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7. Consensus Statement on Circulating Biomarkers for Advanced Prostate Cancer

Author

Sumanasuriya, Semini, Omlin, Aurelius, Armstrong, Andrew, Attard, Gerhardt, Chi, Kim N., Bevan, Charlotte L., Shibakawa, Aki, IJzerman, Maarten J., De Laere, Bram, Lolkema, Martijn, Lorente, David, Luo, Jun, Mehra, Niven, Olmos, David, Scher, Howard, Soule, Howard, Stoecklein, Nikolas H., Terstappen, Leon W.M.M., Waugh, David, and de Bono, Johann S.

Published
2018
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8. Measuring antigen expression of cancer cell lines and circulating tumour cells

Author

Mentink, Anouk, Isebia, Khrystany T., Kraan, Jaco, Terstappen, Leon W.M.M., Stevens, Michiel, and Medical Oncology

Subjects
Multidisciplinary, SDG 3 - Good Health and Well-being
Abstract

When evaluating EpCAM-based enrichment technologies for circulating tumour cells (CTCs), the cell lines used should closely resemble real CTCs, meaning the EpCAM expression of CTCs needs to be known, but also the EpCAM expression of cell lines at different institutions and times is important. As the number of CTCs in the blood is low, we enriched CTCs through the depletion of leukocytes from diagnostic leukapheresis products of 13 prostate cancer patients and measured EpCAM expression using quantitative flow cytometry. Antigen expression was compared between multiple institutions by measuring cultures from each institution. Capture efficiency was also measured for one of the used cell lines. Results show CTCs derived from castration-sensitive prostate cancer patients have varying but relatively low EpCAM expression, with median expression per patient ranging from 35 to 89,534 (mean 24,993) molecules per cell. A large variation in the antigen expression of identical cell lines cultured at different institutions was found, resulting in recoveries when using the CellSearch system ranging from 12 up to 83% for the same cell line. We conclude that large differences in capture efficiency can occur while using the same cell line. To closely resemble real CTCs from castration-sensitive prostate cancer patients, a cell line with a relatively low EpCAM expression should be used, and its expression should be monitored frequently.

Published
2023

11. Table S2 from Single-Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis

Author

Lambros, Maryou B., primary, Seed, George, primary, Sumanasuriya, Semini, primary, Gil, Veronica, primary, Crespo, Mateus, primary, Fontes, Mariane, primary, Chandler, Rob, primary, Mehra, Niven, primary, Fowler, Gemma, primary, Ebbs, Berni, primary, Flohr, Penny, primary, Miranda, Susana, primary, Yuan, Wei, primary, Mackay, Alan, primary, Ferreira, Ana, primary, Pereira, Rita, primary, Bertan, Claudia, primary, Figueiredo, Ines, primary, Riisnaes, Ruth, primary, Rodrigues, Daniel Nava, primary, Sharp, Adam, primary, Goodall, Jane, primary, Boysen, Gunther, primary, Carreira, Suzanne, primary, Bianchini, Diletta, primary, Rescigno, Pasquale, primary, Zafeiriou, Zafeiris, primary, Hunt, Joanne, primary, Moloney, Deirdre, primary, Hamilton, Lucy, primary, Neves, Rui P., primary, Swennenhuis, Joost, primary, Andree, Kiki, primary, Stoecklein, Nikolas H., primary, Terstappen, Leon W.M.M., primary, and de Bono, Johann S., primary

Published
2023
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14. Figure S5 from Single-Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis

