scholarly journals A Novel Approach for the Discovery of Biomarkers of Radiotherapy Response in Breast Cancer

2021 ◽  
Vol 11 (8) ◽  
pp. 796
Author(s):  
James Meehan ◽  
Mark Gray ◽  
Carlos Martínez-Pérez ◽  
Charlene Kay ◽  
Jimi C. Wills ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Breast Conserving Surgery ◽  
Therapeutic Benefit ◽  
Survival Times ◽  
Clinical Role ◽  
Protein Levels ◽  
Treatment Regimens ◽  
Novel Approach ◽  
Intrinsic Radiosensitivity

Radiotherapy (RT) is an important treatment modality for the local control of breast cancer (BC). Unfortunately, not all patients that receive RT will obtain a therapeutic benefit, as cancer cells that either possess intrinsic radioresistance or develop resistance during treatment can reduce its efficacy. For RT treatment regimens to become personalised, there is a need to identify biomarkers that can predict and/or monitor a tumour’s response to radiation. Here we describe a novel method to identify such biomarkers. Liquid chromatography-mass spectrometry (LC-MS) was used on conditioned media (CM) samples from a radiosensitive oestrogen receptor positive (ER+) BC cell line (MCF-7) to identify cancer-secreted biomarkers which reflected a response to radiation. A total of 33 radiation-induced secreted proteins that had higher (up to 12-fold) secretion levels at 24 h post-2 Gy radiation were identified. Secretomic results were combined with whole-transcriptome gene expression experiments, using both radiosensitive and radioresistant cells, to identify a signature related to intrinsic radiosensitivity. Gene expression analysis assessing the levels of the 33 proteins showed that 5 (YBX3, EIF4EBP2, DKK1, GNPNAT1 and TK1) had higher expression levels in the radiosensitive cells compared to their radioresistant derivatives; 3 of these proteins (DKK1, GNPNAT1 and TK1) underwent in-lab and initial clinical validation. Western blot analysis using CM samples from cell lines confirmed a significant increase in the release of each candidate biomarker from radiosensitive cells 24 h after treatment with a 2 Gy dose of radiation; no significant increase in secretion was observed in the radioresistant cells after radiation. Immunohistochemistry showed that higher intracellular protein levels of the biomarkers were associated with greater radiosensitivity. Intracellular levels were further assessed in pre-treatment biopsy tissues from patients diagnosed with ER+ BC that were subsequently treated with breast-conserving surgery and RT. High DKK1 and GNPNAT1 intracellular levels were associated with significantly increased recurrence-free survival times, indicating that these two candidate biomarkers have the potential to predict sensitivity to RT. We suggest that the methods highlighted in this study could be utilised for the identification of biomarkers that may have a potential clinical role in personalising and optimising RT dosing regimens, whilst limiting the administration of RT to patients who are unlikely to benefit.

scholarly journals Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ashley A. Krull ◽  
Deborah O. Setter ◽  
Tania F. Gendron ◽  
Sybil C. L. Hrstka ◽  
Michael J. Polzin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebrospinal Fluid ◽  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Large Scale ◽  
Therapeutic Benefit ◽  
Protein Levels ◽  
Genes Encoding ◽  
Intrathecal Space

Abstract Background Mesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases. Methods In this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS). Results Our results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs. Conclusions Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.

Ultrasonography Mapping Combined With Mammography Before Breast-Conserving Surgery for Primary Breast Cancer With Microcalcifications: A Novel Approach

2014 ◽  
Vol 14 (5) ◽  
pp. 352-357 ◽  
Author(s):  
Gensuke Akaike ◽  
Hiroko Tsunoda ◽  
Naoki Hayashi ◽  
Toshinao Onoda ◽  
Satoshi Honda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Breast Conserving Surgery ◽  
Novel Approach

scholarly journals The effect of 10 weeks endurance training on protein levels of NF-kB and gene expression of Atrogin-1 and MuRF-1 in cardiac myocytes of female

2021 ◽  
Vol 43 (1) ◽  
pp. 134-141
Author(s):  
Naiemeh Yazdan Shenas ◽  
Maghsoud Peeri ◽  
Maryam Delfan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Endurance Training ◽  
Cardiac Myocyte ◽  
Training Session ◽  
Training Group ◽  
Left Ventricular ◽  
Control Group ◽  
Protein Levels ◽  
Cardiac Atrophy

