauer, O Hoffmann, D Wallwiener, R Kimmig, T Fehm. Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells.

Breast Cancer Res 14(1):R15, 2012

 

5,785

2.

EF Solomayer, G Gebauer, P Hirnle, W Janni, HJ Lück, S Becker, J Huober, B Krämer, B Wackwitz, D Wallwiener, T Fehm. Influence of zoledronic acid on disseminated tumor cells in primary breast cancer patients.

Ann Oncol 2012 epub

 

6,452

 

2011

 

3.

B Kraemer, R Rothmund, M Banys, N Krawczyk, EF Solomayer, C Mack, D Wallwiener, T Fehm: Impaired bone microenvironment: correlation between bone density and presence of disseminated tumor cells.

Anticancer Res 31(12):4423-8, 2011

 

1,656

4.

AD Hartkopf, M Banys, N Krawczyk, A Staebler, S Becker, J Hoffmann, M Hahn, M Wallwiener, T Fehm: Bone marrow versus sentinel lymph node involvement in breast cancer: a comparison of early hematogenous and early lymphatic tumor spread. Breast Cancer Res Treat  2011 epub

 

4,859

5.

CW Wallwiener, M Wallwiener, RR Kurth, C Röhm, H Neubauer, MJ Banys, A Staebler, B Schönfisch, SC Meuer, T Giese, T Fehm: Molecular detection of breast cancer metastasis in sentinel lymph nodes by reverse transcriptase polymerase chain reaction (RT-PCR): identifying, evaluating and establishing multi-marker panels. Breast Cancer Res Treat 2011 epub

 

4,859

6.

V Muller, S Riethdorf, B Rack, W Janni, P Fasching, E Solomayer, B Aktas, S Kasimir-Bauer, J Zeitz, K Pantel, T Fehm, Detect Study Group. Prospective evaluation of serum tissue inhibitor of metalloproteinase 1 and carbonic anhydrase IX in correlation to circulating tumor cells in patients with metastatic breast cancer.

Breast Cancer Res 13(4):R71, 2011 epub

 

5,790

7.

B Aktas, V Müller, M Tewes, J Zeitz, S Kasimir-Bauer, CR Loehberg, B Rack, A Schneeweiss, T Fehm: Comparison of estrogen and progesterone receptor status of circulating tumor cells and the primary tumor in metastatic breast cancer patients.

Gynecol Oncol 122(2):356-60, 2011

 

3,760

8.

M Banys, I Gruber, N Krawczyk, S Becker, R Kurth, D Wallwiener, J Jakubowska, J Hoffmann, R Rothmund, A Staebler, T Fehm: Hematogenous and lymphatic tumor cell dissemination may be detected in patients diagnosed with ductal carcinoma in situ of the breast.

Breast Cancer Res Treat 124(2):403-12, 2011

 

4,859

9.

B Lawrenz, M Banys, M Henes, E Neunhoeffer, EM Grischke, T Fehm: Pregnancy after breast cancer: case report and review of the literature.

Arch Gynecol Obstet  283(4):837-43, 2011 epub

 

1,072

 

2010

 

10.

B Lawrenz, E Neunhoeffer, M Henes, S Lessmann-Bechle, B Krämer, T Fehm: Management of fertility preservation in young breast cancer patients in a large breast cancer centre.

Arch Gynecol Obstet 282(5): 547-551, 2010

 

1,072

11.

B Lawrenz, E Neunhoeffer, M Henes, T Fehm: Fertilitätsprotektion bei jungen Patientinnen vor zytotoxischer Therapie: Klinische Erfahrungen bei über 130 beratenen Patientinnen und Review der Literatur.

Geburtsh Frauenheilk 70:1-5, 2010

 

0,342

 

2009

 

12.

S Becker, E Solomayer,  R Hornung, R Kurek, M Banys, B Aydeniz, Franz H, D Wallwiener, T Fehm: Optimal treatment for patients with ectopic pregnancies and a history of fertility-reducing factors.

Arch Gynecol Obstet 283(1):41-5, 2011 (2009 epub)

 

0,912

13.

N Krawczyk, M Banys, H Neubauer, EF Solomayer, C Gall, M Hahn, S Becker, R Bachmann, D Wallwiener, T Fehm: HER2 Status on persistent disseminated tumor cells after adjuvant therapy may differ from initial HER2 status on primary tumor.

Anticancer Res 29(10):4019-24, 2009

 

1,428

14.

M Banys, EF Solomayer, S Becker, K Gardanis, N Krawczyk, A Staebler, H Neubauer, D Wallwiener, T Fehm: Disseminated tumor cells in bone marrow may effect prognosis of patients with gynecologic malignancies.

Int J Gynecol Cancer  19(5):948-52, 2009

 

2,179

15.

H Neubauer, G Adam, H Seeger, A. Mück, E Solomayer, D Wallwiener, T Fehm: Membrane-initiated effects of progesterone on proliferation and activation of VEGF in breast cancer cells.