Author

Lambros, Maryou B., primary, Seed, George, primary, Sumanasuriya, Semini, primary, Gil, Veronica, primary, Crespo, Mateus, primary, Fontes, Mariane, primary, Chandler, Rob, primary, Mehra, Niven, primary, Fowler, Gemma, primary, Ebbs, Berni, primary, Flohr, Penny, primary, Miranda, Susana, primary, Yuan, Wei, primary, Mackay, Alan, primary, Ferreira, Ana, primary, Pereira, Rita, primary, Bertan, Claudia, primary, Figueiredo, Ines, primary, Riisnaes, Ruth, primary, Rodrigues, Daniel Nava, primary, Sharp, Adam, primary, Goodall, Jane, primary, Boysen, Gunther, primary, Carreira, Suzanne, primary, Bianchini, Diletta, primary, Rescigno, Pasquale, primary, Zafeiriou, Zafeiris, primary, Hunt, Joanne, primary, Moloney, Deirdre, primary, Hamilton, Lucy, primary, Neves, Rui P., primary, Swennenhuis, Joost, primary, Andree, Kiki, primary, Stoecklein, Nikolas H., primary, Terstappen, Leon W.M.M., primary, and de Bono, Johann S., primary

Published
2023
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16. Supplementary Figure S2A from Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer

Author

Janni, Wolfgang J., primary, Rack, Brigitte, primary, Terstappen, Leon W.M.M., primary, Pierga, Jean-Yves, primary, Taran, Florin-Andrei, primary, Fehm, Tanja, primary, Hall, Carolyn, primary, de Groot, Marco R., primary, Bidard, François-Clement, primary, Friedl, Thomas W.P., primary, Fasching, Peter A., primary, Brucker, Sara Y., primary, Pantel, Klaus, primary, and Lucci, Anthony, primary

Published
2023
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17. Supplementary Table S1 from Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer

Author

Janni, Wolfgang J., primary, Rack, Brigitte, primary, Terstappen, Leon W.M.M., primary, Pierga, Jean-Yves, primary, Taran, Florin-Andrei, primary, Fehm, Tanja, primary, Hall, Carolyn, primary, de Groot, Marco R., primary, Bidard, François-Clement, primary, Friedl, Thomas W.P., primary, Fasching, Peter A., primary, Brucker, Sara Y., primary, Pantel, Klaus, primary, and Lucci, Anthony, primary

Published
2023
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18. supplemental figure legend from Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer

Author

Janni, Wolfgang J., primary, Rack, Brigitte, primary, Terstappen, Leon W.M.M., primary, Pierga, Jean-Yves, primary, Taran, Florin-Andrei, primary, Fehm, Tanja, primary, Hall, Carolyn, primary, de Groot, Marco R., primary, Bidard, François-Clement, primary, Friedl, Thomas W.P., primary, Fasching, Peter A., primary, Brucker, Sara Y., primary, Pantel, Klaus, primary, and Lucci, Anthony, primary

Published
2023
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19. Supplementary Table S1 from Global Gene Expression Profiling of Circulating Tumor Cells

Author

Smirnov, Denis A., primary, Zweitzig, Daniel R., primary, Foulk, Bradley W., primary, Miller, M. Craig, primary, Doyle, Gerald V., primary, Pienta, Kenneth J., primary, Meropol, Neal J., primary, Weiner, Louis M., primary, Cohen, Steven J., primary, Moreno, Jose G., primary, Connelly, Mark C., primary, Terstappen, Leon W.M.M., primary, and O'Hara, S. Mark, primary

Published
2023
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20. Supplementary Figure S1 from Global Gene Expression Profiling of Circulating Tumor Cells

Author

Smirnov, Denis A., primary, Zweitzig, Daniel R., primary, Foulk, Bradley W., primary, Miller, M. Craig, primary, Doyle, Gerald V., primary, Pienta, Kenneth J., primary, Meropol, Neal J., primary, Weiner, Louis M., primary, Cohen, Steven J., primary, Moreno, Jose G., primary, Connelly, Mark C., primary, Terstappen, Leon W.M.M., primary, and O'Hara, S. Mark, primary

Published
2023
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23. Supplementary Figure Legends 1-5 from Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

