Interaction Between Ionizing Radiation, Estrogens and Antiestrogens in the Modification of Tumor Microenvironment in Estrogen Dependent Multicellular Spheroids

Villalobos, Mercedes; Aranda, M.; Núñez, María Isabel; Becerra, Diana; Olea, Nicolás; Almodóvar, Mariano Ruiz de; Pedraza, Vicente

doi:10.3109/02841869509094000

Cited by 22 publications

(7 citation statements)

References 19 publications

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“…This G1 phase block can be enhanced by tamoxifen and attenuated by estrogen. These observations have been confirmed by several studies with similar experimental conditions [ 62 , 63 , 64 ]. Interestingly, it has been demonstrated that anti-estrogen therapy can change radiosensitivity independent of the ER status, indicating that hormonal modulators might exert their effect via ERs but also in a non-receptor mode of action.…”

Section: The Combination Of Anti-estrogen and Irradiation Therapy supporting

confidence: 82%

Estrogen Receptor Signaling in Radiotherapy: From Molecular Mechanisms to Clinical Studies

Chen

Meinert

Heß

2018

IJMS

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Numerous studies have established a proof of concept that abnormal expression and function of estrogen receptors (ER) are crucial processes in initiation and development of hormone-related cancers and also affect the efficacy of anti-cancer therapy. Radiotherapy has been applied as one of the most common and potent therapeutic strategies, which is synergistic with surgical excision, chemotherapy and targeted therapy for treating malignant tumors. However, the impact of ionizing radiation on ER expression and ER-related signaling in cancer tissue, as well as the interaction between endocrine and irradiation therapy remains largely elusive. This review will discuss recent findings on ER and ER-related signaling, which are relevant for cancer radiotherapy. In addition, we will summarize pre-clinical and clinical studies that evaluate the consequences of anti-estrogen and irradiation therapy in cancer, including emerging studies on head and neck cancer, which might improve the understanding and development of novel therapeutic strategies for estrogen-related cancers.

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Section: The Combination Of Anti-estrogen and Irradiation Therapy supporting

confidence: 82%

Estrogen Receptor Signaling in Radiotherapy: From Molecular Mechanisms to Clinical Studies

Chen

Meinert

Heß

2018

IJMS

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“…In contrast, incubation of the MCF-7 cells with 17β-estradiol (E2) increased the radiosensitivity of the cells. Similar results have been reported by others [3][4][5], using similar experimental conditions (table 1). Tamoxifen treatment altered the survival of the irradiated MCF-7 cells by widening the shoulder portion of the survival curve, pointing towards an increased repair of radiation-induced potentially lethal DNA damage.…”

Section: In Vitro Experiments On the Interaction Of Estrogens Antiessupporting

confidence: 80%

“…In the receptor negative cell line MDA-MB-231 tamoxifen did not alter the intrinsic radiosensitivity [6]. Flow cytometry of MCF-7 cells after 48 h incubation with 1 µM or 5 µM tamoxifen showed an increased number of cells in the G0/G1 phase of the cell cycle and a decreased number of cells in the S phase, as observed for plateau-phase cells [3,4]. This supported the notion that tamoxifen increased the repair of potentially lethal damage following irradiation in hormone receptor positive cells.…”

Section: In Vitro Experiments On the Interaction Of Estrogens Antiesmentioning

confidence: 93%

Combination of Anti-Estrogenic Therapy with Radiation in Breast Cancer: Simultaneous or Sequential Treatment?

Schmidberger

Hermann²,

Hess³

et al. 2005

Oncol Res Treat

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Adjuvant radiotherapy and adjuvant endocrine therapy are commonly given to patients with invasive breast cancer or with ductal carcinoma in situ (DCIS). Although both therapies have been well established through a number of randomized studies, little is known about a possible interaction of both treatment modalities if they are given simultaneously. A number of in vitro studies indicated that tamoxifen treatment might reduce the intrinsic radiosensitivity of MCF-7 breast cancer cells. Conversely, estradiol treatment increased the intrinsic radiosensitivity of MCF-7 cells. This phenomenon has not been found in clinical studies. Retrospective analyses of prospectively randomized clinical studies did not indicate an antagonistic effect of tamoxifen on the effectiveness of ionizing radiation (XRT), since local control has been consistently higher when XRT was combined with tamoxifen, compared to treatment with XRT alone, regardless of whether tamoxifen was started simultaneously with radiotherapy or after completion of radiotherapy. Currently there are no clinical data available that would suggest an adverse effect of adjuvant tamoxifen treatment started prior to or simultaneously with radiotherapy in breast cancer or DCIS. However, since an antagonistic effect of tamoxifen and simulteneous chemotherapy has been reported recently, the issue of simultaneous

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“…For example, taking advantage of the fact that MCF-7 multicellular spheroids are oestrogen-dependent, it would be possible to synchronise the cells in different cycle phases using anti-oestrogens [37]. In this way the effects on the hypersensitivity due to the cellular cycle phase can be studied, and one would be able to evaluate whether the expression of the proteins produced by the various genes involved in cell repair, such as p53, ATM or PARP, is different from those with MCF-7 cells growing in monolayers [38,39].…”

Section: Low-dose Radiation Hyper-radiosensitivitymentioning

confidence: 99%

Low-dose radiation hyper-radiosensitivity in multicellular tumour spheroids

Guirado¹,

Aranda²,

Ortiz³

et al. 2012

BJR

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Objective: We propose and study a new model aimed at describing the low-dose hyperradiosensitivity phenomenon appearing in the survival curves of different cell lines. Methods: The model uses the induced repair assumption, considering that the critical dose at which this mechanism begins to act varies from cell to cell in a given population. The model proposed is compared with the linear-quadratic model and the modified linear-quadratic model, which is commonly used in literature and in which the induced repair is taken into account in a heuristic way. The survival curve for the MCF-7 line of human breast cancer is measured at low absorbed doses and the uncertainties in these doses are estimated using thermoluminiscent dosemeters. Results: It is shown that these multicellular spheroids present low-dose hyperradiosensitivity. The new model permits an accurate description of the data of two human cell lines (previously published) and of the multicellular spheroids of the MCF-7 line here measured. Conclusion: The model shows enough flexibility to account for data with very different characteristics and considers in a faithful way the hypothesis of the repair induction.

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Interaction Between Ionizing Radiation, Estrogens and Antiestrogens in the Modification of Tumor Microenvironment in Estrogen Dependent Multicellular Spheroids

Cited by 22 publications

References 19 publications

Estrogen Receptor Signaling in Radiotherapy: From Molecular Mechanisms to Clinical Studies

Estrogen Receptor Signaling in Radiotherapy: From Molecular Mechanisms to Clinical Studies

Combination of Anti-Estrogenic Therapy with Radiation in Breast Cancer: Simultaneous or Sequential Treatment?

Low-dose radiation hyper-radiosensitivity in multicellular tumour spheroids

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