Cytokine profile of breast cell lines after different radiation doses.

PURPOSE: Ionizing radiation (IR) treatment activates inflammatory processes causing the release of a great amount of molecules able to affect the cell survival. The aim of this study was to analyze the cytokine signature of conditioned medium produced by non-tumorigenic mammary epithelial cell line MCF10A, as well as MCF7 and MDA-MB-231 breast cancer cell lines, after single high doses of IR in order to understand their role in high radiation response. MATERIALS AND METHODS: We performed a cytokine profile of irradiated conditioned media of MCF10A, MCF7 and MDA-MB-231 cell lines treated with 9 or 23 Gy, by Luminex and ELISA analyses. RESULTS: Overall, our results show that both 9 Gy and 23 Gy of IR induce the release within the first 72 h of cytokines and growth factors potentially able to influence the tumor outcome, with a dose-independent and cell-line dependent signature. Moreover, our results show that the cell-senescence phenomenon does not correlate with the amount of 'senescence-associated secretory phenotype' (SASP) molecules released in media. Thus, additional mechanisms are probably involved in this process. CONCLUSIONS: These data open the possibility to evaluate cytokine profile as useful marker in modulating the personalized radiotherapy in breast cancer care.

High-Intensity Focused Ultrasound- and Radiation Therapy-Induced Immuno-Modulation: Comparison and Potential Opportunities.

In recent years, high-intensity focused ultrasound (HIFU) has emerged as a new and promising non-invasive and non-ionizing ablative technique for the treatment of localized solid tumors. Extensive pre-clinical and clinical studies have evidenced that, in addition to direct destruction of the primary tumor, HIFU-thermoablation may elicit long-term systemic host anti-tumor immunity. In particular, an important consequence of HIFU treatment includes the release of tumor-associated antigens (TAAs), the secretion of immuno-suppressing factors by cancer cells and the induction of cytotoxic T lymphocyte (CTL) activity. Radiation therapy (RT) is the main treatment modality used for many types of tumors and about 50% of all cancer patients receive RT, often used in combination with surgery and chemotherapy. It is well known that RT can modulate anti-tumor immune responses, modifying micro-environment and stimulating inflammatory factors that can greatly affect cell invasion, bystander effects, radiation tissue complications (such as fibrosis), genomic instability and thus, intrinsic cellular radio-sensitivity. To date, various combined therapeutic strategies (such as immuno-therapy) have been performed in order to enhance RT success in treating locally advanced and recurrent tumors. Recent works suggested the combined use of HIFU and RT treatments to increase the tumor cell radio-sensitivity, in order to synergize the effects reaching the maximum results with minimal doses of ionizing radiation (IR). Here, we highlight the opposite immuno-modulation roles of RT and HIFU, providing scientific reasons to test, by experimental approaches, the use of HIFU immune-stimulatory capacity to improve tumor radio-sensitivity, to reduce the RT induced inflammatory response and to decrease the dose-correlated side effects in normal tissues.

Portrait of inflammatory response to ionizing radiation treatment.

Ionizing radiation (IR) activates both pro-and anti-proliferative signal pathways producing an imbalance in cell fate decision. IR is able to regulate several genes and factors involved in cell-cycle progression, survival and/or cell death, DNA repair and inflammation modulating an intracellular radiation-dependent response. Radiation therapy can modulate anti-tumour immune responses, modifying tumour and its microenvironment. In this review, we report how IR could stimulate inflammatory factors to affect cell fate via multiple pathways, describing their roles on gene expression regulation, fibrosis and invasive processes. Understanding the complex relationship between IR, inflammation and immune responses in cancer, opens up new avenues for radiation research and therapy in order to optimize and personalize radiation therapy treatment for each patient.

Identification of three particular morphological phenotypes in sporadic thoracic aortic aneurysm: phenotype III as sporadic thoracic aortic aneurysm biomarker in aged individuals.

Aging has a striking impact on the heart and the vascular system, and particularly on the large elastic arteries (i.e., aorta), resulting in a multitude of changes at different structural and functional levels. As result, medial degeneration (MD) occurs. A characteristic example of MD is sporadic thoracic aortic aneurysm (S-TAA), whose patho-physiological mechanisms remain unclear. In this study, typical MD morphological phenotypes were researched in S-TAA cases and control aorta specimens using histopathological and mainly immunohistochemical analyses. Three phenotypes (I, II, and III) were detected, but the phenotype III was observed. Elevated cystic MD, plurifocal medial apoptosis, and increased metalloproteinase-9 amount characterize it. In addition, it was significantly correlated with the severity of elastic fragmentation, hypertension, and smoking, and particularly with advancing age. Thus, phenotype III might represent the typical MD phenotype associated with S-TAA in old people that have a major risk of aorta rupture and dissection independently on aneurysm diameter. This might permit the assumption that phenotype III with its typical histological abnormalities is an optimal biomarker of rupture and/or dissection in aged individuals and is useful both for applying different surgical approaches and providing appropriate surgical indications.