Author

Attard, Gerhardt, primary, Swennenhuis, Joost F., primary, Olmos, David, primary, Reid, Alison H.M., primary, Vickers, Elaine, primary, A'Hern, Roger, primary, Levink, Rianne, primary, Coumans, Frank, primary, Moreira, Joana, primary, Riisnaes, Ruth, primary, Oommen, Nikhil Babu, primary, Hawche, George, primary, Jameson, Charles, primary, Thompson, Emilda, primary, Sipkema, Ronald, primary, Carden, Craig P., primary, Parker, Christopher, primary, Dearnaley, David, primary, Kaye, Stan B., primary, Cooper, Colin S., primary, Molina, Arturo, primary, Cox, Michael E., primary, Terstappen, Leon W.M.M., primary, and de Bono, Johann S., primary

Published
2023
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24. Supplementary Tables 1-4 from Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

Author

Attard, Gerhardt, primary, Swennenhuis, Joost F., primary, Olmos, David, primary, Reid, Alison H.M., primary, Vickers, Elaine, primary, A'Hern, Roger, primary, Levink, Rianne, primary, Coumans, Frank, primary, Moreira, Joana, primary, Riisnaes, Ruth, primary, Oommen, Nikhil Babu, primary, Hawche, George, primary, Jameson, Charles, primary, Thompson, Emilda, primary, Sipkema, Ronald, primary, Carden, Craig P., primary, Parker, Christopher, primary, Dearnaley, David, primary, Kaye, Stan B., primary, Cooper, Colin S., primary, Molina, Arturo, primary, Cox, Michael E., primary, Terstappen, Leon W.M.M., primary, and de Bono, Johann S., primary

Published
2023
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25. Data from Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

Author

Attard, Gerhardt, primary, Swennenhuis, Joost F., primary, Olmos, David, primary, Reid, Alison H.M., primary, Vickers, Elaine, primary, A'Hern, Roger, primary, Levink, Rianne, primary, Coumans, Frank, primary, Moreira, Joana, primary, Riisnaes, Ruth, primary, Oommen, Nikhil Babu, primary, Hawche, George, primary, Jameson, Charles, primary, Thompson, Emilda, primary, Sipkema, Ronald, primary, Carden, Craig P., primary, Parker, Christopher, primary, Dearnaley, David, primary, Kaye, Stan B., primary, Cooper, Colin S., primary, Molina, Arturo, primary, Cox, Michael E., primary, Terstappen, Leon W.M.M., primary, and de Bono, Johann S., primary

Published
2023
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26. Supplementary Figure 4 from Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

Author

Attard, Gerhardt, primary, Swennenhuis, Joost F., primary, Olmos, David, primary, Reid, Alison H.M., primary, Vickers, Elaine, primary, A'Hern, Roger, primary, Levink, Rianne, primary, Coumans, Frank, primary, Moreira, Joana, primary, Riisnaes, Ruth, primary, Oommen, Nikhil Babu, primary, Hawche, George, primary, Jameson, Charles, primary, Thompson, Emilda, primary, Sipkema, Ronald, primary, Carden, Craig P., primary, Parker, Christopher, primary, Dearnaley, David, primary, Kaye, Stan B., primary, Cooper, Colin S., primary, Molina, Arturo, primary, Cox, Michael E., primary, Terstappen, Leon W.M.M., primary, and de Bono, Johann S., primary

Published
2023
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27. Supplementary Figure 5 from Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

Author

Attard, Gerhardt, primary, Swennenhuis, Joost F., primary, Olmos, David, primary, Reid, Alison H.M., primary, Vickers, Elaine, primary, A'Hern, Roger, primary, Levink, Rianne, primary, Coumans, Frank, primary, Moreira, Joana, primary, Riisnaes, Ruth, primary, Oommen, Nikhil Babu, primary, Hawche, George, primary, Jameson, Charles, primary, Thompson, Emilda, primary, Sipkema, Ronald, primary, Carden, Craig P., primary, Parker, Christopher, primary, Dearnaley, David, primary, Kaye, Stan B., primary, Cooper, Colin S., primary, Molina, Arturo, primary, Cox, Michael E., primary, Terstappen, Leon W.M.M., primary, and de Bono, Johann S., primary

Published
2023
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28. Supplementary Figures 1-3 from Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