Climacteric  12(3):230-9, 2009

 

2,568

16.

H Neubauer, A Ruoff, E Solomayer, D Wallwiener, T Fehm: Laminin-1 regulates estrogen receptor beta expression in MDA-MB 231 breast cancer cell line.

Oncol Rep 21(2):475-81, 2009

 

1,588

17.

S Becker, M Banys, G Becker-Pergola, D Wallwiener, FE Solomayer, CS Schuetz, T Fehm: Evaluation of a RT-PCR based routine screening tool for the detection of disseminated epithelial cells in bone marrow of breast cancer patients.

Breast Cancer Res Treat 117(2):227-33, 2009

 

5,236

Koautor:

Geleisteter Beitrag:

1 Konzeption & Design der Studie, 2 Datensammling, 3 Datenanalyse und Interpretation, 4 Verfassen des Manuskripts 

 

 

 

 

IF

 

2011

 

1.

I Keklikoglou, C Koerner, C Schmidt, JD Zhang, D Heckmann, A Shavinskaya, H Allgayer, B Gückel, T Fehm, A Schneeweiss, O Sahin, S Wiemann, U Tschulena: MicroRNA-520/373 family functions as a tumor suppressor in estrogen receptor negative breast cancer by targeting NF-κB and TGF-β signaling pathways.

Oncogene 2011 epub

 

7,414

2,3   

2.

HG Kopp, K Krauss, T Fehm, A Staebler, J Zahm, W Vogel, L Kanz, F Mayer: Symptomatic bone marrow involvement in breast cancer - clinical presentation, treatment, and prognosis: a single institution review of 22 cases.

Anticancer Res 31(11):4025-30, 2011

 

1,656

2,3,4  

3.

C Bachmann, S Bachmann, T Fehm, A Staebler, S Becker, R Rothmund, C Gardanis, EM Grischke, D Wallwiener, EF Solomayer: Nodal status-its impact on prognosis in advanced ovarian cancer.

J Cancer Res Clin Oncol 2011 epub

 

2,485

1,2,3,4   

4.

I Königsrainer, S Beckert, S Becker, D Zieker, T Fehm, EM Grischke, O Lauk, J Glatzle, B Brücher, D Wallwiener, A Königsrainer: Cytoreductive surgery and HIPEC in peritoneal recurrent ovarian cancer: experience and lessons learned. Langenbecks Arch Surg  396(7):1077-81, 2011

 

1,951

1,2,3,4   

6.

B Lawrenz, J Henes, M Henes, E Neunhoeffer, M Schmalzing, T Fehm, I Kïtter: Impact of systemic lupus erythematosus on ovarian reserve in premenopausal women: evaluation by using anti-Muellerian hormone.

Lupus  20(11):1193-7, 2011

 

2,600

3,4  

7.

H Bösmüller, S Haitchi-Petnehazy, G Webersinke, R Marschon, F Roithmeier, W Stummvoll, T Fehm, M Klier-Richter, I Bonzheim, A Staebler, F Fend: Intratumoral lymphocyte density in serous ovarian carcinoma is superior to ERCC1 expression for predicting response to platinum-based therapy.

Virchows Arch 2011 epub

 

2,336

2,3   

8.

S Schott, M Wallwiener, B Kootz, H Seeger, T Fehm, H Neubauer: Cytotoxicity of the new antimetabolite-bisphosphonate (5-FdU-alendronate) in comparison to standard therapeutics on breast and ovarian cancer cell lines in the ATP tumor chemosensitivity assay.

Invest New Drugs 2011 epub

 

3,007

2,3,4   

9.

M Banys, N Krawczyk, S Becker, J Jakubowska, A Staebler, D Wallwiener, T Fehm, R Rothmund: The influence of removal of primary tumor on incidence and phenotype of circulating tumor cells in primary breast cancer.

Breast Cancer Res Treat  2011 epub

 

4,859

1,2,3,4   

10.

B Lawrenz, M Henes, E Neunhoeffer, T Fehm, P Lang, CP Schwarze: Fertility preservation in girls and adolescents before chemotherapy and radiation - review of the literature.

Klin Padiatr  223(3):126-30, 2011

 

1,583

3,4  

11.

W Janni, FD Vogl, G Wiedswang, M Synnestvedt, TN Fehm, J Jueckstock, B Rack, E Borgen, S Braun, E Solomayer, K Pantel, JM Nesland, K Friese, B Naume: Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse - a European Pooled Analysis.

Clin Cancer Res 17(9):2967-76, 2011

 

7,338

1,2,3,4

12.

H Neubauer, Y Yang, H Seeger, MA Cahill, T Fehm, AO Mueck: The presence of a membrane-bound progesterone receptor sensitizes the estradiol-induced effect on the proliferation of human breast cancer cells.

Menopause  epub 2011

 

 3,318

2,3,4   

           

13.

