Home > Resources : CellSearch® > 複数種のがん症例、その他のがん症例 【33報】

複数種のがん症例、その他のがん症例 【33報】


                                                                              2014/01/20 掲載 


Circulating Tumor Cells: Application as a Biomarker for Molecular Characterization and Predictor of Survival in an All-Comer Solid Tumor Phase I Clinical Study.

Haifeng Bao, Patricia A. Burke, Jiaqi Huang, Xiaoru Chen, Philip Z. Brohawn, Yihong Yao, Robert J. Lechleider, Robert S. Sikorski, Manuela Buzoianu, Jianliang Zhang, Xiaoqing Shi, Laura K. Richman, Theresa M. LaVallee.

PLoS One. 2013 Aug 21;8(8):e58557


  侵襲性の低い方法を用いた予後予測バイオマーカーは、疾患の特性評価、患者選定、薬効評価の早期検出を可能にし、治療が成功する可能性を高めると考えられ ています。CTC(Circulating tumor cell)の計測や分子的特性評価はこうしたいくつかの需要に応え得るものです。本研究では、Phase I 固形がん臨床試験におけるCTCの計測および分子的特性評価の有用性を評価しました。

 MEDI-575のmulti-center all-comer  Phase I studyにおいて、24名のがん患者からCTC解析に使用する血液検体が提供されました。患者の内訳は、大腸がん10名(41.7%)、非小細胞肺がん 3名(12.5%)、前立腺がん3名(12.5%)、乳がん1名(4.2%)、卵巣がん1名(4.2%)、子宮内膜がん1名(4.2%)、その他5名 (20.8%)でした。

 検体をスクリーニングし、CellSearchを使用して血液検体中のCTCを計測しました。また、CTC濃縮サンプルからRNAを抽出し、新規手法であるMultimarker qRT-PCR法を用いて、CTCの発現遺伝子を解析しました。

  ベースライン(スクリーニング)時の患者21名中14名で、7.5mLあたり1個以上のCTCが検出されました。ベースライン時にCTCを検出しなかった 患者群の無増悪生存率(PFS)は8.8ヵ月であったのに対して、CTC検出数が1~3個の群では1.4ヵ月、CTC検出数が3個以上の群では1.3ヵ月 でした(P=0.02)。全生存率(OS)は、CTCを検出しなかった患者群では9.0ヵ月、CTC検出数が1~3個の群では7.4ヵ月、3個以上の群で は3.5ヵ月でした(P=0.20)。CTCが検出されなかった患者群のPFS、OSは他2グループよりも長い結果となりました。


Multimarker qRT-PCR法を用いた解析では、15名の患者のうち6名で、上皮/腫瘍マーカーであるCK20、CEA、AGR2のいずれかを発現していました。本研究においてdrug targetの探索的遺伝子であるHER3DLL4EPHA2は、3名がHER3を、4名がDLL4を、3名がEPHA2を発現していました。

 All-comer studyにおいて、患者のCTC計測は有効で、層別化した患者のPFSやOSにおいて、治験薬の効果を評価し得るものです。CTCの計測と分子的特性評価は、患者の病状や治療について有益なバイオマーカーとなり得ます。








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Interpretation of changes in circulating tumor cell counts.

Coumans FA, Ligthart ST, Terstappen LW.

Transl Oncol. 2012 Dec;5(6):486-91. Epub 2012 Dec 1.



Biomarker Utility of Circulating Tumor Cells in Metastatic Cutaneous Melanoma.

Khoja L, Lorigan P, Zhou C, Lancashire M, Booth J, Cummings J, Califano R, Clack G, Hughes A, Dive C.

J Invest Dermatol. 2012 Dec 6. doi: 10.1038/jid.2012.468.



User-defined protein marker assay development for characterization of circulating tumor cells using the CellSearch® system.

Lori E. Lowes, Benjamin D. Hedley, Mike Keeney, Alison L. Allan

Cytometry A. 2012 Aug 16. doi: 10.1002/cyto.a.22158.



Detection of circulating tumor cells in cancers of biliary origin.

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J Gastrointest Oncol. 2012 Jun;3(2):97-104.



A fluid biopsy as investigating technology for the fluid phase of solid tumors.

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Automated identification of circulating tumor cells by image cytometry.

Tycho M. Scholtens, Frederik Schreuder, Sjoerd T. Ligthart, Joost F. Swennenhuis, Jan Greve, and Leon W. M. M. Terstappen.

Cytometry, 81A(2):138–148, 2012.




Circulating melanoma cells and survival in metastatic melanoma.