Author

Attard, Gerhardt, primary, Swennenhuis, Joost F., primary, Olmos, David, primary, Reid, Alison H.M., primary, Vickers, Elaine, primary, A'Hern, Roger, primary, Levink, Rianne, primary, Coumans, Frank, primary, Moreira, Joana, primary, Riisnaes, Ruth, primary, Oommen, Nikhil Babu, primary, Hawche, George, primary, Jameson, Charles, primary, Thompson, Emilda, primary, Sipkema, Ronald, primary, Carden, Craig P., primary, Parker, Christopher, primary, Dearnaley, David, primary, Kaye, Stan B., primary, Cooper, Colin S., primary, Molina, Arturo, primary, Cox, Michael E., primary, Terstappen, Leon W.M.M., primary, and de Bono, Johann S., primary

Published
2023
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29. Supplementary Tables 5-8 from Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

Author

Attard, Gerhardt, primary, Swennenhuis, Joost F., primary, Olmos, David, primary, Reid, Alison H.M., primary, Vickers, Elaine, primary, A'Hern, Roger, primary, Levink, Rianne, primary, Coumans, Frank, primary, Moreira, Joana, primary, Riisnaes, Ruth, primary, Oommen, Nikhil Babu, primary, Hawche, George, primary, Jameson, Charles, primary, Thompson, Emilda, primary, Sipkema, Ronald, primary, Carden, Craig P., primary, Parker, Christopher, primary, Dearnaley, David, primary, Kaye, Stan B., primary, Cooper, Colin S., primary, Molina, Arturo, primary, Cox, Michael E., primary, Terstappen, Leon W.M.M., primary, and de Bono, Johann S., primary

Published
2023
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32. MicroRNA in the Tumor Stroma

Author

Lu, Tao, Terstappen, Leon W.M.M., Prakash, Jai, Biomaterials Science and Technology, TechMed Centre, Medical Cell Biophysics, and Advanced Organ bioengineering and Therapeutics

Subjects
NLA
Abstract

In this chapter, the author highlight dysregulated MicroRNAs (miRNA), as potential therapeutic targets in different tumor stromal cells describe their functions in the regulation of the tumor microenvironment. They also discusses the role of tumor-related miRNAs as biomarkers for cancer diagnosis and prognosis. TAMs show the ability to promote the tumor development and progression by enhancing angiogenesis, immune suppression, tumor cell invasion, and metastatic programming of tumor tissue, and thus reducing patient survival. MiRNAs can also be delivered by inorganic nanoparticle–based vectors, such as gold nanoparticles, iron-nanoparticles and silica-based nanoparticles. Tumor stroma plays an essential role during tumor growth, thus targeting tumor stromal cells provides possibilities to inhibit the promotion activities in tumor progression and metastasis. The authors summarizes various miRNA delivery approaches that have been or can potentially be applied to deliver miRNA as therapeutics into the stromal cells.

Published
2022

34. Abstract GS4-08: Clinical utility of repeated circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) - a global pooled analysis with individual patient data

Author

Janni, Wolfgang J, primary, Yab, Tracy C., additional, Hayes, Daniel F., additional, Cristofanilli, Massimo, additional, Bidard, Francois-Clement, additional, Ignatiadis, Michail, additional, Regan, Meredith M., additional, Alix-Panabières, Catherine, additional, Barlow, William E., additional, Caldas, Carlos, additional, Carey, Lisa A., additional, Dirix, Luc, additional, Fehm, Tanja, additional, Garcia-Saenz, Jose A., additional, Gazzaniga, Paola, additional, Generali, Daniele, additional, Gerratana, Lorenzo, additional, Gisbert-Criado, Rafael, additional, Jacot, William, additional, Jiang, Zefei, additional, Lianidou, Evi, additional, Magbanua, Mark J.M., additional, Manso, Luis, additional, Mavroudis, Dimitrios, additional, Müller, Volkmar, additional, Munzone, Elisabetta, additional, Pantel, Klaus, additional, Pierga, Jean-Yves, additional, Rack, Brigitte, additional, Riethdorf, Sabine, additional, Rugo, Hope S., additional, Sideras, Kostandinos, additional, Sleijfer, Stefan, additional, Smerage, Jeffrey, additional, Stebbing, Justin, additional, Terstappen, Leon W.M.M., additional, Vidal-Martínez, José, additional, Zamarchi, Rita, additional, Giridhar, Karthik, additional, Friedl, Thomas W.P., additional, and Liu, Minetta C., additional

Published
2021
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35. Analysis of Released Circulating Tumor Cells During Surgery for Non-Small Cell Lung Cancer: are they what they appear to be?