Background: Cardiac atrophy is the most important complications resulted by cancer Given the role of exercise in protecting against cancer complications, the aim of the present study was to determine the effect of 10 weeks of endurance training on protein levels of NF-kB and gene expression of Atrogin-1 and MuRF-1 in cardiac myocyte of female Balb/C mic with breast cancer. Methods: The present study was an experimental study. Twelve female BALB/c mice after inducing breast cancer were randomly divided into two groups (n=6) including endurance training group (E) and the control group (C). E group performed 65 min at a constant running speed corresponding to 60% vVo2max at 15% inclination, ten weeks (five days a week). The Left ventricular of animals was extracted 24h following the last training session. Protein levels of NF-kB and gene expression of Atrogin-1 and MuRF-1 were determined by, respectively, western blot and qReal-time PCR. Statistic data values also were measured by independent samples t-test at the 0.05 levels of significance. Results: The results of the present study showed a significant decreased in cardiac protein levels of NF-kB (p<0.001) and cardiac gene expression of Atrogin-1 (p<0.001) and MuRF-1 (p=0.003) in comparison with control group. Endurance training group had significantly greater heart weights compared to control group (p<0.001). Conclusion: it seems that 10 weeks of endurance training possibly affect mechanisms involved in cancer-induced cardiac atrophy such as NF-kB/Atrogin-1/MuRF-1 axis results in decreasing cardiac atrophy in mice with breast cancer.

scholarly journals Tumour response 3 months after neoadjuvant single-fraction radiotherapy for low-risk breast cancer

2020 ◽  
Vol 27 (3) ◽  
Author(s):  
D. Tiberi ◽  
P. Vavassis ◽  
D. Nguyen ◽  
M. C. Guilbert ◽  
A. Simon-Cloutier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Tumour Response ◽  
Breast Conserving Surgery ◽  
Early Stage Breast Cancer ◽  
Primary Breast Tumor ◽  
Luminal A ◽  
Single Fraction ◽  
Novel Approach ◽  
Microscopic Evaluation

Introduction Standard treatment for early-stage invasive breast cancer consists of breast-conserving surgery (BCS) and several weeks of adjuvant radiotherapy (RT). Neoadjuvant single-fraction RT is a novel approach for early-stage breast cancer. We sought to investigate the effect of delaying surgery after neoadjuvant RT with respect to the rates pathological response (PR).   Materials and Methods Women aged 65 years or older with a new diagnosis of stage I, luminal A, breast cancer were eligible for inclusion. A single dose of 20 Gy to the primary breast tumor was given followed by BCS 3 months later. The primary endpoint was the rate of PR as assessed by microscopic evaluation using the Miller-Payne system.   Results 10 patients were successfully treated to date. The median age of the patients was 72 years (65-84). 8 patients had a pathological tumor response (PR) to neoadjuvant RT with a median residual cellularity of 3%. No immediate RT complications were noted other than mild dermatitis. Conclusions This study demonstrates a method for delivering single fraction RT that can lead to high levels of PR in most patients. Continued accrual of this study and subsequent trials are needed to determine the feasibility, safety and role of this novel technique in the management of early-stage breast cancer.  

Harmonic scalpel versus traditional ligation in axillary dissection for breast cancer: a retrospective multivariate analysis

2020 ◽  
Vol 99 (11) ◽  
Keyword(s):  
Breast Cancer ◽  
Axillary Dissection ◽  
Harmonic Scalpel ◽  
Breast Conserving Surgery ◽  
Seroma Formation ◽  
Nodal Involvement ◽  
Single Centre ◽  
Absorbable Material ◽  
Drain Removal ◽  
The Mean

Introduction: The aim of this pilot retrospective study is to evaluate the complication rate in patients after axillary dissection comparing preparation with harmonic scalpel vs traditional ligation technique, and to analyse risk factors for complications occurrence. Methods: 144 patients with 148 axillary dissections operated in a single centre between January 2014 and 2019 were included into the study. Axillary dissection was performed using harmonic scalpel in 73 and absorbable ligations in 70 cases. Results: Seroma formation was observed in 41 patients (56.2%) in the harmonic scalpel group and in 21 patients (30.0%) in the ligations group (p=0.003). The mean period from the surgery to drain removal was 4.0 days in the harmonic scalpel group and 3.0 days in the ligations group (p<0.001). The mean amount of the drained fluid after mastectomy was 300.9 ml in the harmonic scalpel group and 168.7 ml in the ligations group (p=0.005); after breast conserving surgery, it was 241.9 ml and 107.4 ml, respectively (p =0.023). Conclusion: In comparison with traditional ligations with absorbable material, axillary dissection using harmonic scalpel significantly increases the risk of postoperative seroma formation, prolongs the time from the surgery to drain removal, and increases the amount of drained fluid.ut any suspicion of nodal involvement, hemithyroidectomy is considered to be a sufficient procedure or the method of choice, respectively.

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