C. Rao, T. Bui, M. Connelly, G. Doyle, I. Karydis, M. R. Middleton, G. Clack, M. Malone, F. A. Coumans, and L. W. Terstappen.

International journal of oncology, 38(3):755–760, March 2011.



Baseline circulating tumor cell counts significantly enhance a prognostic score for patients participating in phase i oncology trials.

David Olmos, Richard D. Baird, Timothy A. Yap, Christophe Massard, Lorna Pope, Shahneen K. Sandhu, Juliet Dukes, Dionysis Papadatos-Pastos, Philippa Grainger, Stanley B. Kaye, and Johann S. de Bono.

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Detection of EpCAM-negative and Cytokeratin-Negative circulating tumor cells in peripheral blood.

Stephen D. Mikolajczyk, Lisa S. Millar, Pavel Tsinberg, Stephen M. Coutts, Maryam Zomorrodi, Tam Pham, Farideh Z. Bischoff, and Tony J. Pircher.

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Circulating tumor cells and EpCAM expression in neuroendocrine tumors.

Mohid S. Khan, Theodora Tsigani, Mohammed Rashid, Jeremy S. Rabouhans, Dominic Yu, Tu V. Luong, Martyn Caplin, and Tim Meyer.

Clinical Cancer Research, 17(2):337–345, January 2011.



External quality assurance of circulating tumor cell enumeration using the CellSearch system: A feasibility study.

Jaco Kraan, Stefan Sleijfer, Michiel H. Strijbos, Michail Ignatiadis, Dieter Peeters, Jean-Yves Pierga, Francoise Farace, Sabine Riethdorf, Tanja Fehm, Laura Zorzino, Arjan G. J. Tibbe, Marisa Maestro, Rafael Gisbert-Criado, Graeme Denton, Johann S. de Bono, Caroline Dive, John A. Foekens, and Jan W. Gratama.

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Circulating tumor cells as pharmacodynamic biomarker in early clinical oncological trials.

Lot A. Devriese, Emile E. Voest, Jos H. Beijnen, and Jan H. M. Schellens. Cancer Treatment 37(8):579–589, December 2011. Reviews,


Detection of circulating tumor cells in advanced head and neck cancer using the cellsearch system.

Anthony C. Nichols, Lori E. Lowes, Christopher C. T. Szeto, John Basmaji, Sandeep Dhaliwal, Corina Chapeskie, Biljana Todorovic, Nancy Read, Varugar Venkatesan, Alex Hammond, David A. Palma, Eric Winquist, Scott Ernst, Kevin Fung, Jason H. Franklin, John Yoo, James Koropatnick, Joe S. Mymryk, John W. Barrett, and Alison L. Allan.

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A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas.

F. Farace, C. Massard, N. Vimond, F. Drusch, N. Jacques, F. Billiot, A. Laplanche, A. Chauchereau, L. Lacroix, D. Planchard, S. Le Moulec, F. Andre, K. Fizazi, J. C. Soria, and P. Vielh.

Br J Cancer, 105(6):847–853, September 2011.



Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: A gynecologic oncology group study.

Kian Behbakht, Michael W. Sill, Kathleen M. Darcy, Stephen C. Rubin, Robert S. Mannel, Steven Waggoner, Russell J. Schilder, Kathy Q. Cai, Andrew K. Godwin, and R. Katherine Alpaugh.

Gynecologic Oncology, July 2011.



Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis.

Pavlos Msaouel and Michael Koutsilieris.

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M30 neoepitope expression in epithelial cancer: Quantification of apoptosis in circulating tumor cells by CellSearch analysis.

Elisabetta Rossi, Umberto Basso, Romina Celadin, Francesca Zilio, Salvatore Pucciarelli, Michele Aieta, Carmen Barile, Teodoro Sava, Giorgio Bonciarelli, Salvatore Tumolo, Cristina Ghiotto, Cristina Magro, Antonio Jirillo, Stefano Indraccolo, Alberto Amadori, and Rita Zamarchi.

Clinical Cancer Research, 16(21):5233–5243, November 2010.



Molecular biomarker analyses using circulating tumor cells.

Elizabeth A. Punnoose, Siminder K. Atwal, Jill M. Spoerke, Heidi Savage, Ajay Pandita, Ru-Fang F. Yeh, Andrea Pirzkall, Bernard M. Fine, Lukas C. Amler, Daniel S. Chen, and Mark R. Lackner.

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Circulating tumour cells in cancer patients: challenges and perspectives.

Klaus Pantel and Catherine Alix-Panabières.