Author

Tamminga, Menno, de Wit, Sanne, van der Wauwer, Caroline, van den Bos, Hilda, Swennenhuis, Joost F., Klinkenberg, Theo. J., Hiltermann, T. Jeroen N., Andree, Kiki C., Spierings, Diana.C.J., Lansdorp, Peter M., van den Berg, Anke, Timens, Wim, Terstappen, Leon W.M.M., Groen, Harry J.M., Damage and Repair in Cancer Development and Cancer Treatment (DARE), Translational Immunology Groningen (TRIGR), Stem Cell Aging Leukemia and Lymphoma (SALL), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Research Institute for Asthma and COPD (GRIAC), and Medical Cell Biophysics

Subjects
PULMONARY VENOUS-BLOOD, RESECTION, IMPACT, IN-SITU, THORACOTOMY, SURGICAL MANIPULATION, 22/2 OA procedure, SURVIVAL, VESSEL LIGATION, ASSOCIATION, RECURRENCE
Abstract

Purpose: Tumor cells from patients with lung cancer are expelled from the primary tumor into the blood, but difficult to detect in the peripheral circulation. We studied the release of circulating tumor cells (CTCs) during surgery to test the hypothesis that CTC counts are influenced by hemodynamic changes (caused by surgical approach) and manipulation. Experimental Design: Patients undergoing video-assisted thoracic surgery (VATS) or open surgery for (suspected) primary lung cancer were included. Blood samples were taken before surgery (T0) from the radial artery (RA), from both the RA and pulmonary vein (PV) when the PV was located (T1) and when either the pulmonary artery (T2 open) or the PV (T2 VATS) was dissected. The CTCs were enumerated using the CellSearch system. Single-cell whole-genome sequencing was performed on isolated CTCs for aneuploidy. Results: CTCs were detected in 58 of 138 samples (42%) of 31 patients. CTCs were more often detected in the PV (70%) compared with the RA (22%, P < 0.01) and in higher counts (P < 0.01). After surgery, the RA but not the PV showed less often CTCs (P ¼ 0.02). Type of surgery did not influence CTC release. Only six of 496 isolated CTCs showed aneuploidy, despite matched primary tumor tissue being aneuploid. Euploid so-called CTCs had a different morphology than aneuploid. Conclusions: CTCs defined by CellSearch were identified more often and in higher numbers in the PV compared with the RA, suggesting central clearance. The majority of cells in the PV were normal epithelial cells and outnumbered CTCs. Release of CTCs was not influenced by surgical approach.

Published
2020

36. uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues

Author

Meng, Songdong, Tripathy, Debu, Shete, Sanjay, Ashfaq, Raheela, Saboorian, Hossein, Haley, Barbara, Frenkel, Eugene, Euhus, David, Leitch, Marilyn, Osborne, Cynthia, Clifford, Edward, Perkins, Steve, Beitsch, Peter, Khan, Amanullah, Morrison, Larry, Herlyn, Dorothee, Terstappen, Leon W.M.M., Lane, Nancy, Wang, Jianqiang, and Uhr, Jonathan

Subjects
Cancer cells -- Genetic aspects, Breast cancer -- Research, Oncogenes -- Research, Science and technology
Abstract

