Skip to content

Research at St Andrews

Determining tamoxifen sensitivity using primary breast cancer tissue in collagen-based three-dimensional culture

Research output: Contribution to journalArticlepeer-review

Author(s)

Alexander D. Leeper, Joanne Farrell, Linda J. Williams, Jeremy S. Thomas, J. Michael Dixon, Sarah E. Wedden, David James Harrison, Elad Katz

School/Research organisations

Abstract

We developed a three-dimensional assay prepared from primary breast cancer tissue and quantified tumor response to tamoxifen therapy. Freshly harvested breast cancer biopsies obtained at the time of curative surgical resection were fragmented and embedded into collagen I cushions. Changes in proliferation, apoptosis and tumor volume in response to tamoxifen treatment were quantified using image analysis software and optical projection tomography. Individual and collective invasion of epithelial cells into the surrounding collagen I was observed over the course of the experiment using phase contrast light microscopy and histopathological methods. Addition of tamoxifen to preparations derived from ER+ tumors demonstrated a range of response as measured by proliferative and apoptotic markers. In keeping with published data, tamoxifen reduced the percentage of apoptotic cells expressing cleaved caspase-3 (p = 0.02, Poisson regression analysis). Tamoxifen also reduced residual epithelial volume in ER+ tumors (p = 0.001, Mann Whitney test), but not in ER low/- tumors (p = 0.78). Changes in tumor volume, as measured by optical projection tomography, allowed stratification into responsive and non-responsive tumors. The model mirrors observations of breast cancer response and histopathological changes to tamoxifen in neo-adjuvant trials. This assay provides a method of screening a battery of therapeutics against individual cancers, informing subsequent design of neo-adjuvant trials. (C) 2011 Elsevier Ltd. All rights reserved.

Close

Details

Original languageEnglish
Pages (from-to)907-915
Number of pages9
JournalBiomaterials
Volume33
Issue number3
DOIs
Publication statusPublished - Jan 2012

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Assessment of immunological features in muscle-invasive bladder cancer prognosis using ensemble learning

    Gavriel, C., Dimitriou, N., Brieu, N., Nearchou, I. P., Arandelovic, O., Schmidt, G., Harrison, D. J. & Caie, P. D., 1 Apr 2021, In: Cancers. 13, 7, 1624.

    Research output: Contribution to journalArticlepeer-review

  2. Automated detection and classification of desmoplastic reaction at the colorectal tumour front using deep learning

    Nearchou, I. P., Ueno, H., Kajiwara, Y., Lillard, K., Mochizuki, S., Takeuchi, K., Harrison, D. J. & Caie, P. D., 31 Mar 2021, In: Cancers. 13, 7, 1615.

    Research output: Contribution to journalArticlepeer-review

  3. A Phase IB open-label, dose-escalation study of NUC 1031 in combination with carboplatin for recurrent ovarian cancer

    Kazmi, F., Nicum, S., Roux, R., Spiers, L., Gnanaranjan, C., Sukumaran, A., Gabra, H., Ghazaly Kerwash, E., McCracken, N., Harrison, D. J. & Blagden, S. P., 19 Mar 2021, In: Clinical Cancer Research.

    Research output: Contribution to journalArticlepeer-review

  4. Recommendations for cellular and molecular pathology input into clinical trials: a systematic review and meta-aggregation

    Lim, S. J., Gurusamy, K., O'Connor, D., Shaaban, A. M., Brierley, D., Lewis, I., Harrison, D., Kendall, T. J. & Robinson, M., 26 Feb 2021, In: The Journal of Pathology: Clinical Research. Early View, 12 p.

    Research output: Contribution to journalReview articlepeer-review

Related by journal

  1. Human astrocytic grid networks patterned in parylene-C inlayed SiO2 trenches

    Jordan, M. D., Raos, B. J., Bunting, A. S., Murray, A. F., Graham, E. S. & Unsworth, C. P., Oct 2016, In: Biomaterials. 105, p. 117-126 10 p.

    Research output: Contribution to journalArticlepeer-review

  2. The formation of poly(ester–urea) networks in the absence of isocyanate monomers

    Zimmermann, J., Loontjens, T., Scholtens, B. J. R. & Mülhaupt, R., 2004, In: Biomaterials. 25, p. 2713-2719 7 p.

    Research output: Contribution to journalArticlepeer-review

ID: 23159110

Top