B Gerber, G von Minckwitz, H Stehle, T Reimer, R Felberbaum, N Maass, D Fischer, H Sommer, B Conrad, Ortmann, T Fehm, M Rezai, K Mehta, S Loibl on behalf of the German Breast Group O Investigators: Effect of LHRH agonists on ovarian function after modern-type adjuvant breast cancer chemotherapy: The GBG 37 “ZORO” study.

J Clin Oncol  29(17):2334-41, 2011

 

18,970

2,3,4   

14.

A Hartkopf, P Wagner, D Wallwiener, T Fehm, R Rothmund: Changing levels of circulating tumor cells to monitor chemotherapy response in metastatic breast cancer patients.

Anticancer Res  31(3):979-84, 2011

 

1,656

1,2,3,4

 

15.

TE Mürdter, W Schroth, L Bacchus-Gerybadze, S Winte, G Heinkele, W Simon, PA Fasching, T Fehm, The German Tamoxifen and AI clinicians group. M Eichelbaum, M Schwab, H Brauch: Biological activities of tamoxifen and its metabolites at the estrogen receptor and the impact of genetic polymorphisms of phase I and phase II enzymes on their plasma levels.

Clinical Pharmacol Ther 89(5):708-17, 2011

 

6,378

3,4

16.

B Lawrenz, T Fehm, E Neunhoeffer, B Krämer, M Soekler, L Kanz, M Henes, F Mayer: Fertility preservation in young female lymphoma patients: review of available options and initial experiences with their implementation in clinical routine.

Onkologie 34(3):88-93, 2011

 

1,156

3,4  

 

17.

J Kraan, S Sleijfer, MH Strijbos, M Ignatiadis, D Peeters, JY Pierga,  F Farace, S Riethdorf, T Fehm, L Zorzino, AG Tibbe, M Maestro, R Gisbert-Criado, G Denton, JS de Bono, C Dive, JA Foekens, JW Gratama: External quality assurance of circulating tumor cell enumeration using the CellSearch(®) system:

Cytometry B Clin Cytom 80(2):112-8, 2011

 

1,960

2,3,4  

 

2010

 

 

 

 

18.

 

M Wurster, A Ruoff, C Meisner, H Seeger, U Vogel, I Juhasz-Böss, E Solomayer, D Wallwiener, T Fehm, H Neubauer: Evaluation of ERalpha, PR and ERbeta isoforms in neoadjuvant treated breast cancer.

Oncol Rep 24(3):653-9, 2010

 

1,686

1,2,3,4

 

19.

I Juhasz-Böss, T Fehm, A Nauth, S Becker, R Rothmund, K Gardanis, B Krämer, D Wallwiener, E Solomayer: Number of hysteroscopies and the time interval between hysteroscopy and surgery: influence on peritoneal cytology in patients with endometrial cancer.

Anticancer Res 30(6):2425-30, 2010

 

1,656

1,2,3,4

 

20.

G von Minckwitz, H Eidtmann, S Loibl, JU Blohmer, SD Costa, PA Fasching, R Kreienberg, J Hilfrich, B Gerber, C Hanusch, T Fehm, D Strumberg, C Solbach, V Nekljudova, M Untch: Integrating bevacizumab, everolimus, and lapatinib into current neoadjuvant chemotherapy regimen for primary breast cancer. Safety results of the GeparQuinto trial.

Ann Oncol  22(2):301-6, 2011 (2010 epub)

 

6,452

2,3,4

 

21.

M Wurster, A Ruoff, C Meisner, H Seeger, U Vogel, I Juhasz-Böss, E Solomayer, D Wallwiener, T Fehm, Hans Neubauer:: Evaluation of ER alpha, PR and ER beta isoforms in neoadjuvant treated breast cancer.

Oncol Rep 24(3):653-9, 2010

 

1,686

1,2,3,4

 

22.

S Riethdorf, V Müller, L Zhang, T Rau, S Loibl, M Komor M Roller, J Huober, T Fehm, I Schrader, J Hilfrich, F Holms, H Tesch, H Eidtmann, M Untch, G von Minckwitz, K Pantel: Detection and HER2 expression of circulating tumor cells - prospective monitoring in breast cancer patients treated in the neoadjuvant "Geparquattro" trial.

Clin Cancer Res 16(9):2634-45,2010

 

7,338

1,2,3,4

 

 

 

 

 

2009

 

 

 

 

23.

S Schott, M Wallwiener, B Kootz, H Seeger, T Fehm, H Neubauer: ATP chemosensitivity testing of new antitumor duplex drugs linking 3;-C-ethynylycytidine (ECyd) and 2 -deoxy-5-fluorouridine (5-FdU) in comparison to standard cytostatica and combinations thereof.

Invest New Drugs 29(3):506-13, 2011 (epub 2009)

 

3,072

3,4

24.

B Aktas, M Tewes, T Fehm, S Hauch, R Kimmig, S Kasimir-Bauer: Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients.

Breast Cancer Res 2009,11:R46 (epub)

 

5,326

1,2,3,4

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