Overexpression of urokinase plasminogen activator system or HER-2 (erbB-2) in breast cancer is associated with a poor prognosis. HER-2 overexpression is caused by HER-2 gene amplification. The anti-HER-2 antibody trastuzumab significantly improves clinical outcome for HER2-positive breast cancer. Drugs that target the uPA system are in early clinical trials. The aims of this study were to determine whether urokinase plasminogen activator receptor (uPAR) gene amplification occurs and whether analysis of individual tumor cells (TCs) in the blood or tissue can add information to conventional pathological analysis that could help in diagnosis and treatment. Analysis of individual TCs indicates that uPAR amplification occurs in a significant portion of primary breast cancers and also circulating tumor cells (CTCs) from patients with advanced disease. There was complete concordance between touch preps (TPs) and conventional pathological examination of HER-2 and uPAR gene status in primary tumors. There was also excellent concordance of HER-2 gene status between primary tumors and CTCs provided that acquisition of HER-2 gene amplification in CTCs was taken into account. Unexpectedly, gene amplification of HER-2 and uPAR occurred most frequently in the same TC and patient, suggesting a biological bias and potential advantage for co-amplification. Expression of HER-2 and uPAR in primary tumors predicted gene status in 100 and 92% of patients, respectively. oncogene coamplification | expression | amplification

Published
2006

38. Circulating tumor cells, disease progression, and survival in metastatic breast cancer

Author

Cristofanilli, Massimo, Budd, G. Thomas, Ellis, Matthew J., Stopeck, Alison, Matera, Jeri; Hayes, Daniel F., Miller, Craig M., Reuben, James M., Allard, W Jeffrey, Doyle, Gerald V., and Terstappen, Leon W.M.M.

Subjects
Cancer patients -- Care and treatment, Breast cancer -- Risk factors, Breast cancer -- Diagnosis, T cells -- Research
Abstract

The results of the trial indicate that in metastatic breast cancer the level of circulating tumor cells before a new therapy is initiated and, even more important, the level measured at the first follow-up visit are useful predictors of progression-free survival and overall survival. Measurable metastatic breast cancers for levels of circulating tumor cell in 177 patients were tested.

Published
2004

39. HER-2 gene amplification can be acquired as breast cancer progresses

Author

Meng, Songdong, Tripathy, Debasish, Shete, Sanjay, Ashfaq, Raheela, Haley, Barbara, Perkins, Steve, Beitsch, Peter, Khang, Amanullah, Euhush, David, Osborne, Cynthia, Frenkel, Eugene, Hoover, Susan, Leitch, Marilyn, Clifford, Edward, Vitetta, Ellen, Morrison, Larry, Herlyn, Dorothee, Terstappen, Leon W.M.M., Fleming, Timothy, Fehm, Tanja, Tucker, Thomas, Lane, Nancy, Wang, Jianqiang, and Uhra, Jonathan

Subjects
Breast cancer -- Research, Science and technology
Abstract

Amplification and overexpression of the HER-2 oncogene in breast cancer is felt to be stable over the course of disease and concordant between primary tumor and metastases. Therefore, patients with HER-2-negative primary tumors rarely will receive anti-Her-2 antibody (trastuzumab, Herceptin} therapy. A very sensitive blood test was used to capture circulating tumor cells (CTCs) and evaluate their HER-2 gene status by fluorescence in situ hybridization. The HER-2 status of the primary tumor and corresponding CTCs in 31 patients showed 97% agreement, with no false positives. In 10 patients with HER-2-positive tumors, the HER-2/chromosome enumerator probe 17 ratio in each tumor was about twice that of the corresponding CTCs (mean 6.64 [+ or -] 2.72 vs. 2.8 [+ or -] 0.6). Hence, the ratio of the CTCs is a reliable surrogate marker for the expected high ratio in the primary tumor. Her-2 protein expression of 10 CTCs was sufficient to make a definitive diagnosis of the HER-2 gene status of the whole population of CTCs in 19 patients with recurrent breast cancer. Nine of 24 breast cancer patients whose primary tumor was HER-2-negative each acquired HER-2 gene amplification in their CTCs during cancer progression, i.e., 37.5% (95% confidence interval of 18.8-59.4%). Four of the 9 patients were treated with Herceptin-containing therapy. One had a complete response and 2 had a partial response.

