Assessment of γ-H2AX levels in circulating tumor cells from patients receiving chemotherapy
Circulating tumor cells (CTCs) are prognostic markers in a variety of solid tumor malignancies. The potential of CTCs to be used as a liquid biopsy to monitor a patient’s condition and predict drug response and resistance is currently under investigation. Using a negative depletion, enrichment meth...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-10-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2012.00128/full |
| _version_ | 1819238104880381952 |
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| author | Alejandra eGarcia-Villa Priya eBalsubramanian Brandon eMiller Maryam eLustberg Bhuvaneswari eRamaswamy Jeffrey eChalmers |
| author_facet | Alejandra eGarcia-Villa Priya eBalsubramanian Brandon eMiller Maryam eLustberg Bhuvaneswari eRamaswamy Jeffrey eChalmers |
| author_sort | Alejandra eGarcia-Villa |
| collection | DOAJ |
| description | Circulating tumor cells (CTCs) are prognostic markers in a variety of solid tumor malignancies. The potential of CTCs to be used as a liquid biopsy to monitor a patient’s condition and predict drug response and resistance is currently under investigation. Using a negative depletion, enrichment methology, CTCs isolated from the peripheral blood of breast cancer patients with stage IV breast cancer undergoing DNA damaging therapy with platinum based therapy were enriched. The enriched cell suspensions, were stained with an optimized labeling protocol targeting: nuclei, cytokeratins 8, 18, and 19, the surface marker CD45, and the presence of the protein ɣ-H2AX. As a direct or indirect result of platinum therapy, double strand break of DNA initiates phosphorylation of the histone H2AX, at serine 139; this phosphorylated form is referred to as ɣ-H2AX. In addition to ɣ-H2AX staining in specific locations with the cell nuclei, consistent with previous reports and referred to as foci, more general staining in the cell cytoplamim was also observed in some cells suggesting the potential of cell apoptosis. Our study underscores the utility and the complexity of investigating CTCs as predictive markers of response to various therapies. Additional studies are ongoing to evaluate the diverse γ-H2AX staining patterns we report here which needs to be further correlated with patient outcomes |
| first_indexed | 2024-12-23T13:30:56Z |
| format | Article |
| id | doaj.art-5b0dfa76a7e449e3b9049b35c11dedd2 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-23T13:30:56Z |
| publishDate | 2012-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-5b0dfa76a7e449e3b9049b35c11dedd22022-12-21T17:45:10ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2012-10-01210.3389/fonc.2012.0012831296Assessment of γ-H2AX levels in circulating tumor cells from patients receiving chemotherapyAlejandra eGarcia-Villa0Priya eBalsubramanian1Brandon eMiller2Maryam eLustberg3Bhuvaneswari eRamaswamy4Jeffrey eChalmers5The Ohio State UniversityThe Ohio State UniversityThe Ohio State UniversityJames Cancer Hospital and Ohio State University Comprehensive Cancer CenterJames Cancer Hospital and Ohio State University Comprehensive Cancer CenterThe Ohio State UniversityCirculating tumor cells (CTCs) are prognostic markers in a variety of solid tumor malignancies. The potential of CTCs to be used as a liquid biopsy to monitor a patient’s condition and predict drug response and resistance is currently under investigation. Using a negative depletion, enrichment methology, CTCs isolated from the peripheral blood of breast cancer patients with stage IV breast cancer undergoing DNA damaging therapy with platinum based therapy were enriched. The enriched cell suspensions, were stained with an optimized labeling protocol targeting: nuclei, cytokeratins 8, 18, and 19, the surface marker CD45, and the presence of the protein ɣ-H2AX. As a direct or indirect result of platinum therapy, double strand break of DNA initiates phosphorylation of the histone H2AX, at serine 139; this phosphorylated form is referred to as ɣ-H2AX. In addition to ɣ-H2AX staining in specific locations with the cell nuclei, consistent with previous reports and referred to as foci, more general staining in the cell cytoplamim was also observed in some cells suggesting the potential of cell apoptosis. Our study underscores the utility and the complexity of investigating CTCs as predictive markers of response to various therapies. Additional studies are ongoing to evaluate the diverse γ-H2AX staining patterns we report here which needs to be further correlated with patient outcomeshttp://journal.frontiersin.org/Journal/10.3389/fonc.2012.00128/fullchemotherapyCirculating Tumor Cells (CTCs)metastatic breast cancergamma H2AXHer2neu |
| spellingShingle | Alejandra eGarcia-Villa Priya eBalsubramanian Brandon eMiller Maryam eLustberg Bhuvaneswari eRamaswamy Jeffrey eChalmers Assessment of γ-H2AX levels in circulating tumor cells from patients receiving chemotherapy Frontiers in Oncology chemotherapy Circulating Tumor Cells (CTCs) metastatic breast cancer gamma H2AX Her2neu |
| title | Assessment of γ-H2AX levels in circulating tumor cells from patients receiving chemotherapy |
| title_full | Assessment of γ-H2AX levels in circulating tumor cells from patients receiving chemotherapy |
| title_fullStr | Assessment of γ-H2AX levels in circulating tumor cells from patients receiving chemotherapy |
| title_full_unstemmed | Assessment of γ-H2AX levels in circulating tumor cells from patients receiving chemotherapy |
| title_short | Assessment of γ-H2AX levels in circulating tumor cells from patients receiving chemotherapy |
| title_sort | assessment of γ h2ax levels in circulating tumor cells from patients receiving chemotherapy |
| topic | chemotherapy Circulating Tumor Cells (CTCs) metastatic breast cancer gamma H2AX Her2neu |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2012.00128/full |
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