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Monitoring drug-induced gammaH2AX as a pharmacodynamic biomarker in individual circulating tumor cells.

Lihua H. Wang, Thomas D. Pfister, Ralph E. Parchment, Shivaani Kummar, Larry Rubinstein, Yvonne A. Evrard, Martin E. Gutierrez, Anthony J. Murgo, Joseph E. Tomaszewski, James H. Doroshow, and Robert J. Kinders.

Clinical Cancer Research, 16(3):1073–1084, February 2010.



Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors.

Paola Gazzaniga, Giuseppe Naso, Angela Gradilone, Enrico Cortesi, Orietta Gandini, Walter Gianni, Maria A. Fabbri, Bruno Vincenzi, Franco di Silverio, Luigi Frati, Anna M. Aglianò, and Massimo Cristofanilli.

Int J Cancer. 2010 May 15;126(10):2437-47.



Significance of circulating tumor cells detected by the CellSearch system in patients with metastatic breast colorectal and prostate cancer.

M. Craig Miller, Gerald V. Doyle, and Leon W. Terstappen.

Journal of oncology, 2010, 2010.




Circulating tumor cells in solid tumor in metastatic and localized stages.

Luisa M. Maestro, Javier Sastre, Sara B. Rafael, Silvia B. Veganzones, Marta Vidaurreta, Miguel Martín, Carlos Olivier, Virginia B. De la Orden, Jose A. Garcia-Saenz, Rosario Alfonso, Manuel Arroyo, and Eduardo Diaz-Rubio.

Anticancer Research, 29(11):4839–4843, November 2009.



Tumor Self-Seeding: Bidirectional flow of tumor cells.

Cheuk T. Leung and Joan S. Brugge.

Cell, 139(7):1226–1228, December 2009.



Tumor Self-Seeding by circulating cancer cells.

Mi-Young Kim, Thordur Oskarsson, Swarnali Acharyya, Don X. Nguyen, Xiang H. F. Zhang, Larry Norton, and Joan Massagué.

Cell, 139(7):1315–1326, December 2009.



Unique localization of circulating tumor cells in patients with hepatic metastases.

Long R. Jiao, Christos Apostolopoulos, Jimmy Jacob, Richard Szydlo, Natalia Johnson, Nicole Tsim, Nagy A. Habib, R. Charles Coombes, and Justin Stebbing.

Journal of Clinical Oncology, 27(36):6160–6165, December 2009.



Circulating endothelial cells: A potential parameter of organ damage in sickle cell anemia?

Michiel H. Strijbos, Precious P. Landburg, Erfan Nur, Tom Teerlink, Frank W. G. Leebeek, Anita W. Rijneveld, Bart J. Biemond, Stefan Sleijfer, Jan W. Gratama, and Ashley J. Duits.

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The detection of circulating tumor cells expressing E6/E7 HR-HPV oncogenes in peripheral blood in cervical cancer patients after radical hysterectomy.

Weismann P, Weismanova E, Masak L, Mlada K, Keder D, Ferancikova Z, Vizvaryova M, Konecny M, Zavodna K, Kausitz J, Benuska J, Repiska V.

Neoplasma, 56(3):230–238, 2009.




Circulating tumor cells in melanoma: a review of the literature and description of a novel technique.

Shawn Steen, John Nemunaitis, Tammy Fisher, and Joseph Kuhn.

Proceedings (Baylor University. Medical Center), 21(2):127–132, April 2008.



Monitoring circulating tumor cells in cancer vaccine trials.

J. D. Gates, L. C. Benavides, A. Stojadinovic, E. A. Mittendorf, J. P. Holmes, M. G. Carmichael, S. McCall, A. L. Milford, G. A. Merrill, S. Ponniah, and G. E. Peoples.

Human vaccines, 4(5):389–392, 2008.




Comparison of two methods for enumerating circulating tumor cells in carcinoma patients.

Marija Balic, Nadia Dandachi, Günter Hofmann, Hellmut Samonigg, Hans Loibner, Andreas Obwaller, Alexander van der Kooi, Arjan G. J. Tibbe, Gerald V. Doyle, Leon W. M. M. Terstappen, and Thomas Bauernhofer.

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Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases.

Chandra Rao, Arjan G. J. Tibbe, Jonathan W. Uhr, and Leon W. M. M. Terstappen. W. Jeffrey Allard, Jeri Matera, M. Craig Miller, Madeline Repollet, Mark C. Connelly,

Clinical Cancer Research, 10(20):6897–6904, October 2004.


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