Published
2004

44. Detection and characterization of carcinoma cells in the blood

Author

Racila, Emilian, Euhus, David, Weiss, Arthur J., Rao, Chandra, McConnell, John, Terstappen, Leon W.M.M., and Uhr, Jonathan W.

Subjects
Cancer cells -- Research, Blood diseases -- Research, Science and technology
Abstract

A highly sensitive assay combining immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis has been developed to detect, enumerate, and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood. Peripheral blood (10-20 ml) from 30 patients with carcinoma of the breast, from 3 patients with prostate cancer, and from 13 controls was examined by flow cytometry for the presence of circulating epithelial cells defined as nucleic [acid.sup.+], CD[45.sup.-], and [cytokeratin.sup.+]. Highly significant differences in the number of circulating epithelial cells were found between normal controls and patients with cancer including 17 with organ-confined disease. To determine whether the circulating epithelial cells in the cancer patients were neoplastic cells, cytospin preparations were made after immunomagnetic enrichment and were analyzed. Epithelial cells from patients with breast cancer generally stained with mAbs against cytokeratin and 3 of 5 for mucin-1. In contrast, no cells that stained for these antigens were observed in the blood from normal controls. The morphology of the stained cells was consistent with that of neoplastic cells. Of 8 patients with breast cancer followed for 1-10 months, there was a good correlation between changes in the level of tumor cells in the blood with both treatment with chemotherapy and clinical status. The present assay may be helpful in early detection, in monitoring disease, and in prognostication.

Published
1998

45. A microfluidic droplet serial dilutor with enhanced mixing

Author

Rho, Hoon Suk, Yang, Yoonsun, Terstappen, Leon W.M.M., Habibović, Pamela, le Gac, Séverine, Tseng, Fan-Gang, Lee, Gwo-Bin, Applied Microfluidics for BioEngineering Research, and Medical Cell Biophysics

Subjects
Microvalve, Serial dilution, Microfluidics, eye diseases, Droplets
Abstract

We present the development of an automated microfluidic platform that is capable of creating logarithmic serial dilution by adapting pneumatically actuated microvalves. A valve-assisted droplet manipulator integrated with a peristaltic mixer allowed the accurate formation of droplets with controlled sizes and the dilution of reagent sequentially. Hence, serial dilution with flexible dilution factors was obtained in a series of nanoliter-scale droplets. We validated the mixing efficiency and droplet generating performance of the chip at various operating conditions and demonstrated an example of logarithmic serial dilution with two different dilution factors. The microfluidic droplet serial dilutor could be used as an analytical tool to evaluate various complex chemical and biochemical reactions.

Published
2018

48. Brief report: donor-derived long-term multilineage hematopoiesis in a liver-transplant recipient

Author

Collins, Robert H., Jr., Anastasi, John, Terstappen, Leon W.M.M., Nikaein, Afzal, Feng, Jiajia, Fay, Joseph W., Klintmalm, Goran, and Stone, Marvin J.

Subjects
Liver -- Transplantation, Hematopoiesis -- Physiological aspects, Transplantation of organs, tissues, etc. -- Physiological aspects
Abstract

A woman whose immune system had been damaged by graft-versus-host disease (GVHD) following a liver transplant experienced recovery of immune function from stem cells that migrated from the donor's liver to her bone marrow. She had received the liver of a 17-year-old boy after she developed liver cirrhosis. Twelve days after transplantation, her white cell count began to drop and she was diagnosed with GVHD. She responded to corticosteroids, but ultimately died of recurrent GVHD. At autopsy, DNA analysis revealed that many of her blood cells were male (had an X and Y chromosome) and contained antigens similar to those of the donor. These included mature blood cells as well as immature stem cells in her bone marrow. Many of the stem cells in her bone marrow were male. In addition, male cells were found in her spleen, lungs and lymph nodes. Many mature blood cells may have come from blood in the donor's liver, but the presence of male stem cells indicates that the donated liver contained cells capable of restoring the woman's immune system.

Published
1993

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