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- Guimei, Maha, et al.
(author)
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Inhibition of Yes-Associated Protein-1 (YAP1) Enhances the Response of Invasive Breast Cancer Cells to the Standard Therapy
- 2020
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In: Breast Cancer. - : DOVE MEDICAL PRESS LTD. - 1179-1314. ; 12, s. 189-199
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Journal article (peer-reviewed)abstract
- Purpose: The deregulation of the Hippo pathway results in translocation ofYes-associated protein-1 (YAP1) to the nucleus to exert an oncogenic effect. This effect has been demonstrated in several malignancies, yet, in breast cancer (BC), it remains controversial. The present study aimed to investigate the significance of YAP1 expression in BC, its relation to cancer stem cells (CSCs), and the effect of its inhibition on tumor cell survival. Patients and Methods: We evaluated the expression of YAP1 protein and gene using immunohistochemistry (IHC) and RT-qPCR in FFPE tissue from normal and breast cancer cases. We also studied its association with CSC expression (OCT4, NANOG, and SOX2) and with different clinicopathologic characteristics. Two BC cell lines (MCF7 and MDA-MB -231) were exposed to different concentrations of YAP1 inhibitor "verteporfin" and cell viability was subsequently assessed. Results: YAP1 mRNA was higher in BC compared to the normal breast tissue (p-value=0.040) and was higher in luminal tumors compared to triple-negative breast cancer (TNBC) (p-value= 0.017). Its expression in tumors was significantly associated with the expression of pluripotency markers (OCT4 and NANOG) (p-value= 0.030 and 0.035, respectively) and its inhibition resulted in a significant reduction of CSC expression in both MCF-7 and MDA-MB-231 cells. YAP1 nuclear expression by IHC, which signifies its activation, was more evident in invasive carcinomas compared to normal breast tissue and in-situ foci where the expression was limited to the cytoplasm. The pretreatment of BC cells (MCF7 and MDA-MB-231) with YAP1 inhibitor "verteporfin" resulted in their sensitization to the effect of tamoxifen and doxorubicin, respectively, and significantly decreased tumor cell proliferation and survival. Conclusion: Our results imply that YAP1 is highly expressed and activated in BC and its inhibition could represent a possible novel therapeutic strategy that should be further explored and investigated to improve the outcome of breast cancer patients.
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| 2. |
- Isfoss, Björn Logi, et al.
(author)
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The absence of aldehyde dehydrogenase 1 A1-positive cells in benign mammary stroma is associated with risk factors for breast cancer
- 2016
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In: Breast Cancer: Targets and Therapy. - 1179-1314. ; 8, s. 117-124
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Journal article (peer-reviewed)abstract
- In this study, aldehyde dehydrogenase 1 (ALDH1)-expressing cells in stroma of histologically normal breast tissue from premenopausal women were investigated in situ regarding cellular morphology, cell distribution, and relation to the additional stem cell markers, CD44 (+) and CD24 (-). These results were correlated with hormonal and genetic risk factors for breast cancer. Triple immunofluorescence labeling was performed on tissues from premenopausal women with a family history of breast cancer, and breast reduction specimens from premenopausal women with no family history of breast cancer were used as a control group. The majority of ALDH1-immunoreactive cells in stroma were spindle-shaped or polygonal, and such cells that were CD44- and CD24- were absent in the breast stroma of a significantly larger number of nulliparous than parous women. A less common morphological type of ALDH1-positive cells in stroma was round or oval in shape, and such cells that were CD44+ and CD24- were absent in a significant number of women with a family history of breast cancer. The CD44+/CD24- immunophenotype is consistent with stem cells, and the round/oval morphology suggests mesenchymal cells. This study demonstrates that there are two morphologically distinct types of ALDH1-positive cells in histologically benign mammary stroma, and the absence of these cells is correlated with clinical risk factors for breast cancer in premenopausal women.
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| 5. |
- Valachis, Antonis, et al.
(author)
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Cardiac risk in the treatment of breast cancer : assessment and management
- 2015
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In: Breast Cancer. - 1179-1314. ; 7, s. 21-35
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Research review (peer-reviewed)abstract
- As the number of long-term breast cancer survivors has increased, the side effects of adjuvant cancer therapy, such as cardiac toxicity, remain clinically important. Although the cardiac toxicity due to anthracyclines, radiotherapy, or trastuzumab is well-documented, several issues need to be clarified and are the subjects of extensive ongoing clinical research. This review summarizes the incidence of cardiac toxicity due to breast cancer adjuvant therapy and highlights the current trends in early detection and management of cardiac toxicities.
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