Irradiation of normal mouse tissue increases the invasiveness of mammary cancer cells

Purpose:?Treatment of breast tumours frequently involves irradiating the whole breast to reach malignant microfoci scattered throughout the breast. In this study, we determined whether irradiation of normal tissues could increase the invasiveness of breast cancer cells in a mouse model.

Materials and methods:?Non-irradiated MC7-L1 mouse mammary carcinoma cells were injected subcutaneously in irradiated and non-irradiated thighs of Balb/c mice. The invasion volume, tumour volume, blood vessel permeability and interstitial volumes were monitored by magnetic resonance imaging (MRI). Slices of normal tissue invaded by cancer cells were examined by histology. Activity of matrix metalloproteinase -2 and -9 (MMP -2 and -9) in healthy and irradiated tissues was determined, and the proliferation index of the invading cancer cells was evaluated.

Results:?Three weeks after irradiation, enhancement of MC7-L1 cells invasiveness in irradiated thighs was already detected by MRI. The tumour invasion volume continued to extend 28- to 37-fold compared to the non-irradiated implantation site for the following three weeks, and it was associated with an increase of MMP-2 and -9 activities in healthy tissues. The interstitial volume associated with invading cancer cells was significantly larger in the pre–irradiated sites; while the blood vessels permeability was not altered. Cancer cells invading the healthy tissues were proliferating at a lower rate compared to non-invading cancer cells.

Conclusion:?Implantation of non-irradiated mammary cancer cells in previously irradiated normal tissue enhances the invasive capacity of the mammary cancer cells and is associated with an increased activity of MMP-2 and -9 in the irradiated normal tissue.     

Exploring the radiosensitizing potential of magnetotherapy: a pilot study in breast cancer cells

Abstract

Aim: To explore the influence of electromagnetic fields (EMFs) on the cell cycle progression of MDA-MB-231 and MCF-7 breast cancer cell lines and to evaluate the radiosensitizing effect of magnetotherapy during therapeutic co-exposure to EMFs and radiotherapy.

Material and methods: Cells were exposed to EMFs (25, 50 and 100?Hz; 8 and 10?mT). In the co-treatment, cells were first exposed to EMFs (50?Hz/10?mT) for 30?min and then to ionizing radiation (IR) (2?Gy) 4?h later. Cell cycle progression and free radical production were evaluated by flow cytometry, while radiosensitivity was explored by colony formation assay.

Results: Generalized G1-phase arrest was found in both cell lines several hours after EMF exposure. Interestingly, a marked G1-phase delay was observed at 4?h after exposure to 50?Hz/10?mT EMFs. No cell cycle perturbation was observed after repeated exposure to EMFs. IR-derived ROS production was enhanced in EMF-exposed MCF-7 cells at 24?h post-exposure. EMF-exposed cells were more radiosensitive in comparison to sham-exposed cells.

Conclusions: These results highlight the potential benefits of concomitant treatment with magnetotherapy before radiotherapy sessions to enhance the effectiveness of breast cancer therapy. Further studies are warranted to identify the subset(s) of patients who would benefit from this multimodal treatment.     

Radioactive seed localisation (RSL) in the treatment of non-palpable breast cancers: Systematic review and meta-analysis

IntroductionThis systematic review compares the outcomes of radioactive seed localisation (RSL) versus standard wire-guided localisation (WGL) in the management of non-palpable breast cancers.MethodsWe performed a literature search of PubMed, EMBASE and the Cochrane database to identify clinical studies using RSL. Included studies examined invasive breast cancer and reported objective pathological outcome measurements. Quantitative data analyses were performed.Results197 papers were identified with eight being clinically relevant to our study. From these eight studies there was only one identified as being a randomised controlled trial (RCT) and four as cohort studies having a control WGL group and included in the quantitative analysis. This provided an overall combined odds ratio (OR) 0.51 (95% CI, 0.36–0.72; z = 3.88; p = 0.0001) for involved surgical margin status; OR, 0.47 (95% CI, 0.33–0.69; z = 3.96; p < 0.0001) for re-operation rates and mean difference (MD) ?1.32 (95% CI, ?2.32, ?0.32; z = 2.58; p = 0.01) for operative time favouring RSL over WGL. In the case of volume of specimens excised, MD 1.46; (95% CI, ?22.35, 25.26; z = 0.12; p = 0.90) showing no statistical significance for volume of tissue excised in specimens between the two groups.ConclusionsThe results of this systematic review demonstrate a statistically significant benefit of RSL over the gold standard of WGL in terms of involved margin status, re-operation rates and reduced operative time but no statistically significant difference with WGL in terms of volume of tissue excised in the treatment of non-palpable breast cancers. Adequately powered, multicentre RCTs are needed to validate these results.     

Chemotherapy causes cancer! A case report of therapy related acute myeloid leukaemia in early stage breast cancer.

Use of chemotherapy and radiotherapy in the adjuvant setting has improved survival for many patients with malignancy. Unfortunately multimodality treatment can come at a price, in particular therapy-related malignancies. This has importance in that patients must be made aware of this potential detriment from therapy and doctors must consider this diagnosis in those patients who are cancer survivors and presenting with health problems. We present a case report and brief overview of the literature regarding chemotherapy-induced acute myeloid leukaemia (AML) following therapy for early stage breast cancer.     

Sense-antisense gene-pairs in breast cancer and associated pathological pathways

More than 30% of human protein-coding genes form hereditary complex genome architectures composed of sense-antisense (SA) gene pairs (SAGPs) transcribing their RNAs from both strands of a given locus. Such architectures represent important novel components of genome complexity contributing to gene expression deregulation in cancer cells. Therefore, the architectures might be involved in cancer pathways and, in turn, be used for novel drug targets discovery. However, the global roles of SAGPs in cancer pathways has not been studied. Here we investigated SAGPs associated with breast cancer (BC)-related pathways using systems biology, prognostic survival and experimental methods. Gene expression analysis identified 73 BC-relevant SAGPs that are highly correlated in BC. Survival modelling and metadata analysis of the 1161 BC patients allowed us to develop a novel patient prognostic grouping method selecting the 12 survival-significant SAGPs. The qRT-PCR-validated 12-SAGP prognostic signature reproducibly stratified BC patients into low- and high-risk prognostic subgroups. The 1381 SAGP-defined differentially expressed genes common across three studied cohorts were identified. The functional enrichment analysis of these genes revealed the GABPA gene network, including BC-relevant SAGPs, specific gene sets involved in cell cycle, spliceosomal and proteasomal pathways. The co-regulatory function of GABPA in BC cells was supported using siRNA knockdown studies. Thus, we demonstrated SAGPs as the synergistically functional genome architectures interconnected with cancer-related pathways and associated with BC patient clinical outcomes. Taken together, SAGPs represent an important component of genome complexity which can be used to identify novel aspects of coordinated pathological gene networks in cancers.